Lee J

References (132)

Title : Genetic and Transcriptional Regulatory Mechanisms of Lipase Activity in the Plant Pathogenic Fungus Fusarium graminearum - Kim_2023_Microbiol.Spectr__e0528522
Author(s) : Kim S , Lee J , Park J , Choi S , Bui DC , Kim JE , Shin J , Kim H , Choi GJ , Lee YW , Chang PS , Son H
Ref : Microbiol Spectr , :e0528522 , 2023
Abstract : Lipases, which catalyze the hydrolysis of long-chain triglycerides, diglycerides, and monoglycerides into free fatty acids and glycerol, participate in various biological pathways in fungi. In this study, we examined the biological functions and regulatory mechanisms of fungal lipases via two approaches. First, we performed a systemic functional characterization of 86 putative lipase-encoding genes in the plant-pathogenic fungus Fusarium graminearum. The phenotypes were assayed for vegetative growth, asexual and sexual reproduction, stress responses, pathogenicity, mycotoxin production, and lipase activity. Most mutants were normal in the assessed phenotypes, implying overlapping roles for lipases in F. graminearum. In particular, FgLip1 and Fgl1 were revealed as core extracellular lipases in F. graminearum. Second, we examined the lipase activity of previously constructed transcription factor (TF) mutants of F. graminearum and identified three TFs and one histone acetyltransferase that significantly affect lipase activity. The relative transcript levels of FgLIP1 and FGL1 were markedly reduced or enhanced in these TF mutants. Among them, Gzzc258 was identified as a key lipase regulator that is also involved in the induction of lipase activity during sexual reproduction. To our knowledge, this study is the first comprehensive functional analysis of fungal lipases and provides significant insights into the genetic and regulatory mechanisms underlying lipases in fungi. IMPORTANCE Fusarium graminearum is an economically important plant-pathogenic fungus that causes Fusarium head blight (FHB) on wheat and barley. Here, we constructed a gene knockout mutant library of 86 putative lipase-encoding genes and established a comprehensive phenotypic database of the mutants. Among them, we found that FgLip1 and Fgl1 act as core extracellular lipases in this pathogen. Moreover, several putative transcription factors (TFs) that regulate the lipase activities in F. graminearum were identified. The disruption mutants of F. graminearum-lipase regulatory TFs all showed defects in sexual reproduction, which implies a strong relationship between sexual development and lipase activity in this fungus. These findings provide valuable insights into the genetic mechanisms regulating lipase activity as well as its importance to the developmental stages of this plant-pathogenic fungus.
ESTHER : Kim_2023_Microbiol.Spectr__e0528522
PubMedSearch : Kim_2023_Microbiol.Spectr__e0528522
PubMedID: 37093014

Title : Effects of two alternative plasticizers on the growth hormone-related endocrine system, neurodevelopment, and oxidative stress of zebrafish larvae - Yun_2023_Environ.Pollut_341_122947
Author(s) : Yun K , Jeon H , Lee J , Kho Y , Ji K
Ref : Environ Pollut , 341 :122947 , 2023
Abstract : In response to the restriction of phthalate plasticizers, acetyl tributyl citrate (ATBC) and acetyl triethyl citrate (ATEC) have been used in medical devices and food packaging. In the present study, the effects of ATBC and ATEC on the development, behavior, growth hormone (GH)-related endocrine system, neurotransmitters, and oxidative stress of zebrafish embryo or larvae were investigated. After exposure of zebrafish to ATBC and ATEC (0, 0.03, 0.3, 3, 30, and 300 microg/L) for 96 h, developmental toxicity, behavioral changes under light/dark condition, changes in hormones and genes involved in GH/insulin-like growth factors (IGFs) axis, changes in hormone, enzyme, and genes related to neurodevelopment, antioxidant enzymes activities were determined. Larvae exposed to 30 or 300 microg/L ATBC showed significant reductions in body length and moving distance and speed, whereas no significant effects on development and locomotor behavior were observed in larvae exposed to ATEC. The contents of GH and IGF-I were significantly reduced in larvae exposed to 3, 30, and 300 microg/L ATBC. Hormonal changes in fish exposed to ATBC are well supported by regulation of genes related to GH (gh1) and the activity of IGF-I (igf1). In fish exposed to ATBC, reduced acetylcholinesterase activity and down-regulation of genes related to the central nervous system development (ache, gap43, mbpa, and syn21) were observed. ATBC increased the production of reactive oxygen species and the levels of superoxide dismutase, catalase, and glutathione peroxidase. Notably, pre-treatment with the classic antioxidant N-acetylcysteine alleviated ATBC-induced GH-related endocrine disruption and neurotoxicity. Our observations showed that exposure to low levels of ATBC could disturb the regulatory systems of GH/IGFs axis and neurobehavior, ultimately leading to developmental inhibition and hypoactivity, and that increased oxidative stress plays a major role in these toxicities.
ESTHER : Yun_2023_Environ.Pollut_341_122947
PubMedSearch : Yun_2023_Environ.Pollut_341_122947
PubMedID: 37977359

Title : Cholinesterase inhibitors and falls, syncope and injuries in patients with cognitive impairment: a systematic review and meta-analysis - Ahuja_2023_Age.Ageing_52_
Author(s) : Ahuja M , Siddhpuria S , Karimi A , Lewis K , Wong E , Lee J , Reppas-Rindlisbacher C , Sood E , Gabor C , Patterson C
Ref : Age Ageing , 52 : , 2023
Abstract : BACKGROUND: Cholinesterase inhibitors are commonly used to treat patients with neurocognitive disorders, who often have an elevated risk of falling. Effective use of these medications requires a thoughtful assessment of risks and benefits. OBJECTIVE: To provide an update on previous reviews and determine the association between cholinesterase inhibitors and falls, syncope, fracture and accidental injuries in patients with neurocognitive disorders. METHODS: Embase, MEDLINE, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature and AgeLine were systematically searched through March 2023 to identify all randomised controlled trials of cholinesterase inhibitors (donepezil, galantamine, rivastigmine) in patients with cognitive impairment. Corresponding authors were contacted for additional data necessary for meta-analysis. Inclusion criteria consisted of adults <=19 years, with a diagnosis of dementia, Parkinson's disease, mild cognitive impairment or traumatic brain injury. Data were extracted in duplicate for the aforementioned primary outcomes and all outcomes were analysed using random-effects meta-analysis. RESULTS: Fifty three studies (30 donepezil, 14 galantamine, 9 rivastigmine) were included providing data on 25, 399 patients. Cholinesterase inhibitors, compared to placebo, were associated with reduced risk of falls (risk ratio [RR] 0.84 [95% confidence interval [CI] = 0.73-0.96, P = 0.009]) and increased risk of syncope (RR 1.50 [95% CI = 1.02-2.21, P = 0.04]). There was no association with accidental injuries or fractures. CONCLUSION: In patients with neurocognitive disorders, cholinesterase inhibitors were associated with decreased risk of falls, increased risk of syncope and no association with accidental trauma or fractures. These findings will help clinicians better evaluate risks and benefits of cholinesterase inhibitors.
ESTHER : Ahuja_2023_Age.Ageing_52_
PubMedSearch : Ahuja_2023_Age.Ageing_52_
PubMedID: 37993407

Title : GABAergic-like dopamine synapses in the brain - Kim_2023_Cell.Rep_42_113239
Author(s) : Kim HJ , Hwang B , Reva M , Lee J , Lee BE , Lee Y , Cho EJ , Jeong M , Lee SE , Myung K , Baik JH , Park JH , Kim JI
Ref : Cell Rep , 42 :113239 , 2023
Abstract : Dopamine synapses play a crucial role in volitional movement and reward-related behaviors, while dysfunction of dopamine synapses causes various psychiatric and neurological disorders. Despite this significance, the true biological nature of dopamine synapses remains poorly understood. Here, we show that dopamine transmission is strongly correlated with GABA co-transmission across the brain and dopamine synapses are structured and function like GABAergic synapses with marked regional heterogeneity. In addition, GABAergic-like dopamine synapses are clustered on the dendrites, and GABA transmission at dopamine synapses has distinct physiological properties. Interestingly, the knockdown of neuroligin-2, a key postsynaptic protein at GABAergic synapses, unexpectedly does not weaken GABA co-transmission but instead facilitates it at dopamine synapses in the striatal neurons. More importantly, the attenuation of GABA co-transmission precedes deficits in dopaminergic transmission in animal models of Parkinson's disease. Our findings reveal the spatial and functional nature of GABAergic-like dopamine synapses in health and disease.
ESTHER : Kim_2023_Cell.Rep_42_113239
PubMedSearch : Kim_2023_Cell.Rep_42_113239
PubMedID: 37819757

Title : Mumefural Improves Recognition Memory and Alters ERK-CREB-BDNF Signaling in a Mouse Model of Chronic Cerebral Hypoperfusion - Kim_2023_Nutrients_15_
Author(s) : Kim MS , Kim BY , Kim JI , Lee J , Jeon WK
Ref : Nutrients , 15 : , 2023
Abstract : Cognitive impairment resulting from chronic cerebral hypoperfusion (CCH) is known as vascular dementia (VaD) and is associated with cerebral atrophy and cholinergic deficiencies. Mumefural (MF), a bioactive compound found in a heated fruit of Prunus mume Sieb. et Zucc, was recently found to improve cognitive impairment in a rat CCH model. However, additional evidence is necessary to validate the efficacy of MF administration for treating VaD. Therefore, we evaluated MF effects in a mouse CCH model using unilateral common carotid artery occlusion (UCCAO). Mice were subjected to UCCAO or sham surgery and orally treated with MF daily for 8 weeks. Behavioral tests were used to investigate cognitive function and locomotor activity. Changes in body and brain weights were measured, and levels of hippocampal proteins (brain-derived neurotrophic factor (BDNF), extracellular signal-regulated kinase (ERK), cyclic AMP-response element-binding protein (CREB), and acetylcholinesterase (AChE)) were assessed. Additionally, proteomic analysis was conducted to examine the alterations in protein profiles induced by MF treatment. Our study showed that MF administration significantly improved cognitive deficits. Brain atrophy was attenuated and MF treatment reversed the increase in AChE levels. Furthermore, MF significantly upregulated p-ERK/ERK, p-CREB/CREB, and BDNF levels after UCCAO. Thus, MF treatment ameliorates CCH-induced cognitive impairment by regulating ERK/CREB/BDNF signaling, suggesting that MF is a therapeutic candidate for treating CCH.
ESTHER : Kim_2023_Nutrients_15_
PubMedSearch : Kim_2023_Nutrients_15_
PubMedID: 37513692

Title : Inhibition of Soluble Epoxide Hydrolase Activity by Components of Glycyrrhiza uralensis - Kim_2023_Int.J.Mol.Sci_24_6485
Author(s) : Kim JH , Huh YC , Hur M , Park WT , Moon YH , Kim TI , Kim YI , Kim SM , Lee J , Lee IS
Ref : Int J Mol Sci , 24 :6485 , 2023
Abstract : Soluble epoxide hydrolase (sEH) is a target enzyme for the treatment of inflammation and cardiovascular disease. A Glycyrrhiza uralensis extract exhibited ~50% inhibition of sEH at 100 microg/mL, and column chromatography yielded compounds 1-11. Inhibitors 1, 4-6, 9, and 11 were non-competitive; inhibitors 3, 7, 8, and 10 were competitive. The IC(50) value of inhibitor 10 was below 2 microM. Molecular simulation was used to identify the sEH binding site. Glycycoumarin (10) requires further evaluation in cells and animals.
ESTHER : Kim_2023_Int.J.Mol.Sci_24_6485
PubMedSearch : Kim_2023_Int.J.Mol.Sci_24_6485
PubMedID: 37047457

Title : Lignan-Rich Sesame (Sesamum indicum L.) Cultivar Exhibits In Vitro Anti-Cholinesterase Activity, Anti-Neurotoxicity in Amyloid-beta Induced SH-SY5Y Cells, and Produces an In Vivo Nootropic Effect in Scopolamine-Induced Memory Impaired Mice - Kim_2023_Antioxidants.(Basel)_12_
Author(s) : Kim MY , Kim S , Lee J , Kim JI , Oh E , Kim SW , Lee E , Cho KS , Kim CS , Lee MH
Ref : Antioxidants (Basel) , 12 : , 2023
Abstract : Alzheimer's disease, a major cause of dementia, is characterized by impaired cholinergic function, increased oxidative stress, and amyloid cascade induction. Sesame lignans have attracted considerable attention owing to their beneficial effects on brain health. This study investigated the neuroprotective potential of lignan-rich sesame cultivars. Among the 10 sesame varieties studied, Milyang 74 (M74) extracts exhibited the highest total lignan content (17.71 mg/g) and in vitro acetylcholinesterase (AChE) inhibitory activity (66.17%, 0.4 mg/mL). M74 extracts were the most effective in improving cell viability and inhibiting reactive oxygen species (ROS) and malondialdehyde (MDA) generation in amyloid-beta(25-35) fragment-treated SH-SY5Y cells. Thus, M74 was used to evaluate the nootropic effects of sesame extracts and oil on scopolamine (2 mg/kg)-induced memory impairment in mice compared to the control cultivar (Goenback). Pretreatment with the M74 extract (250 and 500 mg/kg) and oil (1 and 2 mL/kg) effectively improved memory disorder in mice (demonstrated by the passive avoidance test), inhibited AChE, and enhanced acetylcholine (Ach) levels. Moreover, immunohistochemistry and Western blot results showed that the M74 extract and oil reversed the scopolamine-induced increase in APP, BACE-1, and presenilin expression levels in the amyloid cascade and decreased BDNF and NGF expression levels in neuronal regeneration.
ESTHER : Kim_2023_Antioxidants.(Basel)_12_
PubMedSearch : Kim_2023_Antioxidants.(Basel)_12_
PubMedID: 37237976

Title : Heterologous expression, purification, and characterization of a recombinant Cordyceps militaris lipase from Candida rugosa-like family in Pichia pastoris - Lee_2023_Enzyme.Microb.Technol_168_110254
Author(s) : Lee J , Lee H , Chang PS
Ref : Enzyme Microb Technol , 168 :110254 , 2023
Abstract : Multiple sequence alignments of three lipase isoforms from the filamentous fungus, Cordyceps militaris, have revealed that the deduced protein from their common sequence belongs to the Candida rugosa lipase-like group. To express the protein in its active form, recombinant lipase from C. militaris (rCML) was extra cellularly expressed in Pichia pastoris X-33 after removing its signal peptide. Purified rCML was a stable monomeric protein with a molecular mass of 90 kDa, and was highly N-mannosylated compared to the native protein (69 kDa). The catalytic efficiency (k(cat)/K(m)) of rCML was greater than the native protein (1244.35 +/- 50.88 and 1067.17 +/- 29.07 mM(-1).min(-1), respectively), yet they had similar optimal pH values and temperatures (40 degreesC and pH 7.0-7.5), and showed preferences for Tween esters and short-chain triacylglycerols. Despite its monomeric conformation, interfacial activation was not observed for rCML, unlike the classical lipases. From the structural model of rCML, the binding pocket of rCML was predicted as a funnel-like structure consisting of a hollow space and an intramolecular tunnel, which is typical of C. rugosa lipase-like lipases. However, a blockage shortened the tunnel to 12-15 A, which endows strict short-chain selectivity towards triacylglycerols and a perfect match for tricaproin (C6:0). The limited depth of the tunnel may enable accommodation of triacylglycerols with medium-to-long-chain fatty acids, which differentiates rCML from other C. rugosa lipase-like lipases with broad substrate specificities.
ESTHER : Lee_2023_Enzyme.Microb.Technol_168_110254
PubMedSearch : Lee_2023_Enzyme.Microb.Technol_168_110254
PubMedID: 37201411
Gene_locus related to this paper: cormm-g3j8e9

Title : Identification of New N-methyl-piperazine Chalcones as Dual MAO-B\/AChE Inhibitors - El-Damasy_2023_Pharmaceuticals.(Basel)_16_
Author(s) : El-Damasy AK , Park JE , Kim HJ , Lee J , Bang EK , Kim H , Keum G
Ref : Pharmaceuticals (Basel) , 16 : , 2023
Abstract : Monoamine oxidase-B (MAO-B), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) have been considered target enzymes of depression and neurodegenerative diseases, including Alzheimer's disease (AD). In this study, seventeen N-methyl-piperazine chalcones were synthesized, and their inhibitory activities were evaluated against the target enzymes. Compound 2k (3-trifluoromethyl-4-fluorinated derivative) showed the highest selective inhibition against MAO-B with an IC(50) of 0.71 microM and selectivity index (SI) of 56.34, followed by 2n (2-fluoro-5-bromophenyl derivative) (IC(50) = 1.11 microM, SI = 16.04). Compounds 2k and 2n were reversible competitive MAO-B inhibitors with K(i) values of 0.21 and 0.28 microM, respectively. Moreover, 2k and 2n effectively inhibited AChE with IC(50) of 8.10 and 4.32 microM, which underscored their multi-target inhibitory modes. Interestingly, compound 2o elicited remarkable inhibitions over MAO-B, AChE, and BChE with IC(50) of 1.19-3.87 microM. A cell-based assay of compounds 2k and 2n against Vero normal cells pointed out their low cytotoxicity. In a docking simulation, 2k showed the lowest energy for MAO-B (-11.6 kcal/mol) with four hydrogen bonds and two Pi-Pi interactions. Furthermore, in silico studies were conducted, and disclosed that 2k and 2n are expected to possess favorable pharmacokinetic properties, such as the ability to penetrate the blood-brain barrier (BBB). In view of these findings, compounds 2k and 2n could serve as promising potential candidates for the treatment of neurodegenerative diseases.
ESTHER : El-Damasy_2023_Pharmaceuticals.(Basel)_16_
PubMedSearch : El-Damasy_2023_Pharmaceuticals.(Basel)_16_
PubMedID: 36678580

Title : Validation of an SH-SY5Y Cell-Based Acetylcholinesterase Inhibition Assay for Water Quality Assessment - Lee_2022_Environ.Toxicol.Chem__
Author(s) : Lee J , Huchthausen J , Schlichting R , Scholz S , Henneberger L , Escher BI
Ref : Environ Toxicol Chem , : , 2022
Abstract : The acetylcholinesterase (AChE) inhibition assay has been frequently applied for environmental monitoring to capture insecticides such as organo(thio)phosphates (O(T)P) and carbamates. However, natural organic matter such as dissolved organic carbon (DOC) co-extracted with solid-phase extraction from environmental samples can produce false-negative AChE inhibition in free enzyme-based AChE assays. We aimed to evaluate whether disturbance by DOC can be alleviated in a cell-based AChE assay using differentiated human neuroblastoma SH-SY5Y cells. The exposure duration was set at an optimum of 3 h considering the effects of O(T)Ps and carbamates. Since loss to the airspace was expected for the more volatile OTPs (chlorpyrifos, diazinon, and parathion), the chemical loss in this bioassay set-up was investigated using a solid-phase microextraction followed by chemical analysis. The three OTPs were relatively well retained (loss < 34%) during 3 h of exposure in the 384-well plate but higher losses occurred upon prolonged exposure, accompanied by slight cross-contamination of adjacent wells. AChE inhibition by paraoxon-ethyl was not altered in the presence of up to 68 mg(c) /L Aldrich humic acid used as surrogate for DOC. Binary mixtures of paraoxon-ethyl and water extracts showed concentration-additive effects. These experiments confirmed that the matrix in water extracts does not disturb the assay unlike purified enzyme-based AChE assays. The cell-based AChE assay proved to be suitable for testing water samples with effect concentrations causing 50% inhibition of AChE at relative enrichments of 0.5 to 10 in river water samples, which were distinctly lower than corresponding cytotoxicity, confirming the high sensitivity of the cell-based AChE inhibition assay and its relevance for water quality monitoring. This article is protected by copyright. All rights reserved. Environ Toxicol Chem 2022;00:0-0. 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
ESTHER : Lee_2022_Environ.Toxicol.Chem__
PubMedSearch : Lee_2022_Environ.Toxicol.Chem__
PubMedID: 36165561

Title : 2,4-Diacetylphloroglucinol Reduces Beta-Amyloid Production and Secretion by Regulating ADAM10 and Intracellular Trafficking in Cellular and Animal Models of Alzheimer's Disease - Jang_2022_Cells_11_
Author(s) : Jang BG , Choi B , Kim S , Lee DS , Lee J , Koh YH , Jo SA , Kim JE , Kang TC , Kim MJ
Ref : Cells , 11 : , 2022
Abstract : There is currently no effective treatment against Alzheimer's disease (AD), although many strategies have been applied to reduce beta-amyloid (Abeta) levels. Here, we investigated 2,4-diacetylphloroglucinol (DAPG) effects on Abeta levels and mechanisms of action. DAPG was the most effective phloroglucinol derivative for reducing Abeta levels, without being toxic, in various models including HEK293 cells overexpressing Swedish mutant amyloid precursor protein (APP) (293sw), primary astrocytes isolated from APPsw/PS1dE9 transgenic mice, and after intrahippocampal injection of DAPG in APPsw/PS1dE9 transgenic mice. DAPG-mediated Abeta reduction was associated with increased soluble APPalpha (sAPPalpha) levels mediated by a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) but not ADAM17. ADAM10 inhibition in DAPG-treated cells prevented the effects on sAPPalpha but only partly on intracellular and secreted Abeta. To identify regulators of sAPPalpha and Abeta secretion, various inhibitors of intracellular trafficking were administered with DAPG. Brefeldin A (BFA) reversed DAPG-mediated changes in Abeta secretion in 293sw cells, whereas golgicide A (GCA) and BFA were effective in primary astrocytes, indicating a cell type-specific regulation of the trafficking. Moreover, GCA or BFA effects on sAPPalpha, but not Abeta, levels in primary astrocytes resembled those of ADAM10 inhibition, indicating at least partly independent trafficking pathways for sAPPalpha and Abeta. In conclusion, DAPG might be a promising drug candidate against AD regulating ADAM10 and intracellular trafficking, but optimizing DAPG ability to cross the BBB will be needed.
ESTHER : Jang_2022_Cells_11_
PubMedSearch : Jang_2022_Cells_11_
PubMedID: 36010661

Title : Molecular and kinetic properties of three acetylcholinesterases in the Varroa mite, Varroa destructor - Kim_2022_Pestic.Biochem.Physiol_188_105277
Author(s) : Kim S , Yoon KA , Cho S , Lee J , Lim Y , Lee SH
Ref : Pestic Biochem Physiol , 188 :105277 , 2022
Abstract : The Varroa mite, Varroa destructor, poses one of the most serious threats to honey bees worldwide. Although coumaphos, an anticholinesterase pesticide, is widely used for varroa mite control, little information is available on the properties of Varroa mite acetylcholinesterases (VdAChEs). In this study, three putative VdAChEs were annotated and named VdAChE1, VdAChE2, and VdAChE3. All VdAChEs possessed most of the functionally important signature domains, suggesting that they are catalytically active. Phylogenetic analysis revealed that VdAChE1 was clustered into a clade containing most arthropod AChE1s, whereas VdAChE2 and VdAChE3 formed a unique clade with other arachnid AChEs. VdAChE1 was determined to be membrane-anchored, but both VdAChE2 and VdAChE3 are soluble, as judged by electrophoresis in conjunction with western blotting. Tissue-specific transcription profiling revealed that VdAChE1 was most predominantly expressed in the synganglion. In contrast, VdAChE2 was most predominantly expressed in the legs and cuticle. VdAChE3 showed negligible expression levels in all the tissues examined. In a kinetic analysis using recombinant VdAChEs, VdAChE1 exhibited the highest catalytic efficiency, followed by VdAChE2 and VdAChE3. Inhibition experiments revealed that VdAChE1 was most sensitive to all tested inhibitors. Taken together, VdAChE1 appears to be the major synaptic enzyme with a more toxicological relevance, whereas VdAChE2 is involved in other noncatalytic functions, including chemical defense against xenobiotics. Current findings contribute to a more detailed understanding of the evolutionary and functional traits of VdAChEs and to the design of novel anticholinesterase varroacides.
ESTHER : Kim_2022_Pestic.Biochem.Physiol_188_105277
PubMedSearch : Kim_2022_Pestic.Biochem.Physiol_188_105277
PubMedID: 36464382
Gene_locus related to this paper: varde-VdAChE1 , varde-VdAChE2 , varde-VdAChE3

Title : Isolation and characterization of plasma-derived exosomes from olive flounder (Paralichthys olivaceus) and their wound healing and regeneration activities - Jayathilaka_2022_Fish.Shellfish.Immunol_128_196
Author(s) : Jayathilaka E , Edirisinghe SL , Lee J , Nikapitiya C , De Zoysa M
Ref : Fish Shellfish Immunol , 128 :196 , 2022
Abstract : Exosomes have garnered enormous interest for their role in physiological and pathological processes and their potential for therapeutic and diagnostic applications. In this study, exosomes were isolated from plasma of olive flounder (Paralichthys olivaceus) and their physiochemical and morphological characteristics, as well as wound healing and regeneration activities were determined. Isolated exosomes had typical characteristics, including average particle diameter (151.82 +/- 9.17 nm), concentration (6.31 x 10(10) particles/mL) with a membrane-bound, cup-shaped morphology. Exosome marker proteins, tetraspanins (CD63, CD9, and CD81), and acetylcholinesterase were detected, indicating the presence of exosomes in olive flounder plasma. Exosomes exhibited no toxicity in in vitro and in vivo studies, even at the highest treatment concentrations (100 and 400 microg/mL, respectively), confirming their suitability for further functional studies. Following exosome treatment (50 and 100 microg/mL), substantial cell migration with rapid closure of the open wound area in in vitro scratch wound healing assay and faster zebrafish larvae fin regeneration rate was observed compared to that of the vehicle. Moreover, exosomes exhibited immunomodulatory properties associated with wound healing, based on mRNA expression patterns in fathead minnow (FHM) cells. In conclusion, exosomes isolated from olive flounder plasma using ultracentrifugation exhibited minimal toxicity and enhanced wound healing and tissue regeneration activities. Identification and in-depth investigation of olive flounder plasma-derived exosome constituents will support the development of exosomes as an efficient therapeutic carrier system for fish medicine in the future.
ESTHER : Jayathilaka_2022_Fish.Shellfish.Immunol_128_196
PubMedSearch : Jayathilaka_2022_Fish.Shellfish.Immunol_128_196
PubMedID: 35932983

Title : Divergent substrate specificities and regioselectivities of three lipase isoforms from Cordyceps militaris: Combinatorial advantages for entomopathogenicity and prospects as biocatalysts - Lee_2022_Enzyme.Microb.Technol_161_110117
Author(s) : Lee J , Kim NH , Choi Y , Yang E , Yu H , Kwon CW , Chang PS
Ref : Enzyme Microb Technol , 161 :110117 , 2022
Abstract : Cordyceps militaris, an entomopathogenic Cordyceps mushroom, is a crucial ethnopharmacological agricultural product with applications in traditional oriental remedies in East Asia. Since lipases are reported to serve as key enzymatic equipment for entomopathogenic fungi during the host infection, the presence of various lipases with different biochemical features in C. militaris was elucidated. Three lipases from C. militaris (CML) of 60-70 kDa were isolated according to protein hydrophobicity; isoform relationships were identified by peptide mapping using liquid chromatography-electrospray ionization-tandem mass spectrometry. The CML isoforms exhibited distinct substrate specificities, which were related to the hydrophobicity of each isoform. Furthermore, the integral stereoselectivity of each lipase towards trioleoylglycerol diverged into two classes (sn-1,3 and sn-2 regioselectivity) that are rare in canonical fungal lipases. Overall, our results demonstrate that C. militaris secretes lipase isoforms with cocktail-like enzyme functions that may contribute to the entomopathogenic life cycle of C. militaris. Each CML isoform has distinct advantages for biocatalyst applications in the food and oleochemical industries.
ESTHER : Lee_2022_Enzyme.Microb.Technol_161_110117
PubMedSearch : Lee_2022_Enzyme.Microb.Technol_161_110117
PubMedID: 36049397
Gene_locus related to this paper: cormm-g3j6x7

Title : A genetic screen for aldicarb resistance of C. elegans dauer larvae uncovers two alleles of dach-1, a cytochrome P450 gene - Son_2022_G3.(Bethesda)__
Author(s) : Son S , Choi MK , Lim DS , Shim J , Lee J
Ref : G3 (Bethesda) , : , 2022
Abstract : Animals exhibit phenotypic plasticity through the interaction of genes with the environment, and little is known about the genetic factors that change synaptic function at different developmental stages. Here, we investigated the genetic determinants of how animal's sensitivity to drugs that alter synaptic activity is regulated at a specific developmental stage using the free-living nematode Caenorhabditis elegans. C. elegans enters the stress-resistant dauer larval stage under harsh conditions. Although dauer is known to have reduced permeability and increased resistance to most known exogenous chemicals, we discovered that dauer is hypersensitive to a cholinesterase inhibitor, aldicarb. To investigate genes regulating dauer-specific acetylcholine transduction, we first screened for aldicarb-resistant mutations in dauer and then performed a secondary screen to rule out aldicarb-resistant mutations that also affect adults. We isolated two different mutations of a single gene called cyp-34A4 or dach-1 encoding a cytochrome P450. In the non-dauer stages, dach-1 is mainly expressed in the intestine, but its expression is robustly increased in the epidermis of dauers. By tissue-specific rescue experiments, we found that dach-1 modulates aldicarb sensitivity in a cell non-autonomous manner. In addition, dach-1 plays pleiotropic functions in dauers by regulating quiescence and surviving heat shock and hyperosmolar stress. Our study reveals novel functions of the cytochrome P450 in synaptic and physiological changes during developmental plasticity.
ESTHER : Son_2022_G3.(Bethesda)__
PubMedSearch : Son_2022_G3.(Bethesda)__
PubMedID: 36194018

Title : Post-market utilization patterns of Alzheimer's disease treatments in South Korea: comparison with countries with universal health coverage - Lee_2021_Eur.J.Clin.Pharmacol__
Author(s) : Lee HJ , Roughead EE , Han E , Lee J , Kalisch Ellett L
Ref : European Journal of Clinical Pharmacology , : , 2021
Abstract : PURPOSE: This study aimed to compare the utilization of Alzheimer's disease (AD) treatments, donepezil, galantamine, rivastigmine, and memantine, in Korea with Australia and other countries with universal health coverage. METHODS: Reimbursement criteria and the patent status of four AD treatments in Korea and Australia were reviewed. The monthly spending and utilization of the treatments were extracted from the national electronic database in Korea and Australia. The defined daily dose per 1000 elderly population per day (DDD/1000e/day) were calculated from July 2008 to June 2019. Annual cost trends of Norway and England were compared with Korea and Australia. RESULTS: With the highest share of the use of donepezil in both countries, the cost and utilization of AD treatments in Korea increased more rapidly and remained higher than Australia. The cost of AD treatments in Korea increased by 15.5% every year during the study period, while the spending of the same drugs in Australia decreased by 10.5% annually. The utilization in DDD/1000e/day of AD treatments in Korea increased by 18.3% annually compared with 1.4% in Australia. When compared with Norway and England, countries with similar universal health coverage (UHC) system and elderly polupation, the cost of AD treatments in Korea was still higher with the opposite trend from other countries. CONCLUSIONS: Despite the similar UHC systems, there were considerable differences in the post-market utilization of AD treatments in Korea from Australia and other countries. This results can be attributed to differences in re-assessment system, pricing and reimbursement policies, and prescribing culture. This study provides a baseline to explore more comprehensive cross-country studies on rational use of medicines.
ESTHER : Lee_2021_Eur.J.Clin.Pharmacol__
PubMedSearch : Lee_2021_Eur.J.Clin.Pharmacol__
PubMedID: 33409682

Title : Discovery of Natural Inhibitors of Cholinesterases from Hydrangea: In Vitro and In Silico Approaches - Hwang_2021_Nutrients_13_
Author(s) : Hwang J , Youn K , Lim G , Lee J , Kim DH , Jun M
Ref : Nutrients , 13 : , 2021
Abstract : Alzheimer's disease (AD) is a neurodegenerative disease conceptualized as a clinical-biological neurodegenerative construct where amyloid-beta pathophysiology is supposed to play a role. The loss of cognitive functions is mostly characterized by the rapid hydrolysis of acetylcholine by cholinesterases including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Moreover, both enzymes are responsible for non-catalytic actions such as interacting with amyloid beta peptide (Abeta) which further leads to promote senile plaque formation. In searching for a natural cholinesterase inhibitor, the present study focused on two isocoumarines from hydrangea, thunberginol C (TC) and hydrangenol 8-O-glucoside pentaacetate (HGP). Hydrangea-derived compounds were demonstrated to act as dual inhibitors of both AChE and BChE. Furthermore, the compounds exerted selective and non-competitive mode of inhibition via hydrophobic interaction with peripheral anionic site (PAS) of the enzymes. Overall results demonstrated that these natural hydrangea-derived compounds acted as selective dual inhibitors of AChE and BChE, which provides the possibility of potential source of new type of anti-cholinesterases with non-competitive binding property with PAS.
ESTHER : Hwang_2021_Nutrients_13_
PubMedSearch : Hwang_2021_Nutrients_13_
PubMedID: 33477276

Title : Effects of a DPP-4 Inhibitor and RAS Blockade on Clinical Outcomes of Patients with Diabetes and COVID-19 - Rhee_2021_Diabetes.Metab.J__
Author(s) : Rhee SY , Lee J , Nam H , Kyoung DS , Shin DW , Kim DJ
Ref : Diabetes Metab J , : , 2021
Abstract : BACKGROUND: Dipeptidyl peptidase-4 inhibitor (DPP-4i) and renin-angiotensin system (RAS) blockade are reported to affect the clinical course of coronavirus disease 2019 (COVID-19) in patients with diabetes mellitus (DM). METHODS: As of May 2020, analysis was conducted on all subjects who could confirm their history of claims related to COVID-19 in the National Health Insurance Review and Assessment Service (HIRA) database in Korea. Using this dataset, we compared the short-term prognosis of COVID-19 infection according to the use of DPP-4i and RAS blockade. Additionally, we validated the results using the National Health Insurance Service (NHIS) of Korea dataset. RESULTS: Totally, data of 67,850 subjects were accessible in the HIRA dataset. Of these, 5,080 were confirmed COVID-19. Among these, 832 subjects with DM were selected for analysis in this study. Among the subjects, 263 (31.6%) and 327 (39.3%) were DPP4i and RAS blockade users, respectively. Thirty-four subjects (4.09%) received intensive care or died. The adjusted odds ratio for severe treatment among DPP-4i users was 0.362 (95% confidence interval [CI], 0.135 to 0.971), and that for RAS blockade users was 0.599 (95% CI, 0.251 to 1.431). These findings were consistent with the analysis based on the NHIS data using 704 final subjects. The adjusted odds ratio for severe treatment among DPP-4i users was 0.303 (95% CI, 0.135 to 0.682), and that for RAS blockade users was 0.811 (95% CI, 0.391 to 1.682). CONCLUSION: This study suggests that DPP-4i is significantly associated with a better clinical outcome of patients with COVID-19.
ESTHER : Rhee_2021_Diabetes.Metab.J__
PubMedSearch : Rhee_2021_Diabetes.Metab.J__
PubMedID: 33752274

Title : No prominent toxicity of polyethylene microplastics observed in neonatal mice following intratracheal instillation to dams during gestational and neonatal period - Han_2021_Toxicol.Res_37_443
Author(s) : Han Y , Song Y , Kim GW , Ha C , Lee J , Kim M , Son H , Lee G , Gautam R , Heo Y
Ref : Toxicol Res , 37 :443 , 2021
Abstract : Microplastics (MPs) have been recently recognized as a global environmental threat and its exposure as a risk factor to human health. Health effects through MPs exposure have been recently reported, especially through oral route of exposure. Since MPs could be exposed to humans through routes other than oral, this study was designed to evaluate whether MPs exposed through the inhalation route could be delivered to fetal mice and exhibit systemic toxicity. Polyethylene (PE) with 10-45 microm diameter were administered at 0 (distilled water, vehicle control), 6 (low administration), and 60 (high administration) microg/mouse/day to 3 pregnant dams per group from gestational day 9 to postnatal day (PND) 7 through intratracheal instillation. Dams and neonates were sacrificed at PND 7 and blood was collected. Various neonatal organs including brain, lung, heart, stomach, intestine, kidneys, and ovaries were collected for histopathological observation and weight measurement. No influence of PE-MPs administration was observed on the number of offsprings born, but the body and organs' weight were heavier overall in the high administration group of dams and neonates than the other groups with statistical significance achieved in the heart and spleen weight. Level of serum acetylcholinesterase and glutathione peroxidase activity was decreased in the high administration group of dams and neonates compared with the other groups. Lung was the organ with highest number of PE-MPs present in the both administration groups of dams, and PE-MPs were also detected in liver and intestine of the high administration dams. Whereas, PND7 neonates showed accountable numbers of PE-MPs only in kidneys of the high administration group. Overall, the present study indicates that PE-MPs instilled intratracheally could be delivered to neonates from dams. Even though adverse effects from PE-MPs exposure during pregnant and lactational period are less prominent on both dam and neonate, potential of second-generation toxicity could be considered for further investigation.
ESTHER : Han_2021_Toxicol.Res_37_443
PubMedSearch : Han_2021_Toxicol.Res_37_443
PubMedID: 34631501

Title : Hevin-calcyon interaction promotes synaptic reorganization after brain injury - Kim_2021_Cell.Death.Differ__
Author(s) : Kim JH , Jung HG , Kim A , Shim HS , Hyeon SJ , Lee YS , Han J , Jung JH , Lee J , Ryu H , Park JY , Hwang EM , Suk K
Ref : Cell Death Differ , : , 2021
Abstract : Hevin, also known as SPARC-like protein 1 (SPARCL1 or SC1), is a synaptogenic protein secreted by astrocytes and modulates the formation of glutamatergic synapses in the developing brain by interacting with synaptic adhesion proteins, such as neurexin and neuroligin. Here, we identified the neuron-specific vesicular protein calcyon as a novel interaction partner of hevin and demonstrated that this interaction played a pivotal role in synaptic reorganization after an injury in the mature brain. Astrocytic hevin was upregulated post-injury in a photothrombotic stroke model. Hevin was fragmented by MMP3 induced during the acute stage of brain injury, and this process was associated with severe gliosis. At the late stage, the functional hevin level was restored as MMP3 expression decreased. The C-terminus of hevin interacted with the N-terminus of calcyon. By using RNAi and binding competitor peptides in an ischemic brain injury model, we showed that this interaction was crucial in synaptic and functional recoveries in the sensory-motor cortex, based on histological and electrophysiological analyses. Regulated expression of hevin and calcyon and interaction between them were confirmed in a mouse model of traumatic brain injury and patients with chronic traumatic encephalopathy. Our study provides direct evidence for the causal relationship between the hevin-calcyon interaction and synaptic reorganization after brain injury. This neuron-glia interaction can be exploited to modulate synaptic reorganization under various neurological conditions.
ESTHER : Kim_2021_Cell.Death.Differ__
PubMedSearch : Kim_2021_Cell.Death.Differ__
PubMedID: 33753902

Title : Biological and Computational Studies for Dual Cholinesterases Inhibitory Effect of Zerumbone - Hwang_2020_Nutrients_12_
Author(s) : Hwang J , Youn K , Ji Y , Lee S , Lim G , Lee J , Ho CT , Leem SH , Jun M
Ref : Nutrients , 12 : , 2020
Abstract : Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) mediate the degradation of acetylcholine (ACh), a primary neurotransmitter in the brain. Cholinergic deficiency occurs during the progression of Alzheimer's disease (AD), resulting in widespread cognitive dysfunction and decline. We evaluated the potential effect of a natural cholinesterase inhibitor, zerumbone, using in vitro target enzyme assays, as well as in silico docking and ADMET (absorption, distribution, metabolism, excretion, and toxicity) simulation. Zerumbone showed a predominant cholinesterase inhibitory property with IC50 values of 2.74 +/- 0.48 microM and 4.12 +/- 0.42 microM for AChE and BChE, respectively; however, the modes of inhibition were different. Computational docking simulation indicated that Van der Waals interactions between zerumbone and both the cholinesterases were the main forces responsible for its inhibitory effects. Furthermore, zerumbone showed the best physicochemical properties for both bioavailability and blood-brain barrier (BBB) permeability. Together, in the present study, zerumbone was clearly identified as a unique dual AChE and BChE inhibitor with high permeability across the BBB, suggesting a strong potential for its physiological benefits and/or pharmacological e ffi cacy in the prevention of AD.
ESTHER : Hwang_2020_Nutrients_12_
PubMedSearch : Hwang_2020_Nutrients_12_
PubMedID: 32344943

Title : Memory-enhancing effects of Ishige foliacea extract: In vitro and in vivo study - Kim_2020_J.Food.Biochem__e13162
Author(s) : Kim TE , Son HJ , Lim DW , Yoon M , Lee J , Kim YT , Han D , Lee C , Um MY
Ref : J Food Biochem , :e13162 , 2020
Abstract : Ishige foliacea is used as a functional food in East-Asian countries. We evaluated the memory-enhancing effect of an ethanol extract of I. foliacea (EEI) using in vitro and in vivo models. In vitro acetylcholinesterase and beta-secretase inhibitory activities, antioxidant properties, and neuroprotective effects against human neuronal cell death by H2 O2 and beta-amyloid (Abeta) were investigated. We explored the memory-enhancing effect and its underlying mechanism in a mouse model of scopolamine (SCO)-induced memory deficits. EEI showed free radical scavenging and acetylcholinesterase and beta-secretase inhibition activities. Additionally, EEI significantly decreased neuronal cell death induced by H2 O2 or Abeta in human neuroblastoma SH-SY5Y cells. In behavior tests, SCO-induced memory deficits was improved by EEI administration. EEI increased the protein expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) and phosphorylated extracellular signal-regulated kinase, which are related to synaptic plasticity in the hippocampus. EEI may ameliorate memory deficits and prevent neurodegenerative disorders. PRACTICAL APPLICATIONS: As the population ages, dementia, a neurodegenerative disease, is becoming an important problem. Various Alzheimer's drugs have been developed based on the disease mechanism, but alternative treatments are required because of the low bioavailability and hepatotoxicity of current medications. Ishige foliacea is a type of brown algae containing various bioactive substances. Phlorotannins, known as brown algae polyphenols, have been studied for their various functionalities such as, anticancer, anti-obesity, antioxidant, and sleep improvement effects, and have attracted attention as raw materials for developing new natural products. We found that the EEI mitigates SCO-induced damage by protecting neurons from oxidative stress-induced cell damage, controlling synthesis mechanisms of the causative agents of AD, and activating BDNF-TrkB-ERK signaling to promote memory function in the hippocampus. The results of this study can serve as a foundation for further research. Additionally, I. foliacea may be useful for treating and improving AD.
ESTHER : Kim_2020_J.Food.Biochem__e13162
PubMedSearch : Kim_2020_J.Food.Biochem__e13162
PubMedID: 32020642

Title : Flexible Total Synthesis of 11-Deoxylandomycins and Their Non-Natural Analogues by Way of Asymmetric Metal Catalysis - Lee_2020_Angew.Chem.Int.Ed.Engl_59_2349
Author(s) : Lee J , Kang J , Lee S , Rhee YH
Ref : Angew Chem Int Ed Engl , 59 :2349 , 2020
Abstract : A de novo first collective total synthesis of 11-deoxylandomycins is reported. A signature step is featured by the Pd-catalyzed asymmetric addition of alcohol to ene-alkoxyallenes that assembles oligomeric 2,3,6-trideoxyoligosaccharides. The unique feature of the protocol is illustrated by a flexible access to various natural 11-deoxylandomycins as well as non-natural analogues.
ESTHER : Lee_2020_Angew.Chem.Int.Ed.Engl_59_2349
PubMedSearch : Lee_2020_Angew.Chem.Int.Ed.Engl_59_2349
PubMedID: 31737974
Gene_locus related to this paper: aspa1-anee

Title : Simultaneous Analysis of Fenthion and Its Five Metabolites in Produce Using Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry - Lee_2020_Molecules_25_1938
Author(s) : Lee J , Kim JH
Ref : Molecules , 25 :1938 , 2020
Abstract : A simultaneous analytical method for the organophosphorus insecticide fenthion and its five metabolites (fenthion oxon, fenthion oxon sulfoxide, fenthion oxon sulfone, fenthion sulfoxide, and fenthion sulfone) was developed based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Five matrices (brown rice, chili pepper, orange, potato, and soybean) were selected to validate the method. The target compounds were analyzed using positive electrospray ionization in the multiple reaction monitoring mode. For the best sensitivity in regard to the detector response, water and methanol containing formic acid (0.1%) were selected as the mobile phase. The optimum extraction efficiency was obtained through a citrate-buffered QuEChERS (quick, easy, cheap, effective, rugged, and safe) method. Recovery tests were carried out at three spiking levels (n = 3). At all fortification levels, the accuracy and precision results were between 70% and 120% with a relative standard deviation of >=15%. The limit of quantitation was 0.01 mg/kg, and the correlation coefficients (r(2)) of the matrix-matched calibration curves were >0.99. Significant signal suppression in the detector responses were observed for all matrices, suggesting that a compensation method, such as matrix-matched calibration, is required to provide accurate quantitative results. The applicability of the presented method was confirmed for the simultaneous analysis of fenthion and its metabolites in various crops.
ESTHER : Lee_2020_Molecules_25_1938
PubMedSearch : Lee_2020_Molecules_25_1938
PubMedID: 32331373

Title : Acute Myasthenia Crisis: A Critical Emergency Department Differential - Hogan_2020_Cureus_12_e9760
Author(s) : Hogan C , Lee J , Sleigh BC , Banerjee PR , Ganti L
Ref : Cureus , 12 :e9760 , 2020
Abstract : Myasthenia gravis (MG) is the most common autoimmune disorder of the neuromuscular junction (NMJ). It is caused by autoantibodies blocking acetylcholine receptors (AChRs) or structural receptors of the NMJ: agrin, LRP4, and MuSK. These antibodies can block, change, or destroy AChRs or structural proteins of the NMJ, preventing the binding of ACh and therefore, muscle contractions. This molecular dysfunction can manifest as any of the following symptoms: ptosis, diplopia, bulbar dysfunction, or impaired vision in bright light. Symptoms fluctuate in severity throughout the day and with prolonged use of respective muscles. Typical treatment for mild cases is acetylcholinesterase inhibition combined with an immunosuppressor. Myasthenia crisis results from the exacerbation of the aforementioned symptoms and requires intubation for respiratory support. Intensive care along with intensified immunosuppressive treatments and constant monitoring are recommended. We present the case of a 76-year-old man arriving to the emergency department (ED) with symptoms of fatigue and dysphagia, diagnosed as acute myasthenia crisis. Here, we highlight the symptoms of MG, acute myasthenia crisis, and the critical measures that need to be taken.
ESTHER : Hogan_2020_Cureus_12_e9760
PubMedSearch : Hogan_2020_Cureus_12_e9760
PubMedID: 32944474

Title : Antiviral activity against Middle East Respiratory Syndrome Coronavirus by Montelukast, an anti-asthma drug - Gan_2020_Antiviral.Res__104996
Author(s) : Gan HJ , Harikishore A , Lee J , Jeon S , Rajan S , Chen MW , Neo JL , Kim S , Yoon HS
Ref : Antiviral Res , :104996 , 2020
Abstract : Middle East respiratory syndrome (MERS) is a respiratory disease caused by a coronavirus (MERS-CoV). Since its emergence in 2012, nosocomial amplifications have led to its high epidemic potential and mortality rate of 34.5 %. To date, there is an unmet need for vaccines and specific therapeutics for this disease. Available treatments are either supportive medications in use for other diseases or those lacking specificity requiring higher doses. The viral infection mode is initiated by the attachment of the viral Spike glycoprotein to the human Dipeptidyl Peptidase IV (DPP4). Our attempts to screen antivirals against MERS led us to identify montelukast sodium hydrate (MSH), an FDA-approved anti-asthma drug, as an agent attenuating MERS-CoV infection. We showed that MSH directly binds to MERS-CoV-Receptor-Binding Domain (RBD) and inhibits its molecular interaction with DPP4 in a dose-dependent manner. Our cell-based inhibition assays using MERS pseudovirions demonstrated that viral infection was significantly inhibited by MSH and was further validated using infectious MERS-CoV culture. Thus, we propose MSH as a potential candidate for therapeutic developments against MERS-CoV infections.
ESTHER : Gan_2020_Antiviral.Res__104996
PubMedSearch : Gan_2020_Antiviral.Res__104996
PubMedID: 33309540

Title : ARS2\/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages - Yin_2020_Nat.Commun_11_2978
Author(s) : Yin J , Kim SS , Choi E , Oh YT , Lin W , Kim TH , Sa JK , Hong JH , Park SH , Kwon HJ , Jin X , You Y , Kim JH , Kim H , Son J , Lee J , Nam DH , Choi KS , Shi B , Gwak HS , Yoo H , Iavarone A , Park JB
Ref : Nat Commun , 11 :2978 , 2020
Abstract : The interplay between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAMs) promotes progression of glioblastoma multiforme (GBM). However, the detailed molecular mechanisms underlying the relationship between these two cell types remain unclear. Here, we demonstrate that ARS2 (arsenite-resistance protein 2), a zinc finger protein that is essential for early mammalian development, plays critical roles in GSC maintenance and M2-like TAM polarization. ARS2 directly activates its novel transcriptional target MGLL, encoding monoacylglycerol lipase (MAGL), to regulate the self-renewal and tumorigenicity of GSCs through production of prostaglandin E2 (PGE2), which stimulates beta-catenin activation of GSC and M2-like TAM polarization. We identify M2-like signature downregulated by which MAGL-specific inhibitor, JZL184, increased survival rate significantly in the mouse xenograft model by blocking PGE2 production. Taken together, our results suggest that blocking the interplay between GSCs and TAMs by targeting ARS2/MAGL signaling offers a potentially novel therapeutic option for GBM patients.
ESTHER : Yin_2020_Nat.Commun_11_2978
PubMedSearch : Yin_2020_Nat.Commun_11_2978
PubMedID: 32532977

Title : Casticin ameliorates scopolamine-induced cognitive dysfunction in mice - Kim_2020_J.Ethnopharmacol__112843
Author(s) : Kim J , Seo YH , Goo N , Jeong Y , Bae HJ , Jung SY , Lee J , Ryu JH
Ref : J Ethnopharmacol , :112843 , 2020
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Vitex rotundifolia L. (Verbenaceae) has been used in traditional medicine as sedative or analgesic agent for headache. Recent population-based cohort studies have shown that headache including migraines is a risk factor for dementia. Thus, the fruit of V. rotundifolia may be useful for treating cognitive dysfunction observed in dementia. AIM OF THE STUDY: We had previously found that the ethanolic extract of the fruit of V. rotundifolia ameliorated cognitive dysfunction and isolated casticin as an active compound. In the present study, we studied the effect of casticin on a mouse model of cognitive impairment induced by scopolamine. MATERIALS AND METHODS: Mice were treated with the ethanolic extract of the fruit of V. rotundifolia (EEVR; 30, 100 or 300mg/kg, p.o.) or casticin (0.3, 1 or 3mg/kg, p.o.). We examined the effect of casticin or EEVR using the passive avoidance test, the Morris water maze test and the novel object recognition test. Scopolamine (1mg/kg, i.p.) was used to induce cognitive impairment by blocking cholinergic neurotransmitter system. We investigated the effects of casticin on acetylcholinesterase (AchE) activity and the phosphorylation levels of extracellular signal-regulated kinase (ERK), cAMP response element binding protein (CREB), and the expression levels of brain-derived neurotrophic factor (BDNF). RESULTS: EEVR (100 and 300mg/kg, p.o.) significantly ameliorated the latency in the passive avoidance test, and casticin (1 and 3mg/kg, p.o.) also significantly improved the latency in the passive avoidance test, novel object preference in the novel object recognition test, and swimming time in the target quadrant of the Morris water maze test. Casticin also decreased AChE activity in ex vivo analysis and increased the phosphorylation levels of memory-related signaling molecules, such as ERK, CREB and BDNF in the cortex. CONCLUSION: These results suggest that casticin ameliorates cholinergic blockade-induced cognitive impairment, in part, through the inhibition of AChE and the activation of the ERK-CREB-BDNF signaling pathway. Taken together, the results suggest that casticin may be useful for treating the cognitive dysfunction observed during cholinergic impairment.
ESTHER : Kim_2020_J.Ethnopharmacol__112843
PubMedSearch : Kim_2020_J.Ethnopharmacol__112843
PubMedID: 32380246

Title : Neuromuscular blockade reversal with sugammadex versus pyridostigmine\/glycopyrrolate in laparoscopic cholecystectomy: a randomized trial of effects on postoperative gastrointestinal motility - An_2020_Korean.J.Anesthesiol_73_137
Author(s) : An J , Noh H , Kim E , Lee J , Woo K , Kim H
Ref : Korean J Anesthesiol , 73 :137 , 2020
Abstract : BACKGROUND: Acetylcholinesterase inhibitors (e.g., pyridostigmine bromide) are used for neuromuscular blockade (NMB) reversal in patients undergoing surgery under general anesthesia (GA). Concurrent use of anticholinergic agents (e.g., glycopyrrolate) decreases cholinergic side effects but can impede bowel movements. Sugammadex has no cholinergic effects; its use modifies recovery of gastrointestinal (GI) motility following laparoscopic cholecystectomy compared to pyridostigmine/glycopyrrolate. This study evaluated the contribution of sugammadex to the recovery of GI motility compared with pyridostigmine and glycopyrrolate. METHODS: We conducted a prospective study of patients who underwent laparoscopic cholecystectomy. Patients were randomly allocated to the experimental group (sugammadex, Group S) or control group (pyridostigmine-glycopyrrolate, Group P). After anesthesia (propofol and rocuronium, and 2% sevoflurane), recovery was induced by injection of sugammadex or a pyridostigmine-glycopyrrolate mixture. As a primary outcome, patients recorded the time of their first passage of flatus ('gas-out time') and defecation. The secondary outcome was stool types. RESULTS: One-hundred and two patients participated (Group S, 49; Group P, 53). Mean time from injection of NMB reversal agents to gas-out time was 15.03 (6.36-20.25) h in Group S and 20.85 (16.34-25.86) h in Group P (P = 0.001). Inter-group differences were significant. Time until the first defecation as well as types of stools was not significantly different. CONCLUSIONS: Sugammadex after laparoscopic cholecystectomy under GA resulted in an earlier first postoperative passage of flatus compared with the use of a mixture of pyridostigmine and glycopyrrolate. These findings suggest that the use of sugammadex has positive effects on the recovery of GI motility.
ESTHER : An_2020_Korean.J.Anesthesiol_73_137
PubMedSearch : An_2020_Korean.J.Anesthesiol_73_137
PubMedID: 31636242

Title : Multiple reactivities of flavonoids towards pathological elements in Alzheimer's disease: structure-activity relationship - Nam_2020_Chem.Sci_11_10243
Author(s) : Nam G , Hong M , Lee J , Lee HJ , Ji Y , Kang J , Baik MH , Lim MH
Ref : Chem Sci , 11 :10243 , 2020
Abstract : Amyloid-beta (Abeta) accumulation, metal ion dyshomeostasis, oxidative stress, and cholinergic deficit are four major characteristics of Alzheimer's disease (AD). Herein, we report the reactivities of 12 flavonoids against four pathogenic elements of AD: metal-free and metal-bound Abeta, free radicals, and acetylcholinesterase. A series of 12 flavonoids was selected based on the molecular structures that are responsible for multiple reactivities including hydroxyl substitution and transfer of the B ring from C2 to C3. Our experimental and computational studies reveal that the catechol moiety, the hydroxyl groups at C3 and C7, and the position of the B ring are important for instilling multiple functions in flavonoids. We establish a structure-activity relationship of flavonoids that should be useful for designing chemical reagents with multiple reactivities against the pathological factors of AD.
ESTHER : Nam_2020_Chem.Sci_11_10243
PubMedSearch : Nam_2020_Chem.Sci_11_10243
PubMedID: 34094290

Title : Dual BACE1 and Cholinesterase Inhibitory Effects of Phlorotannins from Ecklonia cava-An In Vitro and in Silico Study - Lee_2019_Mar.Drugs_17_
Author(s) : Lee J , Jun M
Ref : Mar Drugs , 17 : , 2019
Abstract : Alzheimer's disease (AD) is one of the most common neurodegenerative diseases with a multifactorial nature. beta-Secretase (BACE1) and acetylcholinesterase (AChE), which are required for the production of neurotoxic beta-amyloid (Abeta) and the promotion of Abeta fibril formation, respectively, are considered as prime therapeutic targets for AD. In our efforts towards the development of potent multi-target, directed agents for AD treatment, major phlorotannins such as eckol, dieckol, and 8,8'-bieckol from Ecklonia cava (E. cava) were evaluated. Based on the in vitro study, all tested compounds showed potent inhibitory effects on BACE1 and AChE. In particular, 8,8'-bieckol demonstrated the best inhibitory effect against BACE1 and AChE, with IC50 values of 1.62 +/- 0.14 and 4.59 +/- 0.32 microM, respectively. Overall, kinetic studies demonstrated that all the tested compounds acted as dual BACE1 and AChE inhibitors in a non-competitive or competitive fashion, respectively. In silico docking analysis exhibited that the lowest binding energies of all compounds were negative, and specifically different residues of each target enzyme interacted with hydroxyl groups of phlorotannins. The present study suggested that major phlorotannins derived from E. cava possess significant potential as drug candidates for therapeutic agents against AD.
ESTHER : Lee_2019_Mar.Drugs_17_
PubMedSearch : Lee_2019_Mar.Drugs_17_
PubMedID: 30717208

Title : A caffeic acid-ferulic acid hybrid compound attenuates lipopolysaccharide-mediated inflammation in BV2 and RAW264.7 cells - Kwon_2019_Biochem.Biophys.Res.Commun_515_565
Author(s) : Kwon MY , Kim SM , Park J , Lee J , Cho H , Lee H , Jeon C , Park JH , Han IO
Ref : Biochemical & Biophysical Research Communications , 515 :565 , 2019
Abstract : In the present study, we synthesized and evaluated the anti-inflammatory effects of the two component hybrids, caffeic acid (CA)-ferulic acid (FA), FA-Tryptamine (Trm), CA-Piperonyl Triazol (PT) and FA-PT. Of these five hybrids, CA-FA had the most potent inhibitory effect on butyrylcholinesterase (BuChE) activity. The CA containing hybrids, CA-FA, CA-Trm, and CA-PT, dose-dependently inhibited LPS-induced nitric oxide (NO) generation in BV2 cells, whereas FA-PT, FA-Trm, CA, FA, Trm, and PT did not. Although CA-FA, CA-Trm and CA-PT had similar inhibitory effects on LPS-induced NO generation, CA-FA best protected BV2 cells from LPS-induced cell death. CA-FA, but not CA or FA, dose-dependently inhibited LPS-induced up-regulations of NO synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions in BV2 and RAW264.7cells. Furthermore, CA-FA inhibited LPS-induced iNOS, COX-2, interleukin-6, and interleukin-1beta mRNA expressions in BV2 cells. CA-FA also inhibited the LPS-induced phosphorylations of STAT3, Akt, and IkappaB and selectively inhibited LPS-induced NF-kappaB activation. Overall, our data suggest that CA-FA has BuChE inhibitory effects and down-regulates inflammatory responses by inhibiting NF-kappaB, which indicates CA-FA be viewed as a potential therapeutic agent for the treatment of inflammatory diseases of the peripheral system and central nervous systems.
ESTHER : Kwon_2019_Biochem.Biophys.Res.Commun_515_565
PubMedSearch : Kwon_2019_Biochem.Biophys.Res.Commun_515_565
PubMedID: 31178135

Title : Fluorescence-Based Quantitative Synapse Analysis for Cell Type-Specific Connectomics - Kuljis_2019_eNeuro_6_
Author(s) : Kuljis DA , Park E , Telmer CA , Lee J , Ackerman DS , Bruchez MP , Barth AL
Ref : eNeuro , 6 : , 2019
Abstract : Anatomical methods for determining cell type-specific connectivity are essential to inspire and constrain our understanding of neural circuit function. We developed genetically-encoded reagents for fluorescence-synapse labeling and connectivity analysis in brain tissue, using a fluorogen-activating protein (FAP)-coupled or YFP-coupled, postsynaptically-localized neuroligin-1 (NL-1) targeting sequence (FAP/YFPpost). FAPpost expression did not alter mEPSC or mIPSC properties. Sparse AAV-mediated expression of FAP/YFPpost with the cell-filling, red fluorophore dTomato (dTom) enabled high-throughput, compartment-specific detection of putative synapses across diverse neuron types in mouse somatosensory cortex. We took advantage of the bright, far-red emission of FAPpost puncta for multichannel fluorescence alignment of dendrites, FAPpost puncta, and presynaptic neurites in transgenic mice with saturated labeling of parvalbumin (PV), somatostatin (SST), or vasoactive intestinal peptide (VIP)-expressing neurons using Cre-reporter driven expression of YFP. Subtype-specific inhibitory connectivity onto layer 2/3 (L2/3) neocortical pyramidal (Pyr) neurons was assessed using automated puncta detection and neurite apposition. Quantitative and compartment-specific comparisons show that PV inputs are the predominant source of inhibition at both the soma and the dendrites and were particularly concentrated at the primary apical dendrite. SST inputs were interleaved with PV inputs at all secondary-order and higher-order dendritic branches. These fluorescence-based synapse labeling reagents can facilitate large-scale and cell-type specific quantitation of changes in synaptic connectivity across development, learning, and disease states.
ESTHER : Kuljis_2019_eNeuro_6_
PubMedSearch : Kuljis_2019_eNeuro_6_
PubMedID: 31548370

Title : Baicalein as a Potential Inhibitor against BACE1 and AChE: Mechanistic Comprehension through In Vitro and Computational Approaches - Han_2019_Nutrients_11_
Author(s) : Han J , Ji Y , Youn K , Lim G , Lee J , Kim DH , Jun M
Ref : Nutrients , 11 : , 2019
Abstract : One of the major neurodegenerative features of Alzheimer's disease (AD) is the presence of neurotoxic amyloid plaques composed of amyloid beta peptide (Abeta). beta-Secretase (BACE1) and acetylcholinesterase (AChE), which promote Abeta fibril formation, have become attractive therapeutic targets for AD. P-glycoprotein (P-gp), the major efflux pump of the blood-brain barrier (BBB), plays a critical role in limiting therapeutic molecules. In pursuit of discovering a natural anti-AD candidate, the bioactivity, physicochemical, drug-likeness, and molecular docking properties of baicalein, a major compound from Scutellaria baicalensis, was investigated. Baicalein exhibited strong BACE1 and AChE inhibitory properties (IC50 23.71 +/- 1.91 microM and 45.95 +/- 3.44 microM, respectively) and reacted in non-competitive and competitive manners with substrates, respectively. in Silico docking analysis was in full agreement with the in vitro results, demonstrating that the compound exhibited powerful binding interaction with target enzymes. Particularly, three continuous hydroxyl groups on the A ring demonstrated strong H-bond binding properties. It is also noteworthy that baicalein complied with all requirements of Lipinski's rule of five by its optimal physicochemical properties for both oral bioavailability and blood-brain barrier permeability. Overall, the present study strongly demonstrated the possibility of baicalein having in vivo pharmacological efficacy for specific targets in the prevention and/or treatment of AD.
ESTHER : Han_2019_Nutrients_11_
PubMedSearch : Han_2019_Nutrients_11_
PubMedID: 31703329

Title : Focused ultrasound-induced blood-brain barrier opening improves adult hippocampal neurogenesis and cognitive function in a cholinergic degeneration dementia rat model - Shin_2019_Alzheimers.Res.Ther_11_110
Author(s) : Shin J , Kong C , Lee J , Choi BY , Sim J , Koh CS , Park M , Na YC , Suh SW , Chang WS , Chang JW
Ref : Alzheimers Res Ther , 11 :110 , 2019
Abstract : BACKGROUND: The persistence of adult hippocampal neurogenesis (AHN) is sharply decreased in Alzheimer's disease (AD). The neuropathologies of AD include the presence of amyloid-beta deposition in plaques, tau hyperphosphorylation in neurofibrillary tangles, and cholinergic system degeneration. The focused ultrasound (FUS)-mediated blood-brain barrier opening modulates tau hyperphosphorylation, the accumulation of amyloid-beta proteins, and increases in AHN. However, it remains unclear whether FUS can modulate AHN in cholinergic-deficient conditions. In this study, we investigated the effect of FUS on AHN in a cholinergic degeneration rat model of dementia. METHODS: Adult male Sprague-Dawley rats (n = 48; 200-250 g) were divided into control (phosphate-buffered saline injection), 192 IgG-saporin (SAP), and SAP+FUS groups; in the two latter groups, SAP was injected bilaterally into the lateral ventricle. We applied FUS to the bilateral hippocampus with microbubbles. Immunohistochemistry, enzyme-linked immunosorbent assay, immunoblotting, 5-bromo-2'-deoxyuridine labeling, an acetylcholinesterase assay, and the Morris water maze test were performed to assess choline acetyltransferase, acetylcholinesterase activity, brain-derived neurotrophic factor expression, neural proliferation, and spatial memory, respectively. Statistical significance of differences in between groups was calculated using one-way and two-way analyses of variance followed by Tukey's multiple comparison test to determine the individual and interactive effects of FUS on immunochemistry and behavioral analysis. P < 0.05 was considered significant. RESULTS: Cholinergic degeneration in rats significantly decreased the number of choline acetyltransferase neurons (P < 0.05) in the basal forebrain, as well as AHN and spatial memory function. Rats that underwent FUS-mediated brain-blood barrier opening exhibited significant increases in brain-derived neurotrophic factor (BDNF; P < 0.05), early growth response protein 1 (EGR1) (P < 0.01), AHN (P < 0.01), and acetylcholinesterase activity in the frontal cortex (P < 0.05) and hippocampus (P < 0.01) and crossing over (P < 0.01) the platform in the Morris water maze relative to the SAP group after sonication. CONCLUSIONS: FUS treatment increased AHN and improved spatial memory. This improvement was mediated by increased hippocampal BDNF and EGR1. FUS treatment may also restore AHN and protect against neurodegeneration, providing a potentially powerful therapeutic strategy for AD.
ESTHER : Shin_2019_Alzheimers.Res.Ther_11_110
PubMedSearch : Shin_2019_Alzheimers.Res.Ther_11_110
PubMedID: 31881998

Title : Molecular and biochemical characterization of the bed bug salivary gland cholinesterase as an acetylcholine-sequestering enzyme - Kim_2018_Insect.Biochem.Mol.Biol_102_52
Author(s) : Kim JH , Hwang CE , Yoon KA , Seong KM , Lee J , Lee SH
Ref : Insect Biochemistry & Molecular Biology , 102 :52 , 2018
Abstract : The common bed bug, Cimex lectularius, possesses a cholinesterase expressed exclusively in the salivary gland (ClSChE). In this study, we investigated the molecular forms, tissue distribution patterns and biochemical properties of ClSChE and showed that ClSChE exists as a soluble monomeric form or a soluble dimeric form connected by a disulfide bridge. Immunohistochemical analysis confirmed that ClSChE was expressed in the epithelial cells of both the salivary gland and the duct. In addition, the secretion of monomeric ClSChE through the proboscis during feeding was confirmed by western blotting using a ClSChE-specific antibody. To predict the role of ClSChE injected into the tissue of an animal host, we analyzed the extent of hydrolysis of acetylcholine (ACh) by ClSChE by ultra-performance liquid chromatography-tandem mass spectrometry. ClSChE binding to ACh was not clearly resolved in the binding assay format used in this study, probably due to the weak but detectable ACh-hydrolytic activity of ClSChE. Nevertheless, kinetic analysis revealed that ClSChE possesses extremely low Km (high affinity to ACh) and Vmax values. These findings suggest that ClSChE functions virtually as an ACh-sequestering protein by having a very strong affinity to ACh but an extremely long turnover time. Given that ACh regulates a wide variety of host physiologies, we discuss the tentative roles of ClSChE in blood vessel constriction and itch/pain regulation in the host.
ESTHER : Kim_2018_Insect.Biochem.Mol.Biol_102_52
PubMedSearch : Kim_2018_Insect.Biochem.Mol.Biol_102_52
PubMedID: 30266661
Gene_locus related to this paper: cimle-d1fqg8

Title : Association Between Timed Up and Go Test and Future Dementia Onset - Lee_2018_J.Gerontol.A.Biol.Sci.Med.Sci_73_1238
Author(s) : Lee JE , Shin DW , Jeong SM , Son KY , Cho B , Yoon JL , Park BJ , Kwon IS , Lee J , Kim S
Ref : J Gerontol A Biol Sci Med Sci , 73 :1238 , 2018
Abstract : Background: This study evaluated whether baseline results of the Timed Up and Go (TUG) test is associated with future dementia occurrence. Methods: Using the Korean National Health Insurance Service-National Health Screening Cohort database, we identified 49,283 subjects without a dementia diagnosis who participated in the National Screening Program for Transitional Ages at 66 years of age during 2007-2012. Gait impairment was defined as taking longer than 10 seconds to perform the TUG test. Dementia occurrence was defined by the first prescription for acetylcholinesterase inhibitors or N-Methyl-D-Aspartate receptor antagonist with an International Classification of Diseases 10th Revision (ICD-10) code for dementia (F00, F01, F02, F03, G30, F051, or G311) during 2007-2013. Cox proportional hazard regression models were used to assess the hazard ratios for dementia occurrence according to baseline TUG test results. Results: Mean follow-up period was 3.8 years. Incidence rates of dementia were 4.6 and 6.8 cases per 1,000 person-years in the normal and impaired TUG groups, respectively. The impaired TUG group showed a higher risk of total dementia incidence (adjusted hazard ratio [aHR], 1.34; 95% confidence interval [95% CI], 1.14-1.57). Subtype analysis showed that the impaired TUG group had a higher risk of Alzheimer's disease (aHR, 1.26; 95% CI, 1.06-1.51) and vascular dementia (aHR, 1.65; 95% CI, 1.19-2.30). Conclusions: The TUG test result was associated with future dementia occurrence. More vigilant follow-up and early intervention to prevent dementia would benefit elderly people with impaired TUG test result.
ESTHER : Lee_2018_J.Gerontol.A.Biol.Sci.Med.Sci_73_1238
PubMedSearch : Lee_2018_J.Gerontol.A.Biol.Sci.Med.Sci_73_1238
PubMedID: 29346523

Title : Terminalia chebula extract prevents scopolamine-induced amnesia via cholinergic modulation and anti-oxidative effects in mice - Kim_2018_BMC.Complement.Altern.Med_18_136
Author(s) : Kim MS , Lee DY , Lee J , Kim HW , Sung SH , Han JS , Jeon WK
Ref : BMC Complement Altern Med , 18 :136 , 2018
Abstract : BACKGROUND: Terminalia chebula Retz. (Combretaceae) is a traditional herbal medicine that is widely used in the treatment of diabetes, immunodeficiency diseases, and stomach ulcer in Asia. However, the anti-amnesic effect of T. chebula has not yet been investigated. The present study was designed to determine whether T. chebula extract (TCE) alleviates amnesia induced by scopolamine in mice. We also investigated possible mechanisms associated with cholinergic system and anti-oxidant effects. METHODS: TCE (100 or 200 mg/kg) was orally administered to mice for fourteen days (days 1-14), and scopolamine was intraperitoneally injected to induce memory impairment for seven days (days 8-14). Learning and memory status were evaluated using the Morris water maze. Hippocampal levels of acetylcholine (ACh), acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) were measured ex vivo. Levels of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA) in the hippocampus were also examined. RESULTS: In the Morris water maze task, TCE treatment reversed scopolamine-induced learning and memory deficits in acquisition and retention. TCE reduced hippocampal AChE activities and increased ChAT and ACh levels in the scopolamine-induced model. Moreover, TCE treatment suppressed scopolamine-induced oxidative damage by ameliorating the increased levels of ROS, NO, and MDA. CONCLUSION: These findings suggest that TCE exerts potent anti-amnesic effects via cholinergic modulation and anti-oxidant activity, thus providing evidence for its potential as a cognitive enhancer for amnesia.
ESTHER : Kim_2018_BMC.Complement.Altern.Med_18_136
PubMedSearch : Kim_2018_BMC.Complement.Altern.Med_18_136
PubMedID: 29716575

Title : Analysis of the Draft Genome of the Red Seaweed Gracilariopsis chorda Provides Insights into Genome Size Evolution in Rhodophyta - Lee_2018_Mol.Biol.Evol_35_1869
Author(s) : Lee J , Yang EC , Graf L , Yang JH , Qiu H , Zelzion U , Chan CX , Stephens TG , Weber APM , Boo GH , Boo SM , Kim KM , Shin Y , Jung M , Lee SJ , Yim HS , Lee JH , Bhattacharya D , Yoon HS
Ref : Molecular Biology Evolution , 35 :1869 , 2018
Abstract : Red algae (Rhodophyta) underwent two phases of large-scale genome reduction during their early evolution. The red seaweeds did not attain genome sizes or gene inventories typical of other multicellular eukaryotes. We generated a high-quality 92.1 Mb draft genome assembly from the red seaweed Gracilariopsis chorda, including methylation and small (s)RNA data. We analyzed these and other Archaeplastida genomes to address three questions: 1) What is the role of repeats and transposable elements (TEs) in explaining Rhodophyta genome size variation, 2) what is the history of genome duplication and gene family expansion/reduction in these taxa, and 3) is there evidence for TE suppression in red algae? We find that the number of predicted genes in red algae is relatively small (4,803-13,125 genes), particularly when compared with land plants, with no evidence of polyploidization. Genome size variation is primarily explained by TE expansion with the red seaweeds having the largest genomes. Long terminal repeat elements and DNA repeats are the major contributors to genome size growth. About 8.3% of the G. chorda genome undergoes cytosine methylation among gene bodies, promoters, and TEs, and 71.5% of TEs contain methylated-DNA with 57% of these regions associated with sRNAs. These latter results suggest a role for TE-associated sRNAs in RNA-dependent DNA methylation to facilitate silencing. We postulate that the evolution of genome size in red algae is the result of the combined action of TE spread and the concomitant emergence of its epigenetic suppression, together with other important factors such as changes in population size.
ESTHER : Lee_2018_Mol.Biol.Evol_35_1869
PubMedSearch : Lee_2018_Mol.Biol.Evol_35_1869
PubMedID: 29688518
Gene_locus related to this paper: 9flor-a0a2v3j1b8

Title : The enhancing effect of Aubang Gahl Soo on the hippocampal synaptic plasticity and memory through enhancing cholinergic system in mice - Lee_2018_J.Ethnopharmacol_224_91
Author(s) : Lee J , Kwon H , Yu J , Cho E , Jeon J , Lee S , Ryu JH , Lee YC , Kim DH , Jung JW
Ref : J Ethnopharmacol , 224 :91 , 2018
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Aubang Gahl Soo (AGS) is a Korean traditional drink manufactured from medicinal plants and fruits using sugar or honey. Although traditional old book stated its effects on body, there is no scientific evidence yet. Therefore, in the present study, we tested AGS on brain functions. AIM OF THIS STUDY: In this study, we tried to uncover the effect of on brain functions. To do this we examined the action of AGS on the hippocampal synaptic function and memory in mice. MATERIALS AND METHODS: To examine the effect of AGS on synaptic plasticity, we observed input-output curves (I/O curve), paired-pulse facilitation (PPF), and long-term potentiation (LTP) using mouse hippocampal slices. Moreover, to investigate the functional relevance of the effect of AGS on synaptic plasticity, we conducted passive avoidance, Y-maze and Morris water maze tests. To examine relevant mechanism, acetylcholinesterase (AChE) activity and acetylcholine (ACh) level assay were also conducted. RESULTS: In the basal synaptic transmission study, we found that AGS did not affect I/O curves and PPF. However, AGS facilitated hippocampal LTP in a concentration-dependent manner. Moreover, AGS blocked AChE activity (IC50 = 485mug/ml). Moreover, ACh level was increased by AGS (100mug/ml) treatment. Along with this, facilitating effect of AGS on hippocampal LTP also blocked by scopolamine, a muscarinic acetylcholine receptor antagonist. Moreover, AGS also ameliorated memory impairments induced by scopolamine in passive avoidance, Y-maze, and Morris water maze tests. CONCLUSIONS: These results suggest that AGS facilitates hippocampal LTP through activating cholinergic system and ameliorates cholinergic dysfunction-induced memory deficit.
ESTHER : Lee_2018_J.Ethnopharmacol_224_91
PubMedSearch : Lee_2018_J.Ethnopharmacol_224_91
PubMedID: 29842961

Title : Effect of Placenta-Derived Mesenchymal Stem Cells in a Dementia Rat Model via Microglial Mediation: a Comparison between Stem Cell Transplant Methods - Cho_2018_Yonsei.Med.J_59_406
Author(s) : Cho JS , Lee J , Jeong DU , Kim HW , Chang WS , Moon J , Chang JW
Ref : Yonsei Med J , 59 :406 , 2018
Abstract : PURPOSE: Loss of cholinergic neurons in the hippocampus is a hallmark of many dementias. Administration of stem cells as a therapeutic intervention for patients is under active investigation, but the optimal stem cell type and transplantation modality has not yet been established. In this study, we studied the therapeutic effects of human placenta-derived mesenchymal stem cells (pMSCs) in dementia rat model using either intracerebroventricular (ICV) or intravenous (IV) injections and analyzed their mechanisms of therapeutic action. MATERIALS AND METHODS: Dementia modeling was established by intraventricular injection of 192 IgG-saporin, which causes lesion of cholinergic neurons. Sixty-five male Sprague-Dawley rats were divided into five groups: control, lesion, lesion+ICV injection of pMSCs, lesion+IV injection of pMSCs, and lesion+donepezil. Rats were subjected to the Morris water maze and subsequent immunostaining analyses. RESULTS: Both ICV and IV pMSC administrations allowed significant cognitive recovery compared to the lesioned rats. Acetylcholinesterase activity was significantly rescued in the hippocampus of rats injected with pMSCs post-lesion. Choline acetyltransferase did not co-localize with pMSCs, showing that pMSCs did not directly differentiate into cholinergic cells. Number of microglial cells increased in lesioned rats and significantly decreased back to normal levels with pMSC injection. CONCLUSION: Our results suggest that ICV and IV injections of pMSCs facilitate the recovery of cholinergic neuronal populations and cognitive behavior. This recovery likely occurs through paracrine effects that resemble microglia function rather than direct differentiation of injected pMSCs into cholinergic neurons.
ESTHER : Cho_2018_Yonsei.Med.J_59_406
PubMedSearch : Cho_2018_Yonsei.Med.J_59_406
PubMedID: 29611403

Title : Preparation of High Purity delta5-Olefinic Acids from Pine Nut Oil via Repeated Lipase-Catalyzed Esterification - Kim_2018_J.Oleo.Sci_67_1435
Author(s) : Kim H , Choi N , Kim HR , Lee J , Kim IH
Ref : J Oleo Sci , 67 :1435 , 2018
Abstract : delta5-Olefinic acids have been characterized in gymnosperm plants and have been reported to have several biological health benefits. delta5-Olefinic acids from pine nut oil were effectively concentrated by repeated lipase-catalyzed esterification. The pine nut oil contained three major delta5-olefinic acids, namely taxoleic acid (C18:2 delta5,9), pinolenic acid (C18:3 delta5,9,12), and sciadonic acid (C20:3 delta5,11,14). The fatty acids present in pine nut oil were selectively esterified with ethanol using Lipozyme RM IM from Rhizomucor miehei as a biocatalyst. The delta5-olefinic acids were concentrated in the unesterified fatty acid fraction. The optimum molar ratio of the substrates (fatty acid:ethanol), temperature, the enzyme loading, and the reaction time were 1:7, 25 degC, 5% of total substrate weight, and 6 h, respectively. There was no significant effect in the concentration of delta5-olefinic acids when water was added in the reaction mixture. The same protocol and optimum conditions were employed for two times repeated lipase-catalyzed esterifications. In first lipase-catalyzed esterification, the delta5-olefinic acids content in the pine nut oil increased from 17 mol% to 51 mol% with a yield of 40 mol%. In a second lipase-catalyzed esterification, with the delta5-olefinic acids-concentrated fatty acids obtained from the first reaction as the substrate, the delta5-olefinic acids content increased to 86 mol% with a yield of 15 mol%. Finally, a maximum delta5-olefinic acids content of ca. 96 mol% with a yield of 6 mol% was obtained via a third lipase-catalyzed esterification.
ESTHER : Kim_2018_J.Oleo.Sci_67_1435
PubMedSearch : Kim_2018_J.Oleo.Sci_67_1435
PubMedID: 30404964

Title : In Silico Docking and In Vitro Approaches towards BACE1 and Cholinesterases Inhibitory Effect of Citrus Flavanones - Lee_2018_Molecules_23_
Author(s) : Lee S , Youn K , Lim G , Lee J , Jun M
Ref : Molecules , 23 : , 2018
Abstract : Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease, distinctively characterized by senile plaques, neurofibrillary tangles, and synaptic loss, finally resulting in neuronal death. β-Site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) and cholinesterases have been identified as therapeutic targets for AD, and the discovery of their inhibitors is of critical importance for developing preventive strategies for AD. To discover natural multi-target compounds possessing BACE1, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitory properties, major citrus flavanones including hesperetin, naringenin, and hesperidin were evaluated. In vitro anti-AD activities were performed via BACE1 and cholinesterases inhibition assays, as well as enzyme kinetic predictions. For the design of potential inhibitors of AD-related enzymes, molecular docking analysis was performed. Based on the biological evaluation, hesperidin demonstrated the best inhibitory properties toward BACE1, AChE, and BChE, with IC50 values of 10.02 +/- 1.12, 22.80 +/- 2.78, and 48.09 +/- 0.74 µM, respectively. Kinetic studies revealed that all tested compounds were found to be noncompetitive inhibitors against BACE1 and cholineseterases. In addition, molecular docking studies of these compounds demonstrated negative binding energies for BACE1, AChE, and BChE, indicating high affinity and tight binding capacity for the target enzymes. The present study suggested that the selected citrus flavanones could act together as multiple inhibitors of BACE1, AChE, and BChE, indicating preventive and therapeutic potential against AD.
ESTHER : Lee_2018_Molecules_23_
PubMedSearch : Lee_2018_Molecules_23_
PubMedID: 29932100

Title : Novel tacrine-pyridinium hybrid reactivators of organophosphorus-inhibited acetylcholinesterase: Synthesis, molecular docking, and in vitro reactivation study - Kim_2018_Bioorg.Med.Chem.Lett_28_3784
Author(s) : Kim J , Malpani YR , Lee J , Shin JS , Han SB , Jung YS
Ref : Bioorganic & Medicinal Chemistry Lett , 28 :3784 , 2018
Abstract : First-line medical treatment against nerve agents consists of co-administration of anticholinergic agents and oxime reactivators, which reactivate inhibited AChE. Pralidoxime, a commonly used oxime reactivator, is effective against some nerve agents but not against others; thus, new oxime reactivators are needed. Novel tacrine-pyridinium hybrid reactivators in which 4-pyridinealdoxime derivatives are connected to tacrine moieties by linear carbon chains of different lengths (C2-C7) were prepared (Scheme 1, 5a-f). Their binding affinities to electric eel AChE were tested because oximes can inhibit free AChE, and the highest AChE activity (95%, 92%, and 90%) was observed at 1muM concentrations of the oximes (5a, 5b, and 5c, respectively). Based on their inhibitory affinities towards free AChE, 1muM concentrations of the oxime derivatives (5) were used to examine reactivation of paraoxon-inhibited AChE. Reactivation ability increased as the carbon linker chains lengthened (n=2-5), and 5c and 5d showed remarkable reactivation ability (41%) compared to that of 2-PAM (16%) and HI-6 (4%) against paraoxon-inhibited electric eel AChE at 1muM concentrations. Molecular docking simulation showed that the most stable binding free energy was observed in 5c at 73.79kcalmol(-1), and the binding mode of 5c is acceptable for the oxygen atom of oximate to attack the phosphorus atom of paraoxon and reactivate paraoxon-inhibited eel AChE model structure.
ESTHER : Kim_2018_Bioorg.Med.Chem.Lett_28_3784
PubMedSearch : Kim_2018_Bioorg.Med.Chem.Lett_28_3784
PubMedID: 30301674

Title : Identifying the appropriate time for deep brain stimulation to achieve spatial memory improvement on the Morris water maze - Jeong_2017_BMC.Neurosci_18_29
Author(s) : Jeong DU , Lee J , Chang WS , Chang JW
Ref : BMC Neurosci , 18 :29 , 2017
Abstract : BACKGROUND: The possibility of using deep brain stimulation (DBS) for memory enhancement has recently been reported, but the precise underlying mechanisms of its effects remain unknown. Our previous study suggested that spatial memory improvement by medial septum (MS)-DBS may be associated with cholinergic regulation and neurogenesis. However, the affected stage of memory could not be distinguished because the stimulation was delivered during the execution of all memory processes. Therefore, this study was performed to determine the stage of memory affected by MS-DBS. Rats were administered 192 IgG-saporin to lesion cholinergic neurons. Stimulation was delivered at different times in different groups of rats: 5 days before the Morris water maze test (pre-stimulation), 5 days during the training phase of the Morris water maze test (training-stimulation), and 2 h before the Morris water maze probe test (probe-stimulation). A fourth group of rats was lesioned but received no stimulation. These four groups were compared with a normal (control) group.
RESULTS: The most effective memory restoration occurred in the pre-stimulation group. Moreover, the pre-stimulation group exhibited better recall of the platform position than the other stimulation groups. An increase in the level of brain derived neurotrophic factor (BDNF) was observed in the pre-stimulation group; this increase was maintained for 1 week. However, acetylcholinesterase activity in the pre-stimulation group was not significantly different from the lesion group. CONCLUSION: Memory impairment due to cholinergic denervation can be improved by DBS. The improvement is significantly correlated with the up-regulation of BDNF expression and neurogenesis. Based on the results of this study, the use of MS-DBS during the early stage of disease may restore spatial memory impairment.
ESTHER : Jeong_2017_BMC.Neurosci_18_29
PubMedSearch : Jeong_2017_BMC.Neurosci_18_29
PubMedID: 28264667

Title : Genome expansion and lineage-specific genetic innovations in the forest pathogenic fungi Armillaria - Sipos_2017_Nat.Ecol.Evol_1_1931
Author(s) : Sipos G , Prasanna AN , Walter MC , O'Connor E , Balint B , Krizsan K , Kiss B , Hess J , Varga T , Slot J , Riley R , Boka B , Rigling D , Barry K , Lee J , Mihaltcheva S , LaButti K , Lipzen A , Waldron R , Moloney NM , Sperisen C , Kredics L , Vagvolgyi C , Patrignani A , Fitzpatrick D , Nagy I , Doyle S , Anderson JB , Grigoriev IV , Guldener U , Munsterkotter M , Nagy LG
Ref : Nat Ecol Evol , 1 :1931 , 2017
Abstract : Armillaria species are both devastating forest pathogens and some of the largest terrestrial organisms on Earth. They forage for hosts and achieve immense colony sizes via rhizomorphs, root-like multicellular structures of clonal dispersal. Here, we sequenced and analysed the genomes of four Armillaria species and performed RNA sequencing and quantitative proteomic analysis on the invasive and reproductive developmental stages of A. ostoyae. Comparison with 22 related fungi revealed a significant genome expansion in Armillaria, affecting several pathogenicity-related genes, lignocellulose-degrading enzymes and lineage-specific genes expressed during rhizomorph development. Rhizomorphs express an evolutionarily young transcriptome that shares features with the transcriptomes of both fruiting bodies and vegetative mycelia. Several genes show concomitant upregulation in rhizomorphs and fruiting bodies and share cis-regulatory signatures in their promoters, providing genetic and regulatory insights into complex multicellularity in fungi. Our results suggest that the evolution of the unique dispersal and pathogenicity mechanisms of Armillaria might have drawn upon ancestral genetic toolkits for wood-decay, morphogenesis and complex multicellularity.
ESTHER : Sipos_2017_Nat.Ecol.Evol_1_1931
PubMedSearch : Sipos_2017_Nat.Ecol.Evol_1_1931
PubMedID: 29085064
Gene_locus related to this paper: armos-armb

Title : Phytochemical Quantification and the In Vitro Acetylcholinesterase Inhibitory Activity of Phellodendron chinense and Its Components - Kim_2017_Molecules_22_
Author(s) : Kim YJ , Lim HS , Kim Y , Lee J , Kim BY , Jeong SJ
Ref : Molecules , 22 : , 2017
Abstract : The dried bark of Phellodendron chinense has been used as a traditional herbal medicine to remove damp heat, relieve consumptive fever, and cure dysentery and diarrhea. In the present study, we performed quantitative analyses of the two components of P. chinense, phellodendrine and berberine, using high-performance liquid chromatography. A 70% ethanol extract of P. chinense was prepared and the two components were separated on a C-18 analytical column using a gradient solvent system of acetonitrile and 0.1% (v/v) aqueous trifluoroacetic acid. The ultraviolet wavelength used for detection was 200 nm for phellodendrine and 226 nm for berberine. The analytical method established here showed high linearity (correlation coefficient, >/=0.9991). The amount of phellodendrine and berberine used was 22.255 +/- 0.123 mg/g and 269.651 +/- 1.257 mg/g, respectively. Moreover, we performed an in vitro acetylcholinesterase (AChE) activity assay and an amyloid-beta aggregation test to examine the biological properties of phellodendrine and berberine as therapeutic drugs for Alzheimer's disease. Phellodendrine and berberine inhibited AChE activity in a dose-dependent manner (IC50 = 36.51 and 0.44 muM, respectively). In contrast, neither phellodendrine nor berberine had an effect on amyloid-beta aggregation. The P. chinense extract and phellodendrine, but not berberine, exhibited antioxidant activity by increasing radical scavenging activity. Moreover, P. chinense demonstrated a neuroprotective effect in hydrogen peroxide-treated HT22 hippocampal cells. Overall, our findings suggest that P. chinense has potential as an anti-Alzheimer's agent via the suppression of the enzymatic activity of acetylcholinesterase and the stimulation of antioxidant activity.
ESTHER : Kim_2017_Molecules_22_
PubMedSearch : Kim_2017_Molecules_22_
PubMedID: 28574473

Title : The protective effect of fermented Curcuma longa L. on memory dysfunction in oxidative stress-induced C6 gliomal cells, proinflammatory-activated BV2 microglial cells, and scopolamine-induced amnesia model in mice - Eun_2017_BMC.Complement.Altern.Med_17_367
Author(s) : Eun CS , Lim JS , Lee J , Lee SP , Yang SA
Ref : BMC Complement Altern Med , 17 :367 , 2017
Abstract : BACKGROUND: Curcuma longa L. is a well-known medicinal plant that has been used for its anti-cancer, neuroprotective, and hepatoprotective effects. However, the neuroprotective effect of fermented C. longa (FCL) has not been reported. Therefore, in this study, the effectiveness of FCL for the regulation of memory dysfunction was investigated in two brain cell lines (rat glioma C6 and murine microglia BV2) and scopolamine-treated mice.
METHODS: C. longa powder was fermented by 5% Lactobacillus plantarum K154 containing 2% (w/v) yeast extract at 30 degrees C for 72 h followed by sterilization at 121 degrees C for 15 min. The protective effects of fermented C. longa (FCL) on oxidative stress induced cell death were analyzed by MTT assay in C6 cells. The anti-inflammatory effects of FCL were investigated by measuring the production of nitric oxide (NO) and prostaglandin E2 (PGE2) as well as the expression levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated BV2 cells. The step-through passive avoidance test, Morris water maze test, acetylcholinesterase (AChE) activity, and expression of cAMP response element-binding protein (CREB) and brain-derived neurotropic factor (BDNF) were employed to determine the effects of FCL on scopolamine-induced memory deficit in mice. The contents of curcuminoids were analyzed through LC/MS.
RESULTS: Pretreatment with FCL effectively prevented the cell death induced by oxidative stress in C6 cells. Moreover, FCL inhibited the production NO and PGE2 via the inhibition of iNOS and COX-2 expression in BV2 cells. FCL significantly attenuated scopolamine-induced memory impairment in mice and prevented scopolamine-induced AChE activity in the hippocampus. Additionally, FCL reversed the reduction of CREB and BDNF expression. The curcuminoids content in FCL was 1.44%. CONCLUSION: FCL pretreatment could alleviate scopolamine-induced memory impairment in mice, as well as oxidative stress and inflammation in C6 and BV2 cells, respectively. Thus, FCL might be a useful material for preventing impairment of learning and memory.
ESTHER : Eun_2017_BMC.Complement.Altern.Med_17_367
PubMedSearch : Eun_2017_BMC.Complement.Altern.Med_17_367
PubMedID: 28716085

Title : Anti-Metastatic Effect of Dehydrocorydaline on H1299 Non-Small Cell Lung Carcinoma Cells via Inhibition of Matrix Metalloproteinases and B Cell Lymphoma 2 - Lee_2017_Phytother.Res_31_441
Author(s) : Lee J , Sohn EJ , Yoon SW , Kim CG , Lee S , Kim JY , Baek N , Kim SH
Ref : Phytother Res , 31 :441 , 2017
Abstract : Though Dehydrocorydaline, an alkaloid isolated from Corydalis turtschaninovii tuber, was known to have anti-coronary artery disease, anti-inflammatory, apoptotic, anti-allergic, anti-acetylcholinesterase, and antitumor effects, the underlying anti-metastatic mechanism of Dehydrocorydalin was never elucidated in lung cancer cells so far. Thus, in the present study, the anti-metastatic effect of Dehydrocorydaline was examined in non-small cell lung carcinoma (NSCLC) cells, mainly targeting matrix metalloproteinases (MMPs) and B cell lymphoma-2 (Bcl-2) signaling. Here, Dehydrocorydaline exerted weak cytotoxicity and attenuated the protein expression of Bcl-2 and activated Bax in a concentration-dependent manner in NSCLC cells, such as A549, H460, H1299, and H596 cells. Also, Dehydrocorydaline suppressed the migration of H1299 cells by wound healing assay and transwell migration assay. Consistently, Dehydrocorydaline attenuated mRNA and protein levels of MMP7 and MMP9 as metastasis biomarkers in H1299 cells by quantitative reverse transcription polymerase chain reaction. Of note, Bcl-2 overexpression reduced the cytotoxic and anti-metastatic effects of Dehydrocorydaline on pCDNA-Bcl-2 transfected H1299 cells. Overall, our findings provide scientific evidence that Dehydrocorydaline exerts anti-metastatic potential via suppression of MMPs and Bcl-2 signaling in NSCLC cells. Copyright (c) 2017 John Wiley & Sons, Ltd.
ESTHER : Lee_2017_Phytother.Res_31_441
PubMedSearch : Lee_2017_Phytother.Res_31_441
PubMedID: 28144994

Title : Neuroprotective Effect of Corydalis ternata Extract and Its Phytochemical Quantitative Analysis - Kim_2017_Chem.Pharm.Bull.(Tokyo)_65_826
Author(s) : Kim YJ , Lim HS , Kim Y , Lee J , Kim BY , Jeong SJ
Ref : Chem Pharm Bull (Tokyo) , 65 :826 , 2017
Abstract : The tubers of Corydalis ternata have been used to treat cardiovascular diseases such as hypertension and cardiac arrhythmia. Its active components have anticholinesterase, antiamnesic, and anti-inflammatory activities, and analgesic effects. In the present study, we performed quantitative analyses of the two components of C. ternata, coptisine and berberine, using HPLC. A 70% ethanol extract of C. ternata was prepared and the two components were separated using a C-18 analytical column on a gradient solvent system of acetonitrile and 0.1% (v/v) aqueous trifluoroacetic acid. Recordings were performed at a UV wavelength of 265 nm for two standard components. The established analytical method showed high linearity (correlation coefficient (r)=1.0000) and proper precision (0.49-3.88%), accuracy (97.88-102.7%), and recovery (95.12-103.79%) for two standard components. The amount of the coptisine and berberine was 4.968+/-0.089 mg/g and 3.73+/-0.075 mg/g, respectively. In addition, we investigated the effects of coptisine and berberine on acetylcholinesterase activity and amyloid-beta aggregation, which are major biomarkers of dementia. Coptisine and berberine decreased acetylcholinesterase activity in a dose-dependent manner (IC50=0.74 and 0.48 microM, respectively). The C. ternata extract exerted an antioxidant activity by stimulating the radical scavenging activity of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), but not 2,2-diphenyl-1-picrylhydrazyl (DPPH). Furthermore, the C. ternata extract reversed the hydrogen peroxide-induced death of HT22 hippocampal cells, indicating its neuroprotective effect. Our results suggest the potential of C. ternata as a therapeutic agent against dementia via the inhibition of acetylcholinesterase activity and neuronal cell death.
ESTHER : Kim_2017_Chem.Pharm.Bull.(Tokyo)_65_826
PubMedSearch : Kim_2017_Chem.Pharm.Bull.(Tokyo)_65_826
PubMedID: 28867709

Title : New reference genome sequences of hot pepper reveal the massive evolution of plant disease-resistance genes by retroduplication - Kim_2017_Genome.Biol_18_210
Author(s) : Kim S , Park J , Yeom SI , Kim YM , Seo E , Kim KT , Kim MS , Lee JM , Cheong K , Shin HS , Kim SB , Han K , Lee J , Park M , Lee HA , Lee HY , Lee Y , Oh S , Lee JH , Choi E , Lee SE , Jeon J , Kim H , Choi G , Song H , Lee SC , Kwon JK , Koo N , Hong Y , Kim RW , Kang WH , Huh JH , Kang BC , Yang TJ , Lee YH , Bennetzen JL , Choi D
Ref : Genome Biol , 18 :210 , 2017
Abstract : BACKGROUND: Transposable elements are major evolutionary forces which can cause new genome structure and species diversification. The role of transposable elements in the expansion of nucleotide-binding and leucine-rich-repeat proteins (NLRs), the major disease-resistance gene families, has been unexplored in plants. RESULTS: We report two high-quality de novo genomes (Capsicum baccatum and C. chinense) and an improved reference genome (C. annuum) for peppers. Dynamic genome rearrangements involving translocations among chromosomes 3, 5, and 9 were detected in comparison between C. baccatum and the two other peppers. The amplification of athila LTR-retrotransposons, members of the gypsy superfamily, led to genome expansion in C. baccatum. In-depth genome-wide comparison of genes and repeats unveiled that the copy numbers of NLRs were greatly increased by LTR-retrotransposon-mediated retroduplication. Moreover, retroduplicated NLRs are abundant across the angiosperms and, in most cases, are lineage-specific. CONCLUSIONS: Our study reveals that retroduplication has played key roles for the massive emergence of NLR genes including functional disease-resistance genes in pepper plants.
ESTHER : Kim_2017_Genome.Biol_18_210
PubMedSearch : Kim_2017_Genome.Biol_18_210
PubMedID: 29089032
Gene_locus related to this paper: capch-q75qh4 , capan-a0a1u8fuf5 , capan-a0a1u8gmz3 , capch-a0a2g3bqp0 , capba-a0a2g2vcw4 , capan-a0a1u8flz5 , capch-a0a2g3bau3 , capch-a0a2g3b6c0 , capan-a0a2g2y016 , capch-a0a2g3cje8 , capba-a0a2g2xr67 , capan-a0a1u8fpc9 , capan-a0a1u8fqs3 , capan-a0a1u8ft99 , capan-a0a2g2xtt0 , capan-a0a1u8eu02 , capan-a0a1u8hd13 , capan-a0a2g2y0b6

Title : Expression and purification of biologically active recombinant human paraoxonase 1 from a Drosophila S2 stable cell line - Yun_2016_Protein.Expr.Purif_131_34
Author(s) : Yun H , Yu J , Kim S , Lee N , Lee J , Lee S , Kim ND , Yu C , Rho J
Ref : Protein Expr Purif , 131 :34 , 2016
Abstract : Many pesticides and chemical warfare nerve agents are highly toxic organophosphorus compounds (OPs), which inhibit acetylcholinesterase activity. Human paraoxonase 1 (PON1) has demonstrated significant potential for use as a catalytic bioscavenger capable of hydrolyzing a broad range of OPs. However, there are several limitations to the use of human PON1 as a catalytic bioscavenger, including the relatively difficult purification of PON1 from human plasma and its dependence on the presence of hydrophobic binding partners to maintain stability. Therefore, research efforts to efficiently produce recombinant human PON1 are necessary. In this study, we developed a Drosophila S2 stable cell line expressing recombinant human PON1. The recombinant human PON1 was fused with the human immunoglobulin Fc domain (PON1-hFc) to improve protein stability and purification efficiency. We purified the recombinant human PON1-hFc from the S2 stable cell line and characterized its enzymatic properties for OP hydrolysis. We purified the recombinant human PON1-hFc from the S2 stable cell line and characterized its enzymatic properties for OP hydrolysis compared with those of the recombinant human PON1 derived from E. coli. We observed that the recombinant human PON1-hFc is functionally more stable for OP hydrolyzing activities compared to the recombinant human PON1. The catalytic efficiency of the recombinant PON1-hFc towards diisopropyl fluorophosphate (DFP, 0.26 x 106 M-1 min-1) and paraoxon hydrolysis (0.015 x 106 M-1 min-1) was 1.63- and 1.24-fold higher, respectively, than the recombinant human PON1. Thus, we report that the recombinant PON1-hFc exerts hydrolytic activity against paraoxon and DFP.
ESTHER : Yun_2016_Protein.Expr.Purif_131_34
PubMedSearch : Yun_2016_Protein.Expr.Purif_131_34
PubMedID: 27838376

Title : Ginkgo biloba L. extract protects against chronic cerebral hypoperfusion by modulating neuroinflammation and the cholinergic system - Kim_2016_Phytomedicine_23_1356
Author(s) : Kim MS , Bang JH , Lee J , Han JS , Baik TG , Jeon WK
Ref : Phytomedicine , 23 :1356 , 2016
Abstract : BACKGROUND: Ginkgo biloba extract (GBE)-a widely used nutraceutical-is reported to have diverse functions, including positive effects on memory and vasodilatory properties. Although numerous studies have assessed the neuroprotective properties of GBE in ischemia, only a few studies have investigated the neuro-pharmacological mechanisms of action of GBE in chronic cerebral hypoperfusion (CCH). PURPOSE: In the present study, we sought to determine the effects of GBE on CCH-induced neuroinflammation and cholinergic dysfunction in a rat model of bilateral common carotid artery occlusion (BCCAo).
METHODS: Chronic BCCAo was induced in adult male Wistar rats to reflect the CCH conditions. On day 21 after BCCAo, the animals were treated orally with saline or GBE (5, 10, 20, and 40mg/kg) daily for 42 days. After the final treatment, brain tissues were isolated for the immunohistochemical analysis of glial markers and choline acetyltransferase (ChAT), as well as for the western blot analysis of proinflammatory cytokines, toll-like receptor (TLR)-related pathway, receptor for advanced glycation end products (RAGE), angiotensin-II (Ang-II), and phosphorylated mitogen-activated protein kinases (MAPKs).
RESULTS: BCCAo increased glial proliferation in the hippocampus and white matter, whereas proliferation was significantly attenuated by GBE treatment. GBE also attenuated the BCCAo-related increases in the hippocampal expression of proinflammatory cytokines (TNF-alpha, IL-1beta, and IL-6), TLR4, myeloid differentiation primary response gene 88, RAGE, Ang-II, and phosphorylated MAPKs (ERK, p38, and JNK). Furthermore, GBE treatment restored the ChAT expression in the basal forebrain following BCCAo.
CONCLUSIONS: These findings suggest that GBE has specific neuroprotective effects that may be useful for the treatment of CCH. The pharmacological mechanism of GBE partly involves the modulation of inflammatory mediators and the cholinergic system.
ESTHER : Kim_2016_Phytomedicine_23_1356
PubMedSearch : Kim_2016_Phytomedicine_23_1356
PubMedID: 27765355

Title : Cognitive enhancing effect of the fermented Gumiganghwal-tang on scopolamine-induced memory impairment in mice - Weon_2016_Nutr.Neurosci_19_125
Author(s) : Weon JB , Lee J , Eom MR , Jung YS , Ma CJ
Ref : Nutr Neurosci , 19 :125 , 2016
Abstract : Gumiganghwal-tang (GT) is a traditional herbal medicine that is widely used for its anti-inflammatory, analgesic, and antipyretic actions. Fermented GT has been reported to inhibit acetylcholinesterase (AChE) activity and to exert a neuroprotective effect. In this study, we investigated the effect of fermented GT against scopolamine-induced memory impairment in mice using the Morris water maze and passive avoidance tests. The results of the Morris water maze test indicated that fermented GT significantly decreased escape latency, as compared with that observed in the scopolamine-treated group. In the prove test, fermented GT attenuated the decreased time spent in the target quadrant observed after scopolamine treatment. The results of the passive avoidance test indicated that the treatment with fermented GT increased latency time when compared with the scopolamine-treated group. Moreover, fermented GT inhibited AChE activity in the hippocampi of the treated mice. These results suggest that fermented GT reduced scopolamine-induced amnesia in mice through AChE inhibition. Therefore, we hypothesize that fermented GT may be a useful therapeutic agent for the prevention or treatment of neurodegenerative diseases.
ESTHER : Weon_2016_Nutr.Neurosci_19_125
PubMedSearch : Weon_2016_Nutr.Neurosci_19_125
PubMedID: 25216329

Title : Production of Biodiesel from Acid Oil via a Two-Step Enzymatic Transesterification - Choi_2016_J.Oleo.Sci_65_913
Author(s) : Choi N , Lee JS , Kwak J , Lee J , Kim IH
Ref : J Oleo Sci , 65 :913 , 2016
Abstract : A two-step enzymatic transesterification process in a solvent-free system has been developed as a novel approach to the production of biodiesel using acid oil from rice bran oil soapstock. The acid oil consisted of 53.7 wt% fatty acids, 2.4 wt% monoacylglycerols, 9.1 wt% diacylglycerols, 28.8 wt% triacylglycerols, and 6.0 wt% others. Three immobilized lipases were evaluated as potential biocatalysts, including Novozym 435 from Candida antarctica, Lipozyme RM IM from Rhizomucor miehei, and Lipozyme TL IM from Thermomyces lanuginosus. The effects of molar ratio of acid oil to ethanol, temperature, and enzyme loading were investigated to determine the optimum conditions for the transesterification with the three immobilized lipases. The optimum conditions of the three immobilized lipases were a molar ratio of 1:5 (acid oil to ethanol), the temperature range of 30-40 degC, and the enzyme loading range of 5-10%. The two-step transesterification was then conducted under the optimum conditions of each lipase. The stepwise use of Novozym 435 and Lipozyme TL IM or Lipozyme RM IM and Lipozyme TL IM resulted in similar or higher levels of yield to the individual lipases. The maximum yields obtained in both stepwise uses were ca. 92%.
ESTHER : Choi_2016_J.Oleo.Sci_65_913
PubMedSearch : Choi_2016_J.Oleo.Sci_65_913
PubMedID: 27733740

Title : Treatment of Alzheimer's Disease with Repetitive Transcranial Magnetic Stimulation Combined with Cognitive Training: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study - Lee_2016_J.Clin.Neurol_12_57
Author(s) : Lee J , Choi BH , Oh E , Sohn EH , Lee AY
Ref : J Clin Neurol , 12 :57 , 2016
Abstract : BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) has been examined as a potential treatment for many neurological disorders. High-frequency rTMS in particular improves cognitive functions such as verbal fluency and memory. This study explored the effect of rTMS combined with cognitive training (rTMS-COG) on patients with Alzheimer's disease (AD).
METHODS: A prospective, randomized, double-blind, placebo-controlled study was performed with 27 AD patients (18 and 8 in the treatment and sham groups, respectively, and 1 drop-out). The participants were categorized into mild [Mini-Mental State Examination (MMSE) score=21-26] and moderate (MMSE score=18-20) AD groups. The rTMS protocols were configured for six cortical areas (both dorsolateral prefrontal and parietal somatosensory associated cortices and Broca's and Wernicke's areas; 10 Hz, 90-110% intensity, and 5 days/week for 6 weeks). Neuropsychological assessments were performed using the AD Assessment Scale-cognitive subscale (ADAS-cog), Clinical Global Impression of Change (CGIC), and MMSE before, immediately after, and 6 weeks after the end of rTMS-COG treatment.
RESULTS: Data from 26 AD patients were analyzed in this study. There was no significant interactive effect of time between the groups. The ADAS-cog score in the treatment group was significantly improved compared to the sham group (4.28 and 5.39 in the treatment group vs. 1.75 and 2.88 in the sham group at immediately and 6 weeks after treatment, respectively). The MMSE and CGIC scores were also improved in the treatment group. Based on subgroup analysis, the effect of rTMS-COG was superior for the mild group compared to the total patients, especially in the domains of memory and language.
CONCLUSIONS: The present results suggest that rTMS-COG represents a useful adjuvant therapy with cholinesterase inhibitors, particularly during the mild stage of AD. The effect of rTMS-COG was remarkable in the memory and language domains, which are severely affected by AD.
ESTHER : Lee_2016_J.Clin.Neurol_12_57
PubMedSearch : Lee_2016_J.Clin.Neurol_12_57
PubMedID: 26365021

Title : Flavisolibacter tropicus sp. nov., isolated from tropical soil - Lee_2016_Int.J.Syst.Evol.Microbiol_66_3413
Author(s) : Lee JJ , Kang MS , Kim GS , Lee CS , Lim S , Lee J , Roh SH , Kang H , Ha JM , Bae S , Jung HY , Kim MK
Ref : Int J Syst Evol Microbiol , 66 :3413 , 2016
Abstract : A Gram-stain-negative, non-motile, deep yellow, rod-shaped bacterium, designated strain LCS9T, was isolated from a soil sample at the tropical zone within the Ecorium of the National Institute of Ecology in Seocheon, central-western Korea. 16S rRNA gene sequence analysis showed that strain LCS9T clustered with members of the genus Flavisolibacter of the family Chitinophagaceae, phylum Bacteroidetes. Sequence similarities between strain LCS9T and the type strains of the genus Flavisolibacter ranged from 94.6 to 94.9 %. Strain LCS9T grew at 10-37 degrees C (optimum, 25 degrees C) and at pH 6.0-10.0 (optimum, pH 7); was positive for catalase and oxidase; and negative for nitrate reduction and production of indole. Cells showed pigment absorbance peaks at 451 and 479 nm, and had 0.03 % survival following exposure to 3 kGy gamma radiation. Strain LCS9T had the following chemotaxonomic characteristics: the major quinone was menaquinone-7 (MK-7); the major fatty acids were iso-C15 : 0 and iso-C17 : 0 3-OH; polar lipids included phosphoatidylethanolamine, an unidentified aminophospholipid, unidentified aminolipidsand unidentified lipids. The DNA G+C content was 39.4 mol%. Based on polyphasic analysis, the type strain LCS9T (=KCTC 42070T=JCM 19972T) represents a novel species for which the name Flavisolibacter tropicus sp. nov. is proposed. Radiation resistance in the genus Flavisolibacter has not been reported to date, and so this is the first report of low-level radiation resistance of a member of the genus.
ESTHER : Lee_2016_Int.J.Syst.Evol.Microbiol_66_3413
PubMedSearch : Lee_2016_Int.J.Syst.Evol.Microbiol_66_3413
PubMedID: 27259556
Gene_locus related to this paper: 9bact-a0a172try1

Title : Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex - Jeong_2016_Yonsei.Med.J_57_165
Author(s) : Jeong da U , Oh JH , Lee JE , Lee J , Cho ZH , Chang JW , Chang WS
Ref : Yonsei Med J , 57 :165 , 2016
Abstract : PURPOSE: Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. MATERIALS AND
METHODS: We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by (1)(8)F-2-fluoro-2-deoxyglucose positron emission tomography.
RESULTS: During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. CONCLUSION: Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.
ESTHER : Jeong_2016_Yonsei.Med.J_57_165
PubMedSearch : Jeong_2016_Yonsei.Med.J_57_165
PubMedID: 26632397

Title : Odanacatib, a selective cathepsin K inhibitor, demonstrates comparable pharmacodynamics and pharmacokinetics in older men and postmenopausal women - Anderson_2014_J.Clin.Endocrinol.Metab_99_552
Author(s) : Anderson MS , Gendrano IN , Liu C , Jeffers S , Mahon C , Mehta A , Mostoller K , Zajic S , Morris D , Lee J , Stoch SA
Ref : J Clinical Endocrinology Metab , 99 :552 , 2014
Abstract : BACKGROUND: Odanacatib is a cathepsin K inhibitor in development for the treatment of osteoporosis. Evaluation of therapies to ensure that treatment effects are relevant regardless of sex is clinically important.
METHODS: In this double-blind, randomized controlled trial, older men (aged 50-75 years) and postmenopausal women (aged 45-75 years) were given odanacatib 50 mg once weekly or placebo for 4 weeks. Pharmacodynamic (PD) evaluation measured weighted average inhibition (WAI) of urine amino-terminal cross-linked telopeptide of type I collagen/creatinine (uNTx/Cr) after odanacatib administration. Pharmacokinetic (PK) parameter data were collected, and an analysis of sex as a factor in the PK/PD relationship was conducted. Adverse events were monitored. The hypotheses were that WAI of uNTx/Cr would be >40% (including >40% for the lower limit of the 90% confidence intervals [CIs]) for older men and postmenopausal women, that there would be no important differences in area under the curve from 0 to 168 hours (AUC0-168 h) between men and women, and that odanacatib would be safe and well tolerated.
RESULTS: A total of 44 subjects (32 men and 12 women) were randomized. The least squares mean WAI (uNTx/Cr) at week 4 was 42.8% (90% CI, 35.5%-49.3%) for men and 42.7% (90% CI, 30.3%-52.9%) for women; mean values were >40%, but lower bounds were <40% as prespecified in the primary hypothesis. The differences among men and women in PD parameters were not meaningful (0.1; 90% CI, -14.7 to 14.9). PK parameters for both groups were comparable (geometric mean ratio of AUC0-168 h, 0.90; 90% CI, 0.75-1.07). A PK/PD analysis found that the EC50 and maximum fractional inhibition were similar in male and female subjects. There were no notable or serious adverse events in this study.
CONCLUSIONS: Although the primary hypothesis was not met, there were no clinically meaningful differences in PD, PK, or PK/PD parameters between older men and postmenopausal women, supporting further research on odanacatib (50 mg once weekly) as a treatment for male osteoporosis. Odanacatib was generally well tolerated.
ESTHER : Anderson_2014_J.Clin.Endocrinol.Metab_99_552
PubMedSearch : Anderson_2014_J.Clin.Endocrinol.Metab_99_552
PubMedID: 24276460

Title : Cognitive Enhancing and Neuroprotective Effect of the Embryo of the Nelumbo nucifera Seed - Kim_2014_Evid.Based.Complement.Alternat.Med_2014_869831
Author(s) : Kim ES , Weon JB , Yun BR , Lee J , Eom MR , Oh KH , Ma CJ
Ref : Evid Based Complement Alternat Med , 2014 :869831 , 2014
Abstract : The aim of the present study was to evaluate the effect of ENS on cognitive impairment induced by scopolamine and its potential neuroprotective effect against glutamate-induced cytotoxicity in HT22 cell and to investigate the underlying mechanisms. ENS (3, 10, 30, and 100 mg/kg), scopolamine (1 mg/kg), and donepezil (1 mg/kg) were administered to mice during a test period. Scopolamine impaired memory and learning in a water maze test and a passive avoidance test. The neuroprotective effect of ENS (10 and 100 mug/mL) was investigated on glutamate-induced cell death in HT22 cells by MTT assay. We investigated acetylcholinesterase inhibition in hippocampus and antioxidant activity, ROS levels, and Ca(2+) influx in HT22 cells to elucidate the potential mechanisms of ENS. We found that ENS significantly ameliorated scopolamine-induced memory impairment and inhibited AChE activity in hippocampus. In vitro, ENS showed potent neuroprotective effects against glutamate-induced neurotoxicity in the HT22 cell. In addition, ENS induced a decrease in ROS production and intercellular Ca(2+) accumulation and showed DPPH radical and H2O2 scavenging activity. In conclusion, ENS showed both a memory improving effect and a neuroprotective effect. Our results indicate that ENS may be of use in the treatment and prevention of neurodegenerative disorders.
ESTHER : Kim_2014_Evid.Based.Complement.Alternat.Med_2014_869831
PubMedSearch : Kim_2014_Evid.Based.Complement.Alternat.Med_2014_869831
PubMedID: 25610484

Title : Alteration in cellular acetylcholine influences dauer formation in Caenorhabditis elegans - Lee_2014_BMB.Rep_47_80
Author(s) : Lee J , Kim KY , Paik YK
Ref : BMB Rep , 47 :80 , 2014
Abstract : Altered acetylcholine (Ach) homeostasis is associated with loss of viability in flies, developmental defects in mice, and cognitive deficits in human. Here, we assessed the importance of Ach in Caenorhabditis elegans development, focusing on the role of Ach during dauer formation. We found that dauer formation was disturbed in choline acetyltransferase (cha-1) and acetylcholinesterase (ace) mutants defective in Ach biosynthesis and degradation, respectively. When examined the potential role of G-proteins in dauer formation, goa-1 and egl-30 mutant worms, expressing mutated versions of mammalian Go and Gq homolog, respectively, showed some abnormalities in dauer formation. Using quantitative mass spectrometry, we also found that dauer larvae had lower Ach content than did reproductively grown larvae. In addition, a proteomic analysis of acetylcholinesterase mutant worms, which have excessive levels of Ach, showed differential expression of metabolic genes. Collectively, these results indicate that alterations in Ach release may influence dauer formation in C. elegans. [BMB Reports 2014; 47(2): 080-085].
ESTHER : Lee_2014_BMB.Rep_47_80
PubMedSearch : Lee_2014_BMB.Rep_47_80
PubMedID: 24219868

Title : Cognitive-Enhancing Effect of Steamed and Fermented Codonopsis lanceolata: A Behavioral and Biochemical Study - Weon_2014_Evid.Based.Complement.Alternat.Med_2014_319436
Author(s) : Weon JB , Yun BR , Lee J , Eom MR , Ko HJ , Lee HY , Park DS , Chung HC , Chung JY , Ma CJ
Ref : Evid Based Complement Alternat Med , 2014 :319436 , 2014
Abstract : Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory impairment. Codonopsis lanceolata (C. lanceolata) has been employed clinically for lung inflammatory diseases such as asthma, tonsillitis, and pharyngitis. The present study was undertaken to evaluate the effect of fermented C. lanceolata (300, 500, and 800 mg/kg) on learning and memory impairment induced by scopolamine by using the Morris water maze and passive avoidance tests. To elucidate possible mechanism of cognitive-enhancing activity, we measured acetylcholinesterase (AchE) activity, brain-derived neurotrophic factor (BDNF), and cyclic AMP response element-binding protein (CREB) expression in the brain of mice. Administration of fermented C. lanceolata (800 mg/kg) led to reduced scopolamine-induced memory impairment in the Morris water maze and passive avoidance tests. Accordingly, the administration of fermented C. lanceolata inhibited AchE activity. Interestingly, the level of CREB phosphorylation and BDNF expression in hippocampal tissue of scopolamine-treated mice was significantly increased by the administration of fermented C. lanceolata. These results indicate that fermented C. lanceolata can ameliorate scopolamine-induced memory deficits in mouse and may be an alternative agent for the treatment of AD.
ESTHER : Weon_2014_Evid.Based.Complement.Alternat.Med_2014_319436
PubMedSearch : Weon_2014_Evid.Based.Complement.Alternat.Med_2014_319436
PubMedID: 25031604

Title : Postsynaptic actin regulates active zone spacing and glutamate receptor apposition at the Drosophila neuromuscular junction - Blunk_2014_Mol.Cell.Neurosci_61_241
Author(s) : Blunk AD , Akbergenova Y , Cho RW , Lee J , Walldorf U , Xu K , Zhong G , Zhuang X , Littleton JT
Ref : Molecular & Cellular Neurosciences , 61 :241 , 2014
Abstract : Synaptic communication requires precise alignment of presynaptic active zones with postsynaptic receptors to enable rapid and efficient neurotransmitter release. How transsynaptic signaling between connected partners organizes this synaptic apparatus is poorly understood. To further define the mechanisms that mediate synapse assembly, we carried out a chemical mutagenesis screen in Drosophila to identify mutants defective in the alignment of active zones with postsynaptic glutamate receptor fields at the larval neuromuscular junction. From this screen we identified a mutation in Actin 57B that disrupted synaptic morphology and presynaptic active zone organization. Actin 57B, one of six actin genes in Drosophila, is expressed within the postsynaptic bodywall musculature. The isolated allele, act(E84K), harbors a point mutation in a highly conserved glutamate residue in subdomain 1 that binds members of the Calponin Homology protein family, including spectrin. Homozygous act(E84K) mutants show impaired alignment and spacing of presynaptic active zones, as well as defects in apposition of active zones to postsynaptic glutamate receptor fields. act(E84K) mutants have disrupted postsynaptic actin networks surrounding presynaptic boutons, with the formation of aberrant actin swirls previously observed following disruption of postsynaptic spectrin. Consistent with a disruption of the postsynaptic actin cytoskeleton, spectrin, adducin and the PSD-95 homolog Discs-Large are all mislocalized in act(E84K) mutants. Genetic interactions between act(E84K) and neurexin mutants suggest that the postsynaptic actin cytoskeleton may function together with the Neurexin-Neuroligin transsynaptic signaling complex to mediate normal synapse development and presynaptic active zone organization.
ESTHER : Blunk_2014_Mol.Cell.Neurosci_61_241
PubMedSearch : Blunk_2014_Mol.Cell.Neurosci_61_241
PubMedID: 25066865

Title : A stress-responsive Escherichia coli protein, CysQ is a highly effective solubility enhancer for aggregation-prone heterologous proteins - Lee_2014_Protein.Expr.Purif_101C_91
Author(s) : Lee JH , Lee JY , Song JA , Han KY , Lee DS , Lee J
Ref : Protein Expr Purif , 101C :91 , 2014
Abstract : When used as an N-terminal fusion expression partner, the Escherichia coli stress-responsive protein, CysQ dramatically increased the cytoplasmic solubility of various aggregation-prone heterologous proteins: Pseudomonas putida cutinase (CUT), human granulocyte colony-stimulating factor (hG-CSF), human ferritin light chain (hFTN-L), arginine deiminase (ADI), human interleukin-2 (IL2), human activation induced cytidine deaminase (AID), and deletion mutant of human glutamate decarboxylase (GAD448-585). As compared with well-known fusion tags such as glutathione-S-transferase (GST) and maltose-binding protein (MBP), the performance of CysQ as solubility enhancer was evidently better than GST and was similar to or better than MBP for the seven heterologous proteins above. This is likely due to the intrinsic ability of CysQ to form its native conformation, probably promoting the binding of molecular chaperones during the folding of CysQ-fusion protein. When used as a substrate, p-nitrophenyl butyrate (PNB) was successfully hydrolyzed to p-nitrophenol by CysQ-CUT fusion mutant. Even after CysQ was removed, the solubility of hFTN-L and hG-CSF, the secondary structure of hG-CSF, and self-assembly activity of hFTN-L were successfully maintained. Conclusively, it seems that CysQ is a highly effective solubility enhancer and fusion expression partner for the production of a variety of bio-active recombinant proteins.
ESTHER : Lee_2014_Protein.Expr.Purif_101C_91
PubMedSearch : Lee_2014_Protein.Expr.Purif_101C_91
PubMedID: 24945073

Title : Anithiactins A-C, modified 2-phenylthiazoles from a mudflat-derived Streptomyces sp - Kim_2014_J.Nat.Prod_77_2716
Author(s) : Kim H , Yang I , Patil RS , Kang S , Lee J , Choi H , Kim MS , Nam SJ , Kang H
Ref : Journal of Natural Products , 77 :2716 , 2014
Abstract : Intensive investigation of the chemical components of a Streptomyces sp. isolated from mudflat sediments collected on the southern coast of the Korean peninsula led to the isolation of three new compounds, anithiactins A-C (1-3). The chemical structures of anithiactins A and C were determined by interpretation of NMR data analyses, while the chemical structure of anithiactin B was established from a combination of NMR spectroscopic and crystallographic data analyses. The structure of anithiactin A was also confirmed by total synthesis. These three anithiactins displayed moderate acetylcholinesterase inhibitory activity with no significant cytotoxicity.
ESTHER : Kim_2014_J.Nat.Prod_77_2716
PubMedSearch : Kim_2014_J.Nat.Prod_77_2716
PubMedID: 25455147

Title : Neuroprotective effect of the fermented Gumiganghwal-tang - Yun_2014_J.Biosci.Bioeng_118_235
Author(s) : Yun BR , Weon JB , Lee J , Eom MR , Ma CJ
Ref : J Biosci Bioeng , 118 :235 , 2014
Abstract : Gumiganghwal-tang (GT) is a traditional herbal prescription widely used to treat inflammatory diseases in Asia. In this study, we evaluated neuroprotective effect and acetylcholinesterase (AChE) inhibitory activity of GT and compared with fermented GT (FGT). In order to better understand the neuroprotective mechanism, intracellular reactive oxygen species (ROS) production was investigated and high-performance liquid chromatography with diode-array detection (HPLC-DAD) analysis of contents of GT and FGT were conducted. As a result, FGT showed more potent protective effect against glutamate-induced HT22 cell death than GT and inhibited AChE activity. The neuroprotective effect of FGT is associated with inhibition of ROS production. The HPLC-DAD analytical results indicated that FGT contains higher content of bergapten and atractylenolide III than that of GT. In conclusion, FGT have neuroprotective effect and AChE inhibition, and may be useful source for treatment of neurodegenerative disease.
ESTHER : Yun_2014_J.Biosci.Bioeng_118_235
PubMedSearch : Yun_2014_J.Biosci.Bioeng_118_235
PubMedID: 24503423

Title : Subchronic treatment of donepezil rescues impaired social, hyperactive, and stereotypic behavior in valproic Acid-induced animal model of autism - Kim_2014_PLoS.One_9_e104927
Author(s) : Kim JW , Seung H , Kwon KJ , Ko MJ , Lee EJ , Oh HA , Choi CS , Kim KC , Gonzales EL , You JS , Choi DH , Lee J , Han SH , Yang SM , Cheong JH , Shin CY , Bahn GH
Ref : PLoS ONE , 9 :e104927 , 2014
Abstract : Autism spectrum disorder (ASD) is a group of pervasive developmental disorders with core symptoms such as sociability deficit, language impairment, and repetitive/restricted behaviors. Although worldwide prevalence of ASD has been increased continuously, therapeutic agents to ameliorate the core symptoms especially social deficits, are very limited. In this study, we investigated therapeutic potential of donepezil for ASD using valproic acid-induced autistic animal model (VPA animal model). We found that prenatal exposure of valproic acid (VPA) induced dysregulation of cholinergic neuronal development, most notably the up-regulation of acetylcholinesterase (AChE) in the prefrontal cortex of affected rat and mouse offspring. Similarly, differentiating cortical neural progenitor cell in culture treated with VPA showed increased expression of AChE in vitro. Chromatin precipitation experiments revealed that acetylation of histone H3 bound to AChE promoter region was increased by VPA. In addition, other histone deacetyalse inhibitors (HDACIs) such as trichostatin A and sodium butyrate also increased the expression of AChE in differentiating neural progenitor cells suggesting the essential role of HDACIs in the regulation of AChE expression. For behavioral analysis, we injected PBS or donepezil (0.3 mg/kg) intraperitoneally to control and VPA mice once daily from postnatal day 14 all throughout the experiment. Subchronic treatment of donepezil improved sociability and prevented repetitive behavior and hyperactivity of VPA-treated mice offspring. Taken together, these results provide evidence that dysregulation of ACh system represented by the up-regulation of AChE may serve as an effective pharmacological therapeutic target against autistic behaviors in VPA animal model of ASD, which should be subjected for further investigation to verify the clinical relevance.
ESTHER : Kim_2014_PLoS.One_9_e104927
PubMedSearch : Kim_2014_PLoS.One_9_e104927
PubMedID: 25133713

Title : Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects - Yore_2014_Cell_159_318
Author(s) : Yore MM , Syed I , Moraes-Vieira PM , Zhang T , Herman MA , Homan EA , Patel RT , Lee J , Chen S , Peroni OD , Dhaneshwar AS , Hammarstedt A , Smith U , McGraw TE , Saghatelian A , Kahn BB
Ref : Cell , 159 :318 , 2014
Abstract : Increased adipose tissue lipogenesis is associated with enhanced insulin sensitivity. Mice overexpressing the Glut4 glucose transporter in adipocytes have elevated lipogenesis and increased glucose tolerance despite being obese with elevated circulating fatty acids. Lipidomic analysis of adipose tissue revealed the existence of branched fatty acid esters of hydroxy fatty acids (FAHFAs) that were elevated 16- to 18-fold in these mice. FAHFA isomers differ by the branched ester position on the hydroxy fatty acid (e.g., palmitic-acid-9-hydroxy-stearic-acid, 9-PAHSA). PAHSAs are synthesized in vivo and regulated by fasting and high-fat feeding. PAHSA levels correlate highly with insulin sensitivity and are reduced in adipose tissue and serum of insulin-resistant humans. PAHSA administration in mice lowers ambient glycemia and improves glucose tolerance while stimulating GLP-1 and insulin secretion. PAHSAs also reduce adipose tissue inflammation. In adipocytes, PAHSAs signal through GPR120 to enhance insulin-stimulated glucose uptake. Thus, FAHFAs are endogenous lipids with the potential to treat type 2 diabetes.
ESTHER : Yore_2014_Cell_159_318
PubMedSearch : Yore_2014_Cell_159_318
PubMedID: 25303528

Title : Genome sequence of mungbean and insights into evolution within Vigna species - Kang_2014_Nat.Commun_5_5443
Author(s) : Kang YJ , Kim SK , Kim MY , Lestari P , Kim KH , Ha BK , Jun TH , Hwang WJ , Lee T , Lee J , Shim S , Yoon MY , Jang YE , Han KS , Taeprayoon P , Yoon N , Somta P , Tanya P , Kim KS , Gwag JG , Moon JK , Lee YH , Park BS , Bombarely A , Doyle JJ , Jackson SA , Schafleitner R , Srinives P , Varshney RK , Lee SH
Ref : Nat Commun , 5 :5443 , 2014
Abstract : Mungbean (Vigna radiata) is a fast-growing, warm-season legume crop that is primarily cultivated in developing countries of Asia. Here we construct a draft genome sequence of mungbean to facilitate genome research into the subgenus Ceratotropis, which includes several important dietary legumes in Asia, and to enable a better understanding of the evolution of leguminous species. Based on the de novo assembly of additional wild mungbean species, the divergence of what was eventually domesticated and the sampled wild mungbean species appears to have predated domestication. Moreover, the de novo assembly of a tetraploid Vigna species (V. reflexo-pilosa var. glabra) provides genomic evidence of a recent allopolyploid event. The species tree is constructed using de novo RNA-seq assemblies of 22 accessions of 18 Vigna species and protein sets of Glycine max. The present assembly of V. radiata var. radiata will facilitate genome research and accelerate molecular breeding of the subgenus Ceratotropis.
ESTHER : Kang_2014_Nat.Commun_5_5443
PubMedSearch : Kang_2014_Nat.Commun_5_5443
PubMedID: 25384727
Gene_locus related to this paper: vigrr-a0a1s3ue92 , vigrr-a0a1s3v914 , vigrr-a0a1s3tyf7 , phaan-a0a0s3s998 , vigrr-a0a1s3ux10 , vigrr-a0a1s3ubl0 , vigrr-a0a1s3u036 , vigrr-a0a1s3tul4 , phaan-a0a0l9ujf5 , vigrr-a0a1s3tqd3 , vigrr-a0a1s3udb1 , vigrr-a0a1s3ukc0 , vigrr-a0a1s3ur22 , vigrr-a0a3q0ez52 , vigrr-a0a1s3twy0

Title : Lipid droplet protein LID-1 mediates ATGL-1-dependent lipolysis during fasting in Caenorhabditis elegans - Lee_2014_Mol.Cell.Biol_34_4165
Author(s) : Lee JH , Kong J , Jang JY , Han JS , Ji Y , Lee J , Kim JB
Ref : Molecular & Cellular Biology , 34 :4165 , 2014
Abstract : Lipolysis is a delicate process involving complex signaling cascades and sequential enzymatic activations. In Caenorhabditis elegans, fasting induces various physiological changes, including a dramatic decrease in lipid contents through lipolysis. Interestingly, C. elegans lacks perilipin family genes which play a crucial role in the regulation of lipid homeostasis in other species. Here, we demonstrate that in the intestinal cells of C. elegans, a newly identified protein, lipid droplet protein 1 (C25A1.12; LID-1), modulates lipolysis by binding to adipose triglyceride lipase 1 (C05D11.7; ATGL-1) during nutritional deprivation. In fasted worms, lipid droplets were decreased in intestinal cells, whereas suppression of ATGL-1 via RNA interference (RNAi) resulted in retention of stored lipid droplets. Overexpression of ATGL-1 markedly decreased lipid droplets, whereas depletion of LID-1 via RNAi prevented the effect of overexpressed ATGL-1 on lipolysis. In adult worms, short-term fasting increased cyclic AMP (cAMP) levels, which activated protein kinase A (PKA) to stimulate lipolysis via ATGL-1 and LID-1. Moreover, ATGL-1 protein stability and LID-1 binding were augmented by PKA activation, eventually leading to increased lipolysis. These data suggest the importance of the concerted action of lipase and lipid droplet protein in the response to fasting signals via PKA to maintain lipid homeostasis.
ESTHER : Lee_2014_Mol.Cell.Biol_34_4165
PubMedSearch : Lee_2014_Mol.Cell.Biol_34_4165
PubMedID: 25202121

Title : Lipase-catalyzed enantioselective synthesis of (R,R)-lactide from alkyl lactate to produce PDLA (poly D-lactic acid) and stereocomplex PLA (poly lactic acid) - Jeon_2013_J.Biotechnol_168_201
Author(s) : Jeon BW , Lee J , Kim HS , Cho DH , Lee H , Chang R , Kim YH
Ref : J Biotechnol , 168 :201 , 2013
Abstract : R-lactide, a pivotal monomer for the production of poly (D-lactic acid) (PDLA) or stereocomplex poly (lactic acid) (PLA) was synthesized from alkyl (R)-lactate through a lipase-catalyzed reaction without racemization. From among several types of lipase, only lipase B from Candida antarctica (Novozym 435; CAL-B) was effective in the reaction that synthesized (R,R)-lactide. Enantiopure (R,R)-lactide, which consisted of over 99% enantiomeric excess, was synthesized from methyl (R)-lactate through CAL-B catalysis. Removal of the methanol by-product was critical to obtain a high level of lactide conversion. The (R,R)-lactide yield was 56% in a reaction containing 100 mg of Novozym 435, 10 mM methyl (R)-lactate and 1500 mg of molecular sieve 5A in methyl tert-butyl ether (MTBE). The important monomer (R,R)-lactide that is required for the production of the widely recognized bio-plastic PDLA and the PLA stereocomplex can be obtained using this novel synthetic method.
ESTHER : Jeon_2013_J.Biotechnol_168_201
PubMedSearch : Jeon_2013_J.Biotechnol_168_201
PubMedID: 23845270
Gene_locus related to this paper: canar-LipB

Title : Association of LIPC and advanced age-related macular degeneration - Lee_2013_Eye.(Lond)_27_265
Author(s) : Lee J , Zeng J , Hughes G , Chen Y , Grob S , Zhao L , Lee C , Krupa M , Quach J , Luo J , Wei X , Zhang X , Zhu J , Duan Y , Ferreyra H , Goldbaum M , Haw W , Shaw PX , Tang L , Zhang K
Ref : Eye (Lond) , 27 :265 , 2013
Abstract : PURPOSE: To determine whether there is an association between hepatic lipase (LIPC) and age-related macular degeneration (AMD) in two independent Caucasian cohorts.
METHODS: A discovery cohort of 1626 patients with advanced AMD and 859 normal controls and a replication cohort of 2159 cases and 1150 controls were genotyped for two single-nucleotide polymorphisms (SNPs) in the promoter region of LIPC. The associations between the SNPs and AMD were examined by chi(2) tests.
RESULTS: In the discovery cohort, rs493258 and rs10468017 were both associated with advanced AMD (P=9.63E-3 and P=0.048, respectively). The association was corroborated in the replication cohort (P=4.48E-03 for rs493258 and P=0.015 for rs10468017). Combined analysis resulted in even more significant associations (P=1.21E-04 for rs493258 and P=1.67E-03 for rs10468017). CONCLUSION: The LIPC promoter variants rs493258 and rs10468017 were associated with advanced AMD in two independent Caucasian populations, confirming that LIPC polymorphisms may be a genetic risk factor for AMD in the Caucasian population.
ESTHER : Lee_2013_Eye.(Lond)_27_265
PubMedSearch : Lee_2013_Eye.(Lond)_27_265
PubMedID: 23348725

Title : Dominant protein interactions that influence the pathogenesis of conformational diseases - Wright_2013_J.Clin.Invest_123_3124
Author(s) : Wright J , Wang X , Haataja L , Kellogg AP , Lee J , Liu M , Arvan P
Ref : J Clinical Investigation , 123 :3124 , 2013
Abstract : Misfolding of exportable proteins can trigger endocrinopathies. For example, misfolding of insulin can result in autosomal dominant mutant INS gene-induced diabetes of youth, and misfolding of thyroglobulin can result in autosomal recessive congenital hypothyroidism with deficient thyroglobulin. Both proinsulin and thyroglobulin normally form homodimers; the mutant versions of both proteins misfold in the ER, triggering ER stress, and, in both cases, heterozygosity creates potential for cross-dimerization between mutant and WT gene products. Here, we investigated these two ER-retained mutant secretory proteins and the selectivity of their interactions with their respective WT counterparts. In both cases and in animal models of these diseases, we found that conditions favoring an increased stoichiometry of mutant gene product dominantly inhibited export of the WT partner, while increased relative level of the WT gene product helped to rescue secretion of the mutant partner. Surprisingly, the bidirectional consequences of secretory blockade and rescue occur simultaneously in the same cells. Thus, in the context of heterozygosity, expression level and stability of WT subunits may be a critical factor influencing the effect of protein misfolding on clinical phenotype. These results offer new insight into dominant as well as recessive inheritance of conformational diseases and offer opportunities for the development of new therapies.
ESTHER : Wright_2013_J.Clin.Invest_123_3124
PubMedSearch : Wright_2013_J.Clin.Invest_123_3124
PubMedID: 23722904

Title : Complete Genome Sequence of Raoultella ornithinolytica Strain B6, a 2,3-Butanediol-Producing Bacterium Isolated from Oil-Contaminated Soil - Shin_2013_Genome.Announc_1_e00395
Author(s) : Shin SH , Um Y , Beak JH , Kim S , Lee S , Oh MK , Kim YR , Lee J , Yang KS
Ref : Genome Announc , 1 : , 2013
Abstract : Here we report the full genome sequence of Raoultella ornithinolytica strain B6, a Gram-negative aerobic bacillus belonging to the family Enterobacteriaceae. This 2,3-butanediol-producing bacterium was isolated from oil-contaminated soil on Backwoon Mountain in South Korea. Strain B6 contains 5,398,151 bp with 4,909 protein-coding genes, 104 structural RNAs, and 55.88% G+C content.
ESTHER : Shin_2013_Genome.Announc_1_e00395
PubMedSearch : Shin_2013_Genome.Announc_1_e00395
PubMedID: 23814034
Gene_locus related to this paper: raoor-a0a038cvm6 , kleox-h3msf7 , raoor-m9w187 , raopl-a0a085if40

Title : Mixed-effect circadian rhythm model for human erythrocyte acetylcholinesterase activity--application to the proof of concept of cholinesterase inhibition by acorn extract in healthy subjects with galantamine as positive control - Han_2012_Eur.J.Clin.Pharmacol_68_599
Author(s) : Han S , Lee J , Jeon S , Hong T , Yim DS
Ref : European Journal of Clinical Pharmacology , 68 :599 , 2012
Abstract : PURPOSE: The aim of this study was to develop a non-linear mixed effect circadian rhythm model of acetylcholinesterase (AChE) activity variation and to evaluate the inhibitory effect of acorn extract (2 g) and galantamine (16 mg), used as positive control, on human AChE in red blood cells (RBC). METHODS: This was an open-label, randomized, three-way crossover study involving 12 healthy subjects who received one of the treatments in each study period: no treatment, acorn extract, and galantamine. RBC AChE activity was measured in peripheral blood samples collected at 0 (pre-dose), 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16 and 24 h post-dose administration. Non-linear mixed effect modeling was performed using NONMEM (ver. 7.0). RESULTS: The circadian variation of AChE activity was best described using two mixed effect cosine functions, with periods of 24 and 12 h, respectively. When the inhibitory effect terms were added, the model was significantly improved for both acorn extract and galantamine. In terms of the effect, a 2-g single dose of acorn extract showed AChE inhibition (about 5%) similar to that of a 16-mg single dose of galantamine, in the first 24 h after administration. CONCLUSIONS: Based on the very pronounced inter- and intra-day variation in AChE activity in RBC, we conclude that the model-based approach is essential for the proof of concept and quantitation of AChE inhibition in human subjects.
ESTHER : Han_2012_Eur.J.Clin.Pharmacol_68_599
PubMedSearch : Han_2012_Eur.J.Clin.Pharmacol_68_599
PubMedID: 22207414

Title : Inhaled essential oil from Chamaecyparis obtuse ameliorates the impairments of cognitive function induced by injection of beta-amyloid in rats - Bae_2012_Pharm.Biol_50_900
Author(s) : Bae D , Seol H , Yoon HG , Na JR , Oh K , Choi CY , Lee DW , Jun W , Youl Lee K , Lee J , Hwang K , Lee YH , Kim S
Ref : Pharm Biol , 50 :900 , 2012
Abstract : CONTEXT: Chamaecyparis obtusa Sieb. & Zucc., Endlicher (Cupressaceae) forest bathing or aromatherapy has been shown in various studies to have biological functions such as anticancer, antiallergies, antiinflammatory, and antioxidant activity. However, no reports exist on the pharmacological or biological activities of the essential oil of C. obtusa (EOCO) or its effects on central nervous system. OBJECTIVE: The aggregation and formation of beta-amyloid peptides (Abeta) into fibrils are central events in the pathogenesis of Alzheimer's disease (AD), and overproduction and aggregation of Abeta into oligomers have been known to trigger neurotoxicity. In this study, we investigated the effects of inhaled EOCO on cognitive function and neuronal apoptosis in rats intrahippocampally injected with Abeta. MATERIALS AND METHODS: To model AD, 4 mug of aggregated Abeta was injected into the hippocampus. To test the effects of EOCO, behavioral performance in the Morris water maze was tested 4 days after injection. After behavioral testing, brain sections were prepared for TTC staining and TUNEL assay. RESULTS: Inhaled EOCO protected spatial learning and memory from the impairments induced by Abeta(1-40) injection. In addition, the behavioral deficits accompanying Abeta(1-40)-induced AD were attenuated by inhalation of EOCO. Furthermore, acetylcholinesterase (AChE) activity and neuronal apoptosis were significantly inhibited in rats treated with Abeta(1-40) and EOCO compared to rats treated only with Abeta(1-40). DISCUSSION AND CONCLUSION: EOCO suppressed both AD-related neuronal cell apoptosis and AD-related dysfunction of the memory system. Thus, the results of this study support EOCO as a candidate drug for the treatment of AD.
ESTHER : Bae_2012_Pharm.Biol_50_900
PubMedSearch : Bae_2012_Pharm.Biol_50_900
PubMedID: 22468783

Title : Complete genome sequence of Enterobacter aerogenes KCTC 2190 - Shin_2012_J.Bacteriol_194_2373
Author(s) : Shin SH , Kim S , Kim JY , Lee S , Um Y , Oh MK , Kim YR , Lee J , Yang KS
Ref : Journal of Bacteriology , 194 :2373 , 2012
Abstract : This is the first complete genome sequence of the Enterobacter aerogenes species. Here we present the genome sequence of E. aerogenes KCTC 2190, which contains 5,280,350 bp with a G + C content of 54.8 mol%, 4,912 protein-coding genes, and 109 structural RNAs.
ESTHER : Shin_2012_J.Bacteriol_194_2373
PubMedSearch : Shin_2012_J.Bacteriol_194_2373
PubMedID: 22493190
Gene_locus related to this paper: entcl-a0a157v5g4

Title : Sarcospan-dependent Akt activation is required for utrophin expression and muscle regeneration - Marshall_2012_J.Cell.Biol_197_1009
Author(s) : Marshall JL , Holmberg J , Chou E , Ocampo AC , Oh J , Lee J , Peter AK , Martin PT , Crosbie-Watson RH
Ref : Journal of Cell Biology , 197 :1009 , 2012
Abstract : Utrophin is normally confined to the neuromuscular junction (NMJ) in adult muscle and partially compensates for the loss of dystrophin in mdx mice. We show that Akt signaling and utrophin levels were diminished in sarcospan (SSPN)-deficient muscle. By creating several transgenic and knockout mice, we demonstrate that SSPN regulates Akt signaling to control utrophin expression. SSPN determined alpha-dystroglycan (alpha-DG) glycosylation by affecting levels of the NMJ-specific glycosyltransferase Galgt2. After cardiotoxin (CTX) injury, regenerating myofibers express utrophin and Galgt2-modified alpha-DG around the sarcolemma. SSPN-null mice displayed delayed differentiation after CTX injury caused by loss of utrophin and Akt signaling. Treatment of SSPN-null mice with viral Akt increased utrophin and restored muscle repair after injury, revealing an important role for the SSPN-Akt-utrophin signaling axis in regeneration. SSPN improved cell surface expression of utrophin by increasing transportation of utrophin and DG from endoplasmic reticulum/Golgi membranes. Our experiments reveal functions of utrophin in regeneration and new pathways that regulate utrophin expression at the cell surface.
ESTHER : Marshall_2012_J.Cell.Biol_197_1009
PubMedSearch : Marshall_2012_J.Cell.Biol_197_1009
PubMedID: 22734004

Title : Complete genome sequence of the 2,3-butanediol-producing Klebsiella pneumoniae strain KCTC 2242 - Shin_2012_J.Bacteriol_194_2736
Author(s) : Shin SH , Kim S , Kim JY , Lee S , Um Y , Oh MK , Kim YR , Lee J , Yang KS
Ref : Journal of Bacteriology , 194 :2736 , 2012
Abstract : Here we report the full genome sequence of Klebsiella pneumoniae KCTC 2242,consisting of a 5.26-Mb chromosome (57.6% GC%; 5,035 genes [4,923 encoding known proteins, 112 RNA genes]) and a 202-kb plasmid (50.2% GC%; 229 genes [229 encoding known proteins]).
ESTHER : Shin_2012_J.Bacteriol_194_2736
PubMedSearch : Shin_2012_J.Bacteriol_194_2736
PubMedID: 22535926
Gene_locus related to this paper: klep7-menh , klep7-y1077 , klepn-w8uta0

Title : Nicotine and pathological angiogenesis - Lee_2012_Life.Sci_91_1058
Author(s) : Lee J , Cooke JP
Ref : Life Sciences , 91 :1058 , 2012
Abstract : This paper describes the role of endothelial nicotinic acetylcholine receptors (nAChR) in diseases where pathological angiogenesis plays a role. An extensive review of the literature was performed, focusing on studies that investigated the effect of nicotine upon angiogenesis. Nicotine induces pathological angiogenesis at clinically relevant concentrations (i.e. at tissue and plasma concentrations similar to those of a light to moderate smoker). Nicotine promotes endothelial cell migration, proliferation, survival, tube formation and nitric oxide (NO) production in vitro, mimicking the effect of other angiogenic growth factors. These in vitro findings indicate that there may be an angiogenic component to the pathophysiology of major tobacco related diseases such as carcinoma, atherosclerosis, and age-related macular degeneration. Indeed, nicotine stimulates pathological angiogenesis in pre-clinical models of these disorders. Subsequently, it has been demonstrated that nicotine stimulates nAChRs on the endothelium to induce angiogenic processes, that these nAChRs are largely of the alpha7 homomeric type, and that there are synergistic interactions between the nAChRs and angiogenic growth factor receptors at the phosphoproteomic and genomic levels. These findings are of potential clinical relevance, and provide mechanistic insights into tobacco-related disease. Furthermore, these findings may lead to novel therapies for diseases characterized by insufficient or inappropriate angiogenesis.
ESTHER : Lee_2012_Life.Sci_91_1058
PubMedSearch : Lee_2012_Life.Sci_91_1058
PubMedID: 22796717

Title : Ionic-surfactant-coated Burkholderia cepacia lipase as a highly active and enantioselective catalyst for the dynamic kinetic resolution of secondary alcohols -
Author(s) : Kim H , Choi YK , Lee J , Lee E , Park J , Kim MJ
Ref : Angew Chem Int Ed Engl , 50 :10944 , 2011
PubMedID: 21954139

Title : Genetically lowered microsomal epoxide hydrolase activity and tobacco-related cancer in 47,000 individuals - Lee_2011_Cancer.Epidemiol.Biomarkers.Prev_20_1673
Author(s) : Lee J , Dahl M , Nordestgaard BG
Ref : Cancer Epidemiol Biomarkers Prev , 20 :1673 , 2011
Abstract : BACKGROUND: Two functional polymorphisms of the microsomal epoxide hydrolase (mEH) gene (EPHX1), Tyr113His (rs1051740) and His139Arg (rs2234922), have variably been found to influence susceptibility to various cancer forms. We tested whether genetically lowered mEH activity affects risk of developing cancer in the general population.
METHODS: We genotyped 47,089 individuals from the Danish general population for the Tyr113His and His139Arg polymorphisms in the EPHX1 gene and divided them into groups with predicted fast, intermediate, and slow mEH activity. Using Cox proportional hazards models, we calculated HRs for 26 individual cancer diagnoses and for groups of any cancer, tobacco-related cancers, estrogen-related female cancers, and other cancers.
RESULTS: Of the 47,089 individuals, 7,590 experienced a cancer event, and of these, 1,466 were tobacco-related. After multifactorial adjustment, the HRs (95% CI) for tobacco-related cancer were 1.1 (0.8-1.5) and 1.5 (1.1-2.0) in individuals with intermediate and slow mEH activity versus individuals with the fast phenotype (P(trend) = 0.003). The corresponding HRs among ever-smokers were 1.1 (0.8-1.5) and 1.5 (1.1-2.0; P(trend) = 0.003), whereas HRs among never-smokers did not differ from 1.0.
CONCLUSIONS: Our results indicate that genetically lowered mEH activity is associated with increased risk of developing tobacco-related cancer among smokers in the general population; however, additional studies are needed to confirm our findings. IMPACT: To our knowledge, this is the largest study to investigate the association of mEH phenotype and genotype with tobacco-related cancers combined in the general population.
ESTHER : Lee_2011_Cancer.Epidemiol.Biomarkers.Prev_20_1673
PubMedSearch : Lee_2011_Cancer.Epidemiol.Biomarkers.Prev_20_1673
PubMedID: 21653646

Title : Repeat motif-containing regions within thyroglobulin - Lee_2011_J.Biol.Chem_286_26327
Author(s) : Lee J , Arvan P
Ref : Journal of Biological Chemistry , 286 :26327 , 2011
Abstract : Thyroglobulin (precursor for thyroid hormone synthesis) is a large secreted glycoprotein comprising contiguous region I (multiple type-1 repeating units engaging the first approximately 1,191 residues, followed by a approximately 245-residue hinge region), regions II-III (multiple type-2 and 3 repeating units, comprising approximately 720 residues), and the C-terminal cholinesterase-like (ChEL) domain ( approximately 570 residues). A signal peptide attached to ChEL makes an independent secretory protein that binds to I-II-III, stabilizing it and rescuing the secretion of I-II-III that would otherwise be trapped in the endoplasmic reticulum (ER). In this study, we found that a signal peptide attached to regions II-III also makes for an efficient secretory protein that neither demonstrably interacts nor has its secretion enhanced by the presence of secretory ChEL. By contrast, region I, either with or without the hinge region, cannot be secreted on its own and remains in the ER where it is bound to ER chaperones BiP and GRP94. Whereas ChEL can rescue secretion of I-II-III, it can rescue I-II only very weakly, and region I not at all. Yet, ChEL begins to rescue region I in cells that also co-express secretory II-III. The data suggest that conformational maturation of region I is a limiting step in the thyroglobulin maturation process, and this step is facilitated by the presence of both regions II-III and ChEL. Mutations causing hypothyroidism might induce solely local/regional misfolding or may interfere more globally by impeding interactions between regions that are required for thyroglobulin secretion.
ESTHER : Lee_2011_J.Biol.Chem_286_26327
PubMedSearch : Lee_2011_J.Biol.Chem_286_26327
PubMedID: 21636579

Title : EPHX1 polymorphisms, COPD and asthma in 47,000 individuals and in meta-analysis - Lee_2011_Eur.Respir.J_37_18
Author(s) : Lee J , Nordestgaard BG , Dahl M
Ref : Eur Respir J , 37 :18 , 2011
Abstract : We tested the hypothesis that two well-characterised functional polymorphisms of the microsomal epoxide hydrolase gene (EPHX1), T113C and A139G, may influence susceptibility to chronic obstructive pulmonary disease (COPD) and asthma. We genotyped participants from the Copenhagen City Heart Study (n = 10,038) and the Copenhagen General Population Study (n = 37,022) for the T113C and A139G variants in the EPHX1 gene and measured lung function and recorded COPD hospitalisation and asthma and smoking history. Finally, we meta-analysed results from 19 studies including 7,489 COPD cases and 42,970 controls. The OR for spirometry-defined COPD or COPD hospitalisation did not differ from 1.0 for any of the EPHX1 genotypes or phenotypes overall, or in smokers or nonsmokers separately (p-value for trend 0.18-0.91). Likewise, EPHX1 genotypes or phenotypes did not associate with risk of asthma (p-value for trend 0.46-0.98). In meta-analysis, random effects OR for COPD in T113C heterozygotes and homozygotes versus non-carriers were 1.17 (0.99-1.38) and 1.38 (1.09-1.74), respectively. Corresponding values for A139G were 0.93 (0.83-1.05) and 0.89 (0.78-1.02). Our results indicate that genetically reduced microsomal epoxide hydrolase activity is not a major risk factor for COPD or asthma in the Danish population; however, meta-analysis cannot completely exclude a minor effect on COPD risk.
ESTHER : Lee_2011_Eur.Respir.J_37_18
PubMedSearch : Lee_2011_Eur.Respir.J_37_18
PubMedID: 20516053

Title : Adolescent binge drinking alters adult brain neurotransmitter gene expression, behavior, brain regional volumes, and neurochemistry in mice - Coleman_2011_Alcohol.Clin.Exp.Res_35_671
Author(s) : Coleman LG, Jr. , He J , Lee J , Styner M , Crews FT
Ref : Alcohol Clin Exp Res , 35 :671 , 2011
Abstract : BACKGROUND: Binge drinking is common in human adolescents. The adolescent brain is undergoing structural maturation and has a unique sensitivity to alcohol neurotoxicity. Therefore, adolescent binge ethanol may have long-term effects on the adult brain that alter brain structure and behaviors that are relevant to alcohol-use disorders.
METHODS: To determine whether adolescent ethanol (AE) binge drinking alters the adult brain, male C57BL/6 mice were treated with either water or ethanol during adolescence (5 g/kg/d, i.g., postnatal days P28 to P37) and assessed during adulthood (P60 to P88). An array of neurotransmitter-specific genes, behavioral tests (i.e., reversal learning, prepulse inhibition, and open field), and postmortem brain structure using magnetic resonance imaging (MRI) and immunohistochemistry, were employed to assess persistent alterations in adult brain.
RESULTS: At P38, 24 hours after AE binge, many neurotransmitter genes, particularly cholinergic and dopaminergic, were reduced by ethanol treatment. Interestingly, dopamine receptor type 4 mRNA was reduced and confirmed using immunohistochemistry. Normal control maturation (P38 to P88) resulted in decreased neurotransmitter mRNA, e.g., an average decrease of 56%. Following AE treatment, adults showed greater gene expression reductions than controls, averaging 73%. Adult spatial learning assessed in the Morris water maze was not changed by AE treatment, but reversal learning experiments revealed deficits. Assessment of adult brain region volumes using MRI indicated that the olfactory bulb and basal forebrain were smaller in adults following AE. Immunohistochemical analyses found reduced basal forebrain area and fewer basal forebrain cholinergic neurons.
CONCLUSIONS: Adolescent binge ethanol treatment reduces adult neurotransmitter gene expression, particularly cholinergic genes, reduces basal forebrain and olfactory bulb volumes, and causes a reduction in the density of basal forebrain acetylcholine neurons. Loss of cholinergic neurons and forebrain structure could underlie adult reversal learning deficits following adolescent binge drinking.
ESTHER : Coleman_2011_Alcohol.Clin.Exp.Res_35_671
PubMedSearch : Coleman_2011_Alcohol.Clin.Exp.Res_35_671
PubMedID: 21223304

Title : Improvement of enzymatic biodiesel production by controlled substrate feeding using silica gel in solvent free system - Lee_2011_Enzyme.Microb.Technol_49_402
Author(s) : Lee M , Lee J , Lee D , Cho J , Kim S , Park C
Ref : Enzyme Microb Technol , 49 :402 , 2011
Abstract : A silica gel-based substrate feeding system was developed to prevent methanol inhibiting the catalyst during enzymatic biodiesel synthesis. In the system, silica gel swelled upon methanol addition and subsequently released it in a controlled manner to prevent excess methanol affecting the enzyme. Biodiesel was synthesized by the enzymatic transesterification of canola oil with methanol. For this reaction, enzyme loading, methanol/oil molar ratio, silica gel dosage, glycerol content, and methanol feeding method were tested using commercial immobilized enzymes (Novozym 435 and Lipozyme RM IM from Novozymes). The results showed that conversion was highest with controlled substrate feeding rather than direct methanol addition, suggesting that the method developed here can easily prevent enzyme inhibition by limiting methanol concentration to an acceptable level.
ESTHER : Lee_2011_Enzyme.Microb.Technol_49_402
PubMedSearch : Lee_2011_Enzyme.Microb.Technol_49_402
PubMedID: 22112567

Title : New insights into thyroglobulin pathophysiology revealed by the study of a family with congenital goiter - Peteiro-Gonzalez_2010_J.Clin.Endocrinol.Metab_95_3522
Author(s) : Peteiro-Gonzalez D , Lee J , Rodriguez-Fontan J , Castro-Piedras I , Cameselle-Teijeiro J , Beiras A , Bravo SB , Alvarez CV , Hardy DM , Targovnik HM , Arvan P , Lado-Abeal J
Ref : J Clinical Endocrinology Metab , 95 :3522 , 2010
Abstract : CONTEXT: Thyroglobulin (TG) gene mutations cause congenital hypothyroidism (CH) with goiter. A founder effect has been proposed for some frequent mutations. Mutated proteins have a defect in intracellular transport causing intracellular retention with ultrastructural changes that resemble an endoplasmic reticulum storage disease. OBJECTIVE: To reveal new aspects of thyroglobulin pathophysiology through clinical, cellular, molecular, and genetic studies in a family presenting with CH due to TG mutations from Galicia, an iodine-deficient area of Spain. DESIGN: The included clinical evaluation of family members, DNA sequencing for TG gene mutation and haplotyping analysis, ultrastructural analysis of thyroid tissue specimens from affected subjects, analysis of effects of mutations found on TG gene transcription, and in vitro studies of cellular production and secretion of mutated proteins. SETTING: Locations included primary care and university hospitals.
RESULTS: Family members with CH, mental retardation, and goiter were compound heterozygous for c.886C-->T (p.R277X) and g.IVS35+1delG. For c.886C-->T, a founder effect cannot be excluded, and its transcription was hardly detectable. g.IVS35+1delG caused an in-frame deletion in exon 35 and produced a protein that, although synthesized, could not be secreted. Ultrastructural analyses showed morphological changes consistent with an endoplasmic reticulum storage disease. CONCLUSION: The shorter thyroglobulin resulting from the novel g.IVS35+1delG was retained within the endoplasmic reticulum of thyrocytes, and together with p.R227X caused severe hypothyroidism with goiter. p.R277X, the most commonly described TG mutation, is caused by a TG exon-7 highly mutation-prone region, and the possibility that some cases were introduced to South America from Galicia cannot be excluded.
ESTHER : Peteiro-Gonzalez_2010_J.Clin.Endocrinol.Metab_95_3522
PubMedSearch : Peteiro-Gonzalez_2010_J.Clin.Endocrinol.Metab_95_3522
PubMedID: 20410234
Gene_locus related to this paper: human-TG

Title : Cis and trans actions of the cholinesterase-like domain within the thyroglobulin dimer - Wang_2010_J.Biol.Chem_285_17564
Author(s) : Wang X , Lee J , Di Jeso B , Treglia AS , Comoletti D , Dubi N , Taylor P , Arvan P
Ref : Journal of Biological Chemistry , 285 :17564 , 2010
Abstract : Thyroglobulin (Tg, precursor for thyroid hormone synthesis) is a large secreted glycoprotein composed of upstream regions I-II-III, followed by the approximately 570 residue cholinesterase-like (ChEL) domain. ChEL has two identified functions: 1) homodimerization, and 2) binding to I-II-III that facilitates I-II-III oxidative maturation required for intracellular protein transport. Like its homologs in the acetylcholinesterase (AChE) family, ChEL possesses two carboxyl-terminal alpha-helices. We find that a Tg-AChE chimera (swapping AChE in place of ChEL) allows for dimerization with monomeric AChE, proving exposure of the carboxyl-terminal helices within the larger context of Tg. Further, we establish that perturbing trans-helical interaction blocks homodimerization of the Tg ChEL domain. Additionally, ChEL can associate with neuroligins (a related family of cholinesterase-like proteins), demonstrating potential for Tg cross-dimerization between non-identical partners. Indeed, when mutant rdw-Tg (Tg-G2298R, defective for protein secretion) is co-expressed with wild-type Tg, the two proteins cross-dimerize and secretion of rdw-Tg is partially restored. Moreover, we find that AChE and soluble neuroligins also can bind to the upstream Tg regions I-II-III; however, they cannot rescue secretion, because they cannot facilitate oxidative maturation of I-II-III. These data suggest that specific properties of distinct Tg ChEL mutants may result in distinct patterns of Tg monomer folding, cross-dimerization with wild-type Tg, and variable secretion behavior in heterozygous patients.
ESTHER : Wang_2010_J.Biol.Chem_285_17564
PubMedSearch : Wang_2010_J.Biol.Chem_285_17564
PubMedID: 20353937

Title : The potential effects of ethyl acetate fraction from Curcuma longa L. on lipolysis in differentiated 3T3-L1 adipocytes - Lee_2010_J.Med.Food_13_364
Author(s) : Lee J , Yoon HG , Lee YH , Park J , You Y , Kim K , Jang JY , Yang JW , Jun W
Ref : J Med Food , 13 :364 , 2010
Abstract : The effects of the turmeric ethyl acetate fraction (TEF) from the methanolic extract from Curcuma longa L. on lipid metabolism and underlying mechanisms of lipolysis were investigated in 3T3-L1 adipocytes. The intracellular lipid droplets were stained with Oil red O dye and quantified. Compared to the control, lipid accumulation was significantly decreased by 46.6% with treatment by TEF at the concentration of 20 microg/mL. The intracellular triglyceride (TG) level was also reduced by 37.9% at the concentration of 20 microg/mL. To determine the mechanism for TG content reduction, levels of glucose uptake and glycerol release were measured. Incubation of the 3T3-L1 adipocytes with TEF for 4 hours significantly lowered the cellular level of glucose in a dose-dependent manner. Furthermore, cellular expression of insulin-responsive glucose transporter (GLUT)-4 was decreased by 46%, indicating that reduced glucose uptake was due to a decrease in cellular GLUT-4 expression. In addition, the level of free glycerol released into the cultured medium was increased by 36.4% with the treatment by TEF. In subsequent measurements using quantitative real-time polymerase chain reaction, mRNA levels of hormone-sensitive lipase (HSL) and adipose TG lipase (ATGL) were elevated by 34.8% and 16.9%, respectively, at the concentration of 20 microg/mL. These results suggest that TEF partially inhibits lipogenesis by the suppression of glucose uptake via the decreased expression of cellular GLUT-4 and stimulates lipolysis through the induction of HSL and/or ATGL gene expression, resulting in the increased glycerol release.
ESTHER : Lee_2010_J.Med.Food_13_364
PubMedSearch : Lee_2010_J.Med.Food_13_364
PubMedID: 20412020

Title : Population pharmacokinetics of CPT-11 (irinotecan) in gastric cancer patients with peritoneal seeding after its intraperitoneal administration - Ahn_2010_Eur.J.Clin.Pharmacol_66_1235
Author(s) : Ahn BJ , Choi MK , Park YS , Lee J , Park SH , Park JO , Lim HY , Kang WK , Ko JW , Yim DS
Ref : European Journal of Clinical Pharmacology , 66 :1235 , 2010
Abstract : PURPOSE: It is well known that CPT-11 (irinotecan) is biotransformed to its active metabolite, SN-38, by carboxylesterase in the liver and other tissues. However, little is known about its pharmacokinetics (PK) when administered intraperitoneally. The aim of our study was to develop a population pharmacokinetic model for CPT-11 and SN-38 following the intraperitoneal (IP) administration of CPT-11. METHODS: Pharmacokinetic data obtained from 16 gastric adenocarcinoma patients with peritoneal seeding were used. Administered doses ranged from 50 to 250 mg/m(2). To measure CPT-11 and SN-38 levels, we collected samples of peritoneal fluid, plasma and urine 0, 0.5, 1.5, 2, 3.5, 8, 12, 25.5, 49 and 56 h after IP infusion. Several multicompartmental pharmacokinetic models were tested for CPT-11 and SN-38 in the sampled peritoneal fluid, plasma and urine. NONMEM ver. 6 was used throughout the model-building process. RESULTS: Peak concentrations were achieved earlier for peritoneal SN-38 than for plasma SN-38. The apparent metabolic clearance of peritoneal and plasma CPT-11 to peritoneal and plasma SN-38 accounted for 0.2 and 7.3% of the total clearance of peritoneal and plasma CPT-11, respectively. The typical values of steady-state volume of distribution (Vss) (46.6 L/m(2)), inter-compartment clearance (6.70 L/h/m(2)) and clearance (16.0 L/h/m(2)) for plasma CPT-11 were estimated in a two-compartment PK model. CONCLUSIONS: Our results demonstrate that a small fraction of intraperitoneally administered CPT-11 was metabolized in situ to active SN-38 and that the Vss of plasma CPT-11 following IP administration in our patient cohort was lower than that estimated in previous reports following the intravenous administration of CPT-11.
ESTHER : Ahn_2010_Eur.J.Clin.Pharmacol_66_1235
PubMedSearch : Ahn_2010_Eur.J.Clin.Pharmacol_66_1235
PubMedID: 20827550

Title : LOVely enzymes - towards engineering light-controllable biocatalysts - Krauss_2010_Microb.Biotechnol_3_15
Author(s) : Krauss U , Lee J , Benkovic SJ , Jaeger KE
Ref : Microb Biotechnol , 3 :15 , 2010
Abstract : Light control over enzyme function represents a novel and exciting field of biocatalysis research. Blue-light photoreceptors of the Light, Oxygen, Voltage (LOV) family have recently been investigated for their applicability as photoactive switches. We discuss here the primary photochemical events leading to light activation of LOV domains as well as the proposed signal propagation mechanism to the respective effector domain. Furthermore, we describe the construction of LOV fusions to different effector domains, namely a dihydrofolate reductase from Escherichia coli and a lipase from Bacillus subtilis. Both fusion partners retained functionality, and alteration of enzyme activity by light was also demonstrated. Hence, it appears that fusion of LOV photoreceptors to functional enzyme target sites via appropriate linker structures may represent a straightforward strategy to design light controllable biocatalysts.
ESTHER : Krauss_2010_Microb.Biotechnol_3_15
PubMedSearch : Krauss_2010_Microb.Biotechnol_3_15
PubMedID: 21255302

Title : Characterization and optimization of carboxylesterase-catalyzed esterification between capric acid and glycerol for the production of 1-monocaprin in reversed micellar system - Park_2010_N.Biotechnol_27_46
Author(s) : Park KM , Kwon OT , Ahn SM , Lee J , Chang PS
Ref : N Biotechnol , 27 :46 , 2010
Abstract : Calotropis procera R. Br. carboxylesterase (EC solubilized in reversed micellar glycerol droplets containing a very small amount of water (less than 5ppm) and stabilized by a surfactant effectively catalyzed the esterification between glycerol and capric acid to produce 1-monocaprin. Reaction variables including surfactant types, organic solvent media, reaction time, G-value ([glycerol]/[capric acid]), R-value ([water]/[surfactant]), pH, temperature, and types of metal ion inhibitors on the carboxylesterase-catalyzed esterification were characterized and optimized to efficiently produce 1-monocaprin. Bis(2-ethylhexyl) sodium sulfosuccinate (AOT) and isooctane were the most effective surfactant and organic solvent medium, respectively, for 1-monocaprin formation in reversed micelles. The optimum G- and R-values were 3.0 and 0.05, respectively, and the optimum pH and temperature were determined to be 10.0 and 60 degrees C, respectively. K(m,app.) and V(max,app.) were calculated from a Hanes-Woolf plot, and the values were 9.64 mM and 2.45 microM/min mg protein, respectively. Among various metal ions, Cu(2+) and Fe(2+) severely inhibited carboxylesterase-catalyzed esterification activity (less than 6.0% of relative activity).
ESTHER : Park_2010_N.Biotechnol_27_46
PubMedSearch : Park_2010_N.Biotechnol_27_46
PubMedID: 19931658
Gene_locus related to this paper: pig-EST1

Title : The cholinesterase-like domain, essential in thyroglobulin trafficking for thyroid hormone synthesis, is required for protein dimerization - Lee_2009_J.Biol.Chem_284_12752
Author(s) : Lee J , Wang X , Di Jeso B , Arvan P
Ref : Journal of Biological Chemistry , 284 :12752 , 2009
Abstract : The carboxyl-terminal cholinesterase-like (ChEL) domain of thyroglobulin (Tg) has been identified as critically important in Tg export from the endoplasmic reticulum. In a number of human kindreds suffering from congenital hypothyroidism, and in the cog congenital goiter mouse and rdw rat dwarf models, thyroid hormone synthesis is inhibited because of mutations in the ChEL domain that block protein export from the endoplasmic reticulum. We hypothesize that Tg forms homodimers through noncovalent interactions involving two predicted alpha-helices in each ChEL domain that are homologous to the dimerization helices of acetylcholinesterase. This has been explored through selective epitope tagging of dimerization partners and by inserting an extra, unpaired Cys residue to create an opportunity for intermolecular disulfide pairing. We show that the ChEL domain is necessary and sufficient for Tg dimerization; specifically, the isolated ChEL domain can dimerize with full-length Tg or with itself. Insertion of an N-linked glycan into the putative upstream dimerization helix inhibits homodimerization of the isolated ChEL domain. However, interestingly, co-expression of upstream Tg domains, either in cis or in trans, overrides the dimerization defect of such a mutant. Thus, although the ChEL domain provides a nidus for Tg dimerization, interactions of upstream Tg regions with the ChEL domain actively stabilizes the Tg dimer complex for intracellular transport.
ESTHER : Lee_2009_J.Biol.Chem_284_12752
PubMedSearch : Lee_2009_J.Biol.Chem_284_12752
PubMedID: 19276074

Title : Functional fusion mutant of Candida antarctica lipase B (CalB) expressed in Escherichia coli - Seo_2009_Biochim.Biophys.Acta_1794_519
Author(s) : Seo HS , Kim SE , Han KY , Park JS , Kim YH , Sim SJ , Lee J
Ref : Biochimica & Biophysica Acta , 1794 :519 , 2009
Abstract : Candida antarctica lipase B (CalB) was functionally expressed in the cytoplasm of Escherichia coli Origami(DE3) with the N-terminus fusion of E. coli endogenous proteins. The previously-identified stress responsive proteins through comparative proteome analyses such as malate dehydrogenase (Mdh), spermidine/putrescine-binding periplasmic protein (PotD), and FKBP-type peptidyl-prolyl cis-trans isomerase (PPIases) (SlyD) dramatically increased the solubility of CalB in E. coli cytoplasm when used as N-terminus fusion partners. We demonstrated that Mdh, PotD, and SlyD were powerful solubility enhancers that presumably facilitated the protein folding of CalB. Moreover, among the various fusion mutants, Mdh-CalB showed the highest hydrolytic activity and was as biologically active as standard CalB. Similarly to the previous report, the electrophoretic properties of CalB indicate that CalB seems to form dimer-based oligomer structures. We evaluated the structural compatibility between the fusion partner protein and CalB, which seems to be of crucial importance upon the bioactive dimer formation of CalB and might affect the substrate accessibility to the enzyme active site, thereby determining the biological activities of the fusion mutants.
ESTHER : Seo_2009_Biochim.Biophys.Acta_1794_519
PubMedSearch : Seo_2009_Biochim.Biophys.Acta_1794_519
PubMedID: 19159700

Title : Defective protein folding and intracellular retention of thyroglobulin-R19K mutant as a cause of human congenital goiter - Kim_2008_Mol.Endocrinol_22_477
Author(s) : Kim PS , Lee J , Jongsamak P , Menon S , Li B , Hossain SA , Bae JH , Panijpan B , Arvan P
Ref : Mol Endocrinol , 22 :477 , 2008
Abstract : It has been suggested that a thyroglobulin (Tg)-R19K missense mutation may be a newly identified cause of human congenital goiter, which is surprising for this seemingly conservative substitution. Here, we have examined the intracellular fate of recombinant mutant Tg expressed in COS-7 cells. Incorporation of the R19K mutation largely blocked Tg secretion, and this mutant was approximately 90% degraded intracellularly over a 24-h period after synthesis. Before its degradation, the Tg-R19K mutant exhibited abnormally increased association with molecular chaperones BiP, calnexin, and protein disulfide isomerase, and was unable to undergo anterograde advance from the endoplasmic reticulum (ER) through the Golgi complex. Inhibitors of proteasomal proteolysis and ER mannosidase-I both prevented ER-associated degradation of the Tg-R19K mutant and increased its association with ER molecular chaperones. ER quality control around Tg residue 19 is not dependent upon charge but upon side-chain packing, because Tg-R19Q was efficiently secreted. Whereas a Tg mutant truncated after residue 174 folds sufficiently well to escape ER quality control, introduction of the R19K point mutation blocked its secretion. The data indicate that the R19K mutation induces local misfolding in the amino-terminal domain of Tg that has global effects on Tg transport and thyroid hormonogenesis.
ESTHER : Kim_2008_Mol.Endocrinol_22_477
PubMedSearch : Kim_2008_Mol.Endocrinol_22_477
PubMedID: 17916655
Gene_locus related to this paper: human-TG

Title : The cholinesterase-like domain of thyroglobulin functions as an intramolecular chaperone - Lee_2008_J.Clin.Invest_118_2950
Author(s) : Lee J , Di Jeso B , Arvan P
Ref : J Clinical Investigation , 118 :2950 , 2008
Abstract : Thyroid hormonogenesis requires secretion of thyroglobulin, a protein comprising Cys-rich regions I, II, and III (referred to collectively as region I-II-III) followed by a cholinesterase-like (ChEL) domain. Secretion of mature thyroglobulin requires extensive folding and glycosylation in the ER. Multiple reports have linked mutations in the ChEL domain to congenital hypothyroidism in humans and rodents; these mutations block thyroglobulin from exiting the ER and induce ER stress. We report that, in a cell-based system, mutations in the ChEL domain impaired folding of thyroglobulin region I-II-III. Truncated thyroglobulin devoid of the ChEL domain was incompetent for cellular export; however, a recombinant ChEL protein ("secretory ChEL") was secreted efficiently. Coexpression of secretory ChEL with truncated thyroglobulin increased intracellular folding, promoted oxidative maturation, and facilitated secretion of region I-II-III, indicating that the ChEL domain may function as an intramolecular chaperone. Additionally, we found that the I-II-III peptide was cosecreted and physically associated with secretory ChEL. A functional ChEL domain engineered to be retained intracellularly triggered oxidative maturation of I-II-III but coretained I-II-III, indicating that the ChEL domain may also function as a molecular escort. These insights into the role of the ChEL domain may represent potential therapeutic targets in the treatment of congenital hypothyroidism.
ESTHER : Lee_2008_J.Clin.Invest_118_2950
PubMedSearch : Lee_2008_J.Clin.Invest_118_2950
PubMedID: 18596923
Gene_locus related to this paper: human-TG

Title : Genetic variations in soluble epoxide hydrolase and graft function in kidney transplantation - Lee_2008_Transplant.Proc_40_1353
Author(s) : Lee SH , Lee J , Cha R , Park MH , Ha JW , Kim S , Kim YS
Ref : Transplant Proc , 40 :1353 , 2008
Abstract : BACKGROUND: Epoxyeicosatrienoic acids (EETs) are endothelium-derived hyperpolarizing factors that contribute renal protective actions. The aim of this study was to identify the association between genetic variations in soluble epoxide hydrolase (EPHX2, EET-metabolizing enzyme) and kidney allograft dysfunction.
MATERIALS AND METHODS: Data from 204 kidney transplant donor-recipient pairs were examined for polymorphisms of exon 8 (R287Q, rs751141 G/A) and 3' untranslated region (3' UTR, rs1042032 A/G) of the EPHX2 gene and correlated with clinical data.
RESULTS: The mean duration of follow-up for recipients was 58 +/- 45.3 months who were 39 +/- 11.8 years old at the time of operation and displayed estimated glomerular filtration rate (eGFR) of 68 +/- 16.5 mL/min/1.73 m2 at 1 month after transplantation. AA, AG, and GG genotype frequencies in 3' UTR were 28%, 55%, and 16%, respectively. Twenty-one recipients experienced allograft dysfunction with eGFR <30 mL/min/1.73 m2; 10 had AA genotype of rs1042032 polymorphism (chi-square test; A/A vs A/G+G/G; P = .04). Recipients without rs1042032 polymorphism variant allele showed a significant risk for allograft dysfunction (A/A vs A/G+G/G; P = .04; odds ratio, 2.65; 95% confidence interval [CI], 1.03-6.81). Multivariate analysis of the characteristics of patients using a Cox proportional hazard model showed that the AA genotype of rs1042032 polymorphism was predictive of allograft dysfunction (Hazard Ratio = 3.26; P = .04; 95% CI, 1.08-9.59). CONCLUSION: The present study suggested that the presence of the rs1042032 variant allele in EPHX2 was associated with a protective role for allograft function.
ESTHER : Lee_2008_Transplant.Proc_40_1353
PubMedSearch : Lee_2008_Transplant.Proc_40_1353
PubMedID: 18589104

Title : Cholinesterase inhibitory and anti-amnesic activity of alkaloids from Corydalis turtschaninovii - Hung_2008_J.Ethnopharmacol_119_74
Author(s) : Hung TM , Na M , Dat NT , Ngoc TM , Youn U , Kim HJ , Min BS , Lee J , Bae K
Ref : J Ethnopharmacol , 119 :74 , 2008
Abstract : In the course of screening plants used in Korean folk medicine as memory enhancers, a 70% ethanol extract of tuber from Corydalis turtschaninovii Besser (Papaveraceae) showed significant acetylcholinesterase (AChE) inhibitory activity. Repeated column chromatography led to the isolation of a new aporphine alkaloid, oxoglaucidaline (9), and a new protoberberine, pseudodehydrocorydaline (13) together with 14 known compounds (1-8, 10-12, and 14-16). The chemical structures of isolated compounds were elucidated base on extensive 1D and 2D NMR spectroscopic data. Compounds 1-16 were investigated in vitro for their anti-cholinesterase activity using the mice cortex AChE enzyme. In further study, the anti-amnesic activities of pseudoberberine (16) in mice on the learning and memory impairments induced by scopolamine (1.0 mg/kg, i.p.) were examined. This alkaloid (5.0 mg/kg, p.o.) administration significantly reversed cognitive impairments in mice by passive avoidance test (P<0.05). It also reduced escape latencies in training trials and prolonged swimming times in the target quadrant during the probe trial in the water maze task (P<0.05). These results indicated that Corydalis turtschaninovii due to its alkaloids have anti-cholinesterase activity and pseudoberberine and other alkaloids have anti-amnesic activities that may be useful for cognitive impairment treatment.
ESTHER : Hung_2008_J.Ethnopharmacol_119_74
PubMedSearch : Hung_2008_J.Ethnopharmacol_119_74
PubMedID: 18601993

Title : Compound heterozygosity of novel missense mutations (Ser45 --> Gly, Cys278 --> Arg) in the lipoprotein lipase gene in a newborn Korean infant -
Author(s) : Lee J , Ko K , Ryu S , Lee K , Son C
Ref : Clinica Chimica Acta , 387 :172 , 2008
PubMedID: 17884031

Title : High-resolution structure of ybfF from Escherichia coli K12: a unique substrate-binding crevice generated by domain arrangement. - Park_2008_J.Mol.Biol_376_1426
Author(s) : Park SY , Lee SH , Lee J , Nishi K , Kim YS , Jung CH , Kim JS
Ref : Journal of Molecular Biology , 376 :1426 , 2008
Abstract : Esterases are one of the most common enzymes and are involved in diverse cellular functions. ybfF protein from Escherichia coli (Ec_ybfF) belongs to the esterase family for the large substrates, palmitoyl coenzyme A and malonyl coenzyme A, which are important cellular intermediates for energy conversion and biomolecular synthesis. To obtain molecular information on ybfF esterase, which is found in a wide range of microorganisms, we elucidated the crystal structures of Ec_ybfF in complexes with small molecules at resolutions of 1.1 and 1.68 A, respectively. The structure of Ec_ybfF is composed of a globular alpha/beta hydrolase domain with a three-helical bundle cap, which is linked by a kinked helix to the alpha/beta hydrolase domain. It contains a catalytic tetrad of Ser-His-Asp-Ser with the first Ser acting as a nucleophile. The unique spatial arrangement and orientation of the helical cap with respect to the alpha/beta hydrolase domain form a substrate-binding crevice for large substrates. The helical cap is also directly involved in catalysis by providing a substrate anchor, viz., the conserved residues of Arg123 and Tyr208. The high-resolution structure of Ec_ybfF shows that the inserted helical bundle structure and its spatial orientation with respect to the alpha/beta hydrolase domain are critical for creating a large inner space and constituting a specific active site, thereby providing the broad substrate spectrum toward large biomolecules.
ESTHER : Park_2008_J.Mol.Biol_376_1426
PubMedSearch : Park_2008_J.Mol.Biol_376_1426
PubMedID: 18215690
Gene_locus related to this paper: ecoli-ybff

Title : Enhanced degradation and toxicity reduction of dihexyl phthalate by Fusarium oxysporum f. sp. pisi cutinase - Kim_2007_J.Appl.Microbiol_102_221
Author(s) : Kim YH , Seo HS , Min J , Kim YC , Ban YH , Han KY , Park JS , Bae KD , Gu MB , Lee J
Ref : J Appl Microbiol , 102 :221 , 2007
Abstract : AIMS: This research aims to investigate the efficiency of two lipolytic enzymes--fungal cutinase and yeast esterase--upon the biodegradation of dihexyl phthalate (DHP).
METHOD AND RESULTS: During the enzymatic degradation of DHP dissolved in methanol, several degradation products were detected and their time-course changes were monitored using GC/MS. The DHP-degradation rate of cutinase was surprisingly high; i.e. almost 70% of the initial DHP (500 mg l(-1)) was decomposed within 4.5 h. Although the same amount of esterase was employed, more than 85% of the DHP remained after 3 days. Almost all the DHP was converted by cutinase into 1,3-isobenzofurandione (IBF), whereas hexyl methyl phthalate and IBF were abundantly produced by esterase. In addition, the toxicities of the DHP-degraded products by esterase were evaluated using various recombinant bioluminescent bacteria, which caused oxidative and protein damage, whereas the hydrolysis products from cutinase never caused any cellular damage in the methanol-containing reaction system.
CONCLUSIONS: Cutinase starts to act as a DHP-degrader much earlier and faster than esterase, with high stability in ester-hydrolytic activity, therefore a plausible approach to the practical application of cutinase for DHP degradation in the DHP-contaminated environments may be possible. SIGNIFICANCE AND IMPACT OF THE STUDY: This study describes the enhanced degradation and detoxification of DHP using Fusarium oxysporum f. sp. pisi cutinase.
ESTHER : Kim_2007_J.Appl.Microbiol_102_221
PubMedSearch : Kim_2007_J.Appl.Microbiol_102_221
PubMedID: 17184338
Gene_locus related to this paper: fusox-CUT

Title : Lipoproteini lipase-derived fatty acids: physiology and dysfunction - Lee_2007_Curr.Hypertens.Rep_9_462
Author(s) : Lee J , Goldberg IJ
Ref : Curr Hypertens Rep , 9 :462 , 2007
Abstract : Under normal circumstances, most energy substrate used for heart contraction derives from fatty acids in the form of nonesterified fatty acids bound to albumin or fatty acids derived from lipolysis of lipoprotein-bound triglyceride by lipoprotein lipase (LpL). By creating LpL knockout mice (hLpL0), we learned that loss of cardiac LpL leads to myocardial dysfunction; therefore, neither nonesterified fatty acids nor increased glucose metabolism can replace LpL actions. hLpL0 mice do not survive abdominal aortic constriction and they develop more heart failure with hypertension. Conversely, we created a mouse overexpressing cardiomyocyte-anchored LpL. This transgene produced cardiac lipotoxicity and dilated cardiomyopathy. Methods to alter this phenotype and the causes of other models of lipotoxicity are currently being studied and will provide further insight into the physiology of lipid metabolism in the heart.
ESTHER : Lee_2007_Curr.Hypertens.Rep_9_462
PubMedSearch : Lee_2007_Curr.Hypertens.Rep_9_462
PubMedID: 18367009

Title : Oxidoreductase interactions include a role for ERp72 engagement with mutant thyroglobulin from the rdw\/rdw rat dwarf - Menon_2007_J.Biol.Chem_282_6183
Author(s) : Menon S , Lee J , Abplanalp WA , Yoo SE , Agui T , Furudate S , Kim PS , Arvan P
Ref : Journal of Biological Chemistry , 282 :6183 , 2007
Abstract : Newly synthesized thyroglobulin (Tg), the secretory glycoprotein that serves as precursor in thyroid hormone synthesis, normally forms transient covalent protein complexes with oxidoreductases of the endoplasmic reticulum (ER). The Tg-G2320R mutation is responsible for congenital hypothyroidism in rdw/rdw rats, in which a lack of secondary thyroid enlargement (goiter) implicates death of thyrocytes as part of disease pathogenesis. We found that mutant Tg-G2320R was retained within the ER with no detectable synthesis of thyroxine, had persistent exposure of free cysteine thiols, and was associated with activated ER stress response but incomplete ER-associated degradation (ERAD). Tg-G2320R associated with multiple ER resident proteins, most notably ERp72, including covalent Tg-ERp72 interactions. In PC Cl3 thyrocytes, inducible overexpression of ERp72 increased the ability of cells to maintain Tg cysteines in a reduced state. Noncovalent interactions of several ER chaperones with newly synthesized Tg-G2320R diminished over time in parallel with ERAD of the mutant protein, yet a small ERAD-resistant Tg fraction remained engaged in covalent association with ERp72 even 2 days post-synthesis. Such covalent protein aggregates may set the stage for apoptotic thyrocyte cell death, preventing thyroid goiter formation in rdw/rdw rats.
ESTHER : Menon_2007_J.Biol.Chem_282_6183
PubMedSearch : Menon_2007_J.Biol.Chem_282_6183
PubMedID: 17200118
Gene_locus related to this paper: ratno-thyro

Title : The use of a cholinesterase inhibitor review committee in long-term care - Lee_2007_J.Am.Med.Dir.Assoc_8_243
Author(s) : Lee J , Monette J , Sourial N , Monette M , Bergman H
Ref : J Am Med Dir Assoc , 8 :243 , 2007
Abstract : OBJECTIVE: The objective of the study was to document the effectiveness of a Cholinesterase Inhibitor (ChE-I) Review Committee in a long-term care (LTC) institution in Montreal, Canada. DESIGN: Retrospective cohort study. SETTING: Maimonides Geriatric Centre (MGC), a 387-bed LTC facility in Montreal, Canada, in which 352 patients have dementia. PARTICIPANTS: Fifty-two patients on ChE-I who were reviewed at least once by the ChE-I Review Committee between January and November 2005. MEASUREMENTS: Recommendations for discontinuation, actual discontinuation, and restarting of ChE-I, along with reasons underlying these decisions, were collected from the patients' charts over a 4-month period following Review Committee assessment. RESULTS: The Review Committee recommended discontinuation of ChE-I in 17 (32.7%) of the 52 patients. After 1 patient died and therefore was excluded from the study, 13 (81.3%) of the remaining 16 were actually discontinued. The most common reasons for recommendation to discontinue ChE-I were insufficient benefit on cognition, activities of daily living (ADL), and behavior. Subsequently, ChE-I was resumed in 4 (30.8%) of the 13 patients discontinued, 2 because of ADL deterioration and 2 at the request of the family. CONCLUSIONS: Through the review process, almost one third of ChE-I users were recommended for discontinuation because of insufficient benefit; the majority of these were discontinued. Fewer than one third were subsequently restarted. A ChE-I Review Committee seemed to be an effective and acceptable model for decision making regarding ChE-I use in LTC.
ESTHER : Lee_2007_J.Am.Med.Dir.Assoc_8_243
PubMedSearch : Lee_2007_J.Am.Med.Dir.Assoc_8_243
PubMedID: 17498608

Title : Crystallization and preliminary X-ray diffraction analysis of ybfF, a new esterase from Escherichia coli K12 - Park_2007_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_63_1051
Author(s) : Park SY , Lee SH , Lee J , Jung CH , Kim JS
Ref : Acta Crystallographica Sect F Struct Biol Cryst Commun , 63 :1051 , 2007
Abstract : The product of the recently discovered ybfF gene, which belongs to the esterase family, does not show high sequence similarity to other esterases. To provide the molecular background to the enzymatic mechanism of the ybfF esterase, the ybfF protein from Escherichia coli K12 (Ec_ybfF) was cloned, expressed and purified. The Ec_ybfF protein was crystallized from 60% Tacsimate and 0.1 M bis-Tris propane buffer pH 7.0. Diffraction data were collected to 1.10 A resolution using synchrotron radiation. The crystal belongs to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 66.09, b = 90.71, c = 92.88 A. With two Ec_ybfF molecules in the asymmetric unit, the crystal volume per unit protein weight is 2.17 A(3) Da(-1), corresponding to a solvent content of 42%.
ESTHER : Park_2007_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_63_1051
PubMedSearch : Park_2007_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_63_1051
PubMedID: 18084091
Gene_locus related to this paper: ecoli-ybff

Title : Evolutionary and biomedical insights from the rhesus macaque genome - Gibbs_2007_Science_316_222
Author(s) : Gibbs RA , Rogers J , Katze MG , Bumgarner R , Weinstock GM , Mardis ER , Remington KA , Strausberg RL , Venter JC , Wilson RK , Batzer MA , Bustamante CD , Eichler EE , Hahn MW , Hardison RC , Makova KD , Miller W , Milosavljevic A , Palermo RE , Siepel A , Sikela JM , Attaway T , Bell S , Bernard KE , Buhay CJ , Chandrabose MN , Dao M , Davis C , Delehaunty KD , Ding Y , Dinh HH , Dugan-Rocha S , Fulton LA , Gabisi RA , Garner TT , Godfrey J , Hawes AC , Hernandez J , Hines S , Holder M , Hume J , Jhangiani SN , Joshi V , Khan ZM , Kirkness EF , Cree A , Fowler RG , Lee S , Lewis LR , Li Z , Liu YS , Moore SM , Muzny D , Nazareth LV , Ngo DN , Okwuonu GO , Pai G , Parker D , Paul HA , Pfannkoch C , Pohl CS , Rogers YH , Ruiz SJ , Sabo A , Santibanez J , Schneider BW , Smith SM , Sodergren E , Svatek AF , Utterback TR , Vattathil S , Warren W , White CS , Chinwalla AT , Feng Y , Halpern AL , Hillier LW , Huang X , Minx P , Nelson JO , Pepin KH , Qin X , Sutton GG , Venter E , Walenz BP , Wallis JW , Worley KC , Yang SP , Jones SM , Marra MA , Rocchi M , Schein JE , Baertsch R , Clarke L , Csuros M , Glasscock J , Harris RA , Havlak P , Jackson AR , Jiang H , Liu Y , Messina DN , Shen Y , Song HX , Wylie T , Zhang L , Birney E , Han K , Konkel MK , Lee J , Smit AF , Ullmer B , Wang H , Xing J , Burhans R , Cheng Z , Karro JE , Ma J , Raney B , She X , Cox MJ , Demuth JP , Dumas LJ , Han SG , Hopkins J , Karimpour-Fard A , Kim YH , Pollack JR , Vinar T , Addo-Quaye C , Degenhardt J , Denby A , Hubisz MJ , Indap A , Kosiol C , Lahn BT , Lawson HA , Marklein A , Nielsen R , Vallender EJ , Clark AG , Ferguson B , Hernandez RD , Hirani K , Kehrer-Sawatzki H , Kolb J , Patil S , Pu LL , Ren Y , Smith DG , Wheeler DA , Schenck I , Ball EV , Chen R , Cooper DN , Giardine B , Hsu F , Kent WJ , Lesk A , Nelson DL , O'Brien W E , Prufer K , Stenson PD , Wallace JC , Ke H , Liu XM , Wang P , Xiang AP , Yang F , Barber GP , Haussler D , Karolchik D , Kern AD , Kuhn RM , Smith KE , Zwieg AS
Ref : Science , 316 :222 , 2007
Abstract : The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.
ESTHER : Gibbs_2007_Science_316_222
PubMedSearch : Gibbs_2007_Science_316_222
PubMedID: 17431167
Gene_locus related to this paper: macmu-3neur , macmu-ACHE , macmu-BCHE , macmu-f6rul6 , macmu-f6sz31 , macmu-f6the6 , macmu-f6unj2 , macmu-f6wtx1 , macmu-f6zkq5 , macmu-f7aa58 , macmu-f7ai42 , macmu-f7aim4 , macmu-f7buk8 , macmu-f7cfi8 , macmu-f7cnr2 , macmu-f7cu68 , macmu-f7flv1 , macmu-f7ggk1 , macmu-f7hir7 , macmu-g7n054 , macmu-KANSL3 , macmu-TEX30 , macmu-Y4neur , macmu-g7n4x3 , macmu-i2cy02 , macmu-f7ba84 , macmu-CES2 , macmu-h9er02 , macmu-a0a1d5rbr3 , macmu-a0a1d5q4k5 , macmu-g7mxj6 , macmu-f7dn71 , macmu-f7hkw9 , macmu-f7hm08 , macmu-g7mke4 , macmu-a0a1d5rh04 , macmu-h9fud6 , macmu-f6qwx1 , macmu-f7h4t2 , macmu-h9zaw9 , macmu-f7h550 , macmu-a0a1d5q9w1 , macmu-f7gkb9 , macmu-f7hp78 , macmu-a0a1d5qvu5

Title : Accelerated degradation of dipentyl phthalate by Fusarium oxysporum f. sp. pisi cutinase and toxicity evaluation of its degradation products using bioluminescent bacteria - Ahn_2006_Curr.Microbiol_52_340
Author(s) : Ahn JY , Kim YH , Min J , Lee J
Ref : Curr Microbiol , 52 :340 , 2006
Abstract : The efficiency of two lipolytic enzymes (fungal cutinase and yeast esterase) in the degradation of dipentyl phthalate (DPeP) was investigated. The DPeP degradation rate of fungal cutinase was surprisingly high, i.e., almost 60% of the initial DPeP (500 mg/L) was decomposed within 2.5 hours, and nearly 40% of the degraded DPeP disappeared within the initial 15 minutes. With the yeast esterase, despite the same concentration, >87% of the DPeP remained even after 3 days of treatment. The final chemical composition after 3 days was significantly dependent on the enzyme used. During degradation with cutinase, most DPeP was converted into 1,3-isobenzofurandione (IBF) by diester hydrolysis. However, in the degradation by esterase, pentyl methyl phthalate, in addition to IBF, was produced in abundance. Toxicity monitoring using various recombinant bioluminescent bacteria showed that the degradation products from yeast esterase contained a toxic hazard, causing oxidative stress and damage to protein synthesis.
ESTHER : Ahn_2006_Curr.Microbiol_52_340
PubMedSearch : Ahn_2006_Curr.Microbiol_52_340
PubMedID: 16586026
Gene_locus related to this paper: fusox-CUT

Title : Biodegradation and detoxification of organophosphate insecticide, malathion by Fusarium oxysporum f. sp. pisi cutinase - Kim_2005_Chemosphere_60_1349
Author(s) : Kim YH , Ahn JY , Moon SH , Lee J
Ref : Chemosphere , 60 :1349 , 2005
Abstract : Efficiencies of two lypolytic enzymes (fungal cutinase and yeast esterase) in malathion degradation were investigated. Surprisingly, degradation rate of malathion by fungal cutinase was very high, i.e. almost 60% of initial malathion (500 mg l(-1)) was decomposed within 0.5 h, and nearly 50% of the degraded malathion disappeared within initial 15 min. With the yeast esterase, despite the same concentration, more than 65% of malathion remained even after 2-day treatment. During enzymatic degradation of malathion, two malathion-derived compounds were detected, and time-course changes in composition were also monitored. In the degradation by both fungal cutinase and yeast esterase, two additional organic chemicals were produced from malathion: malathion monoacid (MMA) and malathion diacid (MDA) by ester hydrolysis. Final chemical composition after 2 d was significantly dependent on the enzyme used. Fungal cutinase produced MDA as a major degradation compound. However in the malathion degradation by yeast esterase, an isomer of MMA was produced in abundance in addition to MDA. Toxic effects of malathion and its final degradation products were investigated using various recombinant bioluminescent bacteria. As a result, the degradation products (including MMA) by esterase severely caused membrane damage and inhibition of protein synthesis in bacterial cells, while in the fungal cutinase processes, malathion was significantly degraded to non-toxic MDA after the extended period (2 days).
ESTHER : Kim_2005_Chemosphere_60_1349
PubMedSearch : Kim_2005_Chemosphere_60_1349
PubMedID: 16054903
Gene_locus related to this paper: fusox-CUT

Title : Enzymatic degradation of dibutyl phthalate and toxicity of its degradation products - Kim_2005_Biotechnol.Lett_27_635
Author(s) : Kim YH , Lee J
Ref : Biotechnol Lett , 27 :635 , 2005
Abstract : Dibutyl phthalate (DBP) was more efficiently degraded by cutinase compared to yeast esterase; i.e. almost 80% of initial DBP (500 mg l(-1)) was decomposed within 7.5 h, and nearly 50% of the degraded DBP disappeared within the initial 30 min. The toxicity of the final DBP degradation products were investigated using various recombinant bioluminescent bacteria. Butyl methyl phthalate, the major product of degradation by the esterase, was an oxidative toxic hazard that damaged protein synthesis.
ESTHER : Kim_2005_Biotechnol.Lett_27_635
PubMedSearch : Kim_2005_Biotechnol.Lett_27_635
PubMedID: 15977070
Gene_locus related to this paper: fusox-CUT

Title : Biodegradation of dipropyl phthalate and toxicity of its degradation products: a comparison of Fusarium oxysporum f. sp. pisi cutinase and Candida cylindracea esterase - Kim_2005_Arch.Microbiol_184_25
Author(s) : Kim YH , Min J , Bae KD , Gu MB , Lee J
Ref : Arch Microbiol , 184 :25 , 2005
Abstract : The efficiency of two lypolytic enzymes (fungal cutinase, yeast esterase) in the degradation of dipropyl phthalate (DPrP) was investigated. The DPrP-degradation rate of fungal cutinase was surprisingly high, i.e., almost 70% of the initial DPrP (500 mg/l) was decomposed within 2.5 h and nearly 50% of the degraded DPrP disappeared within the initial 15 min. With the yeast esterase, despite the same concentration, more than 90% of the DPrP remained even after 3 days of treatment. During the enzymatic degradation of DPrP, several DPrP-derived compounds were detected and time-course changes in composition were also monitored. The final chemical composition after 3 days was significantly dependent on the enzyme used. During degradation with fungal cutinase, most DPrP was converted into 1,3-isobenzofurandione (IBF) by diester hydrolysis. However, in the degradation by yeast esterase, propyl methyl phthalate (PrMP) was produced in abundance in addition to IBF. The toxic effects of the final degradation products were investigated using various recombinant bioluminescent bacteria. As a result, the degradation products (including PrMP) from yeast esterase severely caused oxidative stress and damage to protein synthesis in bacterial cells, while in the fungal cutinase processes, DPrP was significantly degraded to non-toxic IBF after the extended period (3 days).
ESTHER : Kim_2005_Arch.Microbiol_184_25
PubMedSearch : Kim_2005_Arch.Microbiol_184_25
PubMedID: 16059706
Gene_locus related to this paper: fusox-CUT

Title : A case with cholinesterase inhibitor responsive asymmetric posterior cortical atrophy - Kim_2005_Clin.Neurol.Neurosurg_108_97
Author(s) : Kim E , Lee Y , Lee J , Han SH
Ref : Clin Neurol Neurosurg , 108 :97 , 2005
Abstract : A 55-year-old right-handed woman presented initially with mild amnestic and depressive episodes but slowly developed progressive neurobehavioral symptoms, indicative of posterior cortical atrophy in ensuing years. A more detailed neurobehavioral test suggested predominant right temporo-parietal dysfunction with executive functional deficits. SPECT and MRI findings revealed right unilateral temporo-parietal involvement. Cholinesterase inhibitor administration led to amelioration of symptoms. We suggest that cases of posterior cortical atrophy or visual variant of Alzheimer's disease may be responsive to cholinesterase inhibitor therapy; however, the observation in a single case should be confirmed on larger populations in a clinical trial design with placebo control.
ESTHER : Kim_2005_Clin.Neurol.Neurosurg_108_97
PubMedSearch : Kim_2005_Clin.Neurol.Neurosurg_108_97
PubMedID: 16311158

Title : The cerebral response during subjective choice with and without self-reference - Johnson_2005_J.Cogn.Neurosci_17_1897
Author(s) : Johnson SC , Schmitz TW , Kawahara-Baccus TN , Rowley HA , Alexander AL , Lee J , Davidson RJ
Ref : J Cogn Neurosci , 17 :1897 , 2005
Abstract : The anterior medial prefrontal (AMPFC) and retrosplenial (RSC) cortices are active during self-referential decision-making tasks such as when participants appraise traits and abilities, or current affect. Other appraisal tasks requiring an evaluative decision or mental representation, such as theory of mind and perspective-taking tasks, also involve these regions. In many instances, these types of decisions involve a subjective opinion or preference, but also a degree of ambiguity in the decision, rather than a strictly veridical response. However, this ambiguity is generally not controlled for in studies that examine self-referential decision-making. In this functional magnetic resonance imaging experiment with 17 healthy adults, we examined neural processes associated with subjective decision-making with and without an overt self-referential component. The task required subjective decisions about colors-regarding self-preference (internal subjective decision) or color similarity (external subjective decision) under conditions where there was no objectively correct response. Results indicated greater activation in the AMPFC, RSC, and caudate nucleus during internal subjective decision-making. The findings suggest that self-referential processing, rather than subjective judgments among ambiguous response alternatives, accounted for the AMPFC and RSC response.
ESTHER : Johnson_2005_J.Cogn.Neurosci_17_1897
PubMedSearch : Johnson_2005_J.Cogn.Neurosci_17_1897
PubMedID: 16356327

Title : The lipoprotein lipase S447X polymorphism and plasma lipids: interactions with APOE polymorphisms, smoking, and alcohol consumption - Lee_2004_J.Lipid.Res_45_1132
Author(s) : Lee J , Tan CS , Chia KS , Tan CE , Chew SK , Ordovas JM , Tai ES
Ref : J Lipid Res , 45 :1132 , 2004
Abstract : We studied 4,058 subjects from a representative sample of the Singapore population 1) to determine the association between the S447X polymorphism at the LPL locus and serum lipid concentration in Chinese, Malays, and Asian Indians living in Singapore and 2) to explore any interactions with apolipoprotein E (APOE) genotype, exercise, obesity, cigarette smoking, and alcohol intake. Information on obesity, lifestyle factors (including smoking, alcohol consumption, and exercise frequency), glucose tolerance, and fasting lipids was obtained. Male and female carriers of the X447 allele had lower serum triglyceride concentrations and higher HDL cholesterol (HDL-C) concentrations. The association between the X447 allele and serum HDL-C concentration was modulated by APOE genotype in males and cigarette smoking and alcohol intake in females. The effect of the X447 allele was greatest in men who carried the E4 allele and women who smoked or consumed alcohol. The X447 allele at the LPL locus is common and associated with a less atherogenic lipid profile in Asian populations. Interactions with APOE genotype, cigarette smoking, and alcohol intake reinforce the importance of examining genetic associations, such as this one, in the context of the population of interest.
ESTHER : Lee_2004_J.Lipid.Res_45_1132
PubMedSearch : Lee_2004_J.Lipid.Res_45_1132
PubMedID: 15060087

Title : Ethanol-response genes and their regulation analyzed by a microarray and comparative genomic approach in the nematode Caenorhabditis elegans - Kwon_2004_Genomics_83_600
Author(s) : Kwon JY , Hong M , Choi MS , Kang S , Duke K , Kim S , Lee S , Lee J
Ref : Genomics , 83 :600 , 2004
Abstract : The nematode shows responses to acute ethanol exposure that are similar to those observed in humans, mice, and Drosophila, namely hyperactivity followed by uncoordination and sedation. We used in this report the nematode Caenorhabditis elegans as a model system to identify and characterize the genes that are affected by ethanol exposure and to link those genes functionally into an ethanol-induced gene network. By analyzing the expression profiles of all C. elegans ORFs using microarrays, we identified 230 genes affected by ethanol. While the ethanol response of some of the identified genes was significant at early time points, that of the majority was at late time points, indicating that the genes in the latter case might represent the physiological consequence of the ethanol exposure. We further characterized the early response genes that may represent those involved directly in the ethanol response. These genes included many heat shock protein genes, indicating that high concentration of ethanol acts as a strong stress to the animal. Interestingly, we identified two non-heat-shock protein genes that were specifically responsive to ethanol. glr-2 was the only glutamate receptor gene to be induced by ethanol. T28C12.4, which encodes a protein with limited homology to human neuroligin, was also specific to ethanol stress. Finally, by analyzing the promoter regions of the early response genes, we identified a regulatory element, TCTGCGTCTCT, that was necessary for the expression of subsets of ethanol response genes.
ESTHER : Kwon_2004_Genomics_83_600
PubMedSearch : Kwon_2004_Genomics_83_600
PubMedID: 15028283
Gene_locus related to this paper: caeel-t28c12.4

Title : Effect of fimbria-fornix lesion on 125I-angiotensin IV (Ang IV) binding in the guinea pig hippocampus - Lee_2003_Brain.Res_979_7
Author(s) : Lee J , Chai SY , Morris MJ , Mendelsohn FA , Allen AM
Ref : Brain Research , 979 :7 , 2003
Abstract : Central administration of angiotensin IV (Ang IV) and its analogues facilitates memory retention and retrieval in normal animals and reverses amnesia induced by scopolamine or by bilateral perforant pathway lesions. Ang IV binds with high affinity and specificity to a novel binding site designated the AT(4) receptor. AT(4) receptors are abundant in the medial septum and hippocampus, a cholinergic pathway associated with memory processing. The aim of this study was to determine whether AT(4) receptors in the guinea pig hippocampus were associated with the neural input from the basal forebrain. The fimbria-fornix was lesioned by a unilateral-knife cut and the brain was processed for 125I-Ang IV binding, acetylcholinesterase, and cresyl violet staining. Unilateral lesions of the fimbria-fornix significantly reduced acetylcholinesterase staining in the ipsilateral hippocampus. The loss in cholinergic input to the hippocampus was associated with a small, but significant, reduction in 125I-Ang IV binding in the CA2 (-9%; P=0.001), and CA3 (-5%; P=0.003) of the rostral hippocampus. No other changes in 125I-Ang IV binding were observed. These results provide evidence that the majority of AT(4) receptor binding occurs in a post-synaptic locus in the guinea pig hippocampus.
ESTHER : Lee_2003_Brain.Res_979_7
PubMedSearch : Lee_2003_Brain.Res_979_7
PubMedID: 12850565

Title : Degradation of an endocrine disrupting chemical, DEHP [di-(2-ethylhexyl)-phthalate], by Fusarium oxysporum f. sp. pisi cutinase - Kim_2003_Appl.Microbiol.Biotechnol_63_75
Author(s) : Kim YH , Lee J , Moon SH
Ref : Applied Microbiology & Biotechnology , 63 :75 , 2003
Abstract : The efficiency of two lypolytic enzymes (fungal cutinase, yeast esterase) in the degradation of di-(2-ethylhexyl)-phthalate (DEHP) was investigated. The DEHP-degradation rate of fungal cutinase was surprisingly high, i.e. almost 70% of the initial DEHP (500 mg/l) was decomposed within 2.5 h and nearly 50% of the degraded DEHP disappeared within the initial 15 min. With the yeast esterase, despite the same concentration, more than 85% of the DEHP remained even after 3 days of treatment. During the enzymatic degradation of DEHP, several DEHP-derived compounds were detected and time-course changes in composition were also monitored. During degradation with fungal cutinase, most DEHP was converted into 1,3-isobenzofurandione (IBF) by diester hydrolysis. In the degradation by yeast esterase, two organic chemicals were produced from DEHP: IBF and an unidentified compound (X). The final chemical composition after 3 days was significantly dependent on the enzyme used. Fungal cutinase produced IBF as a major degradation compound. However, in the DEHP degradation by yeast esterase, compound X was produced in abundance in addition to IBF. The toxic effects of the final degradation products were investigated, using various recombinant bioluminescent bacteria and, as a result, the degradation products from yeast esterase were shown to contain a toxic hazard, causing oxidative stress and damage to protein synthesis.
ESTHER : Kim_2003_Appl.Microbiol.Biotechnol_63_75
PubMedSearch : Kim_2003_Appl.Microbiol.Biotechnol_63_75
PubMedID: 12750855
Gene_locus related to this paper: fusox-CUT

Title : The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment - Clark_2003_Genome.Res_13_2265
Author(s) : Clark HF , Gurney AL , Abaya E , Baker K , Baldwin D , Brush J , Chen J , Chow B , Chui C , Crowley C , Currell B , Deuel B , Dowd P , Eaton D , Foster J , Grimaldi C , Gu Q , Hass PE , Heldens S , Huang A , Kim HS , Klimowski L , Jin Y , Johnson S , Lee J , Lewis L , Liao D , Mark M , Robbie E , Sanchez C , Schoenfeld J , Seshagiri S , Simmons L , Singh J , Smith V , Stinson J , Vagts A , Vandlen R , Watanabe C , Wieand D , Woods K , Xie MH , Yansura D , Yi S , Yu G , Yuan J , Zhang M , Zhang Z , Goddard A , Wood WI , Godowski P , Gray A
Ref : Genome Res , 13 :2265 , 2003
Abstract : A large-scale effort, termed the Secreted Protein Discovery Initiative (SPDI), was undertaken to identify novel secreted and transmembrane proteins. In the first of several approaches, a biological signal sequence trap in yeast cells was utilized to identify cDNA clones encoding putative secreted proteins. A second strategy utilized various algorithms that recognize features such as the hydrophobic properties of signal sequences to identify putative proteins encoded by expressed sequence tags (ESTs) from human cDNA libraries. A third approach surveyed ESTs for protein sequence similarity to a set of known receptors and their ligands with the BLAST algorithm. Finally, both signal-sequence prediction algorithms and BLAST were used to identify single exons of potential genes from within human genomic sequence. The isolation of full-length cDNA clones for each of these candidate genes resulted in the identification of >1000 novel proteins. A total of 256 of these cDNAs are still novel, including variants and novel genes, per the most recent GenBank release version. The success of this large-scale effort was assessed by a bioinformatics analysis of the proteins through predictions of protein domains, subcellular localizations, and possible functional roles. The SPDI collection should facilitate efforts to better understand intercellular communication, may lead to new understandings of human diseases, and provides potential opportunities for the development of therapeutics.
ESTHER : Clark_2003_Genome.Res_13_2265
PubMedSearch : Clark_2003_Genome.Res_13_2265
PubMedID: 12975309
Gene_locus related to this paper: human-CES3 , human-CES4A

Title : Enhanced Degradation of an Endocrine-Disrupting Chemical, Butyl Benzyl Phthalate, by Fusarium oxysporum f. sp. pisi Cutinase - Kim_2002_Appl.Environ.Microbiol_68_4684
Author(s) : Kim YH , Lee J , Ahn JY , Gu MB , Moon SH
Ref : Applied Environmental Microbiology , 68 :4684 , 2002
Abstract : Compared to yeast esterase, fungal cutinase degraded butyl benzyl phthalate (BBP) far more efficiently; i.e., almost 60% of the BBP disappeared within 7.5 h. Also, the final chemical composition significantly depended on the enzyme used. Toxicity monitoring using bioluminescent bacteria showed that butyl methyl phthalate, a major product of degradation by esterase, was an oxidative toxic hazard.
ESTHER : Kim_2002_Appl.Environ.Microbiol_68_4684
PubMedSearch : Kim_2002_Appl.Environ.Microbiol_68_4684
PubMedID: 12200333
Gene_locus related to this paper: fusox-CUT

Title : Identification of deoxynivalenol- and nivalenol-producing chemotypes of Gibberella zeae by using PCR - Lee_2001_Appl.Environ.Microbiol_67_2966
Author(s) : Lee T , Oh DW , Kim HS , Lee J , Kim YH , Yun SH , Lee YW
Ref : Applied Environmental Microbiology , 67 :2966 , 2001
Abstract : Gibberella zeae, a major cause of cereal scab, may be divided into two chemotypes based on production of the trichothecenes deoxynivalenol (DON) and nivalenol (NIV). We cloned and sequenced the gene cluster for trichothecene biosynthesis from each chemotype. G. zeae H-11 is a DON producer isolated from corn, and G. zeae 88-1 is a NIV producer from barley. We sequenced a 23-kb gene cluster from H-11 and a 26-kb cluster from 88-1, along with the unlinked Tri101 genes. Each gene cluster contained 10 Tri gene homologues in the same order and transcriptional directions as those of Fusarium sporotrichioides. Between H-11 and 88-1 all of the Tri homologues except Tri7 were conserved, with identities ranging from 88 to 98% and 82 to 99% at the nucleotide and amino acid levels, respectively. The Tri7 sequences were only 80% identical at the nucleotide level. We aligned the Tri7 genes and found that the Tri7 open reading frame of H-11 carried several mutations and an insertion containing 10 copies of an 11-bp tandem repeat. The Tri7 gene from 88-1 carried neither the repeat nor the mutations. We assayed 100 G. zeae isolates of both chemotypes by PCR amplification with a primer pair derived from the Tri7 gene and could differentiate the chemotypes by polyacrylamide gel electrophoresis. The PCR-based method developed in this study should provide a simple and reliable diagnostic tool for differentiating the two chemotypes of G. zeae.
ESTHER : Lee_2001_Appl.Environ.Microbiol_67_2966
PubMedSearch : Lee_2001_Appl.Environ.Microbiol_67_2966
PubMedID: 11425709
Gene_locus related to this paper: gibze-Q96W93 , gibze-TRI8

Title : A simple and efficient in vitro method for metabolism studies of radiotracers - Lee_2001_Nucl.Med.Biol_28_391
Author(s) : Lee SY , Choe YS , Kim DH , Park BN , Kim SE , Choi Y , Lee KH , Lee J , Kim BT
Ref : Nucl Med Biol , 28 :391 , 2001
Abstract : In vitro metabolism of acetylcholinesterase inhibitors containing 3-[(18)F]fluoromethylbenzyl- ([(18)F]1) and 4-[(18)F]fluorobenzyl-piperidine moieties ([(18)F]2) was studied and compared with the in vivo metabolism. Defluorination of the [(18)F]1 mainly occurred to generate [(18)F]fluoride ion both in vitro and in vivo. In contrast, the [(18)F]2 was converted into an unknown polar metabolite in both metabolism methods and another metabolite, 4-[(18)F]fluorobenzoic acid in vitro. These results demonstrated that the in vitro method can be used to predict the in vivo metabolism of both radiotracers.
ESTHER : Lee_2001_Nucl.Med.Biol_28_391
PubMedSearch : Lee_2001_Nucl.Med.Biol_28_391
PubMedID: 11395311

Title : Cloning and sequence analysis of the estA gene encoding enzyme for producing (R)-beta-acetylmercaptoisobutyric acid from Pseudomonas aeruginosa 1001 - Lee_2000_J.Biosci.Bioeng_90_684
Author(s) : Lee J , Boyapati G , Song K , Rhee S , Kim C
Ref : J Biosci Bioeng , 90 :684 , 2000
Abstract : The estA gene encoding the enzyme that catalyzes the production of (R)-beta-acetylmercaptoisobutyric acid from (R,S)-ester from Pseudomonas aeruginosa 1001, was cloned in Escherichia coli and its nucleotide sequence was determined, revealing the presumed open reading frame encoding a polypeptide of 316 amino acid residues (948 nucleotides). The overall A + T and C + G compositions were 32.59% and 67.41%, respectively. The amino acid sequence of the estA gene product showed a significant similarity with that of the triacylglycerol lipase from Psychrobacter immobilis (38% identity), triacylglycerol lipase from Moraxella sp. (36% identity), and two forms of carboxyl esterases from Acinetobacter calcoaceticus (17% and 17% identities). The deduced amino acid sequences have a pentapeptide consensus sequence, G-X-S-X-G, having an active serine residue, and another active site, dipeptides H-G, located at 70-100 amino acids upstream of the G-X-S-X-G consensus sequence.
ESTHER : Lee_2000_J.Biosci.Bioeng_90_684
PubMedSearch : Lee_2000_J.Biosci.Bioeng_90_684
PubMedID: 16232934
Gene_locus related to this paper: pseae-PA2949

Title : Synthesis and biological evaluation of 1-(4-[18F]fluorobenzyl)-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine for in vivo studies of acetylcholinesterase - Lee_2000_Nucl.Med.Biol_27_741
Author(s) : Lee SY , Choe YS , Sugimoto H , Kim SE , Hwang SH , Lee K , Choi Y , Lee J , Kim B
Ref : Nucl Med Biol , 27 :741 , 2000
Abstract : We synthesized and evaluated 1-(4-fluorobenzyl)-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine (4-FDP), which is an analog of donepezil. The 4-[(18)F]FDP was prepared by reductive alkylation of debenzylated donepezil with 4-[(18)F]fluorobenzaldehyde in high radiochemical yield (decay-corrected, 40-52%) and with high effective specific activity (30-38 GBq/micromol). Tissue distribution studies in mice demonstrated nonspecific distribution of the 4-[(18)F]FDP in brain regions, suggesting that this radioligand may not be a suitable agent for in vivo studies of acetylcholinesterase (AChE), despite its potent in vitro biological activity.
ESTHER : Lee_2000_Nucl.Med.Biol_27_741
PubMedSearch : Lee_2000_Nucl.Med.Biol_27_741
PubMedID: 11150705

Title : Carboxyl methylation regulates phosphoprotein phosphatase 2A by controlling the association of regulatory B subunits - Tolstykh_2000_EMBO.J_19_5682
Author(s) : Tolstykh T , Lee J , Vafai S , Stock JB
Ref : EMBO Journal , 19 :5682 , 2000
Abstract : Phosphoprotein phosphatase 2A (PP2A) is a major phosphoserine/threonine protein phosphatase in all eukaryotes. It has been isolated as a heterotrimeric holoenzyme composed of a 65 kDa A subunit, which serves as a scaffold for the association of the 36 kDa catalytic C subunit, and a variety of B subunits that control phosphatase specificity. The C subunit is reversibly methyl esterified by specific methyltransferase and methylesterase enzymes at a completely conserved C-terminal leucine residue. Here we show that methylation plays an essential role in promoting PP2A holoenzyme assembly and that demethylation has an opposing effect. Changes in methylation indirectly regulate PP2A phosphatase activity by controlling the binding of regulatory B subunits to AC dimers.
ESTHER : Tolstykh_2000_EMBO.J_19_5682
PubMedSearch : Tolstykh_2000_EMBO.J_19_5682
PubMedID: 11060019
Gene_locus related to this paper: human-PPME1

Title : Carboxyl methylation of the phosphoprotein phosphatase 2A catalytic subunit promotes its functional association with regulatory subunits in vivo - Wu_2000_EMBO.J_19_5672
Author(s) : Wu J , Tolstykh T , Lee J , Boyd K , Stock JB , Broach JR
Ref : EMBO Journal , 19 :5672 , 2000
Abstract : The phosphoprotein phosphatase 2A (PP2A) catalytic subunit contains a methyl ester on its C-terminus, which in mammalian cells is added by a specific carboxyl methyltransferase and removed by a specific carboxyl methylesterase. We have identified genes in yeast that show significant homology to human carboxyl methyltransferase and methylesterase. Extracts of wild-type yeast cells contain carboxyl methyltransferase activity, while extracts of strains deleted for one of the methyltransferase genes, PPM1, lack all activity. Mutation of PPM1 partially disrupts the PP2A holoenzyme in vivo and ppm1 mutations exhibit synthetic lethality with mutations in genes encoding the B or B' regulatory subunit. Inactivation of PPM1 or overexpression of PPE1, the yeast gene homologous to bovine methylesterase, yields phenotypes similar to those observed after inactivation of either regulatory subunit. These phenotypes can be reversed by overexpression of the B regulatory subunit. These results demonstrate that Ppm1 is the sole PP2A methyltransferase in yeast and that its activity is required for the integrity of the PP2A holoenzyme.
ESTHER : Wu_2000_EMBO.J_19_5672
PubMedSearch : Wu_2000_EMBO.J_19_5672
PubMedID: 11060018
Gene_locus related to this paper: yeast-ppme1

Title : Computational studies of essential dynamics of Pseudomonas cepacia lipase - Lee_2000_J.Biomol.Struct.Dyn_18_297
Author(s) : Lee J , Suh SW , Shin S
Ref : J Biomol Struct Dyn , 18 :297 , 2000
Abstract : In order to investigate the interfacial activation of a lipase from Pseudomonas cepacia (PcL), molecular dynamics (MD) simulations and essential dynamics (ED) analysis were performed in different solvent environments: vacuum and explicit water solvents. Starting from the active (open) structure of PcL, the essential dynamics analysis of the simulations revealed large correlated motions, which may be responsible for the activation of the enzyme. Fluctuations in the U1 (active-site lid) and U2 domains are found to be important in the activation of PcL. In contrast, the catalytic triad exhibits very little displacement. These results are consistent with the previous X-ray structural determination. A combined analysis of the trajectories showed some differences for the simulations in different solvent environments. It was found that the region around the helix alpha5 showed larger displacements in the water simulations. It can be concluded that the open structure of PcL becomes unstable in water solvents, leading to the closing of the so-called 'lid' region. The simulations and ED analysis on the closed structure of PgL provided additional information concerning the structural changes involved in the activation of the lipases. It was found that structural changes for PcL and PgL, which are responsible for the essential motions of the protein, showed contrasting behavior in the different solvent environments.
ESTHER : Lee_2000_J.Biomol.Struct.Dyn_18_297
PubMedSearch : Lee_2000_J.Biomol.Struct.Dyn_18_297
PubMedID: 11089650

Title : Staphylococcus haemolyticus lipase: biochemical properties, substrate specificity and gene cloning - Oh_1999_FEMS.Microbiol.Lett_179_385
Author(s) : Oh B , Kim H , Lee J , Kang S , Oh T
Ref : FEMS Microbiology Letters , 179 :385 , 1999
Abstract : Lipase of Staphylococcus haemolyticus L62 was purified from culture supernatant and its molecular mass was estimated to be 45 kDa by SDS-PAGE. Its optimum temperature and pH for the hydrolysis of olive oil was 28 degrees C and pH 8.5, respectively. The enzyme was stable up to 50 degrees C in the presence of Ca(2+)and over the pH range 5-11. It had high hydrolytic activity against tributyrin, tripropionin, and trimyristin among various triglycerides. The gene encoding the lipase was cloned in Escherichia coli. Sequence analysis showed an open reading frame of 2136 bp, which encodes a preproenzyme of 711 amino acids. The preproenzyme is composed of a signal peptide (60 aa), a pro-peptide (259 aa), and a mature enzyme (392 aa). The mature enzyme has 49-67% amino acid sequence homology with other staphylococcal lipases.
ESTHER : Oh_1999_FEMS.Microbiol.Lett_179_385
PubMedSearch : Oh_1999_FEMS.Microbiol.Lett_179_385
PubMedID: 10518741
Gene_locus related to this paper: staha-Q9RGZ6

Title : Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana - Lin_1999_Nature_402_761
Author(s) : Lin X , Kaul S , Rounsley S , Shea TP , Benito MI , Town CD , Fujii CY , Mason T , Bowman CL , Barnstead M , Feldblyum TV , Buell CR , Ketchum KA , Lee J , Ronning CM , Koo HL , Moffat KS , Cronin LA , Shen M , Pai G , Van Aken S , Umayam L , Tallon LJ , Gill JE , Adams MD , Carrera AJ , Creasy TH , Goodman HM , Somerville CR , Copenhaver GP , Preuss D , Nierman WC , White O , Eisen JA , Salzberg SL , Fraser CM , Venter JC
Ref : Nature , 402 :761 , 1999
Abstract : Arabidopsis thaliana (Arabidopsis) is unique among plant model organisms in having a small genome (130-140 Mb), excellent physical and genetic maps, and little repetitive DNA. Here we report the sequence of chromosome 2 from the Columbia ecotype in two gap-free assemblies (contigs) of 3.6 and 16 megabases (Mb). The latter represents the longest published stretch of uninterrupted DNA sequence assembled from any organism to date. Chromosome 2 represents 15% of the genome and encodes 4,037 genes, 49% of which have no predicted function. Roughly 250 tandem gene duplications were found in addition to large-scale duplications of about 0.5 and 4.5 Mb between chromosomes 2 and 1 and between chromosomes 2 and 4, respectively. Sequencing of nearly 2 Mb within the genetically defined centromere revealed a low density of recognizable genes, and a high density and diverse range of vestigial and presumably inactive mobile elements. More unexpected is what appears to be a recent insertion of a continuous stretch of 75% of the mitochondrial genome into chromosome 2.
ESTHER : Lin_1999_Nature_402_761
PubMedSearch : Lin_1999_Nature_402_761
PubMedID: 10617197
Gene_locus related to this paper: arath-At2g45610 , arath-AT2G03550 , arath-AT2G05260 , arath-AT2G12480 , arath-At2g15230 , arath-At2g18360 , arath-At2g19550 , arath-At2g19620 , arath-At2g24280 , arath-AT2G24320 , arath-At2g26740 , arath-At2g26750 , arath-SCP51 , arath-AT2G36290 , arath-At2g42450 , arath-AT2G42690 , arath-AT2G44970 , arath-At2g47630 , arath-AT3g62590 , arath-CGEP , arath-F12L6.6 , arath-F12L6.7 , arath-F12L6.8 , arath-At3g50790 , arath-MES6 , arath-MES7 , arath-MES4 , arath-MES8 , arath-MES2 , arath-MES3 , arath-MES1 , arath-o80731 , arath-pip , arath-PLA11 , arath-PLA13 , arath-PLA16 , arath-PLA19 , arath-q84w08 , arath-SCP8 , arath-SCP9 , arath-SCP10 , arath-SCP11 , arath-SCP12 , arath-SCP13 , arath-SCP23 , arath-SCP26 , arath-SCP28 , arath-SCP46 , arath-T26B15.8 , arath-SCP22 , arath-SFGH , arath-MES19

Title : Insecticide Resistance in the Tobacco Cutworm, Spodoptera litura (Fabricius) (Lepidoptera: Noctuiae) - Yonggyun_1998_J.Asia.Pac.Entomol_1_115
Author(s) : Yonggyun K , Cho JR , Lee J , Kang S , Han SC , Hong KJ , Kim HS , Yoo JK , Lee JO
Ref : Journal of Asia-Pacific Entomology , 1 :115 , 1998
Abstract : Field populations of the tobacco cutworm, Spodoptera litura (Fabricius), showed resistance to commonly used insecticides. Development of resistance in the field populations to pyrethroids (cypermethrin, deltamethrin, ethofenprox, ethofenprox+PAP and fenvalerate) ranged from 100- to 2,700-fold, showing the highest resistance level to deltamethrin. Resistance to organophosphorus insecticides (chlorpyrifos, chlorpyrifos-methyl, EPN and pyraclofos) ranged from 2- to 32-fold with the highest level to chlorpyrifos. Resistance to carbamates (carbaryl and methomyl) ranged from 4- to 80-fold with the higher level to carbaryl. Detoxifying enzyme assays revealed that esterase and glutathione S-transferase activities were varied from 2- to 6-fold among the field populations. In addition, the bimolecular rate constants for inhibition of acetylcholinesterase by dichlorvos, eserine and monocrotophos showed 1.5-, 4.5- and 4.3-fold differences, respectively, between two different field populations. These results indicated that the broad spectrum of insecticide resistance observed in the filed populations was due to multiple resistance mechanisms, including increased detoxification of these insecticides and insensitive acetyl-cholinesterase.
ESTHER : Yonggyun_1998_J.Asia.Pac.Entomol_1_115
PubMedSearch : Yonggyun_1998_J.Asia.Pac.Entomol_1_115

Title : Age Variation in Insecticide Susceptibility and Biochemical Changes of Beet Armyworm, Spodoptera exigua (Hubner) - Kim_1998_J.Asia.Pac.Entomol_1_109
Author(s) : Kim Y , Lee J , Kang S , Han S
Ref : Journal of Asia-Pacific Entomology , 1 :109 , 1998
Abstract : The susceptibility of Spodoptera exigua (Hubner) to bifenthrin and chlorpyrifosmethyl in relation to larval development was investigated. Increased tolerances to these insecticides were associated with increasing larval instars. The insecticide tolerance increased linealy with larval body weights in bifenthrin but did exponentially in chlorpyrifos-methyl. Esterase (EST), acetylcholinesterase (AChE), and glutathione S-transferase(GST) of different larval ages were analyzed to elucidate variation of insecticide susceptibilities according to larval development within a population. Total EST activity increased linearly with body weights though the specific activities were not varied among ages. Both total and specific activity changes of GST, however, surpassed the rates of body weight gains as the larvae developed. AChE activities decreased significantly with larval development. This change of AChE activities was due to the developmental change of its catalytic function. The fifth instar larvae had the lowest catalytic capacity: the highest Km(187.39muM) and the lowest Vmax (0.58 nM/min/mug). Therefore, different insecticide tolerance of S. exigua according to larval ages can be explained by both enhanced detoxification enzymes and altered AchE.
ESTHER : Kim_1998_J.Asia.Pac.Entomol_1_109
PubMedSearch : Kim_1998_J.Asia.Pac.Entomol_1_109

Title : Genome-wide search for asthma susceptibility loci in a founder population. The Collaborative Study on the Genetics of Asthma - Ober_1998_Hum.Mol.Genet_7_1393
Author(s) : Ober C , Cox NJ , Abney M , Di Rienzo A , Lander ES , Changyaleket B , Gidley H , Kurtz B , Lee J , Nance M , Pettersson A , Prescott J , Richardson A , Schlenker E , Summerhill E , Willadsen S , Parry R
Ref : Hum Mol Genet , 7 :1393 , 1998
Abstract : Founder populations offer many advantages for mapping genetic traits, particularly complex traits that are likely to be genetically heterogeneous. To identify genes that influence asthma and asthma-associated phenotypes, we conducted a genome-wide screen in the Hutterites, a religious isolate of European ancestry. A primary sample of 361 individuals and a replication sample of 292 individuals were evaluated for asthma phenotypes according to a standardized protocol. A genome-wide screen has been completed using 292 autosomal and three X-Y pseudoautosomal markers. Using the semi-parametric likelihood ratio chi2 test and the transmission-disequilibrium test, we identified 12 markers in 10 regions that showed possible linkage to asthma or an associated phenotype (likelihood ratio P < 0.01). Markers in four regions (5q23-31, 12q15-24.1, 19q13 and 21q21) showed possible linkage in both the primary and replication samples and have also shown linkage to asthma phenotypes in other samples; two adjacent markers in one additional region (3p24.2-22) showing possible linkage is reported for the first time in the Hutterites. The results suggest that even in founder populations with a relatively small number of independent genomes, susceptibility alleles at many loci may influence asthma phenotypes and that these susceptibility alleles are likely to be common polymorphisms in the population.
ESTHER : Ober_1998_Hum.Mol.Genet_7_1393
PubMedSearch : Ober_1998_Hum.Mol.Genet_7_1393
PubMedID: 9700192
Gene_locus related to this paper: human-PLA2G7

Title : A specific protein carboxyl methylesterase that demethylates phosphoprotein phosphatase 2A in bovine brain - Lee_1996_Proc.Natl.Acad.Sci.U.S.A_93_6043
Author(s) : Lee J , Chen Y , Tolstykh T , Stock J
Ref : Proc Natl Acad Sci U S A , 93 :6043 , 1996
Abstract : Phosphoprotein phosphatase 2A (PP2A) is one of the four major protein serine/threonine phosphatases found in all eukaryotic cells. We have shown that the 36-kDa catalytic subunit of PP2A is carboxyl methylated in eukaryotic cells, and we have previously identified and purified a novel methyltransferase (MTase) that is responsible for this modification. Here, we describe a novel protein carboxyl methyl-esterase (MEase) from bovine brain that demethylates PP2A. The enzyme has been purified to homogeneity as a monomeric 46-kDa soluble protein. The MEase is highly specific for PP2A. It does not catalyze the demethylation of other protein or peptide methylesters. Moreover, MEase activity is dramatically inhibited by nanomolar concentrations of okadaic acid, a specific inhibitor of PP2A. From these results, we conclude that PP2A methylation is controlled by two specific enzymes, a MTase and a MEase. Since PP2A methylation is highly conserved in eukaryotes ranging from human to yeast, it is likely that this system plays an important role in phosphatase regulation.
ESTHER : Lee_1996_Proc.Natl.Acad.Sci.U.S.A_93_6043
PubMedSearch : Lee_1996_Proc.Natl.Acad.Sci.U.S.A_93_6043
PubMedID: 8650216
Gene_locus related to this paper: human-PPME1

Title : Molecular cloning of cDNA coding for the gamma subunit of Torpedo acetylcholine receptor - Ballivet_1982_Proc.Natl.Acad.Sci.U.S.A_79_4466
Author(s) : Ballivet M , Patrick J , Lee J , Heinemann S
Ref : Proc Natl Acad Sci U S A , 79 :4466 , 1982
Abstract : From the electric organ of Torpedo californica, we purified mRNA that, when translated in vitro, produces polypeptides immunoprecipitable by antibodies against purified acetylcholine receptor. A novel cloning system [Okayama, H. & Berg, P. (1982) Mol. Cell. Biol. 2, 161-170] was used to produce a cDNA library from this mRNA. This library contained clones with receptor sequences identified by differential hybridization and hybridization-selection. We describe a clone of 2,030 base pairs with sequences appropriate for the amino-terminal amino acids of the gamma subunit of acetylcholine receptor. This clone contains 82 bases 5' of the codon for the amino-terminal amino acid of the mature protein. A portion of this sequence codes for a methionine followed by a 16-amino acid polypeptide that is contiguous to the amino-terminal amino acid of the mature protein and that has the characteristics of a leader peptide. The cDNA insert hybridizes to a 2,100-base RNA present in electric organ but not in the brain of T. californica.
ESTHER : Ballivet_1982_Proc.Natl.Acad.Sci.U.S.A_79_4466
PubMedSearch : Ballivet_1982_Proc.Natl.Acad.Sci.U.S.A_79_4466
PubMedID: 6956875