Kim HJ


Full name : Kim Hye-Jin

First name : Hye-Jin

Mail : Division of Applied Life Science (BK21 Program), IALS, Gyeongsang National University, Jinju 660-701

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Country : Korea

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References (69)

Title : Balance-directed protein engineering of IsPETase enhances both PET hydrolysis activity and thermostability - Lee_2023_bioRxiv__
Author(s) : Lee SH , Seo H , Hong H , Park J , Ki D , Kim M , Kim HJ , Kim KJ
Ref : Biorxiv , : , 2023
Abstract : A mesophilic PETase from Ideonella sakaiensis (IsPETase) has been shown to exhibit high PET hydrolysis activity, but its low thermostability limits its industrial applications. We herein developed an engineering strategy for IsPETase to enhance PET hydrolysis activity, thermostability, and protein folding of the enzyme. Balance-directed Z1-PETase variant outperforms the stability-directed Z2-PETase variant under both mesophilic and thermophilic conditions, although Z2-PETase exhibits higher thermostability than Z1-PETase. The Z1-PETase is also superior to Fast-PETase, Dura-PETase, and LC-CICCG in terms of depolymerization rate regardless of temperature conditions we tested. Thus, maintaining a balance between PET hydrolysis activity and thermostability is essential for the developmentof high-performance PET hydrolases. In a pH-stat bioreactor, Z1-PETase depolymerized >90% of both transparent and colored post-consumer PET powders within 24 and 8 hours at 40C and 55C, respectively, demonstrating that the balance-directed IsPETase variant produced herein may be applicable in the bio-recycling of PET.
ESTHER : Lee_2023_bioRxiv__
PubMedSearch : Lee_2023_bioRxiv__
Gene_locus related to this paper: idesa-peth

Title : Three-directional engineering of IsPETase with enhanced protein yield, activity, and durability - Lee_2023_J.Hazard.Mater_459_132297
Author(s) : Lee SH , Seo H , Hong H , Park J , Ki D , Kim M , Kim HJ , Kim KJ
Ref : J Hazard Mater , 459 :132297 , 2023
Abstract : The mesophilic PETase from Ideonella sakaiensis (IsPETase) has been shown to exhibit high PET hydrolysis activity, but its low stability limits its industrial applications. Here, we developed a variant, Z1-PETase, with enhanced soluble protein yield and durability while maintaining or improving activity at lower temperatures. The selected Z1-PETase not only exhibited a 20-fold improvement in soluble protein yield compared to the previously engineered IsPETase(S121E/D186H/S242T/N246D) (4p) variant, but also demonstrated a 30% increase in low-temperature activity at 40 degreesC, along with an 11 degreesC increase in its Tm(D) value. The PET depolymerization test across a temperature range low to high (30-70 degreesC) confirmed that Z1-PETase exhibits high accessibility of mesophilic PET hydrolase and rapid depolymerizing rate at higher temperature in accordance with the thermal behaviors of polymer and enzyme. Additionally, structural interpretation indicated that the stabilization of specific active site loops in Z1-PETase contributes to enhanced thermostability without adversely impacting enzymatic activity. In a pH-stat bioreactor, Z1-PETase depolymerized > 90% of both transparent and colored post-consumer PET powders within 24 and 8 h at 40 degreesC and 55 degreesC, respectively, demonstrating that the utility of this IsPETase variant in the bio-recycling of PET.
ESTHER : Lee_2023_J.Hazard.Mater_459_132297
PubMedSearch : Lee_2023_J.Hazard.Mater_459_132297
PubMedID: 37595467
Gene_locus related to this paper: idesa-peth

Title : Maximization of 3-hydroxyhexanoate fraction in poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) using lauric acid with engineered Cupriavidus necator H16 - Oh_2023_Int.J.Biol.Macromol_256_128376
Author(s) : Oh SJ , Choi TR , Kim HJ , Shin N , Hwang JH , Bhatia SK , Kim W , Yeon YJ , Yang YH
Ref : Int J Biol Macromol , 256 :128376 , 2023
Abstract : As polyhydroxybutyrate (P(3HB)) was struggling with mechanical properties, efforts have been directed towards increasing mole fraction of 3-hydroxyhexanoate (3HHx) in P(3HB-co-3HHx) to improve the properties of polyhydroxyalkanoates (PHAs). Although genetic modification had significant results, there were several issues related to cell growth and PHA production by deletion of PHA synthetic genes. To find out easier strategy for high 3HHx mole fraction without gene deletion, Cupriavidus necator H16 containing phaC2(Ra)-phaA(Cn)-phaJ1(Pa) was examined with various oils resulting that coconut oil gave the highest 3HHx mole fraction. When fatty acid composition analysis with GC-MS was applied, coconut oil was found to have very different composition from other vegetable oil containing very high lauric acid (C12) content. To find out specific fatty acid affecting 3HHx fraction, different fatty acids from caproic acid (C6) to stearic acid (C18) was evaluated and the 3HHx mole fraction was increased to 26.5 +/- 1.6 % using lauric acid. Moreover, the 3HHx mole fraction could be controlled from 9 % to 31.1 % by mixing bean oil and lauric acid with different ratios. Produced P(3HB-co-3HHx) exhibited higher molecular than P(3HB-co-3HHx) from phaB-deletion mutant. This study proposes another strategy to increase 3HHx mole fraction with easier way by modifying substrate composition without applying deletion tools.
ESTHER : Oh_2023_Int.J.Biol.Macromol_256_128376
PubMedSearch : Oh_2023_Int.J.Biol.Macromol_256_128376
PubMedID: 38007029

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 : Synthesis and Biological Evaluation of O(6)-Aminoalkyl-Hispidol Analogs as Multifunctional Monoamine Oxidase-B Inhibitors towards Management of Neurodegenerative Diseases - Hassan_2023_Antioxidants.(Basel)_12_
Author(s) : Hassan AHE , Kim HJ , Park K , Choi Y , Moon S , Lee CH , Kim YJ , Cho SB , Gee MS , Lee D , Park JH , Lee JK , Ryu JH , Park KD , Lee YS
Ref : Antioxidants (Basel) , 12 : , 2023
Abstract : Oxidative catabolism of monoamine neurotransmitters by monoamine oxidases (MAOs) produces reactive oxygen species (ROS), which contributes to neuronal cells' death and also lowers monoamine neurotransmitter levels. In addition, acetylcholinesterase activity and neuroinflammation are involved in neurodegenerative diseases. Herein, we aim to achieve a multifunctional agent that inhibits the oxidative catabolism of monoamine neurotransmitters and, hence, the detrimental production of ROS while enhancing neurotransmitter levels. Such a multifunctional agent might also inhibit acetylcholinesterase and neuroinflammation. To meet this end goal, a series of aminoalkyl derivatives of analogs of the natural product hispidol were designed, synthesized, and evaluated against both monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B). Promising MAO inhibitors were further checked for the inhibition of acetylcholinesterase and neuroinflammation. Among them, compounds 3aa and 3bc were identified as potential multifunctional molecules eliciting submicromolar selective MAO-B inhibition, low-micromolar AChE inhibition, and the inhibition of microglial PGE(2) production. An evaluation of their effects on memory and cognitive impairments using a passive avoidance test confirmed the in vivo activity of compound 3bc, which showed comparable activity to donepezil. In silico molecular docking provided insights into the MAO and acetylcholinesterase inhibitory activities of compounds 3aa and 3bc. These findings suggest compound 3bc as a potential lead for the further development of agents against neurodegenerative diseases.
ESTHER : Hassan_2023_Antioxidants.(Basel)_12_
PubMedSearch : Hassan_2023_Antioxidants.(Basel)_12_
PubMedID: 37237899

Title : Revealing the key gene involved in bioplastic degradation from superior bioplastic degrader Bacillus sp. JY35 - Kim_2023_Int.J.Biol.Macromol_244_125298
Author(s) : Kim SH , Cho JY , Nara S , Hwang JH , Kim HJ , Oh SJ , Bhatia SK , Yun J , Lee SH , Yang YH
Ref : Int J Biol Macromol , 244 :125298 , 2023
Abstract : The use of bioplastics, which can alleviate environmental pollution caused by non-degradable bioplastics, has received attention. As there are many types of bioplastics, method that can treat them simultaneously is important. Therefore, Bacillus sp. JY35 which can degrade different types of bioplastics, was screened in previous study. Most types of bioplastics, such as polyhydroxybutyrate (PHB), (P(3HB-co-4HB)), poly(butylene adipate-co-terephthalate) (PBAT), polybutylene succinate (PBS), and polycaprolactone (PCL), can be degraded by esterase family enzymes. To identify the genes that are involved in bioplastic degradation, analysis with whole-genome sequencing was performed. Among the many esterase enzymes, three carboxylesterase and one triacylglycerol lipase were identified and selected based on previous studies. Esterase activity using p-nitrophenyl substrates was measured, and the supernatant of JY35_02679 showed strong emulsion clarification activity compared with others. In addition, when recombinant E. coli was applied to the clear zone test, only the JY35_02679 gene showed activity in the clear zone test with bioplastic containing solid cultures. Further quantitative analysis showed 100 % PCL degradation at 7 days and 45.7 % PBS degradation at 10 days. We identified a gene encoding a bioplastic-degrading enzyme in Bacillus sp. JY35 and successfully expressed the gene in heterologous E. coli, which secreted esterases with broad specificity.
ESTHER : Kim_2023_Int.J.Biol.Macromol_244_125298
PubMedSearch : Kim_2023_Int.J.Biol.Macromol_244_125298
PubMedID: 37315675
Gene_locus related to this paper: bacpu-q6rsn0

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 : Codium fragile Suppresses PM(2.5)-Induced Cognitive Dysfunction by Regulating Gut-Brain Axis via TLR-4\/MyD88 Pathway - Kim_2023_Int.J.Mol.Sci_24_12898
Author(s) : Kim TY , Kim JM , Lee HL , Go MJ , Joo SG , Kim JH , Lee HS , Lee DY , Kim HJ , Heo HJ
Ref : Int J Mol Sci , 24 :12898 , 2023
Abstract : This study was conducted to evaluate the cognitive dysfunction improvement effect of aqueous extract of Codium fragile (AECF) by regulating the imbalance of the gut-brain axis in chronic particulate matter (PM)(2.5)-exposed mice. The physiological compounds of AECF were identified as hexadecanamide, oleamide, octadecanamide, stearidonic acid, and linolenic acid by the ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC Q-TOF MS(E)) analysis. To evaluate the effect of PM(2.5) on the antioxidant system, superoxide dismutase (SOD) contents, reduced glutathione (GSH) contents, and malondialdehyde (MDA) contents were measured in colon and brain tissues. AECF significantly ameliorated the imbalance of the antioxidant systems. Also, AECF improved intestinal myeloperoxidase (MPO) activity, the abundance of the gut microbiome, short-chain fatty acids (SCFAs) contents, and tight junction protein expression against PM(2.5)-induced damage. In addition, AECF prevented PM(2.5)-induced inflammatory and apoptotic expression via the toll-like receptor-4 (TLR-4)/myeloid differentiation primary response 88 (MyD88) pathway in colon and brain tissues. Additionally, AECF enhanced the mitochondrial function, including the mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) contents in brain tissues. Furthermore, AECF regulated the cholinergic system, such as acetylcholine (ACh) contents, acetylcholinesterase (AChE) activity, and protein expression levels of AChE and choline acetyltransferase (ChAT) in brain tissues. To evaluate the effect of cognitive dysfunction caused by PM(2.5)-induced intestinal dysfunction, behavior tests such as Y-maze, passive avoidance, and Morris water maze tests were performed. From the results of the behavior tests, AECF ameliorated spatial learning and memory, short-term memory, and long-term learning and memory function. This study confirmed that AECF reduced PM(2.5)-induced cognitive dysfunction by regulating gut microbiome and inflammation, apoptosis, and mitochondrial function by enhancing the gut-brain axis. Based on these results, this study suggests that AECF, which contains fatty acid amides, might be a potential material for ameliorating PM(2.5)-induced cognitive dysfunction via gut-brain axis improvement.
ESTHER : Kim_2023_Int.J.Mol.Sci_24_12898
PubMedSearch : Kim_2023_Int.J.Mol.Sci_24_12898
PubMedID: 37629080

Title : Photobiomodulation improves the synapses and cognitive function and ameliorates epileptic seizure by inhibiting downregulation of Nlgn3 - Hong_2023_Cell.Biosci_13_8
Author(s) : Hong N , Kim HJ , Kang K , Park JO , Mun S , Kim HG , Kang BH , Chung PS , Lee MY , Ahn JC
Ref : Cell Biosci , 13 :8 , 2023
Abstract : BACKGROUND: Temporal lobe epilepsy (TLE) remains one of the most drug-resistant focal epilepsies. Glutamate excitotoxicity and neuroinflammation which leads to loss of synaptic proteins and neuronal death appear to represent a pathogen that characterizes the neurobiology of TLE. Photobiomodulation (PBM) is a rapidly growing therapy for the attenuation of neuronal degeneration harboring non-invasiveness benefits. However, the detailed effects of PBM on excitotoxicity or neuroinflammation remain unclear. We investigated whether tPBM exerts neuroprotective effects on hippocampal neurons in epilepsy mouse model by regulating synapse and synapse-related genes. METHODS: In an in vitro study, we performed imaging analysis and western blot in primary hippocampal neurons from embryonic (E17) rat pups. In an in vivo study, RNA sequencing was performed to identify the gene regulatory by PBM. Histological stain and immunohistochemistry analyses were used to assess synaptic connections, neuroinflammation and neuronal survival. Behavioral tests were used to evaluate the effects of PBM on cognitive functions. RESULTS: PBM was upregulated synaptic connections in an in vitro. In addition, it was confirmed that transcranial PBM reduced synaptic degeneration, neuronal apoptosis, and neuroinflammation in an in vivo. These effects of PBM were supported by RNA sequencing results showing the relation of PBM with gene regulatory networks of neuronal functions. Specifically, Nlgn3 showed increase after PBM and silencing the Nlgn3 reversed the positive effect of PBM in in vitro. Lastly, behavioral alterations including hypoactivity, anxiety and impaired memory were recovered along with the reduction of seizure score in PBM-treated mice. CONCLUSIONS: Our findings demonstrate that PBM attenuates epileptic excitotoxicity, neurodegeneration and cognitive decline induced by TLE through inhibition of the Nlgn3 gene decrease induced by excitotoxicity.
ESTHER : Hong_2023_Cell.Biosci_13_8
PubMedSearch : Hong_2023_Cell.Biosci_13_8
PubMedID: 36635704

Title : A Multinational, Multicenter, Randomized, Double-Blind, Active Comparator, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Donepezil Transdermal Patch in Patients With Alzheimer's Disease - Han_2022_J.Clin.Neurol_18_428
Author(s) : Han HJ , Park MY , Park KW , Park KH , Choi SH , Kim HJ , Yang DW , Ebenezer E , Yang YH , Kewalram GM , Han SH
Ref : J Clin Neurol , 18 :428 , 2022
Abstract : BACKGROUND AND PURPOSE: Oral administration of cholinesterase inhibitors is often associated with adverse gastrointestinal effects, and so developing an alternative administration route, such as transdermal, is urgently needed. The primary objective of this study was to determine the efficacy and safety of the IPI-301 donepezil transdermal patch compared with donepezil tablets (control) in mild-to-moderate probable Alzheimer's disease (AD). METHODS: This prospective, randomized, double-blind, double-dummy, two-arm parallel, multicenter trial included 399 patients, among whom 303 completed the trial. For randomization, the patients were stratified based on previous treatment and donepezil dose; patients in each stratum were randomized to the test and control groups at a 1:1 ratio. RESULTS: The difference between the control group and the IPI-301 group, quantified as the Hodges-Lehmann estimate of location shift, was 0.00 (95% confidence interval: -1.00 to 1.33), with an upper limit of less than 2.02. The change in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) score differed significantly between the IPI-301 and control groups (p=0.02). However, the changes in the full-itemized ADCS-ADL scores at week 24 did not differ significantly between the two groups. There were no differences between the two groups regarding the scores for the Clinician Interview-Based Impression of Change (p=0.9097), Mini-Mental State Examination (p=0.7018), Neuropsychiatric Inventory (p=0.7656), or Clinical Dementia Rating (p=0.9990). Adverse events, vital signs, and laboratory test results were comparable between the two groups. CONCLUSIONS: IPI-301 was safe and efficacious in improving cognitive function in patients with mild-to-moderate AD.
ESTHER : Han_2022_J.Clin.Neurol_18_428
PubMedSearch : Han_2022_J.Clin.Neurol_18_428
PubMedID: 35796268

Title : Patterns of dementia treatment in older adults with Parkinson's disease using nationwide medical claims data - Yoon_2022_BMC.Geriatr_22_353
Author(s) : Yoon B , Kim HJ
Ref : BMC Geriatr , 22 :353 , 2022
Abstract : BACKGROUND: Dementia is a common feature in Parkinson's disease (PD); however, data on dementia treatment patterns in patients with PD are scarce. This study aimed to evaluate the incidence of dementia in individuals with PD and to describe the dementia treatment patterns in the Korean elderly population. METHODS: We conducted a retrospective population-based cohort study using data obtained from the Korean National Health Insurance Service-Senior Cohort (NHIS-SC) database. The dataset comprised more than 500,000 health insurance beneficiaries from January 1, 2002 to December 31, 2015. We estimated the incidence of patients newly diagnosed with dementia during this observational period, compared patient demographics, and analyzed the exposure to anticholinergic drugs among PD patients with (PD + D) and without (PD-D) dementia. Furthermore, the duration to dementia diagnosis and patterns of dementia treatment were evaluated. RESULTS: A cohort of 28,537 patients aged 60 years or older who were diagnosed with PD by the NHIS was established. Within this cohort, 8620 patients were eligible study participants according to strict inclusion/exclusion criteria. Of these individuals, 3879 (45.0%) patients were newly diagnosed with dementia; the incidence of dementia in PD was 15.2 per 1000 person-years. The proportion of women was higher in the PD + D (64.6%) than the PD-D group (58.2%) (P < 0.001); furthermore, the use of anticholinergic medication was greater in PD + D (37.6%) than in PD-D (24.0%) patients. The incidence curves for dementia over time were the steepest during the first year and decreased every year thereafter. Approximately 60% of PD patients were diagnosed with dementia during the first 3 years. Regarding the use of anti-dementia drugs, 2539 (65.5%) of 3879 PD + D were prescribed medication. During the observation period, 1799 (70.9%) patients were prescribed only one type of anti-dementia drug. In this monotherapy group, the most commonly prescribed medication was donepezil (1313[73.0%]), followed by rivastigmine (capsule and patch; 246[13.7%]), memantine (187[10.4%]), and galantamine (53[2.9%]). CONCLUSIONS: In Korea, dementia was observed to occur relatively soon after the diagnosis of PD. Anti-dementia medication was prescribed to approximately 66% of PD + D patients, with the majority receiving donepezil as monotherapy.
ESTHER : Yoon_2022_BMC.Geriatr_22_353
PubMedSearch : Yoon_2022_BMC.Geriatr_22_353
PubMedID: 35459128

Title : Scalable Functionalization of Polyaniline-Grafted rGO Field-Effect Transistors for a Highly Sensitive Enzymatic Acetylcholine Biosensor - Park_2022_Biosensors.(Basel)_12_
Author(s) : Park D , Lee D , Kim HJ , Yoon DS , Hwang KS
Ref : Biosensors (Basel) , 12 : , 2022
Abstract : For decades, acetylcholine (Ach) has been considered a critical biomarker for several degenerative brain diseases, including Alzheimer's, Parkinson's disease, Huntington's disease, and schizophrenia. Here, we propose a wafer-scale fabrication of polyaniline (PAni)-grafted graphene-based field-effect transistors (PGFET) and their biosensing applications for highly sensitive and reliable real-time monitoring of Ach in flow configuration. The grafted PAni provides suitable electrostatic binding sites for enzyme immobilization and enhances the pH sensitivity (2.68%/pH), compared to that of bare graphene-FET (1.81%/pH) for a pH range of 3-9 without any pH-hysteresis. We further evaluated the PGFET's sensing performance for Ach detection with a limit of detection at the nanomolar level and significantly improved sensitivity (~103%) in the concentration range of 108 nM to 2 mM. Moreover, the PGFET exhibits excellent selectivity against various interferences, including glucose, ascorbic acid, and neurotransmitters dopamine and serotonin. Finally, we investigated the effects of an inhibitor (rivastigmine) on the AchE activity of the PGFET. From the results, we demonstrated that the PGFET has great potential as a real-time drug-screening platform by monitoring the inhibitory effects on enzymatic activity.
ESTHER : Park_2022_Biosensors.(Basel)_12_
PubMedSearch : Park_2022_Biosensors.(Basel)_12_
PubMedID: 35624580

Title : Immature Persimmon Suppresses Amyloid Beta (Abeta) Mediated Cognitive Dysfunction via Tau Pathology in ICR Mice - Yoo_2021_Curr.Issues.Mol.Biol_43_405
Author(s) : Yoo SK , Kim JM , Lee U , Kang JY , Park SK , Han HJ , Park HW , Kim HJ , Kim CW , Kim MJ , Heo HJ
Ref : Curr Issues Mol Biol , 43 :405 , 2021
Abstract : This study confirmed the ameliorating effect of immature persimmon (Diospyros kaki) ethanolic extract (IPEE) on neuronal cytotoxicity in amyloid beta (Abeta)(1-42)-induced ICR mice. The administration of IPEE ameliorated the cognitive dysfunction in Abeta(1-42)-induced mice by improving the spatial working memory, the short-term and long-term memory functions. IPEE protected the cerebral cholinergic system, such as the acetylcholine (ACh) level and acetylcholinesterase (AChE) activity, and antioxidant system, such as the superoxide dismutase (SOD), reduced glutathione (GSH) and malondialdehyde (MDA) contents. In addition, mitochondrial dysfunction against Abeta(1-42)-induced toxicity was reduced by regulating the reactive oxygen species (ROS), mitochondrial membrane potential and ATP contents. In addition, IPEE regulated the expression levels of tau signaling, such as TNF-alpha, p-JNK, p-Akt, p-GSK3beta, p-tau, p-NF-kappaB, BAX and caspase 3. Finally, gallic acid, ellagic acid and quercetin 3-O-(6''-acetyl-glucoside) were identified as the physiological compounds of IPEE using ultra-performance liquid chromatography ion mobility separation quadrupole time-of-flight/tandem mass spectrometry (UPLC IMS Q-TOF/MS(2)).
ESTHER : Yoo_2021_Curr.Issues.Mol.Biol_43_405
PubMedSearch : Yoo_2021_Curr.Issues.Mol.Biol_43_405
PubMedID: 34205542

Title : Ecklonia cava Attenuates PM(2.5)-Induced Cognitive Decline through Mitochondrial Activation and Anti-Inflammatory Effect - Park_2021_Mar.Drugs_19_
Author(s) : Park SK , Kang JY , Kim JM , Kim HJ , Heo HJ
Ref : Mar Drugs , 19 : , 2021
Abstract : To evaluate the effects of Ecklonia cava (E. cava) on ambient-pollution-induced neurotoxicity, we used a mouse model exposed to particulate matter smaller than 2.5 microm in aerodynamic diameter (PM(2.5)). The intake of water extract from E. cava (WEE) effectively prevented the learning and memory decline. After a behavioral test, the toll-like receptor (TLR)-4-initiated inflammatory response was confirmed by PM(2.5) exposure in the lung and brain tissues, and the WEE was regulated through the inhibition of nuclear factor-kappa B (NF-kappaB)/inflammasome formation signaling pathway and pro-inflammatory cytokines (IL-6 and IFN-gamma). The WEE also effectively improved the PM(2.5)-induced oxidative damage of the lungs and brain through the inhibition of malondialdehyde (MDA) production and the activation of mitochondrial activity (mitochondrial ROS content, mitochondria membrane potential (MMP), adenosine triphosphate (ATP) content, and mitochondria-mediated apoptotic molecules). In particular, the WEE regulated the cognition-related proteins (a decreased amyloid precursor protein (APP) and p-Tau, and an increased brain-derived neurotrophic factor (BDNF)) associated with PM(2.5)-induced cognitive dysfunction. Additionally, the WEE prevented the inactivation of acetylcholine (ACh) synthesis and release as a neurotransmitter by regulating the acetylcholinesterase (AChE) activity, choline acetyltransferase (ChAT), and ACh receptor (AChR)-alpha3 in the brain tissue. The bioactive compounds of the WEE were detected as the polysaccharide (average Mw; 160.13 kDa) and phenolic compounds including 2'-phloroeckol.
ESTHER : Park_2021_Mar.Drugs_19_
PubMedSearch : Park_2021_Mar.Drugs_19_
PubMedID: 33673531

Title : RORalpha regulates hepatic lipolysis by inducing transcriptional expression of PNPLA3 in mice - Han_2020_Mol.Cell.Endocrinol__111122
Author(s) : Han YH , Kim HJ , Lee MO
Ref : Mol Cell Endocrinol , :111122 , 2020
Abstract : Nonalcoholic fatty liver diseases (NAFLDs) are characterized by excessive triacylglycerol (TAG) accumulation in the liver which contributes to hepatocyte dysfunction, inflammation, and fibrosis. Patatin-like phospholipase domain-containing 3 (PNPLA3; also known as adiponutrin) has emerged as an important enzyme leading to hepatic TAG hydrolysis. Because the I148M substitution in the PNPLA3 gene markedly reduces hepatic TAG hydrolase activity, this genetic variation is strongly associated with increased hepatic TAG in the full spectrum of NAFLDs. The Retinoic acid-related orphan receptor alpha (RORalpha) regulates various target genes related to lipid metabolism. Here, we investigated the role of RORalpha on PNPLA3-mediated hepatic lipid hydrolysis. With blockade of lipid esterification and beta-oxidation, RORalpha enhanced TAG hydrolysis, resulting in increased free glycerol levels. We found a putative RORalpha response element on the upstream of PNPLA3 gene that was activated by RORalpha. Furthermore, the inhibitory action of cJUN on the RORalpha/PNPLA3 axis was enhanced under lipid stress and contributed to hepatic lipid accumulation. In summary, we showed for the first time that RORalpha activates the transcription of PNPLA3, which suggests that RORalpha and its ligands represent potential precision therapeutic approaches for NAFLDs.
ESTHER : Han_2020_Mol.Cell.Endocrinol__111122
PubMedSearch : Han_2020_Mol.Cell.Endocrinol__111122
PubMedID: 33347955

Title : Structural and Biophysical Analyses of Human N-Myc Downstream-Regulated Gene 3 (NDRG3) Protein - Kim_2020_Biomolecules_10_
Author(s) : Kim KR , Kim KA , Park JS , Jang JY , Choi Y , Lee HH , Lee DC , Park KC , Yeom YI , Kim HJ , Han BW
Ref : Biomolecules , 10 : , 2020
Abstract : The N-Myc downstream-regulated gene (NDRG) family belongs to the alpha/beta-hydrolase fold and is known to exert various physiologic functions in cell proliferation, dierentiation, and hypoxia-induced cancer metabolism. In particular, NDRG3 is closely related to proliferation and migration of prostate cancer cells, and recent studies reported its implication in lactate-triggered hypoxia responses or tumorigenesis. However, the underlying mechanism for the functions of NDRG3 remains unclear. Here, we report the crystal structure of human NDRG3 at 2.2 resolution, with six molecules in an asymmetric unit. While NDRG3 adopts the alpha/beta-hydrolase fold, complete substitution of the canonical catalytic triad residues to non-reactive residues and steric hindrance around the pseudo-active site seem to disable the alpha/beta-hydrolase activity. While NDRG3 shares a high similarity to NDRG2 in terms of amino acid sequence and structure, NDRG3 exhibited remarkable structural differences in a flexible loop corresponding to helix alpha6 of NDRG2 that is responsible for tumor suppression. Thus, this flexible loop region seems to play a distinct role in oncogenic progression induced by NDRG3. Collectively, our studies could provide structural and biophysical insights into the molecular characteristics of NDRG3.
ESTHER : Kim_2020_Biomolecules_10_
PubMedSearch : Kim_2020_Biomolecules_10_
PubMedID: 31935861
Gene_locus related to this paper: human-NDRG3

Title : Anti-Amnesic Effect of Walnut via the Regulation of BBB Function and Neuro-Inflammation in Abeta(1-42)-Induced Mice - Kim_2020_Antioxidants.(Basel)_9_
Author(s) : Kim JM , Lee U , Kang JY , Park SK , Shin EJ , Kim HJ , Kim CW , Kim MJ , Heo HJ
Ref : Antioxidants (Basel) , 9 : , 2020
Abstract : This study was conducted to assess the protective effect of walnut (Juglans regia L.) extract on amyloid beta (Abeta)(1-42)-induced institute of cancer research (ICR) mice. By conducting a Y-maze, passive avoidance, and Morris water maze tests with amyloidogenic mice, it was found that walnut extract ameliorated behavioral dysfunction and memory deficit. The walnut extract showed a protective effect on the antioxidant system and cholinergic system by regulating malondialdehyde (MDA) levels, superoxide dismutase (SOD) contents, reduced glutathione (GSH) contents, acetylcholine (ACh) levels, acetylcholinesterase (AChE) activity, and protein expression of AChE and choline acetyltransferase (ChAT). Furthermore, the walnut extract suppressed Abeta-induced abnormality of mitochondrial function by ameliorating reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP contents. Finally, the walnut extract regulated the expression of zonula occludens-1 (ZO-1) and occludin concerned with blood-brain barrier (BBB) function, expression of tumor necrosis factor-alpha (TNF-alpha), tumor necrosis factor receptor 1 (TNFR1), phosphorylated c-Jun N-terminal kinase (p-JNK), phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (p-IkappaB), cyclooxygenase-2 (COX-2), and interleukin 1 beta (IL-1beta), related to neuroinflammation and the expression of phosphorylated protein kinase B (p-Akt), caspase-3, hyperphosphorylation of tau (p-tau), and heme oxygenase-1 (HO-1), associated with the Abeta-related Akt pathway.
ESTHER : Kim_2020_Antioxidants.(Basel)_9_
PubMedSearch : Kim_2020_Antioxidants.(Basel)_9_
PubMedID: 33053754

Title : Profiling the phyto-constituents of Punica granatum fruits peel extract and accessing its in-vitro antioxidant, anti-diabetic, anti-obesity, and angiotensin-converting enzyme inhibitory properties - Mayasankaravalli_2020_Saudi.J.Biol.Sci_27_3228
Author(s) : Mayasankaravalli C , Deepika K , Esther Lydia D , Agada R , Thagriki D , Govindasamy C , Chinnadurai V , Othman Gatar OM , Khusro A , Kim YO , Kim HJ
Ref : Saudi J Biol Sci , 27 :3228 , 2020
Abstract : This context was investigated to assess the in vitro antioxidant, anti-diabetic, anti-obesity, and angiotensin-converting enzyme (ACE) inhibition traits of Punica granatum fruits peel extract. Initially, among various extracts tested, aqueous and ethanolic peel extracts depicted the presence of diverse phytoconstituents. In vitro antioxidative properties of peel extracts were determined using standard methodologies. Results showed that aqueous and ethanolic extracts had IC(50) values of 471.7 and 509.16 g/mL, respectively in terms of 1,1,diphenyl 2,2,picrylhydrazyl scavenging. Likewise, IC(50) values of aqueous and ethanol extract were obtained as 488.76 and 478.47 g/mL towards the degradation of hydrogen peroxide. The ethanolic extract exhibited the highest inhibition of alpha-glucosidase by showing activity of 53.34 +/- 2.0 to 15.18 +/- 1.4 U/L in a dose dependent manner (100-1000 microg/mL). Ethanolic extract was reported as the most active inhibitor of lipase with an IC(50) value of 603.50 microg/mL. Ethanolic extract showed increased inhibition of ACE in a concentration dependent manner (100-1000 microg/mL) with IC(50) value of 519.45 microg/mL. Fourier transform-infrared spectrum revealed the availability of various functional groups in the ethanolic extract of peel. Gas chromatography-mass spectrometry chromatogram of peel extract illustrated 23 diversified chemical constituents including 1,2,3,4-butanetetrol, Dimethyl sulfone, 9-octadecenamide, and Pentadecanoic acid as predominant compounds. In summary, P. granatum fruits peel extract revealed promising antioxidant, anti-diabetic, anti-obesity, and anti-hypertensive properties.
ESTHER : Mayasankaravalli_2020_Saudi.J.Biol.Sci_27_3228
PubMedSearch : Mayasankaravalli_2020_Saudi.J.Biol.Sci_27_3228
PubMedID: 33304128

Title : Pharmacological evaluation and safety of a donepezil patch - Shin_2020_Pharmazie_75_656
Author(s) : Shin CY , Kim HS , Cha K , Kim HJ , Choi WS , Jang SW , Sohn UD
Ref : Pharmazie , 75 :656 , 2020
Abstract : Our aim was to assess the feasibility of transdermal delivery of donepezil and evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of donepezil patch in vitro and in vivo. Donepezil patches were applied to the skin of rabbits and humans for 7 days, then, the PK profiles were observed in a dose-dependent manner. Donepezil was continuously released from the patch for 7 days as compared to oral administration in hairless rats and rabbits. In hairless rats, peak acetylcholinesterase (AChE) inhibition of 34.7+/-2.0% was observed within 8 h after oral administration of 4 mg/head donepezil, and lasted for less than 24 h, consistent with changes in the plasma donepezil concentration. Peak AChE inhibition by the donepezil patch was equivalent to that in the orally administered group. Donepezil was released continuously from the patch for 7 days with a linear PK in both rats and rabbits. AChE activity inhibition was dependent on donepezil plasma concentration. The data exhibited excellent PK/PD correlation. There was no dermal irritation (erythema/edema) in placebo or donepezil patch group during the study period in minipigs. Thus, Dong-A's donepezil patch appeared to be generally safe and was well tolerated.
ESTHER : Shin_2020_Pharmazie_75_656
PubMedSearch : Shin_2020_Pharmazie_75_656
PubMedID: 33303060

Title : Protein Hydrolysate of Silkworm Pupa Prevents Memory Impairment Induced by Oxidative Stress in Scopolamine-Induced Mice via Modulating the Cholinergic Nervous System and Antioxidant Defense System - Baek_2020_Prev.Nutr.Food.Sci_25_389
Author(s) : Baek SY , Li FY , Kim JH , Ahn C , Kim HJ , Kim MR
Ref : Prev Nutr Food Sci , 25 :389 , 2020
Abstract : Silkworm pupae (Bombyx mori) is an edible insect that has been reported to contain high-quality proteins, lipids, minerals, and vitamins, and to possess high antioxidant activity. However, there have been no studies on the neuroprotective effects of silkworm pupae. Therefore, we investigated a water extract of silkworm pupae with protease (WSP) as a functional and therapeutic candidate for neurodegenerative disorders. First, we evaluated the effect of WSP on oxidative stress-induced mouse hippocampal neuronal cells (HT-22 cells). Cell viability diminished by addition of glutamate but was significantly recovered by WSP treatment. Furthermore, WSP significantly decreased the release of lactate dehydrogenase and generation of intracellular reactive oxygen species in oxidative stress-induced cells. In addition, in scopolamine-treated mice, WSP attenuated memory impairment, as demonstrated in the Morris water maze and passive avoidance tests, indicating protection of neuronal cells against oxidative damage. Moreover, WSP prevented scopolamine-induced increases in acetylcholinesterase activity and decreases in choline-acetyltransferase activity. Finally, treatment with WSP enhanced the antioxidant defense system by regulating the activities of antioxidant enzymes. Overall, this study showed that WSP exerted antioxidant and memory enhancing action against oxidative stress.
ESTHER : Baek_2020_Prev.Nutr.Food.Sci_25_389
PubMedSearch : Baek_2020_Prev.Nutr.Food.Sci_25_389
PubMedID: 33505933

Title : The grease trap: Uncovering the mechanism of the hydrophobic lid in Cutibacterium acnes lipase - Kim_2020_J.Lipid.Res__
Author(s) : Kim HJ , Lee BJ , Kwon AR
Ref : J Lipid Res , : , 2020
Abstract : Acne is one of the most common dermatological conditions, but the details of its pathology are unclear, and current management regimens often have adverse effects. Cutibacterium acnes is known as a major acne-associated bacterium that derives energy from lipase-mediated sebum lipid degradation. C. acnes is commensal, but lipase activity has been observed to differ among C. acnes types. For example, higher populations of the type IA strains are present in acne lesions with higher lipase activity. In the present study, we examined a conserved lipase in type IB and II, but truncated in type IA C. acnes strains. Closed, blocked, and open structures of C. acnes ATCC11828 lipases were elucidated by X-ray crystallography at 1.6-2.4 A. The closed crystal structure, which is the most common form in aqueous solution, revealed that hydrophobic lid domain shields the active site. By comparing closed, blocked, and open structures, we found that the lid domain-opening mechanisms of C. acnes lipases involve the lid-opening residues, Phe- 179 and Phe-211. To the best of our knowledge, this is the first structure-function study of C. acnes lipases, which may help shed light on the mechanisms involved in acne development and may aid in future drug design.
ESTHER : Kim_2020_J.Lipid.Res__
PubMedSearch : Kim_2020_J.Lipid.Res__
PubMedID: 32165394
Gene_locus related to this paper: cutac-e6dae5

Title : Newly developed reversible MAO-B inhibitor circumvents the shortcomings of irreversible inhibitors in Alzheimer's disease - Park_2019_Sci.Adv_5_eaav0316
Author(s) : Park JH , Ju YH , Choi JW , Song HJ , Jang BK , Woo J , Chun H , Kim HJ , Shin SJ , Yarishkin O , Jo S , Park M , Yeon SK , Kim S , Kim J , Nam MH , Londhe AM , Cho SJ , Cho S , Lee C , Hwang SY , Kim SW , Oh SJ , Cho J , Pae AN , Lee CJ , Park KD
Ref : Sci Adv , 5 :eaav0316 , 2019
Abstract : Monoamine oxidase-B (MAO-B) has recently emerged as a potential therapeutic target for Alzheimer's disease (AD) because of its association with aberrant gamma-aminobutyric acid (GABA) production in reactive astrocytes. Although short-term treatment with irreversible MAO-B inhibitors, such as selegiline, improves cognitive deficits in AD patients, long-term treatments have shown disappointing results. We show that prolonged treatment with selegiline fails to reduce aberrant astrocytic GABA levels and rescue memory impairment in APP/PS1 mice, an animal model of AD, because of increased activity in compensatory genes for a GABA-synthesizing enzyme, diamine oxidase (DAO). We have developed a potent, highly selective, and reversible MAO-B inhibitor, KDS2010 (IC(50) = 7.6 nM; 12,500-fold selectivity over MAO-A), which overcomes the disadvantages of the irreversible MAO-B inhibitor. Long-term treatment with KDS2010 does not induce compensatory mechanisms, thereby significantly attenuating increased astrocytic GABA levels and astrogliosis, enhancing synaptic transmission, and rescuing learning and memory impairments in APP/PS1 mice.
ESTHER : Park_2019_Sci.Adv_5_eaav0316
PubMedSearch : Park_2019_Sci.Adv_5_eaav0316
PubMedID: 30906861

Title : Superior immune responses induced by intranasal immunization with recombinant adenovirus-based vaccine expressing full-length Spike protein of Middle East respiratory syndrome coronavirus - Kim_2019_PLoS.One_14_e0220196
Author(s) : Kim MH , Kim HJ , Chang J
Ref : PLoS ONE , 14 :e0220196 , 2019
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) causes an acute and severe lower respiratory illness as well as vomiting, diarrhea, and renal failure. Because no licensed MERS-CoV vaccines are currently available, preventive and therapeutic measures are urgently needed. The surface spike (S) glycoprotein of MERS-CoV, which binds to the cellular receptor dipeptidyl peptidase 4 (DPP4), is considered as a major target for MERS-CoV vaccine development. Here, we designed recombinant replication-deficient adenovirus-based vaccines expressing the N-terminal domain (rAd/NTD) and receptor-binding domain (rAd/RBD) of the MERS-CoV S1 subunit and full-length Spike protein (rAd/Spike). We found that immunization with candidate vaccines via intranasal route induced S1-specific IgG antibodies and neutralizing antibodies against MERS spike pseudotyped virus. Especially, rAd/Spike induced the highest neutralizing antibody titer and the strongest cytokine-induced T cell responses among the three candidate vaccines. To compare the immune responses induced by different administration routes, rAd/Spike was administered via intranasal, sublingual, or intramuscular route. All these administration routes exhibited neutralizing effects in the serum. MERS-CoV-specific neutralizing IgA antibodies in the bronchoalveolar lavage fluid were only induced by intranasal and sublingual administration but not by intramuscular administration. Intranasal administration with rAd/Spike also created resident memory CD8 T cells in the airway and lung parenchyma. Taken together, our results showed that both the humoral and cellular immune responses are highly induced by rAd/Spike administration, suggesting that rAd/Spike may confer protection against MERS-CoV infection.
ESTHER : Kim_2019_PLoS.One_14_e0220196
PubMedSearch : Kim_2019_PLoS.One_14_e0220196
PubMedID: 31329652

Title : Panax ginseng as an adjuvant treatment for Alzheimer's disease - Kim_2018_J.Ginseng.Res_42_401
Author(s) : Kim HJ , Jung SW , Kim SY , Cho IH , Kim HC , Rhim H , Kim M , Nah SY
Ref : J Ginseng Res , 42 :401 , 2018
Abstract : Longevity in medicine can be defined as a long life without mental or physical deficits. This can be prevented by Alzheimer's disease (AD). Current conventional AD treatments only alleviate the symptoms without reversing AD progression. Recent studies demonstrated that Panax ginseng extract improves AD symptoms in patients with AD, and the two main components of ginseng might contribute to AD amelioration. Ginsenosides show various AD-related neuroprotective effects. Gintonin is a newly identified ginseng constituent that contains lysophosphatidic acids and attenuates AD-related brain neuropathies. Ginsenosides decrease amyloid beta-protein (Abeta) formation by inhibiting beta- and gamma-secretase activity or by activating the nonamyloidogenic pathway, inhibit acetylcholinesterase activity and Abeta-induced neurotoxicity, and decrease Abeta-induced production of reactive oxygen species and neuroinflammatory reactions. Oral administration of ginsenosides increases the expression levels of enzymes involved in acetylcholine synthesis in the brain and alleviates Abeta-induced cholinergic deficits in AD models. Similarly, gintonin inhibits Abeta-induced neurotoxicity and activates the nonamyloidogenic pathway to reduce Abeta formation and to increase acetylcholine and choline acetyltransferase expression in the brain through lysophosphatidic acid receptors. Oral administration of gintonin attenuates brain amyloid plaque deposits, boosting hippocampal cholinergic systems and neurogenesis, thereby ameliorating learning and memory impairments. It also improves cognitive functions in patients with AD. Ginsenosides and gintonin attenuate AD-related neuropathology through multiple routes. This review focuses research demonstrating that ginseng constituents could be a candidate as an adjuvant for AD treatment. However, clinical investigations including efficacy and tolerability analyses may be necessary for the clinical acceptance of ginseng components in combination with conventional AD drugs.
ESTHER : Kim_2018_J.Ginseng.Res_42_401
PubMedSearch : Kim_2018_J.Ginseng.Res_42_401
PubMedID: 30337800

Title : Unique binding mode of Evogliptin with human dipeptidyl peptidase IV - Lee_2017_Biochem.Biophys.Res.Commun_494_452
Author(s) : Lee HK , Kim MK , Kim HD , Kim HJ , Kim JW , Lee JO , Kim CW , Kim EE
Ref : Biochemical & Biophysical Research Communications , 494 :452 , 2017
Abstract : Evogliptin ((R)-4-((R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl) piperazine-2-one)) is a highly potent selective inhibitor of dipeptidyl peptidase IV (DPP4) that was approved for the treatment of type 2 diabetes in South Korea. In this study, we report the crystal structures of Evogliptin, DA-12166, and DA-12228 (S,R diastereomer of Evogliptin) complexed to human DPP4. Analysis of both the structures and inhibitory activities suggests that the binding of the trifluorophenyl moiety in the S1 pocket and the piperazine-2-one moiety have hydrophobic interactions with Phe357 in the S2 extensive subsite, and that the multiple hydrogen bonds made by the (R)-beta-amine group in the S2 pocket and the contacts made by the (R)-tert-butyl group with Arg125 contribute to the high potency observed for Evogliptin.
ESTHER : Lee_2017_Biochem.Biophys.Res.Commun_494_452
PubMedSearch : Lee_2017_Biochem.Biophys.Res.Commun_494_452
PubMedID: 29061303
Gene_locus related to this paper: human-DPP4

Title : 3,4-Dihydroquinazoline derivatives inhibit the activities of cholinesterase enzymes - Park_2017_Bioorg.Med.Chem.Lett_27_1179
Author(s) : Park B , Nam JH , Kim JH , Kim HJ , Onnis V , Balboni G , Lee KT , Park JH , Catto M , Carotti A , Lee JY
Ref : Bioorganic & Medicinal Chemistry Lett , 27 :1179 , 2017
Abstract : A series of 3,4-dihydroquinazoline derivatives consisting of the selected compounds from our chemical library on the diversity basis and the new synthetic compounds were in vitro tested for their inhibitory activities for both acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum) enzymes. It was discovered that most of the compounds displayed weak AChE and strong BuChE inhibitory activities. In particular, compound 8b and 8d were the most active compounds in the series against BChE with IC50 values of 45nM and 62nM, as well as 146- and 161-fold higher affinity to BChE, respectively. To understand the excellent activity of these compounds, molecular docking simulations were performed to get better insights into the mechanism of binding of 3,4-dihydroquinazoline derivatives. As expected, compound 8b and 8d bind to both catalytic anionic site (CAS) and peripheral site (PS) of BChE with better interaction energy values than AChE, in agreement with our experimental data. Furthermore, the non-competitive/mixed-type inhibitions of both compounds further confirmed their dual binding nature in kinetic studies.
ESTHER : Park_2017_Bioorg.Med.Chem.Lett_27_1179
PubMedSearch : Park_2017_Bioorg.Med.Chem.Lett_27_1179
PubMedID: 28189420

Title : An engineered FGF21 variant, LY2405319, can prevent non-alcoholic steatohepatitis by enhancing hepatic mitochondrial function - Lee_2016_Am.J.Transl.Res_8_4750
Author(s) : Lee JH , Kang YE , Chang JY , Park KC , Kim HW , Kim JT , Kim HJ , Yi HS , Shong M , Chung HK , Kim KS
Ref : Am J Transl Res , 8 :4750 , 2016
Abstract : Non-alcoholic fatty liver disease (NAFLD) is a prevalent obesity-related disease that affects large populations throughout the world due to excessive calorie intake and an increasingly sedentary lifestyle. Fibroblast growth factor 21 (FGF21) has recently emerged as a promising therapeutic candidate for the treatment of obesity and diabetes. FGF21 is a starvation-induced pleiotropic hormone with various beneficial metabolic effects, and pharmacological treatment in rodents has been shown to improve insulin sensitivity and decrease simple fatty liver disease. However, its effects on reversing the symptoms of advanced liver disease have yet to be validated. Here, we investigated the protective effects of the LY2405319 compound, an engineered FGF21 variant, in a non-alcoholic steatohepatitis (NASH) model using leptin-deficient ob/ob mice and a methionine- and choline-deficient (MCD) diet to induce steatohepatitis. LY2405319 treatment in ob/ob mice corroborated previous results showing that improvements in the metabolic parameters were due to increased mitochondrial oxygen consumption rate and fatty acid oxidation. LY2405319 treatment in ob/ob mice on an MCD diet significantly reduced the symptoms of steatohepatitis, as confirmed by Masson's trichrome staining intensity. Serum levels of AST and ALT were also reduced, suggesting an attenuation of liver injury, while detection of inflammatory markers showed decreased mRNA expression of TGF-beta1 and type-I collagen, and decreased phosphorylation of NF-kB p65, JNK1/2, and p38. Collectively, these data show that LY2405319 treatment attenuated MCD diet-induced NASH progression. We propose that the LY2405319 compound is a potential therapeutic candidate for the treatment of advanced liver disease.
ESTHER : Lee_2016_Am.J.Transl.Res_8_4750
PubMedSearch : Lee_2016_Am.J.Transl.Res_8_4750
PubMedID: 27904677

Title : NORE1\/SAUL1 integrates temperature-dependent defense programs involving SGT1b and PAD4 pathways and leaf senescence in Arabidopsis - Lee_2016_Physiol.Plant_158_180
Author(s) : Lee IH , Lee IC , Kim J , Kim JH , Chung EH , Kim HJ , Park SJ , Kim YM , Kang SK , Nam HG , Woo HR , Lim PO
Ref : Physiol Plant , 158 :180 , 2016
Abstract : Leaf senescence is not only primarily governed by developmental age but also influenced by various internal and external factors. Although some genes that control leaf senescence have been identified, the detailed regulatory mechanisms underlying integration of diverse senescence-associated signals into the senescence programs remain to be elucidated. To dissect the regulatory pathways involved in leaf senescence, we isolated the not oresara1-1 (nore1-1) mutant showing accelerated leaf senescence phenotypes from an EMS-mutagenized Arabidopsis thaliana population. We found that altered transcriptional programs in defense response-related processes were associated with the accelerated leaf senescence phenotypes observed in nore1-1 through microarray analysis. The nore1-1 mutation activated defense program, leading to enhanced disease resistance. Intriguingly, high ambient temperature effectively suppresses the early senescence and death phenotypes of nore1-1. The gene responsible for the phenotypes of nore1-1 contains a missense mutation in SENESCENCE-ASSOCIATED E3 UBIQUITIN LIGASE 1 (SAUL1), which was reported as a negative regulator of premature senescence in the light intensity- and PHYTOALEXIN DEFICIENT 4 (PAD4)-dependent manner. Through extensive double mutant analyses, we recently identified suppressor of the G2 Allele of SKP1b (SGT1b), one of the positive regulators for disease resistance conferred by many resistance (R) proteins, as a downstream signaling component in NORE1-mediated senescence and cell death pathways. In conclusion, NORE1/SAUL1 is a key factor integrating signals from temperature-dependent defense programs and leaf senescence in Arabidopsis. These findings provide a new insight that plants might utilize defense response program in regulating leaf senescence process, possibly through recruiting the related genes during the evolution of the leaf senescence program.
ESTHER : Lee_2016_Physiol.Plant_158_180
PubMedSearch : Lee_2016_Physiol.Plant_158_180
PubMedID: 26910207

Title : Molecular and biochemical characterizations of the monoacylglycerol lipase gene family of Arabidopsis thaliana - Kim_2016_Plant.J_85_758
Author(s) : Kim RJ , Kim HJ , Shim D , Suh MC
Ref : Plant J , 85 :758 , 2016
Abstract : Monoacylglycerol lipase (MAGL) catalyzes the last step of triacylglycerol breakdown, which is the hydrolysis of monoacylglycerol (MAG) to fatty acid and glycerol. Arabidopsis harbors over 270 genes annotated as 'lipase', the largest class of acyl lipid metabolism genes that have not been characterized experimentally. In this study, computational modeling suggested that 16 Arabidopsis putative MAGLs (AtMAGLs) have a three-dimensional structure that is similar to a human MAGL. Heterologous expression and enzyme assays indicated that 11 of the 16 encoded proteins indeed possess MAG lipase activity. Additionally, AtMAGL4 displayed hydrolase activity with lysophosphatidylcholine and lysophosphatidylethanolamine (LPE) substrates and AtMAGL1 and 2 utilized LPE as a substrate. All recombinant AtMAGLs preferred MAG substrates with unsaturated fatty acids over saturated fatty acids and AtMAGL8 exhibited the highest hydrolase activities with MAG containing 20:1 fatty acids. Except for AtMAGL4, -14 and -16, all AtMAGLs showed similar activity with both sn-1 and sn-2 MAG isomers. Spatial, temporal and stress-induced expression of the 16 AtMAGL genes was analyzed by transcriptome analyses. AtMAGL:eYFP fusion proteins provided initial evidence that AtMAGL1, -3, -6, -7, -8, -11, -13, -14 and -16 are targeted to the endoplasmic reticulum and/or Golgi network, AtMAGL10, -12 and -15 to the cytosol and AtMAGL2, -4 and -5 to the chloroplasts. Furthermore, AtMAGL8 was associated with the surface of oil bodies in germinating seeds and leaves accumulating oil bodies. This study provides the broad characterization of one of the least well-understood groups of Arabidopsis lipid-related enzymes and will be useful for better understanding their roles in planta.
ESTHER : Kim_2016_Plant.J_85_758
PubMedSearch : Kim_2016_Plant.J_85_758
PubMedID: 26932457
Gene_locus related to this paper: arath-At1g18360 , arath-At2g47630 , arath-At5g11650 , arath-At5g16120 , arath-AT5G19290 , arath-F2G14.100 , arath-F12L6.7 , arath-F12L6.8 , arath-F14G24.3 , arath-T5M16.2 , arath-T9L24.33 , arath-T19D16.3 , arath-T26I12.60 , arath-T26I12.70

Title : Deer bone extract prevents against scopolamine-induced memory impairment in mice - Du_2015_J.Med.Food_18_157
Author(s) : Du CN , Min AY , Kim HJ , Shin SK , Yu HN , Sohn EJ , Ahn CW , Jung SU , Park SH , Kim MR
Ref : J Med Food , 18 :157 , 2015
Abstract : Deer bone has been used as a health-enhancing food as well as an antiaging agent in traditional Oriental medicine. Recently, the water extract of deer bone (DBE) showed a neuroprotective action against glutamate or Abeta1-42-induced cell death of mouse hippocampal cells by exerting antioxidant activity through the suppression of MAP kinases. The present study is to examine whether DBE improves memory impairment induced by scopolamine. DBE (50, 100 or 200 mg/kg) was administered orally to mice for 14 days, and then scopolamine (2 mg/kg, i.p.) was administered together with DBE for another 7 days. Memory performance was evaluated in the Morris water maze (MWM) test and passive avoidance test. Also, brain acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activity, biomarkers of oxidative stress and the loss of neuronal cells in the hippocampus, was evaluated by histological examinations. Administration of DBE significantly restored memory impairments induced by scopolamine in the MWM test (escape latency and number of crossing platform area), and in the passive avoidance test. Treatment with DBE inhibited the AChE activity and increased the ChAT activity in the brain of memory-impaired mice induced by scopolamine. Additionally, the administration of DBE significantly prevented the increase of lipid peroxidation and the decrease of glutathione level in the brain of mice treated with scopolamine. Also, the DBE treatment restored the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase to control the level. Furthermore, scopolamine-induced oxidative damage of neurons in hippocampal CA1 and CA3 regions were prevented by DBE treatment. It is suggested that DBE may be useful for memory improvement through the regulation of cholinergic marker enzyme activities and the suppression of oxidative damage of neurons in the brain of mice treated with scopolamine.
ESTHER : Du_2015_J.Med.Food_18_157
PubMedSearch : Du_2015_J.Med.Food_18_157
PubMedID: 25546299

Title : Characterization of Novel Family IV Esterase and Family I.3 Lipase from an Oil-Polluted Mud Flat Metagenome - Kim_2015_Mol.Biotechnol_57_781
Author(s) : Kim HJ , Jeong YS , Jung WK , Kim SK , Lee HW , Kahng HY , Kim J , Kim H
Ref : Mol Biotechnol , 57 :781 , 2015
Abstract : Two genes encoding lipolytic enzymes were isolated from a metagenomic library constructed from oil-polluted mud flats. An esterase gene, est3K, encoded a protein of 299 amino acids (ca. 32,364 Da). Est3K was a family IV esterase with typical motifs, HGGG, and HGF. Although est3K showed high identity to many genes with no information on their enzymatic properties, Est3K showed the highest identity (36 %) to SBLip5.1 from forest soil metagenome when compared to the enzymes with reported properties. A lipase gene, lip3K, encoded a protein of 616 amino acids (ca. 64,408 Da). Lip3K belonged to family I.3 lipase with a C-terminal secretion signal and showed the highest identity (93 %) to the lipase of Pseudomonas sp. MIS38. The presence of several newly identified conserved motifs in Est3K and Lip3K are suggested. Both Est3K and Lip3K exerted their maximal activity at pH 9.0 and 50 degrees C. The activity of Lip3K was significantly increased by the presence of 30 % methanol. The ability of the enzymes to retain activities in the presence of methanol and the substrates may offer a merit to the biotechnological applications of the enzymes such as transesterification. The activity and the thermostability of Lip3K were increased by Ca(2+). Est3K and Lip3K preferred p-nitrophenyl butyrate (C4) and octanoate (C8), respectively, as the substrate and acted independently on the substrates with no synergistic effect.
ESTHER : Kim_2015_Mol.Biotechnol_57_781
PubMedSearch : Kim_2015_Mol.Biotechnol_57_781
PubMedID: 25943044

Title : Characterization of an Alkaline Family I.4 Lipase from Bacillus sp. W130-35 Isolated from a Tidal Mud Flat with Broad Substrate Specificity - Kim_2015_J.Microbiol.Biotechnol_25_2024
Author(s) : Kim HJ , Jung WK , Lee HW , Yoo W , Kim TD , Kim H
Ref : J Microbiol Biotechnol , 25 :2024 , 2015
Abstract : A gene encoding lipolytic enzyme, lip7-3, was isolated from Bacillus sp. W130-35 isolated from a tidal mud flat. The gene encoded a protein of 215 amino acids with a signal peptide composed of 34 amino acid residues. Lip7-3 belonged to the family I.4 lipase and showed its maximal activity at pH 9.0 and 60 degrees C. Its activity increased in the presence of 30% methanol and, remarkably, increased as well to 154.6% in the presence of Ca(2+). Lip7-3 preferred pnitrophenyl octanoate (C8) as a substrate and exhibited broad specificity for short- to longchain fatty acid esters. Additionally, Lip7-3 showed a low degree of enantioselectivity for an S-enantiomer (e.g., (S)-methyl-3-hydroxy-2-methylpropionate). It efficiently hydrolyzed glyceryl tributyrate, but did not hydrolyze glyceryl trioleate, fish oil, or olive oil. Its substrate specificity and activation by the solvent might offer a merit to the biotechnological enzyme applications like transesterification in the production of biodiesel.
ESTHER : Kim_2015_J.Microbiol.Biotechnol_25_2024
PubMedSearch : Kim_2015_J.Microbiol.Biotechnol_25_2024
PubMedID: 26370800
Gene_locus related to this paper: bacpu-w8rkh7

Title : Lipase-Catalyzed Production of 6-O-cinnamoyl-sorbitol from D-sorbitol and Cinnamic Acid Esters - Kim_2015_Appl.Biochem.Biotechnol_176_244
Author(s) : Kim JH , Bhatia SK , Yoo D , Seo HM , Yi DH , Kim HJ , Lee JH , Choi KY , Kim KJ , Lee YK , Yang YH
Ref : Appl Biochem Biotechnol , 176 :244 , 2015
Abstract : To overcome the poor properties of solubility and stability of cinnamic acid, cinnamate derivatives with sugar alcohols were produced using the immobilized Candida antarctica lipase with vinyl cinnamate and D-sorbitol as substrate at 45 degrees C. Immobilized C. antarctica lipase was found to synthesize 6-O-cinnamoyl-sorbitol and confirmed by HPLC and (1)H-NMR and had a preference for vinyl cinnamate over other esters such as allyl-, ethyl-, and isobutyl cinnamate as co-substrate with D-sorbitol. Contrary to D-sorbitol, vinyl cinnamate, and cinnamic acid, the final product 6-O-cinnamoyl-sorbitol was found to have radical scavenging activity. This would be the first report on the biosynthesis of 6-O-cinnamoyl-sorbitol with immobilized enzyme from C. antarctica.
ESTHER : Kim_2015_Appl.Biochem.Biotechnol_176_244
PubMedSearch : Kim_2015_Appl.Biochem.Biotechnol_176_244
PubMedID: 25809993

Title : Biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (P(HB-co-HHx)) from butyrate using engineered Ralstonia eutropha - Jeon_2014_Appl.Microbiol.Biotechnol_98_5461
Author(s) : Jeon JM , Brigham CJ , Kim YH , Kim HJ , Yi DH , Kim H , Rha C , Sinskey AJ , Yang YH
Ref : Applied Microbiology & Biotechnology , 98 :5461 , 2014
Abstract : Polyhydroxyalkanoates (PHAs), a promising family of bio-based polymers, are considered to be alternatives to traditional petroleum-based plastics. Copolymers like poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (P(HB-co-HHx)) have been shown to exhibit favorable physical and mechanical properties, due to decreased crystallinity resulting from the presence of medium-chain-length 3-hydroxyhexanoate (3HHx) monomers. In this study, we produced P(HB-co-HHx) using engineered Ralstonia eutropha strains containing deletions of the acetoacetyl-CoA reductase (phaB) genes and replacing the native PHA synthase with phaC2 from Rhodococcus aetherivorans I24 and by using butyrate, a short-chain organic acid, as the carbon source. Although the wild-type R. eutropha did not produce P(HB-co-HHx) when grown on mixed acids or on butyrate as the sole carbon source, we are able to produce polymer containing up to 40 wt% 3HHx monomer with the aforementioned engineered R. eutropha strains using various concentrations of just butyrate as the sole carbon source. This is the first report for the production of P(HB-co-HHx) copolymer in R. eutropha using butyrate.
ESTHER : Jeon_2014_Appl.Microbiol.Biotechnol_98_5461
PubMedSearch : Jeon_2014_Appl.Microbiol.Biotechnol_98_5461
PubMedID: 24615385

Title : Black Soybean Extract Protects Against TMT-Induced Cognitive Defects in Mice - Jeong_2014_J.Med.Food_17_83
Author(s) : Jeong JH , Jo YN , Kim HJ , Jin DE , Kim DO , Heo HJ
Ref : J Med Food , 17 :83 , 2014
Abstract : Abstract To find a neuroactive compound with a potent inhibitory effect on acetylcholinesterase (AChE) and in vivo anti-amnesic activity from natural resources, we evaluated anthocyanins and nonanthocyanins from black soybean extract. Nonanthocyanins from black soybean extract were the most potent and dose-dependent AChE inhibitors. Intracellular reactive oxygen species accumulation resulting from H2O2 treatment was significantly decreased compared with cells treated with H2O2 only. Nonanthocyanins were also neuroprotective against H2O2 treated neurotoxicity by 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assay. Finally, nonanthocyanins from black soybean in the preadministration group attenuated trimethyltin (TMT)-induced memory injury in both in vivo tests. AChE, prepared from mice brain tissues, was inhibited by nonanthocyanins from black soybean in a dose-dependent manner. Malondialdehyde generation in the brain homogenates of mice treated with nonanthocyanins from black soybean was decreased. We concluded that nonanthocyanins from black soybean had an efficacious in vitro AChE inhibitory activity, and protected against H2O2-induced neurotoxicity. In addition, our findings suggest that nonanthocyanins from black soybean may improve the TMT-induced learning and memory deficit because of AChE inhibition of mice brain tissue. Consequently, these results demonstrate that the nonanthocyanins from black soybean could possess a wide range of beneficial activities for neurodegenerative disorders.
ESTHER : Jeong_2014_J.Med.Food_17_83
PubMedSearch : Jeong_2014_J.Med.Food_17_83
PubMedID: 24456358

Title : Effects of ginseol k-g3, an Rg3-enriched fraction, on scopolamine-induced memory impairment and learning deficit in mice - Pena_2014_J.Ginseng.Res_38_1
Author(s) : Pena ID , Yoon SY , Kim HJ , Park S , Hong EY , Ryu JH , Park IH , Cheong JH
Ref : J Ginseng Res , 38 :1 , 2014
Abstract : BACKGROUND: Although ginsenosides such as Rg1, Rb1 and Rg3 have shown promise as potential nutraceuticals for cognitive impairment, their use has been limited due to high production cost and low potency. In particular, the process of extracting pure Rg3 from ginseng is laborious and expensive.
METHODS: We described the methods in preparing ginseol k-g3, an Rg3-enriched fraction, and evaluated its effects on scopolamine-induced memory impairment in mice.
RESULTS: Ginseol k-g3 (25-200 mg/kg) significantly reversed scopolamine-induced cognitive impairment in the passive avoidance, but not in Y-maze testing. Ginseol k-g3 (50 and 200 mg/kg) improved escape latency in training trials and increased swimming times within the target zone of the Morris water maze. The effect of ginseol k-g3 on the water maze task was more potent than that of Rg3 or Red ginseng. Acute or subchronic (6 d) treatment of ginseol k-g3 did not alter normal locomotor activity of mice in an open field. Ginseol k-g3 did not inhibit acetylcholinesterase activity, unlike donezepil, an acetylcholinesterase inhibitor. Rg3 enrichment through the ginseol k-g3 fraction enhanced the efficacy of Rg3 in scopolamine-induced memory impairment in mice as demonstrated in the Morris water maze task. CONCLUSION: The effects of ginseol k-g3 in ameliorating scopolamine-induced memory impairment in the passive avoidance and Morris water maze tests indicate its specific influence on reference or long-term memory. The mechanism underlying the reversal of scopolamine-induced amnesia by ginseol k-g3 is not yet known, but is not related to anticholinesterase-like activity.
ESTHER : Pena_2014_J.Ginseng.Res_38_1
PubMedSearch : Pena_2014_J.Ginseng.Res_38_1
PubMedID: 24558303

Title : An investigation into the ameliorating effect of black soybean extract on learning and memory impairment with assessment of neuroprotective effects - Jeong_2014_BMC.Complement.Altern.Med_14_482
Author(s) : Jeong JH , Kim HJ , Park SK , Jin DE , Kwon OJ , Heo HJ
Ref : BMC Complement Altern Med , 14 :482 , 2014
Abstract : BACKGROUND: The physiological effects of the non-anthocyanin fraction (NAF) in a black soybean seed coat extract on Abeta-induced oxidative stress were investigated to confirm neuroprotection. In addition, we examined the preventive effect of NAF on cognitive defects induced by the intracerebroventricular (ICV) injection of Abeta.
METHODS: Levels of cellular oxidative stress were measured using 2[prime],7[prime]-dichlorofluorescein diacetate (DCF-DA). Neuronal cell viability was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assay. To investigate in vivo anti-amnesic effects of NAF by using Y-maze and passive avoidance tests, the learning and memory impairment in mice was induced by Abeta. After in vivo assays, acetylcholinesterase (AChE) activity and level of malondialdehyde (MDA) in the mouse brain were determined to confirm the cognitive effect. Individual phenolics of NAF were qualitatively analyzed by using an ultra-performance liquid chromatography (UPLC) Accurate-Mass Quadrupole Time of-Flight (Q-TOF) UPLC/MS.
RESULTS: A NAF showed cell protective effects against oxidative stress-induced cytotoxicity. Intracellular ROS accumulated through Abeta1-40 treatment was significantly reduced in comparison to cells only treated with Abeta1-40. In MTT and LDH assay, the NAF also presented neuroprotective effects on Abeta1-40-treated cytotoxicity. Finally, the administration of this NAF in mice significantly reversed the Abeta1-40-induced cognitive defects in in vivo behavioral tests. After behavioral tests, the mice brains were collected in order to examine lipid peroxidation and AChE activity. AChE, preparation was inhibited by NAF in a dose-dependent manner. MDA generation in the brain homogenate of mice treated with the NAF was decreased. Q-TOF UPLC/MS analyses revealed three major phenolics from the non-anthocyanin fraction; epicatechin, procyanidin B1, and procyanidin B2.
CONCLUSIONS: The results suggest that the NAF in black soybean seed coat extracts may improve the cytotoxicity of Abeta in PC12 cells, possibly by reducing oxidative stress, and also have an anti-amnesic effect on the in vivo learning and memory deficits caused by Abeta. Q-TOF UPLC/MS analyses showed three major phenolics; (-)-epicatechin, procyanidin B1, and procyanidin B2. Above results suggest that (-)-epicatechins are the major components, and contributors to the anti-amnesic effect of the NAF from black soybean seed coat.
ESTHER : Jeong_2014_BMC.Complement.Altern.Med_14_482
PubMedSearch : Jeong_2014_BMC.Complement.Altern.Med_14_482
PubMedID: 25496367

Title : Purification, characterization and preliminary X-ray diffraction analysis of a cold-active lipase (CpsLip) from the psychrophilic bacterium Colwellia psychrerythraea 34H - Do_2013_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_69_920
Author(s) : Do H , Lee JH , Kwon MH , Song HE , An JY , Eom SH , Lee SG , Kim HJ
Ref : Acta Crystallographica Sect F Struct Biol Cryst Commun , 69 :920 , 2013
Abstract : The putative lipase CpsLip from the psychrophilic bacterium Colwellia psychrerythraea 34H encodes a 34 538 Da, 308-amino-acid protein. In this study, CpsLip (UniProtKB code Q486T5) was expressed as an N-terminal hexahistidine fusion protein in Escherichia coli and purified by affinity and size-exclusion chromatography. The expression and purification of CpsLip enabled characterization of the lipase enzymatic properties of the protein. The optimal activity temperature and pH of the recombinant protein were 298 K and pH 7, respectively. CpsLip maintained over 80% activity in the low-temperature range (278-288 K), thereby suggesting that CpsLip is a cold-active lipase. Substrate-specificity analysis demonstrated that CpsLip exhibits maximum activity towards the C12 acyl group. In addition, sequence-alignment results revealed that CpsLip has a highly conserved catalytic triad in the active site consisting of residues Ser111, Asp135 and His283. Moreover, purified CpsLip was successfully crystallized using the hanging-drop vapour-diffusion method and a complete diffraction data set was collected to 4.0 A resolution using synchrotron radiation on the BL-5A beamline of the Photon Factory.
ESTHER : Do_2013_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_69_920
PubMedSearch : Do_2013_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_69_920
PubMedID: 23908044

Title : Complete Genome Sequence of Mycobacterium bovis BCG Korea, the Korean Vaccine Strain for Substantial Production - Joung_2013_Genome.Announc_1_e0006913
Author(s) : Joung SM , Jeon SJ , Lim YJ , Lim JS , Choi BS , Choi IY , Yu JH , Na KI , Cho EH , Shin SS , Park YK , Kim CK , Kim HJ , Ryoo SW
Ref : Genome Announc , 1 :e0006913 , 2013
Abstract : Mycobacterium bovis bacillus Calmette-Guerin (BCG) is the only vaccine available against tuberculosis, and the strains used worldwide represent a family of daughter strains with distinct genotypic characteristics. Here, we report the complete genome sequence of M. bovis BCG Korea, the strain that will be actually used in Korea for vaccine production.
ESTHER : Joung_2013_Genome.Announc_1_e0006913
PubMedSearch : Joung_2013_Genome.Announc_1_e0006913
PubMedID: 23516200
Gene_locus related to this paper: myctu-cut3 , myctu-RV1215C , myctu-Rv2045c

Title : Effects of allantoin on cognitive function and hippocampal neurogenesis - Ahn_2013_Food.Chem.Toxicol_64C_210
Author(s) : Ahn YJ , Park SJ , Woo H , Lee HE , Kim HJ , Kwon G , Gao Q , Jang DS , Ryu JH
Ref : Food & Chemical Toxicology , 64C :210 , 2013
Abstract : Allantoin is contained in Nelumbo nucifera (lotus) and a well-known cosmetic ingredient reported to have anti-oxidative and anti-inflammatory activities. In the present study, we investigated whether allantoin affects cognitive function in mice. The subchronic administration of allantoin (1, 3 or 10mg/kg, for 7days) significantly increased the latency time measured during the passive avoidance task in scopolamine-induced cholinergic blockade and normal naive mice. Allantoin treatment (3 or 10mg/kg, for 7days) also increased the expression levels of phosphorylated phosphatidylinositide 3-kinase (PI3K), phosphorylated protein kinase B (Akt) and phosphorylated glycogen synthase kinase-3beta (GSK-3beta). Doublecortin and 5-bromo-2-deoxyuridine immunostaining revealed that allantoin significantly increased the neuronal cell proliferation of immature neurons in the hippocampal dentate gyrus region. In conclusion, allantoin has memory-enhancing effects, and these effects may be partly mediated by the PI3K-Akt-GSK-3beta signal pathway. These findings suggest that allantoin has therapeutic potential for the cognitive dysfunctions observed in Alzheimer's disease.
ESTHER : Ahn_2013_Food.Chem.Toxicol_64C_210
PubMedSearch : Ahn_2013_Food.Chem.Toxicol_64C_210
PubMedID: 24296131

Title : Blueberry (Vaccinium virgatum) Leaf Extracts Protect Against Abeta-Induced Cytotoxicity and Cognitive Impairment - Jeong_2013_J.Med.Food_16_968
Author(s) : Jeong HR , Jo YN , Jeong JH , Kim HJ , Kim MJ , Heo HJ
Ref : J Med Food , 16 :968 , 2013
Abstract : Abstract The ethylacetate (EtOAc) fraction of blueberry leaf extract was investigated to examine the in vivo antiamnesic effects against amyloid beta protein (Abeta)-induced learning and memory deficit. The fraction showed the highest antioxidant activities, and the generation of intracellular reactive oxygen species was significantly decreased. Cell viability assays revealed the in vitro cytoprotective effects of the fraction, and the cytoplasmic lactate dehydrogenase release into the medium was dose-dependently inhibited. In addition, a chlorogenic acid was identified as a predominant phenolic compound by high-performance liquid chromatography analysis. Antiamnesic effects were evaluated by using in vivo the Y-maze and passive avoidance tests, and preadministration of the fraction attenuated Abeta-induced memory impairment in both in vivo experiments. Acetylcholinesterase prepared from mice brain was inhibited by the fraction, and malondialdehyde generation in the brain homogenate was also decreased. These findings suggest that the EtOAc fraction of blueberry leaf extract could possess a wide range of physiological effects against neurodegenerative diseases.
ESTHER : Jeong_2013_J.Med.Food_16_968
PubMedSearch : Jeong_2013_J.Med.Food_16_968
PubMedID: 24117094

Title : Inhibitory evaluation of sulfonamide chalcones on beta-secretase and acylcholinesterase - Kang_2012_Molecules_18_140
Author(s) : Kang JE , Cho JK , Curtis-Long MJ , Ryu HW , Kim JH , Kim HJ , Yuk HJ , Kim DW , Park KH
Ref : Molecules , 18 :140 , 2012
Abstract : The action of beta-secretase (BACE1) is strongly correlated with the onset of Alzheimer's disease (AD). Aminochalcone derivatives were examined for their ability to inhibit BACE1. Parent aminochalcones showed two digit micromolar IC(50)s against BACE1. Potency was enhanced 10-fold or more by introducing benzenesulfonyl derivatives to the amino group: 1 (IC(50) = 48.2 muM) versus 4a (IC(50) = 1.44 muM) and 2 (IC(50) = 17.7 muM) versus 5a (IC(50) = 0.21 muM). The activity was significantly influenced by position and number of hydroxyl groups on the chalcone B-ring: 3,4-dihydroxy 5a (IC(50) = 0.21 muM) > 4-hydroxy 4a (IC(50) = 1.44 muM) > 2,4-dihydroxy 6 (IC(50) = 3.60 muM) > 2,5-dihydroxy 7 (IC(50) = 16.87 muM) > des hydroxy 4b (IC(50) = 168.7 muM). Lineweaver-Burk and Dixon plots and their secondary replots indicate that compound 5a was a mixed inhibitor with reversible and time-dependent behavior. Potent BACE1 inhibitors 4a,c,f, 5a-c showed moderate inhibition against two other enzymes implicated in AD pathogenesis, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with IC(50)s ranging between 56.1 ~ 95.8 muM and 19.5 ~ 79.0 muM, respectively.
ESTHER : Kang_2012_Molecules_18_140
PubMedSearch : Kang_2012_Molecules_18_140
PubMedID: 23344193

Title : DA-1229, a novel and potent DPP4 inhibitor, improves insulin resistance and delays the onset of diabetes - Kim_2012_Life.Sci_90_21
Author(s) : Kim MK , Chae YN , Kim HD , Yang EK , Cho EJ , Choi SH , Cheong YH , Kim HS , Kim HJ , Jo YW , Son MH , Kim SH , Shin CY
Ref : Life Sciences , 90 :21 , 2012
Abstract : AIM: To characterize the pharmacodynamic profile of DA-1229, a novel dipeptidyl peptidase (DPP) 4 inhibitor. MAIN
METHODS: Enzyme inhibition assays against DPP4, DPP8 and DPP9. Antidiabetic effects of DA-1229 in HF-DIO mice and young db/db mice. KEY FINDINGS: DA-1229 was shown to potently inhibit the DPP4 enzyme in human and murine soluble forms and the human membrane-bound form with IC(50) values of 0.98, 3.59 and 1.26 nM, respectively. As a reversible and competitive inhibitor, DA-1229 was more selective to human DPP4 (6000-fold) than to human DPP8 and DPP9. DA-1229 (0.1-3mg/kg) dose-dependently inhibited plasma DPP4 activity, leading to increased levels of plasma GLP-1 and insulin, and thereby lowering blood glucose levels in mice. In high fat diet-fed (HF) mice, a single oral dose of 100mg/kg of DA-1229 reduced plasma DPP4 activity by over 80% during a 24h period. Long-term treatment with DA-1229 for 8 weeks revealed significant improvements in glucose intolerance and insulin resistance, accompanied by significant body weight reduction. However, it remains unclear whether there is a direct causal relationship between DPP4 inhibition and body weight reduction. In young db/db mice, the DA-1229 treatment significantly reduced blood glucose excursions for the first 2 weeks, resulting in significantly lower levels of HbA1c at the end of the study. Furthermore, the pancreatic insulin content of the treatment group was significantly higher than that of the db/db control. SIGNIFICANCE: DA-1229 as a novel and selective DPP4 inhibitor improves the insulin sensitivity in HF mice and delays the onset of diabetes in young db/db mice.
ESTHER : Kim_2012_Life.Sci_90_21
PubMedSearch : Kim_2012_Life.Sci_90_21
PubMedID: 22056373

Title : A novel dipeptidyl peptidase IV inhibitor DA-1229 ameliorates streptozotocin-induced diabetes by increasing beta-cell replication and neogenesis - Cho_2011_Diabetes.Res.Clin.Pract_91_72
Author(s) : Cho JM , Jang HW , Cheon H , Jeong YT , Kim DH , Lim YM , Choi SH , Yang EK , Shin CY , Son MH , Kim SH , Kim HJ , Lee MS
Ref : Diabetes Res Clin Pract , 91 :72 , 2011
Abstract : We studied the effect of a novel dipeptidyl peptidase IV (DPP IV) inhibitor, DA-1229, on blood glucose profile and pancreatic beta-cell mass in established diabetes after streptozotocin (STZ) treatment. Mice that developed diabetes after administration of STZ 100mg/kg were treated with DA-1229 for 13 weeks. DA-1229 significantly reduced plasma DPP IV activity, and enhanced glucagon-like peptide 1 (GLP-1) levels. In STZ-treated mice fed DA-1229 (STZ-DA), blood glucose levels were significantly lower than those in diabetic mice fed normal chow (STZ-NC). Basal and glucose-stimulated insulin secretion and glucose tolerance assessed by intraperitoneal glucose tolerance test were significantly improved by DA-1229 administration. Volume density of beta-cell was significantly increased in STZ-DA mice compared to STZ-NC mice, suggesting that DA-1229-mediated amelioration of established diabetes was due to beneficial effect of DA-1229 on beta-cell mass. The number of replicating beta-cells and that of scattered small beta-cell unit representing beta-cell neogenesis were significantly increased in STZ-DA mice compared to STZ-NC mice, explaining increased beta-cell mass by DA-1229. The expression of PDX-1, a downstream mediator of GLP-1 action, was increased in islets of STZ-DA mice compared to STZ-NC mice. These results suggest a therapeutic potential of DA-1229 in diabetes, particularly that associated with decreased beta-cell mass.
ESTHER : Cho_2011_Diabetes.Res.Clin.Pract_91_72
PubMedSearch : Cho_2011_Diabetes.Res.Clin.Pract_91_72
PubMedID: 21093089

Title : Genome sequence of strain IMCC9480, a xanthorhodopsin-bearing betaproteobacterium isolated from the Arctic Ocean - Oh_2011_J.Bacteriol_193_3421
Author(s) : Oh HM , Lee K , Jang Y , Kang I , Kim HJ , Kang TW , Kim SY , Cho JC
Ref : Journal of Bacteriology , 193 :3421 , 2011
Abstract : Strain IMCC9480 is a novel member of the family Oxalobacteraceae of the Betaproteobacteria, isolated from the Arctic Ocean by dilution-to-extinction culturing. Here we present the draft genome sequence of strain IMCC9480. The genome is predicted to contain genes for xanthorhodopsin, retinoid biosynthesis, carbon monoxide dehydrogenase, and C(1) metabolism.
ESTHER : Oh_2011_J.Bacteriol_193_3421
PubMedSearch : Oh_2011_J.Bacteriol_193_3421
PubMedID: 21572000
Gene_locus related to this paper: 9burk-f1vv61 , 9burk-f1vzd3 , 9burk-f1w2e1 , 9burk-f1w0q2

Title : Discovery of DA-1229: a potent, long acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes - Kim_2011_Bioorg.Med.Chem.Lett_21_3809
Author(s) : Kim HJ , Kwak WY , Min JP , Lee JY , Yoon TH , Kim HD , Shin CY , Kim MK , Choi SH , Kim HS , Yang EK , Cheong YH , Chae YN , Park KJ , Jang JM , Choi SJ , Son MH , Kim SH , Yoo M , Lee BJ
Ref : Bioorganic & Medicinal Chemistry Lett , 21 :3809 , 2011
Abstract : A series of beta-amino amide containing substituted piperazine-2-one derivatives was synthesized and evaluated as inhibitors of dipeptidyl pepdidase-4 (DPP-4) for the treatment of type 2 diabetes. As results of intensive SAR study of the series, (R)-4-[(R)-3-amino-4-(2,4,5-trifluorophenyl)-butanoyl]-3-(t-butoxymethyl)-piperaz in-2-one (DA-1229) displayed potent DPP-4 inhibition pattern in several animal models, was selected for clinical development.
ESTHER : Kim_2011_Bioorg.Med.Chem.Lett_21_3809
PubMedSearch : Kim_2011_Bioorg.Med.Chem.Lett_21_3809
PubMedID: 21570283

Title : Genome sequence of strain IMCC2047, a novel marine member of the Gammaproteobacteria - Kang_2011_J.Bacteriol_193_3688
Author(s) : Kang I , Kang D , Oh HM , Kim H , Kim HJ , Kang TW , Kim SY , Cho JC
Ref : Journal of Bacteriology , 193 :3688 , 2011
Abstract : Strain IMCC2047 was isolated from the Yellow Sea using dilution-to-extinction culturing. The strain was shown to occupy a distinct phylogenetic position within the Gammaproteobacteria. Here we present the genome sequence of strain IMCC2047, which harbors genes for various metabolic pathways, including proteorhodopsin and ribulose bisphosphate carboxylase.
ESTHER : Kang_2011_J.Bacteriol_193_3688
PubMedSearch : Kang_2011_J.Bacteriol_193_3688
PubMedID: 21602327
Gene_locus related to this paper: 9gamm-f3kbt3 , 9gamm-f3kec2

Title : Complete genome sequence of the polycyclic aromatic hydrocarbon-degrading bacterium Alteromonas sp. strain SN2 - Jin_2011_J.Bacteriol_193_4292
Author(s) : Jin HM , Jeong H , Moon EJ , Math RK , Lee K , Kim HJ , Jeon CO , Oh TK , Kim JF
Ref : Journal of Bacteriology , 193 :4292 , 2011
Abstract : Alteromonas sp. strain SN2, able to metabolize polycyclic aromatic hydrocarbons, was isolated from a crude oil-contaminated sea-tidal flat. Here we report the complete 4.97-Mb genome sequence and annotation of strain SN2. These will advance the understanding of strain SN2's adaptation to the sea-tidal flat ecosystem and its pollutant metabolic versatility.
ESTHER : Jin_2011_J.Bacteriol_193_4292
PubMedSearch : Jin_2011_J.Bacteriol_193_4292
PubMedID: 21705606
Gene_locus related to this paper: altss-f5zcy5 , altss-f5z698

Title : Incretin secretion and serum DPP-IV activity in Korean patients with type 2 diabetes - Han_2010_Diabetes.Res.Clin.Pract_89_e49
Author(s) : Han SJ , Kim HJ , Choi SE , Kang Y , Lee KW , Kim DJ
Ref : Diabetes Res Clin Pract , 89 :e49 , 2010
Abstract : We evaluated incretin secretion and dipeptidyl peptidase (DPP)-IV activity in Korean type 2 diabetic patients compared with non-diabetic subjects. Type 2 diabetic patients showed intact GLP-1 and total GIP levels similar to those in non-diabetic subjects. Serum DPP-IV activity was significantly higher in type 2 diabetic patients (p=0.022).
ESTHER : Han_2010_Diabetes.Res.Clin.Pract_89_e49
PubMedSearch : Han_2010_Diabetes.Res.Clin.Pract_89_e49
PubMedID: 20621378

Title : Prenatally detected congenital perineal mass using 3D ultrasound which was diagnosed as lipoblastoma combined with anorectal malformation: case report - Ahn_2010_J.Korean.Med.Sci_25_1093
Author(s) : Ahn KH , Boo YJ , Seol HJ , Park HT , Hong SC , Oh MJ , Kim T , Kim HJ , Kim YT , Kim SH , Lee KW
Ref : J Korean Med Sci , 25 :1093 , 2010
Abstract : We report a case of prenatally diagnosed congenital perineal mass which was combined with anorectal malformation. The mass was successfully treated with posterior sagittal anorectoplasty postnatally. On ultrasound examination at a gestational age of 23 weeks the fetal perineal mass were found on the right side. Any other defects were not visible on ultrasonography during whole gestation. Amniocentesis was performed to evaluate the fetal karyotyping and acetylcholinesterase which were also normal. As the fetus grew up, the mass size was slowly increased more and more. At birth, a female neonate had a perineal mass on the right side as expected. During operation, the anal sphincteric displacement was found near the mass and reconstructed through posterior sagittal incision. This is the first reported case of prenatally diagnosed congenital perineal mass, after birth which was diagnosed as lipoblastoma and even combined with anorectal malformation. This case shows that it can be of clinical importance to be aware of this rare fetal perineal mass in prenatal diagnosis and counseling.
ESTHER : Ahn_2010_J.Korean.Med.Sci_25_1093
PubMedSearch : Ahn_2010_J.Korean.Med.Sci_25_1093
PubMedID: 20592907

Title : BT-11 improves stress-induced memory impairments through increment of glucose utilization and total neural cell adhesion molecule levels in rat brains - Shin_2009_J.Neurosci.Res_87_260
Author(s) : Shin KY , Won BY , Heo C , Kim HJ , Jang DP , Park CH , Kim S , Kim HS , Kim YB , Lee HG , Lee SH , Cho ZH , Suh YH
Ref : Journal of Neuroscience Research , 87 :260 , 2009
Abstract : In Oriental medicine, roots of Polygala tenuifolia Willdenow have been known to be an important herb that exhibits sedative effects in insomnia, palpitation with anxiety, restlessness, and disorientation in humans. We previously reported that BT-11, extracted from those roots, improved scopolamine-induced amnesia in rats and inhibited acetylcholinesterase activities in vitro. Therefore, we proposed that BT-11 could remedy stress-induced memory deficits in rats. In this study, the stress-induced memory impairments in rats were significantly reversed almost to the control level by BT-11 treatment. To seek an active component of BT-11 that plays an important role in antipsychotic effects, we compared BT-11 with 3,4,5-trimethoxycinnamic acid (TMCA), which is a constituent of those root extracts. However, the effects of TMCA were less or were not consistent with those of BT-11 in some of tests. In particular, BT-11 reversed the stress-induced reduction of glucose utilization by [(18)fluorodeoxyglucose]FDG-PET and the levels of neural cell adhesion molecule (NCAM) in rat brains to the control levels, whereas TMCA did not. Therefore, BT-11 improved stress-induced memory impairments through increment of glucose utilization and total NCAM levels in rat brains. In conclusion, BT-11 may be strongly effective against stress-induced amnesia in rats, through the combined effects of TMCA and other active components of BT-11.
ESTHER : Shin_2009_J.Neurosci.Res_87_260
PubMedSearch : Shin_2009_J.Neurosci.Res_87_260
PubMedID: 18712849

Title : Pancreatic lipase-related protein (PY-PLRP) highly expressed in the vitellogenic ovary of the scallop, Patinopecten yessoensis - Kim_2008_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_151_52
Author(s) : Kim KS , Kim BK , Kim HJ , Yoo MS , Mykles DL , Kim HW
Ref : Comparative Biochemistry & Physiology B Biochem Mol Biol , 151 :52 , 2008
Abstract : A cDNA (1206 bp) encoding a pancreatic lipase-related protein (PY-PLRP) was obtained from the ovary of the scallop, Patinopecten yessoensis, using a differentially expressed gene system. The open reading frame specified a protein containing 353 amino acids (~38 kDa). The N-terminal catalytic domain, which contained the catalytic triad of serine, aspartate, and histidine residues, 10 cysteine residues involved in disulfide bridges, and the conserved lid domain, indicated that the protein would be catalytically active. However, PY-PLRP lacked the C-terminal colipase-binding domain present in mammalian PLRPs. Sequence analysis of the catalytic domains of PY-PLRP with members of the pancreatic triglyceride lipase (PTL) family suggested that PY-PLRP was related to mammalian PLRP1, PLRP2, and PTL. End-point reverse transcriptase-polymerase chain reaction (RT-PCR) after 25 cycles showed that PY-PLRP was expressed at a high level in the ovary and at low levels in testis and mantle; expression was not detected in gill, digestive gland, and adductor muscle. Quantitative PCR of RNA from ovaries at different stages of development showed that PY-PLRP was expressed at a significantly higher level in the late growth stage than in the ripe and spent stages. These data suggest that PY-PLRP plays a role in lipid metabolism associated with oocyte maturation and vitellogenesis that occurs during ovarian growth.
ESTHER : Kim_2008_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_151_52
PubMedSearch : Kim_2008_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_151_52
PubMedID: 18602322
Gene_locus related to this paper: mizye-a0a210q4j1

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 : Functional analysis of mutations in expressed acetylcholinesterasenext term that result in azinphosmethyl and carbofuran resistance in Colorado potato beetle - Kim_2007_Pestic.Biochem.Physiol_88_181
Author(s) : Kim HJ , Yoon KS , Clark JM
Ref : Pesticide Biochemistry and Physiology , 88 :181 , 2007
Abstract : The functional attributes of specific point mutations, R30K, S291G, and I392T, associated with full-length acetylcholinesterase (AChE) cDNAs of organophosphate (OP)- and carbamate-resistant Colorado potato beetles (CPB), were determined using site-directed mutagenesis and baculovirus expression. Enzymatic and inhibitory properties of altered recombinant acetylcholinesterases(rAChEs) were examined. S291G increased the hydrolysis of substrates with larger substituted alkyl groups (e.g., BTC vs ATC) and increased the inhibitory action of inhibitors with larger alkyl groups (e.g., paraoxon, DFP, and N-propyl carbofuran vs. azinphosmethyl-oxon and N-methyl carbofuran). R30K in conjunction with S291G enhanced the hydrolysis activity of larger substrates and the inhibitory action of larger inhibitors. I392T attenuated the effects of S291G in that the altered rAChE with both S291G and I392T elicited substrate specificity and inhibitory properties more similar to the susceptible form of AChE without mutations.
ESTHER : Kim_2007_Pestic.Biochem.Physiol_88_181
PubMedSearch : Kim_2007_Pestic.Biochem.Physiol_88_181
Gene_locus related to this paper: lepde-ACHE

Title : The seed extract of Cassia obtusifolia ameliorates learning and memory impairments induced by scopolamine or transient cerebral hypoperfusion in mice - Kim_2007_J.Pharmacol.Sci_105_82
Author(s) : Kim DH , Yoon BH , Kim YW , Lee S , Shin BY , Jung JW , Kim HJ , Lee YS , Choi JS , Kim SY , Lee KT , Ryu JH
Ref : J Pharmacol Sci , 105 :82 , 2007
Abstract : In the present study, we assessed the effect of the ethanolic extract of the seeds of Cassia obtusifolia (COE) on the learning and memory impairments induced by scopolamine or transient bilateral common carotid artery occlusion (2VO). In a study of the cholinergic dysfunction induced by scopolamine, single COE (25, 50, or 100 mg/kg, p.o.) administration significantly attenuated scopolamine-induced cognitive impairments as determined by the passive avoidance and Y-maze tasks (P<0.05) and also reduced escape-latency on the Morris water maze task (P<0.05). In the 2VO study, COE (50 mg/kg, p.o.) significantly reversed 2VO-induced cognitive impairments in mice by the passive avoidance and the Y-maze tasks (P<0.05). Moreover, COE (50 mg/kg, p.o.) also reduced escape-latency and prolonged swimming time in the target quadrant during a probe trial of the Morris water maze task (P<0.05). In an in vitro study, COE was found to inhibit acetylcholinesterase activity in a dose-dependent manner (IC(50) value: 81.6 microg/ml). Furthermore, COE also inhibited acetylcholinesterase activity in an ex vivo study. These results suggest that COE attenuates memory impairment induced by scopolamine or 2VO and that these effects are mediated by enhancing the cholinergic nervous system via acetylcholinesterase inhibition.
ESTHER : Kim_2007_J.Pharmacol.Sci_105_82
PubMedSearch : Kim_2007_J.Pharmacol.Sci_105_82
PubMedID: 17895591

Title : Development of inhibitors against lipase and alpha-glucosidase from derivatives of monascus pigment - Kim_2007_FEMS.Microbiol.Lett_276_93
Author(s) : Kim JH , Kim HJ , Park HW , Youn SH , Choi DY , Shin CS
Ref : FEMS Microbiology Letters , 276 :93 , 2007
Abstract : New derivatives of monascus pigment were produced during Monascus fermentation by the addition of unnatural amino acids, and the inhibitory activities of the derivatives against diet-related lipase and alpha-glucosidase were tested. Derivatives with penicillamine (H-Pen), cyclohexylalanine (H-Cha), butylglycine (L-t-Bg), and norleucine (H-Nle) showed relatively high inhibitory activities against lipase. The H-Pen derivative exhibited the highest inhibitory activity, with an IC(50) (50% inhibition) value of 24.0 microM. The four derivatives all showed noncompetitive inhibition patterns against lipase. The inhibition constant (K(i)) of the H-Pen derivative was estimated to be 20.7 microM. The H-Pen derivative also exhibited a relatively high inhibitory activity against alpha-glucosidase, with an IC(50) value of 50.9 microM. The inhibition pattern of the H-Pen derivative against alpha-glucosidase appeared to be of a mixed type. The inhibition constants K(i) and were estimated to be 25.9, and 98.9 microM, respectively.
ESTHER : Kim_2007_FEMS.Microbiol.Lett_276_93
PubMedSearch : Kim_2007_FEMS.Microbiol.Lett_276_93
PubMedID: 17937667

Title : In vitro refolding of PEGylated lipase - Kim_2007_J.Biotechnol_131_177
Author(s) : Kim MY , Kwon JS , Kim HJ , Lee EK
Ref : J Biotechnol , 131 :177 , 2007
Abstract : Covalent modification of proteins with polyethylene glycol (PEG) has become a well established drug enhancement strategy in the biopharmaceutical industry. The general benefits of PEGylation, such as prolonged serum half-lives or reduced in vivo immunogenicity, are well known. To date, the PEGylation process has been performed with purified proteins, which often requires additional multi-step purification steps to harvest the desired PEGylate. However, it would be beneficial for bioprocessing if 'renaturation,' i.e. in vitro refolding and 'modification,' and PEGylation can be integrated, especially for inclusion body proteins. We investigated the feasibility of protein PEGylation under denaturing conditions and of protein refolding with the attached PEG molecule. Using lipase as a model protein, PEGylation occurred in 8 M urea and covalently attached PEG did not appear to hinder subsequent refolding.
ESTHER : Kim_2007_J.Biotechnol_131_177
PubMedSearch : Kim_2007_J.Biotechnol_131_177
PubMedID: 17683821

Title : Target site insensitivity and mutational analysis of acetylcholinesterase from a carbofuran-resistant population of Colorado potato beetle, Leptinotarsa decemlineata (Say) - Kim_2006_Pestic.Biochem.Physiol_84_165
Author(s) : Kim HJ , Dunnb JB , Yoon KS , Clark JM
Ref : Pesticide Biochemistry and Physiology , 84 :165 , 2006
Abstract : The BERTS strain of Colorado potato beetle (CPB) was found to be highly resistant to N-methyl carbofuran but relatively susceptible to azinphosmethyl. N-Methyl carbofuran resistance was found to correlate well with acetylcholinesterase (AChE) insensitivity. In becoming resistant to N-methyl carbofuran, the AChE of the BERTS strain became more sensitive to N-propyl carbofuran inhibition. This negative cross-insensitivity correlated well to the increased relative toxicity of the BERTS strain to N-propyl carbofuran compared to the susceptible SS strain. BERTS beetles were sorted into BERTS-R and BERTS-S substrains using their AChE activity profiles. Sequence comparisons of AChE cDNAs from the two substrains revealed the presence of the point mutation that results in the S291G substitution previously found in the AChE of the azinphosmethyl-resistant AZ-R strain of CPB. A novel mutation present only in BERTS-S CPB, however, resulted in an additional I392T substitution in the AChE and apparently reverses the resistance conferring properties of the S291G substitution.
ESTHER : Kim_2006_Pestic.Biochem.Physiol_84_165
PubMedSearch : Kim_2006_Pestic.Biochem.Physiol_84_165
Gene_locus related to this paper: lepde-ACHE

Title : Ontogeny of hepatic and plasma metabolism of deltamethrin in vitro: role in age-dependent acute neurotoxicity - Anand_2006_Drug.Metab.Dispos_34_389
Author(s) : Anand SS , Kim KB , Padilla S , Muralidhara S , Kim HJ , Fisher JW , Bruckner JV
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 34 :389 , 2006
Abstract : Deltamethrin (DLM) is a relatively potent and widely used pyrethroid insecticide. Inefficient detoxification has been proposed to be the primary reason for the greater sensitivity of immature rats to the acute neurotoxicity of DLM. The objective of this study was to test this hypothesis by characterizing the age dependence of DLM metabolism in vitro, as well as toxic signs and blood levels of the neurotoxic parent compound following administration of 10 mg DLM/kg p.o. in glycerol formal. Metabolism was quantified in vitro by monitoring the disappearance of the parent compound from plasma [via carboxylesterases (CaEs)] and liver microsomes [via CaEs and cytochromes P450 (P450s)] obtained from 10-, 21-, and 40-day-old male Sprague-Dawley rats. Mean (+/-S.E.) intrinsic clearances (Vmax/Km) in these respective age groups by liver P450s (4.99+/-0.32, 16.99+/-1.85, and 38.45+/-7.03) and by liver CaEs (0.34+/-0.05, 1.77+/-0.38, and 2.53+/-0.19) and plasma CaEs (0.39+/-0.06, 0.80+/-0.09, and 2.28+/-0.56) increased significantly (p<or=0.05) with age, because of progressive increases in Vmax. Intrinsic clearance of DLM by plasma CaEs and liver P450s reached adult levels by 40 days, but clearance by liver CaEs did not. Hepatic P450s played the predominant role in DLM biotransformation in young and adult rats. The incidence and severity of neurotoxic effects varied inversely with age. Correspondingly, blood DLM areas under the concentration versus time curve (AUCs) and Cmax values progressively decreased with increasing age. Internal exposure to DLM (blood AUCs) was closely correlated with toxic signs (salivation and tremors). The present study provides evidence that the limited metabolic capacity of immature rats contributes to elevated systemic exposure and ensuing neurotoxic effects of DLM.
ESTHER : Anand_2006_Drug.Metab.Dispos_34_389
PubMedSearch : Anand_2006_Drug.Metab.Dispos_34_389
PubMedID: 16326812

Title : Development of a physiologically based pharmacokinetic model for deltamethrin in the adult male Sprague-Dawley rat - Mirfazaelian_2006_Toxicol.Sci_93_432
Author(s) : Mirfazaelian A , Kim KB , Anand SS , Kim HJ , Tornero-Velez R , Bruckner JV , Fisher JW
Ref : Toxicol Sci , 93 :432 , 2006
Abstract : Deltamethrin (DLT) is a type II pyrethroid insecticide widely used in agriculture and public health. DLT is a potent neurotoxin that is primarily cleared from the body by metabolism. To better understand the dosimetry of DLT in the central nervous system, a physiologically based pharmacokinetic (PBPK) model for DLT was constructed for the adult, male Sprague-Dawley rat that employed both flow-limited (brain, gastrointestinal [GI] tract, liver, and rapidly perfused tissues) and diffusion-limited (fat, blood/plasma, and slowly perfused tissues) rate equations. The blood was divided into plasma and erythrocytes. Cytochrome P450-mediated metabolism was accounted for in the liver and carboxylesterase (CaE)-mediated metabolism in plasma and liver. Serial blood, brain, and fat samples were taken for DLT analysis for up to 48 h after adult rats received 2 or 10 mg DLT/kg po. Hepatic biotransformation accounted for approximately 78% of these administered doses. Plasma CaEs accounted for biotransformation of approximately 8% of each dosage. Refined PBPK model forecasts compared favorably to the 2- and 10-mg/kg po blood, plasma, brain, and fat DLT profiles, as well as profiles subsequently obtained from adult rats given 1 mg/kg iv. DLT kinetic profiles extracted from published reports of oral and iv experiments were also used for verification of the model's simulations. There was generally good agreement in most instances between predicted and the limited amount of empirical data. It became clear from our modeling efforts that there is considerably more to be learned about processes that govern GI absorption and exsorption, transport, binding, brain uptake and egress, fat deposition, and systemic elimination of DLT and other pyrethroids. The current model can serve as a foundation for construction of models for other pyrethroids and can be improved as more definitive information on DLT kinetic processes becomes available.
ESTHER : Mirfazaelian_2006_Toxicol.Sci_93_432
PubMedSearch : Mirfazaelian_2006_Toxicol.Sci_93_432
PubMedID: 16831841

Title : Lipase-catalyzed synthesis of sorbitol-fatty acid esters at extremely high substrate concentrations - Kim_2006_J.Biotechnol_123_174
Author(s) : Kim HJ , Youn SH , Shin CS
Ref : J Biotechnol , 123 :174 , 2006
Abstract : Lipase-catalyzed synthesis of sorbitol-fatty acid esters was performed in eutectic media with extremely high substrate concentrations. Homogeneous eutectic melts of sorbitol and fatty acids of C6-C16 were prepared using an adjuvant mixture. Enhanced homogeneity of mixtures was confirmed by X-ray diffraction analysis. The substrate concentration was 3.63-6.67 M in the eutectic media, whereas in organic media the concentration was below 0.10 M. Esters were synthesized with an immobilized Candida antarctica lipase, and optimum conditions were analyzed. Compared to reactions in organic media, the initial reaction rate of ester synthesis and the overall productivity were significantly enhanced in eutectic media while the conversion yields were similar. Based on the kinetic analysis, highly viscous eutectic media were shown to influence the initial reaction rate and the apparent activation energy resulting in diffusion limitations.
ESTHER : Kim_2006_J.Biotechnol_123_174
PubMedSearch : Kim_2006_J.Biotechnol_123_174
PubMedID: 16356573

Title : Effect of enzymatic pretreatment on solubilization and volatile fatty acid production in fermentation of food waste - Kim_2005_Water.Sci.Technol_52_51
Author(s) : Kim HJ , Choi YG , Kim GD , Kim SH , Chung TH
Ref : Water Sci Technol , 52 :51 , 2005
Abstract : Food waste can be a valuable carbon source in biological nutrient removal (BNR) systems because of the high C/N and C/P ratio. However, pretreatment is necessary to promote hydrolysis of food waste because of the high concentration of volatile solids associated with organic matter. The influence of the enzymatic pretreatment on acid fermentation of food waste was investigated in this study. Solubilization of particulate matter in food waste was carried out using commercial enzymes. The acidification efficiency and the volatile fatty acid (VFA) production potential of enzymatically pretreated food waste were examined. The highest volatile suspended solid (VSS) reduction was obtained with an enzyme mixture ratio of 1:2:1 for carbohydrase: protease: lipase. An optimum enzyme dosage for solubilization of food waste was 0.1% (V/V) with the enzyme mixture ratio of 1:2:1. In the acid fermentation of enzymatically pretreated food waste, the maximum VFA production and the highest VFA fraction in soluble COD (SCOD) were also achieved at 0.1% (V/N) of total enzyme dosage. Increase in VFA production at this level of enzyme dosage was over 300% compared with the control fermenter. The major form of VFA produced by fermentation was n-butyrate followed by acetate.
ESTHER : Kim_2005_Water.Sci.Technol_52_51
PubMedSearch : Kim_2005_Water.Sci.Technol_52_51
PubMedID: 16459776

Title : Hormone-sensitive lipase knockout mice have increased hepatic insulin sensitivity and are protected from short-term diet-induced insulin resistance in skeletal muscle and heart - Park_2005_Am.J.Physiol.Endocrinol.Metab_289_E30
Author(s) : Park SY , Kim HJ , Wang S , Higashimori T , Dong J , Kim YJ , Cline G , Li H , Prentki M , Shulman GI , Mitchell GA , Kim JK
Ref : American Journal of Physiology Endocrinol Metab , 289 :E30 , 2005
Abstract : Insulin resistance in skeletal muscle and heart plays a major role in the development of type 2 diabetes and diabetic heart failure and may be causally associated with altered lipid metabolism. Hormone-sensitive lipase (HSL) is a rate-determining enzyme in the hydrolysis of triglyceride in adipocytes, and HSL-deficient mice have reduced circulating fatty acids and are resistant to diet-induced obesity. To determine the metabolic role of HSL, we examined the changes in tissue-specific insulin action and glucose metabolism in vivo during hyperinsulinemic euglycemic clamps after 3 wk of high-fat or normal chow diet in awake, HSL-deficient (HSL-KO) mice. On normal diet, HSL-KO mice showed a twofold increase in hepatic insulin action but a 40% decrease in insulin-stimulated cardiac glucose uptake compared with wild-type littermates. High-fat feeding caused a similar increase in whole body fat mass in both groups of mice. Insulin-stimulated glucose uptake was reduced by 50-80% in skeletal muscle and heart of wild-type mice after high-fat feeding. In contrast, HSL-KO mice were protected from diet-induced insulin resistance in skeletal muscle and heart, and these effects were associated with reduced intramuscular triglyceride and fatty acyl-CoA levels in the fat-fed HSL-KO mice. Overall, these findings demonstrate the important role of HSL on skeletal muscle, heart, and liver glucose metabolism.
ESTHER : Park_2005_Am.J.Physiol.Endocrinol.Metab_289_E30
PubMedSearch : Park_2005_Am.J.Physiol.Endocrinol.Metab_289_E30
PubMedID: 15701680
Gene_locus related to this paper: mouse-hslip

Title : Characterization of an extracellular medium-chain-length poly(3-hydroxyalkanoate) depolymerase from Streptomyces sp. KJ-72 - Kim_2003_Antonie.Van.Leeuwenhoek_83_183
Author(s) : Kim HJ , Kim DY , Nam JS , Bae KS , Rhee YH
Ref : Antonie Van Leeuwenhoek , 83 :183 , 2003
Abstract : A bacterial strain capable of degrading medium-chain-length polyhydroxyalkanoates (MCL-PHAs) was isolated from a soil sample. This organism, which was identified as Streptomyces sp. KJ-72, secreted MCL-PHA depolymerase into the culture fluid only when it was cultivated on MCL-PHAs. The extracellular MCL-PHA depolymerase of the organism was purified to electrophoretic homogeneity by ion exchange column chromatography and gel filtration. The enzyme consisted of a monomeric subunit having a molecular mass of 27.1 kDa and isoelectric point of 4.7. The maximum activity was observed at pH 8.7 and 50 degrees C. The enzyme was sensitive to N-bromosuccinimide and acetic anhydride, indicating the presence of tryptophan and lysine residues in the catalytic domain. The enzyme was able to hydrolyze various chain-length p-nitrophenyl esters of fatty acids and polycaprolactone as well as various types of MCL-PHAs. However, lipase activity of the enzyme was not detected. The main hydrolysis product of poly(3-hydroxyheptanoate) was identified to be the dimer of 3-hydroxyheptanoate.
ESTHER : Kim_2003_Antonie.Van.Leeuwenhoek_83_183
PubMedSearch : Kim_2003_Antonie.Van.Leeuwenhoek_83_183
PubMedID: 12785312

Title : Effects of extract from Angelica keiskei and its component, cynaroside, on the hepatic bromobenzene-metabolizing enzyme system in rats - Park_2002_Phytother.Res_16 Suppl 1_S24
Author(s) : Park JC , Park JG , Kim HJ , Hur JM , Lee JH , Sung NJ , Chung SK , Choi JW
Ref : Phytother Res , 16 Suppl 1 :S24 , 2002
Abstract : The effects of Angelica keiskei Koidz. on hepatic lipid peroxide and the activities of free radical generating and scavenging enzymes were investigated in bromobenzene-induced hepatic lipid peroxidation in rats. The level of lipid peroxide elevated by bromobenzene was significantly reduced by the methanol extract from the aerial parts of A. keiskei and its component, cynaroside. Epoxide hydrolase activity was decreased significantly by the treatment of bromobenzene. However, the enzyme activity was restored in the liver of rats given the methanol extract and cynaroside. The results suggest that the reduction of bromobenzene-induced hepatic lipid peroxidation by the extract of A. keiskei and cynaroside under our experimental conditions is thought to be through enhancing the activity of epoxide hydrolase, an enzyme removing bromobenzene epoxide.
ESTHER : Park_2002_Phytother.Res_16 Suppl 1_S24
PubMedSearch : Park_2002_Phytother.Res_16 Suppl 1_S24
PubMedID: 11933135

Title : DNA-based genotyping techniques for the detection of point mutations associated with insecticide resistance in Colorado potato beetle Leptinotarsa decemlineata - Clark_2001_Pest.Manag.Sci_57_968
Author(s) : Clark JM , Lee SH , Kim HJ , Yoon KS , Zhang A
Ref : Pest Manag Sci , 57 :968 , 2001
Abstract : Three DNA-based genotyping techniques, bi-directional PCR amplification of specific allele (bi-PASA), single-stranded conformational polymorphism (SSCP) and minisequencing, have been developed and compared for the detection of the S291G (insensitive acetylcholinesterase) and L1014F (insensitive sodium channel) mutations associated with azinphos-methyl and permethrin resistance, respectively, in the Colorado potato beetle (Leptinotarsa decemlineata). Extraction of genomic DNA from individual neonates that were hatched from previously collected egg masses is the most efficient and reliable means to obtain suitable templates in terms of convenience, economy, speed and DNA quality. Bi-PASA, employing two allele-specific primers, appears to be the most efficient and rapid genotyping method for the simultaneous detection of both resistant/susceptible homozygous (SS, RR) and heterozygous (SR) alleles. Its resolution, however, is strongly dependent on the quality of template genomic DNA. SSCP also allows unambiguous genotyping, including the detection of heterozygous alleles, and is less dependent on template DNA quality, but requires a longer processing time. Minisequencing is amenable to a 96-well microtiter plate format for the processing of a large number of samples and allows direct detection of resistant/susceptible homozygous alleles but is not as efficient as the PASA and SSCP in detecting heterozygous alleles. In considering the advantages and disadvantages of each technique, DNA-based genotyping is best employed in combinations, with the bi-PASA as the primary method and the SSCP and minisequencing as the secondary validating methods. These methods are rugged, rapid, cost-effective and capable of resolving SS, RR and SR individuals. The availability of such DNA-based genotyping techniques, using neonate genomic DNA as templates, will enable the precise monitoring of the resistant and susceptible allele frequencies, including those of heterozygote individuals, in field populations of L. decemlineata.
ESTHER : Clark_2001_Pest.Manag.Sci_57_968
PubMedSearch : Clark_2001_Pest.Manag.Sci_57_968
PubMedID: 11695191
Gene_locus related to this paper: lepde-ACHE

Title : Inhibition of lipopolysaccharide-induced I-kappaB degradation and tumor necrosis factor-alpha expression by dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB): minor role in hepatic detoxifying enzyme expression - Kim_2000_Liver_20_319
Author(s) : Kim SG , Kim HJ , Choi SH , Ryu JY
Ref : Liver , 20 :319 , 2000
Abstract : AIMS/BACKGROUND: Dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB) is active against a variety of hepatotoxins and has been used as a curative agent for patients with acute and chronic viral hepatitis. Effects of DDB on the expression of xenobiotic-metabolizing enzymes and on nuclear factor-kappaB (NF-kappaB) activation and tumor necrosis factor-alpha (TNF-alpha) production by lipopolysaccharide (LPS), an endotoxin involved in inflammatory responses, were examined in rats and in RAW264.7 cells to investigate mechanistic aspects.
METHODS: Expression of hepatic cytochrome P450s, microsomal epoxide hydrolase and glutathione S-transferases was determined by immunoblot and Northern blot analyses. Activation of hepatic NF-kappaB and I-kappaBalpha degradation was assessed by gel mobility shift and immunoblot analyses, respectively. LPS-induced TNF-alpha expression was monitored in rats and in RAW264.7 cells by enzyme-linked immunosorbent assay and/or reverse transcription-polymerase chain reaction analysis.
RESULTS: DDB failed to alter the expression of hepatic cytochrome P450 1A and 2C11, microsomal epoxide hydrolase and glutathione S-transferases in rats with slight inhibition of P450 2E1 expression, but induced P450 2B1/2. Pretreatment of rats with DDB prevented LPS-induced hepatic I-kappaBalpha degradation and the resultant NF-kappaB activation, and inhibited the LPS-induced plasma TNF-alpha protein and hepatic TNF-alpha mRNA expression in a dose-dependent manner. LPS-induced I-kappaBalpha degradation and TNF-alpha production were also inhibited by DDB in RAW264.7 cells, which was consistent with the results in rats.
CONCLUSIONS: The present study demonstrated that DDB may inhibit inflammatory responses in association with reduction of NF-kappaB activation through prevention of I-kappaBalpha degradation and subsequent TNF-alpha production, but not with modulation of the detoxifying enzyme expression.
ESTHER : Kim_2000_Liver_20_319
PubMedSearch : Kim_2000_Liver_20_319
PubMedID: 10959811

Title : Purification and immunoreactivity of three components from the 30\/32-kilodalton antigen 85 complex in Mycobacterium tuberculosis - Lim_1999_Infect.Immun_67_6187
Author(s) : Lim JH , Park JK , Jo EK , Song CH , Min D , Song YJ , Kim HJ
Ref : Infect Immun , 67 :6187 , 1999
Abstract : The three proteins of the antigen 85 complex (85A, 85B, and 85C), which are major secretory products of Mycobacterium tuberculosis, were purified to homogeneity in large amounts by a combination of chromatography on hydroxylapatite, DEAE-Sepharose, and DEAE-Sephacel and gel filtration from M. tuberculosis culture filtrate. Then we examined the immunological reactivity of the three proteins in tuberculosis patients and healthy controls. Antibody responses to the 85B and 85A proteins in patients were significantly greater than responses to the 85C protein. In contrast, all three antigens induced significant lymphoproliferation and gamma interferon production in peripheral blood mononuclear cells from healthy tuberculin reactors.
ESTHER : Lim_1999_Infect.Immun_67_6187
PubMedSearch : Lim_1999_Infect.Immun_67_6187
PubMedID: 10531287

Title : No association between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset Alzheimer's disease - Ki_1999_Am.J.Med.Genet_88_113
Author(s) : Ki CS , Na DL , Kim JW , Kim HJ , Kim DK , Yoon BK
Ref : American Journal of Medicine Genet , 88 :113 , 1999
Abstract : Butyrylcholinesterase (BChE) as well as acetylcholinesterase has been suggested to be associated with Alzheimer's disease (AD). Lehmann et al. [1997: Hum Mol Genet 6:1933-1936] recently reported the synergism between the gene for the K variant of BChE (BCHE-K) and the epsilon4 allele of apolipoprotein E (APOE epsilon4) in late-onset confirmed AD with Caucasian subjects. The authors found that the allelic frequency of BCHE-K was 0.17 in 74 subjects with late-onset histopathologically diagnosed AD, which was higher than the frequencies in elderly control subjects (0.09) and in other dementias (0.07-0.10). The association of BCHE-K with late-onset AD was limited to carriers of APOE epsilon4, giving odds ratios of confirmed late-onset AD of 6.9-12.8. In the present study, we report the BCHE-K allelic frequencies in late-onset AD cases and in age-matched controls of the Korean population, which were 0.22 and 0.17, respectively. We could not find any association between BCHE-K and AD regardless of APOE epsilon4 carrier status. However, APOE epsilon4 clearly showed higher frequency in AD (0.33) than in elderly controls (0.09), giving an odds ratio of 5.2 (95% confidence interval, 2.7-10.0). Our results do not support the conclusion that BCHE-K, or a nearby gene on chromosome 3, acts in synergy with APOE epsilon4 as a susceptibility gene for late-onset AD, at least in the Korean population.
ESTHER : Ki_1999_Am.J.Med.Genet_88_113
PubMedSearch : Ki_1999_Am.J.Med.Genet_88_113
PubMedID: 10206226