Park SJ

References (30)

Title : Combinatorial expression of neurexin genes regulates glomerular targeting by olfactory sensory neurons - Park_2024_bioRxiv__
Author(s) : Park SJ , Wang IH , Lee N , Jiang HC , Uemura T , Futai K , Kim D , Macosko E , Greer P
Ref : Biorxiv , : , 2024
Abstract : Precise connectivity between specific neurons is essential for the formation of the complex neural circuitry necessary for executing intricate motor behaviors and higher cognitive functions. While trans -interactions between synaptic membrane proteins have emerged as crucial elements in orchestrating the assembly of these neural circuits, the synaptic surface proteins involved in neuronal wiring remain largely unknown. Here, using unbiased single-cell transcriptomic and mouse genetic approaches, we uncover that the neurexin family of genes enables olfactory sensory neuron (OSNs) axons to form appropriate synaptic connections with their mitral and tufted (M/T) cell synaptic partners, within the mammalian olfactory system. Neurexin isoforms are differentially expressed within distinct populations of OSNs, resulting in unique pattern of neurexin expression that is specific to each OSN type, and synergistically cooperate to regulate axonal innervation, guiding OSN axons to their designated glomeruli. This process is facilitated through the interactions of neurexins with their postsynaptic partners, including neuroligins, which have distinct expression patterns in M/T cells. Our findings suggest a novel mechanism underpinning the precise assembly of olfactory neural circuits, driven by the trans -interaction between neurexins and their ligands.
ESTHER : Park_2024_bioRxiv__
PubMedSearch : Park_2024_bioRxiv__
PubMedID: 38617205

Title : Efficient Production of Naringin Acetate with Different Acyl Donors via Enzymatic Transesterification by Lipases - Baek_2022_Int.J.Environ.Res.Public.Health_19_
Author(s) : Baek Y , Lee S , Son J , Lee T , Oh JM , Lee SH , Kim HU , Seo SW , Park SJ , Yoo HY , Park C
Ref : Int J Environ Research Public Health , 19 : , 2022
Abstract : Naringin, one of the citrus flavonoids and known as a natural antioxidant, has limited bioavailability owing to its low stability and solubility. However, naringin esters formed via acylation have recently been reported to possess improved physical and chemical properties. The development of these compounds has a great potential in the food, cosmetic and pharmaceutical industries, but low conversion and productivity are barriers to industrial applications. This study aimed to improve the conversion of naringin acetate, which is formed via the enzymatic reaction between naringin and an acyl donor. An optimal reaction condition was determined by evaluating the effect of various variables (enzyme type, enzyme concentration, acyl donor, molar ratio of reactants, reaction temperature, and solvent) on the synthesis of naringin acetate. The optimal condition was as follows: 3 g/L of Lipozyme TL IM, molar ratio of 1:5 (naringin:acyl donor), reaction temperature of 40 degreesC, and acetonitrile as the reaction solvent. Under this condition, the maximum conversion to naringin acetate from acetic anhydride and vinyl acetate was achieved at approximately 98.5% (8 h) and 97.5% (24 h), respectively. Compared to the previously reported values, a high conversion was achieved within a short time, confirming the commercial potential of the process.
ESTHER : Baek_2022_Int.J.Environ.Res.Public.Health_19_
PubMedSearch : Baek_2022_Int.J.Environ.Res.Public.Health_19_
PubMedID: 35270665

Title : Assessments of the In Vitro and In Vivo Linker Stability and Catabolic Fate for the Ortho Hydroxy-Protected Aryl Sulfate Linker by Immuno-Affinity Capture Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometric Assay - Lee_2021_Pharmaceutics_13_
Author(s) : Lee BI , Park SJ , Park Y , Shin SH , Choi JM , Park MJ , Lim JH , Kim SY , Lee H , Shin YG
Ref : Pharmaceutics , 13 : , 2021
Abstract : Antibody-drug conjugate (ADC) linkers play an important role in determining the safety and efficacy of ADC. The Ortho Hydroxy-Protected Aryl Sulfate (OHPAS) linker is a newly developed linker in the form of a di-aryl sulfate structure consisting of phenolic payload and self-immolative group (SIG). In this study, using two bioanalytical approaches (namely "bottom-up" and "middle-up" approaches) via the liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qTOF-MS) method, in vitro and in vivo linker stability experiments were conducted for the OHPAS linker. For comparison, the valine-citrulline-p-aminobenzyloxycarbonyl (VC-PABC) linker was also evaluated under the same experimental conditions. In addition, the catabolite identification experiments at the subunit intact protein level were simultaneously performed to evaluate the catabolic fate of ADCs. As a result, the OHPAS linker was stable in the in vitro mouse/human plasma as well as in vivo pharmacokinetic studies in mice, whereas the VC-PABC linker was relatively unstable in mice in vitro and in vivo. This is because the VC-PABC linker was sensitive to a hydrolytic enzyme called carboxylesterase 1c (Ces1c) in mouse plasma. In conclusion, the OHPAS linker appears to be a good linker for ADC, and further experiments would be warranted to demonstrate the efficacy and toxicity related to the OHPAS linker.
ESTHER : Lee_2021_Pharmaceutics_13_
PubMedSearch : Lee_2021_Pharmaceutics_13_
PubMedID: 33478046
Gene_locus related to this paper: mouse-Ces1c

Title : CRISPR-Knockout of CSE Gene Improves Saccharification Efficiency by Reducing Lignin Content in Hybrid Poplar - Jang_2021_Int.J.Mol.Sci_22_
Author(s) : Jang HA , Bae EK , Kim MH , Park SJ , Choi NY , Pyo SW , Lee C , Jeong HY , Lee H , Choi YI , Ko JH
Ref : Int J Mol Sci , 22 : , 2021
Abstract : Caffeoyl shikimate esterase (CSE) has been shown to play an important role in lignin biosynthesis in plants and is, therefore, a promising target for generating improved lignocellulosic biomass crops for sustainable biofuel production. Populus spp. has two CSE genes (CSE1 and CSE2) and, thus, the hybrid poplar (Populus alba x P. glandulosa) investigated in this study has four CSE genes. Here, we present transgenic hybrid poplars with knockouts of each CSE gene achieved by CRISPR/Cas9. To knockout the CSE genes of the hybrid poplar, we designed three single guide RNAs (sg1-sg3), and produced three different transgenic poplars with either CSE1 (CSE1-sg2), CSE2 (CSE2-sg3), or both genes (CSE1/2-sg1) mutated. CSE1-sg2 and CSE2-sg3 poplars showed up to 29.1% reduction in lignin deposition with irregularly shaped xylem vessels. However, CSE1-sg2 and CSE2-sg3 poplars were morphologically indistinguishable from WT and showed no significant differences in growth in a long-term living modified organism (LMO) field-test covering four seasons. Gene expression analysis revealed that many lignin biosynthetic genes were downregulated in CSE1-sg2 and CSE2-sg3 poplars. Indeed, the CSE1-sg2 and CSE2-sg3 poplars had up to 25% higher saccharification efficiency than the WT control. Our results demonstrate that precise editing of CSE by CRISPR/Cas9 technology can improve lignocellulosic biomass without a growth penalty.
ESTHER : Jang_2021_Int.J.Mol.Sci_22_
PubMedSearch : Jang_2021_Int.J.Mol.Sci_22_
PubMedID: 34575913
Gene_locus related to this paper: arath-F14G24.3

Title : Chemo-Biological Upcycling of Poly(ethylene terephthalate) to Multifunctional Coating Materials - Kim_2021_ChemSusChem_14_4251
Author(s) : Kim HT , Ryu MH , Jung YJ , Lim S , Song HM , Park J , Hwang SY , Lee HS , Yeon YJ , Sung BH , Bornscheuer UT , Park SJ , Joo JC , Oh DX
Ref : ChemSusChem , 14 :4251 , 2021
Abstract : Chemo-biological upcycling of poly(ethylene terephthalate) (PET) developed in this study includes the following key steps: chemo-enzymatic PET depolymerization, biotransformation of terephthalic acid (TPA) into catechol, and its application as a coating agent. Monomeric units were first produced through PET glycolysis into bis(2-hydroxyethyl) terephthalate (BHET), mono(2-hydroxyethyl) terephthalate (MHET), and PET oligomers and enzymatic hydrolysis of these glycolyzed products using Bacillus subtilis esterase (Bs2Est). Bs2Est efficiently hydrolyzed glycolyzed products into TPA as a key enzyme for chemo-enzymatic depolymerization. Furthermore, catechol solution produced from TPA via a whole-cell biotransformation (Escherichia coli) could be directly used for functional coating on various substrates just after simple cell removal from the culture medium without further purification and water-evaporation. This work demonstrates a proof-of-concept of a PET upcycling strategy via a combination of chemo-biological conversion of PET waste into multifunctional coating materials.
ESTHER : Kim_2021_ChemSusChem_14_4251
PubMedSearch : Kim_2021_ChemSusChem_14_4251
PubMedID: 34339110
Gene_locus related to this paper: bacsu-pnbae

Title : Improving the organic solvent resistance of lipase a from Bacillus subtilis in water-ethanol solvent through rational surface engineering - Min_2021_Bioresour.Technol_337_125394
Author(s) : Min K , Kim HT , Park SJ , Lee S , Jung YJ , Lee JS , Yoo YJ , Joo JC
Ref : Bioresour Technol , 337 :125394 , 2021
Abstract : Given that lipase is an enzyme applicable in various industrial fields and water-miscible organic solvents are important reaction media for developing industrial-scale biocatalysis, a structure-based strategy was explored to stabilize lipase A from Bacillus subtilis in a water-ethanol cosolvent. Site-directed mutagenesis of ethanol-interacting sites resulted in 4 mutants, i.e., Ser16Gly, Ala38Gly, Ala38Thr, and Leu108Asn, which were stable in 50% ethanol and had up to 1.8-fold higher stability than the wild-type. In addition, Leu108Asn was more thermostable at 45 degreesC than the wild type. The results discussed in this study not only provide insights into strategies for enzyme engineering to improve organic solvent resistance but also suggest perspectives on pioneering routes for constructing enzyme-based biorefineries to produce value-added fuels and chemicals.
ESTHER : Min_2021_Bioresour.Technol_337_125394
PubMedSearch : Min_2021_Bioresour.Technol_337_125394
PubMedID: 34134054

Title : Dracocephalum moldavica attenuates scopolamine-induced cognitive impairment through activation of hippocampal ERK-CREB signaling in mice - Deepa_2020_J.Ethnopharmacol__
Author(s) : Deepa P , Bae HJ , Park HB , Kim SY , Kim S , Choi JW , Kim DH , Liu XQ , Ryu JH , Park SJ
Ref : J Ethnopharmacol , : , 2020
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Dracocephalum moldavica (Moldavian balm) has been traditionally used for the treatment of intellectual disabilities, migraines and cardiovascular problems in East Asia. Recent scientific studies have demonstrated the usefulness of this plant to treat neurodegenerative disorders, including Alzheimer's disease. AIM OF THE STUDY: This study aimed to investigate the effects of the ethanolic extract of D. moldavica leaves (EEDM) on scopolamine-induced cognitive impairment in mice and the underlying mechanisms of action. MATERIALS AND METHODS: The behavioral effects of EEDM were examined using the step-through passive avoidance and Morris water maze tasks. To elucidate the underlying mechanism, we tested whether EEDM affects acetylcholinesterase activity and the expression of memory-related signaling molecules including extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB) in the hippocampus. RESULTS: EEDM (25, 50 or 100mg/kg) significantly ameliorated the scopolamine-induced step-through latency reduction in the passive avoidance task in mice. In the Morris water maze task, EEDM (50mg/kg) significantly attenuated scopolamine-induced memory impairment. Furthermore, the administration of EEDM increased the phosphorylation levels of ERK and CREB in the hippocampus but did not alter acetylcholinesterase activity. CONCLUSIONS: These findings suggest that EEDM significantly attenuates scopolamine-induced memory impairment in mice and may be a promising therapeutic agent for improving memory impairment.
ESTHER : Deepa_2020_J.Ethnopharmacol__
PubMedSearch : Deepa_2020_J.Ethnopharmacol__
PubMedID: 32035879

Title : ABHD12 Knockdown Suppresses Breast Cancer Cell Proliferation, Migration and Invasion - Jun_2020_Anticancer.Res_40_2601
Author(s) : Jun S , Kim SW , Lim JY , Park SJ
Ref : Anticancer Research , 40 :2601 , 2020
Abstract : BACKGROUND/AIM: Alpha/beta-hydrolase domain containing 12 (ABHD12) is a serine hydrolase that regulates immunological and neurological mechanisms. This study aimed to elucidate the oncogenic effect of ABHD12 on human breast cancer. MATERIALS AND METHODS: ABHD12 expression was confirmed in breast cancer tissues and breast cancer cell lines by immunohistochemistry and quantitative RT-PCR. To determine the role of ABHD12, ABHD12 siRNA-suppressed breast cancer cells (MCF7 and MDA-MB-231 cells) were investigated for cell proliferation, migration, and invasion capabilities using MTT assays, EdU assays, colony formation assays, and Boyden chamber assays. RESULTS: Immunohistochemical staining showed a higher ABHD12 expression in breast cancer tissues than in normal tissues. Additionally, ABHD12 knockdown was found to inhibit cell growth, proliferation, migration, and invasion in breast cancer cells. CONCLUSION: ABHD12 plays a crucial role in cell proliferation, migration, and invasion of breast cancer cells.
ESTHER : Jun_2020_Anticancer.Res_40_2601
PubMedSearch : Jun_2020_Anticancer.Res_40_2601
PubMedID: 32366405
Gene_locus related to this paper: human-ABHD12

Title : M1 muscarinic acetylcholine receptor dysfunction in moderate Alzheimer's disease pathology - Yi_2020_Brain.Commun_2_fcaa058
Author(s) : Yi JH , Whitcomb DJ , Park SJ , Martinez-Perez C , Barbati SA , Mitchell SJ , Cho K
Ref : Brain Commun , 2 :fcaa058 , 2020
Abstract : Aggregation of amyloid beta and loss of cholinergic innervation in the brain are predominant components of Alzheimer's disease pathology and likely underlie cognitive impairment. Acetylcholinesterase inhibitors are one of the few treatment options for Alzheimer's disease, where levels of available acetylcholine are enhanced to counteract the cholinergic loss. However, these inhibitors show limited clinical efficacy. One potential explanation for this is a concomitant dysregulation of cholinergic receptors themselves as a consequence of the amyloid beta pathology. We tested this hypothesis by examining levels of M1 muscarinic acetylcholine receptors in the temporal cortex from seven Alzheimer's disease and seven non-disease age-matched control brain tissue samples (control: 85 +/- 2.63 years old, moderate Alzheimer's disease: 84 +/- 2.32 years old, P-value = 0.721; eight female and six male patients). The samples were categorized into two groups: 'control' (Consortium to Establish a Registry for Alzheimer's Disease diagnosis of 'No Alzheimer's disease', and Braak staging pathology of I-II) and 'moderate Alzheimer's disease' (Consortium to Establish a Registry for Alzheimer's Disease diagnosis of 'possible/probable Alzheimer's disease', and Braak staging pathology of IV). We find that in comparison to age-matched controls, there is a loss of M1 muscarinic acetylcholine receptors in moderate Alzheimer's disease tissue (control: 2.17 +/- 0.27 arbitrary units, n = 7, Mod-AD: 0.83 +/- 0.16 arbitrary units, n = 7, two-tailed t-test, t = 4.248, P = 0.00113). Using a functional rat cortical brain slice model, we find that postsynaptic muscarinic acetylcholine receptor function is dysregulated by aberrant amyloid beta-mediated activation of metabotropic glutamate receptor 5. Crucially, blocking metabotropic glutamate receptor 5 restores muscarinic acetylcholine receptor function and object recognition memory in 5XFAD transgenic mice. This indicates that the amyloid beta-mediated activation of metabotropic glutamate receptor 5 negatively regulates muscarinic acetylcholine receptor and illustrates the importance of muscarinic acetylcholine receptors as a potential disease-modifying target in the moderate pathological stages of Alzheimer's disease.
ESTHER : Yi_2020_Brain.Commun_2_fcaa058
PubMedSearch : Yi_2020_Brain.Commun_2_fcaa058
PubMedID: 32766549

Title : Carboxylesterase-2-Selective Two-Photon Ratiometric Probe Reveals Decreased Carboxylesterase-2 Activity in Breast Cancer Cells - Park_2018_Anal.Chem_90_9465
Author(s) : Park SJ , Kim YJ , Kang JS , Kim IY , Choi KS , Kim HM
Ref : Analytical Chemistry , 90 :9465 , 2018
Abstract : Human carboxylesterase-2 (CE2) is a carboxylesterase that catalyzes the hydrolysis of endogenous and exogenous substrates. Abnormal CE2 levels are associated with various cancers, and CE2 is a key mediator of anticancer prodrugs, including irinotecan. Here, we developed a two-photon ratiometric probe for detecting CE2 activity using succinate ester as a recognition site for CE2. The probe showed high selectivity to CE2, a clear emission color change, high photostability, and bright two-photon microscopy (TPM) imaging capability, allowing the quantitative detection of CE2 activity in live cells. Using TPM ratio analysis, we show for the first time that CE2 activity was much lower in breast cancer cells than in normal cells. In CE2 overexpression studies, cancer cells had a markedly enhanced sensitivity to the cytotoxic effect of irinotecan, corresponding well with the TPM ratio of the probe. These results may provide useful information for quantitatively measuring CE2 activity in situ and predicting the responsiveness to anticancer drugs.
ESTHER : Park_2018_Anal.Chem_90_9465
PubMedSearch : Park_2018_Anal.Chem_90_9465
PubMedID: 30016861

Title : Oleanolic acid ameliorates cognitive dysfunction caused by cholinergic blockade via TrkB-dependent BDNF signaling - Jeon_2017_Neuropharmacol_113_100
Author(s) : Jeon SJ , Lee HJ , Lee HE , Park SJ , Gwon Y , Kim H , Zhang J , Shin CY , Kim DH , Ryu JH
Ref : Neuropharmacology , 113 :100 , 2017
Abstract : Oleanolic acid is a naturally occurring triterpenoid and is widely present in food and medicinal plants. To examine the effect of oleanolic acid on memory deficits, we employed a cholinergic blockade-induced cognitive deficit mouse model. A single administration of oleanolic acid significantly increased the latency on the passive avoidance task and affected the alternation behavior on the Y-maze task and the exploration time on the novel object recognition task, indicating that oleanolic acid reverses the cognitive impairment induced by scopolamine. In accordance with previous reports, oleanolic acid enhanced extracellular-signal-regulated kinase 1/2 (ERK1/2) and cAMP response element-binding protein (CREB) phosphorylation and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Interestingly, ameliorating effect of oleanolic acid on scopolamine-induced memory impairment was abolished by N2-(2-{[(2-oxoazepan-3-yl)amino]carbonyl}phenyl)benzo[b]thiophene-2-carboxamide (ANA-12), a potent and specific inhibitor of tropomyosin receptor kinase B (TrkB), in the passive avoidance task. Similarly, oleanolic acid significantly evoked long-term potentiation in a dose-dependent manner, which was diminished by ANA-12 treatment as shown in the electrophysiology study. Together, these results imply that oleanolic acid ameliorates scopolamine-induced memory impairment by modulating the BDNF-ERK1/2-CREB pathway through TrkB activation in mice, suggesting that oleanolic acid would be a potential therapeutic agent for the treatment of cognitive deficits.
ESTHER : Jeon_2017_Neuropharmacol_113_100
PubMedSearch : Jeon_2017_Neuropharmacol_113_100
PubMedID: 27470063

Title : Carboxylic Acid-Functionalized Conducting-Polymer Nanotubes as Highly Sensitive Nerve-Agent Chemiresistors - Kwon_2016_Sci.Rep_6_33724
Author(s) : Kwon OS , Park CS , Park SJ , Noh S , Kim S , Kong HJ , Bae J , Lee CS , Yoon H
Ref : Sci Rep , 6 :33724 , 2016
Abstract : Organophosphates are powerful inhibitors of acetylcholinesterase, which is critical to nerve function. Despite continuous research for detecting the highly toxic organophosphates, a new and improved methodology is still needed. Herein we demonstrate simple-to-fabricate chemiresistive gas sensors using conducting-polymer polypyrrole (PPy) nanotube transducers, which are chemically specific and capable of recognizing sub-ppb concentrations (ca. 0.5 ppb) of dimethyl methylphosphonate (DMMP), a simulant of nerve agent sarin. Interestingly, the introduction of carboxylic groups on the surface of PPy nanotube transistors resulted in enhanced sensitivity to DMMP via intermolecular hydrogen bonding. Furthermore, it was found that the sensitivity of the nanotube transducer depended on the degree of the carboxylic group introduced. Finally, a sensor array composed of 5 different transducers including the carboxylated nanotubes exhibited excellent selectivity to DMMP in 16 vapor species.
ESTHER : Kwon_2016_Sci.Rep_6_33724
PubMedSearch : Kwon_2016_Sci.Rep_6_33724
PubMedID: 27650635

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 : A carboxylesterase-selective ratiometric fluorescent two-photon probe and its application to hepatocytes and liver tissues - Park_2016_Chem.Sci_7_3703
Author(s) : Park SJ , Lee HW , Kim HR , Kang C , Kim HM
Ref : Chem Sci , 7 :3703 , 2016
Abstract : Carboxylesterases (CEs) are widely distributed enzymes in the human body that catalyze hydrolysis of various endogenous and exogenous substrates. They are directly linked to hepatic drug metabolisms and steatosis, and their regulations are important issues in pharmacological and clinical applications. In this work, we have developed an emission ratiometric two-photon probe (SE1) for quantitatively detecting CE in situ. This probe is based on a translation of intramolecular charge transfer character upon reaction with CE. It shows a sensitive blue-to-yellow emission change in response to human CE activity, easy loading into cells, insensitivity to pH and other metabolites including ROS and RNS, high photostability, and low cytotoxicity. Using live hepatocytes and liver tissues, we found that ratiometric two-photon microscopic imaging with SE1 is an effective tool for monitoring CE activities at the subcellular level in live tissues. This probe will find useful applications in biomedical research, including studies of hepatic steatosis and drug developments.
ESTHER : Park_2016_Chem.Sci_7_3703
PubMedSearch : Park_2016_Chem.Sci_7_3703
PubMedID: 30008999

Title : Spirosoma radiotolerans sp. nov., a gamma-radiation-resistant bacterium isolated from gamma ray-irradiated soil - Lee_2014_Curr.Microbiol_69_286
Author(s) : Lee JJ , Srinivasan S , Lim S , Joe M , Im S , Bae SI , Park KR , Han JH , Park SH , Joo BM , Park SJ , Kim MK
Ref : Curr Microbiol , 69 :286 , 2014
Abstract : A Gram-negative, short-rod-shaped bacterial strain with gliding motility, designated as DG5A(T), was isolated from a rice field soil in South Korea. Phylogenic analysis using 16S rRNA gene sequence of the new isolate showed that strain DG5A(T) belong to the genus Spirosoma in the family Spirosomaceae, and the highest sequence similarities were 95.5 % with Spirosoma linguale DSM 74(T), 93.4 % with Spirosoma rigui WPCB118(T), 92.8 % with Spirosoma luteum SPM-10(T), 92.7 % with Spirosoma spitsbergense SPM-9(T), and 91.9 % with Spirosoma panaciterrae Gsoil 1519(T). Strain DG5A(T) revealed resistance to gamma and UV radiation. Chemotaxonomic data showed that the most abundant fatty acids were summed feature C(16:1) omega7c/C(16:1) omega6c (36.90 %), C(16:1) omega5c (29.55 %), and iso-C(15:0) (14.78 %), and the major polar lipid was phosphatidylethanolamine (PE). The DNA G+C content of strain DG5A(T) was 49.1 mol%. Together, the phenotypic, phylogenetic, and chemotaxonomic data supported that strain DG5A(T) presents a novel species of the genus Spirosoma, for which the name Spirosoma radiotolerans sp. nov., is proposed. The type strain is DG5A(T) (=KCTC 32455(T) = JCM19447(T)).
ESTHER : Lee_2014_Curr.Microbiol_69_286
PubMedSearch : Lee_2014_Curr.Microbiol_69_286
PubMedID: 24748440
Gene_locus related to this paper: 9bact-a0a0e3v606 , 9bact-a0a0e3zrk0 , 9bact-a0a0e3zva1 , 9bact-a0a0e3zvi6 , 9bact-a0a0e3zsw1 , 9bact-a0a0e3vah2 , 9bact-a0a0e4a055

Title : Amyrin attenuates scopolamine-induced cognitive impairment in mice - Park_2014_Biol.Pharm.Bull_37_1207
Author(s) : Park SJ , Ahn YJ , Oh SR , Lee Y , Kwon G , Woo H , Lee HE , Jang DS , Jung JW , Ryu JH
Ref : Biol Pharm Bull , 37 :1207 , 2014
Abstract : Alzheimer's disease, a neurodegenerative disorder, is characterized by progressive cognitive impairment associated with the disruption of cholinergic neurotransmission. The aim of the present study was to evaluate the effect of alpha- or beta-amyrin, a type of pentacyclic triterpene, on the cognitive impairment induced by scopolamine, a muscarinic acetylcholine receptor antagonist. To measure the abilities of various types of learning and memory, we conducted step-through passive avoidance task. Scopolamine induced deficits in learning and memory processes in mice, which were antagonized by a single administration of alpha-amyrin (2 or 4 mg/kg) or beta-amyrin (4 mg/kg), respectively. Additionally, in vitro analysis revealed that acetylcholinesterase activity was inhibited by beta-amyrin, but not by alpha-amyrin. Furthermore, Western blot analysis revealed that the expression levels of phosphorylated extracellular signal-regulated kinase 1/2 (pERK) and phosphorylated glycogen synthase kinase-3beta (pGSK-3beta) were significantly enhanced by a single administration of alpha- and beta-amyrin in the hippocampus. Finally, the memory ameliorating effects of alpha- or beta-amyrin on the scopolamine-induced cognitive impairments were significantly blocked by ERK inhibitor U0126. The present study suggests that alpha- and beta-amyrin may ameliorate the cognitive impairment induced by hypocholinergic neurotransmission via the activation of ERK as well as GSK-3beta signaling.
ESTHER : Park_2014_Biol.Pharm.Bull_37_1207
PubMedSearch : Park_2014_Biol.Pharm.Bull_37_1207
PubMedID: 24989012

Title : Expression of a lipase on the cell-surface of Escherichia coli using the OmpW anchoring motif and its application to enantioselective reactions - Lee_2013_Biotechnol.Lett_35_1677
Author(s) : Lee H , Park SJ , Han MJ , Eom GT , Choi MJ , Kim SH , Oh YH , Song BK , Lee SH
Ref : Biotechnol Lett , 35 :1677 , 2013
Abstract : Microbial-surface display is the expression of proteins or peptides on the surface of cells by fusing an appropriate protein as an anchoring motif. Here, the outer membrane protein W (OmpW) was selected as a fusion partner for functional expression of Pseudomonas fluorescence SIK W1 lipase (TliA) on the cell-surface of Escherichia coli. Localization of the truncated OmpW-TliA fusion protein on the cell-surface was confirmed by immunoblotting and functional assay of lipase activity. Enantioselective hydrolysis of rac-phenylethyl butanoate by the displayed lipase resulted in optically active (R)-phenyl ethanol with 96 % enantiomeric excess and 44 % of conversion in 5 days. Thus, a small outer membrane protein OmpW, is a useful anchoring motif for displaying an active enzyme of ~50 kDa on the cell-surface and the surface-displayed lipase can be employed as an enantioselective biocatalyst in organic synthesis.
ESTHER : Lee_2013_Biotechnol.Lett_35_1677
PubMedSearch : Lee_2013_Biotechnol.Lett_35_1677
PubMedID: 23881313

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 : Inactivation of JAK2\/STAT3 signaling axis and downregulation of M1 mAChR cause cognitive impairment in klotho mutant mice, a genetic model of aging - Park_2013_Neuropsychopharmacology_38_1426
Author(s) : Park SJ , Shin EJ , Min SS , An J , Li Z , Hee Chung Y , Hoon Jeong J , Bach JH , Nah SY , Kim WK , Jang CG , Kim YS , Nabeshima Y , Nabeshima T , Kim HC
Ref : Neuropsychopharmacology , 38 :1426 , 2013
Abstract : We previously reported cognitive dysfunction in klotho mutant mice. In the present study, we further examined novel mechanisms involved in cognitive impairment in these mice. Significantly decreased janus kinase 2 (JAK2) and signal transducer and activator of transcription3 (STAT3) phosphorylation were observed in the hippocampus of klotho mutant mice. A selective decrease in protein expression and binding density of the M1 muscarinic cholinergic receptor (M1 mAChR) was observed in these mice. Cholinergic parameters (ie, acetylcholine (ACh), choline acetyltransferase (ChAT), and acetylcholinesterase (AChE)) and NMDAR-dependent long-term potentiation (LTP) were significantly impaired in klotho mutant mice. McN-A-343 (McN), an M1 mAChR agonist, significantly attenuated these impairments. AG490 (AG), a JAK2 inhibitor, counteracted the attenuating effects of McN, although AG did not significantly alter the McN-induced effect on AChE. Furthermore, AG significantly inhibited the attenuating effects of McN on decreased NMDAR-dependent LTP, protein kinase C betaII, p-ERK, p-CREB, BDNF, and p-JAK2/p-STAT3-expression in klotho mutant mice. In addition, k252a, a BDNF receptor tyrosine kinase B (TrkB) inhibitor, significantly counteracted McN effects on decreased ChAT, ACh, and M1 mAChR and p-JAK2/p-STAT3 expression. McN-induced effects on cognitive impairment in klotho mutant mice were consistently counteracted by either AG or k252a. Our results suggest that inactivation of the JAK2/STAT3 signaling axis and M1 mAChR downregulation play a critical role in cognitive impairment observed in klotho mutant mice.
ESTHER : Park_2013_Neuropsychopharmacology_38_1426
PubMedSearch : Park_2013_Neuropsychopharmacology_38_1426
PubMedID: 23389690

Title : The memory-ameliorating effects of Artemisia princeps var. orientalis against cholinergic dysfunction in mice - Liu_2012_Am.J.Chin.Med_40_993
Author(s) : Liu X , Kim DH , Kim JM , Park SJ , Cai M , Jang DS , Ryu JH
Ref : Am J Chin Med , 40 :993 , 2012
Abstract : Artemisia princeps var. orientalis (Compositae) is widely distributed in China, Japan and Korea and is known to have anti-inflammatory and anti-oxidative activities. The ethyl acetate fraction of ethanolic extract of A. princeps var. orientalis (AEA) was found to inhibit acetylcholinesterase activity in a dose-dependent manner in vitro (IC(50) value: 541.4 +/- 67.5 mug/ml). Therefore, we investigated the effects of AEA on scopolamine-induced learning and memory impairment using the passive avoidance, the Y-maze, and the Morris water maze tasks in mice. AEA (100 or 200 mg/kg, p.o.) significantly ameliorated scopolamine-induced cognitive impairments in the passive avoidance and Y-maze tasks (p < 0.05). In the Morris water maze task, AEA (200 mg/kg, p.o.) significantly shortened escape latencies in training trials and increased both swimming time spent in the target zone and probe crossing numbers during the probe trial as compared with scopolamine-treated mice (p < 0.05). Additionally, the ameliorating effect of AEA on scopolamine-induced memory impairment was antagonized by a subeffective dose of MK-801. These results suggest that AEA could be an effective treatment against cholinergic dysfunction and its effect is mediated by the enhancement of the cholinergic neurotransmitter system via NMDA receptor signaling or acetylcholinesterase inhibition.
ESTHER : Liu_2012_Am.J.Chin.Med_40_993
PubMedSearch : Liu_2012_Am.J.Chin.Med_40_993
PubMedID: 22928830

Title : The memory ameliorating effects of INM-176, an ethanolic extract of Angelica gigas, against scopolamine- or Abeta(1-42)-induced cognitive dysfunction in mice - Park_2012_J.Ethnopharmacol_143_611
Author(s) : Park SJ , Jung JM , Lee HE , Lee YW , Kim DH , Kim JM , Hong JG , Lee CH , Jung IH , Cho YB , Jang DS , Ryu JH
Ref : J Ethnopharmacol , 143 :611 , 2012
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease is a neurodegenerative disorder associated with cognitive impairment and cholinergic neuronal death. INM-176 is a standardized ethanolic extract of Angelica gigas Nakai that has been traditionally used in herbal medicine in China, Japan, and Korea to treat anemia or as a sedative. We investigated whether INM-176 exhibits anti-amnesic effects. MATERIALS AND METHODS: Memory impairment was induced by scopolamine, a cholinergic muscarinic receptor antagonist, or amyloid beta(1-42) (Abeta(1-42)) protein. Anti-amnesic effects of INM-176 were measured by the passive avoidance and the Morris water maze tasks in mice. We also examined the effect of INM-176 on the acetylcholinesterase activity, as well as Abeta(1-42) protein-induced astrogliosis or cholinergic neuronal loss in the brain. RESULTS: Scopolamine-induced cognitive dysfunction was significantly attenuated by a single or sub-chronic administration of INM-176 in the passive avoidance and the Morris water maze tasks. A single or sub-chronic administration of INM-176 also ameliorated memory impairments induced by Abeta(1-42) protein. INM-176 inhibited acetylcholinesterase activity in the hippocampal tissue in vitro and ex vivo. In addition, INM-176 attenuated the Abeta(1-42) protein-induced astrocyte activation in the hippocampus as well as cholinergic neuronal damage in the CA3 region of the hippocampus and the nucleus basalis of Meynert. CONCLUSION: These results suggest that the memory ameliorating effects of INM-176 on scopolamine- or Abeta(1-42) protein-induced memory impairment are mediated, in part, via acetylcholinesterase inhibition and neuroprotective activities.
ESTHER : Park_2012_J.Ethnopharmacol_143_611
PubMedSearch : Park_2012_J.Ethnopharmacol_143_611
PubMedID: 22846435

Title : Draft genome sequence of the sulfur-oxidizing bacterium Candidatus Sulfurovum sediminum AR, which belongs to the Epsilonproteobacteria - Park_2012_J.Bacteriol_194_4128
Author(s) : Park SJ , Ghai R , Martin-Cuadrado AB , Rodriguez-Valera F , Jung MY , Kim JG , Rhee SK
Ref : Journal of Bacteriology , 194 :4128 , 2012
Abstract : Sulfur-oxidizing bacteria are common microorganisms in a variety of sulfide-rich environments. They play important roles in the global sulfur cycle on earth. Here, we present a high-quality draft genome sequence of a sulfur-oxidizing bacterium, "Candidatus Sulfurovum sediminum" strain AR, which belongs to the class Epsilonproteobacteria and dominated an enrichment culture from a marine sediment collected off Svalbard, within the Arctic Circle. Its genome contains genes for sulfur oxidation and carbon fixation. The size of the draft genome is 2.12 Mb, and the G+C content is 39.4%.
ESTHER : Park_2012_J.Bacteriol_194_4128
PubMedSearch : Park_2012_J.Bacteriol_194_4128
PubMedID: 22815446
Gene_locus related to this paper: 9prot-i2k4p9 , 9prot-i2k925

Title : Complete genome sequence of Vibrio vulnificus MO6-24\/O - Park_2011_J.Bacteriol_193_2062
Author(s) : Park JH , Cho YJ , Chun J , Seok YJ , Lee JK , Kim KS , Lee KH , Park SJ , Choi SH
Ref : Journal of Bacteriology , 193 :2062 , 2011
Abstract : Vibrio vulnificus is the causative agent of life-threatening septicemia and severe wound infections. Here, we announce the complete annotated genome sequence of V. vulnificus MO6-24/O, isolated from a patient with septicemia. When it is compared with previously known V. vulnificus genomes, the genome of this bacterium shows a unique genetic makeup, including phagelike elements, carbohydrate metabolism-related genes, and the superintegron.
ESTHER : Park_2011_J.Bacteriol_193_2062
PubMedSearch : Park_2011_J.Bacteriol_193_2062
PubMedID: 21317338
Gene_locus related to this paper: vibvu-VV10305 , vibvu-VV11137 , vibvu-VV11321 , vibvu-VV20739 , vibvu-VV20967 , vibvu-VV21548 , vibvy-y856

Title : FrsA functions as a cofactor-independent decarboxylase to control metabolic flux - Lee_2011_Nat.Chem.Biol_7_434
Author(s) : Lee KJ , Jeong CS , An YJ , Lee HJ , Park SJ , Seok YJ , Kim P , Lee JH , Lee KH , Cha SS
Ref : Nat Chemical Biology , 7 :434 , 2011
Abstract : The interaction between fermentation-respiration switch (FrsA) protein and glucose-specific enzyme IIA(Glc) increases glucose fermentation under oxygen-limited conditions. We show that FrsA converts pyruvate to acetaldehyde and carbon dioxide in a cofactor-independent manner and that its pyruvate decarboxylation activity is enhanced by the dephosphorylated form of IIA(Glc) (d-IIA(Glc)). Crystal structures of FrsA and its complex with d-IIA(Glc) revealed residues required for catalysis as well as the structural basis for the activation by d-IIA(Glc).
ESTHER : Lee_2011_Nat.Chem.Biol_7_434
PubMedSearch : Lee_2011_Nat.Chem.Biol_7_434
PubMedID: 21623357
Gene_locus related to this paper: vibvy-y856

Title : Tailor-made type II Pseudomonas PHA synthases and their use for the biosynthesis of polylactic acid and its copolymer in recombinant Escherichia coli - Yang_2011_Appl.Microbiol.Biotechnol_90_603
Author(s) : Yang TH , Jung YK , Kang HO , Kim TW , Park SJ , Lee SY
Ref : Applied Microbiology & Biotechnology , 90 :603 , 2011
Abstract : Previously, we have developed metabolically engineered Escherichia coli strains capable of producing polylactic acid (PLA) and poly(3-hydroxybutyrate-co-lactate) [P(3HB-co-LA)] by employing evolved Clostridium propionicum propionate CoA transferase (Pct(Cp)) and Pseudomonas sp. MBEL 6-19 polyhydroxyalkanoate (PHA) synthase 1 (PhaC1(Ps6-19)). Introduction of mutations four sites (E130, S325, S477, and Q481) of PhaC1( Ps6-19) have been found to affect the polymer content, lactate mole fraction, and molecular weight of P(3HB-co-LA). In this study, we have further engineered type II Pseudomonas PHA synthases 1 (PhaC1s) from Pseudomonas chlororaphis, Pseudomonas sp. 61-3, Pseudomonas putida KT2440, Pseudomonas resinovorans, and Pseudomonas aeruginosa PAO1 to accept short-chain-length hydroxyacyl-CoAs including lactyl-CoA and 3-hydroxybutyryl-CoA as substrates by site-directed mutagenesis of four sites (E130, S325, S477, and Q481). All PhaC1s having mutations in these four sites were able to accept lactyl-CoA as a substrate and supported the synthesis of P(3HB-co-LA) in recombinant E. coli, whereas the wild-type PhaC1s could not accumulate polymers in detectable levels. The contents, lactate mole fractions, and the molecular weights of P(3HB-co-LA) synthesized by recombinant E. coli varied depending upon the source of the PHA synthase and the mutants used. PLA homopolymer could also be produced at ca. 7 wt.% by employing the several PhaC1 variants containing E130D/S325T/S477G/Q481K quadruple mutations in wild-type E. coli XL1-Blue.
ESTHER : Yang_2011_Appl.Microbiol.Biotechnol_90_603
PubMedSearch : Yang_2011_Appl.Microbiol.Biotechnol_90_603
PubMedID: 21221571
Gene_locus related to this paper: psech-PHAC1

Title : Cloning and expression analysis of the duplicated genes for carbon monoxide dehydrogenase of Mycobacterium sp. strain JC1 DSM 3803 - Song_2010_Microbiology_156_999
Author(s) : Song T , Park SW , Park SJ , Kim JH , Yu JY , Oh JI , Kim YM
Ref : Microbiology , 156 :999 , 2010
Abstract : Carbon monoxide dehydrogenase (CO-DH) is an enzyme catalysing the oxidation of CO to carbon dioxide in Mycobacterium sp. strain JC1 DSM 3803. Cloning of the genes encoding CO-DH from the bacterium and sequencing of overlapping clones revealed the presence of duplicated sets of genes for three subunits of the enzyme, cutB1C1A1 and cutB2C2A2, in operons, and a cluster of genes encoding proteins that may be involved in CO metabolism, including a possible transcriptional regulator. Phylogenetic analysis based on the amino acid sequences of large subunits of CO-DH suggested that the CO-DHs of Mycobacterium sp. JC1 and other mycobacteria are distinct from those of other types of bacteria. The growth phenotype of mutant strains lacking cutA genes and of a corresponding complemented strain showed that both of the duplicated sets of CO-DH genes were functional in this bacterium. Transcriptional fusions of the cutB genes with lacZ revealed that the cutBCA operons were expressed regardless of the presence of CO and were further inducible by CO. Primer extension analysis indicated two promoters, one expressed in the absence of CO and the other induced in the presence of CO. This is believed to be the first report to show the presence of multiple copies of CO-DH genes with identical sequences and in close proximity in carboxydobacteria, and to present the genetic evidence for the function of the genes in mycobacteria.
ESTHER : Song_2010_Microbiology_156_999
PubMedSearch : Song_2010_Microbiology_156_999
PubMedID: 20035005
Gene_locus related to this paper: 9myco-d5g1y8

Title : Anti-amnesic effect of ESP-102 on Abeta(1-42)-induced memory impairment in mice - Kim_2010_Pharmacol.Biochem.Behav_97_239
Author(s) : Kim DH , Jung WY , Park SJ , Kim JM , Lee S , Kim YC , Ryu JH
Ref : Pharmacol Biochem Behav , 97 :239 , 2010
Abstract : The aim of this study was to characterize the effects of ESP-102 on the memory impairments and pathological changes induced by amyloid-beta (Abeta)(1-42) peptide in mice. The ameliorating effect of ESP-102 on memory impairment was investigated using the passive avoidance and the Morris water maze tasks, and the pathological changes were identified by immunohistochemistry and western blotting. Abeta(1-42) peptide (3mug/3mul) was administered by intracerebroventricular injection. By the single administration of ESP-102 (100mg/kg, p.o), the memory impairment induced by Abeta(1-42) peptide was significantly attenuated (P<0.05). Moreover, ESP-102 (100mg/kg, p.o) significantly inhibited acetylcholinesterase (AChE) activity in the hippocampus compared to the Abeta(1-42) peptide-injected control group. In the subchronic treatment study, ESP-102 (50 or 100mg/kg/day, p.o) administration for seven days ameliorated the memory impairments induced by Abeta(1-42) peptide. Moreover, ESP-102 inhibited lipid peroxidation induced by Abeta(1-42) peptide in the hippocampus. Abeta(1-42)-induced increases in the expression of GFAP (an astrocyte marker) and inducible nitric oxide synthase (iNOS) in the hippocampal region were also attenuated by ESP-102 treatment. These results suggest that the ameliorating effect of ESP-102 on Abeta(1-42) peptide-induced memory impairment is mediated via its AChE inhibitory, antioxidative, and/or anti-inflammatory activities.
ESTHER : Kim_2010_Pharmacol.Biochem.Behav_97_239
PubMedSearch : Kim_2010_Pharmacol.Biochem.Behav_97_239
PubMedID: 20728465

Title : Growth hormone-releaser diet attenuates beta-amyloid(1-42)-induced cognitive impairment via stimulation of the insulin-like growth factor (IGF)-1 receptor in mice - Shin_2009_J.Pharmacol.Sci_109_139
Author(s) : Shin EJ , Chae JS , Park SJ , Kim SC , Koo KH , Yamada K , Nabeshima T , Kim HC
Ref : J Pharmacol Sci , 109 :139 , 2009
Abstract : We previously demonstrated that the growth hormone (GH)-releaser diet ameliorated beta-amyloid (A beta) (1-42)-induced memory impairment, but the underlying mechanism remained to be characterized. We show here that the GH-releaser diet significantly attenuated A beta(1-42)-induced impairment in context-dependent conditioned fear, with a reduction in GH levels and changes in hippocampal acetylcholine, acetylcholinesterase, choline acetyltransferase, insulin-like growth factor (IGF)-1, and IGF-1-receptor activity in mice. JB-1, an IGF-1-receptor antagonist, significantly blocked GH-releaser diet-mediated pharmacological actions. Our results suggest that the GH-releaser diet prevents A beta(1-42)-induced cognitive deficits via stimulation of the hippocampal IGF-1 receptor.
ESTHER : Shin_2009_J.Pharmacol.Sci_109_139
PubMedSearch : Shin_2009_J.Pharmacol.Sci_109_139
PubMedID: 19151546

Title : Fustin flavonoid attenuates beta-amyloid (1-42)-induced learning impairment - Jin_2009_J.Neurosci.Res_87_3658
Author(s) : Jin CH , Shin EJ , Park JB , Jang CG , Li Z , Kim MS , Koo KH , Yoon HJ , Park SJ , Choi WC , Yamada K , Nabeshima T , Kim HC
Ref : Journal of Neuroscience Research , 87 :3658 , 2009
Abstract : Natural flavonoids ameliorate amyloid-beta peptide (Abeta)-induced neurotoxicity. We examined whether the fustin flavonoid affects Abeta-induced learning impairment in mice. Repeated treatment with fustin significantly attenuated Abeta (1-42)-induced conditioned fear and passive avoidance behaviors. This effect was comparable to that of EGb761, a standard extract of ginkgo. Fustin treatment significantly prevented decreases in acetylcholine (ACh) levels, choline acetyltransferase (ChAT) activity, and ChAT gene expression induced by Abeta (1-42). Fustin also consistently suppressed increases in acetyl cholinesterase (AChE) activity and AChE gene expression induced by Abeta (1-42). In addition, fustin significantly attenuated Abeta (1-42)-induced selective decreases in muscarinic M1 receptor gene expression and muscarinic M1 receptor binding activity (as determined by [(3)H]pirenzepine binding) by modulating extracellular signal-regulated kinase 1/2 (ERK 1/2) and cAMP response-element binding protein (CREB) phosphorylation and brain-derived neurotrophic factor (BDNF) expression. These effects of fustin were reversed by treatment with dicyclomine, a muscarinic M1 receptor antagonist, and SL327, a selective ERK inhibitor, but not by chelerythrine, a pan-protein kinase C (PKC) inhibitor. Taken together, our results suggest that fustin attenuates Abeta (1-42)-impaired learning, and that the ERK/CREB/BDNF pathway is important for the M1 receptor-mediated cognition-enhancing effects of fustin.
ESTHER : Jin_2009_J.Neurosci.Res_87_3658
PubMedSearch : Jin_2009_J.Neurosci.Res_87_3658
PubMedID: 19533734

Title : Growth hormone releaser attenuates beta-amyloid (1 - 42)-induced memory impairment in mice - Shin_2005_J.Pharmacol.Sci_99_117
Author(s) : Shin EJ , Jhoo JH , Nabeshima T , Jhoo WK , Kwon MS , Lim YK , Chae JS , Jung ME , Park SJ , Jang KJ , Kim HC
Ref : J Pharmacol Sci , 99 :117 , 2005
Abstract : Accumulating evidence indicates that growth hormone (GH) might be effective at preventing the development of Alzheimer's disease. However, exogenous GH treatment has exhibited side effects for clinical application; thus supplementation with amino acids to promote the release of GH could be a possible alternative treatment. In this study, mice that were fed with a diet of GH-releasing supplements had significantly attenuated memory impairments and hippocampal changes in the acetylcholinesterase activity and acetylcholine level induced by amyloid beta protein (Abeta) (1 - 42). Our results suggest that the use of GH-releasing supplement exerts beneficial effects on the memory impairment induced by Abeta (1 - 42).
ESTHER : Shin_2005_J.Pharmacol.Sci_99_117
PubMedSearch : Shin_2005_J.Pharmacol.Sci_99_117
PubMedID: 16141634