Kim SJ

References (62)

Title : Investigations of Limeum indicum Plant for Diabetes Mellitus and Alzheimer's disease Dual Therapy: Phytochemical, GC-MS Chemical Profiling, Enzyme Inhibition, Molecular Docking and In-vivo Studies - Shamim_2024_Chem.Biodivers__e202301858
Author(s) : Shamim T , Asif HM , Ejaz SA , Hussain Z , Wani TA , Sumreen L , Abdullah M , Ahmed Z , Iqbal J , Kim SJ , Shah MK
Ref : Chem Biodivers , :e202301858 , 2024
Abstract : Limeum indicum has been widely utilized in traditional medicine but no experimental work has been done on this herb. The primary objective of this study was to conduct a phytochemical analysis and assess the multifunctional capabilities of aforementioned plant in dual therapy for Alzheimer's disease (AD) and Type 2 diabetes (T2D). The phytochemical screening of ethanol, methanol extract, and their derived fractions of Limeum indicum was conducted using GC-MS, HPLC, UV-analysis and FTIR. The antioxidant capacity was evaluated by DPPH method. The inhibitory potential of the extracts/fractions against alpha-, beta-glucosidase acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoaminine oxidases (MAO-A & B) was evaluated. Results revealed that acetonitrile fraction has highest inhibitory potential against alpha-glucosidase (IC50=68.47+/-0.05microg/mL), methanol extract against beta-glucosidase (IC50=91.12+/-0.07microg/mL), ethyl acetate fraction against AChE (IC50=59.0+/-0.02 microg/mL), ethanol extract against BChE (28.41+/-0.01microg/mL), n-hexane fraction against MAO-A (IC50=150.5+/-0.31microg/mL) and methanol extract for MAO-B (IC50=75.95+/-0.13microg/mL). The docking analysis of extracts\fractions suggested the best binding scores within the active pocket of the respective enzymes. During the in-vivo investigation, ethanol extract produced hypoglycemic effect (134.52+/-2.79 and 119.38+/-1.40 mg/dl) after 21 days treatment at dose level of 250 and 500 mg/Kg. Histopathological findings further supported the in-vivo studies.
ESTHER : Shamim_2024_Chem.Biodivers__e202301858
PubMedSearch : Shamim_2024_Chem.Biodivers__e202301858
PubMedID: 38608202

Title : Identification of Novel Natural Product Inhibitors against Matrix Metalloproteinase 9 Using Quantum Mechanical Fragment Molecular Orbital-Based Virtual Screening Methods - Lim_2022_Int.J.Mol.Sci_23_
Author(s) : Lim H , Hong H , Hwang S , Kim SJ , Seo SY , No KT
Ref : Int J Mol Sci , 23 : , 2022
Abstract : Matrix metalloproteinases (MMPs) are calcium-dependent zinc-containing endopeptidases involved in multiple cellular processes. Among the MMP isoforms, MMP-9 regulates cancer invasion, rheumatoid arthritis, and osteoarthritis by degrading extracellular matrix proteins present in the tumor microenvironment and cartilage and promoting angiogenesis. Here, we identified two potent natural product inhibitors of the non-catalytic hemopexin domain of MMP-9 using a novel quantum mechanical fragment molecular orbital (FMO)-based virtual screening workflow. The workflow integrates qualitative pharmacophore modeling, quantitative binding affinity prediction, and a raw material search of natural product inhibitors with the BMDMS-NP library. In binding affinity prediction, we made a scoring function with the FMO method and applied the function to two protein targets (acetylcholinesterase and fibroblast growth factor 1 receptor) from DUD-E benchmark sets. In the two targets, the FMO method outperformed the Glide docking score and MM/PBSA methods. By applying this workflow to MMP-9, we proposed two potent natural product inhibitors (laetanine 9 and genkwanin 10) that interact with hotspot residues of the hemopexin domain of MMP-9. Laetanine 9 and genkwanin 10 bind to MMP-9 with a dissociation constant (K(D)) of 21.6 and 0.614 microM, respectively. Overall, we present laetanine 9 and genkwanin 10 for MMP-9 and demonstrate that the novel FMO-based workflow with a quantum mechanical approach is promising to discover potent natural product inhibitors of MMP-9, satisfying the pharmacophore model and good binding affinity.
ESTHER : Lim_2022_Int.J.Mol.Sci_23_
PubMedSearch : Lim_2022_Int.J.Mol.Sci_23_
PubMedID: 35457257

Title : Ethanol and its nonoxidative metabolites promote acute liver injury by inducing ER stress, adipocyte death and lipolysis - Park_2022_Cell.Mol.Gastroenterol.Hepatol__
Author(s) : Park SH , Seo W , Xu MJ , Mackowiak B , Lin Y , He Y , Fu Y , Hwang S , Kim SJ , Guan Y , Feng D , Yu L , Lehner R , Liangpunsakul S , Gao B
Ref : Cell Mol Gastroenterol Hepatol , : , 2022
Abstract : BACKGROUND & AIMS: Binge drinking in patients with metabolic syndrome accelerates the development of alcohol-associated liver disease (ALD). However, the underlying mechanisms remain elusive. We investigated if oxidative and non-oxidative alcohol metabolism pathways, diet-induced obesity, and adipose tissues influence the development of acute liver injury in a single ethanol binge model. METHODS & RESULTS: A single ethanol binge was administered to chow-fed or high-fat diet (HFD)-fed wild-type and genetically modified mice. Oral administration of a single dose of ethanol induced acute liver injury and hepatic ER stress in chow- or HFD-fed mice. Disruption of the alcohol dehydrogenase 1 (Adh1) gene elevated blood ethanol concentration and exacerbated acute ethanol-induced ER stress and liver injury in both chow-fed and HFD-fed mice, while disruption of the aldehyde dehydrogenase 2 (Aldh2) gene did not affect such hepatic injury despite high blood acetaldehyde levels. Mechanistic studies revealed that alcohol, not acetaldehyde, promoted hepatic ER stress, fatty acid synthesis, increased adipocyte death and lipolysis, contributing to acute liver injury. Elevated serum fatty acid ethyl esters (FAEEs), which are formed by an enzyme-mediated esterification of ethanol with fatty acids, were detected in mice post ethanol gavage with higher levels in Adh1 knockout mice than that in wild-type mice. Deletion of the carboxylesterase 1d (Ces1d) gene in mice markedly reduced acute ethanol-induced elevation of blood FAEE levels with slight but significant reduction of serum aminotransferase levels. CONCLUSION: Ethanol and its non-oxidative metabolites, FAEEs, not acetaldehyde, promoted acute alcohol-induced liver injury by inducing ER stress, adipocyte death, and lipolysis.
ESTHER : Park_2022_Cell.Mol.Gastroenterol.Hepatol__
PubMedSearch : Park_2022_Cell.Mol.Gastroenterol.Hepatol__
PubMedID: 36243320

Title : WS-5 Extract of Curcuma longa, Chaenomeles sinensis, and Zingiber officinale Contains Anti-AChE Compounds and Improves beta-Amyloid-Induced Memory Impairment in Mice - Kim_2019_Evid.Based.Complement.Alternat.Med_2019_5160293
Author(s) : Kim JE , Shrestha AC , Kim HS , Ham HN , Kim JH , Kim YJ , Noh YJ , Kim SJ , Kim DK , Jo HK , Kim DS , Moon KH , Lee JH , Jeong KO , Leem JY
Ref : Evid Based Complement Alternat Med , 2019 :5160293 , 2019
Abstract : Alzheimer's disease (AD) is linked to an extensive neuron loss via accumulation of amyloid-beta (Abeta) as senile plaques associated with reactive astrocytes and microglial activation in the brain. The objective of this study was to assess the therapeutic effect of WS-5 ethanol extract in vitro and in vivo against Abeta-induced AD in mice and to identify the extract's active constituents. In the present study, WS-5 exerted a significant inhibitory effect on acetylcholinesterase (AChE). Analysis by transmission electron microscopy (TEM) revealed that WS-5 prevented Abeta oligomerization via inhibition of Abeta 1-42 aggregation. Evaluation of antioxidant activities using 1, 1-diphenyl-2-picrylhydrazyl (DPPH) demonstrated that WS-5 possessed a high antioxidant activity, which was confirmed by measuring the total antioxidant status (TAS). Furthermore, the anti-inflammatory properties of WS-5 were examined using lipopolysaccharide-stimulated BV-2 microglial cells. WS-5 significantly inhibited the lipopolysaccharide-induced production of nitric oxide and two proinflammatory cytokines, TNF-alpha and IL-6. The memory impairment in mice with Abeta-induced AD was studied using the Morris water maze and passive avoidance test. Immunohistochemistry was performed to monitor pathological changes in the hippocampus and cortex region of the mouse brain. The animal study showed that WS-5 (250 mg/kg) treatment improved learning and suppressed memory impairment as well as reduced Abeta plaque accumulation in Abeta-induced AD. HPLC analysis identified the extract's active compounds that exert anti-AChE activity. In summary, our findings suggest that WS-5 could be applied as a natural product therapy with a focus on neuroinflammation-related neurodegenerative disorders.
ESTHER : Kim_2019_Evid.Based.Complement.Alternat.Med_2019_5160293
PubMedSearch : Kim_2019_Evid.Based.Complement.Alternat.Med_2019_5160293
PubMedID: 31057649

Title : Protective effects of cultured and fermented ginseng extracts against scopolamine-induced memory loss in a mouse model - Han_2018_Lab.Anim.Res_34_37
Author(s) : Han SH , Kim SJ , Yun YW , Nam SY , Lee HJ , Lee BJ
Ref : Lab Anim Res , 34 :37 , 2018
Abstract : This study was performed to investigate the effect of a concentrate of fermented wild ginseng root culture (HLJG0701) on memory improvement in the scopolamine (SPL)-induced memory-deficient mouse model. Eight-week-old male ICR mice were used to evaluate the protective effect of HLJG0701 against the SPL-induced memory loss animal model. The Morris water maze test, which measures hippocampus-dependent learning ability, and the Y-maze test, a short-term memory assessment test, were performed and related markers were analyzed. HLJG0701-treated groups displayed significantly reduced acetylcholinesterase activity and increased acetylcholine level compared with the SPL-administered group (SPL-G) (P<0.05). In the Y-maze test, the spontaneous alternation in al HLJG0711-treated groups was significantly increased compared with that in SPL-G (P<0.05). In the Morris water maze test, the escape latency and time spent in the target quadrant in all HLJG0701-treated groups were significantly decreased and increased, respectively, compared with those in SPL-G (P<0.05). In addition, the brain-derived neurotrophic factor level in groups treated with HLJG0701 300 and 600 mg/kg body weight was significantly increased compared with that in SPL-G (P<0.05). These results suggest that the HLJG0701 may protect against memory loss by inhibiting acetylcholinesterase activity and preventing acetylcholine deficiency.
ESTHER : Han_2018_Lab.Anim.Res_34_37
PubMedSearch : Han_2018_Lab.Anim.Res_34_37
PubMedID: 29628975

Title : Effects of clarithromycin on the pharmacokinetics of evogliptin in healthy volunteers - Oh_2017_J.Clin.Pharm.Ther_42_689
Author(s) : Oh ES , Choi C , Kim CO , Kim KH , Kim YN , Kim SJ , Park MS
Ref : J Clin Pharm Ther , 42 :689 , 2017
Abstract : WHAT IS KNOWN AND OBJECTIVE: Evogliptin (DA-1229), a novel dipeptidyl peptidase (DPP)-4 inhibitor with high potency and selectivity, was approved in Korea for the treatment of type 2 diabetes. Preclinical studies suggest that it is metabolized by cytochrome (CYP) P450 isozymes. Based on these findings, a clinical study was designed to investigate the pharmacokinetic (PK) interaction of evogliptin with a CYP inhibitor, clarithromycin. METHODS: An open-label, two-phase, crossover study was conducted with 12 healthy subjects. On day 1, a single dose of evogliptin 5 mg was administered alone to assess the reference PK profile of evogliptin. On day 10, after a 2-day pretreatment with clarithromycin, evogliptin 5 mg was administered again to evaluate the effect of CYP inhibition on the PK profile of evogliptin. Administration of clarithromycin continued until day 14. Blood sampling in the reference and test phases was performed until 96 and 168 hours after dosing, respectively for PK assays. RESULTS: Eleven of the 12 subjects completed the study, and their data were analysed. In the presence of clarithromycin, exposure to evogliptin increased without any serious adverse events and the geometric mean peak plasma concentration (Cmax ) and area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-infinity ) of evogliptin increased by 116.5% and 89.6%, respectively. WHAT IS NEW AND CONCLUSION: Administration of clarithromycin significantly increased exposure to evogliptin in healthy subjects.
ESTHER : Oh_2017_J.Clin.Pharm.Ther_42_689
PubMedSearch : Oh_2017_J.Clin.Pharm.Ther_42_689
PubMedID: 28806472

Title : Complete Genome Sequence of the Proteorhodopsin-Containing Marine Bacterium Sediminicola sp. YIK13 - Kwon_2016_Genome.Announc_4_e01635
Author(s) : Kwon YM , Kim SJ
Ref : Genome Announc , 4 :e01635 , 2016
Abstract : Sediminicola sp. YIK13 is a marine flavobacterium, isolated from tidal flat sediment. Here, we present the first complete genome sequence of this genus, which consists of 3,569,807 bp with 39.4% GC content. This strain contains proteorhodopsin, as well as retinal biosynthesis genes, allowing it to utilize sunlight as an energy source.
ESTHER : Kwon_2016_Genome.Announc_4_e01635
PubMedSearch : Kwon_2016_Genome.Announc_4_e01635
PubMedID: 26823585
Gene_locus related to this paper: 9flao-a0a0s1s9x7

Title : Pharmacokinetic and pharmacodynamic interactions between metformin and a novel dipeptidyl peptidase-4 inhibitor, evogliptin, in healthy subjects - Rhee_2016_Drug.Des.Devel.Ther_10_2525
Author(s) : Rhee SJ , Choi Y , Lee S , Oh J , Kim SJ , Yoon SH , Cho JY , Yu KS
Ref : Drug Des Devel Ther , 10 :2525 , 2016
Abstract : Evogliptin is a newly developed dipeptidyl peptidase-4 (DPP-4) inhibitor, which is expected to be combined with metformin for treating type 2 diabetes mellitus. We investigated the potential pharmacokinetic and pharmacodynamic interactions between evogliptin and metformin. A randomized, open-label, multiple-dose, six-sequence, three-period crossover study was conducted in 36 healthy male subjects. All subjects received three treatments, separated by 7-day washout intervals: evogliptin, 5 mg od for 7 days (EVO); metformin IR, 1,000 mg bid for 7 days (MET); and the combination of EVO and MET (EVO + MET). After the last dose in a period, serial blood samples were collected for 24 hours for pharmacokinetic assessments. During steady state, serial blood samples were collected for 2 hours after an oral glucose tolerance test, and DPP-4, active glucagon-like peptide-1, glucose, glucagon, insulin, and C-peptide were measured to assess pharmacodynamic properties. EVO + MET and EVO showed similar steady state maximum concentration and area under the concentration-time curve at steady state values for evogliptin; the geometric mean ratios (90% confidence interval) were 1.06 (1.01-1.12) and 1.02 (0.99-1.06), respectively. EVO + MET slightly reduced steady state maximum concentration and area under the concentration-time curve at steady state values for metformin compared to MET, with geometric mean ratios (90% confidence interval) of 0.84 (0.79-0.89) and 0.94 (0.89-0.98), respectively. EVO + MET and EVO had similar DPP-4 inhibition efficacy, but EVO + MET increased active glucagon-like peptide-1 and reduced glucose to larger extents than either EVO or MET alone. Our results suggested that EVO+MET could provide therapeutic benefits without clinically significant pharmacokinetic interactions. Thus, the EVO + MET combination is a promising option for treating type 2 diabetes mellitus.
ESTHER : Rhee_2016_Drug.Des.Devel.Ther_10_2525
PubMedSearch : Rhee_2016_Drug.Des.Devel.Ther_10_2525
PubMedID: 27570447

Title : Characterization of a novel cold-active esterase isolated from swamp sediment metagenome - Seo_2014_World.J.Microbiol.Biotechnol_30_879
Author(s) : Seo S , Lee YS , Yoon SH , Kim SJ , Cho JY , Hahn BS , Koo BS , Lee CM
Ref : World J Microbiol Biotechnol , 30 :879 , 2014
Abstract : A functional screen of a metagenomic library from "Upo" swamp sediment in Korea identified a gene EstL28, the product of which displayed lipolytic properties on a tributyrin-supplemented medium. The EstL28 sequence encodes a 290 amino acid protein (designated as EstL28), with a predicted molecular weight of 31.3 kDa. The encoded EstL28 protein exhibited the highest sequence similarity (45 %) to a hydrolase found in Streptococcus sanguinis. Phylogenetic analysis indicated that EstL28 belongs to a currently uncharacterized family of esterases. Within the conserved alpha/beta-hydrolase 6 domain, the EstL28 retains the catalytic triad Ser103-Asp248-His268 that is typical of esterases. The Ser103 residue in the catalytic triad is located in the consensus pentapeptide motif GXSXG. The purified EstL28 enzyme worked optimally at 35 degrees C and pH 8.5 and remained stable at temperatures lower than 20 degrees C. The catalytic activity of EstL28 was maximal with p-nitrophenyl butyrate, indicating that it was an esterase. This enzyme also exhibited stable activity in the presence of methanol, ethanol, isopropanol, and dimethyl sulfoxide. Therefore, the level of stability in organic solvents and cold temperature suggests that EstL28 has potential for many biotechnological applications.
ESTHER : Seo_2014_World.J.Microbiol.Biotechnol_30_879
PubMedSearch : Seo_2014_World.J.Microbiol.Biotechnol_30_879
PubMedID: 24353039
Gene_locus related to this paper: 9bact-i3rtt4

Title : Improvements in memory after medial septum stimulation are associated with changes in hippocampal cholinergic activity and neurogenesis - Jeong_2014_Biomed.Res.Int_2014_568587
Author(s) : Jeong da U , Lee JE , Lee SE , Chang WS , Kim SJ , Chang JW
Ref : Biomed Res Int , 2014 :568587 , 2014
Abstract : Deep brain stimulation (DBS) has been found to have therapeutic effects in patients with dementia, but DBS mechanisms remain elusive. To provide evidence for the effectiveness of DBS as a treatment for dementia, we performed DBS in a rat model of dementia with intracerebroventricular administration of 192 IgG-saporins. We utilized four groups of rats, group 1, unlesioned control; group 2, cholinergic lesion; group 3, cholinergic lesion plus medial septum (MS) electrode implantation (sham stimulation); group 4, cholinergic lesions plus MS electrode implantation and stimulation. During the probe test in the water maze, performance of the lesion group decreased for measures of time spent and the number of swim crossings over the previous platform location. Interestingly, the stimulation group showed an equivalent performance to the normal group on all measures. And these are partially reversed by the electrode implantation. Acetylcholinesterase activity in the hippocampus was decreased in lesion and implantation groups, whereas activity in the stimulation group was not different from the normal group. Hippocampal neurogenesis was increased in the stimulation group. Our results revealed that DBS of MS restores spatial memory after damage to cholinergic neurons. This effect is associated with an increase in hippocampal cholinergic activity and neurogenesis.
ESTHER : Jeong_2014_Biomed.Res.Int_2014_568587
PubMedSearch : Jeong_2014_Biomed.Res.Int_2014_568587
PubMedID: 25101288

Title : Angelica keiskei Ameliorates Scopolamine-Induced Memory Impairments in Mice - Oh_2013_Biol.Pharm.Bull_36_82
Author(s) : Oh SR , Kim SJ , Kim DH , Ryu JH , Ahn EM , Jung JW
Ref : Biol Pharm Bull , 36 :82 , 2013
Abstract : Memory impairment is the most common symptom in patients with Alzheimer's disease (AD). Angelica keiskei (AK) has traditionally been used as a diuretic, laxative, analeptic and galactagogue. However, the anti-amnesic effects of AK and its molecular mechanisms have yet to be clearly elucidated. The aim of the present study is to evaluate the effects of AK on scopolamine-induced memory impairments in mice. The regulatory effect of AK on memory impairment was investigated using passive avoidance, Y-maze and the Morris water maze tasks. Acetylcholinesterase (AChE) activity assay was performed to investigate the cholinergic antagonistic effect of AK in the hippocampus. The effect of AK on phosphorylation of cAMP response element-binding protein (CREB) and expression of brain-derived neurotrophic factor (BDNF) were evaluated by Western blot assays and immunohistochemistry. The findings showed that AK significantly attenuated scopolamine-induced cognitive impairment in mice. Increase of AChE activity caused by scopolamine was significantly attenuated by AK. Additionally, AK significantly recovered the phosphorylation of CREB and expression of BDNF reduced by scopolamine in the hippocampus. Taken together, these results provide experimental evidence that AK might be a useful agent in preventing deficit of learning and memory caused by AD and aging.
ESTHER : Oh_2013_Biol.Pharm.Bull_36_82
PubMedSearch : Oh_2013_Biol.Pharm.Bull_36_82
PubMedID: 23132631

Title : Isolation and biochemical characterization of Bacillus pumilus lipases from the Antarctic - Arifin_2013_J.Microbiol.Biotechnol_23_661
Author(s) : Arifin AR , Kim SJ , Yim JH , Suwanto A , Kim HK
Ref : J Microbiol Biotechnol , 23 :661 , 2013
Abstract : Lipase-producing bacterial strains were isolated from Antarctic soil samples using the tricaprylin agar plate method. Seven strains with relatively strong lipase activities were selected. All of them turned out to be Bacillus pumilus strains by the 16S rRNA gene sequence analysis. Their corresponding lipase genes were cloned, sequenced, and compared. Finally, three different Bacillus pumilus lipases (BPL1, BPL2, and BPL3) were chosen. Their amino acid sequence identities were in the range of 92-98% with the previous Bacillus pumilus lipases. Their optimum temperatures and pHs were measured to be 40 degrees C and pH 9. Lipase BPL1 and lipase BPL2 were stable up to 30 degrees C, whereas lipase BPL3 was stable up to 20 degrees C. Lipase BPL2 was stable within a pH range of 6-10, whereas lipase BPL1 and lipase BPL3 were stable within a pH range of 5-11, showing strong alkaline tolerance. All these lipases exhibited high hydrolytic activity toward pnitrophenyl caprylate (C8). In addition, lipase BPL1 showed high hydrolytic activity toward tributyrin, whereas lipase BPL2 and lipase BPL3 hydrolyzed tricaprylin and castor oil preferentially. These results demonstrated that the three Antarctic Bacillus lipases were alkaliphilic and had a substrate preference toward short- and mediumchain triglycerides. These Antarctic Bacillus lipases might be used in detergent and food industries.
ESTHER : Arifin_2013_J.Microbiol.Biotechnol_23_661
PubMedSearch : Arifin_2013_J.Microbiol.Biotechnol_23_661
PubMedID: 23648856

Title : Neuroprotective Effects of AMP-Activated Protein Kinase on Scopolamine Induced Memory Impairment - Kim_2013_Korean.J.Physiol.Pharmacol_17_331
Author(s) : Kim SJ , Lee JH , Chung HS , Song JH , Ha J , Bae H
Ref : Korean Journal of Physiology Pharmacology , 17 :331 , 2013
Abstract : AMP-activated protein kinase (AMPK), an important regulator of energy metabolism, is activated in response to cellular stress when intracellular levels of AMP increase. We investigated the neuroprotective effects of AMPK against scopolamine-induced memory impairment in vivo and glutamate-induced cytotoxicity in vitro. An adenovirus expressing AMPK wild type alpha subunit (WT) or a dominant negative form (DN) was injected into the hippocampus of rats using a stereotaxic apparatus. The AMPK WT-injected rats showed significant reversal of the scopolamine induced cognitive deficit as evaluated by escape latency in the Morris water maze. In addition, they showed enhanced acetylcholinesterase (AChE)-reactive neurons in the hippocampus, implying increased cholinergic activity in response to AMPK. We also studied the cellular mechanism by which AMPK protects against glutamate-induced cell death in primary cultured rat hippocampal neurons. We further demonstrated that AMPK WT-infected cells increased cell viability and reduced Annexin V positive hippocampal neurons. Western blot analysis indicated that AMPK WT-infected cells reduced the expression of Bax and had no effects on Bcl-2, which resulted in a decreased Bax/Bcl-2 ratio. These data suggest that AMPK is a useful cognitive impairment treatment target, and that its beneficial effects are mediated via the protective capacity of hippocampal neurons.
ESTHER : Kim_2013_Korean.J.Physiol.Pharmacol_17_331
PubMedSearch : Kim_2013_Korean.J.Physiol.Pharmacol_17_331
PubMedID: 23946693

Title : Genome sequence of benzo(a)pyrene-degrading bacterium Novosphingobium pentaromativorans US6-1 - Luo_2012_J.Bacteriol_194_907
Author(s) : Luo YR , Kang SG , Kim SJ , Kim MR , Li N , Lee JH , Kwon KK
Ref : Journal of Bacteriology , 194 :907 , 2012
Abstract : Novosphingobium pentaromativorans US6-1 showed a good ability to degrade high-molecular-weight polycyclic aromatic hydrocarbons. We report the draft genome sequence of strain US6-1, which contains a main chromosome (5,096,413 bp, G+C content of 63.1%) and two plasmids (188,476 and 60,085 bp). The majority of the aromatic-hydrocarbon-degrading genes are encoded in the larger plasmid.
ESTHER : Luo_2012_J.Bacteriol_194_907
PubMedSearch : Luo_2012_J.Bacteriol_194_907
PubMedID: 22275104
Gene_locus related to this paper: 9sphn-g6e733 , 9sphn-g6efp8 , 9sphn-g6eg77 , 9sphn-g6e775 , 9sphn-g6ecp9

Title : Identification of a new subfamily of salt-tolerant esterases from a metagenomic library of tidal flat sediment - Jeon_2012_Appl.Microbiol.Biotechnol_93_623
Author(s) : Jeon JH , Lee HS , Kim JT , Kim SJ , Choi SH , Kang SG , Lee JH
Ref : Applied Microbiology & Biotechnology , 93 :623 , 2012
Abstract : To search for novel lipolytic enzymes, a metagenomic library was constructed from the tidal flat sediment of Ganghwa Island in South Korea. By functional screening using tributyrin agar plates, 3 clones were selected from among the 80,050 clones of the fosmid library. The sequence analysis revealed that those clones contained different open reading frames, which showed 50-57% amino acid identity with putative lipolytic enzymes in the database. Based on the phylogenetic analysis, they were identified to encode novel members, which form a distinct and new subfamily in the family IV of bacterial lipolytic enzymes. The consensus sequence, GT(S)SA(G)G, encompassing the active site serine of the enzymes was different from the GDSAG motif, conserved in the other subfamily. The genes were expressed in Escherichia coli and recombinant proteins were purified as active soluble forms. The enzymes showed the highest activity toward p-nitrophenyl valerate (C5) and exhibited optimum activities at mesophilic temperature ranges and slightly alkaline pH. In particular, the enzymes displayed salt tolerance with over 50% of the maximum activity remained in the presence of 3 M NaCl (or KCl). In this study, we demonstrated that the metagenomic approach using marine tidal flat sediment as a DNA source expanded the diversity of lipolytic enzyme-encoding genes.
ESTHER : Jeon_2012_Appl.Microbiol.Biotechnol_93_623
PubMedSearch : Jeon_2012_Appl.Microbiol.Biotechnol_93_623
PubMedID: 21720822
Gene_locus related to this paper: 9bact-E40 , 9bact-E25 , 9bact-d8v1j5 , 9bact-d8v1j4 , 9bact-d8v1j3

Title : Novel lipolytic enzymes identified from metagenomic library of deep-sea sediment - Jeon_2011_Evid.Based.Complement.Alternat.Med_2011_271419
Author(s) : Jeon JH , Kim JT , Lee HS , Kim SJ , Kang SG , Choi SH , Lee JH
Ref : Evid Based Complement Alternat Med , 2011 :271419 , 2011
Abstract : Metagenomic library was constructed from a deep-sea sediment sample and screened for lipolytic activity. Open-reading frames of six positive clones showed only 33-58% amino acid identities to the known proteins. One of them was assigned to a new group while others were grouped into Families I and V or EstD Family. By employing a combination of approaches such as removing the signal sequence, coexpression of chaperone genes, and low temperature induction, we obtained five soluble recombinant proteins in Escherichia coli. The purified enzymes had optimum temperatures of 30-35 degrees C and the cold-activity property. Among them, one enzyme showed lipase activity by preferentially hydrolyzing p-nitrophenyl palmitate and p-nitrophenyl stearate and high salt resistance with up to 4 M NaCl. Our research demonstrates the feasibility of developing novel lipolytic enzymes from marine environments by the combination of functional metagenomic approach and protein expression technology.
ESTHER : Jeon_2011_Evid.Based.Complement.Alternat.Med_2011_271419
PubMedSearch : Jeon_2011_Evid.Based.Complement.Alternat.Med_2011_271419
PubMedID: 21845199
Gene_locus related to this paper: 9bact-d8v1j0 , 9bact-d8v1i9 , 9bact-d8v1i5 , 9bact-d8v1i8 , 9bact-d8v1i6 , 9bact-d8v1i7

Title : Genome sequence of the algicidal bacterium Kordia algicida OT-1 - Lee_2011_J.Bacteriol_193_4031
Author(s) : Lee HS , Kang SG , Kwon KK , Lee JH , Kim SJ
Ref : Journal of Bacteriology , 193 :4031 , 2011
Abstract : Kordia algicida OT-1 is an algicidal bacterium against the bloom-forming microalgae. The genome sequence of K. algicida revealed a number of interesting features, including the degradation of macromolecules, the biosynthesis of carotenoid pigment and secondary metabolites, and the capacity for gliding motility, which might facilitate the understanding of algicidal mechanisms.
ESTHER : Lee_2011_J.Bacteriol_193_4031
PubMedSearch : Lee_2011_J.Bacteriol_193_4031
PubMedID: 21622754
Gene_locus related to this paper: 9flao-a9dk52

Title : Novel metagenome-derived carboxylesterase that hydrolyzes beta-lactam antibiotics - Jeon_2011_Appl.Environ.Microbiol_77_7830
Author(s) : Jeon JH , Kim SJ , Lee HS , Cha SS , Lee JH , Yoon SH , Koo BS , Lee CM , Choi SH , Lee SH , Kang SG
Ref : Applied Environmental Microbiology , 77 :7830 , 2011
Abstract : It has been proposed that family VIII carboxylesterases and class C beta-lactamases are phylogenetically related; however, none of carboxylesterases has been reported to hydrolyze beta-lactam antibiotics except nitrocefin, a nonclinical chromogenic substrate. Here, we describe the first example of a novel carboxylesterase derived from a metagenome that is able to cleave the amide bond of various beta-lactam substrates and the ester bond of p-nitrophenyl esters. A clone with lipolytic activity was selected by functional screening of a metagenomic library using tributyrin agar plates. The sequence analysis of the clone revealed the presence of an open reading frame (estU1) encoding a polypeptide of 426 amino acids, retaining an S-X-X-K motif that is conserved in class C beta-lactamases and family VIII carboxylesterases. The gene was overexpressed in Escherichia coli, and the purified recombinant protein (EstU1) was further characterized. EstU1 showed esterase activity toward various chromogenic p-nitrophenyl esters. In addition, it exhibited hydrolytic activity toward nitrocefin, leading us to investigate whether EstU1 could hydrolyze beta-lactam antibiotics. EstU1 was able to hydrolyze first-generation beta-lactam antibiotics, such as cephalosporins, cephaloridine, cephalothin, and cefazolin. In a kinetic study, EstU1 showed a similar range of substrate affinities for both p-nitrophenyl butyrate and first-generation cephalosporins while the turnover efficiency for the latter was much lower. Furthermore, site-directed mutagenesis studies revealed that the catalytic triad of EstU1 plays a crucial role in hydrolyzing both ester bonds of p-nitrophenyl esters and amide bonds of the beta-lactam ring of antibiotics, implicating the predicted catalytic triad of EstU1 in both activities.
ESTHER : Jeon_2011_Appl.Environ.Microbiol_77_7830
PubMedSearch : Jeon_2011_Appl.Environ.Microbiol_77_7830
PubMedID: 21908637

Title : Sitagliptin (MK0431) inhibition of dipeptidyl peptidase IV decreases nonobese diabetic mouse CD4+ T-cell migration through incretin-dependent and -independent pathways - Kim_2010_Diabetes_59_1739
Author(s) : Kim SJ , Nian C , McIntosh CH
Ref : Diabetes , 59 :1739 , 2010
Abstract : OBJECTIVE: Treatment of NOD mice with the dipeptidyl peptidase-IV (DPP-IV) inhibitor sitagliptin preserved islet transplants through a pathway involving modulation of splenic CD4(+) T-cell migration. In the current study, effects of sitagliptin on migration of additional subsets of CD4(+) T-cells were examined and underlying molecular mechanisms were further defined. RESEARCH DESIGN AND METHODS: Effects of sitagliptin on migration of NOD mouse splenic, thymic, and lymph node CD4(+) T-cells were determined. Signaling modules involved in DPP-IV-, Sitagliptin- and incretin-mediated modulation of CD4(+) T-cell migration were studied using Western blot and Rac1 and nuclear factor-kappaB (NF-kappaB) activity assays. RESULTS: Migration of splenic and lymph node CD4(+) T-cells of diabetic NOD mice was reduced by sitagliptin treatment. In vitro treatment of splenic, but not thymic or lymph node CD4(+) T-cells, from nondiabetic NOD mice with soluble (s) DPP-IV increased migration. Sitagliptin abolished sDPP-IV effects on splenic CD4(+) T-cell migration, whereas incretins decreased migration of lymph node, but not splenic, CD4(+) T-cells. Splenic CD4(+) T-cells demonstrating increased in vitro migration in response to sDPP-IV and lymph node CD4(+) T-cells that were nonresponsive to incretins selectively infiltrated islets of NOD mice, after injection. Sitagliptin decreases migration of splenic CD4(+) T-cells through a pathway involving Rac1/vasodilator-stimulated phosphoprotein, whereas its inhibitory effects on the migration of lymph node CD4(+) T-cells involve incretin-activation of the NF-kappaB pathway. CONCLUSIONS: Benefits of sitagliptin treatment in diabetic NOD mice may be mediated through selective effects on subpopulations of T-cells that are related to autoimmunity.
ESTHER : Kim_2010_Diabetes_59_1739
PubMedSearch : Kim_2010_Diabetes_59_1739
PubMedID: 20368408

Title : Effects of lipase, lipoxygenase, peroxidase and free fatty acids on volatile compound found in boiled buckwheat noodles - Suzuki_2010_J.Sci.Food.Agric_90_1232
Author(s) : Suzuki T , Kim SJ , Mukasa Y , Morishita T , Noda T , Takigawa S , Hashimoto N , Yamauchi H , Matsuura-Endo C
Ref : J Sci Food Agric , 90 :1232 , 2010
Abstract : BACKGROUND: Relationships between buckwheat (Fagopyrum esculentum Moench) flour lipase, lipoxygenase and peroxidase activity, along with levels of individual free fatty acids (FFAs) and levels of headspace volatile compounds of boiled buckwheat noodles, were investigated for 12 different buckwheat varieties. Enzyme activities and FFA levels in flour were correlated with their respective varietal arrays of boiled noodle headspace volatile compounds, measured by gas chromatography-mass spectrometry. RESULTS: The volatiles hexanal, tentative butanal, tentative 3-methylbutanal and tentative 2-methylbutanal showed significant positive correlation with one another, indicating that they may be generated through similar mechanisms. These important volatile components of buckwheat flavor were also positively correlated with lipase and/or peroxidase activity, indicating that enzymatic reactions are important in flavor generation in boiled buckwheat noodles. On the other hand, pentanal, which showed no significant correlation with any enzyme activity, showed a significant positive correlation to the levels of C18:2 and C18:3 FFAs, suggesting the existence of a 'non-enzymatic' and/or 'uncertain enzymatic pathway' for flavor generation in boiled buckwheat noodles. CONCLUSION: Lipase and peroxidase in buckwheat flour are important for flavor generation of boiled buckwheat noodles. This information is important for increasing desirable flavor of buckwheat products as well as for selecting varieties with improved flavor.
ESTHER : Suzuki_2010_J.Sci.Food.Agric_90_1232
PubMedSearch : Suzuki_2010_J.Sci.Food.Agric_90_1232
PubMedID: 20394006

Title : Enantioselective hydrolysis of racemic epichlorohydrin using an epoxide hydrolase from Novosphingobium aromaticivorans - Woo_2010_J.Biosci.Bioeng_110_295
Author(s) : Woo JH , Hwang YO , Kang JH , Lee HS , Kim SJ , Kang SG
Ref : J Biosci Bioeng , 110 :295 , 2010
Abstract : Previously we reported that an epoxide hydrolase (EHase) from Novosphingobium aromaticivorans could preferentially hydrolyze (R)-styrene oxide. In this study, we demonstrate that the purified NEH could be also effective in chiral resolution of racemic epichlorohydrin (ECH). Particularly, the purified NEH showed excellent hydrolyzing activity toward ECH to complete the reaction at a short period of incubation time. Enantiopure (S)-ECH could be obtained with a high enantiopurity of more than 99.99% enantiomeric excess (ee) and yield of 20.7% (theoretical, 50%). The chiral resolution of the purified NEH toward ECH was not susceptible to substrate inhibition by 500 mM racemic ECH.
ESTHER : Woo_2010_J.Biosci.Bioeng_110_295
PubMedSearch : Woo_2010_J.Biosci.Bioeng_110_295
PubMedID: 20547378
Gene_locus related to this paper: novad-q2g620

Title : Biocatalytic resolution of glycidyl phenyl ether using a novel epoxide hydrolase from a marine bacterium, Maritimibacter alkaliphilus KCCM 42376 [corrected] - Woo_2010_J.Biosci.Bioeng_109_539
Author(s) : Woo JH , Kang JH , Hwang YO , Cho JC , Kim SJ , Kang SG
Ref : J Biosci Bioeng , 109 :539 , 2010
Abstract : As a continuous effort of developing highly enantioselective epoxide hydrolase from marine microorganisms, it was found that Maritimibacter alkaliphilus KCCM 42376 [corrected] was highly enantioselective toward racemic glycidyl phenyl ether (GPE). An open reading frame (ORF) encoding a putative epoxide hydrolase (EHase) was cloned from the genome of Maritimibacter alkaliphilus KCCM 42376 [corrected], followed by expression and purification in Escherichia coli. The purified EHase (REH) hydrolyzed (S)-GPE preferentially over (R)-GPE. Enantiopure (R)-GPE from kinetic resolution of 29.2 mM racemic GPE using the purified REH could be obtained with enantiopurity of more than 99.9% enantiomeric excess (ee) and 38.4% yield (theoretical, 50%) within 20 min (enantiomeric ratio (E-value): 38.4). The enantioselective activity of REH toward GPE was also confirmed by the analysis of the vicinal diol, 3-phenoxy-1,2-propanediol. To our knowledge, this study demonstrates the highest enantioselective resolution of racemic GPE using a purified biocatalyst among the known native EHases.
ESTHER : Woo_2010_J.Biosci.Bioeng_109_539
PubMedSearch : Woo_2010_J.Biosci.Bioeng_109_539
PubMedID: 20471590
Gene_locus related to this paper: 9rhob-a3vif4

Title : GIP increases human adipocyte LPL expression through CREB and TORC2-mediated trans-activation of the LPL gene - Kim_2010_J.Lipid.Res_51_3145
Author(s) : Kim SJ , Nian C , McIntosh CH
Ref : J Lipid Res , 51 :3145 , 2010
Abstract : GIP (glucose-dependent insulinotropic polypeptide) is a gastrointestinal hormone that regulates pancreatic islet function. Additionally, emerging evidence suggests an important physiological role for GIP in the regulation of adipocyte metabolism. In previous studies on the lipogenic effects of GIP, it was shown to increase adipocyte lipoprotein lipase (LPL) activity in both differentiated 3T3-L1 cells and human adipocytes through a pathway involving activation of protein kinase B (PKB)/Akt. In the current study, we examined the effects of GIP on LPL gene expression. GIP in the presence of insulin increased LPL gene expression in human adipocytes and LPL promoter activity in GIP receptor-expressing HEK-293 cells, and both effects were greatly reduced by the transcription inhibitor actinomycin D. Subsequent studies established that GIP increased phosphorylation of Serine 133 in cAMP-response element binding protein (CREB) and the nuclear localization of cAMP-responsive CREB coactivator 2 (TORC2) through a pathway involving phosphatidylinositol 3-kinase (PI3-K), PKB, and AMP-activated protein kinase (AMPK). However, in the presence of insulin, GIP failed to activate the cAMP/PKA pathway. Knockdown of CREB and TORC2 using RNA interference reduced LPL expression, supporting a functional regulatory role. GIP-induced phospho-CREB and TORC2 were shown to bind to a cAMP-response element (-II) site in the human LPL promoter and GIP increased protein-protein interactions of these two factors. The lipogenic effects of GIP in the presence of insulin are therefore at least partially mediated by upregulation of adipocyte LPL gene transcription through a pathway involving PI3-K/PKB/AMPK-dependent CREB/TORC2 activation.
ESTHER : Kim_2010_J.Lipid.Res_51_3145
PubMedSearch : Kim_2010_J.Lipid.Res_51_3145
PubMedID: 20693566

Title : Omega-3 and omega-6 fatty acids suppress ER- and oxidative stress in cultured neurons and neuronal progenitor cells from mice lacking PPT1 - Kim_2010_Neurosci.Lett_479_292
Author(s) : Kim SJ , Zhang Z , Saha A , Sarkar C , Zhao Z , Xu Y , Mukherjee AB
Ref : Neuroscience Letters , 479 :292 , 2010
Abstract : Reactive oxygen species (ROS) damage brain lipids, carbohydrates, proteins, as well as DNA and may contribute to neurodegeneration. We previously reported that ER- and oxidative stress cause neuronal apoptosis in infantile neuronal ceroid lipofuscinosis (INCL), a lethal neurodegenerative storage disease, caused by palmitoyl-protein thioesterase-1 (PPT1) deficiency. Polyunsaturated fatty acids (PUFA) are essential components of cell membrane phospholipids in the brain and excessive ROS may cause oxidative damage of PUFA leading to neuronal death. Using cultured neurons and neuroprogenitor cells from mice lacking Ppt1, which mimic INCL, we demonstrate that Ppt1-deficient neurons and neuroprogenitor cells contain high levels of ROS, which may cause peroxidation of PUFA and render them incapable of providing protection against oxidative stress. We tested whether treatment of these cells with omega-3 or omega-6 PUFA protects the neurons and neuroprogenitor cells from oxidative stress and suppress apoptosis. We report here that both omega-3 and omega-6 fatty acids protect the Ppt1-deficient cells from ER- as well as oxidative stress and suppress apoptosis. Our results suggest that PUFA supplementation may have neuroprotective effects in INCL.
ESTHER : Kim_2010_Neurosci.Lett_479_292
PubMedSearch : Kim_2010_Neurosci.Lett_479_292
PubMedID: 20561933
Gene_locus related to this paper: mouse-ppt

Title : Complete genome sequence of Candidatus Puniceispirillum marinum IMCC1322, a representative of the SAR116 clade in the Alphaproteobacteria - Oh_2010_J.Bacteriol_192_3240
Author(s) : Oh HM , Kwon KK , Kang I , Kang SG , Lee JH , Kim SJ , Cho JC
Ref : Journal of Bacteriology , 192 :3240 , 2010
Abstract : The complete genome sequence of "Candidatus Puniceispirillum marinum" IMCC1322, the first cultured representative of the SAR116 clade in the Alphaproteobacteria, is reported here. The genome contains genes for proteorhodopsin, aerobic-type carbon monoxide dehydrogenase, dimethylsulfoniopropionate demethylase, and C(1) compound metabolism. The genome information proposes the SAR116 group to be metabolic generalists in ocean nutrient cycling.
ESTHER : Oh_2010_J.Bacteriol_192_3240
PubMedSearch : Oh_2010_J.Bacteriol_192_3240
PubMedID: 20382761
Gene_locus related to this paper: punmi-d5bnj7 , punmi-d5bsr5 , punmi-d5bsm1

Title : Structural and functional analysis of a novel EstE5 belonging to the subfamily of hormone-sensitive lipase - Nam_2009_Biochem.Biophys.Res.Commun_379_553
Author(s) : Nam KH , Kim MY , Kim SJ , Priyadarshi A , Lee WH , Hwang KY
Ref : Biochemical & Biophysical Research Communications , 379 :553 , 2009
Abstract : Hormone-sensitive lipase (HSL) plays an important role in the regulation of rodent fat cell lipolysis. It is regarded as an adipose tissue-specific enzyme whose sole metabolic role is the catalysis of hormone-stimulated lipolysis in mammalian cells. In this report we describe the functional and structural analysis of an EstE5 protein from a soil metagenome library. Function analysis results indicated that EstE5 preferentially hydrolyzes short-chain ester compounds, and our kinetic studies revealed the optimal pH and temperature. Based on the structural analysis, we defined the active site and the binding pocket. Structurally, EstE5 belongs to the HSL family and these structural studies may have applications in the production of value-added products, including pharmaceuticals.
ESTHER : Nam_2009_Biochem.Biophys.Res.Commun_379_553
PubMedSearch : Nam_2009_Biochem.Biophys.Res.Commun_379_553
PubMedID: 19116143
Gene_locus related to this paper: 9bact-Q0GMU2

Title : The crystal structure of an HSL-homolog EstE5 complex with PMSF reveals a unique configuration that inhibits the nucleophile Ser144 in catalytic triads - Nam_2009_Biochem.Biophys.Res.Commun_389_247
Author(s) : Nam KH , Kim SJ , Priyadarshi A , Kim HS , Hwang KY
Ref : Biochemical & Biophysical Research Communications , 389 :247 , 2009
Abstract : The esterase/lipase family (EC represents a diverse group of hydrolases that catalyze the cleavage of ester bonds and are widely distributed in animals, plants and microorganisms. Among these enzymes, hormone-sensitive lipases, play a critical role in the regulation of rodent fat cell lipolysis and are regarded as adipose tissue-specific enzymes. Recently, we reported the structural and biological characterization of EstE5 from the metagenome library [K.H. Nam, M.Y. Kim, S.J. Kim, A. Priyadarshi, W.H. Lee, K.Y. Hwang, Structural and functional analysis of a novel EstE5 belonging to the subfamily of hormone-sensitive lipase, Biochem. Biophys. Res. Commun. 379 (2009) 553-556]. The structure of this protein revealed that it belongs to the HSL-family. Here, we report the inhibition of the activity of the HSL-homolog EstE5 protein as determined by the use of esterase/lipase inhibitors. Our results revealed that the EstE5 protein is significantly inhibited by PMSF. In addition, this is the first study to identify the crystal structures of EstE5-PMSF at 2.4 and 2.5A among the HSL-homolog structures. This structural configuration is similar to that adopted when serine proteases are inhibited by PMSF. The results presented here provide valuable information regarding the properties of the HSL-family.
ESTHER : Nam_2009_Biochem.Biophys.Res.Commun_389_247
PubMedSearch : Nam_2009_Biochem.Biophys.Res.Commun_389_247
PubMedID: 19715665
Gene_locus related to this paper: 9bact-Q0GMU2

Title : Cloning and characterization of a new cold-active lipase from a deep-sea sediment metagenome - Jeon_2009_Appl.Microbiol.Biotechnol_81_865
Author(s) : Jeon JH , Kim JT , Kim YJ , Kim HK , Lee HS , Kang SG , Kim SJ , Lee JH
Ref : Applied Microbiology & Biotechnology , 81 :865 , 2009
Abstract : To search for new cold-active lipases, a metagenomic library was constructed using cold-sea sediment samples at Edison Seamount and was screened for lipolytic activities by plating on a tricaprylin medium. Subsequently, a fosmid clone was selected, and the whole sequence of 36 kb insert of the fosmid clone was determined by shotgun sequencing. The sequence analysis revealed the presence of 25 open reading frames (ORF), and ORF20 (EML1) showed similarities to lipases. Phylogenetic analysis of EML1 suggested that the protein belonged to a new family of esterase/lipase together with LipG. The EML1 gene was expressed in Escherichia coli, and purified by metal-chelating chromatography. The optimum activity of the purified EML1 (rEML1) occurred at pH 8.0 and 25 degrees C, respectively, and rEML1 displayed more than 50% activity at 5 degrees C. The activation energy for the hydrolysis of olive oil was determined to be 3.28 kcal/mol, indicating that EML1 is a cold-active lipase. rEML1 preferentially hydrolyzed triacylglycerols acyl-group chains with long chain lengths of > or = 8 carbon atoms and displayed hydrolyzing activities toward various natural oil substrates. rEML1 was resistant to various detergents such as Triton X-100 and Tween 80. This study represents an example which developed a new cold-active lipase from a deep-sea sediment metagenome.
ESTHER : Jeon_2009_Appl.Microbiol.Biotechnol_81_865
PubMedSearch : Jeon_2009_Appl.Microbiol.Biotechnol_81_865
PubMedID: 18773201
Gene_locus related to this paper: 9bact-a0ejl0

Title : Cloning and characterization of an epoxide hydrolase from Novosphingobium aromaticivorans - Woo_2009_Appl.Microbiol.Biotechnol_82_873
Author(s) : Woo JH , Kang JH , Kang SG , Hwang YO , Kim SJ
Ref : Applied Microbiology & Biotechnology , 82 :873 , 2009
Abstract : A gene encoding a putative epoxide hydrolase (EHase) was identified by analyzing an open reading frame of the genome sequence of Novosphingobium aromaticivorans, retaining the conserved catalytic residues such as the catalytic triad (Asp177, Glu328, and His355) and the oxyanion hole. The enantioselective EHase gene (neh) was cloned, and the recombinant EHase could be purified to apparent homogeneity by one step of metal affinity chromatography and further characterized. The purified N. aromaticivorans enantioselective epoxide hydrolase (NEH) showed enantioselective hydrolysis toward styrene oxide, glycidyl phenyl ether, epoxybutane, and epichlorohydrin. The optimal EHase activity toward styrene oxide occurred at pH 6.5 and 45 degrees C. The purified NEH could preferentially hydrolyze (R)-styrene oxide with enantiomeric excess of more than 99% and 11.7% yield after 20-min incubation at an optimal condition. The enantioselective hydrolysis of styrene oxide was also confirmed by the analysis of the vicinal diol, 1-phenyl-1,2-ethanediol. The hydrolyzing rates of the purified NEH toward epoxide substrates were not affected by as high as 100 mM racemic styrene oxide.
ESTHER : Woo_2009_Appl.Microbiol.Biotechnol_82_873
PubMedSearch : Woo_2009_Appl.Microbiol.Biotechnol_82_873
PubMedID: 19083233
Gene_locus related to this paper: novad-q2g620

Title : Dipeptidyl peptidase IV inhibition with MK0431 improves islet graft survival in diabetic NOD mice partially via T-cell modulation - Kim_2009_Diabetes_58_641
Author(s) : Kim SJ , Nian C , Doudet DJ , McIntosh CH
Ref : Diabetes , 58 :641 , 2009
Abstract : OBJECTIVE: The endopeptidase dipeptidyl peptidase-IV (DPP-IV) has been shown to NH2-terminally truncate incretin hormones, glucose-dependent insulinotropic polypeptide, and glucagon-like peptide-1, thus ablating their ability to potentiate glucose-stimulated insulin secretion. Increasing the circulating levels of incretins through administration of DPP-IV inhibitors has therefore been introduced as a therapeutic approach for the treatment of type 2 diabetes. DPP-IV inhibitor treatment has also been shown to preserve islet mass in rodent models of type 1 diabetes. The current study was initiated to define the effects of the DPP-IV inhibitor sitagliptin (MK0431) on transplanted islet survival in nonobese diabetic (NOD) mice, an autoimmune type 1 diabetes model. RESEARCH DESIGN AND METHODS: Effects of MK0431 on islet graft survival in diabetic NOD mice were determined with metabolic studies and micropositron emission tomography imaging, and its underlying molecular mechanisms were assessed. RESULTS: Treatment of NOD mice with MK0431 before and after islet transplantation resulted in prolongation of islet graft survival, whereas treatment after transplantation alone resulted in small beneficial effects compared with nontreated controls. Subsequent studies demonstrated that MK0431 pretreatment resulted in decreased insulitis in diabetic NOD mice and reduced in vitro migration of isolated splenic CD4+ T-cells. Furthermore, in vitro treatment of splenic CD4+ T-cells with DPP-IV resulted in increased migration and activation of protein kinase A (PKA) and Rac1. CONCLUSIONS: Treatment with MK0431 therefore reduced the effect of autoimmunity on graft survival partially by decreasing the homing of CD4+ T-cells into pancreatic beta-cells through a pathway involving cAMP/PKA/Rac1 activation.
ESTHER : Kim_2009_Diabetes_58_641
PubMedSearch : Kim_2009_Diabetes_58_641
PubMedID: 19073764

Title : Characterization and its potential application of two esterases derived from the arctic sediment metagenome - Jeon_2009_Mar.Biotechnol.(NY)_11_307
Author(s) : Jeon JH , Kim JT , Kang SG , Lee JH , Kim SJ
Ref : Mar Biotechnol (NY) , 11 :307 , 2009
Abstract : Two esterase genes (designated as estAT1 and estAT11, respectively) were cloned by activity-based screening of a fosmid library constructed with seashore sediment sample of the Arctic. The sequence analysis of the genes revealed that these esterase genes encoded proteins of 303 and 312 amino acids, respectively, and showed 40-50% identities to members of the hormone-sensitive lipase (HSL) family retaining a catalytic triad with a conserved GDSAG sequence and an oxyanion hole (HGGG). The esterases genes were overexpressed in Escherichia coli by co-expressing GroEL-GroES chaperonine, and the recombinant proteins (rEstAT1 and rEstAT11) were purified to homogeneity. The purified EstAT1 and EstAT11 were active in a broad range of temperature from 20 to 40 degrees C with an optimum temperature at 30 degrees C. The activation energies of rEstAT1 and rEstAT11 to hydrolyze p-nitrophenyl esters of butyrate were determined to be 12.65 kcal/mol and 11.26 kcal/mol, respectively, indicating that they are cold-adapted esterases. The purified EstAT1 and EstAT11 could hydrolyze racemic ofloxacin esters, and further rEstAT11 hydrolyzed preferentially (S)-racemic ofloxacin butyl ester with an enantiomeric excess (ee(p)) value of 70.3%. This work represents an example that develops enzymes from the Arctic using metagenomic approach, potentially applicable to chiral resolution of heat-labile substrates.
ESTHER : Jeon_2009_Mar.Biotechnol.(NY)_11_307
PubMedSearch : Jeon_2009_Mar.Biotechnol.(NY)_11_307
PubMedID: 18814017
Gene_locus related to this paper: 9bact-d8v1j6

Title : Complete genome sequence of Rhodobacter sphaeroides KD131 - Lim_2009_J.Bacteriol_191_1118
Author(s) : Lim SK , Kim SJ , Cha SH , Oh YK , Rhee HJ , Kim MS , Lee JK
Ref : Journal of Bacteriology , 191 :1118 , 2009
Abstract : Rhodobacter sphaeroides is a purple nonsulfur photosynthetic bacterium that is considered a possible source of H(2) production. R. sphaeroides KD131, which was isolated from sea mud in South Korea, was found to produce high levels of H(2). Here we report the complete and annotated genome sequence of R. sphaeroides KD131.
ESTHER : Lim_2009_J.Bacteriol_191_1118
PubMedSearch : Lim_2009_J.Bacteriol_191_1118
PubMedID: 19028901
Gene_locus related to this paper: rhos1-a3ph69 , rhos4-q3ixk0 , rhos4-q3iye8 , rhos4-q3iym6 , rhos4-q3j3q4 , rhos4-q3j204 , rhos4-q3j479 , rhos4-q3j480 , rhosh-BchO , rhosh-q1l7n7 , rhosk-b9kl36 , rhosk-b9kmj1 , rhosk-b9kqs4

Title : Structural and functional analysis of a novel hormone-sensitive lipase from a metagenome library -
Author(s) : Nam KH , Kim MY , Kim SJ , Priyadarshi A , Kwon ST , Koo BS , Yoon SH , Hwang KY
Ref : Proteins , 74 :1036 , 2009
PubMedID: 19089974
Gene_locus related to this paper: 9bact-Q0GMU1

Title : Inhibition of dipeptidyl peptidase IV with sitagliptin (MK0431) prolongs islet graft survival in streptozotocin-induced diabetic mice - Kim_2008_Diabetes_57_1331
Author(s) : Kim SJ , Nian C , Doudet DJ , McIntosh CH
Ref : Diabetes , 57 :1331 , 2008
Abstract : OBJECTIVE: Dipeptidyl peptidase-IV (DPP-IV) inhibitors have been introduced as therapeutics for type 2 diabetes. They partially act by blocking degradation of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), thus increasing circulating levels of active hormones. In addition to their insulinotropic actions, GLP-1 and GIP also promote beta-cell proliferation and survival, and DPP-IV inhibitors exert similar effects in rodent type 2 diabetes models. The study objective was to establish whether DPP-IV inhibitor treatment prolonged survival of transplanted islets and to determine whether positron emission tomography (PET) was appropriate for quantifying the effect of inhibition on islet mass. RESEARCH DESIGN & METHODS: Effects of the DPP-IV inhibitor MK0431 (sitagliptin) on glycemic control and functional islet mass in a streptozotocin (STZ)-induced type 1 diabetes mouse model were determined with metabolic studies and microPET imaging. RESULTS: The type 1 diabetes mouse model exhibited elevated plasma DPP-IV levels that were substantially inhibited in mice on an MK0431 diet. Residual beta-cell mass was extremely low in STZ-induced diabetic mice, and although active GLP-1 levels were increased by the MK0431 diet, there were no significant effects on glycemic control. After islet transplantation, mice fed normal diet rapidly lost their ability to regulate blood glucose, reflecting the suboptimal islet transplant. By contrast, the MK0431 group fully regulated blood glucose throughout the study, and PET imaging demonstrated a profound protective effect of MK0431 on islet graft size. CONCLUSIONS: Treatment with a DPP-IV inhibitor can prolong islet graft retention in an animal model of type 1 diabetes.
ESTHER : Kim_2008_Diabetes_57_1331
PubMedSearch : Kim_2008_Diabetes_57_1331
PubMedID: 18299314

Title : RAGE signaling contributes to neuroinflammation in infantile neuronal ceroid lipofuscinosis - Saha_2008_FEBS.Lett_582_3823
Author(s) : Saha A , Kim SJ , Zhang Z , Lee YC , Sarkar C , Tsai PC , Mukherjee AB
Ref : FEBS Letters , 582 :3823 , 2008
Abstract : Palmitoyl-protein thioesterase-1 (PPT1) deficiency causes infantile neuronal ceroid lipofuscinosis (INCL), a devastating childhood neurodegenerative storage disorder. We previously reported that neuronal apoptosis in INCL is mediated by endoplasmic reticulum-stress. ER-stress disrupts Ca(2+)-homeostasis and stimulates the expression of Ca(2+)-binding proteins. We report here that in the PPT1-deficient human and mouse brain the levels of S100B, a Ca(2+)-binding protein, and its receptor, RAGE (receptor for advanced glycation end-products) are elevated. We further demonstrate that activation of RAGE signaling in astroglial cells mediates pro-inflammatory cytokine production, which is inhibited by SiRNA-mediated suppression of RAGE expression. We propose that RAGE signaling contributes to neuroinflammation in INCL.
ESTHER : Saha_2008_FEBS.Lett_582_3823
PubMedSearch : Saha_2008_FEBS.Lett_582_3823
PubMedID: 18948101
Gene_locus related to this paper: mouse-ppt , human-PPT1

Title : A cold-adapted epoxide hydrolase from a strict marine bacterium, Sphingophyxis alaskensis - Kang_2008_J.Microbiol.Biotechnol_18_1445
Author(s) : Kang JH , Woo JH , Kang SG , Hwang YO , Kim SJ
Ref : J Microbiol Biotechnol , 18 :1445 , 2008
Abstract : An open reading frame (ORF) encoding a putative epoxide hydrolase (EHase) was identified by analyzing the genome sequence of Sphingophyxis alaskensis. The EHase gene (seh) was cloned and expressed in E. coli. To facilitate purification, the gene was fused in-frame to 6x histidine at the C-terminus. The recombinant EHase (rSEH) was highly soluble and could be purified to apparent homogeneity by one step of metal affinity chromatography. The purified SEH displayed hydrolyzing activities toward various epoxides such as styrene oxide, glycidyl phenyl ether, epoxyhexane, epoxybutane, epichlorohydrin, and epifluorohydrin. The optimum activity toward styrene oxide was observed at pH 6.5 and 35 degrees . The purified SEH showed a cold-adapted property, displaying more than 40% of activity at low temperature of 10 degrees compared with the optimum activity. Despite the catalytic efficiency, the purified SEH did not hydrolyze various epoxides enantioselectively. Km and kcat of SEH toward (R)-styrene oxide were calculated as 4+/-0.3 mM and 7.42 s(-1), respectively, whereas Km and kcat of SEH toward (S)-styrene oxide were 5.25+/-0.3 mM and 10.08 s(-1), respectively.
ESTHER : Kang_2008_J.Microbiol.Biotechnol_18_1445
PubMedSearch : Kang_2008_J.Microbiol.Biotechnol_18_1445
PubMedID: 18756107
Gene_locus related to this paper: 9sphn-q3vax0

Title : ER and oxidative stresses are common mediators of apoptosis in both neurodegenerative and non-neurodegenerative lysosomal storage disorders and are alleviated by chemical chaperones - Wei_2008_Hum.Mol.Genet_17_469
Author(s) : Wei H , Kim SJ , Zhang Z , Tsai PC , Wisniewski KE , Mukherjee AB
Ref : Hum Mol Genet , 17 :469 , 2008
Abstract : It is estimated that more than 40 different lysosomal storage disorders (LSDs) cumulatively affect one in 5000 live births, and in the majority of the LSDs, neurodegeneration is a prominent feature. Neuronal ceroid lipofuscinoses (NCLs), as a group, represent one of the most common (one in 12,500 births) neurodegenerative LSDs. The infantile NCL (INCL) is the most devastating neurodegenerative LSD, which is caused by inactivating mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. We previously reported that neuronal death by apoptosis in INCL, and in the PPT1-knockout (PPT1-KO) mice that mimic INCL, is at least in part caused by endoplasmic reticulum (ER) and oxidative stresses. In the present study, we sought to determine whether ER and oxidative stresses are unique manifestations of INCL or they are common to both neurodegenerative and non-neurodegenerative LSDs. Unexpectedly, we found that ER and oxidative stresses are common manifestations in cells from both neurodegenerative and non-neurodegenerative LSDs. Moreover, all LSD cells studied show extraordinary sensitivity to brefeldin-A-induced apoptosis, which suggests pre-existing ER stress conditions. Further, we uncovered that chemical disruption of lysosomal homeostasis in normal cells causes ER stress, suggesting a cross-talk between the lysosomes and the ER. Most importantly, we found that chemical chaperones that alleviate ER and oxidative stresses are also cytoprotective in all forms of LSDs studied. We propose that ER and oxidative stresses are common mediators of apoptosis in both neurodegenerative and non-neurodegenerative LSDs and suggest that the beneficial effects of chemical/pharmacological chaperones are exerted, at least in part, by alleviating these stress conditions.
ESTHER : Wei_2008_Hum.Mol.Genet_17_469
PubMedSearch : Wei_2008_Hum.Mol.Genet_17_469
PubMedID: 17989065

Title : Complete genome sequence of Neisseria gonorrhoeae NCCP11945 - Chung_2008_J.Bacteriol_190_6035
Author(s) : Chung GT , Yoo JS , Oh HB , Lee YS , Cha SH , Kim SJ , Yoo CK
Ref : Journal of Bacteriology , 190 :6035 , 2008
Abstract : Neisseria gonorrhoeae is an obligate human pathogen that is the etiological agent of gonorrhea. We explored variations in the genes of a multidrug-resistant N. gonorrhoeae isolate from a Korean patient in an effort to understand the prevalence, antibiotic resistance, and importance of horizontal gene transfer within this important, naturally competent organism. Here, we report the complete annotated genome sequence of N. gonorrhoeae strain NCCP11945.
ESTHER : Chung_2008_J.Bacteriol_190_6035
PubMedSearch : Chung_2008_J.Bacteriol_190_6035
PubMedID: 18586945
Gene_locus related to this paper: neig1-bioh , neig1-q5f6r7 , neig1-q5f908 , neigo-pip , neima-metx , neime-NMB0276 , neime-NMB1828 , neime-NMB1877

Title : Structural basis for the cold adaptation of psychrophilic M37 lipase from Photobacterium lipolyticum - Jung_2008_Proteins_71_476
Author(s) : Jung SK , Jeong DG , Lee MS , Lee JK , Kim HK , Ryu SE , Park BC , Kim JH , Kim SJ
Ref : Proteins , 71 :476 , 2008
Abstract : The M37 lipase from Photobacterium lipolyticum shows an extremely low activation energy and strong activity at low temperatures, with optimum activity seen at 298 K and more than 75% of the optimum activity retained down to 278 K. Though the M37 lipase is most closely related to the filamentous fungal lipase, Rhizomucor miehei lipase (RML) at the primary structure level, their activity characteristics are completely different. In an effort to identify structural components of cold adaptation in lipases, we determined the crystal structure of the M37 lipase at 2.2 A resolution and compared it to that of nonadapted RML. Structural analysis revealed that M37 lipase adopted a folding pattern similar to that observed for other lipase structures. However, comparison with RML revealed that the region beneath the lid of the M37 lipase included a significant and unique cavity that would be occupied by a lid helix upon substrate binding. In addition, the oxyanion hole was much wider in M37 lipase than RML. We propose that these distinct structural characteristics of M37 lipase may facilitate the lateral movement of the helical lid and subsequent substrate hydrolysis, which might explain its low activation energy and high activity at low temperatures.
ESTHER : Jung_2008_Proteins_71_476
PubMedSearch : Jung_2008_Proteins_71_476
PubMedID: 18186467
Gene_locus related to this paper: 9gamm-q5drn8

Title : The complete genome sequence of Thermococcus onnurineus NA1 reveals a mixed heterotrophic and carboxydotrophic metabolism - Lee_2008_J.Bacteriol_190_7491
Author(s) : Lee HS , Kang SG , Bae SS , Lim JK , Cho Y , Kim YJ , Jeon JH , Cha SS , Kwon KK , Kim HT , Park CJ , Lee HW , Kim SI , Chun J , Colwell RR , Kim SJ , Lee JH
Ref : Journal of Bacteriology , 190 :7491 , 2008
Abstract : Members of the genus Thermococcus, sulfur-reducing hyperthermophilic archaea, are ubiquitously present in various deep-sea hydrothermal vent systems and are considered to play a significant role in the microbial consortia. We present the complete genome sequence and feature analysis of Thermococcus onnurineus NA1 isolated from a deep-sea hydrothermal vent area, which reveal clues to its physiology. Based on results of genomic analysis, T. onnurineus NA1 possesses the metabolic pathways for organotrophic growth on peptides, amino acids, or sugars. More interesting was the discovery that the genome encoded unique proteins that are involved in carboxydotrophy to generate energy by oxidation of CO to CO(2), thereby providing a mechanistic basis for growth with CO as a substrate. This lithotrophic feature in combination with carbon fixation via RuBisCO (ribulose 1,5-bisphosphate carboxylase/oxygenase) introduces a new strategy with a complementing energy supply for T. onnurineus NA1 potentially allowing it to cope with nutrient stress in the surrounding of hydrothermal vents, providing the first genomic evidence for the carboxydotrophy in Thermococcus.
ESTHER : Lee_2008_J.Bacteriol_190_7491
PubMedSearch : Lee_2008_J.Bacteriol_190_7491
PubMedID: 18790866
Gene_locus related to this paper: theon-b6ywd5

Title : Screening enantioselective epoxide hydrolase activities from marine microorganisms: detection of activities in Erythrobacter spp - Hwang_2008_Mar.Biotechnol.(NY)_10_366
Author(s) : Hwang YO , Kang SG , Woo JH , Kwon KK , Sato T , Lee EY , Han MS , Kim SJ
Ref : Mar Biotechnol (NY) , 10 :366 , 2008
Abstract : To develop an enantioselective epoxide hydrolase (EHase) from marine microorganisms, marine samples were collected from a variety of marine environments. Strains isolated by the capability of living on styrene oxide (SO) were screened for retaining enantioselective EHase activities toward SO by combining spectrophotometric, GC, and HPLC analysis. Consequently, one strain, JCS358, was selected, and the sequence analysis of 16S rRNA gene showed that the strain belonged to Erythrobacter cluster. Twelve additional Erythrobacter strains from this study or acquired from culture collections were thereby tested for displaying EHase activities, and most of tested strains showed enantioselective hydrolysis toward SO and glycidyl phenyl ether. Kinetic resolution of racemic SO using whole cell of Erythrobacter sp. JCS358 was performed. Enantiopure (S)-SO could be obtained with an enantiomeric excess (ee) higher than 99% after 15 h incubation. The determination of 1-phenyl-1,2-ethanediol configuration derived from racemic SO confirmed the enantioselective hydrolyzing activity of Erythrobacter sp. JCS358.
ESTHER : Hwang_2008_Mar.Biotechnol.(NY)_10_366
PubMedSearch : Hwang_2008_Mar.Biotechnol.(NY)_10_366
PubMedID: 18214609

Title : Palmitoyl protein thioesterase-1 deficiency impairs synaptic vesicle recycling at nerve terminals, contributing to neuropathology in humans and mice - Kim_2008_J.Clin.Invest_118_3075
Author(s) : Kim SJ , Zhang Z , Sarkar C , Tsai PC , Lee YC , Dye L , Mukherjee AB
Ref : J Clinical Investigation , 118 :3075 , 2008
Abstract : Neuronal ceroid lipofuscinoses represent the most common childhood neurodegenerative storage disorders. Infantile neuronal ceroid lipofuscinosis (INCL) is caused by palmitoyl protein thioesterase-1 (PPT1) deficiency. Although INCL patients show signs of abnormal neurotransmission, manifested by myoclonus and seizures, the molecular mechanisms by which PPT1 deficiency causes this abnormality remain obscure. Neurotransmission relies on repeated cycles of exo- and endocytosis of the synaptic vesicles (SVs), in which several palmitoylated proteins play critical roles. These proteins facilitate membrane fusion, which is required for neurotransmitter exocytosis, recycling of the fused SV membrane components, and regeneration of fresh vesicles. However, palmitoylated proteins require depalmitoylation for recycling. Using postmortem brain tissues from an INCL patient and tissue from the PPT1-knockout (PPT1-KO) mice that mimic INCL, we report here that PPT1 deficiency caused persistent membrane anchorage of the palmitoylated SV proteins, which hindered the recycling of the vesicle components that normally fuse with the presynaptic plasma membrane during SV exocytosis. Thus, the regeneration of fresh SVs, essential for maintaining the SV pool size at the synapses, was impaired, leading to a progressive loss of readily releasable SVs and abnormal neurotransmission. This abnormality may contribute to INCL neuropathology.
ESTHER : Kim_2008_J.Clin.Invest_118_3075
PubMedSearch : Kim_2008_J.Clin.Invest_118_3075
PubMedID: 18704195
Gene_locus related to this paper: mouse-ppt , human-PPT1

Title : Biomarker responses in caged rockfish (Sebastes schlegeli) from Masan Bay and Haegeumgang, South Korea - Jung_2008_Mar.Pollut.Bull_57_599
Author(s) : Jung JH , Kim SJ , Lee TK , Shim WJ , Woo S , Kim DJ , Han CH
Ref : Mar Pollut Bull , 57 :599 , 2008
Abstract : The purpose of this study was to compare enzymatic biomarker activities in fish caged at two sites, Masan Bay (contaminated) and Haeguemgang (reference). In the present study, ethoxyresorufin O-deethylase (EROD), brain acetyl cholinesterase (bAChE), muscle acetyl cholinesterase (mAChE) and butyryl cholinesterase (mBChE) in caged rockfish (Sebastes schlegeli) were measured 0, 1, 3, 7, 14, 21 and 30 days after caging. The level of CYP1A mRNA and Protein expression was induced higher in Masan Bay at 1, 3, 7, 14 and 30 days after caging. EROD activity in the caged fish was significantly higher in Masan Bay than in Haeguemgang 3 and 7 days after caging, but not at 14 and 30 days after caging. bAChE activity was significantly inhibited at 7 and 14 days after caging in Masan Bay. However, mBChE activity was not significantly inhibited during the experiment. Taken together, the data suggest that the caged fish were exposed, at least transiently, to CYP1A inducers and ChE inhibitors, which is consistent with our previous observations.
ESTHER : Jung_2008_Mar.Pollut.Bull_57_599
PubMedSearch : Jung_2008_Mar.Pollut.Bull_57_599
PubMedID: 18234237

Title : Production of lysophosphatidylcholine by cPLA2 in the brain of mice lacking PPT1 is a signal for phagocyte infiltration - Zhang_2007_Hum.Mol.Genet_16_837
Author(s) : Zhang Z , Lee YC , Kim SJ , Choi MS , Tsai PC , Saha A , Wei H , Xu Y , Xiao YJ , Zhang P , Heffer A , Mukherjee AB
Ref : Hum Mol Genet , 16 :837 , 2007
Abstract : In the majority of neurodegenerative storage disorders, neuronal death in the brain is followed by infiltration of phagocytic cells (e.g. activated microglia, astroglia and macrophages) for the efficient removal of cell corpses. However, it is increasingly evident that these phagocytes may also cause death of adjoining viable neurons contributing to rapid progression of neurodegeneration. Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating, neurodegenerative, lysosomal storage disorder caused by inactivating mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. PPT1 catalyzes the cleavage of thioester linkages in S-acylated (palmitoylated) proteins and its deficiency leads to abnormal accumulation of thioesterified polypeptides (ceroid) in lysosomes causing INCL pathogenesis. PPT1-knockout (PPT1-KO) mice mimic the clinical and pathological features of human INCL including rapid neuronal death by apoptosis and phagocyte infiltration. We previously reported that in PPT1-KO mice, the neurons undergo endoplasmic reticulum stress activating unfolded protein response, which mediates caspase-12 activation and apoptosis. However, the molecular mechanism(s) by which the phagocytic cells are recruited in the PPT1-KO mouse brain remains poorly understood. We report here that increased production of lysophosphatidylcholine (LPC), catalyzed by the activation of cytosolic phospholipase A(2) (cPLA(2)) in the PPT1-KO mouse brain, is a 'lipid signal' for phagocyte recruitment. We also report that an age-dependent increase in LPC levels in the PPT1-KO mouse brain positively correlates with elevated expression of the genes characteristically associated with phagocytes. We propose that increased cPLA(2)-catalyzed LPC production in the brain is at least one of the mechanisms that mediate phagocyte infiltration contributing to INCL neuropathology.
ESTHER : Zhang_2007_Hum.Mol.Genet_16_837
PubMedSearch : Zhang_2007_Hum.Mol.Genet_16_837
PubMedID: 17341491
Gene_locus related to this paper: mouse-ppt

Title : Cloning and characterization of three epoxide hydrolases from a marine bacterium, Erythrobacter litoralis HTCC2594 - Woo_2007_Appl.Microbiol.Biotechnol_76_365
Author(s) : Woo JH , Hwang YO , Kang SG , Lee HS , Cho JC , Kim SJ
Ref : Applied Microbiology & Biotechnology , 76 :365 , 2007
Abstract : Previously, we reported that ten strains belonging to Erythrobacter showed epoxide hydrolase (EHase) activities toward various epoxide substrates. Three genes encoding putative EHases were identified by analyzing open reading frames of Erythrobacter litoralis HTCC2594. Despite low similarities to reported EHases, the phylogenetic analysis of the three genes showed that eeh1 was similar to microsomal EHase, while eeh2 and eeh3 could be grouped with soluble EHases. The three EHase genes were cloned, and the recombinant proteins (rEEH1, rEEH2, and rEEH3) were purified. The functionality of purified proteins was proved by hydrolytic activities toward styrene oxide. EEH1 preferentially hydrolyzed (R)-styrene oxide, whereas EEH3 preferred to hydrolyze (S)-styrene oxide, representing enantioselective hydrolysis of styrene oxide. On the other hand, EEH2 could hydrolyze (R)- and (S)-styrene oxide at an equal rate. The optimal pH and temperature for the EHases occurred largely at neutral pHs and 40-55 degrees C. The substrate selectivity of rEEH1, rEEH2, and rEEH3 toward various epoxide substrates were also investigated. This is the first representation that a strict marine microorganism possessed three EHases with different enantioselectivity toward styrene oxide.
ESTHER : Woo_2007_Appl.Microbiol.Biotechnol_76_365
PubMedSearch : Woo_2007_Appl.Microbiol.Biotechnol_76_365
PubMedID: 17541582
Gene_locus related to this paper: 9sphn-q2n9r2 , 9sphn-q2n9t8 , 9sphn-q2nav3 , 9sphn-q2nch7

Title : Altererythrobacter epoxidivorans gen. nov., sp. nov., an epoxide hydrolase-active, mesophilic marine bacterium isolated from cold-seep sediment, and reclassification of Erythrobacter luteolus Yoon et al. 2005 as Altererythrobacter luteolus comb. nov - Kwon_2007_Int.J.Syst.Evol.Microbiol_57_2207
Author(s) : Kwon KK , Woo JH , Yang SH , Kang JH , Kang SG , Kim SJ , Sato T , Kato C
Ref : Int J Syst Evol Microbiol , 57 :2207 , 2007
Abstract : A novel marine bacterium, strain JCS350(T), was isolated from marine sediment samples collected from a cold-seep area. The 16S rRNA gene sequence of the isolate showed high similarity to that of Erythrobacter luteolus SW-109(T) (95.9 % sequence similarity). Lower 16S rRNA gene sequence similarities were shown to other members of the genus Erythrobacter (94.6-95.4 %) and members of the genus Porphyrobacter (94.5-95.2 %). Phylogenetic analysis with all members of the family Erythrobacteraceae and several members of the family Sphingomonadaceae revealed that the isolate formed a phyletic line with [Erythrobacter] luteolus that was distinct from other members of the family Erythrobacteraceae. The dominant fatty acids of strain JCS350(T) were 18 : 1omega7c, 16 : 1omega7c and cyclopropane 17 : 0. The major respiratory quinone was ubiquinone 10. The DNA G+C content was 54.5 mol%. The isolate did not contain bacteriochlorophyll a. Optimal growth required the presence of 2 % (w/v) NaCl with either 0.18 % CaCl(2) or 0.59 % MgCl(2), at pH 6.5 and at 35 degrees C. On the basis of the evidence of this polyphasic taxonomic study, strain JCS350(T) should be classified in a novel genus and species in the family Erythrobacteraceae, for which the name Altererythrobacter epoxidivorans gen. nov., sp. nov. is proposed. The misclassified species [Erythrobacter] luteolus is transferred to the new genus as Altererythrobacter luteolus comb. nov. The type strain of Altererythrobacter epoxidivorans is JCS350(T) (=KCCM 42314(T) =JCM 13815(T)) and the type strain of Altererythrobacter luteolus is SW-109(T) (=KCTC 12311(T) =JCM 12599(T)).
ESTHER : Kwon_2007_Int.J.Syst.Evol.Microbiol_57_2207
PubMedSearch : Kwon_2007_Int.J.Syst.Evol.Microbiol_57_2207
PubMedID: 17911284

Title : Resistin is a key mediator of glucose-dependent insulinotropic polypeptide (GIP) stimulation of lipoprotein lipase (LPL) activity in adipocytes - Kim_2007_J.Biol.Chem_282_34139
Author(s) : Kim SJ , Nian C , McIntosh CH
Ref : Journal of Biological Chemistry , 282 :34139 , 2007
Abstract : Studies on the physiological roles of the incretin hormone, glucose-dependent insulinotropic polypeptide (GIP) have largely focused on its insulinotropic action and ability to regulate beta-cell mass. In previous studies on the stimulatory effect of GIP on adipocyte lipoprotein lipase (LPL), a pathway was identified involving increased phosphorylation of protein kinase B (PKB) and reduced phosphorylation of LKB1 and AMP-activated protein kinase (AMPK). The slow time of onset of the responses suggested that GIP may have induced release of an intermediary molecule, and the current studies focused on the possible contribution of the adipokine resistin. In differentiated 3T3-L1 adipocytes, GIP, in the presence of insulin, increased resistin secretion through a pathway involving p38 mitogen-activated protein kinase (p38 MAPK) and the stress-activated protein kinase/Jun amino-terminal kinase (SAPK/JNK). The other major incretin hormone, glucagon-like peptide-1 (GLP-1), exhibited no significant effects. Chronic elevation of circulating GIP levels in the Vancouver Diabetic Fatty (VDF) Zucker rat resulted in increases in circulating resistin levels and activation of p38 MAPK or SAPK/JNK in epididymal fat tissue, suggesting the existence of identical pathways in vivo as well as in vitro. Administration of resistin to 3T3-L1 adipocytes mimicked the effects of GIP on the PKB/LKB1/AMPK/LPL pathway: increasing phosphorylation of PKB, reducing levels of phosphorylated LKB1 and AMPK, and increasing LPL activity. Knockdown of resistin using RNA interference attenuated the effect of GIP on the PKB/LKB1/AMPK/LPL pathway in 3T3-L1 adipocytes, supporting a role for resistin as a mediator.
ESTHER : Kim_2007_J.Biol.Chem_282_34139
PubMedSearch : Kim_2007_J.Biol.Chem_282_34139
PubMedID: 17890220

Title : A new esterase showing similarity to putative dienelactone hydrolase from a strict marine bacterium, Vibrio sp. GMD509 - Park_2007_Appl.Microbiol.Biotechnol_77_107
Author(s) : Park SY , Kim JT , Kang SG , Woo JH , Lee JH , Choi HT , Kim SJ
Ref : Applied Microbiology & Biotechnology , 77 :107 , 2007
Abstract : Vibrio sp. GMD509, a marine bacterium isolated from eggs of the sea hare, exhibited lipolytic activity on tributyrin (TBN) plate, and the gene representing lipolytic activity was cloned. As a result, an open reading frame (ORF) consisting of 1,017 bp (338 aa) was found, and the deduced amino acid sequence of the ORF showed low similarity (< 20%) to alpha/beta hydrolases such as dienelactone hydrolases and esterase/lipase with G-X(1)-S-X(2)-G sequence conserved. Phylogenetic analysis suggested that the protein belonged to a new family of esterase/lipase together with various hypothetical proteins. The enzyme was overexpressed in Escherichia coli and purified to homogeneity. The purified enzyme (Vlip509) showed the best hydrolyzing activity toward p-nitrophenyl butyrate (C(4)) among various p-nitrophenyl esters (C(2) to C(18)), and optimal activity of Vlip509 occurred at 30 degrees C and pH 8.5, respectively. Kinetic parameters toward p-nitrophenyl butyrate were determined as K (m) (307 muM), k (cat) (5.72 s(-1)), and k (cat)/K (m) (18.61 s(-1) mM(-1)). Furthermore, Vlip509 preferentially hydrolyzed the S-enantiomer of racemic ofloxacin ester. Despite its sequence homology to dienelactone hydrolase, Vlip509 showed no dienelactone hydrolase activity. This study represents the identification of a novel lipolytic enzyme from marine environment.
ESTHER : Park_2007_Appl.Microbiol.Biotechnol_77_107
PubMedSearch : Park_2007_Appl.Microbiol.Biotechnol_77_107
PubMedID: 17712554
Gene_locus related to this paper: 9vibr-a8jy01

Title : Cloning, expression and enantioselective hydrolytic catalysis of a microsomal epoxide hydrolase from a marine fish, Mugil cephalus - Lee_2007_Biotechnol.Lett_29_237
Author(s) : Lee SJ , Kim HS , Kim SJ , Park S , Kim BJ , Shuler ML , Lee EY
Ref : Biotechnol Lett , 29 :237 , 2007
Abstract : The cDNA of a marine fish microsomal epoxide hydrolase (mEH) gene from Mugil cephalus was cloned by rapid amplification of cDNA ends (RACE) techniques. The homology model for the mEH of M. cephalus showed a characteristic structure of alpha/beta-hydrolase-fold main domain with a lid domain over the active site. The characteristic catalytic triad, consisting of Asp(238), His(444), and Glu(417), was highly conserved. The cloned mEH gene was expressed in Escherichia coli and the recombinant mEH exhibited (R)-preferred hydrolysis activity toward racemic styrene oxide. We obtained enantiopure (S)-styrene oxide with a high enantiopurity of more than 99% enantiomeric excess and yield of 15.4% by batch kinetic resolution of 20 mM racemic styrene oxide.
ESTHER : Lee_2007_Biotechnol.Lett_29_237
PubMedSearch : Lee_2007_Biotechnol.Lett_29_237
PubMedID: 17151961
Gene_locus related to this paper: mucge-c4paw7

Title : Screening and its potential application of lipolytic activity from a marine environment: characterization of a novel esterase from Yarrowia lipolytica CL180 - Kim_2007_Appl.Microbiol.Biotechnol_74_820
Author(s) : Kim JT , Kang SG , Woo JH , Lee JH , Jeong BC , Kim SJ
Ref : Applied Microbiology & Biotechnology , 74 :820 , 2007
Abstract : To develop an enantioselective lipase/esterase hydrolyzing racemic ofloxacin ester to levofloxacin, samples were collected from a variety of marine environments such as cold sea, hydrothermal vent area, sediment, tidal flat area, arctic sea, marine organisms, and so on. Microorganisms were isolated by plating on an enrichment medium with simultaneous detection of lipolytic activities and screened for the hydrolysis of ofloxacin ester. Three candidates among isolates were selected, and one of them, identified as Yarrowia lipolytica CL180, hydrolyzed preferentially S-enantiomer of racemic ofloxacin ester. The lipase/esterase gene (yli180) was cloned by screening a genomic library. The sequence analysis revealed an open reading frame consisting of 1,431 bp that encoded a protein of 476 amino acids with a molecular mass of 53 kDa. The yli180 gene was expressed in Escherichia coli and purified to homogeneity. The optimum activity of the recombinant protein (rYli180) occurred at pH 7.5 and 35 degrees C, respectively. rYli180 preferentially hydrolyzed p-nitrophenyl esters of fatty acids with short chain lengths of < or =10 carbon atoms. This study represents a novel esterase of type B1 carboxylesterase/lipase family from a marine isolate, showing a potential usage as a biocatalyst because of enantioselectivity toward racemic ofloxacin ester.
ESTHER : Kim_2007_Appl.Microbiol.Biotechnol_74_820
PubMedSearch : Kim_2007_Appl.Microbiol.Biotechnol_74_820
PubMedID: 17119955

Title : Activation of lipoprotein lipase by glucose-dependent insulinotropic polypeptide in adipocytes. A role for a protein kinase B, LKB1, and AMP-activated protein kinase cascade - Kim_2007_J.Biol.Chem_282_8557
Author(s) : Kim SJ , Nian C , McIntosh CH
Ref : Journal of Biological Chemistry , 282 :8557 , 2007
Abstract : Glucose-dependent insulinotropic polypeptide (GIP) has been mainly studied because of its glucose-dependent insulinotropic action and its ability to regulate beta-cell proliferation and survival. Considerably less is known about the effects of GIP on fat metabolism, and the present study was directed at identifying the mechanisms underlying its stimulatory action on lipoprotein lipase (LPL). In differentiated 3T3-L1 adipocytes, GIP, in the presence of insulin, increased LPL activity and triglyceride accumulation through a pathway involving increased phosphorylation of protein kinase B (PKB) and reductions in phosphorylated LKB1 and AMP-activated protein kinase (AMPK). Knockdown of AMPK using RNA interference and application of the AMPK inhibitor, Compound C, supported this conclusion. In contrast, the other major incretin hormone, glucagon-like peptide-1, exhibited no significant effects on LPL activity or PKB, LKB1, or AMPK phosphorylation. Cultured subcutaneous human adipocytes showed similar responses to GIP but with greater sensitivity. Chronic elevation of circulating GIP levels in the Vancouver diabetic fatty Zucker rat in vivo resulted in increased LPL activity and elevated triglyceride accumulation in epididymal fat tissue, combined with a modulation of PKB, LKB1, and AMPK phosphorylation similar to that observed in vitro. This appears to be the first demonstration of a GIP-stimulated signal transduction pathway involved in increasing fat storage in adipocytes.
ESTHER : Kim_2007_J.Biol.Chem_282_8557
PubMedSearch : Kim_2007_J.Biol.Chem_282_8557
PubMedID: 17244606

Title : Applications of dipeptidyl peptidase IV inhibitors in diabetes mellitus - McIntosh_2006_Int.J.Biochem.Cell.Biol_38_860
Author(s) : McIntosh CH , Demuth HU , Kim SJ , Pospisilik JA , Pederson RA
Ref : International Journal of Biochemistryistry & Cell Biology , 38 :860 , 2006
Abstract : A number of alternative therapies for type 2 diabetes are currently under development that take advantage of the actions of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide on the pancreatic beta-cell. One such approach is based on the inhibition of dipeptidyl peptidase IV (DP IV), the major enzyme responsible for degrading the incretins in vivo. DP IV exhibits characteristics that have allowed the development of specific inhibitors with proven efficacy in improving glucose tolerance in animal models of diabetes and type 2 human diabetics. While enhancement of insulin secretion, resulting from blockade of incretin degradation, has been proposed to be the major mode of inhibitor action, there is also evidence that inhibition of gastric emptying, reduction in glucagon secretion and important effects on beta-cell differentiation, mitogenesis and survival, by the incretins and other DP IV-sensitive peptides, can potentially preserve beta-cell mass, and improve insulin secretory function and glucose handling in diabetics.
ESTHER : McIntosh_2006_Int.J.Biochem.Cell.Biol_38_860
PubMedSearch : McIntosh_2006_Int.J.Biochem.Cell.Biol_38_860
PubMedID: 16442340

Title : Palmitoyl-protein thioesterase-1 deficiency mediates the activation of the unfolded protein response and neuronal apoptosis in INCL - Zhang_2006_Hum.Mol.Genet_15_337
Author(s) : Zhang Z , Lee YC , Kim SJ , Choi MS , Tsai PC , Xu Y , Xiao YJ , Zhang P , Heffer A , Mukherjee AB
Ref : Hum Mol Genet , 15 :337 , 2006
Abstract : Numerous proteins undergo modification by palmitic acid (S-acylation) for their biological functions including signal transduction, vesicular transport and maintenance of cellular architecture. Although palmitoylation is an essential modification, these proteins must also undergo depalmitoylation for their degradation by lysosomal proteases. Palmitoyl-protein thioesterase-1 (PPT1), a lysosomal enzyme, cleaves thioester linkages in S-acylated proteins and removes palmitate residues facilitating the degradation of these proteins. Thus, inactivating mutations in the PPT1 gene cause infantile neuronal ceroid lipofuscinosis (INCL), a devastating neurodegenerative storage disorder of childhood. Although rapidly progressing brain atrophy is the most dramatic pathological manifestation of INCL, the molecular mechanism(s) remains unclear. Using PPT1-knockout (PPT1-KO) mice that mimic human INCL, we report here that the endoplasmic reticulum (ER) in the brain cells of these mice is structurally abnormal. Further, we demonstrate that the level of growth-associated protein-43 (GAP-43), a palmitoylated neuronal protein, is elevated in the brains of PPT1-KO mice. Moreover, forced expression of GAP-43 in PPT1-deficient cells results in the abnormal accumulation of this protein in the ER. Consistent with these results, we found evidence for the activation of unfolded protein response (UPR) marked by elevated levels of phosphorylated translation initiation factor, eIF2alpha, increased expression of chaperone proteins such as glucose-regulated protein-78 and activation of caspase-12, a cysteine proteinase in the ER, mediating caspase-3 activation and apoptosis. Our results, for the first time, link PPT1 deficiency with the activation of UPR, apoptosis and neurodegeneration in INCL and identify potential targets for therapeutic intervention in this uniformly fatal disease.
ESTHER : Zhang_2006_Hum.Mol.Genet_15_337
PubMedSearch : Zhang_2006_Hum.Mol.Genet_15_337
PubMedID: 16368712
Gene_locus related to this paper: mouse-ppt

Title : Endoplasmic reticulum stress-induced caspase-4 activation mediates apoptosis and neurodegeneration in INCL - Kim_2006_Hum.Mol.Genet_15_1826
Author(s) : Kim SJ , Zhang Z , Hitomi E , Lee YC , Mukherjee AB
Ref : Hum Mol Genet , 15 :1826 , 2006
Abstract : Infantile neuronal ceroid lipofuscinosis (INCL), a neurodegenerative storage disorder of childhood, is caused by mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. PPT1 cleaves thioester linkages in S-acylated (palmitoylated) proteins and its mutation causes abnormal intracellular accumulation of fatty-acylated proteins and peptides leading to INCL pathogenesis. Although apoptosis is the suggested cause of neurodegeneration in INCL, the molecular mechanism(s) of apoptosis remains unclear. Using the PPT1-knockout (PPT1-KO) mice that mimic INCL, we previously reported that one mechanism of apoptosis involves endoplasmic reticulum (ER) stress-induced caspase-12 activation. However, the human caspase-12 gene contains several mutations, which make it functionally inactive. Thus, it has been suggested that human caspase-4 is the counterpart of murine caspase-12. Here we report that in the human INCL brain ER stress-induced activation of unfolded protein response (UPR) mediates caspase-4 and caspase-3 activation and apoptosis. Moreover, we show that the INCL brain contains high level of growth-associated protein-43 (GAP-43), which is known to undergo palmitoylation. We also demonstrate that transfection of cultured INCL cells with a green fluorescent protein-GAP-43 cDNA construct shows abnormal localization of this protein in the ER. Further, INCL cells manifest evidence of ER stress and UPR (elevated levels of Grp-78/Bip and GADD153), caspase-4 as well as caspase-3 activation and cleavage of poly(ADP)-ribose polymerase, a compelling sign of apoptosis. Most importantly, we show that inhibition of caspase-4 activity protects INCL cells from undergoing apoptosis. Our results provide insight into at least one of the molecular mechanisms of apoptosis in INCL and may allow the identification of potential targets for therapeutic intervention.
ESTHER : Kim_2006_Hum.Mol.Genet_15_1826
PubMedSearch : Kim_2006_Hum.Mol.Genet_15_1826
PubMedID: 16644870
Gene_locus related to this paper: human-PPT1

Title : Palmitoyl-protein thioesterase-1 deficiency leads to the activation of caspase-9 and contributes to rapid neurodegeneration in INCL - Kim_2006_Hum.Mol.Genet_15_1580
Author(s) : Kim SJ , Zhang Z , Lee YC , Mukherjee AB
Ref : Hum Mol Genet , 15 :1580 , 2006
Abstract : The infantile neuronal ceroid lipofuscinosis (INCL), a rare (one in 100 000 births) but one of the most lethal inherited neurodegenerative storage disorders of childhood, is caused by inactivating mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. PPT1 cleaves thioester linkages in s-acylated (palmitoylated) proteins and facilitates their degradation and/or recycling. Thus, PPT1-deficiency leads to an abnormal intracellular accumulation of s-acylated proteins causing INCL pathogenesis. Although neuronal apoptosis is the suggested cause of neurodegeneration in this disease, the molecular mechanism(s) remains poorly understood. We recently reported that one of the major pathways of neuronal apoptosis in PPT1-knockout (PPT1-KO) mice that mimic INCL, is mediated by endoplasmic reticulum (ER) stress-induced caspase-12 activation. ER stress also increases the production of reactive oxygen species (ROS), disrupts Ca(2+) homeostasis and increases the potential for destabilizing mitochondrial membrane. Mitochondrial membrane destabilization activates caspase-9 present in this organelle, and can mediate apoptosis. We report here that the levels of superoxide dismutase (SOD), most likely induced by ROS, in human INCL as well as PPT1-KO mouse brain tissues are markedly elevated. Moreover, we demonstrate that activated caspase-3 and cleaved-PARP, indicative of apoptosis, are also increased in these tissues. Using cultured neurospheres from PPT1-KO and wild-type mouse fetuses, we further demonstrate that the levels of ROS, SOD-2, cleaved-caspase-9, activated caspase-3 and cleaved-PARP are elevated. We propose that: (i) ER stress due to PPT1-deficiency increases ROS and disrupts calcium homeostasis activating caspase-9 and (ii) caspase-9 activation mediates caspase-3 activation and apoptosis contributing to rapid neurodegeneration in INCL.
ESTHER : Kim_2006_Hum.Mol.Genet_15_1580
PubMedSearch : Kim_2006_Hum.Mol.Genet_15_1580
PubMedID: 16571600
Gene_locus related to this paper: mouse-ppt

Title : Effects of lipase, lipoxygenase, peroxidase, and rutin on quality deteriorations in buckwheat flour - Suzuki_2005_J.Agric.Food.Chem_53_8400
Author(s) : Suzuki T , Honda Y , Mukasa Y , Kim SJ
Ref : Journal of Agricultural and Food Chemistry , 53 :8400 , 2005
Abstract : To investigate the effects of changes in lipase, lipoxygenase, peroxidase (POX), and rutin concentrations on the quality of buckwheat flour, 14 buckwheat varieties were stored for 0, 4, 10, and 30 days at 5 or 20 degrees C. During the storage period, lipase activity correlated to pH (significantly negative) and water-soluble acid (WSA) (significantly positive). The lipoxygenase 1 protein concentration had a negative correlation to WSA (significant at 0 and 4 storage days at 5 degrees C and at 0 and 10 storage days at 20 degrees C). POX had significant correlation to pH and peroxide value (POV) at 5 degrees C, whereas it was not significant at 20 degrees C. The rutin concentration had negative correlations to WSA (significant at 30 days of storage at 5 degrees C and at 4 days of storage at 20 degrees C). Thus, lipase activity plays an important role that relates to lipid degradation in quality deterioration of buckwheat flour.
ESTHER : Suzuki_2005_J.Agric.Food.Chem_53_8400
PubMedSearch : Suzuki_2005_J.Agric.Food.Chem_53_8400
PubMedID: 16218693

Title : Carbofuran induces apoptosis of rat cortical neurons and down-regulates surface alpha7 subunit of acetylcholine receptors - Kim_2004_Mol.Cells_17_242
Author(s) : Kim SJ , Kim JE , Ko BH , Moon IS
Ref : Mol Cells , 17 :242 , 2004
Abstract : Carbofuran (CF), an anticholinesterase carbamate, is one of the most widely used N-methylcarbamate esters in insect and nematode control. Despite its serious adverse health effects on wildlife and humans, cellular and molecular studies of the damage of CF to CNS neurons are very limited. We have examined the cytotoxic effects of CF on cultured rat cortical cells, and the expression of the alpha7 subunit of the nicotinic acetylcholine receptor (alpha7 nAChR) in hippocampal neurons. CF was cytotoxic with an IC50 approximately 730 and approximately 640 microm when assessed by the lactate dehydrogenase (LDH) assay and propidium iodide (PI) staining, respectively, 3 days after treatment. CF induced DNA fragmentation and exposure of phosphatidyl serine (PS) on the cell surface. Surface labeling of the alpha7 nAChR with Alexa Fluor 488-conjugated alpha-bungarotoxin (alphaBgt) revealed a significant decrease in the density of the subunits in treated (500 microm CF) hippocampal neurons. Our data indicate that CF induces neuronal death by apoptosis and down-regulates nAChRs.
ESTHER : Kim_2004_Mol.Cells_17_242
PubMedSearch : Kim_2004_Mol.Cells_17_242
PubMedID: 15179037

Title : Memory enhancing actions of Asiasari radix extracts via activation of insulin receptor and extracellular signal regulated kinase (ERK) I\/II in rat hippocampus - Han_2003_Brain.Res_974_193
Author(s) : Han Y , Kim SJ
Ref : Brain Research , 974 :193 , 2003
Abstract : Brain insulin receptor and ERK I/II are suggested to play a role in memory formation. We designed a series of experiments to explore if Asiasari radix (AR) extracts could display memory enhancing actions possibly via the activation of insulin receptor and ERK I/II in mice and rats. Methanol extract of AR had significantly increased survival time in the NaNO(2) intoxication assay in mice. Methanol extract of Asiasari radix (fraction 1) and its subfractions, chloroform-soluble fraction (fraction 2) and chloroform-insoluble, methanol-soluble fraction (fraction 4) were further tested for memory formation. In eight-arm radial maze experiments, both reference memory errors and working memory errors were significantly decreased in mice by fractions 1, 2 and 4. In addition, these fractions were also effective in promoting memory in the passive avoidance test in mice and rats. To gain insight into the mechanism of memory enhancing effects by Asiasari radix extracts, the activities of hippocampal insulin receptors and ERK I/II were tested in mice and rats. Fraction 1 significantly stimulated tyrosine phosphorylation of the insulin receptor, whereas ERK I/II were stimulated by fractions 1, 2 and 4. These fractions also inhibited cholinesterase activities in rats. These results suggest that Asiasari radix extracts may exert memory enhancing effects via activation of insulin receptor and ERK I/II as well as decreasing cholinesterase activity.
ESTHER : Han_2003_Brain.Res_974_193
PubMedSearch : Han_2003_Brain.Res_974_193
PubMedID: 12742637

Title : Novel zinc-binding center and a temperature switch in the Bacillus stearothermophilus L1 lipase - Jeong_2002_J.Biol.Chem_277_17041
Author(s) : Jeong ST , Kim HK , Kim SJ , Chi SW , Pan JG , Oh TK , Ryu SE
Ref : Journal of Biological Chemistry , 277 :17041 , 2002
Abstract : The bacterial thermoalkalophilic lipases optimally hydrolyze saturated fatty acids at elevated temperatures. They also have significant sequence homology with staphylococcal lipases, and both the thermoalkalophilic and staphylococcal lipases are grouped as the lipase family I.5. We report here the first crystal structure of the lipase family I.5, the structure of a thermoalkalophilic lipase from Bacillus stearothermophilus L1 (L1 lipase) determined at 2.0-A resolution. The structure is in a closed conformation, and the active site is buried under a long lid helix. Unexpectedly, the structure exhibits a zinc-binding site in an extra domain that accounts for the larger molecular size of the family I.5 enzymes in comparison to other microbial lipases. The zinc-coordinated extra domain makes tight interactions with the loop extended from the C terminus of the lid helix, suggesting that the activation of the family I.5 lipases may be regulated by the strength of the interactions. The unusually long lid helix makes strong hydrophobic interactions with its neighbors. The structural information together with previous biochemical observations indicate that the temperature-mediated lid opening is triggered by the thermal dissociation of the hydrophobic interactions.
ESTHER : Jeong_2002_J.Biol.Chem_277_17041
PubMedSearch : Jeong_2002_J.Biol.Chem_277_17041
PubMedID: 11859083
Gene_locus related to this paper: geost-lipas

Title : Crystallization and preliminary X-ray analysis of a thermoalkalophilic lipase from Bacillus stearothermophilus L1 - Jeong_2001_Acta.Crystallogr.D.Biol.Crystallogr_57_1300
Author(s) : Jeong ST , Kim HK , Kim SJ , Pan JG , Oh TK , Ryu SE
Ref : Acta Crystallographica D Biol Crystallogr , 57 :1300 , 2001
Abstract : A thermoalkalophilic lipase from Bacillus stearothermophilus L1 (L1 lipase) was crystallized in two different crystal forms using a low concentration of the enzyme and a calcium-exchange process. The first, needle-like, crystal form, which diffracts to about 3.5 A, belongs to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 67.84, b = 72.96, c = 104.41 A. The second, monoclinic, crystal form, which behaves better than the first form for crystallographic analyses, belongs to the monoclinic space group C2 and has unit-cell parameters a = 119.62, b = 85.05, c = 98.36 A, beta = 99.73 degrees. From the monoclinic crystals, a native data set and a samarium-derivative data set were collected to 2.0 and 2.3 A resolution, respectively. The difference Patterson map between the two data sets shows strong heavy-atom peaks, indicating that the crystals are suitable for a high-resolution structure determination.
ESTHER : Jeong_2001_Acta.Crystallogr.D.Biol.Crystallogr_57_1300
PubMedSearch : Jeong_2001_Acta.Crystallogr.D.Biol.Crystallogr_57_1300
PubMedID: 11526325

Title : Anticholinesterase induces nicotinic receptor modulation - Sung_1998_Muscle.Nerve_21_1135
Author(s) : Sung JJ , Kim SJ , Lee HB , Chung JM , Choi YM , Cha CI , Suh YH , Lee KW
Ref : Muscle & Nerve , 21 :1135 , 1998
Abstract : The effects of carbamate anticholinesterases, pyridostigmine and physostigmine, on the function of the nicotinic receptor (nAChR) in TE671 cells was studied, precluding their inhibition of acetylcholine hydrolysis by carbachol usage. In radioassay, the simultaneous application of carbachol and carbamates dose-dependently decreased carbachol-induced 22Na+ influx, compared with carbachol activation alone. Increasing cell preincubation in the presence of carbamates, however, potentiated influx at low concentrations in a time-dependent manner. This facilitating effect of carbamates, even at high concentrations, was significantly increased by washing out these drugs and was blocked by pretreatment with diisopropylfluorophosphate. Similar results were also obtained in whole-cell patch-clamp study. There were insignificant changes in desensitization properties during facilitation. It is thus supposed that facilitation cannot be explained by the inhibition of acetylcholine hydrolysis. These results support a previous hypothesis that acetylcholinesterase might modulate nAChR by an unknown mechanism. In addition, the clinical effects of carbamates may be partly attributed to this facilitation.
ESTHER : Sung_1998_Muscle.Nerve_21_1135
PubMedSearch : Sung_1998_Muscle.Nerve_21_1135
PubMedID: 9703439

Title : Sequence analysis of the phnD gene encoding 2-hydroxymuconic semialdehyde hydrolase in Pseudomonas sp. strain DJ77 - Shin_1997_Biochem.Biophys.Res.Commun_232_288
Author(s) : Shin HJ , Kim SJ , Kim YC
Ref : Biochemical & Biophysical Research Communications , 232 :288 , 1997
Abstract : The 6.8-kb XhoI fragment of chromosomal DNA of Pseudomonas sp. DJ77 contains the phnDEFG genes involved in the degradation of polyaromatic hydrocarbons and chlorinated aromatics. Here, we report the nucleotide sequence of the phnD gene encoding a 2-hydroxymuconic semialdehyde hydrolase and its substrate specificity. The PhnD hydrolase contains 286 amino acids with a M(r) of 31301. The deduced amino acid sequence of the PhnD enzyme is 31.0-50.5% identical to those of homologous enzymes encoded by the dmp, tod, xyl, and bph operons. The PhnD enzyme is required for conversion of 2-hydroxymuconic semialdehyde, which is produced from catechol by the PhnE catechol 2,3-dioxygenase, to 2-hydroxypent-2,4-dienoate. We now confirm that the phnD gene is located immediately upstream of the catechol 2,3-dioxygenase gene (phnE) unlike other meta-cleavage operons.
ESTHER : Shin_1997_Biochem.Biophys.Res.Commun_232_288
PubMedSearch : Shin_1997_Biochem.Biophys.Res.Commun_232_288
PubMedID: 9125165
Gene_locus related to this paper: sphsp-phnD