Han W

References (28)

Title : Inhibition of cannabinoid degradation enhances hippocampal contextual fear memory and exhibits anxiolytic effects - Zhang_2024_iScience_27_108919
Author(s) : Zhang J , Yuan R , Han W , Chang Y , Kong L , Wei C , Zheng Q , Zhu X , Liu Z , Ren W , Han J
Ref : iScience , 27 :108919 , 2024
Abstract : Recent studies have demonstrated the pivotal involvement of endocannabinoids in regulating learning and memory, but the conclusions obtained from different paradigms or contexts are somewhat controversial, and the underlying mechanisms remain largely elusive. Here, we show that JZL195, a dual inhibitor of fatty acid amide hydrolase and monoacylglycerol lipase, can enhance the performance of mice in a contextual fear conditioning task and increase the time spent in open arms in the elevated zero maze (EZM). Although the effect of JZL195 on fear memory could not be inhibited by antagonists of cannabinoid receptors, the effect on the EZM seems to be mediated by CB1R. Simultaneously, hippocampal neurons are hyperactive, and theta oscillation power is significantly increased during the critical period of memory consolidation upon treatment with JZL195. These results suggest the feasibility of targeting the endocannabinoid system for the treatment of various mental disorders.
ESTHER : Zhang_2024_iScience_27_108919
PubMedSearch : Zhang_2024_iScience_27_108919
PubMedID: 38318362

Title : Biodegradation of poly(ethylene terephthalate) through PETase surface-display: From function to structure - Han_2024_J.Hazard.Mater_461_132632
Author(s) : Han W , Zhang J , Chen Q , Xie Y , Zhang M , Qu J , Tan Y , Diao Y , Wang Y , Zhang Y
Ref : J Hazard Mater , 461 :132632 , 2024
Abstract : Polyethylene terephthalate (PET) is one of the most used plastics which has caused some environmental pollution and social problems. Although many newly discovered or modified PET hydrolases have been reported at present, there is still a lack of comparison between their hydrolytic capacities, as well as the need for new biotechnology to apply them for the PET treatment. Here, we systematically studied the surface-display technology for PET hydrolysis using several PET hydrolases. It is found that anchoring protein types had little influence on the surface-display result under T7 promoter, while the PET hydrolase types were more important. By contrast, the newly reported FAST-PETase showed the strongest hydrolysis effect, achieving 71.3% PET hydrolysis in 24 h by pGSA-FAST-PETase. Via model calculation, FAST-PETase indeed exhibited higher temperature tolerance and catalytic capacity. Besides, smaller particle size and lower crystallinity favored the hydrolysis of PET pellets. Through protein structure comparison, we summarized the common characteristics of efficient PET-hydrolyzing enzymes and proposed three main crystal structures of PET enzymes via crystal structural analysis, with ISPETase being the representative and main structure. Surface co-display of FAST-PETase and MHETase can promote the hydrolysis of PET, and the C-terminal of the fusion protein is crucial for PET hydrolysis. The results of our research can be helpful for PET contamination removal as well as other areas involving the application of enzymes. SYNOPSIS: This research can promote the development of better PET hydrolase and its applications in PET pollution treatment via bacteria surface-display.
ESTHER : Han_2024_J.Hazard.Mater_461_132632
PubMedSearch : Han_2024_J.Hazard.Mater_461_132632
PubMedID: 37804764

Title : Integrated Analysis Identifies DPP7 as a Prognostic Biomarker in Colorectal Cancer - Zhang_2023_Cancers.(Basel)_15_3954
Author(s) : Zhang W , Wang H , Xu C , Zhao R , Yao J , Zhai C , Han W , Pan H , Sheng J
Ref : Cancers (Basel) , 15 :3954 , 2023
Abstract : Colorectal cancer has a poor prognosis and is prone to recurrence and metastasis. DPP7, a prolyl peptidase, is reported to regulate lymphocyte quiescence. However, the correlation of DPP7 with prognosis in CRC remains unclear. With publicly available cohorts, the Wilcoxon rank-sum test and logistic regression were employed to analyze the relationship between DPP7 expression and the clinicopathological features of CRC patients. Specific pathways of differentially expressed genes were determined through biofunctional analysis and gene set enrichment analysis (GSEA). qPCR and immunohistochemical staining were used to determine DPP7 expression levels in surgical specimens. The public dataset and analysis of the biospecimens of CRC patients revealed that DPP7, in the CRC samples, was expressed significantly higher than in non-tumor tissues. Moreover, increased DPP7 was significantly associated with a higher N stage, lymphatic invasion, and shorter overall survival. Functionally, DPP7 is involved in neuroactive ligand-receptor interaction and olfactory transduction signaling. We identified a series of targeted drugs and small-molecule drugs with responses to DPP7. To conclude, DPP7 is a valuable diagnostic and prognostic biomarker for CRC and considered as a new therapeutic target.
ESTHER : Zhang_2023_Cancers.(Basel)_15_3954
PubMedSearch : Zhang_2023_Cancers.(Basel)_15_3954
PubMedID: 37568770
Gene_locus related to this paper: human-DPP7

Title : Regulation of NLGN3 and the synaptic Rho-GEF signaling pathway by CDK5 - Jeong_2023_J.Neurosci__
Author(s) : Jeong J , Han W , Hong E , Pandey S , Li Y , Lu W , Roche KW
Ref : Journal of Neuroscience , : , 2023
Abstract : Neuroligins (NLGNs) are postsynaptic cell adhesion molecules that are involved in synapse assembly and function. The NLGN gene family consists of 5 genes (NLGN1-3, 4X, and 4Y). NLGN3 forms heterodimers with other NLGNs and is expressed at both excitatory and inhibitory synapses, although the distinct role at different synapses is not fully understood. Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase that targets various neuronal substrates to impact neuronal migration, neurite outgrowth, synaptic transmission, and plasticity. Both NLGNs and their presynaptic binding partners neurexins are highly associated with neurodevelopmental disorders. The NLGN3 gene is on the X chromosome and variants in NLGN3 have been linked to the pathophysiology in neurodevelopmental disorders. To better understand the endogenous modulation of NLGN3, we generated an HA-tagged knock-in (KI) mouse. We found that Cdk5 associates with NLGN3 in vivo and phosphorylates NLGN3 on serine 725 (S725) in the KI mouse of either sex. The phosphorylation affects the NLGN3 association with Kalirin-7, a postsynaptic guanine nucleotide exchange factors (GEFs) for Rho GTPase family proteins. We further observed that the phosphorylation modulates NLGN3 surface expression and NLGN3-mediated synaptic currents in cultured rat neurons. Thus, we characterized NLGN3 as a novel Cdk5 substrate and revealed the functional consequences of NLGN3 S725 phosphorylation in neurons. Our study provides a novel molecular mechanism underlying Cdk5-mediated regulation of postsynaptic cell adhesion molecules.Significance StatementNLGN3 is involved in synapse assembly and function at both excitatory and inhibitory synapses and has been associated with the pathophysiology of neurodevelopmental disorders. Cdk5 has a brain-specific activity and involved in neuronal transmission, synapse function and plasticity. Here, we characterize NLGN3 as a Cdk5 substrate for the first time and show Cdk5-mediated phosphorylation regulates NLGN3 function. We demonstrate NLGN3 S725 is a Cdk5 phosphorylation site and reveal the site is important for NLGN3 association with Kalirin-7, NLGN3 surface expression, and NLGN3-mediated synaptic transmission.
ESTHER : Jeong_2023_J.Neurosci__
PubMedSearch : Jeong_2023_J.Neurosci__
PubMedID: 37699715

Title : Inhibition mechanism of fisetin on acetylcholinesterase and its synergistic effect with galantamine - Shi_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_305_123452
Author(s) : Shi W , Han W , Liao Y , Wen J , Zhang G
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 305 :123452 , 2023
Abstract : The search for acetylcholinesterase (AChE) inhibitors produced by natural sources is of great significance for the prevention and therapy of Alzheimer's disease and has been widely concerned. In this study, fisetin, a flavonoid compound of plant origin, displayed a mixed inhibition mode on AChE (IC(50) = 8.88 +/- 0.14 microM). Fluorescence spectra analysis revealed that fisetin statically quenched AChE fluorescence, and the ground state complex was formed by hydrogen bonds and hydrophobic interactions. Circular dichroism assays showed that fisetin induced AChE structure loosened with a decrease in alpha-helix structure (from 20.6 % to 19.5 %). Computer simulation exhibited that fisetin bound to both the peripheral anionic site (PAS) and the catalytic active site (CAS) and increased the stability of the AChE. Interestingly, the combination of fisetin and galantamine enhanced the binding affinity between AChE and galantamine and induced AChE structure further loosened, while the inhibition mode was still the mixed type. The heatmap analysis indicated that galantamine (0.2 microM) combined with fisetin (2.25 microM) had a significant synergy on AChE inhibition, probably because fisetin binding at the PAS-AChE induced conformation changes of the gorge and CAS, which enhanced galantamine binding affinity with CAS, and a further loose structure of AChE was induced by the mixture, so finally the interaction between the substrate and AChE was strongly affected. This work may offer a theoretical reference for the functional research of fisetin as a potential AChE inhibitor and an enhanced supplement for galantamine.
ESTHER : Shi_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_305_123452
PubMedSearch : Shi_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_305_123452
PubMedID: 37769468

Title : An esterase-activatable prodrug formulated liposome strategy: potentiating the anticancer therapeutic efficacy and drug safety - Shi_2022_Nanoscale.Adv_4_952
Author(s) : Shi L , Wu X , Li T , Wu Y , Song L , Zhang W , Yin L , Han W , Yang Y
Ref : Nanoscale Adv , 4 :952 , 2022
Abstract : Liposomal nanomedicine represents a common and versatile carrier for the delivery of both lipophilic and hydrophilic drugs. However, the direct formulation of many chemotherapeutics into a liposomal system remains an enormous challenge. Using the topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin (SN38) as a model drug, we combined lipophilic prodrug construction with subsequent integration into an exogenous liposomal scaffold to assemble a prodrug-formulated liposome for systemic administration. Reconstructing SN38 with lipid cholesterol via the esterase-activatable bond endows the resulting prodrug with elevated miscibility with liposomal compositions and esterase-responsive drug release in cancerous cells. The systemic administration of the prodrug-based nanoassemblies (Chol-SN38@LP) exhibited preferential accumulation of therapeutic payloads in tumor lesions. Compared to the SN38 clinical counterpart irinotecan, our prodrug-based nanoassemblies with adaptive features showed elevated therapeutic efficacy (-1.5 times increase of tumor inhibition) in a preclinical A549 lung carcinoma cell-derived mouse model and improved drug tolerability (i.e., alleviated bloody diarrhea and liver damage) in multiple mice models. These results may be ascribed to extended systemic circulation and preferential tumor accumulation of our nanodrugs. Hence, our findings demonstrate that rational engineering of therapeutic nanomedicine is a promising approach for effective and safe delivery of antitumor chemotherapeutics, especially to rescue drug candidates that have failed in clinical trials owing to poor PK properties or severe toxicity in patients.
ESTHER : Shi_2022_Nanoscale.Adv_4_952
PubMedSearch : Shi_2022_Nanoscale.Adv_4_952
PubMedID: 36131817

Title : Dysphagia Risk in Patients Prescribed Rivastigmine: A Systematic Analysis of FDA Adverse Event Reporting System - Bu_2022_J.Alzheimers.Dis__
Author(s) : Bu K , Patel D , Morris R , Han W , Umeukeje G , Zhu T , Cheng F
Ref : J Alzheimers Dis , : , 2022
Abstract : BACKGROUND: Dysphagia has been reported as an adverse event for patients receiving rivastigmine for Alzheimer's disease (AD) treatment. OBJECTIVE: The purpose of this study was to determine the association between dysphagia and the usage of rivastigmine by using the pharmacovigilance data from the FDA Adverse Event Reporting System (FAERS). METHODS: The risk of dysphagia in patients who took rivastigmine was compared with those of patients who took other medications. In addition, this study sought to determine if the dysphagia risk was influenced by sex, age, dosage, and medication routes of administration. RESULTS: When compared to patients prescribed donepezil, galantamine, or memantine, individuals prescribed rivastigmine were almost twice as likely to report dysphagia as an adverse event. The dysphagia risk in individuals prescribed rivastigmine is comparable to individuals prescribed penicillamine but significantly higher than clozapine, drugs of which have been previously shown to be associated with elevated dysphagia likelihood. Individuals older than 80 were 122% more likely to report having dysphagia after being prescribed rivastigmine than patients that were 50-70 years of age. Oral administration of rivastigmine was associated with approximately 2 times greater likelihood of reporting dysphagia relative to users of the transdermal patch. In addition, dysphagia showed higher association with pneumonia than other commonly reported adverse events. CONCLUSION: Patients prescribed rivastigmine were at greater risk of reporting dysphagia as an adverse event than patients prescribed many other medicines. This increase in dysphagia occurrence may be attributed to the dual inhibition of both acetylcholinesterase and butyrylcholinesterase.
ESTHER : Bu_2022_J.Alzheimers.Dis__
PubMedSearch : Bu_2022_J.Alzheimers.Dis__
PubMedID: 35964196

Title : Soluble Epoxide Hydrolase Inhibitor t-AUCB Ameliorates Vascular Endothelial Dysfunction by Influencing the NF-kB\/miR-155-5p\/eNOS\/NO\/IkB Cycle in Hypertensive Rats - Wang_2022_Antioxidants.(Basel)_11_
Author(s) : Wang X , Han W , Zhang Y , Zong Y , Tan N , Li L , Liu C , Liu L
Ref : Antioxidants (Basel) , 11 : , 2022
Abstract : Epoxyeicosatrienoic acids (EETs), angiogenic mediators degraded by soluble epoxide hydrolase (sEH), have been shown to exert beneficial effects on the cardiovascular system. The current study assessed the impact of increased EETs with an sEH inhibitor, t-AUCB, on two-kidney-one-clip (2K1C)-induced renovascular endothelial dysfunction, associated with hypertension, in rats. The hypertensive rats exhibited increased systolic blood pressure, reduced renal blood flow, impaired endothelium-dependent relaxation and eNOS phosphorylation in the renal arteries, elevated ROS production in the endothelium of the renal arteries, and decreased EET levels in plasma, the renal arteries, and endothelial cells; however, t-AUCB reversed all the deleterious effects. Moreover, we found that the stimulation of AMPK/UCP2 scavenged ROS and restored endothelial function in the renal arteries of hypertensive rats undergoing therapy with t-AUCB. In addition, we were the first to reveal the potential role of miR-155-5p in the occurrence and development of vascular endothelial dysfunction in hypertension. Importantly, t-AUCB recovered NO bioavailability by regulating the NF-kappaB/miR-155-5p/eNOS/NO/IkappaB cycle after the activation of AMPK/UCP2 and the subsequent inhibition of ROS in hypertensive rat renal artery endothelial cells. This study will provide evidence for this additional new mechanism, underlying the benefits of EETs and the related agents against hypertensive vasculopathy.
ESTHER : Wang_2022_Antioxidants.(Basel)_11_
PubMedSearch : Wang_2022_Antioxidants.(Basel)_11_
PubMedID: 35883863

Title : Protein tyrosine phosphatase 1B (PTP1B) inhibitorsfrom the deep-sea fungus Penicillium chrysogenum SCSIO 07007 - Han_2020_Bioorg.Chem_96_103646
Author(s) : Han W , Cai J , Zhong W , Xu G , Wang F , Tian X , Zhou X , Liu Q , Liu Y , Wang J
Ref : Bioorg Chem , 96 :103646 , 2020
Abstract : Three new compounds, including two new 3,4,6-trisubstituted alpha-pyrone derivatives, chrysopyrones A and B (1 and 2), and one new indolyl diketopiperazine derivative, penilline C (3), along with twelve known compounds (4-15), were isolated and identified from the fungus Penicillium chrysogenum SCSIO 07007, separated from deep-sea hydrothermal vent environment sample collected from the Western Atlantic. Their structures and absolute configurations were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. All of the isolated compounds (1-15) were evaluated for their cytotoxic, antibacterial activities and enzyme inhibitory activities against acetylcholinesterase (AChE), alpha-glycosidase, and protein tyrosine phosphatase 1B (PTP1B). Among them, new compounds chrysopyrones A and B (1 and 2) displayed obvious inhibitory activities against PTP1B with IC50 values of 9.32 and 27.8 mug/mL, respectively. Furthermore, molecular docking was performed to investigate the inside perspective of the action in PTP1B enzyme.
ESTHER : Han_2020_Bioorg.Chem_96_103646
PubMedSearch : Han_2020_Bioorg.Chem_96_103646
PubMedID: 32036160

Title : Monobutyl phthalate (MBP) can dysregulate the antioxidant system and induce apoptosis of zebrafish liver - Jiao_2020_Environ.Pollut_257_113517
Author(s) : Jiao Y , Tao Y , Yang Y , Diogene T , Yu H , He Z , Han W , Chen Z , Wu P , Zhang Y
Ref : Environ Pollut , 257 :113517 , 2020
Abstract : In this paper, the acute toxicity of monobutyl phthalate (MBP), the main hydrolysis product of dibutyl phthalate, on adult zebrafish liver antioxidant system was studied. Compared the toxicity effect of MBP and DBP by histopathology and apoptosis experiments, we speculated that the toxic effects of DBP on animals may be caused by its metabolite MBP. The results indicated that the antioxidant Nrf2-Keap1 pathway was insufficient to resist MBP-induced hepatotoxicity and led to an imbalance of membrane ion homeostasis and liver damage. Decreased cell viability, significant tissue lesions and early hepatocyte apoptosis were observed in the zebrafish liver in MBP exposure at high concentration (10 mg/L). The activities of antioxidant enzymes and ATPases in zebrafish liver were inhibited with increased malondialdehyde (MDA) content and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Integrated biomarker response (IBR) calculation results indicated that MBP mainly inhibited catalase (CAT) activity. Simultaneously, the expression of antioxidant-related genes (SOD, CAT, GPx, Nrf2, HO-1) was down-regulated, while apoptosis-related genes (p53, bax, cas3) were significantly up-regulated.
ESTHER : Jiao_2020_Environ.Pollut_257_113517
PubMedSearch : Jiao_2020_Environ.Pollut_257_113517
PubMedID: 31761585

Title : Serum Triglyceride Lipase Concentrations are Independent Risk Factors for Coronary Artery Disease and In-Stent Restenosis - Yu_2019_J.Atheroscler.Thromb_26_762
Author(s) : Yu X , Lu J , Li J , Guan W , Deng S , Deng Q , Ye H , Han W , Yu Y , Zhang R
Ref : J Atheroscler Thromb , 26 :762 , 2019
Abstract : AIM: Endothelial lipase (EL), hepatic lipase (HL), and lipoprotein lipase (LPL) are all triglyceride lipases and are associated with coronary artery disease (CAD). However, whether they can be simultaneous independent risk factors for CAD is unknown. In the present study, we investigated whether the three lipases can be independent risk factors simultaneously for CAD and whether combining these lipases could provide greater predictive power than high-density lipoprotein cholesterol (HDL-c) for the development of CAD. METHODS: Eighty-six patients with CAD and 65 healthy controls were enrolled in the study. Additionally, 38 patients who underwent one-year follow-up angiography after percutaneous coronary intervention with stent implantation were collected to investigate in-stent restenosis. Serum EL, HL, and LPL concentrations were measured and compared with other coronary risk factors. RESULTS: Serum EL and HL concentrations were both significantly increased in patients with CAD or in-stent restenosis, whereas serum LPL concentration was reduced significantly in patients with CAD. Multivariate logistic regression analysis indicated that the three lipases were simultaneous independent risk factors for CAD. However, only serum EL concentration was considered an independent risk factor for in-stent restenosis. Importantly, the receiver operating characteristic curve showed that the combined measurement of the three lipases displayed better predictive power than HDL-c or any one of the three lipases for CAD. CONCLUSIONS: Serum EL concentration was an independent risk factor for both CAD and in-stent restenosis. Moreover, the combined assessment of serum EL, HL, and LPL concentrations as multiple risk factors provided potent predictive power for CAD.
ESTHER : Yu_2019_J.Atheroscler.Thromb_26_762
PubMedSearch : Yu_2019_J.Atheroscler.Thromb_26_762
PubMedID: 30651409

Title : A Conserved Tyrosine Residue in Slitrk3 Carboxyl-Terminus Is Critical for GABAergic Synapse Development - Li_2019_Front.Mol.Neurosci_12_213
Author(s) : Li J , Han W , Wu K , Li YD , Liu Q , Lu W
Ref : Front Mol Neurosci , 12 :213 , 2019
Abstract : Single-passing transmembrane protein, Slitrk3 (Slit and Trk-like family member 3, ST3), is a synaptic cell adhesion molecule highly expressed at inhibitory synapses. Recent studies have shown that ST3, through its extracellular domain, selectively regulates inhibitory synapse development via the trans-synaptic interaction with presynaptic cell adhesion molecule, receptor protein tyrosine phosphatase delta (PTPdelta) and the cis-interaction with postsynaptic cell adhesion molecule, Neuroligin 2 (NL2). However, little is known about the physiological function of ST3 intracellular, carboxyl (C)-terminal region. Here we report that in heterologous cells, ST3 C-terminus is not required for ST3 homo-dimerization and trafficking to the cell surface. In contrast, in hippocampal neurons, ST3 C-terminus, more specifically, the conserved tyrosine Y969 (in mice), is critical for GABAergic synapse development. Indeed, overexpression of ST3 Y969A mutant markedly reduced the gephyrin puncta density and GABAergic transmission in hippocampal neurons. In addition, single-cell genetic deletion of ST3 strongly impaired GABAergic transmission. Importantly, wild-type (WT) ST3, but not the ST3 Y969A mutant, could fully rescue GABAergic transmission deficits in neurons lacking endogenous ST3, confirming a critical role of Y969 in the regulation of inhibitory synapses. Taken together, our data identify a single critical residue in ST3 C-terminus that is important for GABAergic synapse development and function.
ESTHER : Li_2019_Front.Mol.Neurosci_12_213
PubMedSearch : Li_2019_Front.Mol.Neurosci_12_213
PubMedID: 31551708

Title : Theoretical Study on Zearalenol Compounds Binding with Wild Type Zearalenone Hydrolase and V153H Mutant - Liu_2018_Int.J.Mol.Sci_19_
Author(s) : Liu Y , Wan Y , Zhu J , Yu Z , Tian X , Han J , Zhang Z , Han W
Ref : Int J Mol Sci , 19 : , 2018
Abstract : Zearalenone hydrolase (ZHD) is the only reported alpha/beta-hydrolase that can detoxify zearalenone (ZEN). ZHD has demonstrated its potential as a treatment for ZEN contamination that will not result in damage to cereal crops. Recent researches have shown that the V153H mutant ZHD increased the specific activity against alpha-ZOL, but decreased its specific activity to beta-ZOL. To understand whyV153H mutation showed catalytic specificity for alpha-ZOL, four molecular dynamics simulations combining with protein network analysis for wild type ZHD alpha-ZOL, ZHD beta-ZOL, V153H alpha-ZOL, and V153H beta-ZOL complexes were performed using Gromacs software. Our theoretical results indicated that the V153H mutant could cause a conformational switch at the cap domain (residues Gly161(-)Thr190) to affect the relative position catalytic residue (H242). Protein network analysis illustrated that the V153H mutation enhanced the communication with the whole protein and residues with high betweenness in the four complexes, which were primarily assembled in the cap domain and residues Met241 to Tyr245 regions. In addition, the existence of alpha-ZOL binding to V153H mutation enlarged the distance from the OAE atom in alpha-ZOL to the NE2 atom in His242, which prompted the side chain of H242 to the position with catalytic activity, thereby increasing the activity of V153H on the alpha-ZOL. Furthermore, alpha-ZOL could easily form a right attack angle and attack distance in the ZHD and alpha-ZOL complex to guarantee catalytic reaction. The alanine scanning results indicated that modifications of the residues in the cap domain produced significant changes in the binding affinity for alpha-ZOL and beta-ZOL. Our results may provide useful theoretical evidence for the mechanism underlying the catalytic specificity of ZHD.
ESTHER : Liu_2018_Int.J.Mol.Sci_19_
PubMedSearch : Liu_2018_Int.J.Mol.Sci_19_
PubMedID: 30231501
Gene_locus related to this paper: biooc-ZHD101

Title : Understanding the interactions of different substrates with wild-type and mutant acylaminoacyl peptidase using molecular dynamics simulations - Zhu_2017_J.Biomol.Struct.Dyn__1
Author(s) : Zhu J , Wang Y , Li X , Han W , Zhao L
Ref : J Biomol Struct Dyn , :1 , 2017
Abstract : Acylaminoacylpeptidase (AAP) belongs to peptidase protein family (POP), which can degrade amyloid beta-peptide forms in the brains of patients and hence leads to Alzheimer's disease. And so, AAP is considered to be a novel target in the design of drugs against Alzheimer's disease. In this investigation, six molecular dynamics simulations were used to find that the interaction between the wild-type and R526V AAP with two different substrates (p-nitrophenylcaprylate and Ac-Leu-p-nitroanilide). Our results were as follows: firstly, Ac-Leu-p-nitroanilide bound to R526V AAP to form a more disordered loop (residues 552-562) in the alpha/beta-hydrolase fold like of AAP, which caused an open and inactive AAP domain form, secondly, binding p-nitrophenylcaprylate and Ac-Leu-p-nitroanilide to AAP can decrease the flexibility of residues 225-250, 260-270 and 425-450, in which the ordered secondary structures may contain the suitable geometrical structure and so it is useful to serine attack. Our theoretical results showed that the binding of the two substrates can induce specific conformational changes responsible for the diverse AAP catalytic specificity. These theoretical substrate-induced structural diversities can help explain the abilities of AAPs to recognize and hydrolyze extremely different substrates.
ESTHER : Zhu_2017_J.Biomol.Struct.Dyn__1
PubMedSearch : Zhu_2017_J.Biomol.Struct.Dyn__1
PubMedID: 29235404
Gene_locus related to this paper: aerpe-APE1547

Title : Molecular Dissection of Neuroligin 2 and Slitrk3 Reveals an Essential Framework for GABAergic Synapse Development - Li_2017_Neuron_96_808
Author(s) : Li J , Han W , Pelkey KA , Duan J , Mao X , Wang YX , Craig MT , Dong L , Petralia RS , McBain CJ , Lu W
Ref : Neuron , 96 :808 , 2017
Abstract : In the brain, many types of interneurons make functionally diverse inhibitory synapses onto principal neurons. Although numerous molecules have been identified to function in inhibitory synapse development, it remains unknown whether there is a unifying mechanism for development of diverse inhibitory synapses. Here we report a general molecular mechanism underlying hippocampal inhibitory synapse development. In developing neurons, the establishment of GABAergic transmission depends on Neuroligin 2 (NL2), a synaptic cell adhesion molecule (CAM). During maturation, inhibitory synapse development requires both NL2 and Slitrk3 (ST3), another CAM. Importantly, NL2 and ST3 interact with nanomolar affinity through their extracellular domains to synergistically promote synapse development. Selective perturbation of the NL2-ST3 interaction impairs inhibitory synapse development with consequent disruptions in hippocampal network activity and increased seizure susceptibility. Our findings reveal how unique postsynaptic CAMs work in concert to control synaptogenesis and establish a general framework for GABAergic synapse development.
ESTHER : Li_2017_Neuron_96_808
PubMedSearch : Li_2017_Neuron_96_808
PubMedID: 29107521

Title : ChAT-positive neurons participate in subventricular zone neurogenesis after middle cerebral artery occlusion in mice - Wang_2017_Behav.Brain.Res_316_145
Author(s) : Wang J , Fu X , Zhang D , Yu L , Li N , Lu Z , Gao Y , Wang M , Liu X , Zhou C , Han W , Yan B
Ref : Behavioural Brain Research , 316 :145 , 2017
Abstract : The mechanisms of post-stroke neurogenesis in the subventricular zone (SVZ) are unclear. However, neural stem cell-intrinsic and neurogenic niche mechanisms, as well as neurotransmitters, have been shown to play important roles in SVZ neurogenesis. Recently, a previously unknown population of choline acetyltransferase (ChAT)+ neurons residing in rodent SVZ were identified to have direct control over neural stem cell proliferation by indirectly activating fibroblast growth factor receptor (FGFR). This finding revealed possible neuronal control over SVZ neurogenesis. In this study, we assessed whether these ChAT+ neurons also participate in stroke-induced neurogenesis. We used a permanent middle cerebral artery occlusion (MCAO) model produced by transcranial electrocoagulation in mice, atropine (muscarinic cholinergic receptor [mAchR] antagonist), and donepezil (acetylcholinesterase inhibitor) to investigate the role of ChAT+ neurons in stroke-induced neurogenesis. We found that mAchRs, phosphorylated protein kinase C (p-PKC), and p-38 levels in the SVZ were upregulated in mice on day 7 after MCAO. MCAO also significantly increased the number of BrdU/doublecortin-positive cells and protein levels of phosphorylated-neural cell adhesion molecule and mammalian achaete scute homolog-1. FGFR was activated in the SVZ, and doublecortin-positive cells increased in the peri-infarction region. These post-stroke neurogenic effects were enhanced by donepezil and partially decreased by atropine. Neither atropine nor donepezil affected peri-infarct microglial activation or serum concentrations of TNF-alpha, IFN-gamma, or TGF-beta on day 7 after MCAO. We conclude that ChAT+ neurons in the SVZ may participate in stroke-induced neurogenesis, suggesting a new mechanism for neurogenesis after stroke.
ESTHER : Wang_2017_Behav.Brain.Res_316_145
PubMedSearch : Wang_2017_Behav.Brain.Res_316_145
PubMedID: 27609645

Title : Quality of Care Provided by a Comprehensive Dementia Care Comanagement Program - Jennings_2016_J.Am.Geriatr.Soc_64_1724
Author(s) : Jennings LA , Tan Z , Wenger NS , Cook EA , Han W , McCreath HE , Serrano KS , Roth CP , Reuben DB
Ref : J Am Geriatr Soc , 64 :1724 , 2016
Abstract : Multiple studies have shown that quality of care for dementia in primary care is poor, with physician adherence to dementia quality indicators (QIs) ranging from 18% to 42%. In response, the University of California at Los Angeles (UCLA) Health System created the UCLA Alzheimer's and Dementia Care (ADC) Program, a quality improvement program that uses a comanagement model with nurse practitioner dementia care managers (DCM) working with primary care physicians and community-based organizations to provide comprehensive dementia care. The objective was to measure the quality of dementia care that nurse practitioner DCMs provide using the Assessing Care of Vulnerable Elders (ACOVE-3) and Physician Consortium for Performance Improvement QIs. Participants included 797 community-dwelling adults with dementia referred to the UCLA ADC program over a 2-year period. UCLA is an urban academic medical center with primarily fee-for-service reimbursement. The percentage of recommended care received for 17 dementia QIs was measured. The primary outcome was aggregate quality of care for the UCLA ADC cohort, calculated as the total number of recommended care processes received divided by the total number of eligible quality indicators. Secondary outcomes included aggregate quality of care in three domains of dementia care: assessment and screening (7 QIs), treatment (6 QIs), and counseling (4 QIs). QIs were abstracted from DCM notes over a 3-month period from date of initial assessment. Individuals were eligible for 9,895 QIs, of which 92% were passed. Overall pass rates of DCMs were similar (90-96%). All counseling and assessment QIs had pass rates greater than 80%, with most exceeding 90%. Wider variation in adherence was found among QIs addressing treatments for dementia, which patient-specific criteria triggered, ranging from 27% for discontinuation of medications associated with mental status changes to 86% for discussion about acetylcholinesterase inhibitors. Comprehensive dementia care comanagement with a nurse practitioner can result in high quality of care for dementia, especially for assessment, screening, and counseling. The effect on treatment QIs is more variable but higher than previous reports of physician-provided dementia care.
ESTHER : Jennings_2016_J.Am.Geriatr.Soc_64_1724
PubMedSearch : Jennings_2016_J.Am.Geriatr.Soc_64_1724
PubMedID: 27355394

Title : Preparation of Diacylglycerol-enriched Rice Bran Oil by Lipase-catalyzed Deacidification in Packed-bed Reactors by Continuous Dehydration - Lu_2016_J.Oleo.Sci_65_151
Author(s) : Lu Y , Zou X , Han W , Jiang Y , Jin Q , Li L , Xu X , Wang X
Ref : J Oleo Sci , 65 :151 , 2016
Abstract : Diacylglycerol-enriched rice bran oil (RBO-DAG) was produced by deacidification of high-acid rice bran oil (RBO) with glycerol (Gly) using Lipozyme RM IM by continuous dehydration by combination of two enzyme columns (column 1 and 3, used for deacidification) with one molecular sieves column (column 2, used for dehydration). The conditions for three columns were respectively optimized. Response surface methodology (RSM) was used to optimize the conditions of column 1. The content of DAG and conversion of free fatty acid (FFA) were used as indicators and the effects of the enzyme load (8-12 g), flow rate (0.3-0.6 mL/min), substrate molar ratio (4-6) and reaction temperature (55-75 degC) were investigated. The content of DAG and conversion of FFA were significantly correlated to the flow rate and substrate molar ratio. Most desirable conditions of the reaction with respect to the maximal DAG content and FFA conversion was attained under the residence time of 40 min, substrate molar ratio of 5.52 (Gly: RBO) and temperature of 66 degC. The conditions for column 2 were investigated by varying molecular sieves load and flow rate, and the maximal dehydration rate of 85.22% was obtained under the optimal conditions. For column 3, the optimum conditions were obtained as: flow rate, 0.2mL/min; temperature, 65 degC, and the content of DAG and FFA were 38.99% and 3.04%, respectively under these conditions. The catalytic activity of the lipase was stable in twelve continuous operations with 83.22% of its original ability, demonstrating its potential in the continuous packed-bed reactors (PBRs) system. These results showed that packed-bed reactors combined with continuous deacidification and dehydration in one system had great value in industrial production for high-acid RBO with the improved conversion rate.
ESTHER : Lu_2016_J.Oleo.Sci_65_151
PubMedSearch : Lu_2016_J.Oleo.Sci_65_151
PubMedID: 26833284

Title : Pretreatment serum pseudocholinesterase level as a novel prognostic biomarker for upper tract urothelial carcinoma - Zhang_2016_Int.Urol.Nephrol_48_1993
Author(s) : Zhang B , Shen C , Jin J , Song Y , Zhao Z , Zhang X , Wang G , Fan Y , Mi Y , Hu S , Cui Y , Zhou L , He Z , Yu W , Han W
Ref : International Urology & Nephrology , 48 :1993 , 2016
Abstract : PURPOSE: Pretreatment serum pseudocholinesterase (PChE) has been reported to be a prognostic predictor in several cancers. However, the prognostic significance of serum PChE level in patients with upper tract urothelial carcinoma (UTUC) remains unknown.
METHODS: A total of 180 patients who underwent radical nephroureterectomy (RNU) for UTUC were included in this retrospective analysis. The associations of pretreatment serum PChE levels with clinicopathological characteristics and clinical outcomes were assessed.
RESULTS: The median (IQR) pretreatment serum PChE level was 6385 (5449-7260) IU/L, and an optimal cutoff value of 5336 IU/L was set according to ROC analysis. Decreased pretreatment serum PChE levels were significantly correlated with older patient age, higher preoperative chronic kidney disease (CKD) stage and pT stage (all P < 0.05). On multivariate analysis, adjusting for preoperative variables, decreased pretreatment serum PChE levels independently predicted higher pT stage (P = 0.011). Moreover, Kaplan-Meier curves suggested that patients with PChE levels <5336 IU/L were predicted to have a shorter overall survival (OS) and cancer-specific survival (CSS) than those with PChE levels >/=5336 IU/L (both P < 0.001). On multivariate analysis, decreased pretreatment serum PChE levels were significantly associated with shorter OS (HR 0.553; 95 %CI 0.322-0.951; P = 0.032) and CSS (HR 0.484; 95 %CI 0.269-0.870; P = 0.015).
CONCLUSIONS: Decreased pretreatment serum PChE level is an independent predictor for higher pT stage, shorter OS and CSS in patients with UTUC. Pretreatment serum PChE levels may act as a simple and effective parameter to predict prognosis for UTUC patients after RNU.
ESTHER : Zhang_2016_Int.Urol.Nephrol_48_1993
PubMedSearch : Zhang_2016_Int.Urol.Nephrol_48_1993
PubMedID: 27554671

Title : Exploration of the chlorpyrifos escape pathway from acylpeptide hydrolases using steered molecular dynamics simulations - Wang_2016_J.Biomol.Struct.Dyn_34_749
Author(s) : Wang D , Jin H , Wang J , Guan S , Zhang Z , Han W
Ref : J Biomol Struct Dyn , 34 :749 , 2016
Abstract : Acylpeptide hydrolases (APH) catalyze the removal of an N-acylated amino acid from blocked peptides. APH is significantly more sensitive than acetylcholinesterase, a target of Alzheimer's disease, to inhibition by organophosphorus (OP) compounds. Thus, OP compounds can be used as a tool to probe the physiological functions of APH. Here, we report the results of a computational study of molecular dynamics simulations of APH bound to the OP compounds and an exploration of the chlorpyrifos escape pathway using steered molecular dynamics (SMD) simulations. In addition, we apply SMD simulations to identify potential escape routes of chlorpyrifos from hydrolase hydrophobic cavities in the APH-inhibitor complex. Two previously proposed APH pathways were reliably identified by CAVER 3.0, with the estimated relative importance of P1 > P2 for its size. We identify the major pathway, P2, using SMD simulations, and Arg526, Glu88, Gly86, and Asn65 are identified as important residues for the ligand leaving via P2. These results may help in the design of APH-targeting drugs with improved efficacy, as well as in understanding APH selectivity of the inhibitor binding in the prolyl oligopeptidase family.
ESTHER : Wang_2016_J.Biomol.Struct.Dyn_34_749
PubMedSearch : Wang_2016_J.Biomol.Struct.Dyn_34_749
PubMedID: 26155973
Gene_locus related to this paper: aerpe-APE1547

Title : Astragalus Polysaccharide Suppresses 6-Hydroxydopamine-Induced Neurotoxicity in Caenorhabditis elegans - Li_2016_Oxid.Med.Cell.Longev_2016_4856761
Author(s) : Li H , Shi R , Ding F , Wang H , Han W , Ma F , Hu M , Ma CW , Huang Z
Ref : Oxid Med Cell Longev , 2016 :4856761 , 2016
Abstract : Astragalus membranaceus is a medicinal plant traditionally used in China for a variety of conditions, including inflammatory and neural diseases. Astragalus polysaccharides are shown to reduce the adverse effect of levodopa which is used to treat Parkinson's disease (PD). However, the neuroprotective effect of Astragalus polysaccharides per se in PD is lacking. Using Caenorhabditis elegans models, we investigated the protective effect of astragalan, an acidic polysaccharide isolated from A. membranaceus, against the neurotoxicity of 6-hydroxydopamine (6-OHDA), a neurotoxin that can induce parkinsonism. We show that 6-OHDA is able to degenerate dopaminergic neurons and lead to the deficiency of food-sensing behavior and a shorter lifespan in C. elegans. Interestingly, these degenerative symptoms can be attenuated by astragalan treatment. Astragalan is also shown to alleviate oxidative stress through reducing reactive oxygen species level and malondialdehyde content and increasing superoxide dismutase and glutathione peroxidase activities and reduce the expression of proapoptotic gene egl-1 in 6-OHDA-intoxicated nematodes. Further studies reveal that astragalan is capable of elevating the decreased acetylcholinesterase activity induced by 6-OHDA. Together, our results demonstrate that the protective effect of astragalan against 6-OHDA neurotoxicity is likely due to the alleviation of oxidative stress and regulation of apoptosis pathway and cholinergic system and thus provide an important insight into the therapeutic potential of Astragalus polysaccharide in neurodegeneration.
ESTHER : Li_2016_Oxid.Med.Cell.Longev_2016_4856761
PubMedSearch : Li_2016_Oxid.Med.Cell.Longev_2016_4856761
PubMedID: 27885333

Title : Molecular dynamics simulations of acylpeptide hydrolase bound to chlorpyrifosmethyl oxon and dichlorvos - Jin_2015_Int.J.Mol.Sci_16_6217
Author(s) : Jin H , Zhou Z , Wang D , Guan S , Han W
Ref : Int J Mol Sci , 16 :6217 , 2015
Abstract : Acylpeptide hydrolases (APHs) catalyze the removal of N-acylated amino acids from blocked peptides. Like other prolyloligopeptidase (POP) family members, APHs are believed to be important targets for drug design. To date, the binding pose of organophosphorus (OP) compounds of APH, as well as the different OP compounds binding and inducing conformational changes in two domains, namely, alpha/beta hydrolase and beta-propeller, remain poorly understood. We report a computational study of APH bound to chlorpyrifosmethyl oxon and dichlorvos. In our docking study, Val471 and Gly368 are important residues for chlorpyrifosmethyl oxon and dichlorvos binding. Molecular dynamics simulations were also performed to explore the conformational changes between the chlorpyrifosmethyl oxon and dichlorvos bound to APH, which indicated that the structural feature of chlorpyrifosmethyl oxon binding in APH permitted partial opening of the beta-propeller fold and allowed the chlorpyrifosmethyl oxon to easily enter the catalytic site. These results may facilitate the design of APH-targeting drugs with improved efficacy.
ESTHER : Jin_2015_Int.J.Mol.Sci_16_6217
PubMedSearch : Jin_2015_Int.J.Mol.Sci_16_6217
PubMedID: 25794283
Gene_locus related to this paper: aerpe-APE1547

Title : Quantitative Proteomics Analysis of the Hepatitis C Virus Replicon High-Permissive and Low-Permissive Cell Lines - Ye_2015_PLoS.One_10_e0142082
Author(s) : Ye F , Xin Z , Han W , Fan J , Yin B , Wu S , Yang W , Yuan J , Qiang B , Sun W , Peng X
Ref : PLoS ONE , 10 :e0142082 , 2015
Abstract : Chronic hepatitis C virus (HCV) infection is one of the leading causes of severe hepatitis. The molecular mechanisms underlying HCV replication and pathogenesis remain unclear. The development of the subgenome replicon model system significantly enhanced study of HCV. However, the permissiveness of the HCV subgenome replicon greatly differs among different hepatoma cell lines. Proteomic analysis of different permissive cell lines might provide new clues in understanding HCV replication. In this study, to detect potential candidates that might account for the differences in HCV replication. Label-free and iTRAQ labeling were used to analyze the differentially expressed protein profiles between Huh7.5.1 wt and HepG2 cells. A total of 4919 proteins were quantified in which 114 proteins were commonly identified as differentially expressed by both quantitative methods. A total of 37 differential proteins were validated by qRT-PCR. The differential expression of Glutathione S-transferase P (GSTP1), Ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1), carboxylesterase 1 (CES1), vimentin, Proteasome activator complex subunit1 (PSME1), and Cathepsin B (CTSB) were verified by western blot. And over-expression of CTSB or knock-down of vimentin induced significant changes to HCV RNA levels. Additionally, we demonstrated that CTSB was able to inhibit HCV replication and viral protein translation. These results highlight the potential role of CTSB and vimentin in virus replication.
ESTHER : Ye_2015_PLoS.One_10_e0142082
PubMedSearch : Ye_2015_PLoS.One_10_e0142082
PubMedID: 26544179

Title : Modulated dye retention for the signal-on fluorometric determination of acetylcholinesterase inhibitor - Liao_2013_Anal.Chem_85_4968
Author(s) : Liao S , Han W , Ding H , Xie D , Tan H , Yang S , Wu Z , Shen G , Yu R
Ref : Analytical Chemistry , 85 :4968 , 2013
Abstract : A novel fluorometric assay method based on target-induced signal on was developed for acetylcholinesterase (AChE) inhibitor with obviously improved detection sensitivity. In this method, the AChE molecules catalyzed the hydrolysis of acetylthiocholine (ATCl) to form thiocholine, which in turn can specifically react with fluorescent squaraine derivative, a specific chemodosimeter for thiol-containing compounds, resulting in fluorescence quenching and offering a low fluorometric background for the further detection of AChE inhibitor. In the presence of AChE inhibitor, the catalytic hydrolysis of ATCl is blocked, and then the squaraine derivative remains intact and shows signal-on fluorescence. The amount of the remaining fluorescent squaraine derivative is positively correlated with that of the AChE inhibitor in solution. This new designed sensing system shows an obviously improved sensitivity toward target with a detection limit of 5 pg mL(-1) (0.018 nM) for the AChE inhibitor, comparing favorably with previously reported fluorometric methods. To our best knowledge, this new method is the first example of fluorometric enzymatic assay for AChE inhibitors based on such a signal-on principle and using a specific reaction, which has potential to offer an effective strategy for the detection of AChE inhibitors.
ESTHER : Liao_2013_Anal.Chem_85_4968
PubMedSearch : Liao_2013_Anal.Chem_85_4968
PubMedID: 23597308

Title : Acetylcholinesterase liquid crystal biosensor based on modulated growth of gold nanoparticles for amplified detection of acetylcholine and inhibitor - Liao_2012_Anal.Chem_84_45
Author(s) : Liao S , Qiao Y , Han W , Xie Z , Wu Z , Shen G , Yu R
Ref : Analytical Chemistry , 84 :45 , 2012
Abstract : A novel acetylcholinesterase (AChE) liquid crystal (LC) biosensor based on enzymatic growth of gold nanoparticles (Au NPs) has been developed for amplified detection of acetylcholine (ACh) and AChE inhibitor. In this method, AChE mediates the hydrolysis of acetylthiocholine (ATCl) to form thiocholine, and the latter further reduces AuCl(4)(-) to Au NPs without Au nanoseeds. This process, termed biometallization, leads to a great enhancement in the optical signal of the LC biosensor due to the large size of Au NPs, which can greatly disrupt the orientational arrangement of LCs. On the other hand, the hydrolysis of ATCl is inhibited in the presence of ACh or organophosphate pesticides (OPs, a AChE inhibitor), which will decrease the catalytic growth of Au NPs and, as a result, reduce the orientational response of LCs. On the basis of such an inhibition mechanism, the AChE LC biosensor can be used as an effective way to realize the detection of ACh and AChE inhibitors. The results showed that the AChE LC biosensor was highly sensitive to ACh with a detection limit of 15 mumol/L and OPs with a detection limit of 0.3 nmol/L. This study provides a simple and sensitive AChE LC biosensing approach and offers effective signal enhanced strategies for the development of enzyme LC biosensors.
ESTHER : Liao_2012_Anal.Chem_84_45
PubMedSearch : Liao_2012_Anal.Chem_84_45
PubMedID: 22148672

Title : The macro domain protein family: structure, functions, and their potential therapeutic implications - Han_2011_Mutat.Res_727_86
Author(s) : Han W , Li X , Fu X
Ref : Mutat Res , 727 :86 , 2011
Abstract : Macro domains are ancient, highly evolutionarily conserved domains that are widely distributed throughout all kingdoms of life. The 'macro fold' is roughly 25kDa in size and is composed of a mixed alpha-beta fold with similarity to the P loop-containing nucleotide triphosphate hydrolases. They function as binding modules for metabolites of NAD(+), including poly(ADP-ribose) (PAR), which is synthesized by PAR polymerases (PARPs). Although there is a high degree of sequence similarity within this family, particularly for residues that might be involved in catalysis or substrates binding, it is likely that the sequence variation that does exist among macro domains is responsible for the specificity of function of individual proteins. Recent findings have indicated that macro domain proteins are functionally promiscuous and are implicated in the regulation of diverse biological functions, such as DNA repair, chromatin remodeling and transcriptional regulation. Significant advances in the field of macro domain have occurred in the past few years, including biological insights and the discovery of novel signaling pathways. To provide a framework for understanding these recent findings, this review will provide a comprehensive overview of the known and proposed biochemical, cellular and physiological roles of the macro domain family. Recent data that indicate a critical role of macro domain regulation for the proper progression of cellular differentiation programs will be discussed. In addition, the effect of dysregulated expression of macro domain proteins will be considered in the processes of tumorigenesis and bacterial pathogenesis. Finally, a series of observations will be highlighted that should be addressed in future efforts to develop macro domains as effective therapeutic targets.
ESTHER : Han_2011_Mutat.Res_727_86
PubMedSearch : Han_2011_Mutat.Res_727_86
PubMedID: 21421074

Title : Genome and proteome of long-chain alkane degrading Geobacillus thermodenitrificans NG80-2 isolated from a deep-subsurface oil reservoir - Feng_2007_Proc.Natl.Acad.Sci.U.S.A_104_5602
Author(s) : Feng L , Wang W , Cheng J , Ren Y , Zhao G , Gao C , Tang Y , Liu X , Han W , Peng X , Liu R , Wang L
Ref : Proc Natl Acad Sci U S A , 104 :5602 , 2007
Abstract : The complete genome sequence of Geobacillus thermodenitrificans NG80-2, a thermophilic bacillus isolated from a deep oil reservoir in Northern China, consists of a 3,550,319-bp chromosome and a 57,693-bp plasmid. The genome reveals that NG80-2 is well equipped for adaptation into a wide variety of environmental niches, including oil reservoirs, by possessing genes for utilization of a broad range of energy sources, genes encoding various transporters for efficient nutrient uptake and detoxification, and genes for a flexible respiration system including an aerobic branch comprising five terminal oxidases and an anaerobic branch comprising a complete denitrification pathway for quick response to dissolved oxygen fluctuation. The identification of a nitrous oxide reductase gene has not been previously described in Gram-positive bacteria. The proteome further reveals the presence of a long-chain alkane degradation pathway; and the function of the key enzyme in the pathway, the long-chain alkane monooxygenase LadA, is confirmed by in vivo and in vitro experiments. The thermophilic soluble monomeric LadA is an ideal candidate for treatment of environmental oil pollutions and biosynthesis of complex molecules.
ESTHER : Feng_2007_Proc.Natl.Acad.Sci.U.S.A_104_5602
PubMedSearch : Feng_2007_Proc.Natl.Acad.Sci.U.S.A_104_5602
PubMedID: 17372208
Gene_locus related to this paper: geotd-g3jwz2 , geoka-q5l1n0 , geotn-a4ijt0 , geotn-a4ilq0 , geotn-a4is13 , geotn-a4isp0 , geotn-a4isp3

Title : The repression of human differentiation-related gene NDRG2 expression by Myc via Miz-1-dependent interaction with the NDRG2 core promoter - Zhang_2006_J.Biol.Chem_281_39159
Author(s) : Zhang J , Li F , Liu X , Shen L , Liu J , Su J , Zhang W , Deng Y , Wang L , Liu N , Han W , Ji S , Yang A , Han H , Yao L
Ref : Journal of Biological Chemistry , 281 :39159 , 2006
Abstract : The N-myc downstream-regulated gene 1 (ndrg1) is highly expressed in N-myc knock-out mice through an unknown regulatory mechanism. As one member of the human NDRG gene family, NDRG2 encodes a protein highly homologous to Ndrg1. However, it is uncertain whether the expression of human NDRG2 is regulated by Myc because mouse ndrg2 and -3 are not affected by Myc. In this study, we provide the novel evidence that the expression of human NDRG2 is down-regulated by Myc via transcriptional repression. A high level of NDRG2 was observed as Myc expression was reduced in differentiated cells, whereas a low level of NDRG2 was shown following increased Myc expression upon serum stimulation. The ectopic expression of c-Myc dramatically reduces the cellular Ndrg2 protein and mRNA level. We further identified the core promoter region of NDRG2 that is required for Myc repression on NDRG2 transcription, and we verified the interaction of Myc with the core promoter region both in vitro and in vivo. Moreover, the c-Myc-mediated repression of NDRG2 requires association with Miz-1, and possibly the recruitment of other epigenetic factors, such as histone deacetylases, to the promoter. The regulatory function of Myc on NDRG2 gene expression implicated the role of the Ndrg2 in regulating cell differentiation.
ESTHER : Zhang_2006_J.Biol.Chem_281_39159
PubMedSearch : Zhang_2006_J.Biol.Chem_281_39159
PubMedID: 17050536