7 results on '"Wan, Bin"'
Search Results
2. Identification of protein tyrosine phosphatase SHP-2 as a new target of perfluoroalkyl acids in HepG2 cells
- Author
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Yang, Yu, Lv, Qi-Yan, Guo, Liang-Hong, Wan, Bin, Ren, Xiao-Min, Shi, Ya-Li, and Cai, Ya-Qi
- Published
- 2017
- Full Text
- View/download PDF
3. In vitro inhibition of lysine decarboxylase activity by organophosphate esters.
- Author
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Wang, Sufang, Wan, Bin, Zhang, Lianying, Yang, Yu, and Guo, Liang-Hong
- Subjects
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LYSINE , *DECARBOXYLASES , *ORGANOPHOSPHORUS compounds , *PHOSPHATE esters , *IN vitro studies , *POLLUTANTS , *ENZYME inhibitors , *THERAPEUTICS - Abstract
Organophosphate esters (OPEs), a major group of organophosphorus flame retardants, are regarded as emerging environmental contaminants of health concern. Amino acid decarboxylases catalyze the conversion of amino acids into polyamines that are essential for cell proliferation, hypertrophy and tissue growth. In this paper, inhibitory effect of twelve OPEs with aromatic, alkyl or chlorinated alkyl substituents on the activity of lysine decarboxylase (LDC) was assessed quantitatively with an economic and label-free fluorescence sensor and cell assay. The sensor comprises a macrocyclic host (cucurbit[7]uril) and a fluorescent dye (acridine orange) reporter. The twelve OPEs were found to vary in their capacity to inhibit LDC activity. Alkyl group substituted OPEs had no inhibitory effect. By contrast, six OPEs substituted with aromatic or chlorinated alkyl groups inhibited LDC activity significantly with IC 50 ranging from 1.32 μM to 9.07 μM. Among them, the inhibitory effect of tri- m -cresyl phosphate (TCrP) was even more effective as an inhibitor than guanosine 5′-diphosphate-3′-diphosphate (ppGpp) (1.60 μM), an LDC natural inhibitor in vivo . Moreover, at non-cytotoxic concentrations, these six OPEs showed perceptible inhibitory effects on LDC activity in PC12 living cells, and led to a marked loss in the cadaverine content. Molecular docking analysis of the LDC/OPE complexes revealed that different binding modes contribute to the difference in their inhibitory effect. Our finding suggested that LDC, as a new potential biological target of OPEs, might be implicated in toxicological and pathogenic mechanism of OPEs. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
4. Inhibition of O-linked N-acetylglucosamine transferase activity in PC12 cells – A molecular mechanism of organophosphate flame retardants developmental neurotoxicity.
- Author
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Gu, Yuxin, Yang, Yu, Wan, Bin, Li, Minjie, and Guo, Liang-Hong
- Subjects
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N-acetylglucosamine derivatives , *NEURODEVELOPMENTAL treatment , *MOLECULAR docking , *REACTIVE oxygen species , *FIREPROOFING agents , *CHOLINESTERASE reactivators - Abstract
Organophosphate flame retardants (OPFRs), as alternatives of brominated flame retardants, can cause neurodevelopmental effects similar to organophosphate pesticides. However, the molecular mechanisms underlying the toxicity remain elusive. O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) regulates numerous neural processes through the O-GlcNAcylation modification of nuclear and cytoplasmic proteins. In this study, we aimed to investigate the molecular mechanisms accounting for the developmental neurotoxicity of OPFRs by identifying potential targets of OPFRs and the attendant effects. Twelve OPFRs were evaluated for inhibition of OGT activity using an electrochemical biosensor. Their potency differed with substituent groups. The alkyl group substituted OPFRs had no inhibitory effect. Instead, the six OPFRs substituted with aromatic or chlorinated alkyl groups inhibited OGT activity significantly, with tri-m-cresyl phosphate (TCrP) being the strongest. The six OPFRs (0–100 μM exposure) also inhibited OGT activity in PC12 cells and decreased protein O-GlcNAcylation level. Inhibition of OGT by OPFRs might be involved in the subsequent toxic effects, including intracellular reactive oxygen species (ROS), calcium level, as well as cell proliferation and autophagy. Molecular docking of the OGT/OPFR complexes provided rationales for the difference in their structure-dependent inhibition potency. Our findings may provide a new biological target of OPFRs in their neurotoxicological actions, which might be a major molecular mechanism of OPFRs developmental neurotoxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
5. Label-free electrochemical biosensing of small-molecule inhibition on O-GlcNAc glycosylation.
- Author
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Yang, Yu, Gu, Yuxin, Wan, Bin, Ren, Xiaomin, and Guo, Liang-Hong
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N-acetylglucosamine , *GLYCOSYLATION , *SMALL molecules , *ELECTROCHEMICAL sensors , *PEPTIDE analysis , *ALZHEIMER'S disease - Abstract
O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. Specific inhibitors of OGT could be valuable tools to probe the biological functions of O-GlcNAcylation, but a lack of robust nonradiometric assay strategies to detect glycosylation, has impeded efforts to identify such compounds. Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. There is a large difference in the abilities of proteolysis of the glycosylated and the unglycosylated peptides by protease, thus providing a sensing mechanism for OGT activity. When the O-GlcNAcylation is achieved, the glycosylated peptides cannot be cleaved by proteinase K and result in a high current response on indium tin oxide (ITO) electrode. However, when the O-GlcNAcylation is successfully inhibited using a small molecule, the unglycosylated peptides can be cleaved easily and lead to low current signal. Peptide O-GlcNAcylation reaction was performed in the presence of a well-defined small-molecule OGT inhibitor. The results indicated that the biosensor could be used to screen the OGT inhibitors effectively. Our label-free electrochemical method is a promising candidate for protein glycosylation pathway research in screening small-molecule inhibitors of OGT. [ABSTRACT FROM AUTHOR]
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- 2017
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- View/download PDF
6. Arginine decarboxylase: A novel biological target of mercury compounds identified in PC12 cells.
- Author
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Wang, Sufang, Lv, Qiyan, Yang, Yu, Guo, Liang-Hong, Wan, Bin, Ren, Xiaomin, and Zhang, Hui
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ARGININE decarboxylase , *MERCURY compounds , *NEUROTOXICOLOGY , *METHYL aspartate receptors , *GLUTAMATE receptors - Abstract
Mercury compounds are well-known toxic environmental pollutants and potently induce severe neurotoxicological effects in human and experimental animals. Previous studies showed that one of the mechanisms of mercury compounds neurotoxicity arose from the over-activation of the N-methyl d -aspartate (NMDA)-type glutamate receptor induced by increased glutamate release. In this work, we aimed to investigate the molecular mechanisms of Hg compounds neurotoxicities by identifying their biological targets in cells. Firstly, the inhibitory effects of four Hg compounds, including three organic (methyl-, ethyl- and phenyl-mercury) and one inorganic (Hg 2+ ) Hg compounds, on the activity of arginine decarboxylase (ADC), a key enzyme in the central agmatinergic system, were evaluated. They were found to inhibit the ADC activity significantly with methylmercury (MeHg) being the strongest (IC 50 = 7.96 nM). Furthermore, they showed remarkable inhibitory effects on ADC activity in PC12 cells (MeHg > EtHg > PhHg > HgCl 2 ), and led to a marked loss in the level of agmatine, an endogenous neuromodulatory and neuroprotective agent that selectively blocks the activation of NMDA receptors. MeHg was detected in the immunoprecipitated ADC from the cells, providing unequivocal evidence for the direct binding of MeHg with ADC in the cell. Molecular dynamics simulation revealed that Hg compounds could form the coordination bond not only with cofactor PLP of ADC, but also with substrate arginine. Our finding indicated that MeHg could attenuate the neuroprotective effects of agmatine by the inhibition of ADC, a new cellular target of MeHg, which might be implicated in molecular mechanism of MeHg neurotoxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
7. Cellular target recognition of perfluoroalkyl acids: In vitro evaluation of inhibitory effects on lysine decarboxylase.
- Author
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Wang, Sufang, Lv, Qiyan, Yang, Yu, Guo, Liang-Hong, Wan, Bin, and Zhao, Lixia
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FLUOROALKYL compounds , *LYSINE decarboxylase , *PEROXISOME proliferator-activated receptors , *ESTROGEN receptors , *SERUM albumin , *IN vitro studies - Abstract
Perfluoroalkyl acids (PFAAs) have been shown to bind with hepatic peroxisome proliferator receptor α, estrogen receptors and human serum albumin and subsequently cause some toxic effects. Lysine decarboxylase (LDC) plays an important role in cell growth and developmental processes. In this study, the inhibitory effect of 16 PFAAs, including 13 perfluorinated carboxylic acids (PFCAs) and 3 perfluorinated sulfonic acids (PFSAs), on lysine decarboxylase (LDC) activity was investigated. The inhibition constants obtained in fluorescence enzyme assays fall in the range of 2.960 μM to 290.8 μM for targeted PFCAs, and 41.22 μM to 67.44 μM for targeted PFSAs. The inhibitory effect of PFCAs increased significantly with carbon chain (7–18 carbons), whereas the short chain PFCAs (less than 7 carbons) did not show any effect. Circular dichroism results showed that PFAA binding induced significant protein secondary structural changes. Molecular docking revealed that the inhibitory effect could be rationalized well by the cleft binding mode as well as the size, substituent group and hydrophobic characteristics of the PFAAs. At non-cytotoxic concentrations, three selected PFAAs inhibited LDC activity in HepG2 cells, and subsequently resulted in the decreased cadaverine level in the exposed cells, suggesting that LDC may be a possible target of PFAAs for their in vivo toxic effects. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
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