Inhibition of O-linked N-acetylglucosamine transferase activity in PC12 cells - A molecular mechanism of organophosphate flame retardants developmental neurotoxicity
文献类型：期刊论文
| 作者 | Gu, Yuxin; Yang, Yu; Wan, Bin; Li, Minjie; Guo, Liang-Hong |
| 刊名 | BIOCHEMICAL PHARMACOLOGY
 |
| 出版日期 | 2018-06-01 |
| 卷号 | 152页码:21-33 |
| 关键词 | Organophosphate flame retardants O-linked N-acetylglucosamine transferase Inhibition Developmental neurotoxicity Molecular docking |
| ISSN号 | 0006-2952 |
| 文献子类 | Article |
| 英文摘要 | Organophosphate flame retardants (OPFRs), as alternatives of brominated flame retardants, can cause neuro-developmental 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 mu M 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. |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/40968]  |
| 专题 | 生态环境研究中心_环境化学与生态毒理学国家重点实验室 |
| 推荐引用方式 GB/T 7714 | Gu, Yuxin,Yang, Yu,Wan, Bin,et al. Inhibition of O-linked N-acetylglucosamine transferase activity in PC12 cells - A molecular mechanism of organophosphate flame retardants developmental neurotoxicity[J]. BIOCHEMICAL PHARMACOLOGY,2018,152:21-33. |
| APA | Gu, Yuxin,Yang, Yu,Wan, Bin,Li, Minjie,&Guo, Liang-Hong.(2018).Inhibition of O-linked N-acetylglucosamine transferase activity in PC12 cells - A molecular mechanism of organophosphate flame retardants developmental neurotoxicity.BIOCHEMICAL PHARMACOLOGY,152,21-33. |
| MLA | Gu, Yuxin,et al."Inhibition of O-linked N-acetylglucosamine transferase activity in PC12 cells - A molecular mechanism of organophosphate flame retardants developmental neurotoxicity".BIOCHEMICAL PHARMACOLOGY 152(2018):21-33. |
入库方式： OAI收割
来源：生态环境研究中心
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