中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 过程工程研究所
  3. 中国科学院过程工程研究所
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, Yuxin1,2; Yang, Yu1; Wan, Bin1,2; Li, Minjie3; Guo, Liang-Hong1,2
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
DOI10.1016/j.bcp.2018.03.017
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.
WOS关键词GLCNAC TRANSFERASE ; PHOSPHATE TDCPP ; PLASTICIZERS ; GLYCOSYLATION ; GLCNACYLATION ; TOXICITY ; EXPOSURE ; COMPLEX ; NEURODEGENERATION ; PHOSPHORYLATION
资助项目National Natural Science Foundation of China[21377142] ; National Natural Science Foundation of China[21577163] ; National Natural Science Foundation of China[21375143] ; National Natural Science Foundation of China[21477146] ; National Natural Science Foundation of China[21621064] ; National Natural Science Foundation of China[91543203] ; Chinese Academy of Sciences[XDB14040100] ; Chinese Academy of Sciences[QYZDJ-SSW-DQC020]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000433398700003
出版者PERGAMON-ELSEVIER SCIENCE LTD
资助机构National Natural Science Foundation of China ; Chinese Academy of Sciences
源URL[http://ir.ipe.ac.cn/handle/122111/24768]  
专题中国科学院过程工程研究所
通讯作者Yang, Yu; Guo, Liang-Hong
作者单位1.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, POB 2871,18 Shuangqing Rd, Beijing 100085, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Inst Proc Engn, 1 North 2nd St, Beijing 100190, Peoples R China
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：过程工程研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。