New insights into mechanism of bisphenol analogue neurotoxicity: implications of inhibition of O-GlcNAcase activity in PC12 cells
文献类型：期刊论文
| 作者 | Gu, Yu-Xin; Liang, Xiao-Xing; Yin, Nuo-Ya; Yang, Yu; Wan, Bin; Guo, Liang-Hong; Faiola, Francesco6,6 |
| 刊名 | ARCHIVES OF TOXICOLOGY
 |
| 出版日期 | 2019-09-01 |
| 卷号 | 93期号:9页码:2661-2671 |
| 关键词 | Bisphenol analogues O-GlcNAcase Inhibition Neurotoxicity |
| ISSN号 | 0340-5761 |
| 英文摘要 | Bisphenol analogues including bisphenol A and its derivatives are ubiquitous environmental contaminants and have been linked to adverse neurodevelopment effects on animals and humans. Most toxicological research focused on estrogen receptor mediated pathways and did not comprehensively clarify the observed toxicity. O-GlcNAcase (OGA), the highest level in brain, plays a critical role in controlling neuronal functions at multi-levels from molecule to animal behaviors. In this work, we intend to investigate the underlying molecular mechanisms for the neurotoxicity of bisphenol analogues by identifying their cellular targets and the resultant effects. The inhibitory actions of seven bisphenol analogues on the OGA activity at molecular level were investigated by our developed electrochemical biosensor. We found that their potency varied with substituent groups, in which tetrabromo bisphenol A (TBBPA) was the strongest. The seven bisphenol analogues (0-100 mu M exposure) significantly inhibited OGA activity and up-regulated protein O-GlcNAcylation level in PC12 cells. Inhibition of OGA by bisphenol analogues further induced intracellular calcium, ROS, inflammation, repressed proliferation, interfered with cell cycle, induced apoptosis. And especially, 10 mu M tetrabromo bisphenol A (TBBPA) exposure could impair the growth and development of neurite in human neural stem cells (hNSCs). Molecular docking for OGA/bisphenol analogue complexes revealed the hydrophobicity-dominated inhibition potency. OGA, as a new cellular target of bisphenol analogues, would illuminate the molecular mechanism of bisphenol analogues neurotoxicity. |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/42565]  |
| 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 |
| 作者单位 | 1.[Gu, Yu-Xin 2.Liang, Xiao-Xing 3.Yin, Nuo-Ya 4.Yang, Yu 5.Wan, Bin 6.Guo, Liang-Hong 7.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China 8.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Gu, Yu-Xin,Liang, Xiao-Xing,Yin, Nuo-Ya,et al. New insights into mechanism of bisphenol analogue neurotoxicity: implications of inhibition of O-GlcNAcase activity in PC12 cells[J]. ARCHIVES OF TOXICOLOGY,2019,93(9):2661-2671. |
| APA | Gu, Yu-Xin.,Liang, Xiao-Xing.,Yin, Nuo-Ya.,Yang, Yu.,Wan, Bin.,...&Faiola, Francesco.(2019).New insights into mechanism of bisphenol analogue neurotoxicity: implications of inhibition of O-GlcNAcase activity in PC12 cells.ARCHIVES OF TOXICOLOGY,93(9),2661-2671. |
| MLA | Gu, Yu-Xin,et al."New insights into mechanism of bisphenol analogue neurotoxicity: implications of inhibition of O-GlcNAcase activity in PC12 cells".ARCHIVES OF TOXICOLOGY 93.9(2019):2661-2671. |
入库方式： OAI收割
来源：生态环境研究中心
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