Identification of protein tyrosine phosphatase SHP-2 as a new target of perfluoroalkyl acids in HepG2 cells
文献类型：期刊论文
| 作者 | Shi, Ya-Li; Yang, Yu; Lv, Qi-Yan; Guo, Liang-Hong; Wan, Bin; Ren, Xiao-Min; Cai, Ya-Qi |
| 刊名 | ARCHIVES OF TOXICOLOGY
 |
| 出版日期 | 2017-11-07 |
| 卷号 | 91期号:4页码:1697-1707 |
| 关键词 | Perfluoroalkyl Acids Protein Tyrosine Phosphatase Inhibition Cellular Target |
| 英文摘要 | Perfluoroalkyl acids (PFAAs) are widespread environmental contaminants which have been detected in humans and linked to adverse health effects. Previous toxicological studies mostly focused on nuclear receptor-mediated pathways and did not support the observed toxic effects. In this study, we aimed to investigate the molecular mechanisms of PFAA toxicities by identifying their biological targets in cells. Using a novel electrochemical biosensor, 16 PFAAs were evaluated for inhibition of protein tyrosine phosphatase SHP-2 activity. Their potency increased with PFAA chain length, with perfluorooctadecanoic acid (PFODA) showing the strongest inhibition. Three selected PFAAs, 25 mu M perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid, and PFODA, also inhibited SHP-2 activity in HepG2 cells and increased paxillin phosphorylation level. PFOA was detected in the immunoprecipitated SHP-2 from the cells exposed to 250 mu M PFOA, providing unequivocal evidence for the direct binding of PFOA with SHP-2 in the cell. Molecular docking rationalized the formation of PFAA/SHP-2 complex and chain length-dependent inhibition potency. Our results have established SHP-2 as a new cellular target of PFAAs. |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/39335]  |
| 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 | Shi, Ya-Li,Yang, Yu,Lv, Qi-Yan,et al. Identification of protein tyrosine phosphatase SHP-2 as a new target of perfluoroalkyl acids in HepG2 cells[J]. ARCHIVES OF TOXICOLOGY,2017,91(4):1697-1707. |
| APA | Shi, Ya-Li.,Yang, Yu.,Lv, Qi-Yan.,Guo, Liang-Hong.,Wan, Bin.,...&Cai, Ya-Qi.(2017).Identification of protein tyrosine phosphatase SHP-2 as a new target of perfluoroalkyl acids in HepG2 cells.ARCHIVES OF TOXICOLOGY,91(4),1697-1707. |
| MLA | Shi, Ya-Li,et al."Identification of protein tyrosine phosphatase SHP-2 as a new target of perfluoroalkyl acids in HepG2 cells".ARCHIVES OF TOXICOLOGY 91.4(2017):1697-1707. |
入库方式： OAI收割
来源：生态环境研究中心
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。