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| Content Provider | Springer Nature Link |
|---|---|
| Author | Yang, Yu Lv, Qi Yan Guo, Liang Hong Wan, Bin Ren, Xiao Min Shi, Ya Li Cai, Ya Qi |
| Copyright Year | 2016 |
| Abstract | 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 μM 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 μM 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. |
| Starting Page | 1697 |
| Ending Page | 1707 |
| Page Count | 11 |
| File Format | |
| ISSN | 03405761 |
| Journal | Archives of Toxicology |
| Volume Number | 91 |
| Issue Number | 4 |
| e-ISSN | 14320738 |
| Language | English |
| Publisher | Springer Berlin Heidelberg |
| Publisher Date | 2016-08-29 |
| Publisher Place | Berlin, Heidelberg |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Perfluoroalkyl acids Protein tyrosine phosphatase Inhibition Cellular target Pharmacology/Toxicology Occupational Medicine/Industrial Medicine Environmental Health Biomedicine |
| Content Type | Text |
| Resource Type | Article |
| Subject | Health, Toxicology and Mutagenesis Medicine Toxicology |
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