Per- and polyfluoroalkyl substances display structure-dependent inhibition towards UDP-glucuronosyltransferases
文献类型：期刊论文
| 作者 | Liu, Yong-Zhe; Zhang, Zhi-Peng; Fu, Zhi-Wei; Yang, Kun; Ding, Ning6; Hu, Li-Gang; Fang, Zhong-Ze; Zhuo, Xiaozhen6 |
| 刊名 | ENVIRONMENTAL POLLUTION
 |
| 出版日期 | 2019-11-01 |
| 卷号 | 254页码:- |
| ISSN号 | 0269-7491 |
| 关键词 | Per- and polyfluoroalkyl substances (PFASs) UDP-Glucuronosyltransferases (UGTs) Half inhibition concentration (IC50) Inhibition type Inhibition kinetic parameters (Ki) In vitro-in vivo extrapolation (IVIVE) |
| 英文摘要 | Per- and polyfluoroalkyl substances (PFASs) are a large group of chemicals and can be detected in environmental and human samples all over the world. Toxicity of existing and emerging PFASs will be a long-term source of concern. This study aimed to investigate structure-dependent inhibitory effects of 14 PFASs towards the activity of 11 UDP-glucuronosyltransferase (UGT) isoforms. In vitro UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was employed to determine the inhibition of PFASs towards different UGT isoforms. All the PFASs showed <75% of inhibition or stimulation effects on UGTIA3, UGTIA7, UGT1A9, UGT2B4, UGT2B7 and UGT2B17. However, PFASs showed broad inhibition on the activity of UGT1A1 and UGT1A8. The activity of UGT1A1 was inhibited by 98.8%, 98%, 79.9%, 77.1%, and 76.9% at 100 mu moL/L of perfluorodecanoic acid (PFDA), perfluorooctanesulfonic acid potassium salt (PFOS), perfluorotetradecanoic acid (PFTA), perfluorooctanoic acid (PFOA) and perfluorododecanoic acid (PFDoA), respectively. UGT1A8 was inhibited by 97.6%, 94.8%, 86.3%, 83.4% and 77.1% by PFDA, PFTA, perfluorooctadecanoic acid (PFOcDA), PFDoA and PFOS, respectively. Additionally, PFDA significantly inhibited UGT1A6 and UGT1A10 by 96.8% and 91.6%, respectively. PFDoA inhibited the activity of UGT2B15 by 88.2%. PFDA and PFOS exhibited competitive inhibition towards UGT1A1, and PFDA and PFTA showed competitive inhibition towards UGT1A8. The inhibition kinetic parameter (K-i) were 3.15, 1.73, 13.15 and 20.21 mu moL/1. for PFDA-1A1, PFOS-1A1, PFDA-1A8 and PFTA-1A8, respectively. The values were calculated to be 0.3 mu moL/L and 1.3 mu moL/L for the in vivo inhibition of PFDA towards UGT1A1-and UGT1A8-catalyzed metabolism of substances, and 0.21 mu moL/L and 2.0 mu moL/L for the inhibition of PFOS towards UGT1A1 and the inhibition of PFTA towards UGT1A8, respectively. Molecular docking indicated that hydrogen bonds and hydrophobic interactions contributed to the interaction between PFASs and UGT isoforms. In conclusion, exposure to PFASs might inhibit the activity of UGTs to disturb metabolism of endogenous compounds and xenobiotics. The structure-related effects of PFASs on UGTs would be very important for risk assessment of PFASs. (C) 2019 Elsevier Ltd. All rights reserved. |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/42573]  |
| 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.Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Cardiol, 277 West Yanta Rd, Xian 710061, Shaanxi, Peoples R China 2.Tianjin Key Lab Environm Nutr & Publ Hlth, Tianjin 300070, Peoples R China 3.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China 4.Tianjin Med Univ, Natl Demonstrat Ctr Expt Prevent Med Educ, Tianjin 300070, Peoples R China 5.Peking Univ, Hosp 3, Dept Surg, Beijing, Peoples R China 6.Tianjin Med Univ, Sch Publ Hlth, Dept Toxicol & Sanit Chem, Tianjin 300070, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Yong-Zhe,Zhang, Zhi-Peng,Fu, Zhi-Wei,et al. Per- and polyfluoroalkyl substances display structure-dependent inhibition towards UDP-glucuronosyltransferases[J]. ENVIRONMENTAL POLLUTION,2019,254:-. |
| APA | Liu, Yong-Zhe.,Zhang, Zhi-Peng.,Fu, Zhi-Wei.,Yang, Kun.,Ding, Ning.,...&Zhuo, Xiaozhen.(2019).Per- and polyfluoroalkyl substances display structure-dependent inhibition towards UDP-glucuronosyltransferases.ENVIRONMENTAL POLLUTION,254,-. |
| MLA | Liu, Yong-Zhe,et al."Per- and polyfluoroalkyl substances display structure-dependent inhibition towards UDP-glucuronosyltransferases".ENVIRONMENTAL POLLUTION 254(2019):-. |
入库方式： OAI收割
来源：生态环境研究中心
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