Evaluation of the Estrogenic/Antiestrogenic Activities of Perfluoroalkyl Substances and Their Interactions with the Human Estrogen Receptor by Combining In Vitro Assays and In Silico Modeling

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	Evaluation of the Estrogenic/Antiestrogenic Activities of Perfluoroalkyl Substances and Their Interactions with the Human Estrogen Receptor by Combining In Vitro Assays and In Silico Modeling
	Li, Juan; Cao, Huiming; Feng, Hongru; Xue, Qiao; Zhang, Aiqian; Fu, Jianjie
刊名	ENVIRONMENTAL SCIENCE & TECHNOLOGY
	2020-11-17
卷号	54 期号:22 页码:14514-14524
ISSN号	0013-936X
英文摘要	The potential estrogenic activities of perfluoroalkyl substances (PFASs) are controversial. Here, we investigated the estrogenic/antiestrogenic activities of PFASs and explored the corresponding interaction mode of PFASs with the estrogen receptor (ER) by combining in vitro assays and in silico modeling. We found that three PFASs (perfluorobutanoic acid, perfluorobutane sulfonate, and perfluoropentanoic acid) exerted antiestrogenic effects by inhibiting luciferase activity, whereas perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) exerted estrogenic effects by inducing luciferase activity. When coexposed to 17 beta-estradiol (E2), all tested PFASs attenuated the E2-stimulated luciferase activity; unexpectedly, each PFAS could further attenuate the luciferase activity generated by the cotreatment with ICI 182,780 and E2, with a minimal effective concentration comparable to that found in human serum. PFHxS and PFOS significantly induced the gene expression of TFF1; additionally, all PFASs inhibited the E2-induced gene expression of TFF1 and EGR3. Furthermore, the results of the blind docking analyses suggested that the interaction with the coactivator-binding region on the ER surface should be included as a pathway through which PFASs exert estrogenic and antiestrogenic activities. Finally, we revealed the critical molecular property of the zeroorder molecular connectivity index (MCI) ((0)chi) that affects the antiestrogenic activity of PFASs.
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/44681]
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	Li, Juan,Cao, Huiming,Feng, Hongru,et al. Evaluation of the Estrogenic/Antiestrogenic Activities of Perfluoroalkyl Substances and Their Interactions with the Human Estrogen Receptor by Combining In Vitro Assays and In Silico Modeling[J]. ENVIRONMENTAL SCIENCE & TECHNOLOGY,2020,54(22):14514-14524.
APA	Li, Juan,Cao, Huiming,Feng, Hongru,Xue, Qiao,Zhang, Aiqian,&Fu, Jianjie.(2020).Evaluation of the Estrogenic/Antiestrogenic Activities of Perfluoroalkyl Substances and Their Interactions with the Human Estrogen Receptor by Combining In Vitro Assays and In Silico Modeling.ENVIRONMENTAL SCIENCE & TECHNOLOGY,54(22),14514-14524.
MLA	Li, Juan,et al."Evaluation of the Estrogenic/Antiestrogenic Activities of Perfluoroalkyl Substances and Their Interactions with the Human Estrogen Receptor by Combining In Vitro Assays and In Silico Modeling".ENVIRONMENTAL SCIENCE & TECHNOLOGY 54.22(2020):14514-14524.