RCEES OpenIR  > 环境化学与生态毒理学国家重点实验室
Structure-activity relations in binding of perfluoroalkyl compounds to human thyroid hormone T3 receptor
Ren, Xiao-Min; Zhang, Yin-Feng; Guo, Liang-Hong; Qin, Zhan-Fen; Lv, Qi-Yan; Zhang, Lian-Ying
2015-02
Source PublicationARCHIVES OF TOXICOLOGY
Volume89Issue:2Pages:233-242
AbstractPerfluoroalkyl compounds (PFCs) have been shown to disrupt thyroid functions through thyroid hormone receptor (TR)-mediated pathways, but direct binding of PFCs with TR has not been demonstrated. We investigated the binding interactions of 16 structurally diverse PFCs with human TR, their activities on TR in cells, and the activity of perfluorooctane sulfonate (PFOS) in vivo. In fluorescence competitive binding assays, most of the 16 PFCs were found to bind to TR with relative binding potency in the range of 0.0003-0.05 compared with triiodothyronine (T3). A structure-binding relationship for PFCs was observed, where fluorinated alkyl chain length longer than ten, and an acid end group were optimal for TR binding. In thyroid hormone (TH)-responsive cell proliferation assays, PFOS, perfluorohexadecanoic acid, and perfluorooctadecanoic acid exhibited agonistic activity by promoting cell growth. Furthermore, similar to T3, PFOS exposure promoted expression of three TH upregulated genes and inhibited three TH downregulated genes in amphibians. Molecular docking analysis revealed that most of the tested PFCs efficiently fit into the T3-binding pocket in TR and formed a hydrogen bond with arginine 228 in a manner similar to T3. The combined in vitro, in vivo, and computational data strongly suggest that some PFCs disrupt the normal activity of TR pathways by directly binding to TR.
Department环境化学与生态毒理学国家重点实验室
KeywordPerfluoroalkyl Compounds Thyroid Hormone Receptor Agonistic Activity Gene Expression Molecular Docking
WOS Research AreaToxicology
WOS IDWOS:000348917100008
Citation statistics
Cited Times:40[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.rcees.ac.cn/handle/311016/32669
Collection环境化学与生态毒理学国家重点实验室
Recommended Citation
GB/T 7714
Ren, Xiao-Min,Zhang, Yin-Feng,Guo, Liang-Hong,et al. Structure-activity relations in binding of perfluoroalkyl compounds to human thyroid hormone T3 receptor[J]. ARCHIVES OF TOXICOLOGY,2015,89(2):233-242.
APA Ren, Xiao-Min,Zhang, Yin-Feng,Guo, Liang-Hong,Qin, Zhan-Fen,Lv, Qi-Yan,&Zhang, Lian-Ying.(2015).Structure-activity relations in binding of perfluoroalkyl compounds to human thyroid hormone T3 receptor.ARCHIVES OF TOXICOLOGY,89(2),233-242.
MLA Ren, Xiao-Min,et al."Structure-activity relations in binding of perfluoroalkyl compounds to human thyroid hormone T3 receptor".ARCHIVES OF TOXICOLOGY 89.2(2015):233-242.
Files in This Item: Download All
File Name/Size DocType Version Access License
Structure–activity r(1505KB)期刊论文作者接受稿开放获取CC BY-NC-SAView Download
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Ren, Xiao-Min]'s Articles
[Zhang, Yin-Feng]'s Articles
[Guo, Liang-Hong]'s Articles
Baidu academic
Similar articles in Baidu academic
[Ren, Xiao-Min]'s Articles
[Zhang, Yin-Feng]'s Articles
[Guo, Liang-Hong]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Ren, Xiao-Min]'s Articles
[Zhang, Yin-Feng]'s Articles
[Guo, Liang-Hong]'s Articles
Terms of Use
No data!
Social Bookmark/Share
File name: Structure–activity relations in binding of perfluoroalkyl compounds to human thyroid hormone T3 receptor.pdf
Format: Adobe PDF
This file does not support browsing at this time
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.