Structure-activity relations in binding of perfluoroalkyl compounds to human thyroid hormone T3 receptor
文献类型：期刊论文
| 作者 | Ren, Xiao-Min; Zhang, Yin-Feng; Guo, Liang-Hong; Qin, Zhan-Fen; Lv, Qi-Yan; Zhang, Lian-Ying |
| 刊名 | ARCHIVES OF TOXICOLOGY
 |
| 出版日期 | 2015-02 |
| 卷号 | 89期号:2页码:233-242 |
| 关键词 | Perfluoroalkyl compounds Thyroid hormone receptor Agonistic activity Gene expression Molecular docking |
| 英文摘要 | Perfluoroalkyl 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. |
| 研究领域[WOS] | Toxicology |
| WOS记录号 | WOS:000348917100008 |
| 公开日期 | 2016-03-15 |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/32669]  |
| 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 | 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. |
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。