Binding and activity of sulfated metabolites of lower-chlorinated polychlorinated biphenyls towards thyroid hormone receptor alpha

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

	Binding and activity of sulfated metabolites of lower-chlorinated polychlorinated biphenyls towards thyroid hormone receptor alpha
	Ren, Xiao-Min ; Li, Chuan-Hai ; Zhang, Jian-Qing ; Guo, Liang-Hong
刊名	ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
	2019-09-30
卷号	180 页码:686-692
关键词	Lower-chlorinated polychlorinated biphenyls LC-PCB sulfates TR Agonistic activity TH system disruption effect
ISSN号	0147-6513
英文摘要	There has been long-standing evidence that the lower-chlorinated polychlorinated biphenyls (LC-PCBs) can be metabolized to hydroxylated metabolites (OH-PCBs), which play important roles in the LC-PCBs induced toxicity. Recently, multiple studies have demonstrated the further metabolic transformation of OH-PCBs to LC-PCB sulfates in vitro and in vivo. Several studies found LC-PCB sulfates could bind with thyroid hormone (TH) transport proteins in the serum, indicating the potential relevance of these metabolites in the TH system disruption effects. However, the interaction of LC-PCB sulfates with the TH nuclear receptor (TR), another kind of important functional protein in the TH system, has not been explored. Here, by using a fluorescence competitive binding assay, we demonstrated that LC-PCB sulfates could bind with TR alpha. Moreover, the LC-PCB sulfates had higher binding potency than their corresponding OH-PCB precursors. By using a luciferase reporter gene assay, we found the LC-PCB sulfates showed agonistic activity towards the TR alpha signaling pathway. Molecular docking simulation showed all the tested LC-PCB sulfates could fit into the ligand binding pocket of the TR alpha. The LC-PCB sulfates formed hydrogen bond interaction with arginine 228 residue of TR alpha by their sulfate groups, which might facilitate the TR binding and agonistic activity. The present study suggests that interaction with the TR might be another possible mechanism by which LC-PCB sulfate induce TH system disruption effects.
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/42513]
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.Shenzhen Ctr Dis Control & Prevent, 8 Longyuan Rd, Shenzhen 518055, Guangdong, Peoples R China 2.Univ Chinese Acad Sci, Coll Resources & Environm, Beijing 100039, Peoples R China 3.[Li, Chuan-Hai 4.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, 18 Shuangqing Rd,POB 2871, Beijing 100085, Peoples R China 5.Li, Chuan-Hai 6.[Ren, Xiao-Min
推荐引用方式 GB/T 7714	Ren, Xiao-Min,Li, Chuan-Hai,Zhang, Jian-Qing,et al. Binding and activity of sulfated metabolites of lower-chlorinated polychlorinated biphenyls towards thyroid hormone receptor alpha[J]. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY,2019,180:686-692.
APA	Ren, Xiao-Min,Li, Chuan-Hai,Zhang, Jian-Qing,&Guo, Liang-Hong.(2019).Binding and activity of sulfated metabolites of lower-chlorinated polychlorinated biphenyls towards thyroid hormone receptor alpha.ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY,180,686-692.
MLA	Ren, Xiao-Min,et al."Binding and activity of sulfated metabolites of lower-chlorinated polychlorinated biphenyls towards thyroid hormone receptor alpha".ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 180(2019):686-692.