TDCPP mimics thyroid hormones associated with the activation of integrin alpha(v)beta(3) and ERK1/2

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 中国科学院饮用水科学与技术重点实验室

	TDCPP mimics thyroid hormones associated with the activation of integrin alpha(v)beta(3) and ERK1/2
	Li, Jian; Liu, Hedan; Li, Na; Wang, Jinsheng; Song, Liuting
刊名	CHEMOSPHERE
	2020-10
卷号	256 页码:1-9
关键词	TDCPP BDCPP Thyroid disruption Integrin alpha(v)beta(3) ERK1/2
ISSN号	0045-6535
英文摘要	Tri(1,3-dichloropropyl) phosphate (TDCPP) potentially damages the thyroid system in humans and animals. However, knowledge of its toxic effects and underlying mechanisms is limited. The present study was conducted to determine the thyroid hormone-disrupting effects of TDCPP and its major metabolite, bis(1,3-dichloro-2-propyl) phosphate (BDCPP) in rat pituitary cell lines (GH3). TDCPP and BDCPP, that mimic the thyroid hormone (TH), promoted GH3 cell proliferation and modulated the progression of the cell cycle at 20 and 200 mu mol/L, respectively. Similar to T3, TDCPP and BDCPP also significantly upregulated c-fos and downregulated Tsh beta gene expression. Although the binding affinity of these chemicals for thyroid receptor beta (TR beta) was not measured, significant competition between these chemicals to bind to the membrane thyroid hormone receptor (integrin alpha(v)beta(3)) was found, suggesting that TDCPP and BDCPP were strongly bound to integrin alpha(v)beta(3). Results from a molecular docking analysis provided further evidence of strong binding affinities of TDCPP and BDCPP for integrin alpha(v)beta(3), and the ligand binding site of Arg-Gly-Asp (RGD) was identified. Real-time PCR also supported the supposition that, after binding to integrin alpha(v)beta(3), TDCPP and BDCPP may induce the activation of the extracellular signal-regulated protein kinase (ERK1/2) signal transduction pathway. Taken together, our data suggest that TDCPP and BDCPP have the ability to mimic THs and that the underlying mechanism might be associated with their interactions with integrin alpha(v)beta(3) and the activation of the ERK1/2 pathway, providing new insight into the mechanism of TDCPP- and BDCPP-induced cytotoxicity. (C) 2020 Elsevier Ltd. All rights reserved.
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/45366]
专题	生态环境研究中心_中国科学院饮用水科学与技术重点实验室
推荐引用方式 GB/T 7714	Li, Jian,Liu, Hedan,Li, Na,et al. TDCPP mimics thyroid hormones associated with the activation of integrin alpha(v)beta(3) and ERK1/2[J]. CHEMOSPHERE,2020,256:1-9.
APA	Li, Jian,Liu, Hedan,Li, Na,Wang, Jinsheng,&Song, Liuting.(2020).TDCPP mimics thyroid hormones associated with the activation of integrin alpha(v)beta(3) and ERK1/2.CHEMOSPHERE,256,1-9.
MLA	Li, Jian,et al."TDCPP mimics thyroid hormones associated with the activation of integrin alpha(v)beta(3) and ERK1/2".CHEMOSPHERE 256(2020):1-9.