Tricresyl phosphate isomers exert estrogenic effects via G protein-coupled estrogen receptor-mediated pathways
文献类型：期刊论文
| 作者 | Ji, Xiaoya; Li, Na ; Ma, Mei; Rao, Kaifeng; Yang, Rong; Wang, Zijian
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| 刊名 | ENVIRONMENTAL POLLUTION
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| 出版日期 | 2020-09 |
| 卷号 | 264页码:1-10 |
| ISSN号 | 0269-7491 |
| 关键词 | Tricresyl phosphate isomers Estrogenic effect GPER cAMP Calcium mobilization |
| 英文摘要 | Tricresyl phosphates (TCPs), as representative aromatic organophosphate flame retardants (OPFRs), have received much attention due to their potential neurotoxicity and endocrine-disrupting effects. However, the role of estrogen receptor alpha (ER alpha) and G protein-coupled estrogen receptor (GPER) in their estrogen disrupting effects remains poorly understood. Therefore, in this study, three TCP isomers, tri-o-cresyl phosphate (ToCP), tri-m-cresyl phosphate (TmCP) and tri-p-cresyl phosphate (TpCP), were examined for their activities on ER alpha by using two-hybrid yeast assay, and action on GPER by using Boyden chamber assay, cAMP production assay, calcium mobilization assay and molecular docking analysis. The results showed that three TCP isomers were found to act as ER alpha antagonists. Conversely, they had agonistic activity on GPER to promote GPER-mediated cell migration of MCF7 cells and SKBR3 cells. Both ToCP and TpCP activated GPER-mediated cAMP production and calcium mobilization, whereas TmCP had different mode of action, it only triggered GPER-mediated calcium mobilization, as evidenced by using the specific GPER inhibitor (G15) and GPER overexpressing experiments. Molecular docking further revealed that the way of interaction of TmCP and TpCP with GPER was different from that of ToCP with GPER, and higher activity of ToCP in activating GPER-mediated pathways might be associated with the alkyl substitution at the ortho position of the aromatic ring. Our results, for the first time, found a new target, GPER, for TCPs exerting their estrogen-disrupting effects, and demonstrated complex estrogen-disrupting effects of three TCP isomers involved their opposite activities toward ER alpha and GPER. (C) 2020 Elsevier Ltd. All rights reserved. |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/45378]  |
| 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 | Ji, Xiaoya,Li, Na,Ma, Mei,et al. Tricresyl phosphate isomers exert estrogenic effects via G protein-coupled estrogen receptor-mediated pathways[J]. ENVIRONMENTAL POLLUTION,2020,264:1-10. |
| APA | Ji, Xiaoya,Li, Na,Ma, Mei,Rao, Kaifeng,Yang, Rong,&Wang, Zijian.(2020).Tricresyl phosphate isomers exert estrogenic effects via G protein-coupled estrogen receptor-mediated pathways.ENVIRONMENTAL POLLUTION,264,1-10. |
| MLA | Ji, Xiaoya,et al."Tricresyl phosphate isomers exert estrogenic effects via G protein-coupled estrogen receptor-mediated pathways".ENVIRONMENTAL POLLUTION 264(2020):1-10. |
入库方式： OAI收割
来源：生态环境研究中心
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