Binding and Activation of Estrogen-Related Receptor ?: A Novel Molecular Mechanism for the Estrogenic Disruption Effects of DDT and Its Metabolites
文献类型：期刊论文
| 作者 | Wang, Li; Qie, Yu; Yang, Yu ; Zhao, Qiang
|
| 刊名 | ENVIRONMENTAL SCIENCE & TECHNOLOGY
 |
| 出版日期 | 2022-09-06 |
| 卷号 | 56期号:17页码:12358-12367 |
| 关键词 | ERR-GAMMA ALPHA PESTICIDES CANCER |
| ISSN号 | 0013-936X |
| 英文摘要 | DDT and its metabolites (DDTs) can induce estrogenic effects. Previous mechanistic investigations mainly concentrated on activating the genomic transcription of estrogen receptor (ER) pathways. Here, we identified whether estrogen-related receptor gamma (ERR gamma), an orphan nuclear receptor, is a potential target of DDTs by receptor binding, transcriptional activity, and receptor-mediated pathway assays. Fluorescence polarization-based binding assays showed that all eight DDTs bound to ERR gamma directly, with Kd values ranging from 0.73-168.82 mu M. Among them, 2,2-bis(4-chlorophenyl)ethanol (4,4 '-DDOH) exhibited the highest binding affinity, which was 2.5-fold stronger than GSK4716, a well-known ERR gamma agonist. Eight DDTs exhibited agonistic activity toward the ERR gamma pathway, with 4,4 '-DDOH showing the strongest potency. In silico studies revealed that DDTs tended to bind with ERR gamma in the agonistic conformation. Using a SKBR3 breast cancer cell model, we further found that nanomolar or micromolar levels of DDTs significantly activated the ERR gamma pathway in cells and induced cell proliferation through the ERR gamma-modulated cell cycle. These results indicated that the binding and activation of DDTs to ERR gamma might serve as molecular initiating events for subsequent ERR gamma-mediated signaling pathways and adverse outcomes. Overall, our results demonstrated that ERR gamma might be a crucial pathway involved in the estrogenic disruption effects of DDTs. |
| 源URL | [https://ir.rcees.ac.cn/handle/311016/47476]  |
| 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.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Li,Qie, Yu,Yang, Yu,et al. Binding and Activation of Estrogen-Related Receptor ?: A Novel Molecular Mechanism for the Estrogenic Disruption Effects of DDT and Its Metabolites[J]. ENVIRONMENTAL SCIENCE & TECHNOLOGY,2022,56(17):12358-12367. |
| APA | Wang, Li,Qie, Yu,Yang, Yu,&Zhao, Qiang.(2022).Binding and Activation of Estrogen-Related Receptor ?: A Novel Molecular Mechanism for the Estrogenic Disruption Effects of DDT and Its Metabolites.ENVIRONMENTAL SCIENCE & TECHNOLOGY,56(17),12358-12367. |
| MLA | Wang, Li,et al."Binding and Activation of Estrogen-Related Receptor ?: A Novel Molecular Mechanism for the Estrogenic Disruption Effects of DDT and Its Metabolites".ENVIRONMENTAL SCIENCE & TECHNOLOGY 56.17(2022):12358-12367. |
入库方式： OAI收割
来源：生态环境研究中心
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