探地雷达
雌激素受体
蛋白质组学
信号转导
内分泌系统
转录组
雌激素受体α
受体
化学
生物
计算生物学
激素
生物化学
基因
遗传学
基因表达
癌症
乳腺癌
作者
Ruining Guan,Feng Luan,Ningqi Li,Zhiqiang Qiu,Wen‐Cheng Liu,Zeyang Cui,Chunyan Zhao,Xin Li
出处
期刊:Chemosphere
[Elsevier]
日期:2022-11-01
卷期号:307: 135881-135881
被引量:1
标识
DOI:10.1016/j.chemosphere.2022.135881
摘要
Perfluorooctanoic acid (PFOA) can rapidly activate signaling pathways independent of nuclear hormone receptors through membrane receptor regulation, which leads to endocrine disrupting effects. In the present work, the molecular initiating event (MIE) and the key events (KEs) which cause the endocrine disrupting effects of PFOA have been explored and determined based on molecular dynamics simulation (MD), fluorescence analysis, transcriptomics, and proteomics. MD modeling and fluorescence analysis proved that, on binding to the G protein-coupled estrogen receptor-1 (GPER), PFOA could induce a conformational change in the receptor, turning it into an active state. The results also indicated that the binding to GPER was the MIE that led to the adverse outcome (AO) of PFOA. In addition, the downstream signal transduction pathways of GPER, as regulated by PFOA, were further investigated through genomics and proteomics to identify the KEs leading to thr endocrine disrupting effects. Two pathways (Endocrine resistance, ERP and Estrogen signaling pathway, ESP) containing GPER were regulated by different concentration of PFOA and identified as the KEs. The knowledge of MIE, KEs, and AO of PFOA is necessary to understand the links between PFOA and the possible pathways that lead to its negative effects.
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