Phthalate esters and dexamethasone synergistically activate glucocorticoid receptor

文献类型： 外文期刊

第一作者： Leng, Yue

作者： Leng, Yue;Sun, Yonghai;Li, Tiezhu;Huang, Wei;Lv, Chengyu;Cui, Jingyan;Li, Tiezhu;Wang, Yongjun

作者机构：

关键词： Phthalate exposure; environmental contamination; glucocorticoid receptor; endocrine disruption

期刊名称：JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART A-TOXIC/HAZARDOUS SUBSTANCES & ENVIRONMENTAL ENGINEERING （ 影响因子：2.269； 五年影响因子：2.108 ）

ISSN： 1093-4529

年卷期：

页码：

收录情况： SCI

摘要： This study was conducted to determine the endocrine-disrupting effects of phthalate esters (PAEs) on the glucocorticoid receptor (GR) signaling. Potential (anti)glucocorticoid activities of six typical PAEs including di (2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), dibutyl phthalate (DBP), diisobutyl phthalate (DIBP), diethyl phthalate (DEP) and dimethyl phthalate (DMP) were evaluated on human GR using cell viability assessment, reporter gene expression analysis, mRNA analysis, and molecular docking and simulation. For all tested chemicals, co-treatment of DEHP and DINP with dexamethasone (DEX) exhibited a synergistic effect on GR transactivity in the reporter assays. Such co-treatment also synergistically enhanced DEX-induced upregulation of GR mediated gene (PEPCK,FASandMKP-1) mRNA expression in HepG2 cells and A549 cells. Molecular docking and dynamics simulations showed that hydrophobic interactions may stabilize the binding between molecules and GR. In summary, DEHP and DINP may be involved in synergistic effects via human GR, which highlight the potential endocrine-disrupting activities of PAEs as contaminants.

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