期刊
CHEMOSPHERE
卷 265, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.chemosphere.2020.129051
关键词
Bisphenol; Islet of langerhans; Endocrine disrupting chemicals; Estrogen receptors; Molecular dynamics simulation
The study investigated the effects of BPS and BPF on insulin secretion and ion channel activity in pancreatic beta-cells using WT and BERKO mice. Results showed that both compounds enhance insulin release by affecting ion channel activity, with the involvement of the ER beta pathway. Molecular dynamics simulations indicated differences in ER beta ligand-binding domain among different bisphenols and PaPE-1.
Bisphenol-S (BPS) and Bisphenol-F (BPF) are current Bisphenol-A (BPA) substitutes. Here we used pancreatic beta-cells from wild type (WT) and estrogen receptor beta (ER beta) knockout (BERKO) mice to investigate the effects of BPS and BPF on insulin secretion, and the expression and activity of ion channels involved in beta-cell function. BPS or BPF rapidly increased insulin release and diminished ATP-sensitive K+ (K-ATP) channel activity. Similarly, 48 h treatment with BPS or BPF enhanced insulin release and decreased the expression of several ion channel subunits in beta-cells from WT mice, yet no effects were observed in cells from BERKO mice. PaPE-1, a ligand designed to preferentially trigger extranuclear-initiated ER pathways, mimicked the effects of bisphenols, suggesting the involvement of extranuclear-initiated ER beta pathways. Molecular dynamics simulations indicated differences in ER beta ligand-binding domain dimer stabilization and solvation free energy among different bisphenols and PaPE-1. Our data suggest a mode of action involving ER beta whose activation alters three key cellular events in beta-cell, namely ion channel expression and activity, and insulin release. These results may help to improve the hazard identification of bisphenols. (C) 2020 Elsevier Ltd. All rights reserved.
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