当前位置： SCI文献检索 > ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY期刊下所有文献 > Bisphenol A induces apoptosis through GPER-dependent activation of the ROS/Ca2+-ASK1-JNK pathway in human granulosa cell line KGN.

Bisphenol A induces apoptosis through GPER-dependent activation of the ROS/Ca2+-ASK1-JNK pathway in human granulosa cell line KGN.

Abstract：

:Bisphenol A (BPA) is widely distributed in the environment and human surroundings and is closely related to the occurrence of many chronic diseases including female infertility. Although BPA-induced granulosa cell apoptosis has been widely reported, the underlying mechanisms remain unknown. In this study, we evaluated the induction effect of BPA exposure on apoptosis and mechanisms of regulation in KGN cells (a human granulosa-like tumor cell line). Our results indicated that BPA induced apoptosis of KGN cells in a dose- and time-dependent manner. BPA exposure significantly promoted the expression of pro-apoptotic proteins and decreased mitochondrial membrane potential. We also observed that high concentrations of BPA significantly promoted the generation of reactive oxygen species (ROS) and calcium ion (Ca2+) accumulation. The involvement of ROS and Ca2+ in BPA-induced KGN cell apoptosis was confirmed by pretreatment with NAC (an antioxidant) and BAPTA-AM (a calcium chelator). After inhibitors pretreatment to block the corresponding signaling pathways, it was found that BPA-induced phosphorylation of JNK and ASK1 proteins and apoptosis of KGN cells were significantly inhibited. We pretreated with G15 (a GPER inhibitor) and found that BPA-induced ROS generation and Ca2+ accumulation and apoptosis were significantly inhibited. These results suggest that BPA exposure induces KGN cell apoptosis through GPER-dependent activation of the ROS/Ca2+-ASK1-JNK signaling pathway. Our study provides mechanisms by which BPA induced apoptosis of granulosa cells and ovarian dysfunction.

journal_name

Ecotoxicol Environ Saf

journal_title

Ecotoxicology and environmental safety

authors

Huang M,Huang M,Li X,Liu S,Fu L,Jiang X,Yang M

doi

10.1016/j.ecoenv.2020.111429

subject

Has Abstract

pub_date

2021-01-15 00:00:00

pages

111429

eissn

0147-6513

issn

1090-2414

pii

S0147-6513(20)31266-5

journal_volume

208

pub_type

杂志文章

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