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Inhibiting endoplasmic reticulum stress by activation of G‐protein‐coupled estrogen receptor to protect retinal astrocytes under hyperoxia
Author(s) -
Li Rong,
Wang Yao,
Chen Pei,
Meng Jiamin,
Zhang Hongbing
Publication year - 2021
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22641
Subject(s) - endoplasmic reticulum , microbiology and biotechnology , hyperoxia , estrogen receptor , unfolded protein response , retinal , biology , gper , retina , chemistry , endocrinology , medicine , neuroscience , biochemistry , lung , genetics , cancer , breast cancer
Retinal vascularization is arrested at the early (hyperoxia) stage in retinopathy of prematurity (ROP), a leading cause of blindness in children. Estrogen was reported to alleviate ROP by inhibiting reactive oxygen species, the upstream signaling molecules of endoplasmic reticulum stress (ERS). Astrocytes have long been proposed to guide angiogenesis, because they form a reticular network that provides a substrate for migrating endothelial cells. However, the factors that control the vascularization of the immature retina and the therapeutic mechanism of estrogen in early ROP remain poorly understood. This study aimed to investigate the role of G‐protein‐coupled estrogen receptor (GPER), an estrogen receptor distributed in the endoplasmic reticulum (ER), in protecting retinal astrocytes under hyperoxia and the association with ERS. The results showed that GPER was widely expressed in retinal astrocytes. GPER activation increases cell viability, decreases apoptosis, and autophagy of retinal astrocytes, decreases inositol‐1,4,5‐triphosphate receptor activity, and increases Ca 2+ concentration in ER of astrocytes under hyperoxia. GPER blockade reversed all of these changes. Together, our findings indicate that GPER can protect the survival of retinal astrocytes by inhibiting ERS under hyperoxia.