@Article{biocell.2022.018559,
AUTHOR = {YAPING WANG; XIAOHONG XUE; ZHEN ZHAO; XIAOLIN LI; ZHIYONG ZHU},
TITLE = {Hypoxia induced apoptosis of rat gastric mucosal cells by activating autophagy through HIF-1α/TERT/mTORC1 pathway},
JOURNAL = {BIOCELL},
VOLUME = {46},
YEAR = {2022},
NUMBER = {7},
PAGES = {1651--1659},
URL = {http://www.techscience.com/biocell/v46n7/47025},
ISSN = {1667-5746},
ABSTRACT = {The pathogenesis of high altitude-related gastric mucosal injury remains poorly understood, this study aimed to
investigate the role of autophagy in hypoxia-induced apoptosis of rat gastric mucosal cells. Rats were randomized into
four groups which were maintained at an altitude of 400 m (P) or received no treatment (H), autophagy inducer
rapamycin (H+AI) or autophagy inhibitor 3-MA (H+AB) at an altitude of 4,300 m for 1, 7, 14 and 21 days,
respectively, and the morphology, ultrastructure, autophagy, and apoptosis of gastric mucosal tissues were examined.
Gastric mucosal epithelial cells CC-R039 were cultured under conditions of normoxia, 2% O2 (hypoxia), or 2%
O2+anti-mTORC1 for 0, 24, 48, and 72 h, respectively, and the autophagy and apoptosis were analyzed. CC-R039
cells were transfected with siHIF-1α, siTERT, or siRNA and the autophagy was examined. The results showed that the
exposure to hypoxia increased the autophagy and apoptosis of gastric mucosal cells in rats, and apoptosis was
aggravated by rapamycin treatment but alleviated by 3-MA treatment. Increased duration of hypoxia from 0 to 72 h
could increase the autophagy and apoptosis but decrease the proliferation of gastric mucosal cells. Inhibition of
mTORC1 with rapamycin led to further increase in apoptosis and even substantial cell death, and inhibition of HIF-
1α and TERT increased mTORC1 expression and reduced autophagy. Moreover, the inhibition of HIF-1α reduced
TERT expression. In conclusion, hypoxia could induce apoptosis of rat gastric mucosal cells by activating autophagy
through HIF-1α/TERT/mTORC1 pathway},
DOI = {10.32604/biocell.2022.018559}
}