Open Access

ARTICLE

Hypoxia induced apoptosis of rat gastric mucosal cells by activating autophagy through HIF-1α/TERT/mTORC1 pathway

by YAPING WANG^1,2,#,*, XIAOHONG XUE^2,#, ZHEN ZHAO^1,#, XIAOLIN LI², ZHIYONG ZHU¹

1 Department of Digestive Medicine, Wuxi Huishan District People’s Hospital, Wuxi, China
2 Department of Digestive Medicine, Qinghai Provincial People’s Hospital, Xining, China

* Corresponding Author: Yaping Wang,
# These authors contributed equally to this work

(This article belongs to the Special Issue: Biochemical and Epigenetics Changes in Health and Disease)

BIOCELL 2022, 46(7), 1651-1659. https://doi.org/10.32604/biocell.2022.018559

Received 02 August 2021; Accepted 26 September 2021; Issue published 17 March 2022

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

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