Oxidative stress-induced TET1 upregulation mediates active DNA demethylation in human gastric epithelial cells

Mengna Zuo; Jianing He; Qianxi Yin; Xiaoying He; Ying Liu; Yang Liu; Jiwei Liu; Shujun Liu; Libing Ma

doi:10.2131/jts.48.273

Original Article

Oxidative stress-induced TET1 upregulation mediates active DNA demethylation in human gastric epithelial cells

Mengna Zuo, Jianing He, Qianxi Yin, Xiaoying He, Ying Liu, Yang Liu, Jiwei Liu, Shujun Liu, Libing Ma

Author information

Mengna Zuo
School of Life Science and Technology, Inner Mongolia University of Science and Technology, China
Jianing He
School of Life Science and Technology, Inner Mongolia University of Science and Technology, China
Qianxi Yin
School of Life Science and Technology, Inner Mongolia University of Science and Technology, China
Xiaoying He
School of Life Science and Technology, Inner Mongolia University of Science and Technology, China
The Inner Mongolia Key Laboratory of Functional Genome Bioinformatics, Inner Mongolia University of Science and Technology, China
Ying Liu
School of Life Science and Technology, Inner Mongolia University of Science and Technology, China
The Inner Mongolia Key Laboratory of Functional Genome Bioinformatics, Inner Mongolia University of Science and Technology, China
Yang Liu
School of Life Science and Technology, Inner Mongolia University of Science and Technology, China
The Inner Mongolia Key Laboratory of Functional Genome Bioinformatics, Inner Mongolia University of Science and Technology, China
Jiwei Liu
School of Life Science and Technology, Inner Mongolia University of Science and Technology, China
The Inner Mongolia Key Laboratory of Functional Genome Bioinformatics, Inner Mongolia University of Science and Technology, China
Shujun Liu
School of Life Science and Technology, Inner Mongolia University of Science and Technology, China
The Inner Mongolia Key Laboratory of Functional Genome Bioinformatics, Inner Mongolia University of Science and Technology, China
Libing Ma
School of Life Science and Technology, Inner Mongolia University of Science and Technology, China
The Inner Mongolia Key Laboratory of Functional Genome Bioinformatics, Inner Mongolia University of Science and Technology, China
College of Life Science, Inner Mongolia Agricultural University, China

Keywords: Oxidative stress, DNA demethylation, Ten-eleven translocation, Gastric epithelial cells, Human

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2023 Volume 48 Issue 5 Pages 273-283

DOI https://doi.org/10.2131/jts.48.273

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Abstract

The gastrointestinal (GI) tract is more vulnerable to effects by the outside environment, and experiences oxidative stress. A wide diversity of GI disorders can be partially attributed to oxidative stress. However, the mechanism of oxidative stress-caused GI pathological changes is not clear. In the present study, human gastric epithelial cells (hGECs) were treated with hydrogen peroxide (H₂O₂), and oxidative stress was determined. The effect of oxidative stress on the levels of some antioxidative enzymes, proliferation, nuclear DNA damage, apoptosis, expression of ten-eleven translocation (TET), and level of DNA methylation was determined in these cells. The results showed that H₂O₂ treatment caused oxidative stress, increased the levels of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA), decreased the level of glutathione (GSH), inhibited proliferation, caused nuclear DNA damage and apoptosis, upregulated the expression of TET1 gene, and ultimately led to active DNA demethylation in hGECs. The present study presents a mechanism by which oxidative stress induces active DNA demethylation in hGECs. We propose that TET inhibitors can be used to restore the oxidative stress-induced DNA demethylation, and thus inhibit possible malignant transformation of GI cells.

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