Oxidative stress-induced TETI upregulation mediates active DNA demethylation in human gastric epithelial cells
JOURNAL OF TOXICOLOGICAL SCIENCES(2023)
摘要
The gastrointestinal (GI) tract is more vulnerable to effects by the outside environ-ment, and experiences oxidative stress. A wide diversity of GI disorders can be partially attributed to oxi-dative 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 malond-ialdehyde (MDA), decreased the level of glutathione (GSH), inhibited proliferation, caused nuclear DNA damage and apoptosis, upregulated the expression of TETI gene, and ultimately led to active DNA dem-ethylation 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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关键词
Oxidative stress, DNA demethylation, Ten-eleven translocation, Gastric epithelial cells, Human
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