8-Oxoguanine-DNA glycosylase (OGG1) protects cells from senescence via the p53-p21 pathway

Acta Biochim Biophys Sin (Shanghai). 2024 Jan 29. doi: 10.3724/abbs.2023264. Online ahead of print.ABSTRACTCellular senescence is an important factor leading to pulmonary fibrosis. Deficiency of 8-oxoguanine-DNA glycosylase (OGG1) in mice leads to alleviation of bleomycin (BLM)-induced mouse pulmonary fibrosis, and inhibition of the OGG1 enzyme reduces the epithelial mesenchymal transition (EMT) in lung cells. In the present study, we find decreased expression of OGG1 in aged mice and BLM-induced cell senescence. In addition, a decrease in OGG1 expression results in cell senescence, such as increases in the percentage of SA-β-gal-positive cells, and in the p21 and p-H2AX protein levels in response to BLM in lung cells. Furthermore, OGG1 promotes cell transformation in A549 cells in the presence of BLM. We also find that OGG1 siRNA impedes cell cycle progression and inhibits the levels of telomerase reverse transcriptase (TERT) and LaminB1 in BLM-treated lung cells. The increase in OGG1 expression results in the opposite phenomenon. The mRNA levels of senescence-associated secretory phenotype (SASP) components, including IL-1α, IL-1β, IL-6, IL-8, CXCL1/CXCL2, and MMP-3, in the absence of OGG1 are obviously increased in A549 cells treated with BLM. Interestingly, we demonstrate that OGG1 binds to p53 to inhibit the activation of p53 and that silencing of p53 reverses the inhibition of OGG1 on senescence in lung cells. Additionally, the augmented cell senescence is shown in v...

Source: Acta Biochimica et Biophysica Sinica - January 29, 2024 Category: Biochemistry Authors: Shenglan Gao Lujun Chen Ziying Lin Zhiliang Xu Yahong Wang Huayu Ling Zijun Wu Yu Yin Weimin Yao Keng Wu Gang Liu Source Type: research