Glucose-6-phosphate dehydrogenase-deficient cells show an increased propensity for oxidant-induced senescence

Mei Ling Cheng, Hung Yao Ho, Yi Hsuan Wu, Daniel Tsun Yee Chiu*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

54 引文 斯高帕斯(Scopus)

摘要

Glucose-6-phosphate dehydrogenase (G6PD) is involved in the generation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) and the maintenance of cellular redox balance. We previously showed that G6PD-deficient fibroblasts undergo growth retardation and premature cellular senescence. In the present study, we demonstrate abatement of both the intracellular G6PD activity and the ratio NADPH/NADP+ during the serial passage of G6PD-deficient cells. This was accompanied by a significant increase in the level of 8-hydroxy-2-deoxyguanosine (8-OHdG). This suggests that the lowered resistance to oxidative stress and accumulative oxidative damage may account for the premature senescence of these cells. Consistent with this, the G6PD-deficient cells had an increased propensity for hydrogen peroxide (H2O 2)-induced senescence; these cells exhibited such senescent phenotypes as large, flattened morphology and increased senescence-associated β-galactosidase (SA-β-Gal) staining. Decreases in both the intracellular G6PD activity and the NADPH/NADP+ ratio were concomitant with an increase in 8-OHdG level in H2O 2-induced senescent cells. Exogenous expression of G6PD protected the deficient cells from stress-induced senescence. No significant telomere shortening occurred upon repetitive treatment with H2O2. Simultaneous induction of p16INK4a and p53 was detected in G6PD-deficient but not in normal fibroblasts during H2O 2-induced senescence. Our findings support the notion that G6PD status, and thus proper redox balance, is a determinant of cellular senescence.

原文英語
頁(從 - 到)580-591
頁數12
期刊Free Radical Biology and Medicine
36
發行號5
DOIs
出版狀態已出版 - 01 03 2004

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