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*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

54 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)580-591
Number of pages12
JournalFree Radical Biology and Medicine
Volume36
Issue number5
DOIs
StatePublished - 01 03 2004

Keywords

  • 8-OHdG
  • Cell growth
  • Cell senescence
  • Free radicals
  • Glucose-6-phosphate dehydrogenase
  • NADP
  • NADPH
  • Oxidative stress

Fingerprint

Dive into the research topics of 'Glucose-6-phosphate dehydrogenase-deficient cells show an increased propensity for oxidant-induced senescence'. Together they form a unique fingerprint.

Cite this