Low oxygen tension alleviates oxidative damage and delays cellular senescence in G6PD-deficient cells.
Previous studies have shown that glucose-6-phosphate dehydrogenase (G6PD)-deficient cells are under increased oxidative stress and undergo premature cellular senescence. The present study demonstrates that G6PD-deficient cells cultured under 3% oxygen concentration had an extended replicative lifespan, as compared with those cultured under atmospheric oxygen level. This was accompanied by a reduction in the number of senescence-associated beta-galactosidase (SA-beta-Gal) positive and morphologically senile cells at comparable population doubling levels (PDL). Concomitant with the extension of lifespan was decreased production of reactive oxygen species. Additionally, lifespan extension was paralleled by the greatly abated formation of such oxidative damage markers as 8-hydroxy-deoxyguanosine (8-OHdG) as well as the oxidized and cross-linked proteins. Moreover, the mitochondrial mass increased, but the mitochondrial membrane potential DeltaPsim decreased in cells upon serial propagation. These changes were inhibited by lowering the oxygen tension. Our findings provide additional support to the notion that oxidative damage contributes to replicative senescence of G6PD-deficient cells and reduction of oxidative damage by lowering oxygen tension can delay the onset of cellular senescence.
Ho
Hung-Yao
HY
Graduate Institute of Medical Biotechnology, Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Kwei-san, Tao-yuan, Taiwan.
Cheng
Mei-Ling
ML
Cheng
Pei-Fen
PF
Chiu
Daniel Tsun-Yee
DT
D000080242:8-Hydroxy-2'-Deoxyguanosine; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000378:metabolism*; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
D000080242:8-Hydroxy-2'-Deoxyguanosine; D005954:Glucosephosphate Dehydrogenase; D001616:beta-Galactosidase; D003849:Deoxyguanosine; D010100:Oxygen