Telomerase prevents accelerated senescence in glucose-6-phosphate dehydrogenase (G6PD)-deficient human fibroblasts.
Fibroblasts derived from glucose-6-phosphate dehydrogenase (G6PD)-deficient patients display retarded growth and accelerated cellular senescence that is attributable to increased accumulation of oxidative DNA damage and increased sensitivity to oxidant-induced senescence, but not to accelerated telomere attrition. Here, we show that ectopic expression of hTERT stimulates telomerase activity and prevents accelerated senescence in G6PD-deficient cells. Stable clones derived from hTERT-expressing normal and G6PD-deficient fibroblasts have normal karyotypes, and display no sign of senescence beyond 145 and 105 passages, respectively. Activation of telomerase, however, does not prevent telomere attrition in earlier-passage cells, but does stabilize telomere lengths at later passages. In addition, we provide evidence that ectopic expression of hTERT attenuates the increased sensitivity of G6PD-deficient fibroblasts to oxidant-induced senescence. These results suggest that ectopic expression of hTERT, in addition to acting in telomere length maintenance by activating telomerase, also functions in regulating senescence induction.
Wu
Yi-Hsuan
YH
Graduate Institute of Basic Medical Sciences, Chang Gung University, Kwei-San, Tao-Yuan 333, Taiwan. d9101302@stmail.cgu.edu.tw
Cheng
Mei-Ling
ML
Ho
Hung-Yao
HY
Chiu
Daniel Tsun-Yee
DT
Wang
Tzu-Chien V
TC
D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D004249:DNA Damage; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007621:Karyotyping; D016877:Oxidants / Q000494:pharmacology; D010641:Phenotype; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
D016877:Oxidants; D006861:Hydrogen Peroxide; D005954:Glucosephosphate Dehydrogenase; C509186:TERT protein, human; D019098:Telomerase