Telomerase prevents accelerated senescence in glucose-6-phosphate dehydrogenase (G6PD)-deficient human fibroblasts |
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Authors: | Yi-Hsuan Wu Mei-Ling Cheng Hung-Yao Ho Daniel Tsun-Yee Chiu Tzu-Chien V Wang |
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Institution: | (1) Graduate Institute of Basic Medical Sciences, Chang Gung University, Kwei-San, Tao-Yuan, 333, Taiwan;(2) School of Medical Biotechnology, Chang Gung University, Kwei-San, Tao-Yuan, 333, Taiwan;(3) Department of Molecular and Cellular Biology, Chang Gung University, Kwei-San, Tao-Yuan, 333, Taiwan |
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Abstract: | 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. |
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