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Telomerase prevents accelerated senescence in glucose-6-phosphate dehydrogenase (G6PD)-deficient human fibroblasts
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
Journal of Biomedical Science 2009, 16:18 doi:10.1186/1423-0127-16-18Published: 5 February 2009
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.