Oxidative stress response in telomerase-immortalized fibroblasts from a centenarian.
It has been reported that cells with ectopic expression of telomerase are more resistant to apoptotic cell death than their normal counterpart. However, controversial results were obtained when the cellular response to oxidative stress was analyzed. The present research was therefore aimed at defining the effect of the oxidative stress induced by tert-butylhydroperoxide (tBOOH) and 2-deoxy-D-ribose (D-ribose) in human fibroblasts from a centenarian (cen3) and, in parallel, on the same cells after telomerase immortalization (cen3tel cells). By studying different parameters of apoptosis in situ (i.e., chromatin condensation, phosphatidylserine externalization, and DNA fragmentation), we found that both tBOOH and D-ribose induce apoptosis to a greater extent in cen3 than in cen3tel cells, suggesting a protective role of telomerase toward apoptotic death. However, monitoring the cell number during treatment with the drugs, we found a decrease in cell number; since this reduction was lower in cen3 fibroblasts compared to cen3tel cells, it is likely that telomerase does not fully protect cells from drug toxicity.
Mondello
Chiara
C
Istituto di Genetica Molecolare del CNR, Via Abbiategrasso 207, 27100 Pavia, Italy. mondello@igm.cnr.it
Bottone
Maria Grazia
MG
Noriki
Sakon
S
Soldani
Cristiana
C
Pellicciari
Carlo
C
Scovassi
Anna Ivana
AI
D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed; D003855:Deoxyribose / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D019098:Telomerase / Q000502:physiology*; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D003855:Deoxyribose; D020122:tert-Butylhydroperoxide; D019098:Telomerase