Mutant H-ras overexpression inhibits drug and U.V. induced apoptosis.
Various studies have shown that oncogene and oncosuppressor gene activity can enhance or suppress programmed cell death (apoptosis) in various cell systems. Recent data indicates that overexpression of activated H-ras could influence that onset of apoptosis. We investigated the role of activated H-ras in the apoptotic cell death of rat fibroblast lines. We found that forced overexpression of H-ras induced resistance to U.V. and drug induced apoptosis. We examined possible mechanisms for the action of H-ras in resistance to apoptosis. It was found that both ras transfected and ras untransfected lines displayed similar endonuclease activities. In addition, it was found that the irradiated ras transfected line showed inhibited production of peroxides compared to the irradiated ras untransfected line. Drug induced apoptosis did not appear to involve peroxide production. In addition the antioxidant compound PDTC, was found to inhibit U.V. induced apoptosis but not drug induced apoptosis. In addition, we found the ras transfected line to possess elevated levels of catalase compared to the parent untransfected line. Thus we suggest that an anti-oxidant mechanism, possibly mediated by forced overexpression of activated H-ras could protect cells from apoptosis.
Fernandes
R S
RS
Department of Biochemistry, University College Cork, Ireland.
McGowan
A J
AJ
Cotter
T G
TG
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002166:Camptothecin / Q000494:pharmacology*; D002460:Cell Line; D004247:DNA / Q000032:analysis; D003609:Dactinomycin / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology*; D005347:Fibroblasts; D005434:Flow Cytometry; D015870:Gene Expression; D011905:Genes, ras; D006801:Humans; D007700:Kinetics; D016296:Mutagenesis; D051381:Rats; D013997:Time Factors; D014466:Ultraviolet Rays
D000970:Antineoplastic Agents; D003609:Dactinomycin; D005047:Etoposide; D004247:DNA; D002166:Camptothecin