Differential effects of catalase on apoptosis induction in human promonocytic cells. Relationships with heat-shock protein expression.
The administration of the H(2)O(2)-specific scavenger catalase attenuated the generation of apoptosis by the antitumor drugs etoposide, camptothecin, doxorubicin, and cisplatin in U-937 human promonocytic cells. By contrast, the antioxidant potentiated the generation of apoptosis by the inducers of the stress response, heat shock and cadmium, in this and other myeloid cell types. Catalase also increased the heat shock-provoked stimulation of caspase-3 and -9 activities, as well as the release of cytochrome c from mitochondria to the cytosol. The potentiation of cell death by catalase correlated with its capacity to inhibit the stress response, as demonstrated by the suppression of 70- or 27-kDa heat-shock protein expression and the inhibition of heat-shock transcription factor 1 binding activity. Conversely, the toxicity of catalase plus heat shock was attenuated when the cells were preconditioned with a soft heating, which elevated the 70-kDa heat-shock protein levels. By contrast with catalase, the antioxidants superoxide dismutase and probucol did not inhibit heat-shock protein expression or affect apoptosis in U-937 cells. Finally, it was observed that the antitumor drugs did not activate the stress response in U-937 cells and that catalase failed to inhibit HSP expression and to potentiate apoptosis in heat shock-treated RPMI 8866 lymphoblastic cells. Taken together, these results provide the first demonstration of a proapoptotic action of catalase, suggest that H(2)O(2) is a critical regulator of both apoptosis and the stress response, and corroborate the antiapoptotic action of heat-shock proteins in myeloid cells.
Sancho
Patricia
P
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Troyano
Alfonso
A
Fernández
Carlos
C
De Blas
Elena
E
Aller
Patricio
P
D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002374:Catalase / Q000494:pharmacology*; D003574:Cytochrome c Group / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020298:U937 Cells
D003574:Cytochrome c Group; D006360:Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D002374:Catalase; D020169:Caspases