Caspase-dependent and -independent events in apoptosis induced by hydrogen peroxide.
To define the role of caspase-3 in H2O2-induced apoptosis, we introduced caspase-3 cDNA into MCF-7 breast carcinoma cells that otherwise lack caspase-3 expression. H2O2 treatment induced DNA fragmentation and nuclear condensation in the caspase-3-expressing cells, but not in the caspase-3-deficient cells. This indicated that caspase-3 is essential for nuclear events. However, H2O2 induced an externalization of membrane phosphatidylserine (PS) and cell death regardless of caspase-3 expression. These events were not suppressed by Ac-DEVD-CHO and Z-VAD-fmk, which inhibit DEVD-specific caspases and a broad spectrum of caspases, respectively. In Jurkat T cells, these inhibitors abolished H2O2-induced PS relocalization, but not cell death. Therefore, caspases appear to be dispensable for lethality by H2O2, but required for PS redistribution in a cell-type-specific manner.
Kim
D K
DK
Laboratory of Cell Biology, Yonsei Medical Research Center, Seoul, Korea.
Cho
E S
ES
Um
H D
HD
D017302:Annexins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis / Q000235:genetics*; D053938:DNA Fragmentation / Q000187:drug effects / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D019169:Jurkat Cells; D016877:Oxidants / Q000494:pharmacology*; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
D017302:Annexins; D018076:DNA, Complementary; D016877:Oxidants; D006861:Hydrogen Peroxide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases