Cytochrome c is dispensable for fas-induced caspase activation and apoptosis.
Cytochrome c is thought to play an important role in the initiation of apoptosis following its release from mitochondria. It is controversial whether such release is also involved in caspase activation and apoptotic cell death after ligation of the cell surface molecule Fas. We addressed this issue by investigating cells from the human cell lines Jurkat and SKW6 which had been treated with the inhibitor of the mitochondrial F0/F1-ATPase, oligomycin. Oligomycin-treatment led, over a wide range of concentrations, to ATP-depletion and, at similar concentrations, abrogated the appearance of caspase-3-like activity caused by stauroporine. Electroporation of cytochrome c protein into intact cells induced caspase activation in both cell lines and significant nuclear apoptosis in Jurkat cells. In ATP-depleted cells, electroporation of cytochrome c induced neither caspase activation nor nuclear fragmentation. Fas-induced caspase activation and nuclear apoptosis, however, were unaffected by the depletion of ATP. Thus, cytochrome c is unlikely to be an important factor in Fas-induced cell death.
Vier
J
J
Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Trogerstrasse 9, Munich, 81675, Germany.
Linsinger
G
G
Häcker
G
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism*; D003374:Coumarins / Q000378:metabolism; D003574:Cytochrome c Group / Q000008:administration & dosage / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D018274:Electroporation; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D009840:Oligomycins / Q000494:pharmacology; D009842:Oligopeptides / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*
D003374:Coumarins; D003574:Cytochrome c Group; D009840:Oligomycins; D009842:Oligopeptides; C102580:acetyl-aspartyl-glutamyl-valyl-aspartyl-amino-4-methylcoumarin; D019014:fas Receptor; D000255:Adenosine Triphosphate; D020169:Caspases; D006180:Proton-Translocating ATPases; D019311:Staurosporine