Photodynamic therapy: a mitochondrial inducer of apoptosis.
Photodamage to the mitochondria of murine leukemia P388 cells resulted in immediate loss of the mitochondrial membrane potential together with the release of cytochrome c into the cytosol. This was followed by a rapid activation of caspase 3-like proteases, as indicated by a marked rise in DEVDase activity. There was no significant effect on WEHDase or VEIDase activities, suggesting that only the late-stage caspases had been effected. The apoptotic response to mitochondrial photodamage was abolished by the broad-spectrum caspase inhibitor zVAD-fmk, but this did not prevent loss of viability after mitochondrial photodamage. These studies indicate that the release of cytochrome c from photodamaged mitochondria is sufficient to directly initiate a caspase-dependent apoptotic response.
Kessel
D
D
Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. dhkessel@med.wayne.edu
Luo
Y
Y
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000528:radiation effects; D003574:Cytochrome c Group / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000528:radiation effects; D051379:Mice; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000528:radiation effects*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000590:Amino Acid Chloromethyl Ketones; D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D017319:Photosensitizing Agents; D011166:Porphyrins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C051407:porphycene; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D019311:Staurosporine