benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone and porphycene

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.

Topics: Amino Acid Chloromethyl Ketones; Animals; Apoptosis; Caspase 3; Caspases; Cell Survival; Cytochrome c Group; Enzyme Inhibitors; Kinetics; Membrane Potentials; Mice; Microscopy, Fluorescence; Mitochondria; Photochemotherapy; Photosensitizing Agents; Porphyrins; Staurosporine; Tumor Cells, Cultured