oligomycins and acetylleucyl-leucyl-norleucinal

Ganglioside GD3 induced the release of cytochrome c from isolated rat liver mitochondria. This process was completely prevented by cyclosporin A and partially prevented by a cysteine protease inhibitor, n-acetyl-leu-leu-norleucinal. Cyclosporin A is a potent inhibitor of the permeability transition pore, whereas n-acetyl-leu-leu-norleucinal has no effect on this pore. These results indicate that the release of cytochrome c from mitochondria requires both the opening of the permeability transition pore and a cysteine protease inhibitor-sensitive mechanism. Gangliosides GD1a, GD1b, GT1b, and GQ1b along with the synthetic GD3 mimetics TMS-42 and CI-22, which are glycerophospholipids carrying a disialo residue, also induced cytochrome c release. In contrast, gangliosides GM1, GM2, and GM3 did not induce cytochrome c release. These results indicate that two sialo residues must play an important role in the induction of cytochrome c release by gangliosides.

Topics: Animals; Blotting, Western; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; Cell-Free System; Cyclosporine; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; Cytochrome c Group; Dose-Response Relationship, Drug; Egtazic Acid; Gangliosides; Ion Channels; Leupeptins; Membrane Proteins; Mitochondria, Liver; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Molecular Mimicry; Oligomycins; Rats