Ganglioside GD3 and its mimetics induce cytochrome c release from mitochondria.
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.
Inoki
Y
Y
Research Institute of Life Science, Tochigi, 329-05, Japan.
Miura
T
T
Kajimoto
T
T
Kawase
M
M
Kawase
Y
Y
Yoshida
Y
Y
Tsuji
S
S
Kinouchi
T
T
Endo
H
H
Kagawa
Y
Y
Hamamoto
T
T
D000818:Animals; D015153:Blotting, Western; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002474:Cell-Free System; D016572:Cyclosporine / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D005732:Gangliosides / Q000494:pharmacology*; D007473:Ion Channels; D007976:Leupeptins / Q000494:pharmacology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D018716:Molecular Mimicry; D009840:Oligomycins / Q000494:pharmacology; D051381:Rats
C415867:CI 22; D015853:Cysteine Proteinase Inhibitors; D003574:Cytochrome c Group; D005732:Gangliosides; D007473:Ion Channels; D007976:Leupeptins; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009840:Oligomycins; C415866:TMS 42; C031004:oligomycin A; C063261:acetylleucyl-leucyl-norleucinal; C021298:ganglioside, GD1a; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D004533:Egtazic Acid; C026226:ganglioside, GD3; D016572:Cyclosporine; D003546:Cysteine Endopeptidases