TY - JOUR
T1 - Ganglioside GD3 and its mimetics induce cytochrome c release from mitochondria
AU - Inoki, Yutaka
AU - Miura, Tsuyoshi
AU - Kajimoto, Tetsuya
AU - Kawase, Mitsuo
AU - Kawase, Yuji
AU - Yoshida, Yasuko
AU - Tsuji, Shuichi
AU - Kinouchi, Tadatoshi
AU - Endo, Hitoshi
AU - Kagawa, Yasuo
AU - Hamamoto, Toshiro
N1 - Funding Information:
We thank Mr. Shuichi Yanahira (Technology and Research Institute, Snow Brand Milk Product Co., Ltd.) for kindly providing us with ganglioside GD3. This work was supported by the following grants: Grants-in-Aid for Scientific Research on Priority Areas, Nos. 10152263, 10178104, and 10178105, and for Scientific Research, 09680639, 10670126, and 10134231 from the Ministry of Education of Japan.
PY - 2000/10/5
Y1 - 2000/10/5
N2 - 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. (C) 2000 Academic Press.
AB - 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. (C) 2000 Academic Press.
KW - Apoptosis
KW - Cystein protease
KW - Cytochrome c
KW - Gangliosides
KW - Mitochondrial permeability transition
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U2 - 10.1006/bbrc.2000.3601
DO - 10.1006/bbrc.2000.3601
M3 - Article
C2 - 11027612
AN - SCOPUS:0034610054
VL - 276
SP - 1210
EP - 1216
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -