Role of alpha-tocopherol in the regulation of mitochondrial permeability transition.
We previously showed that Ca2+-induced cyclosporin A-sensitive membrane permeability transition (MPT) of mitochondria occurred with concomitant generation of reactive oxygen species (ROS) and release of cytochrome c (Free Rad. Res.38, 29-35, 2004). To elucidate the role of alpha-tocopherol in MPT, we investigated the effect of alpha-tocopherol on mitochondrial ROS generation, swelling and cytochrome c release induced by Ca2+ or hydroxyl radicals. Biochemical analysis revealed that alpha-tocopherol suppressed Ca2+-induced ROS generation and oxidation of critical thiol groups of mitochondrial adenine nucleotide translocase (ANT) but not swelling and cytochrome c release. Hydroxyl radicals also induced cyclosporin A-sensitive MPT of mitochondria. alpha-Tocopherol suppressed the hydroxyl radical-induced lipid peroxidation, swelling and cytochrome c release from mitochondria. These results indicate that alpha-tocopherol inhibits ROS generation, ANT oxidation, lipid peroxidation and the opening of MPT, thereby playing important roles in the prevention of oxidative cell death.
Yorimitsu
Masae
M
Institute of Medical Science, Kurashiki Medical Center, Kurashiki, Japan.
Muranaka
Shikibu
S
Sato
Eisuke F
EF
Fujita
Hirofumi
H
Abe
Kouichi
K
Yasuda
Tatsuji
T
Inoue
Masayasu
M
Utsumi
Kozo
K
D002118:Calcium / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology*
D017382:Reactive Oxygen Species; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D024502:alpha-Tocopherol; D002118:Calcium