Alpha-tocopherol prevents apoptosis of vascular endothelial cells via a mechanism exceeding that of mere antioxidation.
Alpha-tocopherol has been reported to exert an anti-atherogenesis effect. We attempted to clarify the effect of alpha-tocopherol-both as an antioxidant and as a nonantioxidant--on apoptosis induced by oxidized low-density lipoprotein (LDL) or oxysterols. Oxidized LDL and oxysterols induced necrosis and/or apoptosis of vascular endothelial cells. The induction of apoptosis was associated with increased caspase-3 activity and the generation of intracellular reactive oxygen species, both the effects of which were attenuated by alpha-tocopherol. Apoptosis was also decreased by beta-tocopherol or intracellular radical scavengers, but these suppressive effects were less than those of alpha-tocopherol. Neither beta-tocopherol nor the scavengers had pronounced effect on caspase-3 activity, but each of them decreased the generation of reactive oxygen species to the same extent as alpha-tocopherol. Our study suggests that alpha-Toc protects against apoptosis not only by scavenging reactive oxygen species, but also by inhibiting caspase activity, which means that its activity may exceed that of a mere antioxidant.
Uemura
Manabu
M
First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kamigyo, Japan. max1@d4.dion.ne.jp
Manabe
Hiroki
H
Yoshida
Norimasa
N
Fujita
Noriko
N
Ochiai
Jun
J
Matsumoto
Naohisa
N
Takagi
Tomohisa
T
Naito
Yuji
Y
Yoshikawa
Toshikazu
T
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D007653:Ketocholesterols / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology; D009336:Necrosis; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D024502:alpha-Tocopherol / Q000494:pharmacology*
D000975:Antioxidants; D006888:Hydroxycholesterols; D007653:Ketocholesterols; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; C011724:cholest-5-en-3 beta,7 alpha-diol; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D024502:alpha-Tocopherol; C003001:7-ketocholesterol