Alpha-tocotrienol provides the most potent neuroprotection among vitamin E analogs on cultured striatal neurons.
Oxidative stress and apoptosis play pivotal roles in the pathogenesis of neurodegenerative diseases. We investigated the effects of vitamin E analogs on oxidative stress and apoptosis using primary neuronal cultures of rat striatum. A tocotrienol-rich fraction of edible oil derived from palm oil (Tocomin 50%), which contains alpha-tocopherol, and alpha-, gamma- and delta-tocotrienols, significantly inhibited hydrogen peroxide (H2O2)-induced neuronal death. Each of the tocotrienols, purified from Tocomin 50% by high-performance liquid chromatography, significantly attenuated H2O2-induced neurotoxicity, whereas alpha-tocopherol did not. alpha-, gamma- and delta-Tocotrienols also provided significant protection against the cytotoxicity of a superoxide donor, paraquat, and nitric oxide donors, S-nitrosocysteine and 3-morpholinosydnonimine. Moreover, tocotrienols blocked oxidative stress-mediated cell death with apoptotic DNA fragmentation caused by an inhibitor of glutathione synthesis, L-buthionine-[S,R]-sulfoximine. In addition, alpha-tocotrienol, but not gamma- or delta-tocotrienol, prevented oxidative stress-independent apoptotic cell death, DNA cleavage and nuclear morphological changes induced by a non-specific protein kinase inhibitor, staurosporine. These findings suggest that alpha-tocotrienol can exert anti-apoptotic neuroprotective action independently of its antioxidant property. Among the vitamin E analogs examined, alpha-tocotrienol exhibited the most potent neuroprotective actions in rat striatal cultures.
Osakada
Fumitaka
F
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Hashino
Asami
A
Kume
Toshiaki
T
Katsuki
Hiroshi
H
Kaneko
Shuji
S
Akaike
Akinori
A
D000818:Animals; D000963:Antimetabolites / Q000037:antagonists & inhibitors / Q000633:toxicity; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006690:Bisbenzimidazole; D019328:Buthionine Sulfoximine / Q000037:antagonists & inhibitors / Q000633:toxicity; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005456:Fluorescent Dyes; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017072:Neostriatum / Q000166:cytology* / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D019311:Staurosporine / Q000037:antagonists & inhibitors / Q000633:toxicity; D013778:Tetrazolium Salts; D013844:Thiazoles; D024508:Tocotrienols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000963:Antimetabolites; D000975:Antioxidants; D002273:Carcinogens; D005456:Fluorescent Dyes; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D024508:Tocotrienols; D014810:Vitamin E; D019328:Buthionine Sulfoximine; C082032:tocotrienol, alpha; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue; D019311:Staurosporine; D006690:Bisbenzimidazole