[Proapoptotic action of alpha-tocopheryl succinate in rat thymocytes is conditioned by the inhibition of mitochondrial succinate dehydrogenase].
It has been established that alpha-tocopheryl succinate in concenrations 10-100 microM inhibits in a dose-dependent manner the viability of primary culture rats thymocytes and causes the DNA internucleosomal degradation that testifies to apoptotic way of thymocytes destruction. These effects were accompanied by an enhanced production of intracellular superoxide. This is the first report demonstrating that apoptosis induced by alpha-tocopheryl succinate was accompanied by a dose-dependent inhibition of mitochondrial succinate dehydrogenase. Known apoptosis inducers--actinomicin D, staurosporin and hydrogen peroxide decreased a cell survival but neither induced any significant changes in succinate dehydrogenase activity which means that this effect is characteristic only of alpha-tocopheryl succinate and seems to be an important event triggering the apoptotic response by it. It was supposed that alpha-tocopheryl succinate might appear as a pseudosubstrate for mitochondrial succinate dehydrogenase leading to its inhibition, dysfunction of the mitochondrial electron transport chain, generation of reactive oxygen species and iduction of apoptosis.
Petrova
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GV
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D051381:Rats; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors*; D013481:Superoxides / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D013481:Superoxides; D014810:Vitamin E; D013385:Succinate Dehydrogenase; D024505:Tocopherols