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Journal archive > 2006 > N 4 July-August

PROAPOPTOTIC ACTION OF ?-TOCOPHERYL SUCCINATE IN RAT THYMOCYTES
IS CONDITIONED BY THE INHIBITION OF MITOCHONDRIAL
SUCCINATE DEHYDROGENASE

G. V. Petrova

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
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It has been established that ?-tocopheryl succinate in concenrations 10–100 µM 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 ?-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 ?-tocopheryl succinate and seems to be an important event triggering the apoptotic response by it. It was supposed that ?-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.

Key words: ?-tocopheryl succinate, mitochondrial succinate dehydrogenase, apoptosis, thymocytes.

The original article in Russian is available for download in PDF format.

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