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Journal archive > 2012 > N 6 November-December

EFFECTS OF ?-TOCOPHEROL AND ITS ANOLOGUES ON RAT THYMOCYTES
PROGRAMMED DEATH INDUCED BY PROTEIN KINASE INHIBITORS

G. V. Petrova, N. V. Delemenchuk, G. V. Donchenko

Palladin Institute of Вiochemistry, National Academy of Sciences of Ukraine, Kyiv;
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It is established that ?-tocopherol (?-ТPh) shows cytoprotective effect at the induction of rats’ thymocytes apoptosis by endocellular protein kinase inhibitors – staurosporine and phorbol ether in high concentration, and also on necrosis of the cells caused by sphyngosine. The effect of ?-ТPh on thymocytes death caused by protein phosphatase type 2А inhibitor ocadaic acid is much less expressed. The obtained data testify that the known ability of ?-ТPh to the inhibition of PKC and to the activation of protein phosphatase type 2А is not the main mechanism of its cytoprotective action. Partial reproduction of ?-ТPh effects by its analogue ?-tocopheryl acetate which is not capable to enter in redox reactions, and the absence of influence on the studied processes of an antioxidant of N acetyl-L-cysteine do not confirm the antioxidant mechanism of ?-ТPh action in this case. The inhibition by ?-ТPh of the release of cytochrome c in the cytosol of cells testifies to the implementation of its cytoprotective effect at the level of mitochondrial membranes. We assume the existence of the universal mechanism of ?-ТPh cytoprotective action that does not depend on the nature of apoptogenes and realized on the general for the majori­ty of them stage of the cells death induction. The prevention by ?-ТPh of mitochondria dysfunction by stabilizing mitochondrial membranes and reduction of their permeabilization is supposed as that.

Key words: ?-tocopherol, apoptosis, necrosis, thymocytes, protein kinase C, mitochondria.

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

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