[Effects of alpha-tocopherol and its anologues on rat thymocytes programmed death induced by protein kinase...

It is established that alpha-tocopherol (alpha-TPh) 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 alpha-TPh on thymocytes death caused by protein phosphatase type 2A inhibitor ocadaic acid is much less expressed. The obtained data testify that the known ability of alpha-TPh to the inhibition of PKC and to the activation of protein phosphatase type 2A is not the main mechanism of its cytoprotective action. Partial reproduction of alpha-TPh effects by its analogue alpha-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 alpha-TPh action in this case. The inhibition by alpha-TPh 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 alpha-TPh 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 alpha-TPh of mitochondria dysfunction by stabilizing mitochondrial membranes and reduction of their permeabilization is supposed as that.