Alpha-tocopherol prevents a dramatic oxidative stress-induced decline of the Bcl-2 concentration in cortical neurons

We have shown that the protective effect of the prolonged (18 hours) incubation of cortical neurons with alpha-tocopherol (alpha-T) prior the action of H2O2 depends on the concentration in the nanomolar range (100 nM > 10 nM > 1 nM). The higher concentrations of alpha-T (1, 10, and 100 μM) increased the viability of cortical cells approximately equally to 100 nM alpha-T. We found that H2O2 has little effect on the concentration of the anti-apoptotic protein Bcl-2 in mitochondria of the neurons of the cerebral cortex during the first hours of its impact, but causes a dramatic decrease in its level in 12 and 24 hours after the start of its effect in comparison with the baseline values. If neurons are subjected to a prolonged (18 hours) preincubation with 100 nM or 100 μM alpha-T, the concentration of Bcl-2 12 and 24 hours after the application of H2O2 do not differ from the control values; however, it is higher than the concentration of Bcl-2 in neurons after exposure to H2O2 only. The level of the proapoptotic protein Bax in cortical neurons did not undergo prominent changes in the presence of H2O2 and alpha-T. A pronounced significant increase in the Bax/Bcl-2 ratio was found in neurons of the cerebral cortex at 12 and 24 hours after the start of the H2O2 effect on neurons of the cerebral cortex. Such prolonged incubation of neurons with 100 nM and 100 μM alpha-T prior to the H2O2 application normalizes these parameters and reduces the Bax/Bcl-2 ratio to the control values.