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

Abstract

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.