[alpha]-Tocopherol at Nanomolar Concentration Protects Cortical Neurons against Oxidative Stress

The aim of the present work is to study the mechanism of the [alpha]-tocopherol ([alpha]-T) protective action at nanomolar and micromolar concentrations against H sub(2) O sub(2)-induced brain cortical neuron death. The mechanism of [alpha]-T action on neurons at its nanomolar concentrations characteristic for brain extracellular space has not been practically studied yet. Preincubation with nanomolar and micromolar [alpha]-T for 18 h was found to increase the viability of cortical neurons exposed to H sub(2) O sub(2); [alpha]-T effect was concentration-dependent in the nanomolar range. However, preincubation with nanomolar [alpha]-T for 30 min was not effective. Nanomolar and micromolar [alpha]-T decreased the reactive oxygen species accumulation induced in cortical neurons by the prooxidant. Using immunoblotting it was shown that preincubation with [alpha]-T at nanomolar and micromolar concentrations for 18 h prevented Akt inactivation and decreased PKC[delta] activation induced in cortical neurons by H sub(2) O sub(2). [alpha]-T prevented the ERK1/2 sustained activation during 24 h caused by H sub(2) O sub(2). [alpha]-T at nanomolar and micromolar concentrations prevented a great increase of the proapoptotic to antiapoptotic proteins (Bax/Bcl-2) ratio, elicited by neuron exposure to H sub(2) O sub(2). The similar neuron protection mechanism by nanomolar and micromolar [alpha]-T suggests that a "more is better" approach to patients' supplementation with vitamin E or [alpha]-T is not reasonable.