IJMS, Vol. 18, Pages 216: ?-Tocopherol at Nanomolar Concentration Protects Cortical Neurons against Oxidative Stress (International Journal of Molecular Sciences)

The aim of the present work is to study the mechanism of the ?-tocopherol (?-T) protective action at nanomolar and micromolar concentrations against H2O2-induced brain cortical neuron death. The mechanism of ?-T action on neurons at its nanomolar concentrations characteristic for brain extracellular space has not been practically studied yet. Preincubation with nanomolar and micromolar ?-T for 18 h was found to increase the viability of cortical neurons exposed to H2O2; ?-T effect was concentration-dependent in the nanomolar range. However, preincubation with nanomolar ?-T for 30 min was not effective. Nanomolar and micromolar ?-T decreased the reactive oxygen species accumulation induced in cortical neurons by the prooxidant. Using immunoblotting it was shown that preincubation with ?-T at nanomolar and micromolar concentrations for 18 h prevented Akt inactivation and decreased PKC? activation induced in cortical neurons by H2O2. ?-T prevented the ERK1/2 sustained activation during 24 h caused by H2O2. ?-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 H2O2. The similar neuron protection mechanism by nanomolar and micromolar ?-T suggests that a `more is better` approach to patients` supplementation with vitamin E or ?-T is not reasonable.