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

作者：Zakharova Irina O; Sokolova Tatiana V; Vlasova Yulia A; Bayunova Liubov V; Rychkova Maria P; Avrova Natalia F^*

来源：International Journal of Molecular Sciences, 2017, 18(1): 216.

DOI：10.3390/ijms18010216

• brain cortical neurons
• H2O2
• alpha-tocopherol
• nanomolar and micromolar concentrations
• viability
• reactive oxygen species
• ERK1/2
• Akt
• protein kinase C delta
• Bax/Bcl-2 ratio

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 H2O2-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 H2O2; 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 H2O2. alpha-T prevented the ERK1/2 sustained activation during 24 h caused by H2O2. 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 H2O2. 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.

• 出版日期2017-1