α-Tocopherol at Nanomolar Concentration Protects PC12 Cells from Hydrogen Peroxide-Induced Death and Modulates Protein Kinase Activities

International Journal of Molecular Sciences

Irina O. Zakharova¹  Tatyana V. Sokolova¹  Liubov V. Bayunova¹  Yulia A. Vlasova¹  Maria P. Rychkova¹ 

[1] Department of Comparative Neurochemistry, Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, Thorez avenue, 44, Saint-Petersburg 194223, Russia;

关键词: α-tocopherol;    physiological concentrations;    PC12 cells;    oxidative stress;    anti-apoptotic compound;    MEK/ERK signaling pathway;    Akt;   

DOI  :  10.3390/ijms130911543

来源: mdpi

【 摘 要 】

The aim of this work was to compare protective and anti-apoptotic effects of α-tocopherol at nanomolar and micromolar concentrations against 0.2 mM H₂O₂-induced toxicity in the PC12 neuronal cell line and to reveal protein kinases that contribute to α-tocopherol protective action. The protection by 100 nM α-tocopherol against H₂O₂-induced PC12 cell death was pronounced if the time of pre-incubation with α-tocopherol was 3–18 h. For the first time, the protective effect of α-tocopherol was shown to depend on its concentration in the nanomolar range (1 nM < 10 nM < 100 nM), if the pre-incubation time was 18 h. Nanomolar and micromolar α-tocopherol decreased the number of PC12 cells in late apoptosis induced by H₂O₂ to the same extent if pre-incubation time was 18 h. Immunoblotting data showed that α-tocopherol markedly diminished the time of maximal activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) and protein kinase B (Akt)-induced in PC12 cells by H₂O₂. Inhibitors of MEK 1/2, PI 3-kinase and protein kinase C (PKC) diminished the protective effect of α-tocopherol against H₂O₂-initiated toxicity if the pre-incubation time was long. The modulation of ERK 1/2, Akt and PKC activities appears to participate in the protection by α-tocopherol against H₂O₂-induced death of PC12 cells. The data obtained suggest that inhibition by α-tocopherol in late stage ERK 1/2 and Akt activation induced by H₂O₂ in PC12 cells makes contribution to its protective effect, while total inhibition of these enzymes is not protective.

【 授权许可】

CC BY   
© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.