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α-Tocopherol at Nanomolar Concentration Protects PC12 Cells from Hydrogen Peroxide-Induced Death and Modulates Protein Kinase Activities
Department of Comparative Neurochemistry, Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, Thorez avenue, 44, Saint-Petersburg 194223, Russia
* Author to whom correspondence should be addressed.
Received: 9 July 2012; in revised form: 23 August 2012 / Accepted: 4 September 2012 / Published: 14 September 2012
Abstract: 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.
Keywords: α-tocopherol; physiological concentrations; PC12 cells; oxidative stress; anti-apoptotic compound; MEK/ERK signaling pathway; Akt
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Zakharova, I.O.; Sokolova, T.V.; Bayunova, L.V.; Vlasova, Y.A.; Rychkova, M.P.; Avrova, N.F. α-Tocopherol at Nanomolar Concentration Protects PC12 Cells from Hydrogen Peroxide-Induced Death and Modulates Protein Kinase Activities. Int. J. Mol. Sci. 2012, 13, 11543-11568.
Zakharova IO, Sokolova TV, Bayunova LV, Vlasova YA, Rychkova MP, Avrova NF. α-Tocopherol at Nanomolar Concentration Protects PC12 Cells from Hydrogen Peroxide-Induced Death and Modulates Protein Kinase Activities. International Journal of Molecular Sciences. 2012; 13(9):11543-11568.
Zakharova, Irina O.; Sokolova, Tatyana V.; Bayunova, Liubov V.; Vlasova, Yulia A.; Rychkova, Maria P.; Avrova, Natalia F. 2012. "α-Tocopherol at Nanomolar Concentration Protects PC12 Cells from Hydrogen Peroxide-Induced Death and Modulates Protein Kinase Activities." Int. J. Mol. Sci. 13, no. 9: 11543-11568.