Int. J. Mol. Sci. 2012, 13(9), 11543-11568; doi:10.3390/ijms130911543
Article

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

Received: 9 July 2012; in revised form: 23 August 2012 / Accepted: 4 September 2012 / Published: 14 September 2012
(This article belongs to the Special Issue Neuroprotective Strategies 2012)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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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MDPI and ACS Style

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.

AMA Style

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.

Chicago/Turabian Style

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.

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