title: α-Tocopherol at nanomolar concentration protects PC12 cells from hydrogen peroxide-induced death and modulates protein kinase activities.
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 H(2)O(2)-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 H(2)O(2)-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 H(2)O(2) 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 H(2)O(2). Inhibitors of MEK 1/2, PI 3-kinase and protein kinase C (PKC) diminished the protective effect of α-tocopherol against H(2)O(2)-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 H(2)O(2)-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 H(2)O(2) in PC12 cells makes contribution to its protective effect, while total inhibition of these enzymes is not protective.
authors.affiliation: Department of Comparative Neurochemistry, Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, Thorez avenue, 44, Saint-Petersburg 194223, Russia.
authors.forename: Irina O
authors.initials: IO
authors.lastname: Zakharova
authors.affiliation: Department of Comparative Neurochemistry, Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, Thorez avenue, 44, Saint-Petersburg 194223, Russia.
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Sokolova
authors.affiliation: Department of Comparative Neurochemistry, Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, Thorez avenue, 44, Saint-Petersburg 194223, Russia.
authors.forename: Liubov V
authors.initials: LV
authors.lastname: Bayunova
authors.affiliation: Department of Comparative Neurochemistry, Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, Thorez avenue, 44, Saint-Petersburg 194223, Russia.
authors.forename: Yulia A
authors.initials: YA
authors.lastname: Vlasova
authors.affiliation: Department of Comparative Neurochemistry, Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, Thorez avenue, 44, Saint-Petersburg 194223, Russia.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Rychkova
authors.affiliation: Department of Comparative Neurochemistry, Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, Thorez avenue, 44, Saint-Petersburg 194223, Russia.
authors.forename: Natalia F
authors.initials: NF
authors.lastname: Avrova
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D000081082:Phosphoinositide-3 Kinase Inhibitors; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D024502:alpha-Tocopherol
keywords: Akt; MEK/ERK signaling pathway; PC12 cells; anti-apoptotic compound; oxidative stress; physiological concentrations; α-tocopherol