title: α-Tocopherol at Nanomolar Concentration Protects Cortical Neurons against Oxidative Stress.
abstract: The aim of the present work is to study the mechanism of the α-tocopherol (α-T) protective action at nanomolar and micromolar concentrations against H₂O₂-induced brain cortical neuron death. The mechanism of α-T action on neurons at its nanomolar concentrations characteristic for brain extracellular space has not been practically studied yet. Preincubation with nanomolar and micromolar α-T for 18 h was found to increase the viability of cortical neurons exposed to H₂O₂; α-T effect was concentration-dependent in the nanomolar range. However, preincubation with nanomolar α-T for 30 min was not effective. Nanomolar and micromolar α-T decreased the reactive oxygen species accumulation induced in cortical neurons by the prooxidant. Using immunoblotting it was shown that preincubation with α-T at nanomolar and micromolar concentrations for 18 h prevented Akt inactivation and decreased PKCδ activation induced in cortical neurons by H₂O₂. α-T prevented the ERK1/2 sustained activation during 24 h caused by H₂O₂. α-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 α-T suggests that a "more is better" approach to patients' supplementation with vitamin E or α-T is not reasonable.
authors.affiliation: Department of Molecular Endocrinology and Neurochemistry, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Thorez avenue, 44, Saint-Petersburg 194223, Russia. zakhar@iephb.ru.
authors.forename: Irina O
authors.initials: IO
authors.lastname: Zakharova
authors.affiliation: Department of Molecular Endocrinology and Neurochemistry, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Thorez avenue, 44, Saint-Petersburg 194223, Russia. sokolt1956@mail.ru.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Sokolova
authors.affiliation: Department of Molecular Endocrinology and Neurochemistry, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Thorez avenue, 44, Saint-Petersburg 194223, Russia. yousia@mail.ru.|Preventive Medicine Department, Mechnikov North-West StateMedical University, Saint-Petersburg, Kirochnaya ul. 41, Saint-Petersburg 191015, Russia. yousia@mail.ru.
authors.forename: Yulia A
authors.initials: YA
authors.lastname: Vlasova
authors.affiliation: Department of Molecular Endocrinology and Neurochemistry, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Thorez avenue, 44, Saint-Petersburg 194223, Russia. bayunoval@mail.ru.
authors.forename: Liubov V
authors.initials: LV
authors.lastname: Bayunova
authors.affiliation: Department of Molecular Endocrinology and Neurochemistry, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Thorez avenue, 44, Saint-Petersburg 194223, Russia. involved@mail.ru.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Rychkova
authors.affiliation: Department of Molecular Endocrinology and Neurochemistry, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Thorez avenue, 44, Saint-Petersburg 194223, Russia. avrova@iephb.ru.
authors.forename: Natalia F
authors.initials: NF
authors.lastname: Avrova
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000473:pathology*; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009474:Neurons / Q000473:pathology*; D000066829:Neuroprotection / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051745:Protein Kinase C-delta / Q000378:metabolism; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051745:Protein Kinase C-delta; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D024502:alpha-Tocopherol
keywords: Akt; Bax/Bcl-2 ratio; ERK1/2; H2O2; brain cortical neurons; nanomolar and micromolar concentrations; protein kinase Cδ; reactive oxygen species; viability; α-tocopherol