title: A transient treatment of hippocampal neurons with alpha-tocopherol induces a long-lasting protection against oxidative damage via a genomic action.
abstract: Neuroprotection exerted by alpha-tocopherol against oxidative stress was investigated in cultured rat hippocampal neurons. In addition to its direct action as a radical scavenger revealed at concentrations above 10 microM, a transient application of 1 microM alpha-tocopherol phosphate (alpha-TP) to neurons induced a complete delayed long-lasting protection against oxidative insult elicited by exposure to Fe2+ ions, but not against excitotoxicity. A minimal 16-h application of alpha-TP was required to observe the protection against subsequent oxidative stress. This delayed protection could last up to a week after the application of alpha-TP, even when medium was changed after the alpha-TP treatment. Cycloheximide, added either 2 h before or together with alpha-TP, prevented the delayed neuroprotection, but not the acute. However, cycloheximide applied after the 16-h alpha-TP pretreatment did not alter the delayed neuroprotection. Neither Trolox, a cell-permeant analogue of alpha-tocopherol, nor other antioxidants, such as epigallocatechin-gallate and N-acetyl-L-cysteine, elicited a similar long-lasting protection. Only tert-butylhydroquinone could mimic the alpha-TP effect. Depletion of glutathione (GSH) by L-buthionine sulfoximine did not affect the delayed alpha-TP protection. Thus, in addition to its acute anti-radical action, alpha-TP induces a long-lasting protection of neurons against oxidative damage, via a genomic action on antioxidant defenses apparently unrelated to GSH biosynthesis.
authors.affiliation: Laboratory Cerebral Plasticity, FRE 2693 CNRS, University Montpellier II, 34095 Montpellier Cedex 05, France.
authors.forename: Marie Céleste
authors.initials: MC
authors.lastname: de Jesus Ferreira
authors.forename: Nadine
authors.initials: N
authors.lastname: Crouzin
authors.forename: Gérard
authors.initials: G
authors.lastname: Barbanel
authors.forename: Catherine
authors.initials: C
authors.lastname: Cohen-Solal
authors.forename: Max
authors.initials: M
authors.lastname: Récasens
authors.forename: Michel
authors.initials: M
authors.lastname: Vignes
authors.forename: Janique
authors.initials: J
authors.lastname: Guiramand
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003513:Cycloheximide / Q000633:toxicity; D016166:Free Radical Scavengers / Q000494:pharmacology*; D016678:Genome / Q000187:drug effects; D005978:Glutathione / Q000172:deficiency; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D007501:Iron / Q000633:toxicity; D009474:Neurons / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D011500:Protein Synthesis Inhibitors / Q000633:toxicity; D051381:Rats; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D016166:Free Radical Scavengers; D011500:Protein Synthesis Inhibitors; D003513:Cycloheximide; D007501:Iron; D005978:Glutathione; D024502:alpha-Tocopherol