A transient treatment of hippocampal neurons with alpha-tocopherol induces a long-lasting protection against oxidative damage via a genomic action.
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.
de Jesus Ferreira
Marie Céleste
MC
Laboratory Cerebral Plasticity, FRE 2693 CNRS, University Montpellier II, 34095 Montpellier Cedex 05, France.
Crouzin
Nadine
N
Barbanel
Gérard
G
Cohen-Solal
Catherine
C
Récasens
Max
M
Vignes
Michel
M
Guiramand
Janique
J
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*
D016166:Free Radical Scavengers; D011500:Protein Synthesis Inhibitors; D003513:Cycloheximide; D007501:Iron; D005978:Glutathione; D024502:alpha-Tocopherol