title: Physical and chemical modulation of lipid rafts by a dietary n-3 polyunsaturated fatty acid increases ethanol-induced oxidative stress.
abstract: Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported to modulate lipid raft-dependent signaling, but not yet lipid raft-dependent oxidative stress. Previously, we have shown that ethanol-induced membrane remodeling, i.e., an increase in membrane fluidity and alterations in physical and biochemical properties of lipid rafts, participated in the development of oxidative stress. Thus, we decided to study n-3 PUFA effects in this context, by pretreating hepatocytes with eicosapentaenoic acid (EPA), a long-chain n-3 PUFA, before addition of ethanol. EPA was found to increase ethanol-induced oxidative stress through membrane remodeling. Addition of EPA resulted in a marked increase in lipid raft aggregation compared to ethanol alone. In addition, membrane fluidity of lipid rafts was markedly enhanced. Interestingly, EPA was found to preferentially incorporate into nonraft membrane regions, leading to raft cholesterol increase. Lipid raft aggregation by EPA enhanced phospholipase Cγ translocation into these microdomains. Finally, phospholipase Cγ was shown to participate in the potentiation of oxidative stress by promoting lysosome accumulation, a major source of low-molecular-weight iron. To conclude, the ability of EPA to modify lipid raft physical and chemical properties plays a key role in the enhancement, by this dietary n-3 PUFA, of ethanol-induced oxidative stress.
authors.affiliation: EA 4427 SeRAIC/IRSET, IFR 140, UFR des Sciences Pharmaceutiques et Biologiques, Université de Rennes 1, Rennes Cédex, France.
authors.forename: Fatiha
authors.initials: F
authors.lastname: Aliche-Djoudi
authors.forename: Normand
authors.initials: N
authors.lastname: Podechard
authors.forename: Martine
authors.initials: M
authors.lastname: Chevanne
authors.forename: Philippe
authors.initials: P
authors.lastname: Nourissat
authors.forename: Daniel
authors.initials: D
authors.lastname: Catheline
authors.forename: Philippe
authors.initials: P
authors.lastname: Legrand
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Dimanche-Boitrel
authors.forename: Dominique
authors.initials: D
authors.lastname: Lagadic-Gossmann
authors.forename: Odile
authors.initials: O
authors.lastname: Sergent
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D021962:Membrane Microdomains / Q000737:chemistry* / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004042:Dietary Fats, Unsaturated; D000431:Ethanol; D015118:Eicosapentaenoic Acid