%0 Journal Article %T A role for lipid rafts in the protection afforded by docosahexaenoic acid against ethanol toxicity in primary rat hepatocytes. %+ Institut de recherche en santé, environnement et travail (Irset) %+ Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) %+ Stress, membrane et signalisation (SMS) %+ Unité de Toxicologie des Contaminants %+ Laboratoire de Biochimie et Nutrition Humaine %A Aliche-Djoudi, Fatiha %A Podechard, Normand %A Collin, Aurore %A Chevanne, Martine %A Provost, Emilie %A Poul, Martine %A Le Hégarat, Ludovic %A Catheline, Daniel, D. %A Legrand, Philippe, P. %A Dimanche-Boitrel, Marie-Thérèse %A Lagadic-Gossmann, Dominique %A Sergent, Odile %Z European union (FEDER), the Region Bretagne, the Conseil Général d'Ille-et-Vilaine, Rennes Métropole and the French Ministère de l'Enseignement Supérieur et de la Recherche (MESR) are thanked for the financial support of the project Membratox (Contract number 32508, 350 keuros). This work was supported by the Institut de Recherches Scientifiques sur les Boissons (IREB) (contract numbers 2007/26, 2008/25, 2009/28, 2010/18) and the Région Bretagne (which provided a grant to Fatiha Aliche-Djoudi). %< avec comité de lecture %@ 0278-6915 %J Food and Chemical Toxicology %I Elsevier %V 60C %P 286-296 %8 2013-07-29 %D 2013 %R 10.1016/j.fct.2013.07.061 %M 23907024 %K 4-hydroxynonenal %K DHA %K EPA %K EPR %K Ethanol %K GM1 %K GPI %K H(2)FDA %K HNE %K LMW iron %K Lipid peroxidation %K Lipid rafts %K MAL-6 %K O-(2 %K 6-pentafluorobenzyl)hydroxylamine hydrochloride %K O-PFB %K Oxidative stress %K PFBHA*HCl %K PLCγ1 %K ROS %K dihydrofluorescein diacetate %K docosahexaenoic acid %K eicosapentaenoic acid %K electron paramagnetic resonance %K glycosylphosphatidylinositol %K low-molecular-weight iron %K monosialotetrahexosyl ganglioside %K n-3 PUFA %K n-3 Polyunsaturated fatty acids %K n-3 polyunsaturated fatty acid %K pentafluorobenzyl-oxime %K phospholipase C γ1 %K reactive oxygen species %K GSH: reduced glutathione %K tetramethyl-4-maleimidopiperidine-1-oxyl %Z Life Sciences [q-bio]Journal articles %X : Previously, we demonstrated that eicosapentaenoic acid enhanced ethanol-induced oxidative stress and cell death in primary rat hepatocytes via an increase in membrane fluidity and lipid raft clustering. In this context, another n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA), was tested with a special emphasis on physical and chemical alteration of lipid rafts. Pretreatment of hepatocytes with DHA reduced significantly ethanol-induced oxidative stress and cell death. DHA protection could be related to an alteration of lipid rafts. Indeed, rafts exhibited a marked increase in membrane fluidity and packing defects leading to the exclusion of a raft protein marker, flotillin. Furthermore, DHA strongly inhibited disulfide bridge formation, even in control cells, thus suggesting a disruption of protein-protein interactions inside lipid rafts. This particular spatial organization of lipid rafts due to DHA subsequently prevented the ethanol-induced lipid raft clustering. Such a prevention was then responsible for the inhibition of phospholipase C-γ translocation into rafts, and consequently of both lysosome accumulation and elevation in cellular low-molecular-weight iron content, a prooxidant factor. In total, the present study suggests that DHA supplementation could represent a new preventive approach for patients with alcoholic liver disease based upon modulation of the membrane structures. %G English %Z Membratox (Contract number 32508 %Z 350 keuros) %2 https://univ-rennes.hal.science/hal-00860153/document %2 https://univ-rennes.hal.science/hal-00860153/file/Sergent-et-al-incl-figures-accepted.pdf %L hal-00860153 %U https://univ-rennes.hal.science/hal-00860153 %~ ANSES %~ UNIV-RENNES1 %~ UNIV-ANGERS %~ IFR140 %~ UNAM %~ IRSET %~ STATS-UR1 %~ IRSET-SMS %~ IRSET-CCII %~ IRSET-TREC %~ IRSET-HIAEC %~ IRSET-SMLF %~ IRSET-ERD %~ IRSET-VCER %~ IRSET-NEED %~ IRSET-TNGC %~ UR1-UFR-SVE %~ UR1-HAL %~ UR1-SDV %~ AGREENIUM %~ IRSET-2 %~ IRSET-3 %~ TEST-UNIV-RENNES %~ TEST-UR-CSS %~ UNIV-RENNES %~ UR1-BIO-SA %~ INSTITUT-AGRO