A role for lipid rafts in the protection afforded by docosahexaenoic acid against ethanol toxicity in primary rat hepatocytes
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- 作者：Fatiha Aliche-Djoudi ; Norm ; Podechard ; Aurore Collin ; Martine Chevanne ; Emilie Provost ; Martine Poul ; Ludovic Le H¨¦garat ; Daniel Catheline ; Philippe Legr ; Marie-Th¨¦r¨¨se Dimanche-Boitrel ; Dominique Lagadic-Gossmann ; Odile Sergent
- 关键词：DHA ; docosahexaenoic acid ; EPA ; eicosapentaenoic acid ; EPR ; electron paramagnetic resonance ; GM1 ; monosialotetrahexosyl ganglioside ; GPI ; glycosylphosphatidylinositol ; H2FDA ; dihydrofluorescein diacetate ; HNE ; 4-hydroxynonenal ; LMW iron ; low-molecular-wei
- 刊名：Food and Chemical Toxicology
- 出版年：2013
- 出版时间：October, 2013
- 年：2013
- 卷：60
- 期：Complete
- 页码：286-296
- 全文大小：2032 K
文摘
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-¦Ã 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.