Ethanol induces oxidative stress in primary rat hepatocytes through the early involvement of lipid raft clustering. - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Hepatology Année : 2008

Ethanol induces oxidative stress in primary rat hepatocytes through the early involvement of lipid raft clustering.

Résumé

The role of the hepatocyte plasma membrane structure in the development of oxidative stress during alcoholic liver diseases is not yet fully understood. Previously, we have established the pivotal role of membrane fluidity in ethanol-induced oxidative stress, but no study has so far tested the involvement of lipid rafts. In this study, methyl-beta-cyclodextrin or cholesterol oxidase, which were found to disrupt lipid rafts in hepatocytes, inhibited both reactive oxygen species production and lipid peroxidation, and this suggested a role for these microstructures in oxidative stress. By immunostaining of lipid raft components, a raft clustering was detected in ethanol-treated hepatocytes. In addition, we found that rafts were modified by formation of malondialdehyde adducts and disulfide bridges. Interestingly, pretreatment of cells by 4-methyl-pyrazole (to inhibit ethanol metabolism) and various antioxidants prevented the ethanol-induced raft aggregation. In addition, treatment of hepatocytes by a stabilizing agent (ursodeoxycholic acid) or a fluidizing compound [2-(2-methoxyethoxy)ethyl 8-(cis-2-n-octylcyclopropyl)octanoate] led to inhibition or enhancement of raft clustering, respectively, which pointed to a relationship between membrane fluidity and lipid rafts during ethanol-induced oxidative stress. We finally investigated the involvement of phospholipase C in raft-induced oxidative stress upon ethanol exposure. Phospholipase C was shown to be translocated into rafts and to participate in oxidative stress by controlling hepatocyte iron content. Conclusion: Membrane structure, depicted as membrane fluidity and lipid rafts, plays a key role in ethanol-induced oxidative stress of the liver, and its modulation may be of therapeutic relevance.
Fichier non déposé

Dates et versions

hal-00696177 , version 1 (11-05-2012)

Identifiants

Citer

Philippe Nourissat, Marion Travert, Martine Chevanne, Xavier Tekpli, Amélie Rébillard, et al.. Ethanol induces oxidative stress in primary rat hepatocytes through the early involvement of lipid raft clustering.. Hepatology, 2008, 47 (1), pp.59-70. ⟨10.1002/hep.21958⟩. ⟨hal-00696177⟩
187 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More