2012 Fiscal Year Final Research Report

Role of lipid raft on palmitic acid induced-cell death in primary-cultured mouse hepatocytes

Research Project

Project/Area Number	23790814
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Gastroenterology
Research Institution	Juntendo University
Principal Investigator	UCHIYAMA Akira 順天堂大学, 医学部消化器内科, 助教 (60529254)
Project Period (FY)	2011 – 2012
Keywords	リピドラフト / 脂肪性肝炎 / 酸化ストレス
Research Abstract	Excessive saturated free fatty acid (sFFA) causes hepatic steatosis and injury, which explains in part the pathogenesis of nonalcoholic steatohepatitis (NASH). Lipid raft, the plasma membrane subdomain that contains high concentration of cholesterol and glycosphingolipids, is involved in a variety of cellular signal transduction processes. In this study, we investigated the impact of sFFA on structure formation of lipid raft, and oxidative stress-induced cell injury in isolated hepatocytes. PA elicits lipid accumulation and sensitization to oxidative stress-induced cell death in isolated hepatocytes. This process appears to be closely related to the clusterization of lipid raft, and blockade of this phenomenon by CHOX prevents oxidative cell killing in PA-pretreated hepatocytes. Lipid raft most likely plays a pivotal role in oxidative stress-related cell injury in fat-loaded hepatocytes, which provides a potential uniquetarget for the prevention and treatment of NASH.

(3 results)