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

脂筏对棕榈酸诱导的原代培养小鼠肝细胞细胞死亡的作用

• 批准号: 23790814
• 负责人: UCHIYAMA Akira
• 金额: $ 2.5万
• 依托单位: Juntendo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790814/
• 关键词: リピドラフト; 脂肪性肝炎; 酸化ストレス; NASH; ネクローシス; 飽和脂肪酸

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.

过量的饱和游离脂肪酸（sFFA）导致肝脏脂肪变性和损伤，这部分解释了非酒精性脂肪性肝炎（NASH）的发病机制。脂筏是细胞膜上含有高浓度胆固醇和鞘糖脂的亚结构域，参与多种细胞信号转导过程。在这项研究中，我们研究了游离FFA对脂质筏结构形成的影响，以及氧化应激诱导的离体肝细胞损伤。PA在离体肝细胞中增强脂质蓄积和对氧化应激诱导的细胞死亡的敏感性。这一过程似乎与脂筏的聚集密切相关，通过CHOX阻断这一现象可防止PA预处理肝细胞中的氧化性细胞杀伤。脂筏可能在脂肪肝细胞氧化应激相关的细胞损伤中起关键作用，这为NASH的预防和治疗提供了潜在的靶点。

项目成果

生活習慣と消化器疾患・治療薬

生活习惯与消化系统疾病/药物

• 发表时间: 2012
• 作者: 内 山 明 ;渡辺 純夫
• 通讯作者: 渡辺 純夫

飽和脂肪酸負荷によるリピドラフトの形態変化と酸化ストレス応答性の亢進

饱和脂肪酸负荷导致脂筏的形态变化和氧化应激反应性增强

• 发表时间: 2013
• 作者: 飯島沙幸;渡邊綱正;松浦健太郎;飯尾悦子;新海登;村上周子;田中靖人;内山 明
• 通讯作者: 内山 明