| Project/Area Number |
23790814
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Juntendo University |
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Principal Investigator |
UCHIYAMA Akira 順天堂大学, 医学部消化器内科, 助教 (60529254)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 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 |
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| 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.
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