國家衛生研究院 NHRI:Item 3990099045/5376
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    题名: ACSL3 and GSK-3beta are essential for lipid upregulation induced by endoplasmic reticulum stress in liver cells
    其它题名: ACSL3 and GSK-3β are essential for lipid upregulation induced by endoplasmic reticulum stress in liver cells
    作者: Chang, YS;Tsai, CT;Huangfu, CA;Huang, WY;Lei, HY;Lin, CF;Su, IJ;Chang, WT;Wu, PH;Chen, YT;Hung, JH;Young, KC;Lai, MD
    贡献者: Division of Infectious Diseases
    摘要: The endoplasmic reticulum (ER) is essential for lipid biosynthesis, and stress signals in this organelle are thought to alter lipid metabolism. Elucidating the mechanisms that underlie the dysregulation of lipid metabolism in hepatocytes may lead to novel therapeutic approaches for the treatment of lipid accumulation. We first tested the effects of several inhibitors on lipid dysregulation induced by tunicamycin, an ER stress inducer. Triacsin C, an inhibitor of long-chain acyl-CoA synthetase (ACSL) 1, 3, and 4, was the most potent among these inhibitors. We then analyzed the expression of the ACSL family during ER stress. The expression of ACSL3 was induced by ER stress in HuH-7 cells and in mice livers. ACSL3 shRNA, but not ACSL1 shRNA, inhibited the induction of lipid accumulation. GSK-3beta inhibitors attenuated ACSL3 expression and the lipid accumulation induced by ER stress in HuH-7 cells. shRNA that target GSK-3beta also inhibited the upregulation of ACSL3 and lipid accumulation in HuH-7 and HepG2 cells. The hepatitis B virus mutant large surface protein, which is known to induce ER stress, increased the lipid content of cells. Similarly, Triacsin C, and GSK-3beta inhibitors abrogated the lipid dysregulation caused by the hepatitis B virus mutant large surface protein. Altogether, ACSL3 and GSK-3beta represent novel therapeutic targets for lipid dysregulation by ER stress.
    日期: 2011-03
    關聯: Journal of Cellular Biochemistry. 2011 Mar;112(3):881-893.
    Link to: http://dx.doi.org/10.1002/jcb.22996
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0730-2312&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000287910200016
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=79951785549
    显示于类别:[蘇益仁(2002-2015)] 期刊論文

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