| ACSL3 and GSK-3β are essential for lipid upregulation induced by endoplasmic reticulum stress in liver cells. | |
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MedLine Citation:
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PMID: 21328461 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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-3β inhibitors attenuated ACSL3 expression and the lipid accumulation induced by ER stress in HuH-7 cells. shRNA that target GSK-3β 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-3β inhibitors abrogated the lipid dysregulation caused by the hepatitis B virus mutant large surface protein. Altogether, ACSL3 and GSK-3β represent novel therapeutic targets for lipid dysregulation by ER stress. |
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Authors:
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Yung-Sheng Chang; Chien-Ting Tsai; Chien-An Huangfu; Wen-Ya Huang; Huan-Yao Lei; Chiou-Feng Lin; Ih-Jen Su; Wen-Tsan Chang; Pei-Huan Wu; Ya-Ting Chen; Jui-Hsiang Hung; Kung-Chia Young; Ming-Derg Lai |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cellular biochemistry Volume: 112 ISSN: 1097-4644 ISO Abbreviation: J. Cell. Biochem. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-17 Completed Date: 2011-06-10 Revised Date: 2011-11-02 |
Medline Journal Info:
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Nlm Unique ID: 8205768 Medline TA: J Cell Biochem Country: United States |
Other Details:
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Languages: eng Pagination: 881-93 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Wiley-Liss, Inc. |
Affiliation:
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Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line, Tumor Coenzyme A Ligases / metabolism* Endoplasmic Reticulum / physiology* Enzyme Inhibitors / pharmacology Glycogen Synthase Kinase 3 / metabolism* Heat-Shock Proteins / metabolism Hepatocytes / metabolism* Humans Lipids / biosynthesis* Liver / metabolism* Mice Mice, Inbred C57BL RNA Interference Stress, Physiological Triazenes / pharmacology Tunicamycin / pharmacology Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Heat-Shock Proteins; 0/Lipids; 0/Triazenes; 0/molecular chaperone GRP78; 11089-65-9/Tunicamycin; 76896-80-5/triacsin C; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.26/Glycogen Synthase Kinase 3; EC 6.2.1.-/Coenzyme A Ligases; EC 6.2.1.3/long-chain-fatty-acid-CoA ligase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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