| Autophagy regulates cholesterol efflux from macrophage foam cells via lysosomal acid lipase. | |
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MedLine Citation:
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PMID: 21641547 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The lipid droplet (LD) is the major site of cholesterol storage in macrophage foam cells and is a potential therapeutic target for the treatment of atherosclerosis. Cholesterol, stored as cholesteryl esters (CEs), is liberated from this organelle and delivered to cholesterol acceptors. The current paradigm attributes all cytoplasmic CE hydrolysis to the action of neutral CE hydrolases. Here, we demonstrate an important role for lysosomes in LD CE hydrolysis in cholesterol-loaded macrophages, in addition to that mediated by neutral hydrolases. Furthermore, we demonstrate that LDs are delivered to lysosomes via autophagy, where lysosomal acid lipase (LAL) acts to hydrolyze LD CE to generate free cholesterol mainly for ABCA1-dependent efflux; this process is specifically induced upon macrophage cholesterol loading. We conclude that, in macrophage foam cells, lysosomal hydrolysis contributes to the mobilization of LD-associated cholesterol for reverse cholesterol transport. |
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Authors:
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Mireille Ouimet; Vivian Franklin; Esther Mak; Xianghai Liao; Ira Tabas; Yves L Marcel |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell metabolism Volume: 13 ISSN: 1932-7420 ISO Abbreviation: Cell Metab. Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-06-06 Completed Date: 2011-09-20 Revised Date: 2012-01-16 |
Medline Journal Info:
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Nlm Unique ID: 101233170 Medline TA: Cell Metab Country: United States |
Other Details:
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Languages: eng Pagination: 655-67 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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University of Ottawa Heart Institute, Ottawa, Ontario, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Atherosclerosis / metabolism, pathology Autophagy* Bone Marrow Cells / drug effects, metabolism, ultrastructure Cells, Cultured Chloroquine / pharmacology Cholesterol / secretion* Foam Cells / drug effects, metabolism*, ultrastructure Gene Knockout Techniques Lipid Metabolism* Lipolysis Lipoproteins, LDL / metabolism Lysosomes / metabolism Mice Mice, Inbred C57BL Mice, Knockout Microtubule-Associated Proteins / deficiency, genetics, metabolism Paraoxon / pharmacology Sterol Esterase / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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HL057560/HL/NHLBI NIH HHS; R01 HL075662-09/HL/NHLBI NIH HHS; R01 HL106019-03/HL/NHLBI NIH HHS; //Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Atg5 protein, mouse; 0/Lipoproteins, LDL; 0/Microtubule-Associated Proteins; 311-45-5/Paraoxon; 54-05-7/Chloroquine; 57-88-5/Cholesterol; EC 3.1.1.13/Sterol Esterase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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