| Cytoskeleton disruption in J774 macrophages: Consequences for lipid droplet formation and cholesterol flux. | |
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MedLine Citation:
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PMID: 22015387 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Macrophages store excess unesterified cholesterol (free, FC) in the form of cholesteryl ester (CE) in cytoplasmic lipid droplets. The hydrolysis of droplet-CE in peripheral foam cells is critical to HDL-promoted reverse cholesterol transport because it represents the first step in cellular cholesterol clearance, as only FC is effluxed from cells to HDL. Cytoplasmic lipid droplets move within the cell utilizing the cytoskeletal network, but, little is known about the influence of the cytoskeleton on lipid droplet formation. To understand this role we employed cytochalasin D (cyt.D) to promote actin depolymerization in J774 macrophages. Incubating J774 with acetylated LDL creates foam cells having a 4-fold increase in cellular cholesterol content (30-40% cholesterol present as cholesteryl ester (CE)) in cytoplasmic droplets. Lipid droplets formed in the presence of cyt.D are smaller in diameter. CE-deposition and -hydrolysis are decreased when cells are cholesterol-enriched in the presence of cyt.D or latrunculin A, another cytoskeleton disrupting agent. However, when lipid droplets formed in the presence of cyt.D are isolated and incubated with an exogenous CE hydrolase, the CE is more rapidly metabolized compared to droplets from control cells. This is apparently due to the smaller size and altered lipid composition of the droplets formed in the presence of cyt.D. Cytoskeletal proteins found on CE droplets influence droplet lipid composition and maturation in model foam cells. In J774 macrophages, cytoskeletal proteins are apparently involved in facilitating the interaction of lipid droplets and a cytosolic neutral CE hydrolase and may play a role in foam cell formation. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010). |
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Authors:
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Ginny L Weibel; Michelle R Joshi; W Gray Jerome; Sandra R Bates; Kevin J Yu; Michael C Phillips; George H Rothblat |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-8 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: - ISSN: 0006-3002 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier B.V. All rights reserved. |
Affiliation:
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Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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