| Cholesterol rich lipid raft microdomains are gateway for acute phase protein, SERPINA1. | |
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MedLine Citation:
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PMID: 20561599 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cholesterol is the most abundant lipid component of the plasma membrane, and thus the equilibrium between free cholesterol and raft cholesterol act as a determinant of raft function and cell signalling. The mechanisms that regulate the lipid raft cholesterol levels are largely unknown. Here we demonstrate that SERPINA1 (alpha1-antitrypsin), an acute phase protein and the classical neutrophil elastase inhibitor, is localized within lipid rafts in primary human monocytes in vitro. SERPINA1 association with monocytes is inhibited by cholesterol depleting/efflux-stimulating agents (nystatin, filipin, MbetaCD (methyl-beta-cyclodextrin) and oxidized low-density lipoprotein (oxLDL) and conversely, enhanced by free cholesterol. Furthermore, SERPINA1/monocyte association per se depletes lipid raft cholesterol as characterized by the activation of extracellular signal-regulated kinase 2, formation of cytosolic lipid droplets, and a complete inhibition of oxLDL uptake by monocytes. Our findings for the first time highlight that the entry and cell association of SERPINA1 is dependent on lipid raft cholesterol and that SERPINA1 depletes lipid raft cholesterol. |
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Authors:
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Devipriya Subramaniyam; Huiping Zhou; Min Liang; Tobias Welte; Ravi Mahadeva; Sabina Janciauskiene |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-06-16 |
Journal Detail:
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Title: The international journal of biochemistry & cell biology Volume: 42 ISSN: 1878-5875 ISO Abbreviation: Int. J. Biochem. Cell Biol. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-07-26 Completed Date: 2010-11-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9508482 Medline TA: Int J Biochem Cell Biol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1562-70 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Hannover Medical School, Department of Respiratory Medicine, Feodor Lynen Str 23, 30625 Hannover, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Blotting, Western Cell Line Cells, Cultured Cholesterol / metabolism* Electrophoresis Humans Membrane Microdomains / metabolism* Monocytes / metabolism Receptors, Complement 3b / genetics, metabolism alpha 1-Antitrypsin / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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R01AT004148/AT/NCCAM NIH HHS; R21AI068432/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Complement 3b; 0/SERPINA1 protein, human; 0/alpha 1-Antitrypsin; 57-88-5/Cholesterol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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