| Increased macrophage cholesterol biosynthesis and decreased cellular paraoxonase 2 (PON2) expression in Delta6-desaturase knockout (6-DS KO) mice: beneficial effects of arachidonic acid. | |
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MedLine Citation:
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PMID: 20042190 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To analyze the possible role of arachidonic acid (AA) in macrophage cholesterol biosynthesis and in PON2 expression. METHODS AND RESULTS: We used peritoneal macrophages (MPM) from the 6-DS KO mice that were fed a diet without or with AA. Macrophage cholesterol biosynthesis rate and HMGCoA-reductase mRNA levels were substantially increased, by 98% and 67%, respectively, in MPM from 6-DS KO vs. control (C57BL/6) mice. Furthermore, in the 6-DS KO vs. control mice MPM PON2 expression (mRNA and lactonase activity) was substantially decreased. In line with the above results, AA supplementation to 6-DS KO mice significantly decreased MPM cholesterol biosynthesis rate and HMGCoA-reductase mRNA levels, by 45% and by 4-fold respectively, and increased MPM PON2 lactonase activity and PON2 mRNA, by 119% and 2.3-fold, respectively. Similarly, incubation of control mice MPM or J774A.1 with AA, significantly and dose-dependently decreased cellular cholesterol biosynthesis rate, and increased PON2 expression. These effects were specific for AA since incubation of the cells with docosahexaenoic acid (DHA, another product of 6-DS) had no significant effects on cholesterol biosynthesis rate, and on PON2 activity. CONCLUSIONS: AA decreased macrophage cholesterol biosynthesis rate, and increased PON2 expression. These effects could protect the cells from cholesterol accumulation and oxidation, and from foam cell formation, the hallmark of early atherogenesis. |
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Authors:
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Mira Rosenblat; Nina Volkova; Manuel Roqueta-Rivera; Manabu T Nakamura; Michael Aviram |
Publication Detail:
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Type: Journal Article Date: 2009-12-01 |
Journal Detail:
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Title: Atherosclerosis Volume: 210 ISSN: 1879-1484 ISO Abbreviation: Atherosclerosis Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-31 Completed Date: 2010-12-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0242543 Medline TA: Atherosclerosis Country: Ireland |
Other Details:
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Languages: eng Pagination: 414-21 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, 31096 Haifa, Israel. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arachidonic Acid / metabolism* Aryldialkylphosphatase / metabolism* Atherosclerosis Cholesterol / chemistry, metabolism* Docosahexaenoic Acids / metabolism Flow Cytometry / methods Foam Cells / cytology Linoleoyl-CoA Desaturase / genetics* Macrophages / metabolism* Macrophages, Peritoneal / cytology* Mice Mice, Inbred C57BL Mice, Knockout Models, Biological |
| Chemical | |
Reg. No./Substance:
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25167-62-8/Docosahexaenoic Acids; 506-32-1/Arachidonic Acid; 57-88-5/Cholesterol; EC 1.14.19.3/Linoleoyl-CoA Desaturase; EC 3.1.8.1/Aryldialkylphosphatase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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