| Apolipoprotein A-I stimulates cholesteryl ester transfer protein and apolipoprotein E secretion from lipid-loaded macrophages: The role of NF-κB and PKA signaling pathways. | |
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MedLine Citation:
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PMID: 22056562 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Cholesteryl ester transfer protein (CETP) and apolipoprotein E (apoE) are secreted by macrophages. Apolipoprotein A-I (apoA-I) is a potent inducer of apoE secretion from lipid-loaded macrophages, but its effect on CETP is not known. We aimed to identify the signaling pathways involved in apoA-I and HDL-mediated regulation of CETP and apoE secretion from lipid-loaded macrophages. THP-1 macrophages were loaded with lipids by incubation with human copper-oxidized LDL. The cells were subsequently exposed to human purified apoA-I or HDL(3) with/without inhibitors of NF-κB (TPCK) or PKA (H89). CETP and apoE in the cultured cells and media were quantified by real-time PCR and Western blot. Results showed that in lipid-loaded macrophages: (i) CETP and apoE gene expression and secretion were increased in the presence of apoA-I, and further increased by inhibition of NF-kB with TPCK; (ii) CETP and apoE gene expression and secretion were reduced by the inhibition of PKA with H89; (iii) PKA-gamma subunit was activated by oxidized LDL and moreover by apoA-I. We also showed that: (i) siRNA-mediated CETP gene silencing diminished apoE secretion from both non-loaded and lipid-loaded macrophages; (ii) addition of apoA-I partially restored apoE secretion from lipid-loaded macrophages with the silenced CETP gene. In conclusion, our data suggest a new mechanism by which apoA-I stimulates CETP secretion, in addition to apoE, from lipid loaded macrophages, a process involving NF-κB inhibition and/or PKA pathway activation. |
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Authors:
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Loredan S Niculescu; Marius R Robciuc; Gabriela M Sanda; Anca V Sima |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-28 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: - ISSN: 1090-2104 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-11-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier Inc. |
Affiliation:
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Department of Lipoproteins and Atherosclerosis, Institute of Cellular Biology and Pathology "Nicolae Simionescu", Bucharest, Romania. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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