| Apolipoproteins A-I, A-II and E are independently distributed among intracellular and newly secreted HDL of human hepatoma cells. | |
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MedLine Citation:
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PMID: 19635584 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Whereas hepatocytes secrete the major human plasma high density lipoproteins (HDL)-protein, apo A-I, as lipid-free and lipidated species, the biogenic itineraries of apo A-II and apo E are unknown. Human plasma and HepG2 cell-derived apo A-II and apo E occur as monomers, homodimers and heterodimers. Dimerization of apo A-II, which is more lipophilic than apo A-I, is catalyzed by lipid surfaces. Thus, we hypothesized that lipidation of intracellular and secreted apo A-II exceeds that of apo A-I, and once lipidated, apo A-II dimerizes. Fractionation of HepG2 cell lysate and media by size exclusion chromatography showed that intracellular apo A-II and apo E are fully lipidated and occur on nascent HDL and VLDL respectively, while only 45% of intracellular apo A-I is lipidated. Secreted apo A-II and apo E occur on small HDL and on LDL and large HDL respectively. HDL particles containing both apo A-II and apo A-I form only after secretion from both HepG2 and Huh7 hepatoma cells. Apo A-II dimerizes intracellularly while intracellular apo E is monomeric but after secretion associates with HDL and subsequently dimerizes. Thus, HDL apolipoproteins A-I, A-II and E have distinct intracellular and post-secretory pathways of hepatic lipidation and dimerization in the process of HDL formation. These early forms of HDL are expected to follow different apolipoprotein-specific pathways through plasma remodeling and reverse cholesterol transport. |
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Authors:
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Baiba K Gillard; Hu-Yu Alice Lin; John B Massey; Henry J Pownall |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-07-25 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1791 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-11-03 Completed Date: 2010-01-06 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1125-32 Citation Subset: IM |
Affiliation:
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Section of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, MS-A601, Houston, TX 77030, USA. baibag@bcm.tmc.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apolipoprotein A-I
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metabolism* Apolipoprotein A-II / metabolism* Apolipoproteins E / metabolism* Carcinoma, Hepatocellular / secretion* Chromatography, Gel Hep G2 Cells Humans Intracellular Space / metabolism* Lipoproteins, HDL / secretion* Liver Neoplasms / secretion* Models, Biological Protein Binding Protein Multimerization Sepharose / analogs & derivatives Time Factors Ultracentrifugation |
| Grant Support | |
ID/Acronym/Agency:
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HL-30914/HL/NHLBI NIH HHS; HL-56865/HL/NHLBI NIH HHS; R01 HL030914-21/HL/NHLBI NIH HHS; R01 HL056865-09A2/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/APOA1 protein, human; 0/APOA2 protein, human; 0/Apolipoprotein A-I; 0/Apolipoprotein A-II; 0/Apolipoproteins E; 0/Lipoproteins, HDL; 68517-67-9/thiopropyl-sepharose; 9012-36-6/Sepharose |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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