Document Detail


Human ABCA7 supports apolipoprotein-mediated release of cellular cholesterol and phospholipid to generate high density lipoprotein.
MedLine Citation:
PMID:  14570867     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Apolipoprotein-mediated release of cellular cholesterol and phospholipids was induced in HEK293 cells by expressing human ATP-binding cassette transporter A7 (ABCA7) and ABC transporter A1 (ABCA1) proteins, whether transient or stable, to generate cholesterol-rich high density lipoprotein (HDL). Green fluorescent protein (GFP) attached at their C termini did not influence the lipid release reactions. Transfected ABCA7-GFP induced apolipoprotein-mediated assembly of cholesterol-containing HDL also in L929 cells, which otherwise generate only cholesterol-deficient HDL with their endogenous ABCA1. Time-dependent release of cholesterol and phospholipid by apolipoprotein A (apoA)-I was parallel both with ABCA1 and with ABCA7 when highly expressed in HEK293 cells, but dose-dependent profiles of lipid release on apoA-I and apoA-II were somewhat different between ABCA1 and ABCA7. Analyses of the stable clones with ABCA1-GFP (293/2c) and ABCA7-GFP (293/6c) by using the same vector indicated some differences in regulation of their activities by protein kinase modulators. Dibutyryl cyclic AMP increased ABCA1-GFP and the release of cholesterol and phospholipid in 293/2c but increased neither ABCA7-GFP nor the lipid release in 293/6c. Expression of ABCA1-GFP- and apoA-I-mediated lipid release were enhanced in parallel by phorbol 12-myristate 13-acetate (PMA) in 293/2c cells. In contrast, the same treatment of 293/6c increased ABCA7-GFP, but apoA-I-mediated lipid release was significantly suppressed. Despite these different responses to PMA, all of the effects of PMA were reversed by a specific protein kinase C inhibitor Gö6976, suggesting that the changes were in fact due to protein kinase C activation. A thiol protease inhibitor, N-acetyl-Leu-Leu-norleucinal, increased the protein levels of ABCA1-GFP in 293/2c and ABCA7-GFP in 293/6c, indicating their common degradation pathway. The data indicated that human ABCA7 would compensate the function of ABCA1 for release of cell cholesterol in a certain condition(s), but post-transcriptional regulation of their activity is different.
Authors:
Sumiko Abe-Dohmae; Yuika Ikeda; Michinori Matsuo; Michi Hayashi; Kei-ichiro Okuhira; Kazumitsu Ueda; Shinji Yokoyama
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-10-21
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  279     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2003-12-25     Completed Date:  2004-03-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  604-11     Citation Subset:  IM    
Affiliation:
Biochemistry, Molecular Biology and Metabolism 1, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / metabolism*
Apolipoprotein A-I / metabolism
Apolipoproteins / physiology*
Bucladesine / pharmacology
Carbazoles / pharmacology
Cell Line
Cholesterol / metabolism*
Cloning, Molecular
Cysteine Proteinase Inhibitors / pharmacology
DNA, Complementary / genetics
Enzyme Inhibitors / pharmacology
Humans
Indoles / pharmacology
Kinetics
Leupeptins / pharmacology
Lipoproteins, HDL / metabolism*
Phospholipids / metabolism*
Recombinant Proteins / metabolism
Tetradecanoylphorbol Acetate / pharmacology
Transfection
Chemical
Reg. No./Substance:
0/ABCA7 protein, human; 0/ATP binding cassette transporter 1; 0/ATP-Binding Cassette Transporters; 0/Apolipoprotein A-I; 0/Apolipoproteins; 0/Carbazoles; 0/Cysteine Proteinase Inhibitors; 0/DNA, Complementary; 0/Enzyme Inhibitors; 0/Indoles; 0/Leupeptins; 0/Lipoproteins, HDL; 0/Phospholipids; 0/Recombinant Proteins; 110044-82-1/acetylleucyl-leucyl-norleucinal; 136194-77-9/Go 6976; 16561-29-8/Tetradecanoylphorbol Acetate; 362-74-3/Bucladesine; 57-88-5/Cholesterol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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