Source:http://linkedlifedata.com/resource/pubmed/id/14754908
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2004-4-16
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pubmed:abstractText |
Apolipoprotein E (apoE)/ABCA1 interactions were investigated in human intact fibroblasts induced with 22(R)-hydroxycholesterol and 9-cis-retinoic acid (stimulated cells). Here, we show that purified human plasma apoE3 forms a complex with ABCA1 in normal fibroblasts. Lipid-free apoE3 inhibited the binding of (125)I-apoA-I to ABCA1 more efficiently than reconstituted HDL particles (IC(50) = 2.5 +/- 0.4 microg/ml vs. 12.3 +/- 1.3 microg/ml). ApoE isoforms showed similar binding for ABCA1 and exhibited identical kinetics in their abilities to induce ABCA1-dependent cholesterol efflux. Mutation of ABCA1 associated with Tangier disease (C1477R) abolished both apoE3 binding and apoE3-mediated cholesterol efflux. Analysis of apoE3-containing particles generated during the incubation of lipid-free apoE3 with stimulated normal cells showed nascent apoE3/cholesterol/phospholipid complexes that exhibited prebeta-electrophoretic mobility with a particle size ranging from 9 to 15 nm, whereas lipid-free apoE3 incubated with ABCA1 mutant (C1477R) cells was unable to form such particles. These results demonstrate that 1). apoE association with lipids reduced its ability to interact with ABCA1; 2). apoE isoforms did not affect apoE binding to ABCA1; 3). apoE-mediated ABCA1-dependent cholesterol efflux was not affected by apoE isoforms in fibroblasts; and 4). the lipid translocase activity of ABCA1 generates apoE-containing high density-sized lipoprotein particles. Thus, ABCA1 is essential for the biogenesis of high density-sized lipoprotein containing only apoE particles in vivo.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ATP binding cassette transporter 1,
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoproteins E,
http://linkedlifedata.com/resource/pubmed/chemical/Cross-Linking Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-2275
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
45
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
839-48
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:14754908-ATP-Binding Cassette Transporters,
pubmed-meshheading:14754908-Apolipoproteins E,
pubmed-meshheading:14754908-Cells, Cultured,
pubmed-meshheading:14754908-Cross-Linking Reagents,
pubmed-meshheading:14754908-Fibroblasts,
pubmed-meshheading:14754908-Humans,
pubmed-meshheading:14754908-Lipid Metabolism,
pubmed-meshheading:14754908-Mutation,
pubmed-meshheading:14754908-Protein Binding,
pubmed-meshheading:14754908-Protein Isoforms,
pubmed-meshheading:14754908-Skin
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pubmed:year |
2004
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pubmed:articleTitle |
Molecular interactions between apoE and ABCA1: impact on apoE lipidation.
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pubmed:affiliation |
Cardiovascular Genetics Laboratory, Division of Cardiology, McGill University Health Centre/Royal Victoria Hospital, Montréal, Québec H3A 1A1, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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