Linked Life Data

11060345

Source:http://linkedlifedata.com/resource/pubmed/id/11060345

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2000-11-29
pubmed:abstractText
We have identified a G-to-A transition in exon 3 of the APOC3 gene resulting in a novel Ala23Thr apolipoprotein (apo) C-III variant, associated with apoC-III deficiency in three unrelated Yucatan Indians. The Ala23Thr substitution modifies the hydrophobic/hydrophilic repartition of the helical N-terminal peptide and hence could disturb the lipid association. In vitro expression in Escherichia coli of wild-type and mutant apoC-III enabled the characterization of the variant. Compared with wild-type apoC-III-Ala23, the mutant apoC-III-Thr23 showed reduced affinity for dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles with higher amounts of free apoC-III. Displacement of apoE from discoidal apoE:dipalmitoylphosphatidycholine (DPPC) complex by apoC-III-Thr23 was comparable to wild type but the less efficient binding of the apoC-III-Thr23 to the discoidal complex resulted in a higher apoE/apoC-III (mol/mol) ratio (34%) than with wild-type/apoE:DPPC mixtures. The inhibition of lipoprotein lipase (LPL) by apoC-III-Thr23 was comparable to that of wild type, and therefore effects on LPL activity could not explain the lower triglyceride (Tg) levels in Thr-23 carriers. Thus, these in vitro results suggest that in vivo the less efficient lipid binding of apoC-III-Thr23 might lead to a faster catabolism of free apoC-III, reflected in the reduced plasma apoC-III levels identified in Thr-23 carriers, and poorer competition with apoE, which might enhance clearance of Tg-rich lipoproteins and lower plasma Tg levels seen in Thr-23 carriers.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-2275
pubmed:author
pubmed:issnType
Print
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1760-71
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11060345-1,2-Dipalmitoylphosphatidylcholine, pubmed-meshheading:11060345-Amino Acid Sequence, pubmed-meshheading:11060345-Apolipoprotein C-III, pubmed-meshheading:11060345-Apolipoproteins C, pubmed-meshheading:11060345-Apolipoproteins E, pubmed-meshheading:11060345-Central America, pubmed-meshheading:11060345-Chemistry, Physical, pubmed-meshheading:11060345-DNA Mutational Analysis, pubmed-meshheading:11060345-Dimyristoylphosphatidylcholine, pubmed-meshheading:11060345-Enzyme Inhibitors, pubmed-meshheading:11060345-Humans, pubmed-meshheading:11060345-Indians, Central American, pubmed-meshheading:11060345-Lipid Metabolism, pubmed-meshheading:11060345-Lipoprotein Lipase, pubmed-meshheading:11060345-Male, pubmed-meshheading:11060345-Middle Aged, pubmed-meshheading:11060345-Models, Molecular, pubmed-meshheading:11060345-Molecular Sequence Data, pubmed-meshheading:11060345-Mutation, pubmed-meshheading:11060345-Physicochemical Phenomena, pubmed-meshheading:11060345-Polymerase Chain Reaction, pubmed-meshheading:11060345-Recombinant Proteins
pubmed:year
2000
pubmed:articleTitle
Characterization of the lipid-binding properties and lipoprotein lipase inhibition of a novel apolipoprotein C-III variant Ala23Thr.
pubmed:affiliation
Cardiovascular Genetics Division, Department of Medicine, Royal Free and University College London Medical School, London WC1E 6JJ, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't