Document Detail


Domains of apoE4 required for the biogenesis of apoE-containing HDL.
MedLine Citation:
PMID:  21604997     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION. We have studied the functions of truncated apoE4 forms in vitro and in vivo in order to identify the domains of apoE4 required for the biogenesis of apoE-containing high-density lipoprotein (HDL). RESULTS. We have found that apoE4-185, -202, -229, or -259 could promote ATP-binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux in vitro, although less efficiently than Full-length apoE4, and had diminished capacity to activate lecithin cholesterol acyltransferase (LCAT). Formation of HDL in vivo was assessed by various methods following gene transfer in apolipoprotein A-I(-/-) × apoE(-/-) mice. Fast protein liquid chromatography of plasma showed that the truncated apoE forms, except apoE4-185, generated an apoE-containing HDL peak. Two-dimensional gel electrophoresis of plasma and electron microscopy showed that truncated apoE forms generated distinct HDL subpopulations and formed discoidal HDL particles which could be converted to spherical by co-administration of truncated apoE4-202 and LCAT. CONCLUSION. Overall, the in-vivo and in-vitro data are consistent and indicate that apoE4-185 is the shortest truncated form that supports formation of discoidal apoE4-containing HDL particles.
Authors:
Alexander M Vezeridis; Angeliki Chroni; Vassilis I Zannis
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Annals of medicine     Volume:  43     ISSN:  1365-2060     ISO Abbreviation:  Ann. Med.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-24     Completed Date:  2011-10-19     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  8906388     Medline TA:  Ann Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  302-11     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
ATP Binding Cassette Transporter 1
ATP-Binding Cassette Transporters / metabolism,  physiology*
Adenoviridae / genetics
Animals
Apolipoprotein A-I / metabolism,  physiology*
Apolipoprotein E4 / biosynthesis,  chemistry*,  metabolism,  physiology*
Apolipoproteins E / biosynthesis*,  metabolism
Female
Humans
Lipoproteins / biosynthesis,  metabolism
Lipoproteins, HDL / biosynthesis*,  metabolism
Male
Metabolic Networks and Pathways
Mice
Mice, Knockout / genetics
Phosphatidylcholine-Sterol O-Acyltransferase / metabolism
RNA, Messenger
Transduction, Genetic
Grant Support
ID/Acronym/Agency:
R01 HL048739/HL/NHLBI NIH HHS; R01 HL048739-15/HL/NHLBI NIH HHS; R01 HL068216/HL/NHLBI NIH HHS; R01 HL068216-09/HL/NHLBI NIH HHS; T32 HL007969/HL/NHLBI NIH HHS; T32 HL007969-08/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/ATP Binding Cassette Transporter 1; 0/ATP-binding cassette, sub-family A (ABC1), member 1 protein, human; 0/Apolipoprotein A-I; 0/Apolipoprotein E4; 0/Apolipoproteins E; 0/Lipoproteins; 0/Lipoproteins, HDL; 0/RNA, Messenger; 0/apolipoprotein E-rich HDL; 0/discoidal lipoproteins; EC 2.3.1.43/Phosphatidylcholine-Sterol O-Acyltransferase
Comments/Corrections

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


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