Document Detail


Recycling of apoprotein E is associated with cholesterol efflux and high density lipoprotein internalization.
MedLine Citation:
PMID:  12584196     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
After receptor-mediated endocytosis of triglyceride-rich lipoproteins (TRL) into the liver, TRL particles are immediately disintegrated in peripheral endosomal compartments. Whereas core lipids and apoprotein B are delivered for degradation into lysosomes, TRL-derived apoE is efficiently recycled back to the plasma membrane. This is followed by apoE re-secretion and association of apoE with high density lipoproteins (HDL). Because HDL and apoE can independently promote cholesterol efflux, we investigated whether recycling of TRL-derived apoE in human hepatoma cells and fibroblasts could be linked to intracellular cholesterol transport. In this study we demonstrate that HDL(3) does not only act as an extracellular acceptor for recycled apoE but also stimulates the recycling of internalized TRL-derived apoE. Furthermore, radioactive pulse-chase experiments indicate that apoE recycling is accompanied by cholesterol efflux. Confocal imaging reveals co-localization of apoE and cholesterol in early endosome antigen 1-positive endosomes. During apoE re-secretion, HDL(3)-derived apoA-I is found in these early endosome antigen 1, cholesterol-containing endosomes. As shown by time-lapse fluorescence microscopy, apoE recycling involves the intracellular trafficking of apoA-I to pre-existing and TRL-derived apoE/cholesterol-containing endosomes in the periphery. Thus, these studies provide evidence for a new intracellular link between TRL-derived apoE, cellular cholesterol transport, and HDL metabolism.
Authors:
Joerg Heeren; Thomas Grewal; Alexander Laatsch; Daniel Rottke; Franz Rinninger; Carlos Enrich; Ulrike Beisiegel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-02-12
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  278     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-04-14     Completed Date:  2003-05-22     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:  14370-8     Citation Subset:  IM    
Affiliation:
Institute for Medical Biochemistry and Molecular Biology, the Department of Molecular Cell Biology, University Hospital Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. heeren@uke.uni-hamburg.de
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MeSH Terms
Descriptor/Qualifier:
Apolipoproteins E / metabolism*
Blotting, Western
Cells, Cultured
Cholesterol / metabolism*
Dose-Response Relationship, Drug
Fibroblasts / metabolism
Humans
Ligands
Lipoproteins, HDL / metabolism*
Microscopy, Electron
Microscopy, Fluorescence
Protein Binding
Skin / cytology
Time Factors
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Apolipoproteins E; 0/Ligands; 0/Lipoproteins, HDL; 57-88-5/Cholesterol

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