Document Detail


Role of liver sinusoidal endothelial cells and stabilins in elimination of oxidized low-density lipoproteins.
MedLine Citation:
PMID:  21030611     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Atherogenesis is associated with elevated levels of low-density lipoprotein (LDL) and its oxidized form (oxLDL) in the blood. The liver is an important scavenger organ for circulating oxLDLs. The present study aimed to examine endocytosis of mildly oxLDL (the major circulating form of oxLDLs) in liver sinusoidal endothelial cells (LSECs) and the involvement of the scavenger receptors stabilin-1 and stabilin-2 in this process. Freshly isolated LSECs, Kupffer cells (KCs), and stabilin-1- and stabilin-2-transfected human embryonic kidney cells were incubated with fluorescently labeled or radiolabeled oxLDLs [oxidized for 3 h (oxLDL(3)), 6 h, or 24 h (oxLDL(24))] to measure endocytosis. The intracellular localization of oxLDLs and stabilins in LSECs was examined by immunofluorescence and immunogold electron microscopy. Whereas oxLDL(24) was endocytosed both by LSECs and KCs, oxLDL(3) (mildly oxLDL) was taken up by LSECs only. The LSEC uptake of oxLDLs was significantly inhibited by the scavenger receptor ligand formaldehyde-treated serum albumin. Uptake of all modified LDLs was high in stabilin-1-transfected cells, whereas stabilin-2-transfected cells preferentially took up oxLDL(24), suggesting that stabilin-1 is a more important receptor for mildly oxLDLs than stabilin-2. Double immunogold labeling experiments in LSECs indicated interactions of stabilin-1 and stabilin-2 with oxLDL(3) on the cell surface, in coated pits, and endocytic vesicles. LSECs but not KCs endocytosed mildly oxLDL. Both stabilin-1 and stabilin-2 were involved in the LSEC endocytosis of oxLDLs, but experiments with stabilin-transfected cells pointed to stabilin-1 as the most important receptor for mildly oxLDL.
Authors:
Ruomei Li; Ana Oteiza; Karen Kristine Sørensen; Peter McCourt; Randi Olsen; Bård Smedsrød; Dmitri Svistounov
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-28
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  300     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-30     Completed Date:  2011-02-01     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G71-81     Citation Subset:  IM    
Affiliation:
Faculty of Health Sciences, Vascular Biology Research Group, Institute of MedicalBiology, University of Tromsø, Tromsø, Norway
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD36 / biosynthesis
Cell Adhesion Molecules, Neuronal / pharmacology
Endocytosis / physiology*
Endothelial Cells / metabolism*
HEK293 Cells
Humans
Kupffer Cells / metabolism
Lipoproteins, LDL / metabolism*
Liver / cytology*,  metabolism
Male
Mice
Rats
Scavenger Receptors, Class E / biosynthesis
Transfection
Grant Support
ID/Acronym/Agency:
1.R21 AG-026582-01A1/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD36; 0/Cd36 protein, rat; 0/Cell Adhesion Molecules, Neuronal; 0/Lipoproteins, LDL; 0/Oldlr1 protein, rat; 0/Scavenger Receptors, Class E; 0/Stab1 protein, mouse; 0/Stab2 protein, mouse; 0/oxidized low density lipoprotein
Comments/Corrections

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