Document Detail


Apolipoprotein A-I promotes cholesterol release and apolipoprotein E recruitment from THP-1 macrophage-like foam cells.
MedLine Citation:
PMID:  9869653     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Apolipoprotein E (apoE) is synthesized and secreted by arterial macrophages while apolipoprotein A-I (apoA-I) is present in surrounding interstitial fluids. Both apolipoproteins play important roles in macrophage cholesterol homeostasis by forming lipid complexes (nascent-HDL) with cellular phospholipids (PL) and cholesterol (UC) thereby promoting cholesterol efflux. In this study, we evaluated the relative contributions of apoA-I and endogenously produced apoE in mediating the recruitment of cellular cholesterol. THP-1 human monocytes were differentiated (300 nm phorbol dibutyrate) into macrophages and macrophage-foam cells were generated by cholesterol loading with acetylated LDL (50 microg protein/ml). ApoA-I (10 microg/ml) depleted macrophage-foam cell cholesteryl esters by 50% in 24 h. This reduction was accompanied by a significant increase in the UC/PL mole ratio of nascent HDL (UC/PL = 0.80 +/- 0.15) in the medium compared to complexes isolated from macrophages (UC/PL = 0.59 +/- 0.08). Significantly more (70%) nascent-HDL were formed in incubations of apoA-I with macrophage-foam cells than with macrophages. Medium apoE accumulation paralleled the assembly of apoA-I containing nascent HDL where 2- and 4-fold increases were observed with macrophages and macrophage-foam cells, respectively, compared to incubations in the absence of apoA-I. Despite the increase in medium apoE accumulation, a majority (85%) of particles (11, 9, and 7.4 nm in diameter) from macrophages and macrophage-foam cells possessed apoA-I without apoE. ApoA-I plus apoE particles (13-16 nm) were also formed along with a small quantity of apoE-only particles (19-20 nm). The predominance of apoA-I only particles indicates, however, that the assembly of apoA-I-containing nascent-HDL represents a major metabolic pathway of cellular cholesterol recruitment compared to the endogenous production of apoE.
Authors:
J K Bielicki; M R McCall; T M Forte
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of lipid research     Volume:  40     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  1999 Jan 
Date Detail:
Created Date:  1999-03-09     Completed Date:  1999-03-09     Revised Date:  2009-11-03    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  85-92     Citation Subset:  IM    
Affiliation:
Ernest Orlando Lawrence Berkeley National Laboratory, Life Sciences Division 1-213, University of California, Berkeley CA 94720, USA.
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MeSH Terms
Descriptor/Qualifier:
Apolipoprotein A-I / metabolism,  pharmacology*
Apolipoproteins E / metabolism*
Cell Differentiation
Cell Line
Cholesterol / metabolism*
Cholesterol Esters / metabolism
Culture Media, Conditioned
Foam Cells / cytology,  drug effects*,  metabolism*
Humans
Lipoproteins, HDL / chemistry,  metabolism
Monocytes / cytology,  drug effects,  metabolism
Particle Size
Phospholipids / analysis,  classification,  metabolism
Grant Support
ID/Acronym/Agency:
HL 18574/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoprotein A-I; 0/Apolipoproteins E; 0/Cholesterol Esters; 0/Culture Media, Conditioned; 0/Lipoproteins, HDL; 0/Phospholipids; 57-88-5/Cholesterol

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