Document Detail

Effect of apolipoprotein A-I on ATP binding cassette transporter A1 degradation and cholesterol efflux in THP-1 macrophage-derived foam cells.
MedLine Citation:
PMID:  15202507     Owner:  NLM     Status:  MEDLINE    
Cholesterol-loaded macrophage foam cells are a central component of atherosclerotic lesions. ATP binding cassette transporter A1 (ABCA1), the defective molecule in Tangier disease, mediates the efflux of phospholipid and cholesterol from cells to apolipoprotein A-I (apoA-I), reversing foam cell formation. This study investigated the effect of apoA-I on ABCA1 degradation and cholesterol efflux in THP-1 macrophage-derived foam cells. After exposure of the cultured THP-1 macrophage-derived foam cells to apoA-I for different time, cholesterol efflux, ABCA1 mRNA and protein levels were determined by FJ-2107P type liquid scintillator, RT-PCR and Western blot, respectively. The mean ABCA1 fluorescence intensity on THP-1 macrophage-derived foam cells was detected by flow cytometry. Results showed that apoA-I markedly increased ABCA1-mediated cholesterol efflux from THP-1 macrophage-derived foam cells. This was accompanied by an increase in the content of ABCA1. ApoA-I did not alter ABCA1 mRNA abundance. Significantly, thiol protease inhibitors increased the level of ABCA1 protein and slowed its decay in THP-1 macrophage-derived foam cells, whereas none of the proteosome-specific inhibitor lactacystin, other protease inhibitors, or the lysosomal inhibitor NH4Cl showed such effects. The apoA-I-mediated cellular cholesterol efflux was enhanced by thiol protease inhibitors. Our results suggested that thiol protease inhibitors might provide an alternative way to upregulate ABCA1 protein. This strategy is especially appealing since it may mimic the stabilizing effect of the natural ligands apoA-I.
Chao-Ke Tang; Guo-Hua Tang; Guang-Hui Yi; Zuo Wang; Lu-Shan Liu; Shuang Wan; Zhong-Hua Yuan; Xiu-Sheng He; Jun-Hao Yang; Chang-Geng Ruan; Yong-Zong Yang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Acta biochimica et biophysica Sinica     Volume:  36     ISSN:  1672-9145     ISO Abbreviation:  Acta Biochim. Biophys. Sin. (Shanghai)     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-06-18     Completed Date:  2004-10-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  101206716     Medline TA:  Acta Biochim Biophys Sin (Shanghai)     Country:  China    
Other Details:
Languages:  eng     Pagination:  218-26     Citation Subset:  IM    
Institute of Cardiovascular Disease of Nanhua University, Hengyang 421001, China.
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MeSH Terms
ATP-Binding Cassette Transporters / metabolism*
Apolipoprotein A-I / pharmacology*
Cell Line
Cholesterol / metabolism*
Foam Cells / drug effects*,  metabolism*
Macrophages / drug effects,  metabolism
Reg. No./Substance:
0/ATP binding cassette transporter 1; 0/ATP-Binding Cassette Transporters; 0/Apolipoprotein A-I; 57-88-5/Cholesterol

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

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