Effects of apolipoprotein A-Ⅰon ATP binding cassette transporter A1 degradation and cholesterol efflux in THP-1 macrophage-derived foam cells
- VernacularTitle:载脂蛋白A-Ⅰ对三磷酸腺苷结合盒转运体A1的影响
- Author:
Chaoke TANG
;
Xiaoyan DAI
;
Junhao YANG
;
Xiang OU
;
Zhong REN
;
Guanghui YI
;
Zuo WANG
;
Lushan LIU
;
Shuang WANG
- Publication Type:Journal Article
- Keywords:
ATP-binding cassette transporters;
Apolipoproteins A;
Flow cytometry;
Cholesterol;
Lipoproteins;
Foam cells
- From:
Chinese Journal of Pathophysiology
2000;0(07):-
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To study the effects of apolipoprotein (apo) A-Ⅰon ATP binding cassette transporter A1 (ABCA1) degradation and cholesterol efflux in THP-1 macrophage-derived foam cells. METHODS: After exposure of the cultured THP-1 macrophage-derived foam cells to apolipoprotein A-Ⅰ for different time, cholesterol efflux, ABCA1 mRNA and protein level were determined by liquid scintillation counting, reverse transcriptase-polymerase chain reaction and Western blotting, respectively. The mean ABCA1 fluorescence intensity on THP-1 macrophage-derived foam cells was detected by flow cytometry. RESULTS: 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. 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 NH_4Cl showed such effects. The apoA-Ⅰ mediated cellular cholesterol efflux was enhanced by thiol protease inhibitors. CONCLUSION: 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.
