Effects of apolipoprotein A-Ⅰon ATP binding cassette transporter A1 degradation and cholesterol efflux in THP-1 macrophage-derived foam cells / 中国病理生理杂志

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.