Effect Of Apolipoprotein A-Ⅰ On Expression And Function Of ATP-binding Cassette Transporter A1 Through PKA Signaling

Objective: ATP-binding cassette transporter A1 (ABCA1) plays a crucial role in apoA-I binding activity and promotes cellular cholesterol efflux. The aim of this study was to investigate the effect of interaction between apoA-I and ABCA1 on atherosclerosis, and to discover the mechanism of interaction between apoA-I and ABCA1.Methods: THP-1 cells were induced to become the macrophages by the phorbol. Then THP-1 macrophages were induced to the foam cells by ox-LDL. Treatment of THP-1 macrophage derived foam cells with apoA-I , forskolin (an adenyl cyclase activator), and SQ-22536 (an adenyl cyclase inhibitor) for long periods of time (24 hours). In addition, THP-1 macrophage derived foam cells were treated with increasing amounts of forskolin (0,10,20,40 and 80μM)and treated with forskolin for increasing time(0, 6,12 and 24 hours). Cholesterol efflux, ABCA1 mRNA and protein level were determined by FJ-2107P type liquid scintillator, reverse trancriptase-polymerase chain reaction and western blot, respectively. Cellular lipid accumulation was determined by Oil Red O staining and high performance liquid chromatography analysis.Results: ApoA- I up-regulated expression of ABCA1 protein, and increased cholesterol efflux in THP-1 macrophage derived foam cells. The similar condition has been observed in foam cells treated with forskolin. ApoA-I increased level of ABCA1 protein in a concentration- and time-dependent manner. In converse, treatment THP-1 macrophage derived foam cells with SQ-22536 down-regulated expression of ABCA1 protein and decreased cholesterol efflux. However, apoA-I , forskolin and SQ-22536 can not influence expression of ABCA1 mRNA.Conclusions: These findings suggest that apoA-I may stabilize ABCA1 protein, and...