三磷酸腺苷结合盒转运体A1在THP-1巨噬细胞源性泡沫细胞胆固醇流出中的作用

Action of ATP binding cassette transporter A 1 on cholesterol efflux in THP-1 macrophage-derived foam cells

目的 :以THP - 1巨噬细胞源性泡沫细胞为研究对象 ,探讨ABCA1在THP - 1巨噬细胞源性泡沫细胞胆固醇流出中的作用。方法 :用液体闪烁计数器检测胆固醇流出。RT -PCR方法检测ABCA1mRNA的表达。结果 :氧化型低密度脂蛋白可增加THP - 1巨噬细胞胆固醇流出 ,2 2 (R) -羟基胆固醇剂量依赖性增加THP - 1巨噬细胞源性泡沫细胞胆固醇流出 ,而DIDS剂量依赖性减少THP - 1巨噬细胞源性泡沫细胞胆固醇流出 ;逆转录聚合酶链反应显示 ,2 2 (R) -羟基胆固醇可增加THP - 1巨噬细胞源性泡沫细胞ABCA1mRNA的表达 ,DIDS可抑制THP - 1巨噬细胞源性泡沫细胞ABCA1mRNA的表达。结论 :ABCA1在巨噬细胞源性泡沫细胞胆固醇流出中起着重要的作用 ,并为开发和寻找对ABCA1表达有特异性调控作用的药物提供了新的思路。

AIM: To study the action of ATP binding cassette transporter(ABC) A 1 on cholesterol efflux in THP-1 macrophage-derived foam cells. METHODS: After exposure of the cultured THP-1 macrophage-derived foam cells to 22(R)-hydroxycholesterol and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) at different concentration for 24 hours, cholesterol efflux and ABCA1 mRNA level were determined by FJ-2107P type liquid scintillator and reverse trancriptase-polymerase chaim reaction(RT-PCR), respectively. RESULTS: Oxidized LDL promoted cholesterol efflux in THP-1 macrophages and 22(R)-hydroxycholesterol increased cholesterol efflux in THP-1 macrophage-derived foam cells in a dose-dependent manner and DIDS inhibited cholesterol efflux in THP-1 macrophage-derived foam cells in a dose-dependent manner. Exposure of the cultured THP-1 macrophage-derived foam cells to 22(R)-hydroxycholesterol and DIDS at different concentration for 24 hours, resulted in increase and decrease in the expression of ABCA1 mRNA in THP-1 macrophage-derived foam cells in a dose-dependent manner, respectively. CONCLUSION: ABCA1 playes an important role in cholesterol efflux in THP-1 macrophage-derived foam cells.