Scavenger receptor BI promotes high density lipoprotein-mediated cellular cholesterol efflux
Scavenger receptor BI promotes high density lipoprotein-mediated cellular cholesterol efflux
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DOI：
10.1074/jbc.272.34.20982
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发表时间：
1997-08-22
影响因子：
4.8
通讯作者：
Tall, AR
中科院分区：
文献类型：
--
作者：
Ji, Y;Jian, B;Tall, AR
清道夫受体BI（SR-EI）能与高密度脂蛋白（HDL）结合，并介导HDL胆固醇酯的选择性摄取。我们研究了SR-BI对细胞内胆固醇流出的潜在影响。在稳定转染小鼠SR-BI的中国仓鼠卵巢细胞中，SR-BI的过表达导致初始胆固醇流出率增加3-4倍。外排率与细胞中SB-BI表达和培养基中HDL浓度相关。当与合成的不含胆固醇的RDL孵育时，SR-BI转染的细胞显示与对照细胞相比初始流出速率增加了3倍，表明SR-BI表达增强了盘状HDL介导的净胆固醇流出。在六种不同的细胞类型中，包括培养的巨噬细胞，RDL或血清介导的胆固醇流出率与细胞SR-BI表达水平密切相关。此外，原位杂交实验显示SR-BI mRNA在载脂蛋白E基因敲除小鼠动脉粥样硬化的增厚的主动脉内膜中表达。因此，SR-BI是介导细胞胆固醇流出的真实HDL受体，SR-BI可促进动脉壁中HDL介导的胆固醇流出的初始步骤以及涉及肝脏中HDL胆固醇摄取的胆固醇逆向转运的后续步骤。
Scavenger receptor BI (SR-EI) binds high density lipoproteins (HDL) with high affinity and mediates the selective uptake of HDL cholesteryl ester, We examined the potential role of SR-BI ill mediating cellular cholesterol efflux, In Chinese hamster ovary cells stably transfected with murine SR-BI, overexpression of SR-BI resulted in a 3-4-fold stimulation of initial cholesterol efflux rates. Efflux rates correlated with SB-BI expression in cells and HDL concentration in the medium. When incubated with synthetic cholesterol-free RDL, SR-BI-transfected cells showed similar to 3-fold increases in initial rates of efflux compared with control cells, indicating that SR-BI expression enhances net cholesterol efflux mediated by discoidal HDL. In six different cell types, including cultured macrophages, the rate of efflux of cholesterol mediated by RDL or serum was well correlated with cellular SR-BI expression level. In addition, in situ hybridization experiments revealed that SR-BI mRNA was expressed in the thickened intima of atheromatous aorta of apolipoprotein E knockout mice. Thus, SR-BI is an authentic HDL receptor mediating cellular cholesterol efflux, SR-BI may facilitate the initial steps of HDL-mediated cholesterol efflux in the arterial wall as well as later steps of reverse cholesterol transport involving uptake of HDL cholesterol in the liver.