荷脂细胞胆固醇外向转运的工作模式

Model and Regulation of Cholesterol Efflux from Lipid-loaded Cells

荷脂细胞外向转运胆固醇的能力是决定动脉粥样硬化进程与转归的关键。参与调控荷脂细胞胆固醇外向转运的蛋白质很多 ,经归纳、整理 ,我们提出“四个体系、一个中心、偶联转运、网络调控”的工作模式。即小凹蛋白 1胞内转运体系、三磷酸腺苷结合盒A1跨膜转运体系、高密度脂蛋白受体 (清道夫受体B1)跨膜转运体系、高密度脂蛋白—载脂蛋白A1胞外转运体系和小凹转运中心。以小凹为转运枢纽 ,小凹蛋白 1胞内转运体系首先将胆固醇从胞内转运到细胞膜 ,贮存于小凹 ;位于小凹中心的清道夫受体B1跨膜转运体系和三磷酸腺苷结合盒A1跨膜转运体系随后将胆固醇交给高密度脂蛋白—载脂蛋白A1胞外转运体系 ;四个转运体系之间进行网络调控。该工作模式为动脉粥样硬化性疾病的发生发展及治疗提供一个简明的工作思路。

Cholesterol efflux from lipid-loaded cells is a key event associating with stability and subsidence of plaque. There are many proteins and factors participating in regulation of cholesterol efflux of lipid-loaded cells, which is very complex. We propose,by summarizing the recent research,a novel mode of “four systems and one center with coupling transportation and networking regulation'. The novel mode consists of 1) intracellular trafficking system of caveolin-1 complex,2) transmembrane transporting system of ATP binding cassette transporter(ABC)-A1 complex,3) transmembrane transporting system of scavenger receptor (SR-) B1 complex,4) extracelluar trafficking system of high density lipoprotein/apolipoprotein (HDL/Apo)-A1 and 5) caveolae transporting center. In brief,caveolin-1 complex system transports cholesterol from intracellular compartments to caveolae; both ABC-A1 and SR-B1 complex systems transfer cholesterol from caveolae to HDL/Apo-A1. There are networking regulation among four systems. This mode provides a simple and concise way to understand the dynamic process of atherosclerosis.