Johnson W J, Mahlberg F H, Rothblat G H, Phillips M C
Department of Physiology and Biochemistry, Medical College of Pennsylvania, Philadelphia 19129.
Biochim Biophys Acta. 1991 Oct 1;1085(3):273-98. doi: 10.1016/0005-2760(91)90132-2.
Various types of studies in humans and animals suggest strongly that HDL is anti-atherogenic. The anti-atherogenic potential of HDL is thought to be due to its participation in reverse cholesterol transport, the process by which cholesterol is removed from non-hepatic cells and transported to the liver for elimination from the body. Extensive studies in cell culture systems have demonstrated that HDL is an important mediator of sterol transport between cells and the plasma compartment. The topic of this review is the mechanisms that account for sterol movement between HDL and cells. The most prominent and easily measured aspect of sterol movement between HDL and cells is the rapid bidirectional transfer of cholesterol between the lipoprotein and the plasma membrane. This movement occurs by unmediated diffusion, and in most situations its rate in each direction is limited by the rate of desorption of sterol molecules from the donor surface into the adjacent water phase. The net transfer of sterol mass out of cells occurs when there is either a relative enrichment of sterol within the plasma membrane or a depletion of sterol in HDL. Recent studies suggest that certain minor subfractions of HDL (with pre-beta mobility on agarose gel electrophoresis and containing apoprotein A-I but no apo A-II) are unusually efficient at promoting efflux of cell sterol. To what extent efflux to these HDL fractions is balanced by influx from the lipoprotein has not yet been established clearly. The prevention and reversal of atherosclerosis require the mobilization of cholesterol from internal (non-plasma membrane) cellular locations. To some extent, this may involve the retroendocytosis of HDL. However, most mobilization probably involves the transport of internal sterol to the plasma membrane, followed by desorption to extracellular HDL. Several laboratories are investigating the transport of sterol from intracellular locations to the plasma membrane. Studies on biosynthetic sterol (probably originating mostly in the smooth endoplasmic reticulum) suggest that there is rapid transport to the plasma membrane in lipid-rich vesicles. Important features of this transport are that it bypasses the Golgi apparatus and may be positively regulated by the specific binding of HDL to the plasma membrane.(ABSTRACT TRUNCATED AT 400 WORDS)
针对人类和动物的各类研究有力地表明，高密度脂蛋白（HDL）具有抗动脉粥样硬化作用。HDL的抗动脉粥样硬化潜能被认为归因于其参与逆向胆固醇转运，即胆固醇从非肝细胞中被移除并转运至肝脏以便从体内清除的过程。在细胞培养系统中进行的大量研究表明，HDL是细胞与血浆区室之间固醇转运的重要介质。本综述的主题是解释HDL与细胞之间固醇移动的机制。HDL与细胞之间固醇移动最显著且易于测量的方面是脂蛋白与质膜之间胆固醇的快速双向转移。这种移动通过非介导扩散发生，在大多数情况下，其在每个方向上的速率受固醇分子从供体表面解吸进入相邻水相的速率限制。当质膜内固醇相对富集或HDL中固醇耗竭时，固醇质量会从细胞中净转移出去。最近的研究表明，HDL的某些次要亚组分（在琼脂糖凝胶电泳上具有前β迁移率且含有载脂蛋白A-I但不含载脂蛋白A-II）在促进细胞固醇流出方面异常有效。这些HDL组分的流出在多大程度上被来自脂蛋白的流入所平衡，目前尚未明确确定。动脉粥样硬化的预防和逆转需要从细胞内部（非质膜）位置动员胆固醇。在某种程度上，这可能涉及HDL的逆向内吞作用。然而，大多数动员可能涉及将内部固醇转运至质膜，随后解吸至细胞外HDL。几个实验室正在研究固醇从细胞内位置向质膜的转运。对生物合成固醇（可能主要起源于滑面内质网）的研究表明，存在通过富含脂质的囊泡快速转运至质膜的情况。这种转运的重要特征是它绕过高尔基体，并且可能受HDL与质膜的特异性结合正向调节。（摘要截选至400字）
