LIPOPROTEIN RECEPTORS IN THE LIVER - CONTROL SIGNALS FOR PLASMA-CHOLESTEROL TRAFFIC
LIPOPROTEIN RECEPTORS IN THE LIVER - CONTROL SIGNALS FOR PLASMA-CHOLESTEROL TRAFFIC
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DOI：
10.1172/jci111044
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发表时间：
1983-01-01
影响因子：
15.9
通讯作者：
GOLDSTEIN, JL
中科院分区：
文献类型：
--
作者：
BROWN, MS;GOLDSTEIN, JL
十年的深入研究已经确定了脂蛋白受体在调节血浆胆固醇运输中的核心作用。这些受体结合携带胆固醇的脂蛋白，并通过受体介导的内吞作用将其转运到细胞中。低密度脂蛋白（LDL）受体是第一个被发现的；它已被纯化并表征了其结构。在培养的人成纤维细胞中描述了 LDL 受体；现在已知相同的受体在肝脏以及肝外组织中发挥作用。从操作上来说，LDL/LDL受体系统可以被认为是内源性胆固醇的主要转运机制。另一方面，膳食胆固醇以乳糜微粒残余物的形式从肠道转运，通过不同的乳糜微粒残余物受体进入肝细胞。乳糜微粒残余物/残余物受体系统对外源性胆固醇转运，正如LDL/LDL受体系统对外源性胆固醇转运一样。在本文中，我们回顾了这个快速发展领域的最新进展。两种肝脂蛋白受体（图1）。外源（膳食）胆固醇以乳糜微粒残余物的形式输送至肝脏 (1, 2)，乳糜微粒残余物是通过脂蛋白脂肪酶的作用从肠道乳糜微粒中衍生出来的。残余物与特定的残余物受体结合后，通过受体介导的内吞作用迅速进入肝脏 (3-5)。当肝脏将胆固醇与极低密度脂蛋白（VLDL）中的甘油三酯一起分泌到血浆中时，内源性胆固醇转运就开始了。 VLDL的甘油三酯被脂蛋白脂肪酶去除后，重新
A decade of intense investigation has established a central role for lipoprotein receptors in regulating plasma cholesterol traffic. These receptors bind cholesterol-carrying lipoproteins and transport them into cells by receptor-mediated endocytosis. The receptor for low density lipoprotein (LDL) was the first discovered; it has been purified and its structure characterized. The LDL receptor was described in cultured human fibroblasts; identical receptors are now known to function in liver as well as in extrahepatic tissues. Operationally, the LDL/LDL receptor system can be considered the primary transport mechanism for endogenous cholesterol. Dietary cholesterol, on theother hand, is transported from the intestine in chylomicron remnants, which enter hepatocytes via distinct chylomicron remnant receptors. The chylomicron rem-nant/remnant receptor system is to exogenous cholesterol transport as the LDL/LDL receptor system is to endogenous cholesterol transport. In this article, we review recent developments in this rapidly advancing field.Two hepatic lipoprotein receptors (Fig. 1). Exogenous (dietary) cholesterol is delivered to the liver in chylomicron remnants (1, 2), which are derived from intestinal chylomicrons through the action of lipopro-tein lipase. The remnantsrapidly enter the liverby receptor-mediated endocytosis after binding to specific remnant receptors (3-5). Endogenous cholesterol transport begins when the liver secretes cholesterol into plasma together with triglycerides in very low density lipoproteins (VLDL). After the triglycerides of VLDL are removed by lipoprotein lipase, the re-