Windler E E, Greeve J, Daerr W H, Greten H
Medizinische Kernklinik und Poliklinik, Universitäts-Krankenhaus Eppendorf, Hamburg, West Germany.
Biochem J. 1988 Jun 1;252(2):553-61. doi: 10.1042/bj2520553.
Binding and uptake of rat chylomicrons of different metabolic stages by the hepatic low-density-lipoprotein (LDL) receptor were studied. Pure chylomicrons, characterized by apolipoprotein B-48 devoid of contaminating B-100, were labelled in their cholesteryl esters. Lymph chylomicrons and serum chylomicrons, enriched in apolipoprotein E and the C-apolipoproteins, bound poorly to rat hepatic membranes. In contrast, chylomicron remnants, containing the apolipoproteins B-48 and E, bound with high affinity. Specific binding of remnants was virtually completely competed for by LDL free of apolipoprotein E. In addition, in ligand blots both remnants and LDL associated with the same protein with an Mr characteristic of the LDL receptor. Uptake of remnants during a single pass through isolated perfused rat livers was decreased to about 50% by an excess of LDL. It is concluded that rat chylomicron remnants are a ligand of the hepatic LDL receptor. The much higher affinity as compared with LDL is mediated by apolipoprotein E but not B-48, and is inhibited by the C-apolipoproteins. This explains why serum chylomicrons are not taken up by the liver, whereas remnants are rapidly removed from the circulation. Results from experiments in vivo suggest that the LDL receptor makes an important contribution to the hepatic uptake of remnants and may be the principal binding site of the liver responsible for remnant removal.
研究了不同代谢阶段的大鼠乳糜微粒被肝脏低密度脂蛋白（LDL）受体的结合和摄取情况。以不含污染性B-100的载脂蛋白B-48为特征的纯乳糜微粒，其胆固醇酯被标记。富含载脂蛋白E和C-载脂蛋白的淋巴乳糜微粒和血清乳糜微粒与大鼠肝细胞膜的结合较差。相比之下，含有载脂蛋白B-48和E的乳糜微粒残粒具有高亲和力结合。不含载脂蛋白E的LDL几乎完全竞争残粒的特异性结合。此外，在配体印迹中，残粒和LDL与具有LDL受体特征的Mr的同一种蛋白质相关。单次通过分离灌注的大鼠肝脏时，过量的LDL使残粒的摄取减少至约50%。结论是大鼠乳糜微粒残粒是肝脏LDL受体的一种配体。与LDL相比更高的亲和力由载脂蛋白E介导而非B-48，并且被C-载脂蛋白抑制。这解释了为什么血清乳糜微粒不被肝脏摄取，而残粒则迅速从循环中清除。体内实验结果表明，LDL受体对肝脏摄取残粒起重要作用，可能是肝脏负责清除残粒的主要结合位点。
