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肝脏高尔基体脂蛋白:高胆固醇血症大鼠血浆脂蛋白的前体

Hepatic Golgi lipoproteins: precursors to plasma lipoproteins in hypercholesterolemic rats.

作者信息

Swift L L, Soulé P D, LeQuire V S

出版信息

J Lipid Res. 1982 Sep;23(7):962-71.

PMID:7142818
Abstract

Two classes of nascent lipoproteins can be isolated from Golgi apparatus-rich fractions of liver from hypercholesterolemic rats. Golgi very low density lipoproteins (VLDL, d less than 1.006 g/ml) are enriched in cholesteryl esters and are similar in many respects to hypercholesterolemic plasma B-VLDL. Golgi low density lipoproteins (LDL, d 1.006-1.05 g/ml) are cholesteryl ester-rich beta-migrating lipoproteins similar to hypercholesterolemic plasma LDL. To determine if this latter lipoprotein is a precursor to plasma LDL, control and hypercholesterolemic rats were injected with Triton WR 1339 (400 mg/kg) to block intravascular lipoprotein catabolism, followed in 30 min with 100 microCi [3H]leucine. At time intervals up to 3 hours after [3H]leucine injection, rats were killed, and plasma lipoproteins and, in some experiments, Golgi lipoproteins were isolated. Three hours after radioisotope injection, 52% of the total lipoprotein radioactivity was found in the plasma VLDL of hypercholesterolemic rats compared to 82% in chow-fed control rats. Twenty-four percent of the total lipoprotein radioactivity appeared in the plasma IDL fraction in hypercholesterolemic rats, while only 3% was found in the same fraction in control rats. After Triton, the time course of specific activities of the Golgi and plasma lipoproteins was consistent with Golgi VLDL and LDL being precursors to plasma VLDL and IDL, respectively. The time course of specific activities of the tetramethylurea-insoluble proteins of plasma and Golgi lipoproteins provided additional evidence in support of this relationship. Furthermore the composition of plasma VLDL and IDL after Triton injection resembled their hepatic Golgi counterparts. We conclude that the liver of the hypercholesterolemic rat synthesizes, assembles, and secretes a cholesteryl ester-enriched VLDL and a cholesteryl ester-rich, beta-migrating LDL. The former is a precursor to plasma VLDL while the latter is a precursor to plasma IDL.

摘要

从高胆固醇血症大鼠肝脏富含高尔基体的组分中可分离出两类新生脂蛋白。高尔基体极低密度脂蛋白(VLDL,密度小于1.006 g/ml)富含胆固醇酯,在许多方面与高胆固醇血症血浆中的B-VLDL相似。高尔基体低密度脂蛋白(LDL,密度1.006 - 1.05 g/ml)是富含胆固醇酯的β迁移脂蛋白,与高胆固醇血症血浆中的LDL相似。为确定后一种脂蛋白是否是血浆LDL的前体,给对照大鼠和高胆固醇血症大鼠注射曲拉通WR 1339(400 mg/kg)以阻断血管内脂蛋白分解代谢,30分钟后注射100微居里的[3H]亮氨酸。在注射[3H]亮氨酸后长达3小时的时间间隔内,处死大鼠,分离血浆脂蛋白,在一些实验中还分离高尔基体脂蛋白。放射性同位素注射3小时后,高胆固醇血症大鼠血浆VLDL中发现占总脂蛋白放射性的52%,而正常饮食对照大鼠中为82%。高胆固醇血症大鼠血浆中间密度脂蛋白(IDL)组分中出现总脂蛋白放射性的24%,而对照大鼠的同一组分中仅发现3%。注射曲拉通后,高尔基体和血浆脂蛋白比活性的时间进程与高尔基体VLDL和LDL分别作为血浆VLDL和IDL的前体一致。血浆和高尔基体脂蛋白中四甲基脲不溶性蛋白质比活性的时间进程为这种关系提供了额外证据。此外,注射曲拉通后血浆VLDL和IDL的组成类似于其肝脏高尔基体对应物。我们得出结论,高胆固醇血症大鼠的肝脏合成、组装并分泌富含胆固醇酯的VLDL和富含胆固醇酯的β迁移LDL。前者是血浆VLDL的前体,而后者是血浆IDL的前体。

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