Hepatic Golgi lipoproteins: precursors to plasma lipoproteins in hypercholesterolemic rats

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.