Lipoprotein binding to canine hepatic membranes. Metabolically distinct apo-E and apo-B,E receptors.

作者：David Y. Hui, T L Innerarity, Robert W. Mahley · 发表于：Journal of Biological Chemistry · 年份：1981 · DOI：10.1016/s0021-9258(19)69254-9 · 被引用次数：386 · 研究领域：Liver Disease Diagnosis and Treatment、Diet, Metabolism, and Disease、Cholesterol and Lipid Metabolism

Hepatic membranes from adult dog livers have receptors which bind to lipoproteins containing the E apoprotein (the apo-E HDLc) but lack specific receptors for the apo-B-containing low density lipoproteins (LDL). Scatchard analysis of direct binding data for 125I-apo-E-HDLc revealed nonlinearity of the binding which could be resolved into two components, suggesting the presence of two separate binding sites. The binding site for apo-E HDLc that possessed the highest affinity (Kd = 0.23 x 10(-9) M) was calcium-dependent and was sensitive to proteolytic digestion with pronase. The lower affinity (Kd = 20 x 10(-9) M) binding site for apo-E HDLc did not require calcium and was resistant to pronase digestion. Chemical modification of the arginyl or lysyl residues of the apo-E HDLc prevented the HDLc from binding to the higher affinity receptor but had no effect on their binding to the lower affinity site. Adult canine liver membranes also bound canine 125I-HDL. However, the binding of HDL was of lower affinity (Kd = 8.2 x 10(-8) M), did not require calcium, was not blocked by modification of the lysyl or arginyl residues, and may not be of physiologic significance. Although the liver membranes from normal chow-fed adult dogs did not bind canine LDL, it was possible to demonstrate specific high affinity binding of LDL under certain metabolic conditions in dogs. When adult dogs were treated with the hypocholesterolemic agent cholestyramine, the liver membranes from these animals read...