Mas-Oliva J, Velasco-Loyden G, Haines T H
Departamento de Bioenergética, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D.F., Mexico.
Biochem Biophys Res Commun. 1996 Jul 5;224(1):212-8. doi: 10.1006/bbrc.1996.1009.
A critical step in the uptake of dietary cholesterol by the liver is the binding of remnant lipoprotein particles to receptors in the space of Disse. We have found that increases in the cholesterol content of hepactocyte membranes reduces the binding of beta-very low density lipoproteins (beta-VLDL) and decreases internalization. This increase in membrane cholesterol of human hepatoma cells (HepG2) produces a similar effect on binding to primary human fibroblasts. However, receptor-negative familial hypercholesterolemic (FH) fibroblasts lack the ability to respond to membrane cholesterol modification. A polyclonal antibody directed against the C-terminus region of the apo-B,E-(LDL) receptor importantly affects the internalization process, suggesting that protein-protein interactions consolidate the pattern formation of receptors, a process that triggers lipoprotein internalization. We propose that cholesterol interferes with this pattern formation by affecting the lateral movement and organization of the receptors.
肝脏摄取膳食胆固醇的关键步骤是残余脂蛋白颗粒与狄氏间隙中的受体结合。我们发现，肝细胞细胞膜胆固醇含量的增加会降低β-极低密度脂蛋白（β-VLDL）的结合，并减少内化作用。人肝癌细胞（HepG2）细胞膜胆固醇的这种增加对与原代人成纤维细胞的结合产生类似影响。然而，受体阴性的家族性高胆固醇血症（FH）成纤维细胞缺乏对细胞膜胆固醇修饰作出反应的能力。一种针对载脂蛋白B、E（低密度脂蛋白）受体C末端区域的多克隆抗体对内化过程有重要影响，这表明蛋白质-蛋白质相互作用巩固了受体的模式形成，这一过程触发脂蛋白内化。我们提出，胆固醇通过影响受体的侧向移动和组织来干扰这种模式形成。
