Hofmann S L, Eaton D L, Brown M S, McConathy W J, Goldstein J L, Hammer R E
Department of Molecular Genetics, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas 75235.
J Clin Invest. 1990 May;85(5):1542-7. doi: 10.1172/JCI114602.
Lp(a) lipoprotein purified from human plasma bound with high affinity to isolated bovine LDL receptors on nitrocellulose blots and in a solid-phase assay. Lp(a) also competed with 125I-LDL for binding to human LDL receptors in intact fibroblasts. Binding led to cellular uptake of Lp(a) with subsequent stimulation of cholesterol esterification. After intravenous injection, human Lp(a) was cleared slowly from the plasma of normal mice. The clearance was markedly accelerated in transgenic mice that expressed large amounts of LDL receptors. We conclude that the covalent attachment of apo(a) to apo B-100 in Lp(a) does not interfere markedly with the ability of apo B-100 to bind to the LDL receptor and that this receptor has the potential to play a major role in clearance of Lp(a) from the circulation of intact humans.
从人血浆中纯化的Lp(a)脂蛋白在硝酸纤维素膜印迹和固相分析中与分离的牛LDL受体具有高亲和力结合。Lp(a)还在完整的成纤维细胞中与125I-LDL竞争结合人LDL受体。结合导致Lp(a)被细胞摄取，随后刺激胆固醇酯化。静脉注射后，人Lp(a)从正常小鼠血浆中清除缓慢。在表达大量LDL受体的转基因小鼠中，清除明显加快。我们得出结论，Lp(a)中apo(a)与apo B-100的共价连接不会明显干扰apo B-100与LDL受体结合的能力，并且该受体有可能在完整人类循环中Lp(a)的清除中起主要作用。
