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Low-density lipoprotein endocytosis. II. Influence of the multivalent ligand cationized ferritin on acetylated low-density lipoprotein endocytosis in cultured cells.

Abstract：

:Interactions of the basic multivalent ligand cationized ferritin (CF) with cultured cells markedly alter their endocytic function. In this study, the influence of CF treatment on the binding, internalization, and degradation of chemically modified (acetylated) low-density lipoproteins (Ac-LDL) was examined in aortic smooth muscle cells (SMC); and in normal and FH mutant LDL receptor-negative human skin fibroblasts, which lack the Ac-LDL (scavenger) receptor; and in vascular endothelial cells, which normally express the receptor. Although CF treatment of all three cell types at 37 degrees C resulted in the induction of Pronasesensitive, high-capacity, high-affinity binding (Kd = 12.0 +/- 2.0 nM at 4 degrees C) of labeled Ac-LDL, which at 37 degrees C was accompanied by significant internalization and degradation, these processes were not receptor-mediated. CF-induced high-affinity binding was inhibited by unlabeled Ac-LDL, fucoidan, carrageenan, and dextran sulfate but was unaffected by native LDL and albumin and only partially inhibited by acetylated albumin. However, analysis of membrane preparations of the cells for "scavenger" receptor protein by solid-phase filtration assay and Western blotting identified the receptor in endothelial cells and in granuloma (positive control) macrophages, but not in either CF-treated or untreated SMC. In addition, studies with both glutaraldehyde-fixed cells and CF bound to culture dishes indicated that Ac-LDL avidly binds to CF. Further, ultrastructural studies using colloidal gold-conjugated Ac-LDL showed Ac-LDL preferentially binding to CF aggregates on the cell surface. Thus, these studies indicate that treatment of cells with CF induces an endocytic process which, although remarkably similar to the scavenger pathway, is mediated by Ac-LDL binding to membrane-associated CF. These observations have implications in terms of mechanisms that might regulate the endocytosis of modified low-density lipoproteins.

journal_name

Exp Mol Pathol

journal_title

Experimental and molecular pathology

authors

Sprague EA,Edwards EH,Valente AJ,Suenram CA,Kerbacher JJ,Schwartz CJ

doi

10.1016/0014-4800(88)90072-x

subject

Has Abstract

pub_date

1988-06-01 00:00:00

pages

373-90

issue

eissn

0014-4800

issn

1096-0945

pii

0014-4800(88)90072-X

journal_volume

pub_type

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Low-density lipoprotein endocytosis. II. Influence of the multivalent ligand cationized ferritin on acetylated low-density lipoprotein endocytosis in cultured cells.