Expression of the acetyl low density lipoprotein receptor by rabbit fibroblasts and smooth muscle cells. Up-regulation by phorbol esters.
The acetyl low density lipoprotein (LDL), or scavenger, receptor, which binds modified forms of LDL, was thought to be expressed only on macrophages and endothelial cells. We demonstrate that rabbit fibroblasts and smooth muscle cells bind, internalize, and degrade acetoacetylated LDL, a ligand for the acetyl LDL receptor. Degradation is specific in that unlabeled acetoacetylated LDL and fucoidin, a known competitor for binding to the acetyl LDL receptor, are effective competitors, while native LDL is not. The acetyl LDL receptor on these cells is readily regulated. Higher levels of degradation are observed in cells preincubated with serum than in cells preincubated with plasma. This up-regulation of the acetyl LDL receptor is most likely due to the presence of platelet secretory products in serum since secretion products derived from thrombin-stimulated platelets also cause an increase in degradation. In addition, preincubation of rabbit fibroblasts with phorbol esters results in a 16-20-fold increase in specific degradation. These results indicate that rabbit fibroblasts and smooth muscle cells express the acetyl LDL receptor and that increased receptor expression appears to be mediated through activation of the protein kinase C pathway.
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Gladstone Foundation Laboratories for Cardiovascular Disease, Department of Pathology, University of California, San Francisco 94140-0608.
D000818:Animals; D015815:Cell Adhesion Molecules; D003470:Culture Media; D004705:Endocytosis; D005347:Fibroblasts / Q000378:metabolism*; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009130:Muscle, Smooth / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D011817:Rabbits; D011973:Receptors, LDL / Q000378:metabolism*; D051116:Receptors, Scavenger; D015854:Up-Regulation / Q000187:drug effects
D015815:Cell Adhesion Molecules; D003470:Culture Media; D008077:Lipoproteins, LDL; D010703:Phorbol Esters; D011134:Polysaccharides; D011973:Receptors, LDL; D051116:Receptors, Scavenger; C032629:acetyl-LDL; C007789:fucoidan; D011493:Protein Kinase C