Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Expression of the acetyl low density lipoprotein receptor by rabbit fibroblasts and smooth muscle cells. Up-regulation by phorbol esters. 237 9

Very low density lipoproteins Sf 100-400 (VLDL1) from hypertriglyceridemic (HTG) subjects and chylomicrons cause receptor-mediated lipid engorgement in unstimulated macrophages in vitro via the beta-VLDL receptor pathway. We now report that the murine macrophage P388D1 cell line possesses the characteristics of the beta-VLDL receptor pathway observed previously in freshly isolated resident murine peritoneal macrophages or human monocyte-macrophages. HTG-VLDL1 isolated from the plasma of subjects with hypertriglyceridemia types 3, 4, and 5 interact with P388D1 macrophages in a high-affinity, curvilinear manner. beta-VLDL, HTG-VLDL1, chylomicrons, and thrombin-treated HTG-VLDL1 (which do not bind to the LDL receptor) compete efficiently and similarly for the uptake and degradation of HTG-VLDL1. LDL and acetyl LDL do not compete, indicating that uptake of HTG-VLDL1 is via neither the LDL receptor nor the acetyl LDL receptor. Binding of thrombin-treated HTG-VLDL1 to the beta-VLDL receptor indicates that the thrombin-accessible apoE, which is absolutely required for interaction of HTG-VLDL Sf greater than 60 with the LDL receptor, is not required for binding to the beta-VLDL receptor. The uptake and degradation of 125I-labeled HTG-VLDL1 is suppressed up to 80-90% by preincubation of the cells with sterols, acetyl LDL, or beta-VLDL, indicating that this process is not via the irrepressible chylomicron remnant (apoE) receptor. Chylomicrons, HTG-VLDL1, and thrombin-treated HTG-VLDL1-but not normal VLDL1, beta-VLDL, LDL, or acetyl LDL-produce massive triglyceride accumulation (10-20-fold mass increases in 4 hr) in P388D1 macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The beta-VLDL receptor pathway of murine P388D1 macrophages. 372 14