Oxidized low density lipoproteins bind to the scavenger receptor expressed by rabbit smooth muscle cells and macrophages.
We have previously demonstrated that the acetylated low density lipoprotein (LDL), or scavenger, receptor expressed by rabbit smooth muscle cells (SMCs) is regulated. Phorbol ester treatment of the cells increased the number of scavenger receptors expressed and the metabolism of acetoacetylated (AcAc) LDL. The current studies examined the interaction of oxidized (Ox) LDL with the rabbit scavenger receptor. The internalization and degradation of both Ox-LDL and AcAc-LDL were increased to a similar extent by phorbol ester treatment of the SMCs. In cross-competition experiments, both Ox-LDL and AcAc-LDL competed equally for the degradation of 125I-Ox-LDL, suggesting that there is no independent receptor for Ox-LDL on these cells. In contrast, only AcAc-LDL competed totally for the degradation of 125I-AcAc-LDL. Similar results were obtained in cross-competition experiments with rabbit macrophages. To determine whether these data were consistent with the binding of both ligands to a single receptor, competition studies were conducted in Chinese hamster ovary fibroblasts transfected with the bovine scavenger receptor. After transfection, the metabolism of both AcAc-LDL and Ox-LDL was increased, in agreement with the previous data from other investigators, and cross-competition studies yielded essentially identical results to those obtained in the SMCs and macrophages. Northern blot analysis with an antisense rabbit scavenger receptor probe detected the same mRNA species in total RNA from rabbit macrophages and SMCs and showed that scavenger receptor mRNA increased dramatically after phorbol ester treatment of SMCs. The probe also detected bovine scavenger receptor mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Dejager
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S
Department of Pathology, University of California, San Francisco.
Mietus-Synder
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M
Pitas
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D000818:Animals; D001667:Binding, Competitive; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D015151:Immunoblotting; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D011817:Rabbits; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C044102:acetoacetyl-LDL; D012313:RNA