Heparin-Manganese Precipitability of Canine Lipoproteins as Correlated with Binding to the Cell Surface Receptors on Fibroblasts
The binding of specific lipoproteins to cell surface receptors on fibroblasts and smooth muscle cells initiates a series of events which result in uptake and degradation of the lipoproteins, the accumulation of cholesteryl esters, and the regulation of cholesterol synthesis. The specificity for binding certain lipoproteins and not others may reside with the apoprotein content of the lipoproteins. The two classes of lipoproteins demonstrated to bind to the same cell surface receptor include those which contain the B-apoprotein (LDL) (Goldstein and Brown, 1974) and those which contain the arginine-rich apoprotein (e.g., the HDLC of the cholesterol-fed swine) (Bersot et al., 1976). Previously, we also demonstrated that an HDLC fraction from coconut oil-cholesterol-fed dogs had only the arginine-rich apoprotein and was as effective in delivering cholesterol to canine smooth muscle cells as were the LDL (Mahley, 1976). These findings suggested that if the protein were the important determinant for binding, then the receptor recognized both the B- and the arginine-rich apoproteins. The B and ARP may have in common a structural sequence or a similarly charged region which might be responsible for the binding of lipoproteins to the same cell surface receptor. That surface charge is important has been suggested by the studies of Goldstein et al. (1976) in which glycosaminoglycans, in particular heparin, competed with the receptor on fibroblasts for binding with human LDL. The negatively charged heparin is thought to bind to LDL at regions of positive charge (Iverius, 1972), which may also be the portion of the molecule that binds to the receptor.
KeywordsCell Surface Receptor Cholesteryl Ester Competitive Binding Lipoprotein Fraction Final Supernatant
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