© 1997 American Heart Association, Inc.
Articles |
Possible Functional Interactions of Apolipoprotein B-100 Segments That Associate With Cell Proteoglycans and the ApoB/E Receptor
the Wallenberg Laboratory for Cardiovascular Research (U.O, G.C., E.H.-C., K.E., O.W., G.B.), Heart and Lung Department, Goteborg University, Goteborg, and the Preclinical Research Laboratories (G.C.), AB Astra Hassle, Molndal, Sweden.
Correspondence to German Camejo, Preclinical Research Laboratories, AB Astra Hassle, S-431 83, Molndal, Sweden. E-mail german.camejo@hassle.se.astra.com.
The interaction of apoE lipoproteins with cells appears to be mediated by an association with basic sequences of proteoglycans and the apoB/E receptor. ApoB-100 has basic sequences, homologous with those of apoE, that form part of the apoB/E receptor–binding domain. These sequences of apoB-100 also interact with proteoglycans. We investigated whether such segments, in analogy with apoE, could act cooperatively on LDL interactions with proteoglycans and the receptor. As a model we used the two most basic regions of apoB-100, 3147 through 3157 and 3359 through 3367, connected by three glycines (3145-3157–GGG–3359-3367). Such segments may be proximal in LDL by the presence of a disulfide bridge between Cys(3167) and Cys(3297). The apoB heterodimer but not the separated monomers inhibited 125I-LDL degradation in fibroblasts and THP-1 cells by 50% at 
11 µmol/L. The heterodimer affinity with arterial proteoglycans was closer to that of LDL and higher than that of the individual peptides. The heterodimer appears to bind specifically to THP-1 cells, with a Kd of 6.2x10-8 mol/L and a Bmax of 1.3x106 molecules/cell. Monoclonal antibody C-7, which recognizes the apoB receptor, inhibited the binding to cells. Treatment of fibroblasts with chondroitinase ABC or chlorate decreased 125I-LDL degradation markedly. Hydrolysis of pericellular proteoglycans of fibroblasts by chondroitinases reduced mostly the low-affinity, high-capacity component of LDL binding. This compartment appears to hold 70% of the cell-associated LDL when internalization is inhibited at 4°C. Therefore, cell-surface chondroitin sulfate/dermatan sulfate proteoglycans appear to modulate binding and receptor-mediated internalization of LDL. This may be caused, at least in part, by the association of proteoglycans with the apoB-100 segments 3145 through 3157 and 3359 through 3367.
Key Words: apoB-100 • cell-surface proteoglycans • apoB/E receptor • LDL degradation • LDL cell binding
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