Binding of chylomicron remnants and beta-very low density lipoproteins to hepatic and extrahepatic lipoprotein receptors. A process independent of apolipoprotein B48.

D Y Hui,T L Innerarity,R W Milne,Y L Marcel,R W Mahley

doi:10.1016/s0021-9258(17)42514-2

Abstract

The ability of apolipoprotein (apo-) B48 to interact with lipoprotein receptors was investigated using three different types of lipoproteins. First, canine chylomicron remnants, which contained apo-B48 as their primary apoprotein constituent, were generated by the hydrolysis of chylomicrons with milk lipoprotein lipase. These apo-B48-containing chylomicron remnants are deficient in apo-E and reacted very poorly with apo-E receptors on adult dog liver membranes and the low density lipoprotein (apo-B,E) receptors on human fibroblasts. Addition of normal human apo-E3 restored the receptor binding activity of these lipoproteins. Second, beta-very low density lipoproteins (beta-VLDL) from cholesterol-fed dogs were subfractionated into distinct classes containing apo-E along with either apo-B48 or apo-B100. Both classes bound to the apo-B,E and apo-E receptors. Their binding was almost completely mediated by apo-E, as evidenced by the ability of the anti-apo-E to inhibit the receptor interaction. Third, beta-VLDL from type III hyperlipoproteinemic patients were subfractionated by immunoaffinity chromatography into lipoproteins containing apo-E plus either apo-B48 or apo-B100. Both subfractions bound poorly to apo-B,E and apo-E receptors due to the presence of defective apo-E2. However, the residual binding of the apo-B48-containing and apo-B100-containing human beta-VLDL was inhibited by the anti-apo-E. After lipase hydrolysis, apo-B100 became a more prominant determinant responsible for mediating receptor binding to the apo-B,E receptor. By contrast, lipase hydrolysis did not increase the binding activity of the apo-B48-containing beta-VLDL. These results indicate that apo-B48 does not play a direct role in mediating the interaction of lipoproteins with receptors on fibroblasts or liver membranes.

Highlights

The ability of apolipoprotein B48 to interact apo-B species are distributed differently among the lipoprowith lipoprotein receptors was investigated using thterieneclasses
Using monoclonal antibodies againstapo-B or apo-E, it Apolipoprotein’ Bexistsin at least two forms: a was previously shown that receptor-defective apo-E2, and not higher molecular weight form of apo-B, termed apo-B100, and apo-B, was responsible for most of the residual binding activa lower molecular weight form called apo-B48 (I).The two ity of type 111 P-VLDL to both LDL and apo-E
Lipase hydrolysisof the immunoaffinity-purified, apo-B48-containingP-VLDL did not result in any enhancement in their binding to theliver membranes of cholestyramine-treated dogs (Fig. 8)

Summary

A PROCESS INDEPENDENT OF APOLIPOPROTEIN B48*

Both subfractions apo-E particles(chylomicron remnants) suggest a unique role bound poorly to apo-B,E and apo-E receptors due to for different apo-B forms in mediating the catabolism of these the presenceof defective apo-Ea. the residual bindingof the apo-B48-containing and apo-B100containing human fl-VLDL was inhibited by the antiapo-E. Lipoproteins containing either apo-B100 or apo-E have been shown to bind to this receptor [13, 14]. Using monoclonal antibodies againstapo-B or apo-E, it Apolipoprotein (apo-)’ Bexistsin at least two forms: a was previously shown that receptor-defective apo-E2, and not higher molecular weight form of apo-B, termed apo-B100, and apo-B, was responsible for most of the residual binding activa lower molecular weight form called apo-B48 (I).The two ity of type 111 P-VLDL to both LDL (apo-B,E) and apo-E.

MATERIALS AND METHODS

RESULTS

HumanFibroblasts lo ti

Fraction I

DISCUSSION