In vivo removal of beta-VLDL, chylomicron remnants, and alpha 2-macroglobulin in the rat.
The low density lipoprotein receptor-related protein (LRP)/alpha 2-macroglobulin (alpha 2M) receptor has been suggested as a potential chylomicron remnant receptor. To investigate the involvement of LRP in chylomicron remnant metabolism in vivo, cross-competition experiments with chylomicron remnants, beta-VLDL, and receptor-active alpha 2M, complexed with trypsin (alpha 2M-trypsin), were performed in rats. Saturating concentrations of unlabeled beta-VLDL failed to inhibit the plasma clearance and hepatic uptake of 125I-labeled alpha 2M-trypsin and, vice versa, alpha 2M-trypsin failed to retard the removal of 125I-labeled chylomicron remnants. It has been demonstrated previously that bovine lipoprotein lipase (LPL) strongly enhances the binding of apolipoprotein E-containing lipoproteins to LRP (U. Beisiegel, W. Weber, and G. Bengtsson-Olivecrona. 1991. Proc. Natl. Acad. Sci. USA. 88: 8342-8346). Therefore, beta-VLDL were enriched with isolated LPL or heparin was injected simultaneously with beta-VLDL to increase the concentration of endogenous LPL bound to beta-VLDL. Yet, no inhibition of the plasma elimination and the hepatic uptake of 125I-labeled alpha 2M-trypsin was observed after injection of saturating amounts of beta-VLDL enriched with LPL. We conclude that in the rat triglyceride-rich lipoproteins and alpha 2M-trypsin bind in vivo either to different binding domains of LRP or to a different receptor protein.
Jäckle
S
S
Medizinische Kernklinik and Poliklinik, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
Huber
C
C
Moestrup
S
S
Gliemann
J
J
Beisiegel
U
U
D000818:Animals; D001667:Binding, Competitive; D002914:Chylomicrons / Q000097:blood*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008071:Lipoprotein Lipase / Q000494:pharmacology; D008079:Lipoproteins, VLDL / Q000097:blood* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000378:metabolism; D014357:Trypsin / Q000097:blood / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism*
D002914:Chylomicrons; D008079:Lipoproteins, VLDL; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; C028939:alpha-2-macroglobulin-trypsin complex; D000511:alpha-Macroglobulins; D006493:Heparin; D008071:Lipoprotein Lipase; D014357:Trypsin