The human asialoglycoprotein receptor is a possible binding site for low-density lipoproteins and chylomicron remnants.
Binding and internalization of chylomicron remnants from rat mesenteric lymph by HepG2 cells was inhibited by both excess remnants and low-density lipoprotein (LDL) to the same extent. Ligand blots revealed binding of remnants and LDL to the LDL receptor. Measures regulating LDL receptor activity greatly influenced the binding of remnants: ethinyloestradiol, the hydroxymethylglutaryl-CoA reductase inhibitor pravastatin and the absence of LDL all increased binding, whereas high cell density or the presence of LDL decreased binding. Also, asialofetuin, asialomucin, the neoglycoprotein galactosyl-albumin and an antibody against the asialoglycoprotein receptor all decreased substantially the binding of remnants. At high cell density, binding internalization and degradation of chylomicron remnants was inhibited by up to 70-80%, yet binding of LDL was inhibited by no more than 20-30%. In cross-competition studies, the binding of 125I-asialofetuin was efficiently competed for by asialofetuin itself or by the antibody, and also by LDL and remnants, yet remnants displayed an approx. 100-fold higher affinity than LDL. Likewise, remnants of human triacylglycerol-rich lipoproteins and asialofetuin interfered with each others' binding to HepG2 cells or human liver membranes. It is concluded that the LDL receptor mediates the internalization of chylomicron remnants into hepatocytes depending on its activity, according to demand for cholesterol. Additionally, the asialoglycoprotein receptor may contribute to the endocytosis of LDL, but predominantly of chylomicron remnants.
Windler
E
E
Medizinische Kernklinik und Poliklinik, Universitäts-Krankenhaus Eppendorf, Hamburg, Federal Republic of Germany.
Greeve
J
J
Levkau
B
B
Kolb-Bachofen
V
V
Daerr
W
W
Greten
H
H
D000818:Animals; D037263:Asialoglycoprotein Receptor; D001665:Binding Sites; D001667:Binding, Competitive; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002914:Chylomicrons / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008099:Liver / Q000276:immunology / Q000378:metabolism*; D008113:Liver Neoplasms; D008196:Lymph / Q000502:physiology; D008297:Male; D008970:Molecular Weight; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic / Q000302:isolation & purification / Q000378:metabolism*; D011973:Receptors, LDL / Q000302:isolation & purification / Q000378:metabolism*
D037263:Asialoglycoprotein Receptor; D002914:Chylomicrons; D008077:Lipoproteins, LDL; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D011973:Receptors, LDL