Antibodies against high-density lipoprotein binding proteins enhance high-density lipoprotein uptake but do not affect cholesterol efflux from rat hepatoma cells.
High-density lipoprotein plays a key role in the reverse cholesterol transport pathway as well as in the delivery of cholesterol to the liver and steroidogenic tissues. Metabolism of high-density lipoprotein is determined by one of its apolipoproteins, apolipoprotein A-I; however, the identity and function of cellular protein which binds high-density lipoprotein remains unclear. The effect of antibodies against rat high-density lipoprotein binding proteins, HB1 and HB2, on high-density lipoprotein metabolism in a rat hepatoma cell line were studied. Cells were preincubated with the antibodies and 125I-labeled high-density lipoprotein binding and uptake as well as cholesterol biosynthesis and cholesterol efflux to human plasma or isolated high-density lipoprotein were studied. Both antibodies reacted specifically with HB1 and HB2 on the ligand and Western blots, but their binding was not blocked by high-density lipoprotein. Both antibodies inhibited 125I-labeled high-density lipoprotein binding to cells by 20-40%, but stimulated 125I-labeled high-density lipoprotein uptake by up to 2.5-fold. The antibodies had no effect on cholesterol efflux or on cholesterol synthesis. It is concluded that high-density lipoprotein binding proteins, HB1 and HB2, may be involved in high-density lipoprotein uptake in the liver rather than in mediating cholesterol efflux.
Sviridov
D
D
Baker Medical Research Institute, Prahran, Australia.
Sasahara
T
T
Pyle
L E
LE
Nestel
P J
PJ
Fidge
N H
NH
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D016601:RNA-Binding Proteins; D011817:Rabbits; D051381:Rats; D018110:Receptors, Lipoprotein / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000906:Antibodies; D002352:Carrier Proteins; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D018110:Receptors, Lipoprotein; C031616:high density lipoprotein receptors; C075197:high density lipoprotein binding protein; D002784:Cholesterol