Characterization of a human hepatic receptor for high density lipoproteins.
Characterization of the membrane receptor for the low density lipoproteins (LDL) has led to insights into cellular receptor physiology as well as mammalian lipid transport. Result with LDL have stimulated the search for specific receptors for other plasma lipoproteins. Receptors for high density lipoproteins (HDL) have been identified in human fibroblasts and smooth muscle cells. Specificity for this receptor has been difficult to define since normal HDL contains several apolipoproteins, and particles containing apolipoproteins B and E have been shown to compete for HDL binding. In the present study, we demonstrate that HDL isolated from a patient devoid of apolipoprotein E was bound specifically by human hepatic membranes. This binding reached saturation within 2 hours and was EDTA-resistant. Assuming a single receptor model, we found that 2.9 x 10(15) receptors/mg membrane protein bound with an affinity KD = 3.5 x 10(-7) M at 0 to 4 degrees C and KD = 1.9 x 10(-7) M at 37 degrees C. The binding was effectively competed with intact HDL3, with HDL3 that had undergone selective arginine and lysine residue modification, and with antibodies to apolipoproteins A-I and A-II. However, LDL, asialofetuin, and HDL3 which had undergone tyrosine modification by nitration, and anti-apolipoprotein B did not compete with apo A-I HDL binding. In contrast to LDL binding, the human hepatoma cell line, HEPG2, increased HDL binding with cholesterol loading that was specific for HDL3. Thus, hepatic tissue can modulate its recognition of HDL. Finally, hepatic membranes from a patient lacking normal hepatic LDL receptors bound apo A-I HDL normally. These data indicate that a saturable, specific regulatable receptor for apo E-free HDL is present in human liver.
Hoeg
J M
JM
Demosky
S J
SJ
Edge
S B
SB
Gregg
R E
RE
Osborne
J C
JC
Brewer
H B
HB
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency; D001667:Binding, Competitive; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002352:Carrier Proteins; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism; D066298:In Vitro Techniques; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism; D018110:Receptors, Lipoprotein
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D001057:Apolipoproteins E; D002352:Carrier Proteins; D008075:Lipoproteins, HDL; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; C031616:high density lipoprotein receptors; C075197:high density lipoprotein binding protein