title: Apolipoprotein AII enrichment of HDL enhances their affinity for class B type I scavenger receptor but inhibits specific cholesteryl ester uptake.
abstract: Apolipoproteins of high density lipoprotein (HDL) and especially apolipoprotein (apo)AI and apoAII have been demonstrated as binding directly to the class B type I scavenger receptor (SR-BI), the HDL receptor that mediates selective cholesteryl ester uptake. However, the functional relevance of the binding capacity of each apolipoprotein is still unknown. The human adrenal cell line, NCI-H295R, spontaneously expresses a high level of SR-BI, the major apoAI binding protein in these cells. As previously described for murine SR-BI, free apoAI, palmitoyl-oleoyl-phosphatidylcholine (POPC)-AI, and HDL are good ligands for human SR-BI. In vitro displacement of apoAI by apoAII in HDLs or in Lp AI purified from HDL by immunoaffinity enhances their ability to compete with POPC-AI to bind to SR-BI and also enhances their direct binding capacity. The next step was to determine whether the higher affinity of apoAII for SR-BI correlated with the specific uptake of cholesteryl esters from these HDLs. Free apoAII and, to a lesser extent, free apoAI that were added to the cell medium during uptake experiments inhibited the specific uptake of [(3)H]cholesteryl esters from HDL, indicating that binding sites on cells were the same as cholesteryl ester uptake sites. In direct experiments, the uptake of [(3)H]cholesteryl esters from apoAII-enriched HDL was highly reduced compared with the uptake from native HDL. These results demonstrate that in the human adrenal cell line expressing SR-BI as the major HDL binding protein, efficient apoAII binding has an inhibitory effect on the delivery of cholesteryl esters to cells.
authors.affiliation: INSERM U325, Institut Pasteur de Lille et Université Lille 2, Lille, France.
authors.forename: A
authors.initials: A
authors.lastname: Pilon
authors.forename: O
authors.initials: O
authors.lastname: Briand
authors.forename: S
authors.initials: S
authors.lastname: Lestavel
authors.forename: C
authors.initials: C
authors.lastname: Copin
authors.forename: Z
authors.initials: Z
authors.lastname: Majd
authors.forename: J C
authors.initials: JC
authors.lastname: Fruchart
authors.forename: G
authors.initials: G
authors.lastname: Castro
authors.forename: V
authors.initials: V
authors.lastname: Clavey
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000494:pharmacology; D016633:Apolipoprotein A-II / Q000378:metabolism* / Q000494:pharmacology; D001667:Binding, Competitive; D018955:CD36 Antigens; D002788:Cholesterol Esters / Q000378:metabolism*; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D010713:Phosphatidylcholines / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D014316:Tritium; D014407:Tumor Cells, Cultured
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D018955:CD36 Antigens; D002788:Cholesterol Esters; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D010713:Phosphatidylcholines; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D014316:Tritium; C028694:1-palmitoyl-2-oleoylphosphatidylcholine