Peptide model of a highly conserved, N-terminal domain of apolipoprotein E is able to modulate lipoprotein binding to a member of the class A scavenger receptor family.
Apolipoprotein E plays a critical role in plasma lipoprotein clearance. Peptide models of a highly conserved, N-terminal domain of this protein have been shown to increase the binding of low density lipoprotein (LDL) to fibroblast cell surfaces independently of the low density lipoprotein receptor. Here we provide data to show that these peptides not only increase the binding of LDL, but also of high density lipoprotein, though not acetylated LDL. We also have data suggesting that this novel activity is mediated, at least in part, by a member of the scavenger receptor family, SR-AI. Furthermore, we show that this activity is also prominent in macrophages, a cell relevant to atherogenesis. In addition, this current paper provides evidence suggesting that this complex binding activity is initiated by a peptide-receptor interaction, and that our peptides are able to induce activity at physiologically relevant concentrations. This study provides evidence for a possible novel receptor interaction and further anti-atherogenic properties of apolipoprotein E and raises the possibility of a therapeutic potential of our peptide models.
Dominguez
S R
SR
Department of Pathology, University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA.
Miller-Auer
H
H
Reardon
C A
CA
Meredith
S C
SC
D000595:Amino Acid Sequence; D000818:Animals; D001057:Apolipoproteins E / Q000737:chemistry*; D001769:Blood; D002460:Cell Line; D002704:Chlorates / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004622:Embryo, Mammalian; D005347:Fibroblasts; D019763:Heparin Lyase / Q000494:pharmacology; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B
D001057:Apolipoproteins E; D002704:Chlorates; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D004533:Egtazic Acid; D019763:Heparin Lyase; C032706:sodium chlorate