出版社：American Society for Biochemistry and Molecular Biology
摘要：We have previously shown that CD36 recognizes oxidation productsof phospholipids on oxidized LDL (OxLDL) such as 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine(POVPC). The current study was designed to examine whether thephosphocholine (PC) headgroup in POVPC constitutes an obligatorybinding target for CD36. To examine the contribution of PC inthe binding of POVPC to CD36, we used well-defined syntheticoxidized phospholipids (OxPLs) cross-linked to BSA or to a hexapeptide.The OxPL adducts were then tested for their ability to bindto CD36-transfected cells and for their ability to inhibit OxLDLbinding to CD36. Both POVPC-BSA and POVPC-peptide adducts werehigh-affinity ligands for CD36 and potent inhibitors of OxLDLbinding. Enzymatic removal of the entire PC moiety of the POVPC-peptide,or of the choline headgroup alone, as well as substitution ofthe choline headgroup by ethanolamine abrogated the inhibitoryactivity of POVPC. Interestingly, PC by itself or cross-linkedto BSA did not show any intrinsic competition activity.
In conclusion, our data demonstrate that the PC headgroup ofOxPL alone is sufficient for binding to CD36, but only if presentedin the correct conformation as in OxPL of OxLDL or as in POVPC-peptideadducts.Abbreviations: Ac-TGTKGY, Ac-threonine-glycine-threonine-lysine-glycine-tyrosine; apoE, apolipoprotein E; KLH, keyhole limpet hemocyanin; OxLDL, oxidized low density lipoprotein; OxPL, oxidized phospholipid; PAMP, pathogen-associated molecular pattern; PC, phosphocholine; PLC, phospholipase C; PLD, phospholipase D; POVG, 1-palmitoyl-2-(5'-oxovaleroyl)-glycerol; POVPA, 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphatidic acid; POVPC, 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine; POVPE, 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphoethanolamine
Supplementary key words scavenger receptor • oxidized phospholipids • atherosclerosis
