Abstract
We have recently demonstrated that specific oxidized phospholipids (oxPC(CD36)) accumulate at sites of oxidative stress in vivo such as within atherosclerotic lesions, hyperlipidemic plasma, and plasma with low high-density lipoprotein levels. oxPC(CD36) serve as high affinity ligands for the scavenger receptor CD36, mediate uptake of oxidized low density lipoprotein by macrophages, and promote a pro-thrombotic state via platelet scavenger receptor CD36. We now report that oxPC(CD36) represent ligands for another member of the scavenger receptor class B, type I (SR-BI). oxPC(CD36) prevent binding to SR-BI of its physiological ligand, high density lipoprotein, because of the close proximity of the binding sites for these two ligands on SR-BI. Furthermore, oxPC(CD36) interfere with SR-BI-mediated selective uptake of cholesteryl esters in hepatocytes. Thus, oxidative stress and accumulation of specific oxidized phospholipids in plasma may have an inhibitory effect on reverse cholesterol transport.
Highlights
Atherosclerosis is a chronic inflammatory disease in which macrophage accumulation of cholesterol and subsequent foam cell formation are critical events
We report that oxPCCD36 represent ligands for another member of the scavenger receptor class B, type I (SR-BI). oxPCCD36 prevent binding to SR-BI of its physiological ligand, high density lipoprotein, because of the close proximity of the binding sites for these two ligands on SR-BI
The molecular weight was hypothesized that oxLDL could bind to SR-BI via specific oxifound to be close to the predicted value, and purity was typically dized phospholipids that were previously shown to be ligands for CD36
Summary
Tissue culture media and additives were purchased from Invitrogen. Na125I was supplied by ICN Biomedicals, Inc. [3H]Cholesteryl oleate ether (COE) and 1,2-[3H]dihexadecanoyl-sn-glycero-3-phosphocholine (DPPC) were from American Radiolabel Chemicals, Inc. 1-Hexadecanoyl-2-eicosatetra-5Ј,8Ј,11Ј,14Ј-enoyl-snglycero-3-phosphocholine (PAPC), 1-hexadecanoyl-2-octadec9Ј-enoyl-sn-glycero-3-phosphocholine (POPC), 1-hexadecanoyl2-octadec-9Ј,12Ј-dienoyl-sn-glycero-3-phosphocholine (PLPC), and DPPC were purchased from Avanti Polar Lipids (Alabaster, AL). The 9-keto-10-dodecendioic acid and 5-keto-6-octendioic acid esters of 2-lyso-PC (KDdiA-PC and KOdiAPC, respectively) were purchased from Cayman, Inc. Anti-SR-BI blocking antibody was purchased from Novus Biologicals (Littleton, CO). All other reagents were obtained from Sigma unless otherwise specified
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