Ligand specificity of LOX-1, a novel endothelial receptor for oxidized low density lipoprotein.
Endothelial dysfunction, or activation, elicited by oxidized low density lipoprotein (Ox-LDL) and its lipid constituents has been shown to play a key role in the pathogenesis of atherosclerosis. We recently have identified a novel receptor for Ox-LDL-designated lectin-like Ox-LDL receptor (LOX-1) in vascular endothelial cells. To examine ligand specificity of LOX-1, we established CHO cell lines stably expressing both human and bovine LOX-1 (LOX-1-CHO). LOX-1-CHO bound and degraded 125I-labeled Ox-LDL but did not significantly degrade 125I-labeled acetylated LDL (Ac-LDL). Fucoidin and maleylated BSA (M-BSA), which inhibit 125I-Ox-LDL binding to class A scavenger receptors, did not inhibit 125I-Ox-LDL binding or degradation in LOX-1-CHO. Polyinosinic acid and carrageenan, in contrast, significantly reduced 125I-Ox-LDL binding to LOX-1-CHO by 62% and 60%, respectively. Delipidated and untreated 125I-Ox-LDL were bound and degraded equally in LOX-1-CHO; furthermore, excess amounts of unlabeled, delipidated Ox-LDL inhibited binding and degradation of untreated 125I-Ox-LDL. Taken together, LOX-1 is a receptor for Ox-LDL but not for Ac-LDL. LOX-1 recognizes protein moiety of Ox-LDL, and its ligand specificity is distinct from other receptors for Ox-LDL, including class A and B scavenger receptors.
Moriwaki
H
H
Departments of Geriatric Medicine and Pharmacology, Graduate School of Medicine, Kyoto University, Japan.
Kume
N
N
Sawamura
T
T
Aoyama
T
T
Hoshikawa
H
H
Ochi
H
H
Nishi
E
E
Masaki
T
T
Kita
T
T
D000818:Animals; D016466:CHO Cells; D002417:Cattle; D006224:Cricetinae; D006801:Humans; D008024:Ligands; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010084:Oxidation-Reduction; D000071228:Polyelectrolytes; D011108:Polymers / Q000378:metabolism / Q000494:pharmacology; D011973:Receptors, LDL / Q000378:metabolism*; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E
D008024:Ligands; D008077:Lipoproteins, LDL; D000071228:Polyelectrolytes; D011108:Polymers; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; C495137:OLR1 protein, human; C032629:acetyl-LDL; C099252:oxidized low density lipoprotein