Oxidized low density lipoprotein (ox-LDL) binding to ox-LDL receptor-1 in endothelial cells induces the activation of NF-kappaB through an increased production of intracellular reactive oxygen species.
In this study we examined the effect of oxidized low density lipoprotein (ox-LDL) on the intracellular production of reactive oxygen species (ROS) in bovine aortic endothelial cells (BAECs) and whether this increase occurs through its binding to the endothelial receptor lectin-like ox-LDL receptor-1 (LOX-1). Furthermore, this study also aimed to ascertain whether the binding of ox-LDL to LOX-1 is associated with NF-kappaB activation. ox-LDL induced a significant dose-dependent increase in ROS production after a 30-s incubation with BAECs (p < 0.01). ROS formation was markedly reduced in BAECs incubated with anti-LOX-1 monoclonal antibody (p < 0.001), while control nonimmune IgG produced no effect. ox-LDL induced a time- and dose-dependent significant increase in ROS formation only in CHO-K1 cells stably expressing bovine LOX-1 (p < 0.001), while no increase was present in CHO-K1 cells. The activation of the transcription factor NF-kappaB in BAECs was evident after a 5-min incubation with ox-LDL and was attenuated by anti-LOX-1 monoclonal antibody. The conclusion is that one of the pathophysiological consequences of ox-LDL binding to LOX-1 may be the activation of NF-kappaB through an increased ROS production.
Cominacini
L
L
Department of Biomedical and Surgical Sciences, Verona University, 37134 Verona, Italy. comina@medicinad.univr.it
Pasini
A F
AF
Garbin
U
U
Davoli
A
A
Tosetti
M L
ML
Campagnola
M
M
Rigoni
A
A
Pastorino
A M
AM
Lo Cascio
V
V
Sawamura
T
T
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D016466:CHO Cells; D002417:Cattle; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000378:metabolism*; D005452:Fluoresceins / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011341:Probucol / Q000494:pharmacology; D011485:Protein Binding; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D013997:Time Factors
D000924:Anticholesteremic Agents; D000975:Antioxidants; D002839:Chromans; D005452:Fluoresceins; D008077:Lipoproteins, LDL; D016328:NF-kappa B; C495137:OLR1 protein, human; D017382:Reactive Oxygen Species; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; C029569:diacetyldichlorofluorescein; D006861:Hydrogen Peroxide; D011341:Probucol; D001205:Ascorbic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid