Oxidized Low Density Lipoprotein (ox-LDL) Binding to ox-LDL Receptor-1 in Endothelial Cells Induces the Activation of NF-κB through an Increased Production of Intracellular Reactive Oxygen Species

Autor: Luciano Cominacini, Anna Rigoni, Vincenzo Lo Cascio, A. M. Pastorino, Ulisse Garbin, M. Campagnola, Tatsuya Sawamura, Maria L. Tosetti, Anna Fratta Pasini, Anna Davoli
Rok vydání: 2000
Předmět:
Zdroj: Journal of Biological Chemistry. 275:12633-12638
ISSN: 0021-9258
DOI: 10.1074/jbc.275.17.12633
Popis: 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 (p0.01). ROS formation was markedly reduced in BAECs incubated with anti-LOX-1 monoclonal antibody (p0.001), 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 (p0.001), 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.
Databáze: OpenAIRE