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J Biol Chem, Vol. 275, Issue 17, 12633-12638, April 28, 2000

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

Luciano CominaciniDagger , Anna Fratta Pasini, Ulisse Garbin, Anna Davoli, Maria L. Tosetti, Mario Campagnola, Anna Rigoni, Antonio M. Pastorino, Vincenzo Lo Cascio, and Tatsuya Sawamura§

From the Department of Biomedical and Surgical Sciences, Verona University, 37134 Verona, Italy and the § Department of Bioscience, National Cardiovascular Center Research Institute, Fujishirodai, Suita, Osaka 565-8565, Japan

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-kappa B 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-kappa B 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-kappa B through an increased ROS production.


* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Dipartimento di Scienze Biomediche e Chirurgiche, c/o Medicina D-Ospedale Policlinico, Università di Verona, 37134 Verona, Italy. Tel.: 39 045 8074806; Fax: 39 045 583041; E-mail: comina@medicinad.univr.it.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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