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J Biol Chem, Vol. 275, Issue 17, 12633-12638, April 28, 2000
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-
Oxidized Low Density Lipoprotein (ox-LDL) Binding to ox-LDL
Receptor-1 in Endothelial Cells Induces the Activation of NF-
B
through an Increased Production of Intracellular Reactive Oxygen
Species*
,
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-
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-
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.
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.
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