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

J Biol Chem. 2000 Apr 28;275(17):12633-8. doi: 10.1074/jbc.275.17.12633.

Abstract

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.

MeSH terms

  • Animals
  • Anticholesteremic Agents / pharmacology
  • Antioxidants / pharmacology
  • Ascorbic Acid / pharmacology
  • CHO Cells
  • Cattle
  • Cells, Cultured
  • Chromans / pharmacology
  • Cricetinae
  • Endothelium, Vascular / metabolism*
  • Fluoresceins / metabolism
  • Humans
  • Hydrogen Peroxide / metabolism
  • Lipoproteins, LDL / metabolism*
  • NF-kappa B / metabolism*
  • Probucol / pharmacology
  • Protein Binding
  • Reactive Oxygen Species / metabolism*
  • Receptors, LDL / metabolism*
  • Receptors, Oxidized LDL
  • Scavenger Receptors, Class E
  • Time Factors

Substances

  • Anticholesteremic Agents
  • Antioxidants
  • Chromans
  • Fluoresceins
  • Lipoproteins, LDL
  • NF-kappa B
  • OLR1 protein, human
  • Reactive Oxygen Species
  • Receptors, LDL
  • Receptors, Oxidized LDL
  • Scavenger Receptors, Class E
  • oxidized low density lipoprotein
  • diacetyldichlorofluorescein
  • Hydrogen Peroxide
  • Probucol
  • Ascorbic Acid
  • 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid