NF-kappa B binding activity and cyclooxygenase-2 expression in persistent CCl(4)-treated rat liver injury

J Korean Med Sci. 2002 Apr;17(2):193-200. doi: 10.3346/jkms.2002.17.2.193.

Abstract

The involvement of NF-kappa B binding activity is known to be important in the mechanism of acute liver injury and in the induction of cyclooxygenase (COX-2). This study was performed to evaluate NF-kappa B binding activity and the expression of COX-2 in chronic liver injury induced by carbon tetrachloride (CCl(4)). Liver tissues from Sprague-Dawley rats were collected at 1, 3, 5, and 7th week after intraperitoneal injection of 0.1 mL of CCl(4)/100 g body weight twice a week. Reactive oxy-gen species (ROS) were measured in the postmitochondrial fraction by dichlorofluorescein formation with a fluorescent probe. An electrophoretic mobility shift assay was performed for NF-kappa B binding activity. Western blot was performed to measure the level of COX-1, COX-2, p65, p50, and I B proteins. ROS and NF-kappa B activity increased during the CCl4-induced chronic liver injury. The expression of nuclear p65 protein and p50 protein increased compared with that of the control, while the cytoplasmic I B protein decreased as the inflammation persisted. The expression of COX-2 in CCl(4)-treated rat liver increased compared with that of the control. It could be suggested that ROS produced by CCl(4) treatment increased NF-kappa B binding activity and thereby COX-2 expression, and these might be implicated in the progress of chronic liver damage.

MeSH terms

  • Animals
  • Biological Transport
  • Carbon Tetrachloride / administration & dosage
  • Carbon Tetrachloride / adverse effects*
  • Carbon Tetrachloride Poisoning / metabolism*
  • Carbon Tetrachloride Poisoning / pathology
  • Cell Nucleus / metabolism
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cytoplasm / metabolism
  • I-kappa B Proteins / biosynthesis
  • Isoenzymes / biosynthesis*
  • Liver / drug effects
  • Liver / injuries*
  • Liver / pathology
  • Membrane Proteins
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • NF-kappa B p50 Subunit
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Protein Binding
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species
  • Transcription Factor RelA

Substances

  • I-kappa B Proteins
  • Isoenzymes
  • Membrane Proteins
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • Reactive Oxygen Species
  • Transcription Factor RelA
  • Carbon Tetrachloride
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Ptgs1 protein, rat