Dexamethasone attenuates NF-kappa B DNA binding activity without inducing I kappa B levels in rat brain in vivo.

Academic Article

Abstract

  • This investigation tested if glucocorticoid hormones modulate activation of the NF-kappa B transcription factor in rat brain in vivo. Dexamethasone (2 mg/kg) administration decreased NF-kappa B DNA binding in cerebral cortex and hippocampus nuclear extracts, maximally at 3-6 h after dexamethasone, followed by recovery at 24 h. Dexamethasone did not inhibit NF-kappa B by increasing the level of the inhibitory protein I kappa B alpha, as occurs in some peripheral cells, but instead lowered I kappa B alpha levels. Direct protein-protein inhibition by glucocorticoids was indicated by co-precipitation of glucocorticoid receptors with the p65 NF-kappa B subunit. Thus, glucocorticoids inhibit NF-kappa B DNA binding in rat brain, apparently by complexing with NF-kappa B subunits, which may contribute to the detrimental effects of glucocorticoids on neuronal function associated with oxidative stress and excitotoxicity.
  • Authors

    Published In

  • Brain Research  Journal
  • Keywords

  • Animals, Brain, Cell Nucleus, Cerebral Cortex, Cytosol, DNA, DNA-Binding Proteins, Dexamethasone, Hippocampus, I-kappa B Proteins, Kinetics, Male, NF-KappaB Inhibitor alpha, NF-kappa B, Organ Specificity, Rats, Rats, Sprague-Dawley
  • Author List

  • Unlap MT; Jope RS
  • Start Page

  • 83
  • End Page

  • 89
  • Volume

  • 45
  • Issue

  • 1