Dexamethasone attenuates NF-κB DNA binding activity without inducing IκB levels in rat brain in vivo

M. Tino Unlap, Richard S. Jope

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

This investigation tested if glucocorticoid hormones modulate activation of the NF-κB transcription factor in rat brain in vivo. Dexamethasone (2 mg/kg) administration decreased NF-κB 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-κB by increasing the level of the inhibitory protein IκBα, as occurs in some peripheral cells, but instead lowered IκBα levels. Direct protein-protein inhibition by glucocorticoids was indicated by co-precipitation of glucocorticoid receptors with the p65 NF-κB subunit. Thus, glucocorticoids inhibit NF-κB DNA binding in rat brain, apparently by complexing with NF-κB subunits, which may contribute to the detrimental effects of glucocorticoids on neuronal function associated with oxidative stress and excitotoxicity.

Original languageEnglish (US)
Pages (from-to)83-89
Number of pages7
JournalMolecular Brain Research
Volume45
Issue number1
DOIs
StatePublished - Apr 1 1997
Externally publishedYes

Keywords

  • AP-1
  • Glucocorticoid
  • IκB
  • NF-κB
  • Oxidative stress

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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