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.
- Oxidative stress
ASJC Scopus subject areas
- Molecular Biology
- Cellular and Molecular Neuroscience