Dexamethasone attenuates NF-kappa B DNA binding activity without inducing I kappa B levels in rat brain in vivo.
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.
Unlap
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MT
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham 35294-0017, USA.
Jope
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RS
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism; D020672:I-kappa B Proteins; D007700:Kinetics; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D000072000:NF-KappaB Inhibitor alpha; D003907:Dexamethasone; D004247:DNA