Inhibition of NFkB DNA binding activity by glucocorticoids in rat brain.
The influence of glucocorticoids on the transcription factor NFkB was investigated by using the gel mobility shift assay with nuclear extracts prepared from rat cerebral cortex and hippocampus after a variety of in vivo treatments. Following stimulation with each of three treatments, kainate, pilocarpine, or lithium plus pilocarpine-induced seizures, NFkB DNA binding activity was significantly greater in the cortex and hippocampus from adrenalectomized than from adrenal-intact rats. These results indicate that in rat brain glucocorticoids inhibit NFkB activity in addition to the previously reported inhibition of the transcription factor AP-1 (activator protein 1). Impairment of stimulus-induced transcription factor activity may contribute to the deleterious effects of prolonged elevations of glucocorticoids on neuronal function.
Unlap
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Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham 35294, USA.
Jope
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D000315:Adrenalectomy; D000818:Animals; D001483:Base Sequence; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005938:Glucocorticoids / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D018721:Muscarinic Agonists / Q000494:pharmacology; D016328:NF-kappa B / Q000096:biosynthesis*; D018384:Oxidative Stress; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018808:Transcription Factor AP-1 / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D005938:Glucocorticoids; D018721:Muscarinic Agonists; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D010862:Pilocarpine; D004247:DNA; D008094:Lithium; D007608:Kainic Acid