title: Status epilepticus induces p53 sequence-specific DNA binding in mature rat brain.
abstract: Previous studies have implicated the tumor suppressor gene, p53, in neuronal apoptosis due to excitotoxin treatment. To test whether p53 protein functions as a transcription factor during excitotoxic cell death, we used electrophoretic mobility shift assays to measure p53 sequence-specific DNA-binding activity following kainic acid (KA)-induced seizures. A rapid and significant increase in p53 DNA-binding activity was observed in extracts from kainate-vulnerable brain regions at 2.5 h after seizure onset, an effect which lasted up to 16 h after seizure-onset. DNA binding activity returned to normal by 30 h after KA injection. Pre-treatment with the protein synthesis inhibitor cycloheximide, as well as pre-incubation with PAb421, a p53 monoclonal antibody, significantly attenuated p53 DNA-binding activity induced by KA treatment. These results indicate that p53 protein may function as a transcription factor, following KA treatment, to regulate the expression of p53-responsive genes involved in neuronal apoptosis.
authors.affiliation: Program in Neurobiology, University of Southern California, Los Angeles, CA 90089-2520, USA.
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Rong
authors.forename: M
authors.initials: M
authors.lastname: Baudry
authors.forename: S S
authors.initials: SS
authors.lastname: Schreiber
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D016158:Genes, p53; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D009410:Nerve Degeneration; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D011500:Protein Synthesis Inhibitors; D016159:Tumor Suppressor Protein p53; D003513:Cycloheximide; D007608:Kainic Acid