Status epilepticus induces p53 sequence-specific DNA binding in mature rat brain.

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. Copyright 1999 Elsevier Science B.V.