Status epilepticus induces p53 sequence-specific DNA binding in mature rat brain
Status epilepticus induces p53 sequence-specific DNA binding in mature rat brain
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DOI：
10.1016/s0169-328x(98)00285-x
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发表时间：
1999-01-08
期刊：
影响因子：
--
通讯作者：
Schreiber, SS
中科院分区：
文献类型：
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作者：
Liu, W;Rong, YQ;Schreiber, SS
先前的研究表明肿瘤抑制基因 p53 与兴奋毒素治疗引起的神经元凋亡有关。为了测试 p53 蛋白在兴奋毒性细胞死亡过程中是否作为转录因子发挥作用，我们使用电泳迁移率变动分析来测量红藻氨酸 (KA) 诱导的癫痫发作后 p53 序列特异性 DNA 结合活性。癫痫发作后 2.5 小时，在红藻氨酸脆弱脑区的提取物中观察到 p53 DNA 结合活性迅速显着增加，这种作用在癫痫发作后持续长达 16 小时。注射 KA 后 30 小时，DNA 结合活性恢复正常。用蛋白质合成抑制剂放线菌酮预处理，以及用 p53 单克隆抗体 PAb421 预孵育，显着减弱 KA 处理诱导的 p53 DNA 结合活性。这些结果表明，在 KA 处理后，p53 蛋白可能作为转录因子发挥作用，调节参与神经元凋亡的 p53 反应基因的表达。 (C) 1999 Elsevier Science B.V. 保留所有权利。
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. (C) 1999 Elsevier Science B.V. All rights reserved.