Heat shock protein 70 protects against seizure-induced neuronal cell death in the hippocampus following experimental status epilepticus via inhibition of nuclear factor-κB activation-induced nitric oxide synthase II expression

Chiung Chih Chang, Shang Der Chen, Tsu Kung Lin, Wen Neng Chang, Chia Wei Liou, Alice Y.W. Chang, Samuel H.H. Chan, Yao Chung Chuang

研究成果: Article同行評審

30 引文 斯高帕斯(Scopus)

摘要

Status epilepticus induces subcellular changes that may eventually lead to neuronal cell death in the hippocampus. Based on an animal model of status epilepticus, our laboratory showed previously that sustained hippocampal seizure activity activates nuclear factor-κB (NF-κB) and upregulates nitric oxide synthase (NOS) II gene expression, leading to apoptotic neuronal cell death in the hippocampus. The present study examined the potential modulatory role of heat shock protein 70 (HSP70) on NF-κB signaling in the hippocampus following experimental status epilepticus. In Sprague-Dawley rats, kainic acid (KA) was microinjected unilaterally into the hippocampal CA3 subfield to induce prolonged bilateral seizure activity. Expression of HSP70 was elevated as early as 1. h after the elicitation of sustained seizure activity, followed by a progressive elevation that peaked at 24. h. Pretreatment with an antisense oligonucleotide against hsp70 decreased the HSP70 expression, and significantly augmented IκB kinase (IKK) activity and phosphorylation of IκBα, alongside enhanced nuclear translocation and DNA binding activity of NF-κB in the hippocampal CA3 neurons and glial cells. These cellular events were followed by enhanced upregulation of NOS II and peroxynitrite expression 3. h after sustained seizure activity that led to an increase of caspase-3 and DNA fragmentation in the hippocampal CA3 neurons 7. days after experimental status epilepticus. We concluded that HSP70 protects against apoptotic cell death induced by NF-κB activation and NOS II-peroxynitrite signaling cascade in the hippocampal CA3 and glial cells following experimental status epilepticus via suppression of IKK activity and deactivation of IκBα.

原文English
頁(從 - 到)241-249
頁數9
期刊Neurobiology of Disease
62
DOIs
出版狀態Published - 2014 二月

All Science Journal Classification (ASJC) codes

  • 神經內科

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