Transcriptional upregulation of nitric oxide synthase II by nuclear factor-κB promotes apoptotic neuronal cell death in the hippocampus following experimental status epilepticus

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

研究成果: Article同行評審

22 引文 斯高帕斯(Scopus)

摘要

Whereas status epilepticus, or the condition of continuous epileptic seizures, produces a characteristic pattern of preferential neuronal cell loss in the hippocampus, the underlying mechanism is still unsettled. Based on an experimental model of temporal lobe status epilepticus, we demonstrated previously that prolonged seizures prompted an overproduction of nitric oxide (NO) by upregulation of NO synthase II (NOS II) in the hippocampal CA3 subfield, followed by the activation of mitochondrial apoptotic signaling cascade. Using the same animal model, the present study evaluated the hypothesis that transcriptional upregulation of NOS II gene by nuclear factor-κB (NF-κB) promotes apoptotic neuronal cell death in the hippocampus following status epilepticus. In Sprague-Dawley rats, significantly augmented nucleus-bound translocation of NF-κB p50 and p65 subunits and DNA binding activity of NF-κB were observed in hippocampal CA3 neurons as early as 30 min after elicitation of sustained seizure activity by microinjection of kainic acid into the CA3 subfield, followed by a progressive elevation that peaked at 90 min. In addition, application bilaterally into the hippocampal CA3 subfield of a selective NF-κB inhibitor, pyrrolidine dithiocarbamate or double-stranded κB decoy DNA significantly antagonized the activated NOS II-peroxynitrite signaling cascade (3 hr) and the associated manifestations of apoptotic cell death (7 days) in the hippocampus. We conclude that activation of NF-κB in hippocampal CA3 neurons upregulates NOS II gene expression following experimental temporal lobe status epilepticus, leading to apoptotic neuronal cell death in the hippocampus.

原文English
頁(從 - 到)1898-1907
頁數10
期刊Journal of Neuroscience Research
88
發行號9
DOIs
出版狀態Published - 2010 七月 1

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

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