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, Ya-Wen Zhang

研究成果: Article

20 引文 (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

指紋

Status Epilepticus
Nitric Oxide Synthase Type II
Hippocampus
Cell Death
Up-Regulation
Nitric Oxide Synthase
Temporal Lobe
Seizures
Neurons
Peroxynitrous Acid
Kainic Acid
DNA
Microinjections
Sprague Dawley Rats
Epilepsy
Nitric Oxide
Theoretical Models
Animal Models
Gene Expression
Genes

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

引用此文

Chuang, Yao Chung ; Chen, Shang Der ; Lin, Tsu Kung ; Chang, Wen Neng ; Lu, Cheng Hsien ; Liou, Chia Wei ; Chan, Samuel H.H. ; Zhang, Ya-Wen. / Transcriptional upregulation of nitric oxide synthase II by nuclear factor-κB promotes apoptotic neuronal cell death in the hippocampus following experimental status epilepticus. 於: Journal of Neuroscience Research. 2010 ; 卷 88, 編號 9. 頁 1898-1907.
@article{e1e3c034b0464a01b322b61ea98a0d91,
title = "Transcriptional upregulation of nitric oxide synthase II by nuclear factor-κB promotes apoptotic neuronal cell death in the hippocampus following experimental status epilepticus",
abstract = "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.",
author = "Chuang, {Yao Chung} and Chen, {Shang Der} and Lin, {Tsu Kung} and Chang, {Wen Neng} and Lu, {Cheng Hsien} and Liou, {Chia Wei} and Chan, {Samuel H.H.} and Ya-Wen Zhang",
year = "2010",
month = "7",
day = "1",
doi = "10.1002/jnr.22369",
language = "English",
volume = "88",
pages = "1898--1907",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "9",

}

Transcriptional upregulation of nitric oxide synthase II by nuclear factor-κB promotes apoptotic neuronal cell death in the hippocampus following experimental status epilepticus. / Chuang, Yao Chung; Chen, Shang Der; Lin, Tsu Kung; Chang, Wen Neng; Lu, Cheng Hsien; Liou, Chia Wei; Chan, Samuel H.H.; Zhang, Ya-Wen.

於: Journal of Neuroscience Research, 卷 88, 編號 9, 01.07.2010, p. 1898-1907.

研究成果: Article

TY - JOUR

T1 - Transcriptional upregulation of nitric oxide synthase II by nuclear factor-κB promotes apoptotic neuronal cell death in the hippocampus following experimental status epilepticus

AU - Chuang, Yao Chung

AU - Chen, Shang Der

AU - Lin, Tsu Kung

AU - Chang, Wen Neng

AU - Lu, Cheng Hsien

AU - Liou, Chia Wei

AU - Chan, Samuel H.H.

AU - Zhang, Ya-Wen

PY - 2010/7/1

Y1 - 2010/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77953503079&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953503079&partnerID=8YFLogxK

U2 - 10.1002/jnr.22369

DO - 10.1002/jnr.22369

M3 - Article

C2 - 20155797

AN - SCOPUS:77953503079

VL - 88

SP - 1898

EP - 1907

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 9

ER -