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Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling Epilepsy-Induced Hippocampal Endoplasmic Reticulum Stress and Oxidative Damage

Epilepsy is one of the most common chronic neurological disorders which provoke progressive neuronal degeneration. Endoplasmic reticulum (ER) stress has recently been recognized as pivotal etiological factors contributing to epilepsy-induced neuronal damage. However, the specific contribution of epi...

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Autores principales: Zhu, Xinjian, Dong, Jingde, Han, Bing, Huang, Rongrong, Zhang, Aifeng, Xia, Zhengrong, Chang, Huanhuan, Chao, Jie, Yao, Honghong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712337/
https://www.ncbi.nlm.nih.gov/pubmed/29234274
http://dx.doi.org/10.3389/fncel.2017.00377
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author Zhu, Xinjian
Dong, Jingde
Han, Bing
Huang, Rongrong
Zhang, Aifeng
Xia, Zhengrong
Chang, Huanhuan
Chao, Jie
Yao, Honghong
author_facet Zhu, Xinjian
Dong, Jingde
Han, Bing
Huang, Rongrong
Zhang, Aifeng
Xia, Zhengrong
Chang, Huanhuan
Chao, Jie
Yao, Honghong
author_sort Zhu, Xinjian
collection PubMed
description Epilepsy is one of the most common chronic neurological disorders which provoke progressive neuronal degeneration. Endoplasmic reticulum (ER) stress has recently been recognized as pivotal etiological factors contributing to epilepsy-induced neuronal damage. However, the specific contribution of epilepsy made to ER stress remains largely elusive. Here we use pentylenetetrazole (PTZ) kindling, a chronic epilepsy model, to identify neuronal nitric oxide synthase (nNOS) as a signaling molecule triggering PTZ kindling epilepsy-induced ER stress and oxidative damage. By genetic deletion of nNOS gene, we further demonstrated that nNOS acts through peroxynitrite, an important member of reactive nitrogen species, to trigger hippocampal ER stress and oxidative damage in the PTZ-kindled mice. Our findings thus define a specific mechanism for chronic epilepsy-induced ER stress and oxidative damage, and identify a potential therapeutic target for neuroprotection in chronic epilepsy patients.
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spelling pubmed-57123372017-12-11 Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling Epilepsy-Induced Hippocampal Endoplasmic Reticulum Stress and Oxidative Damage Zhu, Xinjian Dong, Jingde Han, Bing Huang, Rongrong Zhang, Aifeng Xia, Zhengrong Chang, Huanhuan Chao, Jie Yao, Honghong Front Cell Neurosci Neuroscience Epilepsy is one of the most common chronic neurological disorders which provoke progressive neuronal degeneration. Endoplasmic reticulum (ER) stress has recently been recognized as pivotal etiological factors contributing to epilepsy-induced neuronal damage. However, the specific contribution of epilepsy made to ER stress remains largely elusive. Here we use pentylenetetrazole (PTZ) kindling, a chronic epilepsy model, to identify neuronal nitric oxide synthase (nNOS) as a signaling molecule triggering PTZ kindling epilepsy-induced ER stress and oxidative damage. By genetic deletion of nNOS gene, we further demonstrated that nNOS acts through peroxynitrite, an important member of reactive nitrogen species, to trigger hippocampal ER stress and oxidative damage in the PTZ-kindled mice. Our findings thus define a specific mechanism for chronic epilepsy-induced ER stress and oxidative damage, and identify a potential therapeutic target for neuroprotection in chronic epilepsy patients. Frontiers Media S.A. 2017-11-28 /pmc/articles/PMC5712337/ /pubmed/29234274 http://dx.doi.org/10.3389/fncel.2017.00377 Text en Copyright © 2017 Zhu, Dong, Han, Huang, Zhang, Xia, Chang, Chao and Yao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Zhu, Xinjian
Dong, Jingde
Han, Bing
Huang, Rongrong
Zhang, Aifeng
Xia, Zhengrong
Chang, Huanhuan
Chao, Jie
Yao, Honghong
Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling Epilepsy-Induced Hippocampal Endoplasmic Reticulum Stress and Oxidative Damage
title Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling Epilepsy-Induced Hippocampal Endoplasmic Reticulum Stress and Oxidative Damage
title_full Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling Epilepsy-Induced Hippocampal Endoplasmic Reticulum Stress and Oxidative Damage
title_fullStr Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling Epilepsy-Induced Hippocampal Endoplasmic Reticulum Stress and Oxidative Damage
title_full_unstemmed Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling Epilepsy-Induced Hippocampal Endoplasmic Reticulum Stress and Oxidative Damage
title_short Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling Epilepsy-Induced Hippocampal Endoplasmic Reticulum Stress and Oxidative Damage
title_sort neuronal nitric oxide synthase contributes to ptz kindling epilepsy-induced hippocampal endoplasmic reticulum stress and oxidative damage
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712337/
https://www.ncbi.nlm.nih.gov/pubmed/29234274
http://dx.doi.org/10.3389/fncel.2017.00377
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