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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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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. |
format | Online Article Text |
id | pubmed-5712337 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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