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Specific inhibition of NADPH oxidase 2 modifies chronic epilepsy
Recent work by us and others has implicated NADPH oxidase (NOX) enzymes as main producers of reactive oxygen species (ROS) following a brain insult such as status epilepticus, contributing to neuronal damage and development of epilepsy. Although several NOX isoforms have been examined in the context...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9712695/ https://www.ncbi.nlm.nih.gov/pubmed/36459714 http://dx.doi.org/10.1016/j.redox.2022.102549 |
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author | Singh, Prince Kumar Saadi, Aseel Sheeni, Yara Shekh-Ahmad, Tawfeeq |
author_facet | Singh, Prince Kumar Saadi, Aseel Sheeni, Yara Shekh-Ahmad, Tawfeeq |
author_sort | Singh, Prince Kumar |
collection | PubMed |
description | Recent work by us and others has implicated NADPH oxidase (NOX) enzymes as main producers of reactive oxygen species (ROS) following a brain insult such as status epilepticus, contributing to neuronal damage and development of epilepsy. Although several NOX isoforms have been examined in the context of epilepsy, most attention has focused on NOX2. In this present study, we demonstrate the effect of gp91ds-tat, a specific competitive inhibitor of NOX2, in in vitro epileptiform activity model as well as in temporal lobe epilepsy (TLE) model in rats. We showed that in in vitro seizure model, gp91ds-tat modulated Ca(2+) oscillation, prevented epileptiform activity-induced ROS generation, mitochondrial depolarization, and neuronal death. Administration of gp91ds-tat 1 h after kainic acid-induced status epilepticus significantly decreased the expression of NOX2, as well as the overall NOX activity in the cortex and the hippocampus. Finally, we showed that upon continuous intracerebroventricular administration to epileptic rats, gp91ds-tat significantly reduced the seizure frequency and the total number of seizures post-treatment compared to the scrambled peptide-treated animals. The results of the study suggest that NOX2 may have an important effect on modulation of epileptiform activity and has a critical role in mediating seizure-induced NOX activation, ROS generation and oxidative stress in the brain, and thus significantly contributes to development of epilepsy following a brain insult. |
format | Online Article Text |
id | pubmed-9712695 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-97126952022-12-02 Specific inhibition of NADPH oxidase 2 modifies chronic epilepsy Singh, Prince Kumar Saadi, Aseel Sheeni, Yara Shekh-Ahmad, Tawfeeq Redox Biol Research Paper Recent work by us and others has implicated NADPH oxidase (NOX) enzymes as main producers of reactive oxygen species (ROS) following a brain insult such as status epilepticus, contributing to neuronal damage and development of epilepsy. Although several NOX isoforms have been examined in the context of epilepsy, most attention has focused on NOX2. In this present study, we demonstrate the effect of gp91ds-tat, a specific competitive inhibitor of NOX2, in in vitro epileptiform activity model as well as in temporal lobe epilepsy (TLE) model in rats. We showed that in in vitro seizure model, gp91ds-tat modulated Ca(2+) oscillation, prevented epileptiform activity-induced ROS generation, mitochondrial depolarization, and neuronal death. Administration of gp91ds-tat 1 h after kainic acid-induced status epilepticus significantly decreased the expression of NOX2, as well as the overall NOX activity in the cortex and the hippocampus. Finally, we showed that upon continuous intracerebroventricular administration to epileptic rats, gp91ds-tat significantly reduced the seizure frequency and the total number of seizures post-treatment compared to the scrambled peptide-treated animals. The results of the study suggest that NOX2 may have an important effect on modulation of epileptiform activity and has a critical role in mediating seizure-induced NOX activation, ROS generation and oxidative stress in the brain, and thus significantly contributes to development of epilepsy following a brain insult. Elsevier 2022-11-28 /pmc/articles/PMC9712695/ /pubmed/36459714 http://dx.doi.org/10.1016/j.redox.2022.102549 Text en © 2022 Published by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Singh, Prince Kumar Saadi, Aseel Sheeni, Yara Shekh-Ahmad, Tawfeeq Specific inhibition of NADPH oxidase 2 modifies chronic epilepsy |
title | Specific inhibition of NADPH oxidase 2 modifies chronic epilepsy |
title_full | Specific inhibition of NADPH oxidase 2 modifies chronic epilepsy |
title_fullStr | Specific inhibition of NADPH oxidase 2 modifies chronic epilepsy |
title_full_unstemmed | Specific inhibition of NADPH oxidase 2 modifies chronic epilepsy |
title_short | Specific inhibition of NADPH oxidase 2 modifies chronic epilepsy |
title_sort | specific inhibition of nadph oxidase 2 modifies chronic epilepsy |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9712695/ https://www.ncbi.nlm.nih.gov/pubmed/36459714 http://dx.doi.org/10.1016/j.redox.2022.102549 |
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