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Diazoxide preconditioning antagonizes cytotoxicity induced by epileptic seizures★

Diazoxide, an activator of mitochondrial ATP-sensitive potassium channels, can protect neurons and astrocytes against oxidative stress and apoptosis. In this study, we established a cellular model of epilepsy by culturing hippocampal neurons in magnesium-free medium, and used this to investigate eff...

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Autores principales: Fu, Qingxi, Sun, Zhiqing, Zhang, Jinling, Gao, Naiyong, Qi, Faying, Che, Fengyuan, Ma, Guozhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145886/
https://www.ncbi.nlm.nih.gov/pubmed/25206393
http://dx.doi.org/10.3969/j.issn.1673-5374.2013.11.005
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author Fu, Qingxi
Sun, Zhiqing
Zhang, Jinling
Gao, Naiyong
Qi, Faying
Che, Fengyuan
Ma, Guozhao
author_facet Fu, Qingxi
Sun, Zhiqing
Zhang, Jinling
Gao, Naiyong
Qi, Faying
Che, Fengyuan
Ma, Guozhao
author_sort Fu, Qingxi
collection PubMed
description Diazoxide, an activator of mitochondrial ATP-sensitive potassium channels, can protect neurons and astrocytes against oxidative stress and apoptosis. In this study, we established a cellular model of epilepsy by culturing hippocampal neurons in magnesium-free medium, and used this to investigate effects of diazoxide preconditioning on the expression of inwardly rectifying potassium channel (Kir) subunits of the ATP-sensitive potassium. We found that neuronal viability was significantly reduced in the epileptic cells, whereas it was enhanced by diazoxide preconditioning. Double immunofluorescence and western blot showed a significant increase in the expression of Kir6.1 and Kir6.2 in epileptic cells, especially at 72 hours after seizures. Diazoxide pretreatment completely reversed this effect at 24 hours after seizures. In addition, Kir6.1 expression was significantly upregulated compared with Kir6.2 in hippocampal neurons after seizures. These findings indicate that diazoxide pretreatment may counteract epileptiform discharge-induced cytotoxicity by suppressing the expression of Kir subunits.
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spelling pubmed-41458862014-09-09 Diazoxide preconditioning antagonizes cytotoxicity induced by epileptic seizures★ Fu, Qingxi Sun, Zhiqing Zhang, Jinling Gao, Naiyong Qi, Faying Che, Fengyuan Ma, Guozhao Neural Regen Res Neurodegenerative Disease and Neural Regeneration Diazoxide, an activator of mitochondrial ATP-sensitive potassium channels, can protect neurons and astrocytes against oxidative stress and apoptosis. In this study, we established a cellular model of epilepsy by culturing hippocampal neurons in magnesium-free medium, and used this to investigate effects of diazoxide preconditioning on the expression of inwardly rectifying potassium channel (Kir) subunits of the ATP-sensitive potassium. We found that neuronal viability was significantly reduced in the epileptic cells, whereas it was enhanced by diazoxide preconditioning. Double immunofluorescence and western blot showed a significant increase in the expression of Kir6.1 and Kir6.2 in epileptic cells, especially at 72 hours after seizures. Diazoxide pretreatment completely reversed this effect at 24 hours after seizures. In addition, Kir6.1 expression was significantly upregulated compared with Kir6.2 in hippocampal neurons after seizures. These findings indicate that diazoxide pretreatment may counteract epileptiform discharge-induced cytotoxicity by suppressing the expression of Kir subunits. Medknow Publications & Media Pvt Ltd 2013-04-15 /pmc/articles/PMC4145886/ /pubmed/25206393 http://dx.doi.org/10.3969/j.issn.1673-5374.2013.11.005 Text en Copyright: © Neural Regeneration Research http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Neurodegenerative Disease and Neural Regeneration
Fu, Qingxi
Sun, Zhiqing
Zhang, Jinling
Gao, Naiyong
Qi, Faying
Che, Fengyuan
Ma, Guozhao
Diazoxide preconditioning antagonizes cytotoxicity induced by epileptic seizures★
title Diazoxide preconditioning antagonizes cytotoxicity induced by epileptic seizures★
title_full Diazoxide preconditioning antagonizes cytotoxicity induced by epileptic seizures★
title_fullStr Diazoxide preconditioning antagonizes cytotoxicity induced by epileptic seizures★
title_full_unstemmed Diazoxide preconditioning antagonizes cytotoxicity induced by epileptic seizures★
title_short Diazoxide preconditioning antagonizes cytotoxicity induced by epileptic seizures★
title_sort diazoxide preconditioning antagonizes cytotoxicity induced by epileptic seizures★
topic Neurodegenerative Disease and Neural Regeneration
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145886/
https://www.ncbi.nlm.nih.gov/pubmed/25206393
http://dx.doi.org/10.3969/j.issn.1673-5374.2013.11.005
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