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Retroviral expression of human arginine decarboxylase reduces oxidative stress injury in mouse cortical astrocytes

BACKGROUND: In physiologic and pathologic conditions of the central nervous system (CNS), astrocytes are a double-edged sword. They not only support neuronal homeostasis but also contribute to increases in neuronal demise. A large body of experimental evidence has shown that impaired astrocytes play...

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Autores principales: Hong, Samin, Son, Mi Ran, Yun, Kyungeun, Lee, Won Taek, Park, Kyung Ah, Lee, Jong Eun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150973/
https://www.ncbi.nlm.nih.gov/pubmed/25156824
http://dx.doi.org/10.1186/1471-2202-15-99
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author Hong, Samin
Son, Mi Ran
Yun, Kyungeun
Lee, Won Taek
Park, Kyung Ah
Lee, Jong Eun
author_facet Hong, Samin
Son, Mi Ran
Yun, Kyungeun
Lee, Won Taek
Park, Kyung Ah
Lee, Jong Eun
author_sort Hong, Samin
collection PubMed
description BACKGROUND: In physiologic and pathologic conditions of the central nervous system (CNS), astrocytes are a double-edged sword. They not only support neuronal homeostasis but also contribute to increases in neuronal demise. A large body of experimental evidence has shown that impaired astrocytes play crucial roles in the pathologic process of cerebral ischemia; therefore, astrocytes may represent a breakthrough target for neuroprotective therapeutic strategies. Agmatine, an endogenous polyamine catalyzed from L-arginine by arginine decarboxylase (ADC), is a neuromodulator and it protects neurons/glia against various injuries. RESULTS: In this investigation, agmatine-producing mouse cortical astrocytes were developed through transduction of the human ADC gene. Cells were exposed to oxygen-glucose deprivation (OGD) and restored to a normoxic glucose-supplied condition. Intracellular levels of agmatine were measured by high performance liquid chromatography. Cell viability was evaluated by Hoechest/propidium iodide nuclear staining and lactate dehydrogenase assay. Expression of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase s (MMPs) were assessed by a reverse transcription polymerase chain reaction, Western immunoblots, and immunofluorescence. We confirmed that ADC gene-expressed astrocytes produce a great amount of agmatine. These cells were highly resistant to not only OGD but also restoration, which mimicked ischemia-reperfusion injury in vivo. The neuroprotective effects of ADC seemed to be related to its ability to attenuate expression of iNOS and MMPs. CONCLUSION: Our findings imply that astrocytes can be reinforced against oxidative stress by endogenous agmatine production through ADC gene transduction. The results of this study provide new insights that may lead to novel therapeutic approaches to reduce cerebral ischemic injuries. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2202-15-99) contains supplementary material, which is available to authorized users.
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spelling pubmed-41509732014-09-03 Retroviral expression of human arginine decarboxylase reduces oxidative stress injury in mouse cortical astrocytes Hong, Samin Son, Mi Ran Yun, Kyungeun Lee, Won Taek Park, Kyung Ah Lee, Jong Eun BMC Neurosci Research Article BACKGROUND: In physiologic and pathologic conditions of the central nervous system (CNS), astrocytes are a double-edged sword. They not only support neuronal homeostasis but also contribute to increases in neuronal demise. A large body of experimental evidence has shown that impaired astrocytes play crucial roles in the pathologic process of cerebral ischemia; therefore, astrocytes may represent a breakthrough target for neuroprotective therapeutic strategies. Agmatine, an endogenous polyamine catalyzed from L-arginine by arginine decarboxylase (ADC), is a neuromodulator and it protects neurons/glia against various injuries. RESULTS: In this investigation, agmatine-producing mouse cortical astrocytes were developed through transduction of the human ADC gene. Cells were exposed to oxygen-glucose deprivation (OGD) and restored to a normoxic glucose-supplied condition. Intracellular levels of agmatine were measured by high performance liquid chromatography. Cell viability was evaluated by Hoechest/propidium iodide nuclear staining and lactate dehydrogenase assay. Expression of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase s (MMPs) were assessed by a reverse transcription polymerase chain reaction, Western immunoblots, and immunofluorescence. We confirmed that ADC gene-expressed astrocytes produce a great amount of agmatine. These cells were highly resistant to not only OGD but also restoration, which mimicked ischemia-reperfusion injury in vivo. The neuroprotective effects of ADC seemed to be related to its ability to attenuate expression of iNOS and MMPs. CONCLUSION: Our findings imply that astrocytes can be reinforced against oxidative stress by endogenous agmatine production through ADC gene transduction. The results of this study provide new insights that may lead to novel therapeutic approaches to reduce cerebral ischemic injuries. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2202-15-99) contains supplementary material, which is available to authorized users. BioMed Central 2014-08-26 /pmc/articles/PMC4150973/ /pubmed/25156824 http://dx.doi.org/10.1186/1471-2202-15-99 Text en © Hong et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Hong, Samin
Son, Mi Ran
Yun, Kyungeun
Lee, Won Taek
Park, Kyung Ah
Lee, Jong Eun
Retroviral expression of human arginine decarboxylase reduces oxidative stress injury in mouse cortical astrocytes
title Retroviral expression of human arginine decarboxylase reduces oxidative stress injury in mouse cortical astrocytes
title_full Retroviral expression of human arginine decarboxylase reduces oxidative stress injury in mouse cortical astrocytes
title_fullStr Retroviral expression of human arginine decarboxylase reduces oxidative stress injury in mouse cortical astrocytes
title_full_unstemmed Retroviral expression of human arginine decarboxylase reduces oxidative stress injury in mouse cortical astrocytes
title_short Retroviral expression of human arginine decarboxylase reduces oxidative stress injury in mouse cortical astrocytes
title_sort retroviral expression of human arginine decarboxylase reduces oxidative stress injury in mouse cortical astrocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150973/
https://www.ncbi.nlm.nih.gov/pubmed/25156824
http://dx.doi.org/10.1186/1471-2202-15-99
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