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Cellular and temporal expression of NADPH oxidase (NOX) isotypes after brain injury
BACKGROUND: Brain injury results in an increase in the activity of the reactive oxygen species generating NADPH oxidase (NOX) enzymes. Preliminary studies have shown that NOX2, NOX3, and NOX4 are the most prominently expressed NOX isotypes in the brain. However, the cellular and temporal expression...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878417/ https://www.ncbi.nlm.nih.gov/pubmed/24344836 http://dx.doi.org/10.1186/1742-2094-10-155 |
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author | Cooney, Sean J Bermudez-Sabogal, Sara L Byrnes, Kimberly R |
author_facet | Cooney, Sean J Bermudez-Sabogal, Sara L Byrnes, Kimberly R |
author_sort | Cooney, Sean J |
collection | PubMed |
description | BACKGROUND: Brain injury results in an increase in the activity of the reactive oxygen species generating NADPH oxidase (NOX) enzymes. Preliminary studies have shown that NOX2, NOX3, and NOX4 are the most prominently expressed NOX isotypes in the brain. However, the cellular and temporal expression profile of these isotypes in the injured and non-injured brain is currently unclear. METHODS: Double immunofluorescence for NOX isotypes and brain cell types was performed at acute (24 hours), sub-acute (7 days), and chronic (28 days) time points after controlled cortical impact-induced brain injury or sham-injury in rats. RESULTS: NOX2, NOX3, and NOX4 isotypes were found to be expressed in neurons, astrocytes, and microglia, and this expression was dependent on both cellular source and post-injury time. NOX4 was found in all cell types assessed, while NOX3 was positively identified in neurons only, and NOX2 was identified in microglia and neurons. NOX2 was the most responsive to injury, increasing primarily in microglia in response to injury. Quantitation of this isotype showed a significant increase in NOX2 expression at 24 hours, with reduced expression at 7 days and 28 days post-injury, although expression remained above sham levels at later time points. Cellular confirmation using purified primary or cell line culture demonstrated similar patterns in microglia, astrocytes, and neurons. Further, inhibition of NOX, and more specifically NOX2, reduced pro-inflammatory activity in microglia, demonstrating that NOX is not only up-regulated after stimulation, but may also play a significant role in post-injury neuroinflammation. CONCLUSIONS: This study illustrates the expression profiles of NOX isotypes in the brain after injury, and demonstrates that NOX2, and to a lesser extent, NOX4, may be responsible for the majority of oxidative stress observed acutely after traumatic brain injury. These data may provide insight into the design of future therapeutic approaches. |
format | Online Article Text |
id | pubmed-3878417 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-38784172014-01-03 Cellular and temporal expression of NADPH oxidase (NOX) isotypes after brain injury Cooney, Sean J Bermudez-Sabogal, Sara L Byrnes, Kimberly R J Neuroinflammation Research BACKGROUND: Brain injury results in an increase in the activity of the reactive oxygen species generating NADPH oxidase (NOX) enzymes. Preliminary studies have shown that NOX2, NOX3, and NOX4 are the most prominently expressed NOX isotypes in the brain. However, the cellular and temporal expression profile of these isotypes in the injured and non-injured brain is currently unclear. METHODS: Double immunofluorescence for NOX isotypes and brain cell types was performed at acute (24 hours), sub-acute (7 days), and chronic (28 days) time points after controlled cortical impact-induced brain injury or sham-injury in rats. RESULTS: NOX2, NOX3, and NOX4 isotypes were found to be expressed in neurons, astrocytes, and microglia, and this expression was dependent on both cellular source and post-injury time. NOX4 was found in all cell types assessed, while NOX3 was positively identified in neurons only, and NOX2 was identified in microglia and neurons. NOX2 was the most responsive to injury, increasing primarily in microglia in response to injury. Quantitation of this isotype showed a significant increase in NOX2 expression at 24 hours, with reduced expression at 7 days and 28 days post-injury, although expression remained above sham levels at later time points. Cellular confirmation using purified primary or cell line culture demonstrated similar patterns in microglia, astrocytes, and neurons. Further, inhibition of NOX, and more specifically NOX2, reduced pro-inflammatory activity in microglia, demonstrating that NOX is not only up-regulated after stimulation, but may also play a significant role in post-injury neuroinflammation. CONCLUSIONS: This study illustrates the expression profiles of NOX isotypes in the brain after injury, and demonstrates that NOX2, and to a lesser extent, NOX4, may be responsible for the majority of oxidative stress observed acutely after traumatic brain injury. These data may provide insight into the design of future therapeutic approaches. BioMed Central 2013-12-17 /pmc/articles/PMC3878417/ /pubmed/24344836 http://dx.doi.org/10.1186/1742-2094-10-155 Text en Copyright © 2013 Cooney et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Cooney, Sean J Bermudez-Sabogal, Sara L Byrnes, Kimberly R Cellular and temporal expression of NADPH oxidase (NOX) isotypes after brain injury |
title | Cellular and temporal expression of NADPH oxidase (NOX) isotypes after brain injury |
title_full | Cellular and temporal expression of NADPH oxidase (NOX) isotypes after brain injury |
title_fullStr | Cellular and temporal expression of NADPH oxidase (NOX) isotypes after brain injury |
title_full_unstemmed | Cellular and temporal expression of NADPH oxidase (NOX) isotypes after brain injury |
title_short | Cellular and temporal expression of NADPH oxidase (NOX) isotypes after brain injury |
title_sort | cellular and temporal expression of nadph oxidase (nox) isotypes after brain injury |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878417/ https://www.ncbi.nlm.nih.gov/pubmed/24344836 http://dx.doi.org/10.1186/1742-2094-10-155 |
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