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Differential gene expression patterns in cyclooxygenase-1 and cyclooxygenase-2 deficient mouse brain
BACKGROUND: Cyclooxygenase (COX)-1 and COX-2 produce prostanoids from arachidonic acid and are thought to have important yet distinct roles in normal brain function. Deletion of COX-1 or COX-2 results in profound differences both in brain levels of prostaglandin E(2 )and in activation of the transcr...
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2007
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1839133/ https://www.ncbi.nlm.nih.gov/pubmed/17266762 http://dx.doi.org/10.1186/gb-2007-8-1-r14 |
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author | Toscano, Christopher D Prabhu, Vinaykumar V Langenbach, Robert Becker, Kevin G Bosetti, Francesca |
author_facet | Toscano, Christopher D Prabhu, Vinaykumar V Langenbach, Robert Becker, Kevin G Bosetti, Francesca |
author_sort | Toscano, Christopher D |
collection | PubMed |
description | BACKGROUND: Cyclooxygenase (COX)-1 and COX-2 produce prostanoids from arachidonic acid and are thought to have important yet distinct roles in normal brain function. Deletion of COX-1 or COX-2 results in profound differences both in brain levels of prostaglandin E(2 )and in activation of the transcription factor nuclear factor-κB, suggesting that COX-1 and COX-2 play distinct roles in brain arachidonic acid metabolism and regulation of gene expression. To further elucidate the role of COX isoforms in the regulation of the brain transcriptome, microarray analysis of gene expression in the cerebral cortex and hippocampus of mice deficient in COX-1 (COX-1(-/-)) or COX-2 (COX-2(-/-)) was performed. RESULTS: A majority (>93%) of the differentially expressed genes in both the cortex and hippocampus were altered in one COX isoform knockout mouse but not the other. The major gene function affected in all genotype comparisons was 'transcriptional regulation'. Distinct biologic and metabolic pathways that were altered in COX(-/- )mice included β oxidation, methionine metabolism, janus kinase signaling, and GABAergic neurotransmission. CONCLUSION: Our findings suggest that COX-1 and COX-2 differentially modulate brain gene expression. Because certain anti-inflammatory and analgesic treatments are based on inhibition of COX activity, the specific alterations observed in this study further our understanding of the relationship of COX-1 and COX-2 with signaling pathways in brain and of the therapeutic and toxicologic consequences of COX inhibition. |
format | Text |
id | pubmed-1839133 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-18391332007-03-30 Differential gene expression patterns in cyclooxygenase-1 and cyclooxygenase-2 deficient mouse brain Toscano, Christopher D Prabhu, Vinaykumar V Langenbach, Robert Becker, Kevin G Bosetti, Francesca Genome Biol Research BACKGROUND: Cyclooxygenase (COX)-1 and COX-2 produce prostanoids from arachidonic acid and are thought to have important yet distinct roles in normal brain function. Deletion of COX-1 or COX-2 results in profound differences both in brain levels of prostaglandin E(2 )and in activation of the transcription factor nuclear factor-κB, suggesting that COX-1 and COX-2 play distinct roles in brain arachidonic acid metabolism and regulation of gene expression. To further elucidate the role of COX isoforms in the regulation of the brain transcriptome, microarray analysis of gene expression in the cerebral cortex and hippocampus of mice deficient in COX-1 (COX-1(-/-)) or COX-2 (COX-2(-/-)) was performed. RESULTS: A majority (>93%) of the differentially expressed genes in both the cortex and hippocampus were altered in one COX isoform knockout mouse but not the other. The major gene function affected in all genotype comparisons was 'transcriptional regulation'. Distinct biologic and metabolic pathways that were altered in COX(-/- )mice included β oxidation, methionine metabolism, janus kinase signaling, and GABAergic neurotransmission. CONCLUSION: Our findings suggest that COX-1 and COX-2 differentially modulate brain gene expression. Because certain anti-inflammatory and analgesic treatments are based on inhibition of COX activity, the specific alterations observed in this study further our understanding of the relationship of COX-1 and COX-2 with signaling pathways in brain and of the therapeutic and toxicologic consequences of COX inhibition. BioMed Central 2007 2007-01-31 /pmc/articles/PMC1839133/ /pubmed/17266762 http://dx.doi.org/10.1186/gb-2007-8-1-r14 Text en Copyright © 2007 Toscano 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 Toscano, Christopher D Prabhu, Vinaykumar V Langenbach, Robert Becker, Kevin G Bosetti, Francesca Differential gene expression patterns in cyclooxygenase-1 and cyclooxygenase-2 deficient mouse brain |
title | Differential gene expression patterns in cyclooxygenase-1 and cyclooxygenase-2 deficient mouse brain |
title_full | Differential gene expression patterns in cyclooxygenase-1 and cyclooxygenase-2 deficient mouse brain |
title_fullStr | Differential gene expression patterns in cyclooxygenase-1 and cyclooxygenase-2 deficient mouse brain |
title_full_unstemmed | Differential gene expression patterns in cyclooxygenase-1 and cyclooxygenase-2 deficient mouse brain |
title_short | Differential gene expression patterns in cyclooxygenase-1 and cyclooxygenase-2 deficient mouse brain |
title_sort | differential gene expression patterns in cyclooxygenase-1 and cyclooxygenase-2 deficient mouse brain |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1839133/ https://www.ncbi.nlm.nih.gov/pubmed/17266762 http://dx.doi.org/10.1186/gb-2007-8-1-r14 |
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