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Zinc regulates iNOS-derived nitric oxide formation in endothelial cells
Aberrant production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathogenesis of endothelial dysfunction and vascular disease. Mechanisms responsible for the fine-tuning of iNOS activity in inflammation are still not fully understood. Zinc is an important structura...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143817/ https://www.ncbi.nlm.nih.gov/pubmed/25180171 http://dx.doi.org/10.1016/j.redox.2014.06.011 |
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author | Cortese-Krott, Miriam M. Kulakov, Larissa Opländer, Christian Kolb-Bachofen, Victoria Kröncke, Klaus-D. Suschek, Christoph V. |
author_facet | Cortese-Krott, Miriam M. Kulakov, Larissa Opländer, Christian Kolb-Bachofen, Victoria Kröncke, Klaus-D. Suschek, Christoph V. |
author_sort | Cortese-Krott, Miriam M. |
collection | PubMed |
description | Aberrant production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathogenesis of endothelial dysfunction and vascular disease. Mechanisms responsible for the fine-tuning of iNOS activity in inflammation are still not fully understood. Zinc is an important structural element of NOS enzymes and is known to inhibit its catalytical activity. In this study we aimed to investigate the effects of zinc on iNOS activity and expression in endothelial cells. We found that zinc down-regulated the expression of iNOS (mRNA+protein) and decreased cytokine-mediated activation of the iNOS promoter. Zinc-mediated regulation of iNOS expression was due to inhibition of NF-κB transactivation activity, as determined by a decrease in both NF-κB-driven luciferase reporter activity and expression of NF-κB target genes, including cyclooxygenase 2 and IL-1β. However, zinc did not affect NF-κB translocation into the nucleus, as assessed by Western blot analysis of nuclear and cytoplasmic fractions. Taken together our results demonstrate that zinc limits iNOS-derived high output NO production in endothelial cells by inhibiting NF-κB-dependent iNOS expression, pointing to a role of zinc as a regulator of iNOS activity in inflammation. |
format | Online Article Text |
id | pubmed-4143817 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-41438172014-09-01 Zinc regulates iNOS-derived nitric oxide formation in endothelial cells Cortese-Krott, Miriam M. Kulakov, Larissa Opländer, Christian Kolb-Bachofen, Victoria Kröncke, Klaus-D. Suschek, Christoph V. Redox Biol Research Paper Aberrant production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathogenesis of endothelial dysfunction and vascular disease. Mechanisms responsible for the fine-tuning of iNOS activity in inflammation are still not fully understood. Zinc is an important structural element of NOS enzymes and is known to inhibit its catalytical activity. In this study we aimed to investigate the effects of zinc on iNOS activity and expression in endothelial cells. We found that zinc down-regulated the expression of iNOS (mRNA+protein) and decreased cytokine-mediated activation of the iNOS promoter. Zinc-mediated regulation of iNOS expression was due to inhibition of NF-κB transactivation activity, as determined by a decrease in both NF-κB-driven luciferase reporter activity and expression of NF-κB target genes, including cyclooxygenase 2 and IL-1β. However, zinc did not affect NF-κB translocation into the nucleus, as assessed by Western blot analysis of nuclear and cytoplasmic fractions. Taken together our results demonstrate that zinc limits iNOS-derived high output NO production in endothelial cells by inhibiting NF-κB-dependent iNOS expression, pointing to a role of zinc as a regulator of iNOS activity in inflammation. Elsevier 2014-07-16 /pmc/articles/PMC4143817/ /pubmed/25180171 http://dx.doi.org/10.1016/j.redox.2014.06.011 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
spellingShingle | Research Paper Cortese-Krott, Miriam M. Kulakov, Larissa Opländer, Christian Kolb-Bachofen, Victoria Kröncke, Klaus-D. Suschek, Christoph V. Zinc regulates iNOS-derived nitric oxide formation in endothelial cells |
title | Zinc regulates iNOS-derived nitric oxide formation in endothelial cells |
title_full | Zinc regulates iNOS-derived nitric oxide formation in endothelial cells |
title_fullStr | Zinc regulates iNOS-derived nitric oxide formation in endothelial cells |
title_full_unstemmed | Zinc regulates iNOS-derived nitric oxide formation in endothelial cells |
title_short | Zinc regulates iNOS-derived nitric oxide formation in endothelial cells |
title_sort | zinc regulates inos-derived nitric oxide formation in endothelial cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143817/ https://www.ncbi.nlm.nih.gov/pubmed/25180171 http://dx.doi.org/10.1016/j.redox.2014.06.011 |
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