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Nuclear Nox4-Derived Reactive Oxygen Species in Myelodysplastic Syndromes
A role for intracellular ROS production has been recently implicated in the pathogenesis and progression of a wide variety of neoplasias. ROS sources, such as NAD(P)H oxidase (Nox) complexes, are frequently activated in AML (acute myeloid leukemia) blasts and strongly contribute to their proliferati...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955662/ https://www.ncbi.nlm.nih.gov/pubmed/24719867 http://dx.doi.org/10.1155/2014/456937 |
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author | Guida, Marianna Maraldi, Tullia Beretti, Francesca Follo, Matilde Y. Manzoli, Lucia De Pol, Anto |
author_facet | Guida, Marianna Maraldi, Tullia Beretti, Francesca Follo, Matilde Y. Manzoli, Lucia De Pol, Anto |
author_sort | Guida, Marianna |
collection | PubMed |
description | A role for intracellular ROS production has been recently implicated in the pathogenesis and progression of a wide variety of neoplasias. ROS sources, such as NAD(P)H oxidase (Nox) complexes, are frequently activated in AML (acute myeloid leukemia) blasts and strongly contribute to their proliferation, survival, and drug resistance. Myelodysplastic syndromes (MDS) comprise a heterogeneous group of disorders characterized by ineffective hematopoiesis, with an increased propensity to develop AML. The molecular basis for MDS progression is unknown, but a key element in MDS disease progression is the genomic instability. NADPH oxidases are now recognized to have specific subcellular localizations, this targeting to specific compartments for localized ROS production. Local Nox-dependent ROS production in the nucleus may contribute to the regulation of redox-dependent cell growth, differentiation, senescence, DNA damage, and apoptosis. We observed that Nox1, 2, and 4 isoforms and p22phox and Rac1 subunits are expressed in MDS/AML cell lines and MDS samples, also in the nuclear fractions. Interestingly, Nox4 interacts with ERK and Akt1 within nuclear speckle domain, suggesting that Nox4 could be involved in regulating gene expression and splicing factor activity. These data contribute to the elucidation of the molecular mechanisms used by nuclear ROS to drive MDS evolution to AML. |
format | Online Article Text |
id | pubmed-3955662 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-39556622014-04-09 Nuclear Nox4-Derived Reactive Oxygen Species in Myelodysplastic Syndromes Guida, Marianna Maraldi, Tullia Beretti, Francesca Follo, Matilde Y. Manzoli, Lucia De Pol, Anto Biomed Res Int Research Article A role for intracellular ROS production has been recently implicated in the pathogenesis and progression of a wide variety of neoplasias. ROS sources, such as NAD(P)H oxidase (Nox) complexes, are frequently activated in AML (acute myeloid leukemia) blasts and strongly contribute to their proliferation, survival, and drug resistance. Myelodysplastic syndromes (MDS) comprise a heterogeneous group of disorders characterized by ineffective hematopoiesis, with an increased propensity to develop AML. The molecular basis for MDS progression is unknown, but a key element in MDS disease progression is the genomic instability. NADPH oxidases are now recognized to have specific subcellular localizations, this targeting to specific compartments for localized ROS production. Local Nox-dependent ROS production in the nucleus may contribute to the regulation of redox-dependent cell growth, differentiation, senescence, DNA damage, and apoptosis. We observed that Nox1, 2, and 4 isoforms and p22phox and Rac1 subunits are expressed in MDS/AML cell lines and MDS samples, also in the nuclear fractions. Interestingly, Nox4 interacts with ERK and Akt1 within nuclear speckle domain, suggesting that Nox4 could be involved in regulating gene expression and splicing factor activity. These data contribute to the elucidation of the molecular mechanisms used by nuclear ROS to drive MDS evolution to AML. Hindawi Publishing Corporation 2014 2014-02-26 /pmc/articles/PMC3955662/ /pubmed/24719867 http://dx.doi.org/10.1155/2014/456937 Text en Copyright © 2014 Marianna Guida et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Guida, Marianna Maraldi, Tullia Beretti, Francesca Follo, Matilde Y. Manzoli, Lucia De Pol, Anto Nuclear Nox4-Derived Reactive Oxygen Species in Myelodysplastic Syndromes |
title | Nuclear Nox4-Derived Reactive Oxygen Species in Myelodysplastic Syndromes |
title_full | Nuclear Nox4-Derived Reactive Oxygen Species in Myelodysplastic Syndromes |
title_fullStr | Nuclear Nox4-Derived Reactive Oxygen Species in Myelodysplastic Syndromes |
title_full_unstemmed | Nuclear Nox4-Derived Reactive Oxygen Species in Myelodysplastic Syndromes |
title_short | Nuclear Nox4-Derived Reactive Oxygen Species in Myelodysplastic Syndromes |
title_sort | nuclear nox4-derived reactive oxygen species in myelodysplastic syndromes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955662/ https://www.ncbi.nlm.nih.gov/pubmed/24719867 http://dx.doi.org/10.1155/2014/456937 |
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