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p47phox-Dependent Reactive Oxygen Species Stimulate Nuclear Translocation of the FoxO1 Transcription Factor During Metabolic Inhibition in Cardiomyoblasts
Reactive oxygen species (ROS) control forkhead box O (FOXO) transcription factor activity by influencing their nuclear translocation. However, knowledge of the ROS cellular source(s) involved herein remains scarce. Recently, we have shown p47(phox)-dependent activation of ROS-producing NADPH oxidase...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097050/ https://www.ncbi.nlm.nih.gov/pubmed/29956081 http://dx.doi.org/10.1007/s12013-018-0847-4 |
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author | ter Horst, Ellis N. Hahn, Nynke E. Geerts, Dirk Musters, René J. P. Paulus, Walter J. van Rossum, Albert C. Meischl, Christof Piek, Jan J. Niessen, Hans W. M. Krijnen, Paul A. J. |
author_facet | ter Horst, Ellis N. Hahn, Nynke E. Geerts, Dirk Musters, René J. P. Paulus, Walter J. van Rossum, Albert C. Meischl, Christof Piek, Jan J. Niessen, Hans W. M. Krijnen, Paul A. J. |
author_sort | ter Horst, Ellis N. |
collection | PubMed |
description | Reactive oxygen species (ROS) control forkhead box O (FOXO) transcription factor activity by influencing their nuclear translocation. However, knowledge of the ROS cellular source(s) involved herein remains scarce. Recently, we have shown p47(phox)-dependent activation of ROS-producing NADPH oxidase (NOX) at the nuclear pore in H9c2 rat cardiomyoblasts in response to ischemia. This localizes NOX perfectly to affect protein nuclear translocation, including that of transcription factors. In the current study, involvement of p47(phox)-dependent production of ROS in the nuclear translocation of FOXO1 was analyzed in H9c2 cells following 4 h of metabolic inhibition (MI), which mimics the effects of ischemia. Nuclear translocation of FOXO1 was determined by quantitative digital-imaging fluorescence and western blot analysis. Subsequently, the effect of inhibiting p47(phox)-dependent ROS production by short hairpin RNA (shRNA) transfection on FOXO1 translocation was analyzed by digital-imaging microscopy. MI induced a significant translocation of FOXO1 into the nucleus. Transfection with p47(phox)-shRNA successfully knocked-down p47(phox) expression, reduced nuclear nitrotyrosine production, an indirect marker for ROS production, and inhibited the nuclear translocation of FOXO1 following MI. With these results, we show for the first time that nuclear import of FOXO1 induced by MI in H9c2 depends critically on p47(phox)-mediated ROS production. |
format | Online Article Text |
id | pubmed-6097050 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-60970502018-08-24 p47phox-Dependent Reactive Oxygen Species Stimulate Nuclear Translocation of the FoxO1 Transcription Factor During Metabolic Inhibition in Cardiomyoblasts ter Horst, Ellis N. Hahn, Nynke E. Geerts, Dirk Musters, René J. P. Paulus, Walter J. van Rossum, Albert C. Meischl, Christof Piek, Jan J. Niessen, Hans W. M. Krijnen, Paul A. J. Cell Biochem Biophys Original Paper Reactive oxygen species (ROS) control forkhead box O (FOXO) transcription factor activity by influencing their nuclear translocation. However, knowledge of the ROS cellular source(s) involved herein remains scarce. Recently, we have shown p47(phox)-dependent activation of ROS-producing NADPH oxidase (NOX) at the nuclear pore in H9c2 rat cardiomyoblasts in response to ischemia. This localizes NOX perfectly to affect protein nuclear translocation, including that of transcription factors. In the current study, involvement of p47(phox)-dependent production of ROS in the nuclear translocation of FOXO1 was analyzed in H9c2 cells following 4 h of metabolic inhibition (MI), which mimics the effects of ischemia. Nuclear translocation of FOXO1 was determined by quantitative digital-imaging fluorescence and western blot analysis. Subsequently, the effect of inhibiting p47(phox)-dependent ROS production by short hairpin RNA (shRNA) transfection on FOXO1 translocation was analyzed by digital-imaging microscopy. MI induced a significant translocation of FOXO1 into the nucleus. Transfection with p47(phox)-shRNA successfully knocked-down p47(phox) expression, reduced nuclear nitrotyrosine production, an indirect marker for ROS production, and inhibited the nuclear translocation of FOXO1 following MI. With these results, we show for the first time that nuclear import of FOXO1 induced by MI in H9c2 depends critically on p47(phox)-mediated ROS production. Springer US 2018-06-29 2018 /pmc/articles/PMC6097050/ /pubmed/29956081 http://dx.doi.org/10.1007/s12013-018-0847-4 Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Paper ter Horst, Ellis N. Hahn, Nynke E. Geerts, Dirk Musters, René J. P. Paulus, Walter J. van Rossum, Albert C. Meischl, Christof Piek, Jan J. Niessen, Hans W. M. Krijnen, Paul A. J. p47phox-Dependent Reactive Oxygen Species Stimulate Nuclear Translocation of the FoxO1 Transcription Factor During Metabolic Inhibition in Cardiomyoblasts |
title | p47phox-Dependent Reactive Oxygen Species Stimulate Nuclear Translocation of the FoxO1 Transcription Factor During Metabolic Inhibition in Cardiomyoblasts |
title_full | p47phox-Dependent Reactive Oxygen Species Stimulate Nuclear Translocation of the FoxO1 Transcription Factor During Metabolic Inhibition in Cardiomyoblasts |
title_fullStr | p47phox-Dependent Reactive Oxygen Species Stimulate Nuclear Translocation of the FoxO1 Transcription Factor During Metabolic Inhibition in Cardiomyoblasts |
title_full_unstemmed | p47phox-Dependent Reactive Oxygen Species Stimulate Nuclear Translocation of the FoxO1 Transcription Factor During Metabolic Inhibition in Cardiomyoblasts |
title_short | p47phox-Dependent Reactive Oxygen Species Stimulate Nuclear Translocation of the FoxO1 Transcription Factor During Metabolic Inhibition in Cardiomyoblasts |
title_sort | p47phox-dependent reactive oxygen species stimulate nuclear translocation of the foxo1 transcription factor during metabolic inhibition in cardiomyoblasts |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097050/ https://www.ncbi.nlm.nih.gov/pubmed/29956081 http://dx.doi.org/10.1007/s12013-018-0847-4 |
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