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Pro-oxidant/antioxidant balance controls pancreatic β-cell differentiation through the ERK1/2 pathway
During embryogenesis, the intrauterine milieu affects cell proliferation, differentiation, and function by modifying gene expression in susceptible cells, such as the pancreatic β-cells. In this limited energy environment, mitochondrial dysfunction can lead to overproduction of reactive oxygen speci...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237262/ https://www.ncbi.nlm.nih.gov/pubmed/25341041 http://dx.doi.org/10.1038/cddis.2014.441 |
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author | Hoarau, E Chandra, V Rustin, P Scharfmann, R Duvillie, B |
author_facet | Hoarau, E Chandra, V Rustin, P Scharfmann, R Duvillie, B |
author_sort | Hoarau, E |
collection | PubMed |
description | During embryogenesis, the intrauterine milieu affects cell proliferation, differentiation, and function by modifying gene expression in susceptible cells, such as the pancreatic β-cells. In this limited energy environment, mitochondrial dysfunction can lead to overproduction of reactive oxygen species (ROS) and to a decline in β-cell function. In opposition to this toxicity, ROS are also required for insulin secretion. Here we investigated the role of ROS in β-cell development. Surprisingly, decreasing ROS production in vivo reduced β-cell differentiation. Moreover, in cultures of pancreatic explants, progenitors were highly sensitive to ROS stimulation and responded by generating β-cells. ROS enhanced β-cell differentiation through modulation of ERK1/2 signaling. Gene transfer and pharmacological manipulations, which diminish cellular ROS levels, also interfered with normal β-cell differentiation. This study highlights the role of the redox balance on β-cell development and provides information that will be useful for improving β-cell production from embryonic stem cells, a step in cell therapy for diabetes. |
format | Online Article Text |
id | pubmed-4237262 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-42372622014-11-26 Pro-oxidant/antioxidant balance controls pancreatic β-cell differentiation through the ERK1/2 pathway Hoarau, E Chandra, V Rustin, P Scharfmann, R Duvillie, B Cell Death Dis Original Article During embryogenesis, the intrauterine milieu affects cell proliferation, differentiation, and function by modifying gene expression in susceptible cells, such as the pancreatic β-cells. In this limited energy environment, mitochondrial dysfunction can lead to overproduction of reactive oxygen species (ROS) and to a decline in β-cell function. In opposition to this toxicity, ROS are also required for insulin secretion. Here we investigated the role of ROS in β-cell development. Surprisingly, decreasing ROS production in vivo reduced β-cell differentiation. Moreover, in cultures of pancreatic explants, progenitors were highly sensitive to ROS stimulation and responded by generating β-cells. ROS enhanced β-cell differentiation through modulation of ERK1/2 signaling. Gene transfer and pharmacological manipulations, which diminish cellular ROS levels, also interfered with normal β-cell differentiation. This study highlights the role of the redox balance on β-cell development and provides information that will be useful for improving β-cell production from embryonic stem cells, a step in cell therapy for diabetes. Nature Publishing Group 2014-10 2014-10-23 /pmc/articles/PMC4237262/ /pubmed/25341041 http://dx.doi.org/10.1038/cddis.2014.441 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International Licence. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0 |
spellingShingle | Original Article Hoarau, E Chandra, V Rustin, P Scharfmann, R Duvillie, B Pro-oxidant/antioxidant balance controls pancreatic β-cell differentiation through the ERK1/2 pathway |
title | Pro-oxidant/antioxidant balance controls pancreatic β-cell differentiation through the ERK1/2 pathway |
title_full | Pro-oxidant/antioxidant balance controls pancreatic β-cell differentiation through the ERK1/2 pathway |
title_fullStr | Pro-oxidant/antioxidant balance controls pancreatic β-cell differentiation through the ERK1/2 pathway |
title_full_unstemmed | Pro-oxidant/antioxidant balance controls pancreatic β-cell differentiation through the ERK1/2 pathway |
title_short | Pro-oxidant/antioxidant balance controls pancreatic β-cell differentiation through the ERK1/2 pathway |
title_sort | pro-oxidant/antioxidant balance controls pancreatic β-cell differentiation through the erk1/2 pathway |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237262/ https://www.ncbi.nlm.nih.gov/pubmed/25341041 http://dx.doi.org/10.1038/cddis.2014.441 |
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