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Gadd45b deficiency promotes premature senescence and skin aging

The GADD45 family of proteins functions as stress sensors in response to various physiological and environmental stressors. Here we show that primary mouse embryo fibroblasts (MEFs) from Gadd45b null mice proliferate slowly, accumulate increased levels of DNA damage, and senesce prematurely. The imp...

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Autores principales: Magimaidas, Andrew, Madireddi, Priyanka, Maifrede, Silvia, Mukherjee, Kaushiki, Hoffman, Barbara, Liebermann, Dan A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053623/
https://www.ncbi.nlm.nih.gov/pubmed/27105496
http://dx.doi.org/10.18632/oncotarget.8854
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author Magimaidas, Andrew
Madireddi, Priyanka
Maifrede, Silvia
Mukherjee, Kaushiki
Hoffman, Barbara
Liebermann, Dan A.
author_facet Magimaidas, Andrew
Madireddi, Priyanka
Maifrede, Silvia
Mukherjee, Kaushiki
Hoffman, Barbara
Liebermann, Dan A.
author_sort Magimaidas, Andrew
collection PubMed
description The GADD45 family of proteins functions as stress sensors in response to various physiological and environmental stressors. Here we show that primary mouse embryo fibroblasts (MEFs) from Gadd45b null mice proliferate slowly, accumulate increased levels of DNA damage, and senesce prematurely. The impaired proliferation and increased senescence in Gadd45b null MEFs is partially reversed by culturing at physiological oxygen levels, indicating that Gadd45b deficiency leads to decreased ability to cope with oxidative stress. Interestingly, Gadd45b null MEFs arrest at the G2/M phase of cell cycle, in contrast to other senescent MEFs, which arrest at G1. FACS analysis of phospho-histone H3 staining showed that Gadd45b null MEFs are arrested in G2 phase rather than M phase. H2O2 and UV irradiation, known to increase oxidative stress, also triggered increased senescence in Gadd45b null MEFs compared to wild type MEFs. In vivo evidence for increased senescence in Gadd45b null mice includes the observation that embryos from Gadd45b null mice exhibit increased senescence staining compared to wild type embryos. Furthermore, it is shown that Gadd45b deficiency promotes senescence and aging phenotypes in mouse skin. Together, these results highlight a novel role for Gadd45b in stress-induced senescence and in tissue aging.
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spelling pubmed-50536232016-10-12 Gadd45b deficiency promotes premature senescence and skin aging Magimaidas, Andrew Madireddi, Priyanka Maifrede, Silvia Mukherjee, Kaushiki Hoffman, Barbara Liebermann, Dan A. Oncotarget Research Paper: Gerotarget (Focus on Aging) The GADD45 family of proteins functions as stress sensors in response to various physiological and environmental stressors. Here we show that primary mouse embryo fibroblasts (MEFs) from Gadd45b null mice proliferate slowly, accumulate increased levels of DNA damage, and senesce prematurely. The impaired proliferation and increased senescence in Gadd45b null MEFs is partially reversed by culturing at physiological oxygen levels, indicating that Gadd45b deficiency leads to decreased ability to cope with oxidative stress. Interestingly, Gadd45b null MEFs arrest at the G2/M phase of cell cycle, in contrast to other senescent MEFs, which arrest at G1. FACS analysis of phospho-histone H3 staining showed that Gadd45b null MEFs are arrested in G2 phase rather than M phase. H2O2 and UV irradiation, known to increase oxidative stress, also triggered increased senescence in Gadd45b null MEFs compared to wild type MEFs. In vivo evidence for increased senescence in Gadd45b null mice includes the observation that embryos from Gadd45b null mice exhibit increased senescence staining compared to wild type embryos. Furthermore, it is shown that Gadd45b deficiency promotes senescence and aging phenotypes in mouse skin. Together, these results highlight a novel role for Gadd45b in stress-induced senescence and in tissue aging. Impact Journals LLC 2016-04-20 /pmc/articles/PMC5053623/ /pubmed/27105496 http://dx.doi.org/10.18632/oncotarget.8854 Text en Copyright: © 2016 Magimaidas et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper: Gerotarget (Focus on Aging)
Magimaidas, Andrew
Madireddi, Priyanka
Maifrede, Silvia
Mukherjee, Kaushiki
Hoffman, Barbara
Liebermann, Dan A.
Gadd45b deficiency promotes premature senescence and skin aging
title Gadd45b deficiency promotes premature senescence and skin aging
title_full Gadd45b deficiency promotes premature senescence and skin aging
title_fullStr Gadd45b deficiency promotes premature senescence and skin aging
title_full_unstemmed Gadd45b deficiency promotes premature senescence and skin aging
title_short Gadd45b deficiency promotes premature senescence and skin aging
title_sort gadd45b deficiency promotes premature senescence and skin aging
topic Research Paper: Gerotarget (Focus on Aging)
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053623/
https://www.ncbi.nlm.nih.gov/pubmed/27105496
http://dx.doi.org/10.18632/oncotarget.8854
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