Cargando…
Histone Modifications in Senescence-Associated Resistance to Apoptosis by Oxidative Stress()()
Aging and age-related diseases are associated with cellular senescence that results in variable apoptosis susceptibility to oxidative stress. Although fibroblast senescence has been associated with apoptosis resistance, mechanisms for this have not been well defined. In this report, we studied epige...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757696/ https://www.ncbi.nlm.nih.gov/pubmed/24024133 http://dx.doi.org/10.1016/j.redox.2012.11.004 |
_version_ | 1782282248777629696 |
---|---|
author | Sanders, Yan Y. Liu, Hui Zhang, Xiangyu Hecker, Louise Bernard, Karen Desai, Leena Liu, Gang Thannickal, Victor J. |
author_facet | Sanders, Yan Y. Liu, Hui Zhang, Xiangyu Hecker, Louise Bernard, Karen Desai, Leena Liu, Gang Thannickal, Victor J. |
author_sort | Sanders, Yan Y. |
collection | PubMed |
description | Aging and age-related diseases are associated with cellular senescence that results in variable apoptosis susceptibility to oxidative stress. Although fibroblast senescence has been associated with apoptosis resistance, mechanisms for this have not been well defined. In this report, we studied epigenetic mechanisms involving histone modifications that confer apoptosis resistance to senescent human diploid fibroblasts (HDFs). HDFs that undergo replicative senescence display typical morphological features, express senescence-associated β-galactosidase, and increased levels of the tumor suppressor genes, p16, p21, and caveolin-1. Senescent HDFs are more resistant to oxidative stress (exogenous H(2)O(2))-induced apoptosis in comparison to non-senescent (control) HDFs; this is associated with constitutively high levels of the anti-apoptotic gene, Bcl-2, and low expression of the pro-apoptotic gene, Bax. Cellular senescence is characterized by global increases in H4K20 trimethylation and decreases in H4K16 acetylation in association with increased activity of Suv420h2 histone methyltransferase (which targets H4K20), decreased activity of the histone acetyltransferase, Mof (which targets H4K16), as well as decreased total histone acetyltransferase activity. In contrast to Bax gene, chromatin immunoprecipitation studies demonstrate marked enrichment of the Bcl-2 gene with H4K16Ac, and depletion with H4K20Me3, predicting active transcription of this gene in senescent HDFs. These data indicate that both global and locus-specific histone modifications of chromatin regulate altered Bcl-2:Bax gene expression in senescent fibroblasts, contributing to its apoptosis-resistant phenotype. |
format | Online Article Text |
id | pubmed-3757696 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-37576962013-09-10 Histone Modifications in Senescence-Associated Resistance to Apoptosis by Oxidative Stress()() Sanders, Yan Y. Liu, Hui Zhang, Xiangyu Hecker, Louise Bernard, Karen Desai, Leena Liu, Gang Thannickal, Victor J. Redox Biol Research Paper Aging and age-related diseases are associated with cellular senescence that results in variable apoptosis susceptibility to oxidative stress. Although fibroblast senescence has been associated with apoptosis resistance, mechanisms for this have not been well defined. In this report, we studied epigenetic mechanisms involving histone modifications that confer apoptosis resistance to senescent human diploid fibroblasts (HDFs). HDFs that undergo replicative senescence display typical morphological features, express senescence-associated β-galactosidase, and increased levels of the tumor suppressor genes, p16, p21, and caveolin-1. Senescent HDFs are more resistant to oxidative stress (exogenous H(2)O(2))-induced apoptosis in comparison to non-senescent (control) HDFs; this is associated with constitutively high levels of the anti-apoptotic gene, Bcl-2, and low expression of the pro-apoptotic gene, Bax. Cellular senescence is characterized by global increases in H4K20 trimethylation and decreases in H4K16 acetylation in association with increased activity of Suv420h2 histone methyltransferase (which targets H4K20), decreased activity of the histone acetyltransferase, Mof (which targets H4K16), as well as decreased total histone acetyltransferase activity. In contrast to Bax gene, chromatin immunoprecipitation studies demonstrate marked enrichment of the Bcl-2 gene with H4K16Ac, and depletion with H4K20Me3, predicting active transcription of this gene in senescent HDFs. These data indicate that both global and locus-specific histone modifications of chromatin regulate altered Bcl-2:Bax gene expression in senescent fibroblasts, contributing to its apoptosis-resistant phenotype. Elsevier 2013-01-31 /pmc/articles/PMC3757696/ /pubmed/24024133 http://dx.doi.org/10.1016/j.redox.2012.11.004 Text en © 2013 The Authors http://creativecommons.org/licenses/BY-NC-SA/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Sanders, Yan Y. Liu, Hui Zhang, Xiangyu Hecker, Louise Bernard, Karen Desai, Leena Liu, Gang Thannickal, Victor J. Histone Modifications in Senescence-Associated Resistance to Apoptosis by Oxidative Stress()() |
title | Histone Modifications in Senescence-Associated Resistance to Apoptosis by Oxidative Stress()() |
title_full | Histone Modifications in Senescence-Associated Resistance to Apoptosis by Oxidative Stress()() |
title_fullStr | Histone Modifications in Senescence-Associated Resistance to Apoptosis by Oxidative Stress()() |
title_full_unstemmed | Histone Modifications in Senescence-Associated Resistance to Apoptosis by Oxidative Stress()() |
title_short | Histone Modifications in Senescence-Associated Resistance to Apoptosis by Oxidative Stress()() |
title_sort | histone modifications in senescence-associated resistance to apoptosis by oxidative stress()() |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757696/ https://www.ncbi.nlm.nih.gov/pubmed/24024133 http://dx.doi.org/10.1016/j.redox.2012.11.004 |
work_keys_str_mv | AT sandersyany histonemodificationsinsenescenceassociatedresistancetoapoptosisbyoxidativestress AT liuhui histonemodificationsinsenescenceassociatedresistancetoapoptosisbyoxidativestress AT zhangxiangyu histonemodificationsinsenescenceassociatedresistancetoapoptosisbyoxidativestress AT heckerlouise histonemodificationsinsenescenceassociatedresistancetoapoptosisbyoxidativestress AT bernardkaren histonemodificationsinsenescenceassociatedresistancetoapoptosisbyoxidativestress AT desaileena histonemodificationsinsenescenceassociatedresistancetoapoptosisbyoxidativestress AT liugang histonemodificationsinsenescenceassociatedresistancetoapoptosisbyoxidativestress AT thannickalvictorj histonemodificationsinsenescenceassociatedresistancetoapoptosisbyoxidativestress |