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Hyperoxia activates ATM independent from mitochondrial ROS and dysfunction
High levels of oxygen (hyperoxia) are often used to treat individuals with respiratory distress, yet prolonged hyperoxia causes mitochondrial dysfunction and excessive reactive oxygen species (ROS) that can damage molecules such as DNA. Ataxia telangiectasia mutated (ATM) kinase is activated by nucl...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430709/ https://www.ncbi.nlm.nih.gov/pubmed/25967673 http://dx.doi.org/10.1016/j.redox.2015.04.012 |
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author | Resseguie, Emily A. Staversky, Rhonda J. Brookes, Paul S. O’Reilly, Michael A. |
author_facet | Resseguie, Emily A. Staversky, Rhonda J. Brookes, Paul S. O’Reilly, Michael A. |
author_sort | Resseguie, Emily A. |
collection | PubMed |
description | High levels of oxygen (hyperoxia) are often used to treat individuals with respiratory distress, yet prolonged hyperoxia causes mitochondrial dysfunction and excessive reactive oxygen species (ROS) that can damage molecules such as DNA. Ataxia telangiectasia mutated (ATM) kinase is activated by nuclear DNA double strand breaks and delays hyperoxia-induced cell death through downstream targets p53 and p21. Evidence for its role in regulating mitochondrial function is emerging, yet it has not been determined if mitochondrial dysfunction or ROS activates ATM. Because ATM maintains mitochondrial homeostasis, we hypothesized that hyperoxia induces both mitochondrial dysfunction and ROS that activate ATM. In A549 lung epithelial cells, hyperoxia decreased mitochondrial respiratory reserve capacity at 12 h and basal respiration by 48 h. ROS were significantly increased at 24 h, yet mitochondrial DNA double strand breaks were not detected. ATM was not required for activating p53 when mitochondrial respiration was inhibited by chronic exposure to antimycin A. Also, ATM was not further activated by mitochondrial ROS, which were enhanced by depleting manganese superoxide dismutase (SOD2). In contrast, ATM dampened the accumulation of mitochondrial ROS during exposure to hyperoxia. Our findings suggest that hyperoxia-induced mitochondrial dysfunction and ROS do not activate ATM. ATM more likely carries out its canonical response to nuclear DNA damage and may function to attenuate mitochondrial ROS that contribute to oxygen toxicity. |
format | Online Article Text |
id | pubmed-4430709 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-44307092015-05-15 Hyperoxia activates ATM independent from mitochondrial ROS and dysfunction Resseguie, Emily A. Staversky, Rhonda J. Brookes, Paul S. O’Reilly, Michael A. Redox Biol Research Paper High levels of oxygen (hyperoxia) are often used to treat individuals with respiratory distress, yet prolonged hyperoxia causes mitochondrial dysfunction and excessive reactive oxygen species (ROS) that can damage molecules such as DNA. Ataxia telangiectasia mutated (ATM) kinase is activated by nuclear DNA double strand breaks and delays hyperoxia-induced cell death through downstream targets p53 and p21. Evidence for its role in regulating mitochondrial function is emerging, yet it has not been determined if mitochondrial dysfunction or ROS activates ATM. Because ATM maintains mitochondrial homeostasis, we hypothesized that hyperoxia induces both mitochondrial dysfunction and ROS that activate ATM. In A549 lung epithelial cells, hyperoxia decreased mitochondrial respiratory reserve capacity at 12 h and basal respiration by 48 h. ROS were significantly increased at 24 h, yet mitochondrial DNA double strand breaks were not detected. ATM was not required for activating p53 when mitochondrial respiration was inhibited by chronic exposure to antimycin A. Also, ATM was not further activated by mitochondrial ROS, which were enhanced by depleting manganese superoxide dismutase (SOD2). In contrast, ATM dampened the accumulation of mitochondrial ROS during exposure to hyperoxia. Our findings suggest that hyperoxia-induced mitochondrial dysfunction and ROS do not activate ATM. ATM more likely carries out its canonical response to nuclear DNA damage and may function to attenuate mitochondrial ROS that contribute to oxygen toxicity. Elsevier 2015-05-02 /pmc/articles/PMC4430709/ /pubmed/25967673 http://dx.doi.org/10.1016/j.redox.2015.04.012 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Paper Resseguie, Emily A. Staversky, Rhonda J. Brookes, Paul S. O’Reilly, Michael A. Hyperoxia activates ATM independent from mitochondrial ROS and dysfunction |
title | Hyperoxia activates ATM independent from mitochondrial ROS and dysfunction |
title_full | Hyperoxia activates ATM independent from mitochondrial ROS and dysfunction |
title_fullStr | Hyperoxia activates ATM independent from mitochondrial ROS and dysfunction |
title_full_unstemmed | Hyperoxia activates ATM independent from mitochondrial ROS and dysfunction |
title_short | Hyperoxia activates ATM independent from mitochondrial ROS and dysfunction |
title_sort | hyperoxia activates atm independent from mitochondrial ros and dysfunction |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430709/ https://www.ncbi.nlm.nih.gov/pubmed/25967673 http://dx.doi.org/10.1016/j.redox.2015.04.012 |
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