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Autophagy Correlates with Maintenance of Salivary Gland Function Following Radiation
The current standard of care for head and neck cancer includes surgical resection of the tumor followed by targeted head and neck radiation. This radiotherapy results in a multitude of negative side effects in adjacent normal tissues. Autophagy is a cellular mechanism that could be targeted to ameli...
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/PMC4047540/ https://www.ncbi.nlm.nih.gov/pubmed/24903000 http://dx.doi.org/10.1038/srep05206 |
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author | Morgan-Bathke, Maria Hill, Grace A. Harris, Zoey I. Lin, Her H. Chibly, Alex M. Klein, Rob R. Burd, Randy Ann, David K. Limesand, Kirsten H. |
author_facet | Morgan-Bathke, Maria Hill, Grace A. Harris, Zoey I. Lin, Her H. Chibly, Alex M. Klein, Rob R. Burd, Randy Ann, David K. Limesand, Kirsten H. |
author_sort | Morgan-Bathke, Maria |
collection | PubMed |
description | The current standard of care for head and neck cancer includes surgical resection of the tumor followed by targeted head and neck radiation. This radiotherapy results in a multitude of negative side effects in adjacent normal tissues. Autophagy is a cellular mechanism that could be targeted to ameliorate these side effects based on its role in cellular homeostasis. In this study, we utilized Atg5(f/f);Aqp5-Cre mice which harbor a conditional knockout of Atg5, in salivary acinar cells. These autophagy-deficient mice display increased radiosensitivity. Treatment of wild-type mice with radiation did not robustly induce autophagy following radiotherapy, however, using a model of preserved salivary gland function by IGF-1-treatment prior to irradiation, we demonstrate increased autophagosome formation 6–8 hours following radiation. Additionally, administration of IGF-1 to Atg5(f/f);Aqp5-Cre mice did not preserve physiological function. Thus, autophagy appears to play a beneficial role in salivary glands following radiation and pharmacological induction of autophagy could alleviate the negative side effects associated with therapy for head and neck cancer. |
format | Online Article Text |
id | pubmed-4047540 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-40475402014-06-12 Autophagy Correlates with Maintenance of Salivary Gland Function Following Radiation Morgan-Bathke, Maria Hill, Grace A. Harris, Zoey I. Lin, Her H. Chibly, Alex M. Klein, Rob R. Burd, Randy Ann, David K. Limesand, Kirsten H. Sci Rep Article The current standard of care for head and neck cancer includes surgical resection of the tumor followed by targeted head and neck radiation. This radiotherapy results in a multitude of negative side effects in adjacent normal tissues. Autophagy is a cellular mechanism that could be targeted to ameliorate these side effects based on its role in cellular homeostasis. In this study, we utilized Atg5(f/f);Aqp5-Cre mice which harbor a conditional knockout of Atg5, in salivary acinar cells. These autophagy-deficient mice display increased radiosensitivity. Treatment of wild-type mice with radiation did not robustly induce autophagy following radiotherapy, however, using a model of preserved salivary gland function by IGF-1-treatment prior to irradiation, we demonstrate increased autophagosome formation 6–8 hours following radiation. Additionally, administration of IGF-1 to Atg5(f/f);Aqp5-Cre mice did not preserve physiological function. Thus, autophagy appears to play a beneficial role in salivary glands following radiation and pharmacological induction of autophagy could alleviate the negative side effects associated with therapy for head and neck cancer. Nature Publishing Group 2014-06-06 /pmc/articles/PMC4047540/ /pubmed/24903000 http://dx.doi.org/10.1038/srep05206 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Article Morgan-Bathke, Maria Hill, Grace A. Harris, Zoey I. Lin, Her H. Chibly, Alex M. Klein, Rob R. Burd, Randy Ann, David K. Limesand, Kirsten H. Autophagy Correlates with Maintenance of Salivary Gland Function Following Radiation |
title | Autophagy Correlates with Maintenance of Salivary Gland Function Following Radiation |
title_full | Autophagy Correlates with Maintenance of Salivary Gland Function Following Radiation |
title_fullStr | Autophagy Correlates with Maintenance of Salivary Gland Function Following Radiation |
title_full_unstemmed | Autophagy Correlates with Maintenance of Salivary Gland Function Following Radiation |
title_short | Autophagy Correlates with Maintenance of Salivary Gland Function Following Radiation |
title_sort | autophagy correlates with maintenance of salivary gland function following radiation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047540/ https://www.ncbi.nlm.nih.gov/pubmed/24903000 http://dx.doi.org/10.1038/srep05206 |
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