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Mitochondria-targeted antioxidant protects against irradiation-induced salivary gland hypofunction
A severe consequence of radiation therapy in patients with head and neck cancer is persistent salivary gland hypofunction which causes xerostomia and oral infections. We previously showed that irradiation (IR) of salivary glands in mice triggers initial transient increases in mitochondrial reactive...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032724/ https://www.ncbi.nlm.nih.gov/pubmed/33833270 http://dx.doi.org/10.1038/s41598-021-86927-3 |
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author | Liu, Xibao Subedi, Krishna P. Zheng, Changyu Ambudkar, Indu |
author_facet | Liu, Xibao Subedi, Krishna P. Zheng, Changyu Ambudkar, Indu |
author_sort | Liu, Xibao |
collection | PubMed |
description | A severe consequence of radiation therapy in patients with head and neck cancer is persistent salivary gland hypofunction which causes xerostomia and oral infections. We previously showed that irradiation (IR) of salivary glands in mice triggers initial transient increases in mitochondrial reactive oxygen species (ROS(mt)), mitochondrial [Ca(2+)] ([Ca(2+)](mt)), and activated caspase-3 in acinar cells. In contrast, loss of salivary secretion is persistent. Herein we assessed the role of ROS(mt) in radiation-induced irreversible loss of salivary gland function. We report that treatment of mice with the mitochondrial-targeted antioxidant, MitoTEMPO, resulted in almost complete protection of salivary gland secretion following either single (15 Gy) or fractionated (5 × 3 Gy) doses of irradiation. Salivary gland cells isolated from MitoTEMPO-treated, irradiated, mice displayed significant attenuation of the initial increases in ROS(mt), ([Ca(2+)](mt), and activated caspase-3 as compared to cells from irradiated, but untreated, animals. Importantly, MitoTEMPO treatment prevented radiation-induced decrease in STIM1, consequently protecting store-operated Ca(2+) entry which is critical for saliva secretion. Together, these findings identify the initial increase in ROS(mt), that is induced by irradiation, as a critical driver of persistent salivary gland hypofunction. We suggest that the mitochondrially targeted antioxidant, MitoTEMPO, can be potentially important in preventing IR-induced salivary gland dysfunction. |
format | Online Article Text |
id | pubmed-8032724 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-80327242021-04-09 Mitochondria-targeted antioxidant protects against irradiation-induced salivary gland hypofunction Liu, Xibao Subedi, Krishna P. Zheng, Changyu Ambudkar, Indu Sci Rep Article A severe consequence of radiation therapy in patients with head and neck cancer is persistent salivary gland hypofunction which causes xerostomia and oral infections. We previously showed that irradiation (IR) of salivary glands in mice triggers initial transient increases in mitochondrial reactive oxygen species (ROS(mt)), mitochondrial [Ca(2+)] ([Ca(2+)](mt)), and activated caspase-3 in acinar cells. In contrast, loss of salivary secretion is persistent. Herein we assessed the role of ROS(mt) in radiation-induced irreversible loss of salivary gland function. We report that treatment of mice with the mitochondrial-targeted antioxidant, MitoTEMPO, resulted in almost complete protection of salivary gland secretion following either single (15 Gy) or fractionated (5 × 3 Gy) doses of irradiation. Salivary gland cells isolated from MitoTEMPO-treated, irradiated, mice displayed significant attenuation of the initial increases in ROS(mt), ([Ca(2+)](mt), and activated caspase-3 as compared to cells from irradiated, but untreated, animals. Importantly, MitoTEMPO treatment prevented radiation-induced decrease in STIM1, consequently protecting store-operated Ca(2+) entry which is critical for saliva secretion. Together, these findings identify the initial increase in ROS(mt), that is induced by irradiation, as a critical driver of persistent salivary gland hypofunction. We suggest that the mitochondrially targeted antioxidant, MitoTEMPO, can be potentially important in preventing IR-induced salivary gland dysfunction. Nature Publishing Group UK 2021-04-08 /pmc/articles/PMC8032724/ /pubmed/33833270 http://dx.doi.org/10.1038/s41598-021-86927-3 Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Liu, Xibao Subedi, Krishna P. Zheng, Changyu Ambudkar, Indu Mitochondria-targeted antioxidant protects against irradiation-induced salivary gland hypofunction |
title | Mitochondria-targeted antioxidant protects against irradiation-induced salivary gland hypofunction |
title_full | Mitochondria-targeted antioxidant protects against irradiation-induced salivary gland hypofunction |
title_fullStr | Mitochondria-targeted antioxidant protects against irradiation-induced salivary gland hypofunction |
title_full_unstemmed | Mitochondria-targeted antioxidant protects against irradiation-induced salivary gland hypofunction |
title_short | Mitochondria-targeted antioxidant protects against irradiation-induced salivary gland hypofunction |
title_sort | mitochondria-targeted antioxidant protects against irradiation-induced salivary gland hypofunction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032724/ https://www.ncbi.nlm.nih.gov/pubmed/33833270 http://dx.doi.org/10.1038/s41598-021-86927-3 |
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