Mitochondria-targeted antioxidant protects against irradiation-induced salivary gland hypofunction

Abstract 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...

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Autores principales:	Xibao Liu, Krishna P. Subedi, Changyu Zheng, Indu Ambudkar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/db207e2ba12f48e08b162307148ad41f
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spelling	oai:doaj.org-article:db207e2ba12f48e08b162307148ad41f2021-12-02T14:17:16ZMitochondria-targeted antioxidant protects against irradiation-induced salivary gland hypofunction10.1038/s41598-021-86927-32045-2322https://doaj.org/article/db207e2ba12f48e08b162307148ad41f2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86927-3https://doaj.org/toc/2045-2322Abstract 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 (ROSmt), mitochondrial [Ca2+] ([Ca2+]mt), and activated caspase-3 in acinar cells. In contrast, loss of salivary secretion is persistent. Herein we assessed the role of ROSmt 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 ROSmt, ([Ca2+]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 Ca2+ entry which is critical for saliva secretion. Together, these findings identify the initial increase in ROSmt, 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.Xibao LiuKrishna P. SubediChangyu ZhengIndu AmbudkarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xibao Liu Krishna P. Subedi Changyu Zheng Indu Ambudkar Mitochondria-targeted antioxidant protects against irradiation-induced salivary gland hypofunction
description	Abstract 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 (ROSmt), mitochondrial [Ca2+] ([Ca2+]mt), and activated caspase-3 in acinar cells. In contrast, loss of salivary secretion is persistent. Herein we assessed the role of ROSmt 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 ROSmt, ([Ca2+]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 Ca2+ entry which is critical for saliva secretion. Together, these findings identify the initial increase in ROSmt, 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	article
author	Xibao Liu Krishna P. Subedi Changyu Zheng Indu Ambudkar
author_facet	Xibao Liu Krishna P. Subedi Changyu Zheng Indu Ambudkar
author_sort	Xibao Liu
title	Mitochondria-targeted antioxidant protects against irradiation-induced salivary gland hypofunction
title_short	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_sort	mitochondria-targeted antioxidant protects against irradiation-induced salivary gland hypofunction
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/db207e2ba12f48e08b162307148ad41f
work_keys_str_mv	AT xibaoliu mitochondriatargetedantioxidantprotectsagainstirradiationinducedsalivaryglandhypofunction AT krishnapsubedi mitochondriatargetedantioxidantprotectsagainstirradiationinducedsalivaryglandhypofunction AT changyuzheng mitochondriatargetedantioxidantprotectsagainstirradiationinducedsalivaryglandhypofunction AT induambudkar mitochondriatargetedantioxidantprotectsagainstirradiationinducedsalivaryglandhypofunction
_version_	1718391637597487104

Mitochondria-targeted antioxidant protects against irradiation-induced salivary gland hypofunction

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