Loss of TRPM2 function protects against irradiation-induced salivary gland dysfunction

Xibao Liu, Ana Cotrim, Leyla Teos, Changyu Zheng, William Swaim, James Mitchell, Yasuo Mori and Indu Ambudkar ()
Additional contact information
Xibao Liu: Secretory Physiology Section, National Cancer Institute, NIH
Ana Cotrim: Translational Research Core, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Cancer Institute, NIH
Leyla Teos: Secretory Physiology Section, National Cancer Institute, NIH
Changyu Zheng: Translational Research Core, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Cancer Institute, NIH
William Swaim: Secretory Physiology Section, National Cancer Institute, NIH
James Mitchell: Radiation Biology Branch, National Cancer Institute, NIH
Yasuo Mori: Laboratory of Molecular Biology, Graduate School of Engineering Kyoto University
Indu Ambudkar: Secretory Physiology Section, National Cancer Institute, NIH

Nature Communications, 2013, vol. 4, issue 1, 1-10

Abstract: Abstract Xerostomia as a result of salivary gland damage is a permanent and debilitating side effect of radiotherapy for head and neck cancers. Effective treatments for protecting, or restoring, salivary gland function are not available. Here we report that irradiation treatment leads to activation of the calcium-permeable channel, transient potential melastatin-like 2 (TRPM2), via stimulation of poly-ADP-ribose polymerase. Importantly, irradiation induced an irreversible loss of salivary gland fluid secretion in TRPM2+/+ mice while a transient loss was seen in TRPM2−/− mice with >60% recovery by 30 days after irradiation. Treatment of TRPM2+/+ mice with the free radical scavenger Tempol or the PARP1 inhibitor 3-aminobenzamide attenuated irradiation-induced activation of TRPM2 and induced significant recovery of salivary fluid secretion. Furthermore, TPL (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) induced complete recovery of function in irradiated TRPM2−/− mice. These novel data demonstrate that TRPM2 is activated by irradiation, via PARP1 activation, and contributes to irreversible loss of salivary gland function.

Date: 2013
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms2526 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2526

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms2526

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().