Radiation inhibits salivary gland function by promoting STIM1 cleavage by caspase-3 and loss of SOCE through a TRPM2-dependent pathway.

ABSTRACT: Store-operated Ca²⁺ entry (SOCE) is critical for salivary gland fluid secretion. We report that radiation treatment caused persistent salivary gland dysfunction by activating a TRPM2-dependent mitochondrial pathway, leading to caspase-3-mediated cleavage of stromal interaction molecule 1 (STIM1) and loss of SOCE. After irradiation, acinar cells from the submandibular glands of TRPM2^+/+ , but not those from TRPM2^-/- mice, displayed an increase in the concentrations of mitochondrial Ca²⁺ and reactive oxygen species, a decrease in mitochondrial membrane potential, and activation of caspase-3, which was associated with a sustained decrease in STIM1 abundance and attenuation of SOCE. In a salivary gland cell line, silencing

SUBMITTER: Liu X 

PROVIDER: S-EPMC5798857 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature