Research Paper Volume 14, Issue 15 pp 6028—6046
Ascorbic acid induces salivary gland function through TET2/acetylcholine receptor signaling in aging SAMP1/Klotho (-/-) mice
- 1 Department of Pathology, School of Dentistry, Chosun University, Gwangju 61452, Republic of Korea
- 2 Department of Biochemistry, School of Oriental Medicine, Dongguk University, Gyeongju 38066, Republic of Korea
Received: March 22, 2022 Accepted: July 27, 2022 Published: August 11, 2022
https://doi.org/10.18632/aging.204213How to Cite
Copyright: © 2022 Toan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Aging affects salivary gland function and alters saliva production and excretion. This study aimed to investigate whether ascorbic acid can be used to treat salivary gland dysfunction in an extensive aging mouse model of SAMP1/Klotho-/- mice. In our previous study, we found that ascorbic acid biosynthesis was disrupted in the salivary glands of SAMP1/Klotho (-/-) mice subjected to metabolomic profiling analysis. In SAMP1/Klotho -/- mice, daily supplementation with ascorbic acid (100 mg/kg for 18 days) significantly increased saliva secretion compared with the control. The expression of salivary gland functional markers (α-amylase, ZO-1, and Aqua5) is upregulated. Additionally, acetylcholine and/or beta-adrenergic receptors (M1AchR, M3AchR, and Adrb1) were increased by ascorbic acid in the salivary glands of aging mice, and treatment with ascorbic acid upregulated the expression of acetylcholine receptors through the DNA demethylation protein TET2. These results suggest that ascorbic acid could overcome the lack caused by dysfunction of ascorbic acid biosynthesis and induce the recovery of salivary gland function.
Abbreviations
SAMP1: Senescence-accelerated mouse prone 1; ZO-1: Zonula occludens-1; Aqua5: Aquaporin 5; M1AchR: Muscarinic acetylcholine receptor M1; M3AchR: Muscarinic acetylcholine receptor M3; Adrb1: Adrenergic receptor β1; TET2: Ten-eleven translocation methyl-cytosine dioxygenase 2; AA: Ascorbic acid; SAMP6: Senescence accelerated mice prone 6; SMP30KO: Senescence marker protein-30 knockout; Ach: Acetylcholine; PSGC: Primary salivary gland cell; ATP2A2: Sarcoplasmic/endoplasmic reticulum calcium ATPase 2; TET: Ten-eleven translocation; mAChR: Muscarinic acetylcholine receptor; GSH/GSSG: Glutathione/Glutathione disulfide.