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


Figure 8. Schematic pathway for the metabolism and roles of ascorbic acid in salivary glands. In most mammals, glycogenolysis, as a major source of UDP-glucuronic acid, leads to ascorbic acid synthesis. The glycogenolysis pathway is involved in the metabolism of glucose under normal and disease conditions and in the regulation of physiological functions. D-Glucose is converted into L-ascorbic acid via D-glucuronic acid, L-gulonic acid, and 2-keto-L-gulonolactone as intermediates. Ascorbic acid stimulates TET2 activity by promoting the recycling of inactive oxidized ferric iron (Fe3+) to actively reduced ferrous iron (Fe2+) in vitro and in vivo. Activation/expression of TET2 is indirectly involved in the expression of muscarinic and adrenergic receptors in salivary glands through global DNA demethylation. Ascorbic acid-induced TET2 promotes the expression of muscarinic and adrenergic receptors, which induce Ca2+ signaling, thereby inducing salivary gland functional protein and ultimately maintaining saliva secretion.