Long-Term Oral Administration of LLHK, LHK, and HK Alters Gene Expression Profile and Restores Age-Dependent Atrophy and Dysfunction of Rat Salivary Glands

Abstract

Xerostomia, also known as dry mouth, is caused by a reduction in salivary secretion and by changes in the composition of saliva associated with the malfunction of salivary glands. Xerostomia decreases quality of life. In the present study, we investigated the effects of peptides derived from β-lactoglobulin C on age-dependent atrophy, gene expression profiles, and the dysfunction of salivary glands. Long-term oral administration of Leu57-Leu58-His59-Lys60 (LLHK), Leu58-His59-Lys60 (LHK) and His59-Lys60 (HK) peptides induced salivary secretion and prevented and/or reversed the age-dependent atrophy of salivary glands in older rats. The transcripts of 78 genes were upregulated and those of 81 genes were downregulated by more than 2.0-fold (p ≤ 0.05) after LHK treatment. LHK upregulated major salivary protein genes such as proline-rich proteins (Prpmp5, Prb3, Prp2, Prb1, Prp15), cystatins (Cst5, Cyss, Vegp2), amylases (Amy1a, Amy2a3), and lysozyme (Lyzl1), suggesting that LLHK, LHK, and HK restored normal salivary function. The AP-2 transcription factor gene (Tcfap2b) was also induced significantly by LHK treatment. These results suggest that LLHK, LHK, and HK-administration may prevent and/or reverse the age-dependent atrophy and functional decline of salivary glands by affecting gene expression.

Effect of Jersey cow defatted dry milk on salivary volume and composition in elderly persons : a pilot study

“…As previously mentioned, oral administration of LHK upregulates proline-rich protein genes (Prpmp5, Prb3, Prp2, Prb1, Prp15), cystatin genes (Cst5, Cyss, Vegp2), amylase genes (Amy1a, Amy2a3), and lysozyme gene (Lyzl1), and AP-2 transcription factor gene (Tcfap2b) (15). The administration of LLHK, LHK, and HTK prevents and / or restores the age-dependent atrophy and functional decline of salivary glands.…”

“…Previously, we reported that the administration of whey from Jersey cow milk mitigates age-dependent atrophy and functional decline of salivary glands accompanied with changes in gene expression in rats (12). We found that the bioactive peptides, which were LLHK, LHK, and HK derived from β-lactoglobulin C variant, prevent and / or restore the age-depending decline in structure and function of salivary gland (15). In those experiments, older rats drank the whey or the peptides.…”

“…The milk induced salivary secretion also in Participant F6, who used Aricept (an acetylcholinesterase inhibitor) and Famotidine (a histamine H2-receptor antagonist). As LLHK, LHK, and HK may activate non-adrenergic and non-cholinergic nerves (15), it seems that medications had little influence on LLHK, LHK, and HK-induced gene expression.…”

“…In previous experiments, we investigated the effects of Leu 57 -Leu 58 -His 59 -Lys 60 (LLHK), Leu 58 -His 59 -Lys 60 (LHK), and His 59 -Lys 60 (HK) peptides on the gene expression profile, age-dependent atrophy, and dysfunction of rat salivary glands. LLHK, LHK, and HK administration prevents and / or restores the age-dependent atrophy and functional decline of salivary glands by affecting gene expression (15). In this study, we investigated the effect…”