Abstract
Aquaporins (AQP) are water channel proteins and the genes coding for AQP2, AQP5, and AQP6 are clustered in 12q13. Since AQP5 is expressed in serous acinar cells of salivary glands, we investigated its involvement in caries. DNA samples from 1,383 individuals from six groups were studied. Genotypes of eight single nucleotide polymorphisms covering the aquaporin locus were tested for association with caries experience. Interaction with genes involved in enamel formation was tested. The association between enamel microhardness at baseline, after creation of artificial caries lesion, and after exposure to fluoride and the genetic markers in AQP5 was tested. Finally, AQP5 expression in human whole saliva, after exposure to fluoride in a mammary gland cell line, which is known to express AQP5, and in Wistar rats was also verified. Nominal associations were found between caries experience and markers in the AQP5 locus. Since these associations suggested that AQP5 may be inhibited by levels of fluoride in the drinking water that cause fluorosis, we showed that fluoride levels above optimal levels change AQP5 expression in humans, cell lines, and rats. We have shown that AQP5 is involved in the pathogenesis of caries and likely interacts with fluoride.
Highlights
Aquaporin 5 (AQP5) is a water channel protein expressed in the apical membranes of serous acinar cells in salivary and lacrimal glands, type I alveolar epithelial cells, surface corneal epithelial cells, and during tooth development [1,2,3,4,5]
In the sample from Pittsburgh, the best model showed that higher caries experience is influenced by a combination of older age, use of medications that cause xerostomia and genetic variation in AQP5 Single Nucleotide Polymorphism (SNP) rs3759129 (p = 0.03) and rs10875989 (p = 0.04)
Studies of the human red blood cell RH protein led to the discovery of a water channel protein, aquaporin 1 (AQP1)
Summary
Aquaporin 5 (AQP5) is a water channel protein expressed in the apical membranes of serous acinar cells in salivary and lacrimal glands, type I alveolar epithelial cells, surface corneal epithelial cells, and during tooth development [1,2,3,4,5]. Aqp null mouse’s saliva is remarkably viscous and of lower volume than saliva collected from wild type and heterozygous mice, total protein secretion and amylase activity are not affected. The abnormal saliva volume, osmolarity, and electrolyte content in Aqp null mice implicate the involvement of AQP5 in transcellular fluid secretion across serous-type acinar cells [7]. The normal protein, pH, and amylase content of saliva from Aqp null mice is consistent with the absence of AQP5 in mucous cells. The hypertonic saliva from Aqp null mice suggests that active acinar cell salt secretion into the gland lumen occurs without adequate amounts of water [7]. AQP5 levels in saliva are decreased in type 1 diabetics and patients with Sjögren’s syndrome, concomitant with a decrease in the salivary secretion of these patients. In Alzheimer patients treated with donepezil, salivary secretion and salivary AQP5 levels are increased compared with those from same-age subjects without Alzheimer’s disease [10]
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