Dataset Information

Aquaporin 5 Interacts with Fluoride and Possibly Protects against Caries.

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.

SUBMITTER: Anjomshoaa I

PROVIDER: S-EPMC4668048 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Aquaporin 5 Interacts with Fluoride and Possibly Protects against Caries.

Anjomshoaa Ida I Briseño-Ruiz Jessica J Deeley Kathleen K Poletta Fernardo A FA Mereb Juan C JC Leite Aline L AL Barreta Priscila A T M PA Silva Thelma L TL Dizak Piper P Ruff Timothy T Patir Asli A Koruyucu Mine M Abbasoğlu Zerrin Z Casado Priscila L PL Brown Andrew A Zaky Samer H SH Bayram Merve M Küchler Erika C EC Cooper Margaret E ME Liu Kai K Marazita Mary L ML Tanboğa İlknur İ Granjeiro José M JM Seymen Figen F Castilla Eduardo E EE Orioli Iêda M IM Sfeir Charles C Owyang Hongjiao H Buzalaf Marília A R MA Vieira Alexandre R AR

PloS one 20151202 12

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 ...[more]

PMID: 26630491

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Project description:The impairment of amyloid-? (A?) clearance in the brain plays a causative role in Alzheimer's disease (AD). Polarity distribution of aquaporin-4 (AQP4) is important to remove A? from brain. AQP4 polarity can be influenced by the ratio of two AQP4 isoforms M1 and M23 (AQP4-M1/M23), however, it is unknown whether the ratio of AQP4-M1/M23 changes in AD. Histone deacetylase 3 has been reported to be significantly increased in AD brain. Moreover, evidence indicated that microRNA-130a (miR-130a) possibly mediates the regulation of histone deacetylase 3 on AQP4-M1/M23 ratio by repressing the transcriptional activity of AQP4-M1 in AD. This study aimed to investigate whether intermittent fasting (IF), increasing the level of an endogenous histone deacetylases inhibitor ?-hydroxybutyrate, restores AQP4 polarity via miR-130a mediated reduction of AQP4-M1/M23 ratio in protection against AD. The results showed that IF ameliorated cognitive dysfunction, prevented brain from A? deposition, and restored the AQP4 polarity in a mouse model of AD (APP/PS1 double-transgenic mice). Additionally, IF down-regulated the expression of AQP4-M1 and histone deacetylase 3, reduced AQP4-M1/M23 ratio, and increased miR-130a expression in the cerebral cortex of APP/PS1 mice. In vitro, ?-hydroxybutyrate was found to down-regulate the expression of AQP4-M1 and histone deacetylase 3, reduce AQP4-M1/M23 ratio, and increase AQP4-M23 and miR-130a expression in 2 ?M A?-treated U251 cells. Interestingly, on the contrary to the result observed in 2 ?M A?-treated cells, AQP4 expression was obviously decreased in cells exposed to 10 ?M A?. miR-130a mimic decreased the expression of AQP4-M1 and the ratio of AQP4-M1/M23, as well as silencing histone deacetylase 3 caused the up-regulation of AQP4 and miR-130a, and the reduction of AQP4-M1/M23 ratio in U251 cells. In conclusion, IF exhibits beneficial effects against AD. The mechanism may be associated with recovery of AQP4 polarity, resulting from the reduction of AQP4-M1/M23 ratio. Furthermore, ?-hydroxybutyrate may partly mediate the effect of IF on the reduction of AQP4-M1/M23 ratio in AD, in which miR-130a and histone deacetylase 3 may be implicated.

Project description:This retrospective analysis of longitudinal data was developed to determine which types, combinations, and intensities of topical fluorides more effectively prevent new caries-related restorations and extractions in high caries risk adults. We included data from October 1, 2008, through June 30, 2018, from electronic dental and medical records and pharmacy database from the US Department of Veterans Affairs. Veterans who were eligible for continuing and comprehensive care, met the criteria of high caries risk (received 2 or more caries-related restorations within a 365-d period), and had 3 y of follow-up were included. Multivariable logistic regression models estimated the odds of caries-related treatment during the 1-y observation period, controlling for age, gender, race and ethnicity, illness burden (Selim comorbidity index), use of prescription medications, attendance at dental prophylaxis appointments, number of caries-related restorations during the index year, and time between first and last caries-related restoration during the index year. The study sample included 68,757 veterans, who were primarily male (91.5%), were White (73.6%), had a mean age of 59.2 ± 13.5 y, and had significant medical comorbidity as measured by the Selim index (3.7 ± 2.4 physical and 1.3 ± 1.2 mental diagnoses). They had 10.8 ± 6.3 prescription VA drug classes, took 0.6 ± 0.8 strong anticholinergic medications, and had 3.9 ± 2.6 teeth restored due to caries during the index year. Adjusted multivariable logistic regression models showed veterans who received a varnish or gel/rinse fluoride intervention versus no fluoride had an approximately 29% decreased odds of receiving caries-related treatment during the observation period (gel/rinse adjusted odds ratio [AOR] = 0.72; 95% confidence interval [CI], 0.67-0.76; varnish AOR = 0.71; 95% CI, 0.67-0.75). The receipt of a varnish and gel/rinse did not demonstrate statistically better odds than each intervention alone (AOR = 0.69; 95% CI, 0.64-0.75). A dose-response effect was observed. Two-plus applications of varnish versus none (AOR = 0.73; 95% CI, 0.69-0.77) and 2-plus applications of gel/rinse versus none (AOR = 0.71; 95% CI, 0.67-0.75) were more effective than 1 application of either modality versus none.

Dataset Information

Aquaporin 5 Interacts with Fluoride and Possibly Protects against Caries.

Publications

Aquaporin 5 Interacts with Fluoride and Possibly Protects against Caries.

Similar Datasets

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