Abstract
A/J and 129P3/J mouse strains have different susceptibilities to dental fluorosis due to their genetic backgrounds. They also differ with respect to several features of fluoride (F) metabolism and metabolic handling of water. This study was done to determine whether differences in F metabolism could be explained by diversities in the profile of protein expression in kidneys. Weanling, male A/J mice (susceptible to dental fluorosis, n = 18) and 129P3/J mice (resistant, n = 18) were housed in pairs and assigned to three groups given low-F food and drinking water containing 0, 10 or 50 ppm [F] for 7 weeks. Renal proteome profiles were examined using 2D-PAGE and LC-MS/MS. Quantitative intensity analysis detected between A/J and 129P3/J strains 122, 126 and 134 spots differentially expressed in the groups receiving 0, 10 and 50 ppmF, respectively. From these, 25, 30 and 32, respectively, were successfully identified. Most of the proteins were related to metabolic and cellular processes, followed by response to stimuli, development and regulation of cellular processes. In F-treated groups, PDZK-1, a protein involved in the regulation of renal tubular reabsorption capacity was down-modulated in the kidney of 129P3/J mice. A/J and 129P3/J mice exhibited 11 and 3 exclusive proteins, respectively, regardless of F exposure. In conclusion, proteomic analysis was able to identify proteins potentially involved in metabolic handling of F and water that are differentially expressed or even not expressed in the strains evaluated. This can contribute to understanding the molecular mechanisms underlying genetic susceptibility to dental fluorosis, by indicating key-proteins that should be better addressed in future studies.
Highlights
The widespread use of F has contributed to the caries decline, but excessive intake may affect both bone metabolism and enamel development, causing skeletal and dental fluorosis, respectively
Most of the 14 proteins up-modulated in the kidney of 129P3/J mice are related with metabolism (57.2%), while 28.6% are involved in cell processes and the remainder in information pathways (7.1%) and transport (7.1%)
We identified proteins potentially involved in renal F metabolism that are either exclusively or differentially expressed in A/J and 129P3/J mice
Summary
The widespread use of F has contributed to the caries decline, but excessive intake may affect both bone metabolism and enamel development, causing skeletal and dental fluorosis, respectively. In the US, 23% of 6- to 39-yr-old subjects present enamel fluorosis, ranging from very low to relatively high in severity [3]. The A/J strain is ‘‘susceptible’’, with a rapid onset and severe development of DF, while the 129P3/J is ‘‘resistant’’, with minimum development of DF [7]. These strains differ regarding their susceptibilities to the effects of F in bone [8,9]
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