The effect of fluoride on the structure, function, and proteome of a renal epithelial cell monolayer

The effect of fluoride on the structure, function, and proteome of a renal epithelial cell monolayer

ABSTRACT High concentrations of fluoride in the body may cause toxic effects. Here, we investigated the effects of fluoride on the structure, function, and proteome of a cortical collecting duct epithelium in vitro. Kidney tubule cells (M‐1) were chosen because the concentration of fluoride in the k...

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Published in:Environmental toxicology Vol. 32; no. 4; pp. 1455 - 1467
Main Authors: Antonio, Ligia S., Jeggle, Pia, MacVinish, Lesley J., Bartram, James C., Miller, Henry, Jarvis, Gavin E., Levy, Flávia M., Santesso, Mariana R., Leite, Aline L., Oliveira, Rodrigo C., Buzalaf, Marília A. R., Edwardson, J. Michael
Format: Journal Article
Language:English
Published: United States Wiley Subscription Services, Inc 01-04-2017
Subjects:
Animals
atomic force microscopy
Cariostatic Agents - toxicity
cell stiffness
Cells, Cultured
Epithelial Cells - drug effects
Epithelial Cells - metabolism
epithelial ion transport
fluoride
Ion Transport - drug effects
kidney
Kidney Tubules - cytology
Membrane Potentials
Mice
Protein Interaction Maps
Proteome - metabolism
Proteomics
Sodium Fluoride - toxicity
kidney
fluoride
cell stiffness
proteomics
atomic force microscopy
epithelial ion transport
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Summary:ABSTRACT High concentrations of fluoride in the body may cause toxic effects. Here, we investigated the effects of fluoride on the structure, function, and proteome of a cortical collecting duct epithelium in vitro. Kidney tubule cells (M‐1) were chosen because the concentration of fluoride in the kidney is 4–5‐fold higher than that in plasma. Mouse M‐1 cell monolayers were incubated in fluoride‐containing media, and the amiloride‐sensitive short‐circuit current and transepithelial resistance were measured. The Young's modulus of the epithelium was determined using atomic force microscopy, and the effect of fluoride on epithelial structure was assessed using scanning and transmission electron microscopy, and immunofluorescence. Differences in the expression of membrane proteins were evaluated using proteomics and bioinformatics. Fluoride exposure reduced both transepithelial Na+ transport and resistance. The IC50 for fluoride was ∼300 µM for both effects, and the half‐times for the decays of ion transport and resistance were 8.4 h and 3.6 days, respectively. Fluoride treatment did not affect the sensitivity of Na+ transport to amiloride. The Young's modulus of the epithelium was also unaffected by fluoride; however, the functional effects of fluoride were accompanied by marked structural effects. Proteomic analysis revealed changes in expression of a number of proteins, and particularly mitochondrial proteins. Treatment with fluoride had profound effects on the structure, function and proteome of a model cortical collecting duct epithelium. Significantly, however, these effects were produced only at concentrations considerably higher than those likely to be encountered in vivo. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1455–1467, 2017.
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ISSN:1520-4081
1522-7278
DOI:10.1002/tox.22338