Metabolic effect of low levels of fluoride in the islets of NOD mice

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Metabolic effect of low levels of fluoride in the islets of NOD mice
Trevizol, Juliana Sanches; Dionizio, Aline; Delgado, Aislan Quintiliano; Ventura, Talita Mendes Oliveira; Ribeiro, Caroline Fernanda da Silva; Ribeiro, Laura; Buzalaf, Nathalia Rabelo; Cestari, Tânia Mary; Magalhães, Ana Carolina; Suzuki, Maiko; Bosqueiro, José Roberto; Buzalaf, Marília Afonso Rabelo, 2023, "Metabolic effect of low levels of fluoride in the islets of NOD mice", https://doi.org/10.48331/scielodata.3XXS60, SciELO Data, V1
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Description
Introduction: Fluoride (F) has been largely employed for the control of dental caries, in addition to studies suggesting beneficial effects against diabetes when a low dose of F is added in the drinking water (10 mgF/L). Objectives: This study evaluated metabolic changes in the pancreatic islets of NOD mice exposed to low dose of F and the main pathways altered by the treatment. Methodology: Forty-two female NOD mice were randomly divided into two groups, taking into account the F concentration administered in the drinking water for 14 weeks: 0 or 10 mgF/L. After the experimental period, the pancreas was collected for morphological and immunohistochemical analysis, and the islets for proteomic analysis. Results: In the morphological and immunohistochemical analysis, no significant differences were found in the percentage of cells labelled for insulin, glucagon and acetylated histone H3, despite the treated group had higher percentages than the control. In addition, no significant differences were found for the average percentages of pancreatic areas occupied by islets and the pancreatic inflammatory infiltrate between the control and treated groups. For proteomic analysis we found great increases in histones H3 and, to a lesser extent, in histone acetyltransferases, concomitant with a decrease in enzymes involved in the formation of acetyl-CoA, besides many changes in proteins involved in several metabolic pathways, especially energy metabolism. The conjunction analysis of these data indicates an attempt of the organism to maintain protein synthesis in the islets, even upon the dramatic changes in energy metabolism. Conclusion: Our data suggests epigenetic alterations in the islets of NOD mice exposed to F levels comparable to those found in the water from the public supply consumed by humans. (2023-10-05)
Subject Chemistry; Medicine, Health and Life Sciences
Keyword Proteomics, Islets of Langerhans, Diabetes Mellitus, Experimental, Fluorides, Mice, Inbred NOD
Related Publication Trevizol JS, Dionizio A, Delgado AQ, Ventura TM, Ribeiro CF, Ribeiro L, et al. Metabolic effect of low levels of fluoride in the islets of NOD mice: integrative morphological, immunohistochemical and proteomic analyses . J Appl Oral Sci. 2023;31:e20230036. doi: 10.1590/1678-7757-2023-0036 doi: 10.1590/1678-7757-2023-0036
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Average percentage: (A) area occupied by islets; (B) inflammatory cell infiltrate; (C) Histone H3 acetylation (acH3K14)-labeling; (D) insulin-labeling and (E) glucagon-labeling in the pancreas of female NOD mice treated with water containing 10 mgF/L or not (control) for 20 weeks. Bars indicate SD. The differences between the groups were not significant (unpaired t tests, p>0.05). n=12, except for acH3K14 (n=5).
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Sections of pancreas from 20-week-old female NOD mice treated with deionized water (control) (A, B, C and D) or with water containing 10 mgF/L (as NaF) for 14 weeks (E, F, G and H). A and E images show H&E staining, with presence of islets inflammatory infiltrate. B, C, F and G images show samples stained (in brown) for insulin (B and F) and glucagon (C and G) and counterstained by hematoxylin. D and H are images of acH3K14 marked on the pancreas. Images were generated at higher resolution 20x; only D and H images were generated at 40x, using Image Scopus software.
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Functional distribution of proteins identified with differential expression in the islets of female NOD mice treated with 10 mgF/L vs. Control Group (0 mgF/L). Categories of proteins based on GO annotation “Biological Process”. Terms significant (Kappa=0.04) and distribution according to the percentage of number of genes. Proteins access number was provided by UNIPROT. Gene ontology was evaluated according to ClueGo® pluggins of Cytoscape® software 3.8.0.24,25
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Subnetwork generated by ClusterMarker® for the comparison 10 mgF/L vs. control (0 mgF/L). The color of the node indicates the differential expression of the protein with its access code, obtained from UniProt protein database (http://www.uniprot.org/). Dark green and dark red nodes represent proteins exclusively identified in 10 mgF/L and control groups, respectively. Light red and light green nodes indicate down and upregulated proteins, respectively, in 10 mgF/L group in respect to control. Gray nodes represent interaction proteins that are offered by CYTOSCAPE®, which were not identified in the present study.
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Analysis in StringApp® application (CYTOSCAPE® 3.9.0 Software) containing 138 proteins found in the 10 mgF/L vs. control (0 mgF/L) group related to different metabolic pathways. The internal stains of the light green and light pink nodes indicate up-regulated and down-regulated proteins, and dark green and dark red nodes indicate proteins exclusive to the 10 mgF/L and control group, respectively. Around the nodes are the colors indicated in the table showing which Gene Ontology, pathways KEEG or Reactome are altered. The value of FDR (False Discovery Rate) means the statistical analysis used, p < 0.05.
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Protein-protein interaction network of histones and histone acetyltransferases. STRING database, version 11.0 (https://string-db.org/). The following proteins are present in the network: was identified network of evidence of histones: Histo1h2ak (Q8CGP7)- Histone H2A type 1-K, Hist1h2ah (Q8CGP6)- Histone H2A type 1-H, Hist1h2af (Q8CGP5)- Histone H2A type 1-F, Hist2h2ac (Q64523)- Histone H2A type 2-C, Hist1h4j (P62806)- Histone H4, Hist1h2ag (C0HKE1)- Histone H2A type 1-B, Hist1h3g (P68433)- Histone H3.1 , Hist2h3c2 (P84228)- Histone H3.2, Hist2h2aa1 (Q6GSS7)- Histone H2A type 2-A, Hist3h2a (Q8BFU2)- Histone H2A type 3, H2afj (Q8R1M2)- Histone H2A.J, Kat6b (Q8BRB7)- Histone acetyltransferase KAT6B, and H3f3a (P84244)- Histone H3.3.
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README.txt
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Supplementary_Table_1
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Proteins expressed differentially or exclusively in the islets of non-obese
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