title: Proteomic analysis of gastrocnemius muscle in rats with streptozotocin-induced diabetes and chronically exposed to fluoride.
abstract: Administration of high doses of fluoride (F) can alter glucose homeostasis and lead to insulin resistance (IR). This study determined the profile of protein expression in the gastrocnemius muscle of rats with streptozotocin-induced diabetes that were chronically exposed to F. Male Wistar rats (60 days old) were randomly distributed into two groups of 18 animals. In one group, diabetes was induced through the administration of streptozotocin. Each group (D-diabetic and ND-non-diabetic) was further divided into 3 subgroups each of which was exposed to a different F concentration via drinking water (0 ppm, 10 ppm or 50 ppm F, as NaF). After 22 days of treatment, the gastrocnemius muscle was collected and submitted to proteomic analysis (2D-PAGE followed by LC-MS/MS). Protein functions were classified by the GO biological process (ClueGO v2.0.7+Clupedia v1.0.8) and protein-protein interaction networks were constructed (PSICQUIC, Cytoscape). Quantitative intensity analysis of the proteomic data revealed differential expression of 75 spots for ND0 vs. D0, 76 for ND10 vs.D10, 58 spots for ND50 vs. D50, 52 spots for D0 vs. D10 and 38 spots for D0 vs. D50. The GO annotations with the most significant terms in the comparisons of ND0 vs. D0, ND10 vs. D10, ND50 vs. D50, D0 vs. D10 and D0 vs. D50, were muscle contraction, carbohydrate catabolic processes, generation of precursor metabolites and energy, NAD metabolic processes and gluconeogenesis, respectively. Analysis of subnetworks revealed that, in all comparisons, proteins with fold changes interacted with GLUT4. GLUT4 interacting proteins, such as MDH and the stress proteins HSPB8 and GRP78, exhibited decreased expression when D animals were exposed to F. The presence of the two stress proteins indicates an increase in IR, which might worsen diabetes. Future studies should evaluate whether diabetic animals treated with F have increased IR, as well as which molecular mechanisms are involved.
authors.affiliation: Department of Biological Sciences, Bauru Dental School, University of São Paulo, Bauru, São Paulo, Brazil; Department of Genetics and Evolution, Center of Biological Sciences and the Health, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Lima Leite
authors.affiliation: Department of Biological Sciences, Bauru Dental School, University of São Paulo, Bauru, São Paulo, Brazil.
authors.forename: Janete
authors.initials: J
authors.lastname: Gualiume Vaz Madureira Lobo
authors.affiliation: Department of Genetics and Evolution, Center of Biological Sciences and the Health, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: Heloísa Aparecida
authors.initials: HA
authors.lastname: Barbosa da Silva Pereira
authors.affiliation: Department of Genetics and Evolution, Center of Biological Sciences and the Health, Federal University of São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: Mileni
authors.initials: M
authors.lastname: Silva Fernandes
authors.affiliation: Department of Biological Sciences, Bauru Dental School, University of São Paulo, Bauru, São Paulo, Brazil.
authors.forename: Tatiani
authors.initials: T
authors.lastname: Martini
authors.affiliation: Department of Biological Sciences, Bauru Dental School, University of São Paulo, Bauru, São Paulo, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Zucki
authors.affiliation: Department of Basic Sciences, Araçatuba Dental School, UNESP - Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil.
authors.forename: Dóris Hissako
authors.initials: DH
authors.lastname: Sumida
authors.affiliation: Bone Biology and Mineral Metabolism Laboratory, National Scientific and Technical Research Council (CONICET) School of Medicine, Rosario National University, Rosario, Santa Fe, Argentina.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Rigalli
authors.affiliation: Department of Biological Sciences, Bauru Dental School, University of São Paulo, Bauru, São Paulo, Brazil.
authors.forename: Marília Afonso Rabelo
authors.initials: MA
authors.lastname: Buzalaf
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D060766:Drinking Water / Q000737:chemistry; D005459:Fluorides / Q000494:pharmacology*; D063990:Gene Ontology; D008297:Male; D058977:Molecular Sequence Annotation; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D060066:Protein Interaction Maps / Q000187:drug effects; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D060766:Drinking Water; D005459:Fluorides