Unraveling molecular characteristic of fluoride neurotoxicity on U87 glial-like cells: insights from transcriptomic and proteomic approach

Autor: Bruna Puty, Leonardo Oliveira Bittencourt, Leidiane Alencar Oliveira Lima, Jéssica Rodrigues Plaça, Aline Dionizio, Marília Afonso Rabelo Buzalaf, Bruno Duarte Gomes, Edivaldo Herculano Correa de Oliveira, Rafael Rodrigues Lima
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Frontiers in Cellular Neuroscience, Vol 17 (2023)
Druh dokumentu: article
ISSN: 1662-5102
DOI: 10.3389/fncel.2023.1153198
Popis: The potential of fluoride (F) as a neurotoxicant in humans is still controversial in the literature. However, recent studies have raised the debate by showing different mechanism of F-induced neurotoxicity, as oxidative stress, energy metabolism and inflammation in the central nervous system (CNS). In the present study, we investigated the mechanistic action of two F concentration (0.095 and 0.22 μg/ml) on gene and protein profile network using a human glial cell in vitro model over 10 days of exposure. A total of 823 genes and 2,084 genes were modulated after exposure to 0.095 and 0.22 μg/ml F, respectively. Among them, 168 were found to be modulated by both concentrations. The number of changes in protein expression induced by F were 20 and 10, respectively. Gene ontology annotations showed that the main terms were related to cellular metabolism, protein modification and cell death regulation pathways, such as the MAP kinase (MAPK) cascade, in a concentration independent manner. Proteomics confirmed the changes in energy metabolism and also provided evidence of F-induced changes in cytoskeleton components of glial cells. Our results not only reveal that F has the potential to modulate gene and protein profiles in human U87 glial-like cells overexposed to F, but also identify a possible role of this ion in cytoskeleton disorganization.
Databáze: Directory of Open Access Journals