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

Frontiers in Cellular Neuroscience

Neuroscience

Aline Dionizio¹  Marília Afonso Rabelo Buzalaf¹  Edivaldo Herculano Correa de Oliveira²  Leidiane Alencar Oliveira Lima³  Rafael Rodrigues Lima³  Leonardo Oliveira Bittencourt³  Bruna Puty⁴  Bruno Duarte Gomes⁵  Jéssica Rodrigues Plaça⁶ 

[1]Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil

[2]Laboratory of Cell Culture and Cytogenetics, Environmental Section, Evandro Chagas Institute, Ananindeua, Brazil

[3]Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil

[4]Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil

[5]Laboratory of Cell Culture and Cytogenetics, Environmental Section, Evandro Chagas Institute, Ananindeua, Brazil

[6]Laboratory of Neurophysiology Eduardo Oswaldo Cruz, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil

[7]National Institute of Science and Technology in Stem Cell and Cell Therapy (INCT/CNPq) and Center for Cell-Based Therapy, Centro de Pesquisa, Inovacão e Desenvolvimento/Fundacão de Amparo á Pesuisa do Estado de São Paulo (CEPID/FAPESP), Ribeirão Preto, Brazil

关键词: neurotoxicity;    fluoride;    proteomic;    transcriptomic;    glia;   

DOI  :  10.3389/fncel.2023.1153198

 received in 2023-01-29, accepted in 2023-05-19,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Puty, Bittencourt, Lima, Plaça, Dionizio, Buzalaf, Gomes, de Oliveira and Lima.