title: Fluoride exposure regulates the elongation phase of protein synthesis in cultured Bergmann glia cells.
abstract: Fluoride is an environmental pollutant present in dental products, food, pesticides and water. The latter, is the greatest source of exposure to this contaminant. Structural and functional damages to the central nervous system are present in exposed population. An established consequence of the neuronal is the release of a substantial amount of glutamate to the extracellular space, leading to an excitotoxic insult. Glutamate exerts its actions through the activation of specific plasma membrane receptors and transporters present in neurons and in glia cells and it is the over-activation of glutamate receptors and transporters, the biochemical hallmark of neuronal and oligodendrocyte cell death. In this context, taking into consideration that fluoride leads to degeneration of cerebellar cells, we took the advantage of the well-established model of cerebellar Bergmann glia cultures to gain insight into the molecular mechanisms inherent to fluoride neurotoxicity that might be triggered in glia cells. We could establish that fluoride decreases [(35)S]-methionine incorporation into newly synthesized polypeptides, in a time-dependent manner, and that this halt in protein synthesis is the result of a decrease in the elongation phase of translation, mediated by an augmentation of eukaryotic elongation factor 2 phosphorylation. These results favor the notion of glial cells as targets of fluoride toxicity and strengthen the idea of a critical involvement of glia cells in the function and dysfunction of the brain.
authors: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, México D.F. 07300, Mexico. Electronic address: maflores@cinvestav.mx.
authors: Marco
authors: M
authors: Flores-Méndez
authors: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, México D.F. 07300, Mexico.
authors: Diana
authors: D
authors: Ramírez
authors: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, México D.F. 07300, Mexico. Electronic address: aalmilloi@cinvestav.mx.
authors: Nely
authors: N
authors: Alamillo
authors: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, México D.F. 07300, Mexico. Electronic address: lcr@cinvestav.mx.
authors: Luisa C
authors: LC
authors: Hernández-Kelly
authors: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, México D.F. 07300, Mexico. Electronic address: ldelrazo@cinvestav.mx.
authors: Luz María
authors: LM
authors: Del Razo
authors: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, México D.F. 07300, Mexico. Electronic address: arortega@cinvestav.mx.
authors: Arturo
authors: A
authors: Ortega
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002531:Cerebellum / Q000166:cytology; D002642:Chick Embryo; D004591:Electrophoresis, Polyacrylamide Gel; D005459:Fluorides / Q000633:toxicity*; D005973:Glutamine / Q000378:metabolism; D007202:Indicators and Reagents; D008715:Methionine / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D020652:Peptide Elongation Factor 2 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects*; D061805:Transcription Elongation, Genetic / Q000187:drug effects*
chemical_list: D007202:Indicators and Reagents; D020652:Peptide Elongation Factor 2; D005973:Glutamine; D001224:Aspartic Acid; D008715:Methionine; D005459:Fluorides
keywords: Bergmann glia; Fluoride toxicity; Translational control