title: Astrocyte-neuron interaction in diphenyl ditelluride toxicity directed to the cytoskeleton.
abstract: Diphenylditelluride (PhTe)2is a neurotoxin that disrupts cytoskeletal homeostasis. We are showing that different concentrations of (PhTe)2caused hypophosphorylation of glial fibrillary acidic protein (GFAP), vimentin and neurofilament subunits (NFL, NFM and NFH) and altered actin organization in co-cultured astrocytes and neurons from cerebral cortex of rats. These mechanisms were mediated by N-methyl-d-aspartate (NMDA) receptors without participation of either L-type voltage-dependent calcium channels (L-VDCC) or metabotropic glutamate receptors. Upregulated Ca2+influx downstream of NMDA receptors activated Ca2+-dependent protein phosphatase 2B (PP2B) causing hypophosphorylation of astrocyte and neuron IFs. Immunocytochemistry showed that hypophosphorylated intermediate filaments (IF) failed to disrupt their organization into the cytoskeleton. However, phalloidin-actin-FITC stained cytoskeleton evidenced misregulation of actin distribution, cell spreading and increased stress fibers in astrocytes. βIII tubulin staining showed that neurite meshworks are not altered by (PhTe)2, suggesting greater susceptibility of astrocytes than neurons to (PheTe)2toxicity. These findings indicate that signals leading to IF hypophosphorylation fail to disrupt the cytoskeletal IF meshwork of interacting astrocytes and neurons in vitro however astrocyte actin network seems more susceptible. Our findings support that intracellular Ca2+is one of the crucial signals that modulate the action of (PhTe)2in co-cultured astrocytes and neurons and highlights the cytoskeleton as an end-point of the neurotoxicity of this compound. Cytoskeletal misregulation is associated with cell dysfunction, therefore, the understanding of the molecular mechanisms mediating the neurotoxicity of this compound is a matter of increasing interest since tellurium compounds are increasingly released in the environment.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: Luana
authors.initials: L
authors.lastname: Heimfarth
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: da Silva Ferreira
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: Paula
authors.initials: P
authors.lastname: Pierozan
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: Moara Rodrigues
authors.initials: MR
authors.lastname: Mingori
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: José Cláudio Fonseca
authors.initials: JC
authors.lastname: Moreira
authors.affiliation: Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: João Batista Teixeira
authors.initials: JB
authors.lastname: da Rocha
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil. Electronic address: rpureur@ufrgs.br.
authors.forename: Regina
authors.initials: R
authors.lastname: Pessoa-Pureur
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D001555:Benzene Derivatives / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication; D018920:Coculture Techniques; D003599:Cytoskeleton / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009942:Organometallic Compounds / Q000633:toxicity*; D010766:Phosphorylation; D051381:Rats
chemical_list: D001555:Benzene Derivatives; D009942:Organometallic Compounds; C434247:diphenylditelluride; D002118:Calcium
keywords: Astrocyte; Cell signaling; Cytoskeleton; Diphenyl ditelluride; Neuron; Neurotoxicity