title: Calcium signaling mechanisms disrupt the cytoskeleton of primary astrocytes and neurons exposed to diphenylditelluride.
abstract: Diphenylditelluride (PhTe)2 is a potent neurotoxin disrupting the homeostasis of the cytoskeleton.
  
  
  
  Cultured astrocytes and neurons were incubated with (PhTe)2, receptor antagonists and enzyme inhibitors followed by measurement of the incorporation of [32P]orthophosphate into intermediate filaments (IFs).
  
  
  
  (PhTe)2 caused hyperphosphorylation of glial fibrillary acidic protein (GFAP), vimentin and neurofilament subunits (NFL, NFM and NFH) from primary astrocytes and neurons, respectively. These mechanisms were mediated by N-methyl-d-aspartate (NMDA) receptors, L-type voltage-dependent calcium channels (L-VDCCs) as well as metabotropic glutamate receptors upstream of phospholipase C (PLC). Upregulated Ca(2+) influx activated protein kinase A (PKA) and protein kinase C (PKC) in astrocytes causing hyperphosphorylation of GFAP and vimentin. Hyperphosphorylated (IF) together with RhoA-activated stress fiber formation, disrupted the cytoskeleton leading to altered cell morphology. In neurons, the high intracellular Ca(2+) levels activated the MAPKs, Erk and p38MAPK, beyond PKA and PKC, provoking hyperphosphorylation of NFM, NFH and NFL.
  
  
  
  Our findings support that intracellular Ca(2+) is one of the crucial signals that modulate the action of (PhTe)2 in isolated cortical astrocytes and neurons modulating the response of the cytoskeleton against the insult.
  
  
  
  Cytoskeletal misregulation is associated with neurodegeneration. This compound could be a valuable tool to induce molecular changes similar to those found in different pathologies of the brain.
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: Samanta Oliveira
authors.initials: SO
authors.lastname: Loureiro
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: JCF
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: JBT
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: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001555:Benzene Derivatives / Q000494:pharmacology* / Q000633:toxicity; D020013:Calcium Signaling; D002478:Cells, Cultured; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001555:Benzene Derivatives; D009942:Organometallic Compounds; C434247:diphenylditelluride
keywords: Astrocyte; Calcium; Cell signaling; Cytoskeleton; Diphenylditelluride; Neuron