title: Signaling mechanisms and disrupted cytoskeleton in the diphenyl ditelluride neurotoxicity.
abstract: Evidence from our group supports that diphenyl ditelluride (PhTe)2 neurotoxicity depends on modulation of signaling pathways initiated at the plasma membrane. The (PhTe)2-evoked signal is transduced downstream of voltage-dependent Ca(2+) channels (VDCC), N-methyl-D-aspartate receptors (NMDA), or metabotropic glutamate receptors activation via different kinase pathways (protein kinase A, phospholipase C/protein kinase C, mitogen-activated protein kinases (MAPKs), and Akt signaling pathway). Among the most relevant cues of misregulated signaling mechanisms evoked by (PhTe)2 is the cytoskeleton of neural cells. The in vivo and in vitro exposure to (PhTe)2 induce hyperphosphorylation/hypophosphorylation of neuronal and glial intermediate filament (IF) proteins (neurofilaments and glial fibrillary acidic protein, resp.) in different brain structures of young rats. Phosphorylation of IFs at specific sites modulates their association/disassociation and interferes with important physiological roles, such as axonal transport. Disrupted cytoskeleton is a crucial marker of neurodegeneration and is associated with reactive astrogliosis and apoptotic cell death. This review focuses the current knowledge and important results on the mechanisms of (PhTe)2 neurotoxicity with special emphasis on the cytoskeletal proteins and their differential regulation by kinases/phosphatases and Ca(2+)-mediated mechanisms in developmental rat brain. We propose that the disrupted cytoskeletal homeostasis could support brain damage provoked by this neurotoxicant.
authors: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, 90035-003 Porto Alegre, RS, Brazil.
authors: Regina
authors: R
authors: Pessoa-Pureur
authors: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, 90035-003 Porto Alegre, RS, Brazil.
authors: Luana
authors: L
authors: Heimfarth
authors: Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
authors: João B
authors: JB
authors: Rocha
mesh_terms: D000818:Animals; D001555:Benzene Derivatives / Q000633:toxicity*; D003599:Cytoskeleton / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D007382:Intermediate Filaments / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D009942:Organometallic Compounds / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D001555:Benzene Derivatives; D009498:Neurotoxins; D009942:Organometallic Compounds; C434247:diphenylditelluride