Cross-talk among intracellular signaling pathways mediates the diphenyl ditelluride actions on the hippocampal cytoskeleton of young rats
| Autor: | Luana Heimfarth, Samanta Oliveira Loureiro, Bárbara Ortiz de Lima, Talita Gandolfi, João Rocha, Karina Pires Reis, Regina Pessoa-Pureur, Rodrigo Narvaes, Fernanda Zamboni |
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| Rok vydání: | 2011 |
| Předmět: |
Benzylamines
Calcium Channels L-Type MAP Kinase Signaling System Blotting Western Hyperphosphorylation Biology In Vitro Techniques Toxicology Hippocampus chemistry.chemical_compound Neurofilament Proteins Glial Fibrillary Acidic Protein Benzene Derivatives Organometallic Compounds Animals Vimentin Phosphorylation Rats Wistar Protein kinase A Protein kinase C Cytoskeleton Protein Kinase C Diacylglycerol kinase Cerebral Cortex Sulfonamides Phospholipase C Diphenyl ditelluride General Medicine Staurosporine Molecular biology Rats Metabotropic receptor chemistry Metabotropic glutamate receptor Calcium Electrophoresis Polyacrylamide Gel Mitogen-Activated Protein Kinases |
| Zdroj: | Chemical research in toxicology. 24(10) |
| ISSN: | 1520-5010 |
| Popis: | In the present report, we showed that diphenyl ditelluride (PhTe)(2) induced in vitro hyperphosphorylation of glial fibrillary acidic protein (GFAP), vimentin and neurofilament (NF) subunits in hippocampus of 21 day-old rats. Hyperphosphorylation was dependent on L-voltage dependent Ca(2+) channels (L-VDCC), N-methyl-d-aspartate (NMDA) and metabotropic glutamate receptors, as demonstrated by the specific inhibitors verapamil, DL-AP5 and MCPG, respectively. Also, dantrolene, a ryanodine channel blocker, EGTA and Bapta-AM, extra and intracellular Ca(2+) chelators respectively, totally prevented this effect. Activation of metabotropic glutamate receptors by (PhTe)(2) upregulates phospholipase C (PLC), producing inositol 1, 4, 5-trisphosphate (IP(3)) and diacylglycerol (DAG). Therefore, high Ca(2+) levels and DAG directly activate Ca(2+)/calmodulin-dependent protein kinase (PKCaMII) and protein kinase C (PCK), resulting in the hyperphosphorylation of Ser-57 in the carboxyl-terminal tail domain of the low molecular weight NF subunit (NF-L). Also, the activation of Erk1/2, and p38MAPK resulted in hyperphosphorylation of KSP repeats of the medium molecular weight NF subunit (NF-M). It is noteworthy that PKCaMII and PKC inhibitors prevented (PhTe)(2)-induced Erk1/2MAPK and p38MAPK activation as well as hyperphosphorylation of KSP repeats on NF-M, suggesting that PKCaMII and PKC could be upstream of this activation. Taken together, our results highlight the role of Ca(2+) as a mediator of the (PhTe)(2)-elicited signaling targeting specific phosphorylation sites on IF proteins of neural cells of rat hippocampus. Interestingly, this action shows a significant cross-talk among signaling pathways elicited by (PhTe)(2), connecting glutamate metabotropic cascade with activation of Ca(2+) channels. The extensively phosphorylated amino- and carboxyl- terminal sites could explain, at least in part, the neural dysfunction associated with (PhTe)(2) exposure. |
| Databáze: | OpenAIRE |
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