Cross-Talk among Intracellular Signaling Pathways Mediates the Diphenyl Ditelluride Actions on the Hippocampal Cytoskeleton of Young Rats

Heimfarth, Luana; Loureiro, Samanta Oliveira; Reis, Karina Pires; Lima, Bárbara Ortiz de; Zamboni, Fernanda; Gandolfi, Talita; Narvaes, Rodrigo; Rocha, João Batista Teixeira da; Pessoa-Pureur, Regina

doi:10.1021/tx200307u

Cited by 15 publications

(9 citation statements)

References 87 publications

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“…Interestingly, PKCaMII and PKC are upstream of MAPK activation implying in a significant cross-talk among signaling pathways elicited by (PhTe) 2 that connect the glutamate metabotropic cascade with the activation of Ca 2+ channels. The final molecular result is the extensive phosphorylation of amino-and carboxyl-terminal sites on IF proteins and deregulated cytoskeletal homeostasis [19].…”

Section: +mentioning

confidence: 99%

Intermediate Filaments as a Target of Signaling Mechanisms in Neurotoxicity

Zamoner¹,

Pessoa-Pureur²

2017

Cytoskeleton - Structure, Dynamics, Function and Disease

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In this chapter, we deal with the current knowledge and important results on the cytoskeletal proteins and their differential regulation by kinases/phosphatases and Ca 2+mediated mechanisms in developmental rat brain. We focus on the misregulation of the phosphorylating system associated with intermediate filament proteins of neural cells and its relevance to cell and tissue dysfunction. Taking into account our findings, we propose that intermediate-filament proteins are dynamic structures whose regulation is crucial for proper neural cell function. Given their relevance, they must be regulated in response to extracellular and intracellular signals. The complexity and connection between signaling pathways regulating intermediate-filament dynamics remain obscure. In this chapter, we get light into some kinase/phosphatase cascades downstream of membrane receptors disrupting the dynamics of intermediate filaments and its association with neural dysfunction. However, intermediate filaments do not act individually into the neural cells. Our results evidence the importance of misregulated cytoskeletal crosstalk in disrupting cytoskeletal dynamics and cell morphology underlying neural dysfunction in experimental conditions mimicking metabolic diseases and nongenomic actions of thyroid hormones and as an end point in the neurotoxicity of organic tellurium.

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Section: +mentioning

confidence: 99%

Intermediate Filaments as a Target of Signaling Mechanisms in Neurotoxicity

Zamoner¹,

Pessoa-Pureur²

2017

Cytoskeleton - Structure, Dynamics, Function and Disease

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“…Hyperphosphorylation is partially dependent on L-VDCC, NMDA, and endoplasmic reticulum Ca 2+ channels. The role of Ca 2+ as an upstream signal of this effect was demonstrated by specific NMDA antagonists and Ca 2+ channel blockers as well as extra- and intracellular Ca 2+ buffering, which totally prevented IF hyperphosphorylation [181] (Figure 5). …”

Section: Central Roles Of Ca2+ and Glutamate Receptors Mediating Tmentioning

confidence: 99%

“…It is noteworthy that PKCaMII and PKC inhibitors (KN-93 and staurosporine, resp.) 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 [181]. Interestingly, this effect implies a significant cross-talk among signaling pathways elicited by (PhTe) 2 , connecting the glutamate metabotropic cascade with activation of Ca 2+ channels.…”

Section: Central Roles Of Ca2+ and Glutamate Receptors Mediating Tmentioning

confidence: 99%

Signaling Mechanisms and Disrupted Cytoskeleton in the Diphenyl Ditelluride Neurotoxicity

Pessoa-Pureur

Heimfarth

Rocha

2014

Oxidative Medicine and Cellular Longevity

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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 Ca2+ 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 Ca2+-mediated mechanisms in developmental rat brain. We propose that the disrupted cytoskeletal homeostasis could support brain damage provoked by this neurotoxicant.

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“…The nanoenzyme showed higher efficiency and provided a platform for the synthesis and designing of polymeric nanoparticles as excellent model of enzyme mimics (Huang et al, 2008). Organotellurium vitro models of animal pathologies (Maciel et al, 2000;Taylor, 1996;Stangherlin et al, 2009;Moretto et al, 2007;Heimfarth et al, 2011;Heimfarth et al, 2012 b;Comparsi et al, 2012).…”

Section: Differential Genotoxicity Of Diphenyl Diselenide (Phse)2 Andmentioning

confidence: 99%

“…Similarly,organoselenides and tellurides can be toxic in different in vivo and in vitro models of animal pathologies (Maciel et al, 2000;Taylor, 1996;Stangherlin et al, 2009;Moretto et al, 2007;Heimfarth et al, 2011;Heimfarth et al, 2012 b;Comparsi et al, 2012). In effect, diphenyl ditelluride (PhTe)2 was found to be extremely toxic to mice and rats after acute or chronic exposure (Maciel et al, 2000;Heimfarth et al, 2012 b ;Comparsi et al, 2012).…”

Section: Micronucleus Testmentioning

confidence: 99%

Differential genotoxicity of diphenyl diselenide (PhSe)2 and diphenyl ditelluride (PhTe)2

Rocha

Meinerz

Allebrandt

et al. 2014

Preprint

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Organoselenium compounds have been pointed out as therapeutic agents. In contrast, the potential therapeutic aspects of tellurides have not yet been demonstrated. The present study evaluated the comparative toxicological effects of diphenyl diselenide (PhSe)2 and diphenyl ditelluride (PhTe)2 in mice after in vivo administration. Genotoxicity (as determined by comet assay) and mutagenicicity were used as end-points of toxicity. Subcutaneous administration of high doses of (PhSe)2 or (PhTe)2 (500 mol/Kg) caused distinct genotoxicity in mice. vivo exposure to ditelluride caused genotoxicity in mice, which may be associated with pro-oxidant effects of diphenyl ditelluride. These results indicated that exposure to ditelluride can be genotoxic to mice and the use of this compound and possibly other related tellurides must be carefully controlled.

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Cross-Talk among Intracellular Signaling Pathways Mediates the Diphenyl Ditelluride Actions on the Hippocampal Cytoskeleton of Young Rats

Cited by 15 publications

References 87 publications

Intermediate Filaments as a Target of Signaling Mechanisms in Neurotoxicity

Intermediate Filaments as a Target of Signaling Mechanisms in Neurotoxicity

Signaling Mechanisms and Disrupted Cytoskeleton in the Diphenyl Ditelluride Neurotoxicity

Differential genotoxicity of diphenyl diselenide (PhSe)2 and diphenyl ditelluride (PhTe)2

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