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Diphenyl diselenide induces apoptotic cell death and modulates ERK1/2 phosphorylation in human neuroblastoma SH-SY5Y cells

  • Molecular Toxicology
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Abstract

Diphenyl diselenide (PhSe)2 is a synthetic organoselenium compound displaying glutathione peroxidase-like activity. Protective and antioxidant potential of (PhSe)2 have been extensively investigated in in vivo and in vitro studies. In spite of this, there is a lack of studies addressed to the investigation of potential cytotoxic effect and signaling pathways modulated by this compound. Herein, we aimed to analyze the effects of 24-h treatment with (PhSe)2 on cell viability and a possible modulation of signaling pathways in human neuroblastoma cell line SH-SY5Y. For this purpose, cells were incubated with (PhSe)2 (0.3–30 μM) for 24 h and cell viability, apoptotic cell death and modulation of MAPKs (ERK1/2 and p38MAPK), and PKC substrates phosphorylation was determined. (PhSe)2 treatment significantly decreased cell viability and increased the number of apoptotic cells with induction of PARP cleavage. An increase in ERK1/2 phosphorylation was observed at (PhSe)2 3 μM. In contrast, higher concentrations of the chalcogenide inhibited ERK1/2, p38MAPK and PKC substrate phosphorylation. Pre-treatment with ERK1/2 inhibitor, U0126, increased cell susceptibility to (PhSe)2. Together, these data indicate a cytotoxic potential of (PhSe)2 in a neuronal cell line, which appears to be mediated by the ERK1/2 pathway.

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Acknowledgments

This work was supported by grant from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). MTP, TP (n°151010/2009-9) and JLF (nº150514/2009-3) were recipients of CNPq fellowship. The authors thank Professor Peter R. Dunkley and Professor Phillip W. Dickson for critical review of the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil

    Thaís Posser, Mariane Trindade de Paula & João Batista T. da Rocha

  2. Campus São Gabriel, Universidade Federal do Pampa, São Gabriel, Rio Grande do Sul, 97300-000, Brazil

    Jeferson Luis Franco

  3. Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, 88040-900, Brazil

    Rodrigo B. Leal

  4. Departamento de Química, Universidade Federal de Santa Maria, Avenida Roraima, nº 1000 Cidade Universitária, Bairro Camobi, Santa Maria, Rio Grande do Sul, CEP: 97105-900, Brazil

    Thaís Posser

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  1. Thaís Posser
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  2. Mariane Trindade de Paula
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  3. Jeferson Luis Franco
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  4. Rodrigo B. Leal
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  5. João Batista T. da Rocha
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Correspondence to Thaís Posser.

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Posser, T., de Paula, M.T., Franco, J.L. et al. Diphenyl diselenide induces apoptotic cell death and modulates ERK1/2 phosphorylation in human neuroblastoma SH-SY5Y cells. Arch Toxicol 85, 645–651 (2011). https://doi.org/10.1007/s00204-010-0602-0

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  • DOI: https://doi.org/10.1007/s00204-010-0602-0

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