The radical scavenger CR-6 protects SH-SY5Y neuroblastoma cells from oxidative stress-induced apoptosis: effect on survival pathways

Authors

  • Nuria Sanvicens,

    1. Cell Development and Disease Laboratory, Department of Biochemistry, Biosciences Research Institute, University College Cork, Cork, Ireland
    Search for more papers by this author
    • 1

      These authors contributed equally to this work.

  • Violeta Gómez-Vicente,

    1. Cell Development and Disease Laboratory, Department of Biochemistry, Biosciences Research Institute, University College Cork, Cork, Ireland
    Search for more papers by this author
    • 1

      These authors contributed equally to this work.

  • Angel Messeguer,

    1. Department of Biological Organic Chemistry, Institut d'Investigacions Químiques i Ambientals de Barcelona, Consejo Superior de Investigaciones Científicas, Jordi Girona, Barcelona, Spain
    Search for more papers by this author
  • Thomas G. Cotter

    1. Cell Development and Disease Laboratory, Department of Biochemistry, Biosciences Research Institute, University College Cork, Cork, Ireland
    Search for more papers by this author

Address correspondence and reprint requests to Thomas G. Cotter, Cell Development and Disease Laboratory, Department of Biochemistry, Biosciences Research Institute, University College Cork, Cork, Ireland. E-mail: t.cotter@ucc.i.e

Abstract

Reactive oxygen species (ROS) and oxidative stress have long been linked to cell death of neurons in many neurodegenerative conditions. However, the exact molecular mechanisms triggered by oxidative stress in neurodegeneration are at present unclear. In the current work we have used the human neuroblastoma SH-SY5Y cell line as a model for studying the molecular events occurring after inducing apoptosis with H2O2. We show that treatment of SH-SY5Y cells with H2O2 up-regulates survival pathways during early stages of apoptosis. Subsequently, the decline of anti-apoptotic protein levels leads to the activation of the calcium-dependent proteases calpains and the cysteine proteases caspases. Additionally, we demonstrate that CR-6 (3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)-benzopyran) acts as a scavenger of ROS and prevents apoptosis by enhancing and prolonging up-regulation of survival pathways. Furthermore, we show that pre-treatment of SH-SY5Y cells with a cocktail containing CR-6, the pan-caspase inhibitor zVAD-fmk (zVal-Ala-Asp-fluoro-methylketone) and the calpain inhibitor SJA6017 confers almost total protection against apoptosis. In summary, the present work characterizes the molecular mechanisms involved in oxidative stress-induced apoptosis in SH-SY5Y cells. Our findings highlight the relevance of CR-6, alone or in combination with other drugs, as potential therapeutic strategy for the treatment of neurodegenerative diseases.

Ancillary