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Peroxiredoxin 2 is Involved in the Neuroprotective Effects of PACAP in Cultured Cerebellar Granule Neurons

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Abstract

The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is known to counteract in vitro the deleterious effects of toxic agents on cerebellar granule cell survival and differentiation. The potent antiapoptotic action of PACAP is mediated through inhibition of caspase-3 activity; however, additional proteins are likely involved and remain to be identified. Two-dimensional gel electrophoresis analysis coupled with mass spectrometry characterization led to the identification of a protein, peroxiredoxin 2, which was induced after a 6-h treatment with PACAP. Western blot analysis confirmed the regulation of peroxiredoxin 2 by PACAP and revealed that this protein is induced by both cyclic AMP and protein kinase C stimulators. Inhibition of peroxiredoxin 2 expression, using two distinct small-interfering RNAs (siRNAs), reduced the effect of PACAP on caspase-3 activity and cerebellar granule cell survival. Peroxiredoxin 2 expression was also induced in vivo and in vitro by ethanol. Although ethanol and PACAP exert opposite effects on caspase-3 activity, inhibition of peroxiredoxin 2 expression, using siRNAs, only reduced the ability of PACAP to prevent ethanol-induced caspase-3 activity. Taken together, these data indicate that peroxiredoxin 2 is probably involved in the neurotrophic effect of PACAP and suggest that this protein may have a therapeutic potential for the treatment of some neurodegenerative diseases.

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Abbreviations

2-D:

two-dimensional

PACAP:

pituitary adenylate cyclase-activating polypeptide

PMA:

phorbol 12-myristate 13-acetate

Prx 2:

peroxiredoxin 2

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Acknowledgments

This work was supported by INSERM (U413), the European Institute for Peptide Research (IFRMP23), the Institut de Recherches Scientifiques sur les Boissons (IREB), an Interreg 3A FEDER project, the ANR (06-JCJC-0071), and the Conseil Régional de Haute-Normandie. The work was conducted with the technical support of the proteomic facility of the IFRMP23 and the Platform for Cell Imaging of Haute-Normandie. BB was a recipient of a doctoral fellowship from the Société Française d’Alcoologie and a fellowship from the Fondation pour la Recherche Médicale. We thank Dr Mickaël Naassila for the quantification of ethanol level in blood samples.

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Authors and Affiliations

  1. INSERM U413, Laboratory of Cellular and Molecular Neuroendocrinology, 76821, Mont-Saint-Aignan, France

    Béatrice Botia, Aurélia Ravni, Anthony Falluel-Morel, Hubert Vaudry, Bruno J. Gonzalez & David Vaudry

  2. International Associated Laboratory Samuel de Champlain, Mont-Saint-Aignan cedex, France

    Béatrice Botia, Aurélia Ravni, Anthony Falluel-Morel, Alain Fournier, Hubert Vaudry, Bruno J. Gonzalez & David Vaudry

  3. European Institute for Peptide Research (IFRMP23), University of Rouen, 76821, Mont-Saint-Aignan cedex, France

    Béatrice Botia, Damien Seyer, Aurélia Ravni, Magalie Bénard, Anthony Falluel-Morel, Pascal Cosette, Thierry Jouenne, Hubert Vaudry, Bruno J. Gonzalez & David Vaudry

  4. CNRS UMR 6522, IBBR group, University of Rouen, 76821, Mont-Saint-Aignan, France

    Damien Seyer, Pascal Cosette & Thierry Jouenne

  5. INRS-Institut Armand Frappier, University of Québec, Pointe-Claire, Canada

    Alain Fournier

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  1. Béatrice Botia
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  2. Damien Seyer
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  9. Hubert Vaudry
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  10. Bruno J. Gonzalez
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  11. David Vaudry
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Correspondence to Hubert Vaudry or David Vaudry.

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Botia, B., Seyer, D., Ravni, A. et al. Peroxiredoxin 2 is Involved in the Neuroprotective Effects of PACAP in Cultured Cerebellar Granule Neurons. J Mol Neurosci 36, 61–72 (2008). https://doi.org/10.1007/s12031-008-9075-5

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