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Tyrosine phosphorylation of insulin receptor substrates during ischemia/reperfusion-induced apoptosis in rat liver

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Abstract

Background

Phosphoregulation of signal transduction pathways is a complex series of reactions that may modulate the cellular response to ischemia–reperfusion (I–R). The aim of this study was to evaluate the effect of normothermic liver I/R-induced apoptosis on phosphorylation and activation of signal proteins in tyrosine kinase pathways.

Materials and methods

In rats, a segmental normothermic ischemia of the liver was induced for 120 min. Liver apoptosis was determined using terminal deoxynucleotide-transferase-mediated deoxyuridine triphosphate nick end labeling assay, and activity of caspases-3 and -7 was determined by fluorescence. Liver tyrosine phosphorylation of proteins was examined by Western blot analysis.

Results

Normothermic I–R resulted in increased in vivo caspases-3 and -7 activity and in liver apoptosis. Shc tyrosine phosphorylation and activation of ERK1/2 were increased after reperfusion, while tyrosine phosphorylation of IRS-1 and activation of PKB/Akt were decreased.

Conclusions

Normothermic liver I–R leads to increased apoptosis and to modifications in protein tyrosine phosphorylation pathways.

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Acknowledgment

This work was supported by the Institut National de la Santé et de la Recherche Médicale, the Association pour la Recherche sur le Cancer, the Université de Nice Sophia Antipolis, the Ligue contre le Cancer, the Groupe Lipha-Merck (Lyon, France) and the European Union (grant QLG1-CT-1999-00674).

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Authors and Affiliations

  1. Laboratoire de Recherches Chirurgicales, IFR 50, Faculté de Médecine, Université de Nice Sophia Antipolis, Nice, France

    Raffaele Cursio & Jean Gugenheim

  2. Service de Chirurgie et Transplantation Hépatique, Hôpital l’Archet 2, Université de Nice Sophia Antipolis, Nice, France

    Raffaele Cursio & Jean Gugenheim

  3. INSERM U895 Equipe 2 C3M, IFR 50, Faculté de Médecine, Université de Nice Sophia Antipolis, Nice, France

    Raffaele Cursio, Pascal Colosetti & Patrick Auberger

  4. INSERM U145, IFR 50, Faculté de Médecine, Université de Nice Sophia Antipolis, Nice, France

    Claudia Miele, Nathalie Filippa & Emmanuel Van Obberghen

  5. Dipartimento di Biologia e Patologia Cellulare e Molecolare e IEOS-CNR, Università Federico II di Napoli, Naples, Italia

    Claudia Miele

  6. U895 Equipe 2 C3M, IFR 50, Faculté de Médecine, 28 Avenue de Valombrose, 06107, Nice Cedex 2, France

    Raffaele Cursio

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  1. Raffaele Cursio
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  2. Claudia Miele
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  3. Nathalie Filippa
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  4. Pascal Colosetti
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  5. Patrick Auberger
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  6. Emmanuel Van Obberghen
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  7. Jean Gugenheim
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Correspondence to Raffaele Cursio.

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Raffaele Cursio and Claudia Miele have contributed equally to this work

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Cursio, R., Miele, C., Filippa, N. et al. Tyrosine phosphorylation of insulin receptor substrates during ischemia/reperfusion-induced apoptosis in rat liver. Langenbecks Arch Surg 394, 123–131 (2009). https://doi.org/10.1007/s00423-008-0394-3

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  • DOI: https://doi.org/10.1007/s00423-008-0394-3

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