title: Tyrosine phosphorylation of insulin receptor substrates during ischemia/reperfusion-induced apoptosis in rat liver.
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.
  
  
  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.
authors.affiliation: Laboratoire de Recherches Chirurgicales, IFR 50, Faculté de Médecine, Université de Nice Sophia Antipolis, Nice, France. cursio@unice.fr
authors.forename: Raffaele
authors.initials: R
authors.lastname: Cursio
authors.forename: Claudia
authors.initials: C
authors.lastname: Miele
authors.forename: Nathalie
authors.initials: N
authors.lastname: Filippa
authors.forename: Pascal
authors.initials: P
authors.lastname: Colosetti
authors.forename: Patrick
authors.initials: P
authors.lastname: Auberger
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Van Obberghen
authors.forename: Jean
authors.initials: J
authors.lastname: Gugenheim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008297:Male; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D011972:Receptor, Insulin / Q000378:metabolism; D015427:Reperfusion Injury / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D053148:Caspase 3; D053179:Caspase 7