Tesis doctoral de María Iñiguez Martinez
Ischemia/reperfusion (i/r) liver injury occurs when blood flow is restored after prolonged ischemia. A short interruption of blood flow (ischetnic preconditioning, ip) induces tolerance to subsequent prolonged ischemia through ill defined mechanisms. Cardiotrophin-1 (ct-1), a cytokine of the interleukin-6 (il-6) family, exerts hepatoprotective effects and activates key survival pathways like jak/stat3. Here we show that administration of ct-1 to rats or mice protects against i/r liver injury and that ct-l-deficient mice are exceedingly sensitive to this type of damage. Ip markedly reduced transaminase levéis and abrogated caspase-3 and c-jun-nh2-terminal kinase activation after i/r in normal mice but not in ct-l-null mice. Moreover, the protective effect afforded by ip was reduced by previous administration of neutralizing anti-ct-1 antibody. Prominent stat3 phosphorylation in liver tissue was observed after ip plus i/r in normal mice but not in ct-l-null mice. Oxidative stress, a process involved in ip-induced hepatoprotection, was found to stimulate ct-1 reléase from isolated hepatocytes. Interestingly, brief ischemia followed by short reperfusion caused mild serum transaminase elevation and strong stat3 activation in normal mice, but failed to activate stat3 and provoked marked hypertransaminasemia in ct-l-null animals. In conclusión, ct-1 is an essential endogenous defense of the liver against i/r and is a key mediator of the protective effect induced by ip.
Datos académicos de la tesis doctoral «Caracterizacion del papel de la cardiotrofina 1 (ct-1) en el daño hepatico por isquemia reperfusion«
- Título de la tesis: Caracterizacion del papel de la cardiotrofina 1 (ct-1) en el daño hepatico por isquemia reperfusion
- Autor: María Iñiguez Martinez
- Universidad: Navarra
- Fecha de lectura de la tesis: 27/11/2006
Dirección y tribunal
- Director de la tesis
- Jesús M. Prieto Valtueña
- Tribunal
- Presidente del tribunal: joan Caballeria rovira
- María José Iraburu elizalde (vocal)
- pablo Ortiz betes (vocal)
- ramon Bataller alberola (vocal)