Adenosine monophosphate-activated protein kinase and nitric oxide in rat steatotic liver transplantation.
OBJECTIVE
Hepatic steatosis is a risk factor for transplantation. We examined the role of AMP-activated protein kinase (AMPK) and nitric oxide (NO) in the benefits of preconditioning in steatotic liver transplantation.


METHODS
Steatotic liver transplantation with or without preconditioning was induced in Zucker rats. The activities of AMPK and NO synthase (NOS) were measured and altered pharmacologically.


RESULTS
Preconditioning or AMPK activation with aminoimidazole-4-carboxamide ribonucleoside (AICAR) increased AMPK and constitutive NOS activities and protected against lipid peroxidation, nitrotyrosine formation and hepatic injury in both grafts. Inhibition of AMPK activity removed the benefits of preconditioning. NO synthesis inhibition abolished the benefits of preconditioning or AICAR. Therefore, preconditioning or AICAR, through AMPK activation, may induce NO synthesis, thus protecting against hepatic injury in both steatotic and non-steatotic liver transplantation. In non-steatotic grafts, NO donors simulated the benefits of preconditioning. However, in steatotic grafts, NO supplementation was ineffective.


CONCLUSIONS
These results indicate (a) a potential relationship between AMPK and NO in the benefits of preconditioning in steatotic liver transplantation, (b) AICAR as a new phamacological strategy in steatotic liver transplantation and (c) a differential effect of NO supplementation in both grafts.
Carrasco-Chaumel
Esther
E
Department of Experimental Pathology, Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior de Investigaciones Científicas, C/Rosellón 161, 7(a) planta, 08036 Barcelona, Spain.
Roselló-Catafau
Joan
J
Bartrons
Ramon
R
Franco-Gou
Rosa
R
Xaus
Carme
C
Casillas
Arani
A
Gelpí
Emili
E
Rodés
Joan
J
Peralta
Carmen
C
D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005234:Fatty Liver / Q000378:metabolism / Q000601:surgery*; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply; D016031:Liver Transplantation; D009097:Multienzyme Complexes / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D018384:Oxidative Stress / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D015427:Reperfusion Injury / Q000517:prevention & control* / Q000628:therapy; D012265:Ribonucleotides / Q000494:pharmacology; D014740:Vidarabine / Q000494:pharmacology
D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D012265:Ribonucleotides; D009569:Nitric Oxide; D000620:Aminoimidazole Carboxamide; D019001:Nitric Oxide Synthase; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D014740:Vidarabine