title: Heat shock proteins and mitogen-activated protein kinases in steatotic livers undergoing ischemia-reperfusion: some answers.
abstract: Ischemic preconditioning protects steatotic livers against ischemia-reperfusion (I/R) injury, but just how this is achieved is poorly understood. Here, I/R or preconditioning plus I/R was induced in steatotic and nonsteatotic livers followed by investigating the effect of pharmacological treatments that modulate heat shock proteins (HSPs) and mitogen-activated protein kinases (MAPKs). MAPKs, HSPs, protein kinase C, and transaminase levels were measured after reperfusion. We report that preconditioning increased HSP72 and heme-oxygenase-1 (HO-1) at 6 and 24 hours of reperfusion, respectively. Unlike nonsteatotic livers, steatotic livers benefited from HSP72 activators (geranylgeranylacetone) throughout reperfusion. This protection seemed attributable to HO-1 induction. In steatotic livers, preconditioning and geranylgeranylacetone treatment (which are responsible for HO-1 induction) increased protein kinase C activity. HO-1 activators (cobalt(III) protoporphyrin IX) protected both liver types. Preconditioning reduced p38 MAPK and c-Jun N-terminal kinase (JNK), resulting in HSP72 induction though HO-1 remained unmodified. Like HSP72, both p38 and JNK appeared not to be crucial in preconditioning, and inhibitors of p38 (SB203580) and JNK (SP600125) were less effective against hepatic injury than HO-1 activators. These results provide new data regarding the mechanisms of preconditioning and may pave the way to the development of new pharmacological strategies in liver surgery.
authors.affiliation: Experimental Hepatology Unit, Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior de Investigaciones Científicas, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Massip-Salcedo
authors.forename: Araní
authors.initials: A
authors.lastname: Casillas-Ramirez
authors.forename: Rosah
authors.initials: R
authors.lastname: Franco-Gou
authors.forename: Ramón
authors.initials: R
authors.lastname: Bartrons
authors.forename: Ismail
authors.initials: I
authors.lastname: Ben Mosbah
authors.forename: Anna
authors.initials: A
authors.lastname: Serafin
authors.forename: Joan
authors.initials: J
authors.lastname: Roselló-Catafau
authors.forename: Carmen
authors.initials: C
authors.lastname: Peralta
mesh_terms: D000818:Animals; D005234:Fatty Liver / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D013997:Time Factors
chemical_list: D006360:Heat-Shock Proteins; D009569:Nitric Oxide; D051547:Heme Oxygenase-1; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases