This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Massip-Salcedo, M. Articles by Peralta, C. Search for Related Content PubMed PubMed Citation Articles by Massip-Salcedo, M. Articles by Peralta, C.

(American Journal of Pathology. 2006;168:1474-1485.)
© 2006 American Society for Investigative Pathology

Heat Shock Proteins and Mitogen-activated Protein Kinases in Steatotic Livers Undergoing Ischemia-Reperfusion: Some Answers

Marta Massip-Salcedo^*, Araní Casillas-Ramirez^*, Rosah Franco-Gou^*, Ramón Bartrons, Ismail Ben Mosbah^*, Anna Serafin^*, Joan Roselló-Catafau^* and Carmen Peralta^*

From the Experimental Hepatology Unit,^* Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior de Investigaciones Científicas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona; and the Departament de Ciències Fisiològiques, Campus de Bellvitge, Universitat de Barcelona, Barcelona, Spain

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.

This article has been cited by other articles:

				A. Casillas-Ramirez, A. Zaouali, S. Padrissa-Altes, I. Ben Mosbah, A. Pertosa, I. Alfany-Fernandez, M. Bintanel-Morcillo, C. Xaus, A. Rimola, J. Rodes, et al. Insulin-Like Growth Factor and Epidermal Growth Factor Treatment: New Approaches to Protecting Steatotic Livers against Ischemia-Reperfusion Injury Endocrinology, July 1, 2009; 150(7): 3153 - 3161. [Abstract] [Full Text] [PDF]

				F. S. Ramalho, I. Alfany-Fernandez, A. Casillas-Ramirez, M. Massip-Salcedo, A. Serafin, A. Rimola, V. Arroyo, J. Rodes, J. Rosello-Catafau, and C. Peralta Are Angiotensin II Receptor Antagonists Useful Strategies in Steatotic and Nonsteatotic Livers in Conditions of Partial Hepatectomy under Ischemia-Reperfusion? J. Pharmacol. Exp. Ther., April 1, 2009; 329(1): 130 - 140. [Abstract] [Full Text] [PDF]

				N. G. Abraham and A. Kappas Pharmacological and Clinical Aspects of Heme Oxygenase Pharmacol. Rev., March 1, 2008; 60(1): 79 - 127. [Abstract] [Full Text] [PDF]