Stimulation of p38 MAPK by hormal preconditioning with atrial natriuretic peptide

摘要

AIM：Stress-activated signaling pathways responsible for hepatic ischemia reperfusion injury and their modulation by protective interventions are widely unknown.Preconditioning of rat livers with Atrial Natriuretic Peptide(ANP)attenuates ischemia reperfusion injury(Gerbes et al.Hepatology1998,18:1309-1317),SinANP has recently been shown to be a regulator of the p38MAPKpathway in endothelial cells(Kiemer et al.CircRes2002,90:874-881).aim of this thudy was to investigate activities of MAPK during ischemia and reperfusion and effects of ANP on MAPK.METHODS:Rat livers were perfused with KH-buffer in the presence or absence of ANP for 20min,kept in cold UWsloution for 24h,and reperfused forupto120min,Activities of p38MAPKand JNKwas determined by in vitro phosphorylation assays using MBP and c-jun as substrates.After SDS/PAGE electrophoresis,gels were quantified by phosphorimaging.RESULTS:Activity of p38MAPKin control organs decreased in the course of ischemia and reperfusion by85%,whereas ANPincreased p38 activity by up to 30-fold.JNKactivation of control livers increased in the course of ischemia and reperfusion by up to three-fold.This increase in JNK activrity was slightly elevated in ANP preconditioned organs.CONCLUSION:This work represents a systematic investigation of MAPK activation during liver ischemia and reperfusion.Employing ANP,for the first time a pharmacological approach to modulate these central signal transduction molecules is presented.