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 Pe...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.展开更多
Human urotension-Ⅱ was synthesized efficiently on Wang resin under microwave irradiation using Fmoc/tBu orthogonal protection strategy. Disulphide bridge was formed on solid phase with the irradiation of microwave, t...Human urotension-Ⅱ was synthesized efficiently on Wang resin under microwave irradiation using Fmoc/tBu orthogonal protection strategy. Disulphide bridge was formed on solid phase with the irradiation of microwave, then the whole peptide was cleaved from the resin. The purity of crude peptide cyclized under microwave irradiation was higher than that under room temperature.展开更多
基金the Deutsche Forschungsgemeinschaft(DFG:Ge 576/14-2 and FOR 440/1-2:KI 702/2)A.K.K.is a recipient of the"Bayerischer Habilitationsfrderpreis".
文摘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.
文摘Human urotension-Ⅱ was synthesized efficiently on Wang resin under microwave irradiation using Fmoc/tBu orthogonal protection strategy. Disulphide bridge was formed on solid phase with the irradiation of microwave, then the whole peptide was cleaved from the resin. The purity of crude peptide cyclized under microwave irradiation was higher than that under room temperature.