1、2008-11-20.L-arginine NO+L-citrullineeNOScalmodulin(CaM)tetrahydrobiopterin(H4B)flavin mononucleotideFADNADPH.eNOS signaling complexSignal transduction moleculesproteinsColocalizationEnzyme activaionNO productionDownstream effector pathway.Activation of PI3KActivation of the serine kinases AktActiva
2、tion of protein kinases AP-eNOSeNOS.PhosphorylationeNOS activity.Robert F.Furchgott Louis J.Ignarro Ferid Murad For their discoveries concerning nitric oxide as a signalling molecule in the cardiovascular system.eNOS uncoupling:electrons flowing from the reductase domain to the heme are diverted to
3、molecular oxygen rather than to the substrate L-arginine,thereby resulting in production of superoxide instead of NO.The signal transduction pathways.Promote vasorelaxationPrevent platelet aggregation and leukocytes adhesionInhibit vascular permeabilityInhibit atherogenesisL-arginineL-citrullineeNOS
4、O2 NADPHNONADP.Ji Y,et al.Proc Natl Acad Sci U S A 2007;104:8839-8844.-Actin,Hsp90,and eNOS were each detected(AC,respectively)by ImmunoGold labeling with electron microscopy.Triple labeling shows multiple areas(arrowed)where-actin(5-nm gold particles),eNOS(10-nm gold particles),and Hsp90(15-nm gold particles)colocalize(D).g,platelet granule.eNOS binding to monomeric-actin was concentration-dependent,and reversible.(B)Preincubation of eNOS with Hsp90 increased the degree of binding to immobilized monomeric-actin,by 2.81.2-fold,and this binding became irreversible.