2001
Distinction between signaling mechanisms in lipid rafts vs. caveolae
Sowa G, Pypaert M, Sessa W. Distinction between signaling mechanisms in lipid rafts vs. caveolae. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 14072-14077. PMID: 11707586, PMCID: PMC61169, DOI: 10.1073/pnas.241409998.Peer-Reviewed Original ResearchConceptsCav-1Raft domainsLipid raftsCholesterol-rich lipid raft domainsLipid raft domainsCaveolae assemblyEndothelial nitric oxide synthaseCaveolae biogenesisAcylated proteinsSignal transductionSpatial regulationPlasma membraneNegative regulationCaveolin-1CaveolaeFirst clear exampleRaftsPhysical interactionProteinCellsRegulationENOS functionBiogenesisDomainClear exampleHeat Shock Protein 90 Mediates the Balance of Nitric Oxide and Superoxide Anion from Endothelial Nitric-oxide Synthase*
Pritchard K, Ackerman A, Gross E, Stepp D, Shi Y, Fontana J, Baker J, Sessa W. Heat Shock Protein 90 Mediates the Balance of Nitric Oxide and Superoxide Anion from Endothelial Nitric-oxide Synthase*. Journal Of Biological Chemistry 2001, 276: 17621-17624. PMID: 11278264, DOI: 10.1074/jbc.c100084200.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseBovine coronary endothelial cellsNitric oxide synthaseHeat shock protein 90Shock protein 90Nitric oxidePhospho-eNOS levelsCoronary endothelial cellsProtein 90ENOS activityAssociation of hsp90Calcium ionophoreEndothelial cellsNitrite productionVascular biologySuperoxide anionAssociationPretreatmentHsp90SynthaseSphingosine 1-Phosphate Activates Akt, Nitric Oxide Production, and Chemotaxis through a GiProtein/Phosphoinositide 3-Kinase Pathway in Endothelial Cells*
Morales-Ruiz M, Lee M, Zöllner S, Gratton J, Scotland R, Shiojima I, Walsh K, Hla T, Sessa W. Sphingosine 1-Phosphate Activates Akt, Nitric Oxide Production, and Chemotaxis through a GiProtein/Phosphoinositide 3-Kinase Pathway in Endothelial Cells*. Journal Of Biological Chemistry 2001, 276: 19672-19677. PMID: 11278592, DOI: 10.1074/jbc.m009993200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, NorthernBlotting, WesternCattleCell MovementChemotaxisCulture Media, Serum-FreeDose-Response Relationship, DrugEndothelial Growth FactorsEndothelium, VascularEnzyme ActivationGenes, DominantGTP-Binding Protein alpha Subunits, Gi-GoLungLymphokinesLysophospholipidsNeovascularization, PhysiologicNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIPhosphatidylinositol 3-KinasesPhosphorylationProtein BindingProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptors, Cell SurfaceSignal TransductionSphingosineTime FactorsVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsVirulence Factors, BordetellaConceptsEndothelial differentiation gene familySerine/threonine kinase AktHeterotrimeric G proteinsThreonine kinase AktEDG-1 receptorGene familyAkt substrateKinase AktEndothelial cell chemotaxisActivates AktENOS phosphorylationAkt activationG proteinsCell survivalEndothelial nitric oxide synthasePhosphorylationAktCell chemotaxisSppSignalingGrowth factorVascular endothelial growth factorChemotaxisEndothelial cellsSphingosine
2000
In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation
Bucci M, Gratton J, Rudic R, Acevedo L, Roviezzo F, Cirino G, Sessa W. In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation. Nature Medicine 2000, 6: 1362-1367. PMID: 11100121, DOI: 10.1038/82176.Peer-Reviewed Original ResearchConceptsCaveolin-1Signal transductionSmall-molecule mimicryCaveolae assemblyInternalization sequenceCoat proteinEndothelial cellsPhysiological importanceEndothelial nitric oxide synthase (eNOS) inhibitorTransductionCholesterol transportNitric oxide synthase inhibitorChimeric peptideInhibits nitric oxide synthesisOxide synthase inhibitorNitric oxide synthesisNew therapeutic approachesNitric oxide productionSelective inhibitionDomainPeptidesCaveolinAcute inflammationCellsSystemic administrationSimvastatin upregulates coronary vascular endothelial nitric oxide production in conscious dogs
Mital S, Zhang X, Zhao G, Bernstein R, Smith C, Fulton D, Sessa W, Liao J, Hintze T. Simvastatin upregulates coronary vascular endothelial nitric oxide production in conscious dogs. AJP Heart And Circulatory Physiology 2000, 279: h2649-h2657. PMID: 11087217, DOI: 10.1152/ajpheart.2000.279.6.h2649.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAdenosineAnimalsAnticholesteremic AgentsConsciousnessCoronary CirculationDogsEndothelium, VascularEnzyme InhibitorsGene Expression Regulation, EnzymologicHeart RateIn Vitro TechniquesMicrocirculationMyocardiumNG-Nitroarginine Methyl EsterNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIINitritesNitroglycerinOxygen ConsumptionRNA, MessengerSimvastatinVasodilationVasodilator AgentsVeratrineConceptsEndothelial nitric oxide synthaseCoronary blood flowCoronary vasodilationConscious dogsSimvastatin administrationVascular endothelial nitric oxide productionVascular endothelial nitric oxide synthaseNO productionEndothelial nitric oxide productionEndothelium-independent vasodilatorCoronary vascular endotheliumShort-term administrationLipid-lowering effectsNitric oxide synthaseEndothelial NO productionMyocardial oxygen consumptionNitric oxide productionNO-dependent regulationPlasma nitrateGeneral anesthesiaENOS proteinCoronary microvesselsOxide synthaseMongrel dogsENOS mRNAMembrane Estrogen Receptor Engagement Activates Endothelial Nitric Oxide Synthase via the PI3-Kinase–Akt Pathway in Human Endothelial Cells
Haynes M, Sinha D, Russell K, Collinge M, Fulton D, Morales-Ruiz M, Sessa W, Bender J. Membrane Estrogen Receptor Engagement Activates Endothelial Nitric Oxide Synthase via the PI3-Kinase–Akt Pathway in Human Endothelial Cells. Circulation Research 2000, 87: 677-682. PMID: 11029403, DOI: 10.1161/01.res.87.8.677.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeBinding SitesCell MembraneCells, CulturedChromonesEndothelium, VascularEnzyme InhibitorsEstradiolGenes, DominantHumansMorpholinesNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptors, EstrogenSerum Albumin, BovineSignal TransductionTransduction, GeneticConceptsPI3-kinaseKinase-Akt pathwayDominant-negative AktPI3-kinase inhibitorRapid eNOS phosphorylationRapid Akt phosphorylationActivation of eNOSAkt-dependent pathwayEndothelial nitric oxide synthaseAkt substratePhosphatidylinositol 3ENOS phosphorylationCritical residuesSerine 473Human endothelial cellsEstrogen receptor antagonist ICI 182Cell membrane sitesHuman endothelial cell lineAkt pathwayAkt phosphorylationPhosphorylationReceptor engagementEndothelial cell lineActivation eventsFunctional involvementAcute modulation of endothelial Akt/PKB activity alters nitric oxide–dependent vasomotor activity in vivo
Luo Z, Fujio Y, Kureishi Y, Rudic R, Daumerie G, Fulton D, Sessa W, Walsh K. Acute modulation of endothelial Akt/PKB activity alters nitric oxide–dependent vasomotor activity in vivo. Journal Of Clinical Investigation 2000, 106: 493-499. PMID: 10953024, PMCID: PMC380252, DOI: 10.1172/jci9419.Peer-Reviewed Original ResearchConceptsDN-AktEndothelial cell nitric oxide synthaseMyr-AktSerine/threonine protein kinase AktProtein kinase AktDominant-negative AktNitric oxideVasomotor toneFemoral arteryAkt functionReplication-defective adenoviral constructKinase AktActive AktEndothelium-dependent vasodilatationKey regulatorEndothelium-independent vasodilatorEndothelium-dependent vasomotionRabbit femoral artery modelNitric oxide synthaseAorta ex vivoImportant regulatorGene transferDoppler flow measurementsAktENOS inhibitorTemporal Events Underlying Arterial Remodeling After Chronic Flow Reduction in Mice
Rudic R, Bucci M, Fulton D, Segal S, Sessa W. Temporal Events Underlying Arterial Remodeling After Chronic Flow Reduction in Mice. Circulation Research 2000, 86: 1160-1166. PMID: 10850968, DOI: 10.1161/01.res.86.11.1160.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarotid Artery, CommonCell DeathDrug CombinationsIn Vitro TechniquesMaleMiceMice, Inbred C57BLMuscle, Smooth, VascularNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IINitric Oxide Synthase Type IIIRegional Blood FlowTime FactorsTunica MediaVasodilator AgentsVasomotor SystemConceptsLeft common carotid arteryRight common carotid arteryCommon carotid arteryCarotid arteryBlood flowLeft external carotid arteryEndothelial NO synthase (eNOS) functionEndothelial NO synthase (eNOS) mRNAExternal carotid arteryNO synthase mRNANitrovasodilator sodium nitroprussideAcute ligationEndothelial dysfunctionArterial remodelingControl arteriesVascular remodelingAdult miceSodium nitroprussideDay 7Structural remodelingArteryLuminal remodelingMarked reductionProtein levelsMiceEnhanced Electron Flux and Reduced Calmodulin Dissociation May Explain “Calcium-independent” eNOS Activation by Phosphorylation*
McCabe T, Fulton D, Roman L, Sessa W. Enhanced Electron Flux and Reduced Calmodulin Dissociation May Explain “Calcium-independent” eNOS Activation by Phosphorylation*. Journal Of Biological Chemistry 2000, 275: 6123-6128. PMID: 10692402, DOI: 10.1074/jbc.275.9.6123.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCalmodulinCattleDimerizationEgtazic AcidElectronsEnzyme ActivationKineticsMutationNADH DehydrogenaseNADPNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktStatic ElectricityConceptsSerine 1179Reductase domainCalmodulin dissociationProtein kinase AktWild-type eNOSBovine endothelial nitric oxide synthaseEndothelial nitric oxide synthaseKinase AktRate-limiting stepReductase activityPhosphorylationENOS activationNOS functionPotential mechanismsAspartateENOS catalytic activityENOS activityCytochrome c reductionAktCalmodulinDomainProteinMutationsProductionActivityEstrogen Stimulates Heat Shock Protein 90 Binding to Endothelial Nitric Oxide Synthase in Human Vascular Endothelial Cells EFFECTS ON CALCIUM SENSITIVITY AND NO RELEASE*
Russell K, Haynes M, Caulin-Glaser T, Rosneck J, Sessa W, Bender J. Estrogen Stimulates Heat Shock Protein 90 Binding to Endothelial Nitric Oxide Synthase in Human Vascular Endothelial Cells EFFECTS ON CALCIUM SENSITIVITY AND NO RELEASE*. Journal Of Biological Chemistry 2000, 275: 5026-5030. PMID: 10671543, DOI: 10.1074/jbc.275.7.5026.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseNitric oxide synthaseHuman umbilical vein endothelial cellsENOS activationOxide synthaseEstrogen receptor antagonist ICINO releaseEndothelium-dependent vasodilationReceptor-mediated modulationReceptor antagonist ICINitric oxide releaseUmbilical vein endothelial cellsVein endothelial cellsAntagonist ICIHeat shock protein 90CGMP productionShock protein 90Oxide releaseEndothelial cellsEndothelial cell effectsCalcium sensitivityCalcium dependenceCell effectsEstrogenProtein 90
1999
Molecular control of nitric oxide synthases in the cardiovascular system
Papapetropoulos A, Rudic R, Sessa W. Molecular control of nitric oxide synthases in the cardiovascular system. Cardiovascular Research 1999, 43: 509-520. PMID: 10690323, DOI: 10.1016/s0008-6363(99)00161-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood PressureCardiovascular DiseasesCardiovascular SystemCentral Nervous SystemGene Expression RegulationHomeostasisHumansImmune SystemMiceMice, KnockoutNeovascularization, PathologicNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type INitric Oxide Synthase Type IINitric Oxide Synthase Type IIIRatsVasomotor SystemHsp90 regulation of endothelial nitric oxide synthase contributes to vascular control in portal hypertension
Shah V, Wiest R, Garcia-Cardena G, Cadelina G, Groszmann R, Sessa W. Hsp90 regulation of endothelial nitric oxide synthase contributes to vascular control in portal hypertension. American Journal Of Physiology 1999, 277: g463-g468. PMID: 10444461, DOI: 10.1152/ajpgi.1999.277.2.g463.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAnimalsBenzoquinonesBlood VesselsHSP90 Heat-Shock ProteinsHypertension, PortalIn Vitro TechniquesLactams, MacrocyclicMaleMethoxamineMicrocirculationNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIQuinonesRatsRats, Sprague-DawleySplanchnic CirculationTissue DistributionVasoconstrictor AgentsVasodilationVasodilator AgentsConceptsEndothelial nitric oxide synthasePortal vein ligationNitric oxide synthasePortal hypertensionMesenteric vasculatureOxide synthaseNormal animalsACh-dependent vasodilationExperimental portal hypertensionExcessive NO productionNO-dependent responsesNOS catalytic activityDependent vasodilationVein ligationVascular controlMesenteric circulationPVL animalsMesenteric vesselsHeat shock protein 90Sodium nitroprussideNO productionEndothelial liningHypertensionShock protein 90MethoxamineRegulation of endothelium-derived nitric oxide production by the protein kinase Akt
Fulton D, Gratton J, McCabe T, Fontana J, Fujio Y, Walsh K, Franke T, Papapetropoulos A, Sessa W. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature 1999, 399: 597-601. PMID: 10376602, PMCID: PMC3637917, DOI: 10.1038/21218.Peer-Reviewed Original ResearchConceptsProtein kinase AktKinase AktSerine/threonine protein kinase AktMutant eNOSRole of phosphorylationEndothelial nitric oxide synthaseSerine 1179Akt substrateSignal transductionGene transferAktAdenovirus-mediated gene transferPhosphorylationGrowth factorVascular endothelial growth factorEndothelial cellsRegulationSynthase isoformsEndothelial growth factorNitric oxide productionTransductionVascular remodellingOxide productionIsoformsProductionNO overproduction by eNOS precedes hyperdynamic splanchnic circulation in portal hypertensive rats
Wiest R, Shah V, Sessa W, Groszmann R. NO overproduction by eNOS precedes hyperdynamic splanchnic circulation in portal hypertensive rats. American Journal Of Physiology 1999, 276: g1043-g1051. PMID: 10198349, DOI: 10.1152/ajpgi.1999.276.4.g1043.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood Flow VelocityBlood PressureEndothelium, VascularHypertension, PortalKineticsLuminescent MeasurementsMaleMesenteric Artery, SuperiorMethoxamineNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIINitroarginineRatsRats, Sprague-DawleySplanchnic CirculationStress, MechanicalConceptsHyperdynamic splanchnic circulationSuperior mesenteric arterySplanchnic circulationSham ratsNitric oxide synthase upregulationHyperdynamic circulatory syndromeNO metabolites concentrationPortal hypertensive ratsENOS protein levelsHigh blood flowSignificant hyporesponsivenessArterial vasodilatationL-NNAPortal hypertensionPVL ratsAgonist methoxamineCirculatory syndromeENOS upregulationHypertensive ratsMesenteric arteryNomega-nitroNO inhibitorBlood flowDay 3L-arginineNitric Oxide in Endothelial Dysfunction and Vascular Remodeling: Clinical Correlates and Experimental Links
Rudic R, Sessa W. Nitric Oxide in Endothelial Dysfunction and Vascular Remodeling: Clinical Correlates and Experimental Links. American Journal Of Human Genetics 1999, 64: 673-677. PMID: 10052999, PMCID: PMC1377782, DOI: 10.1086/302304.Peer-Reviewed Original Research
1998
Hypotension and inflammatory cytokine gene expression triggered by factor Xa–nitric oxide signaling
Papapetropoulos A, Piccardoni P, Cirino G, Bucci M, Sorrentino R, Cicala C, Johnson K, Zachariou V, Sessa W, Altieri D. Hypotension and inflammatory cytokine gene expression triggered by factor Xa–nitric oxide signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 4738-4742. PMID: 9539808, PMCID: PMC22560, DOI: 10.1073/pnas.95.8.4738.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCytokinesEndothelium, VascularFactor XaFibrinogenGene Expression RegulationHistamineHumansHypotensionInflammationInterleukin-6MaleNG-Nitroarginine Methyl EsterNitric OxidePolymerase Chain ReactionRatsRats, WistarSplanchnic CirculationStereoisomerismTumor Necrosis Factor-alphaUmbilical VeinsConceptsEffector cell protease receptor-1Cytokine gene expressionFactor XaReceptor 1NO synthase inhibitor LNitric oxideInflammatory cytokine gene expressionActivation of coagulationNitroarginine methyl esterEndothelial cell releaseTissue factor pathway inhibitorAcute phase responseEndothelial cell ligandsThrombin inhibitor hirudinInterleukin-6 mRNAFactor pathway inhibitorDose-dependent mannerVascular endothelial cellsL-NAMED-NAMEGrowth factor peptidesInterleukin-6Dose-dependent reactionCell ligandsPathway inhibitorDynamic activation of endothelial nitric oxide synthase by Hsp90
García-Cardeña G, Fan R, Shah V, Sorrentino R, Cirino G, Papapetropoulos A, Sessa W. Dynamic activation of endothelial nitric oxide synthase by Hsp90. Nature 1998, 392: 821-824. PMID: 9580552, DOI: 10.1038/33934.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibiotics, AntineoplasticAortaBenzoquinonesCattleCell LineCOS CellsEndothelial Growth FactorsEndothelium, VascularEnzyme ActivationHistamineHSP90 Heat-Shock ProteinsHumansLactams, MacrocyclicLymphokinesMuscle RelaxationNitric OxideNitric Oxide SynthasePrecipitin TestsQuinonesRatsSignal TransductionStress, MechanicalTransfectionVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsActivation of eNOSCellular targetsHeat shock protein 90Binding of HSP90Specific cellular targetsEndothelial nitric oxide synthaseMolecular chaperonesHsp90 associatesSignaling proteinsProtein foldingProtein 90Mechanotransduction pathwaysENOS complexG proteinsFluid shear stressHsp90Activation statePrecise roleGrowth factorDynamic activationVascular endothelial growth factorSynthaseNitric oxide synthaseEndothelial growth factorActivation
1997
17 beta-estradiol regulation of human endothelial cell basal nitric oxide release, independent of cytosolic Ca2+ mobilization.
Caulin-Glaser T, García-Cardeña G, Sarrel P, Sessa W, Bender J. 17 beta-estradiol regulation of human endothelial cell basal nitric oxide release, independent of cytosolic Ca2+ mobilization. Circulation Research 1997, 81: 885-92. PMID: 9351464, DOI: 10.1161/01.res.81.5.885.Peer-Reviewed Original ResearchConceptsHuman umbilical vein endothelial cellsEstrogen receptorCytosolic Ca2ENOS activityBasal nitric oxide releaseEndothelial NO synthase activityCardiovascular protective roleNO synthase activityDevelopment of atherosclerosisFemale human umbilical vein endothelial cellsNitric oxide releaseCritical effector moleculeUmbilical vein endothelial cellsVein endothelial cellsCardiovascular protectionEstradiol exposureAnimal modelsCGMP formationProtective roleOxide releaseEndothelial cellsNO releaseE2Physiological concentrationsEffector moleculesSubstrate Binding and Calmodulin Binding to Endothelial Nitric Oxide Synthase Coregulate Its Enzymatic Activity
Presta A, Liu J, Sessa W, Stuehr D. Substrate Binding and Calmodulin Binding to Endothelial Nitric Oxide Synthase Coregulate Its Enzymatic Activity. Nitric Oxide 1997, 1: 74-87. PMID: 9701047, DOI: 10.1006/niox.1996.0110.Peer-Reviewed Original Research
1996
Palmitoylation of Endothelial Nitric Oxide Synthase Is Necessary for Optimal Stimulated Release of Nitric Oxide: Implications for Caveolae Localization †
Liu J, García-Cardeña G, Sessa W. Palmitoylation of Endothelial Nitric Oxide Synthase Is Necessary for Optimal Stimulated Release of Nitric Oxide: Implications for Caveolae Localization †. Biochemistry 1996, 35: 13277-13281. PMID: 8873592, DOI: 10.1021/bi961720e.Peer-Reviewed Original ResearchConceptsPalmitoylation-deficient mutantMembrane associationN-myristoylationWT enzymeLocalization of eNOSActivation of eNOSEndothelial nitric oxide synthaseCaveolae membranesCaveolar localizationPalmitoylationCysteine palmitoylationWT proteinGolgi complexMutantsIntact cellsCaveolaeVivo significanceHigh saltEnzymeCellsSynthaseNitric oxide synthaseTriton XLocalizationImportant role