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 exampleDynamic regulation of metabolism and respiration by endogenously produced nitric oxide protects against oxidative stress
Paxinou E, Weisse M, Chen Q, Souza J, Hertkorn C, Selak M, Daikhin E, Yudkoff M, Sowa G, Sessa W, Ischiropoulos H. Dynamic regulation of metabolism and respiration by endogenously produced nitric oxide protects against oxidative stress. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 11575-11580. PMID: 11562476, PMCID: PMC58771, DOI: 10.1073/pnas.201293198.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseNitric oxideOxidative stressProtective effectNitric oxide protectsNitric oxide synthaseNitric oxide synthesisECV304 cellsSteady-state levelsMechanism of protectionOxide synthaseOxide synthesisENOS cDNAHuman ECV304 cellsMitochondria respirationDeathMitochondrial respirationExposureSame extentCellsCell metabolismDynamic regulationMetabolismLow steady-state levelsGlycolytic pathwayAkt Down-regulation of p38 Signaling Provides a Novel Mechanism of Vascular Endothelial Growth Factor-mediated Cytoprotection in Endothelial Cells*
Gratton J, Morales-Ruiz M, Kureishi Y, Fulton D, Walsh K, Sessa W. Akt Down-regulation of p38 Signaling Provides a Novel Mechanism of Vascular Endothelial Growth Factor-mediated Cytoprotection in Endothelial Cells*. Journal Of Biological Chemistry 2001, 276: 30359-30365. PMID: 11387313, DOI: 10.1074/jbc.m009698200.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsApoptosisBlotting, WesternCattleCell DeathCell LineCell SurvivalCells, CulturedDose-Response Relationship, DrugDown-RegulationEndothelial Growth FactorsEndothelium, VascularEnzyme ActivationEnzyme InhibitorsFlow CytometryHumansImidazolesLymphokinesMitogen-Activated Protein KinasesP38 Mitogen-Activated Protein KinasesPhosphatidylinositol 3-KinasesPhosphorylationProtein BindingProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktPyridinesSignal TransductionTime FactorsUmbilical VeinsVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsMEKK3 phosphorylationP38 activationMEKK3 kinase activityMitogen-activated protein kinaseP38 mitogen-activated protein kinaseP38-dependent apoptosisP38 MAPK inhibitor SB203580Dominant-negative RacInhibition of PIActivation of MKK3/6Vascular endothelial growth factorMAPK inhibitor SB203580P38 MAPK pathwayP38 MAPK activationEndothelial cellsEndothelial cell survivalGrowth factorRac activationProtein kinaseActive AktPro-apoptotic effectsKinase activityInhibitor SB203580MAPK activationP38 signalingSuppression of Vascular Endothelial Growth Factor-Mediated Endothelial Cell Protection by Survivin Targeting
Mesri M, Morales-Ruiz M, Ackermann E, Bennett C, Pober J, Sessa W, Altieri D. Suppression of Vascular Endothelial Growth Factor-Mediated Endothelial Cell Protection by Survivin Targeting. American Journal Of Pathology 2001, 158: 1757-1765. PMID: 11337373, PMCID: PMC1891951, DOI: 10.1016/s0002-9440(10)64131-4.Peer-Reviewed Original ResearchApoptosisCell MovementCells, CulturedDNADNA, AntisenseDose-Response Relationship, DrugEndothelial Growth FactorsEndothelium, VascularGene Expression RegulationHumansInhibitor of Apoptosis ProteinsLymphokinesMicrotubule-Associated ProteinsNeoplasm ProteinsProteinsRNA, MessengerSurvivinVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsHeat 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 anionAssociationPretreatmentHsp90Synthase
2000
Membrane 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 involvementReconstitution of an Endothelial Nitric-oxide Synthase (eNOS), hsp90, and Caveolin-1 Complex in Vitro EVIDENCE THAT hsp90 FACILITATES CALMODULIN STIMULATED DISPLACEMENT OF eNOS FROM CAVEOLIN-1*
Gratton J, Fontana J, O'Connor D, Garcı́a-Cardeña G, McCabe T, Sessa W. Reconstitution of an Endothelial Nitric-oxide Synthase (eNOS), hsp90, and Caveolin-1 Complex in Vitro EVIDENCE THAT hsp90 FACILITATES CALMODULIN STIMULATED DISPLACEMENT OF eNOS FROM CAVEOLIN-1*. Journal Of Biological Chemistry 2000, 275: 22268-22272. PMID: 10781589, DOI: 10.1074/jbc.m001644200.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseAssociation of eNOSNitric oxide synthaseLung microvascular endothelial cellsCaveolin-1Microvascular endothelial cellsENOS enzymatic activityAction of CaMBovine lung microvascular endothelial cellsENOS functionCalcium-activated calmodulinConcentration of CaMShock protein 90Addition of CaMEndothelial cellsVitro EvidenceCav-1Protein 90AssociationPresence of Hsp90Vascular Endothelial Growth Factor–Stimulated Actin Reorganization and Migration of Endothelial Cells Is Regulated via the Serine/Threonine Kinase Akt
Morales-Ruiz M, Fulton D, Sowa G, Languino L, Fujio Y, Walsh K, Sessa W. Vascular Endothelial Growth Factor–Stimulated Actin Reorganization and Migration of Endothelial Cells Is Regulated via the Serine/Threonine Kinase Akt. Circulation Research 2000, 86: 892-896. PMID: 10785512, DOI: 10.1161/01.res.86.8.892.Peer-Reviewed Original ResearchConceptsSignal transduction mechanismsCell migrationActin reorganizationActive AktMyr-AktSerine/threonine kinase AktCell signal transduction mechanismsTransduction mechanismsThreonine kinase AktVascular endothelial growth factorDominant-negative AktDistinct signal transduction mechanismsBovine lung microvascular endothelial cellsEndothelial cellsAbsence of VEGFActin cytoskeletonGrowth factorMicrovascular endothelial cellsKinase AktActin rearrangementStress fibersF-actinCell locomotionEndothelial growth factorEndothelial cell proliferationAngiopoietin-1 Inhibits Endothelial Cell Apoptosis via the Akt/Survivin Pathway*
Papapetropoulos A, Fulton D, Mahboubi K, Kalb R, O'Connor D, Li F, Altieri D, Sessa W. Angiopoietin-1 Inhibits Endothelial Cell Apoptosis via the Akt/Survivin Pathway*. Journal Of Biological Chemistry 2000, 275: 9102-9105. PMID: 10734041, DOI: 10.1074/jbc.275.13.9102.Peer-Reviewed Original ResearchMeSH KeywordsAngiopoietin-1AnimalsApoptosisCattleCells, CulturedEndothelium, VascularFlow CytometryInhibitor of Apoptosis ProteinsMembrane GlycoproteinsMicrotubule-Associated ProteinsNeoplasm ProteinsPhosphorylationProtein Serine-Threonine KinasesProteinsProto-Oncogene ProteinsProto-Oncogene Proteins c-aktSurvivinConceptsAkt/survivin pathwaySerine-threonine kinaseDeath-inducing stimuliPost-natal angiogenesisDominant-negative survivinEndothelial cellsEndothelial cell survivalAnti-apoptotic pathwaysSurvival machineryEndothelial cell apoptosisSurvivin pathwayApoptosis inhibitorCell survivalCell apoptosisVascular stabilizationAktSurvivinTie-2 receptorAngiogenic responseApoptosisCellsPathwayAngiogenesisMorphogenesisKinaseEstrogen 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
Induction of Nitric Oxide Synthase mRNA by Shear Stress Requires Intracellular Calcium and G-protein Signals and Is Modulated by PI 3 Kinase
Malek A, Jiang L, Lee I, Sessa W, Izumo S, Alper S. Induction of Nitric Oxide Synthase mRNA by Shear Stress Requires Intracellular Calcium and G-protein Signals and Is Modulated by PI 3 Kinase. Biochemical And Biophysical Research Communications 1999, 254: 231-242. PMID: 9920763, DOI: 10.1006/bbrc.1998.9921.Peer-Reviewed Original ResearchConceptsNitric oxide synthase mRNAPTX-sensitive G proteinsENOS mRNA levelsENOS mRNABovine aortic endothelial cellsIntracellular calciumPertussis toxinMRNA upregulationEndothelial nitric oxide synthase (eNOS) mRNAMRNA levelsEndothelin-1 mRNACalmodulin inhibitor WENOS gene promoterG proteinsSynthase mRNAAortic endothelial cellsTime-dependent increaseTyrosine kinase inhibitor herbimycin ACalcium entryBAPTA-AMInhibitor WEndothelial cellsTyrosine kinase activityMicrotubule integrityLaminar fluid shear stress
1998
Biological Action of Leptin as an Angiogenic Factor
Sierra-Honigmann M, Nath A, Murakami C, Garcı́a-Cardeña G, Papapetropoulos A, Sessa W, Madge L, Schechner J, Schwabb M, Polverini P, Flores-Riveros J. Biological Action of Leptin as an Angiogenic Factor. Science 1998, 281: 1683-1686. PMID: 9733517, DOI: 10.1126/science.281.5383.1683.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAmino Acid SequenceAnimalsCarrier ProteinsCells, CulturedCorneal NeovascularizationDNA-Binding ProteinsEndothelial Growth FactorsEndothelium, VascularEnergy MetabolismHumansLeptinLipid MetabolismLymphokinesMolecular Sequence DataNeovascularization, PhysiologicPhosphorylationProteinsRatsRats, ZuckerReceptors, Cell SurfaceReceptors, LeptinSTAT3 Transcription FactorTrans-ActivatorsVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsFa/fa Zucker ratFunctional leptin receptorHuman endothelial cellsNormal ratsFood intakeLeptin receptorVascular endotheliumZucker ratsLeptinOb-RbAngiogenic factorsEndothelial cellsAngiogenic activityPrimary culturesEnergy expenditureBiological actionsHuman vasculatureVivo assaysRatsCorneaReceptorsPhysiological mechanismsHypotension 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 inhibitor
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 moleculesDissecting the Interaction between Nitric Oxide Synthase (NOS) and Caveolin FUNCTIONAL SIGNIFICANCE OF THE NOS CAVEOLIN BINDING DOMAININ VIVO *
Garcı́a-Cardeña G, Martasek P, Masters B, Skidd P, Couet J, Li S, Lisanti M, Sessa W. Dissecting the Interaction between Nitric Oxide Synthase (NOS) and Caveolin FUNCTIONAL SIGNIFICANCE OF THE NOS CAVEOLIN BINDING DOMAININ VIVO *. Journal Of Biological Chemistry 1997, 272: 25437-25440. PMID: 9325253, DOI: 10.1074/jbc.272.41.25437.Peer-Reviewed Original ResearchConceptsCaveolin-1Peripheral membrane proteinsInteraction of eNOSC-terminal tailAmino acids 310Direct interactionCo-transfection experimentsSite-directed mutagenesisNovel functional roleEndothelial nitric oxide synthaseMolecular chaperonesCytoplasmic domainCaveolin isoformsDeletion mutantsMammalian cellsEndothelial cell lysatesGlutathione S-transferaseMembrane proteinsCaveolin-2Coat proteinNegative regulationCaveolin-3Endothelial cellsDirect bindingGolgi region
1996
Endothelial Nitric Oxide Synthase Is Regulated by Tyrosine Phosphorylation and Interacts with Caveolin-1*
García-Cardeña G, Fan R, Stern D, Liu J, Sessa W. Endothelial Nitric Oxide Synthase Is Regulated by Tyrosine Phosphorylation and Interacts with Caveolin-1*. Journal Of Biological Chemistry 1996, 271: 27237-27240. PMID: 8910295, DOI: 10.1074/jbc.271.44.27237.Peer-Reviewed Original ResearchConceptsNovel regulatory mechanismTyrosine phosphorylationCaveolin-1Bovine aortic endothelial cellsRegulatory mechanismsProtein tyrosine phosphatase inhibitorCaveolin-interacting proteinsPhosphoamino acid analysisTyrosine phosphatase inhibitorTreatment of BAECBovine lung microvascular endothelial cellsEndothelial nitric oxide synthaseSubcellular traffickingPhosphatase inhibitorCoat proteinEndothelial cellsMetabolic labelingSodium orthovanadatePhosphorylationCaveolaeAortic endothelial cellsLung microvascular endothelial cellsProteinAcid analysisImmunoprecipitation
1995
Native low-density lipoprotein increases endothelial cell nitric oxide synthase generation of superoxide anion.
Pritchard K, Groszek L, Smalley D, Sessa W, Wu M, Villalon P, Wolin M, Stemerman M. Native low-density lipoprotein increases endothelial cell nitric oxide synthase generation of superoxide anion. Circulation Research 1995, 77: 510-8. PMID: 7543827, DOI: 10.1161/01.res.77.3.510.Peer-Reviewed Original ResearchConceptsLow-density lipoproteinNative low-density lipoproteinN-LDLNitro-L-arginine methyl esterNitric oxideLevels of nitrotyrosineEndothelial cell releaseEC releaseThiobarbituric acid substancesFormation of peroxynitriteSuperoxide anionENOS activityL-arginineNO productionSKF-525ANitrite productionOxidative metabolismThe Golgi Association of Endothelial Nitric Oxide Synthase Is Necessary for the Efficient Synthesis of Nitric Oxide(∗)
Sessa W, Garca-Cardea G, Liu J, Keh A, Pollock J, Bradley J, Thiru S, Braverman I, Desai K. The Golgi Association of Endothelial Nitric Oxide Synthase Is Necessary for the Efficient Synthesis of Nitric Oxide(∗). Journal Of Biological Chemistry 1995, 270: 17641-17644. PMID: 7543089, DOI: 10.1074/jbc.270.30.17641.Peer-Reviewed Original ResearchConceptsHEK-293 cellsHeterologous expression systemEndothelial nitric oxide synthaseNovel GolgiGolgi associationExpression systemIntracellular signalsCultured endothelial cellsGolgiIntact blood vesselsEnzymeParticulate enzymeProteinEndothelial cellsCellsSynthaseNitric oxide synthaseOxide synthaseBlood vesselsCompartmentalizationNitric oxideTarget
1993
20-Hydroxyeicosatetraenoic acid is an endothelium-dependent vasoconstrictor in rabbit arteries
Escalante B, Omata K, Sessa W, Lee S, Falck J, Schwartzman M. 20-Hydroxyeicosatetraenoic acid is an endothelium-dependent vasoconstrictor in rabbit arteries. European Journal Of Pharmacology 1993, 235: 1-7. PMID: 8519270, DOI: 10.1016/0014-2999(93)90812-v.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicArachidonic AcidCarotid ArteriesCattleCells, CulturedDose-Response Relationship, DrugEndothelium, VascularHydroxyeicosatetraenoic AcidsIn Vitro TechniquesMaleMesenteric ArteriesProstaglandin-Endoperoxide SynthasesRabbitsRenal ArteryVasoconstrictionVasoconstrictor AgentsConceptsBlood vesselsEndothelium-dependent vasoconstrictorEndothelial cyclooxygenaseRegulation of hemostasisVasoconstrictor metabolitesContractile potencyContractile effectAortic ringsVascular tonePlatelet functionMuscular arteriesRabbit arteriesArachidonate metabolitesPlatelet aggregationCyclooxygenaseArachidonic acidArteryBlood cellsRabbit kidneySeminal vesiclesEicosatetraenoic acidMajor arachidonate metabolitePotencyRam seminal vesiclesPresent study
1990
Inhibition by l‐glutamine of the release of endothelium‐derived relaxing factor from cultured endothelial cells
Hecker M, Mitchell J, Swierkosz T, Sessa W, Vane J. Inhibition by l‐glutamine of the release of endothelium‐derived relaxing factor from cultured endothelial cells. British Journal Of Pharmacology 1990, 101: 237-239. PMID: 2257431, PMCID: PMC1917688, DOI: 10.1111/j.1476-5381.1990.tb12693.x.Peer-Reviewed Original Research