2007
Variant estrogen receptor–c-Src molecular interdependence and c-Src structural requirements for endothelial NO synthase activation
Li L, Hisamoto K, Kim KH, Haynes MP, Bauer PM, Sanjay A, Collinge M, Baron R, Sessa WC, Bender JR. Variant estrogen receptor–c-Src molecular interdependence and c-Src structural requirements for endothelial NO synthase activation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 16468-16473. PMID: 17921256, PMCID: PMC2034248, DOI: 10.1073/pnas.0704315104.Peer-Reviewed Original ResearchConceptsC-SrcC-Src kinase activityTyrosine kinase c-SrcRapid signal transductionKinase c-SrcC-Src functionC-Src kinaseEndothelial NO synthase activationENOS activationMembrane recruitmentSignal transductionComplex assemblyPlasma membraneKinase activityOestrogen receptor-alpha variantsVenous endothelial cellsER46Pathway activationHormonal stimuliCritical roleArterial responseNO synthase activationSynthase activationStructural requirementsEndothelial cells
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 involvementHuman vascular endothelial cells contain membrane binding sites for estradiol, which mediate rapid intracellular signaling
Russell K, Haynes M, Sinha D, Clerisme E, Bender J. Human vascular endothelial cells contain membrane binding sites for estradiol, which mediate rapid intracellular signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 5930-5935. PMID: 10823945, PMCID: PMC18536, DOI: 10.1073/pnas.97.11.5930.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalCell LineCell Membrane PermeabilityCells, CulturedCyclic GMPEndothelium, VascularEstradiolFlow CytometryHumansMAP Kinase Signaling SystemMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesNitric OxideReceptors, EstrogenRecombinant Fusion ProteinsSerum Albumin, BovineSignal TransductionTime FactorsTransfectionConceptsHuman endothelial cellsEstrogen receptorEndothelial cellsMitogen-activated protein kinaseER antagonist ICIHuman vascular endothelial cellsMembrane estrogen receptorsMembrane-impermeant formVascular endothelial cellsRapid intracellularRapid nongenomic responsesAntagonist ICIVascular functionE2 treatmentAcute effectsERalpha antibodyCGMP productionCardiovascular systemNongenomic responsesCytometric analysisEstrogen inducesGuanylate cyclaseRapid effectsNO releaseEarly effectsEstrogen 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
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 molecules
1996
Effects of 17beta-estradiol on cytokine-induced endothelial cell adhesion molecule expression.
Caulin-Glaser T, Watson C, Pardi R, Bender J. Effects of 17beta-estradiol on cytokine-induced endothelial cell adhesion molecule expression. Journal Of Clinical Investigation 1996, 98: 36-42. PMID: 8690801, PMCID: PMC507398, DOI: 10.1172/jci118774.Peer-Reviewed Original ResearchConceptsCultured human umbilical vein ECEndothelial cell adhesion molecule expressionVascular cell adhesion molecule-1 inductionEstrogen receptor-mediated effectsCardiovascular protective roleCell adhesion molecule expressionAge-matched malesIncidence of atherosclerosisReceptor-mediated effectsAdhesion molecule expressionEndothelial cell activationHuman umbilical vein ECSimilar risk profilesSelectin mRNA levelsIL-1 activationPremenopausal womenAntagonist ICIMolecule expressionMononuclear leukocytesE-selectinChemotactic factorsCytokines resultsProtective roleCell activationLeukocyte adhesion