2014
Endothelial estrogen receptor isoforms and cardiovascular disease
Kim KH, Young BD, Bender JR. Endothelial estrogen receptor isoforms and cardiovascular disease. Molecular And Cellular Endocrinology 2014, 389: 65-70. PMID: 24530925, PMCID: PMC4040324, DOI: 10.1016/j.mce.2014.02.001.BooksMeSH KeywordsAnimalsCardiovascular DiseasesEndothelium, VascularEstrogensHumansProtein IsoformsReceptors, EstrogenSignal TransductionConceptsNitric oxideFull-length ERαPlasma membrane-associated estrogen receptorOvarian steroid hormonesMembrane-associated estrogen receptorsEstrogen receptor isoformsCardiovascular diseaseEstrogen receptorEndothelial responseRapid E2ER isoformsSteroid hormonesReceptor isoformsVascular cellsClinical contextFavorable effectTissue responseEndothelial signalingVascular systemERαER46Transcriptional modulationTransmembrane moleculesSignalingRapid endothelial responses
2008
Vascular cell signaling by membrane estrogen receptors
Kim KH, Moriarty K, Bender JR. Vascular cell signaling by membrane estrogen receptors. Steroids 2008, 73: 864-869. PMID: 18325557, PMCID: PMC2519041, DOI: 10.1016/j.steroids.2008.01.008.Peer-Reviewed Original ResearchConceptsNumerous signal transduction cascadesEndothelial nitric oxide synthaseCaveolin-1 interactionSignal transduction cascadeEndothelial cellsNon-genomic actionsTranscriptional regulationPI3K/AktMembrane estrogen receptorsCaveolar membranesTransduction cascadeCell signalingC-SrcN-terminusHuman endothelial cellsRapid activationMolecular studiesConsequent activationVascular cellsNumerous animalsNitric oxideMultiple biological effectsEstrogen receptor alphaFavorable estrogenic effectsER46
2006
Estrogen Receptor-Mediated Rapid Signaling
Moriarty K, Kim KH, Bender JR. Estrogen Receptor-Mediated Rapid Signaling. Endocrinology 2006, 147: 5557-5563. PMID: 16946015, DOI: 10.1210/en.2006-0729.Peer-Reviewed Original ResearchConceptsMembrane estrogen receptorsPlasma membrane-associated formSplice variantsMembrane-associated formTranscriptional activationMultimolecular complexesRapid signalingSignaling cascadesMolecular componentsSpecific tissuesER splice variantsMolecular levelSpecific fashionEnzymatic pathwaysEstrogen receptorEstrogen responseNuclear responsePathwayPhysiological outcomesReceptorsComplexesSignalingVariantsVascular endotheliumRapid response
2005
Rapid, Estrogen Receptor–Mediated Signaling: Why Is the Endothelium So Special?
Kim KH, Bender JR. Rapid, Estrogen Receptor–Mediated Signaling: Why Is the Endothelium So Special? Science Signaling 2005, 2005: pe28. PMID: 15956360, DOI: 10.1126/stke.2882005pe28.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsCaveolaeCoronary DiseaseEndothelium, VascularEnzyme ActivationEstrogen Replacement TherapyFemaleHumansMaleMiddle AgedNitric OxideNitric Oxide Synthase Type IIIPostmenopausePremenopauseProtein IsoformsProto-Oncogene Proteins pp60(c-src)Randomized Controlled Trials as TopicReceptors, EstrogenSex DistributionSignal TransductionConceptsEstrogen receptorEndothelial NO synthaseNitric oxideEndothelial cellsHormone replacement therapyMembrane estrogen receptorsEndothelial activationVascular healthReplacement therapyCardiovascular diseaseVascular pathologyNO synthasePotent stimulusEstrogen responseFunctional alterationsENOS activationNongenomic responsesNO releaseRegulatory tissuesGenomic effectsCommon formProtective substancesMajor targetEndotheliumReceptors
2003
Plasma membrane localization and function of the estrogen receptor α variant (ER46) in human endothelial cells
Li L, Haynes MP, Bender JR. Plasma membrane localization and function of the estrogen receptor α variant (ER46) in human endothelial cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 4807-4812. PMID: 12682286, PMCID: PMC153637, DOI: 10.1073/pnas.0831079100.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsBase SequenceCell LineCell MembraneCOS CellsEndothelium, VascularEstrogen Receptor alphaGenes, ReporterGenetic VariationHumansNitric Oxide SynthaseNitric Oxide Synthase Type IIIProtein Processing, Post-TranslationalReceptors, EstrogenRecombinant ProteinsRNA, MessengerSubcellular FractionsTranscriptional ActivationTransfectionConceptsPlasma membranePalmitoylation-dependent mannerPlasma membrane localizationInhibition of palmitoylationFull-length ER alphaReporter gene transactivationCOS-7 cellsEndothelial cell proteinsMembrane localizationAlternative splicingEstrogen receptor α variantsOestrogen receptor-alpha variantsN-terminusHuman endothelial cellsCell proteinsER46Synthase pathwayAcid labelingHy926 cellsNonendothelial cellsENOS activationENOS phosphorylationCellsEndothelial cellsMembrane
2002
Src Kinase Mediates Phosphatidylinositol 3-Kinase/Akt-dependent Rapid Endothelial Nitric-oxide Synthase Activation by Estrogen*
Haynes MP, Li L, Sinha D, Russell KS, Hisamoto K, Baron R, Collinge M, Sessa WC, Bender JR. Src Kinase Mediates Phosphatidylinositol 3-Kinase/Akt-dependent Rapid Endothelial Nitric-oxide Synthase Activation by Estrogen*. Journal Of Biological Chemistry 2002, 278: 2118-2123. PMID: 12431978, DOI: 10.1074/jbc.m210828200.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsBlotting, WesternCell LineCells, CulturedElectrophoresis, Polyacrylamide GelEndoplasmic ReticulumEndothelium, VascularEnzyme ActivationEnzyme InhibitorsEstrogensHumansMiceMutationNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IINitric Oxide Synthase Type IIIPhosphatidylinositol 3-KinasesPhosphorylationPrecipitin TestsProtein BindingProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptors, EstrogenSignal TransductionSrc-Family KinasesTime FactorsTransfectionTyrosineConceptsC-SrcPI3-kinaseAkt phosphorylationSrc kinaseUpstream regulatorKinase-dead c-SrcC-Src associationActive c-SrcC-Src phosphorylationMurine embryonic fibroblastsBasal Akt phosphorylationC-Src expressionCritical upstream regulatorEndothelial nitric oxide synthaseSrc familyActive AktEmbryonic fibroblastsComplex formation resultsEndothelial cellsHuman endothelial cellsAkt activationPhosphorylationKinaseAktPhosphatidylinositolRapid vascular cell responses to estrogen and membrane receptors
Haynes MP, Li L, Russell KS, Bender JR. Rapid vascular cell responses to estrogen and membrane receptors. Vascular Pharmacology 2002, 38: 99-108. PMID: 12379956, DOI: 10.1016/s0306-3623(02)00133-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MembraneEndothelium, VascularEstrogensHumansMuscle, Smooth, VascularReceptors, EstrogenSignal TransductionConceptsSignal transduction cascadeTransduction cascadeG protein-coupled receptorsMembrane-localized estrogen receptorsEstrogen receptorTranscription factorsMAP kinaseApparent coronary heart diseaseRapid consequencesCellular responsesCellular localizationMembrane receptorsCoronary heart diseaseAge-matched malesEffects of estrogenVascular cell responsesSmooth muscle cellsVariety of estrogenVascular cellsMuscle cellsComplex formationPremenopausal womenHeart diseaseVascular wallMarked gender differences
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 involvementMolecular mechanisms of estrogen actions on the vasculature
Haynes M, Russell K, Bender J. Molecular mechanisms of estrogen actions on the vasculature. Journal Of Nuclear Cardiology 2000, 7: 500-508. PMID: 11083200, DOI: 10.1067/mnc.2000.109958.Peer-Reviewed Original ResearchConceptsSelective estrogen receptor modulatorsEstrogen receptor modulatorsReceptor modulatorsPlaque-destabilizing effectsEffects of estrogenClinical atherosclerosisPharmacologic therapyVascular responsesMolecular mechanismsEstrogen actionVascular diseaseAnimal studiesBeneficial responseCardiovascular systemEstrogenVascular structuresAdverse effectsVasculatureSpecific pathwaysBroad spectrumAtherosclerosisHistologicInjuryTherapyDiseaseHuman 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 effects
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