2018
T cell LFA-1-induced proinflammatory mRNA stabilization is mediated by the p38 pathway kinase MK2 in a process regulated by hnRNPs C, H1 and K
Rao GK, Wong A, Collinge M, Sarhan J, Yarovinsky TO, Ramgolam VS, Gaestel M, Pardi R, Bender JR. T cell LFA-1-induced proinflammatory mRNA stabilization is mediated by the p38 pathway kinase MK2 in a process regulated by hnRNPs C, H1 and K. PLOS ONE 2018, 13: e0201103. PMID: 30048492, PMCID: PMC6065199, DOI: 10.1371/journal.pone.0201103.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Culture TechniquesCytoplasmELAV-Like Protein 1Heterogeneous-Nuclear RibonucleoproteinsHumansIntracellular Signaling Peptides and ProteinsJurkat CellsLymphocyte Function-Associated Antigen-1Mice, Inbred C57BLMice, KnockoutProtein Serine-Threonine KinasesProteomeRNA StabilityRNA, MessengerSignal TransductionT-LymphocytesConceptsKinase MK2Β2-integrin lymphocyte function-associated antigen-1AU-rich elementsLymphocyte function-associated antigen-1Integrin lymphocyte function-associated antigen-1HuR localizationProtein HuR.Key regulatorMRNA stabilizationCritical activatorCytoplasmic translocationHuR activitySequential activationHuRIntricate processFunction-associated antigen-1MRNAEngagement resultsMK2Antigen 1H1ActivationHnRNPsHuR.Transcripts
2016
Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1&bgr; Production
Ceneri N, Zhao L, Young BD, Healy A, Coskun S, Vasavada H, Yarovinsky TO, Ike K, Pardi R, Qin L, Qin L, Tellides G, Hirschi K, Meadows J, Soufer R, Chun HJ, Sadeghi M, Bender JR, Morrison AR. Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1&bgr; Production. Arteriosclerosis Thrombosis And Vascular Biology 2016, 37: 328-340. PMID: 27834690, PMCID: PMC5269510, DOI: 10.1161/atvbaha.116.308507.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAortic DiseasesApolipoproteins EAtherosclerosisCells, CulturedCoronary Artery DiseaseCoronary VesselsFemaleGenetic Predisposition to DiseaseHumansInflammation MediatorsInterleukin 1 Receptor Antagonist ProteinInterleukin-1betaMacrophagesMaleMice, Inbred C57BLMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleNeuropeptidesPhenotypePlaque, AtheroscleroticPrognosisRac GTP-Binding ProteinsRac1 GTP-Binding ProteinSignal TransductionTransfectionUp-RegulationVascular CalcificationConceptsCoronary calcium burdenIL-1β expressionCalcium burdenSerum IL-1β levelsElevated IL-1βIL-1β levelsCoronary artery diseaseInterleukin-1β expressionCalcified coronary arteryCardiovascular deathCardiovascular eventsArtery diseaseIndependent predictorsClinical outcomesVascular calcificationCoronary arteryIL-1βPlaque calciumAtherosclerotic calcificationExperimental atherogenesisInflammatory regulatorsMacrophage interleukinAtherosclerotic plaquesTherapeutic targetProgressive calcification
2014
Ceramide-Activated Phosphatase Mediates Fatty Acid–Induced Endothelial VEGF Resistance and Impaired Angiogenesis
Mehra VC, Jackson E, Zhang XM, Jiang XC, Dobrucki LW, Yu J, Bernatchez P, Sinusas AJ, Shulman GI, Sessa WC, Yarovinsky TO, Bender JR. Ceramide-Activated Phosphatase Mediates Fatty Acid–Induced Endothelial VEGF Resistance and Impaired Angiogenesis. American Journal Of Pathology 2014, 184: 1562-1576. PMID: 24606881, PMCID: PMC4005977, DOI: 10.1016/j.ajpath.2014.01.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaArteriesCattleCeramidesDiet, High-FatEndothelial CellsEnzyme ActivationExtracellular Signal-Regulated MAP KinasesHaploinsufficiencyHindlimbHumansIschemiaMice, Inbred C57BLNeovascularization, PhysiologicNitric OxideNitric Oxide Synthase Type IIIPalmitic AcidPhosphorylationProtein Phosphatase 2Proto-Oncogene Proteins c-aktSerine C-PalmitoyltransferaseSignal TransductionVascular Endothelial Growth Factor AConceptsPP2A inhibitor okadaic acidProtein phosphatase 2AInhibitor okadaic acidVEGF-induced signalingSerine palmitoyltransferase inhibitor myriocinDe novo ceramide synthesisPhosphatase 2AENOS agonistsNovo ceramide synthesisPalmitic acidAngiogenic responsePotential molecular targetsOkadaic acidEndothelial cellsEarly speciesEndothelial cell responsesCord formationVEGFR2 phosphorylationSaturated free fatty acidVEGF resistanceCeramide synthesisResistance mechanismsMolecular targetsVascular homeostasisPhosphorylationEndothelial 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
2011
Splice isoform estrogen receptors as integral transmembrane proteins
Kim KH, Toomre D, Bender JR. Splice isoform estrogen receptors as integral transmembrane proteins. Molecular Biology Of The Cell 2011, 22: 4415-4423. PMID: 21937726, PMCID: PMC3216666, DOI: 10.1091/mbc.e11-05-0416.Peer-Reviewed Original ResearchConceptsSplice isoformsTotal internal reflection fluorescence microscopySteroid hormone receptorsIntegral transmembrane proteinN-terminal ectodomainReflection fluorescence microscopyHormone receptorsTransmembrane proteinPlasma membraneProtein structureHuman endothelial cellsLigand engagementPotential novel therapeutic targetER46Fluorescence microscopyNovel therapeutic targetEcliptic pHluorinActivation signalsEndothelial nitric oxide synthase activationEstrogen receptor αENOS activationReceptor αIsoformsTherapeutic targetNitric oxide synthase activation
2010
T Cell LFA-1 Engagement Induces HuR-Dependent Cytokine mRNA Stabilization through a Vav-1, Rac1/2, p38MAPK and MKK3 Signaling Cascade
Ramgolam VS, DeGregorio SD, Rao GK, Collinge M, Subaran SS, Markovic-Plese S, Pardi R, Bender JR. T Cell LFA-1 Engagement Induces HuR-Dependent Cytokine mRNA Stabilization through a Vav-1, Rac1/2, p38MAPK and MKK3 Signaling Cascade. PLOS ONE 2010, 5: e14450. PMID: 21206905, PMCID: PMC3012057, DOI: 10.1371/journal.pone.0014450.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, SurfaceCytokinesELAV ProteinsELAV-Like Protein 1GTP PhosphohydrolasesHumansIntegrinsInterferon-gammaLymphocyte Function-Associated Antigen-1MAP Kinase Kinase 3MiceMice, Inbred C57BLNeuropeptidesP38 Mitogen-Activated Protein KinasesProto-Oncogene Proteins c-vavRac GTP-Binding ProteinsRac1 GTP-Binding ProteinRNA-Binding ProteinsSignal TransductionT-LymphocytesTumor Necrosis Factor-alpha
2009
Membrane-initiated actions of estrogen on the endothelium
Kim KH, Bender JR. Membrane-initiated actions of estrogen on the endothelium. Molecular And Cellular Endocrinology 2009, 308: 3-8. PMID: 19549586, PMCID: PMC2701909, DOI: 10.1016/j.mce.2009.03.025.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseNumerous signal transduction cascadesSignal transduction cascadeNitric oxideEndothelial cellsNon-genomic actionsAction of estrogenNitric oxide synthaseCaveolar membranesEstrogen receptor alphaTransduction cascadeC-SrcN-terminusShort isoformHuman endothelial cellsRapid activationProduct nitric oxideVascular studiesOxide synthaseReceptor alphaEstrogenVascular structuresER46Favorable effectCritical role
2008
Rac, PAK, and eNOS ACTion
Rao GK, Bender JR. Rac, PAK, and eNOS ACTion. Circulation Research 2008, 103: 328-330. PMID: 18703782, DOI: 10.1161/circresaha.108.182238.Peer-Reviewed Original ResearchVascular 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 responsePathophysiology of leukocyte–tissue interactions
Molteni R, Fabbri M, Bender JR, Pardi R. Pathophysiology of leukocyte–tissue interactions. Current Opinion In Cell Biology 2006, 18: 491-498. PMID: 16904306, DOI: 10.1016/j.ceb.2006.08.001.Peer-Reviewed Original Research
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
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 activationPhosphorylationKinaseAktPhosphatidylinositolIntegrin‐dependent regulation of gene expression in leukocytes
Rossetti G, Collinge M, Molteni R, Bender J, Pardi R. Integrin‐dependent regulation of gene expression in leukocytes. Immunological Reviews 2002, 186: 189-207. PMID: 12234372, DOI: 10.1034/j.1600-065x.2002.18616.x.Peer-Reviewed Original ResearchConceptsIntegrin engagementGene expression regulationIntegrin-dependent regulationCell cycle restriction pointExpression regulationNumerous genesTransduce signalsMatrix degrading proteinsTranscriptional activationGenetic programTranscription modulatorsIntegrin-dependent mechanismJAK-STATsGene expressionIntercellular adhesionDegrading proteinsCell differentiationAlphaLbeta2 integrinJab-1Restriction pointMRNA transcriptsT cell differentiationEnvironmental stimuliPotent signalCell phenotypeRapid 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 involvementSimvastatin Modulates Cytokine-Mediated Endothelial Cell Adhesion Molecule Induction: Involvement of an Inhibitory G Protein
Sadeghi M, Collinge M, Pardi R, Bender J. Simvastatin Modulates Cytokine-Mediated Endothelial Cell Adhesion Molecule Induction: Involvement of an Inhibitory G Protein. The Journal Of Immunology 2000, 165: 2712-2718. PMID: 10946302, DOI: 10.4049/jimmunol.165.5.2712.Peer-Reviewed Original ResearchMeSH KeywordsAdjuvants, ImmunologicBiological TransportCell Adhesion MoleculesCells, CulturedCholesterolCytokinesDrug SynergismEndothelium, VascularE-SelectinGene Expression RegulationGTP-Binding Protein alpha Subunits, Gi-GoHumansHydroxymethylglutaryl-CoA Reductase InhibitorsIntercellular Adhesion Molecule-1Interleukin-1NF-kappa BRNA, MessengerSignal TransductionSimvastatinSodium FluorideUmbilical VeinsVascular Cell Adhesion Molecule-1ConceptsEffect of simvastatinCytokine-induced expressionIL-1Endothelial CAMsEndothelial cell adhesion molecules E-selectinNF-kappaBProinflammatory cytokines IL-1Cell adhesion molecules E-selectinAdhesion molecules E-selectinPotent immune modulatorG protein activator NaFCytokines IL-1G protein-coupled pathwayInhibitory G proteinCytokine-mediated activationSelectin mRNA levelsBasal toneProinflammatory cytokinesGialpha proteinsImmune modulatorsTNF-alphaICAM-1Pertussis toxinE-selectinEndothelial responseMolecular 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 effectsCD28 and LFA‐1 contribute to cyclosporin A‐resistant T cell growth by stabilizing the IL‐2 mRNA through distinct signaling pathways
Geginat J, Clissi B, Moro M, Dellabona P, Bender J, Pardi R. CD28 and LFA‐1 contribute to cyclosporin A‐resistant T cell growth by stabilizing the IL‐2 mRNA through distinct signaling pathways. European Journal Of Immunology 2000, 30: 1136-1144. PMID: 10760803, DOI: 10.1002/(sici)1521-4141(200004)30:4<1136::aid-immu1136>3.0.co;2-3.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDB7-2 AntigenCalcineurinCD28 AntigensCells, CulturedCyclosporineCytoskeletonDendritic CellsDNA-Binding ProteinsDrug SynergismHumansIntercellular Adhesion Molecule-1Interleukin-2Lymphocyte ActivationLymphocyte Function-Associated Antigen-1Membrane GlycoproteinsMitogen-Activated Protein KinasesNFATC Transcription FactorsNF-kappa BNuclear ProteinsPromoter Regions, GeneticProtein BindingRNA StabilityRNA, MessengerSignal TransductionSuperantigensT-LymphocytesTranscription FactorsConceptsIL-2 mRNALFA-1ICAM-1IL-2 dependentT cell proliferationSubsequent T cell proliferationCostimulatory molecule CD28TCR-induced proliferationSignaling pathwaysT cell growthIL-2 transcriptsGraft rejectionDendritic cellsIL-2Clinical transplantationT lymphocytesMolecule CD28Primary T lymphocytesNF-kappaBCD28Distinct signaling pathwaysLower transcriptional rateDifferent signaling pathwaysProtein kinase activationCell proliferation