Featured Publications
Alcohol-induced Hsp90 acetylation is a novel driver of liver sinusoidal endothelial dysfunction and alcohol-related liver disease
Yang Y, Sangwung P, Kondo R, Jung Y, McConnell MJ, Jeong J, Utsumi T, Sessa WC, Iwakiri Y. Alcohol-induced Hsp90 acetylation is a novel driver of liver sinusoidal endothelial dysfunction and alcohol-related liver disease. Journal Of Hepatology 2021, 75: 377-386. PMID: 33675874, PMCID: PMC8292196, DOI: 10.1016/j.jhep.2021.02.028.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseAlcohol-induced liver injuryLiver sinusoidal endothelial cellsAlcohol-related liver diseaseLiver injuryLSEC dysfunctionHsp90 acetylationNO productionHistone deacetylase 6Liver diseaseTherapeutic strategiesHeat shock protein 90 (Hsp90) acetylationLiver sinusoidal endothelial dysfunctionSinusoidal endothelial cell dysfunctionMouse liver sinusoidal endothelial cellsEndothelial cell dysfunctionNitric oxide synthaseEthanol-fed miceSinusoidal endothelial dysfunctionPotential therapeutic approachPotential therapeutic strategyNitric oxide productionNew therapeutic strategiesSinusoidal endothelial cellsAcetylation of Hsp90
2012
Proteomic Identification of S-Nitrosylated Golgi Proteins: New Insights into Endothelial Cell Regulation by eNOS-Derived NO
Sangwung P, Greco TM, Wang Y, Ischiropoulos H, Sessa WC, Iwakiri Y. Proteomic Identification of S-Nitrosylated Golgi Proteins: New Insights into Endothelial Cell Regulation by eNOS-Derived NO. PLOS ONE 2012, 7: e31564. PMID: 22363674, PMCID: PMC3283662, DOI: 10.1371/journal.pone.0031564.Peer-Reviewed Original ResearchConceptsGolgi proteinsGolgi phosphoprotein 3S-nitrosylationGolgi apparatusCysteine residuesSelective S-nitrosylationPlasma membrane caveolaeGolgi/endoplasmic reticulumProtein S-nitrosylationTarget cysteine residuesEndothelial cellsEndothelial nitric oxide synthaseMembrane caveolaeEndothelial cell lysatesProteomic identificationEndothelial cell regulationGolgi membranesBiotin switchCell regulationEndoplasmic reticulumENOS stimulationCell lysatesProteinImmunoprecipitationWestern blot
2011
S-nitrosylation of proteins: A new insight into endothelial cell function regulated by eNOS-derived NO
Iwakiri Y. S-nitrosylation of proteins: A new insight into endothelial cell function regulated by eNOS-derived NO. Nitric Oxide 2011, 25: 95-101. PMID: 21554971, PMCID: PMC3152628, DOI: 10.1016/j.niox.2011.04.014.BooksConceptsS-nitrosylationCellular processesGolgi apparatusIntracellular membrane domainPlasma membrane caveolaeEndothelial cell functionCell functionProtein traffickingMembrane caveolaeMembrane domainsCytoplasmic faceTarget proteinsCell cycleSignaling mechanismMessenger moleculesCell growthRedox stateProteinNitric oxide synthaseIntracellular reactionsNew insightsEndothelial NOSNitric oxideEndothelial nitric oxide synthaseFamily members
2006
Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state
Abraldes JG, Iwakiri Y, Loureiro-Silva M, Haq O, Sessa WC, Groszmann RJ. Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state. AJP Gastrointestinal And Liver Physiology 2006, 290: g980-g987. PMID: 16603731, DOI: 10.1152/ajpgi.00336.2005.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAnimalsEndothelium, VascularHypertension, PortalIndolesIntestinal MucosaIntestinesJejunumMaleMicrocirculationNeovascularization, PathologicNitric Oxide SynthaseNitric Oxide Synthase Type IIIPortal PressurePyrrolesRatsUp-RegulationVascular Endothelial Growth Factor AVasodilationConceptsEndothelial NO synthasePortal hypertensionPortal vein ligationHyperdynamic circulationPortal pressureENOS expressionMild increaseVEGF expressionUpregulates Vascular Endothelial Growth FactorNitric oxideEndothelial nitric oxide synthaseAdvanced portal hypertensionVascular endothelial growth factorNitric oxide synthaseEndothelial growth factorInhibition of VEGFHyperdynamic statePVL ratsSplanchnic hemodynamicsIntestinal microcirculationPortosystemic shuntingVein ligationSham ratsOxide synthaseNO synthase
2004
Targeting of Endothelial Nitric-oxide Synthase to the Cytoplasmic Face of the Golgi Complex or Plasma Membrane Regulates Akt- Versus Calcium-dependent Mechanisms for Nitric Oxide Release*
Fulton D, Babbitt R, Zoellner S, Fontana J, Acevedo L, McCabe TJ, Iwakiri Y, Sessa WC. Targeting of Endothelial Nitric-oxide Synthase to the Cytoplasmic Face of the Golgi Complex or Plasma Membrane Regulates Akt- Versus Calcium-dependent Mechanisms for Nitric Oxide Release*. Journal Of Biological Chemistry 2004, 279: 30349-30357. PMID: 15136572, DOI: 10.1074/jbc.m402155200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCalciumCalmodulinCell MembraneCOS CellsCysteineCytoplasmEndothelium, VascularGolgi ApparatusHumansMicroscopy, FluorescenceMyristic AcidsNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIPalmitic AcidsPhosphorylationProtein Serine-Threonine KinasesProtein Structure, TertiaryProto-Oncogene ProteinsProto-Oncogene Proteins c-aktSerineTransfectionUmbilical VeinsConceptsPlasma membraneGolgi complexAkt-dependent phosphorylationEndothelial nitricoxide synthasePool of enzymesCalcium-dependent activationCytoplasmic faceGolgi membranesENOS constructMembrane versionFusion proteinCytoplasmic aspectFunctional rolePhosphorylationENOS activationHeterogeneous localizationMembraneCalcium fluxCalcium-dependent mechanismSynthaseActivationEndothelial nitric oxide synthaseFurther activationComplexesNitricoxide synthase
2003
Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice
Gratton J, Lin MI, Yu J, Weiss ED, Jiang ZL, Fairchild TA, Iwakiri Y, Groszmann R, Claffey KP, Cheng Y, Sessa WC. Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice. Cancer Cell 2003, 4: 31-39. PMID: 12892711, DOI: 10.1016/s1535-6108(03)00168-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCapillary PermeabilityCarcinoma, HepatocellularCarcinoma, Lewis LungCaveolin 1CaveolinsDisease ProgressionEndothelium, VascularEnzyme InhibitorsLiver Neoplasms, ExperimentalLung NeoplasmsMaleMiceMice, Inbred C57BLMice, KnockoutMice, NudeNeovascularization, PhysiologicNitric Oxide SynthaseNitric Oxide Synthase Type IINitric Oxide Synthase Type IIIPeptide FragmentsVascular Endothelial Growth Factor AConceptsEndothelial nitric oxide synthaseTumor progressionAntitumor actionDelays tumor progressionENOS knockout miceNitric oxide synthaseTumor blood vesselsTumor microvascular permeabilityOxide synthaseMicrovascular permeabilityKnockout miceAntiangiogenic effectsTumor vasculatureCell-permeable peptideMicrovascular hyperpermeabilityNovel targetNormal vasculatureHyperpermeabilityBlood vesselsCavtratinAntitumor therapyProgressionMiceSelective inhibitionVasculature
2002
Phosphorylation of eNOS initiates excessive NO production in early phases of portal hypertension
Iwakiri Y, Tsai MH, McCabe TJ, Gratton JP, Fulton D, Groszmann RJ, Sessa WC. Phosphorylation of eNOS initiates excessive NO production in early phases of portal hypertension. AJP Heart And Circulatory Physiology 2002, 282: h2084-h2090. PMID: 12003815, DOI: 10.1152/ajpheart.00675.2001.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic alpha-1 Receptor AgonistsAndrostadienesAnimalsEnzyme InhibitorsHypertension, PortalLigationMaleMesenteric Artery, SuperiorMethoxamineNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIOmega-N-MethylargininePhosphorylationPortal VeinProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktRatsRats, Sprague-DawleyVasoconstrictor AgentsWortmanninConceptsEndothelial nitric oxide synthasePortal vein ligationPhosphorylation of eNOSMesenteric arterial bedPortal hypertensionPVL groupArterial bedNO productionMale Sprague-Dawley ratsEarly portal hypertensionMonomethyl-L-arginineNitric oxide synthaseSprague-Dawley ratsExcessive NO productionG protein-coupled receptorsVivo perfusion studiesPVL ratsProtein-coupled receptorsPerfusion pressureSham groupVein ligationENOS expressionOxide synthaseReduced responsivenessKinase/Akt pathway
2001
The phosphorylation of endothelial nitric oxide synthase by Akt increases nitric oxide production in early portal hypertension
Iwakiri Y, Tsai M, Sessa W, Groszmann R. The phosphorylation of endothelial nitric oxide synthase by Akt increases nitric oxide production in early portal hypertension. Gastroenterology 2001, 120: a9. DOI: 10.1016/s0016-5085(08)80044-3.Peer-Reviewed Original ResearchThe phosphorylation of endothelial nitric oxide synthase by Akt increases nitric oxide production in early portal hypertension
IWAKIRI Y, TSAI M, SESSA W, GROSZMANN R. The phosphorylation of endothelial nitric oxide synthase by Akt increases nitric oxide production in early portal hypertension. Gastroenterology 2001, 120: a9-a9. DOI: 10.1016/s0016-5085(01)80044-5.Peer-Reviewed Original Research