2025
Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases
Rubinelli L, Manzo O, Sungho J, Del Gaudio I, Bareja R, Marino A, Palikhe S, Di Mauro V, Bucci M, Falcone D, Elemento O, Ersoy B, Diano S, Sasset L, Di Lorenzo A. Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases. Nature Communications 2025, 16: 1968. PMID: 40000621, PMCID: PMC11862206, DOI: 10.1038/s41467-025-56869-9.Peer-Reviewed Original ResearchConceptsNogo-BEndothelial dysfunctionHFD miceCardiometabolic diseasesSphingolipid signalingDevelopment of therapeutic strategiesBioactive sphingolipidsCeramide degradationSphingosine-1-phosphateHepatic glucose productionIn vivo evidenceEndothelial cellsEndothelial specific deletionCeramideBiosynthesisHigh-fat dietPathological implicationsSphingolipidsGlucose productionHFDIn vivoMale miceMetabolic dysfunctionTherapeutic strategiesMetabolic disorders
2022
N‐Acyl Amides from Neisseria meningitidis and Their Role in Sphingosine Receptor Signaling
Cho W, York AG, Wang R, Wyche TP, Piizzi G, Flavell RA, Crawford JM. N‐Acyl Amides from Neisseria meningitidis and Their Role in Sphingosine Receptor Signaling. ChemBioChem 2022, 23: e202200490-e202200490. PMID: 36112057, PMCID: PMC9762135, DOI: 10.1002/cbic.202200490.Peer-Reviewed Original ResearchMeSH KeywordsAmidesAnimalsCattleHumansMammalsNeisseria meningitidisSignal TransductionSphingosineVirulenceConceptsN-acyl amidesGram-negative opportunistic pathogenNeisseria meningitidisHuman-associated bacteriaBlood-brain barrierBioactive small moleculesInterleukin-10 signalingMacrophage cell typesN-acyltransferaseInterleukin-17AG proteinsHuman diseasesT cellsReceptor signalingCell typesImmune systemHigh mortalityHuman microbiotaRepresentative membersOpportunistic pathogenMeningitidisSignalingSmall moleculesN.Meningitis
2020
Selective expression of claudin-5 in thymic endothelial cells regulates the blood–thymus barrier and T-cell export
Nagatake T, Zhao Y, Ito T, Itoh M, Kometani K, Furuse M, Saika A, Node E, Kunisawa J, Minato N, Hamazaki Y. Selective expression of claudin-5 in thymic endothelial cells regulates the blood–thymus barrier and T-cell export. International Immunology 2020, 33: 171-182. PMID: 33038259, PMCID: PMC7936066, DOI: 10.1093/intimm/dxaa069.Peer-Reviewed Original ResearchConceptsCortico-medullary junctionBlood-thymus barrierEndothelial cellsClaudin-5Biotin tracerCortical vasculatureBlood-borne moleculesCentral tolerance inductionT cell exportThymic endothelial cellsEC cell linesSphingosine-1-PhosphateT cell developmentDendritic cellsThymic cortexTolerance inductionTrans-endothelial resistanceThymocyte egressVascular permeabilityThymic microenvironmentMature thymocytesMedullaBlood circulationSelective expressionMedullary parenchyma
2019
Activation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy
Wang W, Xiang P, Chew W, Torta F, Bandla A, Lopez V, Seow W, Lam B, Chang J, Wong P, Chayaburakul K, Ong W, Wenk M, Sundar R, Herr D. Activation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy. Journal Of Biological Chemistry 2019, 295: 1143-1152. PMID: 31882542, PMCID: PMC6983853, DOI: 10.1074/jbc.ra119.011699.Peer-Reviewed Original ResearchConceptsChemotherapy-induced neuropathyRat model of cisplatin-induced neuropathyManagement of chemotherapy-induced neuropathyTreatment of chemotherapy-induced neuropathyS1P speciesEffects of platinum-based drugsCisplatin-induced neuropathyPlasma S1P levelsDorsal root gangliaS1P<sub>1-5</sub>Human cancer patientsActivating stress-response proteinsPlatinum-based drugsReduced allodyniaSphingosine 1-phosphateOxaliplatin treatmentPharmacodynamic analysisPeripheral neuropathyRat modelS1PCancer patientsLipid-based signaling moleculesS1P concentrationsS1P levelsCYM-5478Reciprocal Multifaceted Interaction Between HDL (High-Density Lipoprotein) and Myocardial Infarction
Sposito A, de Lima-Junior J, Moura F, Barreto J, Bonilha I, Santana M, Virginio V, Sun L, Carvalho L, Soares A, Nadruz W, Feinstein S, Nofer J, Zanotti I, Kontush A, Remaley A. Reciprocal Multifaceted Interaction Between HDL (High-Density Lipoprotein) and Myocardial Infarction. Arteriosclerosis Thrombosis And Vascular Biology 2019, 39: 1550-1564. PMID: 31189429, DOI: 10.1161/atvbaha.119.312880.Peer-Reviewed Original ResearchConceptsMyocardial infarctionHigh-density lipoproteinSphingosine-1-phosphateSpectrum of signaling pathwaysEndothelin-1Cardiac functionCardioprotective benefitsTherapeutic advancesClinical studiesIschemia/reperfusion injuryProinflammatory moleculesAnimal modelsInsulin sensitivityHDLInfarctionMitochondrial channelsFunctional changesOxidative stressSignaling pathway
2016
Lessons Learned From Trials Targeting Cytokine Pathways in Patients With Inflammatory Bowel Diseases
Abraham C, Dulai PS, Vermeire S, Sandborn WJ. Lessons Learned From Trials Targeting Cytokine Pathways in Patients With Inflammatory Bowel Diseases. Gastroenterology 2016, 152: 374-388.e4. PMID: 27780712, PMCID: PMC5287922, DOI: 10.1053/j.gastro.2016.10.018.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCytokinesHumansInflammatory Bowel DiseasesInterleukin-23Janus KinasesLysophospholipidsMolecular Targeted TherapyOligonucleotidesPiperidinesProtein Kinase InhibitorsPyrimidinesPyrrolesSignal TransductionSmad7 ProteinSphingosineTh17 CellsTransforming Growth Factor betaUstekinumabConceptsInflammatory bowel diseaseTreatment of IBDBowel diseaseAnti-inflammatory mechanismsSeverity of colitisInflamed intestinal tissueCell pathwaysBiomarkers of responseImmune system pathwaysIBD pathogenesisInterleukin-23Proinflammatory cytokinesFuture trialsEffects of agentsClinical trialsCytokine pathwaysPatient featuresIntestinal tissueDevelopment of therapeuticsIL23System pathwaysPathway moleculesFunction variantsSelection of therapeuticsTrials
2015
Tumor Necrosis Factor (TNF) Receptor-associated Factor (TRAF)-interacting Protein (TRIP) Negatively Regulates the TRAF2 Ubiquitin-dependent Pathway by Suppressing the TRAF2-Sphingosine 1-Phosphate (S1P) Interaction*
Park E, Choi S, Shin B, Yu J, Yu J, Hwang J, Yun H, Chung Y, Choi J, Choi Y, Rho J. Tumor Necrosis Factor (TNF) Receptor-associated Factor (TRAF)-interacting Protein (TRIP) Negatively Regulates the TRAF2 Ubiquitin-dependent Pathway by Suppressing the TRAF2-Sphingosine 1-Phosphate (S1P) Interaction*. Journal Of Biological Chemistry 2015, 290: 9660-9673. PMID: 25716317, PMCID: PMC4392267, DOI: 10.1074/jbc.m114.609685.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCytokinesGene ExpressionHEK293 CellsHeLa CellsHumansImmunoblottingLysineLysophospholipidsNF-kappa BProtein BindingReverse Transcriptase Polymerase Chain ReactionRNA InterferenceSignal TransductionSphingosineTNF Receptor-Associated Factor 2Tumor Necrosis Factor Receptor-Associated Peptides and ProteinsTumor Necrosis Factor-alphaUbiquitinUbiquitinationConceptsTRAF-interacting proteinTNFR-associated factor 2TNF-induced inflammatory responseE3 ubiquitin (Ub) ligase activityTNF receptor signaling complexE3 Ub ligasesUbiquitin-dependent pathwayCellular binding partnersMitogen-activated protein kinase activationNF-kB activationNegative regulator of proinflammatory cytokine productionProtein kinase activityDownstream signaling cascadesCell proliferationTNF receptorsUb ligasesTNFR signaling pathwayDown-regulation of proinflammatory cytokine productionLigase activityRING domainTumor necrosis factorProinflammatory cytokine productionAdaptor moleculeCellular processesRegulation of proinflammatory cytokine production
2014
Integrated metabolomic profiling of hepatocellular carcinoma in hepatitis C cirrhosis through GC/MS and UPLC/MS‐MS
Fitian A, Nelson D, Liu C, Xu Y, Ararat M, Cabrera R. Integrated metabolomic profiling of hepatocellular carcinoma in hepatitis C cirrhosis through GC/MS and UPLC/MS‐MS. Liver International 2014, 34: 1428-1444. PMID: 24661807, PMCID: PMC4169337, DOI: 10.1111/liv.12541.Peer-Reviewed Original ResearchMeSH Keywords12-Hydroxy-5,8,10,14-eicosatetraenoic AcidAmino AcidsBile Acids and SaltsCarcinoma, HepatocellularChromatography, High Pressure LiquidDicarboxylic AcidsGas Chromatography-Mass SpectrometryHepatitis CHumansHydroxyeicosatetraenoic AcidsLiver CirrhosisLiver NeoplasmsMetabolomeMetabolomicsMultivariate AnalysisROC CurveSphingosineTandem Mass SpectrometryXanthineConceptsPresence of HCCHepatocellular carcinomaUPLC/MS-MSHCC patientsMetabolic alterationsHepatitis C cirrhosisBile acid metabolismHallmarks of HCCMetabolomic profilingAcid metabolismReceiver operator characteristic analysisOperator characteristic analysisGlobal metabolic alterationsMetabolic pathway disturbancesC cirrhosisHCV cirrhosisHepatitis CMetabolic disturbancesHCC developmentSerum metabolomeHealthy volunteersEicosanoid pathwayCirrhosisPathway disturbancesBile acidsGlucocerebrosidase 2 gene deletion rescues type 1 Gaucher disease
Mistry PK, Liu J, Sun L, Chuang WL, Yuen T, Yang R, Lu P, Zhang K, Li J, Keutzer J, Stachnik A, Mennone A, Boyer JL, Jain D, Brady RO, New MI, Zaidi M. Glucocerebrosidase 2 gene deletion rescues type 1 Gaucher disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 4934-4939. PMID: 24639522, PMCID: PMC3977292, DOI: 10.1073/pnas.1400768111.Peer-Reviewed Original ResearchConceptsType 1 Gaucher's diseaseBone formation defectGaucher diseaseSerum ceramide levelsBone formation rateEnzyme replacement therapyViable therapeutic targetGD1 patientsGBA deficiencyEnhanced elevationTherapeutic targetBone volumeMononuclear phagocytesClinical phenotypeGBA geneConditional deletionBioactive lipidsSphingosine levelsDevelopment of inhibitorsCeramide levelsLysosomal glucocerebrosidasePatientsNanomolar concentrationsDiseaseMice
2012
Fingolimod for Multiple Sclerosis
Pelletier D, Hafler DA. Fingolimod for Multiple Sclerosis. New England Journal Of Medicine 2012, 366: 339-347. PMID: 22276823, DOI: 10.1056/nejmct1101691.Peer-Reviewed Original Research
2011
Kinetic Analysis of Autotaxin Reveals Substrate-specific Catalytic Pathways and a Mechanism for Lysophosphatidic Acid Distribution*
Saunders LP, Cao W, Chang WC, Albright RA, Braddock DT, De La Cruz EM. Kinetic Analysis of Autotaxin Reveals Substrate-specific Catalytic Pathways and a Mechanism for Lysophosphatidic Acid Distribution*. Journal Of Biological Chemistry 2011, 286: 30130-30141. PMID: 21719699, PMCID: PMC3191052, DOI: 10.1074/jbc.m111.246884.Peer-Reviewed Original ResearchConceptsLysophosphatidic acidSecreted lysophospholipase DThr-210Synthase cycleVivo substrateSubstrate bindingQuantitative physiological modelsSignaling cascadesPosition 210LPA signalingCatalytic threonineFluorescent lipidLysophospholipase DCancer metastasisSlow catalysisCatalytic pathwayDiazol-4PathwayAutotaxinProduct releaseBindsLPA synthesisFS-3Acid distributionBioactive form
2010
Prevention of Diabetes by FTY720-Mediated Stabilization of Peri-Islet Tertiary Lymphoid Organs
Penaranda C, Tang Q, Ruddle NH, Bluestone JA. Prevention of Diabetes by FTY720-Mediated Stabilization of Peri-Islet Tertiary Lymphoid Organs. Diabetes 2010, 59: 1461-1468. PMID: 20299465, PMCID: PMC2874707, DOI: 10.2337/db09-1129.Peer-Reviewed Original ResearchConceptsTertiary lymphoid organsPancreatic lymph nodesNOD miceLymph nodesDiabetes developmentDiabetic miceLymphoid organsSpontaneous type 1 diabetesB cell compartmentalizationExit of lymphocytesNonobese diabetic (NOD) miceAge-matched miceDevelopment of diabetesPrevention of diabetesNaive T cellsType 1 diabetesB cell compartmentWeeks of ageSignificant insulitisIslet destructionTreatment withdrawalAutoimmune destructionClinical scoresAccelerated diseaseDisease progressionA Role for S1P and S1P1 in Immature-B Cell Egress from Mouse Bone Marrow
Pereira JP, Cyster J, Xu Y. A Role for S1P and S1P1 in Immature-B Cell Egress from Mouse Bone Marrow. PLOS ONE 2010, 5: e9277. PMID: 20174580, PMCID: PMC2823786, DOI: 10.1371/journal.pone.0009277.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesBone MarrowBromodeoxyuridineCell MovementChemotaxis, LeukocyteFemaleFingolimod HydrochlorideImmunosuppressive AgentsLysophospholipidsMaleMiceMice, Inbred C57BLMice, Inbred CBAMice, KnockoutMice, TransgenicPrecursor Cells, B-LymphoidPropylene GlycolsReceptors, LysosphingolipidReverse Transcriptase Polymerase Chain ReactionSignal TransductionSphingosine
2009
T-bet–dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow
Jenne CN, Enders A, Rivera R, Watson SR, Bankovich AJ, Pereira JP, Xu Y, Roots CM, Beilke JN, Banerjee A, Reiner SL, Miller SA, Weinmann AS, Goodnow CC, Lanier LL, Cyster JG, Chun J. T-bet–dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow. Journal Of Experimental Medicine 2009, 206: 2469-2481. PMID: 19808259, PMCID: PMC2768857, DOI: 10.1084/jem.20090525.Peer-Reviewed Original Research
2007
Cross-talk between PDGF and S1P signalling elucidates the inhibitory effect and potential antifibrotic action of the immunomodulator FTY720 in activated HSC-cultures
Brunati A, Tibaldi E, Carraro A, Gringeri E, D’Amico F, Toninello A, Massimino M, Pagano M, Nalesso G, Cillo U. Cross-talk between PDGF and S1P signalling elucidates the inhibitory effect and potential antifibrotic action of the immunomodulator FTY720 in activated HSC-cultures. Biochimica Et Biophysica Acta 2007, 1783: 347-359. PMID: 18157950, DOI: 10.1016/j.bbamcr.2007.11.008.Peer-Reviewed Original ResearchConceptsPlatelet-derived growth factorHepatic stellate cellsTyrosine phosphorylation of PDGF receptorsSignaling pathwayPlatelet-derived growth factor stimulationCross-talkPlatelet-derived growth factor signaling pathwaysPhosphorylation of PDGF receptorS1P signalingStimulation of chemotaxisPlasma membranePhosphorylated formSphingosine-1-phosphateEffect of FTY720Activation of hepatic stellate cellsReceptor-independent wayFTY720 phosphorylationDevelopment of hepatic fibrosisS1P signaling pathwayPDGF receptorsCell typesCell proliferationPhosphorylationAntifibrotic actionMechanism of actionPromotion of Lymphocyte Egress into Blood and Lymph by Distinct Sources of Sphingosine-1-Phosphate
Pappu R, Schwab SR, Cornelissen I, Pereira J, Regard JB, Xu Y, Camerer E, Zheng YW, Huang Y, Cyster JG, Coughlin SR. Promotion of Lymphocyte Egress into Blood and Lymph by Distinct Sources of Sphingosine-1-Phosphate. Science 2007, 316: 295-298. PMID: 17363629, DOI: 10.1126/science.1139221.Peer-Reviewed Original Research
2005
Lymphocyte Sequestration Through S1P Lyase Inhibition and Disruption of S1P Gradients
Schwab SR, Pereira J, Matloubian M, Xu Y, Huang Y, Cyster JG. Lymphocyte Sequestration Through S1P Lyase Inhibition and Disruption of S1P Gradients. Science 2005, 309: 1735-1739. PMID: 16151014, DOI: 10.1126/science.1113640.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde-LyasesAnimalsB-LymphocytesChemotaxis, LeukocyteEnzyme InhibitorsFood Coloring AgentsHematopoietic Stem CellsImidazolesImmunosuppressive AgentsLymphLymph NodesLymphoid TissueLymphopeniaLysophospholipidsMiceMice, Inbred C57BLPyridoxineReceptors, LysosphingolipidRNA InterferenceSphingosineT-LymphocytesThymus GlandVitamin B 6
2004
Sphingosine-1-phosphate mediates calcium signaling in guinea pig enteroglial cells
Segura BJ, Zhang W, Xiao L, Turner D, Cowles RA, Logsdon C, Mulholland MW. Sphingosine-1-phosphate mediates calcium signaling in guinea pig enteroglial cells. Journal Of Surgical Research 2004, 116: 42-54. PMID: 14732348, DOI: 10.1016/s0022-4804(03)00281-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological TransportCalciumCalcium ChannelsCalcium SignalingCulture TechniquesDose-Response Relationship, DrugDrug Administration ScheduleEnzyme ActivationGuinea PigsImmunohistochemistryInositol 1,4,5-Trisphosphate ReceptorsLysophospholipidsMyenteric PlexusNeurogliaPertussis ToxinReceptors, Cytoplasmic and NuclearReceptors, G-Protein-CoupledRNA, MessengerSphingolipidsSphingosineType C PhospholipasesConceptsSignal transduction cascadeEnteric nervous systemEnteric gliaLipid lysophosphatidic acidMajor cell typesRT-PCR analysisTransduction cascadeGlial cellsNervous systemEDG-1Trisphosphate receptorCalcium signalingLysophosphatidic acidCell typesExtracellular receptorsPhospholipase CEdg-3Enteric glial cellsBioactive lipidsEdg-5S1P effectsSphingomyelin metabolitesDigestive activityImmunocytochemical analysisEnteric neurons
2002
Prolonged Activation of Ca2+-Activated K+Current Contributes to the Long-Lasting Refractory Period ofAplysia Bag Cell Neurons
Zhang Y, Magoski NS, Kaczmarek LK. Prolonged Activation of Ca2+-Activated K+Current Contributes to the Long-Lasting Refractory Period ofAplysia Bag Cell Neurons. Journal Of Neuroscience 2002, 22: 10134-10141. PMID: 12451114, PMCID: PMC6758731, DOI: 10.1523/jneurosci.22-23-10134.2002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAplysiaCalciumCells, CulturedElectric StimulationEnzyme ActivatorsEnzyme InhibitorsLarge-Conductance Calcium-Activated Potassium ChannelsNeural InhibitionNeuronsPatch-Clamp TechniquesPhloretinPotassiumPotassium Channel BlockersPotassium Channels, Calcium-ActivatedProtein Kinase CRefractory Period, ElectrophysiologicalSphingosineTetradecanoylphorbol AcetateConceptsBag cell neuronsCell neuronsRefractory periodBK currentsProtein kinase COnset of afterdischargeBK channel activityApplication of phloretinBK channel activatorsProlonged refractory periodAbility of stimulationRole of Ca2Blocker paxillinePharmacological characteristicsChannel activatorIntracellular Ca2Prolonged increaseOutward currentsInhibitor of PKCAfterdischargesNeuronsAdditional stimulationProlonged activationActivator of PKCChannel activitySphingosine-1-phosphate stimulates human Caco-2 intestinal epithelial proliferation via p38 activation and activates ERK by an independent mechanism
THAMILSELVAN V, LI W, SUMPIO BE, BASSON MD. Sphingosine-1-phosphate stimulates human Caco-2 intestinal epithelial proliferation via p38 activation and activates ERK by an independent mechanism. In Vitro Cellular & Developmental Biology - Animal 2002, 38: 246-253. PMID: 12197778, DOI: 10.1290/1071-2690(2002)038<0246:spshci>2.0.co;2.Peer-Reviewed Original ResearchConceptsExtracellular signal-regulated kinases 1Mitogen-activated protein kinaseMAP kinase kinaseCaco-2 proliferationMAPK activationHuman intestinal epithelial proliferationP38 activationCell typesSignal-regulated kinases 1Role of ERKMitogenic effectCaco-2 intestinal epithelial cellsIntracellular second messengerMEK inhibitionP38 MAPK activationCancer cell invasionKinase kinaseHuman Caco-2 intestinal epithelial cellsProtein kinaseStimulation of proliferationCell motilityIntestinal epithelial cell proliferationInhibitor PD98059ERK2ERK activation
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