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
AgRP neurons control feeding behaviour at cortical synapses via peripherally derived lysophospholipids
Endle H, Horta G, Stutz B, Muthuraman M, Tegeder I, Schreiber Y, Snodgrass IF, Gurke R, Liu ZW, Sestan-Pesa M, Radyushkin K, Streu N, Fan W, Baumgart J, Li Y, Kloss F, Groppa S, Opel N, Dannlowski U, Grabe HJ, Zipp F, Rácz B, Horvath TL, Nitsch R, Vogt J. AgRP neurons control feeding behaviour at cortical synapses via peripherally derived lysophospholipids. Nature Metabolism 2022, 4: 683-692. PMID: 35760867, PMCID: PMC9940119, DOI: 10.1038/s42255-022-00589-7.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsDiabetes Mellitus, Type 2Feeding BehaviorHumansHyperphagiaLysophospholipidsMiceNeuronsSynapsesConceptsFasting-induced hyperphagiaCortical excitabilityAgRP neuronsLysophosphatidic acidPeripheral metabolismHigher body mass indexFasting-induced elevationHypothalamic AgRP neuronsEffects of LPABody mass indexHigher cortical excitabilityBrain lipid levelsCentral nervous systemPrevalence of typeGlutamatergic transmissionHypothalamic agoutiMass indexOvernight fastingPeptide neuronsCortical synapsesLipid levelsFood intakeCerebrospinal fluidNervous systemPhospholipid levelsInhibition of the enzyme autotaxin reduces cortical excitability and ameliorates the outcome in stroke
Bitar L, Uphaus T, Thalman C, Muthuraman M, Gyr L, Ji H, Domingues M, Endle H, Groppa S, Steffen F, Koirala N, Fan W, Ibanez L, Heitsch L, Cruchaga C, Lee JM, Kloss F, Bittner S, Nitsch R, Zipp F, Vogt J. Inhibition of the enzyme autotaxin reduces cortical excitability and ameliorates the outcome in stroke. Science Translational Medicine 2022, 14: eabk0135. PMID: 35442704, DOI: 10.1126/scitranslmed.abk0135.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCortical ExcitabilityLysophospholipidsMiceMice, TransgenicPhosphoric Diester HydrolasesReceptors, Lysophosphatidic AcidStrokeConceptsStroke outcomeExperimental strokeGlutamatergic transmissionCortical excitabilityATX concentrationsAstrocyte-specific deletionDifferent time pointsStroke eventsPerisynaptic processesExcess glutamateTherapeutic approachesAnimal modelsTransgenic miceEnzyme autotaxinLPA signalingATX inhibitionPharmacological inhibitionStrokeTranslational potentialTime pointsSingle nucleotide polymorphismsAutotaxinOutcomesExcitabilityInhibitionMycobacterium tuberculosis encodes a YhhN family membrane protein with lysoplasmalogenase activity that protects against toxic host lysolipids
Jurkowitz MS, Azad AK, Monsma PC, Keiser TL, Kanyo J, Lam TT, Bell CE, Schlesinger LS. Mycobacterium tuberculosis encodes a YhhN family membrane protein with lysoplasmalogenase activity that protects against toxic host lysolipids. Journal Of Biological Chemistry 2022, 298: 101849. PMID: 35314194, PMCID: PMC9052158, DOI: 10.1016/j.jbc.2022.101849.Peer-Reviewed Original ResearchConceptsMembrane proteinsIntegral membrane proteinsVinyl ether bondHuman macrophagesPathogen Mycobacterium tuberculosisSn-1 positionSubclass of glycerophospholipidsGrowth advantageHost lipidsProteinFatty aldehydesMycobacterium smegmatisPhospholipase ASn-2 carbonSpheroplastsGlycerol backboneCell densityPlasmalogensCellsMycobacterium tuberculosisMacrophagesGenesOverexpressionLysoplasmenylcholinePLPC
2021
The lysophospholipid‐binding molecule CD1D is not required for the alloimmunization response to fresh or stored RBCs in mice despite RBC storage driving alterations in lysophospholipids
Medved J, Knott BM, Tarrah SN, Li AN, Shah N, Moscovich TC, Boscia AR, Salazar JE, Santhanakrishnan M, Hendrickson JE, Fu X, Zimring JC, Luckey CJ. The lysophospholipid‐binding molecule CD1D is not required for the alloimmunization response to fresh or stored RBCs in mice despite RBC storage driving alterations in lysophospholipids. Transfusion 2021, 61: 2169-2178. PMID: 34181769, PMCID: PMC8856511, DOI: 10.1111/trf.16554.Peer-Reviewed Original ResearchMeSH KeywordsAlarminsAnimalsAntibody SpecificityAntigens, CD1dBlood PreservationBlood TransfusionDuffy Blood-Group SystemErythrocytesFemaleImmunizationImmunoglobulin GImmunoglobulin MIsoantibodiesIsoantigensLysophospholipidsMaleMass SpectrometryMiceMice, Inbred StrainsMice, KnockoutMice, TransgenicMuramidaseOvalbuminReceptors, Cell SurfaceTransfusion ReactionConceptsCD1d-deficient miceCD1d deficiencyRBC alloimmunizationImmune activationNonclassical major histocompatibility complex class IWild-type control miceMajor histocompatibility complex class IHistocompatibility complex class IAdverse clinical consequencesSignificant adverse clinical consequencesLow baseline levelsRBC storageComplex class IHOD RBCsMolecule CD1dRBC transfusionWT miceControl miceImmune responseClinical consequencesMouse modelCD1dCD1d recognitionPolyclonal immunoglobulinsBaseline levels
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
2018
Examining heat treatment for stabilization of the lipidome
Koelmel J, Jones C, Ulmer C, Garrett T, Yost R, Schock T, Bowden J. Examining heat treatment for stabilization of the lipidome. Bioanalysis 2018, 10: 291-305. PMID: 29451398, DOI: 10.4155/bio-2017-0209.Peer-Reviewed Original ResearchConceptsLiquid chromatography-high resolution tandem mass spectrometryEnzymatic productResolution tandem mass spectrometryHigh-resolution tandem mass spectrometryLipid biomarker researchTandem mass spectrometryLipid-based biomarkersEnzyme stabilizerMass spectrometryLipid identificationHeat treatmentSample weighingFlash freezingHeat-treated samplesFlash-frozen samples
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
Lysophosphatidic acid generation by pulmonary NKT cell ENPP-2/autotaxin exacerbates hyperoxic lung injury
Nowak-Machen M, Lange M, Exley M, Wu S, Usheva A, Robson SC. Lysophosphatidic acid generation by pulmonary NKT cell ENPP-2/autotaxin exacerbates hyperoxic lung injury. Purinergic Signalling 2015, 11: 455-461. PMID: 26306905, PMCID: PMC4648788, DOI: 10.1007/s11302-015-9463-6.Peer-Reviewed Original ResearchConceptsPulmonary NKT cellsHyperoxic lung injuryNKT cellsLung injuryBrP-LPALysophosphatidic acidLPA levelsNKT cell numbersNKT cell activationCell numberLPA antagonistsLPA generationIll patientsSerum levelsOrgan oxygenationMouse modelClinical practiceCell activationInjuryEctonucleotide pyrophosphatase/phosphodiesterase 2HyperoxiaToxic effectsVivoPhosphodiesterase 2AutotaxinTumor 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
2013
Autotaxin–Lysophosphatidic Acid Signaling Axis Mediates Tumorigenesis and Development of Acquired Resistance to Sunitinib in Renal Cell Carcinoma
Su SC, Hu X, Kenney PA, Merrill MM, Babaian KN, Zhang XY, Maity T, Yang SF, Lin X, Wood CG. Autotaxin–Lysophosphatidic Acid Signaling Axis Mediates Tumorigenesis and Development of Acquired Resistance to Sunitinib in Renal Cell Carcinoma. Clinical Cancer Research 2013, 19: 6461-6472. PMID: 24122794, PMCID: PMC4191899, DOI: 10.1158/1078-0432.ccr-13-1284.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAnimalsCarcinogenesisCarcinoma, Renal CellCell Line, TumorCell MovementDrug Resistance, NeoplasmFemaleHuman Umbilical Vein Endothelial CellsHumansIndolesKidney NeoplasmsLysophospholipidsMiceMice, Inbred BALB CMice, NudeMicrovesselsNeoplasm InvasivenessPhosphoric Diester HydrolasesPyrrolesSignal TransductionSunitinibTranscriptomeTumor BurdenXenograft Model Antitumor AssaysConceptsLPA receptor 1Lysophosphatidic acidATX-LPAResistance of RCCRenal cell carcinomaGene expression profilesExtracellular lysophospholipase DRCC cell linesTarget genesCell motilityEndothelial cellsExpression profilesIntracellular signalingInvasion responsesRCC tumorigenesisHuman renal cell carcinomaSignaling AxisSensitivity of RCCRCC cellsFunctional roleXenograft modelAltered expressionRenal tumorigenesisCell carcinomaLysophospholipase DBee Venom Phospholipase A2 Induces a Primary Type 2 Response that Is Dependent on the Receptor ST2 and Confers Protective Immunity
Palm NW, Rosenstein RK, Yu S, Schenten DD, Florsheim E, Medzhitov R. Bee Venom Phospholipase A2 Induces a Primary Type 2 Response that Is Dependent on the Receptor ST2 and Confers Protective Immunity. Immunity 2013, 39: 976-985. PMID: 24210353, PMCID: PMC3852615, DOI: 10.1016/j.immuni.2013.10.006.Peer-Reviewed Original ResearchMeSH KeywordsAnaphylaxisAnimalsBee VenomsCrotalid VenomsGenes, ReporterImmunity, InnateImmunoglobulin EImmunoglobulin GInsect ProteinsInterleukin-1 Receptor-Like 1 ProteinInterleukin-33Interleukin-4InterleukinsLymphocyte ActivationLysophospholipidsMelittenMembrane LipidsMiceMice, Inbred BALB CMice, KnockoutMyeloid Differentiation Factor 88OvalbuminPhospholipases A2PhospholipidsReceptors, IgEReceptors, InterleukinTh2 CellsConceptsInnate immune systemBee venom phospholipase A2Components of venomPhospholipase A2Immune responseGroup 2 Innate Lymphoid Cell ActivationVenom phospholipase A2Immune systemInnate lymphoid cell activationType 2 immune responsesLymphoid cell activationType 2 responsesProtective immune responseConfer protective immunityIgE responseInterleukin-33Receptor ST2Protective immunityCell type responsesCell activationLethal doseMajor allergenBee venomAllergensVenom toxins
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
Autotaxin and lipid signaling pathways as anticancer targets.
Braddock DT. Autotaxin and lipid signaling pathways as anticancer targets. Current Opinion In Investigational Drugs 2010, 11: 629-37. PMID: 20496257.Peer-Reviewed Original ResearchA 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
2008
Adenosine induces loss of actin stress fibers and inhibits contraction in hepatic stellate cells via Rho inhibition
Sohail MA, Hashmi AZ, Hakim W, Watanabe A, Zipprich A, Groszmann RJ, Dranoff JA, Torok NJ, Mehal WZ. Adenosine induces loss of actin stress fibers and inhibits contraction in hepatic stellate cells via Rho inhibition. Hepatology 2008, 49: 185-194. PMID: 18844235, PMCID: PMC3129263, DOI: 10.1002/hep.22589.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 action
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