2019
O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth
Singh JP, Qian K, Lee JS, Zhou J, Han X, Zhang B, Ong Q, Ni W, Jiang M, Ruan HB, Li MD, Zhang K, Ding Z, Lee P, Singh K, Wu J, Herzog RI, Kaech S, Wendel HG, Yates JR, Han W, Sherwin RS, Nie Y, Yang X. O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth. Oncogene 2019, 39: 560-573. PMID: 31501520, PMCID: PMC7107572, DOI: 10.1038/s41388-019-0975-3.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAcetylglucosamineAnimalsAntigens, NeoplasmCarrier ProteinsCell Line, TumorDatasets as TopicDisease ProgressionFemaleGene Expression ProfilingGlycolysisHEK293 CellsHistone AcetyltransferasesHumansHyaluronoglucosaminidaseMaleMembrane ProteinsMiceN-AcetylglucosaminyltransferasesNeoplasm GradingNeoplasm StagingNeoplasmsProtein Processing, Post-TranslationalThyroid HormonesTissue Array AnalysisUp-RegulationXenograft Model Antitumor AssaysConceptsPyruvate kinase M2O-GlcNAcaseAerobic glycolysisO-GlcNAcylationKinase M2Lysine acetyltransferase activityTumor growthMetabolic rheostatAcetyltransferase activityGlcNAc transferaseMolecular basisMetabolic shiftHuman cancersGlycolysisCancer cellsHigh glucose conditionsGlucose availabilityTumor progressionGlucose conditionsExquisite controlGrowthRheostatCausative roleTargetEnzyme
2017
Selective proton‐observed, carbon‐edited (selPOCE) MRS method for measurement of glutamate and glutamine 13C‐labeling in the human frontal cortex
De Feyter H, Herzog RI, Steensma BR, Klomp DWJ, Brown PB, Mason GF, Rothman DL, de Graaf R. Selective proton‐observed, carbon‐edited (selPOCE) MRS method for measurement of glutamate and glutamine 13C‐labeling in the human frontal cortex. Magnetic Resonance In Medicine 2017, 80: 11-20. PMID: 29134686, PMCID: PMC5876108, DOI: 10.1002/mrm.27003.Peer-Reviewed Original ResearchExtracellular Mitochondrial DNA Is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary Fibrosis
Ryu C, Sun H, Gulati M, Herazo-Maya J, Chen Y, Osafo-Addo A, Brandsdorfer C, Winkler J, Blaul C, Faunce J, Pan H, Woolard T, Tzouvelekis A, Antin-Ozerkis DE, Puchalski JT, Slade M, Gonzalez AL, Bogenhagen DF, Kirillov V, Feghali-Bostwick C, Gibson K, Lindell K, Herzog RI, Dela Cruz CS, Mehal W, Kaminski N, Herzog EL, Trujillo G. Extracellular Mitochondrial DNA Is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2017, 196: 1571-1581. PMID: 28783377, PMCID: PMC5754440, DOI: 10.1164/rccm.201612-2480oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisNormal human lung fibroblastsExtracellular mitochondrial DNABronchoalveolar lavageIPF fibroblastsPulmonary fibrosisInnate immune ligandsEvent-free survivalSmooth muscle actin expressionMtDNA concentrationsSmooth muscle actin-expressing myofibroblastsGrowth factor-β1Muscle actin expressionHuman lung fibroblastsTGF-β1 stimulationExtracellular mtDNAIPF cohortClinical outcomesControl subjectsDisease progressionGlycolytic reprogrammingSoluble mediatorsTGF-β1Factor-β1Immune ligandsA Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease
Goffredo M, Santoro N, Tricò D, Giannini C, D’Adamo E, Zhao H, Peng G, Yu X, Lam TT, Pierpont B, Caprio S, Herzog RI. A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease. Nutrients 2017, 9: 642. PMID: 28640216, PMCID: PMC5537762, DOI: 10.3390/nu9070642.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseMagnetic resonance imagingBranched-chain amino acidsFatty liver diseaseHepatic fat contentObese adolescentsInsulin resistanceLiver diseaseTwo-step hyperinsulinemic-euglycemic clampOral glucose tolerance testSecond magnetic resonance imagingSubset of patientsGlucose tolerance testHyperinsulinemic-euglycemic clampHigher plasma levelsHepatic insulin sensitivityChain amino acidsPlasma levelsTolerance testInsulin sensitivityMetabolomic signaturePlasma metabolitesResonance imagingValine levelsLipid metabolismElevated α-Hydroxybutyrate and Branched-Chain Amino Acid Levels Predict Deterioration of Glycemic Control in Adolescents
Tricò D, Prinsen H, Giannini C, de Graaf R, Juchem C, Li F, Caprio S, Santoro N, Herzog RI. Elevated α-Hydroxybutyrate and Branched-Chain Amino Acid Levels Predict Deterioration of Glycemic Control in Adolescents. The Journal Of Clinical Endocrinology & Metabolism 2017, 102: 2473-2481. PMID: 28482070, PMCID: PMC5505187, DOI: 10.1210/jc.2017-00475.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAmino Acids, Branched-ChainBiomarkersBlood GlucoseChildCross-Sectional StudiesDiabetes Mellitus, Type 2FemaleGlucose Tolerance TestGlycemic IndexHumansHydroxybutyratesInsulin ResistanceLinear ModelsLongitudinal StudiesMaleMultivariate AnalysisObesityPredictive Value of TestsReference ValuesRisk AssessmentConceptsOral glucose tolerance testBranched-chain amino acidsGlycemic controlInsulin resistanceΑ-hydroxybutyrateGlucose toleranceInsulin sensitivityParameters of IRBody mass index z-scoreType 2 diabetes mellitusEarly metabolic featuresChain amino acid levelsTraditional risk factorsPediatric obesity clinicGlucose tolerance testElevated baseline concentrationsIndex z-scoreType 2 diabetesReduced insulin sensitivityDiabetes mellitusObesity clinicNondiabetic adolescentsProgressive worseningDisposition indexGlucose controlOxidized Derivatives of Linoleic Acid in Pediatric Metabolic Syndrome: Is Their Pathogenic Role Modulated by the Genetic Background and the Gut Microbiota?
Tricò D, Di Sessa A, Caprio S, Chalasani N, Liu W, Liang T, Graf J, Herzog R, Johnson CD, Umano GR, Feldstein AE, Santoro N. Oxidized Derivatives of Linoleic Acid in Pediatric Metabolic Syndrome: Is Their Pathogenic Role Modulated by the Genetic Background and the Gut Microbiota? Antioxidants & Redox Signaling 2017, 30: 241-250. PMID: 28279074, PMCID: PMC6277079, DOI: 10.1089/ars.2017.7049.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAge FactorsBiomarkersChildDelta-5 Fatty Acid DesaturaseDisease SusceptibilityFatty Acid DesaturasesFemaleGastrointestinal MicrobiomeGenetic BackgroundGenetic Predisposition to DiseaseHaplotypesHumansLinoleic AcidLipid MetabolismLipoproteinsMaleMetabolic SyndromeMetabolomeObesityOxidation-ReductionConceptsProatherogenic lipoprotein profilePediatric metabolic syndromeLipoprotein profileGut microbiotaGut bacterial loadMetabolic syndromeObese adolescentsSmall dense low-density lipoproteinBacterial loadAdverse lipoprotein profileLow-density lipoprotein particlesHigher plasma concentrationsLow-density lipoproteinLinoleic acid metabolitesPlasma 9Haplotype AAPathogenic rolePlasma concentrationsGenetic predispositionAcid metabolitesGenetic backgroundLipoprotein particlesMetSSyndromeMicrobiotaMetabolic brain adaptations to recurrent hypoglycaemia may explain the link between type 1 diabetes mellitus and epilepsy and point towards future study and treatment options
Tricò D, Herzog RI. Metabolic brain adaptations to recurrent hypoglycaemia may explain the link between type 1 diabetes mellitus and epilepsy and point towards future study and treatment options. Diabetologia 2017, 60: 938-939. PMID: 28236055, PMCID: PMC5395303, DOI: 10.1007/s00125-017-4231-5.Peer-Reviewed Original Researchβ-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares
Goldberg EL, Asher JL, Molony RD, Shaw AC, Zeiss CJ, Wang C, Morozova-Roche LA, Herzog RI, Iwasaki A, Dixit VD. β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares. Cell Reports 2017, 18: 2077-2087. PMID: 28249154, PMCID: PMC5527297, DOI: 10.1016/j.celrep.2017.02.004.Peer-Reviewed Original ResearchConceptsKetogenic dietGouty flaresΒ-hydroxybutyrateMajor risk factorAnti-inflammatory moleculesNLRP3-dependent mannerAlternate metabolic fuelsGout flaresJoint destructionIL-1βIntense painInterleukin-1βNLRP3 inflammasomeRisk factorsInflammatory neutrophilsBacterial infectionsNeutrophilsNLRP3Immune defenseGoutMetabolic fuelsBHBS100A9 fibrilsDietPain
2015
Hyperglycemia repression of miR-24 coordinately upregulates endothelial cell expression and secretion of von Willebrand factor
Xiang Y, Cheng J, Wang D, Hu X, Xie Y, Stitham J, Atteya G, Du J, Tang WH, Lee SH, Leslie K, Spollett G, Liu Z, Herzog E, Herzog RI, Lu J, Martin KA, Hwa J. Hyperglycemia repression of miR-24 coordinately upregulates endothelial cell expression and secretion of von Willebrand factor. Blood 2015, 125: 3377-3387. PMID: 25814526, PMCID: PMC4447857, DOI: 10.1182/blood-2015-01-620278.Peer-Reviewed Original ResearchConceptsVon Willebrand factorDiabetes mellitusMiR-24Diabetic patientsAdverse thrombotic eventsThrombotic cardiovascular eventsVWF expressionWillebrand factorDiabetic mouse modelNovel therapeutic targetHistamine H1 receptorsEndothelial cell expressionHyperglycemia-induced activationCardiovascular eventsThrombotic eventsH1 receptorsMouse modelVWF levelsTherapeutic targetCell expressionMellitusPatientsEndothelial cellsElevated levelsReactive oxygen species
2013
Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia
Herzog RI, Jiang L, Herman P, Zhao C, Sanganahalli BG, Mason GF, Hyder F, Rothman DL, Sherwin RS, Behar KL. Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia. Journal Of Clinical Investigation 2013, 123: 1988-1998. PMID: 23543056, PMCID: PMC3638906, DOI: 10.1172/jci65105.Peer-Reviewed Original ResearchConceptsAntecedent recurrent hypoglycemiaRecurrent hypoglycemiaHypoglycemic conditionsIntensive insulin therapyTight glycemic controlType 2 diabetesInsulin therapyGlycemic controlBrain metabolismElevated lactateNeuronal metabolismRodent modelsNeuronal activityGlucose metabolismHypoglycemiaLactate uptakeNeuronal functionType 1Metabolic regulatorOxidative capacityModest incrementLactateMetabolismUnexpected findingBrain
2012
Can tight glycemic control in diabetes benefit cognition?
Herzog RI, Sherwin RS. Can tight glycemic control in diabetes benefit cognition? Nature Reviews Neurology 2012, 8: 124-126. PMID: 22290574, PMCID: PMC5515668, DOI: 10.1038/nrneurol.2012.10.Peer-Reviewed Original Research
2008
Increased GABAergic Tone in the Ventromedial Hypothalamus Contributes to Suppression of Counterregulatory Reponses After Antecedent Hypoglycemia
Chan O, Cheng H, Herzog R, Czyzyk D, Zhu W, Wang A, McCrimmon RJ, Seashore MR, Sherwin RS. Increased GABAergic Tone in the Ventromedial Hypothalamus Contributes to Suppression of Counterregulatory Reponses After Antecedent Hypoglycemia. Diabetes 2008, 57: 1363-1370. PMID: 18375441, PMCID: PMC5518793, DOI: 10.2337/db07-1559.Peer-Reviewed Original ResearchConceptsVMH GABA levelsVentromedial hypothalamusGlutamic acid decarboxylaseHypoglycemic animalsHypoglycemic ratsSympathoadrenal responseRecurrent hypoglycemiaCounterregulatory responsesGABAergic toneInhibitory toneGABA levelsHypoglycemia-associated autonomic failureGABAergic inhibitory toneOnset of hypoglycemiaGABA synthetic enzymeQuantitative RT-PCRAntecedent hypoglycemiaAutonomic failureHypoglycemic stimulusReceptor blockadeEpinephrine releaseAcute hypoglycemiaReceptor antagonistInhibitory neurotransmitterSubsequent boutEffect of Acute and Recurrent Hypoglycemia on Changes in Brain Glycogen Concentration
Herzog RI, Chan O, Yu S, Dziura J, McNay EC, Sherwin RS. Effect of Acute and Recurrent Hypoglycemia on Changes in Brain Glycogen Concentration. Endocrinology 2008, 149: 1499-1504. PMID: 18187548, PMCID: PMC2276713, DOI: 10.1210/en.2007-1252.Peer-Reviewed Original ResearchConceptsHypoglycemia-associated autonomic failureRecurrent hypoglycemiaAcute hypoglycemiaAutonomic failureBrain glycogenGlycogen levelsBrain glucoseGlucose levelsRH groupInsulin-induced acute hypoglycemiaSimilar blood glucose levelsIntensive insulin treatmentHyperinsulinemic-hypoglycemic clamp studyBrain glycogen concentrationHypoglycemic clamp studiesBlood glucose levelsBrain glucose levelsCounterregulatory failureDiabetic patientsGlycogen supercompensationRecurrent episodesSingle boutInsulin treatmentClamp studiesAnimal models
2005
Pharmacological properties of neuronal TTX-resistant sodium channels and the role of a critical serine pore residue
Leffler A, Herzog RI, Dib-Hajj SD, Waxman SG, Cummins TR. Pharmacological properties of neuronal TTX-resistant sodium channels and the role of a critical serine pore residue. Pflügers Archiv - European Journal Of Physiology 2005, 451: 454-463. PMID: 15981012, DOI: 10.1007/s00424-005-1463-x.Peer-Reviewed Original Research
2003
The pentapeptide QYNAD does not block voltage-gated sodium channels
Cummins TR, Renganathan M, Stys PK, Herzog RI, Scarfo K, Horn R, Dib-Hajj SD, Waxman SG. The pentapeptide QYNAD does not block voltage-gated sodium channels. Neurology 2003, 60: 224-229. PMID: 12552035, DOI: 10.1212/01.wnl.0000042423.36650.bd.Peer-Reviewed Original ResearchConceptsVoltage-gated sodium channelsSodium channelsDifferent sodium channel subtypesSodium currentDorsal root ganglion neuronsInflammatory neurologic disordersMajor sodium channelPatch-clamp recordingsSodium channel subtypesSodium channel functionNodes of RanvierPentapeptide QYNADOptic nerveGanglion neuronsIntact neuronsNeurologic disordersQYNADChannel subtypesHuman CSFAbnormal myelinFiber tractsElevated levelsEndogenous pentapeptideMicro MChannel function
2001
Nav1.3 Sodium Channels: Rapid Repriming and Slow Closed-State Inactivation Display Quantitative Differences after Expression in a Mammalian Cell Line and in Spinal Sensory Neurons
Cummins TR, Aglieco F, Renganathan M, Herzog RI, Dib-Hajj SD, Waxman SG. Nav1.3 Sodium Channels: Rapid Repriming and Slow Closed-State Inactivation Display Quantitative Differences after Expression in a Mammalian Cell Line and in Spinal Sensory Neurons. Journal Of Neuroscience 2001, 21: 5952-5961. PMID: 11487618, PMCID: PMC6763143, DOI: 10.1523/jneurosci.21-16-05952.2001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxotomyBiolisticsCells, CulturedGanglia, SpinalGene ExpressionGenes, ReporterHumansIon Channel GatingKidneyMaleMembrane PotentialsMutagenesis, Site-DirectedNeurons, AfferentPatch-Clamp TechniquesPolymerase Chain ReactionProtein SubunitsRatsReaction TimeSodiumSodium ChannelsSpinal CordTetrodotoxinConceptsNav1.3 channelsRapid reprimingHEK-293 cellsDRG neuronsTTX-sensitive sodium currentDorsal root ganglion neuronsNav1.3 sodium channelsSodium channelsSpinal sensory neuronsVoltage-gated sodium channelsSteady-state inactivationLarger ramp currentsHuman embryonic kidney 293 cellsPeripheral axotomyEmbryonic kidney 293 cellsGanglion neuronsSlow depolarizationSensory neuronsVoltage-dependent propertiesKidney 293 cellsSodium currentRamp currentsNav1.3NeuronsBeta2 subunit