2022
Brown adipose TRX2 deficiency activates mtDNA-NLRP3 to impair thermogenesis and protect against diet-induced insulin resistance
Huang Y, Zhou JH, Zhang H, Canfrán-Duque A, Singh AK, Perry RJ, Shulman G, Fernandez-Hernando C, Min W. Brown adipose TRX2 deficiency activates mtDNA-NLRP3 to impair thermogenesis and protect against diet-induced insulin resistance. Journal Of Clinical Investigation 2022, 132 PMID: 35202005, PMCID: PMC9057632, DOI: 10.1172/jci148852.Peer-Reviewed Original ResearchConceptsBrown adipose tissueBAT inflammationInsulin resistanceMitochondrial reactive oxygen speciesReactive oxygen speciesAberrant innate immune responsesDiet-induced insulin resistanceSystematic metabolismDiet-induced obesityNLRP3 inflammasome pathwayWhole-body energy metabolismCGAS/STINGInnate immune responseFatty acid oxidationExcessive mitochondrial reactive oxygen speciesMetabolic benefitsImmune responseInflammasome pathwayAdipose tissueInflammationInhibition reversesLipid uptakeLipid metabolismThioredoxin 2Adaptive thermogenesis
2020
Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance
He F, Huang Y, Song Z, Zhou HJ, Zhang H, Perry RJ, Shulman GI, Min W. Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance. Journal Of Experimental Medicine 2020, 218: e20201416. PMID: 33315085, PMCID: PMC7927432, DOI: 10.1084/jem.20201416.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipose TissueAnimalsDiabetes Mellitus, Type 2Diet, High-FatEnergy MetabolismFatty LiverGene DeletionGene TargetingGluconeogenesisHomeostasisHumansHyperglycemiaInflammationInsulin ResistanceLipogenesisLiverMaleMice, Inbred C57BLMice, KnockoutMitochondriaMitophagyNF-kappa BOxidative StressPhenotypeReactive Oxygen SpeciesSequestosome-1 ProteinSignal TransductionThioredoxinsConceptsHepatic insulin resistanceWhite adipose tissueInsulin resistanceAdipose inflammationType 2 diabetes mellitusLipid metabolic disordersNF-κB inhibitorAdipose-specific deletionWhole-body energy homeostasisAltered fatty acid metabolismFatty acid metabolismT2DM progressionT2DM patientsDiabetes mellitusReactive oxygen species pathwayHepatic steatosisMetabolic disordersNF-κBP62/SQSTM1Adipose tissueHuman adipocytesEnergy homeostasisExcessive mitophagyOxygen species pathwayInflammation
2019
Mitochondrial thioredoxin-2 maintains HCN4 expression and prevents oxidative stress-mediated sick sinus syndrome
Yang B, Huang Y, Zhang H, Huang Y, Zhou HJ, Young L, Xiao H, Min W. Mitochondrial thioredoxin-2 maintains HCN4 expression and prevents oxidative stress-mediated sick sinus syndrome. Journal Of Molecular And Cellular Cardiology 2019, 138: 291-303. PMID: 31751569, DOI: 10.1016/j.yjmcc.2019.10.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBradycardiaCardiomyopathy, DilatedEnhancer Elements, GeneticHistone DeacetylasesHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsMEF2 Transcription FactorsMice, KnockoutMitochondria, HeartModels, BiologicalOxidative StressPhenotypeProtein BindingReactive Oxygen SpeciesRNA, MessengerSick Sinus SyndromeSinoatrial NodeThioredoxinsConceptsSick sinus syndromeSinus syndromeHistone deacetylase 4Lower heart rateHeart rateHCN4 expressionConduction systemSinoatrial nodeNormal heart rateCardiac conduction systemHistone 3 acetylationMitochondrial oxidative stressSinus bradycardiaCardiac functionLox/SyndromeHeart rhythmMyosin heavy chainHistological analysisMiceDeletion miceOxidative stressWhole heartProtein levelsUnderlying mechanism
2015
Thioredoxin-2 Inhibits Mitochondrial Reactive Oxygen Species Generation and Apoptosis Stress Kinase-1 Activity to Maintain Cardiac Function
Huang Q, Zhou HJ, Zhang H, Huang Y, Hinojosa-Kirschenbaum F, Fan P, Yao L, Belardinelli L, Tellides G, Giordano FJ, Budas GR, Min W. Thioredoxin-2 Inhibits Mitochondrial Reactive Oxygen Species Generation and Apoptosis Stress Kinase-1 Activity to Maintain Cardiac Function. Circulation 2015, 131: 1082-1097. PMID: 25628390, PMCID: PMC4374031, DOI: 10.1161/circulationaha.114.012725.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCardiomegalyCells, CulturedHumansMAP Kinase Kinase Kinase 5MiceMice, KnockoutMitochondria, HeartReactive Oxygen SpeciesThioredoxinsConceptsMitochondrial reactive oxygen species generationReactive oxygen species generationOxygen species generationASK1-dependent apoptosisMitochondrial reactive oxygen species productionPhosphorylation/activityKey mitochondrial proteinsSpecies generationMitochondrial membrane depolarizationKinase 1 activityMitochondrial proteinsReactive oxygen species productionCellular redoxMitochondrial Trx2Inhibition of ASK1Apoptotic signalingOxygen species productionThioredoxin 2Protein expression levelsKinase 1ATP productionASK1 inhibitionKnockout miceMitochondrial ultrastructureASK1 inhibitors
2009
Endothelial-Specific Expression of Mitochondrial Thioredoxin Promotes Ischemia-Mediated Arteriogenesis and Angiogenesis
Dai S, He Y, Zhang H, Yu L, Wan T, Xu Z, Jones D, Chen H, Min W. Endothelial-Specific Expression of Mitochondrial Thioredoxin Promotes Ischemia-Mediated Arteriogenesis and Angiogenesis. Arteriosclerosis Thrombosis And Vascular Biology 2009, 29: 495-502. PMID: 19150880, PMCID: PMC2734510, DOI: 10.1161/atvbaha.108.180349.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisArteriesBlood Flow VelocityCell MovementDisease Models, AnimalEndothelial CellsHindlimbIschemiaJNK Mitogen-Activated Protein KinasesMaleMAP Kinase Kinase Kinase 5MiceMice, TransgenicMitochondriaMuscle, SkeletalNeovascularization, PhysiologicNitric OxideOxidative StressReactive Oxygen SpeciesRegional Blood FlowSignal TransductionThioredoxinsTime FactorsConceptsEndothelial cellsFlow recoveryFemoral artery ligation modelIschemia-mediated arteriogenesisIschemic reserve capacityLimb perfusion recoveryENOS-deficient miceENOS-KO miceNitric oxide bioavailabilityIschemia-induced angiogenesisEC apoptosisArtery ligation modelEC survivalENOS deletionNontransgenic littermatesStress-induced activationLigation modelPerfusion recoveryLower limbsUpper limbEndothelial-specific expressionSevere impairmentMajor antioxidant proteinsIschemiaMice
2008
SENP1 mediates TNF-induced desumoylation and cytoplasmic translocation of HIPK1 to enhance ASK1-dependent apoptosis
Li X, Luo Y, Yu L, Lin Y, Luo D, Zhang H, He Y, Kim YO, Kim Y, Tang S, Min W. SENP1 mediates TNF-induced desumoylation and cytoplasmic translocation of HIPK1 to enhance ASK1-dependent apoptosis. Cell Death & Differentiation 2008, 15: 739-750. PMID: 18219322, DOI: 10.1038/sj.cdd.4402303.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsAntioxidantsApoptosisCarrier ProteinsCattleCells, CulturedCysteine EndopeptidasesCytoplasmEndopeptidasesEndothelial CellsFibroblastsHumansMAP Kinase Kinase Kinase 5MiceMice, KnockoutMutationProtein KinasesProtein Processing, Post-TranslationalProtein Serine-Threonine KinasesProtein TransportReactive Oxygen SpeciesRecombinant ProteinsRNA InterferenceRNA, Small InterferingSignal TransductionSmall Ubiquitin-Related Modifier ProteinsThioredoxinsTime FactorsTransfectionTumor Necrosis Factor-alphaConceptsASK1-dependent apoptosisASK1-JNK activationCytoplasmic translocationMouse embryonic fibroblast cellsNuclear translocationSUMO-specific proteasesWild-type formEmbryonic fibroblast cellsNuclear importAntioxidant protein thioredoxinHIPK1Mutant formsEndothelial cellsDeSUMOylationProtein thioredoxinSubsequent cytoplasmic translocationSENP1TranslocationCritical functionsThioredoxinFibroblast cellsApoptosisCellsActivationSUMO
2007
Endothelial-Specific Expression of Mitochondrial Thioredoxin Improves Endothelial Cell Function and Reduces Atherosclerotic Lesions
Zhang H, Luo Y, Zhang W, He Y, Dai S, Zhang R, Huang Y, Bernatchez P, Giordano FJ, Shadel G, Sessa WC, Min W. Endothelial-Specific Expression of Mitochondrial Thioredoxin Improves Endothelial Cell Function and Reduces Atherosclerotic Lesions. American Journal Of Pathology 2007, 170: 1108-1120. PMID: 17322393, PMCID: PMC1864879, DOI: 10.2353/ajpath.2007.060960.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaApolipoproteins EAtherosclerosisCells, CulturedEndothelial CellsFlow CytometryImmunoblottingImmunohistochemistryMiceMice, TransgenicMicroscopy, ConfocalMitochondrial ProteinsNitric OxideReactive Oxygen SpeciesReverse Transcriptase Polymerase Chain ReactionThioredoxinsVasodilationConceptsTg miceAtherosclerotic lesionsOxidative stressNitric oxide levelsEC functionDeficient mouse modelEndothelial cell functionAtherosclerosis developmentEnhanced vasodilationVascular EC functionEndothelium functionApolipoprotein EControl littermatesMouse modelOxide levelsMice showCapacity of ECEndothelial-specific expressionEndothelial cellsCritical roleReactive oxygen speciesCell functionMiceTotal antioxidantsLesions