2016
Mitochondrial Reactive Oxygen Species Mediate Cardiac Structural, Functional, and Mitochondrial Consequences of Diet‐Induced Metabolic Heart Disease
Sverdlov AL, Elezaby A, Qin F, Behring JB, Luptak I, Calamaras TD, Siwik DA, Miller EJ, Liesa M, Shirihai OS, Pimentel DR, Cohen RA, Bachschmid MM, Colucci WS. Mitochondrial Reactive Oxygen Species Mediate Cardiac Structural, Functional, and Mitochondrial Consequences of Diet‐Induced Metabolic Heart Disease. Journal Of The American Heart Association 2016, 5: e002555. PMID: 26755553, PMCID: PMC4859372, DOI: 10.1161/jaha.115.002555.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCatalaseDiet, High-FatDietary SucroseDisease Models, AnimalElectron Transport Complex IElectron Transport Complex IIEnergy MetabolismHypertrophy, Left VentricularMice, Inbred C57BLMice, TransgenicMitochondria, HeartMitochondrial DiseasesMutationOxidation-ReductionOxidative StressProtein Processing, Post-TranslationalReactive Oxygen SpeciesVentricular Dysfunction, LeftVentricular Function, LeftConceptsOxidative posttranslational modificationsMitochondrial reactive oxygen speciesPosttranslational modificationsReactive oxygen speciesMetabolic heart diseaseATP synthesisMitochondrial dysfunctionCardiac mitochondrial proteinsSite-directed mutationsMitochondrial proteinsTransgenic miceWild-type miceComplex IMitochondriaMitochondrial abnormalitiesHigh palmitateOxygen speciesCardiac mitochondriaCys100Mitochondrial consequencesCys103Key mediatorProteinH2O2 productionHigh-fat high-sucrose diet
2014
Mitochondrial remodeling in mice with cardiomyocyte-specific lipid overload
Elezaby A, Sverdlov AL, Tu VH, Soni K, Luptak I, Qin F, Liesa M, Shirihai OS, Rimer J, Schaffer JE, Colucci WS, Miller EJ. Mitochondrial remodeling in mice with cardiomyocyte-specific lipid overload. Journal Of Molecular And Cellular Cardiology 2014, 79: 275-283. PMID: 25497302, PMCID: PMC4301992, DOI: 10.1016/j.yjmcc.2014.12.001.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCarnitineCatalaseCeramidesCyclic AMP Response Element-Binding ProteinDiglyceridesElectron Transport Complex IIFatty Acid Transport ProteinsGene Expression RegulationHydrogen PeroxideLipidsMiceMitochondria, HeartModels, BiologicalMyocardiumMyocytes, CardiacOrgan SpecificityOxygen ConsumptionPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPhosphorylationPPAR alphaProtein Kinase CProto-Oncogene Proteins c-aktRNA, MessengerSphingomyelinsTranscription FactorsConceptsMetabolic heart diseaseMitochondrial structureMitochondrial fusion genes Mfn1Mitochondrial-targeted catalaseOverexpression of catalaseMitochondrial oxidative stressStructure/functionPhosphorylation of AktToxic metabolite accumulationTranscriptional regulationMitochondrial structure/functionFatty acid uptakeCardiomyocyte lipid accumulationMitochondrial remodelingMetabolite accumulationDiacylglycerol speciesExcess FAATP synthesisMitochondrial functionMitochondrial dysfunctionLipid speciesFA uptakeMitochondrial sizeHydrogen peroxide productionSubunit BHigh fat, high sucrose diet causes cardiac mitochondrial dysfunction due in part to oxidative post-translational modification of mitochondrial complex II
Sverdlov AL, Elezaby A, Behring JB, Bachschmid MM, Luptak I, Tu VH, Siwik DA, Miller EJ, Liesa M, Shirihai OS, Pimentel DR, Cohen RA, Colucci WS. High fat, high sucrose diet causes cardiac mitochondrial dysfunction due in part to oxidative post-translational modification of mitochondrial complex II. Journal Of Molecular And Cellular Cardiology 2014, 78: 165-173. PMID: 25109264, PMCID: PMC4268348, DOI: 10.1016/j.yjmcc.2014.07.018.Peer-Reviewed Original ResearchConceptsCysteine oxidative post-translational modificationsOxidative post-translational modificationsCardiac mitochondrial proteinsPost-translational modificationsMetabolic heart diseaseMitochondrial proteinsATP synthesisMitochondrial dysfunctionBasic Mitochondrial BiologyCardiac mitochondriaMitochondrial biologyOxidative stressTag labelingCardiac mitochondrial dysfunctionBiotin switchSubunit AATP productionMitochondrial ROSGSH/GSSG ratioFunctional consequencesMitochondriaReversible oxidationGSSG ratioProteinSDHA
2011
A small molecule AMPK activator protects the heart against ischemia–reperfusion injury
Kim AS, Miller EJ, Wright TM, Li J, Qi D, Atsina K, Zaha V, Sakamoto K, Young LH. A small molecule AMPK activator protects the heart against ischemia–reperfusion injury. Journal Of Molecular And Cellular Cardiology 2011, 51: 24-32. PMID: 21402077, PMCID: PMC4005884, DOI: 10.1016/j.yjmcc.2011.03.003.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAMP-Activated Protein KinasesAnimalsApoptosisBiphenyl CompoundsCardiotonic AgentsEnzyme ActivatorsHeartIschemic PreconditioningMiceMice, Inbred C57BLMice, TransgenicMyocardial InfarctionMyocardial Reperfusion InjuryNecrosisNitric Oxide Synthase Type IIIPeptide Elongation Factor 2PyronesThiophenesConceptsIschemia-reperfusion injuryLeft ventricular contractile functionMyocardial ischemia-reperfusion injuryMouse heartsEndothelial nitric oxide synthase activationNitric oxide synthase activationLess myocardial necrosisCoronary artery occlusionIschemia-reperfusion damageVentricular contractile functionEukaryotic elongation factor 2Isolated mouse heartsPost-ischemic reperfusionAMPK activatorArtery occlusionIschemic contractureIschemic injuryInfarct sizeMyocardial stunningMyocardial necrosisCardioprotective mechanismsContractile functionSolid organsTherapeutic targetMyocardial apoptosis
2005
Dual Mechanisms Regulating AMPK Kinase Action in the Ischemic Heart
Baron SJ, Li J, Russell RR, Neumann D, Miller EJ, Tuerk R, Wallimann T, Hurley RL, Witters LA, Young LH. Dual Mechanisms Regulating AMPK Kinase Action in the Ischemic Heart. Circulation Research 2005, 96: 337-345. PMID: 15653571, DOI: 10.1161/01.res.0000155723.53868.d2.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine MonophosphateAdenosine TriphosphateAminoimidazole CarboxamideAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesAnimalsInfusions, IntravenousMaleMultienzyme ComplexesMyocardial IschemiaMyocardiumPhosphorylationProtein KinasesProtein Serine-Threonine KinasesRatsRats, Sprague-DawleyRecombinant ProteinsRibonucleotidesConceptsRecombinant AMPKAMPKK activityAMPK phosphorylationPhosphorylation of Thr172Gamma regulatory subunitsIschemic heartImportant signaling proteinAlpha catalytic subunitRat heartHeterotrimeric AMPKAMPKKHeterotrimeric complexActivation loopRegulatory subunitKinase actionSignaling proteinsCatalytic subunitProtein kinaseAMPK activityLow-flow ischemiaGamma subunitsAMPKInteraction of AMPPhosphorylationAddition of AMP