2015
AMPK is critical for mitochondrial function during reperfusion after myocardial ischemia
Zaha VG, Qi D, Su KN, Palmeri M, Lee HY, Hu X, Wu X, Shulman GI, Rabinovitch PS, Russell RR, Young LH. AMPK is critical for mitochondrial function during reperfusion after myocardial ischemia. Journal Of Molecular And Cellular Cardiology 2015, 91: 104-113. PMID: 26746142, PMCID: PMC4839186, DOI: 10.1016/j.yjmcc.2015.12.032.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCatalaseGene Expression RegulationHydrogen PeroxideMAP Kinase Kinase 4MiceMice, Inbred C57BLMice, TransgenicMitochondria, HeartMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PoreMyocardial InfarctionMyocardial ReperfusionMyocardiumNecrosisProtein Kinase InhibitorsSignal TransductionTransgenesConceptsWild typeProtein kinase kinase 4Mitochondrial functionMitochondrial catalaseKinase-dead AMPKMitochondrial reactive oxygen productionStress-responsive kinaseMPTP openingC-Jun terminal kinaseInhibition of JNKPermeability transition pore openingMitochondrial permeability transition pore openingTransition pore openingAMPK inactivationResponsive kinaseTerminal kinaseCellular metabolismJNK activationMitochondrial integrityReactive oxygen productionTransgenic expressionCell survivalAMPKKinase 4Kinase
2013
NO triggers RGS4 degradation to coordinate angiogenesis and cardiomyocyte growth
Jaba IM, Zhuang ZW, Li N, Jiang Y, Martin KA, Sinusas AJ, Papademetris X, Simons M, Sessa WC, Young LH, Tirziu D. NO triggers RGS4 degradation to coordinate angiogenesis and cardiomyocyte growth. Journal Of Clinical Investigation 2013, 123: 1718-1731. PMID: 23454748, PMCID: PMC3613910, DOI: 10.1172/jci65112.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, BiologicalAnimalsCell EnlargementCells, CulturedCoronary VesselsEndothelium, VascularHeart VentriclesMechanistic Target of Rapamycin Complex 1MiceMice, Inbred C57BLMice, TransgenicMultiprotein ComplexesMyocytes, CardiacNeovascularization, PhysiologicNG-Nitroarginine Methyl EsterNitric OxideNitric Oxide SynthasePlacenta Growth FactorPregnancy ProteinsProteinsProteolysisProto-Oncogene Proteins c-aktRatsRats, Sprague-DawleyRGS ProteinsSignal TransductionTOR Serine-Threonine KinasesConceptsCardiomyocyte growthAkt/mTORC1 signalingNovel NO-dependent mechanismProteasomal degradationCoordination of angiogenesisMTORC1 signalingConditional overexpressionMurine cardiac tissueG proteinsTransgenic expressionAkt/Physiological mechanismsMyocyte growthVessel growthGrowth factorTransgenic miceHypertrophic responseAngiogenesisKnockout miceMyocardial hypertrophyExpressionGrowthCardiac hypertrophyNOS inhibitor L-NAMEInduction
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
AMP-Activated Protein Kinase Activates p38 Mitogen-Activated Protein Kinase by Increasing Recruitment of p38 MAPK to TAB1 in the Ischemic Heart
Li J, Miller EJ, Ninomiya-Tsuji J, Russell RR, Young LH. AMP-Activated Protein Kinase Activates p38 Mitogen-Activated Protein Kinase by Increasing Recruitment of p38 MAPK to TAB1 in the Ischemic Heart. Circulation Research 2005, 97: 872-879. PMID: 16179588, DOI: 10.1161/01.res.0000187458.77026.10.Peer-Reviewed Original ResearchMeSH KeywordsAminoimidazole CarboxamideAMP-Activated Protein KinasesAnimalsAnisomycinCell HypoxiaEnzyme ActivationGlucoseGlucose Transporter Type 4Intracellular Signaling Peptides and ProteinsMaleMAP Kinase Kinase 3MiceMice, Inbred C57BLMice, TransgenicMultienzyme ComplexesMyocardial IschemiaP38 Mitogen-Activated Protein KinasesProtein Serine-Threonine KinasesProtein TransportRatsRats, Sprague-DawleyRibonucleotidesConceptsMitogen-activated protein kinaseP38 mitogen-activated protein kinaseMAPK kinase 3P38 MAPK activationAlpha2 catalytic subunitProtein kinaseMAPK activationCatalytic subunitGlucose transportStress-signaling pathwaysAMPK activator 5Role of AMPKProtein kinase 1Direct molecular targetP38 MAPK inhibitorMouse heartsAMPK complexProtein TAB1Scaffold proteinGLUT4 translocationUpstream kinaseAMPK activationKinase 3Kinase 1MAPK inhibitor
2004
AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury
Russell RR, Li J, Coven DL, Pypaert M, Zechner C, Palmeri M, Giordano FJ, Mu J, Birnbaum MJ, Young LH. AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury. Journal Of Clinical Investigation 2004, 114: 495-503. PMID: 15314686, PMCID: PMC503766, DOI: 10.1172/jci19297.Peer-Reviewed Original ResearchConceptsLow-flow ischemiaGlucose uptakePostischemic reperfusionWT heartsLeft ventricular dPNormal fractional shorteningLV contractile functionPostischemic cardiac dysfunctionInsulin-stimulated glucose uptakeImportant protective roleLong-term inhibitionFatty acid oxidationFractional shorteningHeart failureVentricular dPCardiac consequencesCardiac dysfunctionCaspase-3 activityMyocardial ischemiaContractile functionReperfusionCardiac hypertrophyIschemiaTransgenic miceProtective role
2002
AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation
Zong H, Ren JM, Young LH, Pypaert M, Mu J, Birnbaum MJ, Shulman GI. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 15983-15987. PMID: 12444247, PMCID: PMC138551, DOI: 10.1073/pnas.252625599.Peer-Reviewed Original ResearchMeSH KeywordsAdenine NucleotidesAdenylate KinaseAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2Calcium-Calmodulin-Dependent Protein Kinase Type 4Calcium-Calmodulin-Dependent Protein KinasesEnergy MetabolismEnzyme InductionGene Expression RegulationGenes, DominantGuanidinesMiceMice, TransgenicMitochondria, MuscleMuscle ProteinsMuscle, SkeletalPhosphocreatinePropionatesTranscription FactorsConceptsMitochondrial biogenesisPeroxisome proliferator-activated receptor-gamma coactivator-1alphaDominant negative mutantProliferator-activated receptor-gamma coactivator-1alphaRole of AMPReceptor-gamma coactivator-1alphaGamma coactivator-1alphaProtein kinaseAMPK inactivationEnergy deprivationBiogenesisAMPK activityDN-AMPKMuscle AMPKCritical adaptationKinase IVCritical regulatorAMP kinaseCoactivator-1alphaMitochondrial contentAMPKFuel sensorEnergy statusKinase