2015
LKB1 deletion causes early changes in atrial channel expression and electrophysiology prior to atrial fibrillation
Kim GE, Ross JL, Xie C, Su KN, Zaha VG, Wu X, Palmeri M, Ashraf M, Akar JG, Russell KS, Akar FG, Young LH. LKB1 deletion causes early changes in atrial channel expression and electrophysiology prior to atrial fibrillation. Cardiovascular Research 2015, 108: 197-208. PMID: 26378152, PMCID: PMC4571838, DOI: 10.1093/cvr/cvv212.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsAtrial FibrillationConnexinsHeart AtriaMaleMiceMice, Inbred C57BLNAV1.5 Voltage-Gated Sodium ChannelProtein Serine-Threonine KinasesSignal TransductionConceptsLiver kinase B1Protein kinaseLKB1 deletionMetabolic regulator AMPAtrial fibrillationChannel expressionMHC-CreElectrophysiological functionKnockout mouse modelRelated kinasesLKB1 pathwayGene expressionPerpetuation of AFKinase B1Neonatal atrial myocytesΑMHC-CreKinasePostnatal day 1Patch-clamp recordingsAtrial growthWeeks of ageDeletionSodium current densityAction potential generationSpecific role
2008
AMP-Activated Protein Kinase Conducts the Ischemic Stress Response Orchestra
Young LH. AMP-Activated Protein Kinase Conducts the Ischemic Stress Response Orchestra. Circulation 2008, 117: 832-840. PMID: 18268160, DOI: 10.1161/circulationaha.107.713115.BooksMacrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart
Miller EJ, Li J, Leng L, McDonald C, Atsumi T, Bucala R, Young LH. Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart. Nature 2008, 451: 578-582. PMID: 18235500, DOI: 10.1038/nature06504.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsAntigens, Differentiation, B-LymphocyteCoronary Artery DiseaseEnzyme ActivationGenetic Predisposition to DiseaseGenotypeGlucoseHistocompatibility Antigens Class IIHumansHypoxiaMacrophage Migration-Inhibitory FactorsMiceMultienzyme ComplexesMyocardial IschemiaMyocardial Reperfusion InjuryMyocardiumPolymorphism, GeneticPromoter Regions, GeneticProtein Serine-Threonine KinasesRatsSignal TransductionConceptsIschemic heartMacrophage migration inhibitory factorLower MIF levelsCoronary artery diseaseIschemic heart diseaseMigration inhibitory factorPotential risk markerMIF levelsArtery diseaseRisk markersHeart diseaseIschemic stressCytokine MIFInhibitory factorGlucose uptakePotential drug targetsDiseaseHeartDrug targetsCellular stress responseAMPKMaster regulatorNew studiesPatientsAtherosclerosis
2007
Aging-Associated Reductions in AMP-Activated Protein Kinase Activity and Mitochondrial Biogenesis
Reznick RM, Zong H, Li J, Morino K, Moore IK, Yu HJ, Liu ZX, Dong J, Mustard KJ, Hawley SA, Befroy D, Pypaert M, Hardie DG, Young LH, Shulman GI. Aging-Associated Reductions in AMP-Activated Protein Kinase Activity and Mitochondrial Biogenesis. Cell Metabolism 2007, 5: 151-156. PMID: 17276357, PMCID: PMC1885964, DOI: 10.1016/j.cmet.2007.01.008.Peer-Reviewed Original ResearchConceptsIntracellular lipid metabolismMitochondrial biogenesisAMPK activityMitochondrial functionProtein kinase activityLipid metabolismProtein kinaseKinase activityAge-associated reductionBiogenesisOld ratsAMPKSkeletal muscleRecent studiesInsulin resistanceChronic activationMetabolismAcute stimulationFat oxidationImportant roleAcid feedingKinaseRatsActivityRegulation
2006
AMP-activated protein kinase regulates the assembly of epithelial tight junctions
Zhang L, Li J, Young LH, Caplan MJ. AMP-activated protein kinase regulates the assembly of epithelial tight junctions. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 17272-17277. PMID: 17088526, PMCID: PMC1859922, DOI: 10.1073/pnas.0608531103.Peer-Reviewed Original ResearchMeSH KeywordsAminoimidazole CarboxamideAMP-Activated Protein KinasesAnimalsCalciumCell LineDogsEnzyme ActivationEpithelial CellsMultienzyme ComplexesProtein Serine-Threonine KinasesRibonucleotidesSirolimusTight JunctionsConceptsTight junction assemblyJunction assemblyProtein kinaseLKB1-dependent phosphorylationCell polarization processCellular energy statusActivation of AMPKTight junctionsEukaryotic cellsTight junction structureAMPKMDCK cellsEpithelial tight junctionsEnergy statusKinaseEpithelial cellsAbsence of Ca2AssemblyTransepithelial electrical resistanceParacellular fluxZonula occludens-1CellsRecent studiesOccludens-1LKB1Activation of AMPK α- and γ-isoform complexes in the intact ischemic rat heart
Li J, Coven DL, Miller EJ, Hu X, Young ME, Carling D, Sinusas AJ, Young LH. Activation of AMPK α- and γ-isoform complexes in the intact ischemic rat heart. AJP Heart And Circulatory Physiology 2006, 291: h1927-h1934. PMID: 16648175, DOI: 10.1152/ajpheart.00251.2006.Peer-Reviewed Original ResearchConceptsAMPK activityAMPK complexAlpha subunit activationDifferent subunit isoformsSerine-threonine kinaseCellular metabolic processesGamma subunit isoformsRegulatory betaAlpha-subunit contentHeterotrimeric complexProtein kinaseAMPK αMultiple isoformsKinase activitySubunit isoformsMetabolic processesAMPK phosphorylationAMPKIsoformsPhysiological regulationKinaseMutationsComplexesKey rolePathophysiological importance
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 inhibitorAMP-Activated Protein Kinase: A Key Stress Signaling Pathway in the Heart
Young LH, Li J, Baron SJ, Russell RR. AMP-Activated Protein Kinase: A Key Stress Signaling Pathway in the Heart. Trends In Cardiovascular Medicine 2005, 15: 110-118. PMID: 16039971, DOI: 10.1016/j.tcm.2005.04.005.BooksMeSH KeywordsAMP-Activated Protein KinasesAnimalsHumansMultienzyme ComplexesMyocardiumProtein Serine-Threonine KinasesSignal TransductionStress, PhysiologicalConceptsLeft ventricular contractile dysfunctionVentricular contractile dysfunctionFatty acid oxidationProtein kinaseCardiovascular actionsHeart failureContractile dysfunctionWolff-ParkinsonWhite syndromeTransgenic miceGlycogen overloadStress Signaling PathwaysImportant regulatory mechanismSignaling pathwaysHeartAcid oxidationGlucose transportMolecular mechanismsAnabolic pathwaysRegulatory mechanismsAMPDual 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
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 ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsApoptosisGlucoseGlycolysisMiceMice, Inbred C57BLMice, TransgenicMultienzyme ComplexesMyocardial IschemiaMyocardial Reperfusion InjuryProtein Serine-Threonine KinasesConceptsLow-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 roleRole of the nitric oxide pathway in AMPK-mediated glucose uptake and GLUT4 translocation in heart muscle
Li J, Hu X, Selvakumar P, Russell RR, Cushman SW, Holman GD, Young LH. Role of the nitric oxide pathway in AMPK-mediated glucose uptake and GLUT4 translocation in heart muscle. AJP Endocrinology And Metabolism 2004, 287: e834-e841. PMID: 15265762, DOI: 10.1152/ajpendo.00234.2004.Peer-Reviewed Original ResearchMeSH KeywordsAminoimidazole CarboxamideAMP-Activated Protein KinasesAnimalsBiological TransportEnzyme ActivationGlucoseGlucose Transporter Type 4Hypoglycemic AgentsIn Vitro TechniquesMaleMonosaccharide Transport ProteinsMultienzyme ComplexesMuscle ProteinsNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIPapillary MusclesProtein Serine-Threonine KinasesProtein TransportRatsRats, Sprague-DawleyRibonucleotidesConceptsGLUT4 translocationAMPK stimulationGlucose transportAMPK catalytic subunitGlucose uptakeCell surfaceGlucose transporter GLUT4Serine-threonine kinaseEndothelial NO synthasePotential downstream mediatorsVesicular traffickingCatalytic subunitProtein kinaseAICAR treatmentCellular metabolismNitric oxide pathwayAMPKDownstream mediatorTranslocationEssential roleHeart muscleOxide pathwayCyclase pathwayPathwayAICAR
2003
Physiological role of AMP-activated protein kinase in the heart: graded activation during exercise
Coven DL, Hu X, Cong L, Bergeron R, Shulman GI, Hardie DG, Young LH. Physiological role of AMP-activated protein kinase in the heart: graded activation during exercise. AJP Endocrinology And Metabolism 2003, 285: e629-e636. PMID: 12759223, DOI: 10.1152/ajpendo.00171.2003.Peer-Reviewed Original ResearchConceptsAMPK activityProtein kinasePhysiological roleTotal AMPK activityAlpha2 catalytic subunitCellular metabolic processesAlpha catalytic subunitCardiac AMPK activityAMPK effectsAMPK activationMetabolic processesAMPKAkt phosphorylationKinasePhosphorylationSkeletal muscleSubunitsSubstrate metabolismActivationActivity increasesLesser extentMyocardial substrate metabolismMin of treadmillHigh-intensity exerciseActivity
1999
Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR
Russell R, Bergeron R, Shulman G, Young L. Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR. American Journal Of Physiology 1999, 277: h643-h649. PMID: 10444490, DOI: 10.1152/ajpheart.1999.277.2.h643.Peer-Reviewed Original ResearchMeSH KeywordsAminoimidazole CarboxamideAMP-Activated Protein KinasesAnimalsBiological TransportEnzyme ActivationGlucoseGlucose Transporter Type 4In Vitro TechniquesMaleMonosaccharide Transport ProteinsMultienzyme ComplexesMuscle ProteinsMyocardiumProtein Serine-Threonine KinasesRatsRats, Sprague-DawleyRibonucleotidesSarcolemmaConceptsAMPK activationGLUT-4 translocationGLUT-4Glucose uptakeProtein kinase activityActivator of AMPKActivation of AMPKInsulin-stimulated increasePI3K-independent pathwayInsulin-stimulated glucose uptakePI3K inhibitorsKinase activityAICARDeoxyglucose uptakeAMPKTranslocationIschemia-induced translocationK inhibitorsAdenine 9Myocyte sarcolemmaPathwayImmunofluorescence studiesMuscle glucose uptakeActivationCardiac myocytesEffect of AMPK activation on muscle glucose metabolism in conscious rats
Bergeron R, Russell R, Young L, Ren J, Marcucci M, Lee A, Shulman G. Effect of AMPK activation on muscle glucose metabolism in conscious rats. American Journal Of Physiology 1999, 276: e938-e944. PMID: 10329989, DOI: 10.1152/ajpendo.1999.276.5.e938.Peer-Reviewed Original ResearchMeSH KeywordsAminoimidazole CarboxamideAMP-Activated Protein KinasesAndrostadienesAnimalsBiological TransportDeoxyglucoseElectric StimulationEnzyme ActivationEnzyme InhibitorsIn Vitro TechniquesInsulinMaleMultienzyme ComplexesMuscle ContractionMuscle, SkeletalPhosphatidylinositol 3-KinasesProtein Serine-Threonine KinasesRatsRats, Sprague-DawleyRibonucleotidesTritiumWortmanninConceptsMuscle glucose metabolismGlucose transport activityActivation of AMPKGlucose uptakeGlucose metabolismTransport activitySkeletal muscle glucose metabolismExercise-induced increaseSkeletal muscle glucose transport activityBasal rateAbsence of wortmanninAdenosine receptor antagonistAdditive effectProtein kinase activationVariable infusionConscious ratsReceptor antagonistSaline infusionAwake ratsMedial gastrocnemiusElectrical stimulationEpitrochlearis musclesCellular pathwaysAMPK activationKinase activation