2017
Inhibition of Bcl-xL prevents pro-death actions of ΔN-Bcl-xL at the mitochondrial inner membrane during glutamate excitotoxicity
Park HA, Licznerski P, Mnatsakanyan N, Niu Y, Sacchetti S, Wu J, Polster BM, Alavian KN, Jonas EA. Inhibition of Bcl-xL prevents pro-death actions of ΔN-Bcl-xL at the mitochondrial inner membrane during glutamate excitotoxicity. Cell Death & Differentiation 2017, 24: 1963-1974. PMID: 28777375, PMCID: PMC5635221, DOI: 10.1038/cdd.2017.123.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsBcl-X ProteinBiphenyl CompoundsCell DeathCyclosporineGlutamic AcidMembrane Potential, MitochondrialMitochondrial MembranesMitochondrial Proton-Translocating ATPasesModels, BiologicalMutant ProteinsNeuritesNeurotoxinsNitrophenolsPiperazinesProtein SubunitsRats, Sprague-DawleyRhodaminesSulfonamidesConceptsBcl-xLABT-737ΔN-BclMitochondrial membraneWEHI-539ATP synthase c-subunitMitochondrial inner membrane depolarizationPro-death actionInner membrane depolarizationMitochondrial inner membraneOuter mitochondrial membraneMitochondrial inner membrane potentialATP synthase activityActivation of BaxInner membrane potentialMitochondrial permeability transition poreMitochondrial membrane potentialMembrane potentialPermeability transition poreAnti-apoptotic activityC subunitInner membraneB-cell lymphoma extra-large proteinBax activationGlutamate toxicityΔN-Bcl-xL, a therapeutic target for neuroprotection
Park HA, Jonas EA. ΔN-Bcl-xL, a therapeutic target for neuroprotection. Neural Regeneration Research 2017, 12: 1791-1794. PMID: 29239317, PMCID: PMC5745825, DOI: 10.4103/1673-5374.219033.Peer-Reviewed Original ResearchΔN-BclNeuronal deathNeuronal viabilityMitochondrial dysfunctionPrimary hippocampal neuronsABT-737Excitotoxic injuryGlutamate toxicityHippocampal neuronsAnti-apoptotic proteinsTherapeutic targetB cellsPrimary neuronsNeuronal functionAcute productionNeuroprotectionAltered metabolismMitochondrial damageNeuronsCentral targetMitochondrial functionDysfunctionDeathMitochondrial anti-apoptotic proteinDependent effects
2016
Metabolic Control of Cell Death : The Role of Bcl‐xL
Park H, Licznerski P, Niu Y, Mnatsakanyan N, Miranda P, Wu J, Sacchetti S, Polster B, Alavian K, Jonas E. Metabolic Control of Cell Death : The Role of Bcl‐xL. The FASEB Journal 2016, 30 DOI: 10.1096/fasebj.30.1_supplement.1162.2.Peer-Reviewed Original ResearchΔN-BclMitochondrial permeability transition poreABT-737Glutamate-exposed neuronsBcl-xLGlutamate-induced excitotoxicityGlutamate-induced deathNeuronal energy metabolismMitochondrial potentialCell deathGlutamate challengeBrain ischemiaNeuroprotective propertiesNeuronal survivalFold lower concentrationCyclosporine ASpecific small molecule inhibitorsATP productionSmall molecule inhibitorsMetabolic controlMitochondrial channel activityMalignant cellsPro-apoptotic roleNeuronsDeath
2015
ABT‐737 Inhibits Full Length And Cleaved Pro‐Apoptotic Bcl‐xL, Resulting in Differential Effects on Death And Survival
Park H, Licznerski P, Niu Y, Alavian K, Jonas E. ABT‐737 Inhibits Full Length And Cleaved Pro‐Apoptotic Bcl‐xL, Resulting in Differential Effects on Death And Survival. The FASEB Journal 2015, 29 DOI: 10.1096/fasebj.29.1_supplement.777.4.Peer-Reviewed Original ResearchFull-length Bcl-xLBcl-xLABT-737Mitochondrial potentialATP productionΔN-BclAnti-apoptotic Bcl-2 family proteinsBcl-2 family proteinsCell death stimuliMitochondrial membrane permeabilityATP synthase activityMitochondrial permeability transition porePro-apoptotic BclPro-apoptotic formBcl-xL inhibitorsPermeability transition poreDeath stimuliFamily proteinsBcl-xL.Isolated mitochondriaPharmacological inhibitorsTransition poreCell deathFull lengthSynthase activity
2013
Contributions of Bcl-xL to acute and long term changes in bioenergetics during neuronal plasticity
Jonas EA. Contributions of Bcl-xL to acute and long term changes in bioenergetics during neuronal plasticity. Biochimica Et Biophysica Acta 2013, 1842: 1168-1178. PMID: 24240091, PMCID: PMC4018426, DOI: 10.1016/j.bbadis.2013.11.007.Peer-Reviewed Original ResearchConceptsBcl-xLCaspase activationAnti-death proteinCell death stimuliMitochondrial membrane permeabilitySub-cellular membranesSynaptic vesicle recyclingNeuronal plasticityNormal neuronal plasticityInhibitor ABT-737Ion channel activityMitochondrial Bcl-xLMitochondrial positioningDeath stimuliMitochondrial releaseVesicle recyclingSynaptic growthMitochondrial functionNeurite retractionNeuronal activitySynaptic strengthSynaptic efficacyABT-737Channel activityLong-term decline
2012
N-terminally cleaved Bcl-xL mediates ischemia-induced neuronal death
Ofengeim D, Chen YB, Miyawaki T, Li H, Sacchetti S, Flannery RJ, Alavian KN, Pontarelli F, Roelofs BA, Hickman JA, Hardwick JM, Zukin RS, Jonas EA. N-terminally cleaved Bcl-xL mediates ischemia-induced neuronal death. Nature Neuroscience 2012, 15: 574-580. PMID: 22366758, PMCID: PMC3862259, DOI: 10.1038/nn.3054.Peer-Reviewed Original Research
2008
Bcl-xL induces Drp1-dependent synapse formation in cultured hippocampal neurons
Li H, Chen Y, Jones AF, Sanger RH, Collis LP, Flannery R, McNay EC, Yu T, Schwarzenbacher R, Bossy B, Bossy-Wetzel E, Bennett MV, Pypaert M, Hickman JA, Smith PJ, Hardwick JM, Jonas EA. Bcl-xL induces Drp1-dependent synapse formation in cultured hippocampal neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 2169-2174. PMID: 18250306, PMCID: PMC2542873, DOI: 10.1073/pnas.0711647105.Peer-Reviewed Original ResearchConceptsBcl-xL proteinBcl-xLVesicle clustersDynamin-related protein 1Synapse formationOverexpression of Drp1Mitochondrial fission proteinSynaptic vesicle clustersMitochondrial localizationFission proteinsGTPase activityDrp1Cultured hippocampal neuronsMitochondrial functionHippocampal neuronsNeuronal synapsesRecombinant systemsABT-737Protein 1ProteinTissue lysatesAdult neuronsSpontaneous miniature synaptic currentsOverexpressionMiniature synaptic currents
2007
Bcl-xL Inhibitor ABT-737 Reveals a Dual Role for Bcl-xL in Synaptic Transmission
Hickman JA, Hardwick JM, Kaczmarek LK, Jonas EA. Bcl-xL Inhibitor ABT-737 Reveals a Dual Role for Bcl-xL in Synaptic Transmission. Journal Of Neurophysiology 2007, 99: 1515-1522. PMID: 18160428, PMCID: PMC2836590, DOI: 10.1152/jn.00598.2007.Peer-Reviewed Original ResearchConceptsMitochondrial outer membraneEndogenous Bcl-xLMitochondrial channel activityBcl-xLInhibitor ABT-737ABT-737Outer membraneBcl-xL.Pro-apoptotic cleavage productRecombinant Bcl-xLChannel activityBcl-xL proteinSynaptic functionDual roleGenetic toolsDomain pocketSynaptic transmissionSynaptic activityGiant presynaptic terminalEquivalent modificationEndogenous proteolysisRepetitive synaptic activityBH3Cleavage productsProtein