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