2024
Enzymatic and non-enzymatic transnitrosylation: “SCAN”ning the SNO-proteome
Nakamura T, Lipton S. Enzymatic and non-enzymatic transnitrosylation: “SCAN”ning the SNO-proteome. Molecular Cell 2024, 84: 191-193. PMID: 38242098, DOI: 10.1016/j.molcel.2023.12.018.Peer-Reviewed Original Research
2022
Hidden networks of aberrant protein transnitrosylation contribute to synapse loss in Alzheimer's disease
Lipton S. Hidden networks of aberrant protein transnitrosylation contribute to synapse loss in Alzheimer's disease. Free Radical Biology And Medicine 2022, 193: 171-176. PMID: 36243209, PMCID: PMC9875813, DOI: 10.1016/j.freeradbiomed.2022.10.272.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseParkinson's diseaseNitric oxideSoluble guanylate cyclaseFormation of peroxynitriteSynapse lossNeurocognitive disordersNeurological disordersDiseaseGuanylate cyclaseNeurodevelopmental disordersDisordersProtein S-nitrosylationSuperoxide anionTyrosine nitrationS-nitrosylationHIVS-nitrosationPathogenesisDementiaS-Nitrosylation of cathepsin B affects autophagic flux and accumulation of protein aggregates in neurodegenerative disorders
Kim K, Cho E, Eom J, Oh S, Nakamura T, Oh C, Lipton S, Kim Y. S-Nitrosylation of cathepsin B affects autophagic flux and accumulation of protein aggregates in neurodegenerative disorders. Cell Death & Differentiation 2022, 29: 2137-2150. PMID: 35462559, PMCID: PMC9613756, DOI: 10.1038/s41418-022-01004-0.Peer-Reviewed Original ResearchConceptsS-nitrosylationProtein aggregatesAutophagic fluxProtein S-nitrosylationBlocks autophagic fluxCathepsin BCaspase-dependent neuronal apoptosisPosttranslational modificationsProtease cathepsin BEnzymatic functionLysosomal protease cathepsin BCTSB activityChemical inhibitorsCA-074MeHuman AD brainsEnzymatic activityCysteineNeurodegenerative disordersPostmortem human AD brainTransgenic miceNeuronal apoptosisCTSBAccumulationAD pathogenesisAlzheimer's disease
2021
Protein S-nitrosylation and oxidation contribute to protein misfolding in neurodegeneration
Nakamura T, Oh C, Zhang X, Lipton S. Protein S-nitrosylation and oxidation contribute to protein misfolding in neurodegeneration. Free Radical Biology And Medicine 2021, 172: 562-577. PMID: 34224817, PMCID: PMC8579830, DOI: 10.1016/j.freeradbiomed.2021.07.002.Peer-Reviewed Original ResearchMeSH KeywordsHumansNeurodegenerative DiseasesNitric OxideOxidation-ReductionProtein FoldingProteostasis DeficienciesConceptsProtein misfoldingUbiquitin-proteasome systemCellular protein quality control machineryReactive oxygen speciesS-nitrosylationProtein quality control machineryQuality control machineryPost-translational modificationsNeurodegenerative diseasesProtein S-nitrosylationGenetic mutationsMost neurodegenerative diseasesMolecular chaperonesROS/RNSControl machineryLysosomal pathwayRare genetic mutationsMolecular mechanismsMolecular eventsMisfoldingMitochondrial dysfunctionTyrosine nitrationProteinOxygen speciesNeuronal demiseProtein Transnitrosylation Signaling Networks Contribute to Inflammaging and Neurodegenerative Disorders
Nakamura T, Oh C, Zhang X, Tannenbaum S, Lipton S. Protein Transnitrosylation Signaling Networks Contribute to Inflammaging and Neurodegenerative Disorders. Antioxidants & Redox Signaling 2021, 35: 531-550. PMID: 33957758, PMCID: PMC8388249, DOI: 10.1089/ars.2021.0081.Peer-Reviewed Original ResearchConceptsRelated reactive nitrogen speciesS-nitrosylationRedox-based posttranslational modificationProtein S-nitrosylationGlyceraldehyde-3-phosphate dehydrogenaseInhibitor of apoptosisThiol-containing proteinsNeurodegenerative diseasesSignaling networksPosttranslational modificationsReactive nitrogen speciesTransnitrosylation reactionsNuclear proteinsUnderstanding of agingCysteine thiolsTransnitrosylationBiochemical pathwaysChemical biologyMechanisms of diseaseProteinCaspase-3Nitrogen speciesUCH-L1Neurodegenerative disordersPhysiological concentrationsTCA cycle metabolic compromise due to an aberrant S-nitrosoproteome in HIV-associated neurocognitive disorder with methamphetamine use
Doulias P, Nakamura T, Scott H, McKercher S, Sultan A, Deal A, Albertolle M, Ischiropoulos H, Lipton S. TCA cycle metabolic compromise due to an aberrant S-nitrosoproteome in HIV-associated neurocognitive disorder with methamphetamine use. Journal Of NeuroVirology 2021, 27: 367-378. PMID: 33876414, PMCID: PMC8477648, DOI: 10.1007/s13365-021-00970-4.Peer-Reviewed Original ResearchConceptsNeurocognitive disordersMeth usePathogenesis of HIVHuman postmortem brainAberrant protein S-nitrosylationCNS pathologyControl brainsSynaptic damageS-nitrosylationHIV-1Metabolic compromisePostmortem brainsMethamphetamine useNitric oxideDrug abuseRedox stressNitrosative stressBrainHIVProtein S-nitrosylationDisordersS-nitrosoproteomeSystematic inhibitionTCA cycle enzymesPathogenesisS-nitrosylated TDP-43 triggers aggregation, cell-to-cell spread, and neurotoxicity in hiPSCs and in vivo models of ALS/FTD
Pirie E, Oh C, Zhang X, Han X, Cieplak P, Scott H, Deal A, Ghatak S, Martinez F, Yeo G, Yates J, Nakamura T, Lipton S. S-nitrosylated TDP-43 triggers aggregation, cell-to-cell spread, and neurotoxicity in hiPSCs and in vivo models of ALS/FTD. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2021368118. PMID: 33692125, PMCID: PMC7980404, DOI: 10.1073/pnas.2021368118.Peer-Reviewed Original ResearchConceptsProtein misfolding/aggregationCell spreadMisfolding/aggregationRNA-binding activityOligomerization/aggregationHuman-induced pluripotent stem cellsProtein TDP-43Pluripotent stem cellsALS/FTDTDP-43 aggregationTDP-43Cognate proteinProtein aggregationS-nitrosylationRare genetic mutationsCell-based modelFTD disordersAmyotrophic lateral sclerosisAbsence of mutationsTriggers aggregationStem cellsGenetic mutationsDisulfide linkagesNitrosative stressNeurodegenerative disorders
2011
Redox modulation by S-nitrosylation contributes to protein misfolding, mitochondrial dynamics, and neuronal synaptic damage in neurodegenerative diseases
Nakamura T, Lipton S. Redox modulation by S-nitrosylation contributes to protein misfolding, mitochondrial dynamics, and neuronal synaptic damage in neurodegenerative diseases. Cell Death & Differentiation 2011, 18: 1478-1486. PMID: 21597461, PMCID: PMC3178424, DOI: 10.1038/cdd.2011.65.Peer-Reviewed Original ResearchConceptsS-nitrosylationProtein misfoldingCritical protein thiolsDynamin-related protein 1Protein disulfide isomeraseS-nitrosylation contributesNitrosative stressPosttranslational modificationsMitochondrial dynamicsNeuronal lossSynaptic damageDownstream pathwaysRedox modulationProtein thiolsNormal neuronal signalingMitochondrial dysfunctionN-methyl-D-aspartate (NMDA) receptor activationNeuronal signalingProtein 1Eventual neuronal lossNeuronal cell damageNeuronal cell injuryMisfoldingNeuronal NO synthaseNeurodegenerative diseases
2007
S-Nitrosylation and uncompetitive/fast off-rate (UFO) drug therapy in neurodegenerative disorders of protein misfolding
Nakamura T, Lipton S. S-Nitrosylation and uncompetitive/fast off-rate (UFO) drug therapy in neurodegenerative disorders of protein misfolding. Cell Death & Differentiation 2007, 14: 1305-1314. PMID: 17431424, DOI: 10.1038/sj.cdd.4402138.Peer-Reviewed Original ResearchConceptsS-nitrosylationProtein functionProtein misfoldingCell deathNeuronal cell deathProper protein foldingProtein disulfide isomeraseCysteine thiol groupsHeat shock proteinsExcessive NMDA receptor activityGlucose-regulated protein 78Neurodegenerative disordersProtein foldingExcitotoxic damageFree radical nitric oxideConformational changesMisfoldingForm of neurotoxicityRadical nitric oxideN-methyl-D-aspartate receptorsNitric oxideExcessive activityProteinProtein 78Chronic neurodegenerative disorders
2006
Mitochondrial fission is an upstream and required event for bax foci formation in response to nitric oxide in cortical neurons
Yuan H, Gerencser A, Liot G, Lipton S, Ellisman M, Perkins G, Bossy-Wetzel E. Mitochondrial fission is an upstream and required event for bax foci formation in response to nitric oxide in cortical neurons. Cell Death & Differentiation 2006, 14: 462-471. PMID: 17053808, DOI: 10.1038/sj.cdd.4402046.Peer-Reviewed Original ResearchConceptsMitochondrial fissionNitric oxideFoci formationCortical neuronsMitochondrial fission machineryBcl-2 familyNitrosative stressAntiapoptotic Bcl-xLNeuronal cell deathFission machineryMitofusin 1Puncta formationBioenergetic crisisBax accumulationMitochondrial inhibitorsNeuronal demiseBcl-xLCell deathMitochondrial dysfunctionMitochondriaNeurodegenerative disordersNO donorNeuronsScission siteFission
2005
Response to Comment on "S-Nitrosylation of Parkin Regulates Ubiquitination and Compromises Parkin's Protective Function"
Lipton S, Nakamura T, Yao D, Shi Z, Uehara T, Gu Z. Response to Comment on "S-Nitrosylation of Parkin Regulates Ubiquitination and Compromises Parkin's Protective Function". Science 2005, 308: 1870c-1870c. PMID: 15976289, DOI: 10.1126/science.1110353.Peer-Reviewed Original Research
2003
Nitric oxide signaling regulates mitochondrial number and function
Bossy-Wetzel E, Lipton S. Nitric oxide signaling regulates mitochondrial number and function. Cell Death & Differentiation 2003, 10: 757-760. PMID: 12815458, DOI: 10.1038/sj.cdd.4401244.Peer-Reviewed Original Research
2001
Nitric oxide and respiration
Lipton S. Nitric oxide and respiration. Nature 2001, 413: 119-121. PMID: 11557961, DOI: 10.1038/35093186.Peer-Reviewed Original ResearchErythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-κB signalling cascades
Digicaylioglu M, Lipton S. Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-κB signalling cascades. Nature 2001, 412: 641-647. PMID: 11493922, DOI: 10.1038/35088074.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell NucleusCells, CulturedDNAErythropoietinGenes, ReporterJanus Kinase 2NeuronsNeuroprotective AgentsNF-kappa BNitric OxideN-MethylaspartateProtein BindingProtein TransportProtein-Tyrosine KinasesProto-Oncogene ProteinsRatsReceptors, ErythropoietinSignal TransductionSuperoxide DismutaseTumor Necrosis Factor-alphaConceptsHypoxia-inducible factor-1EPO receptorForm of JAK2Transcription factor hypoxia-inducible factor-1NF-κB-dependent transcriptionNF-κB functionActivation of JAK2Subsequent nuclear translocationTranscription factor NF-κBNF-κBFactor NF-κBSignaling cascadesNitric oxideKinase 2NF-κB signaling cascadesHypoxic-ischemic preconditioningNuclear translocationNeuroprotective genesFactor 1JAK2Neuroprotective pathwaysNeuronal apoptosisCerebrocortical neuronsEPO effectsDegenerative damage
2000
Redox modulation of the NMDA receptor
Choi Y, Lipton S. Redox modulation of the NMDA receptor. Cellular And Molecular Life Sciences 2000, 57: 1535-1541. PMID: 11092448, PMCID: PMC11147125, DOI: 10.1007/pl00000638.Peer-Reviewed Original ResearchConceptsRedox modulationCysteine residuesCritical cysteine residuesMultiple cysteine residuesDifferent NMDA receptor subunitsS-nitrosylationMolecular mechanismsMolecular determinantsNMDA receptor subunitsDistinct mechanismsReceptor subunitsPhysiological conditionsSubunitsNR2A subunitImportant mechanismN-methyl-D-aspartate receptorsResiduesNMDA receptorsRedox formsReceptorsCyclic GMPSpeciesMechanismForm of modulationRegulationNitric oxide (NO·) stabilizes whereas nitrosonium (NO+) enhances filopodial outgrowth by rat retinal ganglion cells in vitro
Cheung S, Bhan I, Lipton S. Nitric oxide (NO·) stabilizes whereas nitrosonium (NO+) enhances filopodial outgrowth by rat retinal ganglion cells in vitro. Brain Research 2000, 868: 1-13. PMID: 10841882, DOI: 10.1016/s0006-8993(00)02161-2.Peer-Reviewed Original ResearchConceptsRat retinal ganglion cellsRetinal ganglion cellsGanglion cellsNitric oxideInhibition of NOSNO synthase substrateGrowth-associated proteinFilopodial outgrowthNOS activityGuanylate cyclaseGrowth cone motilityCyclic nucleotide analogsDistinct actionsSynthase substrateCone motilityNOSS-nitrosylationNucleotide analoguesOutgrowthMolecular basis of NMDA receptor-coupled ion channel modulation by S-nitrosylation
Choi Y, Tenneti L, Le D, Ortiz J, Bai G, Chen H, Lipton S. Molecular basis of NMDA receptor-coupled ion channel modulation by S-nitrosylation. Nature Neuroscience 2000, 3: 15-21. PMID: 10607390, DOI: 10.1038/71090.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineChromatography, High Pressure LiquidCysteineDose-Response Relationship, DrugEthyl MethanesulfonateHumansIndicators and ReagentsIon TransportMesylatesMutagenesis, Site-DirectedN-MethylaspartateNitric OxideNitroso CompoundsOocytesPatch-Clamp TechniquesPeptide FragmentsReceptors, N-Methyl-D-AspartateS-NitrosothiolsTransfectionXenopus laevisConceptsS-nitrosylationMolecular basisIon channelsCritical cysteine residuesEndogenous S-nitrosylationSite-directed mutagenesisEndogenous nitric oxideIon channel activityNR2A subunitNitric oxideCysteine residuesSingle cysteineIon channel modulationChannel activityPhysiological conditionsSubunitsChannel modulationCell systemNMDA receptorsMutagenesisCysteineResiduesRegulationAlanineModulation
1999
Neuronal protection and destruction by NO
Lipton S. Neuronal protection and destruction by NO. Cell Death & Differentiation 1999, 6: 943-951. PMID: 10556970, DOI: 10.1038/sj.cdd.4400580.Peer-Reviewed Original ResearchConceptsS-nitrosylationCysteine residuesCaspase enzyme activityNeuronal apoptotic pathwayProtein functionCritical thiol groupsApoptotic pathwayMolecular switchReactive thiol groupsCritical thiolsN-methyl-D-aspartate receptor activityDisulfide bondsRedox stateThiol groupsDeath of neuronsSpeciesDifferent redox statesEnzyme activityDistinct chemical reactivityCaspasesPhysiological conditionsBiological activityActive siteResiduesReceptor activityAttenuation of NMDA Receptor Activity and Neurotoxicity by Nitroxyl Anion, NO−
Kim W, Choi Y, Rayudu P, Das P, Asaad W, Arnelle D, Stamler J, Lipton S. Attenuation of NMDA Receptor Activity and Neurotoxicity by Nitroxyl Anion, NO−. Neuron 1999, 24: 461-469. PMID: 10571239, DOI: 10.1016/s0896-6273(00)80859-4.Peer-Reviewed Original Research
1998
Chapter 6 Redox modulation of the NMDA receptor by NO-related species
Lipton S, Rayudu P, Choi Y, Sucher N, Chen H. Chapter 6 Redox modulation of the NMDA receptor by NO-related species. Progress In Brain Research 1998, 118: 73-82. PMID: 9932435, DOI: 10.1016/s0079-6123(08)63201-x.Peer-Reviewed Original ResearchConceptsChemical reactionsMechanism of reactionRedox stateReactive thiol groupsCatalytic amountFurther oxidationThiol groupsElectron acceptorPreferred reactionReceptor sulfhydryl groupsChemical evidenceSinglet stateNO groupBiological activityMolecular switchReactionThiolsDisulfide bondsSulfhydryl groupsCritical thiolsO2NOS-nitrosylationRedox modulationBonds