2001
Assembly with the NR1 Subunit Is Required for Surface Expression of NR3A-Containing NMDA Receptors
Pérez-Otaño I, Schulteis C, Contractor A, Lipton S, Trimmer J, Sucher N, Heinemann S. Assembly with the NR1 Subunit Is Required for Surface Expression of NR3A-Containing NMDA Receptors. Journal Of Neuroscience 2001, 21: 1228-1237. PMID: 11160393, PMCID: PMC6762235, DOI: 10.1523/jneurosci.21-04-01228.2001.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumNR1-1aPlasma membrane targetingReceptor complexRelative calcium permeabilityNR2 subunitsNR1 subunitSurface expressionMembrane targetingSubunit oligomerizationHeteromultimeric complexesHeteromeric complexesAdditional subunitsNMDA receptor familyPlasma membraneIntracellular traffickingDistinct single-channel propertiesIntracellular clustersFunctional NMDA receptorsSubunitsReceptor familyCell surfaceNMDA receptor subunitsMembrane expressionReticulum
1998
Calcium tsunamis: do astrocytes transmit cell death messages via gap junctions during ischemia?
Budd S, Lipton S. Calcium tsunamis: do astrocytes transmit cell death messages via gap junctions during ischemia? Nature Neuroscience 1998, 1: 431-432. PMID: 10196536, DOI: 10.1038/2147.Peer-Reviewed Original ResearchRole of Caspases in N‐Methyl‐d‐Aspartate‐Induced Apoptosis in Cerebrocortical Neurons
Tenneti L, D'Emilia D, Troy C, Lipton S. Role of Caspases in N‐Methyl‐d‐Aspartate‐Induced Apoptosis in Cerebrocortical Neurons. Journal Of Neurochemistry 1998, 71: 946-959. PMID: 9721720, DOI: 10.1046/j.1471-4159.1998.71030946.x.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid Chloromethyl KetonesAnimalsApoptosisCalciumCaspase 1Cells, CulturedCerebral CortexCysteine EndopeptidasesCysteine Proteinase InhibitorsIntracellular MembranesLipid PeroxidesMembrane PotentialsMitochondriaNeuronsN-MethylaspartateRatsRats, Sprague-DawleyReactive Oxygen SpeciesSignal TransductionConceptsInterleukin-1beta-converting enzymeMitochondrial membrane potentialReactive oxygen speciesRole of caspasesZ-VAD-FMKROS formationMembrane potentialReceptor activationCaspase activationDownstream eventsPseudosubstrate peptideNeuronal apoptosisMitochondrial depolarizationCysteine proteasesLipid peroxidationCaspasesCerebrocortical neuronsSubstrate cleavageIntracellular processesForm of deathN-methyl-D-aspartate (NMDA) receptor activationCortical neuronal apoptosisApoptosisCatalytic siteNMDA receptor activationCalcium, free radicals and excitotoxins in neuronal apoptosis
Lipton S, Nicotera P. Calcium, free radicals and excitotoxins in neuronal apoptosis. Cell Calcium 1998, 23: 165-171. PMID: 9601612, DOI: 10.1016/s0143-4160(98)90115-4.Peer-Reviewed Original Research
1997
Molecular basis of glutamate toxicity in retinal ganglion cells
Sucher N, Lipton S, Dreyer E. Molecular basis of glutamate toxicity in retinal ganglion cells. Vision Research 1997, 37: 3483-3493. PMID: 9425525, DOI: 10.1016/s0042-6989(97)00047-3.Peer-Reviewed Original ResearchConceptsRetinal ganglion cellsExcitatory amino acidsNMDA receptor antagonistRetinal ischemiaReceptor antagonistGanglion cellsGlutamate toxicityAnterior ischemic optic neuropathyN-methyl-D-aspartate (NMDA) subtypeNMDA receptor-mediated toxicityNon-NMDA receptor subtypesAcute vascular insultCentral artery occlusionOptic nerve traumaIschemic optic neuropathyGlutamate-induced neurotoxicitySelective NMDA receptor antagonistGlutamate-induced depolarizationVoltage-gated Ca2Amino acid glutamateOptic neuritisNerve traumaArtery occlusionFuture clinical useNeuronal loss
1996
Cytoskeletal Breakdown and Apoptosis Elicited by NO Donors in Cerebellar Granule Cells Require NMDA Receptor Activation
Bonfoco E, Leist M, Zhivotovsky B, Orrenius S, Lipton S, Nicotera P. Cytoskeletal Breakdown and Apoptosis Elicited by NO Donors in Cerebellar Granule Cells Require NMDA Receptor Activation. Journal Of Neurochemistry 1996, 67: 2484-2493. PMID: 8931482, DOI: 10.1046/j.1471-4159.1996.67062484.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisAstrocytesCalciumCells, CulturedCerebellumCysteineCytoskeletonDizocilpine MaleateDNA FragmentationEnzyme InhibitorsExcitatory Amino Acid AntagonistsNitric OxidePenicillaminePotassiumRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateSignal TransductionS-Nitroso-N-AcetylpenicillamineS-NitrosothiolsTyrosineConceptsCultured cerebellar granule cellsNMDA receptor activationCerebellar granule cellsCytoskeletal breakdownGranule cellsReceptor activationUncompetitive NMDA receptor antagonistsD-aminophosphonovaleric acidNecrosis of neuronsS-nitrosocysteineNO donor S-nitrosocysteineNMDA receptor antagonistNitric oxide donorTyrosine nitrationReceptor antagonistMK-801Astroglial cellsOxide donorIntracellular Ca2NO donorBreakdown of microtubulesCerebellar astroglial cellsApoptosisUnderwent apoptosisCytoskeletal alterations
1995
Multiple GABA receptor subtypes mediate inhibition of calcium influx at rat retinal bipolar cell terminals
Pan Z, Lipton. Multiple GABA receptor subtypes mediate inhibition of calcium influx at rat retinal bipolar cell terminals. Journal Of Neuroscience 1995, 15: 2668-2679. PMID: 7722621, PMCID: PMC6577770, DOI: 10.1523/jneurosci.15-04-02668.1995.Peer-Reviewed Original ResearchConceptsBipolar cell terminalsGABA receptor subtypesGABA receptorsRetinal bipolar cell terminalsGABAC receptorsGABAA receptorsReceptor subtypesCell terminalsMultiple GABA receptorsDihydropyridine-sensitive Ca2Pharmacologic profileCalcium imaging methodSynaptic transmissionCalcium influxSlow onsetInhibitory effectReceptorsSubtypesReversible increaseAgonistsGABACa2FA kineticsFunctional roleInhibitionN-methyl-d-aspartate receptors are critical for mediating the effects of glutamate on intracellular calcium concentration and immediate early gene expression in cultured hippocampal neurons
Bading H, Segal M, Sucher N, Dudek H, Lipton S, Greenberg M. N-methyl-d-aspartate receptors are critical for mediating the effects of glutamate on intracellular calcium concentration and immediate early gene expression in cultured hippocampal neurons. Neuroscience 1995, 64: 653-664. PMID: 7715778, DOI: 10.1016/0306-4522(94)00462-e.Peer-Reviewed Original ResearchMeSH Keywords2-Amino-5-phosphonovalerate6-Cyano-7-nitroquinoxaline-2,3-dioneAnimalsBlotting, NorthernCalciumCells, CulturedElectrophysiologyGene Expression RegulationGenes, fosGenes, junGlutamic AcidGlyceraldehyde-3-Phosphate DehydrogenasesHippocampusImmunohistochemistryKainic AcidKynurenic AcidNeuronsNifedipineProto-Oncogene Proteins c-fosRatsRats, Inbred StrainsReceptors, N-Methyl-D-AspartateRNA, MessengerConceptsN-methyl-D-aspartate receptorsGene transcriptionCultured hippocampal neuronsD-aspartate receptorsRegulation of transcriptionHippocampal neuronsImmediate early gene transcriptionEarly gene transcriptionImmediate early genesTranscriptional regulationEarly gene expressionCalcium channelsTranscriptional responseCalcium imagingL-type voltage-sensitive calcium channelsN-methyl-D-aspartate (NMDA) subtypeExcitatory amino acid receptorsTranscriptional levelImmediate early gene expressionVoltage-sensitive calcium channelsNuclear runGene expressionL-type calcium channelsAmino acid receptorsRNA analysis
1994
AIDS‐Related Dementia and Calcium Homeostasisa
LIPTON S. AIDS‐Related Dementia and Calcium Homeostasisa. Annals Of The New York Academy Of Sciences 1994, 747: 205-224. PMID: 7847672, DOI: 10.1111/j.1749-6632.1994.tb44411.x.Peer-Reviewed Original ResearchConceptsNeuronal injuryN-methyl-D-aspartate (NMDA) receptor-operated channelsHuman immunodeficiency virus type 1Arachidonic acidHIV-1 envelope protein gp120Immunodeficiency virus type 1Existence of HIVDeath of neuronsBrains of patientsCalcium channel antagonistsVoltage-dependent Ca2Interleukin-1 betaReceptor-operated channelsFuture pharmacological interventionsFinal common pathwayAmyotrophic lateral sclerosisHalf of childrenEnvelope protein gp120Platelet-activating factorThird of adultsVirus type 1Dysfunction of cognitionGamma interferon stimulationNeuropathic painAIDS dementiaExcitatory Amino Acids as a Final Common Pathway for Neurologic Disorders
Epstein F, Lipton S, Rosenberg P. Excitatory Amino Acids as a Final Common Pathway for Neurologic Disorders. New England Journal Of Medicine 1994, 330: 613-622. PMID: 7905600, DOI: 10.1056/nejm199403033300907.Peer-Reviewed Original ResearchChapter 29 Nitric oxide in the central nervous system
Lipton S, Singel D, Stamler J. Chapter 29 Nitric oxide in the central nervous system. Progress In Brain Research 1994, 103: 359-364. PMID: 7886218, DOI: 10.1016/s0079-6123(08)61149-8.Peer-Reviewed Original ResearchConceptsS-nitrosylationProtein S-nitrosylationNMDA receptorsLevels of thiolsPlasma membraneNitric oxideRedox milieuRelated congenersNMDA receptor activityCentral nervous systemNovel therapeutic strategiesRedox stateFormation of peroxynitriteCell functionAIDS dementiaNeuroprotective pathwaysCerebral ischemiaFocal ischemiaExcessive activationRecent findingsTherapeutic strategiesNervous systemNeurological disordersReceptor activityBiological systemsCa2+, N-Methyl-d-Aspartate Receptors, and Aids-Related Neuronal Injury
Lipton S. Ca2+, N-Methyl-d-Aspartate Receptors, and Aids-Related Neuronal Injury. International Review Of Neurobiology 1994, 36: 1-27. PMID: 7822116, DOI: 10.1016/s0074-7742(08)60301-3.Peer-Reviewed Original ResearchConceptsN-methyl-D-aspartate (NMDA) receptor-operated channelsN-methyl-D-aspartate receptorsHIV-1 envelope protein gp120Existence of HIVVoltage-dependent Ca2Receptor-operated channelsFuture pharmacological interventionsFinal common pathwayAmyotrophic lateral sclerosisEnvelope protein gp120Demise of neuronsNeuronal injuryAIDS patientsNeuronal susceptibilityPharmacological interventionsProtein gp120Lateral sclerosisParkinson's diseaseMacrophage productionInduces releaseHIVNitric oxideNeurodegenerative diseasesDiseaseHuntington's disease
1992
Blockade of NMDA receptor-mediated mobilization of intracellular Ca2+ prevents neurotoxicity
Lei S, Zhang D, Abele A, Lipton S. Blockade of NMDA receptor-mediated mobilization of intracellular Ca2+ prevents neurotoxicity. Brain Research 1992, 598: 196-202. PMID: 1486480, DOI: 10.1016/0006-8993(92)90183-a.Peer-Reviewed Original ResearchConceptsIntracellular Ca2Extracellular Ca2Excessive NMDA receptor stimulationRetinal ganglion cell neuronsNMDA receptor-mediated neurotoxicityGanglion cell neuronsNMDA receptor activationReceptor-mediated mobilizationNMDA receptor stimulationNormal extracellular Ca2Neuronal damagePharmacological interventionsPrevents neurotoxicityReceptor stimulationPresence of EGTAIntracellular storesNMDACell neuronsReceptor activationCultured ratDelayed neurotoxicityDantroleneNeurotoxicityElevated Ca2NeuronsEffect of nitric oxide production on the redox modulatory site of the NMDA receptor-channel complex
Lei S, Pan Z, Aggarwal S, Chen H, Hartman J, Sucher N, Lipton S. Effect of nitric oxide production on the redox modulatory site of the NMDA receptor-channel complex. Neuron 1992, 8: 1087-1099. PMID: 1376999, DOI: 10.1016/0896-6273(92)90130-6.Peer-Reviewed Original Research
1991
Redox modulatory site of the NMDA receptor–channel complex: Regulation by oxidized glutathione
Sucher N, Lipton S. Redox modulatory site of the NMDA receptor–channel complex: Regulation by oxidized glutathione. Journal Of Neuroscience Research 1991, 30: 582-591. PMID: 1666131, DOI: 10.1002/jnr.490300316.Peer-Reviewed Original ResearchConceptsRedox modulatory siteNMDA receptor-channel complexReceptor-channel complexModulatory siteNMDA responsesFura-2 digital imagingRetinal ganglion cell neuronsWhole-cell current responsesPatch-clamp recording techniquesGanglion cell neuronsCo-agonist glycineIntracellular calcium concentrationCultures of ratNMDA subtypeNMDA receptorsGlutamate receptorsCell neuronsHigh extracellularExtracellular applicationComplete recoveryCalcium concentrationFurther decrementRecording techniquesPredominant actionNMDASynergistic effects of HIV coat protein and NMDA receptor-mediated neurotoxicity
Lipton S, Sucher N, Kaiser P, Dreyer E. Synergistic effects of HIV coat protein and NMDA receptor-mediated neurotoxicity. Neuron 1991, 7: 111-118. PMID: 1676893, DOI: 10.1016/0896-6273(91)90079-f.Peer-Reviewed Original ResearchConceptsNMDA receptor-mediated neurotoxicityHIV-1 coat protein gp120Whole-cell patch-clamp recordingsHIV coat proteinRat retinal culturesSubsequent neuronal damagePatch-clamp recordingsGlutamate pyruvate transaminaseNeuronal injuryNeuronal damageEndogenous glutamateGanglion cellsNMDA antagonistsProtein gp120Low picomolar concentrationsRetinal culturesGp120NeurotoxicityComplete protectionMinute increasePicomolar concentrationsGlutamateInjuryAntagonistTransaminaseCalcium channel antagonists and human immunodeficiency virus coat protein–mediated neuronal injury
Lipton S. Calcium channel antagonists and human immunodeficiency virus coat protein–mediated neuronal injury. Annals Of Neurology 1991, 30: 110-114. PMID: 1656845, DOI: 10.1002/ana.410300121.Peer-Reviewed Original ResearchConceptsVoltage-dependent calcium channelsCalcium channel antagonistsNeuronal injuryChannel antagonistsCalcium channelsHuman immunodeficiency virus type 1 (HIV-1) envelope proteinImmunodeficiency syndrome dementia complexRat retinal ganglion cellsSubsequent neuronal injuryNeuronal calcium channelsRetinal ganglion cellsVoltage-dependent Ca2Mammalian central neuronsChannel antagonist drugsNeuronal damageDementia complexMaximal doseCentral neuronsGanglion cellsDihydropyridine classIntracellular calciumAntagonist drugsElectrophysiological studiesLow micromolar concentrationsGp120Calcium channel antagonists attenuate NMDA receptor-mediated neurotoxicity of retinal ganglion cells in culture
Sucher N, Lei S, Lipton S. Calcium channel antagonists attenuate NMDA receptor-mediated neurotoxicity of retinal ganglion cells in culture. Brain Research 1991, 551: 297-302. PMID: 1680525, DOI: 10.1016/0006-8993(91)90944-q.Peer-Reviewed Original ResearchConceptsCalcium channel antagonistsRetinal ganglion cellsChannel antagonistsGanglion cellsPostnatal rat retinal ganglion cellsNMDA receptor-operated channelsRat retinal ganglion cellsNMDA receptor-mediated neurotoxicityVoltage-dependent calcium channelsSelective NMDA antagonistDihydropyridine calcium channel antagonistReceptor-operated channelsVoltage-dependent Ca2Patch-clamp recordingsNMDA antagonistsNMDA receptorsSubsequent toxic effectsCalcium channelsExogenous glutamateRetinal culturesAntagonistL-typeEarly riseInjurious effectsToxic effectsHIV‐Related Neurotoxicity
Lipton S. HIV‐Related Neurotoxicity. Brain Pathology 1991, 1: 193-199. PMID: 1669708, DOI: 10.1111/j.1750-3639.1991.tb00659.x.Peer-Reviewed Original ResearchConceptsNeuronal injuryCentral nervous system manifestationsL-type voltage-dependent calcium channelsVoltage-dependent calcium channelsNervous system manifestationsHIV-1 infectionToxic factorsWhite matter lesionsNeuronal cell deathIntracellular calcium concentrationNeuronal cell typesNeuronal lossSystem manifestationsMatter lesionsEndogenous glutamateImmune cellsGlutamate receptorsGp 120Human neuronsCalcium channelsGp120 fragmentRodent neuronsHIVGp120Potential neurotoxinsCalcium Channel Antagonists in the Prevention of Neurotoxicity
Lipton S. Calcium Channel Antagonists in the Prevention of Neurotoxicity. Advances In Pharmacology 1991, 22: 271-297. PMID: 1659865, DOI: 10.1016/s1054-3589(08)60038-1.Peer-Reviewed Original ResearchConceptsCalcium channel antagonistsCalcium channelsImportant calcium channelTypes of neurotoxicityPrevention of neurotoxicityPreliminary human studiesNeuroprotective agentsChannel antagonistsPharmacological antagonistsSystemic effectsHuman studiesPrimary neuronsVivo modelAntagonistNeurotoxicityChannel typesNeuronsPrevention