2022
Modulators of ASIC1a and its potential as a therapeutic target for age-related diseases
Zhou R, Liang H, Hu W, Ding J, Li S, Chen Y, Zhao Y, Lu C, Chen F, Hu W. Modulators of ASIC1a and its potential as a therapeutic target for age-related diseases. Ageing Research Reviews 2022, 83: 101785. PMID: 36371015, DOI: 10.1016/j.arr.2022.101785.Peer-Reviewed Original ResearchConceptsAcid-sensing ion channel 1aAge-related diseasesTherapeutic targetPotential therapeutic targetMost age-related diseasesIon channel 1aNovel drug targetsEffective drugsMultiple organsPathophysiological processesChannel 1aDiseaseChannel family membersPharmacological propertiesImproved treatmentSuch diseasesTissue degenerationCellular apoptosisTreatmentDrug targetsFamily membersPhysiological functionsUrgent needWorldwide populationIschemiaAcid-sensitive ion channel 1a mediates osteoarthritis chondrocyte senescence by promoting Lamin B1 degradation
Ding J, Chen Y, Zhao Y, Chen F, Dong L, Zhang H, Hu W, Li S, Zhou R, Hu W. Acid-sensitive ion channel 1a mediates osteoarthritis chondrocyte senescence by promoting Lamin B1 degradation. Biochemical Pharmacology 2022, 202: 115107. PMID: 35643339, DOI: 10.1016/j.bcp.2022.115107.Peer-Reviewed Original ResearchMeSH KeywordsAcid Sensing Ion ChannelsAnimalsBeclin-1Cartilage, ArticularCellular SenescenceChondrocytesLamin Type BOsteoarthritisRatsRats, Sprague-DawleyConceptsAcid-sensitive ion channel 1aChondrocyte senescenceIon channel 1aChannel 1aBeclin-1Chronic joint diseaseBeclin-1 protein expressionRat OA modelProtein Beclin 1Senescence-related markersJoint diseaseOA modelAging of chondrocytesJoint cavityPsalmotoxin-1Chondrocyte autophagyOsteoarthritisB1 expressionProtein expressionCationic channelsHairpin RNALamin B1Autophagy pathwayArticular cartilageLamin B1 expressionBlockade of ASIC1a inhibits acid-induced rat articular chondrocyte senescence through regulation of autophagy
Yang Y, Ding J, Chen Y, Ma G, Wei X, Zhou R, Hu W. Blockade of ASIC1a inhibits acid-induced rat articular chondrocyte senescence through regulation of autophagy. Human Cell 2022, 35: 665-677. PMID: 35075624, DOI: 10.1007/s13577-022-00676-7.Peer-Reviewed Original ResearchMeSH KeywordsAcid Sensing Ion ChannelsAnimalsAutophagyCartilage, ArticularCellular SenescenceChondrocytesRatsRats, Sprague-DawleyConceptsAcid-sensitive ion channel 1aChondrocyte senescenceRat articular chondrocytesSenescence-related markersExtracellular acidificationSenescence-associated secretory phenotypeTreatment of osteoarthritisPotential therapeutic strategySenescence-associated β-galactosidaseIon channel 1aProtein LC3B-IIArticular chondrocytesC28/I2 chondrocyte cell lineMatrix metalloproteinases genesChondrocyte cell lineTherapeutic strategiesChondrocyte damageControl groupROS expressionPsalmotoxin-1Secretory phenotypeChannel 1aChondrocyte autophagyLC3B-IIMetalloproteinases genes
2020
Acid‐sensing ion channel 1a mediates acid‐induced pyroptosis through calpain‐2/calcineurin pathway in rat articular chondrocytes
Zu S, Feng Y, Zhu C, Wu X, Zhou R, Li G, Dai B, Wang Z, Xie Y, Li Y, Ge J, Chen F. Acid‐sensing ion channel 1a mediates acid‐induced pyroptosis through calpain‐2/calcineurin pathway in rat articular chondrocytes. Cell Biology International 2020, 44: 2140-2152. PMID: 32678496, DOI: 10.1002/cbin.11422.Peer-Reviewed Original ResearchConceptsAcid-sensing ion channel 1aAcid-sensing ion channelsRat articular chondrocytesIon channel 1aChondrocyte pyroptosisTime-dependent mannerCalpain-2Activation of ASICsChannel 1aExtracellular acidosisInhibition of ASIC1aProtein expressionInterleukin-1β levelsArticular chondrocytesSystemic autoimmune diseasePrimary rat articular chondrocytesApoptosis-associated speck-like proteinNLRP3 inflammasome proteinsCalcineurin pathwaySpeck-like proteinCation channel familyRheumatoid arthritisAutoimmune diseasesDegenerative articular cartilageInflammasome proteins17β-estradiol attenuates rat articular chondrocyte injury by targeting ASIC1a-mediated apoptosis
Song S, Tao J, Li S, Qian X, Niu R, Wang C, Zhang Y, Chen Y, Wang K, Zhu F, Zhu C, Ma G, Yang-Yang, Peng X, Zhou R, Chen F. 17β-estradiol attenuates rat articular chondrocyte injury by targeting ASIC1a-mediated apoptosis. Molecular And Cellular Endocrinology 2020, 505: 110742. PMID: 32006608, DOI: 10.1016/j.mce.2020.110742.Peer-Reviewed Original ResearchMeSH KeywordsAcid Sensing Ion ChannelsAnimalsApoptosisAutophagyCartilage, ArticularChondrocytesEstradiolEstrogen Receptor alphaLysosomesMaleProteolysisRats, Sprague-DawleyConceptsAcid-sensing ion channel 1aRheumatoid arthritisChondrocyte injuryTreatment of RAEstradiol replacement therapyProtein levelsAcid-induced damageIon channel 1aAutophagy-lysosomal pathwayJoint swellingCartilage destructionLocal inflammationOvariectomized modelReplacement therapyEstrogen metabolismArticular damageEpidemiological evidenceASIC1a proteinProtective roleAcid-induced apoptosisChannel 1aSodium-permeable channelsInjuryERα receptorMitochondrial function
2019
β-Estradiol Protects Against Acidosis-Mediated and Ischemic Neuronal Injury by Promoting ASIC1a (Acid-Sensing Ion Channel 1a) Protein Degradation
Zhou R, Leng T, Yang T, Chen F, Hu W, Xiong Z. β-Estradiol Protects Against Acidosis-Mediated and Ischemic Neuronal Injury by Promoting ASIC1a (Acid-Sensing Ion Channel 1a) Protein Degradation. Stroke 2019, 50: 2902-2911. PMID: 31412757, PMCID: PMC6756944, DOI: 10.1161/strokeaha.119.025940.Peer-Reviewed Original ResearchMeSH KeywordsAcid Sensing Ion ChannelsAcidosisAnimalsBrain IschemiaEstradiolFemaleMaleMiceMice, Inbred C57BLNeuronsStrokeConceptsIschemic neuronal injuryIschemic brain injuryΒ-estradiol treatmentASIC1a protein expressionNeuronal injuryASIC currentsBrain injuryProtein expressionΒ-estradiolWhole-cell patch-clamp techniqueIntracellular CaAcidosis-induced cytotoxicityAcidosis-mediated injuryActivation of ASIC1aDegree of neuroprotectionOutcome of strokeSeverity of strokeMiddle cerebral arteryTransient focal ischemiaOnline visual overviewAcid-induced elevationEstrogen receptor αReal-time polymerase chain reactionQuantitative real-time polymerase chain reactionPatch-clamp technique
2018
The role of Ca2+ in acid-sensing ion channel 1a-mediated chondrocyte pyroptosis in rat adjuvant arthritis
Wu X, Ren G, Zhou R, Ge J, Chen F. The role of Ca2+ in acid-sensing ion channel 1a-mediated chondrocyte pyroptosis in rat adjuvant arthritis. Laboratory Investigation 2018, 99: 499-513. PMID: 30487596, DOI: 10.1038/s41374-018-0135-3.Peer-Reviewed Original ResearchConceptsAcid-sensitive ion channelsChondrocyte pyroptosisCaspase-1Rheumatoid arthritisIL-18Role of Ca2Autoimmune diseasesIL-1βAdjuvant arthritis rat modelExpression of ASIC1aMain pathogenic featureRat adjuvant arthritisJoints of ratsArthritis rat modelApoptosis-associated speck-like proteinProinflammatory cytokines interleukinExpression of COL2ASpeck-like proteinASIC-1asAdjuvant arthritisPoor prognosisCytokines interleukinNLRP3 inflammasomeAA ratsRat modelNecrostatin-1 ameliorates adjuvant arthritis rat articular chondrocyte injury via inhibiting ASIC1a-mediated necroptosis
Chen Y, Zhu C, Zhu F, Dai B, Song S, Wang Z, Feng Y, Ge J, Zhou R, Chen F. Necrostatin-1 ameliorates adjuvant arthritis rat articular chondrocyte injury via inhibiting ASIC1a-mediated necroptosis. Biochemical And Biophysical Research Communications 2018, 504: 843-850. PMID: 30219231, DOI: 10.1016/j.bbrc.2018.09.031.Peer-Reviewed Original ResearchConceptsRat articular cartilageRheumatoid arthritisNec-1Necrostatin-1Potential therapeutic strategyAcid-induced increaseChannel inhibitor amilorideArticular cartilage damageReceptor interacting protein 1Articular cartilageRIP1/RIP3Chondrocyte injuryAA ratsCartilage damageTherapeutic strategiesRA treatmentCartilage injuryPathophysiological processesPsalmotoxin-1Inhibitor necrostatin-1Expression of RIP1Inhibitor amilorideRIP1 inhibitor necrostatin-1Interacting protein 1ASIC1aAcute Ethanol Exposure Promotes Autophagy-Lysosome Pathway-Dependent ASIC1a Protein Degradation and Protects Against Acidosis-Induced Neurotoxicity
Zhou R, Leng T, Yang T, Chen F, Xiong Z. Acute Ethanol Exposure Promotes Autophagy-Lysosome Pathway-Dependent ASIC1a Protein Degradation and Protects Against Acidosis-Induced Neurotoxicity. Molecular Neurobiology 2018, 56: 3326-3340. PMID: 30120732, PMCID: PMC6378129, DOI: 10.1007/s12035-018-1289-0.Peer-Reviewed Original ResearchConceptsAcid-sensing ion channel 1aAutophagy-lysosome pathwayNeuronal cellsAcidosis-induced cytotoxicityAcute ethanol administrationAcute ethanol exposureActivity/expressionEthanol-induced reductionIon channel 1aAutophagy activator rapamycinAutophagy inhibitor CQEffects of ethanolASIC1a expressionIschemic strokeNeuronal injuryAcute treatmentBrain ischemiaNeuroprotective effectsEthanol administrationASIC currentsEthanol exposureTissue acidosisASIC1a channelsChannel 1aNeurotoxicity
2017
Effects of autophagy on acid-sensing ion channel 1a-mediated apoptosis in rat articular chondrocytes
Xie Y, Li Y, Zhou R, Dai B, Qian Y, Wu X, Ge J, Hu W, Chen F. Effects of autophagy on acid-sensing ion channel 1a-mediated apoptosis in rat articular chondrocytes. Molecular And Cellular Biochemistry 2017, 443: 181-191. PMID: 29273849, DOI: 10.1007/s11010-017-3223-6.Peer-Reviewed Original ResearchConceptsRat articular chondrocytesRheumatoid arthritisEffect of autophagyPathogenesis of RAArticular chondrocytesProgression of RAInhibition of ASIC1aAcid-sensing ion channel 1aMultiple pathogenic factorsDegenerative joint diseaseArticular chondrocyte apoptosisRat knee jointsIon channel 1aShort hairpin RNAPrecise etiologyJoint diseasePathogenic factorsKnee jointPsalmotoxin-1Chondrocyte apoptosisPrimary articular chondrocytesChannel 1aASIC1aAutophagy fluxBeclin-1ASIC2a overexpression enhances the protective effect of PcTx1 and APETx2 against acidosis-induced articular chondrocyte apoptosis and cytotoxicity
Zhou R, Ni W, Dai B, Wu X, Wang Z, Xie Y, Wang Z, Yang W, Ge J, Hu W, Chen F. ASIC2a overexpression enhances the protective effect of PcTx1 and APETx2 against acidosis-induced articular chondrocyte apoptosis and cytotoxicity. Gene 2017, 642: 230-240. PMID: 29141196, DOI: 10.1016/j.gene.2017.11.034.Peer-Reviewed Original ResearchMeSH KeywordsAcid Sensing Ion Channel BlockersAcid Sensing Ion ChannelsAcidosisAlkanesulfonic AcidsAnimalsApoptosisCells, CulturedChondrocytesCnidarian VenomsCollagen Type IIDrug SynergismGene Expression RegulationGenetic VectorsMAP Kinase Signaling SystemMorpholinesPeptidesPlasmidsRatsSpider VenomsConceptsAcid-sensing ion channel 1aArticular chondrocyte apoptosisChondrocyte apoptosisChondrocyte cytotoxicityRheumatoid arthritisProtective effectExpression of ASIC1aAcidosis-induced injuryERK1/2 MAPK signaling pathwaysIon channel 1aAlone groupNeuroprotective effectsChondroprotective effectsMAPK signaling pathwaysProtective roleType II collagenChannel 1aNeuronal cellsAPETx2ASIC2aPcTx1Phosphorylated ERK1/2Pathological charactersInduced apoptosisII collagenASIC1a Promotes Acid-Induced Autophagy in Rat Articular Chondrocytes through the AMPK/FoxO3a Pathway
Dai B, Zhu F, Chen Y, Zhou R, Wang Z, Xie Y, Wu X, Zu S, Li G, Ge J, Chen F. ASIC1a Promotes Acid-Induced Autophagy in Rat Articular Chondrocytes through the AMPK/FoxO3a Pathway. International Journal Of Molecular Sciences 2017, 18: 2125. PMID: 29019932, PMCID: PMC5666807, DOI: 10.3390/ijms18102125.Peer-Reviewed Original ResearchMeSH KeywordsAcid Sensing Ion ChannelsAMP-Activated Protein KinasesAnimalsAutophagyBiomarkersChondrocytesForkhead Box Protein O3MalePrimary Cell CultureRatsRats, Sprague-DawleyInterleukin-1β and tumor necrosis factor-α augment acidosis-induced rat articular chondrocyte apoptosis via nuclear factor-kappaB-dependent upregulation of ASIC1a channel
Zhou R, Dai B, Xie Y, Wu X, Wang Z, Li Y, Wang Z, Zu S, Ge J, Chen F. Interleukin-1β and tumor necrosis factor-α augment acidosis-induced rat articular chondrocyte apoptosis via nuclear factor-kappaB-dependent upregulation of ASIC1a channel. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease 2017, 1864: 162-177. PMID: 28986307, DOI: 10.1016/j.bbadis.2017.10.004.Peer-Reviewed Original ResearchConceptsAcid-sensing ion channel 1aIL-1βRheumatoid arthritisInterleukin-1βNF-κB inhibitor ammonium pyrrolidinedithiocarbamateNF-κB DNA-binding activityPrimary articular chondrocytesProinflammatory cytokine interleukin-1βAcidosis-induced cytotoxicityCytokines interleukin-1βTumor necrosis factorImportant pathological characteristicNF-κB pathwayArticular chondrocyte apoptosisCaspase-3/9 expressionIon channel 1aNuclear factor-kappaBPleiotropic biological effectsArticular chondrocytesAgent BAPTA-AMASIC1a expressionChondrocyte cytotoxicityΚB expressionAdjuvant arthritisPathological characteristics
2015
Interleukin-6 enhances acid-induced apoptosis via upregulating acid-sensing ion channel 1a expression and function in rat articular chondrocytes
Zhou R, Wu X, Wang Z, Ge J, Chen F. Interleukin-6 enhances acid-induced apoptosis via upregulating acid-sensing ion channel 1a expression and function in rat articular chondrocytes. International Immunopharmacology 2015, 29: 748-760. PMID: 26359543, DOI: 10.1016/j.intimp.2015.08.044.Peer-Reviewed Original ResearchMeSH KeywordsAcid Sensing Ion ChannelsAcidsAnimalsAntibodies, Monoclonal, HumanizedApoptosisApoptosis Regulatory ProteinsArthritis, ExperimentalCartilage, ArticularChondrocytesDose-Response Relationship, DrugEnzyme ActivationInterleukin-6L-Lactate DehydrogenaseMalePeptidesRatsRats, Sprague-DawleySpider VenomsUp-RegulationConceptsInflammatory cytokine interleukin-6Acid-sensing ion channelsArticular chondrocyte apoptosisRat articular chondrocytesChondrocyte apoptosisRheumatoid arthritisAcid-induced cell injuryArticular chondrocytesAdjuvant arthritis ratsPrimary rat articular chondrocytesChronic inflammatory diseaseCytokine interleukin-6IL-6 receptorJAK2/STAT3Dose-dependent mannerArthritis ratsInflammatory diseasesInterleukin-6Specific antagonistCell injuryNF-κBAcid-induced apoptosisLDH releaseArthritic cartilageDownregulated expression