個(gè)創(chuàng)新科學(xué)問題小綜述細(xì)胞焦亡

1。其中，細(xì)胞焦亡pyroptosis歸屬于caspase依賴性的調(diào)節(jié)性細(xì)胞RCD1-5。胞NCCDcelldeath,LDCD:lysosome-dependentcelldeathMPT:mitochondrialpermeabilitytransition.解螺旋胞細(xì)胞焦亡是一種由免疫導(dǎo)致的胞外胞內(nèi)穩(wěn)態(tài)失調(diào)的調(diào)節(jié)性細(xì)胞RCD，表現(xiàn)出特殊的形態(tài)包括一種奇特的與凋亡不同的染色質(zhì)凝集，以及細(xì)胞腫脹和質(zhì)膜透化作用（2）11。細(xì)胞焦亡主要在對(duì)抗胞內(nèi)病原體的免疫起作用，在病因?qū)W上涉及諸如致死染性休克的病理狀況12。樣，箭頭所指即焦亡和程序性壞死的細(xì)胞，TS(TNFandsmacmimetic)，TSZ(TNF,smacmimeticandthecaspaseinhibitorz-VAD)，Nignigericin)。解螺旋在分子水平，免疫刺激后，焦亡主要依賴一個(gè)或多個(gè)的CASP的激活包括CASP1、主要觸發(fā)因素。尤其已經(jīng)證明了的當(dāng)革蘭氏菌時(shí)，CASP11負(fù)責(zé)響應(yīng)非CASP1巨噬細(xì)胞15。此外，CASP1缺失可保護(hù)小鼠免受細(xì)胞質(zhì)侵入性細(xì)菌的，以及對(duì)抗全身性LPSpyroptosis16CASP11，一些細(xì)胞類型中，CASP11激活可以在沒有細(xì)胞的情況下驅(qū)動(dòng)IL-1β分泌。現(xiàn)表明，GSDMDC（GSDMD-CRD）N-末端成孔結(jié)構(gòu)域16個(gè)對(duì)稱的原體組成，內(nèi)徑為~10-14nm18。解螺旋以及DAMP通常過(guò)去刺激經(jīng)典炎癥小體信號(hào)進(jìn)而焦亡17。CASP1驅(qū)動(dòng)的焦亡通過(guò)殺死宿CASP1驅(qū)動(dòng)的焦亡在免疫處理細(xì)菌的重要角色。GSDMSMSDGSDM（種DNA損傷性化學(xué)治療劑，和/或水皰性口炎13。在這種情況下，CASP3負(fù)責(zé)激活會(huì)導(dǎo)致多種化學(xué)治療劑的副作用，至少在小鼠中是這樣。有趣的是，GSDME/DFNA5也死表型，進(jìn)一步證明了不同類型的RCD之間存在的升高的相互連接程度。鑒定多個(gè)gasdermin成員作為pyroptosis后期的關(guān)鍵因素，以及CASP3作為GSDME/DFNA5激活劑的特征，擴(kuò)大了這種RCD形式的相關(guān)性，遠(yuǎn)遠(yuǎn)超出了炎癥設(shè)定13,21。MLKLNLRP3IL-1βIL-1βGSDMD22,23Casp-1Gasdermin成員被抑制時(shí)，與細(xì)胞凋亡密切相關(guān)的啟動(dòng)及其介導(dǎo)的蛋白成熟過(guò)程將成為不同RCD的crosstalk表型標(biāo)志物30,31。解螺旋細(xì)胞焦亡作為調(diào)節(jié)性細(xì)胞RCD的一種形式，其關(guān)鍵取決于gasdermin蛋白成32-34、心血管類疾病35、相關(guān)的病3637、神經(jīng)退行性炎癥38和膿毒血癥39,40等。GalluzziL,VitaleI,AaronsonSA,etal.Molecularmechanismsofcelldeath: mendationsoftheNomenclatureCommitteeonCellDeath2018.Celldeathanddifferentiation2018;25(3):486-541.KroemerG,El-DeiryWS,GolsteinP,etal.Classificationofcelldeath: mendationsoftheNomenclatureCommitteeonCellDeath.Celldeathanddifferentiation2005;12Suppl2:1463-7.KroemerG,GalluzziL,VandenabeeleP,etal.Classificationofcelldeath: mendationsoftheNomenclatureCommitteeonCellDeath2009.Celldeathanddifferentiation2009;16(1):3-11.GalluzziL,VitaleI,AbramsJM,etal.Moleculardefinitionsofcelldeathsubroutines:mendationsoftheNomenclatureCommitteeonCellDeath2012.Celldeathanddifferentiation2012;19(1):107-GalluzziL,Bravo-SanPedroJM,VitaleI,etal.Essentialversusaccessoryaspectsofcelldeath:mendationsoftheNCCD2015.Celldeathanddifferentiation2015;22(1):58-73.JorgensenI,MiaoEA.Pyroptoticcelldeathdefendsagainstintracellularpathogens.Immunologicalreviews2015;265(1):130-42.ChenX,HeWT,HuL,etal.Pyroptosisisdrivenbynon-selectivegasdermin-DporeanditsmorphologyisdifferentfromMLKLchannel-mediatednecroptosis.Cellresearch2016;26(9):1007-20.BergsbakenT,FinkSL,CooksonBT.Pyroptosis:hostcelldeathandinfl tion.NaturereviewsMicrobiology2009;7(2):99-109.ShiJ,GaoW,ShaoF.Pyroptosis:Gasdermin-MediatedProgrammedNecroticCellDeath.Trendsinbiochemicalsciences2017;42(4):245-54.ShiJ,ZhaoY,WangY,etal.Infl torycaspasesareinnateimmunereceptorsforintracellularLPS.Nature2014;514(7521):187-92.WangY,GaoW,ShiX,etal.Chemotherapydrugsinducepyroptosisthroughcaspase-3cleavageofagasdermin.Nature2017;547(7661):99-103.FranchiL,EigenbrodT,Munoz-nilloR,NunezG.The some:acaspase-1-tformthatregulatesimmuneresponsesanddiseasepathogenesis.Natureimmunology2009;10(3):KayagakiN,WarmingS,LamkanfiM,etal.Non-canonicalinfl someactivationtargetscaspase-11.Nature2011;479(7371):117-21.KayagakiN,StoweIB,LeeBL,etal.Caspase-11cleavesgasderminDfornon-canonical somesignalling.Nature2015;526(7575):666-71.ShiJ,ZhaoY,WangK,etal.CleavageofGSDMDbyinfl torycaspasesdeterminespyroptoticcelldeath.Nature2015;526(7575):660-5.DingJ,WangK,LiuW,etal.Pore-formingactivityandstructuralautoinhibitionofthegasderminfamily.Nature2016;535(7610):111-6.LiuX,ZhangZ,RuanJ,etal.Infl some-activatedgasderminDcausespyroptosisbyformingmembranepores.Nature2016;535(7610):153-8.JorgensenI,ZhangY,KrantzBA,MiaoEA.Pyroptosistriggerspore-inducedintracellulartraps(PITs)thatcapturebacteriaandleadtotheirclearancebyefferocytosis.TheJournalofexperimentalmedicine2016;213(10):2113-28.RogersC,Fernandes-AlnemriT,MayesL,AlnemriD,CingolaniG,AlnemriES.CleavageofDFNA5bycaspase-3duringapoptosismediatesprogressiontosecondarynecrotic/pyroptoticcelldeath.Naturecommunications2017;8:14128.RussoHM,RathkeyJ,Boyd-TresslerA,KatsnelsonMA,AbbottDW,DubyakGR.ActiveCaspase-1InducessmaMembranePoresThatPrecedePyroptoticLysisandAreBlockedbyLanthanides.Journalofimmunology(Baltimore,Md:1950)2016;197(4):1353-67.ReleaseofIL-1betaIndependentlyofGasdermin-DJournalofimmunologyBaltimoreMd19502017;198(5):2156-64.解螺旋ConosSA,ChenKW,DeNardoD,etal.ActiveMLKLtriggerstheNLRP3infl someinacell-intrinsicmanner.ProcNatlAcadSciUSA2017;114(6):E961-e9.SagulenkoV,ThygesenSJ,SesterDP,etal.AIM2andNLRP3infl andpyroptoticdeathpathwaysviaASC.Celldeathanddifferentiation2013;20(9):1149-60.PieriniR,JurujC,PerretM,etal.AIM2/ASCtriggerscaspase-8-dependentapoptosisinFrancisella-infectedcaspase-1-deficientmacrophages.Celldeathanddifferentiation2012;19(10):1709-21.FelthamR,VinceJE,LawlorKE.Caspase-8:notsosilentlydeadly.Clinical&translationalimmunology2017;6(1):e124.VajjhalaPR,LuA,BrownDL,etal.TheInfl someAdaptorASCInducesProcaspase-8DeathEffectorFilaments.TheJournalofbiologicalchemistry2015;290(49):29217-30.JorgensenI,RayamajhiM,MiaoEA.Programmedcelldeathasadefenceagainstinfection.NaturereviewsImmunology2017;17(3):151-64.JulienO,WellsJA.Caspasesandtheirsubstrates.Celldeathanddifferentiation2017;24(8):1380-KantonoM,GuoB.Infl somesandCancer:TheDynamicRoleoftheInfl Development.Frontiersinimmunology2017;8:1132.ZhouB,ZhangJY,LiuXS,etal.Tom20sensesiron-activatedROSsignalingtopromotemelanomacellpyroptosis.Cellresearch2018.JohnsonDC,TaabazuingCY,OkondoMC,etal.DPP8/DPP9inhibitor-inducedpyroptosisLiuD,ZengX,LiX,MehtaJL,WangX.RoleofNLRP3infl someinthepathogenesisofcardiovasculardiseases.Basicresearchincardiology2017;113(1):5.ManSM,KarkiR,KannegantiTD.Molecularmechanismsandfunctionsofpyroptosis,infl caspasesandinfl somesininfectiousdisease