简介：CleavageofchromosomalDNAintooligonucleosomalsizefragmentsisanintegralpartofapoptosis.ElegantbiochemicalworkidentifiedtheDNAfragmentationfactor(DFF)asamajorapoptoticendonucleaseforDNAfragmentationinvitroGeneticstudiesinmicesupporttheimportenceofDFFinDNAfragmentationandpossiblyinapoptosisinvivo.RecentworkalsosuggeststheexistenceofadditionalendonucleasesforDNAdegradation.Understandingtherolesofindividualendonucleasesinapoptosis,andhowtheymightcoordinatetodegradeDNAindifferenttissuesduringnormaldevelopmentandhomeostasis,aswellasinvariousdiseasedstates,willbeamajorresearchfocusinthenearfuture.

简介：<正>Apoptosisisahighlyregulatedphysiologicalprocesscriticalindevelopmentandtissuehomeostasis.Abnormalapoptosiscanleadtodiseaseconditionsincludingneurodegeneration,autoimmunityandcancer.DNAfragmentationisanintegralpartofapoptosisandhaslongbeensuspectedtobeofcriticalimportanceincleaninguppotentiallyantigenicDNAandgeneticmaterialcapableofinducingneoplasmictransformationinneighboringcells.DirectevidenceforthisfunctionofDNAfragmentationhowever,isstilllacking.TheidentificationofaheterodimericDNAfragmentationfactor45and40(DFF45andDFF40,alsocalledICADforInhibitorofCaspaseActivatedDNaseandCADforCaspaseActivatedDNaserespectively)aswellas

简介：Objective:Toobservehumanneuronalapoptosissecondarytotraumaticbraininjury,andtoelucidateitsregulativemechanismandthechangeofexpressionofapoptosis-relatedgenes.Methods:Specimensofbrainwerecollectedfromcasesoftraumaticbraininjuryinhumans.Thehistologicalandcellularmorphologywasexaminedbylightandelectronmicroscopy.TheextentofDNAinjurytocorticalneuronswasdetectedbyusingTUNEL.ByinsituhybridisationandimmunohistochemistrythemRNAchangesandproteinexpressionofBcl-2,Bax,p53,andcaspase3p20subunitwereobserved.Results:Apoptoticneuronsappearedfollowingtraumaticbraininjury,peakedat24hoursandlastedfor7days.Innormalbraintissueactivatedcaspase3wasrare,butashorttimeaftertraumaitbecameactivated.Theactivitypeakedat20-28hoursandremainedhigherthannormalfor5-7days.TherewasnoexpressionofBcl-2mRNAandBcl-2proteininnormalbraintissuebut8hoursafterinjurytheirexpressionbecameevidentandthenincreased,peakedat2-3daysandremainedhigherthannormalfor5-7days.TheprimaryexpressionofBax-mRNAandBaxproteinwashighinnormalbraintissue.At20-28hourstheyincreasedandremainedhighfor2-3days;onthe7thdaystheyreturnedtoanormallevel.Innormalbraintissue,p53mRNAandP53wereminimallyexpressed.Increasedexpressionwasdetectedatthe8thhour,anddecreasedat20-28hoursbutstillremainedhigherthannormalonthe5thday.Conclusions:Followingtraumaticinjurytothehumanbrain,apoptoticneuronsappeararoundthefocusoftrauma.ThemRNAandproteinexpressionofBcl-2,Baxandp53andtheactivityofcaspase3enzymeareincreased.

简介：Wehaveidentifiedseveralkeyeventsinthymocyteapoptosisoverthepastfewyears,includingarequiredroleforproteasomefunctionandtheproductionofROS.WhileweourdataestablishedthatproteasomefunctionandROSproductionarerequiredforapoptosisinthymocytes,wehadnotestablishedtheorderofeventsleadingfromtheprimaryapoptoticstimulustotheactivationofcaspases.Recently,wehavedemonstratedthatbothTcellreceptorinducedapoptosisandglucocorticoidinducedapoptosissignalthymocytestodiethroughactivationoftheproteasomeandthiseventisupstreamoftheproductionofROS.

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简介：Weisolatedandpurifiedmitochondriafrommouseliversandspinachleaves.WhenaddedintoeggextractsofXenopuslaevis,theycausednucleiofmouselivertoundergoapoptoticchanges.Chromatincondensation,marginationandDNAladderwereobserved.Afterincubatingisolatedmitochondriainsomehypotonicsolutions,andcentrifugingthesemixturesatmghspeed,wegotmitochondrialsupernatants.Itwasfoundthatintheabsenceofcytosolicfactor,thesupernatantalonewasabletoinduceapoptoticchangesinnuclei.Theeffectivecomponentswerepartlyofprotein.DNAfragmentationwaspartlyinhibitedbycaspaseinhibitorsAC-DEVD-CHOandAC-YVAD-CHO.Meanwhile,caspaseinhibitorsfullyblockedchromatincondensation.Primarycharacterizationofthenuclearendonuclease(s)inducedbymitochondrialsupernatantswasalsoconducted.ItwasfoundthatthisendonucleaseisdifferentfromendonucleaseG,cytochromec-inducednuclease,orCa^2+-activatedendonuclease.

简介：OurpreviousstudyshowedthattwoMKN45variants,namelyMKN45Lm-andMKN45Lm+selectedbylamininadhesioninvitro,haddifferentabilitiesofinvasionandmetastasisinvivo(inoculatedinnudemice)andinvitro(inBoydenchamber),alsohaddifferentexpressionofcysteineproteinase.Inthepresentstudy,weinvestigatedthecellapoptosisofthisMKN45variantsbyTUNELandFACSmethods.Theresultswereshownsignificantdifferentofcellapoptosisinthiscellsublines.TheMKN45Lm-cellshadasmallsubdiploidypeak(3.5%)inDNAcontentanalyzedbyflowcytometry,

简介：肺上皮是在各种各样的肺疾病的肺损坏的主要地点。上皮的房间apoptosis被认为是在各种各样的肺疾病的起始的事件。发信号的Apoptosis古典主义地由二条原则小径组成。一个人是从死亡受体结扎的一条直接小径到caspase串联激活和房间死亡。象药，放射，传染代理人和反应的氧种类那样的压力触发的另外的小径被线粒体调停。Endoplasmic蜂窝胃也被显示了是细胞器调停apoptosis.Epithelial房间死亡被改变过程跟随，它由组成上皮并且成纤维细胞激活，cytokine生产，凝结小径的激活，neoangiogenesis，re-epithelialization和fibrosis.Epithelial和间充质的相互作用在这些过程起重要作用。apoptosis由新奇策略发信号和它的规定的进一步的理解可以对各种各样的肺疾病导致有效治疗。我们在apoptosis发信号的理解考察最近的进展并且在肺改变讨论apoptosis的参与。

简介：Apoptosiscanbetriggeredbyavarietyofstimuliincludingdeathfactors,anti-cancerdrugsandfactor-deprivation.Theseapoptoticcellsareswiftlyphagocytosedbymacrophagestopreventthereleaseofnoxiousorinflammatorymaterialsfromdyingcells.ThemolecularanalysisofFasligand(adeathfactor)-inducedapoptosisindicatedthatacascadeofproteases(caspases)isactivatedduringthisprocess,whicheventuallyactivatesaspecificDNase(caspase-activatedDNase).CADexistsasacomplexwithitsinhibitor(ICAD)inproliferatingcells.Whenthecellsaretriggeredtoapoptosis,caspases,inparticularcaspase3,inthedownstreamofthecaspasecascadecleaveICAD,whichreleasesCADtocauseDNAdegradationinnuclei.

简介：ApoptosisplaysanessentialroleinTcellbiology.ThymocytesexpressingnonfunctionalorautoreactiveTCRsareeliminatedbyapoptosisduringdevelopment.ApoptosisalsoleadstothedeletionofexpandedeffectorTcellsduringimmuneresponses.Thedysregulationofapoptosisintheimmunesystemresultsinautoimmunity,tumorogenesisandimmunodeficiency.Twomajorpathwaysleadtoapoptosis:theintrinsiccelldeathpathwaycontrolledbyBcl-2familymembersandtheextrinsiccelldeathpathwaycontrolledbydeathreceptorsignaling.Thesetwopathwaysworktogethertoregu

简介：<正>Acutepromyelocyticleukaemia(APL)hasbeenattractingawideinterestfarbeyondhematologicalfieldinthelastdozenyearsduetothepresenceofspecificchromosometranlocationsandclinicalresponsibilitytoall-transretinoicacid(ATRA)bydifferentiationinductionaswellastoarsenictrioxide(ATO).Most(>95%)APLpatientscarryspecificchromosometranslocationt(15;17),whichleadstodiscoveryofPMLgeneonchromosome15.SuchatranslocationcausesthefusionofPMLtoretinoicacidreceptor-alpha

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简介：Apoptosis,orcontrolledcelldeath,isanormalpartofcellularlifespan.Celldeathofcochlearhaircellscausesdeafness;anapoptoticprocessthatisnotwellunderstood.Worldwide,1.3billionhumanssuffersomeformofhearingloss,while360millionsufferdebilitatinghearinglossasadirectresultoftheabsenceofthesecochlearhaircells(WorldwideHearing,2014).Muchisknownaboutapoptosisinothersystemsandinothercelltypesthankstostudiesdonesincethemid-20thcentury.Herewereviewcurrentliteratureonapoptosisingeneral,andcausesofdeafnessandcochlearhaircellslossasaresultofapoptosis.ThefamilyofB-celllymphoma(Bcl)proteinsareamongthemoststudiedandcharacterized.WewillreviewcurrentliteratureontheBcl2andBcl6proteininteractionsinrelationtoapoptosisandtheirpossiblerolesinvulnerabilityandsurvivalofcochlearhaircells.

简介：<正>Manyvirusesestablishlife-longinfectionsintheirnaturalhostwithfewifanyclinicalmanifestations.Therelationshipbetweenvirusandhostisadynamicprocessinwhichthevirushasevolvedthemeanstocoexistbyreducingitsvisibility,whilethehostimmunesystemattemptstosuppressandeliminateinfectionwithoutdamagetoitself.Wearenowbeginningtounderstandthatvirusescanemployavarietyofstrategiestoevadehostimmuneresponses.TheseincludeescapefromTcellrecognition,resistanceto

简介：Apoptosisisprimarilyexecutedbyactivecaspases,whicharederivedfromtheinactiveprocaspasezymogensthroughproteolyticcleavage.Wedeterminedthecrystalstructuresofacaspasezymogen,procaspase-7,andanactivecaspase-7withoutanyboundinhibitors.Comparedtotheinhibitor-boundcaspase-7,procaspase-7zymogenexhibitssignificantstructuraldifferencessurroundingthecatalyticcleft,whichprecludestheformationofaproductiveconformation.Proteolyticcleavageinbetweenthelargeandsmallsubunitsallowsrearrangementofessentialloopsintheactivesite,primingactivecaspase-7forinhibitor/substratebinding.Strikingly,bindingbyinhibitorscausesa180-degree-flippingoftheN-terminusinthesmallsubunit,whichinteractswithandstabilizesthecatalyticcleft.Theseanalysesrevealthestructuralmechanismsofcaspaseactivationanddemonstratethattheinhibitor/substratebindingisaprocessof

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简介：Stressinducedtheseriousdisorderofcardiacfunctionandcardiovasculardiseases.Apoptosisisthecellularbasisinstressinducedcardiacinjury.Inourpreviousstudywefoundthatmanystressorsresultedinmitochondrialdamage.Itiscertainthatmitochondriaisimportantmediatorintriggeringapoptoticcelldeath,butthemechanism,bywhichthestressinducedmitochondrialinjuryleadstocardiomyocyteapoptosis,remainsunclear.Wedesignedthepresentstudytoinvestigatethechangesofthemitochondriaincardiomyocytesundergoingstressanditsroleininducingapoptosis.Herewereportedthatstresschangedthemembranefluidityofmitochondriaandinducedthelipidperoxidationofmitochondrialmembranein

简介：Apoptosisisaformofgeneticallyprogrammedcelldeath,whichplaysakeyroleinregulationofcellularityinavarietyoftissueandcelltypesincludingthecardiovasculartissues.Underbothphysiologicalandpathophysiologicalconditions,variousbiophysiologicalandbiochemicalfactors,includingmechanicalforces,reactiveoxygenandnitrogenspecies,cytokines,growthfactors,oxidizedlipoproteins,etc.,mayinfluenceapoptosisofvascularcells.TheFas/Fasligand/caspasedeath-signalingpathway,Bcl-2proteinfamily/mitochondria,thetumorsuppressivegenep53,andtheproto-oncogenec-mycmaybeactivatedinatheroscleroticlesions,andmediatesvascularapoptosisduringthedevelopmentofatherosclerosis.Abnormalexpressionanddysfunctionoftheseapoptosis-regulatinggenesmayattenuateoracceleratevascularcellapoptosisandaffecttheintegrityandstabilityofatheroscleroticplaques.Clarificationofthemolecularmechanismthatregulatesapoptosismayhelpdesignanewstrategyfortreatmentofatherosclerosisanditsmajorcomplication,theacutevascularsyndromes.

简介：尽管有在动物模型获得的出色的结果，船边交货ligand(FasL)的临床的使用被严重毒性作为anticancer药限制。死亡ligands的全身的毒性可以被使用编码膜界限死亡ligands的基因阻止，由指向的transgene，通过也的表示指向了transduction或指向了抄写。肿瘤房间死亡的选择正式就职是有希望的anticancer策略。熔化蛋白质被熔化船边交货ligand(FasL)的细胞外的领域到有选择地在肿瘤endothelial房间上指向av3-integrins的肽arginine-glycine-aspartic酸(RGD)创造。这研究的目的是在鼠科的hepatocellular癌(HCC)在肿瘤生长和幸存上评估RGD-FasL的效果肿瘤模型。有与FasL作为与那相比在HCC肿瘤模型上显示明显的镇压效果的RGD-FasL的处理(p<0.05)并且在这个模型在肿瘤生长延期上导致了更多的添加剂效果。RGD-FasL处理显著地提高了老鼠幸存并且没引起有毒的效果，例如重量损失，机关失败，或另外的处理相关的毒性。Apoptosis被流动cytometric分析和TUNEL试金检测；那些结果也证明RGD-FasL比FasL是为H22和H9101房间线的房间apoptosis的更多的有势力inducer(p<0.05)。在结论，RGD-FasL看起来是肿瘤房间死亡的低毒性的选择inducer，它在现出症状之前的潜、临床的研究应得进一步的调查。而且，这条途径与治疗学的recombinant蛋白质为complexing目标ligands提供一种万用的技术。为了在vivo，肿瘤和肝区分FasL的反肿瘤效果，纸巾被收获由染色的Hematoxylin和曙红(H&E)为坏死的房间，肿瘤房间，或apoptotic房间的证据检验。

简介：氮的氧化物(没有)作为一个immunoregulatory分子，主要取决于S-nitrosylation，充当执行它的规定和信号transduction的一个万用的播放器因为施加它有免疫力的房间的多功能和pleiotropy.Apoptosis是结合的复杂进程取决于综合多样的内长、外长的信号和函数在免疫系统支撑动态平衡的积极/否定的选择。这里，不在apoptosis取决于它的集中的双角色被考察，在在apoptotic过程的一个开关模式上面繁殖。从apoptosis死亡的不同开关的后面的评价，开始GSNO的thymocyteapoptosis和NOS-GSNOR双控制的检查点(早荧光点)的新发现是highlighted.Moreover，S-nitrosylation/denitrosylation，作为一个氧化还原作用切换，逻辑地来临到新陈代谢本身和进一步的存取的网络整个的neuroendicrine-immune-free激进分子网络。而且，主人防卫调停了由不在病原体上，经由蛋白质，S-nitrosylation也被讨论。