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

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：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

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

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：Anuranmetamorphosisinvolvessystematictransformationsofindividualorgansinathyroidhormone(TH)-dependentmanner.Morphologicalandcellularstudieshaveshownthattheremovaloflarvalorgans/tissuessuchthetailandthetadpoleintestinalepitheliumisthroughprogrammedcelldeathorapop-tosis.RecentmolecularinvestigationssuggestthatTHregulatesmetamorphosisbyregulatingtargetgeneexpressionthroughthyroidhormonereceptors(TRs),whichareDNA-bindingtranscriptionfactors.Cloning

简介：ApoptosisproducedinBcellsthroughFas(APO-1,CD95)triggeringisregulatedbysignalsderivedfromothersurfacereceptors:CD40engagementproducesupregulationofFasexpressionandmarkedsusceptibilitytoFas-inducedcelldeath,whereasantigenreceptorengagement,orIL-4Rengagement,inhibitsFaskillingandinsodoinginducesastateofFas-resistance,eveninotherwisesensitive,CD40-stimulatedtargets.SurfaceimmunoglobulinandIL-4RutilizeatleastpartiallydistinctpathwaystoproduceFas-resistancethatdifferentiallydependonPKCandSTAT6,respectively.Further,surfaceimmunoglobulinsignalingforinducibleFas-resistancebypassesBtk,requiresNF-κB,andentailsnewmacromolecularsynthesis.TerminaleffectorsofBcellFas-resistanceincludetheknownanti-apoptoticgeneproducts,Bcl-XLandFLIP,andanovelanti-apoptoticgenethatencodesFAIM(FasApoptosisInhibitoryMolecule).faimwasidentifiedbydifferentialdisplayandexistsintwoalternativelysplicedforms;faim-Sisbroadlyexpressed,butfaim-Lexpressionistissue-specific.TheFAIMsequenceishighlyevolutionarilyconserved,suggestinganimportantroleforthismoleculethroughoutphylogeny.InducibleresistancetoFaskillingishypothesizedtoprotectforeignantigen-specificBcellsduringpotentiallyhazardousinteractionswithFasL-bearingTcells,whereasautoreactiveBcellsfailtobecomeFas-resistantandaredeletedviaFas-dependentcytotoxicity.InadvertentoraberrantacquisitionofFas-resistancemaypermitautoreactiveBcellstoescapeFasdeletion,andmalignantlymphocytestoimpedeanti-tumorimmunity.

简介：Apoptosisorprogrammedcelldeath(PCD)isanevolutionarilyconservedcellularprocessthatisessentialfornormaldevelopmentandhomeostasisofmulticellularorganisms.Defectsintheapoptosissignalingresultinmanydiseasesincludingautoimmunediseasesandcancer.TheapoptosissignalingpathwaywasfirstdescribedgeneticallyinthenematodeCaenorhabditiseleganswhichservesasaframeworkforthemorecomplexapoptoticpathwaysthatexistinmammals.Inthisreview,wewilldiscusstheapoptoticpathwaysthatareemerginginmammalsaselucidatedbystudiesofgene-targetedmutantmice.

简介：Acetylcholinesterase(AChE)playsakeyroleinterminatingneurotransmissionatcholinergicsynapses.AChEisalsofoundintissuesdevoidofcholinergicresponses,indicatingitspotentialfunctionbeyondneurotransmission.IthasbeensuggestedthatAChEmayparticipateindevelopment,differentiation,andpathogenicprocessessuchasAlzheimer'sdiseaseandtumorigenesis.WeexaminedAChEexpressioninhumanlungfibroblastcellline(HLF)uponinductionofapoptosisbyUVorG418.AChEisinducedinallapoptoticcellsexaminedasdeterminedbycytochemicalstaining,immunologicalanalysis,affinity

简介：Apoptosis在众多的医药混乱的病原学或致病起一个枢轴的作用，并且这样，apoptotic房间指向可以实质地推进耐心的照顾。在我们为为apoptosis的新奇low-molecular-weight探针的探索，我们集中了于不平常的氨基酸纬-carboxyglutamic酸(Gla)，它在clotting因素的绑定起一个重要作用到否定地控告的phospholipid表面。基于Gla的alkyl-malonic酸主题，我们开发了并且现在介绍ML-10(2-(5-fluoro-pentyl)-2-methyl-malonic酸，MW=206Da)，apoptosis的小分子的察觉者的一个新奇家庭的原型的成员。ML-10被发现在apoptotic房间执行选择举起和累积，当从可行或坏死的房间被排除时。有caspase激活，Annexin-V绑定和mitochondrial膜潜力的混乱的apoptotic特点的ML-10举起相互关联。malonate一半被发现为在apoptosis察觉的ML-10功能关键。ML-10在早apoptosis对房间的特征的唯一的建筑群作出回应，包括膜潜力，房间膜和细胞质的永久使发酸，和膜正直的保藏的不可逆的损失。ML-10因此是迄今为止知道的最紧缩的apoptosis探查。由于它的氟的符号原子，ML-10对顺从与18F同位素标记收音机，向它为apoptosis的临床的正电子排放断层摄影术成像的潜在的未来使用。

简介：<正>Immunologicaltolerancetoselfisessentialformaintainingtheintegrityoftheorgansystems,anditsbreakdownmayleadtothedevelopmentofautoimmunediseases.Tolerancetoselfismaintainedthroughseveralmechanisms,whichincludenegativeselection,functionalinactivation(anergy)andsuppressionofautoreactivelymphocytes.However,onlynegativeselectionpermanentlyremovesautoreactivecellsthroughapoptosis.WhileithaslongbeenknownthatnegativeselectionrequiresaTcellreceptor(TCR)signal,itisunclearwhetheradeathligandsignalisalsoinvolved.TRAIL,thetumornecrosisfactor(TNF)-relatedapoptosis-inducingligand,isanewlydescribedmemberoftheTNFfamily.Unlikeotherdeathligandsof

简介：我们期望有机体发展了机制收集并且使用在他们的环境以内可得到的信息，到向将给最大的健康回来的特点驾驶资源投资决定。Pheromones是社会信号，哪个是充当配偶存在的指示物的一个普通目的。因而，pheromones有潜力充当信号在竞争生活历史特点的上增加或维持繁殖投资。在蟑螂，Nauphoetacinerea(奥利弗)，当没有男性，和男性时，女性们付在复制维持投资的费用生产被知道完成女繁殖结果的pheromones。是否pheromones对资源生理学的影响是未知的。我们最新使eclosed女性遭到了到也男pheromones或控制的合成混合。我们把了在7，12，17或22天的女性。我们在vitellerium以内测量了apoptosis层次和所有卵母细胞的尺寸，并且测量了干燥胖身体质量。合成男pheromone混合没在女繁殖或体的资源生理学的任何措施上有效果。尽管否定结果总是是有问题的，在过去的合成pheromone方法的成功建议女性们可能对在pre-oviposition时期的男pheromones感觉迟钝，并且可以依靠为卵母细胞维护和生长作为暗示交配刺激而非pheromone。在女复制上报导男pheromones的效果的以前的研究建议pheromone敏感的时期可能在交配和出生之间。

简介：XADisanapoptosisspecificDNaseinXenopusandcancutthelinker-DNAbetweennucleosomesduringapoptosisinXenopuslaeviseggextractinducedbycytochromec.XADismostlikelytobethehomologuetoDFF40inhumans.TheactivityofDFF40canbeinhibitedbyDFF45.WereportmolecularcloningandidentificationofanXADinhibitor,IXAD(inhibitorofXAD),inXenopuseggs.WeclonedthecompletecDNAoftheDFF45homologue,IXAD.ThereisaspecificDEVDsequenceinitsN-terminal,whichserves

简介：Inordertostudythemechanismoftheeffectofheparinonapoptosisincarcinomacells,thenasopharyngealcarcinomacelllineCNE2wasusedtoidentifytheeffectofheparinonapoptosisassociatedwiththeexpressionofc-myc,bax,bcl-2proteinsbyuseofHoechst33258staining,terminaldeoxynucleotidyltransferase-mediateddUTPnick-endlabeling(TUNEL),agarosegelelectrophoresis,andflowcytometry,aswellasWesternblotanalysis.TheresultsshowedthatheparininducedapoptosisofCNE2cellsincludingthemorphologicchangessuchasreductioninthevolume,andthenuclearchromatincondensation,aswellasthe“ladderpattern”revealedbyagarosegelelectrophoresisofDNAinaconcentration-dependentmanner.ThenumberofTUNEL-positivecellswasdramaticallyincreasedto33.6±1.2%from2.8±0.3%bytreatmentwithheparinindifferentconcentrations(10～40kU/L).Theapoptoticindexwasincreasedto32.5%from3.5%bydetectingSubG1peaksonflowcytometry.Westernblotanalysisshowedthatlevelsofbcl-2,baxandc-mycweresignificantlyoverexpressedbytreatmentwiththeincreaseofheparinconcentrations.TheseresultssuggestthatheparininducesapoptosisofCNE2cells,whichmayberegulatedbydifferentialexpressionofapoptosis-relatedgenes.