分子細(xì)胞生物學(xué)進(jìn)展：novel concepts on cell death

Celldeath:what’snew細(xì)胞死亡

(Celldeath)

一、

細(xì)胞凋亡的概念

細(xì)胞死亡有兩種形式：細(xì)胞凋亡和細(xì)胞壞死細(xì)胞凋亡（apoptosis):apoptosis為希臘語，原指秋天時(shí)樹葉自然凋零。細(xì)胞凋亡指細(xì)胞在一定的生理和病理?xiàng)l件下，遵循自身的程序，自己結(jié)束生命的過程。細(xì)胞壞死(necrosis):外來致病因素作用下使得細(xì)胞正常代謝活動(dòng)被強(qiáng)行中斷而引起的“意外”的、被動(dòng)性死亡過程；只見于病理情況下。textbook

細(xì)胞壞死細(xì)胞凋亡?程序性細(xì)胞死亡（PCD）指在生長(zhǎng)發(fā)育過程中細(xì)胞在基因調(diào)控下，按照一定時(shí)空順序發(fā)生的生理性死亡。細(xì)胞凋亡是形態(tài)學(xué)的概念，程序性細(xì)胞死亡是功能上的概念。?細(xì)胞凋亡的生物學(xué)意義1.細(xì)胞凋亡與個(gè)體發(fā)育

胚胎、生后2.細(xì)胞凋亡與組織更新上皮、血液、免疫3.細(xì)胞凋亡與損傷修復(fù)4.細(xì)胞凋亡與衰老

通過凋亡可及時(shí)清除衰老細(xì)胞，降低機(jī)體癌變的危險(xiǎn)。

1.形態(tài)學(xué)特征(DNA染色、標(biāo)記特征；電鏡)2.生化特征（DNA電泳特征；caspase活性）3.線粒體結(jié)構(gòu)和功能的改變（染料顯示膜電位、cytoC）4.質(zhì)膜的改變（AnnexinV結(jié)合PS；PI結(jié)合DNA）細(xì)胞凋亡的特征（與檢測(cè)指標(biāo)）to凋亡小體back生化特征（1）胱冬肽酶級(jí)聯(lián)反應(yīng)及其在凋亡中的作用（2）DNA的降解（3）ATP的消耗胱冬肽酶（caspase）構(gòu)成的級(jí)聯(lián)反應(yīng)是凋亡過程的核心。1）胱冬肽酶級(jí)聯(lián)反應(yīng)2）胱冬肽酶的作用底物返回細(xì)胞凋亡的生化特征back

細(xì)胞凋亡的三種基本信號(hào)轉(zhuǎn)導(dǎo)途徑（1）死亡信號(hào)途徑（2）線粒體途徑（3）內(nèi)質(zhì)網(wǎng)途徑（4）溶酶體途徑（酶漏出）NatRevMolCellBiol2005細(xì)胞凋亡的信號(hào)轉(zhuǎn)導(dǎo)卡通1卡通3卡通2Novelcelldeathmechanisms?Apoptosis:Iscaspasesrequired?NatRevMolCellBiol2005CICD:Caspase-independentcelldeathInvitrodataindicatedthatTNFtreatmentaloneinducesthedegenerationofthemitochondrialultrastructure,possiblythroughtheproductionofreactiveoxygenspecies(ROS).Surprisingly,caspaseinhibitionactuallysensitizedmicetoTNFtreatmentbyincreasingoxidativestressandmitochondrialdamageinvivo.MicethatreceivedalethalTNFdosediedabout24hourspost-injection;whereaspretreatmentwithabroad-spectrumcaspaseinhibitor,zVAD-fmk,inducedrapiddeathwithin4hours20.AntioxidantsblockedthesensitizationofzVAD-fmk-treatedmicetoTNF-inducedlethality,whichindicatedthatROSwasresponsibleforcelldeath20.CICDvstissuedamageNecrosis:Aprogrammedcelldeath?Thestereotypedfeaturesofapoptosissuggestedthatitwouldconstitutearegulatedcelldeathprocess,anotionthatwaselegantlyshowninCaenorhabiditiselegansbytheHorvitzlaboratoryin1980–1990.Textbookssoonthoughtofapoptosisandnecrosisasopposedmechanisms,necrosisbeingconsideredasapurelyaccidentalandpassivecelldeathsubroutine.ThefirstmorphologicalclassificationofcelldeathwasproposedbySchweichelandMerker4whodescribed,inratembryosexposedtotoxicants,type

Icelldeathassociatedwithheterophagy,type

IIcelldeathassociatedwithautophagyandtype

IIIcelldeathwithoutdigestion.Today,thesecelldeathmodesarereferredtoasapoptosis,autophagiccelldeathandnecrosis,respectively.Executionofnecroptosis

Mitoticcatastrophe:Aprogrammedcelldeath?mitoticcatastrophe,apoptosis,necrosis,autophagicvacuolization-8SenescencvscelldeathSamestimulus,differentfatesautophgyvscelldeathautophgiccelldeathFunctionalclassificationofcelldeathmodalities.CellDeathDiffer.2012celldeathwithautophgyvscelldeathbyautophgy?Lifeordeath:Tobecoordinatedbythesamesignal?Overviewofmetabolism.