分子細胞生物學(xué)進展：novel concepts on cell death

Celldeath:what’snew細胞死亡

(Celldeath)

一、

細胞凋亡的概念

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

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

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

通過凋亡可及時清除衰老細胞，降低機體癌變的危險。

1.形態(tài)學(xué)特征(DNA染色、標記特征；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）細胞凋亡的特征（與檢測指標）to凋亡小體back生化特征（1）胱冬肽酶級聯(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)成的級聯(lián)反應(yīng)是凋亡過程的核心。1）胱冬肽酶級聯(lián)反應(yīng)2）胱冬肽酶的作用底物返回細胞凋亡的生化特征back

細胞凋亡的三種基本信號轉(zhuǎn)導(dǎo)途徑（1）死亡信號途徑（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細胞凋亡的信號轉(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.