北大细胞生物学课件13细胞凋亡

Chapter13CellapoptosisExtracellular

cotrolofcelldivision,cellgrowth,andapoptosisMitogensstimulateG1-CdkandG1/S-CdkactivitiesPRIZED

Horvitz,andSulstonsharePhysiologyorMedicineNobel（2002）

“fortheirdiscoveriesconcerninggeneticregulationoforgandevelopmentandprogrammedcelldeath”1090–131=959(cells)机体结构细胞增殖细胞分化细胞凋亡细胞信号转导染色体（DNA与蛋白质的相互作用）衰老

AsimplifiedmodelofonewaythatmitogensstimulatecelldivisionHumancellshaveabuilt-inlimitationonthenumberoftimestheycandivideThecelldivisioniscotrollednotonlybyextracellularmitogensbutalsobyintracellularmechanismsthatcanlimitcellproliferation.Cell-cyclearrestorapoptosisinducedbyexcessivestimulationofmitogenicpathways.ExtracellulargrowthfactorsstimulatecellgrowthActivationofcell-surfacereceptorsActivationofPI3-kinaseActivationofelF4E(translationinitiationfactor)andS6kinase(phosphorylatesribosomalproteinS6)Increasingproteinsynthesisandcellgrowth2.Apoptosis,Programmedcelldeath

Biologicalfunctionsofapoptosis

Indevelopment,homeostasis,tumorsurveillance,andthefunctionoftheimmunesystem.

细胞凋亡是多细胞生物在发育过程中，一种由基因控制的主动的细胞生理性自杀行为。

Morphologicalandbiochemicalcharacteristicsofapoptosis

Morphologichanges:

Early:Chromosomecondensation,cellbodyshrink

Later:BlebbingandNucleusandcytoplasmfragment—Apoptoticbodies

Atlast:PhagocytosedA、NormalcellB、Apoptosis:Apoptoticbodies

Biochemicalcharacteristicsofapoptosis

:ApoptosisinducedbyCytoCLane1．0h2．1h3．2h4．3h5．4h6．Control7．Marker

2.0kbp1.00.50.2180~200bpDNAladder,AccumulationoftTG,PSflip-flopContrastofApoptosisandnecrosisApoptosisNecrosisDeathbyapoptosisisaneat,orderlyprocess3.MolecularmechanismsofapoptosisEarlyresearches(MIT:RobertHorrid,1986)C.

elegans:1090cells,TheFindingofCED3mutantWithoutlosinganyoftheircellstoapoptosis.CED3geneplayacrucialroleintheprocessofapoptosis.Celegans:amillimeterlong,transparentbodyonlyafewcelltypes,fromzygotetomatureadultonlyin3.5days.131cellsdeath.线虫体细胞凋亡研究：PCD相关基因15个，分为四组：1、与PCD有关的基因，负责PCD控制：ced-3、ced-4和ced-9。2、与PCD过程吞噬作用有关：ced-1、ced-2、ced-5-8和ced-10。3、核酸酶基因（nuc-1）,控制DNA降解，但非PCD所必须。4、影响特异细胞类型PCD的基因：ces-1、ces-2、cgl-1、和her-1.保守性高，在哺乳动物中有相应同源物：Ced-3=ICE,Ced-4=Apaf-1,Ced-9=Bcl-2.Mammalian:CED3isrelatedtomammalianinterleukin-1ß–convertingenzyme(ICEorcaspase-1)Apoptosisiscarriedoutbyaproteolyticsystem—

caspase

(1)Whycalledcaspase?Activesite:CysteineCleavagesite:Asparaticacid

CysteineAsparaticacidspecificproteaseAps-Xxx天冬氨酸特异性的半光氨酸蛋白水解酶Apoptosiscanbedividedintotwophases：

Activationphase：Thecellrespondsto“deathsignals”thatcommitittoundergoingself-destruction.

Executionphase：

Thedeathsentenceiscarriedout.Apoptosiscellsarerecognizedbyphagocytesbecausetheycarryexposedmarkers,called“