13 细胞凋亡与衰老

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1、Chapter13CellapoptosisExtracellularcotrolofcelldivision,cellgrowth,andapoptosisMitogensstimulateG1-CdkandG1/S-CdkactivitiesPRIZEDHorvitz,andSulstonsharePhysiologyorMedicineNobel（2002）“fortheirdiscoveriesconcerninggeneticregulationoforgandevelopmentandprogrammedcellde

2、ath”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-inlimitationonthenumberoftimestheycandivideThecelldivisioniscotrollednotonlybyextracellularmitogensbutalsobyintracellularmec

3、hanismsthatcanlimitcellproliferation.Cell-cyclearrestorapoptosisinducedbyexcessivestimulationofmitogenicpathways.ExtracellulargrowthfactorsstimulatecellgrowthActivationofcell-surfacereceptorsActivationofPI3-kinaseActivationofelF4E(translationinitiationfactor)andS6kin

4、ase(phosphorylatesribosomalproteinS6)Increasingproteinsynthesisandcellgrowth2.Apoptosis,ProgrammedcelldeathBiologicalfunctionsofapoptosis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。Morphologicala

5、ndbiochemicalcharacteristicsofapoptosisMorphologichanges:Early:Chromosomecondensation,cellbodyshrinkLater:BlebbingandNucleusandcytoplasmfragment—ApoptoticbodiesAtlast:PhagocytosedA、NormalcellB、Apoptosis:ApoptoticbodiesBiochemicalcharacteristicsofapoptosis:Apoptosis

6、inducedbyCytoCLane1．0h2．1h3．2h4．3h5．4h6．Control7．Marker2.0kbp1.00.50.2180~200bpDNAladder,AccumulationoftTG,PSflip-flopContrastofApoptosisandnecrosisApoptosisNecrosisDeathbyapoptosisisaneat,orderlyprocess3.MolecularmechanismsofapoptosisEarlyresearches(MIT:RobertHorrid

7、,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

8、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