基因調(diào)控器官發(fā)育課件

1、The Nobel Prize in Physiology or Medicine 2002 基因調(diào)控器官發(fā)育 AND 程序性細(xì)胞死亡 組員: 巫柏霖 張圍策 楊佩穎 林家榆 郭彥廷 林函融 梁詠慈The Nobel Prize in Physiology Sydney Brenner H. Robert Horvitz John E. Sulston如何發(fā)現(xiàn)Apoptosis?實(shí)驗(yàn)內(nèi)容基因調(diào)控器官發(fā)育課件線蟲實(shí)驗(yàn)線蟲成蟲有959個(gè)細(xì)胞 成長(zhǎng)的過程中有131個(gè)細(xì)胞發(fā)生Apoptosis發(fā)生時(shí)間: 約1Hr線蟲實(shí)驗(yàn)線蟲細(xì)胞凋亡模型線蟲細(xì)胞凋亡模型基因調(diào)控器官發(fā)育課件細(xì)胞凋亡(Apoptosis)

2、Apoptosis的簡(jiǎn)介Apoptosis的分類與細(xì)胞壞死(Necrosis)的比較Apoptosis的作用機(jī)制 細(xì)胞凋亡(Apoptosis)NormalApoptosisNormalApoptosisApoptosis的簡(jiǎn)介細(xì)胞自己計(jì)畫性的死亡 細(xì)胞凋亡是多細(xì)胞生物在發(fā)育過程中，一種由基因控制的主動(dòng)的細(xì)胞生理性自殺行為。Apoptosis的簡(jiǎn)介基因調(diào)控器官發(fā)育課件Apoptosis 和Necrosis的比較Apoptosis 和Necrosis的比較 Necrosis Apoptosis1.性質(zhì) 病理性 生理性/病理性2.誘導(dǎo)因素 強(qiáng)烈刺激, 較弱刺激， 隨機(jī)發(fā)生 非隨機(jī)發(fā)生3.形態(tài)變化

3、細(xì)胞結(jié)構(gòu)全面 胞膜及細(xì)胞器 溶解破壞、 相對(duì)完整 細(xì)胞腫脹. 細(xì)胞皺縮4.凋亡小體 無 有5.基因調(diào)控 無 有 Necrosis ApoptoApoptosis的分類細(xì)胞自戕性程式死亡（apoptotic cell death program）非細(xì)胞自戕性程式死亡（nonapoptotic cell death program） 不同點(diǎn):apoptotic cell death program 有DNA斷裂的出現(xiàn)Apoptosis的分類細(xì)胞自戕性程式死亡（apoptotiApoptosis的作用機(jī)制可分為:Initiation phase(前期)The Death Receptor-Initi

4、ated Pathway The Mitochondrial Pathway 2. Execution phase(後期)Apoptosis的作用機(jī)制可分為:The Death Receptor-Initiated Pathway細(xì)胞膜上有apoptotic signals receptorTumour necrosis factor(TNF)分為:CD95(or fas)TNFR1(TNF receptor-1)TRAIL(TNF-related apoptosis inducing ligand)The Death Receptor-Initiated PCD95CD95TNFR1(TNF

5、 receptor-1)TNFR1(TNF receptor-1)Bcl-2 Family抑制Apoptosis的Bcl-2:bcl-2, Bcl-xL, Mcl-1, Bcl-w, adenovirus E1B 19K, EBV BHRF1, Ced-9 促進(jìn)Apoptosis的Bcl-2:Bax, Bak, Nbk/Bik1, Bad, Bcl-xS Bcl-2 Family抑制Apoptosis的Bcl-2:The Mitochondrial Pathway促進(jìn)性Bcl-2 family 粒線體膜被激活Cytocrome C and Pro-apoptotic proteinCaspas

6、es or ApoptosomeThe Mitochondrial PathwayThe Mitochondrial PathwayThe Mitochondrial Pathway基因調(diào)控器官發(fā)育課件Execution phase(後期)Inactive CapasesActive Capases Caspases cascade 啟動(dòng)apoptosis機(jī)制 Execution phase(後期)Apoptosis啟動(dòng)作用細(xì)胞核外:切割細(xì)胞內(nèi)蛋白質(zhì)&細(xì)胞骨架(Zeiosis)細(xì)胞核內(nèi): 使參與DNA修復(fù)的蛋白質(zhì)失活 (PRAP) 使參與DNA複製的蛋白質(zhì)失活(DNA topoisomeras

7、e II) 分解結(jié)構(gòu)性核蛋白 將DNA分解成片斷 Apoptosis啟動(dòng)作用細(xì)胞核外:分解結(jié)構(gòu)性核蛋白Caspases 6Lamins(一種核內(nèi)蛋白)被降解染色質(zhì)濃縮和核膜被分解 分解結(jié)構(gòu)性核蛋白基因調(diào)控器官發(fā)育課件Apotosis在細(xì)胞核內(nèi)-切割DNACAD(Caspase-activated Dnase): 將DNA切成較大的片段(50300 kb)Ca2+/Mg2+-dependent nucleases : 將大片段切成小碎片(180200 bp)作用流程圖Apotosis在細(xì)胞核內(nèi)-切割DNA細(xì)胞核內(nèi)的DNA切割作用流程圖Caspases ICAD CAD (Caspase-acti

8、vated Dnase) DNA大片段 Ca2+ and Mg2+ dependent endonucleases DNA小碎片細(xì)胞核內(nèi)的DNA切割作用流程圖典型凋亡細(xì)胞DNA電泳（呈現(xiàn)梯狀條帶）典型凋亡細(xì)胞DNA電泳（呈現(xiàn)梯狀條帶）Apoptosis 作用機(jī)制基因調(diào)控器官發(fā)育課件Caspase 3Caspase 3Apoptosis 的作用結(jié)果細(xì)胞凋亡不足：腫瘤，自身免疫病(Ex:AIDS)細(xì)胞凋亡過度：心肌缺血，心力衰竭，神經(jīng)元 退行性疾病，病毒感染平滑肌細(xì)胞增殖（凋亡不足）與內(nèi)皮細(xì)胞凋亡（過度）：動(dòng)脈粥樣硬化Apoptosis 的作用結(jié)果細(xì)胞凋亡不足：腫瘤，自身免疫病 細(xì)胞死亡 Apop

9、tosis NecrosisApoptosis NonapoptosisInitiationDeath recepter mitochondriaintrinsic pathway pathway Execution 參考資料Raffaella Depala, Luigi Nappi, Giuseppe Loverro, Stefano Bettocchi, Maria Lucia Caruso, Anna Maria Valentini, Luigi Selvaggi (2003) Evidence of apoptosis in human primordial and primary f

10、ollicles. Human Reproduction, 18, 2678-2682D.N. Modi, S. Sane, D. Bhartiya (2003) Accelerated germ cell apoptosis in sex chromosome aneuploid fetal human gonads. Molecular Human Reproduction, 9, 219-225Mahmoud R. Hussein (2005) Apoptosis in the ovary: molecular mechanisms. Human Reproduction Update,

11、 11, 162-178/jkimball.ma.ultranet/BiologyPages/A/Apoptosis.html30/language/translatedPage?lp=en_zt&.intl=tw&tt=url&text=http%3a%2f%2fwww.sghms.ac.uk%2fdepts%2fimmunology%2f%257Edash%2fapoptosis%2finduction.htmlen_zt&.intl=tw&tt=url&text=http%3a%2f%2fwww.sghms.ac.uk%2fdepts%2fimmunology%2f%257Edash%2fapoptosis%2finduction.html/jkimball.ma.ultranet/BiologyPages/A/Apoptosis.html/wiki/ApoptosisRobbins and Co