1 / 32

The Nobel Prize in Physiology or Medicine 2002

The Nobel Prize in Physiology or Medicine 2002. 基因調控器官發育 AND 程序性細胞死亡 組員 : 巫柏霖 張圍策 楊佩穎 林家榆 郭彥廷 林函融 梁詠慈. Sydney Brenner H. Robert Horvitz John E. Sulston 如何發現 Apoptosis? 實驗內容. 線蟲實驗. 線蟲成蟲有 959 個細胞 成長的過程中有 131 個細胞發生 Apoptosis 發生時間 : 約 1Hr. 線蟲細胞凋亡模型. 細胞凋亡 (Apoptosis).

weston
Download Presentation

The Nobel Prize in Physiology or Medicine 2002

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. The Nobel Prize in Physiology or Medicine 2002 基因調控器官發育 AND 程序性細胞死亡 組員: 巫柏霖 張圍策 楊佩穎 林家榆 郭彥廷 林函融 梁詠慈

  2. Sydney BrennerH. Robert Horvitz John E. Sulston • 如何發現Apoptosis? • 實驗內容

  3. 線蟲實驗 • 線蟲成蟲有959個細胞 成長的過程中有131個細胞發生Apoptosis • 發生時間: 約1Hr

  4. 線蟲細胞凋亡模型

  5. 細胞凋亡(Apoptosis) • Apoptosis的簡介 • Apoptosis的分類 • 與細胞壞死(Necrosis)的比較 • Apoptosis的作用機制

  6. Apoptosis Normal

  7. Apoptosis的簡介 • 細胞自己計畫性的死亡 細胞凋亡是多细胞生物在發育過程中，一種由基因控制的主動的細胞生理性自殺行為。

  8. Apoptosis 和Necrosis的比較

  9. Necrosis Apoptosis 1.性質 病理性 生理性/病理性 2.誘導因素 強烈刺激, 較弱刺激， 隨機發生 非隨機發生 3.形態變化 細胞結構全面胞膜及細胞器 溶解破壞、相對完整 細胞腫脹. 細胞皺縮 4.凋亡小體 無 有 5.基因調控無 有

  10. Apoptosis的分類 • 細胞自戕性程式死亡（apoptotic cell death program） • 非細胞自戕性程式死亡（nonapoptotic cell death program）  不同點:apoptotic cell death program 有DNA斷裂的出現

  11. Apoptosis的作用機制 可分為: • Initiation phase(前期) • The Death Receptor-Initiated Pathway • The Mitochondrial Pathway 2. Execution phase(後期)

  12. The Death Receptor-Initiated Pathway • 細胞膜上有apoptotic signals receptor • Tumour necrosis factor(TNF)分為: • CD95(or fas) • TNFR1(TNF receptor-1) • TRAIL(TNF-related apoptosis inducing ligand)

  13. CD95

  14. TNFR1(TNF receptor-1)

  15. 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Apoptosis的Bcl-2: Bax, Bak, Nbk/Bik1, Bad, Bcl-xS

  16. The Mitochondrial Pathway 促進性Bcl-2 family 粒線體膜被激活 Cytocrome C and Pro-apoptotic protein Caspases or Apoptosome

  17. The Mitochondrial Pathway

  18. Execution phase(後期) Inactive Capases Active Capases Caspases cascade 啟動apoptosis機制

  19. Apoptosis啟動作用 • 細胞核外: • 切割細胞內蛋白質&細胞骨架(Zeiosis) • 細胞核內: • 使參與DNA修復的蛋白質失活 (PRAP) • 使參與DNA複製的蛋白質失活(DNA topoisomerase II) • 分解結構性核蛋白 • 將DNA分解成片斷

  20. 分解結構性核蛋白 Caspases 6 Lamins(一種核內蛋白)被降解 染色質濃縮和核膜被分解

  21. Apotosis在細胞核內-切割DNA • CAD(Caspase-activated Dnase): 將DNA切成較大的片段(50~300 kb) • Ca2+/Mg2+-dependent nucleases : 將大片段切成小碎片(180~200 bp) 作用流程圖

  22. 細胞核內的DNA切割作用流程圖 Caspases ICAD CAD (Caspase-activated Dnase) DNA大片段 Ca2+ and Mg2+ dependent endonucleases DNA小碎片

  23. 典型凋亡細胞DNA電泳（呈現梯狀條带）

  24. Apoptosis 作用機制

  25. Caspase 3

  26. Apoptosis 的作用結果 • 細胞凋亡不足：腫瘤，自身免疫病(Ex:AIDS) • 細胞凋亡過度：心肌缺血，心力衰竭，神經元 退行性疾病，病毒感染 • 平滑肌細胞增殖（凋亡不足）與內皮細胞凋亡（過度）：動脈粥樣硬化

  27. 細胞死亡 Apoptosis Necrosis Apoptosis Nonapoptosis Initiation Death recepter mitochondria intrinsic pathway pathway Execution

  28. 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 follicles. Human Reproduction, 18, 2678-2682 • D.N. Modi, S. Sane, D. Bhartiya (2003) Accelerated germ cell apoptosis in sex chromosome aneuploid fetal human gonads. Molecular Human Reproduction, 9, 219-225 • Mahmoud R. Hussein (2005) Apoptosis in the ovary: molecular mechanisms. Human Reproduction Update, 11, 162-178 • http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/A/Apoptosis.html • http://202.43.196.230/language/translatedPage?lp=en_zt&.intl=tw&tt=url&text=http%3a%2f%2fwww.sghms.ac.uk%2fdepts%2fimmunology%2f%257Edash%2fapoptosis%2finduction.html • http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/A/Apoptosis.html • http://en.wikipedia.org/wiki/Apoptosis • Robbins and Cotran Pathologic Basis of Disease, edited by Kumar, Abbas and Fausto—7th ed（2004）, p.26-p.32 • www2.zzu.edu.cn/jcyxy/bingsheng/zhaomy/pathophy-kejian/8-%B5%F2%CD%F6.ppt

More Related