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细胞凋亡 Cell apoptosis

细胞凋亡 Cell apoptosis. 倪培华. 第一节 细胞凋亡的生物学意义 Apoptosis of biological signification. 一、细胞凋亡的概念与生物学意义. (一)概述 (Summary). 对于一个多细胞生物来说,要维持 完整性和保持平衡性 ,凋亡是一个非常重要的生物学过程。 For multicellular organism , to maintain the integrity and balance , apoptosis is a very important biological processes.

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细胞凋亡 Cell apoptosis

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  1. 细胞凋亡 Cell apoptosis 倪培华

  2. 第一节 细胞凋亡的生物学意义 Apoptosis of biological signification 一、细胞凋亡的概念与生物学意义 (一)概述(Summary) • 对于一个多细胞生物来说,要维持完整性和保持平衡性,凋亡是一个非常重要的生物学过程。For multicellular organism, to maintain the integrity and balance, apoptosis is a very important biological processes.

  3. 多细胞生物的诞生、生长、发育、存活以及死亡,无一不伴随着细胞凋亡过程。多细胞生物的诞生、生长、发育、存活以及死亡,无一不伴随着细胞凋亡过程。 • Essential part of life for every multicellular organism from worms to humans. (Faddy et al.,1992) • Apoptosis plays a major role from embryonic development to senescence.

  4. Carl Vogt---cell death 1842 John Kerr first used “apoptosis” 1972 Ladder DNA 1973 1976 John Sulston-apoptosis apoptosis and DNA degradation 1980 1983-1986 ced 1985-1988 Bcl-2 1989 Fas was discovered 1991 1991 P53 Cloning of Fas ICE/CED-3 . Yuan JY,Cell 1993 1993 1993 Bax 1996 Caspase named 1996 cytochrome c 1997 Apaf-1 History of cell death research

  5. (二)细胞死亡的方式 • 细胞坏死(necrosis) • 细胞凋亡(apoptosis) • 细胞自噬(autophagy) 程序性死亡Programmed cell death,PCD

  6. Cell death by injury -Mechanical damage -Exposure to toxic chemicals Cell death by suicide -Internal signals -External signals

  7. 影响因素 • 化学因素 strong acid strong base toxic substance • 物理因素 heat radiation • 生物因素 Pathogen • 缺氧 hypoxia (三)、细胞坏死 (necrosis) – Necrosis derived from Greek “nekrosis,”meaning “deadness.” –Necrosis is lethal cell injury or accidental cell death in the living organism.

  8. 坏死细胞的形态改变 Necrosis of the cells to change morphology 早期核无明显形态学变化

  9. 胞质内线粒体和细胞器肿胀,染色质凝聚,崩解胞质内线粒体和细胞器肿胀,染色质凝聚,崩解

  10. 随着胞质内蛋白变性、凝固或碎裂,以及嗜碱性核蛋白的降解,细胞质呈现强嗜酸性,导致细胞结构完全消失,细胞膜和细胞器破裂,DNA降解,细胞内容物流出,引起周围组织炎症反应

  11. Necrosis

  12. 1972 年 Kerr实验 • 结扎大鼠肝的左、中叶门静脉后 • 周围细胞发生缺血性坏死 • 有肝动脉供应区的实质细胞仍存活,只是范围逐渐缩小,其间一些细胞不断转变成细胞质小块,不伴有炎症 • 在正常鼠肝中也偶然见到这一现象

  13. (四)凋亡 Apoptosis凋亡 Cells in the fall as the leaves of the same death Apoptosis derived from Greek “apo,”meaning “away from,” and “ptosis,”meaning “to fall.”

  14. Why should a cell commit suicide? Apoptosis is needed for proper development • 蝌蚪尾巴的脱落

  15. 哺乳动物指(趾)的形成 • 脊椎动物的神经系统的发育

  16. Why should a cell commit suicide? • Apoptosis is needed to destroy cells • Examples: • Cells infected with viruses • Cells of the immune system • Cells with DNA damage • Cancer cells

  17. 凋亡是生物体普遍存在的现象 • 胚胎形成 • 衰老和损伤细胞的清除 • 自身反应性T淋巴细胞的清除 • 肿瘤的发生、发展和转归 • 干细胞 并非每个细胞都能走到终点,相当一部分细胞,甚至绝大部分细胞都会在中途凋亡 • 胸腺的T细胞95%存活不到成熟T细胞阶段 • 原始和幼稚红细胞在骨髓中发生“原位溶血”

  18. 凋亡概念 Concept of apoptosis 细胞凋亡是指为维持内环境稳定,由基因控制的细胞自主的有序的死亡。也称为细胞程序性死亡(programmed cell death,PCD) Apoptosis is a means to maintain the stability of the environment from gene to control the cell's own death in an orderly manner.

  19. 凋亡细胞的主要特征 ①染色质chromatin 聚集、分块、位于核膜上,胞质凝缩,最后核断裂,细胞通过出芽的方式形成许多凋亡小体 ②凋亡小体apoptotic body 有结构完整的细胞器,还有凝缩的染色体,可被邻近细胞吞噬消化,因始终有膜封闭,没有内容物释放,不引起炎症

  20. A、Normal cell B、Apoptosis: Apoptotic bodies

  21. APOPTOSIS: Morphology 细胞器 减少 膜出芽 细胞皱缩 线粒体裂解 核片段化 染色质凝聚

  22. APOPTOSIS: Morphological events 细胞皱缩 细胞器 减少 线粒体裂解 染色质凝聚 核片段化 膜出芽或改变

  23. 出芽 & 凋亡小体 出芽 Apoptotic body MF MF

  24. 早期的细胞核呈 波纹状或呈折缝样部分染色质出现浓缩状态; 细胞核的染色质高度凝聚、边缘化 细胞核裂解为碎块,产生凋亡小体

  25. ③凋亡细胞中仍需要合成一些蛋白质,但是在坏死细胞中ATP和蛋白质合成受阻或终止③凋亡细胞中仍需要合成一些蛋白质,但是在坏死细胞中ATP和蛋白质合成受阻或终止 ④核酸内切酶活化,导致染色质DNA在核小体连接部位断裂,形成约200bp整数倍的核酸片段,凝胶电泳图谱呈梯状 ⑤凋亡通常是生理性变化 细胞坏死是病理性变化

  26. 细胞凋亡的生化特征-DNA阶梯

  27. Summary :Apoptosis and necrosis Apoptosis Necrosis

  28. Distinguish of necrosis and apoptosis

  29. Necrosis vs. Apoptosis Necrosis Apoptosis • Cellular swelling • Membranes are broken • ATP is depleted • Cell lyses, eliciting an inflammatory reaction • DNA fragmentation is random, or smeared • In vivo, whole areas of the tissue are affected • Cellular condensation • Membranes remain intact • Requires ATP • Cell is phagocytosed, no tissue reaction • Ladder-like DNA fragmentation • In vivo, individual cells appear affected

  30. 2002年10月7日 英国人悉尼·布雷诺尔,美国人罗伯特·霍维茨,英国人约翰·苏尔斯顿 在器官发育的遗传调控和细胞程序性死亡方面的研究 ,获诺贝尔生理与医学奖 Sydney Brenner, H. Robert Horvitz, John E Sulston

  31. Death Receptors Initiator Caspase 8 Effector Caspase3 PCD Initiator Caspase 9 Mitochondria/Cytochrome C Apoptosis: Pathways “Extrinsic Pathway” Death Ligands “Intrinsic Pathway” DNA damage & p53

  32. 第二节 细胞凋亡的相关基因 一、细胞凋亡的相关基因 (一)Fas受体是凋亡的主要引发剂 1、Fas受体基因 (Fas receptor gene) 表达:跨膜蛋白 又称作APO-1/CD95 属TNF受体家族

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