apoptosis 细胞凋亡

Two distinct forms of cell death:பைடு நூலகம்apoptosis and necrosis坏死
These electron micrographs show cells that have died by apoptosis (A and B) or by a type of accidental cell death called necrosis (C). The cells in (A) and (C) died in a culture dish, whereas the cell in (B) died in developing tissue and has been ehgulfed by a phagocytic cell. Note that the cells in (A) and (B) have condensed but seem relatively intact, whereas the cell in (C) seems to have exploded. The large vacuoles visible in the cytoplasm of the cell in (A) are a
13.2 Apoptotic Cells Are Morphological and Biochemically Recognizable
Markers of apoptosis – DNA ladder
Cleavage of nuclear DNA into a characteristic ladder pattern of fragments. Mouse thymus lymphocytes were treated with an antibody against the cellsurfuce death receptor Fas, inducing the cells to undergo apoptosis. After various times, DNA was extracted, and the fragments were separated by size by electrophoresis in an agarose gel and stained ethidium bromide.
Sculpting the digits in the developing mouse paw by apoptosis. (A) The paw in this mouse fetus has been stained with a dye that specifically labels cells that have undergone apoptosis. The apoptotic cells appear as bright green dots between the developing digits. (B) The interdigital cell death has eliminated the tissue between the developing digits, as seen one day later, when there are very few apoptotic cells. (From W. Wood et al., Development 2000)
Normal Cell
Apoptotic Cell
The Procedure of Apoptosis
◆Early stage of apoptosis凋亡的起始: 细胞表面的特化结构如微绒
毛消失，细胞间接触的消失，但细胞膜依然完整；线粒体大体完整，
但核糖体逐渐从内质网上脱离，内质网囊腔膨胀，并逐渐与质膜融合； 染色质固缩，形成新月形帽状结构等形态，沿着核膜分布
The role of survival factors and cell death in adjusting the number of developing nerve cells to the amount of target tissue
More nerve cells are produced than can be supported by the limited amount of survival factors released by the target cells. Therefore, some cells receive an insufficient amount of survival factors to avoid apoptosis. This strategy of overproduction followed by culling ensures that all target cells are contacted by nerve cells and that the extra nerve cells are automatically eliminated.
13.1 PCD Eliminates Unwanted Cells
Apoptosis during the metamorphosis if a tadpole into a frog
As a tadpole changes into a frog, the cells in the tadpole tail are induced to undergo apoptosis; as a consequence, the tail is lost. An increase in thyroid hormone in the blood stimulates all the changes that occur during metamorphosis, including apoptosis in the tail.
13.3 Apoptosis Depends on an Intracellular Proteolytic Cascade That Is Mediated by Caspases
• The Intracellular machinery responsible for apoptosis is similar in all animal cells. It depends on a family of proteases that have a cysteine at their active site and cleave their target proteins at specific aspartic acids. • Caspases: c for cysterine and asp for aspartic acid. • Caspases are synthesized in the cell as inactive precursors, or procaspases, which is typically activated by proteolytic cleavage.
Delorme et al., Plant Physi 2000
13.2 Apoptotic Cells Are Morphological and Biochemically Recognizable
Normal Cell
Apoptotic Cell
DNA fragmentation during the process of apoptosis
Characterization of Apoptosis
• Cells die by murder or suicide by an active process of programmed cell death, characterized by cleavage of chromosomal DNA, chromatin condensation, and fragmentation of both the nucleus and the cell. Programmed cell death play a key role both in the maintenance of adult tissues and in embryonic development. • In contrast to the accidental death of cells resulting from an acute injury, programmed cell death takes place by an active process and Genes responsible for both the regulation and execution of apoptosis are conserved from nematodes to humans.
◆Forming apoptotic body凋亡小体的形成：核染色质断裂为大小不
等的片段，与某些细胞器如线粒体一起聚集，为反折的细胞质膜所包 围。细胞表面产生了许多泡状或芽状突起，逐渐形成单个的凋亡小体
◆Apoptotic body are phagocytosed by surrounding cells吞噬.
TUNEL technique
TUNEL was used to label the cut ends of DNA fragments in the nuclei of apoptotic cells in a tissue section of a developing chick leg bud; this cross section through the skin and underlying drawing. The procedure is called the TUNEL (TDT-mediated dUTP nick end labeling) technique because the enzyme terminal deoxynucleotidyl transferase (TdT) adds chains of labeled deoxynucleotide (dUTP) to the 3’OH ends of DNA fragments. (Zuzarte-Luis and Hurle, Int. J. Dev. Biol. 2002)