Apoptosis note - Apoptosis(Programmed Cell Death(Lodish...

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Apoptosis (Programmed Cell Death) (Lodish page 936-944) I. Two types of cell death A. Apoptosis: Programmed cell death by activating an intracellular death program. B. Necrosis: accidental cell death without order caused by injury, radiation, chemicals or lack of nutrition. These dead cells do not send signals to phagocytes and thus often causes inflammation, necrotic cells typically swell and burst. C. Discoveries on apoptosis won the Nobel Prize in 2002. II. Role of apoptosis A. During development, removal of unwanted cells or structures 1. In the nematode C. elegans, 1090 cells develop through cell division. 131 undergo apoptosis (Lodish Fig. 21-36). This has been an important genetic system for studying this process. 2. Sculpting digits from a limb bud (Alberts Fig. 17-35) 3. Removal of the tail of developing tadpole (Alberts Fig. 17-36) 4. Formation of lumen in tissues during development. 5. Regulation of the proper number of neurons (Lodish Fig. 21-34, 35). Most of the neurons that develop in our bodies are removed this way. 6. Eliminate dangerous of injured cells B. In the immune system 1. Removal of lymphocytes after a challenge to the immune system. 2. Killing virus-infected cells. C. In human disease 1. Cells growing uncontrollably undergo apoptosis. Must inhibit this or cancer will develop. 2. Neurons after stroke undergo apoptosis. 3. Other neurodegenerative diseases involve apoptosis. a. Retinitis pigmentosa is a leading cause of blindness in humans. It is caused by mutations in rhodopsin, which slow its inactivation after light stimulation. b. Drosophila model for this disease. Eyes normal when reared in the dark but degenerate over time in light. In both humans and flies, the photoreceptors undergo apoptosis. c. If apoptosis is genetically blocked in the mutant flies with a caspase inhibitor, the eyes don’t degenerate. More importantly, these flies can see fairly well. D. ER stress caused by unfolded protein response can also causes apoptosis, as we discussed earlier. III. Ultrastructural features of apoptosis (Lodish Fig. 21-33) A. Dense chromosome condensation along the nuclear periphery B. Cell shrinks C. Both nucleus and cytoplasm fragment, forming apoptotic bodies. 1. Chromosomal DNA is hydrolyzed into thousands of fragments 2. Can be observed in agarose gels of cellular DNA. 1
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D. Apoptotic bodies are phagocytosed by macrophages or other cell types.
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