Apoptosis
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| apoptosis | programmed cell death, result in safe removal of cellular debris
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| morphology | 1. membrane blebbing
2. loss of membrane asymmetry and attachment
3. cell shrinkage and nuclear fragmentation
4. chromatin condensation and chromosomal DNA fragmentation
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| process | 1. apoptosis begins, condensation of chromosome
2. nucleus fragments, Dna is digested (laddering), cytoplasm fragments
3. apoptotic bodies are ingested by phagocytic cells
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| role in normal physiology | development and metamorphosis
adaptive immune response
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| role in disease | control of cell growth and proliferation
removes damage cell
activate killer cells
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| excessive apo. | stroke, neurodegeneration leading to alzheimer and parkinson
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| defective apo. | neoplasie, autoimmune syndromes
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| Detection with ANNEXIN V | late stage; plasma membrane is compromised and nucleic acid dyes are allowed to entrance the cell and bind with DNA- marker for apoptosis
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| caspases | central component for apo. -> cleavage of proteins. detection by immunoblotting tech.using caspase specific antibody or a dye.
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| intrinsic pathway | triggered by non-receptor stimuli
internal damage;bcl2 inhibition by bac; making holes in MOMP &cytochrome c leakage.
cyto-c-Apaf1 complex-apoptosome;activate caspase 9,cleaves and activates 3&7 leading to digestion os structural protein&dna
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| bcl2 | on the membrane of a healthy cell, inhibits apoptosis
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| caspases | caspase cascade activated by proteolytic cleavage of precursor
DED and CARD domain
executioner caspases
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| DED domain | death effector domain - regulate cellular signalling pathways
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| CARD domain | activation and recruitment of caspases
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| executioner caspases | 6,3,7
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| apoptosis inducing factor AIF | does not use caspases, located at intermembrane space of mitochondria, one signal ; released from mito. migrate to nuclus and binds to DNA where it triggers its destruction
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| extrinsic pathway | external signal join with death receptor (FASL or TNF). signal transmitted to cytoplasm activating caspase 8 that initiates the cascade of caspases activation. phagocytosis
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| proteolysis | hydrolytic breakdown of proteins into simpler substance
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| pro- apoptotic | enhance apoptosis
BAX, BID, BAD, BIM
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| anti apoptotic | inhibits apoptosis
Bcl, BCL-XL
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| in cancer | increased expression of BCL2 so it stops the apoptosis of proliferating cells
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