Apoptosis Flashcards
what is apoptosis?
Controlled cellular suicide
what is another form of controlled cellular suicide besides apoptosis?
autophagy
what is necrosis?
cell death in response to an acute issue; uncontrolled
what are the 4 morphological changes in apoptosis?
- Membrane blebbing or shrinkage and chromatin condensation
- Cytoskeletal collapse
- Disassembly of nuclear envelope
- Chromatin fragmentation
what are the 2 chemical changes in apoptosis?
- Cell surface is altered for phagocytic recognition
- Intracellular proteins act as signals and activators of cell destroyers
for what 6 reasons is apoptosis needed?
- Development- more cells than needed are made just in case they have to be eliminated
- Quality control- during development for abnormal cells (get rid of cells w/o damaging others)
- Organ/tissue sculpting
- Maintenance of short-lived cell supply
- Organelle damage
- Elimination of bad immune system cells, unneeded activated lymphocytes
list 7 reasons stressed out cells die
- Glucocorticoid binding of nuclear receptors
- Radiation
- Heat
- Nutrient deprivation
- Viral infection
- Hypoxia
- High intracellular calcium
what is the last thing that happens to apoptotic cells before phagocytosis?
Cell breaks apart with intact membranes to form apoptotic bodies
what are 4 chemical changes that make apoptotic cells recognizable?
- DNA is fragmented by an endonuclease at the linker regions between nucleosomes
- Membrane phospholipid phosphatidylserine changes conformation and moves to outer leaflet of lipid bilayer
- Release of mitochondrial cytochrome c into cell cytosol
- Vacuole formation related to organelle autophagy
what are capsases? where are they located?
proteases with a cysteine at their active site and cleave target substrates at a specific aspartic acid; in cytoplasm as inactive procaspases
what happens to activated procaspases? what do these do?
become either initiator caspases or executioner caspases; cleave specific proteins such as lamins, endonucleases, cell-cell proteins, and cytoskeletal proteins to either start or stop their function
how are caspase activated? how is this done?
A “death signal” must be received; Procaspase domains with recruitment domain allows them to assemble with “adaptor” proteins into activation complexes
how is the activation complex assembled?
Proximity of initiator procaspases activates them (they cleave each other); this begins the cascade; Executioner procaspases are activated and death signal is amplified
what are the two death signal pathways?
extrinsic- extracellular signal proteins bind to death receptors on a cell surface; intrinsic- Internal response to injury or hypoxia
how do the receptors work in extrinsic apoptosis? What kind of family do they belong to?
Receptors have ligand-binding region, one transmembrane domain and a death domain; Receptors belong to TNF receptor family
what does intrinsic pathway depend on? which proteins bind?
Dependent upon release of cytochrome c and other proteins from mitochondria which in turn activate a caspase cascade; Proteins bind to adaptor protein Apaf1 which becomes an apoptosome which activates procaspases
what is the relationship between extrinsic and intrinsic paths?
sometimes extrinsic path recruits intrinsic path
what protein is required for intrinsic pathway? what does it do?
Bcl2; These are considered regulators of cell death as some are pro-apoptotic and others are anti-apoptotic
what are pro-apoptotic proteins? anti-apoptotic proteins? what are these proteins considered?
BH123 (Bak and Bax) and BH3; Bcl2 and Bcl-XL; membrane guardians
what does p53 do?
If cellular DNA is damaged, p53 (tumor suppressor) accumulates, activates other proteins which in turn trigger the intrinsic pathway
what is required for cell survival?
extracellular signals from other cells to avoid apoptosis
what are two types of survival pathways?
increased production of anti-apoptotic bcl2 family protein; inactivation of pro-apoptotic BH3-only protein
what is cancer?
tumorigenic cells regulate the apoptotic pathway abnormally
how does Bcl2 production relate to cancer?
production increases after a chromosomal translocation, leading to apoptotic inhibition of those cells (lymphocytes)
how does p53 gene relate to cancer?
gene mutated in many cancers so no cell death or cell-cycle arrest = tumors
