Apoptosis

Question 1

what is apoptosis?

Answer 1

Controlled cellular suicide

Question 2

what is another form of controlled cellular suicide besides apoptosis?

Answer 2

autophagy

Question 3

what is necrosis?

Answer 3

cell death in response to an acute issue; uncontrolled

Question 4

what are the 4 morphological changes in apoptosis?

Answer 4

• Membrane blebbing or shrinkage and chromatin condensation
• Cytoskeletal collapse
• Disassembly of nuclear envelope
• Chromatin fragmentation

Question 5

what are the 2 chemical changes in apoptosis?

Answer 5

• Cell surface is altered for phagocytic recognition
• Intracellular proteins act as signals and activators of cell destroyers

Question 6

for what 6 reasons is apoptosis needed?

Answer 6

• 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

Question 7

list 7 reasons stressed out cells die

Answer 7

• Glucocorticoid binding of nuclear receptors
• Radiation
• Heat
• Nutrient deprivation
• Viral infection
• Hypoxia
• High intracellular calcium

Question 8

what is the last thing that happens to apoptotic cells before phagocytosis?

Answer 8

Cell breaks apart with intact membranes to form apoptotic bodies

Question 9

what are 4 chemical changes that make apoptotic cells recognizable?

Answer 9

• 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

Question 10

what are capsases? where are they located?

Answer 10

proteases with a cysteine at their active site and cleave target substrates at a specific aspartic acid; in cytoplasm as inactive procaspases

Question 11

what happens to activated procaspases? what do these do?

Answer 11

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

Question 12

how are caspase activated? how is this done?

Answer 12

A “death signal” must be received; Procaspase domains with recruitment domain allows them to assemble with “adaptor” proteins into activation complexes

Question 13

how is the activation complex assembled?

Answer 13

Proximity of initiator procaspases activates them (they cleave each other); this begins the cascade; Executioner procaspases are activated and death signal is amplified

Question 14

what are the two death signal pathways?

Answer 14

extrinsic- extracellular signal proteins bind to death receptors on a cell surface; intrinsic- Internal response to injury or hypoxia

Question 15

how do the receptors work in extrinsic apoptosis? What kind of family do they belong to?

Answer 15

Receptors have ligand-binding region, one transmembrane domain and a death domain; Receptors belong to TNF receptor family

Question 16

what does intrinsic pathway depend on? which proteins bind?

Answer 16

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

Question 17

what is the relationship between extrinsic and intrinsic paths?

Answer 17

sometimes extrinsic path recruits intrinsic path

Question 18

what protein is required for intrinsic pathway? what does it do?

Answer 18

Bcl2; These are considered regulators of cell death as some are pro-apoptotic and others are anti-apoptotic

Question 19

what are pro-apoptotic proteins? anti-apoptotic proteins? what are these proteins considered?

Answer 19

BH123 (Bak and Bax) and BH3; Bcl2 and Bcl-XL; membrane guardians

Question 20

what does p53 do?

Answer 20

If cellular DNA is damaged, p53 (tumor suppressor) accumulates, activates other proteins which in turn trigger the intrinsic pathway

Question 21

what is required for cell survival?

Answer 21

extracellular signals from other cells to avoid apoptosis

Question 22

what are two types of survival pathways?

Answer 22

increased production of anti-apoptotic bcl2 family protein; inactivation of pro-apoptotic BH3-only protein

Question 23

what is cancer?

Answer 23

tumorigenic cells regulate the apoptotic pathway abnormally

Question 24

how does Bcl2 production relate to cancer?

Answer 24

production increases after a chromosomal translocation, leading to apoptotic inhibition of those cells (lymphocytes)

Question 25

how does p53 gene relate to cancer?

Answer 25

gene mutated in many cancers so no cell death or cell-cycle arrest = tumors