APOPTOSIS

Question 1

Why might a cell be programmed to apoptose?

Answer 1

1. harmful cells eg. cells with viral infection or DNA damage
2. developmentally defective cells eg self expressing b cells
3. excess/unnecessary cells
4. obsolete cells eg. mammary epithelium after lactation
5. exploitation, chemotherapeutic killing of cells

Question 2

define necrosis

Answer 2

unregulated cell death

Question 3

when does necrosis take place?

Answer 3

trauma, cellular disruption and an inflammatory response

when the plasma membrane becomes permeable, cell swelling and rupture of membrane.
release of proteases leading to auto-digestion and stimulates an inflammatory response

Question 4

what is apoptosis

Answer 4

a regulated series of events that causes a controlled disassembly of a cell without disruption of surrounding cells. no inflammatory response

Question 5

what happens after necrosis ?

Answer 5

phagocytes will clear up the debris

the unaffected surrounding cells will proliferate

Question 6

what are the differences between necrosis and apoptosis?

Answer 6

necrosis: uncontrolled, many cells, inflammatory response, plasma membrane ruptures, no ATP required
apoptosis: controlled, one cell at a time/localised , no inflammatory response, plasma membrane stays intact, requires ATP

Question 7

what may be indicative of apoptosis- like PCD (programmed cell death)?

Answer 7

the cells may display phagocytic recognition before plasma membrane lysis

Question 8

what are the rough stages of apoptotic cell death?

Answer 8

1. caspases: the executioners
2. initiating the death programme: death receptors, mitochondria
3. Bcl-2 family
4. stopping death programme

Question 9

what are caspases?

Answer 9

cysteine dependent aspartate-directed proteases

they are the executioners of apoptosis

they need to be activated by proteolysis (clevage) they are autofolded onto themselves so need a protease to clip at certain points and activate.

cascade of activation

Question 10

what is the CARD domain for?

Answer 10

place the caspase at particular sites inside the cell

Question 11

which are the initiator caspases and which are the effector caspases? what domains do they have?

Answer 11

initiator: 2,9,10 & 8
- -> CARD, DED, p20, p10 domains

effector: 3,6,7
- ->p20, p10 domains

Question 12

what are caspases initially synthesised as?

Answer 12

procaspases which are folded

Question 13

what are the mechanisms of caspase activation?

Answer 13

1. activated extrinsically by receptor mediated pathways

2. activated intrinsically by mitochondrial death pathways