L28 Cell Death

Question 1

How do cells die?

Answer 1

Most cells die through Necrosis and apoptosis

Question 2

What is Necrosis ?

Answer 2

Premature death of cells in living tissue. It’s an uncontrolled, chaotic process unlike apoptosis

Question 3

What is apoptosis?

Answer 3

Programmed cell death, is a controlled process by which cells self-destruct

Question 4

When does necrosis occur?

Answer 4

Physical damage:
- trauma e.g. cuts and burns
- extreme temperatures e.g. frostbite

Toxins:
- External e.g. snake venom
- Internal e.g. bacterial toxins

Acute hypoxia/ischaemia e.g. stroke

Question 5

When does apoptosis occur?

Answer 5

Physiological situations:
- Tissue size maintenance
- Developmental cell loss - growth factors
- Removal of immune cells

Pathological situations:
- DNA damage e.g. radiation, oxidative stress
- Virally infected cells

Question 6

What are the characteristics of necrosis?

Answer 6

Reversible:
- Membrane integrity compromised
- Organelle and cell swelling

Irreversible:
- Increased intracellular calcium
- Autolysis
- Cell bursting (cell lysis)
- Elicits an inflammatory response

Question 7

What are the characteristics of apoptosis?

Answer 7

Shrinkage
Nuclear breakdown
Apoptotic bodies
Phagocytosis
No inflammatory response
Requires energy

Controlled cell death
Relationship with autophagy

Question 8

Can both mechanisms be involved in the death of a cell?

Answer 8

Yes. In brain ischaemia, cells in the middle die through necrosis and cells at edge die through apoptosis. This restricts spread of cells death

Question 9

What does developmental apoptosis mean?

Answer 9

1. Developmental apoptosis is very controlled cell death where we can be precise on the count.
2. It involves selective elimination of specific cells.
3. In C.elegans 131 cells die for development.

Question 10

How is developmental apoptosis initiated?

Answer 10

It is initiated through release of local signals.

Question 11

What happens to the cell shape via apoptosis and necrosis?

Answer 11

Apoptosis - shrinkage, condensed
Necrosis - swelling

Question 12

What happens to cellular content after apoptosis vs necrosis?

Answer 12

Apoptosis - packaged in apoptotic bodies
Necrosis - leakage to extra cellular fluid

Question 13

Is ATP required for apoptosis and or necrosis?

Answer 13

ATP required for apoptosis but not necrosis

Question 14

Why is developmental apoptosis important?

Answer 14

Eliminates unnecessary cells which is important for processes like metamorphosis e.g. tadpole - frog

• Surge in thyroid hormone in the blood initiate apoptosis in tail cells

Question 15

How would one study apoptotic pathways?

Answer 15

We would use C- elegans because they provide an excellent model for studying the pathways.

Ced genes involved from recognition of apoptotic signal to engulfment of apoptotic cell by phagocytes

Question 16

What are caspases?

Answer 16

The executioners of cell death = essential for apoptosis

C = cysteine at their active site
asp = aspartic acid are the cleave site in target proteins

Question 17

What are the Ced genes conserved in mammals?

Answer 17

1. Ced 9
2. Ced 4 - Inhibitors
3. Ced 3 - The ones that inititae apoptosis.

Question 18

What does the decrease in Ced 3 and Ced 9 cause in apoptosis?

Answer 18

Decrease in Ced3 causes excess adult cells existence
Decrease in Ced 9 gives massive cell death.

Question 19

What are imitator caspases?

Answer 19

Activated by apoptotic signals
Active executioner caspases

Question 20

What happens when initiator caspases activates executioner caspases?

Answer 20

One initiator caspases can active multiple executioner caspases - amplified proteolytic cascade

Question 21

Describe the mechanism behind initiator caspase activating the executioner caspases. (Listen to the guy and use diagram)

Question 22

What are some of the caspase targets? (3)

Answer 22

• Cause breakdown of nucleus structure, cleavage of nuclear lamins
• Prevents DNA repair by cleaving the DNA repair enzyme PARP
• Cause cytoskeleton changes, cleaves cytoskeleton proteins like Gelsolin

Question 23

What are the two main ways of initiating apoptosis?

Answer 23

Extrinsic pathways
Intrinsic pathways

Question 24

Extrinsic pathway slide

Question 25

What does DISC stand for?

Answer 25

Death - induced signalling complex

Question 26

What triggers intrinsic pathways?

Answer 26

Triggered by:
Stress signals e.g. DNA damage
Developmental signals

Question 27

Describe how an apoptotic stimulus can lead to a caspase cascade leading to apoptosis?

Answer 27

an apoptotic stimulus triggers either the extrinsic or intrinsic pathway, leading to the activation of initiator caspases. These initiator caspases, in turn, activate executioner caspases, which dismantle the cell and lead to its demise.

Question 28

2nd Instrinsic pathway slide (please make the answer make sense to the quesrion)