Apoptosis

Question 1

What are the two ways to turn on cell death?

Answer 1

Absence of trophic/survival factors
Kill signals

Question 2

What are the 3 major pathways of cell death?

Answer 2

Necrosis
Necroptosis
Apoptosis

Question 3

What is necrosis?

Answer 3

Rapid cell destruction
Cell membrane rupture and leakage of cellular contents

Question 4

What causes necrosis?

Answer 4

Trauma
Infections
Other external forces

Question 5

What can necrosis lead to?

Answer 5

Inflammatory and immunological responses

Question 6

What is necroptosis?

Answer 6

Induced necrosis
No activation of caspases triggers permeabilization of cell membrane

Question 7

What is apoptosis?

Answer 7

Normal cell death to balance cell growth
Programmed cell death
Cells remain intact, no membrane rupture

Question 8

What are the roles of apoptosis in embryos?

Answer 8

Form structures, organs and tissues
Deletion of interdigital tissue in digit formation (unwebbing)
Pruning unneeded nerve cells in nervous system

Question 9

What are the roles of apoptosis in adult tissues?

Answer 9

Balances cell proliferation to maintain organ sizes
Maintain constant cell numbers in tissues
Prevents production of new viruses and limits spread
Eliminate cells containing mutations in response to DNA damage - prevent cancer
Remove lymphocytes after infections

Question 10

What triggers apoptosis?

Answer 10

Caspases

Question 11

How to caspases work?

Answer 11

Initiator caspase cleaves and activated the executioner caspase, which catalyzes cellular proteolysis. Nuclease activation - DNA chromatin degradation. Nuclear lamins degrade. Cytoskeletal proteins fragment. Golgi fragments. Cells shrivel.

Question 12

What is the function of endonuclease and how is it activated?

Answer 12

Cleaves DNA in nucleus
Activated by caspase

Question 13

How is apoptosis triggered?

Answer 13

Extrinsic pathway
Intrinsic pathway

Question 14

What are the steps of the extrinsic pathway?

Answer 14

External signals bind to cell surface death receptors (TNF family). Activated internal death domain, signal complex DISC. Activates initiator caspase which activates executioner caspase.

Question 15

How is the extrinsic pathway regulated?

Answer 15

Inhibitor protein c-FLIP inactivates executioner caspase

Question 16

What are the steps of the intrinsic pathway?

Answer 16

Developmental signals or in response to cell stress
Mitochondria releases cytochrome C which binds to Apaf1 protein to form apoptosome. That activates initiator caspase to activate executioner caspase.

Question 17

What regulates the intrinsic pathway?

Answer 17

Bcl2 protein family
-either activates or inhibits

Can be activated by extrinsic pathway

Question 18

What are the inhibitory Bcl2 proteins and how do they work?

Answer 18

Bcl2 and BclXL

Block release of cytochrome C from mitochondria

Question 19

What are the activating Bcl2 proteins and how to the work?

Answer 19

Bax, Bak, Bad, Bid, Puma, and more

Enhance release of cytochrome C
Can be activated by p53 in response to DNA damage

Question 20

What are inhibitors of apoptosis (IAPs) and how do they function?

Answer 20

Internal cellular proteins that prevent apoptosis by inhibiting activated caspases. Some cause degradation of caspase.

Question 21

How are IAPs regulated?

Answer 21

Need to be inactivated by anti-IAP which include Smac/Diablo

Question 22

What are survival factors and how do they function?

Answer 22

External cellular signal proteins that prevent apoptosis.
Bind receptors to stimulate Bcl2 to either activate inhibitory or inhibit activation.