The Embryo: Apoptosis

Question 1

What mechanisms regulate cell survival? (simple)

Answer 1

Lack of trophic (survival) factors

Kill signals

Question 2

What are the major pathways of cell death?

Answer 2

Necrosis
Necroptosis
Apoptosis

Question 3

What occurs during necrosis?

Answer 3

Cell membrane rupture (caused by trauma, infection, other external forces)

Leakage of cellular contents (can cause inflammatory response)

Question 4

What occurs during necroptosis?

Answer 4

Programmed necrosis

Triggers permeabilization of cell membrane

Question 5

What occurs during apoptosis?

Answer 5

Normal process of cell death
Removal of damaged or old cells
Cells become shriveled but remain intact

Question 6

Role of apoptosis in embryonic development?

Answer 6

Form structure, organs, and tissue

Deletion of interdigital tissue

Question 7

Role of apoptosis in adult tissue?

Answer 7

maintain organ size

maintain cell numbers (bone marrow)

Question 8

How is apoptosis triggered?

Answer 8

Specialized proteases: caspases

Requires activation signal > initiator caspase activates executioner caspase

Question 9

What are the specialized forms of caspases?

Answer 9

ICAD inhibitor of DNase: DNA fragmentation

Nuclear lamins: fragmentation of nucleus

Cytoskeletal proteins actin, myosin, alpha-actinin, tubulin, vimentin: cell fragmentation, membrane blebbing

Golgi matrix proteins: fragmentation of golgi

Question 10

How does the extrinsic pathway cause apoptosis?

Answer 10

External signals bind to death receptors (tumor necrosis factor TNF receptor family)
ex. fas ligand in lymphocytes

Internal death domain activates death inducing signal complex (DISK) > activates initiator caspase > activates executioner caspase

Question 11

How is the extrinsic pathway regulated?

Answer 11

Inhibitor protein c-FLIP

inactivates executioner caspase

Question 12

How is the intrinsic pathway triggered for apoptosis?

Answer 12

internal signals (development signals, cell stress etc)

Mitochondrial pathway releases cytochrome C

Question 13

How does cytochrome C cause apoptosis?

Answer 13

Binds to Apaf1 to form apoptosome > activates initiator caspase

Question 14

How is the intrinsic pathway regulated?

Answer 14

By Bcl2 protein family

Anti-apoptotic: Bcl2 and BclXl
Block release of cytochrome C

Pro-apoptotic: Bax,Bak…
Enhance release of cytochrome C

Question 15

Overall inhibitor of apoptosis?

Answer 15

Inhibitors of Apoptosis (IAPs)

Bind and inhibit activated caspases

Have to be inactivated by anti-IAPs for apoptosis to proceed

Question 16

How does phagocytosis occur?

Answer 16

Cell surface signal by phosphatidylserines induces phagocytosis by macrophages