apoptosis

Question 1

Hallmarks of Necrosis (4)

Answer 1

1. cell rupture 2. tissue injury 3. inflammatory response 4. takes hours

Question 2

Hallmarks of Apoptosis (4)

Answer 2

1. cell destruction w/o rupture 2. no tissue damage 3. phagocytosis of cell corpses (apoptotic bodies) 4. takes minutes

Question 3

Examples of apoptosis in the body

Answer 3

1. embryonic development 2. death of immune cells 3. death of cells induced by cytotoxic T cells 4. hormone-dependent involution in adults

Question 4

What happens to the cell in apoptosis?

Answer 4

1. cell seize decreases 2. chromatin condenses 3. DNA is fragmented 4. blebbing of plasma membrane 5. phagocytosis (all 5 steps take about 1 hour)

Question 5

What is the difference between intrinsic and extrinsic mechanisms of apoptosis?

Answer 5

INTRINSIC (cell suicide) - stimulated by withdrawal of growth factors or cytokines, by radiation or radical-induced damage EXTRINSIC (cell murder) - stimulated by cytotoxic T cells via death receptor or Fas/Fas-ligand interaction

Question 6

5 general constituents of the apoptotic pathway

Answer 6

1. signal 2. adaptors 3. regulators 4. caspases 5. scramblase/phagocytosis

Question 7

Intrinsic apoptotic signal

Answer 7

withdrawal of growth factors/cytokines or radiation damage, hypoxia, thermal damage

Question 8

Extrinsic apoptotic signal

Answer 8

death receptor activation or tumor necrosis factor receptor activation (Fas receptor - Apo1 or CD95)

Question 9

Intrinsic apoptotic adaptors

Answer 9

Apaf-1 (Pro-apoptotic protease activating factor -most common) - recognizes signal and can bind many caspases so that they can cross proteolyse and activate each other

Question 10

Extrinsic apoptotic adaptors

Answer 10

FADD (Fas-assocaited w/ death domain) - aggregated caspases when receives signal

Question 11

Intrinsic apoptotic regulators

Answer 11

Bcl-2 family - coiled coil interactions between alpha-helical BH domains to form complexes that can either inhibit or promote cell death - balance is IMPORTANT

Question 12

Bcl-2 family of proteins - pro-survival

Answer 12

Bcl-2 binds Apaf-1 and prevents it from activating caspases, also can bind and inhibit pro-apoptotic members (Bax) in mitochondiral membrane

Question 13

Bcl-2 family of proteins - pro-apoptosis

Answer 13

Bad and Bax. Bad binds Bcl-2, which liberates Bax to form pores in the mitochondrial membrane for cyctochrome C to get out

Question 14

Extrinsic apoptotic pathway

Answer 14

Question 15

Types of Caspases

Answer 15

1. initiating capases (Ced8 & 9) activated by aggregation 2. Execution caspases (Ced 3, 6, & 7) carry out cleavage of proteins inside the cell

Question 16

How do caspases work?

Answer 16

They are proenzymes, they are synthesized in the inactive form and must be cleaved of their autoinhibitory domain to be active. They are specific, so protein degredation is controlled and precise

Question 17

How do cells signal phagocytosis?

Answer 17

enzyme scramblase moves phosphatidyl serine to the outer leaflet of the plasma membrane, which is recognized by CED1 receptor on macrophages

Question 18

Intrinsic apoptotic pathway

Answer 18

Question 19

What happens when apoptosis doesn’t work?

Answer 19

1. suppression = cancer (example - p53 is mutated and can’t trigger apoptosis) 2. excess = neurodegenerative diseases