Week 5 Apoptosis

Question 1

Contrast Necrosis and Apoptosis: stimuli, morphology, host response, insult severity, nucleus dissolution

Answer 1

Necrosis: pathologic, cell swelling and lysis, inflammation, greater insults

Apoptosis: physiologic or pahtologic, cell shrinking, no inflammation, lesser insult

Nucleus dissolves in both!

Question 2

what is the general/morphological progresssion of a cell undergoing apoptosis

Answer 2

nucleus condenses and fragments–>part of the cell Bleb and form apopotic bodies that are eaten by phagocytes

Question 3

name three diseases in which we see excessive apoptosis?

Answer 3

AIDs (excessive loss of lymphocytes), Alzheimers disease (neuron loss), stroke

Question 4

name a disease associated with suppression of apoptosis

Answer 4

cancer

Question 5

what are the pro-apoptotic and anti-apoptotic Bcl-2 subgroups

Answer 5

Pro: Bax family (Bax/Bak), BH2-only family (Bid)

Anti: Bcl-2 family

Question 6

what is the role of Bcl-2

Answer 6

when there is not cell stress Bcl-2 binds and inhibits Bax/Bik preventing them from inducing apoptosis

Question 7

what is the role of Bid? activated?

Answer 7

under cell stress Bid is cleaved (caspase -8 or granzyme-B) and inhibits Bcl-2 binding and thus frees Bax/Bak

Question 8

what is the role of Bax/Bak

Answer 8

when not sequestered Bax/bak create a pore in the mitochondrial membrane and release Cyt C, AIF, and Smac/Diablo

Question 9

what is the role of Smac/Diablo

Answer 9

inhibits IAB which normally inhibits the caspase cascade

Question 10

what is the role of AIF

Answer 10

causes nuclear condensation and DNA fragmentation

Question 11

what is the role of Cyt C?

Answer 11

complexes with Apaf-1 to form an apatosome that activates procaspase-9

Question 12

Activated pro-caspase-9 (caspase-9) does what

Answer 12

initiates caspase cascade which eventually activates execution caspases that degrade cellular components and lead to apoptosis

Question 13

what is the extrinsic pathway of apoptosis?

Answer 13

death receptors at cell surface are sensitive to external signals that mediate apoptosis.

Question 14

which caspase is seen in the extrinsic pathway? significance?

Answer 14

caspase-8 (this is the same caspase that activates Bid of the intrinsic pathway, crosstalk!)

Question 15

what is Granzyme B? what is it released by?

Answer 15

a Ser protease that is released by cytotoxic T cells and NK cells

Question 16

how does granzyme B function?

Answer 16

granzyme-B is released with perforin which enables it to enter cells. once in the cell granzyme-B activates Bid, Caspase 3 and 8.

Question 17

what is the function of p53

Answer 17

tumor suppressor: promotes apoptosis. (Increases Bid transcription, increases death receptors, promotes Bax/Bak activity)