cell death Flashcards

1
Q

how is the autophagosome formed?

A

portions of the cytoplasm are engulfed by a double membrane vacuole

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2
Q

how is the autolysosome formed?

A

autophagosome is acidified

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3
Q

how is autophagy “pro-survival”

A

helps cells to survive in times of low nutrients through catabolism

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4
Q

how is autophagy “pro-death”

A

through autophagy or the induction of apoptosis

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5
Q

which types of dlls can be observed undergoing autophagic death?

A

cells with accumulations of misfiled proteins- Huntington’s dz, prion dz, breast CA cells treated with tamoxifen

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6
Q

what will lead to the intrinsic pathway of apoptosis?

A

intracellular stressors (pH, oxidative stress, mitochondrial stress, DNA damage)

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7
Q

which are the anti-apoptotic proteins?

A

Bcl-2 and Bcl-xl

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8
Q

how do the anti-apoptotic proteins work?

A

present in the mito membrane, inhibit the function of pro-apoptotic proteins

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9
Q

which are the pro-apoptotic proteins?

A

Bax, Bak

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10
Q

how do the pro-apoptotic proteins function?

A

dimerization results (indirectly) in cytochrome c release (ions released first)

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11
Q

what are the “activators”? “decoys”?

A

activators- Bid and Bim

decoys- Bad, Bik

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12
Q

how do the “activators” work?

A

pro-apoptotic

help form the pore

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13
Q

how do the “decoys” work?

A

pro-apoptotic

inhibit the function of the anti-apoptotic

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14
Q

what is the initiator in the intrinsic pathway of apoptosis?

A

procaspase-9

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15
Q

discuss the steps in the intrinsic pathway of apoptosis

A

-cytochrome c is released from mito
-cytochrome c binds Apaf-1 adapter protein
-cytoC+Apaf-1 complexes will aggregate and bind procaspase-9 to form “apoptosome”
-procaspe-9 activated to caspase-9
-caspase cascade triggered
= apoptosis

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16
Q

what are the receptors used with extrinsic apoptosis?

A

Fas receptor, tumor necrosis factor receptor

17
Q

what are FADD/TRADD?

A

death domains that include adapter proteins

18
Q

what is the initiator for the extrinsic apoptosis pathway?

A

procaspase-8

19
Q

what are some of the effects of the caspase cascade (intrinsic/extrinsic)?

A

DFF- DNA fragmentation factor
CD- caspase activated DNase
cleave lamins, fragment nucleus
externalized phos-serine –> “eat me signal”

20
Q

what type of signaling is used in the extrinsic apoptosis pathway?

A

juxtracrine

21
Q

describe the extrinsic apoptotic pathway

A

-fas-ligand on t-cell binds fas-protein on target
- adapter proteins facilitate binding of procaspases to receptor/ligand complexes
- procaspase-8 cleaved to caspase 8
- caspase cascade triggered
= apoptosis

22
Q

what are the links between the intrinsic and extrinsic pathways of apoptosis? (2)

A

1- both caspase 8 and caspase 9 will activate caspase 3

2- caspase 8 (extrinsic) can cleave and activate Bid (pro-apoptotic activator) and trigger intrinsic pathway

23
Q

when does anoikis occur?

A

when cell becomes detached from the ECM

24
Q

what is the relation of anoikis to tumor mets?

A

anoikis must be overcome for mets to occur

25
Q

discuss an “attached cell” in terms of anoikis

A

Bad (decoy) is phosphorylated/inactivated and unable to bind Bcl-2, thus apoptosis is avoided

26
Q

discuss a “detached cell” in terms of anoikis

A

Bad binds bcl-2, thereby inactivating it, Bax forms mito pores and cytochrome c escapes, triggering intrinsic apoptosis

27
Q

what triggers the unfolded protein response?

A

unfolded/misfolded proteins in the ER

28
Q

what can occur with prolonged activation of the unfolded protein response?

A

apoptosis via activation of caspase 12

29
Q

what differentiates apoptosis from necrosis?

A

necrosis involves breakdown of cell membrane integrity

30
Q

what is reperfusion injury?

A

inflammatory mediators cause build up of ROS and NO, these can lead to further damage of mito/membranes and further necrosis

31
Q

what determines the type of cell death that will occur?

A

amount of damage to the cell will determine type of cell death

32
Q

how is apoptosis inhibited?

A

Beclin and Atg proteins cause formation of autophagosome and degradation of caspase 8

33
Q

how is autophagy inhibited?

A

caspases and other proteins cleave beclin and tag proteins

34
Q

what is necroptosis?

A

programmed necrosis

35
Q

what is the receptor in necroptosis?

A

TNF recetpor

36
Q

what proteins are involved with necroptosis?

A

RIP1 and RIP3 (caspase independent)

37
Q

what is entosis?

A

cellular “cannibalism” seen in some tumors

38
Q

what is parthanatos?

A

cell death caused by poly-ADP-ribose polymerase-1