apoptosis Flashcards

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1
Q

what is another term for apoptosis

A

programmed cell death

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2
Q

T or F: apoptosis is necessary during all stages of an animals life

A

true

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3
Q

roughly how many cells in the adult body die due to apoptosis every day

A

10^10-10^11

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4
Q

what types of cells need to undergo apoptosis

A

those that are damaged, nonfunctional, or have already done their job

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5
Q

what happens when there is a failure to carry out apoptosis

A

disease, ie cancer

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6
Q

what happens when there is unnecessary apoptosis

A

disease, ie alzheimers, parkinson’s, or type 1 diabetes

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7
Q

in regards to apoptosis, what are two ways that disease can occur

A

when there is a failure to carry out apoptosis, or if there is unnecessary apoptosis

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8
Q

in apoptosis, what happens to cell shape

A

shrinks

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9
Q

in apoptosis, what happens to chromosomes

A

they condense

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10
Q

in apoptosis, what happens to nuclear envelope

A

it disintegrates

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11
Q

in apoptosis, what happens to the membrane

A

blebbing

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12
Q

in apoptosis, what happens to DNA

A

fragmentation

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13
Q

in apoptosis, what happens to cytoplasm and nucleus fragments

A

they form apoptotic bodies

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14
Q

in apoptosis, what happens to apoptotic bodies formed by nuclear fragments + cytoplasm

A

phagocytosis of apoptotic bodies by macrophages

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15
Q

what do we use to detect chromatin condensation in the lab

A

Hoescht-33342

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16
Q

what is Hoescht-33342

A

a cell permeable fluorescent DNA-binding stain

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17
Q

what is necrossis

A

a process whereby a cell dies due to an acute insult

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18
Q

in necrosis, what happens to the cell shape

A

swelling

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19
Q

in necrosis, what happens to the membrane

A

membrane breaks down

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20
Q

which is explosion: apoptosis or necrosis

A

necrosis

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21
Q

which is implosion: apoptosis or necrosis

A

apoptosis

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22
Q

in which organism was apoptosis discovered

A

C elegans

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23
Q

how was apoptosis discovered in C elegans + how does this apply to humans

A

4 genes were found to play a role in apoptosis, and then homologs of these proteins were found in mammals

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24
Q

name the family of proteases found in mammals but not nematodes

A

caspases

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25
Q

what are caspases

A

a family of proteases

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26
Q

in simple terms, what is the function of a caspase

A

they mediate apoptosis

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27
Q

what type of protease is a caspase

A

it’s a Cysteine protease

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28
Q

where do caspases cleave proteins

A

at sites C terminal to Aspartate residues

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29
Q

what what site does caspase-8 make a cleavage

A

D215

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30
Q

how many caspases do humans have

A

14

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31
Q

T or F: all human caspases are involved in apoptosis

A

false; not all of them are

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32
Q

what are the two types of caspases

A

initiator and executioner

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33
Q

which caspases are initiator

A

8 and 9

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34
Q

which caspases are executioner

A

3, 6, 7

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35
Q

what do initiator caspases do

A

activate executioner caspases

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36
Q

what do executioner caspases do

A

cleave the target

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37
Q

how do caspases exist in the cell

A

exist as precursors

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38
Q

T or F: once a cell is triggered to undergo apoptosis, there is no turning back

A

TRUE

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39
Q

list 5 target proteins that are cleaved during apoptosis

A

nuclear lamins
cell-cell adhesion molecules
cytoskeletal proteins
iCAD
PARP

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40
Q

what does iCAD stand for

A

inhibitor of CAD

41
Q

what does CAD stand for

A

caspase-activated DNase

42
Q

is CAD active or inactive when iCAD is bound

A

inactive

43
Q

what happens to iCAD upon apoptosis initiation

A

iCAD is cleaved

44
Q

what cleaves iCAD in apoptosis initiation

A

caspase-3

45
Q

in apoptosis initiation, what does CAD do once iCAD is cleaved off of it

A

it cleaves DNA at sites between the nucleosomes

46
Q

what is the result of CAD cleaving DNA at sites between nucleosomes

A

DNA laddering effect (ie dif fragments of DNA with lengths that differ by ~200bp)

47
Q

what is the role of PARP

A

PARP helps cells to repair themselves after DNA damage

48
Q

what two types of breaks does PARP help with

A

single stranded and double stranded breaks

49
Q

what does PARP stand for

A

poly ADP ribose polymerase

50
Q

how many kD is the active form of PARP

A

116 kD

51
Q

what targets the active form of PARP

A

caspase-3

52
Q

what happens to the active form of PARP after it’s cleaved by caspase-3

A

produces the inactive form of PARP

53
Q

how many kD is the inactive form of PARP

A

89 + 27 kD

54
Q

why is the presence of inactive PARP evidence of apoptosis

A

because active PARP was cleaved into two fragments by casp-3

55
Q

if cells are undergoing apoptosis, do we want PARP to be active or inactive

A

inactive

56
Q

what are the two types of apoptosis pathways

A

intrinsic and extrinsic

57
Q

what is another term for the intrinsic pathway

A

the mitochondrial pathway

58
Q

what family of proteins controls the intrinsic pathway

A

Bcl2 family

59
Q

what is the role of the Bcl2 family of proteins

A

control the intrinsic pathway of apoptosis

60
Q

how many classes are within the Bcl2 family

A

3

61
Q

describe the relationship between the 3 Bcl2 classes

A

they all share homology in up to 4 characteristic regions: called the Bcl2 homology domains or BH 1-4 domains

62
Q

what two types of functions will the Bcl2 proteins have

A

they will either be pro-apoptotic or anti-apoptotic

63
Q

what do anti-apoptotic proteins do

A

inhibit apoptosis

64
Q

what do pro-apoptotic proteins do

A

induce apoptosis

65
Q

Bcl2 is an __-apoptotic protein

A

anti

66
Q

where is Bcl2 found

A

in the OMM

67
Q

how does Bcl2 function

A

it prevents the release of Cyt c and other proteins in the intermembrane space from diffusing into the cytosol, which would activate apoptotic caspases

68
Q

would cyt c diffusing into the cytosol activate or inhibit apoptosis

A

activate

69
Q

what type of apoptotic proteins are Bak and Bax

A

pro apoptotic

70
Q

where are Bak and Bax found

A

OMM

71
Q

how do Bak and Bax promote apoptosis

A

they form channels in the OMM = release of cyt c

72
Q

what is MOMP

A

mitochondrial outer membrane permeabilization

73
Q

how can Bcl2 interact with Bak/Bax

A

Bcl2 binds to them, inhibiting their oligomerization = no apoptosis

74
Q

what are survival factors

A

specific extracellular signals that cells need to stay alive

75
Q

T or F: in the presence of survival factors, apoptosis is inhibited

A

true

76
Q

T or F: in the presence of a trophic factor, apoptosis occurs

A

false; the cell survives

77
Q

T or F: in the absence of a trophic factor, apoptosis occurs

A

true

78
Q

describe why the cell survives when trophic factors are present (hint: Bad is a pro apoptotic protein)

A

trophic factor binds to receptor = signaling pathway = Bad becomes phosphorylated. Phosphorylated Bad interacts with the 14-3-3 protein which inhibits its activity, so Bad cannot promote apoptosis

79
Q

Is Bad pro or anti apoptotic

A

pro

80
Q

in the presence of a trophic factor in the intrinsic pathway why does Bad not initiate apoptosis even tho it’s pro-apoptotic?

A

Bad becomes phosphorylated and then interacts with the 14-3-3 protein which inhibits it’s activity = no apoptosis

81
Q

describe the intrinsic pathway in the absence of a trophic factor

A

Bad does not become phosphorylated, and so it binds to Bcl2 which causes the release of Bak/Bax, which now form a channel in the OMM. Cyt c goes through the channel into the cytosol = apoptosis is activated

82
Q

how does cyt c release activate apoptosis

A

cyt c binds to Apaf-1, which causes it to assemble into the apoptosome, and then caspases become activated

83
Q

what does cyt c bind to when it activates apoptosis

A

Apaf-1

84
Q

what does Apaf-1 assemble into during apoptosis activation

A

the apoptosome

85
Q

what is another term for the apoptosome

A

the wheel of death

86
Q

how is the apoptosome formed

A

cyt c binds to Apaf-1, which then causes it to interact with other Apaf-1s

87
Q

which initiator caspase is activated when the apoptosome is formed

A

9

88
Q

upon activation of caspase-9 after the formation of the apoptosome, which executioner caspase is cleaved/activated

A

3

89
Q

what type of apoptotic proteins are Bim and Puma

A

pro apoptotic

90
Q

describe how Bim and Puma play a role in apoptosis activation

A

they can bind to Bcl2 and cause it to release from Bak/Bax

91
Q

when are Bim and Puma produced

A

produced in response to apoptotic stimuli

92
Q

when does the extrinsic pathway occur

A

occurs when certain cells produce specific death signals that bind to death receptors

93
Q

is the Fas ligand the death signal or the death receptor

A

the death signal

94
Q

is Fas the death signal or the death receptor

A

the death receptor

95
Q

what is the fas ligans

A

a membrane bound protein

96
Q

on which type of cell is the fas ligand found

A

on cytotoxic T cells

97
Q

on which type of cell is the Fas receptor found

A

on virally infected cells

98
Q

describe the extrinsic pathway

A

the Fas ligand on a cytotoxic T cell binds to the Fas receptor on a virally infected cell. Initiator caspase-8 is activated, which then activates several executioner caspases = apoptosis

99
Q

which initiator caspase is found in the extrinsic pathway

A

8