Apoptosis Flashcards

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1
Q

unintentional cell death

A

necrosis

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2
Q

requires ATP, changes in gene expression, and proteins synthesis

A

apoptosis

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3
Q

Progression of Apoptosis: cell shrinkage and rounding then chromatin undergoes condensation forming patches against the nuclear envelope called

A

pyknosis

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4
Q

Progression of Apoptosis: nuclear envelope becomes discontinuous and DNA is fragmented and this is called

A

karyorrhexis

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5
Q

Progression of Apoptosis: nucleus breaks into discrete chromatin bodies due to degradation of DNA and the cell membrane shows irregular bud called

A

blebs

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6
Q

Progression of Apoptosis: cell breaks apart into several vesicles called what before being phagocytised by neighboring cells

A

apoptotic bodies

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7
Q

apoptosis role during development

A

tissue remodeling (digit formation), elimination of transitory organs and tissues, nervous system formation

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8
Q

three main component of apoptotic pathway

A

regulators, adapters, effectors (caspases)

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9
Q

inhibit apoptosis or initiate apoptotic pathway

A

regulators

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10
Q

bind to procaspases and either facilitate proteolytic of procaspases to active caspases directly or by cause the aggregation of procaspase resulting in self activation

A

adapters

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11
Q

serve to execute apoptosis by targeting various cellular components and enzymes

A

effectors (caspases)

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12
Q

how are procaspases activated

A

they are activated by proteolytic cleaving hence forming active caspase (large and small subunit) and prodomain(cleaved off) then a bunch of active caspases can activate other procaspases

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13
Q

stimuli that activate apoptosis

A
Genotoxic damage
Viral infection Microtubule disruption
ER damage
Hypoxia 
Hypoglycemia 
Reactive oxygen species 
Mitochondrial damage 
Death receptor activation
Growth factor withdrawal 
Anoikis (detachment from ECM)
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14
Q

intrinsic pathway is responsible for eliminating cells in response to

A

genotoxic damage, mitochondrial damage, absence of growth factors, loss of substrate adhesion etc

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15
Q

what is the intrinsic pathway of apoptosis

A

cell and DNA damage activate protein kinases that phosphorylate and activate p53 (TF)

p53 binds to DNA and causes transcription of BAX and cell cycle inhibitor p21

BAX inserts into mito membrane and causes release of cytochrome C from mito

cytochrome C binds to the adapter protein Apaf-1 causing aggregates and binds procaspase (apoptosome complex)

procaspases are cleaved to form active form –> caspases

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16
Q

extrinsic pathway is responsible for elimination of

A

unwanted cells during development, termination of immune responses, and immunosurveillance

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17
Q

extrinsic pathway uses what caspases for initiation of apoptosis

A

caspases 8 and 10

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18
Q

extrinsic pathway is initiated by activation of

A

Tumor Necrosis Factor (TNF) receptor family of “cell death receptors” such as the Fas receptor

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19
Q

extrinsic pathway: first step

A

killer lymphocytes express FAS ligands on their cell surface

20
Q

extrinsic pathway: how do killer lymphocytes bind to target cells

A

through the FAS Death receptors

21
Q

extrinsic pathway: once the FAS ligand and its receptors are bound…what do they do next

A

they recruit adaptor molecules through binding between the receptor death domain and the adapter cell domain —>procaspases aggregate by binding to the “death effector domain” of the adaptor hence forming DISC (Death-inducing signaling complex)

22
Q

extrinsic pathway: what happens after procaspases have aggregated at the death effector domain

A

they are cleaved to form active caspase 8 which then activate other procaspases —> lead to apoptosis

23
Q

how are extrinsic and intrinsic pathways coupled

A

Death Receptors activate Bid which subsequently activates Bak and Bax

24
Q

what pathway is activated in response to viral infected cells

A

perforin/granzyme pathway

25
Q

perforin/granzyme pathway: what secretes perforin and granzyme

A

cytotoxic T cells

26
Q

perforin/granzyme pathway: what does perforin do

A

forms pore in target cells

27
Q

perforin/granzyme pathway: what does granzyme do

A

they enter the cells through the perforin and activate caspase 10 into resulting in inactivation of apoptotic inhibitors and activate caspase 3 to execute apoptosis

28
Q

target of caspases

A

apoptosis regulators, cell adhesion molecules, cytoskeletal proteins, and nuclear structural proteins

29
Q

what can inhibit apoptosis

A

binding of extracellular survival factors to cell surface receptors —> activation and production of apoptotic inhibitors such as Bcl-2 and the inactivation of proapoptotic proteins such as Bad

30
Q

cells that require constant signaling to prevent apoptosis

A

nerve cells during development

31
Q

p53 can induce apoptosis by increasing expression of

A

pro-apoptotic Bcl2 family members, FAS receptors (CD95), IGFBP-3

32
Q

dna fragmentation in apoptotic cells facilitated by

A

caspase activated Dnase enzyme that cleaves at internucleosomal sites

33
Q

cleavage typically occurs at ____ intervals resulting in a ladder effect when apoptotic DNA is visualized by gel electrophoresis.

A

180 bp

34
Q

how are DNA cell fragmentation detected in cells in situ

A

using DNA end labeling techniques such as

TUNEL

35
Q

Changes in the plasma membrane of an apoptotic cell results in the exposure of

A

phosphatidylserine

36
Q

what type of assays can be used to detect active caspase

A

caspase assay

37
Q

labeled antibodies for ______ can label apoptotic cells

A

annexin 5

38
Q

cancer cells express high levels of proteins and low levels of what proteins

A

high level of apoptotic inhibitors Bcl2

low levels of apoptotic cells p53

39
Q

common neurodegenerative disorder

A

Alzheimers

40
Q

Alzheimer’s is characterized by the presence of

A

senile plaques, neurofibrillary tangles, and massive loss of neurons

41
Q

genes implicated in alzheimers

A

amyloid precursor protein (APP)
apolipoprotein E
presenilins 1 (PS1) and 2 (PS2)

42
Q

in alzheimers brain, there is increased levels of

A

proapoptotic Bak and Bad protein

43
Q

amyloid precursor protein (APP), presenilins 1 and 2 (PS1 and PS2) are cleaved by

A

caspase 3 (its activity increased)

44
Q

HIV infection leads to inactivation of what proteins

A

anti apoptotic protein Bcl2 and activation of procaspases

45
Q

HIV infection promotes what pathway in CD4+ cells

A

extrinsic FAS mediated apoptosis

46
Q

HIV proteins such as tat, nef and vpr may induce apoptosis by interacting with

A

p53