14 - Cell Death Flashcards

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1
Q

What are the 2 types of cell death?

A

apoptosis | necrosis

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2
Q

What is apoptosis?

A

a signal is what causes cell death | everything condenses = cell blebbing = apoptotic bodies

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3
Q

What is necrosis?

A

injury causes cell death (ie: lack of O2) | lose integrity of cell = membrane stops working = water rushes in = cell lysis

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4
Q

What is the difference between apoptosis and necrosis?

A

apoptosis = cell membrane remains intact | necrosis = membrane is broken

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5
Q

How can necrosis lead to inflammation?

A

cell lysis = genetic material escapes = immune system sees that and induces inflammation

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6
Q

How are the apoptotic bodies removed?

A

macrophages phagocytose them

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7
Q

What are the 2 pathways to induce apoptosis?

A

intrinsic and extrinsic

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8
Q

What is the intrinsic pathway of apoptosis?

A

mitochondrial pathway

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9
Q

What are the 2 sides to the Bcl-2 family? Who is the main player of each family and who has the bigger family?

A

pro-survival side = Bcl-2 | pro-apoptotic side = Cax (bigger family)

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10
Q

What is the function of the pro-apoptotic proteins?

A

pro-apoptotic proteins inhibit Bcl-2-like proteins and its activities | form an octamer complex on mitochondrial membrane

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11
Q

What is displacement in the mitochondrial pathway (intrinsic)?

A

originally Bax is sequestered by Bcl-2 | Bim displaces Bax = Bcl-2+Bim so Bax can oligomerize = octamer complex on mitochondrial membrane

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12
Q

What is an octamer complex?

A

pore on mitochondrial membrane = stuff inside leaks out into cytoplasm

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13
Q

What is the main reason why octamer complex happens on the mitochondrial reason? Why do you want stuff from mitochondria to leak out?

A

release cytochrome c into cytoplasm

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14
Q

What is the role of cytochrome c in the intrinsic apoptosis pathway?

A

to complete the apoptosome formation

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15
Q

What are the 3 proteins that form the apoptosome?

A

cytochrome c | Apaf-1 | procaspase-9

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16
Q

What is the main function of the apoptosome?

A

to cleave procaspase-9 into caspase-9 = initiates caspase cascade

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17
Q

What are caspases?

A

proteases | inactive unless prodomain is cleaved into smaller subunits which associate = active caspase

18
Q

What is the executioner caspase?

A

caspase 3

19
Q

What is the role of caspase 3?

A

to proteolytically cleave the other inactive caspase = speeds up apoptosis

20
Q

Until when can apoptosis be paused and reversed? What is the point of no return?

A

until the DNA is chopped up

21
Q

In apoptosis, what chops up the DNA and what is the nature of this molecule?

A

CAD = DNase

22
Q

What inhibits CAD?

A

ICAD

23
Q

How is CAD activated?

A

caspase 3 cuts ICAD from CAD = activates CAD

24
Q

What is PARP?

A

a detector of DNA damage like ATM and ATR = tells p53 of the damage

25
Q

In the DNA degradation step of apoptosis, what prevents PARP from telling p53 to fix the DNA degradation happening?

A

caspase 3 cleaves PARP = inactive PARP = no DNA repair

26
Q

What is another term for the extrinsic apoptosis pathway?

A

receptor-mediated apoptosis

27
Q

What are the 2 ways that extrinsic apoptosis pathway can be carried out?

A

death receptors | perforin/granzymes

28
Q

Which cells are responsible for the extrinsic apoptosis pathway?

A

CTLs and killer cells (NK cells)

29
Q

How is the extrinsic apoptosis pathway carried out using perforin/granzymes?

A

CTLs expel perforin = forms pore on target cell membrane | CTLs throw in granzymes that will cleave caspase pro-domains

30
Q

There are many death receptors and all cells have them. What is one that is commonly used and discussed?

A

Fas/Fas ligand

31
Q

How is the extrinsic apoptosis pathway carried out using the death receptors?

A

target cell has Fas receptor | CTL/NK cell has Fas ligand | 3 FasR/FasL = forms complex with procaspases = get cleaved = apoptosis

32
Q

When do cells know they have to die?

A

their telomeres getting short

33
Q

How can cells escape cell death? What are 2 genes should they turn on?

A

telomerase | Bcl-2

34
Q

What are 2 cells that you don’t want to die?

A

stem cells | neurons

35
Q

What are IAPs?

A

inhibitors of apoptosis proteins

36
Q

What is the function of IAPs?

A

to bind to active caspases so they can’t cleave all of their targets

37
Q

Do tumor cells use IAPs?

A

Yes, they up-regulate IAP expression so they don’t die

38
Q

How would you target the DNA of the tumor cell?

A

UV light | drugs that target the DNA

39
Q

What is the key to keeping macrophages away?

A

CD31 adhesion receptor interaction

40
Q

What does the tumor need to do with CD31 in order to not get phagocytosed by macrophages?

A

needs to express CD31 so it repels and detaches macrophages