CDCD Flashcards

1
Q

What are the functions of necrosis?

A

→Removes damaged cells from an organism

→causes acute inflammation to clear cell debris via phagocytosis

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2
Q

What does lack of necrosis lead to?

A

→may lead to chronic inflammation

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3
Q

What are some examples of causes of necrosis?

A
Usually lack of blood supply, e.g.
→injury, 
→infection, 
→cancer, 
→infarction, 
→inflammation
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4
Q

What can be observed in necrosing tissues as distance from blood vessels increases?

A

→ as distance increases

→pH and pO2 reduces

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5
Q

Describe the necrosis process

A

→Lack of oxygen prevents ATP production → increased osmolarity.
→Cells swell due to influx of water (ATP is required for ion pumps to work).
→Lysosomes rupture; enzymes degrade other organelles and nuclear material hapzardly
→Cellular debris released, triggering inflammation

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6
Q

What is a difference between the early and later stages of necrosis?

A

→first stage is reversible mitochondrial changes unlike apoptosis

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7
Q

What are the microscopic changes that occur during necrosis?

A
  1. Chromatin condensation/shrinkage.
  2. Fragmentation of nucleus.
  3. Dissolution of the chromatin by DNAse.
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8
Q

What are the cytoplasmic changes during necrosis?

A
  1. Opacification: protein denaturation & aggregation.

2. Complete digestion of cells by enzymes causing cell to liquify (liquefactive necrosis).

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9
Q

What are the biochemical change that during necrosis?

A
  1. Release of enzymes such as creatine kinase or lactate dehydrogenase
  2. Release of other proteins such as myoglobin
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10
Q

Why are biochemical changes useful for?

A

→to measure the extent of tissue damage

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11
Q

What is the function of apoptosis?

A

Selective process for the deletion of superfluous, infected or transformed cells.

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12
Q

What is apoptosis involved in?

A

→Embryogenesis
→Metamorphosis
→Normal tissue turnover
→Endocrine-dependent tissue atrophy

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13
Q

Describe the apoptosis process

A

→Events are irreversible and energy (ATP) dependent.
→Cells shrink as the cytoskeleton is disassembled.
→Orderly packaging of organelles and nuclear fragments into membrane bound vesicles.
→New molecules are expressed on vesicle membranes that stimulate phagocytosis without an inflammatory response.

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14
Q

What are the differences between apoptosis and necrosis?

A

→apoptosis involves cell death of one of a few cells, necrosis is a group of cells
→ apoptosis is irreversible, necrosis’ early stage is reversible
→ no leakage of cytosolic components

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15
Q

What are the cytoplasmic changes during apoptosis?

A
  1. Shrinkage of cell. Organelles packaged into membrane vesicles.
  2. Cell fragmentation. Membrane bound vesicles bud off.
  3. Phagocytosis of cell fragments by macrophage and adjacent cell.
  4. No leakage of cytosolic components
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16
Q

What are the morphological features of apoptosis?

A

→Cytoplasm shrinks around nucleus

→Vesicles bud from cell (“blebbing”)

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17
Q

What are the nuclear change during apoptosis?

A
  1. Nuclear chromatin condenses on nuclear membrane.

2. DNA cleavage.

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18
Q

What are the biochemical changes apoptosis?

A

→Expression of charged sugar molecules on outer surface of cell membranes
→Protein cleavage by proteases, caspases

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19
Q

Why are charged sugar molecules expressed during apoptosis?

A

→recognised by macrophages to enhance phagocytosis

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20
Q

What does DNA fragmentation show of necrosis and apoptosis?

A
apoptosis= bands down the gel
necrosis= DNA smear, non-specific digestion
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21
Q

Give examples of apoptosis?

A

→Cell death in embryonic hand to form individual fingers.
→Apoptosis induced by growth factor deprivation (neuronal death from lack of NGF).
→If DNA is damaged due to radiation or chemo therapeutic agents, p53 (tumour suppressor gene product) accumulates.
→Cell death in viral diseases (ie viral hepatitis
→Death of neutrophils during an acute inflammatory response

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22
Q

When does p53 trigger apoptosis?

A

→If DNA is damaged due to radiation or chemo therapeutic agents, p53 (tumour suppressor gene product) accumulates.
→This arrests the cell cycle enabling the cell to repair the damage.
→If repair process fails, p53 triggers apoptosis.

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23
Q

Give an example of a viral disease which causes apoptosis

A

→viral hepatitis

24
Q

What are the two types of apoptosis?

A

→intrinsic

→extrinsic

25
Q

What is involved in intrinsic apoptosis?

A
→DNA damage – p53-dependent pathway
→Interruption of the cell cycle
→Inhibition of protein synthesis
→Viral Infection
→Change in redox state
26
Q

What is involved in extrinsic apoptosis?

A

→Withdrawal of survival factors e.g. mitogens
→Extracellular signals (e.g. TNF)
→T cell or NK (Natural Killer) (e.g. Granzyme).

27
Q

What do extrinsic and intrinsic apoptosis have in common?

A

→caspases

28
Q

What are caspases?

A

→cysteine aspartate-specific proteases

→form an activation cascade, where one cleaves and activates the next

29
Q

What are caspases analogous to?

A

→kinase cascades

30
Q

Give examples of initiator caspases

A

→8,9

31
Q

Give examples of effector caspases

A

→1, 3, 6, 7

32
Q

What shape does the caspase cascade form?

A

→pyramidal

→signal amplification

33
Q

Where are lamin proteins found?

A

→found in nuclear membrane

34
Q

Give examples of caspase targets and their function

A
→Lamin A and B=Nuclear envelope
→PARP= DNA repair
→DNA-PK= DNA repair
→Toposiomerase II = DNA replication
→Raf-1= Signalling
→Akt/PKB= Cell survival
→STAT1= Signalling
→eIF4= Translation
35
Q

What does caspase activation lead to?

A

→shrinkage, chromatin condensation,
→DNA fragmentation
→plasma membrane blebbing

36
Q

How are initiator caspases activated?

A

→activate themselves when in close proximity to each other

37
Q

How is extrinsic apoptosis induced?

A

→by ligand binding to receptors, causing receptor dimer- (or multimer-) isation

38
Q

What allows proteins bind together?

A

→shared domains

39
Q

What are the three death domains in ligand-induced multimerization?

A

→death domain
→death effector domain
→protease domain(catalytic)

40
Q

What is FADD?

A

→FAS-Associated protein with Death Domain

41
Q

What is DISC?

A

→Death-inducing signalling complex

42
Q

What is intrinsic apoptosis induced by?

A

cytochrome c released from mitochondria

43
Q

What is an exception to intrinsic apoptosis?

A

→growth factor withdrawal (extrinsic apoptosis) an exception that uses cytochrome c

44
Q

What is cytochrome C?

A

→Mitochondrial matrix protein

→released in response to oxidative stress by a “permeability transition”

45
Q

What are the players in cytochrome C-induced apoptosis?

A

→cytochrome C
→cytochrome c binding site
→APAF domain
→Caspase recruitment domain (CARD)

46
Q

What is APAF-1?

A

→Apoptotic ProteaseActivating Factor

47
Q

What is procaspase-9 involved in?

A

→intrinsic apoptosis

48
Q

How is the release of cytochrome c from the mitochondria regulated?

A

→a pore made of BLC-2 family proteins

49
Q

What does BCL-2 do?

A

→form pore through which cytochrome C leave

50
Q

What can BCL-2 proteins be?

A

→pro or anti apoptosis

51
Q

Give examples of anti-apoptotic BCL-2 proteins

A

→bcl-2, bcl-XL

→Repress cytochrome c release

52
Q

Give examples of pro-apoptotic proteins

A

→Bax, Bad, Bid

→Facilitate cytochrome c release

53
Q

What do BCL-2 proteins have in common?

A

→BH3 domain used to form dimers

54
Q

What does BAD do to BCL-2 protein?

A

→BAD binds strongly to BCL2 so it doesn’t bind to pore

→ cytochrome c Is released

55
Q

If BCL-2 family proteins regulate cytochrome C release from mitochondria, what regulates BCL-2 proteins?

A

→TP53
→TP53 increases BAX transcription
→new pores inserted into membrane
→cytochrome leaves

56
Q

Give an example of growth factors with BAD

A

→survival signals →Akt/PKB phosphorylates of BAD
→BADd doesn’t bind to BCL-2
→BCL-2 is free to bind to pore and cytochrome doesn’t leave cell