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Cell Proliferation and Underlying diseases > Cell Death > Flashcards

Cell Death Flashcards

1
Q

What are the two main forms of cell deah

A

Apoptosis

Necrosis

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2
Q

What is apoptosis?

A

Programmed cell death

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3
Q

What is necrosis?

A

Cell death by injury

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4
Q

When does apoptosis occur?

A

Development
Immune response - destruction of excess cells
Cancer therapy - eliminate tumour cells

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5
Q

What happens if there is too much apoptosis?

A

Neurodegenerative disease

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6
Q

What are the features of an apoptotic cell?

A
  • Cell compaction
  • Blebbing and scrambling of membranes
  • Chromatin condensation
  • DNA fragmentation
  • Cell fragmentation into membrane bound pieces
  • Engulfment by macrophages
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7
Q

Does apoptosis trigger an inflammatory response?

A

No

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8
Q

Does necrosis trigger an inflammatory response?

A

Yes

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9
Q

What causes the inflammatory response in necrosis?

A

Neutrophils, macrophages and other innate cells

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10
Q

What is the inflammatory system alerted by in necrosis?

A

Danger signals released by dying cells (DAMPs)

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11
Q

What are the morphological features of necrosis?

A
  • Increasing translucent cytoplasm
  • Swelling of organelles
  • Condensation of chromatin into small patches
  • Increased cell volume leading to disruption of plasma membrane
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12
Q

Why does a cell undergo apoptosis

A
  • if a cell has sustained a large amount of damage which cannot be repaired or would take a large amount of energy to do so
  • the cell has outlived it’s usefulness
  • the cell has become senescent
  • the death of the cell is needed for the organism to reach it’s final embryonic development
  • the death of a cell is necessary for maintaining part of a physiological process of an organism
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13
Q

Syndactylyl

A

The cells in the interdigital space which have failed to undergo apoptosis and therefore the outcome is that the foetus is born with webbed hands and feet

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14
Q

Which cell can be used for apoptosis?

A

cytotoxic T cells

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15
Q

how are initiator caspases activated?

A

Protein:protein interactions

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16
Q

How are effector caspases activated?

A

proteolytic cleavage

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17
Q

During apoptosis activation, where does proteolytic cleavage occur?

A

Death-effector domain

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18
Q

Where are death effector domains present?

A

Procaspases

Proteins which regulate caspase activity

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19
Q

Give an example of a protein which regulates caspase activity

A

FAS-associating death domain-containing protein (FADD)

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20
Q

Function of FADD

A

recruits procaspase 8 and 10 to the death induced signalling complex (DISC)

21
Q

How does procaspase recruitment occur

A

The interaction between DED of the procaspase and the adaptor molecules associated with TNF receptor

22
Q

Function of caspase 3

A

Cuts DNA

23
Q

Function of caspase 6

A

mediates nuclear shrinkage during inflammation

24
Q

Function of caspase 8

A

linked to two cells which are together, if one is not functional then the signal is sent to caspase 8

25
Q

Function of caspase 9

A

releases cytochrome C, binds to Apaf-1 with dATP

26
Q

What is the extrinsic apoptotic pathway?

A

Fas ligand binds to Fas receptor
Recruitment of Caspase 8 through DED domains to the adaptor protein
Activate Caspase 3

27
Q

Effect of activation of caspase 3

A
  • inhibition of flippase and activation of scramblase
  • Actin cleavage
  • inhibit PARP = no DNA repair
  • ICAD activation -> CAD -> chromatin condensation and DNA fragmentation
28
Q

Function of scramblase

A

translocate phospholipids between the two monolayers of a lipid bilayer and this allows the cell to be eaten by macrophages

29
Q

Examples of BCL-2 pro-apoptotic proteins

A
  • Bax

- Bak

30
Q

Examples of BCL-2 anti-apoptotic proteins

A
  • BCL-2
  • BCLxL
  • MCL-1
31
Q

Where are BCL-2 pro-apoptotic proteins found?

A

Endoplasmic reticulum

32
Q

Where are the BCL-2 anti-apoptotic proteins found?

A

Mitochondria

33
Q

What is the function of BH3 only proteins?

A

Control the interaction between anti- and pro- apoptotic proteins

34
Q

What does BH3 stand for?

A

BCL-2 homology domain 3

35
Q

Where does BCL get it’s name from?

A

B-cell lymphoma

36
Q

Examples of BH3 only proteins?

A
  • Bid

- Bad

37
Q

Function of Bax and Bak

A

oligmoerise and cause mitochondrial outer membrane depolarisation and permeabilisation, releasing cytochrome C in the cytoplasm that will bind to Apaf1 and caspase 9 to form an apoptosome

38
Q

What is Apaf1?

A

Apoptotic protease activating factor

39
Q

What does Apaf-1 exist as?

A

Inactive monomer in the cytoplasm

40
Q

What is an apoptosome?

A

Apaf-1-cytochrome C heterodimer

Requires the conversion of dATP/ATP to dADP/ADP

41
Q

What happens to the nucleus during apoptosis?

A

Fragmentation of DNA
Inactivation of enzymes involved in DNA repair
Breakdown of structural nuclear proteins

42
Q

How does DNA fragmentation occur?

A

Fragmented into nucleosomal units is caused by CAD (caspase activated Dnase)

43
Q

How does CAD exist in the inactive form?

A

as ICAD

44
Q

What enzyme which is involved in DNA repair is inhibited during apoptosis?

A

poly(ADP-ribose)polymerase (PARP)

45
Q

What structural nuclear proteins are broken down during apoptosis?

A

Laminins by caspase 6

46
Q

Whats binds to phosphatiyl serine?

A

Mfg-E8 and Annexin I

Annexin V

47
Q

What are Mf8-E8 and Annexin I

A

Targets for macrophages

48
Q

Function of annexin V

A

tool to detect apoptotic cells

49
Q

4 stages of phagocytosis of apoptotic cells

A

1) Recruitment of ‘find me’ signals
2) Recognition of newly-exposed ‘eat-me’ signals and endocytosis
3) Breakdown through formation of phagolysosomes
4) Antigen presention

Cell Proliferation and Underlying diseases (12 decks)

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