WEEK 12 (Apoptosis)

Question 1

Which processes determine organ and body size?

Answer 1

• Cell growth
• Cell division
• Cell death

Question 2

What is Apoptosis?

Answer 2

A neat orderly process characterised by the overall shrinkage in volume of the cell and its nucleus, the loss of adhesion to neighbouring cells, formation of blebs at the cell surface, dissection of chromatin into small fragments and rapid engulfment of “corpse” by phagocytosis

Question 3

What is necrosis characterised by?

Answer 3

• Swelling of both the cell and its internal membranous organelles
• Membrane breakdown
• Leakage of cell contents into the medium
• Resulting induction of inflammation.

Question 4

What do both apoptosis and necrosis have in common?

Answer 4

Both can occur as a regulated and programmed process

Question 5

What differentiates apoptosis from necrosis?

Answer 5

CELL NECROSIS = cells swell and burst, spilling their contents all over their neighbours

CELL APOPTOSIS = die quickly and cleanly without damaging its neighbours

Question 6

What does the rapid removal of the dying cell in apoptosis allow for?

Answer 6

• Avoids the damaging consequences of cell necrosis
• Allows organic components of the apoptotic cell to be recycled by the cell that ingests it

Question 7

What is the difference between the Intrinsic pathway and the Extrinsic pathway of Apoptosis?

Answer 7

INTRINSIC PATHWAY = Internal stimuli trigger apoptosis by the intrinsic pathway

EXTRINSIC PATHWAY = Signal to commit suicide comes from a neighbouring cell

Question 8

What are caspases?

Answer 8

The molecular machinery responsible for apoptosis and are activated in response to signals that induce apoptosis

Question 9

What are the two types of Caspases?

Answer 9

• INITIATOR CASPASES = cleave and activate downstream executioner caspases
• EXECUTIONER CASPASES = activate additional executioners, kicking off an amplifying, proteolytic cascade and others dismember other key proteins in the cell

Question 10

What are the properties of the Caspase cascade?

Answer 10

• Destructive
• Self-amplifying
• Irreversible

Question 11

What are the main proteins that regulate the activation of caspases?

Answer 11

BAX & BAK

[Bax and Bak are death-promoting members of the Bcl2 family]

Question 12

What happens when Bak or Bax are activated by an apoptotic stimulus?

Answer 12

It AGGREGATES in the outer mitochondrial membrane leading to the release of CYTOCHROME C into the cytosol -> CYTOCHROME C binds to an adaptor and assembles into a seven-armed complex (binds with PROCASPASE-9 to form an APOPTOSOME) -> PROCASPASE-9 becomes activated within the apoptosome and now activates different procaspases in the cytosol -> CASPASE CASCADE and APOPTOSIS

Question 13

Which specific initiator procaspase does Deathinducing signalling complex (DISc) include?

Answer 13

Procaspase 8 or 10

Question 14

How do some extracellular signals activate cell death in a neighbouring cell?

Answer 14

• Affecting the activity of members of the Bcl2 family of proteins
• Activating a set of cell-surface receptor proteins called “death receptors”

Question 15

How does the death receptor “Fas” work?

Answer 15

Fas is activated by a membrane-bound protein called “FAS LIGAND” present on the surface of specialised immune cells called killer lymphocytes

Question 16

Positively acting signal proteins can be classifies into which categories?

Answer 16

• SURVIVAL FACTORS = promote cell survival by suppressing apoptosis
• MITOGENS = stimulate cell division
  [overcome intracellular braking mechanisms that tend to block progression through the cycle]
• GROWTH FACTORS = stimulate cell growth
  [promote synthesis and inhibit degradation of proteins and other macromolecules]

Question 17

How does cell death adjust the number of developing nerve cells to the number of target cells they contact?

Answer 17

More nerve cells are produced than can be supported by the LIMITED SURVIVAL FACTOR released by target cells -> Some cells receive insufficient amounts of SURVIVAL FACTOR to keep their suicide programme suppressed and thus undergo APOPTOSIS -> OVERPRODUCTION followed by CULLING ensures that all target cells are contacted by nerve cells and that ‘extra’ nerve cells are automatically eliminated

Question 18

How do survival factors work?

Answer 18

Survival factors bind to cell-surface receptors -> Activated receptor activates a TRANSCRIPTION REGULATOR in the CYTOSOL -> This moves into the NUCLEUS where it activates a gene encoding Bcl2 (a protein that INHIBITS apoptosis)

Question 19

How do Mitogens work?

Answer 19

• Promote production of CYCLINS that stimulate cell division
• Switch on cell signalling pathways that stimulate the synthesis of G1 cyclins, G1/S cyclins and other proteins involved in DNA synthesis and chromosome duplication

Question 20

What do extracellular growth factors cause?

Answer 20

• Increased macromolecule synthesis
• Decreased macromolecule degradation

Question 21

What is Myostatin?

Answer 21

A secreted signal protein that normally inhibits the growth and proliferation of Myoblasts that fuse to form skeletal muscle cells during development

Question 22

What does a mutation of the myostatin gene lead to?

Answer 22

A dramatic increase in muscle mass

Question 23

What are the different steps in apoptotic cell disassembly?

Answer 23

1) Apoptotic membrane blebbing
2) Formation of apoptotic membrane protrusions
3) Cell fragmentation

Question 24

What is ROCK1?

Answer 24

An important regulator of apoptotic cell membrane blabbing

Question 25

Describe Necroptosis

Answer 25

Necroptotic cell death results in the rupturing of the plasma membrane causing cellular contents to be spilled into the environment and triggering an inflammatory response -> Guides immune cells to a site of infection

Question 26

What does misregulation of the necroptotic pathways result in?

Answer 26

Triggering of inflammatory diseases e.g inflammatory bowel diseases

Question 27

What is the difference between Ulcerative colitis and Crohn’s disease?

Answer 27

ULCERATIVE COLITIS = affects only the inner layer of the bowel wall + begins in rectum and can extend to entire colon

CROHN’S DISEASE = affect all layers of the bowel wall + involves end of small intestine and beginning of colon (may affect any part of the GI tract in a patchy pattern)

Question 28

What are the symptoms of Crohn’s disease?

Answer 28

• Nausea/Vomiting
• Flatulence
• Bloating
• Blood in stool
• Abdominal pain
• Diarrhoea

Question 29

What are the symptoms of Ulcerative Colitis?

Answer 29

• Loss of appetite
• Bowel movement urgency
• Diarrhoea
• Abdominal pain and cramps
• Blood or mucus in stool