Apoptosis

Question 1

Apoptosis

• what is it
• what required for (2)
• what it provides protection against
• Disease it can cause if not regulated properly (4)

Answer 1

-The process of programmed cell death that is an integral part of development in multi-cellular organisms

Required for;

• maintenance of size and shape of organs as new cells added
• removal of immature B lymphocytes

Provides protection against cancer (p53, tumor suppressor protein, induces apoptosis)

If not regulated properly, can cause;

• cancer
• neurodegenerative disease
• multiple sclerosis
• ischaemic stroke

Question 2

Apoptosis vs necrosis

Answer 2

-Apoptosis process: DNA degraded -> cell and nucleus shrink, nucleus fragments -> shrinkage continues, cell engulfed by macrophage -> macrophage phagocytizes apoptotic cell.

Necrosis: Cell swells -> cell lyses and releases cytoplasmic material

• is uncontrolled, and due to physical injury
• inflammation occurs

Question 3

Role of Ced proteins for apoptosis in C. elegans

Answer 3

• Ced-3 is a caspase (cytosine, aspartate proteases - cysteine at catalytic site, target site contains aspartate) that induces apoptosis
  
  • syn as a zymogen (inactive form), that is activated by Ced-4
• Ced-9 complexes with Ced-4 and localizes it on mitochondrial membrane
• availability of Ced-4 in cytoplasm depends on conc. of Ced 9

Ced 3 & 4 = required for apoptosis
ced 9 = prevents apoptosis

Question 4

What activates Caspases?

Answer 4

• Apaf-1 induces apoptosis by caspase activation
• Apaf1 is activated by CytCin cytoplasm
  
  • CytC leakage in cytoplasm is caused by influx of ions through bax dimer
• Bax dimer controlled by Bcl2-Bcl-X(l) dimer that complexes Apar1 as well.
• Binding of Bad to bcl2-Bcl-X(L) dimer allows bac dimer for ion influx

*Apoptosis is therefore controlled by Bad

• Phosphorylated Bad cannot bind to Bcl2-bcl-X(L) dimer - prevents apoptosis
• signal transmitted by cascade of kinases - ultimately phophrylates Bad

Question 5

Factors that induce apoptosis

Answer 5

• Activation of receptors - some signal transduction pathways induce apoptosis
• Attack by cytotoxic T lymphocytes: these cells transfer serine proteases and other lytic components that permeabilises membrane
• Action of tumour suppressor p53 protein: this protein allows death of a canerous cell by inducing apoptosis