L2.Apoptosis

Question 1

Briefly describe Necrosis. What does it induce?

Answer 1

Necrosis is cell death by injury. Highlighted by swelling of the cell leading to cell lysis. Injures adjacent cells and recruits Inflammatory response.

Question 2

What is an iatrogenic cause of apoptosis? Give 2 examples.

Answer 2

Iatrogenic causes of apotosis are medicines designed to treat diseases. Such as cancer drugs (cytotoxic drugs & radiation) as well as some autoimmune treatment drugs.

Question 3

What is a problem associated with cytotoxic cancer drugs that work through iatrogenic apoptotic pathways?

Answer 3

Often the cancer cells were able to proliferate b/c the apoptotic pathway that would remove them from the cell cycle is mutated. Thus, the cancer drugs designed to act by this pathway are ineffective.

Question 4

What are Caspases? Are they innately active or inactive? How are they inactivated or activated from their innate state?

Answer 4

Caspases are Cysteine-dependent, ASParagine directed proteASES.
-Caspases are innately inactive. Caspases require a signal for activation via auto-cleavage or dimerization. Once received, caspases activate in sequence beginning with INITIATOR CASPASES that turn on EFFECTOR or EXECUTION CASPASES.

Question 5

Describe the Extrinsic Initiator Pathway also known as death receptor-initiated pathway? What is an example of a signal molecule and a receptor protein.

Answer 5

Extrinsic Pathway

1. Signaling molecule (Fas) binds to a receptor (TNF receptor) in plasma membrane
2. Signal cascade causes activation of initiator capases

Question 6

Describe the Intrinsic Initiator Pathway also known as the mitochondrial pathway.

Answer 6

1. BCL-2 family receptors sense cell injury (DNA mutation, protein misfolding–>ER stress, virus, etc.)
2. Cell manipulates relative concentrations of Pro and Anti-apoptotic BCL-2 family members to induce mitochondria to open the Permeability Transition Pore Complex (PTPC).
3. The PTPC allows signallers such as Cytochrome c and AIF (Apoptosis Initiating Factor) to be released into cytoplasm.
4. Cyt c forms Apoptosomes, which activate initiator caspaces while AIF initiates caspases directly

Question 7

From the Bcl-2 family, give two examples each for Pro-apoptotic and Anti-apoptotic members.

Answer 7

Pro = bid, bad, bax
Anti = bcl-2, bcl-xL

Question 8

Describe the two mechanisms of the Execution Pathways.

Answer 8

Executioner caspases activated by initiator caspases. Act in 2 different ways
1. Endonuclease activation: Endonuclease causes Nucleosomal fragmentation of the DNA
2. Breakdown of Cytoskeleton: Proteolytic destruction of cytoskeleton
Formation of apoptotic bodies taken up by phagocytic cells.