Cell Death, Apoptotic Pathways and the Caspase Cascade

Question 1

Cell Death

Answer 1

Defined as an
irreversible degeneration of vital cellular functions culminating in the
loss of cellular integrity (permanent
plasma membrane permeabilization
or cellular fragmentation).

Question 2

Necrosis (Messy)

Answer 2

Unprogrammed Cell Death, Accidental Cell Death

Cell Swelling—> Leakage of Contents, Organelle Breakdown——> Inflammation

Necrosis has been
defined as a type of
uncontrolled cell death.
It can occur in response
to infection, toxins,
chemicals, injury, or lack
of blood supply

Question 3

Apoptosis (Clean)

Answer 3

Programmed Cell Death

It is used during early
development to eliminate
unwanted cells; for
example, those between
the fingers of a developing
hand

In adults, apoptosis is
used to rid the body of
cells that have been
damaged beyond repair.

Cell shrinks, Chromatin Condensation —–> Nuclear Collapse, Membrane Budding—–> Apoptotic Body Formation, Phagocytosis

Question 4

Pathophysiological
difference between
necrosis and apoptosis is…

Answer 4

Inflammation

Question 5

Intrinsic and Extrinsic Pathway of Apoptosis Overview

Answer 5

Signaling results
in the activation of a family of Cys (Cysteine) proteases, named caspases.

Activated Caspases act in a proteolytic
cascade to dismantle and remove the dying cell

Question 6

Caspases

Answer 6

Family proteases,
are synthesized as zymogens
with a prodomain, i.e pro-
caspases.
The caspases are activated
through proteolysis at specific
residues within the prodomain.
This results in the generation of
mature active caspases.
Apoptosis

Question 7

Extrinsic Pathway

Answer 7

Begins outside a
cell, when conditions in the extracellular
environment determine that a cell must
die.

After the death signal Procaspase-8
oligomerization drives its activation
through self-cleavage.

Active Caspase-8 then activates
downstream caspases (Caspase-3),
committing the cell to apoptosis.

Question 8

Intrinsic Apoptosis Pathway

Answer 8

Begins when an injury occurs within the cell.

In the intrinsic pathway, the functional
consequence of pro-apoptotic signaling is mitochondrial membrane
perturbation and release ofcytochrome c in the
cytoplasm,
(Point of no return).

This culminates in the formation of the
apoptosome with the activation of
caspase-9.

The initiator caspase-9 then cleaves
and activates the executioner
caspases-3, resulting in cell apoptosis.

Question 9

Cancer

Answer 9

One of the scenarios
where too little apoptosis occurs, resulting in malignant cells that will not die