116A WEEK 12 – Cell death and the future of cell biology
Learning outcomes:
1) Define the main mechanisms of cell death
2) Apoptosis: definition and relevance in physiology and diseases
3) Apoptosis: morphological features, the signalling pathway
4) Apoptosis: mechanisms of regulation
5) Type II: Autophagic cell death
6) Type III: Necrotic cell death
There are at least 3 main cell death mechanisms
- Type I and II are types of controlled managed cell
death
- Necrosis – death – tissue looks discoloured
- Ischaemia (lack of blood flow) can lead to necrosis –
small piece of tissue can block blood vessels, which
can lead to infarction, untreated infarction leads to
cell death. This leads to necrosis due to acute
hypoxia
What do dead cells look like?
- Dead tissue initially is discoloured and then there is a blackening of
tissue. Pigmented substances get left behind and when oxidised,
they turn black
- In dying cells, there is a loss of cell membrane integrity (gaps in
membrane and cell contents leaks out and there is an influx of
extracellular fluid – inflammation/bursting due to unbalanced
osmotic pressure)
- In dying cells there is tissue swelling as cytoskeletal elements leave
the cell and fluid enters the cell. The cytoskeletal elements being
outside triggers an immune response – DAMP (damage associated
molecular pattern)
- The immune system is looking for changes/differences in the
molecular pattern (trauma laceration bruising) – detected by the
immune system (DAMP) leading to inflammation in the surrounding
area
- Texture of tissue: tissue loses its structural integrity – loss of
firmness within the issue – scarring/metaphasis
- Smell: decay due to bacteria
- These characteristics aren’t present in apoptotic cells
Type 1 – Apoptotic cell death
- It happens automatically in cells at the end of their
lifespan: when needed, apoptosis genes turn on and
direct the cell to die
- This is vital for life. Without apoptosis, old and
damaged cells would remain in the body, creating
toxicity and triggering disease
, - An average of 50-70 billion cells/day undergoes apoptosis in adult
human body
- Cells shrink, eventually leading to blebbing (cell budding off)
- It is a relatively slow process as it’s a controlled process
Physiological relevance
- Apoptosis plays a major role in morphogenesis & tissue
remodelling: elimination of organs and tissues
only useful during embryonic stages of
development:
o The tadpole tail is removed by apoptosis
at the time of its metamorphosis into a
frog
o Individualization of digits that occurs in
many animals through the removal of the
inter-digital webs
- Apoptosis eliminates unwanted cells
Apoptosis and disease
- Apoptosis is also associated with numerous pathologies:
o Excessive apoptosis has been linked to neurodegenerative
diseases and organ failure after infarction or toxic insult
o Defective apoptosis has been involved in proliferative
diseases such as cancer
Induction of apoptosis (how its triggered)
- DNA damage
- Hypoxia
- Oxidative stress
- Death receptor ligands
- Drug treatments
Morphological features
- Shrinkage of cells
- Nuclear condensation
- Blebbing phenomena
Hallmarks of apoptosis
Learning outcomes:
1) Define the main mechanisms of cell death
2) Apoptosis: definition and relevance in physiology and diseases
3) Apoptosis: morphological features, the signalling pathway
4) Apoptosis: mechanisms of regulation
5) Type II: Autophagic cell death
6) Type III: Necrotic cell death
There are at least 3 main cell death mechanisms
- Type I and II are types of controlled managed cell
death
- Necrosis – death – tissue looks discoloured
- Ischaemia (lack of blood flow) can lead to necrosis –
small piece of tissue can block blood vessels, which
can lead to infarction, untreated infarction leads to
cell death. This leads to necrosis due to acute
hypoxia
What do dead cells look like?
- Dead tissue initially is discoloured and then there is a blackening of
tissue. Pigmented substances get left behind and when oxidised,
they turn black
- In dying cells, there is a loss of cell membrane integrity (gaps in
membrane and cell contents leaks out and there is an influx of
extracellular fluid – inflammation/bursting due to unbalanced
osmotic pressure)
- In dying cells there is tissue swelling as cytoskeletal elements leave
the cell and fluid enters the cell. The cytoskeletal elements being
outside triggers an immune response – DAMP (damage associated
molecular pattern)
- The immune system is looking for changes/differences in the
molecular pattern (trauma laceration bruising) – detected by the
immune system (DAMP) leading to inflammation in the surrounding
area
- Texture of tissue: tissue loses its structural integrity – loss of
firmness within the issue – scarring/metaphasis
- Smell: decay due to bacteria
- These characteristics aren’t present in apoptotic cells
Type 1 – Apoptotic cell death
- It happens automatically in cells at the end of their
lifespan: when needed, apoptosis genes turn on and
direct the cell to die
- This is vital for life. Without apoptosis, old and
damaged cells would remain in the body, creating
toxicity and triggering disease
, - An average of 50-70 billion cells/day undergoes apoptosis in adult
human body
- Cells shrink, eventually leading to blebbing (cell budding off)
- It is a relatively slow process as it’s a controlled process
Physiological relevance
- Apoptosis plays a major role in morphogenesis & tissue
remodelling: elimination of organs and tissues
only useful during embryonic stages of
development:
o The tadpole tail is removed by apoptosis
at the time of its metamorphosis into a
frog
o Individualization of digits that occurs in
many animals through the removal of the
inter-digital webs
- Apoptosis eliminates unwanted cells
Apoptosis and disease
- Apoptosis is also associated with numerous pathologies:
o Excessive apoptosis has been linked to neurodegenerative
diseases and organ failure after infarction or toxic insult
o Defective apoptosis has been involved in proliferative
diseases such as cancer
Induction of apoptosis (how its triggered)
- DNA damage
- Hypoxia
- Oxidative stress
- Death receptor ligands
- Drug treatments
Morphological features
- Shrinkage of cells
- Nuclear condensation
- Blebbing phenomena
Hallmarks of apoptosis
