Cell Death Flashcards
What are the two types of subleathal injury to cells
Hydropic Change (oncosis) - accumulation of water. Steatosis - accumulation of fat
What is sublethal injury?
When a cell looses the ability to maintain homeostasis
What dangerous molecules are formed in the mitochondria?
Oxygen free radicles
Define necrosis
It is the death of tissue following the bioenergetic failure and loss of plasma membrane integrity
What does necrosis induce and what are the different types?
It induces an inflammatory response. The different types are;
- Coagulative (necrosis in tissue),
- Colliquative (necrosis in the brain),
- Caseous (necrosis seen in tuberculosis),
- Gangrenous (necrosis with rotting tissue),
- Fibrinoid (necrosis in a microscopic feature of arterioles),
- Fat necrosis (may follow trauma)
Describe Apoptosis?
Where individual cells are killed in a control manner and does not trigger inflammation. The cell is broken down into smaller membrane bound fragments which are then destroyed.
What is important about apoptosis involving DNA fragmentation
This can be interfered with using drugs in treatment of disease for example, inhibitors of PARP (molecule that tries to repair DNA when it is fragmented) are used in cancer.
How can macrophages recognise cells that need to be phagocytosed?
They recognise phosphatidylserine which appear on the outer leaflet of a cell when the membrane flips. This is an ‘eat me’ signal
What are the extrinsic and intrinsic factors that cause apoptosis
Extrinsic - receptors and T cells.
Intrinsic - Stress, metabolic, DNA damage and p53.
What are the key features of the extrinsic pathway using receptors
So you have receptor interaction from molecules such as (TNF family, Fas CD95 and inflammation) which trigger cytoplasmic singals activating the caspase cascade.
Describe the T cell Mediated extrinsic pathway
T cell hits target cell (viral cells or transplant cells) and interacts with the receptors. It then injects perforin and granzymes which activate the caspase enzymes.
Describe how the intrinsic pathway works
Endogenous activation of caspase enzymes which often involves mitochondrial damage as the mitochondria release products (Cytochrome C) which activate caspases.
What are apoptosomes and what are their functions
It is a large protein formed from the active components of apoptosis which overcome the suppressor of apoptosis
What is the role of p53
When radiation breaks the strand of DNA, this break is recognised by p53. It acts as a transcription factor causing new genes to be expressed. It can cause cell cycle arrest, DNA repair or cell death, therefore is prevents cancers.
What is the role of the Bcl2 family?
They are a family of proteins that either promote or inhibit apoptosis. They can exist as either homodimerisation or heterodimerisation.
Name an example of a Bcl2 that kills the cell
Bax-bax homodimerisation
Abnormal Bcl2 expression can do what?
Contribute to formation of cancer. This is because genes on the chromosome undergo a translocation and rearrangement mutation.
Name another layer of control in apoptosis and why this is important
IAP - which are inhibitors of apoptosis. Important because it blocks caspases so in cancers a drug could a be used against IAPs, promoting cell death
What are Caspases?
a family of protease enzymes playing essential roles in programmed cell death and inflammation
Name some targets of caspases
- Cleave ICAD which destroys genetic info.
- Cleave PARP which prevents DNA repair.
- Cleave lamin which breaks down nuclear architecture.
- Cleave keratin whch breaks down cytoplasmic architecture
What are some survival factors and why are these important
Important - can block apoptosis. Examples are;
- Increased production on anti-apoptotic Bcl2 protein.
- Inactivation of pro-apoptotic BH3-only Bcl2 protein.
- Inactivation of anti-IAPs
What can arise from apoptosis gone wrong?
Autoimmune disease, cancers and neurodegeneration.
What pathway compounents can be targeted by drugs?
Bcl2 in lymphoma, Caspase 3 in Alzheimer disease and IAP in cancers
What is pyroptosis?
Cell death triggered by salmonella and has features similar to both apoptosis and necrosis. (caspase 1 activation, not caspase 3. Pro-inflammatory and nuclear fragmentation but not cytoplasmic blebbing)
What is anoikis?
Death after losing contact with basement membrane/ECM
