5- Cell Death and Adaptations Flashcards
(42 cards)
What is the path of cell changes during apoptosis?
Cell shrink > Cytoskel degredation> Nuclear envelope disassemble > Chromatin condensation > DNA degradation > Apoptotic bodies > Membrane signalling
Apoptotic bodies- small vesicles occur from membrane blebbing of the cell
No inflammation
What is the apoptotic cell signal?
Phosphatidylserine moves from inner to outer leaflet to signal phagocytic cells to remove apoptotic cell.
No inflammation occurs
What is the big difference with necrosis and apoptosis?
No inflammation in apoptosis
There is inflammation in necrosis. Happens because of trauma
What kind of cells can apoptosis eliminate?
T and B lymphocytes that are self-reactive
Neurons with no connections
lymphocytes activated for infection once it is cleared
Caspases
Where are they cleaved?
what form are they synthesized in?
how are they activated?
proteases that cascade apoptotic pathway
C - cysteine (in active site)
Asp- aspartate (target on protein)
Synthesized in zymogen form– procaspase
Activated by cleavage at 1 or 2 aspartic acids,
2 caspase combine to form active. 2 small 2 large units
Initiator and Executioner caspases.
What is CARD?
Initaitor caspases: cleave and activate downstream caspases.
CARD-Caspase recruitment domain- pro domain, assemble into activation complexes, brought in close proximity to cleave each other.
Executioner caspases- target downstream capsizes AND target protiens that deal with morphological changes
- nuclear lamins, endonuclease inhibiting enzyme, cytoskeletal elements, adhesion proteins.
What are the death receptors characteristics?
three domains: extracellular, transmembrane, intra
homotrimer
Part of TNF receptor family, bind TNF and fas
EXTRINSIC PATHWAY
TNF family pathway for extrinsic apoptosis?
What binds to the deatch receptor?
What complex is formed?
Fas ligand from killer lymphocyte, juxtacrine signalling
Adaptor proteins FADD recruited > recruit initiator procaspases (8 or 10) > forms DISC (death inducing signaling complex) > initiator caspases activate executioner caspases
Intrinsic pathway for apoptosis.
What generally signals for this pathway?
Signaled by mitochondria
Cytochrome c released from mito > Apaf-1 hydrolyzes bound ATP to ADP> Apaf-1s bind cytochrome C form apoptosome (circular oligomerization) > recruited procaspase 9 (via CARD) > caspase 9 activated in apoptosome > downstream cascade
How does BH123 family control release of cytochrome c from mitochondria?
Two that you should definitely know.
Pro apoptotic proteins
Form oligomers in outer mito membrane > pores for cytochrome c to leak out.
Bak- always bound to mito membrane
Bax- translocated when activated (ER stress maybe)
Bcl2 family, how are they related to the proapoptotic proteins?
Which two should you remember?
Anti-apoptotic proteins (Bcl2 and BclX1)
Bind to Bak and Bax to inhibit apoptosis
What do inhibitors of anti-apoptotic proteins do?
Who are the key players?
Inhibit Bcl2 and BclX1 (anti-apoptotic proteins)
Enables Bak and Bax to aggregate
Activated via signal transduction which induces transcription and translation of BH3-only proteins
- MAPK (Ras mek erk)
- -p53- tumor suppresant
How are the extrinsic and intrinsic pathways linked?
BID also inhibit anti apoptotic proteins.
BID activated by caspase 8 (from extrinsic)
Which survival factors do our neurons need?
Neurotrophins (this is a specific example)
In general, when cell no longer has survival factor it will undergo apoptosis.
What markers do you look for in the blood if you suspect MI?
necrosis markers
Also, Cardiac troponins, creatine kinase (CK-MB)
Ischemia
Inadequate BLOOD supply.
How is glaucoma related to apoptosis.
Which specific factor do they think is missing that the cells need?
Glaucoma has elevation in intraoccqular pressure which causes damage
An example of too much apoptosis, neurodegeneration
loss of vision is due to apoptosis of Retinal Ganglion Cells
Some think its that BDNF (neurotrophin) isn’t there to support the cells.
Autoimmune Lymphoproliferative Syndrome
Which gene is mutated?
ALPS- lymphoproliferative disease and susceptible to cx
Defective FAS ligand leads to accumulation of lymphocytes that are autoreactive
usually these are killed by killer lymphocytes with the FAS ligand attached to them.
Body can’t limit amount of reactive lymphocytes that are produced.
Which proteins connected to apoptosis are usually mutated in cancer cells?
Bcl2- leads to B cell lymphoma
p53- p53 mutation in about 50% of cancers.
– usually mutation makes it unable to bind DNA, inhibiting ability to induce p21
Causes of cell Injury
Just read them. Don’t memorize
- Oxygen deprivation
- Physical Insult
- Chemical Agents
- Infectious agents
- Immune reaction
- Genetic Abnormality
- Nutritional imbalance
Reactive oxygen Species (ROS)
Oxygen derived free radical made in peroxisomes or lysosomes.
Released during inflammation with intent to destroy microbes
examples
superoxide O2
hydrogen peroxide H2O2
Hydroxyl radical OH
What are the two main targets of Oxidative stress?
Protein modification: Oxidation of aa R groups and peptide backbone. Destroy 3D confirmation, enhance degradation
DNA lesions: ss or ds breaks, adducts and cross linking
3 Antioxidants to remember
What ratio do we need to know?
- Catalas- H2O2 > O2 and H2O
- Superoxide Dismutase (SOD): superoxide > H2O2
cytosolic and mitochondrial - Glutathione peroxidase:
Breaks H2O2/OH by oxidizing itself to homodimer
oxidized form: GssG Reduced form: GSH
– ratio of reduced to oxidized is important indicator or redox status**
reduced ratio in neurodegenerative diseases because you have more inflammation occurring in those processes
Why does the cell swell in result of hypoxia?
Loss of os/phos > decrease ATP > sodium pump failure > Na+ and H20 build up > swelling
Other ATP requiring processes will be in trouble too.
