SFP: apoptosis and necrosis Flashcards
what are the three modes of cell death
apoptosis: programmed cell death
autophagy: organelle recycling or self eating
necrosis: progressive cell injury
what stimulates autophagy
nutrient depravation
describe the major elements of apoptosis
- shrinkage
- chromatin compaction
- breakup of nuclear envelope
- nuclear fragmentation
-forming of apoptotic bodies that are then taken up by phagocytosis
describe apoptotic bodies: what they are and how they’re recognized
membrane enclosed fragments of cells; they are recognized by phagocytes due to phosphotidyl serine being on the outside instead of the inside of the membrane
when DNA fragmentation is visualized in gen electropheresis, what does it look like?
laddering
what are the two pathways for apoptosis
- extrinsic: signal from a death ligand/receptor
- intrinsic: directly related to mitochondrial dysfunction
briefly describe the extrinsic apoptotic pathway
- TNF or FAS binds to its receptor
- adaptor proteins are created
-initiator caspases cleave executioner caspases
-executioner caspases degrade intracellular components
what is a common mechanism between extrinsic and intrinsic methods
caspases; initiator caspases cleave procaspases into executioner caspases
what is different about the structure of initiator caspases
they have a longer N terminal with CARD or DED domains that are required for activation of procaspases
describe the structure of activated caspases
they are formed into tetramers composed of two small and two large subunits. the prodomain has been cleaved.
briefly describe the intrinsic pathway
- there is a disruption to mitochondrial integrity
- increased ROS and oxidative stress and VDAC pore opening
- increased calcium concentration
- cytochrome C release from mitochondria
- cytochrome C drive apoptosis via capsases
name the steps in a formation of an apoptosome
- cytochrome C release
- cytochrome C binding to apaf1
- apoptosome formed
what is an apoptosome
it acts like an initiator capsase in the intrinsic pathway; it cleaves initiator capsases
what are Bcl2 proteins
they’re proteins on the mitochondria that determine whether the cell will go into apoptosis
what are the pro-apoptotic Bcl2 family proteins? anti-apoptotic?
pro: BAD, bax
anti: bcl2, bcl-xl
BID binds to one of these and depending on what it binds to, cytochrome C will be repressed or released
release of too much calcium can activate ___. what will this do?
calpain; lead to activation of caspases
what are some diseases associated with increased apoptosis
AIDS, neurodegeneration, toxin-induced liver disease
what are some diseses associated with decreased apoptosis
cancer, viral infection
what are the stages of autophagy
- isolation membranes (autophagic vacuoles) are made from the ER
- they surround damaged organelles and form autophagosomes
- lysosomes fuse with autophagosomes
- lysosomal degradation allows the cell components to be recycled and reused.
describe the role of in beclin, ATG, and LC3 in autophagy
beclin and ATG : involved in forming phagophore and elongation of the membrane; can be blocked by Bcl2
LC3: allows for formation of autophagosome
how does insulin regulate autophagy
a lot of insulin will lead to PKB which acitvates mTOR which prevents autophagy
what happens if an animal born is deficient is autophagy
they die in the first 24 hours
describe necrosis
cell death due to unexpected cell damage; the process is highly inflammatory
name the steps of necrosis
- increased intracellular calcium
- calcium activates lytic enzymes that degrade molecules in membranes
- intracellular material spills out of the cell
- intracellular components promote inflammation
what are DAMPS and PAMPS
DAMPS: damage associated molecular patters; intracellular proteins being released from damaged cells
PAMPS: pathogen associated molecular patterns; LPS, cell wall components, flagellin
lead to formation of inflammasome
describe forming of inflammasomes to deal with inflammation
- activate pattern recognition receptors (TLR) via PAMPS or DAMPS that result in forming a scaffold of proteins
- upregulation of inflammatory mediators (IL1 IL18)
- activation of caspase 1
- caspase 1 processes IL18 and mount the inflammatory response
