Apoptosis Flashcards
What is necrosis?
- usually in tissues where injury was extreme or sudden
- mitochondria swells to “high amplitude swelling” and ATP production stops
- starved of ATP, plasma membrane’s ion pumps fail, cell swells and bursts
- intensely proinflammatory
- requires debris removal, injury resolution and, if the storm has been damaged, scar formation
When does apoptosis occur?
cell death that is normal and predictable from relatively minor injury
What are the defining features of apoptosis?
- early in process, produces signals on the cell that it is undergoing apoptosis -> membrane is intact when macrophage eats it
- no release of proinflammatory release of debris
- collapse of the nucleus; chromatin becomes supercondensed into, eventually, spherical beads
- DNA fragmented into smaller units by endonuclease on the DNA linkers
What happens to the cell volume within the first few seconds of apoptosis?
it shrinks, losing about a third of its volume
What is one of the markers for apoptosis?
phospholipid phosphatidylserine, usually on the inner leaflet of the lipid bilayer
What allows for phospholipid phosphatidylserine to be on the exterior of an apoptotic cell?
Scramblase, distribution of PS is equal on both sides
What enzyme prevents phospholipid phosphatidylserine from being on the exterior in a healthy cell?
flippase
What are apoptotic bodies?
after the cell loses 1/3 of it’s volume, tears itself into apoptotic bodies some of which contain chromatin
Does macrophages that recognize a cell as apoptotic become activated?
no, it’s anti-inflammatory
Does low-dose radiation kill lymphocytes?
no, it induces them to kill themselves and must express “death genes”
- theoretically, all cells have “death genes”
Why is morphogenetic death matter?
- determines the final shape of body parts and organs
- death by apoptosis between the digits give the final form to fingers and toes
- neuro - cells that survive are the ones that made the best connection
How many times per second does mitosis occur in an adult human?
25 million times a second (so 25 million cells die)
What happens when apoptosis doesn’t occur in a steady state system?
a tumor - cancer progression can be caused by mutations that inhibit cell death (ex. p53 inactive)
What happens to the mitochondria in the beginning of apoptosis?
- anti-apoptotic members of Bcl-2 protein family (Bcl-2 and Bcl-Xl) are replaced by pro-apoptotic signals Bim and PUMA
- Triggers Bax to make the membrane permeable so it releases cytochrome C into the cytoplasm
- activates Apaf-1 (cytoplasmic protein)
- activates protease caspase-9
- activates protease caspase-3
Caspase-9 is a ________ caspase, caspase-3 is an __________
Caspase-9 is a signal caspase, caspase-3 is an executioner
