Hudmon Lec 2 Flashcards
what is apoptosis
phagocytosis of apoptotic cells and fragments
what is necrosis
enzymatic digestion and leakage of cellular contents
what are the physiological causes of the apoptotic pathways
- Programmed destruction of cells during embryogenesis: many
- Involution of hormone-dependent tissues upon hormone deprivation: endometrial cell breakdown during menstrual cycle
- Cell loss in proliferating cell populations: intestinal crypt epithelia
- Elimination of potentially harmful self-reactive lymphocytes: before or after maturation
- Cell death induced by cytotoxic T lymphocytes
what are the pathological causes of the apoptotic pathways
DNA damage; accumulation of misfolded proteins; cell injury in certain infection (viral infections); pathological atrophy in parenchymal organs after duct obstruction (pancreas, kidney, and parotid gland)
what is the intrinsic pathway
- Mitochondrial (intrinsic) pathway
- Cell injury
GF withdrawal
–> DNA damage (radiation, toxins, free radicals)
–> Protein misfolding (ER stress)
what is the extrinsic pathway
- Death receptor (extrinsic) pathway
- Receptor-ligand interactions
–> Fas
–> TNF receptor
what are the two apoptotic pathways
intrinsic and extrinsic
what is the role of BCL-2 in apoptosis
- Bax, Bak, and Bad proteins can increase mitochondrial membrane permeability by forming a dimer and inserting into the mitochondrial membrane. So this is called pro-apoptotic proteins
- Bcl-2 and Bcl-x can bind Bax family proteins and inhibit their function so this is called anti- apoptotic proteins
1. central players
what is the role of Cytochrome C in apoptosis
- Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases)
- released from mitochondria can activate caspase-9 to initiate caspase cascade
what is the role of the 2 types of caspases in apoptosis
Initiators and executioner (caspase-3 and 7)
what is the role of activated caspases
- activate other proteases
–> Degradation of cytoskeletal proteins - can activate endonucleases
–> Cleavage of DNA leading to DNA fragmentation (DNA ladder)
what is the role of blebs formation
Dying cells collapse into cytoplasmic buds and apoptotic bodies
what is the role of phagocytosis in apoptosis
- bodies of macrophages
- Dead cells are cleared before they can release their cytoplasmic contents
- Prevents triggering an inflammatory response
- Nothing remains of dead cell
what mechanisms of cell injury are there
- ATP depletion
- mitochondria damage
- membrane damage
- increased ROS
- calcium influx
what is the cell size of necrosis vs. apoptosis
necrosis: enlarged
Apoptosis: reduced