cell death and apoptosis Flashcards
what are the two types of cell death
apoptosis and necrosis
what is necrosis
accidental cell death
what is apoptosis
programmed cell death
what are the structural changes that occur during apoptosis
-small blebs form ; organelles are located in the blebs
- the nucleus begins to break apart and DNA breaks into small pieces
-the cell then breaks into several apoptotic bodies
what are the structural changes that occur during necrosis
blebs form and the structure if the nucleus changes
- blebs fuse to become larger; no organelles are located in the blebs
-cell membrane ruptures and content is released; the organelles are not functional
why does cell death occur
in response to infection and damage
- during embryonic development
- to maintain homeostasis
- to eliminate damaged cells
how is apoptosis regulated
by cell-cell interactions
why is apoptosis needed
- to sculpt tissues and organs during embryonic development
- to maintain cell number
- to eliminate dead, infected or potentially cancerous cells
what are the 3 cell stages of apoptosis
-pre apoptotic cell
- early apoptotic cells
- late apoptotic cell
what occurs during pre-apoptotic cell
- mild convolution of membrane
- chromatin compaction
- cytoplasm condensation
- (cell shrinks, DNA fragmentation, nuclear condensation)
what occurs during early apoptotic cell stage
- cell shrinkage
- membrane blebbing
- break up of nuclear envelope
- condensation of nucleus and cytoskeleton
what occurs during late-apoptotic cell stage
- irregular extensions break away and are phagocytosed
what is a caspase
an effector protease involved in apoptosis
what are caspases produced as
inactive monomeric pro-caspases
what must happen to pro-caspases in order to form caspases
they must be cleaved
what type of proteins are caspases and what do they contain
dimeric proteins which contain cysteine residues in their catalytic site which cleaves proteins
what are the two mechanisms of apoptosis
extrinsic and intrinsic
how is the extrinsic apoptosis pathway induced
death receptors
what are the two ways intrinsic apoptosis pathway can be induced
- mitochondrial stress (due to genotoxic damage drugs or growth factor removal)
- genotoxic or ER stress (disrupted protein processing increased Ca ++)
what is an apoptosome made up of
cytochrome c
apaf-1
pro-caspase 9
what is BCL-2
(B-cell lymphoma/leukaemia-2)
it acts as a tumour suppressor
what tumour suppressor can activate the intrinsic pathway
p53
how does p53 activate the intrinsic pathway
it acts as a cellular stressor and initiates apoptosis through the transcriptional activation of BID and BAX (proapoptotic proteins)
what is necrosis
cell death occurring in response to cell injury such as
- hypoxia
- temperatures extremes
- infection
- toxins
what are the stages of necrosis
-swelling
cell rupture
what occurs during the swelling stage of necrosis
- organelle swelling
- cell swelling
- loss of ATP
what occurs during the cell rupture stage of necrosis
- disruption of cell integrity
- plasma membrane rupture
how does injured cells lead to increased mitochondrial permeability
-injured cells become depleted in ATP
- respiratory chain enzymes generate ATP due to the lack of oxygen (in situations like hypoxia)
what are the 3 mechanisms in necrosis
1- ATP Depletion
2- reactive oxygen species (ROS)
3- Inactivation of H+ pumps
what happens in the ATP depletion stage of necrosis
an increase in Na+ and H+
increased cytoplasmic Ca2+ in the mitochondrial matrix
what happens in the reactive oxygen species (ROS) stage of necrosis
elevation of ROS results in opening of mitochondrial permeability transition pore (MPTP), mitochondrial swelling and rupture
what happens in the inactivation of H+ pumps stage of necrosis
lysosomal pH declines, proteases are activated and released into the cytoplasm, digesting cytoskeletal proteins. osmotic imbalance leads to inflow of water into the cell leading to cell swelling and rupture.
what is autophagy
its a self degradation process
- it also removes misfolded or aggregated proteins, clearing damaged organelles, as well as eliminating intra-cellular pathogens
what is autophagy important for
for balancing sources of energy at critical times in development and in response to nutrient stress
