30 Flashcards
what are the 2 ways cells die?
killed by injurious agents
induced to commit suicide
how do cells die from injury?
mechanical damage
exposure to toxic chemicals
what are the characteristic changes that cells experience when undergoing death by injury?
cell & organelles swell - lose their osmotic balance
cell contents leak out, leading to inflammation of surrounded tissues - burst
what occurs when cells are induced to commit suicide?
shrink
develop blebs
DNA degraded
mitochondria break down
break into membrane-wrapped fragments
phospholipid phosphatidylserine is exposed on the surface (usually embedded in the PM)
what effect does phospholipid phosphatidylserine exposed on the surface of the PM have?
triggers the receptors on phagocytes
receptors bind to it & engulf fragments
phagocytes secrete cytokines & inhibit inflammation
PM asymmetry & bilayer diffs signify apoptosis
what are the 2 reasons why a cell commits suicide?
proper development
destroy cells that pose a threat to the integrity of the organism
what are exs of cell death for proper development?
tadpole tail
removal of webbing b/w fingers & toes (lysosomal)
menstruation - removal of the inner lining of the uterus, removal of capillary bed that was formed to support a fertilized egg
nerual innervations - removal of surplus neurons when tissues are formed during development
what are exs when cells that pose a threat to the integrity of the organism are destroyed?
cytotoxic T lymphocytes (CTLs) kill viruses - viruses are trapped in a vesicle & CTLs phagocytose the vesicle to destroy the virus
destruction of CTLs post a heightened immune response (defaults in apoptosis machinery leads is assoc to autoimmune diseases like allergies)
cells with DNA damage - when DNA damage is detected p53 PRO is produced & induces apoptosis
cancer cells - radiation & chemotherapy is used to induce apoptosis of cancer cells
how does apoptosis contribute to elderly fragility?
aren’t receiving full recovery of stem cells post regulatory apoptosis
what are the diseases that defects in apoptosis lead to?
excessive apoptosis causes atrophy (tissue wasting)
insufficient apoptosis results in uncontrolled proliferation (cancer)
how does the rate of apoptosis differ among youth & elderly?
it doesn’t
what makes a cell decide to commit suicide?
the balance b/w:
the withdrawal of positive signals (required for survival) - require continuous stimulation from other cells through contact & adhesion to other cells or substrates
Growth factors & cytokines
received of negative signals - incres oxidants, DNA damage (UV, cytotoxic compounds etc.), accumulation of mis-folded PRO, death activators
what are the 2 general mechanisms to induce apoptosis?
intrinsic factors & extrinsic factors
intrinsic factors
signals arising from within the cell itself often as a result of some damage to key organelles, like mitochondria
extrinsic factors
death activators binding to receptors at PM
intrinsic pathway of apoptosis
- The outer membranes of mitochondria display the PRO Bcl-2 on their surface
- Internal damage to the cell (ex: from reactive oxygen species) causes Bcl-2 to activate a related PRO, Bax, which punches holes in the outer & inner mitochondrial membrane, causing cytochrome c to leak out
o Targets ETC
- The released cytochrome c binds to apoptosis-promoting PROs (Apaf-1 & procaspase-9)
o Pro = doesn’t mean its active, active when protease (caspase) causes it to lose some AAs - These PROs aggregate to form apoptosomes
o Contains: Cty c & other apoptosis PROs - The apoptosomes activate executioner caspases (which are proteases)
o Targets macromolecules within the cell - There is an expanding cascade of many caspases, which digest structural PROs in the cytoplasm, degrade DNA, etc.
- Phagocytes are recruited to destroy the dying cell
what are the apoptosis-promoting PROs in the intrinsic pathway of apoptosis?
Apaf-1 & procaspase-9
what do apoptosomes activate?
executioner caspases, proteases
what do apoptosomes consist of?
cyt c & apoptosis PROs
what activates the Bax PRO?
p53 & Bcl-2
what factors induce intrinsic apoptosis?
p53 - activates Bax
viral dsRNA - detected by a PKR, PRO that stops the cell’s translational machinery (by inhibiting an eIF) & then by inducing caspases (this pathway may also be considered an extrinsic pathway)
extrinsic pathway of apoptosis
- TNF receptors (ex: TNFR1) are integral PROs that detect death factors
- TNFR1 cytoplasmic domains then bind to other PROs, which recruit Procaspase 8
- This leads to activation of caspase 8
- Caspase 8 (like caspase 9) initiates a cascade of caspase activation
- This leads to phagocytosis of the cell
what is the diff b/w intrinsic & extrinsic pathways of apoptosis?
intrinsic - caspase 9
extrinsic - caspase 8
where does a cell receive an extrinsic death activator?
immune sys cells - natural defense against viruses
