How is the caspase family activated during apoptosis?
cytoplasmic calcium concentration increased
How are apoptotic cells removed from the environment?
phagocytosis
How does apoptosis differ from necrosis?
- There is no clean-up mechanism for necrosis after cell death
- apoptosis is non-inflammatory
Would regulation of apoptosis be considered the role of a proto-oncogene or a tumor suppressor gene?
tumor suppressor gene
Which cells are directly affected by ischemia?
- umbra (core)
- penumbra cells still die after even though they had no hypoxic-ischemic insult
When does ischemia occur?
when blood flow drops below 25% of normal perfusion levels
Will treatment of a thrombo-emboli with a form of plasmin save the neurons from damage as perfusion has been restored?
No; most damage comes from reperfusion injury
What is excitotoxicity?
nerve cells are killed by excessive NTs (usually glutamate) stimulated by Ca2+ influx into the presynaptic neuron during nerve starvation (ischemia)
What is oxidative stress?
reactive oxygen and nitrogen species destroy cellular structures
What is apoptosis?
programmed cell death
How does a lack of ATP start excitotoxicity?
- increases Ca2+ in axon terminals and causes release of glutamate
- prevents astrocytes from uptaking glutamate
How does the influx of Ca2+ and Na+ do?
- activates calpains and cathepsins
- activates phospholipase A and C
- activates Calsium-dependent protein kinases
- activation of Ca2+/Mg2+-dependent endonucleases forms DNA ladders
What will the activation of phospholipase C probably do to the cell?
-induce inflammation from arachidonic acid created
-create IP3 which increases Ca2+
NOT destroy DNA through enzymatic degradation
What does the influx of Na+ do to the cells?
increase cytoplasmic volume and cause oncosis or necrosis
What is meant by “electrophoretic uniporter powered by the negative membrane potential”?
Natural electrical “drag” of cations into the cell because of free electrons in the matrix
What is the effect of intake of Ca2+ into the mitochondria?
- impairs oxidative phosphorylation
- mitochondria break down physically
- mitochondria release cytochrome C into cytoplasm
What is oncosis?
Neural damage from various sources can induce oncosis and lead to neuron death; necrosis of a neuron
What is evident of oncosis?
- Massive influxes of H2O and Cl- are observed (swelling opp of apoptosis)
- cellular edema
- no nuclear disruption (opp of apoptosis)
Can oncosis be influenced by tumor suppressor genes?
No; oncosis is induced by cellular damage
tumor suppressor genes cause apoptosis
Can neurons store oxygen?
No; excess amounts of oxygen can easily damage neurons because they have no capacity to store it
What will happen when reperfusion of a damaged tissue is achieved?
- calcium increase
- shut down of mitochondria
- osygen has nowhere to go in the cell*
Which molecule serves as an anti-oxidant to ameliorate oxidative damage to cells?
glutathione
What is the function of endothelial nitrous oxide?
protects against hypoxia
What is the function of neuronal nitrous oxide?
diffuse to adjacent damaged neurons and convert to a free radical and damage DNA
