EXAM 2 - Session 18: Controlling Cell Number Flashcards
Explain what apoptosis is.
Programmed cell death
* process of controlled death
* utilized in normal cell removal and induced tumor cell regression
What participates in tissue homeostasis?
Tightly regulated by controlling cell division AND cell death
During tissue homeostasis, what is the risk that is associated with rapid cancercell growth?
When cancer cells rapidly synthesize, the body wants to maintain tissue homeostasis –> increase rate of cell death.
* rapid cell death can lead to stroke
How does apoptosis contribute to fetal limb development?
Tissue between the fingers and toes start off as webbed
* then cells die in the webbing tissue to seperate the individual fingers
How does apoptosis contribute to developing the nervous system?
The number of nerve cells are matched to the number of target cells
* any unmatched nerve cells die off through apoptosis
How does apoptosis contribute to the adult liver?
Phenobarbital (anticonvulsant drug) - stimulates liver cell replication
* when phenobarbital is stopped –> cells die off until the liver returns to its normal size
Describe the difference between apoptosis and necrosis.
apoptosis - death from internal process but started by external signal
* caspase enzymes are activated
* nuclear & cytoplasmic cytoskeleton collapses
* nuclear DNA is digested
* nuclear membrane is shed as “blebs”
* blebs are endocytosed by macrophages
* limits/prevents inflammation
necrosis - death from external injury
* cells swell, burst, and empty contents
* membrane integrity is lost
* induces inflammation
What are the two pathways that can activate apoptosis?
Intrinsic and extrinsic pathway
Explain the intrinsic pathway.
Mitochondria pathway - signals target mitochondria
* certain apoptosis signals get into the cell (radiation/drugs) –> cause Bax and tBID insertion into the mitochondrial membrane
* membrane is disrupted –> release of several proteins & Ca2+
* Ca2+ activates initiator caspase (caspase 9)
* initiator caspase activation of effector enzymes –> apoptosis
Explain the extrinsic pathway.
Receptor-mediated apoptosis
* peptide (secreted from neighboring damaged cells) binds to extracellular receptor
* receptor shape change signals initiator caspase (caspase-8) auto-activation
* caspase-8 auto-activation –> activation of downstream effector caspases (caspase-3)
* BID is truncated to tBID (chopped)
* tBID (similar to Bax) disrupts mitochondrial membrane integrity –> triggers apoptotic signal in mitochondria
Describe the characteristics of caspases.
A family of cysteine aspartic acid-specific proteases
* protein digesting enzymes that have a specific amino acid sequence
* highly specific for what proteins are degraded
* cleave protein after recognizing a 4 aa repeat in substrate protein (like actin)
* in healthy cells –> present as inactive precursor enzymes zymogens with little to no protease activity
How many members in the caspase family? How many major groups?
~ 14 members
2 major groups
What are the two major groups of the caspase family?
Initiators and effectors
Describe the function of the initiator caspase.
Initiators - able to auto-activate from zymogen form & initiate proteolytic processing of other caspases
* important in controlling start of process
* receives upstream signal
Describe the function of the effector caspase.
Effectors - activated by upstream initiator caspases
* carry out majority of substrate digestion during apoptosis
Describe the post-initiator caspase enzyme cascade.
- effector caspases digest inhibitors of DNAase (iCAD) –> DNAase is released and digests DNA
- DNAases (CADs) move to the nucleus –> digest DNA between nucleosomes
- effector caspases move to nucleus and digest nuclear lamins, microfilaments, adhesion plaque proteins, and translation factors
- protein synthesis is stopped
