Mechanisms of Cell Death Flashcards
What causes DNA ladder formation?
Cleavage of DNA at histones, creating a regular pattern of cleavage
What is the “morphology” of a disease?
The appearance of cells/tissues/organs
Describe the intrinsic pathway of apoptosis.
Mitochondrial signals from within the cell induce release of pro-apoptotic proteins that activate caspases.
What are the hallmark characteristics of necrosis (histologically)?
Pyknosis (loss of nuclei)
Breakdown of membranes
True or false
The ER stress-induced apoptosis mechanism is fully understood.
False
What are the consequences of calcium toxicity within the cell?
ER calcium depletion induces UPR
ER calcium release may activate specific enzymes (Calpain & Calcineurin)
Excessive mitochondrial calcium (releases proapoptotic factors)
What type of tissue damage is depicted here?
Calcification
(basophilic deposits)
What is Anoikis?
Detachment-induced cell death
PIDD = ?
p53-induced death domain
Why is the detection of phosphatidylserine an indicator of apoptotic cell death?
It’s a phospholipid normally found on the intracellular side of the cell membrane. It gets externalized during apoptosis.
What are the four subfamiles of the death domain superfamily?
Death Domain (DD)
Death Effector Domain (DED)
Caspase Recruitment Domain (CARD) subfamily
Pyrin Domain (PYD)
What is necroptosis?
Regulated necrosis
How does p53 function?
Transcription factor for:
- Negative regulators of cell cycle progression
- Apoptosis promoting genes (Bax & Bak)
What type of intracellular accumulation is pictured here? What is it composed of and what tissue is it in?
Lipofuscin (oxidized proteins from cellular components of cells that cannot be broken down)
Cardiac muscle
What are the hallmark characteristics of stressed tissue (histologically)?
Blebbing
Eosinophilia
Swelling
What is the “pathogenesis” of a disease?
The biochemical and molecular mechanisms of disease development
Which caspases are initiator caspases?
2, 8, 9, 10
How does the ER participate in death signaling?
Release of ER calcium primes mitochondria to initiate the intrinsic pathway
What type of necrosis is pictured here?
Coagulative
What type of intracellular accumulation is pictured here? What tissue is it located in?
Fatty deposits
Liver
What are some major morphological features of apoptosis? (4)
Cell rounding/condensation
Nuclear condensation/fragmentation
Membrane blebbing
Formation of apoptotic bodies
Which caspases are executioner caspases?
3, 6, 7
How is caseous necrosis described?
Fragmented cells and granular debris surrounded by inflammation
“Cheese-like” (crumbly)
Which caspase is involved in ER stress-induced apoptosis?
Caspase 12
What is the “manifestation” of a disease?
Functional consequences of morphological structures.
Describe the extrinsic pathway of apoptosis
Death receptors on the plasma membrane are activated and transduce a signal through intracellular signaling pathways to activate caspases
The “etiology” of a disease refers to its _____.
Cause
What type of intracellular accumulation is pictured here?
Protein
True or false. Apoptosis is energy-dependent
True
What are some apoptotic initiators (8)?
Viral infections
Ionizing radiation
Chemical damage to cells
Cytokines (TNF & Fas)
Mitochondrial damage
Unfolded protein response
Calcium influx
Unresolved stress
How do caspases function?
Cleave proteins after aspartic acid residues
How is fibrinoid necrosis described?
Immune complexes and fibrin in walls of blood vessels
What causes stress in the endoplasmic reticulum?
Accumulation of misfolded proteins
What is the consequence of overexpression of p53?
Promotes aging
How is liquefactive necrosis described?
Digestion of cells resulting in viscous mass
What is the function of p53?
Anti-oncogene
Critical in DNA damage and repair
What is a consequence of decreased expression of p53?
Increased cancersusceptibility
What happens if ER stress is not resolved?
ER-stress induced cell death
How is coagulative necrosis described?
Loss of cell architecture but not tissue architecture
What is homotypic binding?
Binding of death domains to similar death domains
Ex: DED binds with other DEDs
What type of necrosis is pictured here?
Fibrinoid necrosis
What is the unfolded protein response (UPR)?
A stress response that promotes the degradation of proteins and increased chaperone production to improve folding
What are four instances of physiological cell death?
Embryogenesis
Tissues that produce new cells as their function
Loss of hormone-dependent tissues when hormone levels fall
Immune function
