Lecture 9 - Apoptosis - Basic Flashcards
What is the point of apoptosis?
Balance the size of tissues - the same number of cells need to die as are born in order to maintain the size of a tissue
True or false: Tissues with the greatest frequencies of cell proliferation also exhibit the greatest frequencies of apoptosis.
True
What are the tissues with the greatest rates of cell proliferation and death?
Thymus, spleen, small intestine, epidermis, ovarian follicles
What triggers necrosis?
Sustained ischemia, physical, or chemical trauma
What triggers apoptosis?
Specific signals that activate specific genes
What happens to necrotic cells?
They swell, the organelles are damaged, and chromatin is randomly degraded. They lyse and organelles are destroyed.
What happens to apoptotic cells?
They shrink, the organelles stay intact, and the chromatin is degraded systematically. Membrane blebs and the cell contents are retained.
What is the end result of necrosis?
Inflammation
What is the end result of apoptosis?
Phagocytosis
What would DNA from a necrotized cell look like? From an apoptotic cell?
A smearBands of about 180 bp
Syndactyly
Webbed digits due to a lack of apoptosis
Polydactyly
Extra digits due to a lack of apoptosis
What is a disease that results from too much apoptosis?
Polycystic kidney disease (PKD)
What is characteristic of PKD?
Numerous cysts on the surface of the kidneys and large empty spaces in histological sections (the spaces should be full of glomeruli)
True or false: Apoptosis involves withdrawing serum and nutrients that are critical to the cell and this is an actin-based retraction process.
True
True or false: There are no varying degrees of serum withdrawal.
False
How is PKD inherited?
There is an autosomal dominant mutation on the PKD1 gene
True or false: Blebbing is not an actin-based process.
False
True or false: Apoptosis elicits an inflammatory response?
False
A DNA ladder is characteristic of what kind of cell death?
Apoptosis
What are the three phases of apoptosis?
Induction, modulation, and execution
What are the different types of apoptosis induction?
Physiologic activators, damage-related activators, and therapy-associated activators
What are the physiologic activators?
TNF-alpha, FasL, growth/survival factor withdrawal, glucocorticoids
What are the damage-related activators?
Viral infection, heat shock, toxins, tumor suppressors, oxidants/free radicals
What are the therapy-associated activators?
UV/gamma irradiation, chemotherapeutic drugs
What are the major pathways of apoptosis induction?
Intrinsic and extrinsic
What does modulation of apoptosis do and what is the most important protein family of modulators?
It can change the rate at which cell death occurs and the most important modulators are the Bcl proteins
Bcl proteins
Modulators of the intrinsic pathway of apoptosis by up- or down-regulating it
Burkitt’s Lymphoma
A cancer that develops as a result of either over-production of anti-apoptotic Bcl proteins or under-production of pro-apoptotic Bcl proteins
Bcl-2
An anti-apoptotic protein
BAD, BAX
Pro-apoptotic proteins
What are the executioners of the cell?
Caspases followed by endonucleases; caspases are directly responsible for blebbing
What is a critical feature of the extrinsic pathway?
It works by death receptors, death receptor domains, and death adapter proteins that are inside the cell and transduce the signal
What are the two major death receptors?
TNF-alpha and Fas
What does TNF stand for?
Tumor necrosis factor
What do the adapter proteins that are triggered by the death receptors activate?
The beginning of the caspase cascade
Which cells die - the cells that express the TNF-alpha and Fas receptors or the ones that send out the ligands?
The ones that express the receptors
What do tumor cells make a lot of?
TNF-alpha
What are two examples of immunologically privileged sites in the human body and what are they protected from?
The back of the eyes and the testes are protected by inflammatory responses
What do capillaries in the eye express constitutively?
Fas ligand
What do lymphocytes express constitutively?
Fas receptor
What is one important executioner caspase?
Caspase III
What is another name for the intrinsic pathway?
The mitochondrial pathway
What is the stimulus of the intrinsic pathway?
Withdrawal of growth factors and hormones
Is this condition/characteristic distinctive of necrosis or apoptosis? If it is apoptosis, which pathway does it go through (extrinsic or intrinsic)?Ischemia
ischemia - necrosis
Is this necrosis or apoptosis? If it is apoptosis, which pathway does it go through (extrinsic or intrinsic)?chemical and physical trauma
chemical and physical trauma - necrosis
Is this condition/characteristic distinctive of necrosis or apoptosis? If it is apoptosis, which pathway does it go through (extrinsic or intrinsic)?p53
p53 - apoptosis - intrinsic pathway (intracellular receptor)
Is this condition/characteristic distinctive of necrosis or apoptosis? If it is apoptosis, which pathway does it go through (extrinsic or intrinsic)?TNF-a
TNF-a: extrinsic pathway of apoptosis - intermembrane receptor
Is this condition/characteristic distinctive of necrosis or apoptosis? If it is apoptosis, which pathway does it go through (extrinsic or intrinsic)?FAS-L / -R
FAS-L / -R: extrinsic pathway of apoptosis - transmembrane receptor
Is this condition/characteristic distinctive of necrosis or apoptosis? If it is apoptosis, which pathway does it go through (extrinsic or intrinsic)?mitochondrial pathway
mitochondrial pathway - intrinsic pathway of apoptosis (in cell)
Is this condition/characteristic distinctive of necrosis or apoptosis? If it is apoptosis, which pathway does it go through (extrinsic or intrinsic)?cell swelling and lysis prior to cell death
cell swelling and lysis prior to cell death - necrosis
Is this condition/characteristic distinctive of necrosis or apoptosis? If it is apoptosis, which pathway does it go through (extrinsic or intrinsic)?organelle damage
organelle damage - necrosis
Is this condition/characteristic distinctive of necrosis or apoptosis? If it is apoptosis, which pathway does it go through (extrinsic or intrinsic)?inflammation
inflammation - necrosis
Is this condition/characteristic distinctive of necrosis or apoptosis? If it is apoptosis, which pathway does it go through (extrinsic or intrinsic)?random chromatin degradation / DNA smear on gel
random chromatin degradation / DNA smear on cell – necrosis
Is this condition/characteristic distinctive of necrosis or apoptosis? If it is apoptosis, which pathway does it go through (extrinsic or intrinsic)?programmed cell death
programmed cell death = apoptosis
Is this condition/characteristic distinctive of necrosis or apoptosis? If it is apoptosis, which pathway does it go through (extrinsic or intrinsic)?radiation
radiation - apoptosis
Is this condition/characteristic distinctive of necrosis or apoptosis? If it is apoptosis, which pathway does it go through (extrinsic or intrinsic)?toxins
toxins - apoptosis
Is this condition/characteristic distinctive of necrosis or apoptosis? If it is apoptosis, which pathway does it go through (extrinsic or intrinsic)?withdrawal of hormones
withdrawal of hormones - apoptosis
Is this condition/characteristic distinctive of necrosis or apoptosis? If it is apoptosis, which pathway does it go through (extrinsic or intrinsic)?cell shrinks andblebs
cell shrinks and blebs - apoptosis
Is this condition/characteristic distinctive of necrosis or apoptosis? If it is apoptosis, which pathway does it go through (extrinsic or intrinsic)?endocytic vesicles and phagocytosis
endocytic vesicles and phagocytosis - apoptosis
Is this condition/characteristic distinctive of necrosis or apoptosis? If it is apoptosis, which pathway does it go through (extrinsic or intrinsic)?endonucleases cut the linkage regions between nucleosomes, resulting in DNA laddering (on a gel)
endonucleases cut the linkage regions between nucleosomes, resulting in DNA laddering (on a gel) - apoptosis
Is this condition/characteristic distinctive of necrosis or apoptosis? If it is apoptosis, which pathway does it go through (extrinsic or intrinsic)?BCL
BCL - pro- and anti-apoptotic factors (intracellular) - intrinsic pathway of apoptosis