Apoptosis Flashcards
- Describe characteristic plasma membrane, cytoplasmic, and nuclear events of apoptosis.
Nuclear Events:
-The defining morphological feature of apoptosis is the collapse of the nucleus; chromatin, which is normally composed of mixed open and condensed regions (heterochromatin and
euchromatin), becomes supercondensed, appearing as crescents around the nuclear envelope and,
eventually, spherical featureless beads.
-The structural correlate of this morphological change is
the fragmentation of DNA into units of one or several nucleosomes in length. (A nucleosome consists of a core of histone proteins wrapped by about 180 base pairs of DNA, and is the first
stage of compaction of DNA.) -This degradation reflects the action of an endonuclease on the DNA in the linkers between nucleosomes; this stretch of DNA is not very well protected by
histones.
-Because a cell can only repair a few simultaneous double-stranded breaks in its DNA,the extensive DNA damage in apoptosis (up to 300,000 breaks/chromosome!) means that even if there were no other changes, the cell would certainly never divide again.
Cytoplasmic events:
- Early in apoptosis cells ►shrink remarkably, losing about a third of their volume in a few seconds.
- This shrinkage is quite apparent in cell culture, and also in vivo, where apoptotic cells in tissue sections often have pulled away from their neighbors.
Plasma Membrane events:
- As might be expected there are cytoskeletal changes that accompany shrinkage, and the result is a peculiar, vigorous “boiling” action of the plasma membrane, which has been called “zeiosis.”
- By this action the apoptotic cell usually ►tears itself apart into apoptotic bodies, some of which contain chromatin.
Apoptotic cells are usually phagocytosed before they reach that point die within phagocyte. That’s why there are so many obvious morphological changes want to ensure it gets taken up by phagocyte so it can die inside instead of dumping contents into ECF.
- Compare and contrast apoptosis and necrosis in terms of morphology, typical triggers of the two phenomena, and relative importance in physiological and pathological processes.
Necrosis:
- In necrosis (generally due to external injury/insult), first organelle to suffer is mitochondria –> which swell to the point of “high-amplitude swelling,” where it can’t maintain its ionic gradients/oxidative phosphorylation so cell runs out of ATP.
- Causes ion pumps in plasma membrane to fail –> water rushes in and cell bursts.
- Lysis releases intracellular contents into ECF –> causes inflammation, which is actually a good thing because it attracts macrophages and WBCs that can come deal with the problem and remove debris.
- Visually speaking, circular swelling.
Apoptosis:
- Apoptosis happens more in short-lived cells that undergo death in response to more minor insults –> more of a physiological death.
- Generally followed by renewal.
- Visually speaking, it shrinks and bubbles.
- Name tissues in which there is most and least apoptosis. Suggest reasons for this difference.
-Some cells die readily and are rapidly replaced; other live as long as we do.
-When normal cells
die, it is almost always by apoptosis, which is a morphological term.
-There is an apoptotic
mechanism, or cell death program. It is expressed in embryos and throughout life.
►Most tissues, and especially the skin, gut, and immune system, depend on well-ordered apoptosis and
cell replacement.
-apoptosis in morphogenetic death in limb development
-apoptosis in neurons, you initially hav 3x neurons that duke it out to make the best connections
-shitty environments like the large intestine dont apopstose frequently but the small intestine does.
- Distinguish between the signaling of the intrinsic and extrinsic apoptosis pathways.
- Describe the role of caspases in apoptosis, and discuss the role that the mitochondrion may play in the process. Identify the roles of Caspases 8, 9, and 3.
is answered along with 5( watch the videos posted at the beginning of handout)
Intrinsic Pathway (mitochondrial):
•Mitochondria associated with BCL-2 & BCL-XL, they function to AVOID apoptosis
•When the apoptotic signal comes the BCL-2 and XL are neutralized by Bim and PUMA; These are pro-apoptotic
•Then Bax and Bak members of BCL family get involved; cyt C is then released from mitochondria and goes to the cytoplasm
•Cyt C interacts with Apaf-1
•Apaf-1 interacts with caspase-9; is an initiator caspase
•9 then activates effector caspase 3 “executioner” activates scramblase and aforementioned events that cause apoptosis.
Extrinsic Pathway (transmembrane): •So killer t cell with FAS ligand interacts with FAS(CD95) of abnormal cell •Then within the cell FAS interacts with adapter FADD •FADD interacts with Caspase 8 (associated with cell membranes) •Caspase 8 then interacts executioner Caspase 3 •BUT!!!!! •Cells have FLIP--> weird cousin of FADD, they compete •When FLIP is active no downstream events--> no apoptosis
There are viruses that have made v-FLIP we can block apoptotic signal; keep cell alive; replicate viral DNA the cell becomes a zombie until the virus gets what it wants out of it.
- Discuss the essential biological difference between phagocytosis of apoptotic and necrotic cells.
Phagocytosis in necrotic cells:
- Called by the inflammation of a burst cell
- macrophages generally aid with debris removal, injury resolution, and scar formation.
Phagocytosis In apoptosis:
- changes in plasma cell membrane call over phagocytes.
- Phosphatidylserine (PS) normally found in inner leaflet of plasma membrane (FLIPase keeps it regulated), but becomes distributed equally on both sides of the membrane in an apoptotic cell.
- Caused by scrambling (via scramblase and FLIPase being turned off) to signal to the immune system that these cells have committed to the apoptotic pathway.
- Then phagocytes come eat them up so the apoptotic cell never has a chance to lyse and release inflammation-causing molecules into ECF.
- “Silent process” the cell dies safely inside
- The way the macrophage comes into this; it acts as in an anti-inflamatory way to make sure that you don’t get chronic inflammation every time it happens.
- Discuss the importance of apoptosis in tumor formation and progression.
- If 1 mitosis = 1 apoptosis, then about 2E12 cells die every day.
- Tumors generally need about 7 mutations to become malignant.
- Start off with one mutation –>exceeds capacity to provide growth and survival support –> undergoes apoptosis.
- But sometimes, before that point, the cell can accumulate more mutations that make them more resistant to apoptosis, allowing them to survive.
- Each mutation = more resistant.
- So, for cancer progression, mutations that inhibit death may be just as important as those that stimulate growth.
- Describe a mechanism by which one cell can induce apoptosis in another cell, and give an example.
what do you think about this guys? what are examples?
