Apoptosis Flashcards
Earliest sign of impending necrosis in cells
Swelling mitochondria, proceeding to a level known as high-amplitude swelling and calcium crystal formation.
How does loss of mitochondria lead to necrosis?
The loss of mitochondria reduces the amount of ATP available in the cell, causing ion pumps to fail, leading to cell swelling and lysing.
How does necrosis lead to inflammation?
Necrosed (lysed) cells release their contents into the ECM, if enough cells necrose in an area, white blood cells must be brought from elsewhere to clean up those contents. Blood vessels swell and WBCs congregate in the area.
How is apoptosis defined?
By morphology. There is no defined bio-chemical pathway, only a general appearance of cells undergoing programmed cell death.
How is DNA degraded in apoptosis
Nuclease is activated and enters nucleus, attacks DNA in linker regions between the nucleosomes. Not sequence specific, just wherever DNA is exposed. Creates DNA fragments in multiples of 180bp, which form very regular patterns on electrophoresis gels.
Why is apoptosis not an inflammatory process?
Cells signal that they are undergoing apoptosis early in the process. This signaling attracts macrophages which devour the apoptotic cell, preventing its contents from reaching the ECM and triggering an inflammatory response. The apoptotic cell dies inside the macrophage.
Under what circumstances may apoptosis trigger an inflammatory response?
If too many cells are undergoing apoptosis at one time and overwhelm the available phagocytic cells. With insufficient phagocytes available to envelop the dying cells, inflammatory responses result. This is the underlying cause of rheumatoid arthritis.
What chemical signal do apoptotic cells display to trigger macrophages?
Phosphatidylserine is a phospholipid that always localizes on the interior of the plasma membrane. Any errant phosphatidylserine found on the exterior is flipped back inside by Flippase. During apoptosis, Scramblease turns phosphatidylserine to the outside of the plasma membrane.
How does a transcription inhibitor, such as Actinomycin D, inhibit apoptosis?
Apoptosis is achieved through the activation of select proteins. Inhibiting transcription prevents those proteins from being produced, thus inhibiting apoptosis. This shows that cells have an inherent suicide pathway.
What is morphogenetic death and where is it seen?
Morphogenetic death is programmed cell death that occurs during embryological development and leads to the development of morphological features. It occurs in hands, causing fingers, in the brain, and other areas.
What is the relationship of cell division and cell death, and how frequently do they both occur?
Every cell division must be matched with a cell death to maintain homeostasis. There are approximately 25,000,000 cell divisions per second in the human body. So 2.2x10^12 divisions and deaths per day.
What are two ways that apoptosis mutations may lead to cancerous growth?
Cell lines with increased growth signaling and decreased apoptosis signaling will grow faster than they die off. Also, cell lines with normal growth signaling and decreased apoptosis signaling will grow faster than they die off.
What is the intrinsic apoptotic pathway?
The intrinsic pathway is activated by cells that have been triggered by internal mechanisms or normal external mechanisms including disease or damage (e.g., X-rays). Involves Cytochrome-C moving from mitochondria to cytoplasm, activating Apaf-1, which activates caspase-9, which activates the main effector of apoptosis: caspase-3.
What are the caspases involved in the intrinsic apoptotic pathway?
procaspase-9 -> caspase-9; initiator caspase
Procaspase-3 -> caspase-3; effector caspase
What is the extrinsic apoptotic pathway?
The extrinsic pathway is activated by killer T-cell that recognize abnormal cells. Killer T-cells have a Fas ligand that binds to Fas protein (CD95) on cell surface, Fas protein interacts with FADD which activates caspase-8, which activates caspase-3.
