Sunday 11 March 2018

why do some cells in the body prefer necrosis to apoptosis as a means of cell death?


There are many programmed cell death pathways, but some cells show a greater preference for some over the other. I'm wondering as to why if necrosis is an inflammatory response that causes damage to neighboring cells, why some cells would prefer this as opposed to a more controlled mechanism such as apoptosis or even autophagy.



Answer



There is actually no preference for apoptosis or necrosis in cells of the human body - both types can occur in all cells and they have different triggers. The main differences can be seen in this figure (from here):


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Apoptosis (also called programmed cell death) has three different triggers (intrinsic, extrinsic and Perforin/Granzyme pathways), see the image below for details (from reference 1):


enter image description here


All three activate different components and caspases in the beginning but finally all activate Caspase 3, which finally activates endonucleases (which degrade the chromosomal DNA), Proteases (which degrade the proteins in the nucleus and the cytoskeleton) which leads to the degradation of the cell. In the end apoptotic bodies are formed from the cell. Additionally the mitochondria break down and release cytochrome c and ATP. Their release from the cell attracts macrophages which take up and eliminate the apoptotic bodies and in turn release cytokines which suppress an inflammatory response.


Apoptosis goes on in a ordered way and does not trigger any further reactions in neighbouring cells (except these receive the same signal). See also reference 1 and 2 for more details.



Necrosis is triggered by external stimuli of the cell as injury of tissues or toxins from infections. Necrotic cells swell, while there internal structures are in a state of unregulated degradation. Finally the membrane will burst and set free cytochrome c and phosphatidylserines from the membranes which cause inflammation in the affected tissue. The necrotic cells are not removed by macrophages which allows the released interior of the cell to spread further and cause problems. See reference 2 and 3 for more details.


Necrosis is usually not as a beneficial process, but there are also publications which see the process as a specific form of cell death (see reference 4).


References:



  1. Apoptosis: A Review of Programmed Cell Death

  2. Apoptosis vs. Necrosis

  3. Cell death by necrosis: towards a molecular definition

  4. Review Necrosis: a specific form of programmed cell death?


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