Apoptosis

• It is coordinated and internally programmed cell death it has significance in various physiological processes like involution of thymus in early age , sculpting of tissues during development of embryo and pathological process like diseases of heart like acute MI and CNS diseases like alzehmeirs disease and parkinson’s disease

In apoptosis single cells or small cluster of cells are involved. When compared to the normal cell the apoptotic cell has more eosinophilic cytoplasm and chromatin condensation.

Apoptotic bodies are membrane bound spherical bodies with cell shrinkage ,chromatin condensation and eosinophilic cytoplasm. Apoptotic bodies are also referred to as Mummified bodies.

DNA changes can be seen by gel electrophoresis by H and E stain to see the chromatin condensation and other stains. Flow cytometry for cell shrinkage.

Apoptosis is not accompanied by inflammation unlike necrosis

Mechanism of apoptosis :-

1. Initiators of apoptosis :- Every cell has built mechanism for the cell survival and to activate the signal of cell death. Apoptosis takes place when there is withdrawal of cell survival signals like growth factors , cytokines. And the agents of cell injury like heat and radiation leads to Apoptosis

2. Initial phase of apoptosis :- There are 2 pathways by which apoptosis takes place that is intrinsic and extrinsic pathway by activating the caspases. Intrinsic pathway is the major pathway of cell death. Caspases are nothing but the protein splitting enzymes that will act on nuclear proteins and other protein components.

Intrinsic pathway :-

This pathway of cell death is by release of protein cytochrome C from mitochondria to cytoplasm. This triggers the cell to Apoptosis. Protein C is the life line of intact mitochondria. This is regulated by pro and anti apoptotic genes. Anti apoptotic genes are bcl2 , Mcl 1 and bcl x. Pro apoptotic genes are bid , bad. The proapoptotic genes will trigger apoptosis that will release Bak and Bax that will damage the mitochondrial membrane and releases the cytochrome c from mitochondria to cytoplasm that will activate caspases

Extrinsic pathway :-

This pathway of cell death is by activation of cell death receptors present on the cell surface. Cell death receptor tumour necrosis factor and related transmembrane protein that is fas and it’s ligand fas l this binding is associated with Fas associated death domain. This will activate caspases

3. Final phase of apoptosis :- There is activation of caspases 8 by intrinsic pathway and caspases 9 and 10 by extrinsic pathway that will act on the nuclear proteins and this leads to the changes in the DNA and cell death.

4. Phagocytosis :- The surface of the cell will undergo changes in order to activate the adjacent macrophages for its phagocytosis. Phosphatidyl serine and thrombospondin molecules is present inside, during apoptosis it comes to the exterior that triggers the cell for its phagocytosis. Phagocytosis is rapid and it’s not accompanied by inflammatory cells.

Reference :- Harsh Mohan

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