Apoptosis

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Apoptosis describes the programmed cell death, the deliberate suicide of a cell in a multicellular organism for the greater good of the whole individual. In contrast to necrosis, apoptosis occurs naturally during development, for example, the differentiation of human fingers requires the cells in between the fingers to initiate apoptosis so the fingers can separate.

Uses of apoptosis

= Cell damage or infection

Apoptosis also occurs when a cell is damaged beyond repair, or infected with a virus. The "decision" for apoptosis can come from the cell itself, or from a call that is part of the immune system. If the apoptosis program of a cell itself is damaged (by mutation), or if the initiation is blocked (by a virus), a damaged cell can start growing without restrictions, developing into cancer.

Immune cell regulation

Some cells of the immune systems, the B cells and T cells, can become autoreactive, attacking healthy body cells. These are destroyed via apoptisis. Also, to prevent T cells from attacking healthy body cells right away, they are tested for autoimmune reactions within their origin tissue, the thymus. About 95% of the freshly produced T cells are killed right away via apoptosis due to autoimmune reactions.

Development

Programmed cell death is an integral part of vertebrate tissue development, and it does not elicit the inflammatory reponse which is characteristic of necrosis. In other words, apoptosis does not resemble the sort of reaction that comes as a result of tissue damage due to accident or pathogenic infection. Instead of swelling and bursting --and, hence, spilling their internal contens into extracellular space--, apoptotic cells and their nucleus shrink, and often fragment. In this way, they can be efficiently phagocytosed (and, as a consequence of this, their components reused) by macrophages or by neighgoring cells.

Homeostasis

In the adult organism, the number of cells within an organ or tissue has to be constant within a certain range. This is called homeostasis. It is achieved when the rate of cell division in the tissue equals the rate of cells going into apoptosis. If this equilibrium is disturbed, either of two things happen:

  • The cells are dividing faster than they die, effectively developing a tumor.
  • The cells are dividing slower than they die, which results in the tissue shrinking until no cells are left.

Both states are usually fatal if they remain untreated.

Apoptosis process

Morphology

A cell undergoing apoptosis shows a characteristic morphology that can be seen under a microscope:

  1. The cell becomes round (circular).
  2. Its DNA condenses.
  3. Its DNA is fragmented, the nucleus is broken into several discrete chromatin bodies.
  4. The cell breaks apart into several vesicles called apoptotic bodies.
  5. The cell is phagocytosed.

Biochemical reactions

Most apoptisis-inducing messages, from both outside and inside the cell, target a central death signal. This signal activates ICE-proteases, which initiate and perform part of the apoptosis program.

Biochemical execution

Apoptosis is executed by enzymes called caspases (see "Controlling the Caspases", by Stephen W. Fesik and Yigong Shi, in Science, Vol. 294, No. 5546, p. 1477, November 16, 2001), which are normally supressed by IAP (inhibitor of apoptosis) proteins. When a cell receives an apoptotic stimulus, IAP activity is relieved after Smac/DIABLO, a mitochondrial protein, is released into the cytosol.

See also: Immunology -- Biochemistry

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