Apoptosis

Definition of apoptosis:

It is thought that cells die by one of two mechanisms: a cell can be killed by an injurious agent (necrosis) or it commits suicide in response to an intrinsic or extrinsic death signal (apoptosis).

Apoptosis is an evolutionarily conserved, genetically regulated, active process characterised by profound and distinct changes in cellular architecture leading to self-destruction of cells (Kerr et al., 1994; White, 1996; Yang & Korsmeyer, 1996). It could be easy to understand why and how the cell dies after it is exposed to a chemical or a mechanical damaging agent. As known, these agents disrupt the controlled membrane permeability leading to intracellular accumulation of ions and water. The cell and its organelles swell and run into a series of events in the death pathway. At the same time, the cell content leak out leading to signs of inflammation, that is considered a sign of necrosis rather than apoptosis.

When and why the cell commits suicide?
If we think about the cell as a part of a host that is in part regulated by the environment of this host, we can see that the outcome of the balance between survival and death signals does not serve the cell itself, but they serve the host development and survival.

Apoptosis has a pivotal role during development of tissues and organs, endocrine-dependent atrophy, normal cell turnover in tissues, selection of immunologically competent subpopulation in both T and B cell lineages during the response to antigen, and cytotoxic T lymphocyte killing (Wyllie, 1997b).


Without apoptosis during fetal development, we would have been born with webs between our fingers and toes, which is not the best fit for their functions. So, apoptosis is needed for proper development and function of tissues and organs.

Apoptosis is also the main mechanism by which organisms destroy cells that threat their normal integrity. This regulated process limits the accumulation of potentially harmful cells, such as self-reactive lymphocytes, virus-infected cells and tumor cells (Reed, 1995). On the other hand, uncontrolled apoptosis contributes to a wide variety of diseases, including cancer, AIDS, stroke, myopathies and various neurodegenerative disorders (Thompson, 1995).

Interestingly, apoptosis is the mechanism by which normal and tumor tissues respond to low or moderate doses of chemotherapeutic agents, ionising radiation and hypoxia (Wyllie, 1997).

History of apoptosis
The first morphological description of naturally occurring cell death was that of Flemming in 1885. Flemming was the first to argue that cell death involved chemical changes within the cell. He coined the word “chromatolysis” at the end of the 19th century, which became accepted as a distinct form of cell death corresponding to the currently used term apoptosis (Clarke & Clarke, 1996).

First evidence of the existence of two morphologically distinct types of cell death came from an Australian pathologist, John Kerr. In 1965, as a result of his Ph.D. studies concerning hepatocyte atrophy, John Kerr recognised a distinct form of cell death and named it shrinkage necrosis.


In 1972 John Kerr, Alastair Currie and Andrew Wyllie introduced the term apoptosis for morphologically distinctive, active, inherently controlled form of cell death, complementary to mitosis in the regulation of animal cell populations, both in physiological and pathological conditions (Kerr et al., 1972).

In 1976 and 1981, studies on irradiated lymphoid tissues led to the notion that chromatin broke down into fragments that produced a typical, ladder-like pattern. This phenomenon was linked to apoptosis by Wyllie in 1984 and it came to serve as a specific biochemical marker for the distinctive morphological changes of apoptotic cells (Wyllie, 1984).
 

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Apoptosis mechanism

Factors involved in the apoptosis process