Physiology in Medicine
Apoptosis: definition, mechanisms, and relevance to disease☆

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Apoptosis and other death forms

Apoptosis can be differentiated from other forms of cell death, termed necrosis, that may occur in response to injury by toxins, physical stimuli, or ischemia. Swelling of cells and disruption of membranes are prominent features of necrosis, and the nuclear chromatin undergoes lysis, not condensation, in this mode of cell death (Figure 1). Because large groups of cells are involved and cellular contents are lost early into the extracellular space, necrotic tissues evoke vigorous inflammatory

Biological significance of apoptosis

For the vast majority of normal cells undergoing apoptosis, little is known about the signals that commit cells to death. Cells may emanate signals that cause neighboring cells to die. Although this seems to be the way some cells are eliminated during development, for example, during morphogenesis of fingers and toes, understanding of the nature of apoptosis-inducing signals and the principles that determine their location and timing is incomplete. Systemic factors may also be necessary to

Caenorhabditis elegans: a worm’s tale of cell death

Apoptosis was first characterized during genetic studies on the nematode worm Caenorhabditis elegans. Programmed cell death during C. elegans development involves the activation of selective death genes that kill exactly 131 cells, leaving 959 cells intact in the worm (2). Further studies revealed that apoptosis consists of three successive stages: (1) commitment to death triggered by extracellular or intracellular signals; (2) execution of cell killing by activation of intracellular proteases;

Apoptosis and disease pathogenesis

In the normal state, cell proliferation and cell death are at equilibrium. Alterations in the rate of cell death or proliferation, or both, can be involved in disease pathogenesis. Abnormalities of apoptosis have been implicated in diverse disease processes (Table 3). Failure of normally required apoptosis in some cell populations as well as abnormally increased apoptosis may result in disease. Some disease processes may depend on both failed and excessive apoptosis during different stages of

Future directions

Evolving recognition that programmed cell death is an important feature of disease will certainly increase further the burgeoning interest in apoptosis research. Although it is clear that apoptosis or its inhibition is involved in disease pathogenesis and in the expression of disease symptoms, there is much room for intensive research to arrive at a deeper understanding. Techniques that allow for accurate and quantitative detection of apoptosis need to be developed. There is also a need to

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      The signaling pathways (intrinsic or extrinsic) of apoptosis are complex in nature, of which always involves the activation of effectors, belonged to the family proteases known as caspases (Wang et al., 2011). Condensation of nuclei, chromatin agglutination, DNA fragmentation, cellular shrinkage, swelling and disintegration of mitochondria are some of the typical features of apoptosis (Saikumar et al., 1999; Gulbins et al., 2000). Previous studies already proved that Mycoplasmas infection induced apoptosis in cells (Sokolova et al., 1998).

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    ☆

    Research grant support was provided to Drs. P. Saikumar, National Institutes of Health (NIH) Grant DK 54472 and Morrison Trust Grant; J. M. Weinberg, NIH Grant DK 34275, Department of Veteran’s Affairs, and Office of Naval Research Grant N00014-95-1-584; and M. A. Venkatachalam, NIH Grants DK37139 and DK48417.

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