APOPTOSIS:The story of suicide in the cell

Apoptosis ( programmed cell death) is a central response to excess oxidative damage (especially DNA damage) , and is also essential to emryogenesis, morphogenesis and normal immune function.An understanding of the cellular events leading leading to apoptosis is important for the design of new chemotherapeutic agents directed against the types of leukemias and lymphomas that are resistant to currently used chemotherapeutic protoclos.

What is Apoptosis

Apoptosis can best be described as "programmed cell death."This means that the death of a cell occurs by an active process that involves a distinct series of biochemical and morphological changes.Apoptosis occurs naturally in the growth and development of organisms and in immune responses.It allows an organism to remove old,dead or unwanted cells.

When a cell sustains DNA damage (e.g. strand breaks) it can respond with DNA repair and,if this is effective, the cell can recover.Wheater a cell undergoes apoptosis or not is dependent on the balance between factors that promote apoptosis )e.g some cytotoxic drugs and cytokines) and this that prevent it (survival signals,e.g other cytokines, oncogenes such as bcl-2).

Apoptosis takes place in a sequence of distinct stages.The first stafe of apoptosis is the condensation of the affected cell.

This condensation phase can be split into two parts:

• Chromation condensation involves action of endogenous endonucleases that fragment the DNA at specific regions.Endonucleolytic cleavage may occur prior to condensation.The relationshop between the two events is diffucult to clarify experimentally.
• This chromatin condensation is followed by cytoplasmic condensation, which results in a breakdown of intercellular interactions as the cell indergoing apoptosis is isolated from its neighbouring cells.This is caused by the disruption of the cytoskeleton and the formation of blebs on the cell surface.The condensation phase lasts only a few minutes.

During the next stage the cell breaks up to form "apoptotic bodies". The final stage involves phagocytosis of the apoptotic bodies by phagocytes and neutrophiles and subsequent degredation of the apoptotic bodies by the lysosomes ofrecipient cells.The apoptotic process takes about three hours to complete.

  RADIATION\          /CYTOTOXIC
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           DNA DAMAGE 
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         SENSING MECHANISM
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        DNA LARGE FRAGMENTATION
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DNA INTERNUCLEOSOMAL FRAGMENTATION
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CYTOPLASMIC CONDENSATION AND CHROMATIC CONDENSATION
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        FRAGMENTATION OF CELL
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    PHAGOCYTOSIS OF FRAGMENTS

Figure 1. The apoptotic process.

Appoptosis is a distinct process from necrosis, which describes the death of a cell resulting from cell injury.Cell necrosus is the result of sever damage to the environtment of the cell (e.g. by ischaemia or by physical trauma) ant it does not invlove the activation of specific enzymes within the target cell.In cell necrosus the cell membrane becomes more permeable to water,so that the cell swells and ultimately bursts.During necrosus there is leakage of intercellular components into the extracllular components into the extracellular space,which sets it apart from apostisis. Another important differnce between necrosis and apoptosis is that the cell rupture which occurs in necrosus stimulates an inflammatory response.In apoptosis an inflammotory response is not elicited because the cell membrane remains intact and inflammatory mediators are not released.Moreover,cell death by apoptosis does not lead to scarring.