Regulation of Apoptosis and Differentiation by p53 in Human ...

CHAPTER 1: Introduction
1.3- APOPTOSIS
Programmed cell death is critical for development and homeostasis in metazoans
(Vaux and Korsmeyer, 1999).
The phenomenon of apoptosis was first described by Carl Vogt in 1842, and its name, introduced
by Kerr, Wyllie and Currie in 1972, is derived from the ancient Greek meaning the ‘‘falling off of
petals from a flower’’ or ‘‘shedding of leaves from a tree in autumn’’. This term was used to
describe a common type of programmed cell death that was observed in various tissues and cell
types. The dying cells shared many morphological features, that were distinct from the features
observed in cells undergoing necrotic cell death, and this could be a result of common and
conserved endogenous cell death programme. Apoptosis is a form of caspase-mediated cell
death with particular morphological features and usually does not lead to inflammation (Fink and
Cookson, 2005). Unlike apoptosis, necrosis denotes a form of cell death usually accompanied by
inflammation (Savill, 1997), is not energy dependent, does not involve caspase activity or gene
regulation.Table 1.3 shows differences these two processes.
TABLE 1.3- Comparison between apoptosis and necrosis (Adapted from Academic Pathology,
Queen's University Belfast, 2003)
Apoptosis
Necrosis
Physiological or pathological
Always pathological
Energy dependent
Energy independent
Cell shrinkage
Cell swelling
Membrane integrity maintained
Membrane integrity lost
Characteristic nuclear changes
Nuclei lost
Apoptotic bodies form
Do not form
DNA cleavage
No DNA cleavage
Evolutionarily conserved
Not conserved
Dead cells ingested by neighbouring cells
Dead cells ingested by neutrophils and
macrophages
Apoptosis should not be used synonymously with programmed cell death (PCD), which can occur
via apoptosis, but is rather used to identify a specific morphology of cell death. The term PCD
refers to time- and position-programmed cell death during development of an organism. However,
apoptosis can be induced by anti-cancer drugs, toxins and other types of stresses (Lawen, 2003).
One of the main reasons for the interest in this process is due to its involvement in many
diseases, such as neurodegenerative and autoimmune diseases (if it occurs too much) and
cancer (if it occurs too little).
1.3.1- Apoptosis in development and homeostasis
During animal development, there are numerous structures or specific populations of cells that
are formed that are later removed by apoptosis. This allows greater flexibility because primordial
structures can be adapted for different functions at various stages of life or in different sexes
(Meier et al., 2000). A classical example of this is the development of the Müllerian duct (that
gives rise to the uterus and oviduct in females) that is removed in males, and the Wolffian duct
(that gives rise to the male reproductive organs) that is deleted in females. Other examples are
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