Roles of Apoptosis in Health and Disease

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The development of a human baby from a fertilized egg involves the four key processes of cell division, differentiation, morphogenesis and apoptosis. Cell death by apoptosis is an integral part ofhuman embryonic development, just as it is in the development of C. elegans, and this inbuilt death programme responds to a complex array of external and internal signals. Obvious manifestations of apoptosis in the embryo include the sculpting of organs and the removal of webs between the digits on hands and feet. The nervous system develops through the overproduction of cells followed by apoptosis ofthose failing to establish functional synaptic connections (Renehan et al., 2001). Apoptosis is an important mechanism in development of the endocrine pancreas and specifically in remodelling of the b-cell mass during neonatal life (Scaglia et al., 1997).

Involution of the thymus has long been recognized as a sensitive marker of malnutrition (Prentice, 1999) and impaired immune function. Thymocytes from young rats made severely malnourished by doubling the number of young suckling each dam had seven times higher rates of spontaneous apoptosis compared with those from well-fed controls (Ortiz et al., 2001). This greater rate of apoptosis may be responsible for the atrophy of the thymus in malnutrition (Ortiz et al., 2001), with serious consequences for both short- and long-term health (Moore et al., 1997). T-lymphocyte homeostasis occurs as a balance between apoptosis, mediated by local concentrations of interleukin-2 (IL-2), and proliferation in response to diverse antigens (Lenardo etal., 1999) including those from food. Nur77 is one of a pair of orphan nuclear receptors (the other is Nurr1), which hetero-dimerizes with the nuclear receptor retinoid X receptor (RXR) to activate gene transcription after binding retinoic acid (the transcriptionally active derivative of vitamin A) (McCaffrey et al, 2001). Nur77 appears to be important in apoptosis in the immune system and in negative selection ofT cells (McCaffrey et al, 2001).

With very few exceptions, such as the nervous system, cell division continues in all tissues throughout life and, as a result, apoptosis is an essential process in adulthood since maintenance ofnormal cell numbers and the integrity oftissues and organs depends on a fine balance between the numbers of new cells born and those dying. Indeed, it has been proposed that the cell's proliferative and apoptotic pathways are coupled (Evan and Littlewood, 1998) although the biochemical machinery for each is quite distinct. Apoptosis also continues to be important for tissue remodelling during wound healing, regression of the uterus after parturition and post-lactational changes in mammary tissue.

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How To Bolster Your Immune System

How To Bolster Your Immune System

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