CELL STRESS AND APOPTOSIS RESEARCH GROUP

The cellular responses to stress can range from adaptive responses to cell death. One of the classical adaptive responses involves the induction or activation of a family of highly conserved proteins called stress or heat shock protein (Hsps). The major Hsps of mammalian cells include proteins of 110, 90, 70, 60, 40 and 27 kDa. Some Hsp members are constitutively expressed whereas others are expressed only after a period of stress (e.g., rise in temperature, exposure to radiation, viral infection, heavy metals and other toxicants). Induction of these proteins in response to stress confers resistance to subsequent stress (thermotolerance). We have shown that this resistance is due to the inhibition of apoptosis. 

 Apoptosis is a highly regulated form of cell death.  It is fundamental physiological process crucial to maintaining homeostasis in multicellular organisms acting as a counterbalance to cell division.  All animal cells are programmed to undergo apoptosis when they cease to function, are no longer needed or are damaged. Dysregulated apoptosis is the underlying mechanism of a number of human diseases. For example inappropriate apoptosis occurs in certain degenerative diseases, while a reduced level of apoptosis is frequently associated with the development of cancer. 

 Apoptosis is characterized by cell shrinkage, nuclear condensation and oligonucleosomal DNA fragmentation. The biochemical basis for the morphological features of apoptosis, which include nuclear condensation and DNA fragmentation, can be traced to the action of a family of proteases called caspases. Mitochondria play a key role in activating caspases by releasing cytochrome c (cyt- c) into cytosol where it binds to Apaf-1, facilitating pro-caspase-9 processing, followed by caspase-9-mediated activation of pro-caspase-3.

 Since dysregulated apoptosis is the underlying mechanism of a number diseases, therefore, a detailed understanding of the signalling pathway in activation of the apoptotic programme provides us with invaluable information for the development of novel therapeutic strategies for the treatment of apoptosis-mediated diseases. Although a number of signalling pathways involved in apoptosis in higher eukaryotes are already delineated, a number of fundamental biological questions yet remain unanswered. 

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