Cellular stress and apoptosis

The morphological characteristics of apoptosis are unique and imply a series of alterations including cell shrinkage, membrane blebbing, nuclear condensation and emergence of apoptotic bodies. Three phases can be determined during the process of apoptosis: these are an induction phase corresponding to the initiation of the apoptotic signal, an effector phase involving proteolysis of important substrates and a degradation phase where cell structures and functions are destroyed. Exposure to low doses of H(2)O(2) provokes apoptosis in a variety of cell types, whereas high doses of this oxidant leads to necrosis. Moreover, in addition to examples of chemically or physically induced apoptosis, physiological stimuli such as tumour necrosis factor-alpha, anti-Fas or growth factor withdrawal are accompanied under certain conditions by the production of free radicals. However, it is now well demonstrated that free radicals can activate the death programme but that they are not an essential part of apoptosis. DNA-damaging agents are able to block the cell cycle in G1 and to induce apoptosis. The DNA strand-breaks sensor will allow the expression of P53 leading to protease activation. However, this pathway is not solely responsible for apoptosis to occur, and ceramide production, stimulation of stress-activated protein kinases and subsequent induction of c-jun are also key events in this cascade.