CELLULAR STRESS AND APOPTOSIS

The morphological characteristics of apoptosis are unique and imply a series of alterations including cell shrinkage, membrane blebbing, nuc lear 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 effe ctor phase involving proteolysis of important substrates and a degrada tion phase where cell structures and functions are destroyed. Exposure to low doses of H2O2 provokes apoptosis in a variety of cell types, w hereas high doses of this oxidant leads to necrosis. Moreover, in addi tion to examples of chemically or physically induced apoptosis, physio logical stimuli such as tumour necrosis factor-alpha, anti-Fas or grow th factor withdrawal are accompanied under certain conditions by the p roduction of free radicals. However, it is now well demonstrated that free radicals can activate the death programme but that they are not a n essential part of apoptosis. DNA-damaging agents are able to block t he cell cycle in G1 and to induce apoptosis. The DNA strand-breaks sen sor will allow the expression of P53 leading to protease activation. H owever, this pathway is not solely responsible for apoptosis to occur, and ceramide production, stimulation of stress-activated protein kina ses and subsequent induction of c-jun are also key events in this casc ade. (C) 1997 Elsevier Science Ltd.