PURINES AND THEIR ROLES IN APOPTOSIS

Purines are ubiquitous endogenous metabolites, and their roles as sign alling molecules, especially in the case of adenosine and ATP, are wel l documented. The release of purines is increased when cells are highl y activated, stressed or damaged, and this is known to have profound e ffects on various organ systems. Recently, purines like adenosine and ATP have been shown to be cytotoxic. Current evidence suggests that ad enosine induces cell death by apoptosis, whereas ATP appears to cause both necrosis and apoptosis. Apoptosis is an important physiological p rocess during normal tissue turnover and in the maturation of the immu ne system, embryogenesis, metamorphosis, endocrine-dependent tissue at rophy, etc. Recently, many of the key components of the apoptotic cell death cascade have become unravelled. In particular, proteases belong ing to the interleukin-1 beta-converting (ICE) enzyme family, also kno wn as caspases, have been shown to act as an intracellular convergence point that orchestrates the morphological and biochemical features of apoptosis. However, little is known about the signalling or the bioch emical mechanisms of purine-mediated cell death. Adenosine appears to act through PI purinoceptors, although the subtype involved remains co ntroversial, whereas ATP may involve both P2X(1) and P2X(7) purinocept ors. More recent evidence suggests that the intracellular levels of pu rines, in addition to the cell surface receptor-mediated responses, ma y also play a critical role by modulating other apoptotic cell death s ignals. Here, we review our current understanding about purines in med iating cell death and raise a number of questions as to the possible m echanisms involved. (C) 1997 Elsevier Science Ltd.