Recent advances in understanding mechanisms of renal tubular injury

Study of cell death has emerged as an important and exciting area of research in cell biology. In this review, we first discuss two kinds of cell death, apoptosis and necrosis, then describe the evidence suggesting a role of endonuclease activation in renal tubular injury. The pathway that is followed by the cell is dependent on both the nature and the severity of the insults and may evolve from the apoptotic to the necrotic form of cell death. It is also conceivable that there are some common pathways that are shared and regulated in the two modes of cell death. Along these lines, interleukin 1 beta-converting enzyme (ICE) and ICE-like proteases, generally associated with the apoptotic mode of cell death, recently have been shown to be important in hypoxic injury. We describe the studies documenting an important role of endonuclease in renal tubular injury and some of the important mechanisms by which it may be regulated. A large body of evidence supports a role of protooncogenes in the regulation and modification of apoptotic cell death. Many of these protooncogenes and related proteins have been shown to be altered in models of acute renal failure, suggesting their potential importance. Therapeutic opportunities may lie in prevention of cell injury or enhancing recovery by inhibiting endonucleases and ICE and ICE-like proteases as well as by induction of certain oncogenes and related proteins.