Role of caspases in renal tubular epithelial cell injury

The regulation of cell death has been investigated in a number of clinical disorders including renal ischemic and toxic acute renal failure. Caspases play a crucial role in the execution or final phase of cell death by cleaving and inactivating various structural and functional intracellular proteins that are essential for cell survival and proliferation. Evidence is now emerging to implicate the caspase pathway in a variety of renal diseases including the pathogenesis of acute renal failure. Among the 14 known members of the caspase family thus far identified several executioner caspases including caspases-3, -6, and -7 and the proinflammatory caspase including caspase-1 may participate in the final degradation of intracellular proteins. The activation of these caspases is regulated by the receptor- and mitochondrial-mediated cell signaling pathways as well as by the endoplasmic reticulum stress response. While the role of some caspases in renal injury is emerging, the roles of various proinflammatory and other executioner caspases remain to be determined. Although many pro- and anti-apoptotic molecules that act upstream of caspase activation have been identified, their regulation is yet to be determined in the pathogenesis of renal injury. A precise description of caspase-mediated cell death pathway and regulation of caspase activation is, therefore, critical to the understanding of the mechanism of renal injury and to the development of therapeutic targets that prevent renal diseases and preserve renal function.