Kaushal Gur P
Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Semin Nephrol. 2003 Sep;23(5):425-31. doi: 10.1016/s0270-9295(03)00086-x.
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.
细胞死亡的调控已在包括肾缺血性和中毒性急性肾衰竭在内的多种临床病症中得到研究。半胱天冬酶通过切割和灭活各种对细胞存活和增殖至关重要的细胞内结构和功能蛋白，在细胞死亡的执行或最后阶段发挥关键作用。目前有证据表明半胱天冬酶途径参与包括急性肾衰竭发病机制在内的多种肾脏疾病。在迄今为止已鉴定出的14个已知半胱天冬酶家族成员中，包括半胱天冬酶-3、-6和-7在内的几种执行性半胱天冬酶以及包括半胱天冬酶-1在内的促炎半胱天冬酶可能参与细胞内蛋白质的最终降解。这些半胱天冬酶的激活受受体和线粒体介导的细胞信号通路以及内质网应激反应的调节。虽然一些半胱天冬酶在肾损伤中的作用正在显现，但各种促炎和其他执行性半胱天冬酶的作用仍有待确定。尽管已经鉴定出许多在半胱天冬酶激活上游起作用的促凋亡和抗凋亡分子，但它们在肾损伤发病机制中的调节尚待确定。因此，对半胱天冬酶介导的细胞死亡途径和半胱天冬酶激活调节的精确描述，对于理解肾损伤机制以及开发预防肾脏疾病和保护肾功能的治疗靶点至关重要。
