PROTEIN KINASE C IN ISCHEMIC RENAL INJURY AND REPAIR

蛋白激酶C（PKC）同工酶是一类细胞激酶 它通过磷酸化 靶蛋白。 PKC在细胞对缺血的反应中起作用 包括肾脏在内的各种组织中。 我们已经证明，表达式 几种PKC同工酶和活化C激酶受体（RACK 1） 在缺血性肾损伤后增强。 概述的研究 该建议旨在描述单个PKC的作用 实验性急性肾小管损伤后肾小管再生的同工酶 使用体外和体内模型的缺血性肾损伤。第一个目标 这项研究的目的是定位单个PKC同工酶， 正在经历再生或死亡的特定细胞。 PKC检测 将进行，以确定哪些个别同工酶是 在缺血性损伤后被激活或下调。 第二个目的 该提案的目的是确定PKC是否在维护 LLCPK1细胞的细胞活力和促进再生 氧化损伤LLCPK1细胞将受到氧化损伤， PKC激活剂和抑制剂的存在及其对细胞的影响 将确定可行性。 LLCPK1细胞过表达个体 将建立PKC同工酶，并将这些细胞系用于 描述了在氧化后恢复中单个同工酶的作用 介导的损伤。 建议的第三个目的是研究 PKC激活剂和抑制剂对大鼠肾再生的影响 急性缺血性肾衰竭 我们的初步数据显示， 缺血前给予大鼠PKC激活剂可改善缺血性脑损伤， 受伤的过程。 这些观察将被扩展到测试 各种PKC激活剂和抑制剂对肾功能的影响， 形态学、细胞增殖、凋亡和分化后 缺血

Protein kinase C (PKC) isozymes comprise a family of cellular kinases that regulate cell growth and differentiation via phosphorylation of target proteins. PKC plays a role in the cellular response to ischemia in various tissues including kidney. We have shown that the expression of several PKC isozymes and the receptor for activated C-kinase(RACK1) are enhanced following ischemic renal injury. The studies outlined in this proposal are designed to delineate the role of individual PKC isozymes in the tubular regeneration following experimental acute ischemic renal injury using in vitro and in vivo models. The first aim of the proposed research is to localize individual PKC isozymes to particular cells that are undergoing regeneration or death. PKC assays will be performed to determine which of the individual isozymes are activated or down-regulated following ischemic injury. The second aim of the proposal is to determine if PKC plays a role in maintaining cellular viability and promoting regeneration of LLCPK1 cells following oxidant injury. LLCPK1 cells will be subjected to oxidant injury in presence of activators and inhibitors of PKC and their effects on cell viability will be determined. LLCPK1 cells overexpressing individual PKC isozymes will be established and these cell lines will be used to delineate the role of individual isozymes in recovery following oxidant mediated injury. The third aim of the proposal is to study the effect of PKC activators and inhibitors on renal regeneration using a rat model of acute ischemic renal failure. Our preliminary data indicate that administration of PKC activators to rats pre-ischemia ameliorates the course of injury. These observations will be extended to test the effects of various PKC activators and inhibitors on renal function, morphology, cell proliferation, apoptosis and differentiation post- ischemia.