Caspase inhibition prevents the increase in caspase-3,-2,-8 and-9 activity and apoptosis in the cold ischemic mouse kidney
Caspase inhibition prevents the increase in caspase-3,-2,-8 and-9 activity and apoptosis in the cold ischemic mouse kidney
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DOI：
10.1111/j.1600-6143.2004.00498.x
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发表时间：
2004-08-01
影响因子：
8.8
通讯作者：
Edelstein, CL
中科院分区：
文献类型：
--
作者：
Jani, A;Ljubanovic, D;Edelstein, CL
冷缺血时间延长是移植物功能延迟发展的危险因素。冷缺血的不利影响可能与肾小管细胞死亡有关。 Caspase-3 是细胞凋亡的主要介质。我们假设半胱天冬酶抑制会减少细胞凋亡和冷缺血的其他特征。 C57BL/6小鼠的肾脏通过左心室用含有pancaspase抑制剂或载体的冷威斯康星大学溶液灌注。对侧右肾用作对照。左肾4℃保存48小时，产生冷缺血。与对照组相比，冷缺血肾脏中的 Caspase-3 活性大幅增加（100 倍）。免疫印迹分析表明，与对照组相比，冷缺血肾脏中 caspase-3 的加工形式有所增加。 caspase-3 的增加与肾小管细胞凋亡和刷状缘损伤显着增加相关。此外，冷缺血肾脏中 caspase-2、-8 和 -9 活性增加。 pancaspase 抑制剂可阻止 caspase-3 加工形式的形成和 caspase 活性的增加，并减少细胞凋亡和刷状缘损伤。半胱天冬酶抑制可能对肾脏保存有用。
Prolonged cold ischemic time is a risk factor for the development of delayed graft function. The adverse impact of cold ischemia may be associated with tubular cell death in the kidney. Caspase-3 is a major mediator of apoptotic cell death. We hypothesized that caspase inhibition would reduce apoptosis and other features of cold ischemia. Kidneys of C57BL/6 mice were perfused with cold University of Wisconsin solution containing a pancaspase inhibitor or vehicle via the left ventricle. The contralateral right kidney was used as a control. The left kidney was stored for 48 h at 4degreesC to produce cold ischemia. Caspase-3 activity was massively (100-fold) increased in cold ischemic kidneys compared with controls. On immunoblot analysis, the processed form of caspase-3 was increased in cold ischemic kidneys compared with controls. The increase in caspase-3 was associated with significantly more renal tubular apoptosis and brush-border injury. In addition, caspase-2, -8 and -9 activities were increased in cold ischemic kidneys. The pancaspase inhibitor prevented the formation of the processed form of caspase-3 and the increase in caspase activity, and reduced apoptosis and brush-border injury. Caspase inhibition may prove useful in kidney preservation.