Actin cytoskeleton derangement induces apoptosis in renal ischemia/reperfusion
Actin cytoskeleton derangement induces apoptosis in renal ischemia/reperfusion
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DOI：
10.1007/s10495-006-4937-1
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发表时间：
2006-04-01
期刊：
影响因子：
7.2
通讯作者：
Hotter, G
中科院分区：
文献类型：
--
作者：
Genescà, M;Sola, A;Hotter, G
本研究评估了与肾保存相关的缺血条件下的细胞骨架改变是否可以决定细胞凋亡。细胞骨架改变是缺血的主要影响之一，并可能诱导细胞凋亡。将大鼠肾脏在威斯康星大学（University of Wisconsin， UW）溶液中保存24小时。一些动物组进行45分钟的热缺血（WI），以评估其对肌动蛋白细胞骨架和凋亡的影响（通过caspase-3活性和TUNEL染色来评估）。使用两种肌动蛋白细胞骨架靶向药物Swinholide A （SwinA）和Latrunculin B （LB）来评估肌动蛋白直接破坏对细胞凋亡的影响。Jasplakinolide （JP）是一种稳定肌动蛋白细丝的化合物，用于评估肌动蛋白稳定的效果。采用离体灌注大鼠肾（IPK）模型，在体外再灌注3 h时评估细胞凋亡。结果：WI再灌注或给药时细胞凋亡增加。稳定剂的使用逆转了先前接受过WI或接受过肌动蛋白干扰剂的肾脏的凋亡。结论：与肾保存相关的缺血状态下肌动蛋白细胞骨架的破坏通过caspase-3激活诱导再灌注时细胞凋亡。
This study evaluated whether cytoskeletal alterations during the ischemic conditions associated with kidney preservation could determine apoptosis. Cytoskeletal alterations are among the main effects of ischemia and may induce apoptosis. Rat kidneys were preserved in University of Wisconsin (UW) solution for 24 h. Some groups of animals underwent 45 min of warm ischemia (WI) to evaluate its effect on both the actin cytoskeleton and apoptosis (assessed by caspase-3 activity and TUNEL staining). Swinholide A (SwinA) and Latrunculin B (LB), two actin cytoskeleton-targeted agents, were administered to assess the effect of direct actin disruption on apoptosis. Jasplakinolide (JP), a compound that stabilizes actin filaments, was administered to evaluate the effect of actin stabilization. Apoptosis was evaluated at 3 h of ex vivo reperfusion using the isolated perfused rat kidney (IPK) model.Results: Apoptosis increased during reperfusion with WI or administration of actin disruptor agents. Administration of stabilizing agents reversed apoptosis in kidneys that had previously undergone WI or had received an actin disruptor agent.Conclusion: The disruption of the actin cytoskeleton during ischemic conditions associated with kidney preservation induces apoptosis upon reperfusion through caspase-3 activation.