Modification of the Hepatic Mitochondrial Proteome in Response to Ischemic Preconditioning Following Ischemia-Reperfusion Injury of the Rat Steatotic Liver.

大鼠脂肪肝缺血再灌注损伤后肝线粒体蛋白质组的修饰对缺血预处理的反应。

基本信息

批准号：
16591367
负责人：
NAKANO Hiroshi
金额：
$ 2.24万
依托单位：
St.Marianna University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

Background/Aim : Ischemic preconditioning (IPC) has been shown to reduce hepatic ischemia-reperfusion (IR) injury of steatotic liver, but the effect of IPC on mitochondrial proteome has not been fully demonstrated. The present study investigated how IPC modifies the mitochondrial proteome after IR injury of the rat steatotic liver.Methods : Zucker steatotic rats were subjected to 25-min portal triad cross-clamping (IR group). In the IPC group, 10-min temporal clamping followed by 10-min reperfusion was performed before the 25-min clamping. The other rats were sham-operated as a control group. Mitochondrial proteome was analyzed 24 hours after IR using two-dimensional differential in-gel electrophoresis and mass spectrometry.Results : Mitochondrial inner-membrane potential and glutathione were lower and serum transaminase was higher in the IPC group than in the IR group. There was a greater degree of up-regulation of the mitochondrial precursor of aldehyde dehydrogenase 2 and alpha-methylacyl-CoA racemase in the IPC group in comparison to the IR group. In contrast, 60S acid ribosomal protein P0, carbonic anhydrase 3, arginase 1, and superoxide dismutase were significantly more down-regulated in the IPC group than in the IR group.Conclusions : A hepato-protective effect was not shown by IPC ; however, IPC caused significant up-or down-regulation of several mitochondrial proteins 24 hours after IR of steatotic liver.

背景/目的：缺血预处理（IPC）已被证明可以减少脂肪肝的缺血再灌注（IR）损伤，但IPC对线粒体蛋白质组的影响尚未得到充分证明。本研究调查了IPC如何在大鼠脂肪肝IR损伤后改变线粒体蛋白质组。方法：对Zucker脂肪肝大鼠进行25分钟的肝门三联交叉钳夹（IR组）。在IPC组中，在25分钟钳夹之前进行10分钟颞部钳夹，随后进行10分钟再灌注。其余大鼠进行假手术作为对照组。 IR后24小时使用二维微分凝胶电泳和质谱分析线粒体蛋白质组。结果：IPC组的线粒体内膜电位和谷胱甘肽低于IR组，血清转氨酶高于IR组。与 IR 组相比，IPC 组中醛脱氢酶 2 和 α-甲基酰基辅酶 A 消旋酶的线粒体前体上调程度更大。相比之下，IPC组中60S酸性核糖体蛋白P0、碳酸酐酶3、精氨酸酶1和超氧化物歧化酶的下调程度显着高于IR组。结论：IPC没有显示出保肝作用；然而，在脂肪肝 IR 后 24 小时，IPC 导致多种线粒体蛋白显着上调或下调。