Manganese porphyrin reduces renal injury and mitochondrial damage during ischemia/reperfusion
Manganese porphyrin reduces renal injury and mitochondrial damage during ischemia/reperfusion
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DOI：
10.1016/j.freeradbiomed.2007.02.016
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发表时间：
2007-05-15
影响因子：
7.4
通讯作者：
MacMillan-Crow, Lee Ann
中科院分区：
文献类型：
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作者：
Saba, Hamida;Batinic-Haberle, Ines;MacMillan-Crow, Lee Ann
肾缺血/再灌注（I/R）损伤通常是血管手术、器官获取或移植的结果。我们以前表明，肾I/R的结果在ATP耗竭，氧化剂的生产，和锰超氧化物歧化酶（MnSOD）失活。有几份报告表明MnSOD的过度表达可保护组织/器官免受I/R相关损伤，因此在I/R期间MnSOD活性的丧失可能有助于组织损伤。本研究使用大鼠肾I/R模型检查了催化抗氧化剂Mn（III）meso-四（N-n-hexylpyridinium-2-yl）卟啉（MnTnHex-2-PyP 5+）的治疗益处。这是第一个研究MnTnHex-2-PyP 5+在氧化应激损伤动物模型中的作用。我们的研究结果表明，卟啉预处理大鼠24它保护ATP耗竭，MnSOD失活，硝基酪氨酸形成，和肾功能障碍。本研究中使用的剂量（50 μ g/kg）低于氧化应激损伤动物模型中常用的各种类型抗氧化剂的剂量。此外，使用新的蛋白质组学技术，我们确定了ATP酶-β亚基是MnTnHex-2-PyP 5+单独治疗诱导的关键蛋白，复合物V（ATP合酶）是肾I/R损伤的靶点。这些结果表明，MnTnHex-2-PyP 5+通过诱导可能能够钝化氧化损伤的关键线粒体蛋白来保护肾I/R损伤。(c)2007爱思唯尔公司All rights reserved.
Renal ischemia/reperfusion (I/R) injury often occurs as a result of vascular surgery, organ procurement, or transplantation. We previously showed that renal I/R results in ATP depletion, oxidant production, and manganese superoxide dismutase (MnSOD) inactivation. There have been several reports that overexpression of MnSOD protects tissues/organs from I/R-related damage, thus a loss of MnSOD activity during I/R likely contributes to tissue injury. The present study examined the therapeutic benefit of a catalytic antioxidant, Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTnHex-2-PyP5+), using the rat renal I/R model. This was the first study to examine the effects of MnTnHex-2-PyP5+ in an animal model of oxidative stress injury. Our results showed that porphyrin pretreatment of rats for 24 It protected against ATP depletion, MnSOD inactivation, nitrotyrosine formation, and renal dysfunction. The dose (50 mu g/kg) used in this study is lower than doses of various types of antioxidants commonly used in animal models of oxidative stress injuries. In addition, using novel proteomic techniques, we identified the ATP synthase-beta subunit as a key protein induced by MnTnHex-2-PyP5+ treatment alone and complex V (ATP synthase) as a target of injury during renal I/R. These results showed that MnTnHex-2-PyP5+ protected against renal I/R injury via induction of key mitochondrial proteins that may be capable of blunting oxidative injury. (c) 2007 Elsevier Inc. All rights reserved.