Role of reduced manganese superoxide dismutase in ischemia-reperfusion injury: a possible trigger for autophagy and mitochondrial biogenesis?
Role of reduced manganese superoxide dismutase in ischemia-reperfusion injury: a possible trigger for autophagy and mitochondrial biogenesis?
复制标题
DOI：
10.1152/ajprenal.00435.2012
复制
发表时间：
2013-02-01
影响因子：
4.2
通讯作者：
MacMillan-Crow, Lee Ann
中科院分区：
文献类型：
--
作者：
Parajuli, Nirmala;MacMillan-Crow, Lee Ann
Parajuli N，MacMillan-Crow LA.还原锰超氧化物歧化酶在缺血再灌注损伤中的作用：自噬和线粒体生物合成的可能触发因素？Am J Physiol Renal Physiol 304：F257-F267，2013。首次发表于2012年11月28日; doi：10.1152/ajprenal.00435.2012.-超氧化物的过度产生和线粒体功能障碍已被描述为缺血再灌注（I/R）损伤过程中的重要事件。我们的实验室已经证明，锰超氧化物歧化酶（MnSOD），一种主要的线粒体抗氧化剂，消除超氧化物，在肾移植和肾I/R过程中失活，并在肾衰竭的发展之前。我们假设MnSOD在肾I/R期间在肾中的敲低增加了肾损伤。使用新表征的肾特异性MnSOD敲除（KO）小鼠，评价I/R后肾损伤和氧化剂产生的程度。这些KO小鼠（无I/R）在远端肾单位中表现出MnSOD的低表达和活性，肾形态改变，氧化剂产生增加，但令人惊讶的是，肾功能没有改变。I/R后，MnSOD KO小鼠与野生型小鼠相比，远端肾单位显示出相似的损伤水平。此外，肾功能，MnSOD活性，肾小管细胞死亡没有显着改变后I/R的两种基因型之间。有趣的是，MnSOD KO单独增加远端肾单位内的自噬体形成、线粒体生物发生和DNA复制/修复。这些结果表明，MnSOD敲低导致的慢性氧化应激诱导了多种协调的细胞存活信号，包括自噬和线粒体生物合成，从而保护肾脏免受I/R后的急性氧化应激。
Parajuli N, MacMillan-Crow LA. Role of reduced manganese superoxide dismutase in ischemia-reperfusion injury: a possible trigger for autophagy and mitochondrial biogenesis? Am J Physiol Renal Physiol 304: F257-F267, 2013. First published November 28, 2012; doi:10.1152/ajprenal.00435.2012.-Excessive generation of superoxide and mitochondrial dysfunction has been described as being important events during ischemia-reperfusion (I/R) injury. Our laboratory has demonstrated that manganese superoxide dismutase (MnSOD), a major mitochondrial antioxidant that eliminates superoxide, is inactivated during renal transplantation and renal I/R and precedes development of renal failure. We hypothesized that MnSOD knockdown in the kidney augments renal damage during renal I/R. Using newly characterized kidney-specific MnSOD knockout (KO) mice the extent of renal damage and oxidant production after I/R was evaluated. These KO mice (without I/R) exhibited low expression and activity of MnSOD in the distal nephrons, had altered renal morphology, increased oxidant production, but surprisingly showed no alteration in renal function. After I/R the MnSOD KO mice showed similar levels of injury to the distal nephrons when compared with wild-type mice. Moreover, renal function, MnSOD activity, and tubular cell death were not significantly altered between the two genotypes after I/R. Interestingly, MnSOD KO alone increased autophagosome formation, mitochondrial biogenesis, and DNA replication/repair within the distal nephrons. These findings suggest that the chronic oxidative stress as a result of MnSOD knockdown induced multiple coordinated cell survival signals including autophagy and mitochondrial biogenesis, which protected the kidney against the acute oxidative stress following I/R.