Zorova Ljubava D, Pevzner Irina B, Chupyrkina Anastasia A, Zorov Savva D, Silachev Denis N, Plotnikov Egor Y, Zorov Dmitry B
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992, Leninskye Gory, House 1, Building 40, Moscow, Russia; International Laser Center, Lomonosov Moscow State University, 119992, Leninskye Gory, House 1, Building 62, Moscow, Russia.
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992, Leninskye Gory, House 1, Building 40, Moscow, Russia.
Chem Biol Interact. 2016 Aug 25;256:64-70. doi: 10.1016/j.cbi.2016.06.020. Epub 2016 Jun 18.
The fate of myoglobin in renal cells was explored in an animal model of rhabdomyolysis known as the pathology highly related to oxidative stress resulting in impairment of renal functioning. The working hypothesis was that the proper degradation of myoglobin in rhabdomyolytic kidney can activate the reparative processes in the tissue. We found that incubation of myoglobin with kidney cells causes its accumulation in the cytoplasm. In rhabdomyolytic rats, the level of heme and free iron in cytoplasm and mitochondria of kidney cells is remarkably increased while inhibition of proteolysis results in further elevation of myoglobin content in the renal tissue. Heme oxygenase and ferritin levels were found to be increased in the kidney tissue at rhabdomyolysis and simulating conditions performed by i/v injection of myoglobin. In addition, the level of peroxidized lipids was high in rhabdomyolytic kidney and became even higher after inhibition of proteolysis by aprotinin. Elevated levels of carbonylated proteins were also observed after rhabdomyolysis, however, if prior to induction of rhabdomyolysis the injection of myoglobin was done, the level of carbonylated proteins dropped versus unprimed kidney tissue thus affording protection to the kidney against oxidative stress. Injection of myoglobin to the rat results in impairment of renal functioning and inhibition of myoglobin degradation in the rhabdomyolytic animal aggravates acute renal failure, demonstrating that degradation of myoglobin is somehow beneficial although it may result in undesired release of free iron which can participate in toxic redox cycling.
在一种横纹肌溶解症的动物模型中，研究了肾细胞中肌红蛋白的命运，该模型的病理学与氧化应激高度相关，会导致肾功能受损。我们的工作假设是，横纹肌溶解症肾脏中肌红蛋白的适当降解可以激活组织中的修复过程。我们发现，将肌红蛋白与肾细胞一起孵育会导致其在细胞质中积累。在横纹肌溶解症大鼠中，肾细胞细胞质和线粒体中的血红素和游离铁水平显著升高，而蛋白水解抑制会导致肾组织中肌红蛋白含量进一步升高。在横纹肌溶解症以及通过静脉注射肌红蛋白模拟的条件下，发现肾组织中的血红素加氧酶和铁蛋白水平升高。此外，横纹肌溶解症肾脏中过氧化脂质水平较高，在用抑肽酶抑制蛋白水解后甚至更高。横纹肌溶解症后也观察到羰基化蛋白水平升高，然而，如果在诱导横纹肌溶解症之前注射肌红蛋白，与未预处理的肾组织相比，羰基化蛋白水平会下降，从而为肾脏提供抗氧化应激的保护。给大鼠注射肌红蛋白会导致肾功能受损，而在横纹肌溶解症动物中抑制肌红蛋白降解会加重急性肾衰竭，这表明肌红蛋白的降解在某种程度上是有益的，尽管它可能导致游离铁的意外释放，而游离铁可能参与有毒的氧化还原循环。
