High membrane protein oxidation in the human cerebral cortex.
High membrane protein oxidation in the human cerebral cortex.
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DOI：
10.1016/j.redox.2014.12.013
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发表时间：
2015
期刊：
影响因子：
11.4
通讯作者：
Hajieva P
中科院分区：
文献类型：
--
作者：
Granold M;Moosmann B;Staib-Lasarzik I;Arendt T;Del Rey A;Engelhard K;Behl C;Hajieva P
氧化应激被认为是人类神经退行性疾病中神经元损伤的主要介质之一。然而，事实证明，对因果关系的剖析非常困难。在这里，我们从膜蛋白和细胞质蛋白羰基化的角度分析了三种不同哺乳动物的整体蛋白质氧化：老年人类皮层和来自阿尔茨海默病患者的小脑，年轻动物和老年动物的小鼠皮层和小脑，成年大鼠海马和皮层遭受或未遭受脑缺血。大多数组织显示出相对相似的蛋白质氧化水平。然而，人类皮层受到严重的膜蛋白氧化影响，而细胞质蛋白氧化低于平均水平。相比之下，小鼠皮质组织的体外自氧化主要诱导水相蛋白氧化，而体内生物老化或脑缺血对脑蛋白氧化无主要影响。脂质过氧化也无法预测人类皮层中膜蛋白氧化水平的异常高，因为人类样本中的异前列腺素免疫反应性水平明显低于啮齿动物组织。我们的研究结果表明，老年人类皮层处于特定的和潜在有害的膜蛋白氧化的稳定压力下。人类、小鼠和大鼠在皮层氧化的主要部位上的显著差异，可能导致了将描述啮齿类动物成功抗氧化神经保护的大量数据转化为治疗方法的尚未解决的困难。来自人类大脑皮层的膜蛋白表现出特异性和严重的氧化。这与人类小脑以及任何年龄的小鼠皮层和小脑形成对比。它还与缺血或不缺血的成年大鼠皮质和海马形成对比。脂质过氧化不是膜蛋白氧化的预测因子。膜蛋白氧化可能与即将发生的神经退行性变有关。
Oxidative stress is thought to be one of the main mediators of neuronal damage in human neurodegenerative disease. Still, the dissection of causal relationships has turned out to be remarkably difficult. Here, we have analyzed global protein oxidation in terms of carbonylation of membrane proteins and cytoplasmic proteins in three different mammalian species: aged human cortex and cerebellum from patients with or without Alzheimer's disease, mouse cortex and cerebellum from young and old animals, and adult rat hippocampus and cortex subjected or not subjected to cerebral ischemia. Most tissues showed relatively similar levels of protein oxidation. However, human cortex was affected by severe membrane protein oxidation, while exhibiting lower than average cytoplasmic protein oxidation. In contrast, ex vivo autooxidation of murine cortical tissue primarily induced aqueous protein oxidation, while in vivo biological aging or cerebral ischemia had no major effect on brain protein oxidation. The unusually high levels of membrane protein oxidation in the human cortex were also not predicted by lipid peroxidation, as the levels of isoprostane immunoreactivity in human samples were considerably lower than in rodent tissues. Our results indicate that the aged human cortex is under steady pressure from specific and potentially detrimental membrane protein oxidation. The pronounced difference between humans, mice and rats regarding the primary site of cortical oxidation might have contributed to the unresolved difficulties in translating into therapies the wealth of data describing successful antioxidant neuroprotection in rodents. Membrane proteins from the human cerebral cortex show specific and severe oxidation. This contrasts to human cerebellum and to mouse cortex and cerebellum of any age. It also contrasts to adult rat cortex and hippocampus with or without ischemia. Lipid peroxidation is not a predictor of membrane protein oxidation. Membrane protein oxidation might be related to impending neurodegeneration.