Kaneko Kazuma, Hineno Akiyo, Yoshida Kunihiro, Ikeda Shu-ichi
Department of Neurology and Rheumatology, Shinshu University School of Medicine, 3-1-1 Asahi, 390-8621 Matsumoto, Japan.
Neurosci Lett. 2008 Nov 28;446(1):56-8. doi: 10.1016/j.neulet.2008.08.089. Epub 2008 Sep 11.
Ceruloplasmin (Cp) is the strongest ferroxidase in human plasma. Hereditary deficiency of this protein, named aceruloplasminemia, is an interesting model to elucidate the pathogenesis and pathophysiology of neurodegeneration induced by oxidative stress. Enhanced oxidative stress due to excessive iron accumulation is observed in the brains of aceruloplasminemia patients. Rotenone, a selective mitochondrial complex I inhibitor, induces neurodegeneration mimicking Parkinson's disease. We investigated the influence of Cp deficiency upon neurodegeneration using rotenone-treated, Cp-deficient mouse brains. Immunohistochemical examination showed that acrolein, one of the products of lipid peroxides, and ubiquitin were more markedly immunoreacted in the brains of rotenone-treated, Cp-deficient mice than in rotenone-untreated, Cp-deficient or rotenone-treated, wild-type mice. These molecules were localized in neuronal cells. These results suggested that rotenone-induced lipid peroxidation and accumulation of ubiquitin immunoreactivity were enhanced in the absence of Cp. Therefore, Cp may protect neuronal cells from oxidative stress-induced neurodegeneration.
铜蓝蛋白（Cp）是人体血浆中最强的铁氧化酶。这种蛋白质的遗传性缺乏，即无铜蓝蛋白血症，是阐明氧化应激诱导神经退行性变的发病机制和病理生理学的一个有趣模型。在无铜蓝蛋白血症患者的大脑中观察到由于铁过度积累导致的氧化应激增强。鱼藤酮是一种选择性线粒体复合物I抑制剂，可诱导模拟帕金森病的神经退行性变。我们使用鱼藤酮处理的无铜蓝蛋白血症小鼠大脑研究了Cp缺乏对神经退行性变的影响。免疫组织化学检查显示，脂质过氧化物的产物之一丙烯醛和泛素在鱼藤酮处理的无铜蓝蛋白血症小鼠大脑中的免疫反应比未用鱼藤酮处理的无铜蓝蛋白血症小鼠或鱼藤酮处理的野生型小鼠更明显。这些分子定位于神经元细胞。这些结果表明，在缺乏Cp的情况下，鱼藤酮诱导的脂质过氧化和泛素免疫反应性的积累增强。因此，Cp可能保护神经元细胞免受氧化应激诱导的神经退行性变。
