Increased vulnerability to rotenone-induced neurotoxicity in ceruloplasmin-deficient mice
Increased vulnerability to rotenone-induced neurotoxicity in ceruloplasmin-deficient mice
复制标题
DOI：
10.1016/j.neulet.2008.08.089
复制
发表时间：
2008-11-28
影响因子：
2.5
通讯作者：
Ikeda, Shu-ichi
中科院分区：
文献类型：
--
作者：
Kaneko, Kazuma;Hineno, Akiyo;Ikeda, Shu-ichi
铜蓝蛋白（Cp）是人血浆中最强的铁氧化酶。这种蛋白质的遗传性缺乏，称为aceruloplasminemia，是一个有趣的模型，以阐明氧化应激诱导的神经退行性变的发病机制和病理生理学。在血浆蛋白血症患者的大脑中观察到由于过量铁积累而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，可诱导类似帕金森病的神经退行性变。我们使用鱼藤酮处理的Cp缺陷小鼠脑研究Cp缺陷对神经变性的影响。免疫组织化学检查表明，丙烯醛，脂质过氧化物的产物之一，和泛素更显着免疫反应的鱼藤酮治疗，CP缺陷小鼠的大脑比鱼藤酮未处理，CP缺陷或鱼藤酮治疗，野生型小鼠。这些分子定位于神经元细胞中。这些结果表明，在不存在Cp的情况下，鱼藤酮诱导的脂质过氧化和遍在蛋白免疫反应性的积累增强。因此，Cp可以保护神经元细胞免受氧化应激诱导的神经变性。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.