Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milano, Italy.
Antioxid Redox Signal. 2009 Jul;11(7):1559-67. doi: 10.1089/ars.2009.2548.
Increased levels of 3-nitrotyrosine in the central nervous system have been found in patients and mouse models of familial ALS (fALS), suggesting a possible use of nitrated proteins as biomarkers. We analyzed peripheral blood mononuclear cells (PBMCs), easily accessible samples, from sporadic ALS (sALS) patients and a rat model of fALS (a) to establish whether an increased level of nitrated proteins was present in PBMCs, too, and (b) to identify possible candidate biomarkers. With a proteomic approach, we identified for the first time the major overnitrated proteins in PBMCs from patients and rats at different disease stages. In the rats, their increased levels already were measured at a presymptomatic stage. Among them, actin, ATP synthase, and vinculin overlap between sALS patients and the rat model. Interestingly, in a previous study, actin and ATPase have been found overnitrated in the spinal cord of a mouse model of fALS before disease onset, suggesting their possible involvement in motor neuron degeneration. In conclusion, we observed that an increased level of nitrated proteins was not restricted to the spinal cord but also was present in peripheral cells of patients and an animal model, and that nitrated proteins are promising candidate biomarkers for early diagnosis of ALS.
在家族性肌萎缩侧索硬化症（fALS）患者和小鼠模型中，中枢神经系统中的 3-硝基酪氨酸水平升高，这表明硝化蛋白可能作为生物标志物被应用。我们分析了散发性肌萎缩侧索硬化症（sALS）患者和 fALS 大鼠模型的外周血单核细胞（PBMC），这是一种易于获取的样本，目的在于确定硝化蛋白是否也存在于 PBMC 中，并（b）鉴定可能的候选生物标志物。通过蛋白质组学方法，我们首次鉴定了不同疾病阶段患者和大鼠 PBMC 中的主要过硝化蛋白。在大鼠中，它们的水平在亚临床阶段就已经升高。其中，肌动蛋白、ATP 合酶和纽蛋白在 sALS 患者和大鼠模型中都有重叠。有趣的是，在之前的一项研究中，在 fALS 小鼠模型发病前的脊髓中已经发现肌动蛋白和 ATP 酶被过硝化，这表明它们可能参与运动神经元的退化。总之，我们观察到，硝化蛋白水平的升高不仅限于脊髓，而且存在于患者和动物模型的外周细胞中，硝化蛋白是 ALS 早期诊断的有希望的候选生物标志物。
