首页> 美国卫生研究院文献>Antioxidants Redox Signaling >May the Evaluation of Nitrosative Stress Through Selective Increase of 3-Nitrotyrosine Proteins Other Than Nitroalbumin and Dominant Tyrosine-125/136 Nitrosylation of Serum α-Synuclein Serve for Diagnosis of Sporadic Parkinsons Disease?
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May the Evaluation of Nitrosative Stress Through Selective Increase of 3-Nitrotyrosine Proteins Other Than Nitroalbumin and Dominant Tyrosine-125/136 Nitrosylation of Serum α-Synuclein Serve for Diagnosis of Sporadic Parkinsons Disease?

机译:是否可以通过选择性增加除血清白蛋白和主要酪氨酸125/136的α-突触核蛋白亚硝化以外的3-硝基酪氨酸蛋白来评估散发性帕金森氏病的亚硝酸盐应激?

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摘要

Nitrosative stress, where nitrosylation of tyrosine (Tyr) leading to 3-nitrotyrosine proteins or free 3-nitrotyrosine is the most prominent change, has been proposed as a pathogenic mechanism in Parkinson's disease (PD). Levels of 3-nitrotyrosine proteins in serum and cerebrospinal fluid (CSF) of patients with PD have not been studied. Nitrosative stress-induced protein changes in serum and CSF were analyzed in patients with PD (n=54) and controls (n=40). Herein, we demonstrate the presence of nitrosative stress in serum and CSF of patients with early PD leading to selective increase of 3-nitrotyrosine proteins other than nitroalbumin, without free 3-nitrotyrosine (Hoehn-Yahr stage 1, p<0.05; stage 2, p<0.01). Among 3-nitrotyrosine proteins, nitro-α-synuclein (N-αSyn) was detected in serum, not CSF, and the sites of Tyr nitrosylation were observed to be modified in patients with early PD. Thus, the intensity of nitrosylation of Tyr125/136 residues is enhanced (stage 1, p<0.05; stage 2, p<0.01), and that of the Tyr39 site is reduced (stage 1, p<0.05), and the ratio between both parameters (α-synuclein with nitrosylated tyrosines 125 and 136 [N-αSyn-Tyr125/136]:α-synuclein with nitrosylated tyrosine 39 [N-αSyn-Tyr39] ratio) is significantly higher in patients with early PD (p<0.01). These observations lead to the hypothesis that evaluating nitrosative stress through enhanced levels of 3-nitrotyrosine proteins in serum and CSF without changes in nitroalbumin, together with the profile of tyrosine nitrosylation of serum αSyn characterized by dominant nitrosylation of Tyr125/136, could serve for the diagnosis of sporadic PD. Antioxid. Redox Signal. 19, 912–918.
机译:已经提出亚硝酸盐胁迫是酪氨酸(Tyr)的亚硝基化导致3-硝基酪氨酸蛋白或游离的3-硝基酪氨酸最显着的变化,它是帕金森氏病(PD)的致病机制。 PD患者血清和脑脊液(CSF)中的3-硝基酪氨酸蛋白水平尚未进行研究。在患有PD(n = 54)和对照组(n = 40)的患者中分析了亚硝酸盐诱导的血清和CSF中蛋白质的变化。在此,我们证明了早期PD患者血清和脑脊液中存在亚硝化应激,导致选择性合成增加了除了游离白蛋白以外的3-硝基酪氨酸而不是游离的3-硝基酪氨酸(Hoehn-Yahr第1阶段,p <0.05;第2阶段p <0.01)。在3-硝基酪氨酸蛋白中,在血清中检测到硝基-α-突触核蛋白(N-αSyn),而非脑脊液,并且观察到早期PD患者的Tyr亚硝化位点被修饰。因此,增强了Tyr125 / 136残基的亚硝化强度(阶段1,p <0.05;阶段2,p <0.01),并且降低了Tyr39位点的硝基化强度(阶段1,p <0.05),并且早期PD患者的两个参数(α-突触核蛋白与亚硝化酪氨酸125和136 [N-αSyn-Tyr125/ 136]:α-突触核蛋白与亚硝化酪氨酸39 [N-αSyn-Tyr39]的比率)在PD早期患者中明显更高(p <0.01 )。这些观察结果得出这样的假设:通过提高血清和脑脊液中3-硝基酪氨酸蛋白的水平而不改变硝基白蛋白来评估亚硝化应激,以及以Tyr125 / 136的显性亚硝基化为特征的血清αSyn酪氨酸亚硝化的概况,可以为诊断散发性PD。抗氧化。氧化还原信号。 19,912–918。

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