Iron and Oxidative Stress in Parkinson's Disease: An Observational Study of Injury Biomarkers.
Iron and Oxidative Stress in Parkinson's Disease: An Observational Study of Injury Biomarkers.
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DOI：
10.1371/journal.pone.0146129
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Fighera MR
中科院分区：
文献类型：
--
作者：
Medeiros MS;Schumacher-Schuh A;Cardoso AM;Bochi GV;Baldissarelli J;Kegler A;Santana D;Chaves CM;Schetinger MR;Moresco RN;Rieder CR;Fighera MR
帕金森病（PD）的特征是由黑质（SN）致密部多巴胺能神经元的进行性丧失引起的进行性运动障碍。除了铁的积累外，活性氧/氮（ROS/RNS）和炎症标志物的产生也增加。这些观察结果表明，铁平衡失调可能在神经退行性变中起关键作用。然而，这种金属相关的氧化应激和神经元损伤的机制尚未完全阐明。确定PD患者外周血铁、铁蛋白和转铁蛋白水平及其与氧化/亚硝化参数的可能关系，同时试图确定这种神经系统疾病的外周血生物标志物概况。40例PD患者和46例对照组比较血清铁、铁蛋白、转铁蛋白、氧化应激标志物（超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、亚硝化应激标志物（NOx）、硫代巴比托酸活性物质（TBARS）、非蛋白硫醇（NPSH）、晚期氧化蛋白产物（AOPP）、血浆铁还原能力（FRAP）和维生素C）以及炎症标志物(ntpases、外泌5′-核苷酸酶、腺苷脱氨酶（ADA）、缺血修饰白蛋白（IMA）和髓过氧化物酶)。PD患者的铁水平较低，而铁蛋白和转铁蛋白没有差异。氧化应激（TBARS和AOPP）和炎症标志物（ntpases， IMA和髓过氧化物酶）在PD中显著升高，而抗氧化剂FRAP，维生素C和非蛋白硫醇在PD中显著降低。SOD、CAT和外泌5′-核苷酸酶在各组间无显著差异，但对照组的NOx和ADA水平显著高于对照组。我们的数据证实了ROS/RNS的产生和神经炎症可能会失调铁稳态，并共同降低铁离子的外周水平，从而导致PD病理生理学的改变。
Parkinson's disease (PD) is characterized by progressive motor impairment attributed to progressive loss of dopaminergic neurons in the substantia nigra (SN) pars compacta. In addition to an accumulation of iron, there is also an increased production of reactive oxygen/nitrogen species (ROS/RNS) and inflammatory markers. These observations suggest that iron dyshomeostasis may be playing a key role in neurodegeneration. However, the mechanisms underlying this metal-associated oxidative stress and neuronal damage have not been fully elucidated. To determine peripheral levels of iron, ferritin, and transferrin in PD patients and its possible relation with oxidative/nitrosative parameters, whilst attempting to identify a profile of peripheral biomarkers in this neurological condition. Forty PD patients and 46 controls were recruited to compare serum levels of iron, ferritin, transferrin, oxidative stress markers (superoxide dismutase (SOD), catalase (CAT), nitrosative stress marker (NOx), thiobarbituric acid reactive substances (TBARS), non-protein thiols (NPSH), advanced oxidation protein products (AOPP), ferric reducing ability of plasma (FRAP) and vitamin C) as well as inflammatory markers (NTPDases, ecto-5’-nucleotidase, adenosine deaminase (ADA), ischemic-modified albumin (IMA) and myeloperoxidase). Iron levels were lower in PD patients, whereas there was no difference in ferritin and transferrin. Oxidative stress (TBARS and AOPP) and inflammatory markers (NTPDases, IMA, and myeloperoxidase) were significantly higher in PD, while antioxidants FRAP, vitamin C, and non-protein thiols were significantly lower in PD. The enzymes SOD, CAT, and ecto-5’-nucleotidase were not different among the groups, although NOx and ADA levels were significantly higher in the controls. Our data corroborate the idea that ROS/RNS production and neuroinflammation may dysregulate iron homeostasis and collaborate to reduce the periphery levels of this ion, contributing to alterations observed in the pathophysiology of PD.