Department of Chemistry, Biology and Biotechnology, University of Perugia, 06123 Perugia, Italy.
Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
Int J Mol Sci. 2020 Apr 16;21(8):2761. doi: 10.3390/ijms21082761.
Oxidative stress is considered to be a key factor of the pathogenesis of Parkinson's disease, a multifactorial neurodegenerative disorder characterized by reduced dopaminergic neurons in the and accumulated protein aggregates. Rotenone is a worldwide-used pesticide that induces the most common features of Parkinson's by direct inhibition of the mitochondrial complex I. Rotenone-induced Parkinson's models, as well as brain tissues from Parkinson's patients, are characterized by the presence of both lipid peroxidation and protein oxidation markers resulting from the increased level of free radical species. Oxidation introduces several modifications in protein structure, including carbonylation and nitrotyrosine formation, which severely compromise cell function. Due to the link existing between oxidative stress and Parkinson's disease, antioxidant molecules could represent possible therapeutic tools for this disease. In this study, we evaluated the effect of curcumin, a natural compound known for its antioxidant properties, in dopaminergic PC12 cells treated with rotenone, a cell model of Parkinsonism. Our results demonstrate that the treatment of PC12 cells with rotenone causes severe protein damage, with formation of both carbonylated and nitrotyrosine-derived proteins, whereas curcumin (10 µM) co-exposure exerts protective effects by reducing the levels of oxidized proteins. Curcumin also promotes proteasome activation, abolishing the inhibitory effect exerted by rotenone on this degradative system.
氧化应激被认为是帕金森病发病机制的关键因素，帕金森病是一种多因素神经退行性疾病，其特征是中脑多巴胺能神经元减少和积累的蛋白质聚集体。鱼藤酮是一种在世界范围内使用的杀虫剂，通过直接抑制线粒体复合物 I 来诱导最常见的帕金森病特征。鱼藤酮诱导的帕金森病模型以及帕金森病患者的脑组织，其特征是存在脂质过氧化和蛋白质氧化标志物，这是由于自由基水平的增加所致。氧化会导致蛋白质结构发生多种修饰，包括羰基化和硝基酪氨酸的形成，从而严重损害细胞功能。由于氧化应激与帕金森病之间存在联系，抗氧化分子可能成为治疗这种疾病的潜在工具。在这项研究中，我们评估了姜黄素（一种以其抗氧化特性而闻名的天然化合物）对鱼藤酮处理的多巴胺能 PC12 细胞（帕金森病的细胞模型）的影响。我们的研究结果表明，鱼藤酮处理 PC12 细胞会导致严重的蛋白质损伤，形成羰基化和硝基酪氨酸衍生的蛋白质，而姜黄素（10 µM）共同暴露则通过降低氧化蛋白质的水平发挥保护作用。姜黄素还促进蛋白酶体的激活，消除鱼藤酮对该降解系统的抑制作用。
