Research Centre for Medical Genetics (RCMG), Moscow 115478, Russia.
Institute of Problems of Chemical Physics of Russian Academy of Sciences, Moscow Region 142432, Russia.
Oxid Med Cell Longev. 2019 Jan 17;2019:4398695. doi: 10.1155/2019/4398695. eCollection 2019.
Oxidative stress is a major issue in a wide number of pathologies (neurodegenerative, cardiovascular, immune diseases, and cancer). Because of this, the search for new antioxidants is an important issue. One of the potential antioxidants that has been enthusiastically discussed in the past twenty years is fullerene and its derivatives. Although in aqueous solutions fullerene derivatives have shown to be antioxidants, their properties in this regard within the cells are controversially discussed. We have studied two different water-soluble fullerene C60 and C70 derivatives on human embryonic lung fibroblasts at a wide range of concentrations. Both of them cause a decrease in cellular ROS at short times of incubation (1 hour). Their prolonged action, however, is fundamentally different: derivative GI-761 causes secondary oxidative stress whereas derivative VI-419-P3K keeps ROS levels under control values. To gain a better understanding of this effect, we assessed factors that could play a role in the response of cells to fullerene derivatives. Increased ROS production occurred due to NOX4 upregulation by GI-761. Derivative VI-419-P3K activated the transcription of antioxidant master regulator NRF2 and caused its translocation to the nucleus. This data suggests that the antioxidant effect of fullerene derivatives depends on their chemical structure.
氧化应激是许多病理学（神经退行性疾病、心血管疾病、免疫疾病和癌症）的一个主要问题。因此，寻找新的抗氧化剂是一个重要的问题。在过去的二十年中，富勒烯及其衍生物是一种备受关注的潜在抗氧化剂。尽管富勒烯衍生物在水溶液中表现出抗氧化特性，但它们在细胞内的这方面性质仍存在争议。我们在广泛的浓度范围内研究了两种不同的水溶性富勒烯 C60 和 C70 衍生物对人胚胎肺成纤维细胞的影响。它们都在短时间孵育（1 小时）内降低细胞内的 ROS。然而，它们的长期作用却截然不同：衍生物 GI-761 引起二次氧化应激，而衍生物 VI-419-P3K 则将 ROS 水平控制在正常值以下。为了更好地理解这种效应，我们评估了可能在细胞对富勒烯衍生物的反应中起作用的因素。GI-761 通过上调 NOX4 导致 ROS 产生增加。衍生物 VI-419-P3K 激活了抗氧化主调控因子 NRF2 的转录，并导致其向核内易位。这些数据表明，富勒烯衍生物的抗氧化作用取决于它们的化学结构。
