Neuromolecular Biology Laboratory, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Jinghua Road 24, Luoyang, 471003, People's Republic of China.
Department of Neurology, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, People's Republic of China.
Neurotox Res. 2023 Jun;41(3):242-255. doi: 10.1007/s12640-023-00636-5. Epub 2023 Feb 4.
Oxidative stress plays a crucial role in the occurrence and development of Parkinson's disease (PD). Rutin, a natural botanical ingredient, has been shown to have antioxidant properties. Therefore, the aim of this study was to investigate the neuroprotective effects of rutin on PD and the underlying mechanisms. MPP(1-methyl-4-phenylpyridinium ions)-treated SH-SY5Y cells were used as an in vitro model of PD. Human PHB2-shRNA lentiviral particles were transfected into SH-SY5Y cells to interfere with the expression of Prohibitin2 (PHB2). The oxidative damage of cells was analyzed by detecting intracellular reactive oxygen species (ROS), malondialdehyde (MDA), and mitochondrial membrane potential (MMP). Western blotting was used to detect the protein expression of antioxidant factors such as nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH quinone oxidoreductase-1 (NQO-1), and mitophagy factors PHB2, translocase of outer mitochondrial membrane 20 (TOM20), and LC3II/LC3I (microtubule-associated protein II light chain 3 (LC3II) to microtubule-associated protein I light chain 3 (LC3I)). In addition, we also examined the expression of PHB2 and LC3II/LC3I by immunofluorescence staining. MPP treatment significantly increased the generation of ROS and MDA and the level of MMP depolarization and decreased the protein expression of Nrf2, HO-1, NQO1, TOM20, PHB2, and LC3II/LC3I. In MPP-treated SH-SY5Y cells, rutin significantly decreased the generation of ROS and MDA and the level of MMP depolarization and increased the protein expression of Nrf2, HO-1, NQO-1, TOM20, PHB2, and LC3II/LC3I. However, the protective role of rutin was inhibited in PHB2-silenced cells. Rutin attenuates oxidative damage which may be associated with PHB2-mediated mitophagy in MPP-induced SH-SY5Y cells. Rutin might be used as a potential drug for the prevention and treatment of PD.
氧化应激在帕金森病（PD）的发生和发展中起着关键作用。芦丁是一种天然植物成分，具有抗氧化特性。因此，本研究旨在探讨芦丁对 PD 的神经保护作用及其潜在机制。MPP（1-甲基-4-苯基吡啶离子）处理的 SH-SY5Y 细胞被用作 PD 的体外模型。将人 PHB2-shRNA 慢病毒颗粒转染到 SH-SY5Y 细胞中，以干扰 Prohibitin2（PHB2）的表达。通过检测细胞内活性氧（ROS）、丙二醛（MDA）和线粒体膜电位（MMP）来分析细胞的氧化损伤。Western blot 用于检测抗氧化因子的蛋白表达，如核因子 E2 相关因子 2（Nrf2）、血红素加氧酶-1（HO-1）、NADPH 醌氧化还原酶-1（NQO-1）和自噬因子 PHB2、外线粒体膜转位酶 20（TOM20）和微管相关蛋白 II 轻链 3（LC3II）到微管相关蛋白 I 轻链 3（LC3I）。此外，我们还通过免疫荧光染色检测了 PHB2 和 LC3II/LC3I 的表达。MPP 处理显著增加了 ROS 和 MDA 的产生以及 MMP 去极化的水平，并降低了 Nrf2、HO-1、NQO1、TOM20、PHB2 和 LC3II/LC3I 的蛋白表达。在 MPP 处理的 SH-SY5Y 细胞中，芦丁显著降低了 ROS 和 MDA 的产生以及 MMP 去极化的水平，并增加了 Nrf2、HO-1、NQO-1、TOM20、PHB2 和 LC3II/LC3I 的蛋白表达。然而，在 PHB2 沉默的细胞中，芦丁的保护作用受到抑制。芦丁减轻氧化损伤可能与 MPP 诱导的 SH-SY5Y 细胞中 PHB2 介导的自噬有关。芦丁可能被用作预防和治疗 PD 的潜在药物。
