Huang Hui, Chen Jun, Lu Huiru, Zhou Mengxue, Chai Zhifang, Hu Yi
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multidisciplinary Research Division, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, 100049, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Biometals. 2017 Aug;30(4):623-628. doi: 10.1007/s10534-017-0023-0. Epub 2017 Jun 12.
Deregulated iron homeostasis is generally believed to be implicated in neurodegenerative diseases, including Parkinson's disease. Nevertheless, it is not fully understood how iron overload can elicit neuronal cell damage. Here we examined mitochondrial reactive oxygen species (ROS) levels in human dopaminergic neuroblastoma SH-SY5Y cells upon iron exposure. A relatively high concentration of iron could significantly increase mitochondrial ROS levels in SH-SY5Y cells. Pharmacological activation of AMP-activated protein kinase (AMPK) almost completely inhibited the effect of iron on mitochondrial ROS. By contrast, AMPK inhibition aggravated the neurotoxicity of iron and enhanced the production of mitochondrial ROS. Collectively, these findings suggested that excess iron may be able to perturb mitochondrial function, and AMPK activity is important for the association of iron and mitochondria.
普遍认为，铁稳态失调与包括帕金森病在内的神经退行性疾病有关。然而，铁过载如何引发神经元细胞损伤尚不完全清楚。在这里，我们检测了铁暴露后人多巴胺能神经母细胞瘤SH-SY5Y细胞中的线粒体活性氧（ROS）水平。相对高浓度的铁可显著增加SH-SY5Y细胞中的线粒体ROS水平。AMP激活蛋白激酶（AMPK）的药理学激活几乎完全抑制了铁对线粒体ROS的影响。相比之下，AMPK抑制加重了铁的神经毒性并增强了线粒体ROS的产生。总的来说，这些发现表明过量的铁可能会扰乱线粒体功能，而AMPK活性对于铁与线粒体的关联很重要。
