Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang, People's Republic of China.
Antioxid Redox Signal. 2013 Jan 10;18(2):158-69. doi: 10.1089/ars.2011.4285. Epub 2012 Aug 28.
Mitochondrial ferritin (MtFt), which was recently discovered, plays an important role in preventing neuronal damage in 6-hydroxydopamine-induced Parkinsonism by maintaining mitochondrial iron homeostasis. Disruption of iron regulation also plays a key role in the etiology of Alzheimer's disease (AD). To explore the potential neuroprotective roles of MtFt, rats and cells were treated with Aβ(25-35) to establish an AD model.
We report that knockdown of MtFt expression significantly enhanced Aβ(25-35)-induced neurotoxicity as shown by dysregulation of iron homeostasis, enhanced oxidative stress, and increased cell apoptosis. Opposite results were obtained when MtFt was overexpressed in SH-SY5Y cells prior to treatment with Aβ(25-35). Further, MtFt inhibited Aβ(25-35)-induced P38 mitogen-activated protein kinase and activated extracellular signal-regulated kinase (Erk) signaling.
MtFt attenuated Aβ(25-35)-induced neurotoxicity and reduced oxidative damage through Erk/P38 kinase signaling.
Our results show a protective role of MtFt in AD and suggest that regulation of MtFt expression in neuronal cells may provide a new neuroprotective strategy for AD.
最近发现的线粒体铁蛋白（MtFt）通过维持线粒体铁稳态在 6-羟多巴胺诱导的帕金森病中防止神经元损伤方面发挥着重要作用。铁调节的破坏在阿尔茨海默病（AD）的发病机制中也起着关键作用。为了探索 MtFt 的潜在神经保护作用，用 Aβ（25-35）处理大鼠和细胞以建立 AD 模型。
我们报告说，下调 MtFt 表达可通过破坏铁稳态、增强氧化应激和增加细胞凋亡，显著增强 Aβ（25-35）诱导的神经毒性。在用 Aβ（25-35）处理之前在 SH-SY5Y 细胞中过表达 MtFt 时，得到了相反的结果。此外，MtFt 抑制了 Aβ（25-35）诱导的 P38 丝裂原活化蛋白激酶并激活了细胞外信号调节激酶（Erk）信号通路。
MtFt 通过 Erk/P38 激酶信号减轻 Aβ（25-35）诱导的神经毒性和减少氧化损伤。
我们的研究结果表明 MtFt 在 AD 中具有保护作用，并提示调节神经元细胞中的 MtFt 表达可能为 AD 提供新的神经保护策略。
