Involvement of ferroptosis in human motor neuron cell death
Involvement of ferroptosis in human motor neuron cell death
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DOI：
10.1016/j.bbrc.2021.05.095
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发表时间：
2021-06-07
影响因子：
3.1
通讯作者：
Yano, Masato
中科院分区：
文献类型：
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作者：
Matsuo, Tsuyoshi;Adachi-Tominari, Keiko;Yano, Masato
铁凋亡是近年来发现的一种依赖于铁和脂质过氧化作用的细胞程序性死亡。它在生物学上不同于其他类型的细胞死亡，如凋亡。虽然铁凋亡在癌症、患者和动物模型中的参与已经被深入研究，但在人类运动神经元模型中的铁凋亡仍然是未知的。在这里，我们使用人iPS细胞衍生的运动神经元（hiMN）仔细评估了铁凋亡。我们发现，几乎所有的hiMN通过谷胱甘肽过氧化物酶4（GPX 4）抑制剂的治疗而死亡。重要的是，细胞死亡被一种抗氧化剂、维生素E乙酸酯、铁螯合剂和具有高动态范围的脂质过氧化物酶抑制剂拯救。最后，这些数据清楚地表明，铁凋亡组成性地发生在hiMN中，表明它可能在运动神经元死亡如运动神经元疾病（MND）/肌萎缩性侧索硬化（ALS）中发挥生物学和病理学重要作用的可能性。(c)2021爱思唯尔公司All rights reserved.
Ferroptosis was recently defined as a novel type of programmed cell death depending on iron and lipid peroxidation. It is biologically different from other types of cell death such as apoptosis. While the involvement of ferroptosis in cancer, patient and animal model have been intensely studied, ferroptosis in human motor neuron model is still clearly unknown. Here we carefully assessed ferroptosis using human iPS cell-derived motor neuron (hiMNs). We found that almost all hiMNs died by the treatment of glutathione peroxidase 4 (GPX4) inhibitors. Importantly, the cell death was rescued by one antioxidant, vitamin E acetate, iron chelators and lipid peroxidase inhibitors with high dynamic ranges. Finally, these data clearly indicated that ferroptosis constitutively occurs in hiMNs, suggesting the possibility that it might play a biologically and pathologically important roles in motor neuron death such as motor neuron disease (MND)/Amyotrophic lateral sclerosis (ALS).(c) 2021 Elsevier Inc. All rights reserved.