50-Hz Magnetic Field Impairs the Expression of Iron-related Genes in the <i>in vitro</i> SOD1<sup>G93A</sup> Model of Amyotrophic Lateral Sclerosis
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<b>Purpose:</b> we characterized the response to the extremely low frequency magnetic field (ELF-MF) in an <i>in vitro</i> model of familial Amyotrophic Lateral Sclerosis (<i>f</i>ALS), carrying two mutant variants of the superoxide dismutase 1 (SOD1) gene. <b>Materials and methods:</b> SH-SY5Y human neuroblastoma cells, stably over-expressing the wild type, the G93A or the H46R mutant SOD1 cDNA, were exposed to either the ELF-MF (50 Hz, 1 mT) or the sham control field, up to 72 hours. Analysis of i) viability, proliferation and apoptosis, ii) reactive oxygen species generation, and iii) assessment of the iron metabolism, were carried out in all clones in response to the MF exposure. <b>Results:</b> we report that 50-Hz MF exposure induces: i) no change in proliferation and viability; ii) no modulation of the intracellular superoxide and H<sub>2</sub>O<sub>2</sub> levels; iii) a significant deregulation in the expression of iron-related genes <i>IRP1</i>, <i>MFRN1</i> and <i>TfR1</i>, this evidence being exclusive for the SOD1<sup>G93A</sup> clone and associated with a slight (<i>P</i> = 0.0512) difference in the total iron content. <b>Conclusions:</b> 50-Hz MF affects iron homeostasis in the <i>in vitro</i> SOD1<sup>G93A</sup> ALS model.
研究目的:本研究在携带超氧化物歧化酶1(superoxide dismutase 1, SOD1)基因两种突变变体的家族性肌萎缩侧索硬化(familial Amyotrophic Lateral Sclerosis, fALS)体外(in vitro)模型中,表征了极低频磁场(extremely low frequency magnetic field, ELF-MF)的应答效应。 材料与方法:将稳定过表达野生型、G93A或H46R突变型SOD1互补脱氧核糖核酸(complementary DNA, cDNA)的人神经母细胞瘤SH-SY5Y细胞,暴露于极低频磁场(50 Hz、1 mT)或假对照磁场中,暴露时长最长达72小时。针对所有细胞克隆,开展以下三项检测以分析磁场暴露的影响:① 细胞活力、增殖与凋亡分析;② 活性氧生成量检测;③ 铁代谢评估。 结果:本研究发现50 Hz磁场暴露可引发如下效应:① 细胞增殖与活力无显著变化;② 细胞内超氧化物及过氧化氢(H₂O₂)水平未出现明显调控;③ 铁相关基因IRP1、MFRN1与TfR1的表达出现显著失调,该现象仅见于SOD1<sup>G93A</sup>细胞克隆,且与总铁含量的微小差异(*P* = 0.0512)相关。 结论:50 Hz极低频磁场可影响体外SOD1<sup>G93A</sup> ALS模型的铁稳态。



