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极低频磁场(ELF-MF)暴露使 SH-SY5Y 细胞对帕金森病毒剂 MPP(.)敏感。

Extremely Low Frequency Magnetic Field (ELF-MF) Exposure Sensitizes SH-SY5Y Cells to the Pro-Parkinson's Disease Toxin MPP(.).

机构信息

Health Protection Technology Division, ENEA-Casaccia, 00123, Rome, Italy.

Department of Biology, Tor Vergata University, Rome, Italy.

出版信息

Mol Neurobiol. 2016 Aug;53(6):4247-4260. doi: 10.1007/s12035-015-9354-4. Epub 2015 Jul 30.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss, with an etiopathogenesis involving both genetic and environmental factors. The occupational/residential exposure to the electromagnetic fields has been recently associated with an increased risk of neurodegenerative diseases; it has been thus proposed that the extremely low frequency magnetic field (ELF-MF) may contribute to neurodegenerative etiopathogenesis, as its interaction with biological systems directly impairs redox homeostasis in specific areas of the brain. The molecular mechanisms elicited by ELF-MF, and their potential involvement in PD onset, still remain unclear. To this end, we set up a generator of ELF-MF able to stably and homogeneously reproduce environmental prolonged exposure to ELF-MF (50 Hz, 1 mT). Results obtained indicate that ELF-MF exposure alters cell response of SH-SY5Y cells to MPP(+). We demonstrate that ELF-MF does not affect per se survival, shape, and morphology of both proliferating and differentiated SH-SY5Y cells but significantly impairs redox homeostasis and thiol content, triggering an increase in protein carbonylation. As a result, toxicity of MPP(+), even at low doses, is highly enhanced in ELF-MF-exposed cells due to a significant increase in ROS levels, potentiation of oxidative damage, and induction of a caspase-dependent apoptosis. Pre-incubation with the thiol antioxidants N-acetyl-L-cysteine and GSH ethyl-ester significantly reduces the extent of oxidative damage and protects cells from death induced by the combined treatment ELF-MF/MPP(+). Taken overall, our results demonstrate the redox-based molecular interaction between ELF-MF and PD neurotoxins in vitro, and open a new scenario for defining the synergy of environmental factors in PD onset.

摘要

帕金森病(PD)是一种神经退行性疾病,其特征是多巴胺能神经元丧失,其病因发病机制涉及遗传和环境因素。最近有研究表明,职业/居住环境电磁场暴露与神经退行性疾病风险增加有关;因此,有人提出极低频磁场(ELF-MF)可能通过直接损害大脑特定区域的氧化还原平衡来促进神经退行性病因发病机制。ELF-MF 引起的分子机制及其在 PD 发病中的潜在作用仍不清楚。为此,我们建立了一个 ELF-MF 发生器,能够稳定且均匀地再现环境中长时间暴露于 ELF-MF(50 Hz,1 mT)。结果表明,ELF-MF 暴露改变了 SH-SY5Y 细胞对 MPP(+)的细胞反应。我们证明 ELF-MF 本身不会影响增殖和分化的 SH-SY5Y 细胞的存活、形状和形态,但会显著破坏氧化还原平衡和巯基含量,引发蛋白质羰基化增加。结果,由于 ROS 水平显著增加、氧化损伤增强和 caspase 依赖性细胞凋亡诱导,即使在低剂量下,MPP(+)的毒性在暴露于 ELF-MF 的细胞中也得到了高度增强。用巯基抗氧化剂 N-乙酰-L-半胱氨酸和 GSH 乙酯进行预孵育可显著降低氧化损伤程度并保护细胞免受 ELF-MF/MPP(+)联合处理诱导的死亡。总体而言,我们的研究结果证明了 ELF-MF 与 PD 神经毒素之间的基于氧化还原的分子相互作用,并为定义环境因素在 PD 发病中的协同作用开辟了新的前景。

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