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对微小RNA表达谱的综合评估揭示了超顺磁性氧化铁纳米颗粒(SPIONs)通过N-甲基-D-天冬氨酸受体产生的神经信号特异性细胞毒性。

Comprehensive evaluation of microRNA expression profiling reveals the neural signaling specific cytotoxicity of superparamagnetic iron oxide nanoparticles (SPIONs) through N-methyl-D-aspartate receptor.

作者信息

Sun Bo, Liu Rui, Ye Nan, Xiao Zhong-Dang

机构信息

State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, P. R. China; Institute of Microbiology, School of Biological Sciences, Seoul National University, Seoul, South Korea.

Laboratory of Biophysics, School of Biological Sciences, Seoul National University, Seoul, South Korea.

出版信息

PLoS One. 2015 Mar 23;10(3):e0121671. doi: 10.1371/journal.pone.0121671. eCollection 2015.

Abstract

Though nanomaterials are considered as drug carriers or imaging reagents targeting the central nervous system their cytotoxicity effect on neuronal cells has not been well studied. In this study, we treated PC12 cells, a model neuronal cell line, with a nanomaterial that is widely accepted for medical use, superparamagnetic iron oxide nanoparticles (SPIONs). Our results suggest that, after treated with SPIONs, the expression pattern of the cellular miRNAs changed widely in PC12 cells. As potential miRNA targets, NMDAR, one of the candidate mRNAs that were selected using GO and KEGG pathway enrichment, was significantly down regulated by SPIONs treatment. We further illustrated that SPIONs may induce cell death through NMDAR suppression. This study revealed a NMDAR neurotoxic effect of SPIONs and provides a reliable approach for assessing the neurocytotoxic effects of nanomaterials based on the comprehensive annotation of miRNA profiling.

摘要

尽管纳米材料被视为靶向中枢神经系统的药物载体或成像试剂,但其对神经元细胞的细胞毒性作用尚未得到充分研究。在本研究中,我们用一种在医学上广泛应用的纳米材料——超顺磁性氧化铁纳米颗粒(SPIONs)处理了一种模型神经元细胞系PC12细胞。我们的结果表明,用SPIONs处理后,PC12细胞中细胞miRNA的表达模式发生了广泛变化。作为潜在的miRNA靶点,使用GO和KEGG通路富集筛选出的候选mRNA之一NMDAR,在SPIONs处理后显著下调。我们进一步证明,SPIONs可能通过抑制NMDAR诱导细胞死亡。本研究揭示了SPIONs的NMDAR神经毒性作用,并基于miRNA谱的综合注释提供了一种评估纳米材料神经细胞毒性作用的可靠方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c43f/4370573/d675000c79d7/pone.0121671.g001.jpg

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