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

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

doi:10.1371/journal.pone.0121671

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

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

Authors

Bo Sun¹, Rui Liu², Nan Ye³, Zhong-Dang Xiao³

Affiliations

¹ 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.
² Laboratory of Biophysics, School of Biological Sciences, Seoul National University, Seoul, South Korea.
³ State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, P. R. China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Death / drug effects
Computational Biology
Ferric Compounds / chemistry
Ferric Compounds / toxicity*
Gene Expression Profiling / methods
Gene Expression Regulation / drug effects*
Materials Testing
Metal Nanoparticles / chemistry
Metal Nanoparticles / toxicity*
MicroRNAs / chemistry
MicroRNAs / metabolism*
Models, Theoretical
PC12 Cells
Rats
Receptors, N-Methyl-D-Aspartate / chemistry
Receptors, N-Methyl-D-Aspartate / drug effects*

Substances

Ferric Compounds
MicroRNAs
Receptors, N-Methyl-D-Aspartate
ferric oxide

Grants and funding

This work was supported by grants from the Natural Science Foundation of Jiangsu Province (No. BK2012122), the National Natural Science Foundation of China (NSFC) (No. 61071047), and the Major State Basic Research Development Program of China (973 Program) (No. 2013CB932902). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.