Abstract
The potential toxicity of nanoparticles, particularly to neurons, is a major concern. In this study, we assessed the cytotoxicity of silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye (MNPs@SiO2(RITC)) in HEK293 cells, SH-SY5Y cells, and rat primary cortical and dopaminergic neurons. In cells treated with 1.0 μg/μl MNPs@SiO2(RITC), the expression of several genes related to the proteasome pathway was altered, and proteasome activity was significantly reduced, compared with control and with 0.1 μg/μl MNPs@SiO2(RITC)-treated cells. Due to the reduction of proteasome activity, formation of cytoplasmic inclusions increased significantly in HEK293 cells over-expressing the α–synuclein interacting protein synphilin-1 as well as in primary cortical and dopaminergic neurons. Primary neurons, particularly dopaminergic neurons, were more vulnerable to MNPs@SiO2(RITC) than SH-SY5Y cells. Cellular polyamines, which are associated with protein aggregation, were significantly altered in SH-SY5Y cells treated with MNPs@SiO2(RITC). These findings highlight the mechanisms of neurotoxicity incurred by nanoparticles.
Highlights
Previous studies have found that certain NPs, such as N-iso-propylacrylamine and N-tert-butylacrylamide copolymer NPs, may play a role in protein fibrillization[8]
We assessed the effect of exposure to 0.1 or 1.0 μg/μl Magnetic nanoparticles (MNPs)@SiO2(RITC) for 12 h in human embryonic kidney 293 (HEK293) cells on ubiquitin proteasome system (UPS)-related genes using microarray expression analysis and MultiExperiment Viewer (MeV) software
The increase in ROS generation by MNPs@SiO2(RITC) in neuronal cells is consistent with our previous finding in HEK293 cells, which was linked to mitochondrial dysfunction and reduced ATP generation[12], and is closely related to decreased proteasome activity[28]
Summary
Previous studies have found that certain NPs, such as N-iso-propylacrylamine and N-tert-butylacrylamide copolymer NPs, may play a role in protein fibrillization[8]. In a cellular model of Huntington’s disease, silica NPs caused nuclear protein aggregation, which was closely linked to proteasome activity[9]. Translocation of nanoparticles into inclusion bodies inside cells has not been studied so far, there is sufficient data to suggest that these particles greatly enhance the process of protein aggregation and fibrillization[10]. ROS generation and UPS dysfunction can be countered successfully in cells as an adaptive mechanism[16], abnormal protein aggregation and the subsequent reduction in proteasome activity are common features of neurodegenerative disorders. The impact and localization of NPs into cytoplasmic inclusions in neurons is not well understood Biogenic polyamines, such as putrescine, spermidine and spermine, are scavengers of ROS23. A comprehensive approach to evaluate MNPs@SiO2(RITC)-induced toxicity was employed by assessing gene expression, protein aggregation, and metabolic changes
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
