title: Silica-coated magnetic nanoparticles impair proteasome activity and increase the formation of cytoplasmic inclusion bodies in vitro.
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.
authors.affiliation: Department of Physiology and Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Geetika
authors.initials: G
authors.lastname: Phukan
authors.affiliation: Department of Physiology and Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea.|Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Shin
authors.affiliation: Department of Physiology and Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Jeom Soon
authors.initials: JS
authors.lastname: Shim
authors.affiliation: College of Pharmacy, Sunchon National University, Suncheon, Republic of Korea.
authors.forename: Man Jeong
authors.initials: MJ
authors.lastname: Paik
authors.affiliation: Department of Chemistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
authors.forename: Sangdun
authors.initials: S
authors.lastname: Choi
authors.affiliation: Pharmicell Co., Ltd. Sungnam, Republic of Korea.
authors.forename: Yong Man
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Applied Chemistry and Institute of Natural Sciences, Kyung Hee University, Yongin-si, Republic of Korea.
authors.forename: Seong Ho
authors.initials: SH
authors.lastname: Kang
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Physiology and Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Yup
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Department of Physiology and Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Soo Hwan
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Center for Neurodegenerative and Neuroimmunologic Diseases, Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ, USA.
authors.forename: M Maral
authors.initials: MM
authors.lastname: Mouradian
authors.affiliation: Department of Physiology and Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Gwang
authors.initials: G
authors.lastname: Lee
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D002479:Inclusion Bodies / Q000187:drug effects*; D058185:Magnetite Nanoparticles / Q000009:adverse effects* / Q000737:chemistry; D061251:Primary Cell Culture; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000235:genetics; D066263:Protein Aggregation, Pathological / Q000139:chemically induced; D051381:Rats; D012235:Rhodamines / Q000737:chemistry; D012822:Silicon Dioxide / Q000009:adverse effects / Q000737:chemistry; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D058185:Magnetite Nanoparticles; D012235:Rhodamines; D051844:alpha-Synuclein; D012822:Silicon Dioxide; C027755:rhodamine isothiocyanate; D046988:Proteasome Endopeptidase Complex