Effects of titanium dioxide nanoparticles on α-synuclein aggregation and the ubiquitin-proteasome system in dopaminergic neurons.
Dopaminergic neurons (PC12 cells) were treated with different doses of titanium dioxide nanoparticles (TiO2-NPs), to investigate their effects on α-Synuclein (α-Syn) aggregation and their mechanism of action. Western blotting and immunofluorescent staining were performed. Exposure to TiO2-NPs increased α-Syn expression (p < 0.05) and induced dose-dependent α-Syn aggregation. Pretreatment with N-acetylcysteine partially inhibited α-Syn expression induced by a 200 μg/ml dose of TiO2-NPs. TiO2-NPs reduced the expressions of parkin and ubiquitin C-terminal hydrolase protein, and were associated with oxidative stress in PC12 cells. Dysfunction of the ubiquitin-proteasome system also contributed to α-Syn aggregation. The potentially neurotoxic TiO2-NPs may cause Parkinson's disease.
a Department of Stomatology , Shandong Medical College , Linyi, Shandong Province , P. R. China.
Jie
J
Wu
b Department of Stomatology , Linyi People's Hospital , Linyi, Shandong Province , P. R. China.
Hongjun
H
Xie
D000818:Animals; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D053758:Nanoparticles; D016716:PC12 Cells; D010316:Particle Size; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D066329:Protein Aggregates; D059748:Proteolysis / Q000187:drug effects; D051381:Rats; D014025:Titanium / Q000737:chemistry / Q000494:pharmacology*; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism
D066329:Protein Aggregates; D025801:Ubiquitin; D051844:alpha-Synuclein; C009495:titanium dioxide; D014025:Titanium; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase; D046988:Proteasome Endopeptidase Complex
dopaminergic neuron; titanium dioxide nanoparticles; ubiquitin-proteasome pathway; α-synuclein