Expression changes of dopaminergic system-related genes in PC12 cells induced by manganese, silver, or copper nanoparticles.
Nanoparticles have received a great deal of attention for producing new engineering applications due to their novel physicochemical characteristics. However, the broad application of nanomaterials has also produced concern for nanoparticle toxicity due to increased exposure from large-scale industry production. This study was conducted to investigate the potential neurotoxicity of manganese (Mn), silver (Ag), and copper (Cu) nanoparticles using the dopaminergic neuronal cell line, PC12. Selective genes associated with the dopaminergic system were investigated for expression changes and their correlation with dopamine depletion. PC12 cells were treated with 10 microg/ml Mn-40 nm, Ag-15 nm, or Cu-90 nm nanoparticles for 24 h. Cu-90 nanoparticles induced dopamine depletion in PC12 cells, which is similar to the effect induced by Mn-40 shown in a previous study. The expression of 11 genes associated with the dopaminergic system was examined using real-time RT-PCR. The expression of Txnrd1 was up-regulated after the Cu-90 treatment and the expression of Gpx1 was down-regulated after Ag-15 or Cu-90 treatment. These alterations are consistent with the oxidative stress induced by metal nanoparticles. Mn-40 induced a down-regulation of the expression of Th; Cu-90 induced an up-regulation of the expression of Maoa. This indicates that besides the oxidation mechanism, enzymatic alterations may also play important roles in the induced dopamine depletion. Mn-40 also induced a down-regulation of the expression of Park2; while the expression of Snca was up-regulated after Mn-40 or Cu-90 treatment. These data suggest that Mn and Cu nanoparticles-induced dopaminergic neurotoxicity may share some common mechanisms associated with neurodegeneration.
Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food & Drug Administration, 3900 NCTR Rd., Jefferson, AR 72079-9502, USA. jianyong.wang@fda.hhs.gov
Jianyong
J
Wang
Mohammed F
MF
Rahman
Helen M
HM
Duhart
Glenn D
GD
Newport
Tucker A
TA
Patterson
Richard C
RC
Murdock
Saber M
SM
Hussain
John J
JJ
Schlager
Syed F
SF
Ali
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003300:Copper / Q000494:pharmacology*; D004298:Dopamine / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005979:Glutathione Peroxidase / Q000235:genetics; D005981:Glutathione Synthase / Q000235:genetics; D006719:Homovanillic Acid / Q000378:metabolism; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008345:Manganese / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics; D053768:Metal Nanoparticles / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008995:Monoamine Oxidase / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D012834:Silver / Q000494:pharmacology*; D054481:Thioredoxin Reductase 1 / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics; D000094765:Glutathione Peroxidase GPX1
D002135:Calcium-Binding Proteins; C119905:Gpr37 protein, rat; D008565:Membrane Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; C091825:syntrophin alpha1; D015102:3,4-Dihydroxyphenylacetic Acid; D012834:Silver; D008345:Manganese; D003300:Copper; D005979:Glutathione Peroxidase; D014446:Tyrosine 3-Monooxygenase; D008995:Monoamine Oxidase; D054481:Thioredoxin Reductase 1; C516126:Txnrd1 protein, rat; D002394:Catechol O-Methyltransferase; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D005981:Glutathione Synthase; D004298:Dopamine; D006719:Homovanillic Acid; D000094765:Glutathione Peroxidase GPX1; C000722069:Gpx1 protein, rat