title: Effects of methylmercury on dopamine release in MN9D neuronal cells.
abstract: Epidemiological evidence has shown associations between prevalence of Parkinson's disease (PD) and exposure to environmental pollutants, but the mechanisms of pathogensis are still unclear. The objective of this study is to investigate effects of methylmercury (MeHg) on a dopaminergic neuronal cell line, MN9D and compare that to 1-methyl-4-phenylpyridinium (MPP+), a well-established agent associated with pathogenesis of PD. MN9D cells were exposed to MeHg (1-10 µM) and MPP+ (10-400 µM) for 24 or 48 h. Our results showed that MeHg induced cell death dose-dependently. MeHg also decreased the release of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) similar to the effects of MPP+. There was an increase in DOPAC + HVA/DA ratio. At the same time, both MeHg and MPP+ decreased the synthesis of tyrosine hydroxylase and dopamine transporter at the mRNA and protein levels. Expression of the α-Synuclein (α-Syn), a hallmark neuropathological indicator of PD, was also up-regulated at the mRNA level but not at the protein level after both MeHg and MPP+ dosing. Monoamine oxidase-B activity was suppressed in all MeHg treatments and MPP+ (1 µM)-treated cells. These findings suggest that MeHg can disrupt the synthesis, the uptake of DA and the metabolism as well as alter the biology of α-Syn similar to MPP+. Exposure to MeHg may potentially be a risk factor for the development of PD.
authors.affiliation: a Natural Resources and Environmental Studies, University of Northern British Columbia , Prince George , BC , Canada and.
authors.forename: Yueting
authors.initials: Y
authors.lastname: Shao
authors.affiliation: b Center for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa , Ottawa , ON , Canada.
authors.forename: Hing Man
authors.initials: HM
authors.lastname: Chan
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D006719:Homovanillic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D007700:Kinetics; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000819:agonists / Q000235:genetics / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D004785:Environmental Pollutants; D008767:Methylmercury Compounds; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C493215:Slc6a3 protein, mouse; C497605:Snca protein, mouse; D051844:alpha-Synuclein; D015102:3,4-Dihydroxyphenylacetic Acid; D014446:Tyrosine 3-Monooxygenase; D008995:Monoamine Oxidase; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine; D006719:Homovanillic Acid
keywords: Heavy metal; MPP+; Parkinson’s disease; neurotoxicity