Journal article
PCB95 and PCB153 change dopamine levels and turn-over in PC12 cells
Toxicology (Amsterdam), Vol.394, pp.93-101
02/01/2018
DOI: 10.1016/j.tox.2017.12.003
PMCID: PMC5756734
PMID: 29233657
Abstract
•PCB153 decreased intracellular dopamine (DA) and increased (24 h) extracellular DA.•PCB153 increased DA metabolites DOPAC, DOPET, and DOPAL.•PCB95 first increased (12 h) then decreased (24 h) intracellular DA.•PCB95 down-regulated VMAT and GPx.•Both PCB congeners may be neurotoxic, but through different mechanisms.
Polychlorinated biphenyls (PCB) exposure at low chronic levels is a significant public health concern. Animal and epidemiological studies indicate that low PCB body burden may cause neurotoxicity and be a risk factor for neurodegenerative diseases. In the current study, we measured the ability of two non-dioxin like PCBs, 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) and 2,2′3,5′,6-pentachlorobiphenyl (PCB95), to alter dopamine (DA) levels and metabolism using the dopaminergic PC12 cell line. Our hypothesis is that treatment of PC12 cells with non-toxic concentrations of PCB153 or PCB95 for 12 and 24 h will have different effects due to different congener structures. Levels of DA and of 3,4-dihydroxyphenylacetaldehyde (DOPAL), 3, 4-dihyroxylphenylethanol (DOPET), and 3,4-dihyroxylphenylacetic acid (DOPAC) metabolite, gene expression of the dopamine synthesis enzyme tyrosine hydroxylase (TH) and the vesicular monoamine transporter (VMAT2), and gene expression of the anti-oxidant enzymes Cu/Zn and Mn superoxide oxidase (Cu/ZnSOD, MnSOD), glutathione peroxidase (GPx) and catalase were determined. PCB153 decreased intracellular and extracellular levels of DA after 12 h exposure and this was consistent with an increase in DA metabolites. After 24 h, the level of DA in medium increased compared to the control. In contrast, PCB95 exposure increased the intracellular DA level and decreased DA in medium consistent with a down-regulation of VMAT2 expression at 12 h. After 24 h exposure, PCB95 increased DA levels in media. Expression of TH mRNA increased slightly following 12 h but not at 24 h exposure. MnSOD mRNA increased up to 6–7 fold and Cu/ZnSOD increased less than two-fold after treatment with both congeners. Catalase expression was up-regulated following 24 h exposure to PCB153 and PCB95, but GPx expression was down-regulated after 12 h exposure to PCB95 only. These results suggest that PCB153 and PCB95 are neurotoxic and affect DA turnover with structure-dependent differences between these two congeners.
Details
- Title: Subtitle
- PCB95 and PCB153 change dopamine levels and turn-over in PC12 cells
- Creators
- Sabah H Enayah - Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, United StatesBrigitte C Vanle - Department of Pharmaceutical Sciences & Experimental Therapeutics, University of Iowa, United StatesLaurence J Fuortes - Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, United StatesJonathan A Doorn - Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, United StatesGabriele Ludewig - Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, United States
- Resource Type
- Journal article
- Publication Details
- Toxicology (Amsterdam), Vol.394, pp.93-101
- DOI
- 10.1016/j.tox.2017.12.003
- PMID
- 29233657
- PMCID
- PMC5756734
- NLM abbreviation
- Toxicology
- ISSN
- 0300-483X
- eISSN
- 1879-3185
- Publisher
- Elsevier B.V
- Grant note
- name: Iowa Superfund Research Program, award: P42ES013661
- Language
- English
- Date published
- 02/01/2018
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Iowa Superfund Research Program; Medicinal and Natural Products Chemistry; Internal Medicine
- Record Identifier
- 9983997314202771
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