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In Vitro Neurotoxicity of PBDE-99: Immediate and Concentration-Dependent Effects on Protein Expression in Cerebral Cortex Cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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2010 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 9, no 3, 1226-1235 p.Article in journal (Refereed) Published
Abstract [en]

Polybrominated diphenyl ethers (PBDEs) are commonly used flame retardants in various consumer products. Pre- and postnatal exposure to congeners of PBDEs disrupts normal brain development in rodents. Two-dimensional difference gel electrophoresis (2D-DIGE) was used to analyze concentration-dependent differences in protein expression in cultured cortical cells isolated from rat fetuses (GD 21) after 24 h exposure to PBDE-99 (3, 10, or 30 muM). Changes on a post-translational level were studied using a 1 h exposure to 30 muM PBDE-99. The effects of 24 h exposure to 3 and 30 muM PBDE-99 on mRNA levels were measured using oligonucleotide microarrays. A total of 62, 46, and 443 proteins were differentially expressed compared to controls after 24 h of exposure to 3, 10, and 30 muM PDBE-99, respectively. Of these, 48, 43, and 238 proteins were successfully identified, respectively. We propose that the biological effects of low-concentration PBDE-99 exposure are fundamentally different than effects of high-concentration exposure. Low-dose PBDE-99 exposure induced marked effects on cytoskeletal proteins, which was not correlated to cytotoxicity or major morphological effects, suggesting that other more regulatory aspects of cytoskeletal functions may be affected. Interestingly, 0.3 and 3 muM, but not 10 or 30 muM increased the expression of phosphorylated (active) Gap43, perhaps reflecting effects on neurite extension processes.

Place, publisher, year, edition, pages
2010. Vol. 9, no 3, 1226-1235 p.
Keyword [en]
PBDE, PBDE-99, brominated flameretardant, neurotoxicity, developmental toxicity, proteomics, dose response, toxicology, functional genomics, cytotoxicity, in vitro, primary cell culture, cytoskeleton, Gap-43
National Category
Biological Sciences Chemical Sciences
Research subject
Toxicology; Biology with specialization in Environmental Toxicology; Developmental Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-118337DOI: 10.1021/pr900723cISI: 000275088100006PubMedID: 19954255OAI: oai:DiVA.org:uu-118337DiVA: diva2:299028
Available from: 2010-02-23 Created: 2010-02-23 Last updated: 2017-12-12Bibliographically approved

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Dencker, Lennart

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