Activation of Mouse and Human Peroxisome Proliferator-Activated Receptors (α, β/δ, γ) by Perfluorooctanoic Acid and Perfluorooctane Sulfonate
Abstract
This study evaluates the potential for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) to activate peroxisome proliferator-activated receptors (PPARs), using a transient transfection cell assay. Cos-1 cells were cultured in Dulbecco's Minimal Essential Medium (DMEM) with fetal bovine serum in 96-well plates and transfected with mouse or human PPARalpha, beta/delta, or gamma reporter plasmids. Transfected cells were exposed to PFOA (0.5-100 microM), PFOS (1-250 microM), positive controls (i.e., known agonists and antagonists), and negative controls (i.e., DMEM, 0.1% water, and 0.1% dimethyl sulfoxide). Following treatment for 24 h, activity was measured using the Luciferase reporter assay. In this assay, PFOA had more transactivity than PFOS with both the mouse and human PPAR isoforms. PFOA significantly increased mouse and human PPARalpha and mouse PPARbeta/delta activity relative to vehicle. PFOS significantly increased activation of mouse PPARalpha and PPARbeta/delta isoforms. No significant activation of mouse or human PPARgamma was observed with PFOA or PFOS. The PPARalpha antagonist, MK-886, significantly suppressed PFOA and PFOS activity of mouse and human PPARalpha. The PPARgamma antagonist, GW9662, significantly suppressed PFOA activity on the human isoform. In conclusion, this study characterized the dose response and differential activation of mouse and human PPARalpha, beta/delta, gamma by PFOA and PFOS. While this model allows opportunities to compare potential activation by perfluoroalkyl acids, it only evaluates the interaction and activation of the PPAR reporter constructs and is not necessarily predictive of a toxicological response in vivo.
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PFOA has been shown to interact with PPARα, γ, and β/δ and induce adipogenesis in 3T3-L1 cells.
“PFOA has been shown to interact with PPARα, γ, and β/δ and induce adipogenesis in 3T3-L1 cells”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Takacs and Abbott, 2007
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“For example, PFOA has been shown to interact with PPARα, γ, and β/δ and induce adipogenesis in 3T3-L1 cells, cells with a fibroblast morphology that can differentiate into a cell with an adipocyte-like phenotype (Takacs and Abbott, 2007; Watkins et al., 2013; Li et al., 2019).”
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- Authors
- Takacs, M. L., & Abbott, B. D.
- Affiliations
- Environmental Protection Agency (US)
- ORCID
- Abbott, Barbara D.
- Venue
- Toxicological Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-10-17
- Volume
- 95
- Issue
- 1
- Pages
- 108-117
- ISSN
- 1096-0929 (ISSN-L)
- 1096-6080
- OpenAlex
- W2120447865
- Cited by
- 396
- References
- 53
- Citations by year
- 2026: 23 · 2025: 29 · 2024: 26 · 2023: 24 · 2022: 24 · 2021: 33 · 2020: 25 · 2019: 15 · 2018: 13 · 2017: 13 · 2016: 13 · 2015: 17 · 2014: 20 · 2013: 16 · 2012: 17
- FWCI
- 13.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Keywords
- perfluorooctanoic acid, PFOS, perfluoroalkyl acids, peroxisome proliferator-activated receptors, PPARα, PPARδ, PPARγ, receptor activation, MK-886, GW9662, dose-response relationship, perfluorinated compounds
- MeSH terms
- Animals, Caprylates, Chlorocebus aethiops, Dose-Response Relationship, Drug, Environmental Pollutants, Fluorocarbons, Humans, Luciferases, Species Specificity, Transfection, Transcriptional Activation, Alkanesulfonic Acids, Genes, Reporter, COS Cells, Peroxisome Proliferator-Activated Receptors, PPAR alpha, PPAR delta, PPAR gamma, PPAR-beta, Mice
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