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 PPARα, β/δ, or γ reporter plasmids. Transfected cells were exposed to PFOA (0.5-100μM), PFOS (1-250μM), 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 PPARα and mouse PPARβ/δ activity relative to vehicle. PFOS significantly increased activation of mouse PPARα and PPARβ/δ isoforms. No significant activation of mouse or human PPARγ was observed with PFOA or PFOS. The PPARα antagonist, MK-886, significantly suppressed PFOA and PFOS activity of mouse and human PPARα. The PPARγ 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 PPARα, β/δ, γ 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. © 2007 Oxford University Press.