In Vitro Assessment of Activation of Baikal Seal (Pusa sibirica) Peroxisome Proliferator-Activated Receptor α by Polybrominated Diphenyl Ethers

摘要

We investigated the Baikal seal (Pusa sibirica) peroxisome proliferator-activated receptor alpha (bsPPAR alpha) transactivation potencies of polybrominated diphenyl ethers (PBDEs) using an in vitro bsPPAR alpha reporter gene assay. BDE47, BDE99, and BDE153 induced bsPPAR alpha-mediated transcriptional activities in a dose-dependent manner. To compare bsPPAR alpha transactivation potencies of PBDEs, perfluorooctanoic acid (PFOA)-based relative potencies (REPs), a ratio of 50% effective concentration of PFOA to the test chemical, were determined. The order of REPs of PBDEs was BDE153 (13) BDE99 (8.1) BDE47 (6.6) PFOA (1.0) BDE100, BDE154, and BDE183 (not activated). PBDEs with two bromine atoms at the ortho position showed higher bsPPARa transactivation potencies than those with three bromine atoms. Comparison of the lowest-observed-effect concentration in bsPPAR alpha reporter gene assays revealed that BDE99 was 7-fold more potent than CB99, a polychlorinated biphenyl congener with the same IUPAC number, indicating that brominated congeners could more efficiently activate bsPPARa than chlorinated congeners. The REPs of PBDEs for bsPPAR alpha transactivation were approximately 7- to 13-fold higher than those of perfluorochemicals (PFCs), suggesting that the effects of PBDEs on the bsPPAR alpha signaling pathway may be superior to those of PFCs. This study provides the first evidence that PBDE congeners activate PPAR alpha in vitro.