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NRS 13, e002 | Figure 9

Oshida K, Vasani N, Jones C, Moore T, Hester S, Nesnow S, Auerbach S, Geter D, Aleksunes L, Thomas R, Applegate D, Klaassen D and Corton J (2015). Identification of chemical modulators of the constitutive activated receptor (CAR) in a gene expression compendium. Nucl Recept Signal 13, e002. doi:10.1621/nrs.13002




Figure 9. Perfluorinated compounds activate CAR in a PPARα-independent manner. A. Effect of exposure to PPARα activators in wild-type and PPARα-null mice on CAR activation. The indicated dose levels are shown. For GSE8396, mice were given one 400uL injection of a 10mg/mL solution of either fenofibrate or WY in 0.5% carboxymethyl cellulose (CMC) or 400 μl of 0.5% CMC only. Abbreviations: Feno, fenofibrate; PFHxS, perfluorohexane sulfonate; PFNA, perfluoronanoic acid; PFOS, perfluorooctane sulfonate; PFOA, perfluorooctanic acid. B. Effects of WY-14,643, PFNA and AGN194,204 on activation of CAR marker genes in wild-type and PPARα-null mice. *Significant from corresponding control at p-value < 0.05; **Significant from corresponding control at p-value < 0.01. C. Liver to body weights of wild-type and CAR-null mice given PFOA or PFOS for 7 days. **Significant from corresponding control at p-value < 0.01. D. Hepatocyte proliferation in wild-type and CAR-null mice exposed to PFOA for 7 days. Hepatocyte proliferation was evaluated as detailed in the Methods. **Significant from corresponding control at p-value < 0.01. E. Expression of marker genes for PPARα, CAR and PXR in the livers of wild-type and CAR-null mice given PFOA for 7 days. *Significant from corresponding control at p-value < 0.05; **Significant from corresponding control at p-value < 0.01; #significant between wild-type and nullizygous comparisons at p-value < 0.05; ##significant between wild-type and nullizygous comparisons at p-value < 0.01. F. Expression of marker genes for PPARα, CAR and PXR in the livers of wild-type and CAR-null mice given PFOS for 7 days. *Significant from corresponding control at p-value < 0.05; **Significant from corresponding control at p-value < 0.01. #Significant from corresponding control at p-value < 0.05; ##significant from corresponding control at p-value < 0.01.