Data from: Neonatal activation of the xenobiotic-sensors PXR and CAR results in acute and persistent down-regulation of PPARα-signaling in mouse liver
Li, Cindy Yanfei, University of Washington
Cheng, Sunny Lihua, University of Washington
Bammler, Theo K., University of Washington
Cui, Julia Yue, University of Washington
Published May 19, 2016 on Dryad.
Cite this dataset
Li, Cindy Yanfei; Cheng, Sunny Lihua; Bammler, Theo K.; Cui, Julia Yue (2016). Data from: Neonatal activation of the xenobiotic-sensors PXR and CAR results in acute and persistent down-regulation of PPARα-signaling in mouse liver [Dataset]. Dryad. https://doi.org/10.5061/dryad.0k90t
Safety concerns have emerged regarding the potential long-lasting effects due to developmental exposure to xenobiotics. The pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are critical xenobiotic-sensing nuclear receptors that are highly expressed in liver. The goal of this study was to test our hypothesis that neonatal exposure to PXR- or CAR-activators not only acutely but also persistently regulates the expression of drug-processing genes (DPGs). A single dose of the PXR-ligand PCN (75 mg/kg), CAR-ligand TCPOBOP (3 mg/kg), or vehicle (corn oil) was administered intraperitoneally to 3-day-old neonatal wild-type mice. Livers were collected 24 h post-dose or from adult mice at 60 days of age, and global gene expression of these mice was determined using Affymetrix Mouse Transcriptome Assay 1.0. In neonatal liver, PCN up-regulated 464 and down-regulated 449 genes, whereas TCPOBOP up-regulated 308 and down-regulated 112 genes. In adult liver, there were 15 persistently up-regulated and 22 persistently down-regulated genes following neonatal exposure to PCN, as well as 130 persistently up-regulated and 18 persistently down-regulated genes following neonatal exposure to TCPOBOP. Neonatal exposure to both PCN and TCPOBOP persistently down-regulated multiple Cyp4a members, which are prototypical-target genes of the lipid-sensor PPARα, and this correlated with decreased PPARα-binding to the Cyp4a gene loci. RT-qPCR, western blotting, and enzyme activity assays in livers of wild-type, PXR-null, and CAR-null mice confirmed that the persistent down-regulation of Cyp4a was PXR and CAR dependent. In conclusion, neonatal exposure to PXR- and CAR-activators both acutely and persistently regulates critical genes involved in xenobiotic and lipid metabolism in liver.
Transcriptome profiles in mouse liver
C57BL/6J mice were administered with corn oil, TCPOBOP, PCN at 3-day-old age, the livers were collected after 24 hours or at 60-day-old age. This excel data sheet contains 18 columns. Three biological replicates for each treatment. The row contains all the transcripts.
This zip file contains 18 CEL files, named with the ages (3-day-old and 60-day-old) and treatments (corn oil [CO], TCPOBOP, PCN).