Project description:This SuperSeries is composed of the following subset Series: GSE12489: Effect of phenobarbital on CAR and PXR regulated genes involved in drug metabolism and cholesterol homeostasis GSE12509: Effect of TCPOBOP on CAR and PXR regulated genes involved in drug metabolism and cholesterol homeostasis Refer to individual Series
Project description:The nuclear receptor CAR (constitutive androstane receptor) mediates the effects of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) on gene transcription. To investigate the relative role of CAR and also PXR in the induction response, cDNA arrays were generated containing 120 (Sterolgene V1) genes which are known to be regulated with these or related nuclear receptors (genes involved in drug metabolism, cholesterol biosynthesis, sterol synthesis/transport, heme synthesis). Samples from livers of wild type and CAR-/-, PXR-/- or CAR/PXR-/- knockout mice were tested after treatment with TCPOBOP for gene expression within the European Framework V program “Steroltalk” (www.steroltalk.net). Results from these experiments show the complex role of CAR receptor in the expression of genes involved in drug metabolism and cholesterol biosynthesis. Animals were injected i.p. 10mg/kg TCPOBOP or vehicle (5% DMSO in corn oil). After 12h they were sacrificed and total RNA was isolated from the livers. Pools of untreated samples were mixed in each genetic variant group (wild type and CAR-/-, PXR-/- or CAR/PXR-/-) with the TCPOBOP treated ones and hybridized to Sterolgene V1 arrays.
Project description:The nuclear receptors CAR (constitutive androstane receptor) and PXR (pregnane X receptor) mediate the effects of phenobarbital (PB) on gene transcription. To investigate the relative role of CAR and PXR in the induction response, cDNA arrays were generated containing 120 genes which are known to be regulated with these or related nuclear receptors (genes involved in drug metabolism, cholesterol biosynthesis, sterol synthesis/transport, heme synthesis). Samples from livers of wild type and CAR-/-, PXR-/- or CAR/PXR-/- knockout mice were tested after treatment with PB for gene expression within the European Framework V program “Steroltalk” (www.steroltalk.net). Results from these experiments unexpectedly revealed that if CAR and PXR are deleted, PB increases the expression of several other nuclear receptors and genes involved in drug metabolism and cholesterol biosynthesis. Animals were injected i.p. 100mg/kg phenobarbital or vehicle (5% DMSO in corn oil). After 12h they were sacrificed and total RNA was isolated from the livers. Pools of untreated samples were mixed in each genetic variant group (wild type and CAR-/-, PXR-/- or CAR/PXR-/-) with the phenobarbital treated ones and hybridized to Sterolgene V1 arrays.
Project description:The nuclear receptor CAR (constitutive androstane receptor) mediates the effects of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) on gene transcription. To investigate the relative role of CAR and also PXR in the induction response, cDNA arrays were generated containing 120 (Sterolgene V1) genes which are known to be regulated with these or related nuclear receptors (genes involved in drug metabolism, cholesterol biosynthesis, sterol synthesis/transport, heme synthesis). Samples from livers of wild type and CAR-/-, PXR-/- or CAR/PXR-/- knockout mice were tested after treatment with TCPOBOP for gene expression within the European Framework V program “Steroltalk” (www.steroltalk.net). Results from these experiments show the complex role of CAR receptor in the expression of genes involved in drug metabolism and cholesterol biosynthesis.
Project description:TCPOBOP (1,4-bis[2-(3,5-dichloropyridyloxy)]benzene) and PCN (pregnenolone 16α-carbonitrile) are inducers of drug metabolism through activation of nuclear receptors CAR (constitutive androstane receptor) and PXR (pregnane X receptor), respectively. Mouse experiment was designed to study the effect of CAR and PXR activation on cholesterol homeostasis genes and other genes, which are present on the Steroltalk v2 microarray. Treatments were combined with standard and high-cholesterol diet to observe the interference of high liver cholesterol on nuclear receptor transcription regulation. All experiments were done within the European sixth Framework program âSteroltalkâ (www.steroltalk.net). Results form these experiments give new knowledge about involvement of âxenosensorsâ CAR and PXR in regulation of endogenous liver metabolism. Animals were injected i.p. 3mg/kg TCPOBOP, 40 mg/kg PCN or vehicle (corn oil) in combination of one week of standard or 1% cholesterol diet prior tretament. After 24h they were sacrificed and total RNA was isolated from the livers. Each sample was hybridized with a reference sample to Steroltalk v2 microarrays.
Project description:The nuclear receptors CAR (constitutive androstane receptor) and PXR (pregnane X receptor) mediate the effects of phenobarbital (PB) on gene transcription. To investigate the relative role of CAR and PXR in the induction response, cDNA arrays were generated containing 120 genes which are known to be regulated with these or related nuclear receptors (genes involved in drug metabolism, cholesterol biosynthesis, sterol synthesis/transport, heme synthesis). Samples from livers of wild type and CAR-/-, PXR-/- or CAR/PXR-/- knockout mice were tested after treatment with PB for gene expression within the European Framework V program “Steroltalk” (www.steroltalk.net). Results from these experiments unexpectedly revealed that if CAR and PXR are deleted, PB increases the expression of several other nuclear receptors and genes involved in drug metabolism and cholesterol biosynthesis.
Project description:TCPOBOP (1,4-bis[2-(3,5-dichloropyridyloxy)]benzene) and PCN (pregnenolone 16α-carbonitrile) are inducers of drug metabolism through activation of nuclear receptors CAR (constitutive androstane receptor) and PXR (pregnane X receptor), respectively. Mouse experiment was designed to study the effect of CAR and PXR activation on cholesterol homeostasis genes and other genes, which are present on the Steroltalk v2 microarray. Treatments were combined with standard and high-cholesterol diet to observe the interference of high liver cholesterol on nuclear receptor transcription regulation. All experiments were done within the European sixth Framework program “Steroltalk” (www.steroltalk.net). Results form these experiments give new knowledge about involvement of ‘xenosensors’ CAR and PXR in regulation of endogenous liver metabolism.
Project description:The nuclear receptor PXR (Pregnane X rreceptor) mediates the effects of pregnenolone-16alpha-carbonitrile (PCN) on gene transcription. The relative role of PXR and also CAR to the induction response by PCN was studied on cDNA arrays containing 320 (Steroltalk V2) genes (genes involved in cyrcadian rhythm, drug metabolism, cholesterol biosynthesis, sterol synthesis/transport, heme synthesis). Samples from livers of wild type and CAR-/-, PXR-/- or CAR/PXR-/- knockout mice were tested after treatment with PCN for gene expression within the European Framework V program âSteroltalkâ (www.steroltalk.net). Results from these experiments show the complex role of PXR receptor in the expression of genes involved in cyrcadian rhythm, drug metabolism and cholesterol biosynthesis. Animals were injected i.p. 40mg/kg PCN or vehicle (5% DMSO in corn oil). After 12h they were sacrificed and total RNA was isolated from the livers. Pools of untreated samples were mixed in each genetic variant group (wild type and CAR-/-, PXR-/- or CAR/PXR-/-) with the PCN treated ones and hybridized to Steroltalk V2 arrays.