Project description:This SuperSeries is composed of the following subset Series: GSE13688: Effect of TCPOBOP and PCN in combination with high-cholesterol diet on genes involved in cholesterol homeostasis GSE13689: Effect of rosuvastatin and atorvastatin in combination with high-cholesterol diet on cholesterol homeostasis Refer to individual Series
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: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: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:With particular emphasis on interactions between cholesterol homeostasis and drug metabolism we investigate the transcriptome of human primary hepatocytes treated by two commonly prescribed cholesterol lowering drugs atorvastatin and rosuvastatin and by rifampicin that serves as an outgroup as well as a model substance for induction of nuclear receptor PXR. Expression profiling with Affymetrix whole genome arrays shows that statins induce extensive transcriptome changes. 7 condition experiment: 3 treatments (atorvastatin, rifampicin, rosuvastatin), each measured at 2 time points (24 and 48 hours), and untreated cells. 4-6 biological replicates for each condition.
Project description:The aim of the study was to see any effect of rosuvastatina or atorvastatin on cholesterol homeostasis after 24 hours in C57BL/6 hyperlipidemic mice (induced by diet). Experiments were perfomed using a custom Steroltalk v2 microarray. Effect of both statins on drug metabolism was also evaluated. All experiments were done within the European sixth Framework program âSteroltalkâ (www.steroltalk.net). Animals were given one peroral application of vehicle (tap water), 20 mg/kg rosuvastatin or 40 mg/kg atorvastatin after one week of 1% cholesterol diet. 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:With particular emphasis on interactions between cholesterol homeostasis and drug metabolism we investigate the transcriptome of human primary hepatocytes treated by two commonly prescribed cholesterol lowering drugs atorvastatin and rosuvastatin and by rifampicin that serves as an outgroup as well as a model substance for induction of nuclear receptor PXR. Expression profiling with dedicated Steroltalk cDNA arrays shows that statins induce extensive transcriptome changes. 10 condition experiment: 3 treatments (atorvastatin, rifampicin, rosuvastatin), each measured at 3 time points (12, 24 and 48 hours), and untreated cells. 3-7 biological replicates for each treatment condition, 20 biological and technical replicates for untreated cells. Common reference design.
