Project description:The aim of the study was to elucidate the effects of pregnane receptor X (PXR) activation by rifampicin on the mononuclear cell gene expression in vivo.
Project description:This SuperSeries is composed of the following subset Series: GSE24186: Atorvastatin, rosuvastatin and rifampicin effect on human primary hepatocyte transcriptome [Steroltalk platform] GSE24187: Atorvastatin, rosuvastatin and rifampicin effect on human primary hepatocyte transcriptome [Affymetrix platform] Refer to individual Series
Project description:Tuberculosis (TB) is still a major life-threatening infectious disease, within which especially the rise of multidrug resistant TB (MDR-TB) is currently worrying. This study focuses on mechanisms of development of rifampicin resistance, since rifampicin seems to play an important role in the development of MDR-TB. To provide further insight in rifampicin resistance, we performed a genome-wide transcriptional profile analysis for Mycobacterium tuberculosis (M. tuberculosis) using microarray technology and qRT-PCR analysis. We exposed a rifampicin-susceptible H37Rv wild type (H37Rv-WT) and a rifampicin-resistant progeny H37Rv strain with a H526Y mutation in the rpoB gene (H37Rv-H526Y) to several concentrations of rifampicin, to define the effect of rifampicin on the transcription profile. Our study showed that there are resistance-dependant differences in response between both M. tuberculosis strains. Gene clusters associated with efflux, transport and virulence were altered in the rifampicin-resistant H37Rv mutant compared to the rifampicin-susceptible H37Rv-WT strain after exposure to rifampicin. We conclude that the small gene cluster Rv0559c-Rv0560c in the H37Rv-H526Y strain was remarkably up-regulated in the microarray analysis and qRT-PCR results and appeared to be dependent on rifampicin concentration and time of exposure. Therefore this study suggests that Rv0559c and Rv0560c play a pivotal role in rifampicin resistance of M. tuberculosis. Further investigation of Rv0559c and Rv0560c is needed to reveal function and mechanism of both genes that were triggered upon rifampicin exposure. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-139]
Project description:Tuberculosis is one of top causes of death among curable infectious diseases; it is an airborne infectious disease that kills 2 million people worldwide. Anti-tuberculosis drug-induced liver injury is the primary cause of drug-induced liver injury (DILI). Rifampicin is one of the most common anti-tuberculosis therapies and has well-known hepatotoxicity. To understand the mechanism of rifampicin-induced liver injury, we performed a global proteomic analysis of liver proteins by LC-MS/MS in a mouse model after the oral administration of 177 and 442.5 mg/kg rifampicin (LD10 and LD25) for 14 days. Based on the biochemical parameters in the plasma after rifampicin treatment, the hepatotoxic effect of rifampicin in the mouse liver was defined as a mixed liver injury. In the present study, we identified 1,101 proteins and quantified 1,038 proteins. A total of 29 and 40 proteins were up-regulated and 27 and 118 proteins were down-regulated in response to 177 and 442.5 mg/kg rifampicin, respectively.
Project description:We have discovered rifampicin as a glycation inhibitor, which increases life span in C elegans. In order to understand the mechanism of rifampicin action, microarray analysis was performed to study the changes in gene expression brought about by the drug.
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: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.
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.
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.
Project description:We measured steady-state E. coli transcript levels in 1) a pykF(C8Y) mutant, 2) a rpoB(T1037P) mutant, and 3) five rifampicin-resistant rpoB mutant strains selected from each of these single mutants, in the presence and absence of rifampicin.