rifampin and Hepatoblastoma

rifampin has been researched along with Hepatoblastoma* in 3 studies

Other Studies

3 other study(ies) available for rifampin and Hepatoblastoma

ArticleYear
Mechanism of rifampicin and pregnane X receptor inhibition of human cholesterol 7 alpha-hydroxylase gene transcription.
    American journal of physiology. Gastrointestinal and liver physiology, 2005, Volume: 288, Issue:1

    Bile acids, steroids, and drugs activate steroid and xenobiotic receptor pregnane X receptor (PXR; NR1I2), which induces human cytochrome P4503A4 (CYP3A4) in drug metabolism and cholesterol 7 alpha-hydroxylase (CYP7A1) in bile acid synthesis in the liver. Rifampicin, a human PXR agonist, inhibits bile acid synthesis and has been used to treat cholestatic diseases. The objective of this study is to elucidate the mechanism by which PXR inhibits CYP7A1 gene transcription. The mRNA expression levels of CYP7A1 and several nuclear receptors known to regulate the CYP7A1 gene were assayed in human primary hepatocytes by quantitative real-time PCR (Q-PCR). Rifampicin reduced CYP7A1 and small heterodimer partner (SHP; NR02B) mRNA expression suggesting that SHP was not involved in PXR inhibition of CYP7A1. Rifampicin inhibited CYP7A1 reporter activity and a PXR binding site was localized to the bile acid response element-I. Mammalian two-hybrid assays revealed that PXR interacted with hepatic nuclear factor 4 alpha (HNF4 alpha, NR2A1) and rifampicin was required. Coimmunoprecipitation assay confirmed PXR interaction with HNF4 alpha. PXR also interacted with peroxisome proliferator-activated receptor gamma coactivator (PGC-1 alpha), which interacted with HNF4 alpha and induced CYP7A1 gene transcription. Rifampicin enhanced PXR interaction with HNF4 alpha and reduced PGC-1 alpha interaction with HNF4 alpha. Chromatin immunoprecipitation assay showed that PXR, HNF4 alpha, and PGC-1 alpha bound to CYP7A1 chromatin, and rifampicin dissociated PGC-1 alpha from chromatin. These results suggest that activation of PXR by rifampicin promotes PXR interaction with HNF4 alpha and blocks PGC-1 alpha activation with HNF4 alpha and results in inhibition of CYP7A1 gene transcription. Rifampicin inhibition of bile acid synthesis may be a protective mechanism against drug and bile acid-induced cholestasis.

    Topics: Bile Acids and Salts; Cholestasis; Cholesterol 7-alpha-Hydroxylase; DNA-Binding Proteins; Enzyme Inhibitors; Hepatoblastoma; Hepatocyte Nuclear Factor 4; Humans; Liver Neoplasms; Phosphoproteins; Pregnane X Receptor; Receptors, Cytoplasmic and Nuclear; Receptors, Glucocorticoid; Receptors, Steroid; Rifampin; RNA, Messenger; Transcription Factors; Transcription, Genetic; Tumor Cells, Cultured; Up-Regulation

2005
Functional analysis of the rat bile salt export pump gene promoter.
    European journal of biochemistry, 2002, Volume: 269, Issue:14

    The 5' flanking region of the bile salt export pump (Bsep) gene was systematically analysed to provide the basis for understanding the mechanisms which regulate Bsep transcription. In addition substrates and drugs were investigated for their ability to alter Bsep promoter activity. Bsep promoter function was restricted to hepatocyte derived HepG2 cells. The 5' deletional analysis revealed a biphasic shape of reporter gene activities, indicating a suppressive element between nucleotides -800 and -512. Two consensus sites for the farnesoid X receptor (FXR) were located at nucleotides -473 and -64. The latter was characterized as functionally active in bile acid-mediated feed-back regulation of Bsep transcription. Bsep promoter activity was reduced by rifampin and beta-estradiol. The anti-estrogen tamoxifen stimulated promoter activity. Dexamethasone, hydrocortisone and phenobarbital had no effect on Bsep promoter activity. In conclusion, the data suggest that transcriptional regulation of the Bsep gene can be modulated by a number of endogenous compounds and xenobiotics. FXR was a major regulatory factor, mediating bile acid feed-back stimulation of Bsep transcription.

    Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 11; ATP-Binding Cassette Transporters; Base Sequence; Bile Acids and Salts; Binding Sites; Dexamethasone; DNA-Binding Proteins; Feedback; Gene Expression Regulation; Genes; Genes, Reporter; Hepatoblastoma; Hepatocytes; Humans; Hydrocortisone; Liver Neoplasms; Molecular Sequence Data; Phenobarbital; Promoter Regions, Genetic; Rats; Receptors, Cytoplasmic and Nuclear; Recombinant Fusion Proteins; Rifampin; Tamoxifen; Transcription Factors; Transcription, Genetic; Transfection; Tumor Cells, Cultured; Xenobiotics

2002
Evaluation of induction of CYP3A mRNA using the HepG2 cell line and reverse transcription-PCR.
    Biological & pharmaceutical bulletin, 1999, Volume: 22, Issue:1

    Cytochrome P-450 3A (CYP3A) is a drug-metabolizing enzyme dominant in the human liver. We have designed a useful method for evaluation of induction of CYP3A mRNA by various drugs using HepG2 cells known to retain liver-cellular functions. Using semi-quantitative reverse transcription-PCR (RT-PCR), we demonstrated that cultured HepG2 cells constitutively expressed CYP3A mRNA. This mRNA was expressed at high levels in culture for several days and was further induced by several drugs (e.g. rifampicin (RFP), dexamethasone). Treatment of HepG2 cells with RFP induced CYP3A mRNA in a dose- and time-dependent manner. Cells in culture for 48 h with 1 and 50 micromol/l RFP increased 2.7- and 5.0-fold in CYP3A mRNA expression in comparison with untreated controls, respectively. In contrast, no change in the amount of CYP3A mRNA was observed when the cells were treated with cimetidine which has been shown to inhibit CYP3A activity. Our method using a combination of HepG2 cells and RT-PCR allowed evaluation of the degree of induction of CYP3A mRNA both easily and rapidly.

    Topics: Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Dexamethasone; Enzyme Induction; Hepatoblastoma; Humans; Liver Neoplasms; Oxidoreductases, N-Demethylating; Phenobarbital; Reverse Transcriptase Polymerase Chain Reaction; Rifampin; RNA, Messenger; Tumor Cells, Cultured

1999