Activated sterol regulatory element-binding protein-2 suppresses hepatocyte nuclear factor-4-mediated Cyp3a11 expression in mouse liver.

Sterol regulatory element-binding protein-2 (SREBP-2) is a key transcription factor for the cholesterol homeostasis. Recent studies have suggested the association of CYP3A enzymes, major drug-metabolizing enzymes, with cholesterol metabolism. In the present study, we have investigated a possible involvement of SREBP-2 in hepatic Cyp3a11 expression.

Role of vitamin D receptor in the lithocholic acid-mediated CYP3A induction in vitro and in vivo.

Lipophilic bile acids are suggested to be involved in the endogenous expression of CYP3A4 in human and experimental animals as ligands of nuclear receptors. To verify the nuclear receptor specificity, the bile acid-mediated induction of CYP3A4 has been studied in vitro and in vivo in the present study. Lithocholic acid (LCA) strongly enhanced the activities of the CYP3A4 reporter gene, which contained multiple nuclear receptor binding elements, in both HepG2 and LS174T cells.

A novel single nucleotide polymorphism of the human methylenetetrahydrofolate reductase gene in Japanese individuals.

The genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) have been associated with increased toxicity of methotrexate (MTX), a folic acid antagonist that is widely used to treat cancer and immunosuppressive disorders such as rheumatoid arthritis. In this study, we analyzed all the exons and exon/intron junctions of the MTHFR gene from 200 Japanese individuals. We detected a novel single nucleotide polymorphism (SNP) 148C>T (Arg46Trp) in exon 1.