Optical Isomers of Atorvastatin, Rosuvastatin and Fluvastatin Enantiospecifically Activate Pregnane X Receptor PXR and Induce CYP2A6, CYP2B6 and CYP3A4 in Human Hepatocytes
Fig 8
Effect of statin enantiomers on the binding of PXR/RXR complex to the DR3 motif of human CYP3A4 gene promoter.
Nuclear fractions of LS174T cells from three independent cell passages were incubated for 2 h at 30°C with DMSO (0.1% v/v), RIF (10 μM) and individual enantiomers of atorvastatin, rosuvastatin and fluvastatin at concentration 10 μM. Treated nuclear extracts were incubated with a biotin-labeled CYP3A4-DR3 probe and electrophoresed on 5% polyacrylamide gel as described under ‘‘Materials and methods section.” A. The complex formation of CYP3A4 DR3 response element with PXR-RXRα heterodimer. B. Simple western blot showing equal expression levels of PXR nuclear extracts used for EMSA (normalized to β-actin levels).