Discovery That Theonellasterol a Marine Sponge Sterol Is a Highly Selective FXR Antagonist That Protects against Liver Injury in Cholestasis
Figure 2
Theonellasterol is an FXR antagonist.
Luciferase reporter assay performed in HepG2 transiently transfected with pSG5-PXR, pSG5-RXR, pCMV-βgal, pCYP3A4promoter-TKLuc vectors and stimulated 18 h with (A) 10 µM of CDCA or theonellasterol and (B) 10 µM of CDCA alone or in combination with theonellasterol 50 µM. Data are the mean ± S.E. of three experiments. *P<0.05 versus cells left untreated. #P<0.05 versus CDCA. (C) CHiP assay of NCoR binding to the OSTα promoter. CDCA displaces NCoR from OSTα and this effect is reversed by theonellasterol. RT-PCR analysis of proteins immune-precipitated with a control IgG are shown as control. Data are the mean ± S.E. of three experiments. *P<0.05 versus anti IgG immunoprecipitates. #P<0.05 CDCA versus cells left untreated; P<0.05 thenollasterol versus CDCA alone.