Statins and transcriptional regulation: the FXR connection.
Farnesoid X receptor (FXR) is a nuclear receptor involved in lipoprotein as well as glucose metabolism. Statins are widely used hypolipidemic agents with many pleiotropic actions. It is known that statins affect other nuclear hormone receptors, but no reports are available on the effect of these drugs on FXR. Employing an animal model (Syrian hamsters), we hereby present evidence to demonstrate that Simvastatin, a broadly prescribed statin, decreases the expression of FXR at both the RNA and protein levels and down-regulates its DNA-binding activity. This novel property may have important implications on the mode statins influence on lipoprotein and carbohydrate homeostasis in the organism.
Habeos
Ioannis
I
Department of Biochemistry, School of Medicine, University of Patras, 26110 Patras, Greece.
Ziros
Panos G
PG
Psyrogiannis
Agathoklis
A
Vagenakis
Apostolos G
AG
Papavassiliou
Athanasios G
AG
D000284:Administration, Oral; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D018160:Receptors, Cytoplasmic and Nuclear; D019821:Simvastatin / Q000494:pharmacology*; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*; D000099150:Receptor, Farnesoid X-Activated
D004268:DNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D019821:Simvastatin; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated