Bile Acids: Natural Ligands for an Orphan Nuclear Receptor

Bile acids regulate the transcription of genes that control cholesterol homeostasis through molecular mechanisms that are poorly understood. Physiological concentrations of free and conjugated chenodeoxycholic acid, lithocholic acid, and deoxycholic acid activated the farnesoid X receptor (FXR; NR1H...

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Veröffentlicht in:	Science (American Association for the Advancement of Science) 1999-05, Vol.284 (5418), p.1365-1368
Hauptverfasser:	Parks, Derek J., Blanchard, Steven G., Bledsoe, Randy K., Chandra, Gyan, Consler, Thomas G., Kliewer, Steven A., Stimmel, Julie B., Willson, Timothy M., Zavacki, Ann Marie, Moore, David D., Lehmann, Jürgen M.
Format:	Artikel
Sprache:	eng
Schlagworte:	Acids Amino acids Animals Bile Bile acids Bile Acids and Salts - chemistry Bile Acids and Salts - metabolism Bile Acids and Salts - pharmacology Biological and medical sciences Carrier Proteins - metabolism Cell Line Cell lines Cell receptors Cell structures and functions Chenodeoxycholic Acid - metabolism Chenodeoxycholic Acid - pharmacology Cholesterol Cholesterol - metabolism Cholesterols Cholic acids Deoxycholic Acid - metabolism Deoxycholic Acid - pharmacology DNA-Binding Proteins - chemistry DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Fundamental and applied biological sciences. Psychology Genes Genetic regulation Genetic transcription Histone Acetyltransferases Homeostasis Humans Ligands Literary Devices Lithocholic Acid - metabolism Lithocholic Acid - pharmacology Mice Miscellaneous Molecular and cellular biology Nuclear Receptor Coactivator 1 Organic Anion Transporters, Sodium-Dependent Orphan nuclear receptors Peptides Physiological aspects Protein Conformation Receptors Receptors, Cytoplasmic and Nuclear - chemistry Receptors, Cytoplasmic and Nuclear - genetics Receptors, Cytoplasmic and Nuclear - metabolism Recombinant Fusion Proteins - metabolism Regulation Signal Transduction Structure-Activity Relationship Symporters Transcription (Genetics) Transcription Factors - chemistry Transcription Factors - genetics Transcription Factors - metabolism Transfection
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Zusammenfassung:	Bile acids regulate the transcription of genes that control cholesterol homeostasis through molecular mechanisms that are poorly understood. Physiological concentrations of free and conjugated chenodeoxycholic acid, lithocholic acid, and deoxycholic acid activated the farnesoid X receptor (FXR; NR1H4), an orphan nuclear receptor. As ligands, these bile acids and their conjugates modulated interaction of FXR with a peptide derived from steroid receptor coactivator 1. These results provide evidence for a nuclear bile acid signaling pathway that may regulate cholesterol homeostasis.
ISSN:	0036-8075 1095-9203
DOI:	10.1126/science.284.5418.1365