Publication Date:
1999-05-21
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parks, D J -- Blanchard, S G -- Bledsoe, R K -- Chandra, G -- Consler, T G -- Kliewer, S A -- Stimmel, J B -- Willson, T M -- Zavacki, A M -- Moore, D D -- Lehmann, J M -- F32 DK09793/DK/NIDDK NIH HHS/ -- R01 DK53366/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1999 May 21;284(5418):1365-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biochemistry, Glaxo Wellcome Research and Development, Research Triangle Park NC, 27709, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10334993" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Bile Acids and Salts/chemistry/*metabolism/pharmacology
;
Carrier Proteins/metabolism
;
Cell Line
;
Chenodeoxycholic Acid/*metabolism/pharmacology
;
Cholesterol/metabolism
;
DNA-Binding Proteins/chemistry/genetics/*metabolism
;
Deoxycholic Acid/metabolism/pharmacology
;
Histone Acetyltransferases
;
Homeostasis
;
Humans
;
Ligands
;
Lithocholic Acid/metabolism/pharmacology
;
Mice
;
Nuclear Receptor Coactivator 1
;
*Organic Anion Transporters, Sodium-Dependent
;
Protein Conformation
;
Receptors, Cytoplasmic and Nuclear/chemistry/genetics/*metabolism
;
Recombinant Fusion Proteins/metabolism
;
Signal Transduction
;
Structure-Activity Relationship
;
*Symporters
;
Transcription Factors/chemistry/genetics/*metabolism
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
