Feedback regulation of bile acid synthesis in human liver: Importance of HNF-4α for regulation of CYP7A1
| Autor: | Ewa Ellis, Lisa-Mari Nilsson, Curt Einarsson, Ingemar Björkhem, Anna Abrahamsson, Ulf Gustafsson, Staffan Sahlin |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
CYP7B1 Biophysics Biology Cholesterol 7 alpha-hydroxylase Biochemistry Gene Expression Regulation Enzymologic Feedback Bile Acids and Salts chemistry.chemical_compound Downregulation and upregulation Internal medicine Chenodeoxycholic acid CYP27A1 medicine Humans RNA Messenger Cholesterol 7-alpha-Hydroxylase Molecular Biology Cholestyramine Cell Biology Phosphoproteins DNA-Binding Proteins Endocrinology Hepatocyte Nuclear Factor 4 Liver Hepatocyte nuclear factor 4 chemistry CYP8B1 Transcription Factors medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 330:395-399 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2005.02.170 |
| Popis: | A great number of nuclear factors are involved in the negative feedback mechanism regulating bile acid synthesis. There are two major ways for the negative feedback to effect the synthesis; the SHP-dependent, involving FXR, and the SHP-independent way, affecting HNF-4alpha. We studied 23 patients with gallstone disease. Eight patients were treated with chenodeoxycholic acid, 7 with cholestyramine prior to operation, and 8 served as controls. Liver biopsies were analyzed with Real-time-PCR. In the cholestyramine-treated group mRNA levels of CYP7A1 were increased about 10-fold. Treatment with CDCA decreased the mRNA levels of CYP7A1 by about 70%. The mRNA levels of CYP8B1, CYP27A1, and CYP7B1 were not significantly altered in the treated groups. The analysis of mRNA levels for HNF-4alpha showed 64% higher levels in the cholestyramine-treated group compared to the controls. These levels showed positive and highly significant correlation to the levels of mRNA of CYP7A1 when studied in all three groups together. FXR, SHP, and LRH-1/FTF were not significantly affected by the different treatments. Our results indicate that when bile acid synthesis is upregulated by cholestyramine treatment the SHP-independent pathway for controlling CYP7A1 transcription dominates over the SHP-dependent pathway. |
| Databáze: | OpenAIRE |
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