Vitamin E activates gene expression via the pregnane X receptor
| Autor: | Dirk Kluth, Hansruedi Glatt, Regina Brigelius-Flohé, Nico Landes, Gaby-Fleur Böl, Ralph Rühl, Marc Birringer, Paul T. Pfluger |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Receptors
Steroid medicine.medical_treatment Gene Expression Receptors Cytoplasmic and Nuclear Biology digestive system Biochemistry Substrate Specificity chemistry.chemical_compound Cytochrome P-450 Enzyme System Tumor Cells Cultured medicine Humans Vitamin E Drug Interactions Elméleti orvostudományok Pharmacology Regulation of gene expression Pregnane X receptor Dose-Response Relationship Drug CYP3A4 Activator (genetics) Pregnane Pregnane X Receptor Cytochrome P450 Orvostudományok digestive system diseases Nuclear receptor chemistry biology.protein |
| Zdroj: | Biochemical Pharmacology. 65:269-273 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/s0006-2952(02)01520-4 |
| Popis: | Tocopherols and tocotrienols are metabolized by side chain degradation via initial omega-oxidation and subsequent beta-oxidation. omega-Oxidation is performed by cytochrome P450 (CYP) enzymes which are often regulated by their substrates themselves. Results presented here show that all forms of Vitamin E are able to activate gene expression via the pregnane X receptor (PXR), a nuclear receptor regulating a variety of drug metabolizing enzymes. In HepG2 cells transfected with the human PXR and the chloramphenicol acetyl transferase (CAT) gene linked to two PXR responsive elements, CAT activity was most strongly induced by alpha- and gamma-tocotrienol followed by rifampicin, delta-, alpha- and gamma-tocopherol. The inductive efficacy was concentration-dependent; its specificity was underscored by a lower response when cotransfection with PXR was omitted. Up-regulation of endogenous CYP3A4 and CYP3A5 mRNA was obtained by gamma-tocotrienol, the most potent activator of PXR, with the same efficacy as with rifampicin. This points to a potential interference of individual forms of Vitamin E with the metabolism and efficacy of drugs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect