Vitamin E activates gene expression via the pregnane X receptor

Nico Landes, Paul Pfluger, Dirk Kluth, Marc Birringer, Ralph Rühl, Gaby Fleur Böl, Hansruedi Glatt, Regina Brigelius-Flohé

Research output: Contribution to journalArticlepeer-review

209 Scopus citations

Abstract

Tocopherols and tocotrienols are metabolized by side chain degradation via initial ω-oxidation and subsequent β-oxidation. ω-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 α- and γ-tocotrienol followed by rifampicin, δ-, α- and γ-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 γ-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.

Original languageEnglish
Pages (from-to)269-273
Number of pages5
JournalBiochemical Pharmacology
Volume65
Issue number2
DOIs
StatePublished - 15 Jan 2003
Externally publishedYes

Keywords

  • Cytochrome P450
  • Drug interference
  • Gene regulation
  • Metabolism
  • Pregnane X receptor
  • Vitamin E

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