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001-es BibID:BIBFORM036657
Első szerző:Landes, Nico
Cím:Vitamin E activates gene expression via the pregnane X receptor / Landes Nico, Pfluger Paul, Kluth Dirk, Birringer Marc, Rühl Ralph, Böl Gaby-Fleur, Glatt Hansruedi, Brigelius-Flohé Regina
Dátum:2003
ISSN:0006-2952
Megjegyzések: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.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Biochemical Pharmacology. - 65 : 2 (2003), p. 269-273. -
További szerzők:Pfluger, Paul Kluth, Dirk Birringer, Marc Rühl, Ralph (1969-) (vegyész) Böl, Gaby-Fleur Glatt, Hansruedi Brigelius-Flohé, Regina
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