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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
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM036652
Első szerző:	Rühl, Ralph (vegyész)
Cím:	Carotenoids and their metabolites are naturally occurring activators of gene expression via the pregnane X receptor / Rühl Ralph, Sczech Ronny, Landes Nico, Pfluger Paul, Kluth Dirk, Schweigert Florian J.
Dátum:	2004
ISSN:	1436-6207
Megjegyzések:	Carotenoids are important micronutrients in the human diet and are present in human serum at micromolar concentrations. In addition to their antioxidant potential, carotenoids obtain physiologically relevant properties such as influencing cellular signal pathways, gene expression or induction of detoxifying enzymes. In this study, we determined the transactivation of PXR by cotransfection with the full-length receptor and a PXR-responsive reporter gene. Carotenoids and retinol revealed a 5-6 fold reporter gene activity in HepG2 cells in comparison to a 7-fold induction by the well-known PXR agonist rifampicin, whereas apo-carotenals and lycopene exerted less or no activation potential. The inductive efficacy was hereby concentration-dependent. In addition, carotenoid- or retinol-mediated gene expression of PXR-responsive genes like CYP3A4/CYP3A7, CYP3A5, MDR-1 and MRP-2 has been determined in HepG2 cells by RT-PCR with up-regulative properties of beta-carotene or retinol being comparable to or even higher than that of rifampicin. In conclusion, PXR-mediated up-regulation of CYP3A4/CYP3A7 and CYP3A5 as well as MDR1 and MRP2 by carotenoids points to a potential interference on the metabolism of xenobiotic and endogenous relevant compounds.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	European Journal Of Nutrition. - 43 : 6 (2004), p. 336-343. -
További szerzők:	Sczech, Ronny Landes, Nico Pfluger, Paul Kluth, Dirk Schweigert, Florian J.
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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