. . "Recent findings show that colchicine (COL) in submicromolar concentrations downregulates the expression of major drug-metabolizing P450 enzymes in human hepatocytes. Concomitantly, the expression of pregnane X receptor (PXR) and constitutive androstane receptor (CAR) was diminished by COL, whereas expression of glucocorticoid receptor (GR) remained unaltered. A tentative mechanism is perturbation of the GR-PXR/CAR-CYP2/3 signaling cascade, resulting in restricted transcriptional activity of GR receptor by colchicine. In this work we focused on 10-demethylcolchicine (colchiceine; EIN), a structural analogue and a putative metabolite of COL that lacks tubulin-binding activity. We investigated the effects of EIN on the expression of PXR, CAR, and GR receptors in primary cultures of human hepatocytes. In contrast with the effects of COL, EIN does not alter the expression of PXR, CAR, and/or GR receptors mRNAs. In addition, EIN had no effects on transcriptional activities of PXR, CAR, and GR receptors in r" . "RIV/61989592:15110/07:00004397" . . "Vilarem, M.-J." . . "15110" . . . "Cell Biology and Toxicology" . "RIV/61989592:15110/07:00004397!RIV08-MSM-15110___" . "Expression and transcriptional activities of nuclear receptors involved in regulation of drug-metabolizing enzymes are not altered by colchicine: focus on PXR, CAR, and GR in primary human hepatocytes"@en . "Ulrichov\u00E1, Jitka" . "Expression and transcriptional activities of nuclear receptors involved in regulation of drug-metabolizing enzymes are not altered by colchicine: focus on PXR, CAR, and GR in primary human hepatocytes"@en . . . "23" . . "0742-2091" . "Expression and transcriptional activities of nuclear receptors involved in regulation of drug-metabolizing enzymes are not altered by colchicine: focus on PXR, CAR, and GR in primary human hepatocytes" . "Dvo\u0159\u00E1k, Zden\u011Bk" . . . "[6FCB72380F14]" . "human hepatocytes; colchiceine; orphan receptors; drug metabolism"@en . . . "Recent findings show that colchicine (COL) in submicromolar concentrations downregulates the expression of major drug-metabolizing P450 enzymes in human hepatocytes. Concomitantly, the expression of pregnane X receptor (PXR) and constitutive androstane receptor (CAR) was diminished by COL, whereas expression of glucocorticoid receptor (GR) remained unaltered. A tentative mechanism is perturbation of the GR-PXR/CAR-CYP2/3 signaling cascade, resulting in restricted transcriptional activity of GR receptor by colchicine. In this work we focused on 10-demethylcolchicine (colchiceine; EIN), a structural analogue and a putative metabolite of COL that lacks tubulin-binding activity. We investigated the effects of EIN on the expression of PXR, CAR, and GR receptors in primary cultures of human hepatocytes. In contrast with the effects of COL, EIN does not alter the expression of PXR, CAR, and/or GR receptors mRNAs. In addition, EIN had no effects on transcriptional activities of PXR, CAR, and GR receptors in r"@en . "NL - Nizozemsko" . "Exprese a transkrip\u010Dn\u00ED aktivity jadern\u00FDch receptor\u016F zapojen\u00FDch do regulace enzym\u016F metabolizuj\u00EDc\u00EDch l\u00E9\u010Diva nejsou zm\u011Bn\u011Bny kolchicinem: Zaost\u0159eno na PXR, CAR a GR v prim\u00E1rn\u00EDch lidsk\u00FDch hepatocytech"@cs . "Exprese a transkrip\u010Dn\u00ED aktivity jadern\u00FDch receptor\u016F zapojen\u00FDch do regulace enzym\u016F metabolizuj\u00EDc\u00EDch l\u00E9\u010Diva nejsou zm\u011Bn\u011Bny kolchicinem: Zaost\u0159eno na PXR, CAR a GR v prim\u00E1rn\u00EDch lidsk\u00FDch hepatocytech"@cs . "3"^^ . "Modriansk\u00FD, Martin" . "Expression and transcriptional activities of nuclear receptors involved in regulation of drug-metabolizing enzymes are not altered by colchicine: focus on PXR, CAR, and GR in primary human hepatocytes" . . "2" . . "Z(MSM6198959216)" . "421407" . "63-73" . . "11"^^ . "Nov\u00E1 data ukazuj\u00ED, \u017Ee kolchicin (COL) p\u0159\u00EDtomn\u00FD submikromol\u00E1rn\u00EDch koncentrac\u00EDch sni\u017Euje expresi d\u016Fle\u017Eit\u00FDch enzym\u016F rodiny P450 v lidsk\u00FDch hepatocytech. Exprese pregnanov\u00E9ho X receptoru (PXR) a konstitutivn\u00EDho androstanov\u00E9ho receptoru (CAR) byla sn\u00ED\u017Eena vlivem COL, naproti tomu exprese glukokortikoidn\u00EDho receptoru (GR) ovlivn\u011Bna nebyla. P\u0159edpokl\u00E1dan\u00FDm mechanismem je poru\u0161en\u00ED sign\u00E1ln\u00ED kask\u00E1dy GR-PXR/CAR-CYP2/3, co\u017E m\u00E1 za n\u00E1sledek omezenou transkrip\u010Dn\u00ED aktivitu GR. V t\u00E9to pr\u00E1ci jsme se soust\u0159edili na 10-demethylkolchicein (EIN), strukturn\u00ED analog a p\u0159edpokl\u00E1dan\u00FD metabolit COL, ov\u0161em postr\u00E1daj\u00EDc\u00ED schopnost v\u00E1zat se na tubulin. Na rozd\u00EDl od COL, EIN nem\u011Bnil expresi mRNA PXR, CAR, a/nebo GR receptor\u016F. Nav\u00EDc, EIN nem\u011Bl \u017E\u00E1dn\u00FD vliv na transkrip\u010Dn\u00ED aktivitu PXR, CAR a GR receptor\u016F, kter\u00E1 byla hodnocena s pomoc\u00ED report\u00E9rov\u00FDch esej\u00ED. Vzhledem k tomu, \u017Ee COL a EIN jsou si strukturn\u011B velmi bl\u00EDzc\u00ED a li\u0161\u00ED se pouze schopnost\u00ED v\u00E1zat se na tubulin, na\u0161e v\u00FDsledky nazna\u010Duj\u00ED, \u017Ee ovlivn\u011Bn\u00ED sign\u00E1ln\u00ED kask\u00E1dy GR-PXR/CAR-CYP2/3 j"@cs . . "Maurel, Patrick" . . "5"^^ .