"RIV/61989592:15310/08:00005344!RIV09-MSM-15310___" . "0006-2952" . "Lemr, Karel" . "75" . "7"^^ . "JNK inhibitor SP600125 is a partial agonist of human aryl hydrocarbon receptor and induces CYP1A1 and CYP1A2 genes in primary human hepatocytes" . . "SP600125, a specific inhibitor of c-Jun-N-Terminal kinase (JNK), was reported as a ligand and antagonist of aryl hydrocarbon receptor (AhR) [Joiakim A, Mathieu PA, Palermo C, Gasiewicz TA, Reiners Jr JJ. The Jun N terminal kinase inhibitor SP600125 is a ligand and antagonist of the aryl hydrocarbon receptor. Drug Metab Dispos 2003;31(11):1279-82]. Here we show that SP600125 is not an antagonist but a partial agonist of human AhR. SP600125 significantly induced CYP1A1 and CYP1A2 mRNAs in primary human hepatocytes and CYP1A1 mRNA in human hepatoma cells HepG2. This effect was abolished by resveratrol, an antagonist of AhR. Consistent with the recent report, SP600125 dose-dependently inhibited CYP1A1 and CYPIA2 genes induction by a prototype AhR ligand 2,3,7,8-tetrachlorodibenzo-p -dioxin (TCDD) in human hepatocytes. Moreover, SP600125 displayed typical behavior of a partial agonist in HepG2 cells transiently transfected with a reporter plasmid containing two inverted repeats of the dioxin responsive el"@en . . . "13"^^ . "Dvo\u0159\u00E1k, Zden\u011Bk" . . . . . "Anzenbacherov\u00E1, Eva" . "Bedn\u00E1\u0159, Petr" . . "2" . "GB - Spojen\u00E9 kr\u00E1lovstv\u00ED Velk\u00E9 Brit\u00E1nie a Severn\u00EDho Irska" . "Vrzal, Radim" . "SP600125, specifick\u00FD inhibitor c-Jun-N-Termin\u00E1ln\u00ED kinasy (JNK), byl pops\u00E1n jako ligand a antagonista aryl uhlovod\u00EDkov\u00E9ho receptoru (AhR) (Joiakim et al. 2003 Drug Metab Dispos 31:1279-82). Zde ukazujeme, \u017Ee SP600125 nen\u00ED antagonista ale parci\u00E1ln\u00ED agonista lidsk\u00E9ho AhR. SP600125 signifikantn\u011B indukoval CYP1A1 a CYP1A2 mRNA v prim\u00E1rn\u00EDch lidsk\u00FDch hepatocytech a CYP1A1 mRNA v lidsk\u00FDch hepatomov\u00FDch bu\u0148k\u00E1ch HepG2. Tento \u00FA\u010Dinek byl vyru\u0161en resveratrolem, antagonistou AhR. Konzistentn\u011B s recentn\u00EDm pozorov\u00E1n\u00EDm, SP600125 koncentra\u010Dn\u011B-z\u00E1visle inhiboval indukci CYP1A1 a CYP1A2 gen\u016F prototypick\u00FDm AhR ligandem 2,3,7,8-tetrachlorodibenzo-p-dioxinem (TCDD) v lidsk\u00FDch hepatocytech. Nav\u00EDc SP600125 vyk\u00E1zal typick\u00E9 chov\u00E1n\u00ED parci\u00E1ln\u00EDho agonisty v HepG2 bu\u0148k\u00E1ch transientn\u011B transfekovan\u00FDch s report\u00E9rov\u00FDm plasmidem obsahuj\u00EDc\u00EDm dva invertovan\u00E9 opakovan\u00E1n\u00ED dioxin responsivn\u00EDho elementu nebo s plasmidem obsahuj\u00EDc\u00EDm 5\u00B4-flanking region lidsk\u00E9ho CYP1A1 gene. SP600125 transaktivoval report\u00E9rov\u00E9 plasmidy s EC50 0.005 uM a 1.89 uM. N"@cs . . "SP600125 je parci\u00E1ln\u00ED atomista lidsk\u00E9ho aryl uhlovod\u00EDkov\u00E9ho receptoru a indukuje CYP1A1 a CYP1A2 geny v prim\u00E1rn\u00EDch lidsk\u00FDch hepatocytech."@cs . . . "aryl hydrocarbon receptor; human hepatocytes; c-Jun-N-terminal kinase; SP600125"@en . . "RIV/61989592:15310/08:00005344" . . "SP600125, a specific inhibitor of c-Jun-N-Terminal kinase (JNK), was reported as a ligand and antagonist of aryl hydrocarbon receptor (AhR) [Joiakim A, Mathieu PA, Palermo C, Gasiewicz TA, Reiners Jr JJ. The Jun N terminal kinase inhibitor SP600125 is a ligand and antagonist of the aryl hydrocarbon receptor. Drug Metab Dispos 2003;31(11):1279-82]. Here we show that SP600125 is not an antagonist but a partial agonist of human AhR. SP600125 significantly induced CYP1A1 and CYP1A2 mRNAs in primary human hepatocytes and CYP1A1 mRNA in human hepatoma cells HepG2. This effect was abolished by resveratrol, an antagonist of AhR. Consistent with the recent report, SP600125 dose-dependently inhibited CYP1A1 and CYPIA2 genes induction by a prototype AhR ligand 2,3,7,8-tetrachlorodibenzo-p -dioxin (TCDD) in human hepatocytes. Moreover, SP600125 displayed typical behavior of a partial agonist in HepG2 cells transiently transfected with a reporter plasmid containing two inverted repeats of the dioxin responsive el" . "Maurel, Patrick" . "P\u00E1vek, Petr" . . . "JNK inhibitor SP600125 is a partial agonist of human aryl hydrocarbon receptor and induces CYP1A1 and CYP1A2 genes in primary human hepatocytes" . "Havl\u00EDk, Roman" . "373988" . . . "P(GA303/07/0128), S, Z(MSM6198959216)" . "\u0160vecov\u00E1, Lucie" . "9"^^ . . . . "JNK inhibitor SP600125 is a partial agonist of human aryl hydrocarbon receptor and induces CYP1A1 and CYP1A2 genes in primary human hepatocytes"@en . . "Henklov\u00E1, Pavla" . "Jan\u010Dov\u00E1, Petra" . "JNK inhibitor SP600125 is a partial agonist of human aryl hydrocarbon receptor and induces CYP1A1 and CYP1A2 genes in primary human hepatocytes"@en . . . "Biochemical Pharmacology" . . "Ehrmann, Ji\u0159\u00ED" . "15310" . "SP600125 je parci\u00E1ln\u00ED atomista lidsk\u00E9ho aryl uhlovod\u00EDkov\u00E9ho receptoru a indukuje CYP1A1 a CYP1A2 geny v prim\u00E1rn\u00EDch lidsk\u00FDch hepatocytech."@cs . "[6569FA1CBCE6]" . . "Ulrichov\u00E1, Jitka" .