Inhibition of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-stimulated Cyp1a1 promoter activity by hypoxic agents.

摘要: Since hypoxia-inducible factor-1alpha (HIF-1alpha) and the arylhydrocarbon receptor (AhR) shared AhR nuclear translocator (Arnt) for hypoxia- AhR-mediated signaling, respectively, it was possible to establish hypothesis that hypoxia could regulate cytochrome P450 1a1 (Cyp1a1) expression. In order test this hypothesis, we undertook examine effect of on Cyp1a1 transcription in Hepa-I cells. Mouse 5'-flanking DNA, 1.6 kb cloned into pGL3 expression vector construct pmCyp1a1-Luc. cells were transfected with pmCyp1a1-Luc treated 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) presence or absence various hypoxic agents such as 1-100 microM cobalt chloride, picolinic acid, desferrioxamine. Luciferase activity reporter gene measured from pmCyp1a1-Luc-transfected cell lysate which contains 2 microgram total protein using luciferin a substrate. Hypoxic desferrioxamine showed inhibition luciferase induced by 1-nM TCDD treatment dose-and time-dependent manner. Concomitant 150 ferrous sulfate acid recovered inhibited TCDD. These data demonstrated iron-chelating dioxin-induced Thus, might suggest inhibits TCDD-induced due competition between HIF-1alpha Arnt