Abstract
We examined the effect of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) on two transcription factors, CAAT/enhancer binding protein-alpha (C/EBPα) and beta (C/EBPβ), involved in the coordination of gene expression in adipose and liver. A single dose of TCDD (100 μg/kg) to male C57BL mice resulted in a time- and dose-dependent decrease in the level of C/EBPα mRNA in adipose tissue and liver, and a reciprocal increase in C/EBPβ mRNA. Gel shift analysis using hepatic nuclear extracts from control and TCDD-treated mice and an oligonucleotide containing a C/EBP recognition element revealed a time-dependent change in DNA–protein complexes formed. Bands corresponding to C/EBPα, as determined by supershift analysis, diminished in TCDD-treated animals over a 7-day time period, whereas two new bands corresponding to C/EBPβ, not present in control extracts, were increased significantly in treated samples. TCDD induced C/EBPβ mRNA in wild-type mouse hepatoma cells, but not in aryl hydrocarbon receptor (AhR) nuclear translocator-deficient hepatoma cells. Induction in wild-type hepatoma cells was antagonized effectively by a molar excess of α-naphthoflavone. These results showed that TCDD caused rapid, reciprocal changes in C/EBPα and C/EBPβ mRNAs and DNA binding in the adipose and liver of male C57BL mice and induced C/EBPβ in hepatoma cells in an AhR-dependent manner. C/EBPs play vital roles in the coordination of energy homeostasis, and their alteration by TCDD may provide insight into the mechanism by which TCDD perturbs energy storage and utilization in vivo.
Published Version
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