The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Letter
5-Aminoimidazole-4-carboxamide-1-β-ribofuranoside (AICAR) prevents nuclear translocation of constitutive androstane receptor by AMP-activated protein kinase (AMPK) independent manner
Yuichiro KannoYoshimi InoueYoshio Inouye
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2010 Volume 35 Issue 4 Pages 571-576

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Abstract

The nuclear receptor superfamily consists of ligand-dependent transcription factors. Among them, constitutive androstane receptor (CAR) plays a key role in the detoxification of xenobiotics, inducing various drug-metabolizing enzymes including human CYP2B6 and its homologues of other species. AMP-activated protein kinase (AMPK) acts as an important energy sensor, being activated by an increased AMP/ATP ratio. CAR is activated by phenobarbital (PB) treatment. It has been recently reported that AMPK is involved in PB-mediated CYP2B induction both in vitro and in vivo. We investigated the relationship between the functions of AMPK and CAR in rat primary hepatocyte. The AMPK-activator 5-aminoimidazole-4-Carboxamide-1-β-Ribofuranoside (AICAR) unexpectedly repressed PB-induced CYP2B mRNA expression as well as AMPK-inhibitor compound C. In contrast, both the AMPK-activator metformin and the constitutive active form of AMPK enhanced PB-induced PB-responsive enhancer module-driven reporter gene expression. We demonstrated that AICAR prevented nuclear translocation of CAR in an AMPK-independent manner in rat primary hepatocytes. AICAR might be a convenient probe for studying the mechanisms of PB-induced activation, especially nuclear translocation, of CAR in rat primary hepatocytes.

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© 2010 The Japanese Society of Toxicology
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