Induction of CYP1 Family Members under Low-glucose Conditions Requires AhR Expression and Occurs through the Nuclear Translocation of AhR

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Author(s)

    • TERASHIMA Jun
    • Pharmacodynamics and Molecular Genetics, School of Pharmacy, Iwate Medical University
    • HABANO Wataru
    • Pharmacodynamics and Molecular Genetics, School of Pharmacy, Iwate Medical University
    • GAMOU Toshie
    • Pharmacodynamics and Molecular Genetics, School of Pharmacy, Iwate Medical University
    • OZAWA Shogo
    • Pharmacodynamics and Molecular Genetics, School of Pharmacy, Iwate Medical University

Abstract

  Cross-talk between the aryl hydrocarbon receptor (AhR) pathway and the typical stress response is thought to be an important signal transduction in response to nutrient-stress conditions, such as glucose deprivation in liver cells. In the present study, we demonstrate that reduction of glucose concentration in the medium of HepG2 cells, a human hepatocellular carcinoma cell line, induces the <i>CYP1</i> family and <i>Nrf2</i>. RNAi for <i>AhR</i> abolishes the induction of expression of <i>CYP1</i> and <i>Nrf2</i>. These inductions are accompanied by the translocation of AhR into the nucleus in response to low-glucose conditions. Endogenous compounds are recruited as AhR ligands to induce various gene expressions, and our present results suggest that an endogenous AhR ligand is produced under low-glucose conditions and that the role of AhR as a transcription factor is related to the low-glucose response. The recommended glucose concentration (4.5 g/L) in the medium for culture of HepG2 was used as the high-glucose concentration in this study. We adopted 1.0 g/L as the low-glucose condition for elucidation of mechanisms of the stress response. These results will be useful to understand the relationship between drug-metabolizing enzymes and mechanisms of the anti-stress response of tumor cells, and will also be useful for investigating preventive remedies against tumor angiogenesis.<br>

Journal

  • Drug Metabolism and Pharmacokinetics

    Drug Metabolism and Pharmacokinetics 26(6), 577-583, 2011

    The Japanese Society for the Study of Xenobiotics

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