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  • Modulation of NAD(P)H:quinone oxidoreductase by vanadium in human hepatoma HepG2 cells.

Modulation of NAD(P)H:quinone oxidoreductase by vanadium in human hepatoma HepG2 cells.

Toxicology in vitro : an international journal published in association with BIBRA (2010-07-06)
Ghada Abdelhamid, Anwar Anwar-Mohamed, Mohey M Elmazar, Ayman O S El-Kadi
ABSTRACT

Recent studies demonstrated the carcinogenicity and the mutagenicity of vanadium compounds. In addition, vanadium (V(5+)) was found to enhance the effects of other genotoxic agents. However, the mechanism by which V(5+) induce toxicity remain unknown. In the current study we examined the effect of V(5+) (as ammonium metavanadate, NH(4)VO(3)) on the expression of NAD(P)H: quinone oxidoreductase 1 (NQO1) in human hepatoma HepG2 cells. Therefore, HepG2 cells were treated with increasing concentrations of V(5+) in the presence of two NQO1 inducers, the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and isothiocyanate sulforaphane (SUL). Our results showed that V(5+) inhibited the TCDD- and SUL-mediated induction of NQO1 at mRNA, protein and activity levels. Investigating the effect of V(5+) at transcriptional levels revealed that V(5+) significantly inhibited the TCDD- and SUL-mediated induction of antioxidant responsive element (ARE)-dependent luciferase reporter gene expression. In addition, V(5+) was able to decrease the TCDD- and SUL-induced nuclear accumulation of nuclear factor erythroid 2-related factor-2 (Nrf2) without affecting Nrf2 mRNA or protein levels. Looking at the post-transcriptional level, V(5+) did not affect NQO1 mRNA stability, thus eliminating the possible role of V(5+) in decreasing NQO1 mRNA levels through this mechanism. In contrast, at post-translational level, V(5+) was able to significantly decrease NQO1 protein half-life. The present study demonstrates for the first time that V(5+) down-regulates NQO1 at the transcriptional and post-translational levels in the human hepatoma HepG2 cells via AhR- and Nrf2-dependent mechanisms.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Ammonium metavanadate, 99.95% trace metals basis
Sigma-Aldrich
Ammonium metavanadate, puriss. p.a., ACS reagent, ≥99.0% (RT)
Sigma-Aldrich
Ammonium metavanadate, 99%
Sigma-Aldrich
Ammonium metavanadate, ACS reagent, ≥99.0%