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CO/HO-1 Induces NQO-1 Expression via Nrf2 Activation

  • Kim, Hyo-Jeong (School of Biological Sciences, University of Ulsan) ;
  • Zheng, Min (Department of Medical Science, University of Ulsan) ;
  • Kim, Seul-Ki (School of Biological Sciences, University of Ulsan) ;
  • Cho, Jung-Jee (Graduate School of Oriental Medicine, University of Wonkwang) ;
  • Shin, Chang-Ho (Graduate School of Oriental Medicine, University of Wonkwang) ;
  • Joe, Yeon-Soo (School of Biological Sciences, University of Ulsan) ;
  • Chung, Hun-Taeg (School of Biological Sciences, University of Ulsan)
  • Received : 2011.10.05
  • Accepted : 2011.11.07
  • Published : 2011.12.31
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Abstract

Background: Carbon monoxide (CO) is a cytoprotective and homeostatic molecule with important signaling capabilities in physiological and pathophysiological situations. CO protects cells/tissues from damage by free radicals or oxidative stress. NAD(P)H:quinone oxidoreductase (NQO1) is a highly inducible enzyme that is regulated by the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway, which is central to efficient detoxification of reactive metabolites and reactive oxygen species (ROS). Methods: We generated NQO1 promoter construct. HepG2 cells were treated with CO Releasing Molecules-2 (CORM-2) or CO gas and the gene expressions were measured by RT-PCR, immunoblot, and luciferase assays. Results: CO induced expression of NQO1 in human hepatocarcinoma cell lines by activation of Nrf2. Exposure of HepG2 cells to CO resulted in significant induction of NQO1 in dose- and time-dependent manners. Analysis of the NQO1 promoter indicated that an antioxidant responsible element (ARE)-containing region was critical for the CO-induced Nrf2-dependent increase of NQO1 gene expression in HepG2 cells. Conclusion: Our results suggest that CO-induced Nrf2 increases the expression of NQO1 which is well known to detoxify reactive metabolites and ROS.

Keywords

References

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