title: CO/HO-1 Induces NQO-1 Expression via Nrf2 Activation.
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.
  
  
  CONCLUSIONS
  Our results suggest that CO-induced Nrf2 increases the expression of NQO1 which is well known to detoxify reactive metabolites and ROS.
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.forename: Seul-Ki
authors.initials: SK
authors.lastname: Kim
authors.forename: Jung Jee
authors.initials: JJ
authors.lastname: Cho
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Shin
authors.forename: Yeonsoo
authors.initials: Y
authors.lastname: Joe
authors.forename: Hun Taeg
authors.initials: HT
authors.lastname: Chung