CO/HO-1 Induces NQO-1 Expression via Nrf2 Activation.
- Author:
Hyo Jeong KIM
1
;
Min ZHENG
;
Seul Ki KIM
;
Jung Jee CHO
;
Chang Ho SHIN
;
Yeonsoo JOE
;
Hun Taeg CHUNG
Author Information
- Publication Type:Original Article
- Keywords: Carbon monoxide; Heme oxygenase-1; Nrf2; NQO1
- MeSH: Carbon Monoxide; Cell Line; Free Radicals; Gene Expression; Heme Oxygenase-1; Hep G2 Cells; Humans; Luciferases; Oxidative Stress; Reactive Oxygen Species; Response Elements
- From:Immune Network 2011;11(6):376-382
- CountryRepublic of Korea
- Language:English
- 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.
