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KMID : 0923620110110060376
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Immune Network
2011 Volume.11 No. 6 p.376 ~ p.382
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CO/HO-1 Induces NQO-1 Expression via Nrf2 Activation
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Kim Hyo-Jeong
Zheng Min
Kim Seul-Ki
Cho Jung-Jee
Shin Chang-Ho
Joe Yeon-Soo
Chung Hun-Taeg
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Abstract
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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.
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KEYWORD
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Carbon monoxide, Heme oxygenase-1, Nrf2, NQO1
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