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

• Published in: Immune network Vol. 11; no. 6; pp. 376 - 382
• Main Authors: Kim, Hyo-Jeong, Zheng, Min, Kim, Seul-Ki, Cho, Jung-Jee, Shin, Chang-Ho, Joe, Yeon-Soo, Chung, Hun-Taeg
• Format: Journal Article
• Language: English
• Published: Korea (South) 대한면역학회 01.12.2011; The Korean Association of Immunologists
• Subjects: Original; 면역학; NQO1; Carbon monoxide; Nrf2; Heme oxygenase-1
• ISSN: 1598-2629; 2092-6685; 2092-6685
• DOI: 10.4110/in.2011.11.6.376

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). 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. 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. Our results suggest that CO-induced Nrf2 increases the expression of NQO1 which is well known to detoxify reactive metabolites and ROS.