CO/HO-1 Induces NQO-1 Expression via Nrf2 Activation
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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. HepG2cells 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.
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. HepG2cells 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.
참고문헌 (40)
- Tenhunen R, "The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase", Proc Natl Acad Sci U S A, 61, pp.748~755 (1968)
- Otterbein LE, "Heme oxygenase-1: unleashing the protective properties of heme", Trends Immunol, 24, pp.449~455 (2003)
- Otterbein LE, "Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury", Nat Med, 9, pp.183~190 (2003)
- Fujimoto H, "Carbon monoxide protects against cardiac ischemia--reperfusion injury in vivo via MAPK and Akt--eNOS pathways", Arterioscler Thromb Vasc Biol, 24, pp.1848~1853 (2004)
- Bauer I, "Bench-to-bedside review: Carbon monoxide-from mitochondrial poisoning to therapeutic use", Crit Care, 13, pp.220~ (2009)
- Siegel D, "NAD(P)H:quinone oxidoreductase 1: role as a superoxide scavenger", Mol Pharmacol, 65, pp.1238~1247
- Siegel D, "The reduction of alpha-tocopherolquinone by human NAD(P)H: quinone oxidoreductase: the role of alpha-tocopherolhydroquinone as a cellular antioxidant", Mol Pharmacol, 52, pp.300~305 (1997)
- Asher G, "Regulation of p53 stability and p53-dependent apoptosis by NADH quinone oxidoreductase 1", Proc Natl Acad Sci U S A, 98, pp.1188~1193 (2001)
- Asher G, "NQO1 stabilizes p53 through a distinct pathway", Proc Natl Acad Sci U S A, 99, pp.3099~3104 (2002)
- Asher G, "Mdm-2 and ubiquitin-independent p53 proteasomal degradation regulated by NQO1", Proc Natl Acad Sci U S A, 99, pp.13125~13130 (2002)
- Iskander K, "Lower induction of p53 and decreased apoptosis in NQO1-null mice lead to increased sensitivity to chemical-induced skin carcinogenesis", Cancer Res, 65, pp.2054~2058 (2005)
- Ahn KS, "Genetic deletion of NAD(P)H: Quinone oxidoreductase 1 abrogates activation of nuclear factor-kappa B, I kappa B alpha kinase, c-Jun N-terminal kinase, Akt, p38, and p44", 42 mitogen-activated protein kinases and potentiates apoptosis, 2006, pp.281(29), 19798~19808[DOI]
- Begleiter A, "Induction of NQO1 in cancer cells", Methods Enzymol, 382, pp.320~351 (2004)
- Dhakshinamoorthy S, "Functional characterization and role of INrf2 in antioxidant response element-mediated expression and antioxidant induction of NAD(P)H:quinone oxidoreductase1 gene", Oncogene, 20, pp.3906~3917 (2001)
- Nioi P, "Contribution of NAD(P)H:quinone oxidoreductase 1 to protection against carcinogenesis, and regulation of its gene by the Nrf2 basic-region leucine zipper and the arylhydrocarbon receptor basic helix-loop-helix transcription factors", Mutat Res, 555, pp.149~171 (2004)
- Jaiswal AK, "Nrf2 signaling in coordinated activation of antioxidant gene expression", Free Radic Biol Med, 36, pp.1199~1207 (2004)
- Kwak MK, "Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway. Identification of novel gene clusters for cell survival", J Biol Chem, 278, pp.8135~8145 (2003)
- Nguyen T, "Regulatory mechanisms controlling gene expression mediated by the antioxidant response element", Annu Rev Pharmacol Toxicol, 43, pp.233~260 (2003)
- Motohashi H, "Nrf2-Keap1 defines a physiologically important stress response mechanism", Trends Mol Med, 10, pp.549~557 (2004)
- Itoh K, "Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain", Genes Dev, 13, pp.76~86 (1999)
- Kang MI, "Scaffolding of Keap1 to the actin cytoskeleton controls the function of Nrf2 as key regulator of cytoprotective phase 2 genes", Proc Natl Acad Sci U S A, 101, pp.2046~2051 (2004)
- Lee BS, "Carbon monoxide mediates heme oxygenase 1 induction via Nrf2 activation in hepatoma cells", Biochemical and Biophysical Research Communications, 343(3), pp.965~972 (2006), Academic Press
- Rushworth SA, "Lipopolysaccharide- induced expression of NAD(P)H:quinone oxidoreductase 1 and heme oxygenase-1 protects against excessive inflammatory responses in human monocytes", J Immunol, 181, pp.6730~6737 (2008)
- Cho HY, "Gene expression profiling of NRF2-mediated protection against oxidative injury", Free Radic Biol Med, 38, pp.325~343 (2005)
- Venugopal R, "Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:quinone oxidoreductase1 gene", Proc Natl Acad Sci U S A, 96, pp.14960~14965 (1996)
- Balogun E, "Curcumin activates the haem oxygenase- 1 gene via regulation of Nrf2 and the antioxidant-responsive element", Biochem J, 371, pp.887~895 (2003)
- 정헌택, "Carbon monoxide induces heme oxygenase-1 via activation of protein kinase R-like endoplasmic reticulum kinase and inhibits endothelial cell apoptosis triggered by endoplasmic reticulum stress", CIRCULATION RESEARCH, 101, pp.919~927, LIPPINCOTT WILLIAMS & WILKINS
- Motterlini R, "The therapeutic potential of carbon monoxide", Nat Rev Drug Discov, 9, pp.728~743 (2010)
- Motohashi H, "Nrf2-Keap1 defines a physiologically important stress response mechanism", Trends Mol Med, 10, pp.549~557 (2004)
- Tanigawa S, "Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin", Free Radic Biol Med, 42, pp.1690~1703 (2007)
- Xie T, "ARE- and TRE-mediated regulation of gene expression. Response to xenobiotics and antioxidants", J Biol Chem, 270, pp.6894~6900 (1995)
- Li Y, "Regulation of human NAD(P)H:quinone oxidoreductase gene. Role of AP1 binding site contained within human antioxidant response element", J Biol Chem, 267, pp.15097~15104 (1992)
- Miao W, "Transcriptional regulation of NF-E2 p45-related factor (NRF2) expression by the aryl hydrocarbon receptor-xenobiotic response element signaling pathway: direct cross-talk between phase I and II drug-metabolizing enzymes", J Biol Chem, 280, pp.20340~20348 (2005)
- Itoh K, "An Nrf2", small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements, 1997, pp.236, 313~322
- Siemankowski LM, "Increased tumor necrosis factor-alpha sensitivity of MCF-7 cells transfected with NAD(P)H:quinone reductase", Cancer Res, 60, pp.3638~3644 (2000)
- Yeligar SM, "Ethanol-induced HO-1 and NQO1 are differentially regulated by HIF-1alpha and Nrf2 to attenuate inflammatory cytokine expression", J Biol Chem, 285, pp.35359~35373 (2010)
- Bian JT, "Association of NAD(P)H:quinone oxidoreductase 1 polymorphism and Alzheimer's disease in Chinese", J Mol Neurosci, 34, pp.235~240 (2008)
- Ryter SW, "Heme oxygenase", carbon monoxide signaling pathways: regulation and functional significance, 2002, pp.234, 249~263
- Song R, "Carbon monoxide inhibits T lymphocyte proliferation via caspase-dependent pathway", J Immunol, 172, pp.1220~1226 (2004)
- 정헌택, "Roles of heme oxygenase-1 in the antiproliferative and antiapoptotic effects of nitric oxide on Jurkat T cells", MOLECULAR PHARMACOLOGY, 66, pp.122~128, AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
