DOI QR코드

DOI QR Code

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

  • Kim, Hyo-Jeong (School of Biological Sciences, University of Ulsan) ;
  • Zheng, Min (Department of Medical Science, University of Ulsan) ;
  • Kim, Seul-Ki (School of Biological Sciences, University of Ulsan) ;
  • Cho, Jung-Jee (Graduate School of Oriental Medicine, University of Wonkwang) ;
  • Shin, Chang-Ho (Graduate School of Oriental Medicine, University of Wonkwang) ;
  • Joe, Yeon-Soo (School of Biological Sciences, University of Ulsan) ;
  • Chung, Hun-Taeg (School of Biological Sciences, University of Ulsan)
  • 투고 : 2011.10.05
  • 심사 : 2011.11.07
  • 발행 : 2011.12.31

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. 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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참고문헌

  1. Tenhunen R, Marver HS, Schmid R: The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc Natl Acad Sci U S A 61;748-755, 1968. https://doi.org/10.1073/pnas.61.2.748
  2. Otterbein LE, Soares MP, Yamashita K, Bach FH: Heme oxygenase- 1: unleashing the protective properties of heme. Trends Immunol 24;449-455, 2003 https://doi.org/10.1016/S1471-4906(03)00181-9
  3. Otterbein LE, Zuckerbraun BS, Haga M, Liu F, Song R, Usheva A, Stachulak C, Bodyak N, Smith RN, Csizmadia E, Tyagi S, Akamatsu Y, Flavell RJ, Billiar TR, Tzeng E, Bach FH, Choi AM, Soares MP: Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury. Nat Med 9;183-190, 2003. https://doi.org/10.1038/nm817
  4. Fujimoto H, Ohno M, Ayabe S, Kobayashi H, Ishizaka N, Kimura H, Yoshida K, Nagai R: Carbon monoxide protects against cardiac ischemia--reperfusion injury in vivo via MAPK and Akt--eNOS pathways. Arterioscler Thromb Vasc Biol 24; 1848-1853, 2004. https://doi.org/10.1161/01.ATV.0000142364.85911.0e
  5. Bauer I, Pannen BH: Bench-to-bedside review: Carbon monoxide-- from mitochondrial poisoning to therapeutic use. Crit Care 13;220, 2009. https://doi.org/10.1186/cc7887
  6. Siegel D, Gustafson DL, Dehn DL, Han JY, Boonchoong P, Berliner LJ, Ross D: NAD(P)H:quinone oxidoreductase 1: role as a superoxide scavenger. Mol Pharmacol 65;1238-1247.
  7. Siegel D, Bolton EM, Burr JA, Liebler DC, Ross 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;300-305, 1997. https://doi.org/10.1124/mol.52.2.300
  8. Asher G, Lotem J, Cohen B, Sachs L, Shaul Y: Regulation of p53 stability and p53-dependent apoptosis by NADH quinone oxidoreductase 1. Proc Natl Acad Sci U S A 98;1188-1193, 2001. https://doi.org/10.1073/pnas.98.3.1188
  9. Asher G, Lotem J, Kama R, Sachs L, Shaul Y: NQO1 stabilizes p53 through a distinct pathway. Proc Natl Acad Sci U S A 99;3099-3104, 2002. https://doi.org/10.1073/pnas.052706799
  10. Asher G, Lotem J, Sachs L, Kahana C, Shaul Y: Mdm-2 and ubiquitin-independent p53 proteasomal degradation regulated by NQO1. Proc Natl Acad Sci U S A 99;13125-13130, 2002. https://doi.org/10.1073/pnas.202480499
  11. Iskander K, Gaikwad A, Paquet M, Long DJ 2nd, Brayton C, Barrios R, Jaiswal AK: Lower induction of p53 and decreased apoptosis in NQO1-null mice lead to increased sensitivity to chemical-induced skin carcinogenesis. Cancer Res 65;2054- 2058, 2005. https://doi.org/10.1158/0008-5472.CAN-04-3157
  12. Ahn KS, Sethi G, Jain AK, Jaiswal AK, Aggarwal BB: Genetic deletion of NAD(P)H:quinone oxidoreductase 1 abrogates activation of nuclear factor-kappaB, IkappaBalpha kinase, c-Jun N-terminal kinase, Akt, p38, and p44/42 mitogen-activated protein kinases and potentiates apoptosis. J Biol Chem 281; 19798-19808, 2006. https://doi.org/10.1074/jbc.M601162200
  13. Begleiter A, Fourie J: Induction of NQO1 in cancer cells. Methods Enzymol 382;320-351, 2004.
  14. Dhakshinamoorthy S, Jaiswal AK: Functional characterization and role of INrf2 in antioxidant response element-mediated expression and antioxidant induction of NAD(P)H:quinone oxidoreductase1 gene. Oncogene 20;3906-3917, 2001. https://doi.org/10.1038/sj.onc.1204506
  15. Nioi P, Hayes JD: 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;149-171, 2004. https://doi.org/10.1016/j.mrfmmm.2004.05.023
  16. Jaiswal AK: Nrf2 signaling in coordinated activation of antioxidant gene expression. Free Radic Biol Med 36;1199-1207, 2004. https://doi.org/10.1016/j.freeradbiomed.2004.02.074
  17. Kwak MK, Wakabayashi N, Itoh K, Motohashi H, Yamamoto M, Kensler TW: 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;8135-8145, 2003. https://doi.org/10.1074/jbc.M211898200
  18. Nguyen T, Sherratt PJ, Pickett CB: Regulatory mechanisms controlling gene expression mediated by the antioxidant response element. Annu Rev Pharmacol Toxicol 43;233-260, 2003. https://doi.org/10.1146/annurev.pharmtox.43.100901.140229
  19. Motohashi H, Yamamoto M: Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol Med 10;549-557, 2004. https://doi.org/10.1016/j.molmed.2004.09.003
  20. Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K, Engel JD, Yamamoto M: Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev 13;76-86, 1999. https://doi.org/10.1101/gad.13.1.76
  21. Kang MI, Kobayashi A, Wakabayashi N, Kim SG, Yamamoto M: 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;2046-2051, 2004. https://doi.org/10.1073/pnas.0308347100
  22. Lee BS, Heo J, Kim YM, Shim SM, Pae HO, Kim YM, Chung HT: Carbon monoxide mediates heme oxygenase 1 induction via Nrf2 activation in hepatoma cells. Biochem Biophys Res Commun 343;965-972, 2006. https://doi.org/10.1016/j.bbrc.2006.03.058
  23. Rushworth SA, MacEwan DJ, O'Connell MA: 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; 6730-6737, 2008. https://doi.org/10.4049/jimmunol.181.10.6730
  24. Cho HY, Reddy SP, Debiase A, Yamamoto M, Kleeberger SR: Gene expression profiling of NRF2-mediated protection against oxidative injury. Free Radic Biol Med 38;325-343, 2005. https://doi.org/10.1016/j.freeradbiomed.2004.10.013
  25. Venugopal R, Jaiswal AK: 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 93;14960-14965, 1996. https://doi.org/10.1073/pnas.93.25.14960
  26. Balogun E, Hoque M, Gong P, Killeen E, Green CJ, Foresti R, Alam J, Motterlini R: Curcumin activates the haem oxygenase- 1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochem J 371;887-895, 2003. https://doi.org/10.1042/BJ20021619
  27. Kim KM, Pae HO, Zheng M, Park R, Kim YM, Chung HT: 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. Circ Res 101;919-927, 2007. https://doi.org/10.1161/CIRCRESAHA.107.154781
  28. Motterlini R, Otterbein LE: The therapeutic potential of carbon monoxide. Nat Rev Drug Discov 9;728-743, 2010. https://doi.org/10.1038/nrd3228
  29. Motohashi H, Yamamoto M: Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol Med 10;549-557, 2004. https://doi.org/10.1016/j.molmed.2004.09.003
  30. Tanigawa S, Fujii M, Hou DX: Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin. Free Radic Biol Med 42;1690-1703, 2007. https://doi.org/10.1016/j.freeradbiomed.2007.02.017
  31. Xie T, Belinsky M, Xu Y, Jaiswal AK: ARE- and TRE-mediated regulation of gene expression. Response to xenobiotics and antioxidants. J Biol Chem 270;6894-6900, 1995. https://doi.org/10.1074/jbc.270.12.6894
  32. Li Y, Jaiswal AK: Regulation of human NAD(P)H:quinone oxidoreductase gene. Role of AP1 binding site contained within human antioxidant response element. J Biol Chem 267; 15097-15104, 1992.
  33. Miao W, Hu L, Scrivens PJ, Batist G: 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;20340-20348, 2005. https://doi.org/10.1074/jbc.M412081200
  34. Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, Oyake T, Hayashi N, Satoh K, Hatayama I, Yamamoto M, Nabeshima Y: An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 236;313-322, 1997. https://doi.org/10.1006/bbrc.1997.6943
  35. Siemankowski LM, Morreale J, Butts BD, Briehl MM: Increased tumor necrosis factor-alpha sensitivity of MCF-7 cells transfected with NAD(P)H:quinone reductase. Cancer Res 60; 3638-3644, 2000.
  36. Yeligar SM, Machida K, Kalra VK: Ethanol-induced HO-1 and NQO1 are differentially regulated by HIF-1alpha and Nrf2 to attenuate inflammatory cytokine expression. J Biol Chem 285; 35359-35373, 2010. https://doi.org/10.1074/jbc.M110.138636
  37. Bian JT, Zhao HL, Zhang ZX, Bi XH, Zhang JW: Association of NAD(P)H:quinone oxidoreductase 1 polymorphism and Alzheimer's disease in Chinese. J Mol Neurosci 34;235-240, 2008. https://doi.org/10.1007/s12031-008-9036-z
  38. Ryter SW, Otterbein LE, Morse D, Choi AM: Heme oxygenase/ carbon monoxide signaling pathways: regulation and functional significance. Mol Cell Biochem 234-235;249-263, 2002.
  39. Song R, Mahidhara RS, Zhou Z, Hoffman RA, Seol DW, Flavell RA, Billiar TR, Otterbein LE, Choi AM: Carbon monoxide inhibits T lymphocyte proliferation via caspase-dependent pathway. J Immunol 172;1220-1226, 2004. https://doi.org/10.4049/jimmunol.172.2.1220
  40. Pae HO, Choi BM, Oh GS, Lee MS, Ryu DG, Rhew HY, Kim YM, Chung HT: Roles of heme oxygenase-1 in the antiproliferative and antiapoptotic effects of nitric oxide on Jurkat T cells. Mol Pharmacol 66;122-128, 2004. https://doi.org/10.1124/mol.66.1.122

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