Auranofin, a gold(I)-containing antirheumatic compound, activates Keap1/Nrf2 signaling via Rac1/iNOS signal and mitogen-activated protein kinase activation

Journal of Pharmacological Sciences

Volumn 113, Issue 3, 2010, Pages 246-254

  Kim, Nam Hoon ^a   Oh, Mi Kyung ^a   Park, Hyo Jung ^a   Kim, In Sook ^a  

^a The Catholic University of Korea   (South Korea)

Author keywords

Auranofin; Heme oxygenase 1 (HO 1); Kelch like ECH associated protein 1 (Keap1); Nuclear factor erythroid 2 related factor 2 (Nrf2); Rac1

Indexed keywords

4 AMINO 6 [2 [[4 (DIETHYLAMINO) 1 METHYLBUTYL]AMINO] 6 METHYL 4 PYRIMIDINYL] 2 METHYLQUINOLINE; AMINOGUANIDINE; ANTIRHEUMATIC AGENT; AURANOFIN; HEME OXYGENASE 1; INDUCIBLE NITRIC OXIDE SYNTHASE; KELCH LIKE ECH ASSOCIATED PROTEIN 1; MITOGEN ACTIVATED PROTEIN KINASE; N(G) NITROARGININE METHYL ESTER; RAC1 PROTEIN; TRANSCRIPTION FACTOR NRF2;

ARTICLE; CANCER CELL CULTURE; CELL LEVEL; CELL NUCLEUS; CHROMATIN IMMUNOPRECIPITATION; COMPLEX FORMATION; CONTROLLED STUDY; DISSOCIATION; DRUG MECHANISM; ENZYME ACTIVATION; ENZYME INDUCTION; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; HUMAN; HUMAN CELL; MONOCYTE; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN STABILITY; SIGNAL TRANSDUCTION; SYNOVIOCYTE; TRANSACTIVATION; WESTERN BLOTTING;

EID: 77954975984     PISSN: 13478613     EISSN: 13478648     Source Type: Journal    
DOI: 10.1254/jphs.09330FP     Document Type: Article

References (34)

1. Champion GD, Graham GG, Ziegler JB. The gold complexes. Baillieres Clin Rheumatol. 1990;4:491-534.
2. Borg G, Allander E, Lund B, Berg E, Brodin U, Pettersson H, et al. Auranofin improves outcome in early rheumatoid arthritis. Results from a 2-year, double blind placebo controlled study. J Rheumatol. 1988;15:1747-1754.
3. Kobayashi H, Takeno M, Saito T, Takeda Y, Kirino Y, Noyori K, et al. Regulatory role of heme oxygenase 1 in inflammation of rheumatoid arthritis. Arthritis Rheum. 2006;54:1132-1142.
4. Kataoka K, Handa H, Nishizawa M. Induction of cellular antioxidative stress genes through heterodimeric transcription factor Nrf2/Small Maf by anti-rheumatic gold(I) compounds. J Biol Chem. 2001;276:34074-34081.
5. Kirino Y, Takeno M, Murakami S, Kobayashi M, Kobayashi H, Miura K, et al. Tumor necrosis factor alpha acceleration of inflammatory responses by down-regulating heme oxygenase 1 in human peripheral monocytes. Arthritis Rheum. 2007;56:464-475.
6. Kim NH, Lee MY, Park SJ, Choi JS, Oh MK, Kim IS. Auranofin blocks interleukin-6 signalling by inhibiting phosphorylation of JAK1 and STAT3. Immunology. 2007;122:607-614.
7. Jeon KI, Jeong JY, Jue DM. Thiol-reactive metal compounds inhibit NF-kappa B activation by blocking I kappa B kinase. J Immunol. 2000;164:5981-5989.
8. Jeon KI, Byun MS, Jue DM. Gold compound auranofin inhibits IkappaB kinase (IKK) by modifying Cys-179 of IKKbeta subunit. Exp Mol Med. 2003;35:61-66.
9. Youn HS, Lee JY, Saitoh SI, Miyake K, Hwang DH. Auranofin, as an anti-rheumatic gold compound, suppresses LPS-induced homodimerization of TLR4. Biochem Biophys Res Commun. 2006;350:866-871.
10. Park SJ, Kim IS. The role of p38 MAPK activation in auranofininduced apoptosis of human promyelocytic leukaemia HL-60 cells. Br J Pharmacol. 2005;146:506-513.
11. Rigobello MP, Gandin V, Folda A, Rundlöf AK, Fernandes AP, Bindoli A, et al. Treatment of human cancer cells with selenite or tellurite in combination with auranofin enhances cell death due to redox shift. Free Radic Biol Med. 2009;47:710-721.
12. Yamashita M, Ohuchi K, Takayanagi M. Effects of chrisotherapeutic gold compounds on prostaglandin E2 production. Curr Drug Targets Inflamm Allergy. 2003;2:216-223.
13. Gandin V, Fernandes AP, Rigobello MP, Dani B, Sorrentino F, Tisato F, et al. Cancer cell death induced by phosphine gold(I) compounds targeting thioredoxin reductase. Biochem Pharmacol. 2010;79:90-101.
14. Thimmulappa RK, Lee H, Rangasamy T, Reddy SP, Yamamoto M, Kensler TW, et al. Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis. J Clin Invest. 2006;116:984-995.
15. Li W, Khor TO, Xu C, Shen G, Jeong WS, Yu S, et al. Activation of Nrf2-antioxidant signaling attenuates NFkappaB-inflammatory response and elicits apoptosis. Biochem Pharmacol. 2008;76: 1485-1489.
16. Innamorato NG, Rojo AI, García-Yagüe AJ, Yamamoto M, de Ceballos ML, Cuadrado A. The transcription factor Nrf2 is a therapeutic target against brain inflammation. J Immunol. 2008; 181:680-689.
17. Innamorato NG, Lastres-Becker I, Cuadrado A. Role of microglial redox balance in modulation of neuroinflammation. Curr Opin Neurol. 2009;22:308-314.
18. Hayashi S, Takamiya R, Yamaguchi T, Matsumoto K, Tojo SJ, Tamatani T, et al. Induction of heme oxygenase-1 suppress venular leukocyte adhesion elicited by oxidative stress: role of bilirubin generated by the enzyme. Circ Res. 1999;85:663-671.
19. Morse D, Pischke SE, Zhou Z, Davis RJ, Flavell RA, Loop T, et al. Suppression of inflammatory cytokine production by carbon monoxide involves the JNK pathway and AP-1. J Biol Chem. 2003;278:36993-36998.
20. Li C, Hossieny P, Wu BJ, Qawasmeh A, Beck K, Stocker R. Pharmacologic induction of heme oxygenase-1. Antioxid Redox Signal. 2007;9:2227-2239.
21. Kensler TW, Wakabayashi N, Biswal S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol. 2007;47:89-116.
22. 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. 2004;101:2046-2051.
23. Furukawa M, Xiong Y. BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase. Mol Cell Biol. 2005;25:162-171.
24. Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K, Engel JD, et al. Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev. 1999;13:76-86.
25. Park SJ, Kim M, Kim NH, Oh MK, Cho JK, Jin JY, et al. Auranofin promotes retinoic acid- or dihydroxyvitamin D3-mediated cell differentiation of promyelocytic leukaemia cells by increasing histone acetylation. Br J Pharmacol. 2008;154:1196-1205.
26. 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. 2008;181:6730-6737.
27. Rushworth SA, MacEwan DJ. HO-1 underlies resistance of AML cells to TNF-induced apoptosis. Blood. 2008;111:3793-3801. 28 Nguyen T, Nioi P, Pickett CB. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem. 2009;284:13291-13295.
28. Dhakshinamoorthy S, Porter AG. Nitric oxide-induced transcriptional up-regulation of protective genes by Nrf2 via the antioxidant response element counteracts apoptosis of neuroblastoma cells. J Biol Chem. 2004;279:20096-20107.
29. Ho TC, Yang YC, Cheng HC, Wu AC, Chen SL, Chen HK, et al. Activation of mitogen-activated protein kinases is essential for hydrogen peroxide -induced apoptosis in retinal pigment epithelial cells. Apoptosis. 2006;11:1899-1908.
30. Hong HY, Jeon WK, Kim BC. Up-regulation of heme oxygenase- 1 expression through the Rac1/NADPH oxidase/ROS/p38 signaling cascade mediates the anti-inflammatory effect of 15-deoxy-delta 12,14-prostaglandin J2 in murine macrophages. FEBS Lett. 2008;582:861-868.
31. Kim JW, Li MH, Jang JH, Na HK, Song NY, Lee C, et al. 15-Deoxy-delta(12,14)-prostaglandin J(2) rescues PC12 cells from H2O2-induced apoptosis through Nrf2-mediated upregulation of heme oxygenase-1: potential roles of Akt and ERK1/2. Biochem Pharmacol. 2008;76:1577-1589.
32. Hong F, Freeman ML, Liebler DC. Identification of sensor cysteines in human Keap1 modified by the cancer chemopreventive agent sulforaphane. Chem Res Toxicol. 2005;18:1917-1926.
33. Buckley BJ, Li S, Whorton AR. Keap1 modification and nuclear accumulation in response to S-nitrosocysteine. Free Radic Biol Med. 2008;44:692-698.
34. Li CQ, Kim MY, Godoy LC, Thiantanawat A, Trudel LJ, Wogan GN. Nitric oxide activation of Keap1/Nrf2 signaling in human colon carcinoma cells. Proc Natl Acad Sci U S A. 2009;106: 14547-14551.