Increased Nrf2 activation in livers from keap1-knockdown mice Increases expression of cytoprotective genes that detoxify electrophiles more than those that detoxify reactive oxygen species

Toxicological Sciences

Volumn 108, Issue 1, 2009, Pages 35-47

  Reisman, Scott A ^a   Yeager, Ronnie L ^a   Yamamoto, Masayuki ^b   Klaassen, Curtis D ^a  

^a UNIVERSITY OF KANSAS SCHOOL OF MEDICINE   (United States)

^b TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

Cytoprotection; Electrophilic stress; Nrf2; Oxidative stress

Indexed keywords

ALDEHYDE DEHYDROGENASE; CATALASE; CHOLESTEROL; COPPER ZINC SUPEROXIDE DISMUTASE; EPOXIDE HYDROLASE; FATTY ACID; GLUCURONOSYLTRANSFERASE; GLUTATHIONE PEROXIDASE; GLUTATHIONE TRANSFERASE; KELCH LIKE ECH ASSOCIATED PROTEIN 1; MANGANESE SUPEROXIDE DISMUTASE; MESSENGER RNA; MULTIDRUG RESISTANCE PROTEIN; PEROXIREDOXIN; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE DEHYDROGENASE; TRANSCRIPTION FACTOR NRF2; TRIACYLGLYCEROL;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CELL PROTECTION; CONTROLLED STUDY; DETOXIFICATION; ELECTROPHILIC STRESS; ENZYME ANALYSIS; GENE EXPRESSION; MALE; MOUSE; NONHUMAN; OXIDATIVE STRESS; PHENOTYPE; PROTEIN LOCALIZATION; WILD TYPE;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANALYSIS OF VARIANCE; ANIMALS; ANTIOXIDANTS; CYTOPROTECTION; CYTOSKELETAL PROTEINS; GENE KNOCKDOWN TECHNIQUES; GLUTATHIONE; LIVER; LIVER FUNCTION TESTS; MALE; METABOLIC DETOXICATION, DRUG; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MICROSOMES, LIVER; NF-E2-RELATED FACTOR 2; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES;

MUS;

EID: 61349117533     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfn267     Document Type: Article

References (62)

1. Aleksunes, L. M., and Manautou, J. E. (2007). Emerging role of Nrf2 in protecting against hepatic and gastrointestinal disease. Toxicol. Pathol. 35, 459-473.
2. Alnouti, Y., and Klaassen, C. D. (2006). Tissue distribution and ontogeny of sulfotransferase enzymes in mice. Toxicol. Sci. 93 242-255.
3. Ballatori, N., and Truong, A. T. (1989). Relation between biliary glutathione excretion and bile acid-independent bile flow. Am. J. Physiol. 256, G22-G30.
4. Brangi, M., Litman, T., Ciotti, M., Nishiyama, K., Kohlhagen, G., Takimoto, C., Robey, R., Pommier, Y., Fojo, T., and Bates, S. E. (1999). Camptothecin resistance: Role of the ATP-binding cassette (ABC), mitoxantrone-resistance half-transporter (MXR), and potential for glucuronidation in MXR-expressing cells. Cancer Res. 59, 5938-5946.
5. Chan, K., Lu, R., Chang, J. C., and Kan, Y. W. (1996). NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development. Proc. Natl. Acad. Sci. U. S. A. 93, 13943-13948.
6. Cheng, X., Maher, J., Dieter, M. Z., and Klaassen, C. D. (2005). Regulation of mouse organic anion-transporting polypeptides (Oatps) in liver by prototypical microsomal enzyme inducers that activate distinct transcription factor pathways. Drug Metab. Dispos. 33, 1276-1282.
7. Cho, H. Y., Jedlicka, A. E., Reddy, S. P., Kensler, T. W., Yamamoto, M., Zhang, L. Y., and Kleeberger, S. R. (2002). Role of NRF2 in protection against hyperoxic lung injury in mice. Am. J. Respir. Cell Mol. Biol. 26, 175-182.
8. Cullinan, S. B., Gordan, J. D., Jin, J., Harper, J. W., and Diehl, J. A. (2004). The Keap1-BTB protein is an adaptor that bridges Nrf2 to a Cul3-based E3 ligase: Oxidative stress sensing by a Cul3-Keap1 ligase. Mol. Cell. Biol. 24, 8477-8486.
9. Dinkova-Kostova, A. T., Holtzclaw, W. D., Cole, R. N., Itoh, K., Wakabayashi, N., Katoh, Y., Yamamoto, M., and Talalay, P. (2002). Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proc. Natl. Acad. Sci. U. S. A. 99, 11908-11913.
10. Doyle, L. A., Yang, W., Abruzzo, L. V., Krogmann, T., Gao, Y., Rishi, A. K., and Ross, D. D. (1998). A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc. Natl. Acad. Sci. U. S. A. 95, 15665-15670.
11. Enomoto, A., Itoh, K., Nagayoshi, E., Haruta, J., Kimura, T., O'Connor, T., Harada, T., and Yamamoto, M. (2001). High sensitivity of Nrf2 knockout mice to acetaminophen hepatotoxicity associated with decreased expression of ARE-regulated drug metabolizing enzymes and antioxidant genes. Toxicol. Sci. 59, 169-177.
12. Evans, W. E., and Relling, M. V. (1999). Pharmacogenomics: Translating functional genomics into rational therapeutics. Science 286, 487-491.
13. Flohe, L., and Gunzler, W. A. (1984). Assays of glutathione peroxidase. Methods Enzymol. 105, 114-121.
14. Gong, P., Stewart, D., Hu, B., Vinson, C., and Alam, J. (2002). Multiple basicleucine zipper proteins regulate induction of the mouse heme oxygenase-1 gene by arsenite. Arch. Biochem. Biophys. 405, 265-274.
15. Harwood, D. T., Kettle, A. J., and Winterbourn, C. C. (2006). Production of glutathione sulfonamide and dehydroglutathione from GSH by myeloperoxidasederived oxidants and detection using a novel LC-MS/MS method. Biochem. J. 399, 161-168.
16. Hayes, J. D., Flanagan, J. U., and Jowsey, I. R. (2005). Glutathione transferases. Annu. Rev. Pharmacol. Toxicol. 45, 51-88.
17. Hiasa, M., Matsumoto, T., Komatsu, T., and Moriyama, Y. (2006). Wide variety of locations for rodent MATE1, a transporter protein that mediates the final excretion step for toxic organic cations. Am. J. Physiol. Cell. Physiol. 291, C678-C686.
18. Itoh, K., Chiba, T., Takahashi, S., Ishii, T., Igarashi, K., Katoh, Y., Oyake, T., Hayashi, N., Satoh, K., Hatayama, I., Yamamoto, M., and Nabeshima, Y. (1997). 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.
19. Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., O'Connor, T., and Yamamoto, M. (2003). Keap1 regulates both cytoplasmic-nuclear shuttling and degradation of Nrf2 in response to electrophiles. Genes Cells 8, 379-391.
20. Jaiswal, A. K. (2000). Regulation of genes encoding NAD(P)H:qUinone oxidoreductases. Free Radic. Biol. Med. 29, 254-262.
21. Jones, C. I., 3rd, Zhu, H., Martin, S. F., Han, Z., Li, Y., and Alevriadou, B. R. (2007). Regulation of antioxidants and phase 2 enzymes by shearinduced reactive oxygen species in endothelial cells. Ann. Biomed. Eng. 35, 683-693.
22. Keum, Y. S., Han, Y. H., Liew, C., Kim, J. H., Xu, C., Yuan, X., Shakarjian, M. P., Chong, S., and Kong, A. N. (2006). Induction of heme oxygenase-1 (HO-1) and NAD[P]H:qUinone oxidoreductase 1 (NQO1) by a phenolic antioxidant, butylated hydroxyanisole (BHA) and its metabolite, tert-butylhydroquinone (tBHQ) in primary-cultured human and rat hepatocytes. Pharm. Res. 23, 2586-2594.
23. Klaassen, C. D., and Lu, H. (2008). Xenobiotic transporters: Ascribing function from gene knockout and mutation studies. Toxicol. Sci. 101, 186-196.
24. Kobayashi, A., Kang, M. I., Okawa, H., Ohtsuji, M., Zenke, Y., Chiba, T., Igarashi, K., and Yamamoto, M. (2004). Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol. Cell. Biol. 24, 7130-7139.
25. Kobayashi, M., and Yamamoto, M. (2006). Nrf2-Keap1 regulation of cellular defense mechanisms against electrophiles and reactive oxygen species. Adv. Enzyme Regul. 46, 113-140.
26. Kwak, M. K., Itoh, K., Yamamoto, M., Sutter, T. R., and Kensler, T. W. (2001). Role of transcription factor Nrf2 in the induction of hepatic phase 2 and antioxidative enzymes in vivo by the cancer chemoprotective agent, 3H1, 2-dimethiole-3-thione. Mol. Med. 7, 135-145.
27. Lamle, J., Marhenke, S., Borlak, J., von Wasielewski, R., Eriksson, C. J., Geffers, R., Manns, M. P., Yamamoto, M., and Vogel, A. (2008). Nuclear factor-eythroid 2-related factor 2 prevents alcohol-induced fulminant liver injury. Gastroenterology 134, 1159-1168.
28. Landowski, C. P., Lorenzi, P. L., Song, X., and Amidon, G. L. (2006). Nucleoside ester prodrug substrate specificity of liver carboxylesterase. J. Pharmacol. Exp. Ther. 316, 572-580.
29. Lee, O. H., Jain, A. K., Papusha, V., and Jaiswal, A. K. (2007). An autoregulatory loop between stress sensors INrf2 and Nrf2 controls their cellular abundance. J. Biol. Chem. 282, 36412-36420.
30. Lee, J. S., and Surh, Y. J. (2005). Nrf2 as a novel molecular target for chemoprevention. Cancer Lett. 224, 171-184.
31. Liby, K., Hock, T., Yore, M. M., Suh, N., Place, A. E., Risingsong, R., Williams, C. R., Royce, D. B., Honda, T., Honda, Y., et al. (2005). The synthetic triterpenoids, CDDO and CDDO-imidazolide, are potent inducers of heme oxygenase-1 and Nrf2/ARE signaling. Cancer Res. 65, 4789-4798.
32. Lickteig, A. J., Cheng, X., Augustine, L. M., Klaassen, C. D., and Cherrington, N. J. (2008). Tissue distribution, ontogeny and induction of the transporters multidrug and toxin extrusion (MATE) 1 and MATE2 mRNA expression levels in mice. Life Sci. 83, 59-64.
33. Litman, T., Brangi, M., Hudson, E., Fetsch, P., Abati, A., Ross, D. D., Miyake, K., Resau, J. H., and Bates, S. E. (2000). The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2). J. Cell. Sci. 113(Pt 11), 2011-2021.
34. Lo, S. C., and Hannink, M. (2006). PGAM5, a Bcl-XL-interacting protein, is a novel substrate for the redox-regulated Keap1-dependent ubiquitin ligase complex. J. Biol. Chem. 281, 37893-37903.
35. Lo, S. C., and Hannink, M. (2008). PGAM5 tethers a ternary complex containing Keap1 and Nrf2 to mitochondria. Exp. Cell Res. 314 1789-1803.
36. Luck, H. (1963). Catalase. In Methods of Enzymatic Analysis (H. U. Bergmeyer, Ed.), pp. 885-888. Academic Press, New York.
37. Maher, J. M., Dieter, M. Z., Aleksunes, L. M., Slitt, A. L., Guo, G., Tanaka, Y., Scheffer, G. L., Chan, J. Y., Manautou, J. E., Chen, Y., et al. (2007). Oxidative and electrophilic stress induces multidrug resistance-associated protein transporters via the nuclear factor-E2-related factor-2 transcriptional pathway. Hepatology 46, 1597-1610.
38. Maher, J. M., Slitt, A. L., Cherrington, N. J., Cheng, X., and Klaassen, C. D. (2005). Tissue distribution and hepatic and renal ontogeny of the multidrug resistance-associated protein (Mrp) family in mice. Drug Metab. Dispos. 33, 947-955.
39. Marsh, S., Xiao, M., Yu, J., Ahluwalia, R., Minton, M., Freimuth, R. R., Kwok, P. Y., and McLeod, H. L. (2004). Pharmacogenomic assessment of carboxylesterases 1 and 2. Genomics 84, 661-668.
40. McMahon, M., Itoh, K., Yamamoto, M., and Hayes, J. D. (2003). Keapl-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression. J. Biol. Chem. 278, 21592-21600.
41. Meister, A., and Anderson, M. E. (1983). Glutathione. Annu. Rev. Biochem. 52, 711-760.
42. Merrell, M. D., Jackson, J. P., Augustine, L. M., Fisher, C. D., Slitt, A. L., Maher, J. M., Huang, W., Moore, D. D., Zhang, Y., Klaassen, C. D., et al. (2008). The Nrf2 activator oltipraz also activates the constitutive androstane receptor. Drug Metab. Dispos. 36, 1716-1721.
43. Miyake, K., Mickley, L., Litman, T., Zhan, Z., Robey, R., Cristensen, B., Brangi, M., Greenberger, L., Dean, M., Fojo, T., et al. (1999). Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone-resistant cells: Demonstration of homology to ABC transport genes. Cancer Res. 59, 8-13.
44. Moinova, H. R., and Mulcahy, R. T. (1999). Up-regulation of the human gamma-glutamylcysteine synthetase regulatory subunit gene involves binding of Nrf-2 to an electrophile responsive element. Biochem. Biophys. Res. Commun. 261, 661-668.
45. Okada, K., Shoda, J., Taguchi, K., Maher, J. M., Ishizaki, K., Inoue, Y., Ohtsuki, M., Goto, N., Takeda, K., Utsunomiya, H., et al. (2008). Ursodeoxycholic acid stimulates Nrf2-mediated hepatocellular transport, detoxification, and antioxidative stress systems in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 295, G735-G747.
46. Okawa, H., Motohashi, ff., Kobayashi, A., Aburatani, H., Kensler, T. W., and Yamamoto, M. (2006). Hepatocyte-specific deletion of the keap1 gene activates Nrf2 and confers potent resistance against acute drug toxicity. Biochem. Biophys. Res. Commun. 339, 79-88.
47. Parkinson, A., and Ogilvie, B. (2008). Biotransformation. In Casarett and Doull's Toxicology: The Basic Science of Poisons (C. D. Klaassen, Ed.), pp. 161-304. McGraw-Hill, New York.
48. Petrick, J. S., and Klaassen, C. D. (2007). Importance of hepatic induction of constitutive androstane receptor and other transcription factors that regulate xenobiotic metabolism and transport. Drug Metab. Dispos. 35, 1806-1815.
49. Ross, D. D., Yang, W., Abruzzo, L. V., Dalton, W. S., Schneider, E., Lage, H., Dierel, M., Greenberger, L., Cole, S. P., and Doyle, L. A. (1999). Atypical multidrug resistance: Breast cancer resistance protein messenger RNA expression in mitoxantrone-selected cell lines. J. Natl. Cancer Inst. 91, 429-433.
50. Taketani, M., Shii, M., Ohura, K., Ninomiya, S., and Imai, T. (2007). Carboxylesterase in the liver and small intestine of experimental animals and human. Life Sci. 81, 924-932.
51. Tanaka, Y., Aleksunes, L. M., Goedken, M. J., Chen, C., Reisman, S. A., Manautou, J. E., and Klaassen, C. D. (2008a). Coordinated induction of Nrf2 target genes protects against iron nitrilotriacetate (FeNTA)-induced nephrotoxicity. Toxicol. Appl. Pharmacol. 231 364-373.
52. Tanaka, Y., Aleksunes, L. M., Yeager, R. L., Gyamfi, M. A., Esterly, N., Guo, G. L., and KJaassen, C. D. (2008b). NF-E2-related factor 2 inhibits lipid accumulation and oxidative stress in mice fed a high-fat diet. J. Pharmacol. Exp. Ther. 325, 655-664.
53. Tappel, A. L. (1978). Glutathione peroxidase and hydroperoxides. Methods Enzymol. 52, 506-513.
54. Terada, T., Masuda, S., Asaka, J., Tsuda, M., Katsura, T., and Inui, K. (2006). Molecular cloning, functional characterization and tissue distribution of rat H+/organic cation antiporter MATE1. Pharm. Res. 23, 1696-1701.
55. Thimmulappa, R. K., Mai, K. H., Srisuma, S., Kensler, T. W., Yamamoto, M., and Biswal, S. (2002). Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer Res. 62, 5196-5203.
56. Trujillo, M., Ferrer-Sueta, G, and Radi, R. (2008). Peroxynitrite detoxification and its biologic implications. Antioxid. Redox Signal. 10, 1607-1620.
57. Umemura, T., Kuroiwa, Y., Kitamura, Y., Ishii, Y., Kanki, K., Kodama, Y., Itoh, K., Yamamoto, M., Nishikawa, A., and Hirose, M. (2006). A crucial role of Nrf2 in in vivo defense against oxidative damage by an environmental pollutant, pentachlorophenol. Toxicol. Sci. 90 111-119.
58. Venugopal, R., and Jaiswal, A. K. (1996). Nrf1 and Nrf2 positively and c-Fos and Fral 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.
59. Wakabayashi, N., Itoh, K., Wakabayashi, J., Motohashi, H., Noda, S., Takahashi, S., Imakado, S., Kotsuji, T., Otsuka, F., Roop, D. R., et al. (2003). Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nat. Genet. 35, 238-245.
60. Wild, A. C., Moinova, H. R., and Mulcahy, R. T. (1999). Regulation of gamma-glutamylcysteine synthetase subunit gene expression by the transcription factor Nrf2. J. Biol. Chem. 274, 33627-33636.
61. Yeh, C. T., and Yen, G. C. (2006). Induction of hepatic antioxidant enzymes by phenolic acids in rats is accompanied by increased levels of multidrug resistance-associated protein 3 mRNA expression. J. Nutr. 136, 11-15.
62. Zhu, H., Itoh, K., Yamamoto, M., Zweier, J. L., and Li, Y. (2005). Role of Nrf2 signaling in regulation of antioxidants and phase 2 enzymes in cardiac fibroblasts: Protection against reactive oxygen and nitrogen species-induced cell injury. FEBS Lett. 579, 3029-3036.