A small-molecule inhibitor of NF-κB-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury

FASEB Journal

Volumn 31, Issue 2, 2017, Pages 711-718

  Ren, Xiaomeng ^a   Li, Xinzhi ^a   Jia, Linna ^a   Chen, Deheng ^b   Hou, Hai ^c   Rui, Liangyou ^d   Zhao, Yujun ^b   Chen, Zheng ^a  

^a NORTHEAST NORMAL UNIVERSITY   (China)

^b SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

^c NORTHWESTERN POLYTECHNICAL UNIVERSITY   (China)

^d UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

CCl4; Inflammation; Liver injury; NIK

Indexed keywords

ALANINE AMINOTRANSFERASE; ANTIINFLAMMATORY AGENT; B 022; CARBON TETRACHLORIDE; EPITHELIAL DERIVED NEUTROPHIL ACTIVATING FACTOR 78; GLUCOSE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 1BETA; INTERLEUKIN 6; LIVER PROTECTIVE AGENT; MESSENGER RNA; MONOCYTE CHEMOTACTIC PROTEIN 1; NUCLEAR FACTOR KAPPA B INDUCING KINASE; NUCLEAR FACTOR KAPPA B2; PHOSPHOTRANSFERASE INHIBITOR; PROTEIN P100; PROTEIN P52; RANTES; REACTIVE OXYGEN METABOLITE; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG; NF-KAPPA B KINASE; PROTEIN SERINE THREONINE KINASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; ENZYME ACTIVITY; EXPERIMENTAL HEPATITIS; EXPERIMENTAL LIVER INJURY; GENE EXPRESSION; GLUCOSE BLOOD LEVEL; IN VITRO STUDY; IN VIVO STUDY; LIVER CELL; LIVER PROTECTION; LIVER WEIGHT; MALE; MOUSE; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL LINE; CHEMICAL AND DRUG INDUCED LIVER INJURY; DRUG EFFECTS; HUMAN; INTOXICATION; METABOLISM; RAW 264.7 CELL LINE;

ANIMALS; CARBON TETRACHLORIDE POISONING; CELL LINE; CHEMICAL AND DRUG INDUCED LIVER INJURY; HUMANS; MALE; MICE; OXIDATIVE STRESS; PROTEIN-SERINE-THREONINE KINASES; RAW 264.7 CELLS; REACTIVE OXYGEN SPECIES; RNA, MESSENGER;

EID: 85011279058     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.201600840R     Document Type: Article

References (26)

1. Berger, M. L., Bhatt, H., Combes, B., and Estabrook, R. W. (1986) CCl4-induced toxicity in isolated hepatocytes: the importance of direct solvent injury. Hepatology 6, 36-45
2. Lee, I.-C., Kim, S.-H., Baek, H.-S., Moon, C., Kang, S.-S., Kim, S.-H., Kim, Y.-B., Shin, I.-S., andKim, J.-C. (2014)The involvementofNrf2 in the protective effects of diallyl disulfide on carbon tetrachlorideinduced hepaticoxidativedamageandinflammatory response inrats. Food Chem. Toxicol. 63, 174-185
3. Kovalovich, K., DeAngelis, R. A., Li, W., Furth, E.E., Ciliberto, G., and Taub, R. (2000) Increased toxin-induced liver injury and fibrosis in interleukin-6-deficient mice. Hepatology 31, 149-159
4. Czaja, M. J., Xu, J., and Alt, E. (1995) Prevention of carbon tetrachloride-induced rat liver injury by soluble tumor necrosis factor receptor. Gastroenterology 108, 1849-1854
5. Slater, T. F. (1966) Necrogenic action of carbon tetrachloride in the rat: a speculative mechanism based on activation. Nature 209, 36-40
6. Shi, J., Aisaki, K., Ikawa, Y., and Wake, K. (1998) Evidence of hepatocyte apoptosis in rat liver after the administration of carbon tetrachloride. Am. J. Pathol. 153, 515-525
7. Shen, H., Sheng, L., Chen, Z., Jiang, L., Su, H., Yin, L., Omary, M. B., and Rui, L. (2014) Mouse hepatocyte overexpression of NF-κBinducing kinase (NIK) triggers fatal macrophage-dependent liver injury and fibrosis. Hepatology 60, 2065-2076
8. Jiang, B., Shen, H., Chen, Z., Yin, L., Zan, L., and Rui, L. (2015) Carboxyl terminus of HSC70-interacting protein (CHIP) downregulates NF-κB-inducing kinase (NIK) and suppresses NIK-induced liver injury. J. Biol. Chem. 290, 11704-11714
9. Xiao, G., Fong, A., and Sun, S.-C. (2004) Inductionof p100 processing by NF-kappaB-inducing kinase involves docking IkappaB kinase a (IKKalpha) to p100 and IKKalpha-mediated phosphorylation. J. Biol. Chem. 279, 30099-30105
10. Xiao, G., Harhaj, E. W., and Sun, S. C. (2001) NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100. Mol. Cell 7, 401-409
11. Senftleben, U., Cao, Y., Xiao, G., Greten, F. R., Krähn, G., Bonizzi, G., Chen, Y., Hu, Y., Fong, A., Sun, S. C., and Karin, M. (2001) Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science 293, 1495-1499
12. Sun, S.C. (2011)Non-canonicalNF-κB signaling pathway. Cell Res. 21, 71-85
13. De Leon-Boenig, G., Bowman, K. K., Feng, J.A., Crawford, T., Everett, C., Franke, Y., Oh, A., Stanley, M., Staben, S. T., Starovasnik, M. A., Wallweber, H. J., Wu, J., Wu, L.C., Johnson, A.R., andHymowitz, S. G. (2012) The crystal structure of the catalytic domain of the NF-κB inducing kinase reveals a narrow but flexible active site. Structure 20, 1704-1714
14. Demchenko, Y. N., Brents, L.A., Li, Z., Bergsagel, L. P., McGee, L. R., and Kuehl, M. W. (2014) Novel inhibitors are cytotoxic for myeloma cells with NFkB inducing kinase-dependent activation of NFkB. Oncotarget 5, 4554-4566
15. Chen, G., Cushing, T. D., Fisher, B., He, X., Li, K., Li, Z., Mcgee, L. R., Pattaropong, V., Faulder, P., Seganish, J. L., Shin, Y. Alkylnyl alcohols as kinase inhibitors. PCT Patent Publication WO 2009159011, December 30, 2009
16. Qin, W., Li, X., Xie, L., Li, S., Liu, J., Jia, L., Dong, X., Ren, X., Xiao, J., Yang, C., Zhou, Y., and Chen, Z. (2016) A long non-coding RNA, APOA4-AS, regulates APOA4 expression depending on HuR inmice. Nucleic Acids Res. 44, 6423-6433
17. Chen, Z., Canet, M. J., Sheng, L., Jiang, L., Xiong, Y., Yin, L., and Rui, L. (2015) Hepatocyte TRAF3 promotes insulin resistance and type 2 diabetes in mice with obesity. Mol. Metab. 4, 951-960
18. Chen, Z., Sheng, L., Shen, H., Zhao, Y., Wang, S., Brink, R., andRui, L. (2012) Hepatic TRAF2 regulates glucose metabolism through enhancing glucagon responses. Diabetes 61, 566-573
19. Chen, Z., Morris, D. L., Jiang, L., Liu, Y., and Rui, L. (2014) SH2B1 in b-cells promotes insulin expression and glucose metabolismin mice. Mol. Endocrinol. 28, 696-705
20. Chen, Z., Shen, H., Sun, C., Yin, L., Tang, F., Zheng, P., Liu, Y., Brink, R., and Rui, L. (2015) Myeloid cell TRAF3 promotes metabolic inflammation, insulin resistance, and hepatic steatosis in obesity. Am. J. Physiol. Endocrinol. Metab. 308, E460-E469
21. Chen, Z., Morris, D. L., Jiang, L., Liu, Y., and Rui, L. (2014) SH2B1 in b-cells regulates glucose metabolismby promoting b-cell survival and islet expansion. Diabetes 63, 585-595
22. Cubero, F. J., Zhao, G., Nevzorova, Y. A., Hatting, M., AlMasaoudi, M., Verdier, J., Peng, J., Schaefer, F. M., Hermanns, N., Boekschoten, M. V., Grouls, C., Gassler, N., Kiessling, F., Muller, M., Davis, R. J., Liedtke, C., and Trautwein, C. (2015) Haematopoietic cell-derived Jnk1 is crucial for chronic inflammation and carcinogenesis in an experimental model of liver injury. J. Hepatol. 62, 140-149
23. Kluwe, J., Pradere, J.-P., Gwak, G.-Y., Mencin, A., De Minicis, S., Osterreicher, C. H., Colmenero, J., Bataller, R., and Schwabe, R. F. (2010) Modulation of hepatic fibrosis by c-Jun-N-terminal kinase inhibition. Gastroenterology 138, 347-359
24. Armendáriz-Borunda, J., Islas-Carbajal, M. C., Meza-García, E., Rincón, A. R., Lucano, S., Sandoval, A. S., Salazar, A., Berumen, J., Alvarez, A., Covarrubias, A., Aréchiga, G., and García, L. (2006) A pilot study in patients with established advanced liver fibrosis using pirfenidone. Gut 55, 1663-1665
25. Fagone, P., Mangano, K., Pesce, A., Portale, T. R., Puleo, S., and Nicoletti, F. (2016) Emerging therapeutic targets for the treatment of hepatic fibrosis. Drug Discov. Today 21, 369-375
26. Rockey, D. C., and Chung, J. J. (1994) Interferon gamma inhibits lipocyte activation and extracellularmatrixmRNA expression during experimental liver injury: implications for treatment of hepatic fibrosis. J. Investig. Med. 42, 660-670