2-Methoxy-7-Acetonyljuglone Isolated from Reynoutria japonica Increases the Activity of Nuclear Factor Erythroid 2-Related Factor-2 through Inhibition of Ubiquitin Degradation in HeLa Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals
2.2. Cell Culture
2.3. Cell Toxicity Assay
2.4. ARE Luciferase Assay
2.5. Western Blot Analysis
2.6. Real-Time PCR Analysis
2.7. Immunocytochemistry
2.8. Protein Stability Assay
2.9. Statistical Analysis
3. Results
3.1. MA Increases the NRF2 Activity through ARE System in HeLa Cells
3.2. MA Increases NRF2 Target Genes in HeLa Cells
3.3. MA Increases NRF2 Activity through p38 and AKT Signaling in HeLa Cells
3.4. MA Increases the NRF2 Stability through Inhibition of Ubiquitin-Mediated Degradation Pathway
4. Discussion
Author Contributions
Funding
Conflicts of Interest
References
- Chun, K.S.; Kundu, J.; Kundu, J.K.; Surh, Y.J. Targeting Nrf2-Keap1 signaling for chemoprevention of skin carcinogenesis with bioactive phytochemicals. Toxicol. Lett. 2014, 229, 73–84. [Google Scholar] [CrossRef] [PubMed]
- Park, J.S.; Kang, D.H.; Lee, D.H.; Bae, S.H. Fenofibrate activates Nrf2 through p62-dependent Keap1 degradation. Biochem. Biophys. Res. Commun. 2015, 465, 542–547. [Google Scholar] [CrossRef] [PubMed]
- Kwak, M.K.; Wakabayashi, N.; Kensler, T.W. Chemoprevention through the Keap1-Nrf2 signaling pathway by phase 2 enzyme inducers. Mutat. Res. 2004, 555, 133–148. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.M.; Johnson, J.A. An important role of Nrf2-ARE pathway in the cellular defense mechanism. J. Biochem. Mol. Biol. 2004, 37, 139–143. [Google Scholar] [CrossRef] [PubMed]
- Nguyen, T.; Sherratt, P.J.; Pickett, C.B. Regulatory mechanisms controlling gene expression mediated by the antioxidant response element. Annu. Rev. Pharmacol. Toxicol. 2003, 43, 233–260. [Google Scholar] [CrossRef]
- Itoh, K.; Chiba, T.; Takahashi, S.; Ishii, T.; Igarashi, K.; Katoh, Y.; Oyake, T.; Hayashi, N.; Satoh, K.; Hatayama, I.; et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem. Biophys. Res. Commun. 1997, 236, 313–322. [Google Scholar] [CrossRef]
- Ryter, S.W.; Alam, J.; Choi, A.M. Heme oxygenase-1/carbon monoxide: From basic science to therapeutic applications. Physiol. Rev. 2006, 86, 583–650. [Google Scholar] [CrossRef]
- Nguyen, T.; Nioi, P.; Pickett, C.B. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J. Biol. Chem. 2009, 284, 13291–13295. [Google Scholar] [CrossRef]
- Yang, S.H.; Sharrocks, A.D.; Whitmarsh, A.J. MAP kinase signalling cascades and transcriptional regulation. Gene 2013, 513, 1–13. [Google Scholar] [CrossRef]
- Bloom, D.A.; Jaiswal, A.K. Phosphorylation of Nrf2 at Ser40 by protein kinase C in response to antioxidants leads to the release of Nrf2 from INrf2, but is not required for Nrf2 stabilization/accumulation in the nucleus and transcriptional activation of antioxidant response element-mediated NAD(P)H:quinone oxidoreductase-1 gene expression. J. Biol. Chem. 2003, 278, 44675–44682. [Google Scholar] [CrossRef]
- Kim, J.H.; Xu, E.Y.; Sacks, D.B.; Lee, J.; Shu, L.; Xia, B.; Kong, A.N. Identification and functional studies of a new Nrf2 partner IQGAP1: A critical role in the stability and transactivation of Nrf2. Antioxid. Redox Signal. 2013, 19, 89–101. [Google Scholar] [CrossRef]
- Nguyen, T.; Sherratt, P.J.; Huang, H.C.; Yang, C.S.; Pickett, C.B. Increased protein stability as a mechanism that enhances Nrf2-mediated transcriptional activation of the antioxidant response element. Degradation of Nrf2 by the 26 S proteasome. J. Biol. Chem. 2003, 278, 4536–4541. [Google Scholar] [CrossRef]
- Zhang, D.D.; Hannink, M. Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Mol. Cell. Biol. 2003, 23, 8137–8151. [Google Scholar] [CrossRef]
- Huang, H.C.; Nguyen, T.; Pickett, C.B. Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription. J. Biol. Chem. 2002, 277, 42769–42774. [Google Scholar] [CrossRef]
- Joo, M.S.; Kim, W.D.; Lee, K.Y.; Kim, J.H.; Koo, J.H.; Kim, S.G. AMPK facilitates nuclear accumulation of Nrf2 by phosphorylating at serine 550. Mol. Cell. Biol. 2016, 36, 1931–1942. [Google Scholar] [CrossRef]
- Martin, D.; Rojo, A.I.; Salinas, M.; Diaz, R.; Gallardo, G.; Alam, J.; De Galarreta, C.M.; Cuadrado, A. Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3-kinase/Akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol. J. Biol. Chem. 2004, 279, 8919–8929. [Google Scholar] [CrossRef]
- Patocka, J.; Navratilova, Z.; Ovando, M. Biologically active compounds of Knotweed (Reynoutria spp.). Mil. Med. Sci. Lett. 2017, 86, 17–31. [Google Scholar] [CrossRef]
- Shan, B.; Yi-Zhong Cai, Y.Z.; Brooks, J.D.; Corke, H. Antibacterial properties of Polygonum cuspidatum roots and their major bioactive constituents. Food Chem. 2008, 109, 530–537. [Google Scholar] [CrossRef]
- Kirino, A.; Takasuka, Y.; Nishi, A.; Kawabe, S.; Yamashita, H.; Kimoto, M.; Ito, H.; Tsuji, H. Analysis and functionality of major polyphenolic components of Polygonum cuspidatum (itadori). J. Nutr. Sci. Vitaminol. 2012, 58, 278–286. [Google Scholar] [CrossRef]
- Peng, W.; Qin, R.; Li, X.; Zhou, H. Botany, phytochemistry, pharmacology, and potential application of Polygonum cuspidatum Sieb.et Zucc.: A review. J. Ethnopharmacol. 2013, 148, 729–745. [Google Scholar] [CrossRef]
- Park, B.S.; Lee, H.K.; Lee, S.E.; Paiao, X.L.; Takeoka, G.R.; Wong, R.Y.; Ahn, Y.J.; Kim, J.H. Antibacterial activity of Tabebuia impetiginosa Martius ex DC (Taheebo) against Helicobacter pylori. J. Ethnopharmacol. 2006, 105, 255–262. [Google Scholar] [CrossRef]
- Kim, H.W.; Lee, C.H.; Lee, H.S. Antibacterial activities of persimmon roots-derived materials and 1,4-naphthoquinone’s derivatives against intestinal bacteria. Food Sci. Biotechnol. 2009, 18, 755–760. [Google Scholar]
- Ryu, C.K.; Chae, M.J. Synthesis and antifungal activity of naphthalene-1,4-diones modified at positions 2, 3, and 5. Arch. Pharm. Res. 2005, 28, 750–755. [Google Scholar] [CrossRef]
- Tandon, V.K.; Singh, R.V.; Yadav, D.B. Synthesis and evaluation of novel 1,4-naphthoquinone derivatives as antiviral, antifungal and anticancer agents. Bioorg. Med. Chem. Lett. 2004, 14, 2901–2904. [Google Scholar] [CrossRef]
- Khalil, A.A.K.; Park, W.S.; Lee, J.; Kim, H.J.; Akter, K.M.; Goo, Y.M.; Bae, J.Y.; Chun, M.S.; Kim, J.H.; Ahn, M.J. A new anti-Helicobacter pylori juglone from Reynoutria japonica. Arch. Pharm. Res. 2019, 42, 505–511. [Google Scholar] [CrossRef]
- Kim, J.H.; Chen, C.; Tony Kong, A.N. Resveratrol inhibits genistein-induced multi-drug resistance protein 2 (MRP2) expression in HepG2 cells. Arch. Biochem. Biophys. 2011, 512, 160–166. [Google Scholar] [CrossRef]
- Kim, J.H.; Yu, S.; Chen, J.D.; Kong, A.N. The nuclear cofactor RAC3/AIB1/SRC-3 enhances Nrf2 signaling by interacting with transactivation domains. Oncogene 2013, 32, 514–527. [Google Scholar] [CrossRef]
- Wahyudi, L.D.; Jeong, J.; Yang, H.; Kim, J.H. Amentoflavone-induced oxidative stress activates NF-E2-related factor 2 via the p38 MAP kinase-AKT pathway in human keratinocytes. Int. J. Biochem. Cell Biol. 2018, 99, 100–108. [Google Scholar] [CrossRef]
- Kobayashi, A.; Kang, M.I.; Okawa, H.; Ohtsuji, M.; Zenke, Y.; Chiba, T.; Igarashi, K.; Yamamoto, M. Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol. Cell. Biol. 2004, 24, 7130–7139. [Google Scholar] [CrossRef]
- McMahon, M.; Itoh, K.; Yamamoto, M.; Hayes, J.D. Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression. J. Biol. Chem. 2003, 278, 21592–21600. [Google Scholar] [CrossRef]
- Zhao, J.; Zhang, B.; Li, S.; Zeng, L.; Chen, Y.; Fang, J. Mangiferin increases Nrf2 protein stability by inhibiting its ubiquitination and degradation in human HL60 myeloid leukemia cells. Int. J. Mol. Med. 2014, 33, 1348–1354. [Google Scholar] [CrossRef] [Green Version]
- Jeong, J.; Wahyudi, L.D.; Keum, Y.S.; Yang, H.; Kim, J.H. E-p-Methoxycinnamoyl-alpha-1-rhamnopyranosyl ester, a phenylpropanoid isolated from Scrophularia buergeriana, increases nuclear factor erythroid-derived 2-related factor 2 stability by inhibiting ubiquitination in human keratinocytes. Molecules 2018, 23, 768. [Google Scholar] [CrossRef]
- Sreelatha, T.; Kandhasamy, S.; Dinesh, R.; Shruthy, S.; Shweta, S.; Mukesh, D.; Karunagaran, D.; Balaji, R.; Mathivanan, N.; Perumal, P.T. Synthesis and SAR study of novel anticancer and antimicrobial naphthoquinone amide derivatives. Bioorg. Med. Chem. Lett. 2014, 24, 3647–3651. [Google Scholar] [CrossRef]
- Ding, S.Z.; Minohara, Y.; Fan, X.J.; Wang, J.; Reyes, V.E.; Patel, J.; Dirden-Kramer, B.; Boldogh, I.; Ernst, P.B.; Crowe, S.E. Helicobacter pylori infection induces oxidative stress and programmed cell death in human gastric epithelial cells. Infect. Immun. 2007, 75, 4030–4039. [Google Scholar] [CrossRef]
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Kim, J.-H.; Khalil, A.A.K.; Kim, H.-J.; Kim, S.-E.; Ahn, M.-J. 2-Methoxy-7-Acetonyljuglone Isolated from Reynoutria japonica Increases the Activity of Nuclear Factor Erythroid 2-Related Factor-2 through Inhibition of Ubiquitin Degradation in HeLa Cells. Antioxidants 2019, 8, 398. https://doi.org/10.3390/antiox8090398
Kim J-H, Khalil AAK, Kim H-J, Kim S-E, Ahn M-J. 2-Methoxy-7-Acetonyljuglone Isolated from Reynoutria japonica Increases the Activity of Nuclear Factor Erythroid 2-Related Factor-2 through Inhibition of Ubiquitin Degradation in HeLa Cells. Antioxidants. 2019; 8(9):398. https://doi.org/10.3390/antiox8090398
Chicago/Turabian StyleKim, Jung-Hwan, Atif Ali Khan Khalil, Hye-Jin Kim, Sung-Eun Kim, and Mi-Jeong Ahn. 2019. "2-Methoxy-7-Acetonyljuglone Isolated from Reynoutria japonica Increases the Activity of Nuclear Factor Erythroid 2-Related Factor-2 through Inhibition of Ubiquitin Degradation in HeLa Cells" Antioxidants 8, no. 9: 398. https://doi.org/10.3390/antiox8090398
APA StyleKim, J.-H., Khalil, A. A. K., Kim, H.-J., Kim, S.-E., & Ahn, M.-J. (2019). 2-Methoxy-7-Acetonyljuglone Isolated from Reynoutria japonica Increases the Activity of Nuclear Factor Erythroid 2-Related Factor-2 through Inhibition of Ubiquitin Degradation in HeLa Cells. Antioxidants, 8(9), 398. https://doi.org/10.3390/antiox8090398