DOI QR코드

DOI QR Code

Isoegomaketone Upregulates Heme Oxygenase-1 in RAW264.7 Cells via ROS/p38 MAPK/Nrf2 Pathway

  • Jin, Chang Hyun (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute) ;
  • So, Yang Kang (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute) ;
  • Han, Sung Nim (Department of Food and Nutrition, College of Human Ecology, Seoul National University) ;
  • Kim, Jin-Baek (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute)
  • Received : 2015.12.02
  • Accepted : 2016.07.12
  • Published : 2016.09.01

Abstract

Isoegomaketone (IK) was isolated from Perilla frutescens, which has been widely used as a food in Asian cuisine, and evaluated for its biological activity. We have already confirmed that IK induced the HO-1 expression via Nrf2 activation in RAW264.7 cells. In this study, we investigated the effect of IK on the mechanism of HO-1 expression. IK upregulated HO-1 mRNA and protein expression in a dose dependent manner. The level of HO-1 mRNA peaked at 4 h after $15{\mu}M$ IK treatment. To investigate the mechanisms of HO-1 expression modulation by IK, we used pharmacological inhibitors for the protein kinase C (PKC) family, PI3K, and p38 MAPK. IK-induced HO-1 mRNA expression was only suppressed by SB203580, a specific inhibitor of p38 MAPK. ROS scavengers (N-acetyl-L-cysteine, NAC, and glutathione, GSH) also blocked the IK-induced ROS production and HO-1 expression. Furthermore, both NAC and SB203580 suppressed the IK-induced Nrf2 activation. In addition, ROS scavengers suppressed other oxidative enzymes such as catalase (CAT), glutathione S-transferase (GST), and NADH quinone oxidoreductase (NQO-1) in IK-treated RAW264.7 cells. Taken together, it can be concluded that IK induced the HO-1 expression through the ROS/p38 MAPK/Nrf2 pathway in RAW264.7 cells.

Keywords

References

  1. Alam, J. and Cook, J. L. (2003) Transcriptional regulation of the heme oxygenase-1 gene via the stress response element pathway. Curr. Pharm. Des. 9, 2499-2511. https://doi.org/10.2174/1381612033453730
  2. Brochers, A. T., Hackman, R. M., Keen, C. L., Stern, J. S. and Gershwin, M. E. (1997) Complementary medicine: a review of immunomodulatory effects of Chinese herbal medicines. Am. J. Clin. Nutr. 66, 1303-1312. https://doi.org/10.1093/ajcn/66.6.1303
  3. Cho, B. O., Jin, C. H., Park, Y. D., Ryu, H. W., Byun, M. W., Seo, K. I. and Jeong, I. Y. (2011) Isoegomaketone induces apoptosis through caspase-dependent and caspase-independent pathways in human DLD1 cells. Biosci. Biotechnol. Biochem. 75, 1306-1311. https://doi.org/10.1271/bbb.110088
  4. Gabunia, K., Ellison, S. P., Singh, H., Datta, P., Kelemen, S. E., Rizzo, V. and Autieri, M. V. (2012) Interleukin-19 (IL-19) induces heme oxygenase-1 (HO-1) expression and decreases reactive oxygen species in human vascular smooth muscle cells. J. Biol. Chem. 287, 2477-2484. https://doi.org/10.1074/jbc.M111.312470
  5. Huang, N., Hauck, C., Yum, M. Y., Rizshsky, L., Widrlechner, M. P., McCoy, J. A., Murphy, P. A., Dixon, P. M., Nikolau, B. J. and Birt, D. F. (2009) Rosmarinic acid in Prunella vulgaris ethanol extract inhibits LPS-induced prostaglandin E2 and nitric oxide in RAW264.7 mouse macrophage. J. Agric. Food Chem. 57, 10579-10589. https://doi.org/10.1021/jf9023728
  6. Jin, C. H., Lee, H. J., Park, Y. D., Choi, D. S., Kim, D. S., Kang, S. Y., Seo, K. I. and Jeong, I. Y. (2010) Isoegomaketone inhibits lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophages through the heme oxygenase-1 induction and inhibition of the interferon-${\beta}$-STAT-1 pathway. J. Agric. Food Chem. 58, 860-867. https://doi.org/10.1021/jf9033333
  7. Kaspar, J. W., Niture, S. K. and Jaiswal, A. K. (2009) Nrf2:INrf2 (Keap1) signaling in oxidative stress. Free Radic. Biol. Med. 47, 1304-1309. https://doi.org/10.1016/j.freeradbiomed.2009.07.035
  8. Khan, M. S., Priyadarshini, M. and Bano, B. (2009) Preventive effect of curcumin and quercetin against nitric oxide mediated modification of goat lung cystatin. J. Agric. Food Chem. 57, 6055-6059. https://doi.org/10.1021/jf900356w
  9. Kim, J. S. and Jobin, C. (2005) The flavonoid luteolin prevents lipopolysaccharide-induced NF-${\kappa}B$ signaling and gene expression by blocking $I{\kappa}B$ kinase activity in intestinal epithelial cells and bonemarrow derived dendritic cells. Immunology 115, 375-387. https://doi.org/10.1111/j.1365-2567.2005.02156.x
  10. Kim, M. J., Kadayat, T., Kim, D. E., Lee, E. S. and Park, P. H. (2014) TI-I-174, a synthetic chalcone derivative, suppresses nitric oxide production in murine macrophages via heme oxygenase-1 induction and inhibition of AP-1. Biomol. Ther. (Seoul) 22, 390-399. https://doi.org/10.4062/biomolther.2014.062
  11. Kwon, S. J., Lee, J. H., Moon, K. D., Jeong, I. Y., Ahn, D. U., Lee, M. K. and Seo, K. I. (2014) Induction of apoptosis by isoegomaketone from Perillafrutescens L. in B16 melanoma cells is mediated through ROS generation and mitochondrial-dependent, -independent pathway. Food Chem. Toxicol. 65, 97-104. https://doi.org/10.1016/j.fct.2013.12.031
  12. Lee, J. H., Cho, H. D., Jeong, I. Y., Lee, M. K. and Seo, K. I. (2014) Sensitization of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant primary prostate cancer cells by isoegomaketone form Perillafrutescens. J. Nat. Prod. 77, 2438-2443. https://doi.org/10.1021/np500452e
  13. Lee, S. E., Jeong, S. I., Kim, G. D., Yang, H., Park, C. S., Jin, Y. H. and Park, Y. S. (2011) Upregulation of heme oxygenase-1 as an adaptive mechanism for protection against crotonaldehyde in human umbilical vein endothelial cells. Toxicol. Lett. 201, 240-248. https://doi.org/10.1016/j.toxlet.2011.01.006
  14. Lee, S. E., Yang, H., Jeong, S. I., Jin, Y. H., Park, C. S. and Park, Y. S. (2012) Induction of heme oxygenase-1 inhibits cell death in crotonaldehyde-stimulated HepG2 cells via the PKC-${\delta}$-p38-Nrf2 pathway. PLoS ONE 7, e41676. https://doi.org/10.1371/journal.pone.0041676
  15. Liu, X. M., Peyton, K. J., Shebib, A. R., Wang, H. and Durante, W. (2011) Compound C stimulates heme oxygenase-1 gene expression via the Nrf2-ARE pathway to preserve human endotherial cell survival. Biochem. Pharmacol. 82, 371-379. https://doi.org/10.1016/j.bcp.2011.05.016
  16. McNally, S. J., Harrison, E. M., Ross, J. A., Garden, O. J. and Wiqmore, S. J. (2007) Curcumin induces hemeoxygenase 1 through generation of reactive oxygen species, p38 activation and phosphatase inhibition. Int. J. Mol. Med. 19, 165-172.
  17. Nishizawa, A., Hoda, G. and Tabata, M. (1989) Determination of final steps in biosynthesis of essential oil components in Perillafrutescens. Planta Med. 55, 251-253. https://doi.org/10.1055/s-2006-961996
  18. Otterbein, L. E. and Choi, A. M. (2000) Hemeoxygenase: colors of defense against cellular stress. Am. J. Physiol. Lung Cell Mol. Physiol. 279, L1029-L1037 https://doi.org/10.1152/ajplung.2000.279.6.L1029
  19. Park, P. H., Kim, H. S., Jin, X. Y., Jin, F., Hur, J., Ko, G. and Sohn, D. H. (2009a) KB-34, a newly synthesized chalcone derivative, inhibits lipopolysaccharide-stimulated nitric oxide production in RAW264.7 macrophages via heme oxygenase-1 induction and blockade of activator protein-1. Eur. J. Pharmacol. 606, 215-224. https://doi.org/10.1016/j.ejphar.2008.12.034
  20. Park, Y. D., Kang, M. A., Lee, H. J., Jin, C. H., Choi, D. S., Kim, D. S., Kang, S. Y., Byun, M. W. and Jeong, I. Y. (2009b) Inhibition of an inducible nitric oxide synthase expression by a hexane extract from Perilla frutescens cv. Chookyoupjaso mutant induced by mutagenesis with gamma-ray. Bangsaseon San Eob Haghoeji 3, 13-18.
  21. Rojo, A. I., Salina, M., Salazar, M., Takahashi, S., Suske, G., Calvo, V., de Sagarra, M. R. and Cuadrado, A. (2006) Regulation of heme oxygenase-1 gene expression through the phosphatidylinositol 3-kinase/PKC-${\zeta}$ pathway and Sp1. Free Radic. Biol. Med. 41, 247-261. https://doi.org/10.1016/j.freeradbiomed.2006.04.002
  22. Ryter, S. W., Alam, J. and Choi, A. M. (2006) Heme oxygenase-1/carbon monoxide: from basic science to therapeutic application. Physiol. Rev. 86, 583-650. https://doi.org/10.1152/physrev.00011.2005
  23. Shih, R. H., Cheng, S. E., Hsiao, L. D., Kou, Y. R. and Yang, C. M. (2011) Cigarette smoke extract upregulates heme oxygenase-1 via PKC/NADPH oxidase/ROS/PDGFR/PI3K/Akt pathway in mouse brain endothelial cells. J. Neuroinflammation 8, 104 https://doi.org/10.1186/1742-2094-8-104
  24. Thapa, D., Meng, P., Bedolla, R. G., Reddick, R. L., Kumar, A. P. and Ghosh, R. (2014) NQO1 suppresses NF-${\kappa}B$-p300 interaction to regulate inflammatory mediators associated with prostate tumorigenesis. Cancer Res. 74, 5644-5655. https://doi.org/10.1158/0008-5472.CAN-14-0562
  25. True, A. L., Olive, M., Boehm, M., San, H., Westrick, R. J., Raghavachari, N., Xu, X., Lynn, E. G., Sack, M. N., Munson, P. J., Gladwin, M. T. and Nabel, E. G. (2007) Heme oxygenase-1 deficiency accelerates formation of arterial thrombosis through oxidative damage to the endothelium, which is rescued by inhaled carbon monoxide. Circ. Res. 101, 893-901. https://doi.org/10.1161/CIRCRESAHA.107.158998
  26. Tsoyi, K., Kim, H. J., Shin, J. S., Kim, D. H., Cho, H. J., Lee, S. S., Ahn, S. K., Yun-Choi, H. S., Lee, J. H., Seo, H. G. and Chang, K. C. (2008) HO-1 and JAK-2/STAT-1 signals are involved in preferential inhibition of iNOS over COX-2 gene expression by newly synthesized tetrahydroisoquinoline alkaloid, CKD712, in cells activated with lipopolysaccharide. Cell. Signal. 20, 1839-1847. https://doi.org/10.1016/j.cellsig.2008.06.012
  27. Turdi, S., Han, X., Huff, A. F., Roe, N. D., Hu, N., Gao, F. and Ren, J. (2012) Cardiac-specific overexpression of catalase attenuates lipopolysaccharide-induced myocardial contractile dysfunction: Role of autophagy. Free Radic. Biol. Med. 53, 1327-1338. https://doi.org/10.1016/j.freeradbiomed.2012.07.084
  28. Ueda, H. and Yamazaki, M. (1997) Inhibition of tumor necrosis factor-${\alpha}$ production by orally administering a perilla leaf extract. Biosci. Biotechnol. Biochem. 61, 1292-1295. https://doi.org/10.1271/bbb.61.1292
  29. Yamada, N., Yamaya, M., Okinaga, S., Nakyama, K., Sekizawa, K., Shibahara, S. and Sasaki, H. (2000) Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema. Am. J. Hum. Genet. 66, 187-195. https://doi.org/10.1086/302729
  30. Zhang, M., An, C., Gao, Y., Leak, R. K., Chen, J. and Zhang, F. (2013) Emerging roles of Nrf2 and phase II antioxidant enzymes in neuroprotection. Prog. Neurobiol. 100, 30-47. https://doi.org/10.1016/j.pneurobio.2012.09.003
  31. Zhang, X., Wang, G., Gurley, E. C. and Zhou, H. (2014) Flavonoid apigenin inhibits lipopolysaccharide-induced inflammatory response through multiple mechanism in macrophages. PLoS ONE 9, e107072. https://doi.org/10.1371/journal.pone.0107072

Cited by

  1. Collaborative Power of Nrf2 and PPARγ Activators against Metabolic and Drug-Induced Oxidative Injury vol.2017, 2017, https://doi.org/10.1155/2017/1378175
  2. Isoegomaketone Alleviates the Development of Collagen Antibody-Induced Arthritis in Male Balb/c Mice vol.22, pp.7, 2017, https://doi.org/10.3390/molecules22071209
  3. A New Monoterpene from the Leaves of a Radiation Mutant Cultivar of Perilla frutescens var. crispa with Inhibitory Activity on LPS-Induced NO Production vol.22, pp.9, 2017, https://doi.org/10.3390/molecules22091471
  4. Matrine‐Type Alkaloids Inhibit Advanced Glycation End Products Induced Reactive Oxygen Species‐Mediated Apoptosis of Aortic Endothelial Cells In Vivo and In Vitro by Targeting MKK3 and p38MAPK Signaling vol.6, pp.12, 2017, https://doi.org/10.1161/JAHA.117.007441
  5. Therapeutic Modulation of Virus-Induced Oxidative Stress via the Nrf2-Dependent Antioxidative Pathway vol.2018, pp.1942-0994, 2018, https://doi.org/10.1155/2018/6208067
  6. Role of Carbon Monoxide in Neurovascular Repair Processing vol.26, pp.2, 2018, https://doi.org/10.4062/biomolther.2017.144
  7. Using Centrifugal Partition Chromatography vol.2019, pp.1687-8779, 2019, https://doi.org/10.1155/2019/8751345
  8. Rhein from Rheum rhabarbarum Inhibits Hydrogen-Peroxide-Induced Oxidative Stress in Intestinal Epithelial Cells Partly through PI3K/Akt-Mediated Nrf2/HO-1 Pathways vol.67, pp.9, 2016, https://doi.org/10.1021/acs.jafc.9b00037
  9. Bisdemethoxycurcumin Protection of Cardiomyocyte Mainly Depends on Nrf2/HO-1 Activation Mediated by the PI3K/AKT Pathway vol.32, pp.9, 2019, https://doi.org/10.1021/acs.chemrestox.9b00222
  10. Heracleum moellendorffii roots inhibit the production of pro-inflammatory mediators through the inhibition of NF-κB and MAPK signaling, and activation of ROS/Nrf2/HO-1 signaling in LPS-stimulate vol.19, pp.1, 2016, https://doi.org/10.1186/s12906-019-2735-x
  11. Water-separated part of Chloranthus serratus alleviates lipopolysaccharide- induced RAW264.7 cell injury mainly by regulating the MAPK and Nrf2/HO-1 inflammatory pathways vol.19, pp.1, 2016, https://doi.org/10.1186/s12906-019-2755-6
  12. Intracellular synthesis of gold nanoparticles by Gluconacetobacter liquefaciens for delivery of peptide CopA3 and ginsenoside and anti-inflammatory effect on lipopolysaccharide-activated macrophages vol.48, pp.1, 2020, https://doi.org/10.1080/21691401.2020.1748639
  13. Anti-Inflammatory and Antioxidant Effects of Carpesium cernuum L. Methanolic Extract in LPS-Stimulated RAW 264.7 Macrophages vol.2020, pp.None, 2016, https://doi.org/10.1155/2020/3164239
  14. Literature-Based Drug Repurposing in Traditional Chinese Medicine: Reduced Inflammatory M1 Macrophage Polarization by Jisil Haebaek Gyeji-Tang Alleviates Cardiovascular Disease In Vitro and Ex Vivo vol.2020, pp.None, 2016, https://doi.org/10.1155/2020/8881683
  15. Flavonoids Activation of the Transcription Factor Nrf2 as a Hypothesis Approach for the Prevention and Modulation of SARS-CoV-2 Infection Severity vol.9, pp.8, 2016, https://doi.org/10.3390/antiox9080659
  16. Ameliorative potentials of Persea americana leaf extract on toxicants - induced oxidative assault in multiple organs of wistar albino rat vol.7, pp.1, 2016, https://doi.org/10.1186/s40816-020-00237-1
  17. Chlorogenic Acid Attenuates Oxidative Stress-Induced Intestinal Epithelium Injury by Co-Regulating the PI3K/Akt and IκBαNF-κB Signaling vol.10, pp.12, 2016, https://doi.org/10.3390/antiox10121915