Herbal Cocktail Sagunja Protects $H_2O_2$-induced H9c2 Cardiomyoblast Cell Death through the Induction of Heme Oxygenase-1

  • Park, Chan-Ny (Vestibulo Cochlear Research Center and Department of Microbiology, School of Medicine) ;
  • Moon, Byung-Soon (Department of Internal Medicine School of Oriental Medicine) ;
  • Jeon, Seon-Bok (Department of Public Health, Graduate School of Wonkwang University) ;
  • Kim, Nam-Song (Department of Public Health, Graduate School of Wonkwang University) ;
  • Chung, Sang-Young (Department of Surgery, Chonnam National University Medical School) ;
  • Park, Jin-Woo (Department of Biochemistry, Chonbuk National University) ;
  • Park, Rae-Kil (Vestibulo Cochlear Research Center and Department of Microbiology, School of Medicine)
  • Published : 2007.08.25

Abstract

Sagunjatang (Sagunja), containing Radix Astragali, Radix Ginseng, Fructus Schizandrae, Radix Ophiopogonis and Radix Glycyrrhizae, has been used as a prescription for ischemic heart and brain diseases in Korean traditional medicine. This study was designed to investigate the protective mechanisms of Sagunja on $H_2O_2$-induced cytotoxicity of H9c2 cardiomyocytes. Treatment with $H_2O_2$ resulted in death of H9c2 cells, characterized by apparent apoptotic features, including the fragmentation of nucleus and increase in sub-GO/G1fraction of cell cycle. However, Sagunja markedly suppressed the apoptotic characteristics of H9c2 cells induced by $H_2O_2$ with decrease of intracellular peroxide level. In addition, Sagunja suppressed the features of mitochondrial dysfunction, including change of mitochondrial membrane potential, in $H_2O_2$- treated cells. Additionally, Sagunja induced the expression of HO-1 protein in both time-and dose-dependent manner. The role of HO-1 in ROS-scavenging activity of Sagunja is proposed.

Keywords

References

  1. Bromme, H.J., Holtz, J. Apoptosis in the heart: when and why? Mol Cell Biochem. pp 163-164, 261-275, 1996
  2. MacLellan, W.R., Schneider, M.D. Death by design. Programmed cell death in cardiovascular biology and disease Circ Res. 81: 137-144, 1997 https://doi.org/10.1161/01.RES.81.2.137
  3. Saraste, A., Pulkki, K., Kallajoki, M., Henriksen, K., Parvinen, M., Voipio-Pulkki, L.M. Apoptosis in human acute myocardial infarction Circulation. 95: 320-323, 1997 https://doi.org/10.1161/01.CIR.95.2.320
  4. Adams, J.M., Cory, S. The Bcl-2 protein family: arbiters of cell survival. Science. 281: 1322-1326, 1998 https://doi.org/10.1126/science.281.5381.1322
  5. Chen, Y.C., Shen, S.C., Lee, W.R., Lin H.Y., Ko, C.H., Lee, T.J. Nitric oxide and prostaglandin E2 participate in lipopolysaccharide/interferon-gamma-induced heme oxygenase-1 and prevent RAW264.7 macrophages from UV-irradiation-induced cell death J Cell Biochem. 86: 331-339, 2002 https://doi.org/10.1002/jcb.10230
  6. Antonsson, B., Montessuit, S., Lauper, S., Eskes, R., Martinou, J.C. Bax oligomerization is required for channel- forming activity in liposomes and to trigger cytochrome c release from mitochondria Biochem J. 345(2):271-278, 2000 https://doi.org/10.1042/0264-6021:3450271
  7. Van Houten, B., Woshner, V., Santos, J.H. Role of mitochondrial DNA in toxic responses to oxidative stress DNA Repair (Amst). 5: 145-152, 2005 https://doi.org/10.1016/j.dnarep.2005.03.002
  8. Adderley, S.R., Fitzgerald, D.J. Oxidative damage of cardiomyocytes is limited by extracellular regulated kinases 1/2-mediated induction of cyclooxygenase-2 J Biol Chem. 274: 5038-5046, 1999 https://doi.org/10.1074/jbc.274.8.5038
  9. Hong, M.Y., Chapkin, R.S., Barhoumi, R., Burghardt, R.C., Turner, N.D., Henderson, C.E., Sanders, L.M., Fan, Y.Y., Davidson, L.A., Murphy, M.E., Spinka, C.M., Carroll, R.J., Lupton, J.R. Fish oil increases mitochondrial phospholipid unsaturation, upregulating reactive oxygen species and apoptosis in rat colonocytes Carcinogenesis. 23: 1919-1925, 2002 https://doi.org/10.1093/carcin/23.11.1919
  10. Petrosillo, G., Ruggiero, F.M., Paradies, G. Role of reactive oxygen species and cardiolipin in the release of cytochrome c from mitochondria Faseb J. 17: 2202-2208, 2003 https://doi.org/10.1096/fj.03-0012com
  11. Helen, A., Krishnakumar, K., Vijayammal, P.L., Augusti, K.T. Antioxidant effect of onion oil (Allium cepa. Linn) on the damages induced by nicotine in rats as compared to alpha-tocopherol Toxicol Lett. 116: 61-68, 2000 https://doi.org/10.1016/S0378-4274(00)00208-3
  12. Suresh, M.V., Sreeranjit Kumar, C.V., Lal, J.J., Indira, M. Impact of massive ascorbic acid supplementation on alcohol induced oxidative stress in guinea pigs Toxicol Lett. 104: 221-229, 1999 https://doi.org/10.1016/S0378-4274(98)00377-4
  13. Kang, S.S. Recommended Prescription of Herbs. Seoul, pp 122-123, 1993
  14. Park, C., So, H.S., Shin, C.H., Baek, S.H., Moon, B.S., Shin, S.H., Lee, H.S., Lee, D.W., Park, R. Quercetin protects the hydrogen peroxide-induced apoptosis via inhibition of mitochondrial dysfunction in H9c2 cardiomyoblast cells Biochem Pharmacol. 66: 1287-1295, 2003 https://doi.org/10.1016/S0006-2952(03)00478-7
  15. Oliveira, P.J., Goncalves, L., Monteiro, P., Providencia, L.A., Moreno, A.J. Are the antioxidant properties of carvedilol important for the protection of cardiac mitochondria? Curr Vasc Pharmacol. 3: 147-158, 2005 https://doi.org/10.2174/1570161053586903
  16. Park, C., So, H.S., Kim, S.J., Youn, M.J., Moon, B.S., Shin, S.H., Lee, I., Moon, S.K., Park, R. Samul extract protects against the $H_2O_2$-induced apoptosis of H9c2 cardiomyoblasts via activation of extracellular regulated kinases (Erk) 1/2 AmJ Chin Med. 34: 695-706, 2006 https://doi.org/10.1142/S0192415X06004211
  17. Park, C., So, H.S., Shin, S.H., Choi, J.Y., Lee, I., Kim, J.K., Chung, S.Y., Park, R. The water extract of Omija protects H9c2 cardiomyoblast cells from hydrogen peroxide through prevention of mitochondrial dysfunction and activation of caspases pathway Phytother Res. 21: 81-88, 2007 https://doi.org/10.1002/ptr.2028
  18. Davis, R.J. The mitogen-activated protein kinase signal transduction pathway J Biol Chem. 268: 14553-14556, 1993
  19. Susin, S.A., Zamzami, N., Castedo, M., Hirsch, T., Marchetti, P., Macho, A., Daugas, E., Geuskens, M., Kroemer, G. Bcl-2 inhibits the mitochondrial release of an apoptogenic protease J Exp Med. 184: 1331-1341, 1996 https://doi.org/10.1084/jem.184.4.1331
  20. Banmeyer, I., Marchand, C., Clippe, A., Knoops, B. Human mitochondrial peroxiredoxin 5 protects from mitochondrial DNA damages induced by hydrogen peroxide FEBS Lett. 579: 2327-2333, 2005 https://doi.org/10.1016/j.febslet.2005.03.027
  21. Chen, K., Gunter, K., Maines, M.D. Protective effect of ginsenoside Rg1 on dopamine-induced apoptosis in PC12 cells J Neurochem. 75: 304-313, 2000 https://doi.org/10.1046/j.1471-4159.2000.0750304.x
  22. Choi, B.M., Pae, H.O., Jeong, Y.R., Oh, G.S., Jun, C.D., Kim, B.R., Kim, Y.M., Chung, H.T. Overexpression of heme oxygenase (HO)-1 renders Jurkat T cells resistant to fas-mediated apoptosis: involvement of iron released by HO-1 Free Radic Biol Med. 36: 858-871, 2004 https://doi.org/10.1016/j.freeradbiomed.2004.01.004
  23. Petrache, I., Otterbein, L.E., Alam, J., Wiegand, G.W., Choi, A.M. Heme oxygenase-1 inhibits TNF-alpha-induced apoptosis in cultured fibroblasts Am J PhysiolLung Cell Mol Physiol. 278: L312-319, 2000 https://doi.org/10.1152/ajplung.2000.278.2.L312
  24. Liu, Z.M., Chen, G.G., Ng, E.K., Leung, W.K., Sung, J.J., Chung, S.C. Upregulation of heme oxygenase-1 and p21 confers resistance to apoptosis in human gastric cancer cells Oncogene. 23: 503-513, 2004 https://doi.org/10.1038/sj.onc.1207173
  25. Chen, C.Y., Jang, J.H., Li, M.H., Surh, Y.J. Resveratrol upregulates heme oxygenase-1 expression via activation of NF-E2-related factor 2 in PC12 cells Biochem Biophys Res Commun. 331: 993-1000, 2005 https://doi.org/10.1016/j.bbrc.2005.03.237
  26. Kroemer, G., Dallaporta, B., Resche-Rigon, M. The mitochondrial death/life regulator in apoptosis and necrosis Annu Rev Physiol. 60: 619-642, 1998 https://doi.org/10.1146/annurev.physiol.60.1.619
  27. Nicholson D.W., Thornberry, N.A. Caspases: killer proteases Trends Biochem Sci. 22: 299-306, 1997 https://doi.org/10.1016/S0968-0004(97)01085-2
  28. Budihardjo, I., Oliver, H., Lutter, M., Luo, X., Wang, X. Biochemical pathways of caspase activation during apoptosis Annu Rev Cell Dev Biol. 15: 269-290, 1999 https://doi.org/10.1146/annurev.cellbio.15.1.269