Protective Effects of Omija-tang on $H_2O_2$-induced apoptotic death of H9c2 cardiomyoblast cells

오미자탕(五味子湯)이 심근세포에 미치는 영향

  • Han, Myoung-Ah (Dept. of Internal Medicine Wonkwang University Oriental Medicine Hospital) ;
  • Choi, Woo-Jung (Dept. of Internal Medicine Wonkwang University Oriental Medicine Hospital) ;
  • Kim, Dong-Woung (Dept. of Internal Medicine Wonkwang University Oriental Medicine Hospital) ;
  • Jung, Dae-Young (Dept. of Internal Medicine Wonkwang University Oriental Medicine Hospital) ;
  • Shin, Sun-Ho (Dept. of Internal Medicine Wonkwang University Oriental Medicine Hospital) ;
  • Choi, Jin-Young (Dept. of Internal Medicine Wonkwang University Oriental Medicine Hospital)
  • 한명아 (원광대학교 전주한방병원 내과) ;
  • 최우정 (원광대학교 전주한방병원 내과) ;
  • 김동웅 (원광대학교 전주한방병원 내과) ;
  • 정대영 (원광대학교 전주한방병원 내과) ;
  • 신선호 (원광대학교 전주한방병원 내과) ;
  • 최진영 (원광대학교 전주한방병원 내과)
  • Published : 2002.06.30

Abstract

The water extract of Omija-tang(OMJT) has been traditionally used for treatment of ischemic heart and brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of OMJT protects cells from such damage. Therefore, this study was conducted to investigate the protective mechanisms of OMJT on $H_2O_2$-induced toxicity in H9c2 cardiomyoblast cells. Treatment of $H_2O_2$ markedly induced death of H9c2 cardiomyoblast cells in a dose-dependent manner. The characteristics of $H_2O_2$-induced death of H9c2 showed apparent apoptotic features, such as DNA fragmentation. However, OMJT significantly reduced both $H_2O_2$-induced cell death and chromatin fragmentation. The decrease of Bcl-XL expression by $H_2O_2$ was inhibited by OMJT. In addition, the increase of Bcl-XS and Bax expression were also inhibited by OMJT. In particular, Fas expression, which is generally recognized as cell death inducing signal by Fas/FasL interaction, was markedly increased by $H_2O_2$ in a time-dependent manner, whereas this increase was completely prevented by OMJT. The combined treatment of OMJT and $H_2O_2$ in H9c2 cells also reduced activation of caspase-9 and caspase-3 like protease. Taken together, this study indicates that the protective effects of the water extract of OMJT against oxidative damage may be mediated by the modulation of BcI-XL/S and Bax expression by way of the regulation of mitochondrial membrane potential and caspase cascades.

Keywords

References

  1. 景岳全書(下) 張介賓
  2. 現代中醫學生理學基礎 李鐘朴
  3. 中醫方劑大辭典(第三冊) 彭부仁
  4. 本草學 辛民敎
  5. 中醫內科學 張伯수
  6. Proc. Natl. Acad. Sci. USA v.90 Oxidants antioxidants and the degenerative diseases of aging Ames, B.N.;Shigenaga, M.K.;Hagen, T.M.
  7. Toxicol. Appl. Pharmacol. v.159 no.3 Metallothionein and apoptosis during differentiation of myoblasts to myotubes protection against free radical toxicity Apostolova, M.D.;Ivanova, I.A.;Cherian, M.G.
  8. Mol. Cell Biochem. v.163;164 Apoptosis in the heart : when and why? Bromme, H.J.;Holtz, J.
  9. Arch. Biochem. Biophys. v.373 no.1 Hydrogen peroxide dose dependent induction of cell death or hypertrophy in cardiomyocytes Chen, Q.M.;Tu, V.C.;Wu, Y.;Bahl, J.J.
  10. Free radicals in biology and medicine Oxygen is poisonous-an introduction oxygen toxocity and free radicals. Halliwell, B.;Gutteridge, J.M.C.
  11. 圓光大學校大學院 博士學位論文 生脈散이 白鼠의 심혈관계에 미치는 영향 金世吉
  12. 慶熙大學校大學院 博士學位論文 生脈散이 스포츠 음료로서 운동수행 능력과 혈액학적 변화에 미치는 영향 이응세
  13. 대한한의학회지 v.19 no.2 산소분압에 의한 심근세포변화에 미치는 生脈散의 효과 申善澔
  14. 동의생리학회지 v.15 no.5 生脈散이 대동맥 평활근 세포에서 NO 생성에 미치는 영향 許胤
  15. Br. Med. Bull. v.9 Free radicals and myocardial reperfusion injury Flitter, W.D.
  16. Circulation v.80 Deleterious effects of oxygen radicals in ischemia/reperfusion. Resolved and unresolved issues Kloner, R.A.;Przyklenk, K.;Whittaker, P.
  17. Cir. Res. v.81 Death by design. Programmed cell death in cardiovascular biology and disease MacLellan, W.R.;Schneider, M.D.
  18. Endocrinology v.140 no.4 Signal transduction of arginine vasopressin-induced arachidonic acid releas in H9c2 cardiac myoblasts: role of ${Ca^2+}$ and the protein kinase C-dependent activation of p42 mitogen-activated protein kinase Chen, W.C.;Chen, C.C.
  19. J. Neurosci. v.7 Glutamate neurotoxicity in cortical cell culture Choi, D.W.;Maulucci-Gedde, M.A.;Kriegstein, A.R.
  20. Annu. Rev. Neurosci. v.21 Zinc and brain injury Choi, D.W.;Koh, J.Y.
  21. Am. J. physiol. v.273 Protection against glutamate-induced cytotoxicity in the C6 glial cells by thiols antioxidants Han, Derick;Sen, Chandan K.;Sashiwati, Roy
  22. J. Neurosci. v.48 A mechanism for glutamate toxicity in the C6 glioma cells involving inhibition of cystine uptake leading to glutathion depletion Kato, S.;Negishi, K.;Mawatari, K.;Kuo, C.H.
  23. Crit. Rev. Toxicol. v.23 Free radicals as mediators of tissue injury and disease Kehrer, J.P.
  24. 失笑散 煎湯液이 배양 심근세포에 미치는 영향 韓東獻
  25. 동의생리학회지 v.14 no.2 炙甘草湯이 배양 심근세포에 미치는 영향 李來春
  26. 本草學 康舜洙
  27. 本草疏證 鄒澍
  28. 本草綱目 李時珍
  29. 韓藥의 藥理 金동均(編譯)
  30. 중약대사전 김창민(외)(완역)
  31. 配合本草學 康秉秀
  32. J. Mol. Cell Cardiol. v.30 Oxidative Stress Induces DNA Fragmentation and Caspase Activation Via the c-Jun NH2-terminal Kinase Pathway in H9c2 Cardiac Muscle Cells Turner, Neil A.;Xia, Fen;Azhar, Gohar;Zhang, Xiaomin;Liu, Lixin;Wei, Jeanne Y.
  33. B. J. Biol. v.274 Regulation of FasLigand expression during activation-induced cell death in T-lymphocytes via nuclear factor Kasibhatla, S.;Genestier, L.;Green, R.
  34. Eur. J. Biochem. v.254 Apoptosis signal by death receptors Klaus, S.O.;Davide, F.
  35. Am. J. Pathol. v.138 Tumor necrosis factor induces apoptosis in normal endotherial cells in vitro Robaye, B.;Mosselmans, R.;Fiers, W.;Dumont, J.E.;Galand, P.
  36. Science v.245 Monoclonal antibody-mediated tumor regression by induction of apoptosis Trauth, B.C.;Klas, C.;Peter, A.M.J.;Matzuku, S.;Moller, P.;Falk, W.;Debatin, K.M.;Krammer, P.H.
  37. Ann. Rev. Immunol. v.12 Function and Activation of NF-${\kappa}$B in the immune system Baeuerle, P.A.;Henkel, T.
  38. Brain Res. v.645 Amyloid beta peptide induces necrosis rather than apoptosis Behl, C.;Davis, J.B.;Killer, F.G.;Schubert, D.
  39. Immunol.(Today) v.14 Apoptosis Cohen, J.J.