Protective Effects of Samul-tang on ${H_2O_2}-induced$ Cell Apoptosis in Cultured Cardiomyoblast Cells

$H_2O_2$에 의한 배양심근세포고사에 미치는 사물탕의 방어효과

  • 박종운 (원광대학교 한의과대학 심계내과학교실) ;
  • 한상혁 (원광대학교 한의학전문대학원) ;
  • 김도환 (원광대학교 한의학전문대학원) ;
  • 문병순 (원광대학교 한의학전문대학원)
  • Published : 2001.12.01

Abstract

Objectives : This study was designed to investigate the protective mechanisms of Samul-tang (SMT) on $H_2O_2$-induced toxicity in H9c2 cardiomyoblast cells. Methods : The cultured cells were pretreated with SMT and exposed to $H_2O_2$. The cell damage was assessed by using MTT assay. Also, we used Hoechst staining, Western blotting analysis. Results : SMT significantly reduced both $H_2O_2$-induced cell death and chromatin fragmentation. The decrease of Bcl2 expression by $H_2O_2$ was inhibited by SMT. In addition, the increase of Bax expression was also inhibited by SMT. In particular, Fas expression, which is generally recognized as cell death inducing signal by Fas/FasL interaction, was markedly decreased by $H_2O_2$ in a time-dependent manner, whereas this decrease was completely prevented by SMT. The cotreatment of SMT and $H_2O_2$ in H9c2 cells also induced the phosphorylation of ERK in a time-dependent manner. Moreover, PD098059, a specific inhibitor of ERKl/2, attenuated the protective effect of SMT on $H_2O_2$-induced toxicity in H9c2 cardiomyoblast cells. Furthermore, the protective effect of SMT was significantly blocked by treatment of SB203580, a specific inhibitor of p38. Conclusions : Taken together, this study suggests that the protective effects of the water extract of SMT against oxidative damages may be mediated by the modulation of Bel2 and Bax expression via the regulation of ERK and p38 signaling pathway.

Keywords

References

  1. 新編丹溪心法附餘 v.下 方廣
  2. 가정의학 醫學敎育硏修阮
  3. 대한한방내과학회지 v.19 no.1 四物湯이 老化白鼠 腦組織의 生化學約 變化에 미치는 影響 박종운;이기상;문병순
  4. 太平惠民和劑局方 陳師文
  5. 醫方集解 汪昻
  6. 素虛後世處方學 趙世衡
  7. 證脈 方藥合編 黃度淵
  8. 東醫臨床方劑學 尹吉榮
  9. HARRISON'S 내과학 해리슨 번역 편찬위원회
  10. 東醫方劑와 處方解說 尹用甲
  11. Mol Cell Biochem v.147 Oxidative stress and heart failure Singh, N.;Dhalla, A.K.;Seneviratne, C.;Singal, P.K.
  12. 허혈성 전처치에 의한 심장보호 효과에 관한 연구 김현
  13. Circulation v.80 Deleterious effects of oxygen radicals in ischemia/reperfusion. Resolved and unresolved issues Kloner, R.A.;Przyklenk, K.;Whittaker, P.
  14. 경희한의대논문집 v.1 四物湯 투여가 家兎의 赤血球像에 미치는 영향에 관한 연구 홍무창
  15. 四物湯 煎湯液이 家兎의 血壓降下에 미치는影響 姜昌洙
  16. 四物湯 및 季節別 活用方이 血液에 미치는 影響 權在龍
  17. 四物湯과 四物湯의 季節別 倍味 및 加味方이 免疫機能과 血液에 미치는 影響 咸昌植
  18. 대한한방내과학회지 v.20 no.1 四物湯이 血管內皮細胞에 미치는 影響 南昌圭
  19. J Biol Chem. v.72 Nitric oxide inhibits apoptosis by preventing increse in caspase-3 like activity via distinct mechanism Kim, Y.M.;Talanian, R.V.;Billiar, T.R.
  20. J Immunology 1 v.163 no.9 Granzyme B-induced loss of mitochondrial innter membrance potential(Delta Psi M) and cytochrome c release are caspase independent Heibein, J.A.;Barry, M.;Motyka, B.;Bleackley, R.C.
  21. Free radicals in biology and medicine The chemistry of oxygen radicals and other oxygen-derived species Halliwell, B.;Gutteridge, J.M.C.
  22. J Mol Cell Cardiol v.19 Mitochondrial hydrogen peroxide generation and activities of glutathione peroxidase and superoxide dismutase following global ischemia Shlafer, M.;Myers, C.L.;Adkins, S.
  23. 심장학 서울대학교 의과대학
  24. 대한한방부인과학회지 v.11 no.1 四物湯과 血槪念의 關係 백승희
  25. 완역 중약대사전 김창민;신민교;안덕균;이경순
  26. 한약의 약리 김형균;김형민;송봉근;이언정;정헌택
  27. Circ Res. v.78 no.4 Mechanism of hydrogen peroxide and hydroxyl free radical-induced intracellular acidification in cultured rat cardiac myoblasts Wu, M.L.;Tsai, K.L.;Wang, S.M.;Wu, J.C.;Wang, B.S.;Lee, Y.T.
  28. 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.
  29. Immunol Today v.14 Apoptosis Cohen, J.J.
  30. CMLS v.54 Mechanism controlling cellular suicide role of Bcl-2 and caspases Allen, R.T.;Cluck, M.W.;Agrawal, D.K.
  31. Pathol Annu v.17 Necrosis and apoptosis distinct modes of cell death with fundamentally different significance Searle, J.;Kerr, J.F.R.;Bishop, C.J.
  32. Eur J Biochem v.254 Apoptosis signal by death receptors Klaus, S.O.;Davide, F.
  33. Cell v.45 Programmed cell death.apoptosis and oncogenesis Williams, G.T.
  34. Circ Res v.85 no.12 ARC inhibits cytochrome c release from mitochondria and protects against hypoxia-induced apoptosis in heart-derived H0c2 cells Ekhterae, D.;Lin, Z.;Lundberg, M.S.;Crow, M.T.;Brosiums, F.C. 3rd;Nunez, G.
  35. Proc Natl Acad Sci USA v.90 no.13 Signal transduction via the MAP kinase. proceed at your own RSK Blenis, J.
  36. J Biol Chem v.275 no.26 Nuclear mitogen-activated protein kinase activation by protein kinase czeta during reoxygenation after ischemic hypoxia Mizukami, Y.;Kobayashi, S.;Uberall, F.;Hellbert, K.;Kobayashi, N.;Yoshida, K.
  37. J Mol Cell Cardiol v.30 no.8 Role of p38 MAP kinase in myocardial stress Nagarkatti, D.S.;Sha'afi, R.I.
  38. Science v.270 Oppersing effect of ERK and JNK-p38 MAP kinase on apoptosis Xia, Z.;Dickens, M.;Raingaud, J.;Davis, R.J.;Greenberg, M.E.