Molecular Biology Reports

, Volume 36, Issue 2, pp 365–370

Shenfu injection suppresses apoptosis by regulation of Bcl-2 and caspase-3 during hypoxia/reoxygenation in neonatal rat cardiomyocytes in vitro

  • Yan-lin Wang
  • Cheng-yao Wang
  • Ben-jing Zhang
  • Zong-ze Zhang
Article

Abstract

Shenfu injection (the major components of which are ginsenosides compound, extract of Panax ginseng shown to have antioxidant properties) is a well-known important Chinese traditional medicine used for the treatment of various diseases especial for cardiac diseases. The precise mechanism of the biological actions of this plant is not fully understood, in order to elucidate the protection of cardiomyocytes. The aim of the present study was to investigate the effect of Shenfu injection on hypoxia/reoxygenation (H/R)-induced apoptosis and the expression of bcl-2 and caspase-3 in cultured neonatal rat cardiomyocytes in vitro. Ventricular myocytes were isolated from neonatal rat hearts and were exposed to 4 h of hypoxia followed by 16 h of reoxygenation. The results indicated that treatment with different doses of Shenfu injection protected cardiacmyocyte cultures from hypoxia/reoxygenation-induced apoptosis. Caspase-3 activation was decreased in hypoxic/reoxygenationed cardiomyocytes co-treated with Shenfu injection when compared to hypoxia/reoxygenation alone treated cultures. Expression of the Bcl-2 proteins was increased in Shenfu injection-treated cardiomyocytes subjected to hypoxia/reoxygenation. In conclusion, ginsenosides compound has obviously protective effects on cardiacmyocytes against apoptosis induced by hypoxia/reoxygenation injury, whose mechanisms probably involve the inhibition of down-regulation of Bcl-2 protein levels and sequential activation of caspase-3.

Keywords

Shenfu injection Cardiomyocytes Hypoxia Reoxygenation Apoptosis Bcl-2 Caspase-3 

Reference

  1. 1.
    Kang PM, Izumo S (2000) Apoptosis and heart failure: a critical review of the literature. Circ Res 86:1107–1113PubMedGoogle Scholar
  2. 2.
    Cheng W, Kajstura J, Nitahara JA et al (1996) Programmed myocyte cell death affects the viable myocardium after infarction in rats. Exp Cell Res 226:316–327PubMedCrossRefGoogle Scholar
  3. 3.
    Narula J, Pandey P, Arbustini E et al (1999) Apoptosis in heart failure: release of cytochrome c from mitochondria and activation of caspase-3 in human cardiomyopathy. Proc Natl Acad Sci USA 96:8144–8149PubMedCrossRefGoogle Scholar
  4. 4.
    Gottlieb RA, Burleson KO, Kloner RA et al (1994) Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J Clin Invest 94:1621–1628PubMedCrossRefGoogle Scholar
  5. 5.
    Umansky SR, Shapiro JP, Cuenco GM, Foehr MW, Bathurst IC, Tomei LD (1997) Prevention of rat neonatal cardiomyocyte apoptosis induced by simulated in vitro ischemia and reperfusion. Cell Death Differ 4:608–616PubMedCrossRefGoogle Scholar
  6. 6.
    Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281:1312–1316PubMedCrossRefGoogle Scholar
  7. 7.
    Cohen GM (1997) Caspases: the executioners of apoptosis. Biochem J 326:1–16PubMedGoogle Scholar
  8. 8.
    Desagher S, Martinou JC (2000) Mitochondria as the central control point of apoptosis. Trends Cell Biol 10:369–377PubMedCrossRefGoogle Scholar
  9. 9.
    Reed JC, Zha H, Aime-Sempe C, Takayama S,Wang HG (1996) Structure–function analysis of Bcl-2 family proteins. Regulators of programmed cell death. Adv Exp Med Biol 406:99–112PubMedGoogle Scholar
  10. 10.
    Kirshenbaum LA, de Moissac D (1997) The bcl-2 gene product prevents programmed cell death of ventricular myocytes. Circulation 96:1580–1585PubMedGoogle Scholar
  11. 11.
    Fortuño MA, Ravassa S , Etayo JC , Díez J (1998) Overexpression of Bax protein and enhanced apoptosis in the left ventricle of spontaneously hypertensive rats: effects of AT1 blockade with losartan. Hypertension 32:280–286PubMedGoogle Scholar
  12. 12.
    Yamamura T, Otani H, Nakao Y, Hattori R, Osako M, Imamura H (2001) IGF-I differentially regulates Bcl-xL and Bax and confers myocardial protection in the rat heart. Am J Physiol Heart Circ Physiol 280:H1191–H1200PubMedGoogle Scholar
  13. 13.
    Postma G., Nemec W, Kleinspehn KL (1999) Large floating clasts in turbidites—a mechanism for their emplacement. Sediment Geol 58(1):47CrossRefGoogle Scholar
  14. 14.
    Zhu ZH, Xiong LZ, Dong HL et al (2000) Dose response effects of Shenfu injection on ischemic reperfusion injury of spinal cord in rabbit. Chin J Anesthesiol 20:664–668Google Scholar
  15. 15.
    Xia ZY, Zhan LY, He YH, Liu XY (2003) The effect of Shenfu on gastrointestinal tract injury and its potential mechanism during cardio-pulmonary bypass in patients undergoing cardiac surgery. Chin J Traumatol 6:245–248PubMedGoogle Scholar
  16. 16.
    Liu XY, Zou HD, Yu JF et al (1997) Protective effect of Shenfu injection on multiple organ damage in rabbit during ischemia reperfusion. Chin J Anesthesiol 17:430–432Google Scholar
  17. 17.
    Zhang BJ, Wang YL Wang CY, Ke JJ (2005) Effect of Shenfu injection on nuclea r factor-κB during myocardial ischemia/reperfusion injury in rats. Chin J Traumatol 8:200–204PubMedGoogle Scholar
  18. 18.
    Buja LM, Hagler HK, Parsons D, Chien K, Reynolds RC, Willerson JT (1988) Alterations of ultra structure and elemental composition in cultured neonatal rat cardiac myocytes after metabolic inhibition with iodoacetic acid. Lab Invest 53:397–412Google Scholar
  19. 19.
    Bo HS, Seung HC, Eun YC et al (2004) Thiamine attenuates hypoxia-induced cell death in cultured neonatal rat cardiomyocytes. Mol Cells 18:133–140Google Scholar
  20. 20.
    Carden DL, Granger DN (2000) Pathophysiology of ischemia-reperfusion injury. J Pathol 190:255–266PubMedCrossRefGoogle Scholar
  21. 21.
    Anderson HV, Willerson JT (1993) Current concepts: thrombolysis in acute myocardial infarction. N Engl J Med 329:703–709PubMedCrossRefGoogle Scholar
  22. 22.
    Vermeiren GLJ, Claeys MJ, Van Bockstaele D et al (2000) Reperfusion injury after focal myocardial ischemia: polymorphonuclear leukocyte activation and its clinical implications. Resuscitation 45:35–61PubMedCrossRefGoogle Scholar
  23. 23.
    Long X, Boluyt MO, Hipolito ML et al (1997) p53 and the hypoxia-induced apoptosis of cultured neonatal rat cardiac myocytes. J Clin Invest 99:2635–2643PubMedCrossRefGoogle Scholar
  24. 24.
    Wang G-W, Zhanxiang Z, Klein JB, Kang YJ (2001) Inhibition of hypoxia/reoxygenation-induced apoptosis in metallothionein-overexpressing cardiomyocytes. AJP—Heart 280:2292–2299Google Scholar
  25. 25.
    Cook SA, Sugden PH, Clerk A (1999) Regulation of bcl-2 family proteins during development and in response to oxidative stress in cardiac myocytes: association with changes in mitochondrial membrane potential. Circ Res 85:940–949PubMedGoogle Scholar
  26. 26.
    Chinnaiyan AM, Orth K, Orourke K, Duan HJ, Poirier GG, Dixit VM Molecular ordering of the cell death pathway-Bcl-2 and Bcl-xL function upstream of the Ced-3-like apoptotic proteases. J Biol Chem 271:4573–4576Google Scholar
  27. 27.
    Cao J, Zhang CD, Zhang GX, Zhang YJ, Min S (2005) Protective effect of Shenfu injection on myocardial mitochondria injured by ischemia-reperfusion in rabbits. Chin Med J 118:505–507PubMedGoogle Scholar
  28. 28.
    Xia ZY, Meng QT, Zhang F, Chen XD (2004) Effect of Shenfu injection (ginesenoside and aconite alkaloid) on the apoptosis of intestinal mucosal epithelial cells and its mechanism during ischemia reperfusion in rats. Chin J Traumatol 7:363–367PubMedGoogle Scholar
  29. 29.
    Kim E-H, Jang M-H, Shin M-C, Shin M-S, Kim C-J (2003) Protective effect of aqueous extract of ginseng radix against 1-methyl-4-phenylpyridinium-induced apoptosis in PC12 Cells. Biol Pharm Bull 26:1668–1673PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • Yan-lin Wang
    • 1
  • Cheng-yao Wang
    • 1
  • Ben-jing Zhang
    • 1
  • Zong-ze Zhang
    • 1
  1. 1.Department of AnesthesiologyZhongnan Hospital, Wuhan UniversityWuhanChina

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