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

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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.

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Reference

  1. Kang PM, Izumo S (2000) Apoptosis and heart failure: a critical review of the literature. Circ Res 86:1107–1113

    PubMed  CAS  Google Scholar 

  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 226:316–327

    Article  PubMed  CAS  Google Scholar 

  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 96:8144–8149

    Article  PubMed  CAS  Google Scholar 

  4. Gottlieb RA, Burleson KO, Kloner RA et al (1994) Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J Clin Invest 94:1621–1628

    Article  PubMed  CAS  Google Scholar 

  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 4:608–616

    Article  PubMed  CAS  Google Scholar 

  6. Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281:1312–1316

    Article  PubMed  CAS  Google Scholar 

  7. Cohen GM (1997) Caspases: the executioners of apoptosis. Biochem J 326:1–16

    PubMed  CAS  Google Scholar 

  8. Desagher S, Martinou JC (2000) Mitochondria as the central control point of apoptosis. Trends Cell Biol 10:369–377

    Article  PubMed  CAS  Google Scholar 

  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 406:99–112

    PubMed  CAS  Google Scholar 

  10. Kirshenbaum LA, de Moissac D (1997) The bcl-2 gene product prevents programmed cell death of ventricular myocytes. Circulation 96:1580–1585

    PubMed  CAS  Google Scholar 

  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 32:280–286

    PubMed  Google Scholar 

  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–H1200

    PubMed  CAS  Google Scholar 

  13. Postma G., Nemec W, Kleinspehn KL (1999) Large floating clasts in turbidites—a mechanism for their emplacement. Sediment Geol 58(1):47

    Article  Google Scholar 

  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 20:664–668

    Google Scholar 

  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 6:245–248

    PubMed  Google Scholar 

  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 17:430–432

    Google Scholar 

  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 8:200–204

    PubMed  Google Scholar 

  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 53:397–412

    Google Scholar 

  19. Bo HS, Seung HC, Eun YC et al (2004) Thiamine attenuates hypoxia-induced cell death in cultured neonatal rat cardiomyocytes. Mol Cells 18:133–140

    Google Scholar 

  20. Carden DL, Granger DN (2000) Pathophysiology of ischemia-reperfusion injury. J Pathol 190:255–266

    Article  PubMed  CAS  Google Scholar 

  21. Anderson HV, Willerson JT (1993) Current concepts: thrombolysis in acute myocardial infarction. N Engl J Med 329:703–709

    Article  PubMed  CAS  Google Scholar 

  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 45:35–61

    Article  PubMed  CAS  Google Scholar 

  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 99:2635–2643

    Article  PubMed  CAS  Google Scholar 

  24. Wang G-W, Zhanxiang Z, Klein JB, Kang YJ (2001) Inhibition of hypoxia/reoxygenation-induced apoptosis in metallothionein-overexpressing cardiomyocytes. AJP—Heart 280:2292–2299

    Google Scholar 

  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 85:940–949

    PubMed  CAS  Google Scholar 

  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 271:4573–4576

  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 118:505–507

    PubMed  CAS  Google Scholar 

  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 7:363–367

    PubMed  CAS  Google Scholar 

  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 26:1668–1673

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

This project was supported by the Science Foundation of Hubei Provincial Health Department (JXB090). We thank Jian-ye Zhou and Chuan-jue Cui for technical assistance with the cell culture and molecular biology in Research Center for Cardiovascular Regenerative Medicine, Cardiovascular Institute and FuWai Hospital in Beijing.

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Correspondence to Yan-lin Wang.

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Wang, Yl., Wang, Cy., Zhang, Bj. et al. Shenfu injection suppresses apoptosis by regulation of Bcl-2 and caspase-3 during hypoxia/reoxygenation in neonatal rat cardiomyocytes in vitro. Mol Biol Rep 36, 365–370 (2009). https://doi.org/10.1007/s11033-007-9188-x

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  • DOI: https://doi.org/10.1007/s11033-007-9188-x

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