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Berberine inhibits norepinephrine-induced apoptosis in neonatal rat cardiomyocytes via inhibiting ROS-TNF-α-caspase signaling pathway

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Abstract

Objective

To determine the effect of berberine (Ber) on norepinephrine (NE)-induced apoptosis in neonatal rat cardiomyocytes.

Methods

The cultured neonatal rat cardiomyocytes were treated with NE in the presence or absence of Ber. The activity of lactate dehydrogenase (LDH) in the culture medium was examined, and apoptosis of cardiomyocytes was assessed by Hoechst 33258, isothiocyanate (FITC)-conjugated annexin-V, and propidine iodide (PI) staining. In addition, the activities of caspases-2 and-3 were measured by a fluorescent assay kit. The level of secreted tumor necrosis factor α (TNF-α) and production of intracellular reactive oxygen species (ROS) were also determined.

Results

NE at a concentration of 50 μ mol/L induced an obvious increase in the activity of LDH in the culture medium (P<0.05), which was inhibited by coincubation with 0.5, 1.0, or 2.0 μ mol/L Ber (P<0.05). Ber also significantly attenuated NE-induced apoptosis in a dose-dependent manner (P<0.01). Moreover, Ber at a dose of 2 μ mol/L markedly decreased the ROS and TNF-α productions (P <0.05) and inhibited the activation of caspases-2 and -3 in cardiomyocytes exposed to NE (P<0.05)h.

Conclusion

The present study suggested that Ber could reduce NE-induced apoptosis in neonatal rat cardiomyocytes through inhibiting the ROS-TNF-α-caspase signaling pathway.

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References

  1. Haskings GJ, Esler MD, Jennings GL, Burton D, Korner PI. Norepinephrine spillover to plasma in patients with chronic congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity. Circulation 1986;73:615–621.

    Article  Google Scholar 

  2. Pepper GS, Lee RW. Sympathetic activation in heart failure and its treatment with beta-blockade. Arch Intern Med 1999;159:225–234.

    Article  PubMed  CAS  Google Scholar 

  3. Communal C, Singh K, Pimentel DR, Colucci WS. Norepinephrine stimulates apoptosis in adult rat ventricular myocytes by activation of the beta-adrenergic pathway. Circulation 1998;98:1329–1334.

    Article  PubMed  CAS  Google Scholar 

  4. Fu YC, Chi CS, Yin SC, Hwang B, Chiu YT, Hsu SL. Norepinephrine induces apoptosis in neonatal rat cardiomyocytes through a reactive oxygen species—TNFα-caspase signaling pathway. Cardiovasc Res 2004;62:558–567.

    Article  PubMed  CAS  Google Scholar 

  5. Narula J, Haider N, Virmani R, Disalvo TG, Kolodgie FD, Hajjar RJ, et al. Apoptosis in myocytes in end-stage heart failure. N Engl J Med 1996;335:1182–1189.

    Article  PubMed  CAS  Google Scholar 

  6. Li Z, Bing OHL, Long X, Robinson KG, Lakatta E. Increased cardiomyocyte apoptosis during transition to heart failure in the spontaneously hypertensive rats. Am J Physiol 1997;272:H2313–H2319.

    PubMed  CAS  Google Scholar 

  7. Sharov VG, Sabbah HN, Shimoyama H, Goussev AV, Lesch M, Goldstein S. Evidence of cardiocyte apoptosis in myocardium of dogs with chronic heart failure. Am J Pathol 1996;148:141–149.

    PubMed  CAS  Google Scholar 

  8. Moorjani N, Ahmad M, Catarino P, Brittin R, Trabzuni D, Al-Mohanna F, et al. Activation of apoptotic caspase cascade during the transition to pressure overload-induced heart failure. J Am Coll Cardiol 2006;48:1451–1458.

    Article  PubMed  CAS  Google Scholar 

  9. Lee Y, Gustafsson AB. Role of apoptosis in cardiovascular disease. Apoptosis 2009;14:536–548.

    Article  PubMed  Google Scholar 

  10. Lau CW, Yao XQ, Chen ZY, Ko WH, Huang Y. Cardiovascular actions of berberine. Cardiovasc Drug Rev 2001;19:234–244.

    Article  PubMed  CAS  Google Scholar 

  11. Hong Y, Hui SC, Chan TY, Hou JY. Effect of berberine on regression of pressure -overload induced cardiac hypertrophy in rats. Am J Chin Med 2002;30:589–599.

    Article  PubMed  CAS  Google Scholar 

  12. Zeng XH, Zeng XJ, Li YY. Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 2003;92:173–176.

    Article  PubMed  CAS  Google Scholar 

  13. Wang Y, Huang Y, Lam KS, Li Y, Wong WT, Ye H, et al. Berberine prevents hyperglycemia-induced endothelial injury and enhances vasodilatation via adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase. Cardiovasc Res 2009;82:484–492.

    Article  PubMed  CAS  Google Scholar 

  14. Zheng L, Zhou Z, Tao D, Lan T. Protective effect of berberine on cardiac myocyte injured by ischemia-reperfusion. J Sichuan Univ (Med Sci Edi) (Chin) 2003;34:452–454.

    CAS  Google Scholar 

  15. Chen HW, Chien CT, Yu SL, Lee YT, Chen WJ. Cyclosporine A regulate oxidative stress-induced apoptosis in cardiomyocytes: mechanisms via ROS generation, iNOS and Hsp70. Br J Pharmacol 2002;37:771–781.

    Article  Google Scholar 

  16. Krown KA, Page MT, Nguyen C, Zechner D, Gutierrez V, Comstock KL, et al. Tumor necrosis factor alphainduced apoptosis in cardiac myocytes: involvement of the sphingolipid signaling cascade in cardiac cell death. J Clin Invest 1996;98:2854–2865.

    Article  PubMed  CAS  Google Scholar 

  17. Remondino A, Kwon SH, Communal C, Pimentel DR, Sawyer DB, Singh K, et al. Beta-Adrenergic receptor stimulated apoptosis in cardiac myocytes is mediated by reactive oxygen species-jun NH2-terminal kinasedependent activation of the mitochondrial pathway. Circ Res 2003;92:136–138.

    Article  PubMed  CAS  Google Scholar 

  18. Mantena SK, Sharma SD, Katiyar SK. Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells. Mol Cancer Ther 2006;5:296–308.

    Article  PubMed  CAS  Google Scholar 

  19. Jantova S, Cipak L, Letasiova S. Berberine induces apoptosis through a mitochondrial/caspase pathway in human promonocytic U937 cells. Toxicol In Vitro 2007;21:25–31.

    Article  PubMed  CAS  Google Scholar 

  20. Meeran SM, Katiyar S, Katiyar SK. Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation. Toxicol Appl Pharmacol 2008;229:33–43.

    Article  PubMed  CAS  Google Scholar 

  21. Ho YT, Lu CC, Yang JS, Chiang JH, Li TC, Lp SW, et al. Berberine induced apoptosis via promoting the expression of caspase-8, -9 and -3, apoptosis-inducing factor and endonuclease G in SCC-4 human tongue squamous carcinoma cancer cells. Anticancer Res 2009;29:4063–4070.

    PubMed  CAS  Google Scholar 

  22. Zhou XQ, Zeng XN, Kong H, Sun XL. Neuroprotective effects of berberine on stroke models in vitro and in vivo. Neurosci Lett 2008;447:31–36.

    Article  PubMed  CAS  Google Scholar 

  23. Robertson JD, Enoksson M, Suomela M, Zhivotovsky B, Orrenius S. Caspase-2 acts upstream of mitochondria to promote cytochrome c release during toposide-induced apoptosis. J Biol Chem 2002;277:29803–29809.

    Article  PubMed  CAS  Google Scholar 

  24. Hong Y, Hui SS, Chan BT, Hou J. Effect of berberine on catecholamine levels in rats with experimental cardiac hypertrophy. Life Sci 2003;72:2499–2507.

    Article  PubMed  CAS  Google Scholar 

  25. Lu DY, Tang CH, Chen YH, Wei IH. Berberine suppresses neuroinflammatory responses through AMP-activated protein kinase activation in BV-2 microglia. J Cell Biochem 2010;110:697–705.

    Article  PubMed  CAS  Google Scholar 

  26. Kewalramani G, Puthanveetil P, Wang F, Kim MS, Deppe S, Abrahani A, et al. AMP-activated protein kinase confers protection against TNF-α-induced cardiac cell death. Cardiovasc Res 2009;84:42–53.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Hua-dong Wang  (王华东).

Additional information

Supported by the National Natural Science Foundation of China (No. 30670826, 30971191), the Science and Technology Foundation from Ministry of Education of the People’s Republic of China (No. 207140), the Guangdong Science and Technology Projects (No. 2008B030301352), the Fundamental Research Funds for the Central Universities (No.21609405), and the Leading Academic Discipline Program, 211 Project for Jinan University (the 3rd phase)

The first two authors contributed equally to this work

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Lv, Xx., Yu, Xh., Wang, Hd. et al. Berberine inhibits norepinephrine-induced apoptosis in neonatal rat cardiomyocytes via inhibiting ROS-TNF-α-caspase signaling pathway. Chin. J. Integr. Med. 19, 424–431 (2013). https://doi.org/10.1007/s11655-011-0856-2

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  • DOI: https://doi.org/10.1007/s11655-011-0856-2

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