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Nardosinone protects H9c2 cardiac cells from angiotensin II-induced hypertrophy

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Summary

Pathological cardiac hypertrophy induced by angiotensin II (AngII) can subsequently give rise to heart failure, a leading cause of mortality. Nardosinone is a pharmacologically active compound extracted from the roots of Nardostachys chinensis, a well-known traditional Chinese medicine. In order to investigate the effects of nardosinone on AngII-induced cardiac cell hypertrophy and the related mechanisms, the myoblast cell line H9c2, derived from embryonic rat heart, was treated with nardosinone (25, 50, 100, and 200 μmol/L) or AngII (1 μmol/L). Then cell surface area and mRNA expression of classical markers of hypertrophy were detected. The related protein levels in PI3K/Akt/mTOR and MEK/ERK signaling pathways were examined by Western blotting. It was found that pretreatment with nardosinone could significantly inhibit the enlargement of cell surface area induced by AngII. The mRNA expression of ANP, BNP and β-MHC was obviously elevated in AngII-treated H9c2 cells, which could be effectively blocked by nardosinone at the concentration of 100 μmol/L. Further study revealed that the protective effects of nardosinone might be mediated by repressing the phosphorylation of related proteins in PI3K/Akt and MEK/ERK signaling pathways. It was suggested that the inhibitory effect of nardosinone on Ang II-induced hypertrophy in H9c2 cells might be mediated by targeting PI3K/Akt and MEK/ERK signaling pathways.

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References

  1. Heineke J, Molkentin Jd. Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat Rev Mol Cell Biol, 2006,7(8):589–600

    Article  CAS  PubMed  Google Scholar 

  2. Finckenberg P, Mervaala E. Novel regulators and drug targets of cardiac hypertrophy. J Hypertens, 2010,28(Suppl 1):S33–S38

    Article  CAS  PubMed  Google Scholar 

  3. Aoyagi T, Matsui T. Phosphoinositide-3 kinase signaling in cardiac hypertrophy and heart failure. Curr Pharm Des, 2011,17(18):1818–1824

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Hunyady L, Turu G. The role of the AT 1 angiotensin receptor in cardiac hypertrophy: angiotensin II receptor or stretch sensor? Trends Endocrinol Metab, 2004,15(9): 405–408

    Article  CAS  PubMed  Google Scholar 

  5. Liu X, Xie R, Liu S, et al. Rat parathyroid hormone 1-34 signals through the MEK/ERK pathway to induce cardiac hypertrophy. J Int Med Res, 2008,36(5):942–950

    Article  PubMed  Google Scholar 

  6. Li P, Matsunaga K, Yamamoto K, et al. Nardosinone, a novel enhancer of nerve growth factor in neurite outgrowth from PC12D cells. Neurosci Lett, 1999,273(1): 53–56

    Article  CAS  PubMed  Google Scholar 

  7. Hwang JS, Lee SA, Hong SS, et al. Inhibitory constituents of nardostachys chinensis on nitric oxide production in raw 264.7 macrophages. Bioorg Med Chem Lett, 2012,22(1):706–708

    Article  CAS  PubMed  Google Scholar 

  8. Schulte, KE, Glauch G, Rucker G. Nardosinone, a new constituent of Nardostachys chinensis Batalin. Tetrahedron Lett (German), 1965 (35):3083–3084

    Google Scholar 

  9. Maulik SK, Kumar S. Oxidative stress and cardiac hypertrophy: a review. Toxicol Mech Methods, 2012,22(5): 359–366

    Article  CAS  PubMed  Google Scholar 

  10. Obayashi M, Yano M, Kohno M, et al. Dose-dependent effect of ANG II-receptor antagonist on myocyte remodeling in rat cardiac hypertrophy. Am J Physiol, 1997,273(4 Pt 2):H1824–H1831

    CAS  PubMed  Google Scholar 

  11. Carneiro-Ramos MS, Diniz GP, Nadu AP, et al. Blockage of angiotensin II type 2 receptor prevents thyroxine-mediated cardiac hypertrophy by blocking Akt activation. Basic Res Cardiol, 2010,105(3):325–335

    Article  CAS  PubMed  Google Scholar 

  12. He KL, Zheng QF, Mu SC, et al. Changes of mitogen-activated protein kinase activity in cardiac tissues, Ang II and cardiac hypertrophy in spontaneously hypertensive rats. Sheng Li Xue Bao (Chinese), 1998,50(5): 539–542

    CAS  Google Scholar 

  13. Liu L, Zhao X, Pierre SV, et al. Association of PI3K-Akt signaling pathway with digitalis-induced hypertrophy of cardiac myocytes. Am J Physiol Cell Physiol, 2007, 293(5):C1489–C1497

    Article  CAS  PubMed  Google Scholar 

  14. Braz JC, Gill RM, Corbly AK, et al. Selective activation of PI3Kalpha/Akt/GSK-3beta signalling and cardiac compensatory hypertrophy during recovery from heart failure. Eur J Heart Fail, 2009,11(8):739–748

    Article  CAS  PubMed  Google Scholar 

  15. Kim YK, Kim SJ, Yatani A, et al. Mechanism of enhanced cardiac function in mice with hypertrophy induced by overexpressed Akt. J Biol Chem, 2003,278(48): 47622–47628

    Article  CAS  PubMed  Google Scholar 

  16. Kemi OJ, Ceci M, Wisloff U, et al. Activation or inactivation of cardiac AKT/MTOR signaling diverges physiological from pathological hypertrophy. J Cell Physiol, 2008,214(2):316–21.

    Article  CAS  PubMed  Google Scholar 

  17. Medeiros C, Frederico MJ, da Luz G, et al. Exercise training reduces insulin resistance and upregulates the mTOR/p70S6k pathway in cardiac muscle of diet-induced obesity rats. J Cell Physiol, 2011,226(3): 666–674

    Article  CAS  PubMed  Google Scholar 

  18. Bueno OF, De Windt LJ, Tymitz KM, et al. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice. Embo J, 2000,19(23):6341–6350

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Sanna B, Bueno OF, Dai YS, et al. Direct and indirect interactions between calcineurin-NFAT and MEK1-extracellular signal-regulated kinase 1/2 signaling pathways regulate cardiac gene expression and cellular growth. Mol Cell Biol, 2005,25(3):865–878

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Song MY, Bae UJ, Lee BH, et al. Nardostachys jatamansi extract protects against cytokine-induced beta-cell damage and streptozotocin-induced diabetes. World J Gastroenterol, 2010,16(26):3249–3257

    Article  PubMed Central  PubMed  Google Scholar 

  21. Rucker G, Kahrs KH, Hembeck HW, et al. The conformation of nardosinone. Arch Pharm (Weinheim) (German), 1975,308(11):858–862

    Article  CAS  Google Scholar 

  22. Rucker G, Dyck E. Photochemical reactions of nardosinone (author’s transl). Arch Pharm (Weinheim) (German), 1977,310(10):835–840

    Article  CAS  Google Scholar 

  23. Li P, Matsunaga K, Yamakuni T, Ohizumi Y. Nardosinone, the first enhancer of neurite outgrowth-promoting activity of staurosporine and dibutyryl cyclic AMP in PC12D cells. Brain Res Dev Brain Res, 2003,145(2):177–183

    Article  CAS  PubMed  Google Scholar 

  24. Li P, Yamakuni T, Matsunaga K, et al. Nardosinone enhances nerve growth factor-induced neurite outgrowth in a mitogen-activated protein kinase- and protein kinase C-dependent manner in PC12D cells. J Pharmacol Sci, 2003,93(1):122–125

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Kai Huang  (黄 恺) or Dan Huang  (黄 丹).

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The authors contributed equally to this work.

This project was supported by the grants from the National Natural Science Foundation of China (No. 30971245 and No. 81000112).

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Du, M., Huang, K., Gao, L. et al. Nardosinone protects H9c2 cardiac cells from angiotensin II-induced hypertrophy. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 33, 822–826 (2013). https://doi.org/10.1007/s11596-013-1205-9

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  • DOI: https://doi.org/10.1007/s11596-013-1205-9

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