Tetrandrine blocks cardiac hypertrophy by disrupting reactive oxygen species-dependent ERK1/2 signalling.

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  • Author(s): Shen DF;Shen DF; Tang QZ; Yan L; Zhang Y; Zhu LH; Wang L; Liu C; Bian ZY; Li H
  • Source:
    British journal of pharmacology [Br J Pharmacol] 2010 Feb; Vol. 159 (4), pp. 970-81. Date of Electronic Publication: 2010 Jan 25.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Wiley Country of Publication: England NLM ID: 7502536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5381 (Electronic) Linking ISSN: 00071188 NLM ISO Abbreviation: Br J Pharmacol Subsets: MEDLINE
    • Publication Information:
      Publication: London : Wiley
      Original Publication: London, Macmillian Journals Ltd.
    • Subject Terms:
      Benzylisoquinolines/*pharmacology ; Cardiomegaly/*prevention & control ; Cardiotonic Agents/*pharmacology ; Heart Failure/*drug therapy ; Mitogen-Activated Protein Kinase 1/*metabolism ; Mitogen-Activated Protein Kinase 3/*metabolism ; Myocytes, Cardiac/*drug effects ; Reactive Oxygen Species/*metabolism ; Signal Transduction/*drug effects; Administration, Oral ; Animals ; Animals, Newborn ; Anti-Inflammatory Agents/pharmacology ; Antioxidants/pharmacology ; Apoptosis ; Benzylisoquinolines/administration & dosage ; Cardiomegaly/diagnostic imaging ; Cardiomegaly/enzymology ; Cardiomegaly/etiology ; Cardiomegaly/physiopathology ; Cardiotonic Agents/administration & dosage ; Cells, Cultured ; Disease Models, Animal ; Enzyme Activation ; Fibrosis ; Heart Failure/complications ; Heart Failure/diagnostic imaging ; Heart Failure/enzymology ; Heart Failure/physiopathology ; Mice ; Myocytes, Cardiac/enzymology ; Myocytes, Cardiac/pathology ; NF-kappa B/genetics ; NF-kappa B/metabolism ; NFATC Transcription Factors/genetics ; NFATC Transcription Factors/metabolism ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Recovery of Function ; Time Factors ; Transfection ; Ultrasonography ; Ventricular Function, Left/drug effects
    • Abstract:
      Background and Purpose: Tetrandrine, a well-known naturally occurring calcium antagonist with anti-inflammatory, antioxidant and anti-fibrogenetic activities, has long been used clinically for treatment of cardiovascular diseases such as hypertension and arrhythmia. However, little is known about the effect of tetrandrine on cardiac hypertrophy. The aims of the present study were to determine whether tetrandrine could attenuate cardiac hypertrophy and to clarify the underlying molecular mechanisms.
      Experimental Approach: Tetrandrine (50 mg x kg(-1) x day(-1)) was administered by oral gavage three times a day for one week and then the mice were subjected to either chronic pressure overload generated by aortic banding (AB) or sham surgery (control group). Cardiac function was determined by echocardiography.
      Key Results: Tetrandrine attenuated the cardiac hypertrophy induced by AB, as assessed by heart weight/body weight and lung weight/body weight ratios, cardiac dilatation and the expression of genes of hypertrophic markers. Tetrandrine also inhibited fibrosis and attenuated the inflammatory response. The cardioprotective effects of tetrandrine were mediated by blocking the increased production of reactive oxygen species and the activation of ERK1/2-dependent nuclear factor-kappaB and nuclear factor of activated T cells that occur in response to hypertrophic stimuli.
      Conclusions and Implications: Taken together, our results suggest that tetrandrine can improve cardiac function and prevent the development of cardiac hypertrophy by suppressing the reactive oxygen species-dependent ERK1/2 signalling pathway.
    • References:
      Free Radic Biol Med. 2006 May 15;40(10):1756-75. (PMID: 16767845)
      Br J Pharmacol. 2000 Oct;131(3):530-6. (PMID: 11015304)
      J Mol Med (Berl). 2009 Mar;87(3):249-60. (PMID: 19096818)
      Int J Cancer. 2009 May 15;124(10):2260-9. (PMID: 19165864)
      Dev Biol. 2004 Feb 1;266(1):1-16. (PMID: 14729474)
      Hypertension. 2007 Jun;49(6):1399-408. (PMID: 17420335)
      Eur J Pharmacol. 2008 Jul 28;589(1-3):288-98. (PMID: 18565510)
      Eur J Pharmacol. 1995 May 4;278(1):1-7. (PMID: 7664810)
      J Cell Mol Med. 2009 May;13(5):909-25. (PMID: 19413885)
      Circ Res. 2007 Dec 7;101(12):1328-38. (PMID: 17916779)
      Int J Biochem Cell Biol. 2008;40(10):2023-39. (PMID: 18407781)
      Eur Heart J. 2006 Apr;27(7):875-81. (PMID: 16434410)
      Am J Physiol Heart Circ Physiol. 2005 Oct;289(4):H1512-8. (PMID: 15863459)
      Cancer Biol Ther. 2008 Jul;7(7):1079. (PMID: 18698164)
      Free Radic Biol Med. 2005 Jan 15;38(2):243-57. (PMID: 15607907)
      Can J Cardiol. 2006 Sep;22(11):953-68. (PMID: 16971981)
      Cardiovasc Res. 2009 Feb 15;81(3):429-38. (PMID: 18852252)
      Acta Pharmacol Sin. 2002 Dec;23(12):1075-85. (PMID: 12466044)
      Br J Pharmacol. 2001 Jan;132(1):159-64. (PMID: 11156573)
      J Cell Physiol. 2007 Aug;212(2):311-22. (PMID: 17450511)
      Acta Pharmacol Sin. 2002 Dec;23(12):1069-74. (PMID: 12466043)
      Cardiovasc Res. 2009 May 1;82(2):240-9. (PMID: 19074824)
      J Mol Cell Cardiol. 2005 May;38(5):803-7. (PMID: 15850574)
      World J Gastroenterol. 2007 Feb 28;13(8):1214-20. (PMID: 17451202)
      Can J Physiol Pharmacol. 2006 Oct;84(10):967-76. (PMID: 17218962)
      J Biol Chem. 2003 Sep 26;278(39):36981-4. (PMID: 12881512)
      Am J Physiol Heart Circ Physiol. 2004 Mar;286(3):H870-7. (PMID: 14766672)
      J Cell Mol Med. 2009 Jul;13(7):1302-13. (PMID: 19413895)
      J Mol Cell Cardiol. 2006 Oct;41(4):580-91. (PMID: 16949095)
      Circulation. 2007 Apr 10;115(14):1885-94. (PMID: 17389268)
      Circ Res. 1996 May;78(5):821-8. (PMID: 8620602)
      Cardiovasc Res. 2004 Aug 15;63(3):467-75. (PMID: 15276472)
      Hypertension. 2009 Mar;53(3):539-48. (PMID: 19204184)
      Int J Cardiol. 1993 Sep;41(2):103-8. (PMID: 8282432)
      Cell. 2008 Jun 13;133(6):978-93. (PMID: 18555775)
      Atherosclerosis. 2004 Jun;174(2):215-23. (PMID: 15136051)
      Trends Pharmacol Sci. 2004 Mar;25(3):120-3. (PMID: 15058281)
      Nat Med. 2004 May;10(5):467-74. (PMID: 15122248)
      Acta Pharmacol Sin. 2002 Dec;23(12):1057-68. (PMID: 12466042)
      Nat Rev Cardiol. 2009 Apr;6(4):283-91. (PMID: 19352332)
      Immunol Lett. 2008 Dec 22;121(2):127-33. (PMID: 18992279)
      J Mol Cell Cardiol. 2009 Jul;47(1):15-22. (PMID: 19374908)
      Br J Pharmacol. 2004 Dec;143(7):919-27. (PMID: 15504755)
    • Accession Number:
      0 (Anti-Inflammatory Agents)
      0 (Antioxidants)
      0 (Benzylisoquinolines)
      0 (Cardiotonic Agents)
      0 (NF-kappa B)
      0 (NFATC Transcription Factors)
      0 (Reactive Oxygen Species)
      29EX23D5AJ (tetrandrine)
      EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
      EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
    • Publication Date:
      Date Created: 20100129 Date Completed: 20100709 Latest Revision: 20211020
    • Publication Date:
      20240829
    • Accession Number:
      PMC2829222
    • Accession Number:
      10.1111/j.1476-5381.2009.00605.x
    • Accession Number:
      20105174