Skip to main content

Advertisement

Log in

Differential effects of a green tea-derived polyphenol (−)-epigallocatechin-3-gallate on the acidosis-induced decrease in the Ca2+ sensitivity of cardiac and skeletal muscle

  • Cardiovascular Physiology
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

(−)-Epigallocatechin-3-gallate (EGCg), a green tea-derived polyphenol, has received much attention as a protective agent against cardiovascular diseases. In this study, we determined its effects on the acidosis-induced change in the Ca2+ sensitivity of myofilaments in myofibrils prepared from porcine ventricular myocardium and chicken pectoral muscle. EGCg (0.1 mM) significantly inhibited the decrease caused by lowering the pH from 7.0 to 6.0 in the Ca2+ sensitivity of myofibrillar ATPase activity in cardiac muscle, but not in skeletal muscle. Studies on recombinant mouse cardiac troponin C (cTnC) and chicken fast skeletal troponin C (sTnC) using circular dichroism and intrinsic and extrinsic fluorescence spectroscopy showed that EGCg bound to cTnC with a dissociation constant of ∼3–4 μM, but did not bind to sTnC. By presumably binding to the cTnC C-lobe, EGCg decreased Ca2+ binding to cTnC and overcame the depressant effect of protons on the Ca2+ sensitivity of the cardiac contractile response. To demonstrate isoform-specific effects of the action of EGCg, the pH sensitivity of the Ca2+ response was examined in cardiac myofibrils in which endogenous cTnC was replaced with exogenous sTnC or cTnC and in skeletal myofibrils in which the endogenous sTn complex was replaced with whole cardiac Tn complex (cTn). The results suggest that the binding of EGCg to the cardiac isoform-specific TnC or Tn complex alters the effect of pH on myofilament Ca2+ sensitivity in striated muscle.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Khan N, Mukhtar H (2007) Tea polyphenols for health promotion. Life Sci 81:519–533

    Article  PubMed  CAS  Google Scholar 

  2. Stangl V, Dreger H, Stangl K, Lorenz M (2007) Molecular targets of tea polyphenols in the cardiovascular system. Cardiovasc Res 73:348–358

    Article  PubMed  CAS  Google Scholar 

  3. Kuriyama S, Shimazu T, Ohmori K, Kikuchi N, Nakaya N, Nishino Y, Tsubono Y, Tsuji I (2006) Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study. JAMA 296:1255–1265

    Article  PubMed  CAS  Google Scholar 

  4. Hirai M, Hotta Y, Ishikawa N, Wakida Y, Fukuzawa Y, Isobe F, Nakano A, Chiba T, Kawamura N (2007) Protective effects of EGCg or GCg, a green tea catechin epimer, against postischemic myocardial dysfunction in guinea-pig hearts. Life Sci 80:1020–1032

    Article  PubMed  CAS  Google Scholar 

  5. Hotta Y, Huang L, Muto T, Yajima M, Miyazeki K, Ishikawa N, Fukuzawa Y, Wakida Y, Tushima H, Ando H, Nonogaki T (2006) Positive inotropic effect of purified green tea catechin derivative in guinea pig hearts: the measurements of cellular Ca2+ and nitric oxide release. Eur J Pharmacol 552:123–130

    Article  PubMed  CAS  Google Scholar 

  6. Aneja R, Hake PW, Burroughs TJ, Denenberg AG, Wong HR, Zingarelli B (2004) Epigallocatechin, a green tea polyphenol, attenuates myocardial ischemia reperfusion injury in rats. Mol Med 10:55–62

    Article  PubMed  CAS  Google Scholar 

  7. Stephanou A (2004) Role of STAT-1 and STAT-3 in ischaemia/reperfusion injury. J Cell Mol Med 8:519–525

    Article  PubMed  CAS  Google Scholar 

  8. Townsend PA, Scarabelli TM, Pasini E, Gitti G, Menegazzi M, Suzuki H, Knight RA, Latchman DS, Stephanou A (2004) Epigallocatechin-3-gallate inhibits STAT-1 activation and protects cardiac myocytes from ischemia/reperfusion-induced apoptosis. FASEB J 18:1621–1623

    PubMed  CAS  Google Scholar 

  9. Kobayashi T, Solaro RJ (2005) Calcium, thin filaments, and the integrative biology of cardiac contractility. Annu Rev Physiol 67:39–67

    Article  PubMed  CAS  Google Scholar 

  10. Gordon AM, Homsher E, Regnier M (2000) Regulation of contraction in striated muscle. Physiol Rev 80:853–924

    PubMed  CAS  Google Scholar 

  11. Li MX, Wang X, Sykes BD (2004) Structural based insights into the role of troponin in cardiac muscle pathophysiology. J Muscle Res Cell Motil 25:559–579

    Article  PubMed  CAS  Google Scholar 

  12. Metzger JM, Westfall MV (2004) Covalent and noncovalent modification of thin filament action: the essential role of troponin in cardiac muscle regulation. Circ Res 94:146–158

    Article  PubMed  CAS  Google Scholar 

  13. Biesiadecki BJ, Kobayashi T, Walker JS, John Solaro R, de Tombe PP (2007) The troponin C G159D mutation blunts myofilament desensitization induced by troponin I Ser23/24 phosphorylation. Circ Res 100:1486–1493

    Article  PubMed  CAS  Google Scholar 

  14. Day SM, Westfall MV, Fomicheva EV, Hoyer K, Yasuda S, La Cross NC, D’Alecy LG, Ingwall JS, Metzger JM (2006) Histidine button engineered into cardiac troponin I protects the ischemic and failing heart. Nat Med 12:181–189

    Article  PubMed  CAS  Google Scholar 

  15. Dargis R, Pearlstone JR, Barrette-Ng I, Edwards H, Smillie LB (2002) Single mutation (A162H) in human cardiac troponin I corrects acid pH sensitivity of Ca2+-regulated actomyosin S1 ATPase. J Biol Chem 277:34662–34665

    Article  PubMed  CAS  Google Scholar 

  16. Li G, Martin AF, Solaro RJ (2001) Localization of regions of troponin I important in deactivation of cardiac myofilaments by acidic pH. J Mol Cell Cardiol 33:1309–1320

    Article  PubMed  CAS  Google Scholar 

  17. Houdusse A, Love ML, Dominguez R, Grabarek Z, Cohen C (1997) Structures of four Ca2+-bound troponin C at 2.0 Å resolution: further insights into the Ca2+-switch in the calmodulin superfamily. Structure 5:1695–1711

    Article  PubMed  CAS  Google Scholar 

  18. Strynadka NCJ, Cherney M, Sielecki AR, Li MX, Smillie LB, James MNG (1997) Structural details of a calcium-induced molecular switch: X-ray crystallographic analysis of the calcium-saturated N-terminal domain of troponin C at 1.75 Å resolution. J Mol Biol 273:238–255

    Article  PubMed  CAS  Google Scholar 

  19. Van Eerd JP, Takahashi K (1975) The amino acid sequence of bovine cardiac troponin-C: comparison with rabbit skeletal troponin-C. Biochem Biophys Res Commun 64:122–127

    Article  PubMed  Google Scholar 

  20. Li Y, Love ML, Putkey JA, Cohen C (2000) Bepridil opens the regulatory N-terminal lobe of cardiac troponin C. Proc Natl Acad Sci USA 97:5140–5145

    Article  PubMed  CAS  Google Scholar 

  21. Pearlstone JR, Sykes BD, Smillie LB (1997) Interactions of structural C and regulatory N domains of troponin C with repeated sequence motifs in troponin I. Biochemistry 36:7601–7606

    Article  PubMed  CAS  Google Scholar 

  22. Liou YM, Chao HL (2007) Fluorescence spectroscopic analysis of the proximity changes between the central helix of troponin C and the C-terminus of troponin T from chicken skeletal muscle. Biochim Biophys Acta 1774:466–473

    PubMed  CAS  Google Scholar 

  23. Potter JD (1982) Preparation of troponin and its subunits. Meth Enzymol 85:241–263

    Article  PubMed  CAS  Google Scholar 

  24. Liou YM, Tseng YC, Cheng JC (2002) Spectrofluorometric analysis of length-dependent conformational changes in cardiac troponin C. J Muscle Res Cell Motil 23:309–315

    Article  PubMed  CAS  Google Scholar 

  25. Gusev NB, Barskaya NV (1984) Investigation of cation-binding properties of cardiac troponin C peptides by circular-dichroism spectroscopy. Biochem J 220:315–320

    PubMed  CAS  Google Scholar 

  26. Van Eyk JE, Kay CM, Hodges RS (1991) A comparative study of the interactions of synthetic peptides of the skeletal and cardiac troponin I inhibitory region with skeletal and cardiac troponin C. Biochemistry 30:9974–9981

    Article  PubMed  Google Scholar 

  27. Fabiato A, Fabiato F (1979) Calculator programs for computing the composition of the multiple metals and ligands used for experiments in skinned muscle cells. J Physiol Paris 75:463–505

    PubMed  CAS  Google Scholar 

  28. Liou YM, Jiang MJ, Wu MC (2002) Changes in thiol reactivity and extractability of myofibril bound cardiac troponin C in porcine malignant hyperthermia. J Biochem 132:317–325

    PubMed  CAS  Google Scholar 

  29. Liou YM, Chen MW (2003) Calcium-dependent protein–protein interactions induce changes in proximity relationships of Cys-48 and Cys-64 in chicken skeletal troponin I. Eur J Biochem 270:3092–3100

    Article  PubMed  CAS  Google Scholar 

  30. Liou YM, Jiang MJ, Wu MC (2000) Altered expression of cardiac myosin isozymes associated with the malignant hyperthermia genotype in swine. Anesthesiology 93:1312–1319

    Article  PubMed  CAS  Google Scholar 

  31. Liou YM, Chang JCH (2004) Differential pH effect on calcium-induced conformational changes of cardiac troponin C complexed with cardiac and fast skeletal isoforms of troponin I and troponin T. J Biochem 136:683–692

    Article  PubMed  CAS  Google Scholar 

  32. She M, Trimble D, Yu LC, Chalovich JM (2000) Factors contributing to troponin exchange in myofibrils and in solution. J Muscle Res Cell Motil 21:737–745

    Article  PubMed  CAS  Google Scholar 

  33. Leavis PC, Kraft EL (1978) Calcium binding to cardiac troponin C. Arch Biochem Biophys 186:411–415

    Article  PubMed  CAS  Google Scholar 

  34. Metzger JM, Parmacek MS, Barr E, Pasyk K, Lin WI, Cochrane KL, Field LJ, Leiden JM (1993) Skeletal troponin C reduces contractile sensitivity to acidosis in cardiac myocytes from transgenic mice. Proc Natl Acad Sci USA 90:9036–9040

    Article  PubMed  CAS  Google Scholar 

  35. Solaro RJ, Kumar P, Blanchard EM, Martin AF (1986) Differential effects of pH on calcium activation of myofilaments of adult and perinatal dog hearts. Evidence for developmental differences in thin filament regulation. Circ Res 58:721–729

    PubMed  CAS  Google Scholar 

  36. Endoh M (2006) Signal transduction and Ca2+ signaling in intact myocardium. J Pharmacol Sci 100:525–537

    Article  PubMed  CAS  Google Scholar 

  37. Tadano N, Yumoto F, Morimoto S, Nagata K, Tanokura M, Ohtsuki I. Epigallocatechin gallate, a major polyphenol in green tea, binds to cardiac troponin C and desensitizes cardiac muscle contraction to Ca2+. “International Symposium Celebrating 40th Anniversary of Troponin Discovery, the 33rd NIPS Conference, Okazaki, JAPAN, October 25–28, 2005 (Abstract)

  38. Lipscomb-Allhouse S, Mulligan IP, Ashley CC (2001) The effects of the inotropic agent EMD 57033 on activation and relaxation kinetics in frog skinned skeletal muscle. Pflugers Arch 442:171–177

    Article  PubMed  CAS  Google Scholar 

  39. Lipscomb S, Preston LC, Robinson P, Redwood CS, Mulligan IP, Ashley CC (2005) Effects of troponin C isoform on the action of the cardiotonic agent EMD 57033. Biochem J 388:905–912

    Article  PubMed  CAS  Google Scholar 

  40. Takeda S, Yamashita A, Maeda K, Maeda Y (2003) Structure of the core domain of human cardiac troponin in the Ca2+-saturated form. Nature 424:35–41

    Article  PubMed  CAS  Google Scholar 

  41. Vinogradova MV, Stone DB, Malanina GG, Karatzaferi C, Cooke R, Mendelson RA, Fletterick RJ (2005) Ca2+-regulated structural changes in troponin. Proc Natl Acad Sci USA 102:5038–5043

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was partly supported by the National Science Council of Taiwan government (NSC 95-2320-B-005-005) and cooperative projects between the Taichung Veterans General Hospital and the NCHU (TCVGH-NCHU 967602).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ying-Ming Liou.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liou, YM., Kuo, SC. & Hsieh, SR. Differential effects of a green tea-derived polyphenol (−)-epigallocatechin-3-gallate on the acidosis-induced decrease in the Ca2+ sensitivity of cardiac and skeletal muscle. Pflugers Arch - Eur J Physiol 456, 787–800 (2008). https://doi.org/10.1007/s00424-008-0456-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-008-0456-y

Keywords

Navigation