Differential effects of a green tea-derived polyphenol (-)-epigallocatechin-3-gallate on the acidosis-induced decrease in the Ca(2+) sensitivity of cardiac and skeletal muscle.
(-)-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 Ca(2+) 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 Ca(2+) 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 approximately 3-4 muM, but did not bind to sTnC. By presumably binding to the cTnC C-lobe, EGCg decreased Ca(2+) binding to cTnC and overcame the depressant effect of protons on the Ca(2+) sensitivity of the cardiac contractile response. To demonstrate isoform-specific effects of the action of EGCg, the pH sensitivity of the Ca(2+) 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 Ca(2+) sensitivity in striated muscle.
Liou
Ying-Ming
YM
Department of Life Sciences, National Chung-Hsing University, 250 Kuokang Road, Taichung, 402, Taiwan. ymlion@dragon.nchu.edu.tw
Kuo
Shih-Chang
SC
Hsieh
Shih-Rong
SR
D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D013662:Tea / Q000737:chemistry; D019209:Troponin C / Q000378:metabolism
D000975:Antioxidants; D020033:Protein Isoforms; D013662:Tea; D019209:Troponin C; D002392:Catechin; C045651:epigallocatechin gallate; D002118:Calcium