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Differential effects of a green tea derived polyphenol (−)‐epigallocatechin‐3‐gallate on the muscle‐specific decrease in calcium response to acidosis
Author(s) -
Liou YingMing,
Kuo ShihChang
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.751.13
Subject(s) - myofibril , chemistry , myofilament , biophysics , skeletal muscle , myosin , actin , cardiac muscle , calcium , troponin c , biochemistry , medicine , troponin i , biology , organic chemistry , myocardial infarction
(−)‐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 the effects of EGCg on changes in pH sensitivity of myofilament response to Ca 2+ in myofibrils prepared from porcine ventricular myocardium and chicken pectoral muscle. In comparison with skeletal muscle, lowering pH from 7.0 to 6.5 and/or 6.0 EGCg has significantly blunted the acidic effect on the reduction of Ca 2+ sensitivity for myofibrillar ATPase activity in cardiac muscle. Studies with recombinant mouse cardiac (cTnC) and chicken fast skeletal troponin C (sTnC) by circular dichroism (CD), intrinsic and extrinsic fluorescence spectroscopy showed that EGCg specifically binds to cTnC with a dissociation constant ~ 3–4 μM, but no effect on sTnC. Presumably binding to the cTnC C‐lobe, EGCg acted to alter the Ca 2+ ‐binding to cTnC and compromised the interference of proton effect on the Ca 2+ binding at acidic pH. To demonstrate the isoform‐specific effects on the action of EGCg, the pH‐sensitivity of Ca 2+ response was examined in cardiac myofibrils replaced with either sTnC or cTnC and skeletal myofibrils exchanged with whole cardiac Tn complex (cTn). The data obtained suggested that EGCg interactions with the cardiac isoform specific TnC or Tn complex could alter the pH effect on myofilament Ca 2+ sensitivity in striated muscle.