Identification of a PKC epsilon-dependent regulation of myocardial contraction by epicatechin-3-gallate

In this study, the effects of tea catechins and tea theaflavins on myocardial contraction were examined in isolated rat hearts using a Langendorff-perfusion system. We found that both tea catechins and theaflavins had positive inotropic effects on the myocardium. Of the tested chemicals, epicatechin-3-gallate ( ECG) and theaflavin-3,3'-digallate (TF4) appear to be the most effective tea catechin and theaflavin, respectively. Further studies of ECG-induced positive inotropy revealed the following insights. First, unlike digitalis drugs, ECG had no effect on intracellular Ca2+ level in cultured adult cardiac myocytes. Second, it activated PKC epsilon, but not PKC alpha, in the isolated hearts as well as in cultured cells. Neither a phospholipase C ( PLC) inhibitor (U73122) nor the antioxidant N-acetyl cysteine (NAC) affected the ECG-induced activation of PKC epsilon. Third, inhibition of PKC epsilon by either chelerythrine chloride (CHE) or PKC epsilon translocation inhibitor peptide ( TIP) caused a partial reduction of ECG-induced increases in myocardial contraction. Moreover, NAC was also effective in reducing the effects of ECG on myocardial contraction. Finally, pretreatment of the heart with both CHE and NAC completely abolished ECG-induced inotropic effects on the heart. Together, these findings indicate that ECG can regulate myocardial contractility via a novel PKC epsilon-dependent signaling pathway.