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

Li D, Yang C, Chen Y, Tian J, Liu L, Dai Q, Wan X, Xie Z. Identification of a PKCε-dependent regulation of myocardial contraction by epicatechin-3-gallate. Am J Physiol Heart Circ Physiol 294: H345–H353, 2008. First published October 19, 2007; doi:10.1152/ajpheart.00785.2007.—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-3gallate (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 Ca level in cultured adult cardiac myocytes. Second, it activated PKCε, but not PKC , 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 PKCε. Third, inhibition of PKCε by either chelerythrine chloride (CHE) or PKCε 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 PKCε-dependent signaling pathway.