Submitted on July 6, 2007
Accepted on October 17, 2007
Identification of a PKC
-dependent Regulation of Myocardial Contraction by Epicatechin-3-gallate
Daxiang Li1, Changjun Yang1, Ying Chen2, Jiang Tian2, Lijun Liu2, Qiuping Dai2, Xiaochun Wan1, and Zijian Xie2*
1 Key Laboratory of Tea Biochemistry and Biotechnology, Anhui Agricultural University, Hefei, China
2 Physiology and Pharmacology, University of Toledo Health Science Campus, Toledo, Ohio, United States
* To whom correspondence should be addressed. E-mail: zxie{at}meduohio.edu.
In this study, the effects of tea catechins and tea theaflavins on myocardial contraction were examined in isolated rat hearts using 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+ in cultured adult cardiac myocytes. Second, it activated PKC
, but not PKC
, in the isolated hearts as well as in cultured cells. Neither a phospholipase C (PLC) inhibitor (U73122) nor antioxidant N-acetyl cysteine (NAC) affected the ECG-induced activation of PKC . Third, inhibition of PKC by either chelerythrine chloride (CHE) or PKC 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. Taken together, these findings indicate that ECG can regulate myocardial contractility via a novel PKC -dependent signaling pathway.
