Identification of a PKCepsilon-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 (TF(4)) 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(2+) level in cultured adult cardiac myocytes. Second, it activated PKCepsilon, but not PKCalpha, 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 PKCepsilon. Third, inhibition of PKCepsilon by either chelerythrine chloride (CHE) or PKCepsilon 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 PKCepsilon-dependent signaling pathway.
Li
Daxiang
D
Department of Physiology and Pharmacology, Health Science Campus, University of Toledo, 3000 Arlington Avenue, Toledo, OH 43614-2598, USA.
Yang
Changjun
C
Chen
Ying
Y
Tian
Jiang
J
Liu
Lijun
L
Dai
Qiuping
Q
Wan
Xiaochun
X
Xie
Zijian
Z
D000111:Acetylcysteine / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D053119:Benzophenanthridines / Q000494:pharmacology; D044946:Biflavonoids / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology; D010455:Peptides / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013662:Tea / Q000737:chemistry; D010738:Type C Phospholipases / Q000378:metabolism
D000470:Alkaloids; D000975:Antioxidants; D053119:Benzophenanthridines; D044946:Biflavonoids; D002316:Cardiotonic Agents; D010455:Peptides; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D013662:Tea; C077197:theaflavin digallate; D005707:Gallic Acid; D002392:Catechin; C062669:epicatechin gallate; C016299:chelerythrine; C497257:Prkce protein, rat; D051744:Protein Kinase C-epsilon; D010738:Type C Phospholipases; D002118:Calcium; D000111:Acetylcysteine