Regulation of protein kinase C isozymes in volume overload cardiac hypertrophy

Abstract

Protein kinase C (PKC) is a family of at least 11 isozymes and known to play a crucial role in myocardial growth. The present study was performed to investigate whether PKC-isozymes are differentially regulated during the development of volume-overload cardiac hypertrophy. After 2, 7 and 30 days of sham or aortocaval shunt operation in male Wistar rats, PKC-activity and the expression of cardiac PKC-isozymes (PKC-alpha, delta and epsilon) were determined at the protein and at the mRNA-level in the left and the right ventricle separately. Myocardial hypertrophy after 2, 7 and 30 days of aortocaval shunt was more pronounced in the right than in the left ventricle. Right ventricular hypertrophy was associated with an increased PKC-enzyme activity, a selectively enhanced protein expression of cytosolic PKC-delta (day 7: +83 +/- 12%, day 30: +94 +/- 14%) and PKC-alpha (day 7: +48 +/- 11%, day 30: +62 +/- 16%) and a transcriptional upregulation of the absolute mRNA-levels of these PKC-isozymes in the aortocaval shunt group as compared to controls. In contrast, the expression of PKC-epsilon was unchanged. A significant upregulation of PKC-delta both on the protein and on the mRNA-level was also noted in volume-overload induced left ventricular hypertrophy, whereas the expression of PKC-alpha and PKC-epsilon were not altered. Furthermore, the expression of calcineurin in both ventricles was not significantly changed in response to volume-overload. This study characterizes in the left and right ventricle a differential regulation of the dominant PKC-isozymes in volume-overload cardiac hypertrophy both at the protein and at the mRNA-level.