Regulation of protein kinase C isozymes in volume overload cardiac hypertrophy

• Published in: Molecular and cellular biochemistry Vol. 262; no. 1-2; pp. 135 - 143
• Main Authors: Braun, Martin U, LaRosée, Paul, Simonis, Gregor, Borst, Mathias M, Strasser, Ruth H
• Format: Journal Article
• Language: English
• Published: Netherlands Springer Nature B.V 01-07-2004
• Subjects: Animals; Cardiac Volume; Cardiomegaly - enzymology; Enzymatic activity; Gene Expression Regulation, Enzymologic - physiology; Heart; Hypertrophy, Left Ventricular - enzymology; Hypertrophy, Right Ventricular - enzymology; Isoenzymes - analysis; Isoenzymes - genetics; Kinases; Male; Protein Kinase C - analysis; Protein Kinase C - genetics; Protein Kinase C-alpha; Protein Kinase C-delta; Protein Kinase C-epsilon; Proteins; Rats; Rats, Wistar; Regulation; RNA, Messenger - analysis; Rodents; Signal Transduction
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1023/b:mcbi.0000038229.23132.9f

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.