Regulation of Protein Kinase C Isozyme and Calcineurin Exression in Isoproterenol Induced Cardiac Hypertrophy

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Abstract
Protein kinase C (PKC) and calcineurin are known to play a pivotal role in the development of cardiomyocyte growth. However, its role in Isoproterenol-induced (Iso) cardiac hypertrophy has not been characterized so far and were focus of the current study. After chronic β-adrenergic stimulation of male Wistar rats with Iso (2mg/kgxday) for 2 and 7 days using osmotic minipumps, we determined a) cardiac PKC-activity, b) the expression of cardiac PKC isozymes (PKC-α, PKC-δ and PKC-ε) both at the protein and the mRNA-level and c) the expression of calcineurin using Western blot analysis. Iso-treatment for 2 and 7 days results in cardiac hypertrophy with an increase of the heart weight-to-body weight ratio by 36% and 27%. Iso-induced myocardial growth was associated with an enhanced total PKC-activity and a significant increased protein expression of cytosolic PKC-α (day 2: +38%; day 7: +43%), PKC-δ (day 2: 85%; day 7: +78%) and PKC-ε (day 7: +58%). The protein amount of calcineurin was not significantly altered by Iso compared with sham-operated controls. The increased expression of PKC-α, PKC-δ and PKC-ε in the cytosol was paralleled by a transcriptional upregulation of the absolute mRNA-levels of these PKC-isozymes as determined by quantitative RT-PCR.