Regulation of protein kinase C isozyme and calcineurin expression in isoproterenol induced cardiac hypertrophy.
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 beta-adrenergic stimulation of male Wistar rats with Iso (2mg/kg x day) for 2 and 7 days using osmotic minipumps, we determined a) cardiac PKC-activity, b) the expression of cardiac PKC isozymes (PKC-alpha, PKC-delta and PKC-epsilon) 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-alpha (day 2: +38%; day 7: +43%), PKC-delta (day 2: 85%; day 7: +78%) and PKC-epsilon (day 7: +58%). The protein amount of calcineurin was not significantly altered by Iso compared with sham-operated controls. The increased expression of PKC-alpha, PKC-delta and PKC-epsilon in the cytosol was paralleled by a transcriptional upregulation of the absolute mRNA-levels of these PKC-isozymes as determined by quantitative RT-PCR.
Braun
Martin
M
Department of Cardiology, Medical Clinic II, University of Technology Dresden, Germany. martin.braun@mailbox.tu-dresden.de
Simonis
Gregor
G
Birkner
Katja
K
Pauke
Bernd
B
Strasser
Ruth H
RH
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D015153:Blotting, Western; D019703:Calcineurin / Q000096:biosynthesis* / Q000235:genetics; D006332:Cardiomegaly / Q000139:chemically induced* / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D007545:Isoproterenol / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009929:Organ Size; D011493:Protein Kinase C / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013347:Subcellular Fractions / Q000201:enzymology; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D007527:Isoenzymes; D011493:Protein Kinase C; D019703:Calcineurin; D007545:Isoproterenol