Increased expression of protein kinase C isoforms in heart failure due to myocardial infarction.
The activities of cardiac protein kinase C (PKC) were examined in hemodynamically assessed rats subsequent to myocardial infarction (MI). Both Ca(2+)-dependent and Ca(2+)-independent PKC activities increased significantly in left ventricular (LV) and right ventricular (RV) homogenates at 1, 2, 4, and 8 wk after MI was induced. PKC activities were also increased in both LV and RV cytosolic and particulate fractions from 8-wk infarcted rats. The relative protein contents of PKC-alpha, -beta, -epsilon, and -zeta isozymes were significantly increased in LV homogenate, cytosolic (except PKC-alpha), and particulate fractions from the failing rats. On the other hand, the protein contents of PKC-alpha, -beta, and -epsilon isozymes, unlike the PKC-zeta isozyme, were increased in RV homogenate and cytosolic fractions, whereas the RV particulate fraction showed an increase in the PKC-alpha isozyme only. These changes in the LV and RV PKC activities and protein contents in the 8-wk infarcted animals were partially corrected by treatment with the angiotensin-converting enzyme inhibitor imidapril. No changes in protein kinase A activity and its protein content were seen in the 8-wk infarcted hearts. The results suggest that the increased PKC activity in cardiac dysfunction due to MI may be associated with an increase in the expression of PKC-alpha, -beta, and -epsilon isozymes, and the improvement of heart function in the infarcted animals by imidapril may be due to partial prevention of changes in PKC activity and isozyme contents.
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada R2H 2A6.
Jingwei
J
Wang
Xueliang
X
Liu
Emmanuelle
E
Sentex
Nobuakira
N
Takeda
Naranjan S
NS
Dhalla
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism; D006333:Heart Failure / Q000201:enzymology* / Q000209:etiology; D006352:Heart Ventricles / Q000187:drug effects / Q000201:enzymology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D015151:Immunoblotting; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D009206:Myocardium / Q000201:enzymology; D011493:Protein Kinase C / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D007527:Isoenzymes; C065166:imidapril; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C