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.
Wang
Jingwei
J
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada R2H 2A6.
Liu
Xueliang
X
Sentex
Emmanuelle
E
Takeda
Nobuakira
N
Dhalla
Naranjan S
NS
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