Protein kinase C in the human heart: differential regulation of the isoforms in aortic stenosis or dilated cardiomyopathy.
OBJECTIVE
Protein kinase C (PKC) is a central enzyme in the regulation of growth and hypertrophy. Little was known on PKC isoform regulation in human heart. Goal of this study was to characterize the isoforms of protein kinase C in human heart, their changes during ontogenesis, and their regulation in myocardial hypertrophy and heart failure.


METHODS
In left ventricular and atrial samples from adults with end-stage dilated cardiomyopathy (DCM), from adults with severe aortic stenosis (AS), from small infants undergoing repair of ventricular septal defects, and from healthy organ donors (CO), activity of protein kinase C and the expression of its isozymes were examined.


RESULTS
In the adult human heart, the isoforms PKC-alpha, PCK-beta, PKC-delta, PKC-epsilon, PKC-lambda/-iota, and PKC-zeta were detected both on protein and on mRNA level. All isozymes are subjected to downregulation during ontogenesis. No evidence, however, exists for an isoform shift from infancy to adulthood. DCM leads to a pronounced upregulation of PKC-beta. Severe left ventricular hypertrophy in AS, however, recruits a distinct isoform pattern, i.e., isoforms PKC-alpha, PKC-delta, PKC-epsilon, PKC-lambda/-iota, and PKC-zeta are upregulated, whereas PKC-beta is not changed under this condition.


CONCLUSIONS
This work gives evidence for a differential recruitment of human PKC isoforms in various forms of myocardial hypertrophy and heart failure.
Simonis
Gregor
G
Department of Medicine/Cardiology, Dresden University of Technology, Fetscherstr. 76, Dresden, 01307, Germany. gsimonis@gmx.de
Briem
Steffen K
SK
Schoen
Steffen P
SP
Bock
Manja
M
Marquetant
Rainer
R
Strasser
Ruth H
RH
D000328:Adult; D000368:Aged; D000818:Animals; D001024:Aortic Valve Stenosis / Q000201:enzymology / Q000235:genetics*; D002311:Cardiomyopathy, Dilated / Q000201:enzymology / Q000235:genetics*; D002675:Child, Preschool; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006801:Humans; D007223:Infant; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D014020:Tissue Extracts / Q000378:metabolism
D020033:Protein Isoforms; D014020:Tissue Extracts; D011493:Protein Kinase C