Expression of protein kinase C beta in the heart causes hypertrophy in adult mice and sudden death in neonates.
Protein kinase C (PKC) activation in the heart has been linked to a hypertrophic phenotype and to processes that influence contractile function. To establish whether PKC activation is sufficient to induce an abnormal phenotype, PKCbeta was conditionally expressed in cardiomyocytes of transgenic mice. Transgene expression in adults caused mild and progressive ventricular hypertrophy associated with impaired diastolic relaxation, whereas expression in newborns caused sudden death associated with marked abnormalities in the regulation of intracellular calcium. Thus, the PKC signaling pathway in cardiocytes has different effects depending on the timing of expression and, in the adult, is sufficient to induce pathologic hypertrophy.
Bowman
J C
JC
Department of Medicine, Albert Einstein College of Medicine, New York, NY 10461, USA.
Steinberg
S F
SF
Jiang
T
T
Geenen
D L
DL
Fishman
G I
GI
Buttrick
P M
PM
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D002118:Calcium / Q000502:physiology; D006332:Cardiomegaly / Q000201:enzymology*; D003645:Death, Sudden; D005260:Female; D007527:Isoenzymes / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D012518:Sarcomeres / Q000502:physiology
D007527:Isoenzymes; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D007545:Isoproterenol; D002118:Calcium