Protein kinase C-mediated desmin phosphorylation is related to myofibril disarray in cardiomyopathic hamster heart.
The cardiomyopathic (CM) Syrian golden hamster (strain UM-X7.1) exhibits a hereditary cardiomyopathy, which causes premature death resulting from congestive heart failure. The CM animals show extensive cardiac myofibril disarray and myocardial calcium overload. The present study has been undertaken to examine the role of desmin phosphorylation in myofibril disarray observed in CM hearts. The data from skinned myofibril protein phosphorylation assays have shown that desmin can be phosphorylated by protein kinase C (PKC). There is no significant difference in the content of desmin between CM and control hamster hearts. However, the desmin from CM hearts has a higher phosphorylation level than that of the normal hearts. Furthermore, we have examined the distribution of desmin and myofibril organization with immunofluorescent microscopy and immunogold electron microscopy in cultured cardiac myocytes after treatment with the PKC-activating phorbol ester, 12-O-tetradecanylphorbol-13-acetate (TPA). When the cultured normal hamster cardiac cells are treated with TPA, desmin filaments are disassembled and the myofibrils become disarrayed. The myofibril disarray closely mimics that observed in untreated CM cultures. These results suggest that disassembly of desmin filaments, which could be caused by PKC-mediated phosphorylation, may be a factor in myofibril disarray in cardiomyopathic cells and that the intermediate filament protein, desmin, plays an important role in maintaining myofibril alignment in cardiac cells.
Huang
Xupei
X
Department of Biomedical Science, Florida Atlantic University, Boca Raton, FL 33431, USA.
Li
Jian
J
Foster
Dalton
D
Lemanski
Sharon L
SL
Dube
Dipak K
DK
Zhang
Chi
C
Lemanski
Larry F
LF
D000818:Animals; D009202:Cardiomyopathies / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D006224:Cricetinae; D003893:Desmin / Q000378:metabolism*; D008647:Mesocricetus; D008854:Microscopy, Electron; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003893:Desmin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate