Summary
Focal adhesion kinase (FAK) and other protein tyrosine kinases (PTKs) found in focal adhesions regulate proliferation and cytoskeletal assembly of nonmuscle cells, but their role in hypertrophic growth of cardiac myocytes has not been investigated. Serum-free, primary cultures of spontaneously contracting and contractile-arrested neonatal rat ventricular myocytes (NRVMs) were used to determine the role of FAK and other PTKs in regulating cardiac gene expression and protein turnover associated with the hypertrophic phenotype. FAK was readily detected in focal adhesions and costameres of spontaneously contracting, hypertrophied myocytes, but was reduced in contractile-arrested cells. Chronic treatment of NRVMs with genistein (50µM), a relatively specific PTK inhibitor, prevented NRVM growth, as demonstrated by significant reductions (by 10–35%) in total protein, total protein/DNA ratio, and myofibrillar protein content. Genistein also significandy reduced myosin heavy chain (MHC) and actin synthesis, and increased MHC and actin degradation. Daidzein (50 µM), a weakly active analogue, had much less of an effect. Genistein also markedly reduced β-myosin heavy chain (β-MHC) and to a lesser extent atrial natriuretic factor (ANF) gene expression, thus reproducing many of the phenotypic features of cardiac myocyte atrophy produced by contractile arrest. Transient transfection of NRVMs with an expression vector containing the full-length coding sequence of chick FAK along with rat β-MHC and ANF promoter-luciferase constructs resulted in a 2–4-fold increase in luciferase activity, indicating that FAK stimulated transcription of fetal genes associated with the hypertrophic phenotype. Thus, FAK and/or other PTKs found in focal adhesions may play a role in both the transcriptional and posttranslational regulation of cardiac myocyte hypertrophy.
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Eble, D.M., Qi, M., Strait, J., Samarel, A.M. (2000). Contraction-Dependent Hypertrophy of Neonatal Rat Ventricular Myocytes: Potential Role for Focal Adhesion Kinase. In: Takeda, N., Nagano, M., Dhalla, N.S. (eds) The Hypertrophied Heart. Progress in Experimental Cardiology, vol 3. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4423-4_8
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DOI: https://doi.org/10.1007/978-1-4615-4423-4_8
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