© 1996 American Heart Association, Inc.
Articles |
Thyroid Hormone Represses Protein Kinase C Isoform Expression and Activity in Rat Cardiac Myocytes
the Departments of Medicine (S.F.S.) and Pharmacology (V.R., S.F.S.), Columbia University, New York, NY.
Correspondence to Susan F. Steinberg, MD, Associate Professor of Medicine and Pharmacology, Department of Pharmacology, Columbia University, College of Physicians and Surgeons, 630 West 168 St, New York, NY 10032.
We have previously demonstrated that at least four isoforms of protein kinase C (PKC; 
, 
, 
, and 
) are expressed in neonatal rat ventricular myocytes and that development is associated with a decline in their expression. The mechanism(s) regulating PKC isoform expression in ventricular myocytes is completely unknown. The developmental decline in PKC expression occurs, in large part, during the first 2 weeks of postnatal life, while thyroid hormone levels are known to be progressively increasing. Accordingly, this study examined the influence of thyroid hormone on PKC isoform expression to determine whether thyroid hormone can be implicated as a potential physiological regulator of PKC gene expression during normal cardiac development. Hypothyroidism was induced in adult rats by surgical thyroidectomy; thyroid status was manipulated in cultured neonatal ventricular myocytes by growth in serum-free medium with varying triiodothyronine (T3) levels. In each case, hypothyroidism was verified by a 10- to 50-fold increase in steady state mRNA for ß-myosin heavy chain. In hypothyroid adult ventricular myocardium, there was a selective 60% increase in the expression of PKC protein that corresponded to an increase in maximally stimulated PKC enzyme activity with PKC substrate peptide (pep) but not with histone as substrate. Northern blot analysis revealed a 70% increase in PKC mRNA, indicating that the regulatory effects of thyroid hormone are mediated, at least in part, at the message level. In neonatal ventricular myocytes, there was a T3-dependent reduction in immunoreactivity for both PKC and PKC that was associated with significant reductions in both histone- and pep-kinase activities. The concentration of T3 that half-maximally repressed PKC and PKC expression was 
0.5 nmol/L. Thyroid hormone had no effect on PKC and PKC expression in neonatal or adult ventricular myocytes. PKC isoform expression in cardiac fibroblasts was not influenced by variations in the thyroid hormone concentration during culture. These results provide evidence that thyroid hormone specifically represses PKC and PKC in the neonatal heart and PKC in the adult heart. Thyroid hormone–induced changes in PKC may play an important permissive role in the modulation of autonomic responsiveness in ventricular cardiomyocytes.
Key Words: thyroid hormone • protein kinase C • cardiac myocytes
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