Effect of thyroid status on basal phosphorylation of cardiac myofibrillar phosphoproteins in rats.

Abstract

The effect of thyroid status on myocardial function and accompanying alterations in the expression of specific genes has been well defined in animals. However, the effects of thyroid hormones on the basal phosphorylation of key cardiac regulatory proteins, which may also contribute to alterations in myocardial function, have not been defined. The present study concerns the phosphorylation status of myofibrillar proteins in hearts from hyperthyroid, euthyroid and hypothyroid rats. Hyperthyroidism was produced by daily subcutaneous injections of L-triiodothyronine, while hypothyroidism was induced with an iodine-deficient diet and KClO4. Two different approaches were used to study changes in the basal phosphorylation levels of troponin I and C protein: 1) direct measurement of the 32P-label associated with these proteins, using intact, beating hearts perfused with [32P]orthophosphate-labeled Krebs buffer; 2) indirect measurement by the back-phosphorylation technique with [gamma-32P]ATP and the catalytic subunit of cAMP-dependent protein kinase in vitro. Measurements of left ventricular contraction (+dP/dt and -dP/dt) were significantly higher in hyperthyroid than in euthyroid animals and this was associated with increases in basal phosphorylation levels of both troponin I and C protein in the myofibrils. In hypothyroid animals, both +dP/dt and -dP/dt were significantly lower than in euthyroid animals and this was associated with decreases in basal phosphorylation levels of troponin I and C protein. The changes in the phosphorylation status of troponin I or C protein correlated with the changes in the speed of myocardial relaxation (-dP/dt) in response to the altered thyroid states.(ABSTRACT TRUNCATED AT 250 WORDS)