EFFECT OF THYROID STATUS ON BASAL PHOSPHORYLATION OF CARDIAC MYOFIBRILLAR PHOSPHOPROTEINS IN RATS

The effect of thyroid status on myocardial function and accompanying a lterations in the expression of specific genes has been well defined i n animals. However, the effects of thyroid hormones on the basal phosp horylation of key cardiac regulatory proteins, which may also contribu te to alterations in myocardial function, have not been defined. The p resent study concerns the phosphorylation status of myofibrillar prote ins in hearts from hyperthyroid, euthyroid and hypothyroid rats. Hyper thyroidism was produced by daily subcutaneous injections of L-triiodot hyronine, while hypothyroidism was induced with an iodine-deficient di et and KClO4. Two different approaches were used to study changes in t he basal phosphorylation levels of troponin I and C protein: 1) direct measurement of the P-32-label associated with these proteins, using i ntact, beating hearts perfused with P-32]orthopbospbate-labeled Krebs buffer; 2) indirect measurement by the back-phosphorylation technique with [gamma-P-32]ATP and the catalytic subunit of cAMP-dependent prote in kinase in vitro. Measurements of left ventricular contraction (+ dP /dt and - dP/dt) were significantly higher in hyperthyroid than in eut hyroid animals and this was associated with increases in basal phospho rylation levels of both troponin I and C protein in the myofibrils. In hypothyroid animals, both + dP/dt and - dP/dt were significantly lowe r 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 wi th the changes in the speed of myocardial relaxation (- dP/dt) in resp onse to the altered thyroid states, These findings suggest that altera tions in basal phosphorylation levels of myofibrillar regulatory prote ins may reflect the adaptation of the myocardium to altered physiologi cal conditions.