In this study, we measured the time courses of change in Na+-K+-ATPase α1-, α2-, and β1-subunit mRNA and protein abundance in cardiac myocytes isolated from euthyroid, hypothyroid, and hyperthyroid (hypothyroids injected daily with 1 μg T3/g body wt) rats. In hypothyroids, α1-, α2-, and β1-protein levels were decreased to 0.55, 0.42, and 0.57 of euthyroids, predicting the decrease in Na+-K+-ATPase activity to 0.53 of control. There was no change in these subunits' mRNA levels, indicating that the decreases in protein levels were not due to decreased subunit transcription rates. In hyperthyroids, the α1-mRNA increased to a steady state of threefold over hypothyroid by 1 day of T3 treatment, and the α1-protein levels increased to twofold over hypothyroid by 4 days of T3. α2-mRNA increased to 5-fold over hypothyroid by 2 days, whereas the α2-protein levels increased to 14- fold above hypothyroid by 4 days of T3. β1-mRNA increased to 12-fold above hypothyroid by 1 day of T3 treatment, whereas β1-protein increased to only 2.5-fold over hypothyroid by 4 days of T3. The discoordinate changes in α2- and β1-mRNA vs. protein can be reconciled with the hypothesis that β1 is rate limiting for assembly in eu- and hypothyroids, and favors assembly with α1, while excess unassembled α2 is degraded. In the hyperthyroids we predict β1 is not rate limiting and there is increased α2β1-assembly. We calculate that T3 decreases the α1-to-α2 ratio from 24:1 in hypothyroid to 3.4:1 in hyperthyroid cardiomyocytes.
|Journal||American Journal of Physiology - Cell Physiology|
|Issue number||2 31-2|
|Publication status||Published - 1992|
All Science Journal Classification (ASJC) codes
- Cell Biology