Synthesis and degradation of myocardial protein during the development and regression of thyroxine-induced cardiac hypertrophy in rats

  • Sanford C
  • Griffin E
  • Wildenthal K
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Abstract

Cardiac hypertrophy was induced in rats by daily injections of L-thyroxine (1.0 mg/kg). Regression from hypertrophy was studied 4 days after discontinuing thyroxine. Isolated, Langendorff-perfused hearts were perfused with Krebs-Henseleit buffer, glucose, insulin, and amino acids. To measure protein synthesis, left ventricular tissue was assayed for incorporation of tritiated phenylalanine into protein. Indices of rates of protein degradation were obtained by measuring the release of cold phenylalanine after blocking protein synthesis with cycloheximide. After 3 days of thyroxine (when cardiac growth was maximally increased), the rate of protein synthesis increased by 22% (P less than 0.001). After 1 week, synthesis was 8% greater than control (P less than 0.05), and by 2 weeks (when hypertrophy was stable and the rate of cardiac growth was similar to controls), synthesis had returned to control levels. In hearts regressing from hypertrophy, synthesis was reduced to 68% of control (P less than 0.001). The rate of protein degradation was decreased by 12% (P less than 0.05) after 3 days of thyroxine, but was not different from control at 1 or 2 weeks. During regression, degradation was 12% below control (P less than 0.05). Changes in the release of several amino acids that are synthesized or metabolized in heart (e.g., alanine, glycine, serine) were different from changes in phenylalanine release. In conclusion thyroxine-induced cardiac hypertrophy and regression are accompanied by changes in protein synthesis and degradation, and amino acid metabolism. The predominant change in hypertrophy is increased protein synthesis with a minor contribution from reduced degradation. Regression of hypertrophy is accompanied by decreased synthesis, not increased degradation.

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Authors

  • C. F. Sanford

  • E. E. Griffin

  • K. Wildenthal

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