- Cardiac hypertrophy was induced in rats by aortic constriction or by daily injections of thyroxine. Rates of protein synthesis or degradation were measured at an early stage of hypertrophy in isolated perfused hearts. Perfusion conditions were selected so that the rates of protein synthesis could be calculated based on the specific radioactivity of phenylalanyl-tRNA, and so that accumulation of free ribosomal subunits, which occurs when rates of peptide chain initiation are inhibited, could be prevented. In both models of hypertrophy, rates of protein synthesis were elevated by 25% compared to control. Tissue contents of ribosomal RNA were also increased by 25% in both models. The proportion of total RNA in free ribosomal subunits in hypertrophying hearts was unchanged from that observed in perfused hearts from control rats and from unperfused normal hearts. These results indicated that increased content of ribosomes rather than more efficient initiation or elongation of peptide chains accounted for faster rates of protein synthesis in hypertrophying hearts.
Protein degradation was measured by monitoring release of phenylalanine from the heart into the perfusate when protein synthesis was inhibited with cycloheximide. Rates of protein degradation in hearts from thyroxine-injected rats were unchanged from those in hearts from untreated animals. The involvement of protein degradation in hypertrophy induced by aortic constriction could not be evaluated by these methods, due to deficiencies in the model.
Ribosome production was investigated by monitoring incorporation of ('3)H-phenylalanine into ribosomal protein. Rates of ribosome production were found to be highly dependent on the presence of insulin, but independent of aortic pressure development when measured in the presence of insulin. When rates of ribosome production were measured in vitro at various times after one injection of thyroxine in vivo, a significant acceleration of the rate was detected 8 hr after injection. Elevated rates of ribosome production were detected at least 16 hr prior to a significant increase in the rate of total protein synthesis. This finding further confirmed that rates of total protein synthesis depended on the number of ribosomes.
- Dissertation Note:
- Ph.D. The Pennsylvania State University 1984.
- Source: Dissertation Abstracts International, Volume: 45-06, Section: B, page: 1694.
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