Contribution of de novo protein synthesis to the hypertrophic effect of IGF-1 but not of thyroid hormones in adult ventricular cardiomyocytes

Background: Enhanced expression of IGF-1 occurs in left ventricular hypertr ophy (LVH) associated with systemic hypertension. Cardiac dysfunction accom panied by LVH is also observed in hyperthyroidism. Objective: to assess the relative contributions of de novo protein synthesis and attenuated protein degradation to increased protein mass associated with cardiomyocyte hypert rophy elicited by IGF-1 and thyroid hormones (tri-iodo thyronine T-3, and l -thyroxine T-4), respectively. Methods: total mass of protein, and both the incorporation, and removal of previously incorporated l-U-C-14-phenylalani ne, indices of protein synthesis and degradation, respectively, were assess ed in quiescent adult rat ventricular cardiomyocytes maintained in shortter m culture, and corrected for DNA content, as a index of cell number. Result s: IGF-1 (1 pM-100 nM) increased cell protein significantly, maximally at 1 nM and by 38% above basal value after 24 h. T-3 (10 pM-2 mu M) and T-4 (10 pM-2 mu M) increased cell protein significantly maximally at 1 mu M and by 33.2 and 30.5%, respectively, above basal value. IGF-1 (less than or equal to 10 pM), T-3 (10 pM-2 mu M) and T-4 (10 pM-2 mu M) did not increase inco rporation of l-U-C-14-phenylalanine above basal values. IGF-1 (100 pM-100 n M) increased incorporation of radiolabel significantly maximally at 100 nM and by 56%. T-4 (100 pM) and IGF-1 (10 pM), concentrations that did not sti mulate de novo protein synthesis, attenuated the degradation of radiolabell ed protein by 13.6 and 11.8%, respectively, compared to control values afte r 48 h. Conclusion: These data indicate that the acute hypertrophic respons e to (i) thyroid hormones cannot be attributed to initiation of de novo pro tein synthesis; (ii) IGF-1 comprises two components; the response elicited by IGF-1 (<10 pM) is independent of, while the response elicited by IGF-1 ( >100 pM) is due to de novo protein synthesis.