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

Bell, D.; Mcdermott, B.J.

Molecular and Cellular Biochemistry 206(1-2): 113-124


ISSN/ISBN: 0300-8177
PMID: 10839201
DOI: 10.1023/a:1007014500965
Accession: 010382347

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Background: Enhanced expression of IGF-1 occurs in left ventricular hypertrophy (LVH) associated with systemic hypertension. Cardiac dysfunction accompanied 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 hypertrophy elicited by IGF-1 and thyroid hormones (tri-iodo thyronine T3, and l-thyroxine T4), respectively. Methods: total mass of protein, and both the incorporation, and removal of previously incorporated l-U-14C-phenylalanine, indices of protein synthesis and degradation, respectively, were assessed in quiescent adult rat ventricular cardiomyocytes maintained in short-term culture, and corrected for DNA content, as a index of cell number. Results: IGF-1 (1 pM-100 nM) increased cell protein significantly, maximally at 1 nM and by 38% above basal value after 24 h. T3 (10 pM-2 muM) and T4 (10 pM-2 muM) increased cell protein significant maximally at 1 muM and by 33.2 and 30.5%, respectively, above basal value. IGF-1 (ltoreq 10 pM), T3 (10 pM-2 muM) and T4 (10 pM-2 muM) did not increase incorporation of l-U-14C-phenylalanine above basal values. IGF-1 (100 pM-100 nM) increased incorporation of radiolabel significantly maximally at 100 nM and by 56%. T4 (100 pM) and IGF-1 (10 pM), concentrations that did not stimulate de novo protein synthesis, attenuated the degradation of radiolabelled protein by 13.6 and 11.8%, respectively, compared to control values after 48 h. Conclusion: These data indicate that the acute hypertrophic response to (i) thyroid hormones cannot be attributed to initiation of de novo protein 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.