D Bell1, B J McDermott. 1. Department of Therapeutics and Pharmacology, The Cardiovascular Research Centre, The School of Medicine, The Queen's University of Belfast, Northern Ireland, UK.
Abstract
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 microM) and T4 (10 pM-2 microM) increased cell protein significantly maximally at 1 microM and by 33.2 and 30.5%, respectively, above basal value. IGF-1 (< or = 10 pM), T3 (10 pM-2 microM) and T4 (10 pM-2 microM) 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.
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 microM) and T4 (10 pM-2 microM) increased cell protein significantly maximally at 1 microM and by 33.2 and 30.5%, respectively, above basal value. IGF-1 (< or = 10 pM), T3 (10 pM-2 microM) and T4 (10 pM-2 microM) 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.
Authors: Barrie D Robison; Robert E Drew; Gordon K Murdoch; Madison Powell; Kenneth J Rodnick; Matt Settles; David Stone; Erin Churchill; Rodney A Hill; Madhusudhan R Papasani; Solange S Lewis; Ronald W Hardy Journal: Comp Biochem Physiol Part D Genomics Proteomics Date: 2008-02-14 Impact factor: 2.674
Authors: Antonio C Bianco; Grant Anderson; Douglas Forrest; Valerie Anne Galton; Balázs Gereben; Brian W Kim; Peter A Kopp; Xiao Hui Liao; Maria Jesus Obregon; Robin P Peeters; Samuel Refetoff; David S Sharlin; Warner S Simonides; Roy E Weiss; Graham R Williams Journal: Thyroid Date: 2013-12-12 Impact factor: 6.568