Angiotensin II directly inhibits protein synthesis in murine myotubes.
Angiotensin II (Ang II) has been implicated in muscle protein loss in cachexia. To determine whether the Ang I/II system directly inhibits protein synthesis in muscle their effect has been monitored in vitro using murine myotubes as a surrogate model system. Ang I inhibited protein synthesis by 40-50% over the concentration range of 0.05-2.5 microM within 30 min of addition, and the inhibition remained relatively constant over 24 h. The effect was attenuated by co-incubation with the angiotensin converting enzyme inhibitor imidaprilat (50 microM) suggesting that inhibition of protein synthesis was due to the formation of Ang II. Ang II also inhibited protein synthesis by 40-50% over the concentration range of 0.1-5 microM, and the inhibition also remained relatively constant between 30 min and 24 h after addition. The effect was attenuated by insulin-like growth factor-1 (IGF-1) (25-100 ng/ml). Thus, Ang I/II have the ability to induce muscle atrophy through inhibition of protein synthesis.
Russell
Steven T
ST
Pharmaceutical Sciences Research Institute, Aston University, Birmingham B4 7ET, UK.
Sanders
Paul M
PM
Tisdale
Michael J
MJ
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004338:Drug Combinations; D048289:Imidazolidines / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D004338:Drug Combinations; D048289:Imidazolidines; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D007334:Insulin-Like Growth Factor I; C078006:imidaprilat