Igf-i Stimulates Protein Synthesis in Skeletal Muscle Through Multiple Signaling Pathways During Sepsis.
From: Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, PA 17033, USA. tvary@psu.edu
American journal of physiology. Regulatory, integrative and comparative physiology
- Publish Date: Feb 2006
- ISSN: 0363-6119
- Volume: 290
- Issue: 2
- Pages: R313-21
- Medium: Print
- Language: English
- Citation (JAMA): Vary Thomas C, et al. Igf-i Stimulates Protein Synthesis in Skeletal Muscle Through Multiple Signaling Pathways During Sepsis.. Am. J. Physiol. Regul. Integr. Comp. Physiol. Feb 2006;290:R313-21
Abstract
Chronic septic abscess formation causes an inhibition of protein synthesis in gastrocnemius not observed in rats with a sterile abscess. Inhibition is associated with an impaired mRNA translation initiation that can be ameliorated by elevating IGF-I but not insulin. The present study investigated the ability of IGF-I signaling to stimulate protein synthesis in gastrocnemius by accelerating mRNA translation initiation. Experiments were performed in perfused hindlimb preparations from rats 5 days after induction of a septic abscess. Protein synthesis in gastrocnemius from septic rats was accelerated twofold by the addition of IGF-I (10 nM) to perfusate. IGF-I increased the phosphorylation of translation repressor 4E-binding protein-1 (4E-BP1). Hyperphosphorylation of 4E-BP1 in response to IGF-I resulted in its dissociation from the inactive eukaryotic initiation factor (eIF) 4E.4E-BP1 complex. Assembly of the active eIF4F complex (as assessed by the association eIF4G with eIF4E) was increased twofold by IGF-I in the perfusate. In addition, phosphorylation of eIF4G and ribosomal protein S6 kinase-1 (S6K1) was also enhanced by IGF-I. Activation of mammalian target of rapamycin, an upstream kinase implicated in phosphorylating both 4E-BP1 and S6K1, was also observed. Thus the ability of IGF-I to accelerate protein synthesis during sepsis may be related to a stimulation of signaling to multiple steps in translation initiation with an ensuing increased phosphorylation of eIF4G, eIF4E availability, and S6K1 phosphorylation.
Mesh Headings (Keywords): Animals, Carrier Proteins, Eukaryotic Initiation Factor-4E, Eukaryotic Initiation Factor-4G, Insulin-Like Growth Factor I, Male, Muscle Proteins, Muscle, Skeletal, Phosphoproteins, Phosphorylation, Protein Kinases, Rats, Rats, Sprague-Dawley, Ribosomal Protein S6 Kinases, Sepsis
Check for Full Text / PubMed Unique Identifier (PMID): 16150839
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