Regulation of Protein Metabolism in Muscle

Jefferson, Leonard S.; Vary, Thomas C.; Kimball, Scot R.

doi:10.1002/cphy.cp070216

Cited by 5 publications

(4 citation statements)

References 208 publications

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“…14). As such, altered mTOR phosphorylation appears to represent an important nexus for the observed changes in translation initiation.…”

Section: Discussionmentioning

confidence: 90%

IGF-I stimulates protein synthesis in skeletal muscle through multiple signaling pathways during sepsis

Vary¹

2006

American Journal of Physiology-Regulatory, Integrative and Comp

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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.

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“…14). As such, altered mTOR phosphorylation appears to represent an important nexus for the observed changes in translation initiation.…”

Section: Discussionmentioning

confidence: 90%

IGF-I stimulates protein synthesis in skeletal muscle through multiple signaling pathways during sepsis

Vary¹

2006

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Central to the acute regulation of mRNA translation initiation is mTOR, which assimilates signals from several different inputs. mTOR is reported to be a common intermediate involved in mRNA translation control produced by growth factors (for review see (13)) by acting as the upstream kinase responsible for phosphorylating 4E-BP1 and S6K1 (14, 15). Activation of mTOR involves phosphorylation of at least two serine residues, Ser 2448 and Ser 2481 , located in the C-terminal repressor domain.…”

Section: Discussionmentioning

confidence: 99%

Partial dissociation of TSC2 and mTOR phosphorylation in cardiac and skeletal muscle of rats in vivo

Forsyth

Vary

2008

Mol Cell Biochem

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Insulin promotes protein accretion in cardiac and skeletal muscle through a stimulation of the mRNA translation initiation phase of protein synthesis. The present set of experiments examined the regulatory TSC2 signaling pathway that potentially contribute to the myocardial responsiveness of protein synthesis to insulin in post-absorptive male Sprague-Dawley rats in vivo. Heart and skeletal muscle were sampled from rats up to one hour following intravenous injection of various doses of insulin. In cardiac muscle, TSC2 phosphorylation was elevated only at the highest plasma insulin concentration (386 ng/ml). In contrast, the extent of mTOR phosphorylation on either Ser( 2448 ) or Ser( 2481 ) was raised at 24-fold less concentration of insulin and corresponded with increased phosphorylation of PKB(Thr 308 ) or PKB(Ser 473 ). In gastrocnemius, TSC2 phosphorylation was elevated at plasma insulin concentrations (16 ng/ml) lower than observed in cardiac muscle (386 ng insulin/ml). The increased TSC2 phosphorylation corresponded with a marked stimulation of PKB phosphorylation. However, mTOR(Ser 2448 ) or mTOR(Ser 2481 ) phosphorylation was not elevated until the plasma insulin concentration reached 97 ng/ml. The results indicate there is a dissociation of TSC2 and mTOR phosphorylation in vivo.

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“…O ganho ou perda de proteínas no músculo esquelético é determinado pelo balanço entre dois processos opostos: síntese e degradação protéica. fatores de alongamento e fatores de liberação (JEFFERSON et al, 2001;KIMBALL et al, 2002).…”

Section: Controle Traducional Da Síntese Protéicaunclassified

“…O segundo passo regulatório é a ligação do mRNA à subunidade 40S e envolve proteínas eIF4. Grau de fosforilação de fatores como eIF4E, eIF4G e 4E-BP1 regulam esta etapa da iniciação (JEFFERSON et al, 2001…”

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Efeito da suplementação à curto prazo de creatina sobre o eixo GH-IGF-I, função neuromuscular e vias de síntese e degradação proteíca muscular em ratos.

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Regulation of Protein Metabolism in Muscle

Cited by 5 publications

References 208 publications

IGF-I stimulates protein synthesis in skeletal muscle through multiple signaling pathways during sepsis

IGF-I stimulates protein synthesis in skeletal muscle through multiple signaling pathways during sepsis

Partial dissociation of TSC2 and mTOR phosphorylation in cardiac and skeletal muscle of rats in vivo

Efeito da suplementação à curto prazo de creatina sobre o eixo GH-IGF-I, função neuromuscular e vias de síntese e degradação proteíca muscular em ratos.

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