Dataset Information

Activated protein synthesis and suppressed protein breakdown signaling in skeletal muscle of critically ill patients.

ABSTRACT:

Background

Skeletal muscle mass is controlled by myostatin and Akt-dependent signaling on mammalian target of rapamycin (mTOR), glycogen synthase kinase 3? (GSK3?) and forkhead box O (FoxO) pathways, but it is unknown how these pathways are regulated in critically ill human muscle. To describe factors involved in muscle mass regulation, we investigated the phosphorylation and expression of key factors in these protein synthesis and breakdown signaling pathways in thigh skeletal muscle of critically ill intensive care unit (ICU) patients compared with healthy controls.

Methodology/principal findings

ICU patients were systemically inflamed, moderately hyperglycemic, received insulin therapy, and showed a tendency to lower plasma branched chain amino acids compared with controls. Using Western blotting we measured Akt, GSK3?, mTOR, ribosomal protein S6 kinase (S6k), eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), and muscle ring finger protein 1 (MuRF1); and by RT-PCR we determined mRNA expression of, among others, insulin-like growth factor 1 (IGF-1), FoxO 1, 3 and 4, atrogin1, MuRF1, interleukin-6 (IL-6), tumor necrosis factor ? (TNF-?) and myostatin. Unexpectedly, in critically ill ICU patients Akt-mTOR-S6k signaling was substantially higher compared with controls. FoxO1 mRNA was higher in patients, whereas FoxO3, atrogin1 and myostatin mRNAs and MuRF1 protein were lower compared with controls. A moderate correlation (r2=0.36, p<0.05) between insulin infusion dose and phosphorylated Akt was demonstrated.

Conclusions/significance

We present for the first time muscle protein turnover signaling in critically ill ICU patients, and we show signaling pathway activity towards a stimulation of muscle protein synthesis and a somewhat inhibited proteolysis.

SUBMITTER: Jespersen JG

PROVIDER: S-EPMC3069050 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Publications

Activated protein synthesis and suppressed protein breakdown signaling in skeletal muscle of critically ill patients.

Jespersen Jakob G JG Nedergaard Anders A Reitelseder Søren S Mikkelsen Ulla R UR Dideriksen Kasper J KJ Agergaard Jakob J Kreiner Frederik F Pott Frank C FC Schjerling Peter P Kjaer Michael M

PloS one 20110331 3

<h4>Background</h4>Skeletal muscle mass is controlled by myostatin and Akt-dependent signaling on mammalian target of rapamycin (mTOR), glycogen synthase kinase 3β (GSK3β) and forkhead box O (FoxO) pathways, but it is unknown how these pathways are regulated in critically ill human muscle. To describe factors involved in muscle mass regulation, we investigated the phosphorylation and expression of key factors in these protein synthesis and breakdown signaling pathways in thigh skeletal muscle of ...[more]

PMID: 21483870

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Project description:BACKGROUND:Ursolic acid altered muscle protein metabolism in normal and resting conditions after acute resistance exercise, suggesting that eating fruits rich in ursolic acid could enhance muscle protein synthesis and decrease muscle degradation. Aronia melanocarpa, a member of the family Rosaceae and native to North America and Eastern Canada, is rich in ursolic acid. In this study, we examined the effects of A. melanocarpa extract (AME) supplementation on the mTORC1 signaling pathway and muscle degradation-related factors in rats, both alone and in combination with resistance exercise. METHODS:Male Sprague-Dawley rats were divided into AME and normal chow (NOR) groups. AME group was fed chow providing a dose of 3?g/kg of AME and 115?mg/kg of ursolic acid for 7?days, whereas NOR rats were fed normal powder chow. The right gastrocnemius muscle of each animal was isometrically exercised (5 sets of ten 3-s contractions, with a 7-s interval between contractions and 3-min rest intervals between sets), while the left gastrocnemius muscle served as an internal control. Western blotting and real-time polymerase chain reaction were used to assess expression of factors involved in the mTORC1 signaling pathway and muscle degradation. RESULTS:At 1?h after resistance exercise, phosphorylation of ERK1/2 was significantly increased by AME consumption. At 6?h after resistance exercise, AME consumption significantly increased the phosphorylation of Akt, p70S6K, rpS6, and AMPK. It also increased MAFbx expression. Furthermore, AME significantly increased the phosphorylation of p70S6K and rpS6 in response to resistance exercise. However, AME did not increase muscle protein synthesis (MPS) after resistance exercise. AME did not affect the expression of any of the mediators of protein degradation, with the exception of MAFbx. CONCLUSIONS:Dietary AME enhanced mTORC1 activation in response to resistance exercise without increasing MPS. Moreover, it neither accelerated muscle protein degradation nor otherwise negatively affected protein metabolism. Further study is needed to clarify the effect of the combination of AME and chronic resistance training on muscle hypertrophy.

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Dataset Information

Activated protein synthesis and suppressed protein breakdown signaling in skeletal muscle of critically ill patients.

Background

Methodology/principal findings

Conclusions/significance

Publications

Activated protein synthesis and suppressed protein breakdown signaling in skeletal muscle of critically ill patients.

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