Mechanosensitive pathways controlling translation regulatory processes in skeletal muscle and implications for adaptation

2019 ◽  
Vol 127 (2) ◽  
pp. 608-618 ◽  
Author(s):  
Tyler J. Kirby
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Protein Metabolism ◽  
Mechanical Load ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Muscle Physiology ◽  
Translation Efficiency ◽  
Ribosomal Biogenesis ◽  
Mechanical Signals

The ability of myofibers to sense and respond appropriately to mechanical signals is one of the primary determinants of the skeletal muscle phenotype. In response to a change in mechanical load, muscle cells alter their protein metabolism, primarily through the regulation of protein synthesis rate. Protein synthesis rates are determined by both translation efficiency and translational capacity within the muscle. Translational capacity is strongly determined by the ribosome content of the muscle; thus the regulation of ribosomal biogenesis by mechanical inputs has been an area of recent interest. Despite the clear association between mechanical signals and changes in protein metabolism, the molecular pathways that link these events are still not fully elucidated. This review focuses on recent studies looking at how mechanosignaling impacts translational events. The role of impaired mechanotransduction in aging is discussed, as is the connection between age-dependent signaling defects and compromised ribosomal biogenesis during mechanical overload. Finally, emerging evidence suggests that the nucleus can act as a mechanosensitive element and that this mode of mechanotransduction may have an important role in skeletal muscle physiology and adaptation.

Total and net muscle protein breakdown in infection determined by amino acid effluxes

1990 ◽  
Vol 258 (5) ◽  
pp. E856-E863 ◽  
Author(s):  
J. Sjolin ◽  
H. Stjernstrom ◽  
G. Friman ◽  
J. Larsson ◽  
J. Wahren
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Urinary Excretion ◽  
Protein Degradation ◽  
Muscle Protein ◽  
Human Infection ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Skeletal Muscle Protein ◽  
Mild Disease

The present investigation was undertaken to study whether, in human infection of varying severity, peripheral 3-methylhistidine efflux and urinary excretion are associated with net protein degradation and to estimate the protein synthesis rate from the combined effluxes of 3-methylhistidine, tyrosine, and phenylalanine. Quadruplicate femoral arteriovenous differences of 3-methylhistidine, tyrosine, and phenylalanine were multiplied by leg plasma flow in 15 infected patients. Leg effluxes for 3-methylhistidine, tyrosine, and phenylalanine were -0.074 +/- 0.011, -2.57 +/- 0.43, and -3.17 +/- 0.44 mumol/min, respectively. There was a significant linear relationship (P less than 0.01) between the effluxes of tyrosine and phenylalanine and the efflux and urinary excretion of 3-methylhistidine. A significant release of tyrosine and phenylalanine was observed in patients studied at the 3-methylhistidine level seen in normal healthy subjects. It is concluded that in infection 1) there is an increased breakdown of skeletal muscle protein and a reduced rate of protein synthesis, with the latter being relatively more important in patients with mild disease; and 2) urinary 3-methylhistidine excretion is associated with net skeletal muscle protein degradation for the patient group studied.

Impact of surgical trauma on human skeletal muscle protein synthesis

2004 ◽  
Vol 107 (6) ◽  
pp. 601-607 ◽  
Author(s):  
Inga TJÄDER ◽  
Pia ESSEN ◽  
Peter J. GARLICK ◽  
Margaret A. McMNURLAN ◽  
Olav ROOYACKERS ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Pilot Study ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Major Surgery ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Surgical Trauma ◽  
Minor Surgery

Muscle protein catabolism is a considerable clinical problem following surgery. However, the impact of surgical trauma on muscle protein synthesis is not well characterized. In this pilot study, we therefore investigated whether the severity of surgical trauma is related to a decrease in muscle protein synthesis rate in humans. Metabolically healthy patients (n=28) were included in the study. Eight of the patients were day-care patients undergoing minor breast surgery (defined as minor surgery). The other 20 patients were subjected to major abdominal surgery and were therefore scheduled to stay overnight in the recovery room during the first postoperative night (defined as major surgery). Protein FSRs (fractional synthesis rates) in skeletal muscle were determined during a measurement period of 90 min before surgery and immediately after termination of surgery. FSR in skeletal muscle of the minor surgery patients was 1.72±0.25%/24 h before surgery and 1.67±0.29%/24 h after surgery (P=0.68). In the major surgery group, FSR was 1.62±0.30%/24 h before surgery and 1.57±0.40%/24 h (P=0.59) immediately following surgery. The observations made in this pilot study could not confirm a size-related decrease in muscle protein synthesis immediately following minor and major surgery. This finding is discussed in relation to confounders, postoperative course and to muscle protein degradation. The shortage of knowledge in this field is emphasized.

Polyadenylated RNA, actin mRNA, and myosin heavy chain mRNA in young and old human skeletal muscle

1996 ◽  
Vol 270 (2) ◽  
pp. E224-E229 ◽  
Author(s):  
S. Welle ◽  
K. Bhatt ◽  
C. Thornton
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Human Skeletal Muscle ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Type I ◽  
Polyadenylated Rna ◽  
Actin Mrna

The myofibrillar protein synthesis rate in old human skeletal muscle is slower than that in young adult muscle. To examine whether this difference in protein synthesis rate is explained by reduced availability of the mRNAs that encode the most abundant myofibrillar proteins, we determined relative hybridization signals from probes for actin mRNA, myosin heavy chain mRNA, and total polyadenylated RNA in vastus lateralis muscle biopsies taken from young (22- to 31-yr-old) and old (61- to 74-yr-old) human subjects. The mean fractional rate of myofibrillar synthesis was 38% slower in the older muscles, as determined by incorporation of a stable isotope tracer. Total actin and myosin heavy chain mRNAs, and polyadenylated RNA, were determined using slot-blot assays. Isoform-specific determinations of alpha-actin mRNA, type I myosin heavy chain mRNA, and type IIa myosin heavy chain mRNA were done with ribonuclease protection assays. Hybridization signals were expressed relative to tissue DNA content. There was no difference between age groups in total polyadenylated RNA or in any of the specific mRNAs. We conclude that the slower myofibrillar synthesis rate in older muscle is not caused by reduced mRNA availability.

Effect of spaceflight on human protein metabolism

1993 ◽  
Vol 264 (5) ◽  
pp. E824-E828 ◽  
Author(s):  
T. P. Stein ◽  
M. J. Leskiw ◽  
M. D. Schluter
Keyword(s):  
Protein Synthesis ◽  
Nitrogen Balance ◽  
Protein Metabolism ◽  
Space Shuttle ◽  
Single Pulse ◽  
Whole Body ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Body Protein ◽  
Space Shuttle Columbia

Nitrogen balance and the whole body protein synthesis rate were measured before, during, and after a 9.5-day spaceflight mission on the space shuttle Columbia. Protein synthesis was measured by the single-pulse [15N]glycine method. Determinations were made 56, 26, and 18 days preflight, on flight days 2 and 8, and on days 0, 6, 14, and 45 postflight. We conclude that nitrogen balance was decreased during spaceflight. The decrease in nitrogen balance was greatest on the 1st day when food intake was reduced and again toward the end of the mission. An approximately 30% increase in protein synthesis above the preflight baseline was found for flight day 8 for all 6 subjects (P < 0.05), indicating that the astronauts showed a stress response to spaceflight.

Early change in skeletal muscle protein synthesis after limb immobilization of rats

1979 ◽  
Vol 47 (5) ◽  
pp. 974-977 ◽  
Author(s):  
F. W. Booth ◽  
M. J. Seider
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Control Level ◽  
Constant Infusion ◽  
Initial Time ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Limb Immobilization

The atrophy of skeletal muscle accruing from disuse, or limb immobilization, is caused by a decreased rate of protein synthesis and an increased rate of protein degradation. Currently, little information is available regarding the initial time of the decline in the rate of protein synthesis in skeletal muscle. The purpose of the present study was to determine, as precisely as possible, the time at which the protein synthesis rate first begins to decline in skeletal muscle, utilizing immobilized limbs of rats for a model. A constant-infusion technique employing [14C]tyrosine was used to estimate protein synthesis rates. During the first 6 h of immobilization, a significant decline of 37% in the fractional rate of protein synthesis from the control level of 5.7%/day was observed. These results suggest that very early changes are occurring in molecular events that regulate protein synthesis in disused or immobilized skeletal muscle.

Effects of low-dose leucine supplementation on gastrocnemius muscle mitochondrial content and protein turnover in tumor-bearing mice

2019 ◽  
Vol 44 (9) ◽  
pp. 997-1004 ◽  
Author(s):  
Harold W. Lee ◽  
Ella Baker ◽  
Kevin M. Lee ◽  
Aaron M. Persinger ◽  
William Hawkins ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Mitochondrial Biogenesis ◽  
Protein Turnover ◽  
C2c12 Myotubes ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Mitochondrial Content ◽  
Leucine Supplementation ◽  
Tumor Bearing

Many forms of cancer are associated with loss of lean body mass, commonly attributed to decreased protein synthesis and stimulation of proteolytic pathways within the skeletal muscle. Leucine has been shown to improve protein synthesis, insulin signaling, and mitochondrial biogenesis, which are key signaling pathways influenced by tumor signaling. The purpose of this study was to examine the effects of leucine supplementation on mitochondrial biogenesis and protein turnover in tumor-bearing mice. Twenty male C57BL/6 mice were divided into 4 groups (n = 5): Chow, leucine (Leu), Lewis lung carcinoma (LLC) implant, and LLC+Leu. At 9–10 weeks of age, mice were inoculated and supplemented with 5% leucine (w/w) in the diet. C2C12 myotubes were treated with 2.5 mmol/L leucine and 25% LLC conditioned media to further elucidate the direct influence of the tumor and leucine on the muscle. Measures of protein synthesis, mitochondrial biogenesis, and inflammation in the gastrocnemius were assessed via Western blot analysis. Gastrocnemius mass was decreased in LLC+Leu relative to LLC (p = 0.040). Relative protein synthesis rate was decreased in LLC mice (p = 0.001). No change in protein synthesis was observed in myotubes. Phosphorylation of STAT3 was decreased in the Leu group relative to the control in both mice (p = 0.019) and myotubes (p = 0.02), but did not significantly attenuate the inflammatory effect of LLC implantation (p = 0.619). LLC decreased markers of mitochondrial content; however, PGC-1α was increased in LLC+Leu relative to LLC (p = 0.001). While leucine supplementation was unable to preserve protein synthesis or mitochondrial content associated with LLC implantation, it was able to increase mitochondrial biogenesis signaling. Novelty This study provides novel insights on the effect of leucine supplementation on mitochondrial biogenesis and protein turnover in tumor-bearing mice. Leucine increased signaling for mitochondrial biogenesis in the skeletal muscle. Leucine supplementation decreased inflammatory signaling in skeletal muscle.

Glucocorticoid-induced skeletal muscle atrophy in vitro is attenuated by mechanical stimulation

1992 ◽  
Vol 262 (6) ◽  
pp. C1471-C1477 ◽  
Author(s):  
J. A. Chromiak ◽  
H. H. Vandenburgh
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Protein Content ◽  
Total Protein ◽  
Weight Lifting ◽  
Mechanical Activity ◽  
Synthesis Rate ◽  
Protein Synthesis Rate

Glucocorticoids induce rapid atrophy of fast skeletal myofibers in vivo, and either weight lifting or endurance exercise reduces this atrophy by unknown mechanisms. We examined the effects of the synthetic glucocorticoid dexamethasone (Dex) on protein turnover in tissue-cultured avian fast skeletal myofibers and determined whether repetitive mechanical stretch altered the myofiber response to Dex. In static cultures after 3-5 days, 10(-8) M Dex decreased total protein content 42-74%, total protein synthesis rates 38-56%, mean myofiber diameter 35%, myosin heavy chain (MHC) content 86%, MHC synthesis rate 44%, and fibronectin synthesis rate 29%. Repetitive 10% stretch-relaxations of the cultured myofibers for 60 s every 5 min for 3-4 days prevented 52% of the Dex-induced decrease in protein content, 42% of the decrease in total protein synthesis rate, 77% of the decrease in MHC content, 42% of the decrease in MHC synthesis rate, and 67% of the decrease in fibronectin synthesis rate. This in vitro model system will complement in vivo studies in understanding the mechanism by which mechanical activity and glucocorticoids interact to regulate skeletal muscle growth.

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