Protein Turnover in Skeletal Muscle. II. The Effect of Starvation and a Protein-Free Diet on the Synthesis and Catabolism of Skeletal Muscle Proteins in Comparison to Liver

1970 ◽  
Vol 39 (5) ◽  
pp. 591-603 ◽  
Author(s):  
D. J. Millward
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Protein Turnover ◽  
Muscle Protein ◽  
Myofibrillar Protein ◽  
Myofibrillar Proteins ◽  
Liver Protein ◽  
Muscle Proteins ◽  
Catabolic Rate ◽  
Protein Free Diet

1. Rates of synthesis and catabolism of liver and muscle sarcoplasmic and myofibrillar protein have been measured in young control, starved and protein (deprived) rats using [14C]Na2CO3 to label protein. 2. Half-lives for synthesis of 1·35, 2·8 and 7·2 days for liver, sarcoplasmic and myofibrillar proteins respectively were obtained, whilst half-lives for catabolism were 1·55, 3·6 and 15·6 days in each case in the control animals. 3. The protein free diet for 3 days caused a small decrease in the rate of synthesis of liver and muscle proteins. The catabolic rate of liver protein was increased by 20% whilst there was a smaller increase in the catabolic rate of myofibrillar proteins. 4. Starvation for 3 days caused a 20% reduction in the rate of liver protein synthesis whilst there were greater reductions in muscle protein synthesis. The catabolic rate of liver protein was only slightly increased whereas there was a 75% increase in the rate of myofibrillar protein breakdown. 5. The total amount of protein synthesis and catabolism in liver and the two muscle protein fractions over the first 3 days of the three regimes were calculated. Muscle protein turnover, in particular myofibrillar, was shown to be very sensitive to dietary protein and/or calorie deficiency. 6. These results are discussed in terms of the mobility and therefore importance of muscle protein metabolism in the economy of the whole animal.

Protein depletion and replenishment in mice: different roles of muscle and liver

1997 ◽  
Vol 273 (6) ◽  
pp. E1158-E1167 ◽  
Author(s):  
Oscar A. Scornik ◽  
Scott K. Howell ◽  
Violeta Botbol
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Gastrointestinal Tract ◽  
Protein Turnover ◽  
Muscle Protein ◽  
Acute Effects ◽  
Protein Loss ◽  
Protein Free Diet ◽  
Exogenous Supply

Fully grown male CD-1 mice, fed a protein-free diet for 3 days, received 1 g of starch with or without 300 mg casein by intragastric intubation. We surveyed the acute effects of these nutrients on protein synthesis in all tissues (by extrapolating to infinity the incorporation of radioactive leucine after its injection in massive doses) and protein degradation in skeletal muscle and liver (by the accumulation of bestatin-induced peptide intermediates). Muscle proteolysis was the major source of N during depletion. Compared with postabsorptive animals, starch suppressed muscle protein loss (synthesis +21%, degradation −24%, P < 0.01) and stimulated hepatic proteolysis (degradation +28%, P < 0.01). Addition of casein to the starch was anabolic in liver (synthesis +41%, degradation −33%, P < 0.01), gastrointestinal tract, pancreas, and skin (synthesis +38, +69 and +38%, respectively, P < 0.01) but had no effect on muscle. Protein turnover proved uniquely sensitive to the dietary supply of carbohydrates in muscle and to the endogenous or exogenous supply of amino acids in liver.

Skeletal and cardiac muscle protein turnover during cold acclimation in young rats

2000 ◽  
Vol 278 (3) ◽  
pp. R705-R711 ◽  
Author(s):  
T. A. McAllister ◽  
J. R. Thompson ◽  
S. E. Samuels
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Cardiac Muscle ◽  
Cold Acclimation ◽  
Protein Turnover ◽  
Muscle Protein ◽  
Muscle Protein Turnover ◽  
Protein Mass ◽  
The Absolute

The effect of long-term cold exposure on skeletal and cardiac muscle protein turnover was investigated in young growing animals. Two groups of 36 male 28-day-old rats were maintained at either 5°C (cold) or 25°C (control). Rates of protein synthesis and degradation were measured in vivo on days 5, 10, 15, and 20. Protein mass by day 20 was ∼28% lower in skeletal muscle (gastrocnemius and soleus) and ∼24% higher in heart in cold compared with control rats ( P < 0.05). In skeletal muscle, the fractional rates of protein synthesis ( k syn) and degradation ( k deg) were not significantly different between cold and control rats, although k syn was lower (approximately −26%) in cold rats on day 5; consequent to the lower protein mass, the absolute rates of protein synthesis (approximately −21%; P < 0.05) and degradation (approximately −13%; P < 0.1) were lower in cold compared with control rats. In heart, overall, k syn(approximately +12%; P < 0.1) and k deg(approximately +22%; P < 0.05) were higher in cold compared with control rats; consequently, the absolute rates of synthesis (approximately +44%) and degradation (approximately +54%) were higher in cold compared with control rats ( P < 0.05). Plasma triiodothyronine concentration was higher ( P < 0.05) in cold compared with control rats. These data indicate that long-term cold acclimation in skeletal muscle is associated with the establishment of a new homeostasis in protein turnover with decreased protein mass and normal fractional rates of protein turnover. In heart, unlike skeletal muscle, rates of protein turnover did not appear to immediately return to normal as increased rates of protein turnover were observed beyond day 5. These data also indicate that increased rates of protein turnover in skeletal muscle are unlikely to contribute to increased metabolic heat production during cold acclimation.

scholarly journals Skeletal muscle and resistance exercise training; the role of protein synthesis in recovery and remodeling

2017 ◽  
Vol 122 (3) ◽  
pp. 541-548 ◽  
Author(s):  
Chris McGlory ◽  
Michaela C. Devries ◽  
Stuart M. Phillips
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Protein Turnover ◽  
Potential Role ◽  
Muscle Protein ◽  
Short Review ◽  
Translational Efficiency ◽  
Exercise Science ◽  
Resistance Exercise Training

Exercise results in the rapid remodeling of skeletal muscle. This process is underpinned by acute and chronic changes in both gene and protein synthesis. In this short review we provide a brief summary of our current understanding regarding how exercise influences these processes as well as the subsequent impact on muscle protein turnover and resultant shift in muscle phenotype. We explore concepts of ribosomal biogenesis and the potential role of increased translational capacity vs. translational efficiency in contributing to muscular hypertrophy. We also examine whether high-intensity sprinting-type exercise promotes changes in protein turnover that lead to hypertrophy or merely a change in mitochondrial content. Finally, we propose novel areas for future study that will fill existing knowledge gaps in the fields of translational research and exercise science.

Regulation of myofibrillar protein turnover during maturation in normal and undernourished rat pups

2000 ◽  
Vol 278 (4) ◽  
pp. R845-R854 ◽  
Author(s):  
Marta L. Fiorotto ◽  
Teresa A. Davis ◽  
Peter J. Reeds
Keyword(s):  
Protein Synthesis ◽  
Protein Turnover ◽  
Myofibrillar Protein ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Myofibrillar Proteins ◽  
Sarcoplasmic Proteins ◽  
Rat Pups ◽  
Sarcoplasmic Protein ◽  
Degradation Rates

The study tested the hypothesis that a higher rate of myofibrillar than sarcoplasmic protein synthesis is responsible for the rapid postdifferentiation accumulation of myofibrils and that an inadequate nutrient intake will compromise primarily myofibrillar protein synthesis. Myofibrillar (total and individual) and sarcoplasmic protein synthesis, accretion, and degradation rates were measured in vivo in well-nourished (C) rat pups at 6, 15, and 28 days of age and compared at 6 and 15 days of age with pups undernourished (UN) from birth. In 6-day-old C pups, a higher myofibrillar than sarcoplasmic protein synthesis rate accounted for the greater deposition of myofibrillar than sarcoplasmic proteins. The fractional synthesis rates of both protein compartments decreased with age, but to a greater degree for myofibrillar proteins (−54 vs. −42%). These decreases in synthesis rates were partially offset by reductions in degradation rates, and from 15 days, myofibrillar and sarcoplasmic proteins were deposited in constant proportion to one another. Undernutrition reduced both myofibrillar and sarcoplasmic protein synthesis rates, and the effect was greater at 6 (−25%) than 15 days (−15%). Decreases in their respective degradation rates minimized the effect of undernutrition on sarcoplasmic protein accretion from 4 to 8 days and on myofibrillar proteins from 13 to 17 days. Although these adaptations in protein turnover reduced overall growth of muscle mass, they mitigated the effects of undernutrition on the normal maturational changes in myofibrillar protein concentration.

scholarly journals Serum extracellular vesicle miR-203a-3p content is associated with skeletal muscle mass and protein turnover during disuse atrophy and regrowth

2020 ◽  
Vol 319 (2) ◽  
pp. C419-C431
Author(s):  
Douglas W. Van Pelt ◽  
Ivan J. Vechetti ◽  
Marcus M. Lawrence ◽  
Kathryn L. Van Pelt ◽  
Parth Patel ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Protein Turnover ◽  
Muscle Protein ◽  
Weight Bearing ◽  
Mirna Content ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Small noncoding microRNAs (miRNAs) are important regulators of skeletal muscle size, and circulating miRNAs within extracellular vesicles (EVs) may contribute to atrophy and its associated systemic effects. The purpose of this study was to understand how muscle atrophy and regrowth alter in vivo serum EV miRNA content. We also associated changes in serum EV miRNA with protein synthesis, protein degradation, and miRNA within muscle, kidney, and liver. We subjected adult (10 mo) F344/BN rats to three conditions: weight bearing (WB), hindlimb suspension (HS) for 7 days to induce muscle atrophy, and HS for 7 days followed by 7 days of reloading (HSR). Microarray analysis of EV miRNA content showed that the overall changes in serum EV miRNA were predicted to target major anabolic, catabolic, and mechanosensitive pathways. MiR-203a-3p was the only miRNA demonstrating substantial differences in HS EVs compared with WB. There was a limited association of EV miRNA content to the corresponding miRNA content within the muscle, kidney, or liver. Stepwise linear regression demonstrated that EV miR-203a-3p was correlated with muscle mass and muscle protein synthesis and degradation across all conditions. Finally, EV miR-203a-3p expression was significantly decreased in human subjects who underwent unilateral lower limb suspension (ULLS) to induce muscle atrophy. Altogether, we show that serum EV miR-203a-3p expression is related to skeletal muscle protein turnover and atrophy. We suggest that serum EV miR-203a-3p content may be a useful biomarker and future work should investigate whether serum EV miR-203a-3p content is mechanistically linked to protein synthesis and degradation.

scholarly journals The sedimentation of rat skeletal-muscle ribosomes. Effect of hydrocortisone, insulin and diet

1968 ◽  
Vol 106 (4) ◽  
pp. 913-919 ◽  
Author(s):  
V. R. Young ◽  
S. C. Chen ◽  
Jane Macdonald
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Sucrose Gradient ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Insulin Injection ◽  
Sedimentation Analysis ◽  
Rat Skeletal Muscle ◽  
Protein Free Diet ◽  
Post Mitochondrial Supernatant

1. The influence of hydrocortisone, insulin and diet on the size distribution of ribosomes in a post-mitochondrial supernatant prepared from rat skeletal muscle was studied by sedimentation analysis with a linear 15–40% (w/v) sucrose gradient. 2. Within 4hr. after the injection of 5mg. of hydrocortisone to well-nourished rats, a decrease in the yield per g. of muscle and proportion of total RNA due to polyribosomes was observed. Similar results were obtained in rats given a protein-free diet for 3 days before administration of the hormone. 3. Insulin injection increased the yield and proportion of polyribosomes within 2hr. and decreased the proportion of the lighter ribosomal aggregates. Similar results were noted in rats given a protein-free diet for 3 days before injection. A protein-free diet given for 3 days decreased the yield and proportion of polyribosomes. Insulin did not increase the yield of polyribosomes if rats were starved for 52hr. before injection, but decreased the yield and proportion of the lighter ribosome species. 4. A 52hr. period of starvation or 2,4-dinitrophenol (15mg./kg. body wt.) given 1hr. before the rats were killed resulted in a decreased yield and proportion of polyribosomes, and, within 6hr. of re-feeding the rats with protein-free diets, an increased concentration of polyribosomes was noted. 5. The effects of a protein-free diet, hydrocortisone and insulin on the sedimentation of muscle ribosomes were found to be in accord with their net effects on muscle protein synthesis.

Skeletal muscle, liver and wool protein synthesis by sheep infected by the nematode Trichostrongylus colubriformis

1975 ◽  
Vol 26 (6) ◽  
pp. 1063
Author(s):  
LEA Symons ◽  
WO Jones
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Liver Protein ◽  
Trichostrongylus Colubriformis ◽  
Intestinal Nematode ◽  
Skeletal Muscle Proteins

Incorporation of radioisotopically labelled L-leucine into skeletal muscle proteins was measured in vivo and in vitro, and into liver proteins in vivo in three groups of sheep: (1) infected by Trichostrongylus colubriformis, (2) uninfected, pair-fed with the infected animals, (3) uninfected, fed ad lib. Incorporation of [14C]L-leucine by an homogenate of wool follicles from infected and uninfected sheep was also measured. Incorporation of leucine by muscle, and hence muscle protein synthesis, was equally depressed in the anorexic infected sheep losing weight, and in pair-fed animals, whether measured in vivo or in vitro, or expressed in terms of either RNA or DNA. Incorporation into protein was elevated equally in vivo in the livers of the infected and pair-fed sheep when expressed in terms of content of tissue nitrogen, but not in terms of cither nucleic acid. Incorporation by the wool follicular homogenate was appreciably depressed by the infection and is consistent with the poor wool growth in nematode infections. These results show that the same depression of skeletal muscle and, possibly, elevation of liver protein synthesis occur in a ruminant as were reported earlier for laboratory monogastric animals with intestinal nematode infections. Pair-feeding uninfected animals in both this and the earlier experiments emphasized the importance of anorexia as a major cause of these effects on protein synthesis. The importance of these effects upon production is discussed briefly.

Modulation of muscle protein synthesis by insulin is maintained during neonatal endotoxemia

2006 ◽  
Vol 291 (1) ◽  
pp. E159-E166 ◽  
Author(s):  
Renan A. Orellana ◽  
Pamela M. J. O'Connor ◽  
Jill A. Bush ◽  
Agus Suryawan ◽  
M. Carole Thivierge ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Gastrocnemius Muscle ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Liver Protein ◽  
Fasting Insulin ◽  
Neonatal Pigs

Sepsis promotes insulin resistance and reduces protein synthesis in skeletal muscle of adults. The effect of sepsis on insulin-stimulated muscle protein synthesis has not been determined in neonates, a highly anabolic population that is uniquely sensitive to insulin. Overnight fasted neonatal pigs were infused for 8 h with endotoxin [lipopolysaccharide (LPS), 0 and 10 μg·kg−1·h−1]. Glucose and amino acids were maintained at fasting levels, insulin was clamped at either fasting or fed (2 or 10 μU/ml) levels, and fractional protein synthesis rates were determined at the end of the infusion. LPS infusion induced a septic-like state, as indicated by a sustained elevation in body temperature, heart rate, and cortisol. At fasting insulin levels, LPS reduced fractional protein synthesis rates in gastrocnemius muscle (−26%) but had no effect on the masseter and heart. By contrast, LPS stimulated liver protein synthesis (+28%). Increasing insulin to fed levels accelerated protein synthesis rates in gastrocnemius (controls by +38%, LPS by +60%), masseter (controls by +50%, LPS by +43%), heart (controls by +34%, LPS by +40%), and diaphragm (controls by +54%, LPS by +29%), and the response to insulin was similar in LPS and controls. Insulin did not alter protein synthesis in liver, kidney, or jejunum in either group. These findings suggest that acute endotoxemia lowers basal fasting muscle protein synthesis in neonates but does not alter the response of protein synthesis to insulin.

scholarly journals Proteome-wide muscle protein fractional synthesis rates predict muscle mass gain in response to a selective androgen receptor modulator in rats

2016 ◽  
Vol 310 (6) ◽  
pp. E405-E417 ◽  
Author(s):  
Mahalakshmi Shankaran ◽  
Todd W. Shearer ◽  
Stephen A. Stimpson ◽  
Scott M. Turner ◽  
Chelsea King ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Androgen Receptor ◽  
Muscle Mass ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Synthesis Rate ◽  
Muscle Proteins ◽  
Receptor Modulator ◽  
Fractional Synthesis

Biomarkers of muscle protein synthesis rate could provide early data demonstrating anabolic efficacy for treating muscle-wasting conditions. Androgenic therapies have been shown to increase muscle mass primarily by increasing the rate of muscle protein synthesis. We hypothesized that the synthesis rate of large numbers of individual muscle proteins could serve as early response biomarkers and potentially treatment-specific signaling for predicting the effect of anabolic treatments on muscle mass. Utilizing selective androgen receptor modulator (SARM) treatment in the ovariectomized (OVX) rat, we applied an unbiased, dynamic proteomics approach to measure the fractional synthesis rates (FSR) of 167–201 individual skeletal muscle proteins in triceps, EDL, and soleus. OVX rats treated with a SARM molecule (GSK212A at 0.1, 0.3, or 1 mg/kg) for 10 or 28 days showed significant, dose-related increases in body weight, lean body mass, and individual triceps but not EDL or soleus weights. Thirty-four out of the 94 proteins measured from the triceps of all rats exhibited a significant, dose-related increase in FSR after 10 days of SARM treatment. For several cytoplasmic proteins, including carbonic anhydrase 3, creatine kinase M-type (CK-M), pyruvate kinase, and aldolase-A, a change in 10-day FSR was strongly correlated ( r2 = 0.90–0.99) to the 28-day change in lean body mass and triceps weight gains, suggesting a noninvasive measurement of SARM effects. In summary, FSR of multiple muscle proteins measured by dynamics of moderate- to high-abundance proteins provides early biomarkers of the anabolic response of skeletal muscle to SARM.

scholarly journals Skeletal Muscle Recovery from Disuse Atrophy: Protein Turnover Signaling and Strategies for Accelerating Muscle Regrowth

2020 ◽  
Vol 21 (21) ◽  
pp. 7940
Author(s):  
Timur M. Mirzoev
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Mass ◽  
Mechanical Loading ◽  
Protein Turnover ◽  
Skeletal Muscle Mass ◽  
Molecular Mechanisms ◽  
Muscle Protein ◽  
Muscle Recovery ◽  
Mechanical Unloading

Skeletal muscle fibers have a unique capacity to adjust their metabolism and phenotype in response to alternations in mechanical loading. Indeed, chronic mechanical loading leads to an increase in skeletal muscle mass, while prolonged mechanical unloading results in a significant decrease in muscle mass (muscle atrophy). The maintenance of skeletal muscle mass is dependent on the balance between rates of muscle protein synthesis and breakdown. While molecular mechanisms regulating protein synthesis during mechanical unloading have been relatively well studied, signaling events implicated in protein turnover during skeletal muscle recovery from unloading are poorly defined. A better understanding of the molecular events that underpin muscle mass recovery following disuse-induced atrophy is of significant importance for both clinical and space medicine. This review focuses on the molecular mechanisms that may be involved in the activation of protein synthesis and subsequent restoration of muscle mass after a period of mechanical unloading. In addition, the efficiency of strategies proposed to improve muscle protein gain during recovery is also discussed.

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