scholarly journals The influence of restraint and infusion on rates of muscle protein synthesis in the rat. Effect of altered respiratory function

1988 ◽  
Vol 251 (2) ◽  
pp. 577-580 ◽  
Author(s):  
V R Preedy ◽  
P J Garlick
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Respiratory Acidosis ◽  
Male Rats ◽  
Gas Measurements ◽  
Nutrient Administration ◽  
Fasted Rats ◽  
Infusion Period

1. Male rats (110-140 g body wt.) were restrained by a standard laboratory technique, by wrapping in a linen towel, and subjected to a constant intravenous infusion of saline (0.15 M-NaCl) for periods of 1 or 6 h. Fractional rates of protein synthesis (ks, %/day) were estimated at the start and at the end of the infusion period, by injection of a large concentration of [3H]phenylalanine. 2. In fed and overnight-fasted rats, restraint and infusion of saline for 1 and 6 h decreased ks in skeletal muscle by 15-20% and 30-35% respectively. Plasma glucose, insulin, glucagon and corticosterone concentrations in restrained and infused rats were not characteristic of immobilization stress. 3. Restrained rats responded to nutrient administration; ks in skeletal muscle increased by 35-40% after infusion of a mixture of amino acids and glucose for 1 or 6 h, as compared with saline-infused rats. 4. Restraint and infusion for 1 or 6 h did not overtly decrease ks and kRNA (protein synthesis per unit of RNA) in hypoxaemia-sensitive tissues, such as heart and liver. Restraint and infusion in an open cage, or in a cloth of open weave, did not decrease ks in muscle after 1 h. Blood gas measurements showed that rats restrained in a linen cloth were hypercapnic and acidotic compared with rats in an open cage. 5. It was concluded that respiratory acidosis, rather than hypoxia, resulting from restraint in a linen cloth decreases muscle protein synthesis.

Availability of eIF4E regulates skeletal muscle protein synthesis during recovery from exercise

1998 ◽  
Vol 274 (2) ◽  
pp. C406-C414 ◽  
Author(s):  
T. A. Gautsch ◽  
J. C. Anthony ◽  
S. R. Kimball ◽  
G. L. Paul ◽  
D. K. Layman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Plasma Concentrations ◽  
Male Rats ◽  
Skeletal Muscle Protein ◽  
Fourfold Increase ◽  
Skeletal Muscle Protein Synthesis ◽  
Translational Inhibitor

We examined the association of the mRNA cap binding protein eIF4E with the translational inhibitor 4E-BP1 in the acute modulation of skeletal muscle protein synthesis during recovery from exercise. Fasting male rats were run on a treadmill for 2 h at 26 m/min and were realimented immediately after exercise with either saline, a carbohydrate-only meal, or a nutritionally complete meal (54.5% carbohydrate, 14% protein, and 31.5% fat). Exercised animals and nonexercised controls were studied 1 h postexercise. Muscle protein synthesis decreased 26% after exercise and was associated with a fourfold increase in the amount of eIF4E present in the inactive eIF4E ⋅ 4E-BP1 complex and a concomitant 71% decrease in the association of eIF4E with eIF4G. Refeeding the complete meal, but not the carbohydrate meal, increased muscle protein synthesis equal to controls, despite similar plasma concentrations of insulin. Additionally, eIF4E ⋅ 4E-BP1 association was inversely related and eIF4E ⋅ eIF4G association was positively correlated to muscle protein synthesis. This study demonstrates that recovery of muscle protein synthesis after exercise is related to the availability of eIF4E for 48S ribosomal complex formation, and postexercise meal composition influences recovery via modulation of translation initiation.

Skeletal muscle protein synthesis and the abundance of the mRNA translation initiation repressor PDCD4 are inversely regulated by fasting and refeeding in rats

2011 ◽  
Vol 300 (6) ◽  
pp. E986-E992 ◽  
Author(s):  
Sana Zargar ◽  
Tracy S. Moreira ◽  
Helena Samimi-Seisan ◽  
Senthure Jeganathan ◽  
Dhanshri Kakade ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mammalian Target Of Rapamycin ◽  
Mrna Translation ◽  
Male Rats ◽  
Skeletal Muscle Protein ◽  
Programmed Cell Death 4 ◽  
In Cells

Optimal skeletal muscle mass is vital to human health, because defects in muscle protein metabolism underlie or exacerbate human diseases. The mammalian target of rapamycin complex 1 is critical in the regulation of mRNA translation and protein synthesis. These functions are mediated in part by the ribosomal protein S6 kinase 1 (S6K1) through mechanisms that are poorly understood. The tumor suppressor programmed cell death 4 (PDCD4) has been identified as a novel substrate of S6K1. Here, we examined 1) the expression of PDCD4 in skeletal muscle and 2) its regulation by feed deprivation (FD) and refeeding. Male rats (∼100 g; n = 6) were subjected to FD for 48 h; some rats were refed for 2 h. FD suppressed muscle fractional rates of protein synthesis and Ser67 phosphorylation of PDCD4 (−50%) but increased PDCD4 abundance ( P < 0.05); refeeding reversed these changes ( P < 0.05). Consistent with these effects being regulated by S6K1, activation of this kinase was suppressed by FD (−91%, P < 0.05) but was increased by refeeding. Gavaging rats subjected to FD with a mixture of amino acids partially restored muscle fractional rates of protein synthesis and reduced PDCD4 abundance relative to FD. Finally, when myoblasts were grown in amino acid- and serum-free medium, phenylalanine incorporation into proteins in cells depleted of PDCD4 more than doubled the values in cells with a normal level of PDCD4 ( P < 0.0001). Thus feeding stimulates fractional protein synthesis in skeletal muscle in parallel with the reduction of the abundance of this mRNA translation inhibitor.

scholarly journals The effect of insulin infusion and food intake on muscle protein synthesis in postabsorptive rats

1983 ◽  
Vol 210 (3) ◽  
pp. 669-676 ◽  
Author(s):  
P J Garlick ◽  
M Fern ◽  
V R Preedy
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Food Intake ◽  
Plasma Insulin ◽  
Insulin Infusion ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Young Male ◽  
Male Rats ◽  
Significant Stimulation

1. Insulin was infused into young male rats in the postabsorptive state. Rates of protein synthesis in skeletal muscle were determined during the final 10 min of infusion from the incorporation of label into protein after intravenous injection of a massive dose of [3H]phenylalanine. Rates of synthesis were not altered during the first 10 min of insulin infusion, but were increased significantly between 10 and 60 min. 2. Rats were infused with different amounts of insulin for 30 min. When concentrations were increased from 10 to 40 microunits/ml of plasma there was no change in muscle protein synthesis, but concentrations higher than 70 microunits/ml caused a significant stimulation. Concentrations below 10 microunits/ml, obtained by infusion of anti-insulin serum, did not depress synthesis below that found in the postabsorptive rat. 3. Infusion of glucose for 30 or 60 min led to an increase in plasma insulin to 40 microunits/ml, but this also failed to stimulate muscle protein synthesis. 4. Rates of synthesis in postabsorptive rats, even when stimulated maximally by insulin, were not so high as those in fed rats or in postabsorptive rats refed for 60 min. However, in fed and refed rats insulin concentrations were below that required to stimulate synthesis in postabsorptive animals. Despite this, infusion of large amounts of insulin into fed rats did not increase synthesis further. 5. The sensitivity of plasma glucose to insulin infusion was different from that of protein synthesis. A decrease in glucose concentration preceded the increase in synthesis and occurred at lower insulin concentrations. 6. It is concluded that changes in circulating insulin may have been partly responsible for the increase in muscle protein synthesis brought about by feeding, but that other factors must also play a part.

scholarly journals Castration differentially alters basal and leucine-stimulated tissue protein synthesis in skeletal muscle and adipose tissue

2009 ◽  
Vol 297 (5) ◽  
pp. E1222-E1232 ◽  
Author(s):  
Qianning Jiao ◽  
Anne M. Pruznak ◽  
Danuta Huber ◽  
Thomas C. Vary ◽  
Charles H. Lang
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Adipose Tissue ◽  
Muscle Protein ◽  
Body Weight Gain ◽  
Muscle Protein Synthesis ◽  
Male Rats ◽  
Whole Body ◽  
Fat Depot

Reduced testosterone as a result of catabolic illness or aging is associated with loss of muscle and increased adiposity. We hypothesized that these changes in body composition occur because of altered rates of protein synthesis under basal and nutrient-stimulated conditions that are tissue specific. The present study investigated such mechanisms in castrated male rats (75% reduction in testosterone) with demonstrated glucose intolerance. Over 9 wk, castration impaired body weight gain, which resulted from a reduced lean body mass and preferential sparing of adipose tissue. Castration decreased gastrocnemius weight, but this atrophy was not associated with reduced basal muscle protein synthesis or differences in plasma IGF-I, insulin, or individual amino acids. However, oral leucine failed to normally stimulate muscle protein synthesis in castrated rats. In addition, castration-induced atrophy was associated with increased 3-methylhistidine excretion and in vitro-determined ubiquitin proteasome activity in skeletal muscle, changes that were associated with decreased atrogin-1 or MuRF1 mRNA expression. Castration decreased heart and kidney weight without reducing protein synthesis and did not alter either cardiac output or glomerular filtration. In contradistinction, the weight of the retroperitoneal fat depot was increased in castrated rats. This increase was associated with an elevated rate of basal protein synthesis, which was unresponsive to leucine stimulation. Castration also decreased whole body fat oxidation. Castration increased TNFα, IL-1α, IL-6, and NOS2 mRNA in fat but not muscle. In summary, the castration-induced muscle wasting results from an increased muscle protein breakdown and the inability of leucine to stimulate protein synthesis, whereas the expansion of the retroperitoneal fat depot appears mediated in part by an increased basal rate of protein synthesis-associated increased inflammatory cytokine expression.

scholarly journals Acute alcohol intoxication increases atrogin-1 and MuRF1 mRNA without increasing proteolysis in skeletal muscle

2008 ◽  
Vol 294 (6) ◽  
pp. R1777-R1789 ◽  
Author(s):  
Thomas C. Vary ◽  
Robert A. Frost ◽  
Charles H. Lang
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Protein Degradation ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Alcohol Intoxication ◽  
Male Rats ◽  
Acute Alcohol Intoxication ◽  
E3 Ligases

Acute alcohol intoxication decreases muscle protein synthesis, but there is a paucity of data on the ability of alcohol to regulate muscle protein degradation. Furthermore, various types of atrophic stimuli appear to regulate ubiquitin-proteasome-dependent proteolysis by increasing the muscle-specific E3 ligases atrogin-1 and MuRF1 (i.e., “atrogenes”). Therefore, the present study was designed to test the hypothesis that acute alcohol intoxication increases atrogene expression leading to an elevated rate of muscle protein breakdown. In male rats, the intraperitoneal injection of alcohol dose- and time-dependently increased atrogin-1 and MuRF1 mRNA in gastrocnemius, the latter of which was most pronounced. A comparable change was absent in the soleus and heart. The ability of in vivo-administered ethanol to increase atrogene expression was independent of the route of alcohol administration (intraperitoneal vs. oral), as well as of nutritional status (fed vs. fasted) and gender (male vs. female). The increase in atrogin-1 and MuRF1 was independent of alcohol metabolism, and the overproduction of endogenous glucocorticoids and could not be prevented by maintaining the circulating concentration of insulin-like growth factor-I. Despite marked changes in atrogene expression, acute alcohol in vivo did not alter the release of either 3-methylhistidine (MH) or tyrosine from the isolated perfused hindlimb, suggesting that the rate of muscle proteolysis remains unchanged. Moreover, alcohol did not increase the directly determined rate of protein degradation in isolated epitrochlearis muscles or cultured myocytes. Finally, no increase in atrogene expression or 3-MH release was detected in muscle from rats fed an alcohol-containing diet. Our results indicate that although acute alcohol intoxication increases atrogin-1 and MuRF1 mRNA preferentially in fast-twitch skeletal muscle, this change was not associated with increased rates of muscle proteolysis. Therefore, the loss of muscle mass/protein in response to chronic alcohol abuse appears to result primarily from a decrement in muscle protein synthesis, not an increase in degradation.

Adaptation to prolonged starvation in the rat: curtailment of skeletal muscle proteolysis

1981 ◽  
Vol 241 (4) ◽  
pp. E321-E327 ◽  
Author(s):  
M. N. Goodman ◽  
M. A. McElaney ◽  
N. B. Ruderman
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Early Event ◽  
Body Protein ◽  
Fed State ◽  
Prolonged Starvation ◽  
Obese Rats ◽  
Old Rats

Previous studies have established that 16-wk-old nonobese and obese rats conserve body protein during prolonged starvation. To determine the basis for this, protein synthesis and degradation in skeletal muscle were evaluated in the isolated perfused hindquarters of these rats, in the fed state and when starved for 2, 5, 10, and 11 days. Rats aged 4 and 8 wk were used as a comparison. The results indicate that the response to starvation depends on several factors: the age of the rat, its degree of adiposity, and the duration of the fast. An early event in starvation was a decline in muscle protein synthesis. This occurred in all groups, albeit this reduction occurred more slowly in the older rats. A later response to starvation was an increase in muscle proteolysis. This occurred between 2 and 5 days in the 8-wk-old rats. In 16-wk-old rats it did not occur until between 5 and 10 days, and it was preceded by a period of decreased proteolysis. In 16-wk-old obese rats, a decrease in proteolysis persisted for upwards of 10 days and the secondary increase was not noted during the period of study. The data suggest that the ability of older and more obese rats to conserve body protein during starvation is due, in part, to a curtailment of muscle proteolysis. This adaptation seems to correlate with the availability of lipid fuels.

scholarly journals Resistance exercise maintains skeletal muscle protein synthesis during bed rest

1997 ◽  
Vol 82 (3) ◽  
pp. 807-810 ◽  
Author(s):  
Arny A. Ferrando ◽  
Kevin D. Tipton ◽  
Marcas M. Bamman ◽  
Robert R. Wolfe
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Resistance Training ◽  
Resistance Exercise ◽  
Lean Body Mass ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Bed Rest ◽  
Skeletal Muscle Protein ◽  
Skeletal Muscle Protein Synthesis

Ferrando, Arny A., Kevin D. Tipton, Marcas M. Bamman, and Robert R. Wolfe. Resistance exercise maintains skeletal muscle protein synthesis during bed rest. J. Appl. Physiol. 82(3): 807–810, 1997.—Spaceflight results in a loss of lean body mass and muscular strength. A ground-based model for microgravity, bed rest, results in a loss of lean body mass due to a decrease in muscle protein synthesis (MPS). Resistance training is suggested as a proposed countermeasure for spaceflight-induced atrophy because it is known to increase both MPS and skeletal muscle strength. We therefore hypothesized that scheduled resistance training throughout bed rest would ameliorate the decrease in MPS. Two groups of healthy volunteers were studied during 14 days of simulated microgravity. One group adhered to strict bed rest (BR; n = 5), whereas a second group engaged in leg resistance exercise every other day throughout bed rest (BREx; n = 6). MPS was determined directly by the incorporation of infusedl-[ ring-13C6]phenylalanine into vastus lateralis protein. After 14 days of bed rest, MPS in the BREx group did not change and was significantly greater than in the BR group. Thus moderate-resistance exercise can counteract the decrease in MPS during bed rest.

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