Lactation induces upregulation of the ubiquitin-mediated proteolytic pathway in skeletal muscle of dairy cows but does not alter hepatic expression

2009 ◽  
Vol 89 (3) ◽  
pp. 309-313 ◽  
Author(s):  
S L Greenwood ◽  
T C Wright ◽  
N G Purdie ◽  
J Doelman ◽  
J P Cant ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Dairy Cows ◽  
Mrna Expression ◽  
Muscle Protein ◽  
Post Partum ◽  
Skeletal Muscle Protein ◽  
Protein Loss ◽  
Body Protein ◽  
Hepatic Expression ◽  
Proteolytic Pathway

The current study investigates regulation of mRNA expression of components of ubiquitin-mediated proteolysis in transition dairy cows. Longissimus dorsi muscle (exp. 1) and liver (exp. 2) biopsies were collected from Holstein dairy cows at 27 and 16 d pre-partum, respectively, and 3 and 10 d post-partum, respectively. Regulation of C8, E2, and ubiquitin mRNA expression was determined. Upregulation of skeletal muscle C8 (P = 0.09) and ubiquitin (P = 0.004) mRNA expression occurred post-partum compared with pre-partum. No regulation of hepatic mRNA expression was observed. In conclusion, ubiquitin-mediated proteolysis may contribute to skeletal muscle protein degradation during the periparturient period, and could provide a potential mechanism for attenuation of body protein loss at the onset of lactation.Key words: Lactation, ubiquitin-mediated proteolytic pathway, muscle (skeletal), liver

Chloroquine does not exert insulin-like actions on human forearm muscle metabolism

1995 ◽  
Vol 268 (5) ◽  
pp. E820-E824 ◽  
Author(s):  
E. J. Barrett ◽  
L. A. Jahn ◽  
D. M. Oliveras ◽  
D. A. Fryburg
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Protein ◽  
Muscle Metabolism ◽  
Whole Body ◽  
Diabetic Patients ◽  
Body Protein ◽  
Proteolytic Pathway ◽  
Lysosomal Proteolysis ◽  
Acute Increase

Insulin's anabolic action on skeletal muscle and whole body protein is attributable to its action to slow tissue proteolysis. The antimalarial chloroquine inhibits lysosomal proteolysis and is reported to improve glycemia in poorly controlled diabetic patients. We infused chloroquine into the brachial artery of seven healthy postabsorptive volunteers over 3 h during a steady-state infusion of L-[ring-2,6-3H]phenylalanine (Phe) to study its effect on muscle glucose and protein turnover. Compared with basal, chloroquine increased forearm blood flow (P < 0.01) but did not change glucose uptake or lactate release. Neither Phe released from muscle by proteolysis (78 +/- 15 vs. 94 +/- 16 nmol Phe.min-1.100 ml-1) nor Phe balance (-37 +/- 7 vs. -50 +/- 6 nmol.min-1.100 ml-1) was reduced from basal. We conclude that in postabsorptive human skeletal muscle: 1) lysosomal proteolysis does not make a major contribution to proteolysis; and 2) chloroquine does not cause an acute increase in glucose uptake. These findings suggest that the inhibition of postabsorptive muscle protein degradation provoked by physiological increases in plasma insulin is likely mediated by a nonlysosomal proteolytic pathway.

Prolonged bed rest decreases skeletal muscle and whole body protein synthesis

1996 ◽  
Vol 270 (4) ◽  
pp. E627-E633 ◽  
Author(s):  
A. A. Ferrando ◽  
H. W. Lane ◽  
C. A. Stuart ◽  
J. Davis-Street ◽  
R. R. Wolfe
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Bed Rest ◽  
Whole Body ◽  
Protein Breakdown ◽  
Skeletal Muscle Protein ◽  
Model Calculations ◽  
Body Protein

We sought to determine the extent to which the loss of lean body mass and nitrogen during inactivity was due to alterations in skeletal muscle protein metabolism. Six male subjects were studied during 7 days of diet stabilization and after 14 days of stimulated microgravity (-6 degrees bed rest). Nitrogen balance became more negative (P < 0.03) during the 2nd wk of bed rest. Leg and whole body lean mass decreased after bed rest (P < 0.05). Serum cortisol, insulin, insulin-like growth factor I, and testosterone values did not change. Arteriovenous model calculations based on the infusion of L-[ring-13C6]-phenylalanine in five subjects revealed a 50% decrease in muscle protein synthesis (PS; P < 0.03). Fractional PS by tracer incorporation into muscle protein also decreased by 46% (P < 0.05). The decrease in PS was related to a corresponding decrease in the sum of intracellular amino acid appearance from protein breakdown and inward transport. Whole body protein synthesis determined by [15N]alanine ingestion on six subjects also revealed a 14% decrease (P < 0.01). Neither model-derived nor whole body values for protein breakdown change significantly. These results indicate that the loss of body protein with inactivity is predominantly due to a decrease in muscle PS and that this decrease is reflected in both whole body and skeletal muscle measures.

Ghrelin inhibits skeletal muscle protein breakdown in rats with thermal injury through normalizing elevated expression of E3 ubiquitin ligases MuRF1 and MAFbx

2009 ◽  
Vol 296 (4) ◽  
pp. R893-R901 ◽  
Author(s):  
Ambikaipakan Balasubramaniam ◽  
Rashika Joshi ◽  
Chunhua Su ◽  
Lou Ann Friend ◽  
Sulaiman Sheriff ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Burn Injury ◽  
Muscle Protein ◽  
Ubiquitin Ligases ◽  
Myofibrillar Protein ◽  
E3 Ubiquitin Ligases ◽  
Protein Breakdown ◽  
Skeletal Muscle Protein ◽  
Muscle Protein Breakdown

We previously determined that ghrelin synthesis was downregulated after burn injury and that exogenous ghrelin retained its ability both to stimulate food intake and to restore plasma growth hormone levels in burned rats. These observations and the finding that anabolic hormones can attenuate skeletal muscle catabolism led us to investigate whether ghrelin could attenuate burn-induced skeletal muscle protein breakdown in rats. These studies were performed in young rats (50–60 g) 24 h after ∼30% total body surface area burn injury. Burn injury increased total and myofibrillar protein breakdown in extensor digitorum longus (EDL) muscles assessed by in vitro tyrosine and 3-methyl-histidine release, respectively. Continuous 24-h administration of ghrelin (0.2 mg·kg−1·h−1) significantly inhibited both total and myofibrillar protein breakdown in burned rats. Ghrelin significantly attenuated burn-induced changes in mRNA expression of IGFBP-1 and IGFBP-3 in liver. In EDL, ghrelin attenuated the increases in mRNA expression of the binding proteins, but had no significant effect on reduced expression of IGF-I. Ghrelin markedly reduced the elevated mRNA expression of TNF-α and IL-6 in EDL muscle that occurred after burn. Moreover, ghrelin normalized plasma glucocorticoid levels, which were elevated after burn. Expression of the muscle-specific ubiquitin-ligating enzyme (E3) ubiquitin ligases MuRF1 and MAFbx were markedly elevated in both EDL and gastrocnemius and were normalized by ghrelin. These results suggest that ghrelin is a powerful anticatabolic compound that reduces skeletal muscle protein breakdown through attenuating multiple burn-induced abnormalities.

Skeletal muscle degradation and nitrogen wasting in rats with chronic metabolic acidosis

1991 ◽  
Vol 80 (5) ◽  
pp. 457-462 ◽  
Author(s):  
Bryan Williams ◽  
Ellis Layward ◽  
John Walls
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Acidosis ◽  
Time Course ◽  
Muscle Protein ◽  
Nitrogen Excretion ◽  
Protein Catabolism ◽  
Skeletal Muscle Protein ◽  
Body Protein ◽  
Chronic Metabolic Acidosis ◽  
Urea Production

1. Chronic metabolic acidosis is associated with impaired growth and negative nitrogen balance, suggesting that it promotes endogenous protein catabolism. 2. Skeletal muscle is the major repository of body protein and is a potential target for stimuli of protein catabolism. 3. This study in vivo examines the effects of chronic metabolic acidosis on the relationship between growth, nitrogen disposal and skeletal muscle catabolism in the rat. 4. Growth, nitrogen utilization and acquisition of body mass were significantly impaired in acidotic animals compared with pair-fed controls. 5. Total nitrogen excretion was significantly increased in acidotic rats despite decreased urea production. The time course of this response to acidosis was synchronous with that of accelerated protein catabolism in skeletal muscle. 6. It is proposed that metabolic acidosis impairs growth by stimulating skeletal muscle protein catabolism. It is suggested that this forms part of a co-ordinated multi-organ homoeostatic response to acidosis, skeletal muscle and down-regulated urea production supplying the nitrogen required for renal ammoniagenesis.

scholarly journals Increase in ubiquitin-protein conjugates concomitant with the increase in proteolysis in rat skeletal muscle during starvation and atrophy denervation

1995 ◽  
Vol 307 (3) ◽  
pp. 639-645 ◽  
Author(s):  
S S Wing ◽  
A L Haas ◽  
A L Goldberg
Keyword(s):  
Skeletal Muscle ◽  
Food Deprivation ◽  
Muscle Protein ◽  
Polyclonal Antibodies ◽  
26S Proteasome ◽  
Protein Breakdown ◽  
Skeletal Muscle Protein ◽  
Protein Conjugates ◽  
Proteolytic Pathway ◽  
Gastrocnemius Muscles

The rapid loss of skeletal-muscle protein during starvation and after denervation occurs primarily through increased rates of protein breakdown and activation of a non-lysosomal ATP-dependent proteolytic process. To investigate whether protein flux through the ubiquitin (Ub)-proteasome pathway is enhanced, as was suggested by related studies, we measured, using specific polyclonal antibodies, the levels of Ub-conjugated proteins in normal and atrophying muscles. The content of these critical intermediates had increased 50-250% after food deprivation in the extensor digitorum longus and soleus muscles 2 days after denervation. Like rates of proteolysis, the amount of Ub-protein conjugates and the fraction of Ub conjugated to proteins increased progressively during food deprivation and returned to normal within 1 day of refeeding. During starvation, muscles of adrenalectomized rats failed to increase protein breakdown, and they showed 50% lower levels of Ub-protein conjugates than those of starved control animals. The changes in the pools of Ub-conjugated proteins (the substrates for the 26S proteasome) thus coincided with and can account for the alterations in overall proteolysis. In this pathway, large multiubiquitinated proteins are preferentially degraded, and the Ub-protein conjugates that accumulated in atrophying muscles were of high molecular mass (> 100 kDa). When innervated and denervated gastrocnemius muscles were fractionated, a significant increase in ubiquitinated proteins was found in the myofibrillar fraction, the proteins of which are preferentially degraded on denervation, but not in the soluble fraction. Thus activation of this proteolytic pathway in atrophying muscles probably occurs initially by increasing Ub conjugation to cell proteins. The resulting accumulation of Ub-protein conjugates suggests that their degradation by the 26S proteasome complex subsequently becomes rate-limiting in these catabolic states.

Effect of glycogen availability on human skeletal muscle protein turnover during exercise and recovery

2010 ◽  
Vol 109 (2) ◽  
pp. 431-438 ◽  
Author(s):  
Krista R. Howarth ◽  
Stuart M. Phillips ◽  
Maureen J. MacDonald ◽  
Douglas Richards ◽  
Natalie A. Moreau ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Protein Turnover ◽  
Muscle Protein ◽  
Whole Body ◽  
Skeletal Muscle Protein ◽  
Protein Balance ◽  
Body Protein ◽  
Muscle Protein Turnover ◽  
Net Protein

We examined the effect of carbohydrate (CHO) availability on whole body and skeletal muscle protein utilization at rest, during exercise, and during recovery in humans. Six men cycled at ∼75% peak O2 uptake (V̇o2peak) to exhaustion to reduce body CHO stores and then consumed either a high-CHO (H-CHO; 71 ± 3% CHO) or low-CHO (L-CHO; 11 ± 1% CHO) diet for 2 days before the trial in random order. After each dietary intervention, subjects received a primed constant infusion of [1-13C]leucine and l-[ring-2H5]phenylalanine for measurements of the whole body net protein balance and skeletal muscle protein turnover. Muscle, breath, and arterial and venous blood samples were obtained at rest, during 2 h of two-legged kicking exercise at ∼45% of kicking V̇o2peak, and during 1 h of recovery. Biopsy samples confirmed that the muscle glycogen concentration was lower in the L-CHO group versus the H-CHO group at rest, after exercise, and after recovery. The net leg protein balance was decreased in the L-CHO group compared with at rest and compared with the H-CHO condition, which was primarily due to an increase in protein degradation (area under the curve of the phenylalanine rate of appearance: 1,331 ± 162 μmol in the L-CHO group vs. 786 ± 51 μmol in the H-CHO group, P < 0.05) but also due to a decrease in protein synthesis late in exercise. There were no changes during exercise in the rate of appearance compared with rest in the H-CHO group. Whole body leucine oxidation increased above rest in the L-CHO group only and was higher than in the H-CHO group. The whole body net protein balance was reduced in the L-CHO group, largely due to a decrease in whole body protein synthesis. These data extend previous findings by others and demonstrate, using contemporary stable isotope methodology, that CHO availability influences the rates of skeletal muscle and whole body protein synthesis, degradation, and net balance during prolonged exercise in humans.

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