Muscle protein breakdown rates in humans based on Nτ-methylhistidine (3-methylhistidine) content of mixed proteins in skeletal muscle and urinary output of Nτ-methylhistidine

We tested the role of interleukin-6 (IL-6) in sepsis-induced muscle proteolysis by determining ubiquitin mRNA levels and protein breakdown rates in incubated extensor digitorum longus muscles from septic and sham-operated IL-6 knockout and wild-type mice. In addition, the effect of treatment of mice with human recombinant IL-6 on muscle protein breakdown rates was determined. Finally, protein breakdown rates were measured in myotubes treated for up to 48 h with different concentrations of IL-6. Sepsis in wild-type mice resulted in an approximately ninefold increase in plasma IL-6 levels, whereas IL-6 was not detectable in plasma of sham-operated or septic IL-6 knockout mice. Total and myofibrillar muscle protein breakdown rates were increased by ∼30% and threefold, respectively, in septic IL-6 wild-type mice with an almost identical response noted in septic IL-6 knockout mice. Ubiquitin mRNA levels determined by dot blot analysis were increased during sepsis in muscles from both IL-6 knockout and wild-type mice, although the increase was less pronounced in IL-6 knockout than in wild-type mice. Treatment of normal mice or of cultured L6 myotubes with IL-6 did not influence protein breakdown rates. The present results suggest that IL-6 does not regulate muscle proteolysis during sepsis.

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Interleukin-6 Induces Skeletal Muscle Protein Breakdown in Rats

Experimental Biology and Medicine ◽

10.3181/00379727-205-43695 ◽

1994 ◽

Vol 205 (2) ◽

pp. 182-185 ◽

Cited By ~ 190

Author(s):

M. N. Goodman

Keyword(s):

Skeletal Muscle ◽

Interleukin 6 ◽

Muscle Protein ◽

Protein Breakdown ◽

Skeletal Muscle Protein ◽

Muscle Protein Breakdown

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Treatment of burned rats with insulin-like growth factor I inhibits the catabolic response in skeletal muscle

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.275.4.r1091 ◽

1998 ◽

Vol 275 (4) ◽

pp. R1091-R1098 ◽

Cited By ~ 20

Author(s):

Cheng-Hui Fang ◽

Bing-Guo Li ◽

Jing Jing Wang ◽

Josef E. Fischer ◽

Per-Olof Hasselgren

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Burn Injury ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Protein Breakdown ◽

Turnover Rates ◽

Breakdown Rates ◽

Igf I ◽

Catabolic Response

Thermal injury is associated with a pronounced catabolic response in skeletal muscle, reflecting inhibited protein synthesis and increased protein breakdown, in particular myofibrillar protein breakdown. Administration of insulin-like growth factor I (IGF-I) has a nitrogen-sparing effect after burn injury, but the influence of this treatment on protein turnover rates in skeletal muscle is not known. In the present study, we examined the effect of IGF-I on muscle protein synthesis and breakdown rates following burn injury in rats. After a 30% total body surface area burn injury or sham procedure, rats were treated with a continuous infusion of IGF-I (3.5 or 7 mg ⋅ kg−1 ⋅ 24 h−1) for 24 h. Protein synthesis and breakdown rates were determined in incubated extensor digitorum longus muscles. Burn injury resulted in increased total and myofibrillar protein breakdown rates and reduced protein synthesis in muscle. The increase in protein breakdown rates was blocked by both doses of IGF-I and the burn-induced inhibition of muscle protein synthesis was partially reversed by the higher dose of the hormone. IGF-I did not influence muscle protein turnover rates in nonburned rats. The results suggest that the catabolic response to burn injury in skeletal muscle can be inhibited by IGF-I.

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Skeletal-muscle growth and protein turnover

Biochemical Journal ◽

10.1042/bj1500235 ◽

1975 ◽

Vol 150 (2) ◽

pp. 235-243 ◽

Cited By ~ 222

Author(s):

D J Millward ◽

P J Garlick ◽

R J C Stewart ◽

D O Nnanyelugo ◽

J C Waterlow

Keyword(s):

Skeletal Muscle ◽

Growth Rate ◽

Protein Synthesis ◽

Muscle Protein ◽

Muscle Growth ◽

Muscle Size ◽

Synthesis Rate ◽

Protein Breakdown ◽

Breakdown Rate ◽

Breakdown Rates

Because of turnover, protein synthesis and breakdown can each be involved in the regulation of the growth of tissue protein. To investigate the regulation of skeletal-muscle-protein growth we measured rates of protein synthesis and breakdown in growing rats during development on a good diet, during development on a marginally low-protein diet and during rehabilitation on a good diet after a period of severe protein deficiency. Rates of protein synthesis were measured in vivo with a constant intravenous infusion of [14C]tyrosine. The growth rate of muscle protein was measured and the rate of breakdown calculated as breakdown rate=synthesis rate-growth rate. These measurements showed that during development on a good diet there was a fall with age in the rate of protein synthesis resulting from a fall in capacity (RNA concentration) and activity (synthesis rate per unit of RNA). There was a fall with age in the breakdown rate so that the rate was highest in the weaning rats, with a half-life of 3 days. There was a direct correlation between the fractional growth and breakdown rates. During rehabilitation on the good diet, rapid growth was also accompanied by high rates of protein breakdown. During growth on the inadequate diet protein synthesis rates were lesss than in controls, but growth occurred because of decreased rates of protein breakdown. This compression was not complete, however, since ultimate muscle size was only one-half that of controls. It is suggested that increased rates of protein breakdown are a necessary accompaniment to muscle growth and may result from the way in which myofibrils proliferate.

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Insulin resistance is associated with skeletal muscle protein breakdown in non-diabetic chronic hemodialysis patients

Kidney International ◽

10.1038/sj.ki.5001984 ◽

2007 ◽

Vol 71 (2) ◽

pp. 146-152 ◽

Cited By ~ 98

Author(s):

E.D. Siew ◽

L.B. Pupim ◽

K.M. Majchrzak ◽

A. Shintani ◽

P.J. Flakoll ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Muscle Protein ◽

Hemodialysis Patients ◽

Chronic Hemodialysis ◽

Protein Breakdown ◽

Skeletal Muscle Protein ◽

Muscle Protein Breakdown

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Tumor necrosis factor induces skeletal muscle protein breakdown in rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1991.260.5.e727 ◽

1991 ◽

Vol 260 (5) ◽

pp. E727-E730 ◽

Cited By ~ 34

Author(s):

M. N. Goodman

Keyword(s):

Skeletal Muscle ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Muscle Protein ◽

Nitrogen Excretion ◽

Protein Breakdown ◽

Skeletal Muscle Protein ◽

Muscle Protein Breakdown ◽

Necrosis Factor

The metabolic response to infection includes loss of lean tissue and increased nitrogen excretion. The loss of muscle tissue during infection results in large part from accelerated skeletal muscle protein breakdown. Recent studies suggest that macrophage-derived products secreted during infection may signal increased muscle proteolysis. To test this, in the present report the ability of interleukin (IL-1) and tumor necrosis factor (TNF) to enhance muscle proteolysis was examined. Young rats were injected intravenously with either recombinant human IL-1 or TNF. For comparison some rats were injected with bacterial endotoxin. Eight hours after each treatment, the extensor digitorum longus muscles were isolated and incubated in vitro to assess muscle proteolysis by measuring tyrosine and 3-methyl-L-histidine release by the incubated muscles. Treatment of rats with either IL-1, TNF, or endotoxin all induced fever, increased serum lactate, and reduced serum zinc levels. Despite similar metabolic changes, muscle proteolysis responded differently. As expected, endotoxin treatment enhanced muscle protein breakdown, whereas IL-1 treatment was without effect. On the other hand, TNF was effective in accelerating muscle protein breakdown. TNF addition in vitro failed to enhance muscle proteolysis by incubated muscles, suggesting that its effects may be mediated in an indirect manner; however, a direct mode of action cannot yet be ruled out. Overall, the data indicate that the acute administration of TNF can signal increased muscle proteolysis similar to that observed during infection.

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