Prevention of skeletal muscle catabolism in sepsis does not impair visceral protein metabolism

1996 ◽  
Vol 270 (4) ◽  
pp. E621-E626 ◽  
Author(s):  
R. N. Cooney ◽  
E. Owens ◽  
D. Slaymaker ◽  
T. C. Vary
Keyword(s):  
Protein Synthesis ◽  
Small Intestine ◽  
Protein Content ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Interleukin 1 ◽  
Intestinal Protein ◽  
Muscle Catabolism ◽  
Induced Changes ◽  
Septic Insult

We investigated whether the preservation of gastrocnemius proteins by interleukin-1 receptor antagonist (IL-1ra) during sepsis altered protein metabolism in visceral tissues. Sepsis was induced by creation of an abdominal abscess followed by infusion of saline of IL-1ra. Five days later, the tissue protein content and rate of protein synthesis were measured. IL-1ra did not significantly alter hepatic protein metabolism in septic or control animals. In kidney, the protein content and rate of protein synthesis were both decreased by sepsis and significantly ameliorated by the infusion of IL-1ra. Sepsis decreased the rate of protein synthesis in the small intestine. IL-1ra increased intestinal protein synthesis in both control and septic animals; however, the effects were localized to the seromuscular layer. The preservation of muscle protein by IL-1ra in sepsis did not adversely affect protein synthesis in any of the visceral tissues examined. IL-1 appears to mediate the sepsis-induced changes in protein synthesis in kidney and small intestine but not in liver or spleen. Protein synthesis in each visceral organ responds differently to the septic insult and modulation of IL-1 bioactivity.

Interleukin-1 receptor antagonist prevents sepsis-induced inhibition of protein synthesis

1994 ◽  
Vol 267 (5) ◽  
pp. E636-E641 ◽  
Author(s):  
R. Cooney ◽  
E. Owens ◽  
C. Jurasinski ◽  
K. Gray ◽  
J. Vannice ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Receptor Antagonist ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Interleukin 1 ◽  
Skeletal Muscle Protein ◽  
Inhibition Of Protein Synthesis ◽  
Muscle Protein Metabolism

To understand the role of interleukin-1 (IL-1) as a mediator of the sepsis-induced skeletal muscle catabolism, we investigated the effects of a specific IL-1 receptor antagonist (IL-1ra) on skeletal muscle protein metabolism in a rodent model of chronic abdominal sepsis. A constant infusion of IL-1ra (2 mg.kg-1.h-1) or saline was begun immediately after the induction of sepsis and continued for 5 days. The effect of IL-1ra on protein metabolism was examined in individual muscles (gastrocnemius, soleus, heart) containing different fiber types. Infusion of IL-1ra in control animals did not alter protein metabolism in any of the muscles examined. Muscle weight, protein content, and the rate of protein synthesis in gastrocnemius were reduced by sepsis, whereas none of these parameters were affected in soleus or heart. Infusion of IL-1ra prevented the sepsis-induced loss of muscle protein and inhibition of protein synthesis in gastrocnemius but was without effect in soleus or heart. IL-1ra infusion restored translational efficiency in the gastrocnemius of septic rats and was without effect on the RNA content. These results provide evidence for a role of IL-1 as a mediator of the sepsis-induced abnormalities in skeletal muscle protein metabolism.

Chronic α-tocopherol supplementation in rats does not ameliorate either chronic or acute alcohol-induced changes in muscle protein metabolism

2003 ◽  
Vol 104 (3) ◽  
pp. 287-294 ◽  
Author(s):  
Michael KOLL ◽  
Julie A. BEESO ◽  
Frank J. KELLY ◽  
Ulrich A. SIMANOWSKI ◽  
Helmut K. SEITZ ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Protein Content ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Disease ◽  
Plantaris Muscle ◽  
Dna Contents ◽  
Rna And Dna

Chronic alcohol muscle disease is characterized by reduced skeletal muscle mass precipitated by acute reduction in protein synthesis. The pathogenic mechanisms remain obscure, but several lines of evidence suggest that increased oxidative stress occurs in muscle in response to alcohol and this may be associated with impaired α-tocopherol status. Potentially, this implies a therapeutic role for α-tocopherol, especially as we have shown that supplemental α-tocopherol may increase the rate of protein synthesis in normal rats [Reilly, Patel, Peters and Preedy (2000) J. Nutr. 130, 3045–3049]. We investigated the therapeutic effect of α-tocopherol on plantaris muscle protein synthesis in rats treated either acutely, chronically or chronically+acutely with ethanol. Protein synthesis rates were measured with a flooding dose of L-[4-3H]phenylalanine. Protein, RNA and DNA contents were determined by standard laboratory methods. Ethanol caused defined metabolic changes in muscle, including decreased protein, RNA and DNA contents in chronically treated rats. In acute or chronic+acute studies, ethanol suppressed fractional rates of protein synthesis. α-Tocopherol supplementation did not ameliorate the effects of either acute, chronic or chronic+acute alcohol on plantaris muscle protein content or rates of protein synthesis. In control animals (not treated with alcohol), α-tocopherol supplementation decreased muscle protein content owing to increases in protein turnover (both synthesis and degradation). α-Tocopherol supplementation is not protective against the deleterious effects of alcohol on protein metabolism in skeletal muscle.

scholarly journals Comprehensive assessment of post-prandial protein handling by the application of intrinsically labelled protein in vivo in human subjects

2021 ◽  
pp. 1-9
Author(s):  
Jorn Trommelen ◽  
Andrew M. Holwerda ◽  
Philippe J. M. Pinckaers ◽  
Luc J. C. van Loon
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Stable Isotope ◽  
Dietary Protein ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Human Subjects ◽  
Whole Body ◽  
Body Protein

All human tissues are in a constant state of remodelling, regulated by the balance between tissue protein synthesis and breakdown rates. It has been well-established that protein ingestion stimulates skeletal muscle and whole-body protein synthesis. Stable isotope-labelled amino acid methodologies are commonly applied to assess the various aspects of protein metabolism in vivo in human subjects. However, to achieve a more comprehensive assessment of post-prandial protein handling in vivo in human subjects, intravenous stable isotope-labelled amino acid infusions can be combined with the ingestion of intrinsically labelled protein and the collection of blood and muscle tissue samples. The combined application of ingesting intrinsically labelled protein with continuous intravenous stable isotope-labelled amino acid infusion allows the simultaneous assessment of protein digestion and amino acid absorption kinetics (e.g. release of dietary protein-derived amino acids into the circulation), whole-body protein metabolism (whole-body protein synthesis, breakdown and oxidation rates and net protein balance) and skeletal muscle metabolism (muscle protein fractional synthesis rates and dietary protein-derived amino acid incorporation into muscle protein). The purpose of this review is to provide an overview of the various aspects of post-prandial protein handling and metabolism with a focus on insights obtained from studies that have applied intrinsically labelled protein under a variety of conditions in different populations.

Pentoxifylline decreases body weight loss and muscle protein wasting characteristics of sepsis

1993 ◽  
Vol 265 (4) ◽  
pp. E660-E666 ◽  
Author(s):  
D. Breuille ◽  
M. C. Farge ◽  
F. Rose ◽  
M. Arnal ◽  
D. Attaix ◽  
...  
Keyword(s):  
Body Weight ◽  
Protein Synthesis ◽  
Acute Phase ◽  
Protein Metabolism ◽  
Muscle Wasting ◽  
Acute Phase Protein ◽  
Muscle Protein ◽  
Liver Protein ◽  
Phase Protein

Sepsis induces metabolic disorders that include loss of body weight, muscle wasting, and acute-phase protein synthesis in liver. Cytokines are generally recognized as active mediators of these disorders, and the implication of tumor necrosis factor (TNF) has been frequently discussed in the recent past. However, the identity of the active agent in alterations of protein metabolism is still controversial. To improve our understanding of the role of cytokines in mediating muscle wasting observed in sepsis, we investigated muscle and liver protein metabolism in the following three groups of rats: infected control rats (INF-C); infected rats pretreated with pentoxifylline (PTX-INF), which is a potent inhibitor of TNF secretion; and pair-fed rats for the PTX-INF group pretreated with pentoxifylline. Pentoxifylline nearly completely suppressed TNF secretion but did not influence the transient fall in rectal temperature, the decreased hematocrit, and the increased liver protein mass and synthesis observed in INF-C rats. Pentoxifylline decreased the anorexia, the loss of body weight and muscle protein observed in INF-C animals, and partially prevented the decrease in muscle protein synthesis induced by infection. The overall data indicate that pentoxifylline is an effective agent in mitigating the characteristic muscle protein wasting induced by sepsis and confirm the limited role of TNF in the mediation of the acute-phase protein synthesis. Our results suggest a probable implication of TNF in the regulation of protein balance in muscle but do not allow discarding possible implication of other mediators that would be inhibited by pentoxifylline.

scholarly journals Mechanisms Underlying Muscle Protein Imbalance Induced by Alcohol

2018 ◽  
Vol 38 (1) ◽  
pp. 197-217 ◽  
Author(s):  
Scot R. Kimball ◽  
Charles H. Lang
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Cardiac Contractility ◽  
Metabolic Phenotype ◽  
Alcoholic Myopathy ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Induced Changes ◽  
Skeletal Muscle Strength

Both acute intoxication and longer-term cumulative ingestion of alcohol negatively impact the metabolic phenotype of both skeletal and cardiac muscle, independent of overt protein calorie malnutrition, resulting in loss of skeletal muscle strength and cardiac contractility. In large part, these alcohol-induced changes are mediated by a decrease in protein synthesis that in turn is governed by impaired activity of a protein kinase, the mechanistic target of rapamycin (mTOR). Herein, we summarize recent advances in understanding mTOR signal transduction, similarities and differences between the effects of alcohol on this central metabolic controller in skeletal muscle and in the heart, and the effects of acute versus chronic alcohol intake. While alcohol-induced alterations in global proteolysis via activation of the ubiquitin-proteasome pathway are equivocal, emerging data suggest alcohol increases autophagy in muscle. Further studies are necessary to define the relative contributions of these bidirectional changes in protein synthesis and autophagy in the etiology of alcoholic myopathy in skeletal muscle and the heart.

Cachectin/TNF or IL-1 alpha induces cachexia with redistribution of body proteins

1989 ◽  
Vol 256 (3) ◽  
pp. R659-R665 ◽  
Author(s):  
Y. Fong ◽  
L. L. Moldawer ◽  
M. Marano ◽  
H. Wei ◽  
A. Barber ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Content ◽  
Muscle Protein ◽  
Interleukin 1 ◽  
Metabolic Effects ◽  
Liver Protein ◽  
Mrna Levels ◽  
Skeletal Muscle Protein ◽  
Male Wistar Rats

Macrophage secretory products are suspected to participate in the severe lean tissue wasting related to chronic illness. The protein metabolic effects of chronic, 7-day cachectin/tumor necrosis factor (cachectin) or interleukin 1 alpha (IL-1 alpha) administration in vivo were studied in male Wistar rats that were 1) freely fed, 2) pair fed, 3) total protein and calorie starved, 4) twice daily lipopolysaccharide (LPS) administered, 5) twice daily cachectin administered, and 6) twice daily IL-1 alpha administered. LPS, cachectin, or IL-1 alpha administration produced anorexia; weight loss in these groups was comparable to respective pair-fed animals. However, LPS, cachectin, or IL-1 alpha accelerated peripheral protein wasting while preserving liver protein content, unlike the pattern in the pair-fed or starved animals in which loss of liver proteins and relative preservation of skeletal muscle protein were observed. The decrease in skeletal muscle protein content in LPS- or cytokine-treated animals was associated with coordinate decreases in muscle mRNA levels for the myofibrillar proteins myosin heavy chain, myosin light chain, actin, and in the 18S and 28S subunits of ribosomal RNA. We conclude that chronic exposure to the cytokines, IL-1 alpha or cachectin, can simulate those body and muscle protein changes seen in experimental LPS administration or chronic disease and markedly differ from the pattern of protein redistribution due to caloric restriction.

scholarly journals Effects of acute oral feeding on protein metabolism and muscle protein synthesis in individuals with cancer

Nutrition ◽  
2019 ◽  
Vol 67-68 ◽  
pp. 110531 ◽  
Author(s):  
Barbara S. van der Meij ◽  
Lynette M. De Groot ◽  
Nicolaas E.P. Deutz ◽  
Mariëlle P.K.J. Engelen
Keyword(s):  
Protein Synthesis ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Oral Feeding

TNF-binding protein ameliorates inhibition of skeletal muscle protein synthesis during sepsis

1999 ◽  
Vol 276 (4) ◽  
pp. E611-E619 ◽  
Author(s):  
Robert Cooney ◽  
Scot R. Kimball ◽  
Rebecca Eckman ◽  
George Maish ◽  
Margaret Shumate ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Content ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Binding Protein ◽  
Initiation Factor ◽  
Translational Efficiency ◽  
Skeletal Muscle Protein ◽  
Muscle Weight ◽  
Initiation Factors

We examined the effects of TNF-binding protein (TNFBP) on regulatory mechanisms of muscle protein synthesis during sepsis in four groups of rats: Control; Control+TNFBP; Septic; and Septic+TNFBP. Saline (1.0 ml) or TNFBP (1 mg/kg, 1.0 ml) was injected daily starting 4 h before the induction of sepsis. The effect of TNFBP on gastrocnemius weight, protein content, and the rate of protein synthesis was examined 5 days later. Sepsis reduced the rate of protein synthesis by 35% relative to controls by depressing translational efficiency. Decreases in protein synthesis were accompanied by similar reductions in protein content and muscle weight. Treatment of septic animals with TNFBP for 5 days prevented the sepsis-induced inhibition of protein synthesis and restored translational efficiency to control values. TNFBP treatment of Control rats for 5 days was without effect on muscle protein content or protein synthesis. We also assessed potential mechanisms regulating translational efficiency. The phosphorylation state of p70S6 kinase was not altered by sepsis. Sepsis reduced the gastrocnemius content of eukaryotic initiation factor 2Bε (eIF2Bε), but not eIF2α. The decrease in eIF2Bε content was prevented by treatment of septic rats with TNFBP. TNFBP ameliorates the sepsis-induced changes in protein metabolism in gastrocnemius, indicating a role for TNF in the septic process. The data suggest that TNF may impair muscle protein synthesis by reducing expression of specific initiation factors during sepsis.

Protein metabolism in cardiac hypertrophy and heart failure

1964 ◽  
Vol 206 (2) ◽  
pp. 294-298 ◽  
Author(s):  
Sigmundur Gudbjarnason ◽  
Michael Telerman ◽  
Richard J. Bing
Keyword(s):  
Heart Failure ◽  
Protein Synthesis ◽  
Chronic Heart Failure ◽  
Cardiac Hypertrophy ◽  
Protein Metabolism ◽  
Heart Muscle ◽  
Protein Turnover ◽  
Turnover Rate ◽  
Muscle Protein ◽  
Myocardial Failure

The rate of myocardial protein synthesis was studied in hearts of normal rabbits and in hearts of animals with experimentally produced cardiac hypertrophy and with acute and chronic myocardial failure. Cardiac hypertrophy was accompanied by an increase in protein synthesis; however, there was no increased myocardial protein turnover rate. In acute heart failure the rate of myocardial protein synthesis was diminished as compared to protein synthesis during the development of cardiac hypertrophy. In chronic heart failure the relative incorporation of glycine-2-C14 into heart muscle protein was diminished. The turnover rate of myocardial proteins during cardiac hypertrophy was not altered.

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