Sepsis in mice stimulates muscle proteolysis in the absence of IL-6

1998 ◽  
Vol 275 (6) ◽  
pp. R1983-R1991 ◽  
Author(s):  
Arthur Williams ◽  
Jing Jing Wang ◽  
Li Wang ◽  
Xiaoyan Sun ◽  
Josef E. Fischer ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Muscle Protein ◽  
Mrna Levels ◽  
Protein Breakdown ◽  
Wild Type ◽  
Dot Blot ◽  
Muscle Protein Breakdown ◽  
L6 Myotubes ◽  
Identical Response ◽  
Breakdown Rates

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.

scholarly journals The NF-κB Inhibitor Curcumin Blocks Sepsis-Induced Muscle Proteolysis

2008 ◽  
Vol 2008 ◽  
pp. 1-13 ◽  
Author(s):  
Vitaliy Poylin ◽  
Moin U. Fareed ◽  
Patrick O'Neal ◽  
Nima Alamdari ◽  
Natasha Reilly ◽  
...  
Keyword(s):  
Muscle Protein ◽  
Cathepsin L ◽  
Cecal Ligation ◽  
P38 Map Kinase ◽  
Protein Breakdown ◽  
Muscle Protein Breakdown ◽  
Breakdown Rates ◽  
Dependent Protein ◽  
Absolute Correlation

We tested the hypothesis that treatment of rats with curcumin prevents sepsis-induced muscle protein degradation. In addition, we determined the influence of curcumin on different proteolytic pathways that are activated in septic muscle (i.e., ubiquitin-proteasome-, calpain-, and cathepsin L-dependent proteolysis) and examined the role of NF-κB and p38/MAP kinase inactivation in curcumin-induced inhibition of muscle protein breakdown. Rats were made septic by cecal ligation and puncture or were sham-operated. Groups of rats were treated with three intraperitoneal doses (600 mg/kg) of curcumin or corresponding volumes of solvent. Protein breakdown rates were measured as release of tyrosine from incubated extensor digitorum longus muscles. Treatment with curcumin prevented sepsis-induced increase in muscle protein breakdown. Surprisingly, the upregulated expression of the ubiquitin ligases atrogin-1 and MuRF1 was not influenced by curcumin. When muscles from septic rats were treated with curcumin in vitro, proteasome-, calpain-, and cathepsin L-dependent protein breakdown rates were reduced, and nuclear NF-κB/p65 expression and activity as well as levels of phosphorylated (activated) p38 were decreased. Results suggest that sepsis-induced muscle proteolysis can be blocked by curcumin and that this effect may, at least in part, be caused by inhibited NF-κB and p38 activities. The results also suggest that there is not an absolute correlation between changes in muscle protein breakdown rates and changes in atrogin-1 and MuRF1 expression during treatment of muscle wasting.

Sepsis-induced increase in muscle proteolysis is blocked by specific proteasome inhibitors

1998 ◽  
Vol 274 (1) ◽  
pp. R30-R37 ◽  
Author(s):  
Scott C. Hobler ◽  
Greg Tiao ◽  
Josef E. Fischer ◽  
John Monaco ◽  
Per-Olof Hasselgren
Keyword(s):  
Molecular Mechanisms ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Proteasome Inhibitors ◽  
Mrna Levels ◽  
Protein Breakdown ◽  
Catalytic Core ◽  
Muscle Protein Breakdown ◽  
Dependent Inhibition

Recent studies suggest that sepsis stimulates ubiquitin-dependent protein breakdown in skeletal muscle. The 20S proteasome is the catalytic core of the ubiquitin-dependent proteolytic pathway. We tested the effects in vitro of the proteasome inhibitors N-acetyl-l-leucinyl-l-leucinal-l-norleucinal (LLnL) and lactacystin on protein breakdown in incubated muscles from septic rats. LLnL resulted in a dose- and time-dependent inhibition of protein breakdown in muscles from septic rats. Lactacystin blocked both total and myofibrillar muscle protein breakdown. In addition to inhibiting protein breakdown, LLnL reduced muscle protein synthesis and increased ubiquitin mRNA levels, probably reflecting inhibited proteasome-associated ribonuclease activity. Inhibited muscle protein breakdown caused by LLnL or lactacystin supports the concept that the ubiquitin-proteasome pathway plays a central role in sepsis-induced muscle proteolysis. The results suggest that muscle catabolism during sepsis may be inhibited by targeting specific molecular mechanisms of muscle proteolysis.

Proteasome blockers inhibit protein breakdown in skeletal muscle after burn injury in rats

1998 ◽  
Vol 95 (2) ◽  
pp. 225-233 ◽  
Author(s):  
Cheng-Hui FANG ◽  
Jing Jing WANG ◽  
Scott HOBLER ◽  
Bing Guo LI ◽  
Josef E. FISCHER ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Burn Injury ◽  
Muscle Protein ◽  
Total Body Surface Area ◽  
26S Proteasome ◽  
20S Proteasome ◽  
Mrna Levels ◽  
Protein Breakdown ◽  
Turnover Rates ◽  
Muscle Protein Breakdown

1.Burn injury stimulates ubiquitin-dependent protein breakdown in skeletal muscle. The 20S proteasome is the proteolytic core of the 26S proteasome that degrades ubiquitin conjugates. We examined the effects of the proteasome inhibitors N-acetyl-l-leucinyl-L-leucinal-l-norleucinal (LLnL), lactacystin and β-lactone on protein breakdown in muscles from burned rats. 2.A full-thickness burn of 30% total body surface area was inflicted on the back of rats. Control rats underwent a sham procedure. After 24 ;h, extensor digitorum longus muscles were incubated in the absence or presence of 20S proteasome blocker and protein turnover rates and ubiquitin mRNA levels were determined. 3.LLnL resulted in a dose- and time-dependent inhibition of total protein breakdown in incubated muscles from burned rats. Lactacystin and β-lactone blocked both total and myofibrillar muscle protein breakdown. In addition to inhibiting protein breakdown, LLnL increased ubiquitin mRNA levels, possibly reflecting inhibited proteasome-associated RNase activity. 4.Inhibited muscle protein breakdown caused by LLnL, lactacystin and β-lactone supports the concept that the ubiquitin–proteasome pathway plays a central role in burn-induced muscle proteolysis. Because the proteasome has multiple important functions in the cell, in addition to regulating general protein breakdown, further studies are needed to test the role of proteasome blockers in the treatment or prevention of muscle catabolism.

scholarly journals Acute Effect of the Timing of Resistance Exercise and Nutrient Intake on Muscle Protein Breakdown

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1177
Author(s):  
Wataru Kume ◽  
Jun Yasuda ◽  
Takeshi Hashimoto
Keyword(s):  
Resistance Exercise ◽  
Nutrient Intake ◽  
Plasma Insulin ◽  
Muscle Protein ◽  
Optimal Timing ◽  
Protein Breakdown ◽  
Mixed Meal ◽  
Muscle Protein Breakdown ◽  
Meal Intake ◽  
Post Condition

Background: Combining resistance exercise (RE) with nutrient intake stimulates muscle protein net balance. However, it is still unclear whether the optimal timing of nutrient intake is before or after RE, especially on muscle protein breakdown (MPB) for an augmented muscle anabolic response. The aim of this study was to investigate the effect of a substantial mixed meal (i.e., nutrient- and protein-dense whole foods) before or after RE, compared with RE without a meal on the acute response of MPB in a crossover-design study. Methods: Eight healthy young men performed three trials: (1) meal intake before RE (Pre), (2) meal intake after RE (Post), and (3) RE without meal intake (No). Plasma insulin and 3-methylhistidine (3-MH), an MPB marker, were measured. Results: Time course change in plasma insulin level after RE was significantly higher in the Post condition than in the Pre and No conditions. The area under the curve of 3-MH concentration was significantly lower in the Post condition than in the Pre and No conditions. Conclusions: These results suggest that a substantial mixed meal immediately after RE may effectively suppress MPB in the morning.

scholarly journals Assessing the Role of Muscle Protein Breakdown in Response to Nutrition and Exercise in Humans

2018 ◽  
Vol 48 (S1) ◽  
pp. 53-64 ◽  
Author(s):  
Kevin D. Tipton ◽  
D. Lee Hamilton ◽  
Iain J. Gallagher
Keyword(s):  
Muscle Protein ◽  
Protein Breakdown ◽  
Muscle Protein Breakdown ◽  
Exercise In Humans
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