Progressive skeletal muscle weakness in transgenic mice expressing CTG expansions is associated with the activation of the ubiquitin–proteasome pathway

2010 ◽  
Vol 20 (5) ◽  
pp. 319-325 ◽  
Author(s):  
Alban Vignaud ◽  
Arnaud Ferry ◽  
Aline Huguet ◽  
Martin Baraibar ◽  
Capucine Trollet ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transgenic Mice ◽  
Muscle Weakness ◽  
Ubiquitin Proteasome Pathway ◽  
Skeletal Muscle Weakness ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

Mergla K + channel induces skeletal muscle atrophy by activating the ubiquitin proteasome pathway

2006 ◽  
Vol 20 (9) ◽  
pp. 1531-1533 ◽  
Author(s):  
Xun Wang ◽  
Gregory H. Hockerman ◽  
Henry W. Green ◽  
Charles F. Babbs ◽  
Sulma I. Mohammad ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Skeletal Muscle Atrophy ◽  
K Channel ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

Mechanisms of Cancer Cachexia

2009 ◽  
Vol 89 (2) ◽  
pp. 381-410 ◽  
Author(s):  
Michael J. Tisdale
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Adipose Tissue ◽  
Protein Degradation ◽  
Initiation Factor ◽  
Tissue Loss ◽  
Α Subunit ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

Up to 50% of cancer patients suffer from a progressive atrophy of adipose tissue and skeletal muscle, called cachexia, resulting in weight loss, a reduced quality of life, and a shortened survival time. Anorexia often accompanies cachexia, but appears not to be responsible for the tissue loss, particularly lean body mass. An increased resting energy expenditure is seen, possibly arising from an increased thermogenesis in skeletal muscle due to an increased expression of uncoupling protein, and increased operation of the Cori cycle. Loss of adipose tissue is due to an increased lipolysis by tumor or host products. Loss of skeletal muscle in cachexia results from a depression in protein synthesis combined with an increase in protein degradation. The increase in protein degradation may include both increased activity of the ubiquitin-proteasome pathway and lysosomes. The decrease in protein synthesis is due to a reduced level of the initiation factor 4F, decreased elongation, and decreased binding of methionyl-tRNA to the 40S ribosomal subunit through increased phosphorylation of eIF2 on the α-subunit by activation of the dsRNA-dependent protein kinase, which also increases expression of the ubiquitin-proteasome pathway through activation of NFκB. Tumor factors such as proteolysis-inducing factor and host factors such as tumor necrosis factor-α, angiotensin II, and glucocorticoids can all induce muscle atrophy. Knowledge of the mechanisms of tissue destruction in cachexia should improve methods of treatment.

scholarly journals Ubiquitin‐proteasome pathway and nuclear factor‐κB activity in skeletal muscle of mildly weight‐losing cancer patients

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Ramon C Langen ◽  
Ronnie Minnaard ◽  
Marco Kelders ◽  
Anne‐Marie Dingemans ◽  
Matthijs Hesselink ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cancer Patients ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

Anti-TNF treatment reduces rat skeletal muscle wasting in monocrotaline-induced cardiac cachexia

2008 ◽  
Vol 105 (6) ◽  
pp. 1950-1958 ◽  
Author(s):  
Brian T. Steffen ◽  
Simon J. Lees ◽  
Frank W. Booth
Keyword(s):  
Skeletal Muscle ◽  
Tnf Receptor ◽  
Sprague Dawley ◽  
Western Blots ◽  
Cardiac Cachexia ◽  
Ubiquitin Proteasome Pathway ◽  
General Inhibitor ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Soluble Tnf Receptor

The aim was to explore efficacy of tumor necrosis factor (TNF) inhibitors in attenuating increases in anorexia and ubiquitin proteasome pathway transcripts in cardiac cachexia, a potentially lethal condition that responds poorly to current treatments. Cardiac cachexia was rapidly induced with monocrotaline in Sprague-Dawley rats. Either soluble TNF receptor-1 or the general inhibitor of TNF production, pentoxifylline, was given to diminish TNF action on the first indication of cachexia. Animals were anesthetized with a ketamine-xylazine-acepromazine cocktail, and then skeletal muscles were removed for subsequent measurements including ubiquitin proteasome pathway transcripts and Western blots. Both soluble TNF receptor-1 and pentoxifylline attenuated losses in both body and skeletal muscle masses and also reduced increases in selected ubiquitin proteasome pathway transcripts. The action of soluble TNF receptor-1 was partly through reversal of reduced food consumption, while the effects of pentoxifylline were independent of food intake. Here we demonstrate, for the first time, that attenuation of anorexia by soluble TNF receptor-1 treatment in monocrotaline-induced cardiac cachexia is responsible for attenuating increases in some ubiquitin proteasome pathway transcripts as well as preserving body mass and attenuating loss of skeletal muscle mass.

IGF-I has no effect on postexercise suppression of the ubiquitin-proteasome system in rat skeletal muscle

2002 ◽  
Vol 92 (6) ◽  
pp. 2277-2284 ◽  
Author(s):  
Anthony J. Kee ◽  
Alan J. Taylor ◽  
Anthony R. Carlsson ◽  
Andre Sevette ◽  
Ross C. Smith ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Exercise ◽  
Protein Turnover ◽  
Muscle Protein ◽  
Male Rats ◽  
Ubiquitin Proteasome Pathway ◽  
Muscle Protein Turnover ◽  
Igf I ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

Both exercise and insulin-like growth factor I (IGF-I) are known to have major hypertrophic effects in skeletal muscle; however, the interactive effect of exogenous IGF-I and exercise on muscle protein turnover or the ubiquitin-proteasome pathway has not been reported. In the present study, we have examined the interaction between endurance exercise training and IGF-I treatment on muscle protein turnover and the ubiquitin-proteasome pathway in the postexercise period. Adult male rats (270–280 g) were randomized to receive 5 consecutive days of progressive treadmill exercise and/or IGF-I treatment (1 mg · kg body wt−1 · day−1). Twenty-four hours after the last bout of exercise, the rate of protein breakdown in incubated muscles was significantly reduced compared with that in unexercised rats. This was associated with a significant reduction in the chymotrypsin-like activity of the proteasome and the rate of ubiquitin-proteasome-dependent casein hydrolysis in muscle extracts from exercised compared with unexercised rats. In contrast, the muscle expression of the 20S proteasome subunit β-1, ubiquitin, and the 14-kDa E2 ubiquitin-conjugating enzyme was not altered by exercise or IGF-I treatment 24 h postexercise. Exercise had no effect on the rates of total mixed muscle protein synthesis in incubated muscles 24 h postexercise. IGF-I treatment had no effect on muscle weights or the rates of protein turnover 24 h after endurance exercise. These results suggest that a suppression of the ubiquitin-proteasome proteolytic pathway after endurance exercise may contribute to the acute postexercise net protein gain.

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