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

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.

Innate link between NF-κB activity and ubiquitin-like modifiers

2008 ◽  
Vol 36 (5) ◽  
pp. 853-857 ◽  
Author(s):  
Valérie Lang ◽  
Manuel S. Rodríguez
Keyword(s):  
Transcription Factor ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Post Translational Modifications ◽  
Macromolecular Complexes ◽  
The Status ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Pathway Regulation ◽  
The One

Among the several signalling pathways regulated by ubiquitin and ubiquitin-like proteins, the one activating NF-κB (nuclear factor κB) is certainly one of the best characterized. The regulation of the activity of this transcription factor by members of the ubiquitin family occurs at various levels, imposing overlapping controls of security of intriguing complexity. The formation of active macromolecular complexes such as the IKK [IκB (inhibitory κB) kinase] complex is tightly regulated by these post-translational modifications probably due to the fact that many signals converge on this signal's roundabout. An additional, very important level of NF-κB control occurs through the partial or total proteolysis of precursor and inhibitor molecules exerted by the ubiquitin–proteasome pathway. Regulation at this level implicates various conjugating and de-conjugating activities for ubiquitin, SUMO (small ubiquitin-related modifier) and NEDD8. Here, we summarize some of these events and underline the importance of the interconnecting ubiquitin and ubiquitin-like conjugating pathways that determine the status of the activity of this critical transcription factor.

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.

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