Clenbuterol induces muscle-specific attenuation of atrophy through effects on the ubiquitin-proteasome pathway

2005 ◽  
Vol 99 (1) ◽  
pp. 71-80 ◽  
Author(s):  
Tossaporn Yimlamai ◽  
Stephen L. Dodd ◽  
Stephen E. Borst ◽  
Sooyeon Park
Keyword(s):  
Muscle Atrophy ◽  
Tibialis Anterior ◽  
Weight Bearing ◽  
Ubiquitin Proteasome Pathway ◽  
Igf I ◽  
Ubiquitin Conjugating Enzyme ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Slow Twitch Fibers ◽  
Fast Twitch

The ubiquitin-proteasome pathway is primarily responsible for myofibrillar protein degradation during hindlimb unweighting (HU). β-Adrenergic agonists such as clenbuterol (CB) induce muscle hypertrophy and attenuate muscle atrophy due to disuse or inactivity. However, the molecular mechanism by which CB exerts these effects remains poorly understood. The aims of this study were to investigate whether CB attenuates HU-induced muscle atrophy through an inhibition of the ubiquitin-proteasome pathway and whether insulin-like growth factor I (IGF-I) mediates this inhibition. Rats were randomized to the following groups: weight-bearing control, 14-day CB-treated, 14-day HU, and CB + HU. HU-induced atrophy was associated with increased proteolysis and upregulation of components of the ubiquitin-proteasome pathway (ubiquitin conjugates, ubiquitin conjugating enzyme E2-14kDa, and 20S proteasome activity). Upregulation of the ubiquitin proteasome occurred in all muscles tested but was more pronounced in muscles composed primarily of slow-twitch fibers (soleus) than in fast-twitch muscles (plantaris and tibialis anterior). Although CB induced hypertrophy in all muscles, CB attenuated the HU-induced atrophy and reduced ubiquitin conjugates only in the fast plantaris and tibialis anterior and not in the slow soleus muscle. CB did not elevate IGF-I protein content in either of the muscles examined. These results suggest that CB induces hypertrophy and alleviates HU-induced atrophy, particularly in the fast muscles, at least in part through a muscle-specific inhibition of the ubiquitin-proteasome pathway and that these effects are not mediated by the local production of IGF-I in skeletal muscle.

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

Role of the ubiquitin-proteasome pathway in muscle atrophy in cachexia

2008 ◽  
Vol 2 (4) ◽  
pp. 262-266 ◽  
Author(s):  
Didier Attaix ◽  
Lydie Combaret ◽  
Daniel Béchet ◽  
Daniel Taillandier
Keyword(s):  
Muscle Atrophy ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

scholarly journals Role of Ubiquitin-Conjugating Enzyme UBE2C in Gastrointestinal Cancers

2021 ◽  
Vol 5 (5) ◽  
pp. 64-72
Author(s):  
Ce Guo ◽  
Xing Guo ◽  
Zhen Wei ◽  
Qian Wang ◽  
Huiqing Zhang
Keyword(s):  
Prognostic Marker ◽  
Therapeutic Target ◽  
Potential Role ◽  
Gastrointestinal Cancers ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Conjugating Enzyme ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Conjugating Enzyme

Ubiquitin-conjugating enzyme UBE2C is one of the important members of ubiquitin-proteasome pathway (UPP). Amplification and/or overexpression of UBE2C have been reported in many malignancies, and a high expression of UBE2C is associated with poor clinical outcomes. In this review, the pathological role of dysregulated UBE2C in gastrointestinal cancers and its potential role as a diagnostic and/or a prognostic marker as well as a therapeutic target in these cancers are discussed.

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.

Mechanical ventilation induces alterations of the ubiquitin-proteasome pathway in the diaphragm

2005 ◽  
Vol 98 (4) ◽  
pp. 1314-1321 ◽  
Author(s):  
Keith C. DeRuisseau ◽  
Andreas N. Kavazis ◽  
Melissa A. Deering ◽  
Darin J. Falk ◽  
Darin Van Gammeren ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Control Group ◽  
20S Proteasome ◽  
Mrna Levels ◽  
Α Subunit ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Conjugating Enzyme ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Conjugating Enzyme

Prolonged mechanical ventilation (MV) results in diaphragmatic atrophy due, in part, to an increase in proteolysis. These experiments tested the hypothesis that MV-induced diaphragmatic proteolysis is accompanied by increased expression of key components of the ubiquitin-proteasome pathway (UPP). To test this postulate, we investigated the effect of prolonged MV on UPP components and determined the trypsin-like and peptidylglutamyl peptide hydrolyzing activities of the 20S proteasome. Adult Sprague-Dawley rats were assigned to either control or 12-h MV groups ( n = 7/group). MV animals were anesthetized, tracheostomized, and ventilated with room air for 12 h. Animals in the control group were acutely anesthetized but not exposed to MV. Compared with controls, MV animals demonstrated increased diaphragmatic mRNA levels of two ubiquitin ligases, muscle atrophy F-box (+8.3-fold) and muscle ring finger 1 (+19.0-fold). However, MV did not alter mRNA levels of 14-kDa ubiquitin-conjugating enzyme, polyubiquitin, proteasome-activating complex PA28, or 20S α-subunit 7. Protein levels of 14-kDa ubiquitin-conjugating enzyme and proteasome-activating complex PA28 were not altered following MV, but 20S α-subunit 7 levels declined (−17.7%). MV increased diaphragmatic trypsin-like activity (+31%) but did not alter peptidylglutamyl peptide hydrolyzing activity. Finally, compared with controls, MV increased ubiquitin-protein conjugates in both the myofibrillar (+24.9%) and cytosolic (+54.7%) fractions of the diaphragm. These results are consistent with the hypothesis that prolonged MV increases diaphragmatic levels of key components within the UPP and that increases in 20S proteasome activity contribute to MV-induced diaphragmatic proteolysis and atrophy.

Chronic hypobaric hypoxia mediated skeletal muscle atrophy: role of ubiquitin–proteasome pathway and calpains

2012 ◽  
Vol 364 (1-2) ◽  
pp. 101-113 ◽  
Author(s):  
Pooja Chaudhary ◽  
Geetha Suryakumar ◽  
Rajendra Prasad ◽  
Som Nath Singh ◽  
Shakir Ali ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Hypobaric Hypoxia ◽  
Skeletal Muscle Atrophy ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

scholarly journals High Fat Diet-Induced Skeletal Muscle Wasting Is Decreased by Mesenchymal Stem Cells Administration: Implications on Oxidative Stress, Ubiquitin Proteasome Pathway Activation, and Myonuclear Apoptosis

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Johanna Abrigo ◽  
Juan Carlos Rivera ◽  
Javier Aravena ◽  
Daniel Cabrera ◽  
Felipe Simon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Stem Cells ◽  
Muscle Atrophy ◽  
High Fat Diet ◽  
Muscle Wasting ◽  
High Fat ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

Obesity can lead to skeletal muscle atrophy, a pathological condition characterized by the loss of strength and muscle mass. A feature of muscle atrophy is a decrease of myofibrillar proteins as a result of ubiquitin proteasome pathway overactivation, as evidenced by increased expression of the muscle-specific ubiquitin ligases atrogin-1 and MuRF-1. Additionally, other mechanisms are related to muscle wasting, including oxidative stress, myonuclear apoptosis, and autophagy. Stem cells are an emerging therapy in the treatment of chronic diseases such as high fat diet-induced obesity. Mesenchymal stem cells (MSCs) are a population of self-renewable and undifferentiated cells present in the bone marrow and other mesenchymal tissues of adult individuals. The present study is the first to analyze the effects of systemic MSC administration on high fat diet-induced skeletal muscle atrophy in the tibialis anterior of mice. Treatment with MSCs reduced losses of muscle strength and mass, decreases of fiber diameter and myosin heavy chain protein levels, and fiber type transitions. Underlying these antiatrophic effects, MSC administration also decreased ubiquitin proteasome pathway activation, oxidative stress, and myonuclear apoptosis. These results are the first to indicate that systemically administered MSCs could prevent muscle wasting associated with high fat diet-induced obesity and diabetes.

scholarly journals Mechanisms of glucocorticoid-induced myopathy

2008 ◽  
Vol 197 (1) ◽  
pp. 1-10 ◽  
Author(s):  
O Schakman ◽  
H Gilson ◽  
J P Thissen
Keyword(s):  
Muscle Atrophy ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Ubiquitin Proteasome System ◽  
Cross Sectional ◽  
New Therapeutic Approaches ◽  
Anabolic Action ◽  
Igf I ◽  
Ubiquitin Proteasome ◽  
Fast Twitch

Glucocorticoid-induced muscle atrophy is characterized by fast-twitch or type II muscle fiber atrophy illustrated by decreased fiber cross-sectional area and reduced myofibrillar protein content. Muscle proteolysis, in particular through the ubiquitin– proteasome system (UPS), is considered to play a major role in the catabolic action of glucocorticoids. The stimulation by glucocorticoids of the UPS is mediated through the increased expression of several atrogenes (‘genes involved in atrophy’), such as atrogin-1 and MuRF-1, two ubiquitin ligases involved in the targeting of protein to be degraded by the proteasome machinery. Glucocorticoids also exert an anti-anabolic action by blunting muscle protein synthesis. These changes in protein turnover may result from changes in the production of two growth factors which control muscle mass, namely IGF-I and myostatin respectively anabolic and catabolic toward the skeletal muscle. The decreased production of IGF-I as well as the increased production of myostatin have been both demonstrated to contribute to the muscle atrophy caused by glucocorticoids. At the molecular level, IGF-I antagonizes the catabolic action of glucocorticoids by inhibiting, through the PI3-kinase/Akt pathway, the activity of the transcription factor FOXO, a major switch for the stimulation of several atrogenes. These recent progress in the understanding of the glucocorticoid-induced muscle atrophy should allow to define new therapies aiming to minimize this myopathy. Promising new therapeutic approaches for treating glucocorticoid-induced muscle atrophy are also presented in this review.

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