Torbafylline (HWA 448) inhibits enhanced skeletal muscle ubiquitin‒proteasome-dependent proteolysis in cancer and septic rats

Combaret, Lydie; Tilignac, Thomas; Claustre, Agnès; Voisin, Laure; Taillandier, Daniel; Obled, Christiane; Tanaka, Keiji; Attaix, Didier

doi:10.1042/0264-6021:3610185

Cited by 56 publications

(63 citation statements)

References 51 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inhibition of TNF-a synthesis by xanthine derivatives prevents muscle protein breakdown in septic rats and prevents cancer and sepsis-induced increase in muscular ubiquitin gene expression (Combaret et al 2002). The discrepancy between these findings and our results might be due to the fact that xanthine derivatives inhibit TNF-a synthesis, thus decreasing local and circulating TNF; but in our study, PEG-sTNFRI administration only prevents the effect of circulating TNF.…”

Section: Discussioncontrasting

confidence: 56%

“…Anti-TNF antibodies prevented increased protein breakdown and increased expression of ubiquitin in skeletal muscle from rats with hepatoma (Costelli et al 1993, Llovera et al 1996. Moreover, inhibition of TNF production in vivo by xanthine derivatives, such as pentoxifylline or torbafylline prevented muscle wasting and suppressed the enhanced ubiquitin-proteasome-dependent proteolysis in septic and cancer rats , Combaret et al 2002. In arthritic rats, the increase in muscular MuRF-1 and MAFbx gene expression was accompanied by the increase in the gene expression of TNF-a (Granado et al 2005).…”

Section: Introductionmentioning

confidence: 93%

See 1 more Smart Citation

Tumour necrosis factor blockade did not prevent the increase of muscular muscle RING finger-1 and muscle atrophy F-box in arthritic rats

Granado¹,

Martín²,

Priego³

et al. 2006

Journal of Endocrinology

View full text Add to dashboard Cite

Chronic inflammation is associated with a decrease in body weight and cachexia, which is characterized by anorexia and skeletal muscle wasting. The expression of atrogens muscle RING finger-1 (MuRF-1) and muscle atrophy F-box (MAFbx) are increased in muscle atrophy and it is known that tumour necrosis factor (TNF) regulates skeletal muscle loss through TNF receptor p55 (TNFRI). The aim of this study was to examine the effect of polyethylene glycol linked to soluble TNFRI (PEG-sTNFRI) on gene expression of the atrogens MuRF-1 and MAFbx in skeletal muscle of arthritic rats. Rats were injected with Freund's adjuvant and, 15 days later, arthritic and control rats were injected daily with PEG-sTNFRI (1 mg/kg, s.c.) or saline for 8 days. Arthritis decreased body weight gain, the weight of skeletal muscle and adipose mass. PEG-sTNFRI administration increased body weight gain and adipose mass of arthritic rats; however, it did not modify the skeletal muscle weight. The gene expression of TNF-a, MuRF1 and MAFbx, IGF-I and IGFBP-5 were increased in the skeletal muscle of arthritic rats, and the administration of PEG-sTNFRI did not modify these parameters. These data suggest that the anti-TNF agent PEG-sTNFRI did not prevent the increase in E3 ubiquitinligating enzymes, MuRF1 and MAFbx, gene expression in the skeletal muscle of arthritic rats.

show abstract

Section: Discussioncontrasting

confidence: 56%

Section: Introductionmentioning

confidence: 93%

Tumour necrosis factor blockade did not prevent the increase of muscular muscle RING finger-1 and muscle atrophy F-box in arthritic rats

Granado¹,

Martín²,

Priego³

et al. 2006

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Increased expression of some 19S cap subunits have also been reported but is not as consistent a finding 44,[48][49][50] . Proteasome activity in muscle, as measured by in vitro assays, has also been found to be increased in some catabolic conditions [51][52][53] .…”

Section: Understanding Muscle Wasting -Exploring the Roles Of Proteolmentioning

confidence: 91%

Proteolysis in illness-associated skeletal muscle atrophy: from pathways to networks

Wing

Lecker

Jagoe

2011

Critical Reviews in Clinical Laboratory Sciences

View full text Add to dashboard Cite

Improvements in health in the past decades have resulted in increased numbers of the elderly in both developed and developing regions of the world. Advances in therapy have also increased the prevalence of patients with chronic and degenerative diseases. Muscle wasting, a feature of most chronic diseases, is prominent in the elderly and contributes to both morbidity and mortality. A major research goal has been to identify the proteolytic system(s) that is responsible for the degradation of proteins that occurs in muscle atrophy. Findings over the past 20 years have clearly confirmed an important role of the ubiquitin proteasome system in mediating muscle proteolysis, particularly that of myofibrillar proteins. However, recent observations have provided evidence that autophagy, calpains and caspases also contribute to the turnover of muscle proteins in catabolic states, and furthermore, that these diverse proteolytic systems interact with each other at various levels. Importantly, a number of intracellular signaling pathways such as the IGF1/AKT, myostatin/Smad, PGC1, cytokine/NFκB, and AMPK pathways are now known to interact and can regulate some of these proteolytic systems in a coordinated manner. A number of loss of function studies have identified promising therapeutic approaches to the prevention and treatment of wasting. However, additional biomarkers and other approaches to improve early identification of patients who would benefit from such treatment need to be developed. The current data suggests a network of interacting proteolytic and signaling pathways in muscle. Future studies are needed to improve understanding of the nature and control of these interactions and how they work to preserve muscle function under various states of growth and atrophy.

show abstract

“…69). Administration of TNF-␣ can induce cachexia (69), and blockade of TNF-␣ by torbafylline in rats with either cancer or sepsis prevents muscle wasting (15). TNF-␣ treatment alone also leads to increased protein degradation in cultured muscle cells (62).…”

Section: Tnf-␣ and Other Cytokinesmentioning

confidence: 99%

The molecular basis of skeletal muscle atrophy

Jackman¹,

Kandarian²

2004

American Journal of Physiology-Cell Physiology

816

708

View full text Add to dashboard Cite

. The molecular basis of skeletal muscle atrophy. Am J Physiol Cell Physiol 287: C834 -C843, 2004; 10.1152/ajpcell.00579.2003.-Skeletal muscle atrophy attributable to muscular inactivity has significant adverse functional consequences. While the initiating physiological event leading to atrophy seems to be the loss of muscle tension and a good deal of the physiology of muscle atrophy has been characterized, little is known about the triggers or the molecular signaling events underlying this process. Decreases in protein synthesis and increases in protein degradation both have been shown to contribute to muscle protein loss due to disuse, and recent work has delineated elements of both synthetic and proteolytic processes underlying muscle atrophy. It is also becoming evident that interactions among known proteolytic pathways (ubiquitin-proteasome, lysosomal, and calpain) are involved in muscle proteolysis during atrophy. Factors such as TNF-␣, glucocorticoids, myostatin, and reactive oxygen species can induce muscle protein loss under specified conditions. Also, it is now apparent that the transcription factor NF-B is a key intracellular signal transducer in disuse atrophy. Transcriptional profiles of atrophying muscle show both up-and downregulation of various genes over time, thus providing further evidence that there are multiple concurrent processes involved in muscle atrophy. The purpose of this review is to synthesize our current understanding of the molecular regulation of muscle atrophy. We also discuss how ongoing work should uncover more about the molecular underpinnings of muscle wasting, particularly that due to disuse. protein synthesis; protein degradation; nuclear factor-B; disuse; unloading; cachexia OVERVIEW Skeletal muscle atrophy is a change that occurs in muscles of adult animals as a result of the conditions of disuse (e.g., immobilization, denervation, muscle unloading), aging, starvation, and a number of disease states (i.e., cachexia). Regardless of the inciting event, skeletal muscle atrophy is characterized by a decrease in protein content, fiber diameter, force production, and fatigue resistance. The different types of conditions producing atrophy imply different types of molecular triggers and signaling pathways for muscle wasting. This review focuses on our current knowledge of the molecules involved in disuse atrophy.Although the molecular aspects of atrophy have received increased attention in the literature, the detailed reviews on disuse atrophy are concerned with the characterization of morphological and physiological changes (12,20,90). With cachexia, there have been multiple reviews, each having a slightly different focus, that summarize work on putative triggers and signaling molecules and on details of the proteolytic processes governing this type of muscle wasting (37,38,57,58). There are no comprehensive reviews, however, on the molecular basis of disuse atrophy with an organized discussion on the whole process, from the potential triggers and signaling molecules to the fi...

show abstract

Torbafylline (HWA 448) inhibits enhanced skeletal muscle ubiquitin‒proteasome-dependent proteolysis in cancer and septic rats

Cited by 56 publications

References 51 publications

Tumour necrosis factor blockade did not prevent the increase of muscular muscle RING finger-1 and muscle atrophy F-box in arthritic rats

Tumour necrosis factor blockade did not prevent the increase of muscular muscle RING finger-1 and muscle atrophy F-box in arthritic rats

Proteolysis in illness-associated skeletal muscle atrophy: from pathways to networks

The molecular basis of skeletal muscle atrophy

Contact Info

Product

Resources

About