Ubiquitin gene expression is increased in skeletal muscle of tumour‐bearing rats

Llovera, Marta; Garcı́a-Martı́nez, Cèlia; Agell, Neus; M, Marzàbal; López‐Soriano, Francisco J.; Argilés, Josep Μ.

doi:10.1016/0014-5793(94)80290-4

Cited by 130 publications

(79 citation statements)

References 53 publications

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“…As previously shown (Llovera et al, 1994), the accelerated muscle protein breakdown in the AH-130 hosts is associated with activation of the ATP-ubiquitin-dependent proteolytic system. Two polyubiquitin mRNA species (2.4 kb and 1.2 kb) were found in tibialis muscle (Figure 1).…”

Section: Resultssupporting

confidence: 55%

“…Recently, this proteolytic system has been involved in the perturbations of protein metabolism in skeletal muscle in many pathological conditions (see Argilés and López-Soriano, 1996 for review). Previous studies from our laboratory have shown that the lysosomal pathway is only marginally involved in the development of muscle protein hypercatabolism in the AH-130 hosts (Llovera et al, 1994;Tessitore et al, 1994), while an important activation of the ATP-dependent proteolysis seems to be the major mechanism (Llovera et al, 1994;Costelli et al, 1995). It is very interesting to observe that the preventive effect exerted by IL-15 on the acceleration of muscle protein breakdown is associated with a normalization of the hyperexpression of both the C8 proteasome subunit and the ubiquitin mRNAs.…”

Section: Discussionmentioning

confidence: 80%

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Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats

et al. 2000

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Tissue protein hypercatabolism (TPH) is an important feature in cancer cachexia, particularly with regard to the skeletal muscle. The Yoshida AH-130 rat ascites hepatoma is a model system for studying the mechanisms involved in the processes that lead to tissue depletion, since it induces in the host a rapid and progressive muscle wasting, primarily due to TPH. The present study was aimed at investigating if IL-15, which is known to favour muscle fibre hypertrophy, could antagonize the enhanced muscle protein breakdown in this cancer cachexia model. Indeed, IL-15 treatment partly inhibited skeletal muscle wasting in AH-130-bearing rats by decreasing (8-fold) protein degradative rates (as measured by 14 C-bicarbonate pre-loading of muscle proteins) to values even lower than those observed in non-tumour-bearing animals. These alterations in protein breakdown rates were associated with an inhibition of the ATP-ubiquitin-dependent proteolytic pathway (35% and 41% for 2.4 and 1.2 kb ubiquitin mRNA, and 57% for the C8 proteasome subunit, respectively). The cytokine did not modify the plasma levels of corticosterone and insulin in the tumour hosts. The present data give new insights into the mechanisms by which IL-15 exerts its preventive effect on muscle protein wasting and seem to warrant the implementation of experimental protocols involving the use of the cytokine in the treatment of pathological states characterized by TPH, particularly in skeletal muscle, such as in the present model of cancer cachexia. © 2000 Cancer Research Campaign

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Section: Resultssupporting

confidence: 55%

Section: Discussionmentioning

confidence: 80%

Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats

et al. 2000

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“…Nevertheless, we cannot rule out the possibility that other pathways that we did not examine may have been activated by circulating TNF-α in aging muscles. For example, TNF-α has been shown to directly promote protein degradation [33][34][35][36] and apoptosis [37] within skeletal muscle. Furthermore, intravenous injection of recombinant TNF-α increases protein degradation in rat skeletal muscles and this is associated with the increased activity of the ubiquitin-dependent proteolytic pathway [33,34,36,38].…”

Section: Effects Of Tnf-α In Skeletal Musclementioning

confidence: 99%

“…For example, TNF-α has been shown to directly promote protein degradation [33][34][35][36] and apoptosis [37] within skeletal muscle. Furthermore, intravenous injection of recombinant TNF-α increases protein degradation in rat skeletal muscles and this is associated with the increased activity of the ubiquitin-dependent proteolytic pathway [33,34,36,38]. In addition, elevated TNF-α concentrations in cell culture for 24-48 h increases apoptosis in skeletal myoblasts as determined by DNA fragmentation [39,40].…”

Section: Effects Of Tnf-α In Skeletal Musclementioning

confidence: 99%

Death receptor-associated pro-apoptotic signaling in aged skeletal muscle

2006

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Tumor necrosis factor-alpha (TNF-α) is elevated in the serum as a result of aging and it promotes pro-apoptotic signaling upon binding to the type I TNF receptor. It is not known if activation of this apoptotic pathway contributes to the well-documented age-associated decline in muscle mass (i.e. sarcopenia). We tested the hypothesis that skeletal muscles from aged rodents would exhibit elevations in markers involved in the extrinsic apoptotic pathway when compared to muscles from young adult rodents, thereby contributing to an increased incidence of nuclear apoptosis in these muscles. The plantaris (fast) and soleus (slow) muscles were studied in young adult (5-7 mo, n = 8) and aged (33 mo, n = 8) Fischer 344 × Brown Norway rats. Muscles from aged rats were significantly smaller while exhibiting a greater incidence of apoptosis. Furthermore, muscles from aged rats had higher type I TNF receptor and Fas associated death domain protein (FADD) mRNA, protein contents for FADD, BCL-2 Interacting Domain (Bid), FLICE-inhibitory protein (FLIP), and enzymatic activities of caspase-8 and caspase-3 than muscles from young adult rats. Significant correlations were observed in the plantaris muscle between caspase activity and muscle weight and the apoptotic index, while similar relationships were not found in the soleus. These data demonstrate that pro-apoptotic signaling downstream of the TNF receptor is active in aged muscles. Furthermore, our data extend the previous demonstration that type II fibers are preferentially affected by aging and support the hypothesis that type II fiber containing skeletal muscles may be more susceptible to muscle mass loses via the extrinsic apoptotic pathway.

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“…The same proteolytic pathway has been implicated in muscle breakdown caused by denervation (11), fasting (12), acidosis (13), cancer (14), and burn injury (15).…”

Section: Introductionmentioning

confidence: 99%

Energy-ubiquitin-dependent muscle proteolysis during sepsis in rats is regulated by glucocorticoids.

Tiao

Fagan²,

Roegner³

et al. 1996

J. Clin. Invest.

224

198

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Recent studies suggest that sepsis-induced increase in muscle proteolysis mainly reflects energy-ubiquitin-dependent protein breakdown. We tested the hypothesis that glucocorticoids activate the energy-ubiquitin-dependent proteolytic pathway in skeletal muscle during sepsis. Rats underwent induction of sepsis by cecal ligation and puncture or were sham-operated and muscle protein breakdown rates were measured 16 h later. The glucocorticoid receptor antagonist RU 38486 or vehicle was administered to groups of septic and sham-operated rats. In other experiments, dexamethasone (2.5 or 10 mg/kg) was injected subcutaneously in normal rats. Total and myofibrillar proteolysis was determined in incubated extensor digitorum longus muscles as release of tyrosine and 3-methylhistidine, respectively. Energydependent proteolysis was determined in incubated muscles depleted of energy with 2-deoxyglucose and 2,4-dinitrophenol. Levels of muscle ubiquitin mRNA and free and conjugated ubiquitin were determined by Northern and Western blot, respectively. RU 38486 inhibited the sepsis-induced increase in total and myofibrillar energy-dependent protein breakdown rates and blunted the increase in ubiquitin mRNA levels and free ubiquitin. Some, but not all, sepsisinduced changes in ubiquitin protein conjugates were inhibited by RU 38486. Injection of dexamethasone in normal rats increased energy-dependent proteolysis and ubiquitin mRNA levels. The results suggest that glucocorticoids regulate the energy-ubiquitin-dependent proteolytic pathway in skeletal muscle during sepsis.

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Ubiquitin gene expression is increased in skeletal muscle of tumour‐bearing rats

Cited by 130 publications

References 53 publications

Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats

Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats

Death receptor-associated pro-apoptotic signaling in aged skeletal muscle

Energy-ubiquitin-dependent muscle proteolysis during sepsis in rats is regulated by glucocorticoids.

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