Muscle protein waste in tumor-bearing rats is effectively antagonized by a beta 2-adrenergic agonist (clenbuterol). Role of the ATP-ubiquitin-dependent proteolytic pathway.

Abstract

The present data give new insights into the mechanisms by which clenbuterol exerts its preventive effect on muscle protein waste and seem to warrant the implementation of experimental protocols involving the use of clenbuterol or alike drugs in the treatment of pathological states involving TPH, particularly in skeletal muscle and heart, such as in the present model of cancer cachexia. (J. Clin. Invest. 1995Invest. . 95:2367Invest. -2372

Formoterol and cancer muscle wasting in rats: Effects on muscle force and total physical activity

“…Similar results were previously described by our research group (19,23). Indeed, formoterol and other β 2 -agonists such as clenbuterol were found to be effective in ameliorating muscle weight loss during wasting (19,23,24). At the biochemical level, the mechanisms underlying the effects of the β 2 -agonist are complex.…”

Cancer cachexia: Physical activity and muscle force in tumour-bearing rats

“…The implantation of the tumour leads to a very fast weight loss, which is accompanied by anorexia in the terminal state. The weight loss is associated with both fat and skeletal muscle wasting, as has been shown previously by our research group (5)(6)(7).…”

“…At day 10 after tumour inoculation, the reduction in food intake accounts for 87%. Previous studies carried out in our laboratory have shown that weight loss in this animal model is associated with both adipose and skeletal muscle wasting (6,7). The muscle loss is due to several factors that include increased proteolysis (5), increased apoptosis (15), increased amino acid oxidation (19,20) and decreased muscle regeneration (21,22).…”

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

“…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.…”