Effects of formoterol on protein metabolism in myotubes during hyperthermia.

Proteolysis in skeletal muscle is mainly carried out by the activity of the ubiquitin-dependent proteolytic system. For the study of protein degradation through the ubiquitin-proteasome pathway, we used a model of hyperthermia in murine myotubes. In C2C12 cells, hyperthermia (41°C) induced a significant increase in both the rate of protein synthesis (18%) and degradation (51%).

Modulations of the calcineurin/NF-AT pathway in skeletal muscle atrophy.

Calcineurin has been proposed to regulate skeletal muscle hypertrophy, while its relevance to the pathogenesis of muscle atrophy is unknown. The present study was aimed to investigate if perturbations of the calcineurin pathway may be involved in causing skeletal muscle atrophy in two different experimental conditions: cancer cachexia (rats bearing the AH-130 hepatoma), and hyperglycemia (rats treated with streptozotocin). Calcineurin expression in the gastrocnemius was comparable between tumor hosts and controls.

Interleukin-15 decreases proteolysis in skeletal muscle: a direct effect.

Incubation of rat isolated skeletal muscles (extensor digitorum longus) in the presence of 100 ng/ml of human recombinant interleukin-15 (IL-15) resulted in a significant decrease in total proteolytic rate, while it had no effect on total protein synthesis as measured by the incorporation of (14)C-phenylalanine into muscle protein. In addition, IL-15 had no effect on either amino acid uptake (as determined by the tissue uptake of labelled [1-(14)C]MeAIB) or alanine utilization by incubated skeletal muscles. Similarly, a single injection of IL-15 (100 microg/kg) in vivo did not result in any changes in amino acid uptake (as measured by the tissue uptake of alpha-[1-(14)C]AIB) or alanine metabolism, with the exception of alanine carbon incorporation into lipids, which was significantly increased in adipose tissue as a result of IL-15 administration.

Anticachectic effects of formoterol: a drug for potential treatment of muscle wasting.

In cancer cachexia both cardiac and skeletal muscle suffer an important protein mobilization as a result of increased proteolysis. Administration of the beta2-agonist formoterol to both rats and mice bearing highly cachectic tumors resulted in an important reversal of the muscle-wasting process. The anti-wasting effects of the drug were based on both an activation of the rate of protein synthesis and an inhibition of the rate of muscle proteolysis.