Résumé :
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Skeletal muscle atrophy is a significant co-morbidity seen in a variety of diseases, including Congestive Heart Failure, renal failure, cancer, and AIDS. Even during simple muscle inactivity, such as when a cast is put on a limb, the affected muscle can decrease by as much as 50% in mass, with a coincident decrease in strength. The loss of muscle during aging is referred to as "sarcopenia" and may occur due to distinct mechanisms. Two E3 ubiquitin ligases MuRF1 (Muscle RING Finger 1) and MAFbx (Muscle Atrophy Fbox protein, which is also known as Atrogin), are transcriptionally upregulated in all physiological settings of muscle atrophy that have been analyzed. The pathways which regulate these ligases will be discussed. Also, more recently, potential substrates of MuRF1- which comprise part of the skeletal muscle contractile apparatus - have been elucidated. These substrates, including components of the sarcomeric thick filament, will be discussed, as well as conditions that can modulate MuRF1's activity. An additional important modulator of muscle mass is myostatin, a TGF-beta family member. We have recently conducted studies demonstrating the ways that myostatin perturbs muscle mass and function, which both confirms other studies showing an inhibitory effect on muscle differentiation, but which also shows several important points of cross-talk between myostatin signaling and Akt/TORC1 signaling. We have recently found additional E3 ligases that control the hypertrophy pathway, which will be discussed at this meeting. Finally, an expression study was conducted on sarcopenic muscle, in order to understand whether the loss of muscle seen in aging occurs via similar mechanisms as those found during acute skeletal muscle atrophy.
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