ROYAL MONACO RIVIERA WEB MAGAZINE
PAGINA WEB AMBASCIATA D'ITALIA NEL PRINCIPATO DI MONACO
MEDICINE & CHINESE TRADITIONAL MEDICINE
Luigi Mattera is a certified by CERFPA (St. Laurent du Var-France) in HOMEOPATHY & ZUO TUINA MASSAGE OF TRADITIONAL CHINESE MEDICINE - Online certificate from TEXAS CHIROPRACTIC COLLEGE (Pasadena-Texas 2007) in CHIROPRACTIC SPORTS & CHIROPRACTIC TREATMENT OF GOLF INJURIES
The Proteasome Inhibitor MG132 Reduces Immobilization-Induced Skeletal Muscle Atrophy in Mice
BMC Musculoskeletal Disorders 2011, 12:185doi:10.1186/1471-2474-12-185
|Published:||15 August 2011|
Skeletal muscle atrophy is a serious concern for the rehabilitation of patients afflicted by prolonged limb restriction. This debilitating condition is associated with a marked activation of NFkappaB activity. The ubiquitin-proteasome pathway degrades the NFkappaB inhibitor IkappaBalpha, enabling NFkappaB to translocate to the nucleus and bind to the target genes that promote muscle atrophy. Although several studies showed that proteasome inhibitors are efficient to reduce atrophy, no studies have demonstrated the ability of these inhibitors to preserve muscle function under catabolic condition.
We recently developed a new hindlimb immobilization procedure that induces significant skeletal muscle atrophy and used it to show that an inflammatory process characterized by the up-regulation of TNFalpha, a known activator of the canonical NFkappaB pathway, is associated with the atrophy. Here, we used this model to investigate the effect of in-vivo proteasome inhibition on the muscle integrity by histological approach. TNFalpha, IL-1, IL-6, MuRF-1 and Atrogin/MAFbx mRNA level were determined by qPCR. Also, a functional measurement of locomotors activity was performed to determine if the treatment can shorten the rehabilitation period following immobilization.
In the present study, we showed that the proteasome inhibitor MG132 significantly inhibited IkappaBalpha degradation thus preventing NFkappaB activation in vitro. MG132 preserved muscle and myofiber cross-sectional area by downregulating the muscle-specific ubiquitin ligases atrogin-1/MAFbx and MuRF-1 in vivo. This effect resulted in a diminished rehabilitation period.
These finding demonstrate that proteasome inhibitors show potential for the development of pharmacological therapies to prevent muscle atrophy and thus favor muscle rehabilitation.