6533b86cfe1ef96bd12c8a28

RESEARCH PRODUCT

Oxidative Stress and Ubiquitin Ligases: their involvement in skeletal muscle atrophy

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description

Introduction Muscle atrophy plays a relevant role in the many very prevalent diseases. Generation of reactive oxygen species (mainly by the xanthine oxidase) and inflammation are two of the main triggers of muscle atrophy. Aim The major aim of our study was to determine the mechanism by which reactive oxygen species activate E3 ubiquitin ligases (MuRF-1 and MAFbx) cause muscle atrophy. Possible prevention by allopurinol, a well-known xanthine oxidase inhibitor widely used in clinical practice; and by indomethacin, a non-steroidal antiinflamatory drug was also studied. Materials and methods Male C57BL/6J mice (3 months old) conditioned by 14 days of hindlimb unloading with or without each treatment or the combination of both of them (n=48) were compared with freely ambulating controls (n=48). Results After the experimental intervention, we found that hindlimb unloading induced a significant increase in xanthine oxidase activity and prostaglandins in plasma ( 209%, p Conclusions Our data point out the potential benefit of allopurinol and indomethacin administration for bedridden, astronauts or muscle disuse; as well as a potential benefit in other atrophy models such as pathology-related cachexia or sarcopenia. Acknowledgments This work was supported by grants SAF2010- 19498, ISCIII2006-RED13-027, PROMETEO2010/074, 35NEURO GentxGent and EU Funded COSTB35 and CM1001. The study has been co-financed by FEDER funds from the European Union.