title: Curcumin treatment prevents increased proteasome and apoptosome activities in rat skeletal muscle during reloading and improves subsequent recovery.
abstract: Immobilization is characterized by activation of the ubiquitin (Ub)-proteasome-dependent proteolytic system (UPS) and of the mitochondrial apoptotic pathway. Increased oxidative stress and inflammatory response occur in immobilized skeletal muscles. Curcumin exhibits antioxidant and anti-inflammatory properties, blocked proteasome activation in intact animals, and may favor skeletal muscle regeneration. We therefore measured the effects of curcumin on immobilization-induced muscle atrophy and subsequent recovery. Rats were subjected to hindlimb immobilization for 8 days (I8) and allowed to recover for 10 days (R10). Fifty percent of the rats were injected daily with either curcumin or vehicle. Proteolytic and apoptotic pathways were studied in gastrocnemius muscles. Curcumin treatment prevented the enhanced proteasome chymotrypsin-like activity and the trend toward increased caspase-9-associated apoptosome activity at I8 in immobilized muscles. By contrast, the increase of these two activities was blunted by curcumin at R10. Curcumin did not reduce muscle atrophy at I8 but improved muscle recovery at R10 and the cross-sectional area of muscle fibers of immobilized muscles. Curcumin reduced the increased protein levels of Smac/DIABLO induced by immobilization and enhanced the elevation of X-linked inhibitory apoptotic protein levels at R10. Ub-conjugate levels and caspase-3 activity increased at I8 and were normalized at R10 without being affected by curcumin treatment. Altogether, the data show that curcumin treatment improved recovery during reloading. The effect of curcumin during the atrophic phase on proteasome activities may facilitate the initiation of muscle recovery after reloading. These data also suggest that this compound may favor the initial steps of muscle regeneration.
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Vazeille
authors.forename: Lamia
authors.initials: L
authors.lastname: Slimani
authors.forename: Agnès
authors.initials: A
authors.lastname: Claustre
authors.forename: Hugues
authors.initials: H
authors.lastname: Magne
authors.forename: Roland
authors.initials: R
authors.lastname: Labas
authors.forename: Daniel
authors.initials: D
authors.lastname: Béchet
authors.forename: Daniel
authors.initials: D
authors.lastname: Taillandier
authors.forename: Dominique
authors.initials: D
authors.lastname: Dardevet
authors.forename: Thierry
authors.initials: T
authors.lastname: Astruc
authors.forename: Didier
authors.initials: D
authors.lastname: Attaix
authors.forename: Lydie
authors.initials: L
authors.lastname: Combaret
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D053478:Apoptosomes / Q000187:drug effects* / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D019417:Hindlimb Suspension; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009133:Muscular Atrophy / Q000188:drug therapy; D010936:Plant Extracts / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D053478:Apoptosomes; D009124:Muscle Proteins; D010936:Plant Extracts; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D046988:Proteasome Endopeptidase Complex; D003474:Curcumin