title: The worsening of tibialis anterior muscle atrophy during recovery post-immobilization correlates with enhanced connective tissue area, proteolysis, and apoptosis.
abstract: Sustained muscle wasting due to immobilization leads to weakening and severe metabolic consequences. The mechanisms responsible for muscle recovery after immobilization are poorly defined. Muscle atrophy induced by immobilization worsened in the lengthened tibialis anterior (TA) muscle but not in the shortened gastrocnemius muscle. Here, we investigated some mechanisms responsible for this differential response. Adult rats were subjected to unilateral hindlimb casting for 8 days (I8). Casts were removed at I8, and animals were allowed to recover for 10 days (R1 to R10). The worsening of TA atrophy following immobilization occurred immediately after cast removal at R1 and was sustained until R10. This atrophy correlated with a decrease in type IIb myosin heavy chain (MyHC) isoform and an increase in type IIx, IIa, and I isoforms, with muscle connective tissue thickening, and with increased collagen (Col) I mRNA levels. Increased Col XII, Col IV, and Col XVIII mRNA levels during TA immobilization normalized at R6. Sustained enhanced peptidase activities of the proteasome and apoptosome activity contributed to the catabolic response during the studied recovery period. Finally, increased nuclear apoptosis prevailed only in the connective tissue compartment of the TA. Altogether, the worsening of the TA atrophy pending immediate reloading reflects a major remodeling of its fiber type properties and alterations in the structure/composition of the extracellular compartment that may influence its elasticity/stiffness. The data suggest that sustained enhanced ubiquitin-proteasome-dependent proteolysis and apoptosis are important for these adaptations and provide some rationale for explaining the atrophy of reloaded muscles pending immobilization in a lengthened position.
authors.affiliation: Institut National de Recherche Agronomique (INRA), Unite Mixte de Recherche (UMR), 1019 Unité de Nutrition Humaine 63122, Saint Genès Champanelle, France.
authors.forename: Lamia
authors.initials: L
authors.lastname: Slimani
authors.forename: Didier
authors.initials: D
authors.lastname: Micol
authors.forename: Julien
authors.initials: J
authors.lastname: Amat
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Delcros
authors.forename: Bruno
authors.initials: B
authors.lastname: Meunier
authors.forename: Daniel
authors.initials: D
authors.lastname: Taillandier
authors.forename: Cécile
authors.initials: C
authors.lastname: Polge
authors.forename: Daniel
authors.initials: D
authors.lastname: Béchet
authors.forename: Dominique
authors.initials: D
authors.lastname: Dardevet
authors.forename: Brigitte
authors.initials: B
authors.lastname: Picard
authors.forename: Didier
authors.initials: D
authors.lastname: Attaix
authors.forename: Anne
authors.initials: A
authors.lastname: Listrat
authors.forename: Lydie
authors.initials: L
authors.lastname: Combaret
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D003094:Collagen / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D003239:Connective Tissue Cells; D007103:Immobilization / Q000009:adverse effects*; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D009133:Muscular Atrophy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000145:classification / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology; D013997:Time Factors; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D025801:Ubiquitin; D003094:Collagen; D046988:Proteasome Endopeptidase Complex; D018995:Myosin Heavy Chains