title: Slow recovery of the impaired fatigue resistance in postunloading mouse soleus muscle corresponding to decreased mitochondrial function and a compensatory increase in type I slow fibers.
abstract: Unloading or disuse rapidly results in skeletal muscle atrophy, switching to fast-type fibers, and decreased resistance to fatigue. The recovery process is of major importance in rehabilitation for various clinical conditions. Here we studied mouse soleus muscle during 60 days of reloading after 4 wk of hindlimb suspension. Unloading produced significant atrophy of soleus muscle with decreased contractile force and fatigue resistance, accompanied by switches of myosin isoforms from IIa to IIx and IIb and fast troponin T to more low-molecular-weight splice forms. The total mass, fiber size, and contractile force of soleus muscle recovered to control levels after 15 days of reloading. However, the fatigue resistance showed a trend of worsening during this period with significant infiltration of inflammatory cells at days 3 and 7, indicating reloading injuries that were accompanied by active regeneration with upregulations of filamin-C, αB-crystallin, and desmin. The fatigue resistance partially recovered after 30-60 days of reloading. The expression of peroxisome proliferator-activated receptor γ coactivator 1α and mitofusin-2 showed changes parallel to that of fatigue resistance after unloading and during reloading, suggesting a causal role of decreased mitochondrial function. Slow fiber contents in the soleus muscle were increased after 30-60 days of reloading to become significantly higher than the normal level, indicating a secondary adaption to compensate for the slow recovery of fatigue resistance.
authors.affiliation: Department of Physiology, Wayne State University, Detroit, Michigan;
authors.forename: Han-Zhong
authors.initials: HZ
authors.lastname: Feng
authors.affiliation: Department of Physiology, Wayne State University, Detroit, Michigan;
authors.forename: Xuequn
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Health Care Sciences, Wayne State University, Detroit, Michigan.
authors.forename: Moh H
authors.initials: MH
authors.lastname: Malek
authors.affiliation: Department of Physiology, Wayne State University, Detroit, Michigan; jjin@med.wayne.edu.
authors.forename: J-P
authors.initials: JP
authors.lastname: Jin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D019417:Hindlimb Suspension; D008297:Male; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000473:pathology; D009119:Muscle Contraction; D018763:Muscle Fatigue; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism / Q000473:pathology; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020127:Recovery of Function; D012038:Regeneration; D013997:Time Factors
chemical_list: D009124:Muscle Proteins
keywords: in situ fatigue resistance; peroxisome proliferator-activated receptor γ coactivator 1α; reloading injury and adaptation; skeletal muscle unloading; type I slow fiber