title: Effect of flywheel-based resistance exercise on processes contributing to muscle atrophy during unloading in adult rats.
abstract: Flywheel-based resistance exercise (RE) attenuates muscle atrophy during hindlimb suspension. We have previously shown that protein synthesis is elevated in response to RE, but the effect on protein degradation, cell proliferation, or apoptosis was not investigated. We hypothesized that, in addition to affecting protein synthesis, RE inhibits processes that actively contribute to muscle atrophy during hindlimb suspension. Male rats were housed in regular cages (control), tail suspended for 2 wk (HS), or HS with RE every other day for 2 wk (HSRE). Although RE attenuated soleus muscle atrophy during HS, the observed fivefold elevation in apoptosis and the 53% decrease in cell proliferation observed with HS were unaffected by RE. Expression of genes encoding components of the ubiquitin-proteasome pathway of protein degradation were elevated with HS, including ubiquitin, MAFbx, Murf-1, Nedd4, and XIAP, and proteasome subunits C2 and C9. Total ubiquitinated protein was increased with HS, but proteasome activity was not different from control. RE selectively altered the expression of different components of this pathway: MAFbx, Murf-1, and ubiquitin mRNA abundance were downregulated, whereas C2 and C9 subunits remained elevated. Similarly, Nedd4 and XIAP continued to be upregulated, potentially accounting for the observed augmentation in total ubiquitinated protein with RE. Thus a different constellation of proteins is likely ubiquitinated with RE due to altered ubiquitin ligase composition. In summary, the flywheel-based resistance exercise paradigm used in this study is associated with the inhibition of some mechanisms associated with muscle atrophy, such as the increase in MAFbx and Murf-1, but not with others, such as proteasome subunit remodeling, apoptosis, and decreased proliferation, potentially accounting for the inability to completely restore muscle mass. Identifying specific exercise parameters that affect these latter processes may be useful in designing effective exercise strategies in the elderly or during spaceflight.
authors.affiliation: Department of Geriatrics, University of Arkansas for Medical Sciences, 4301 West Markham #807, Little Rock, Arkansas 72205, USA. dupontesthere@uams.edu
authors.forename: Esther E
authors.initials: EE
authors.lastname: Dupont-Versteegden
authors.forename: James D
authors.initials: JD
authors.lastname: Fluckey
authors.forename: Micheal
authors.initials: M
authors.lastname: Knox
authors.forename: Dana
authors.initials: D
authors.lastname: Gaddy
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Peterson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation; D056827:Endosomal Sorting Complexes Required for Transport; D005786:Gene Expression Regulation / Q000502:physiology; D006112:Gravitation; D019417:Hindlimb Suspension / Q000502:physiology*; D007537:Isometric Contraction / Q000502:physiology*; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000473:pathology / Q000503:physiopathology*; D000075702:Nedd4 Ubiquitin Protein Ligases; D010805:Physical Conditioning, Animal / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000032:analysis / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D016474:Weight-Bearing; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin; D051636:X-Linked Inhibitor of Apoptosis Protein; C000618479:NEDD4L protein, rat; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618484:Nedd4 protein, rat; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; C499086:Trim63 protein, rat; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex