title: Time course of ubiquitin-proteasome and macroautophagy-lysosome pathways in skeletal muscle in rats with heart failure.
abstract: Patients with heart failure have limited exercise capacity due to not only the myocardial dysfunction but also skeletal muscle atrophy. However, the mechanisms and time course of protein degradation in skeletal muscle during heart failure remain unclear, and there is no established standard treatment. The purpose of the present study was to investigate the time course of major protein degradation pathways in skeletal muscle during heart failure. Four-week-old male Wistar rats were randomly assigned to heart failure induced by monocrotaline or control groups. At 14 and 21 days after monocrotaline injection, the lungs, heart, and gastrocnemius and soleus muscles were removed and analyzed. There was no significant difference in body weight between the groups at 14 days after monocrotaline injection. Although there were no morphological changes in the skeletal muscle of the monocrotaline group at this time point, ubiquitin-proteasome and macroautophagylysosome pathways were activated in the monocrotaline group. Additionally, the pathways were less strongly activated in the soleus muscle than in the gastrocnemius muscle. These results suggest that physical exercise that shifts to slow muscle characteristics should begin when there is no indication of skeletal muscle atrophy to prevent exercise intolerance with heart failure.
authors.affiliation: Department of Musculoskeletal Functional Research and Regeneration, Graduate School of Biomedicine and Health Sciences, Hiroshima University.
authors.forename: Naoto
authors.initials: N
authors.lastname: Fujita
authors.forename: Hidemi
authors.initials: H
authors.lastname: Fujino
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Jyunya
authors.initials: J
authors.lastname: Takegaki
authors.forename: Masataka
authors.initials: M
authors.lastname: Deie
mesh_terms: D000818:Animals; D001343:Autophagy; D001835:Body Weight; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000473:pathology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D016686:Monocrotaline / Q000633:toxicity; D018482:Muscle, Skeletal / Q000378:metabolism*; D009133:Muscular Atrophy / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; D016686:Monocrotaline; D046988:Proteasome Endopeptidase Complex