title: Immobilization-induced activation of key proteolytic systems in skeletal muscles is prevented by a mitochondria-targeted antioxidant.
abstract: Long periods of skeletal muscle disuse result in muscle fiber atrophy, and mitochondrial production of reactive oxygen species (ROS) appears to be a required signal for the increase in protein degradation that occurs during disuse muscle atrophy. The experiments detailed here demonstrate for the first time in limb muscle that the inactivity-induced increases in E3 ligase expression and autophagy biomarkers result from increases in mitochondrial ROS emission. Treatment of animals with a mitochondrial-targeted antioxidant also prevented the disuse-induced decrease in anabolic signaling (Akt/mammalian target of rapamycin signaling) that is normally associated with prolonged inactivity in skeletal muscles. Additionally, our results confirm previous findings that treatment with a mitochondrial-targeted antioxidant is sufficient to prevent casting-induced skeletal muscle atrophy, mitochondrial dysfunction, and activation of the proteases calpain and caspase-3. Collectively, these data reveal that inactivity-induced increases in mitochondrial ROS emission play a required role in activation of key proteolytic systems and the downregulation of important anabolic signaling molecules in muscle fibers exposed to prolonged inactivity.
authors.affiliation: University of Florida, Gainesville, Florida, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Talbert
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Smuder
authors.forename: Kisuk
authors.initials: K
authors.lastname: Min
authors.forename: Oh Sung
authors.initials: OS
authors.lastname: Kwon
authors.forename: Hazel H
authors.initials: HH
authors.lastname: Szeto
authors.forename: Scott K
authors.initials: SK
authors.lastname: Powers
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D002154:Calpain / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D007103:Immobilization; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009133:Muscular Atrophy / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D010447:Peptide Hydrolases; D002154:Calpain; D053148:Caspase 3; D046988:Proteasome Endopeptidase Complex
keywords: disuse atrophy; mitochondrial signaling; oxidative stress