title: PGC-1α overexpression by in vivo transfection attenuates mitochondrial deterioration of skeletal muscle caused by immobilization.
abstract: Prolonged immobilization (IM) causes skeletal muscle atrophy characterized by mitochondrial deterioration and proteolysis. Muscle remobilization (RM) increases reactive oxygen species generation, proinflammatory cytokine expression, and oxidative stress, preventing muscle from quick recovery. Thus, we hypothesized that overexpression of peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) via in vivo transfection would promote mitochondrial biogenesis and antioxidant defense, thus ameliorating the aforementioned deteriorations in a mouse model with 14-d IM followed by 5-d RM. PGC-1α transfection in tibialis anterior muscle resulted in a 7.2- and 4-fold increase in PGC-1α content in cytosol and nucleus, respectively. Mitochondrial biogenic (cytochrome c, mitochondrial transcription factor A), morphologic (mitochondrial density, mDNA/nDNA ratio), and functional (cytochrome c oxidase activity, ATP synthesis rate) markers, as well as fiber cross-sectional area, significantly increased in IM-RM muscle by PGC-1α overexpression. These effects were accompanied by an 18% decrease in H2O2, 30% decrease in nuclear factor-κB-DNA binding, and 25% reduction of IL-1β and-6 production in IM-RM muscle. There was a 34% increase in superoxide dismutase-2 activity, along with a 3.5-fold increase in NAD-dependent deacetylase sirtuin-3 expression caused by enhanced PGC-1α-estrogen-related receptor α binding. Our findings highlighted the importance of PGC-1α in protecting muscle from metabolic and redox disturbances caused by IM.
authors.affiliation: *Laboratory of Physiological Hygiene and Exercise Science, School of Kinesiology, University of Minnesota at Twin Cities, Minneapolis, Minnesota, USA; and Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: Chounghun
authors.initials: C
authors.lastname: Kang
authors.affiliation: *Laboratory of Physiological Hygiene and Exercise Science, School of Kinesiology, University of Minnesota at Twin Cities, Minneapolis, Minnesota, USA; and Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Goodman
authors.affiliation: *Laboratory of Physiological Hygiene and Exercise Science, School of Kinesiology, University of Minnesota at Twin Cities, Minneapolis, Minnesota, USA; and Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: Troy A
authors.initials: TA
authors.lastname: Hornberger
authors.affiliation: *Laboratory of Physiological Hygiene and Exercise Science, School of Kinesiology, University of Minnesota at Twin Cities, Minneapolis, Minnesota, USA; and Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA llji@umn.edu.
authors.forename: Li Li
authors.initials: LL
authors.lastname: Ji
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology; D009133:Muscular Atrophy / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017382:Reactive Oxygen Species / Q000378:metabolism; D012149:Restraint, Physical / Q000009:adverse effects / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D000099156:Superoxide Dismutase 2
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D014157:Transcription Factors; D000099156:Superoxide Dismutase 2; C485290:Ppargc1a protein, mouse
keywords: atrophy; inflammation; oxidative stress