title: Activation of alternative NF-κB signaling during recovery of disuse-induced loss of muscle oxidative phenotype.
abstract: Physical inactivity-induced loss of skeletal muscle oxidative phenotype (OXPHEN), often observed in chronic disease, adversely affects physical functioning and quality of life. Potential therapeutic targets remain to be identified, since the molecular mechanisms involved in reloading-induced recovery of muscle OXPHEN remain incompletely understood. We hypothesized a role for alternative NF-κB, as a recently identified positive regulator of muscle OXPHEN, in reloading-induced alterations in muscle OXPHEN. Markers and regulators (including alternative NF-κB signaling) of muscle OXPHEN were investigated in gastrocnemius muscle of mice subjected to a hindlimb suspension/reloading (HLS/RL) protocol. Expression levels of oxidative phosphorylation subunits and slow myosin heavy chain isoforms I and IIA increased rapidly upon RL. After an initial decrease upon HLS, mRNA levels of peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC) molecules PGC-1α and PGC-1β and mRNA levels of mitochondrial transcription factor A (Tfam) and estrogen-related receptor α increased upon RL. PPAR-δ, nuclear respiratory factor 1 (NRF-1), NRF-2α, and sirtuin 1 mRNA levels increased during RL although expression levels were unaltered upon HLS. In addition, both Tfam and NRF-1 protein levels increased significantly during the RL period. Moreover, upon RL, IKK-α mRNA and protein levels increased, and phosphorylation of P100 and subsequent processing to P52 were elevated, reflecting alternative NF-κB activation. We conclude that RL-induced recovery of muscle OXPHEN is associated with activation of alternative NF-κB signaling.
authors.affiliation: NUTRIM School for Nutrition, Toxicology, and Metabolism, Department of Respiratory Medicine, Maastricht University Medical Center +, Maastricht, The Netherlands.
authors.forename: A H V
authors.initials: AH
authors.lastname: Remels
authors.forename: N A
authors.initials: NA
authors.lastname: Pansters
authors.forename: H R
authors.initials: HR
authors.lastname: Gosker
authors.forename: A M W J
authors.initials: AM
authors.lastname: Schols
authors.forename: R C J
authors.initials: RC
authors.lastname: Langen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D019417:Hindlimb Suspension; D007103:Immobilization / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D020966:Muscular Disorders, Atrophic / Q000209:etiology / Q000378:metabolism* / Q000534:rehabilitation; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000819:agonists / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011897:Random Allocation; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016474:Weight-Bearing; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D024101:Mitochondrial Proteins; D018995:Myosin Heavy Chains; D016328:NF-kappa B; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011960:Receptors, Estrogen; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; C485290:Ppargc1a protein, mouse; C081930:Tfam protein, mouse
keywords: alternative nuclear factor-κB; peroxisome proliferator-activated receptor-γ coactivator; reloading; skeletal muscle