title: Biphasic stress response in the soleus during reloading after hind limb unloading.
abstract: BACKGROUND
  Extreme disuse and spaceflight elicit rapid skeletal muscle atrophy, accompanied by elevated proinflammatory signaling and impaired stress response proteins (e.g., heat shock proteins (HSP), insulin-like growth factor 1 (IGF-1)). Recovery of muscle mass is delayed during the early stage of reloading after prolonged unloading, with a concomitant impairment of HSP70 and IGF-1. We postulated that proinflammatory signaling and stress response alterations would characterize early and late phases of signaling during reloading.
  
  
  METHODS
  Twenty-four adult SD rats were divided into the following groups: controls, 28 d of hind limb unloading (HU), HU + early (7 d) reloading (HU-R7), and HU + late (28 d) reloading (HU-R28).
  
  
  RESULTS
  Soleus mass decreased (-55%) with HU and remained depressed (-41%) at HU-R7. Nuclear factor κB activation and oxidative stress were elevated with HU and remained high during reloading. HU elevated inducible nitric oxide synthase and returned to baseline during reloading, whereas 3-nitrotyrosine did not increase with HU and peaked at HU-R7. HU depressed levels of HSP25 phosphorylation at Ser82 and IGF-1. Although p-HSP25 and Akt phosphorylation (Ser473) recovered during early reloading, HSP70, heat shock factor 1, and IGF-1 remained depressed. HSP70, heat shock factor 1, and IGF-1 recovered, whereas p-Akt and 3-nitrotyrosine decreased to control levels at HU-R28.
  
  
  CONCLUSIONS
  Reloading elicited an early phase characterized by elevated nuclear factor κB activation, 3-nitrotyrosine, p-HSP25, and p-Akt levels and a delayed phase with recovery of HSP70, IGF-1, and muscle mass. We conclude that the reloading phenotype in skeletal muscle is expressed in two distinct phases related to (a) pro-inflammatory signaling and (b) muscle mass recovery.
authors: Redox Biology & Cell Signaling Laboratory, Department of Health and Kinesiology, Texas A&M University, College Station, TX 77843-4243, USA. jml2621@neo.tamu.edu
authors: John M
authors: JM
authors: Lawler
authors: Hyo-Bum
authors: HB
authors: Kwak
authors: Jong-Hee
authors: JH
authors: Kim
authors: Yang
authors: Y
authors: Lee
authors: Jeffrey M
authors: JM
authors: Hord
authors: Daniel A
authors: DA
authors: Martinez
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000032:analysis; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D019417:Hindlimb Suspension / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000502:physiology*; D009133:Muscular Atrophy / Q000378:metabolism / Q000503:physiopathology; D016328:NF-kappa B / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D009929:Organ Size / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013312:Stress, Physiological; D014157:Transcription Factors / Q000032:analysis; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C486114:Hspb1 protein, rat; D016328:NF-kappa B; D014157:Transcription Factors; C548904:insulin-like growth factor-1, rat; C002744:3-nitrotyrosine; D014443:Tyrosine; D012694:Serine; D007334:Insulin-Like Growth Factor I; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat