Biphasic Stress Response in the Soleus during Reloading after Hind Limb Unloading

• Published in: Medicine and science in sports and exercise 2012-04, Vol.44 (4), p.600-609
• Main Authors: LAWLER, John M, KWAK, Hyo-Bum, KIM, Jong-Hee, LEE, Yang, HORD, Jeffrey M, MARTINEZ, Daniel A
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; DNA-Binding Proteins - analysis; Fundamental and applied biological sciences. Psychology; Heat Shock Transcription Factors; Hindlimb Suspension - physiology; HSP27 Heat-Shock Proteins - metabolism; HSP70 Heat-Shock Proteins; Insulin-Like Growth Factor I - analysis; Male; Muscle, Skeletal - anatomy & histology; Muscle, Skeletal - physiology; Muscular Atrophy - metabolism; Muscular Atrophy - physiopathology; NF-kappa B - physiology; Nitric Oxide Synthase Type II - analysis; Organ Size - physiology; Oxidative Stress - physiology; Phosphorylation; Rats; Rats, Sprague-Dawley; Serine - metabolism; Signal Transduction - physiology; Space life sciences; Stress, Physiological; Transcription Factors - analysis; Tyrosine - analogs & derivatives; Tyrosine - analysis; Tyrosine - physiology; Vertebrates: body movement. Posture. Locomotion. Flight. Swimming. Physical exercise. Rest. Sports
• ISSN: 0195-9131; 1530-0315
• DOI: 10.1249/mss.0b013e31823ab37a

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. 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). 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. 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.