title: Differential response of heat shock proteins to hindlimb unloading and reloading in the soleus.
abstract: Hindlimb unloading (HU) results in oxidative stress, skeletal muscle atrophy, and increased damage upon reloading. Heat shock proteins (HSPs) protect against oxidative stress. However, it is unknown whether HSPs are depressed with long-term unloading (28 days) or reloading. We tested the hypotheses that long-term HU would depress Hsp70 and Hsp25 pathways, whereas reloading would allow recovery in the soleus. Adult Sprague-Dawley rats were divided into three groups: controls; HU for 28 days; and HU + 7 days of reloading (HU-R). Soleus mass decreased with HU, and did not recover to control values with reloading. Hsp70 decreased with HU (-78.5%) and did not recover with HU-R (-81.4%). Upstream heat shock factor-1 was depressed with HU and HU-R. Hsp25 was reduced with HU, but recovered with reloading. Downstream of Hsp25, NADP-specific isocitrate dehydrogenase and glutathione peroxidase decreased with unloading, but only NADP-specific isocitrate dehydrogenase recovered with HU-R. Lipid peroxidation increased in both HU and HU-R. These data indicate that prolonged unloading and subsequent reloading results in complex, differential regulation of Hsp70 and Hsp25 pathways in the rat soleus muscle. Thus dysregulation and uncoupling of the Hsp70 and Hsp25 pathways may lead not only to muscle atrophy with prolonged unloading, but also impaired recovery of muscle mass during early reloading.
authors.affiliation: Redox Biology and Cell Signaling Laboratory, 276B Read Building, Department of Health and Kinesiology, Texas A&M University, College Station, 77843-4243, USA. jm12621@neo.tamu.edu
authors.forename: John M
authors.initials: JM
authors.lastname: Lawler
authors.forename: Wook
authors.initials: W
authors.lastname: Song
authors.forename: Hyo-Bum
authors.initials: HB
authors.lastname: Kwak
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004789:Enzyme Activation; D005979:Glutathione Peroxidase / Q000235:genetics / Q000502:physiology; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000097:blood / Q000235:genetics / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000097:blood / Q000235:genetics / Q000502:physiology*; D019417:Hindlimb Suspension / Q000502:physiology*; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000737:chemistry / Q000201:enzymology / Q000502:physiology*; D009133:Muscular Atrophy / Q000235:genetics / Q000503:physiopathology; D019255:NADPH Oxidases / Q000235:genetics / Q000502:physiology; D009363:Neoplasm Proteins / Q000097:blood / Q000235:genetics / Q000502:physiology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D009195:Peroxidase / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics
chemical_list: D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D007521:Isocitrate Dehydrogenase; D009195:Peroxidase; D005979:Glutathione Peroxidase; D019255:NADPH Oxidases