title: Attenuation of unloading-induced rat soleus atrophy with the heat-shock protein inducer 17-(allylamino)-17-demethoxygeldanamycin.
abstract: We hypothesized that pharmacological induction of HSP70 would attenuate soleus atrophy development under 3 d of rat hindlimb unloading. Male Wistar rats were divided into control (C; n=7), 3-d hindlimb unloading (HUL; n=7), HUL with HSP90 inducer administration, 17-allylamino-17-emethoxygeldanamycin (17-AAG; 60 mg/kg, HUL+17-AAG, n=8). The relative weight of soleus muscle to body weight [soleus wt (mg)/body wt (g)] in the HUL group was less than that of the C and HUL+17-AAG groups (P<0.05). We revealed HSP90, HSP70 mRNA decrease in the HUL group (but not the HUL+17-AAG group) vs. C (P<0.05). The unloading resulted in significant increases of μ-calpain and conjugated ubiquitin (Ub) levels (proteins as well as mRNAs) vs. the C group, whereas 17-AAG administration prevented these alterations (studied by SDS-PAGE and RT-PCR). pFOXO3 protein was decreased in the HUL group vs. C, but not in HUL+17-AAG. Content of E3-lygase (MuRF-1, MAFbx) mRNA was increased in both suspended groups. In summary, 17-AAG administration attenuates soleus muscle atrophy, μ-calpain, and Ub increases under hindlimb unloading as well as decrease of pFOXO3.
authors: Faculty of Basic Medicine, Lomonosov Moscow State University, 117191 Lomonosovsky pr. 31/5, Moscow, Russia.
authors: Yulia N
authors: YN
authors: Lomonosova
authors: Boris S
authors: BS
authors: Shenkman
authors: Tatyana L
authors: TL
authors: Nemirovskaya
mesh_terms: D000818:Animals; D016227:Benzoquinones / Q000627:therapeutic use*; D015153:Blotting, Western; D002154:Calpain / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006614:Hindlimb / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D047029:Lactams, Macrocyclic / Q000627:therapeutic use*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D016227:Benzoquinones; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D025801:Ubiquitin; C112765:tanespimycin; D044767:Ubiquitin-Protein Ligases; D002154:Calpain; C449002:mu-calpain