Attenuation of unloading-induced rat soleus atrophy with the heat-shock protein inducer 17-(allylamino)17-demethoxygeldanamycin

作者：Lomonosova Yulia N; Shenkman Boris S; Nemirovskaya Tatyana L^*

来源：The FASEB Journal, 2012, 26(10): 4295-4301.

DOI：10.1096/fj.12-204412

• musculus soleus atrophy
• HSP90/HSP70
• E3-ligases
• P-p70/S6-kinase

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 mu-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, mu-calpain, and Ub increases under hindlimb unloading as well as decrease of pFOXO3.-Lomonosova, Y. N., Shenkman, B S., Nemirovskaya, T. L. Attenuation of unloading-induced rat soleus atrophy with the heat-shock protein inducer 17-(allylamino)-17-demethoxygeldanamycin. FASEB J. 26, 4295-4301 (2012). www.fasebj.org

• 出版日期2012-10