PURPOSE: Bed rest, microgravity, prolonged disuse and hindlimb suspension (HLS) cause debilitating alterations in skeletal muscle function including changes in protein metabolism, fiber type composition and atrophy. Here we examined the efficacy of histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) in preventing muscle atrophy and muscle fiber type composition. METHODS: Male Fischer 344/NNiaHSD X Brown Norway / BiNia (F344XBN) rats were divided into 4 groups: Control, Control+TSA, HLS and HLS+TSA. Rats in Control+TSA and HLS+TSA groups underwent 14-day TSA treatment (500ug/kg/day-s/c). Control and HLS rats did not receive any treatment. Immunoblot analysis was used to examine the alterations in expression of total- and phospho-Nf-κB-p65, phospho-Akt (Ser308 and Ser473). RESULTS: The expression levels of Nf-κB-p65 and phospho-Nf-κB-p65 were 75±4% and 685±47% of Control in 14-day HLS group, respectively, while those in 14-day HLS+TSA group were 101±1 % and 285±8% of Control, respectively. The expression of phospho-Akt(Ser308) and phospho-Akt (Ser473) was 245±6% and 90±17% of Control in 14-day HLS group, respectively, while those in 14-day HLS+TSA group were 307±6% and 136±20% of Control, respectively. CONCLUSIONS: TSA appears to reverse the elevated expression of phospho-Nf-κB-p65, which is a key regulator of muscle atrophy during HLS with no significant effect on phospho-Akt expression. This suggests that TSA may attenuate disuseinduced muscle atrophy via inhibition of pro-atrophy Nf-κB signaling, without significant effect on the pro-growth Akt signaling. Supported by funds from NSF-EPSCoR Grant 0314742 to MU, WV-NASA, and NIH Grant 027103-1 to EB
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