Paradoxical effect of IKK???2 inhibition on the expression of E3 ubiquitin ligases and unloading?￠????induced skeletal muscle atrophy

摘要

We tested whether NF?￠???? ???o B pathway is indispensable for the increase in expression of E3?￠????ligases and unloading?￠????induced muscle atrophy using IKK???2 inhibitor IMD?￠????0354. Three groups of rats were used: nontreated control (C), 3????days of unloading/hindlimb suspension with (HS+IMD) or without (HS) IMD?￠????0354. Levels of I ???o B ???± were higher in HS+IMD (1.16?￠????fold) and lower in HS (0.82?￠????fold) when compared with C group. IMD?￠????0354 treatment during unloading: had no effect on loss of muscle mass; increased mRNA levels of MuRF1 and MAFbx; increased levels of pFoxO3; and had no effect on levels of Bcl?￠????3, p105, and p50 proteins. Our study for the first time showed that inhibiting IKK ???2 in????vivo during 3?￠????day unloading failed to diminish expression of ubiquitin ligases and prevent muscle atrophy.