Paradoxical effect of IKKß inhibition on the expression of E3 ubiquitin ligases and unloading-induced skeletal muscle atrophy.

ABSTRACT

We tested whether NF-κB pathway is indispensable for the increase in expression of E3-ligases and unloading-induced muscle atrophy using IKKß 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 IκBα 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 IKKß in vivo during 3-day unloading failed to diminish expression of ubiquitin ligases and prevent muscle atrophy.