Abstract
We tested whether NF‐κB pathway is indispensable for the increase in expression of E3‐ligases and unloading‐induced muscle atrophy using IKKβ 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 IKK β in vivo during 3‐day unloading failed to diminish expression of ubiquitin ligases and prevent muscle atrophy.
Highlights
Activation of nuclear factor-jB (NF-jB) pathway is important for skeletal muscle atrophy in response to diverse physiological and pathological stimuli including muscle unloading (Jackman et al 2013; Bodine and Baehr 2014)
Skeletal muscle-specific E3 ubiquitin ligases MuRF1 and MAFbx are upregulated during unloadinginduced muscle atrophy
We evaluated the levels of expression of two E3 ligases involved in protein degradation. mRNA expression of MuRF1 and MAFbx (Atrogin1) was significantly increased in both HS and HS+IMD groups when compared with control (Fig. 3A)
Summary
Activation of nuclear factor-jB (NF-jB) pathway is important for skeletal muscle atrophy in response to diverse physiological and pathological stimuli including muscle unloading (Jackman et al 2013; Bodine and Baehr 2014). Skeletal muscle-specific E3 ubiquitin ligases MuRF1 and MAFbx are upregulated during unloadinginduced muscle atrophy. Both NF-jB and transcription factor FoxO3 can activate MuRF1 and MAFbx expression in response to unloading and immobilization. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society
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