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 IKKβ in vivo during 3-day unloading failed to diminish expression of ubiquitin ligases and prevent muscle atrophy.
Keywords:
FoxO3; MAFbx; MuRF1; nuclear factor‐κB; skeletal muscle; unloading.
© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
MeSH terms
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Animals
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Benzamides / pharmacology
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Enzyme Inhibitors / pharmacology
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Forkhead Box Protein O3 / metabolism
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Hindlimb Suspension / adverse effects
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I-kappa B Kinase / antagonists & inhibitors*
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I-kappa B Kinase / metabolism
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Male
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Muscle Proteins / genetics*
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Muscle Proteins / metabolism
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Muscle, Skeletal / drug effects
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Muscle, Skeletal / metabolism*
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Muscular Atrophy / etiology
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Muscular Atrophy / metabolism*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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SKP Cullin F-Box Protein Ligases / genetics
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SKP Cullin F-Box Protein Ligases / metabolism
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Tripartite Motif Proteins / genetics*
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Tripartite Motif Proteins / metabolism
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Ubiquitin-Protein Ligases / genetics*
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Ubiquitin-Protein Ligases / metabolism
Substances
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Benzamides
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Enzyme Inhibitors
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FOXO3 protein, rat
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Forkhead Box Protein O3
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Muscle Proteins
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RNA, Messenger
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Tripartite Motif Proteins
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N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide
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Fbxo32 protein, rat
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SKP Cullin F-Box Protein Ligases
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Trim63 protein, rat
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Ubiquitin-Protein Ligases
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I-kappa B Kinase