Abstract

BackgroundUnloading of skeletal muscle causes atrophy and loss of contractile function. In part, this response is believed to be mediated by the transcription factor nuclear factor-kappa B (NF-κB). Both curcumin, a component of the spice turmeric, and N-acetylcysteine (NAC), an antioxidant, inhibit activation of NF-κB by inflammatory stimuli, albeit by different mechanisms. In the present study, we tested the hypothesis that dietary curcumin or NAC supplementation would inhibit unloading-induced NF-κB activity in skeletal muscle and thereby protect muscles against loss of mass and function caused by prolonged unloading.MethodsWe used hindlimb suspension to unload the hindlimb muscles of adult mice. Animals had free access to drinking water or drinking water supplemented with 1% NAC and to standard laboratory diet or diet supplemented with 1% curcumin. For 11 days, half the animals in each dietary group were suspended by the tail (unloaded) and half were allowed to ambulate freely.ResultsUnloading caused a 51–53% loss of soleus muscle weight and cross-sectional area relative to freely-ambulating controls. Unloading also decreased total force and force per cross-sectional area developed by soleus. Curcumin supplementation decreased NF-κB activity measured in peripheral tissues of ambulatory mice by gel shift analysis. In unloaded animals, curcumin supplementation did not inhibit NF-κB activity or blunt the loss of muscle mass in soleus. In contrast, NAC prevented the increase in NF-κB activity induced by unloading but did not prevent losses of muscle mass or function.ConclusionIn conclusion, neither dietary curcumin nor dietary NAC prevents unloading-induced skeletal muscle dysfunction and atrophy, although dietary NAC does prevent unloading induced NF-κB activation.

Highlights

  • Unloading of skeletal muscle causes atrophy and loss of contractile function

  • Body weight and diet The curcumin and NAC treatments were well-tolerated by the mice; no overt changes in behavior, grooming, or response to handling were observed in the treated mice

  • nuclear factor-κB (NF-κB) activation is associated with stimulation of the ubiquitin-proteasome pathway and loss of skeletal muscle protein [6,8,12], suggesting that unloading-induced NF-κB activation may contribute to the catabolic response to muscle unloading [6]

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Summary

Introduction

Unloading of skeletal muscle causes atrophy and loss of contractile function. In part, this response is believed to be mediated by the transcription factor nuclear factor-kappa B (NFκB). This response is believed to be mediated by the transcription factor nuclear factor-kappa B (NFκB) Both curcumin, a component of the spice turmeric, and N-acetylcysteine (NAC), an antioxidant, inhibit activation of NF-κB by inflammatory stimuli, albeit by different mechanisms. Prolonged exposure to microgravity causes muscle atrophy, resulting in weakness and predisposition to fatigue. Such changes can markedly degrade astronauts' performance, especially upon return to Earth [1]. There is considerable interest in the development of countermeasures that oppose the complications of muscle disuse

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