Effects of dietary curcumin or N-acetylcysteine on NF-kappaB activity and contractile performance in ambulatory and unloaded murine soleus.

Effects of dietary curcumin or N-acetylcysteine on NF-kappaB activity and contractile performance in ambulatory and unloaded murine soleus.
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DOI:
10.1186/1743-7075-2-20
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发表时间:
2005-08-26
影响因子:
4.5
通讯作者:
Durham WJ
Durham WJ
中科院分区:
医学3区
文献类型:
--
作者:
Farid M;Reid MB;Li YP;Gerken E;Durham WJ

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骨骼肌的卸载会导致萎缩和收缩功能丧失。在某种程度上,这种反应被认为是由转录因子核因子-κB (NF-κB) 介导的。姜黄素(香料姜黄的一种成分)和 N-乙酰半胱氨酸 (NAC)(一种抗氧化剂)都能抑制炎症刺激引起的 NF-κB 激活,尽管机制不同。在本研究中,我们测试了这样的假设:膳食姜黄素或 NAC 补充剂会抑制骨骼肌中卸载诱导的 NF-κB 活性,从而保护肌肉免受长时间卸载引起的质量和功能损失。我们使用后肢悬挂来减轻成年小鼠后肢肌肉的负荷。动物可以自由获取饮用水或补充有1% NAC的饮用水以及标准实验室饮食或补充有1%姜黄素的饮食。在 11 天的时间里,每个饮食组中一半的动物被尾巴悬吊(无负载),另一半则被允许自由走动。相对于自由行走的对照组,卸载导致比目鱼肌重量和横截面积减少 51-53%。卸载还降低了比目鱼肌产生的总力和单位横截面积的力。通过凝胶位移分析测量,补充姜黄素可降低活动小鼠外周组织中的 NF-κB 活性。在空腹动物中,补充姜黄素不会抑制 NF-κB 活性或减缓比目鱼肌肌肉质量的损失。相比之下,NAC 可以阻止卸载引起的 NF-κB 活性增加,但不能阻止肌肉质量或功能的损失。总之,膳食姜黄素和膳食 NAC 都不能防止卸载引起的骨骼肌功能障碍和萎缩,尽管膳食 NAC 确实可以防止卸载引起的 NF-κB 激活。
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 (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. We 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. Unloading 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. In 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.