Preventive effect of dietary quercetin on disuse muscle atrophy by targeting mitochondria in denervated mice
Preventive effect of dietary quercetin on disuse muscle atrophy by targeting mitochondria in denervated mice
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DOI：
10.1016/j.jnutbio.2016.02.001
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发表时间：
2016-05-01
影响因子：
5.6
通讯作者：
Terao, Junji
中科院分区：
文献类型：
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作者：
Mukai, Rie;Matsui, Naoko;Terao, Junji
槲皮素是水果和蔬菜中的主要膳食类黄酮。我们的目的是阐明膳食槲皮素对废用性肌肉萎缩的预防作用及其潜在机制。我们通过切断右腿的坐骨神经（SNX 手术）来建立小鼠去神经模型，使后肢缺乏活动能力。在 SNX 手术前预摄入槲皮素混合饮食 14 天，可以防止腓肠肌 (GM) 的肌肉质量损失和肌纤维萎缩。 Akt 的磷酸化是抑制蛋白质降解的关键磷酸化途径，在接受或不接受 SNX 手术的槲皮素混合饮食组中均被激活。摄入槲皮素混合饮食可抑制源自线粒体的过氧化氢的产生，并通过 SNX 手术提高 GM 中线粒体过氧化物酶体增殖物激活受体 - γ 共激活剂 1 α mRNA 的表达以及 NADH 脱氢酶 4 的表达。槲皮素及其共轭代谢物减少了从萎缩肌肉中获得的线粒体部分中过氧化氢的产生。在 C2C12 肌管中，槲皮素到达线粒体部分。这些研究结果表明，膳食槲皮素可以通过保护线粒体免受生物合成减少和减少线粒体过氧化氢释放来靶向骨骼肌组织中的线粒体，从而防止废用性肌肉萎缩，这可能与过氧化氢产生减少和/或线粒体抗氧化能力提高有关。 (C) 2016 Elsevier Inc. 保留所有权利。
Quercetin is a major dietary flavonoid in fruits and vegetables. We aimed to clarify the preventive effect of dietary quercetin on disuse muscle atrophy and the underlying mechanisms. We established a mouse denervation model by cutting the sciatic nerve in the right leg (SNX surgery) to lack of mobilization in hind-limb. Preintake of a quercetin-mixed diet for 14 days before SNX surgery prevented loss of muscle mass and atrophy of muscle fibers in the gastrocnemius muscle (GM). Phosphorylation of Akt, a key phosphorylation pathway of suppression of protein degradation, was activated in the quercetin-mixed diet group with and without SNX surgery. Intake of a quercetin-mixed diet suppressed the generation of hydrogen peroxide originating from mitochondria and elevated mitochondrial peroxisome proliferator-activated receptor-gamma coactivator 1 alpha mRNA expression as well as NADH dehydrogenase 4 expression in the GM with SNX surgery. Quercetin and its conjugated metabolites reduced hydrogen peroxide production in the mitochondrial fraction obtained from atrophied muscle. In C2C12 myotubes, quercetin reached the mitochondrial fraction. These findings suggest that dietary quercetin can prevent disuse muscle atrophy by targeting mitochondria in skeletal muscle tissue through protecting mitochondria from decreased biogenesis and reducing mitochondrial hydrogen peroxide release, which can be related to decreased hydrogen peroxide production and/or improvements on antioxidant capacity of mitochondria. (C) 2016 Elsevier Inc. All rights reserved.