Polyphenols prevent clinorotation-induced expression of atrogenes in mouse C2C12 skeletal myotubes
Polyphenols prevent clinorotation-induced expression of atrogenes in mouse C2C12 skeletal myotubes
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DOI：
10.2152/jmi.56.26
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发表时间：
2009-02-01
影响因子：
0.7
通讯作者：
Nikawa, Takeshi
中科院分区：
文献类型：
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作者：
Hemdan, Dalia Ismaeil Ibrahim;Hirasaka, Katsuya;Nikawa, Takeshi
氧化应激是刺激骨骼肌中与肌肉萎缩相关的泛素连接酶 atrogenes 表达的关键因素，并在卸载过程中诱导肌肉萎缩。然而，抗氧化营养素对 atrogene 表达的影响尚未得到证实。我们报告了多酚，如表儿茶素 (EC)、表儿茶素没食子酸酯 (ECg) 和表没食子儿茶素没食子酸酯 (EGCg) 和槲皮素，对三维 (3D) 旋转或糖皮质激素上调的 atrogene 表达的抑制作用。这些治疗显着提高了小鼠 C2C12 成肌细胞和肌管中 atrogenes 的表达，包括 atrogin-1 和 MuRF-1。有趣的是，EC、ECg、EGCg和槲皮素显着降低了3D旋转上调的atrogin-1和MuRF-1的表达，而它们几乎不影响地塞米松诱导的atrogene表达。 ERK 信号传导是众所周知的介导氧化应激的 MAPK 途径。因此，我们还研究了这些多酚对 C2C12 肌管中 ERK 磷酸化的影响。正如预期的那样，EC、ECg、EGCg 和槲皮素显着抑制 ERK 磷酸化，这与 3D 旋转诱导的 atrogenes 上调相对应。这些结果表明，儿茶素和槲皮素等抗氧化营养素可能通过抑制 ERK 信号传导来抑制骨骼肌细胞中 atrogene 的表达。因此，儿茶素和槲皮素可以预防卸载介导的肌肉萎缩。
Oxidative stress is a key factor in stimulating the expression of atrogenes, which are muscle atrophy-related ubiquitin ligases, in skeletal muscle, and it induces muscle atrophy during unloading. However, the effects of antioxidative nutrients on atrogene expression have not been demonstrated. We report on the inhibitory effects of polyphenols, such as epicatechin (EC), epicatechin gallate (ECg) and epigallocatechin gallate (EGCg) and quercetin, on atrogene expression up-regulated by three dimensional (3D)-clinorotation or glucocorticoid. These treatments markedly elevated the expression of atrogenes, including atrogin-1 and MuRF-1, in mouse C2C12 myoblasts and myotubes. Interestingly, EC, ECg, EGCg and quercetin significantly decreased the expression of atrogin-1 and MuRF-1 up-regulated by 3D-clinorotation, whereas they hardly affected atrogene expression induced by dexamethasone. ERK signaling is a well known MAPK pathway to mediate oxidative stress. Therefore, we also investigated the effect of these polyphenols on phosphorylation of ERK in C2C12 myotubes. As expected, EC, ECg, EGCg, and quercetin significantly suppressed phosphorylation of ERK, corresponding to the up-regulation of atrogenes induced by 3D-clinorotation. These results suggest that antioxidative nutrients, such as catechins and quercetin, suppress atrogene expression in skeletal muscle cells, possibly through the inhibition of ERK signaling. Thus, catechins and quercetin may prevent unloading-mediated muscle atrophy.