Flavones Inhibit LPS-Induced Atrogin-1/MAFbx Expression in Mouse C2C12 Skeletal Myotubes
Flavones Inhibit LPS-Induced Atrogin-1/MAFbx Expression in Mouse C2C12 Skeletal Myotubes
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DOI：
10.3177/jnsv.61.188
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发表时间：
2015-04-01
影响因子：
1.6
通讯作者：
Nikawa, Takeshi
中科院分区：
文献类型：
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作者：
Shiota, Chieko;Abe, Tomoki;Nikawa, Takeshi
肌肉萎缩是一个复杂的过程，是各种压力事件的结果。肌肉萎缩相关基因（atrogenes）如atrogin-1/IVIAFbx和MuRF-1在萎缩过程的早期被诱导，其表达的增加先于肌肉重量的损失。虽然抗氧化营养素抑制骨骼肌细胞atrogen的表达，但类黄酮对炎症诱导的atrogin-1/MAFbx表达的抑制作用尚未阐明。在这里，我们研究了类黄酮对脂多糖（LPS）诱导的atrogin-1/MAFbx表达的抑制作用。我们研究了是否属于6类黄酮类化合物的9类黄酮抑制atrogin-1/MAFbx在小鼠C2 C12肌管的表达。两种主要的黄酮类化合物，芹菜素和毛地黄黄酮，对atrogin-1/MAFbx表达表现出有效的抑制作用。芹菜素和木犀草素预处理可显著防止LPS刺激引起的C2 C12肌管直径的减小。重要的是，用这些黄酮预处理LPS刺激的成肌细胞显著抑制C2 C12肌管中LPS诱导的JNK磷酸化，导致atrogin-1/MAFbx启动子活性的显著抑制。这些结果表明，芹菜素和毛地黄黄酮通过抑制C2 C12肌管中的JNK信号通路来防止LPS介导的atrogin-1/MAFbx表达。因此，这些黄酮、芹菜素和毛地黄黄酮可能是预防脂多糖诱导的肌肉萎缩的有希望的药物。
Muscle atrophy is a complex process that occurs as a consequence of various stress events. Muscle atrophy-associated genes (atrogenes) such as atrogin-1/IVIAFbx and MuRF-1 are induced early in the atrophy process, and the increase in their expression precedes the loss of muscle weight. Although antioxidative nutrients suppress atrogene expression in skeletal muscle cells, the inhibitory effects of flavonoids on inflammation-induced atrogin-1/MAFbx expression have not been clarified. Here, we investigated the inhibitory effects of flavonoids on lipopolysaccharide (LPS)-induced atrogin-1/MAFbx expression. We examined whether nine flavonoids belonging to six flavonoid categories inhibited atrogin-1/MAFbx expression in mouse C2C12 myotubes. Two major flavones, apigenin and luteolin, displayed potent inhibitory effects on atrogin-1/MAFbx expression. The pretreatment with apigenin and luteolin significantly prevented the decrease in C2C12 myotube diameter caused by LPS stimulation. Importantly, the pretreatment of LPS-stimulated myoblasts with these flavones significantly inhibited LPS-induced JNK phosphorylation in C2C12 myotubes, resulting in the significant suppression of atrogin-1/MAFbx promoter activity These results suggest that apigenin and luteolin, prevent LPS-mediated atrogin-1/MAFbx expression through the inhibition of the JNK signaling pathway in C2C12 myotubes. Thus, these flavones, apigenin and luteolin, may be promising agents to prevent LPS-induced muscle atrophy.