Emodin attenuates TNF-α-induced apoptosis and autophagy in mouse C2C12 myoblasts though the phosphorylation of Akt
Emodin attenuates TNF-α-induced apoptosis and autophagy in mouse C2C12 myoblasts though the phosphorylation of Akt
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DOI：
10.1016/j.intimp.2016.02.023
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发表时间：
2016-05-01
影响因子：
5.6
通讯作者：
Wang, Ming
中科院分区：
文献类型：
--
作者：
Chen, Dexiu;Liu, Junshan;Wang, Ming
大黄素是掌大黄的主要成分之一，有报道称其对神经组织的凋亡和自噬具有显著的保护作用。然而，大黄素在肌肉萎缩中的作用及其潜在机制仍不明确。在本研究中，我们研究了大黄素对小鼠C2C12成肌细胞凋亡和自噬的保护作用及其机制。Hoechst 33342染色和膜联蛋白V/PI分析显示，不同浓度的大黄素均能降低tnf - α诱导的C2C12成肌细胞的凋亡。大黄素还能抑制tnf - α刺激的C2C12成肌细胞线粒体膜电位的崩溃和活性氧的产生。与此结果一致的是，大黄素处理后Bcl-2的表达增加，而Bax、裂解型caspase 3和裂解型parp的表达降低。这些数据表明，大黄素通过线粒体信号通路减轻了tnf - α刺激的C2C12成肌细胞的凋亡。此外，大黄素通过抑制LC3-II、Beclin-1和Atg7的表达，抑制tnf - α刺激的C2C12成肌细胞的自噬。大黄素也导致Akt磷酸化形式的上调。综上所述，这些结果表明大黄素可能通过激活磷酸化的Akt抑制tnf α诱导的C2C12成肌细胞的凋亡和自噬。我们的发现提示大黄素可能是一种潜在的治疗肌肉萎缩的药物。(C) 2016 Elsevier B.V.版权所有
Emodin, a major component of Rheum palmatum, has been reported to significantly protect neural tissue against apoptosis and autophagy. However, the effects and underlying mechanisms of action of emodin in muscle atrophy are still poorly defined. In this study, we investigated the protective effects and the underlying mechanisms by which emodin acts on tumor necrosis factor alpha (TNF-alpha)-induced apoptosis and autophagy in mouse C2C12 myoblasts. Emodin, at various concentrations, decreased TNF-alpha-induced apoptosis in C2C12 myoblasts, which were analyzed by Hoechst 33342 staining and annexin V/PI analysis. Emodin also inhibited the collapse of the mitochondrial membrane potential and the generation of reactive oxygen species in TNF-alpha-stimulated C2C12 myoblasts. Consistent with these results, the expression of Bcl-2 was increased, whereas the expression of Bax, cleaved-caspase 3 and cleaved-PARP was decreased after emodin treatment. These data demonstrate that emodin attenuated apoptosis in TNF-alpha-stimulated C2C12 myoblasts through mitochondrial signaling pathways. In addition, emodin inhibited autophagy in TNF-alpha-stimulated C2C12 myoblasts by suppressing the expression of LC3-II, Beclin-1 and Atg7. Emodin also resulted in the upregulation of the phosphorylated forms of Akt. Taken together, these results suggest that emodin inhibited apoptosis and autophagy in TNF-alpha-induced C2C12 myoblasts, possibly through the activation of phosphorylated Akt. Our findings suggest that emodin could be a potential therapeutic agent in the treatment of muscle atrophy. (C) 2016 Elsevier B.V. All rights reserved.