Resveratrol initiates differentiation of mouse skeletal muscle-derived C2C12 myoblasts
Resveratrol initiates differentiation of mouse skeletal muscle-derived C2C12 myoblasts
复制标题
DOI：
10.1016/j.bcp.2012.08.023
复制
发表时间：
2012-11-15
影响因子：
5.8
通讯作者：
Latruffe, Norbert
中科院分区：
文献类型：
--
作者：
Kaminski, Jacques;Lancon, Allan;Latruffe, Norbert
白藜芦醇是研究最广泛的生物活性植物多酚之一。虽然其对内皮血管细胞、癌细胞、炎症过程和神经退行性事件的影响已被充分记录，但对这种植物酚在分化过程中的含义，特别是在骨骼肌细胞中的含义知之甚少。在这里，我们通过评估白藜芦醇摄取、细胞增殖、细胞形状变化以及编码肌肉特异性转录因子或收缩蛋白的基因表达，报道了白藜芦醇对小鼠骨骼肌来源细胞（C2C12）在未分化（成肌细胞）或分化状态（肌管）的影响。白藜芦醇：(1)通过被动和促进的过程在细胞内迅速积累；(2)不强烈影响细胞活力、细胞周期和凋亡；(3)作为一种促分化剂，表现为细胞的延长，导致肌管表型；(4)暴露于白藜芦醇12 h后，肌肉促分化标志物和转录因子（myogenin, Scrp3）开始上调，暴露于白藜芦醇18 h后，重链肌球蛋白含量显著增加；(5)增加miRNA-133b的靶mRNA Sri：转录因子的转录水平，而miRNA-133b本身被该多酚下调。这些结果提出了白藜芦醇对骨骼肌的新的促分化调节特性，至少部分是通过调节特定的mirna。(C) 2012爱思唯尔公司版权所有。
Resveratrol is one of the most widely studied bio-active plant polyphenols. While its effect on endothelial blood vessel cells, cancer cells, inflammatory processes and neurodegenerative events is well documented, little is known about the implication of this phytophenol in differentiating processes, particularly in skeletal muscle cells. Here, we report the effects of resveratrol on mouse skeletal muscle-derived cells (C2C12) in either a nondifferentiated (myoblasts) or differentiated state (myotubes) by evaluating resveratrol uptake, cell proliferation, changes in cell shape, and the expression of genes encoding muscle-specific transcription factors or contractile proteins. Resveratrol: (1) rapidly accumulates within cells through passive and facilitated processes: (2) does not strongly affect cell viability, cell cycle and apoptosis; (3) behaves as a pro-differentiating agent as shown by the lengthening of cells, leading to a myotube phenotype; (4) upregulates muscular pro-differentiation markers and transcription factors (myogenin, Scrp3) starting after 12 h of exposure and strongly increases heavy chain myosin content after 18 h of exposure to resveratrol; (5) increases the Sri: transcription factor's transcript level, a target mRNA of the miRNA-133b, which is itself downregulated by this polyphenol. These results put forward new pro-differentiating regulatory properties of resveratrol on skeletal muscles at least partly via modulation of specific miRNAs. (C) 2012 Elsevier Inc. All rights reserved.