Folic acid promotes the myogenic differentiation of C2C12 murine myoblasts through the Akt signaling pathway
Folic acid promotes the myogenic differentiation of C2C12 murine myoblasts through the Akt signaling pathway
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DOI：
10.3892/ijmm.2015.2311
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发表时间：
2015-10-01
影响因子：
5.4
通讯作者：
Kim, Nam Deuk
中科院分区：
文献类型：
--
作者：
Hwang, Seong Yeon;Kang, Yong Jung;Kim, Nam Deuk
叶酸是一种水溶性维生素b族复合物，健康、生长和发育需要外源性摄入。作为辅助因子的前体，叶酸在DNA碱基和其他必需生物分子的合成中是单碳供体所必需的。饮食中缺乏叶酸会导致叶酸缺乏，从而导致多种健康问题，包括大细胞性贫血、血浆同型半胱氨酸水平升高、心血管疾病、出生缺陷、致癌、肌肉无力和行走困难。以往的研究表明，叶酸对骨骼肌功能有积极作用。然而，叶酸在骨骼肌细胞分化中的确切作用仍然知之甚少。因此，在本研究中，我们用C2C12小鼠成肌细胞研究了叶酸对新肌管成熟和分化的影响。我们发现叶酸促进了多核肌管的形成，并以浓度依赖性的方式提高了融合指数和肌酸激酶（CK）活性。此外，western blot分析显示，在叶酸处理的肌管中，肌肉特异性标记物myosin heavy chain （MyHC）的表达水平以及MyoD和myogenin的表达水平在成肌分化过程中升高。叶酸也促进了Akt通路的激活，但这种作用被LY294002 （Akt抑制剂）处理C2C12细胞所抑制。用一种特定的抑制剂阻断Akt通路表明，这是介导叶酸对肌肉细胞分化和融合的刺激作用所必需的。综上所述，我们的数据表明叶酸通过激活Akt通路促进C2C12细胞的分化。
Folic acid is a water-soluble vitamin in the B-complex group, and an exogenous intake is required for health, growth and development. As a precursor to co-factors, folic acid is required for one-carbon donors in the synthesis of DNA bases and other essential biomolecules. A lack of dietary folic acid can lead to folic acid deficiency and can therefore result in several health problems, including macrocytic anemia, elevated plasma homocysteine levels, cardiovascular disease, birth defects, carcinogenesis, muscle weakness and difficulty in walking. Previous studies have indicated that folic acid exerts a positive effect on skeletal muscle functions. However, the precise role of folic acid in skeletal muscle cell differentiation remains poorly understood. Thus, in the present study, we examined the effects of folic acid on neomyotube maturation and differentiation using C2C12 murine myoblasts. We found that folic acid promoted the formation of multinucleated myotubes, and increased the fusion index and creatine kinase (CK) activity in a concentration-dependent manner. In addition, western blot analysis revealed that the expression levels of the muscle-specific marker, myosin heavy chain (MyHC), as well as those of the myogenic regulatory factors (MRFs), MyoD and myogenin, were increased in the folic acid-treated myotubes during myogenic differentiation. Folic acid also promoted the activation of the Akt pathway, and this effect was inhibited by treatment of the C2C12 cells with LY294002 (Akt inhibitor). Blocking of the Akt pathway with a specific inhibitor revealed that it was necessary for mediating the stimulatory effects of folic acid on muscle cell differentiation and fusion. Taken together, our data suggest that folic acid promotes the differentiation of C2C12 cells through the activation of the Akt pathway.