Expressions and Regulatory Effects of P38/ERK/JNK Mapks in the Adipogenic Trans-Differentiation of C2C12 Myoblasts
Expressions and Regulatory Effects of P38/ERK/JNK Mapks in the Adipogenic Trans-Differentiation of C2C12 Myoblasts
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DOI：
10.1159/000486169
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发表时间：
2017-01-01
影响因子：
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通讯作者：
Huang, Jinxiu
中科院分区：
文献类型：
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作者：
Qi, Renli;Liu, Hong;Huang, Jinxiu
背景/目的：成肌细胞和肌肉卫星细胞具有转分化为脂肪细胞或脂肪细胞样细胞的潜力。先前的研究表明丝裂原激活蛋白激酶（MAPK）对于肌肉细胞的脂肪形成转分化至关重要。 ERK1/2、P38和JNK是MAPK家族的三个主要成员；研究了它们在成肌细胞的成脂转分化过程中的激活和调节功能。方法：培养并诱导C2C12成肌细胞进行成脂转分化。使用蛋白质微阵列和蛋白质印迹分析 MAPK 的激活模式。三种特定的 MAPK 阻断剂 U0126、SB20358 和 SP600125 用于阻断转分化过程中的 ERK1/2、P38 和 JNK。使用细胞染色和形态学观察以及脂肪形成基因的表达变化来测量细胞脂肪形成。结果：抑制剂减少相应 MAPK 的磷酸化并产生独特的细胞效应。抑制 P38 促进脂肪形成转分化并增强分化细胞中的脂肪分解代谢。然而，抑制 ERK1/2 对脂肪生成具有相反的作用，并且对脂肪分解没有影响。阻断 JNK 会弱阻断转分化，但会刺激脂肪分解并诱导细胞凋亡。结论：三种MAPK通过控制成脂和脂肪分解代谢参与成肌细胞成脂转分化的调节。
Background/Aims: Myoblasts and muscle satellite cells have the potential to trans-differentiate into adipocytes or adipocyte-like cells. Previous studies suggest that mitogen-activated protein kinase (MAPK) is critical to adipogenic trans-differentiation of muscle cells. ERK1/2, P38 and JNK are three major MAPK family members; their activation and regulatory functions during adipogenic trans-differentiation of myoblasts are investigated. Methods: C2C12 myoblasts were cultured and induced for adipogenic trans-differentiation. Activation patterns of MAPKs were assayed using protein microarray and Western blot. Three specific MAPK blockers, U0126, SB20358 and SP600125, were used to block ERK1/2, P38 and JNK during trans-differentiation. Cellular adipogenesis was measured using staining and morphological observations of cells and expression changes in adipogenic genes. Results: Inhibitors reduced phosphorylation of corresponding MAPK and produced unique cellular effects. Suppressing P38 promoted adipogenic trans-differentiation and intensified adipolytic metabolism in differentiated cells. However, inhibition of ERK1/2 had the opposite effects on adipogenesis and no effect on adipolysis. Blocking JNK weakly blocked trans-differentiation but stimulated adipolysis and induced apoptosis. Conclusion: Three MAPKs participate in the regulation of myoblast adipogenic trans-differentiation by controlling adipogenic and adipolysis metabolism.