Extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase pathway is involved in inhibition of myogenic differentiation of myoblasts by hypoxia
Extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase pathway is involved in inhibition of myogenic differentiation of myoblasts by hypoxia
复制标题
细胞外信号调节激酶1/2丝裂原激活蛋白激酶途径参与缺氧抑制成肌细胞的生肌分化
DOI：
10.1113/expphysiol.2011.061382
复制
发表时间：
2012-02-01
影响因子：
2.7
通讯作者：
Fan, Ming
中科院分区：
文献类型：
--
作者：
Li, Xiang;Wang, Xu;Fan, Ming
氧条件影响细胞的多种生物过程，包括细胞生长、存活和分化的改变。然而，关于缺氧对成肌细胞增殖和分化的影响的研究很少。本研究通过观察缺氧（3% O2）对C2C12成肌细胞成肌分化的影响，探索缺氧调控成肌细胞成肌分化的可能机制。免疫细胞化学染色和Western blot检测肌球蛋白重链的表达。采用RT-PCR和Western blot检测肌肉调节转录因子的表达。通过强迫表达丝裂原活化蛋白激酶1（MEK1(E)）和Western blot分析细胞外信号调节激酶（ERK1/2）的活性。我们发现缺氧抑制成肌细胞的成肌分化。缺氧可下调C2C12成肌细胞中肌肉调节转录因子的表达。在缺氧对成肌分化的抑制过程中，ERK1/2的激活受到抑制，通过强制表达MEK1(E)来增加ERK1/2的活性可以部分逆转缺氧对成肌分化的抑制。这些结果提示，erk1 /2丝裂原活化蛋白激酶途径可能是缺氧抑制成肌分化的一个可能机制。
Oxygen conditions influence a variety of biological processes of cells, including alterations in cellular growth, survival and differentiation. However, there have been few studies on the effects of hypoxia on proliferation and differentiation of myoblasts. In this study, we observed the effects of hypoxia (3% O2) on myogenic differentiation of C2C12 myoblasts and sought a possible mechanism involved in the regulation of myogenic differentiation of myoblasts by hypoxia. The expression of myosin heavy chain was detected by immunocytochemistry staining and Western blot analysis. The expression of muscle regulatory transcription factors was examined by RT-PCR analysis and Western blot analysis. The activity of extracellular signal-regulated kinases (ERK1/2) was investigated by forced expression of mitogen-activated protein kinase kinase 1 (MEK1(E)) and using Western blot analysis. We found that hypoxia inhibited myogenic differentiation of myoblasts. The expression of muscle regulatory transcription factors was downregulated by hypoxia in C2C12 myoblasts. During the inhibition of myogenic differentiation by hypoxia, ERK1/2 activation was suppressed, and increasing ERK1/2 activity by forced expression of MEK1(E) could partly reverse the inhibition of myogenic differentiation by hypoxia. These results suggest that the ERK1/2mitogen-activated protein kinase pathway might be a possible mechanism involved in the inhibition of myogenic differentiation by hypoxia.