Differentiation of H9c2 cardiomyoblasts: The role of adenylate cyclase system
Differentiation of H9c2 cardiomyoblasts: The role of adenylate cyclase system
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DOI：
10.1002/jcp.10420
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发表时间：
2004-03-01
影响因子：
5.6
通讯作者：
Illiano, G
中科院分区：
文献类型：
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作者：
Pagano, M;Naviglio, S;Illiano, G
腺苷环化酶(AC)/cAMP/cAMP依赖的蛋白激酶通路控制着许多生物现象。CAMP诱导分化或增殖的另一种承诺的分子机制仍不完全清楚。成肌细胞系分化为肌细胞/肌管代表了骨骼肌分化的成熟模型。我们对H9c2成肌细胞终末分化过程中的AC/cAMP通路进行了分析。当H9c2成肌细胞在含低血清的培养液中培养时，退出细胞周期，分化为肌细胞/肌管。这一过程的一个关键步骤是表达肌生成素，这是一种终末分化为肌细胞所必需的转录因子。在这一现象中，我们观察到cAMP水平和AC活性都下降，这表明cAMP在H9c2细胞的分化过程中起着功能上的负面作用。8-溴-cAMP和其他cAMP提升剂，如Forsklin、IBMX和异丙肾上腺素，对H9c2成肌细胞的骨骼肌分化有负面影响。AC活性下调和细胞内cAMP减少都伴随着AC系统膜蛋白(AC催化亚单位G(alphai-1)、G(Alphas))水平的显著变化。讨论了AC系统细胞内cAMP含量与蛋白质水平之间的函数关系。(C)2003年Wiley-Liss，Inc.
The adenylate cyclase (AC)/cAMP/cAMP-dependent protein kinase pathway controls many biological phenomena. The molecular mechanisms by which cAMP induces alternative commitment towards differentiation or proliferation are not still completely known. The differentiation of myoblast cell lines into myocytes/myotubes represents a well-established model of skeletal muscle differentiation. We analyzed the AC/cAMP pathway during terminal differentiation of H9c2 myoblasts. When cultured in low-serum containing medium, H9c2 myoblasts exit the cell cycle and differentiate into myocytes/myotubes. A key step of this process is the expression of myogenin, an essential transcription factor for the terminal differentiation into myocytes. During this phenomenon we observed a decrease in both cAMP levels and AC activity, which suggests a functional negative role of cAMP on the differentiation process of H9c2 cells. 8-Br-cAMP and other cAMP-elevating agents, such as forskolin, IBMX, and isoproterenol, negatively affected skeletal muscle differentiation of H9c2 myoblasts. Both AC activity down-regulation and intracellular cAMP reduction were accompanied by significant variations in the levels of membrane proteins belonging to the AC system (AC catalytic subunit, G(alphai-1), G(alphas)). The functional relationship between intracellular cAMP content and protein levels of AC system is discussed. (C) 2003 Wiley-Liss, Inc.