Extracellular ATP signaling during differentiation of C2C12 skeletal muscle cells: role in proliferation
Extracellular ATP signaling during differentiation of C2C12 skeletal muscle cells: role in proliferation
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DOI：
10.1007/s11010-011-0726-4
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发表时间：
2011-05-01
影响因子：
4.3
通讯作者：
Betto, Romeo
中科院分区：
文献类型：
--
作者：
Martinello, Tiziana;Baldoin, Maria Cristina;Betto, Romeo
有证据表明，细胞外 ATP 信号影响骨骼肌的肌生成、再生和生理机能。目前的工作旨在表征骨骼肌 C2C12 细胞分化过程中的细胞外 ATP 信号系统。我们发现机械和电刺激会从分化的肌管中产生大量 ATP 释放，但不会从增殖的成肌细胞中释放 ATP。细胞外 ATP 水解活性在成肌细胞中较低，而在肌管中较高，这与分化过程中细胞外酶表达的增加一致。用细胞外核苷酸刺激细胞会产生大量的 Ca2+ 瞬变，其幅度和形状在分化过程中发生变化。一致的是，C2C12 细胞表达多种 P2X 和 P2Y 受体，其水平随着成熟阶段而变化。补充 ATP 或 UTP 会刺激 C2C12 成肌细胞的增殖，而过量则具有细胞毒性。数据表明骨骼肌发育伴随着细胞外 ATP 信号传导的主要功能变化。
Evidence shows that extracellular ATP signals influence myogenesis, regeneration and physiology of skeletal muscle. Present work was aimed at characterizing the extracellular ATP signaling system of skeletal muscle C2C12 cells during differentiation. We show that mechanical and electrical stimulation produces substantial release of ATP from differentiated myotubes, but not from proliferating myoblasts. Extracellular ATP-hydrolyzing activity is low in myoblasts and high in myotubes, consistent with the increased expression of extracellular enzymes during differentiation. Stimulation of cells with extracellular nucleotides produces substantial Ca2+ transients, whose amplitude and shape changed during differentiation. Consistently, C2C12 cells express several P2X and P2Y receptors, whose level changes along with maturation stages. Supplementation with either ATP or UTP stimulates proliferation of C2C12 myoblasts, whereas excessive doses were cytotoxic. The data indicate that skeletal muscle development is accompanied by major functional changes in extracellular ATP signaling.