Mitochondrial-dependent regulation of myoblast proliferation
Mitochondrial-dependent regulation of myoblast proliferation
复制标题
DOI：
10.1016/j.yexcr.2004.05.017
复制
发表时间：
2004-09-10
影响因子：
3.7
通讯作者：
Freyssenet, D
中科院分区：
文献类型：
--
作者：
Duguez, S;Sabido, O;Freyssenet, D
本研究的目的是确定线粒体活性是否可以调节成肌细胞增殖。我们证明，L6E9成肌细胞的线粒体活性的增加可以很容易地通过简单地提高细胞外丙酮酸浓度的培养皿中获得。在此条件下，L6E9成肌细胞经历了一个快速的生长停滞在G1 + S期伴随着显着的细胞肥大。没有明显的成肌细胞融合迹象。这伴随着增殖细胞核抗原表达的下调和p21表达的增加。线粒体生物合成也受到刺激，如线粒体含量增加两倍所示。这些细胞表现出大量增加的活性氧的生产，可能有助于观察到的表型改变。然而，暴露于抗氧化剂的阿托伐他汀处理的细胞没有逆转生长停滞。同样，对照细胞暴露于氧化剂也不会诱导生长停滞。我们的观察结果表明，线粒体活性似乎在调节成肌细胞增殖中起着核心作用。他们还强烈支持逆行通讯，建立了线粒体对核基因表达的控制，这种控制可以通过线粒体活性来调节。(C)2004年爱思唯尔公司All rights reserved.
The aim of the present study was to determine whether mitochondrial activity could regulate myoblast proliferation. We demonstrate that an increase in mitochondrial activity of L6E9 myoblasts can be easily obtained by simply raising extracellular pyruvate concentration in the culture dish. Under this condition, L6E9 myoblasts underwent a rapid growth arrest in G1 + S phases concomitant to a marked cellular hypertrophy. No sign of myoblast fusion was evident. This was accompanied by the down-regulation of proliferating cell nuclear antigen expression and an increase in p21 expression. Mitochondrial biogenesis was also stimulated, as indicated by a twofold increase in mitochondrial content. These cells exhibited a large increase in the production of reactive oxygen species that could contribute to the observed phenotypic alterations. However, exposure of pyruvate-treated cells to antioxidants did not reverse growth arrest. Similarly, exposure of control cells to oxidants did not induce growth arrest. Our observations suggest that mitochondrial activity appears to play a central role in regulating myoblast proliferation. They also argue strongly in favor of a retrograde communication establishing a mitochondrial control of nuclear gene expression that could be modulated by mitochondrial activity. (C) 2004 Elsevier Inc. All rights reserved.