ROS up-regulatlion mediates Ras-induced changes of cell morphology and motility
ROS up-regulatlion mediates Ras-induced changes of cell morphology and motility
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DOI：
10.1016/j.yexcr.2006.03.004
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发表时间：
2006-07-01
影响因子：
3.7
通讯作者：
Kopnin, Boris P.
中科院分区：
文献类型：
--
作者：
Alexandrova, Antonina Y.;Kopnin, Pauel B.;Kopnin, Boris P.
活化 Ras 的表达导致细胞内活性氧 (ROS) 含量增加。为了确定 ROS 上调在介导 Ras 诱导的形态转变和细胞运动增加中的作用，我们研究了过氧化氢和抗氧化剂 NAC 对 REF52 大鼠成纤维细胞的形态及其体外迁移到伤口的能力的影响。用低剂量的过氧化氢处理导致细胞内ROS水平增加1.5至2倍，诱导细胞形状、肌动蛋白细胞骨架组织、细胞粘附和迁移的变化，类似于Ras转化细胞中的变化。另一方面，NAC 处理可减弱条件性或组成型表达活化 Ras 的细胞中 ROS 上调，导致形态转变部分逆转并降低细胞运动性。 ROS 对细胞形态和运动的影响可能是由于 Rac1、Rho 和丝切蛋白的活性调节所致，这些蛋白在肌动蛋白动力学的调节中发挥着关键作用。获得的数据与ROS上调介导Ras诱导的形态转化和细胞运动中两个关键事件的观点一致：它负责Rac1激活，并且对于实现Ras诱导的cofilin去磷酸化是必要的（尽管不够）。 (c) 2006 Elsevier Inc. 保留所有权利。
Expression of activated Ras causes an increase in intracellular content of reactive oxygen species (ROS). To determine the role of ROS up-regulation in mediation of Ras-induced morphological transformation and increased cell motility, we studied the effects of hydrogen peroxide and antioxidant NAC on morphology of REF52 rat fibroblasts and their ability to migrate into the wound in vitro. Treatment with low dosages of hydrogen peroxide leading to 1.5- to 2-fold increase in intracellular ROS levels induced changes of cell shape, actin cytoskeleton organization, cell adhesions and migration resembling those in Ras-transformed cells. On the other hand, treatment with NAC attenuating ROS up-regulation in cells with conditional or constitutive expression of activated Ras led to partial reversion of morphological transformation and decreased cell motility. The effect of ROS on cell morphology and motility probably results from modulation of activity of Rac1, Rho, and cofilin proteins playing a key role in regulation of actin dynamics. The obtained data are consistent with the idea that ROS up-regulation mediates two key events in Ras-induced morphological transformation and cell motility: it is responsible for Rac1 activation and is necessary (though insufficient) for realization of Ras-induced cofilin dephosphorylation. (c) 2006 Elsevier Inc. All rights reserved.