Reactive oxygen species regulate F-actin dynamics in neuronal growth cones and neurite outgrowth.
Reactive oxygen species regulate F-actin dynamics in neuronal growth cones and neurite outgrowth.
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DOI：
10.1111/j.1471-4159.2008.05787.x
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发表时间：
2009-02
影响因子：
4.7
通讯作者：
Suter DM
中科院分区：
文献类型：
--
作者：
Munnamalai V;Suter DM
众所周知，活性氧因其对脂质、蛋白质和DNA的氧化而产生破坏作用，最终导致细胞死亡。越来越多的证据表明，活性氧在细胞增殖、分化、细胞运动和凋亡中也具有重要的信号转导功能。在这里，我们测试的假设是否活性氧发挥生理作用，在调节F-肌动蛋白的结构和动力学神经生长锥。用自由基清除剂N-叔丁基-α-苯基硝酮降低细胞质活性氧水平，或通过抑制活性氧的特定来源，如NADPH氧化酶或脂氧合酶，降低生长锥外周区域的F-肌动蛋白含量。荧光散斑显微镜显示，这些治疗引起肌动蛋白组装抑制，减少逆行肌动蛋白流和增加的肌动蛋白结构的收缩性的过渡区称为弧，可能通过激活Rho通路。活性氧水平的降低最终导致肌动蛋白细胞骨架的解体。当神经元在自由基减少的条件下培养过夜时，生长锥形成和神经突生长严重受损。因此，我们得出结论，生理水平的活性氧是至关重要的，以维持一个动态的F-肌动蛋白细胞骨架和控制神经突起的生长。
Reactive oxygen species are well known for their damaging effects due to oxidation of lipids, proteins and DNA that ultimately result in cell death. Accumulating evidence indicates that reactive oxygen species also have important signaling functions in cell proliferation, differentiation, cell motility and apoptosis. Here, we tested the hypothesis whether reactive oxygen species play a physiological role in regulating F-actin structure and dynamics in neuronal growth cones. Lowering cytoplasmic levels of reactive oxygen species with a free radical scavenger, N-tert-butyl-α-phenylnitrone, or by inhibiting specific sources of reactive oxygen species, such as NADPH oxidases or lipoxygenases, reduced the F-actin content in the peripheral domain of growth cones. Fluorescent speckle microscopy revealed that these treatments caused actin assembly inhibition, reduced retrograde actin flow and increased contractility of actin structures in the transition zone referred to as arcs, possibly by activating the Rho pathway. Reduced levels of reactive oxygen species ultimately resulted in disassembly of the actin cytoskeleton. When neurons were cultured overnight in conditions of reduced free radicals, growth cone formation and neurite outgrowth were severely impaired. Therefore, we conclude that physiological levels of reactive oxygen species are critical for maintaining a dynamic F-actin cytoskeleton and controlling neurite outgrowth.
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影响因子：
7.8
作者：
Chang, S;Rathjen, F G;Raper, J A
通讯作者：
Raper, J A
影响因子：
5.5
作者：
Duan, Yuntao;Gross, Robert A.;Sheu, Shey-Shing
通讯作者：
Sheu, Shey-Shing
DOI：
10.1016/s0167-4889(98)00126-8
发表时间：
1998-11-19
影响因子：
5.1
作者：
Kotake, Y;Sang, H;Wallis, GL
通讯作者：
Wallis, GL
DOI：
10.1083/jcb.119.5.1219
发表时间：
1992-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lewis AK;Bridgman PC
通讯作者：
Bridgman PC
影响因子：
4.8
作者：
Fiaschi, Tania;Cozzi, Giacomo;Chiarugi, Paola
通讯作者：
Chiarugi, Paola