Melatonin prevents cytoskeletal alterations and oxidative stress induced by okadaic acid in N1E-115 cells
Melatonin prevents cytoskeletal alterations and oxidative stress induced by okadaic acid in N1E-115 cells
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DOI：
10.1016/s0014-4886(03)00085-2
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发表时间：
2003-07-01
影响因子：
5.3
通讯作者：
Antón-Tay, F
中科院分区：
文献类型：
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作者：
Benitez-King, G;Túnez, I;Antón-Tay, F
在神经老化和神经退行性疾病中，神经元细胞结构的进行性丧失是神经元死亡之前的主要事件。神经退行性疾病中的细胞骨架的特征在于过度磷酸化的tau蛋白组装在神经元缠结中。Tau蛋白促进微管扩大，其过度磷酸化抑制微管蛋白组装。冈田酸（OA）引起氧化应激、tau蛋白过度磷酸化和改变的细胞骨架组织，类似于在痴呆患者的神经元中观察到的那些。由于褪黑激素的作用，扩大微管和作为一种自由基清除剂，在这项工作中，我们研究了褪黑激素的影响，改变OA诱导的细胞骨架组织在N1 E-115神经母细胞瘤细胞。光学显微镜，形态测定分析，和微管蛋白免疫荧光染色的神经母细胞瘤细胞与50 nM OA孵育显示一个完整的微管网络的神经突的轮廓类似于观察到的车辆孵育的细胞时，褪黑激素加入到孵育培养基2小时前OA。褪黑激素对OA引起的细胞骨架结构改变的作用呈剂量依赖性，且不能被mt（1）褪黑激素受体拮抗剂luzindole消除。此外，增加的脂质过氧化和增加的N1 E-115细胞与50 nM OA孵育的凋亡被褪黑素阻止。结果支持褪黑激素可用于治疗神经退行性疾病的假设。(C)2003 Elsevier Science（美国）。All rights reserved.
Progressive loss of neuronal cytoarchitecture is a major event that precedes neuronal death, both in neural aging and in neurodegenerative diseases. Cytoskeleton in neurodegenerative diseases is characterized by hyperphosphorylated tau assembled in neurofibrillary tangles. Tau protein promotes microtubule enlargement and its hyperphosphorylation inhibits tubulin assembly. Okadaic acid (OA) causes oxidative stress, tau hyperphosphorylation, and altered cytoskeletal organization similar to those observed in neurons of patients with dementia. Since melatonin acts by both enlarging microtubules and as a free-radical scavenger, in this work we studied the effects of melatonin on altered cytoskeletal organization induced by OA in N1E-115 neuroblastoma cells. Optic microscopy, morphometric analysis, and tubulin immunofluorescence staining of neuroblastoma cells incubated with 50 nM OA showed an intact microtubule network following the neurite profile similar to that observed in the vehicle-incubated cells when melatonin was added to the incubation media 2 h before OA. The melatonin effects on altered cytoskeletal organization induced by OA were dose-dependent and were not abolished by luzindole, the mt(1) melatonin antagonist receptor. Also, increased lipid peroxidation and augmented apoptosis in N1E-115 cells incubated with 50 nM OA were prevented by melatonin. The results support the hypothesis that melatonin can be useful in the treatment of neurodegenerative diseases. (C) 2003 Elsevier Science (USA). All rights reserved.