...
首页> 外文期刊>Neurotoxicity research >Microtubule-Targeting Agents Eribulin and Paclitaxel Differentially Affect Neuronal Cell Bodies in Chemotherapy-Induced Peripheral Neuropathy
【24h】

Microtubule-Targeting Agents Eribulin and Paclitaxel Differentially Affect Neuronal Cell Bodies in Chemotherapy-Induced Peripheral Neuropathy

机译:微管靶向剂Eribulin和紫杉醇差异地影响化疗诱导的周围神经病变中的神经元细胞体

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

       

摘要

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of anticancer treatment with microtubule-targeted agents (MTAs). The frequency of severe CIPN, which can be dose limiting and even life threatening, varies widely among different MTAs. For example, paclitaxel induces a higher frequency of severe CIPN than does eribulin. Different MTAs also possess distinct mechanisms of microtubule-targeted action. Recently, we demonstrated that paclitaxel and eribulin differentially affect sciatic nerve axons, with paclitaxel inducing more pronounced neurodegenerative effects and eribulin inducing greater microtubule stabilizing biochemical effects. Here, we complement and extend these axonal studies by assessing the effects of paclitaxel and eribulin in the cell bodies of sciatic nerve axons, housed in the dorsal root ganglia (DRG). Importantly, the microtubule network in cell bodies is known to be significantly more dynamic than in axons. Paclitaxel induced activating transcription factor 3 expression, a marker of neuronal stress/injury. Paclitaxel also increased expression levels of acetylated tubulin and end binding protein 1, markers of microtubule stability and growth, respectively. These effects are hypothesized to be detrimental to the dynamic microtubule network within the cell bodies. In contrast, eribulin had no significant effect on any of these parameters in the cell bodies. Taken together, DRG cell bodies and their axons, two distinct neuronal cell compartments, contain functionally distinct microtubule networks that exhibit unique biochemical responses to different MTA treatments. We hypothesize that these distinct mechanistic actions may underlie the variability seen in the initiation, progression, persistence, and recovery from CIPN.
机译:化疗诱导的周围神经病变(CIPN)是抗癌治疗与微管靶向剂(MTA)的常见副作用。严重CIPN的频率可以是剂量限制甚至危及生命,在不同的MTA中变化很大。例如,紫杉醇诱导严重CIPN的较高频率,而不是Eribulin。不同的MTA也具有明显的微管靶向作用机制。最近,我们证明了紫杉醇和埃吡林差异地影响坐骨神经轴突,用紫杉醇诱导更明显的神经变性效应和纤维蛋白诱导更大的微管稳定生化作用。在此,我们通过评估坐骨神经轴颈细胞体在坐骨神经轴突(DRG)中的坐骨神经轴突中的紫杉醇和二林蛋白的影响来补充并延长这些轴突研究。重要的是,已知细胞体中的微管网络比轴突中的动态显着更大。紫杉醇诱导激活转录因子3表达,是神经元应力/损伤的标志物。紫杉醇还增加了乙酰化微管蛋白和末端结合蛋白1的表达水平,分别是微管稳定性和生长的标记。这些效果被假设为对细胞体内的动态微管网络有害。相比之下,Eribulin对细胞体中的任何这些参数没有显着影响。一起使用DRG细胞体和其轴突,两个不同的神经元细胞隔室含有功能性不同的微管网络,其对不同的MTA治疗具有独特的生化反应。我们假设这些独特的机制行为可能使得从CIPN开始,进展,持久性和恢复中所见的可变性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号