• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >The accumulation of neurotoxic proteins, induced by proteasome inhibition, is reverted by trehalose, an enhancer of autophagy, in human neuroblastoma cells.
【24h】

The accumulation of neurotoxic proteins, induced by proteasome inhibition, is reverted by trehalose, an enhancer of autophagy, in human neuroblastoma cells.

机译：在人成神经细胞瘤细胞中，由蛋白酶体抑制引起的神经毒性蛋白的积累被海藻糖（一种自噬增强剂）所恢复。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Neurodegenerative diseases like Parkinson's disease, Alzheimer's disease, Huntington's disease and others are due to accumulation of abnormal proteins which fold improperly and impair neuronal function. Accumulation of these proteins could be achieved by several mechanisms including mutation, overproduction or impairment of its degradation. Inhibition of the normal protein degradation is produced by blockade of the ubiquitin proteasome system. We have shown that epoxomicin, a proteasome inhibitor, increases the levels of proteins involved in neurodegenerative disorders such as alpha-synuclein and hyper phosphorylated tau in NB69 human neuroblastoma cells and that such increase correlates with an enhanced rate of cell death. We then investigated whether the stimulation of autophagy, an alternative mechanism for elimination of abnormal proteins, by treatment with trehalose, counteracts the effects of proteasomal blockade. Trehalose, a disaccharide present in many non-mammalian species, known to enhance autophagy, protects cells against various environmental stresses. Treatment with trehalose produced a dose and time-dependent increase in the number of autophagosomes and markers of autophagy in NB69 cells. Trehalose did not change the number of total neither the number of dividing cells in the culture but it completely prevented the necrosis of NB69 induced by epoxomicin. In addition, the treatment with trehalose reverted the accumulation, induced by epoxomicin, of polyubiquitinated proteins, total and phosphorylated tau, p-GSK-3, and alpha-synuclein, as well as the alpha-synuclein intracellular aggregates. The effects of trehalose were not mediated through activation of free radical scavenging compounds, like GSH, or mitochondrial proteins, like DJ1, but trehalose reduced the activation of ERK and chaperone HSP-70 induced by epoxomicin. Inhibition of ERK phosphorylation prevented the epoxomicin-induced cell death. Inhibition of autophagy reverted the neuroprotective effects of trehalose in epoxomicin-induced cell death. These results suggest that trehalose is a powerful modifier of abnormal protein accumulation in neurodegenerative diseases.
机译：帕金森氏病，阿尔茨海默氏病，亨廷顿氏病等神经退行性疾病是由于异常蛋白质的积累造成的，这些蛋白质折叠不正确并损害神经元功能。这些蛋白质的积累可以通过几种机制来实现，包括突变，过度生产或对其降解的损害。正常蛋白降解的抑制作用是通过阻断泛素蛋白酶体系统产生的。我们已经表明，埃博霉素，一种蛋白酶体抑制剂，可增加NB69人神经母细胞瘤细胞中神经退行性疾病（如α-突触核蛋白和高磷酸化tau蛋白）所涉及的蛋白质水平，并且这种增加与细胞死亡率增加相关。然后，我们研究了用海藻糖刺激自噬（一种消除异常蛋白质的替代机制）的刺激是否抵消了蛋白酶体阻滞的作用。海藻糖是存在于许多非哺乳动物物种中的一种二糖，已知会增强自噬作用，可保护细胞免受各种环境压力。用海藻糖处理可使NB69细胞中自噬体的数量和自噬标记物呈剂量和时间依赖性增加。海藻糖既不改变培养物中总分裂细胞的数目，也不完全改变由环氧霉素引起的NB69的坏死。另外，用海藻糖处理可逆转由环氧霉素诱导的多泛素化蛋白，总和磷酸化的tau，p-GSK-3和α-突触核蛋白以及α-突触核蛋白细胞内聚集体的积累。海藻糖的作用不是通过自由基清除化合物（例如GSH）或线粒体蛋白（例如DJ1）的活化来介导的，但海藻糖减少了由环氧霉素诱导的ERK和伴侣HSP-70的活化。抑制ERK磷酸化阻止了环氧霉素诱导的细胞死亡。自噬的抑制恢复了海藻糖在环氧霉素诱导的细胞死亡中的神经保护作用。这些结果表明，海藻糖是神经退行性疾病中异常蛋白质积累的有力调节剂。

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