一个窗口进入细胞内事件在肌炎通过亚细胞蛋白质组的细胞内事件
Jennifer M Peterson1, Valérie Leclair2, Olumide E Oyebode3
1Department of Exercise and Rehabilitative Sciences, The University of Toledo, 2801 W. Bancroft St., MS 119, Toledo, OH, 43606, USA. jennifer.peterson@utoledo.edu.
概括
异常性炎症性肌肉病包括超出蛋白质聚合物的广泛分子变化,影响骨肌肉中的核,线粒体和膜蛋白. 这项研究揭示了新的蛋白质变化,有助于这些条件下的肌肉退化.
科学领域:
- 肌肉生物学 肌肉生物学
- 蛋白质组学是指蛋白质组学.
- 分子医学是分子医学.
背景情况:
- 异形性炎症性肌肉病 (IIM) 是一种复杂的肌肉疾病,其原因尚不清楚.
- 线粒体功能障碍和蛋白质聚合与IIM的骨肌肉退化有关.
- 精确的分子通路驱动骨肌肉中的蛋白质聚合仍然不清楚.
研究的目的:
- 为了研究具有异常性炎症性肌肉病 (IIM) 的患者骨肌肉中的分子变化.
- 为了确定受影响肌肉组织的各种细胞部分的新型蛋白质变化.
- 探索线粒体功能障碍和蛋白质聚合在IIM病变发生中的作用.
主要方法:
- 从肌肉活检中分离与膜结合的器官 (细胞核,线粒体,ER,戈尔吉细胞,血膜).
- 使用Orbitrap融合质谱仪进行全球蛋白质组分析.
- 无监督的蛋白质组数据聚类,以区分正常,线粒体肌肉病和IIM肌肉样本.
主要成果:
- 证实了已知的蛋白质变化,并在IIM骨肌中确定了许多新的变化.
- 发现了参与细胞分裂,转录和RNA调节的核蛋白的差异表达.
- 观察到与蛋白质折叠和贩运相关的ER / Golgi蛋白质的改变表达,以及能量代谢中的线粒体蛋白质.
- 在肌肉的细胞骨和收缩机械中发现了变化.
结论:
- 在IIM骨肌中的分子变化超出了细胞质蛋白质聚合物的范围.
- 显著的变化发生在核,线粒体和膜结合的部分.
- 这些发现为IIM的分子病理学提供了更广泛的理解.
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