...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Neuromuscular disorders: NMD >Abnormal distribution of heterogeneous nuclear ribonucleoproteins in sporadic inclusion body myositis
【24h】

Abnormal distribution of heterogeneous nuclear ribonucleoproteins in sporadic inclusion body myositis

机译：散发性包涵体肌炎中异质核核糖核蛋白的异常分布

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Previous histopathologic studies of sporadic inclusion body myositis (sIBM) identified sarcoplasmic aggregation and myonuclear depletion of the predominantly nuclear heterogeneous nuclear ribonucleoprotein (hnRNP) TDP-43 in sIBM myofibers. Here, we examined sIBM muscle for abnormalities in two other hnRNPs hnRNPA1 and hnRNPA2B1, mutations in which cause multisystem proteinopathy associated with rimmed-vacuolar myopathies. Muscle biopsy specimens from 13 patients with sIBM and 13 patients without sIBM (dermatomyositis N= 3, polymyositis N= 3, muscular dystrophy N= 3, motor neuron disease N= 2, non-neuromuscular disease N= 2) underwent immunohistochemistry for hnRNPA1, hnRNPA2B1, and TDP-43. Muscle transcriptional microarray data from 27 patients with sIBM and 12 patients without neuromuscular disease was analyzed. Depletion of hnRNPA1 and hnRNPA2B1 was present in 15% and 7% of sIBM myonuclei, respectively, compared with 1% and 0% of myonuclei in non-sIBM muscle. Sarcoplasmic aggregates of hnRNPA1 and hnRNPA2B1 distinct from TDP-43 aggregates were also found in sIBM. hnRNPA1 and hnRNPA2B1, as well as other hnRNPs, gene expression was unaltered in sIBM compared to normal muscle. Along with TDP-43, other hnRNPs, including hnRNPA1 and hnRNPA2B1, are depleted from sIBM myonuclei at the protein but not transcript level. The depletion of multiple hnRNPs from sIBM myonuclei together with their sarcoplasmic aggregation suggests that one aspect of sIBM pathophysiology may involve abnormal RNA metabolism that includes hyperassembly of ribonucleoprotein granules mediated by prion-like domains in hnRNPs, evolving into pathological aggregates.
机译：以前的散发性包涵体肌炎（sIBM）的组织病理学研究确定了sIBM肌纤维中主要为核异质核核糖核蛋白（hnRNP）TDP-43的肌浆聚集和肌核耗竭。在这里，我们检查了sIBM肌肉中其他两个hnRNP hnRNPA1和hnRNPA2B1的异常，这些突变会导致与边缘气管肌病相关的多系统蛋白病。对13例sIBM的患者和13例无sIBM的患者（皮肌炎N = 3，多肌炎N = 3，肌肉营养不良N = 3，运动神经元疾病N = 2，非神经肌肉疾病N = 2）的肌肉活检标本进行了hnRNPA1免疫组织化学检查hnRNPA2B1和TDP-43。分析了来自27位sIBM患者和12位无神经肌肉疾病的患者的肌肉转录微阵列数据。 sRN的15％和7％分别存在hnRNPA1和hnRNPA2B1的消耗，相比之下，非sIBM肌肉中nyRNA的消耗为1％和0％。在sIBM中也发现了不同于TDP-43聚集体的hnRNPA1和hnRNPA2B1的肌质聚集体。 hnRNPA1和hnRNPA2B1以及其他hnRNP，与正常肌肉相比，sIBM中的基因表达没有改变。与TDP-43一起，其他hnRNP（包括hnRNPA1和hnRNPA2B1）在蛋白质上而不是在转录本水平上都从sIBM肌核中耗尽。 sIBM肌核中多个hnRNP的耗竭及其胞浆聚集表明，sIBM病理生理学的一个方面可能涉及异常的RNA代谢，包括核糖核蛋白颗粒的过度组装，该核糖蛋白颗粒由hnRNPs中的pr病毒样结构域介导，演变为病理性聚集体。

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