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Progressive Proteome Changes in the Myocardium of a Pig Model for Duchenne Muscular Dystrophy.
iScience ( IF 5.8 ) Pub Date : 2020-09-01 , DOI: 10.1016/j.isci.2020.101516
Hathaichanok Tamiyakul 1 , Elisabeth Kemter 2, 3 , Miwako Kösters 1 , Stefanie Ebner 2 , Andreas Blutke 4 , Nikolai Klymiuk 2, 3 , Florian Flenkenthaler 1 , Eckhard Wolf 1, 2, 3 , Georg J Arnold 1 , Thomas Fröhlich 1
Affiliation  

Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is characterized by progressive muscle weakness. Even though DMD manifests first in skeletal muscle, heart failure is a major cause of death in late-stage DMD. To get insights into DMD-associated cardiomyopathy, we performed a proteome analysis of myocardium from a genetically engineered porcine DMD model resembling clinical and pathological hallmarks of human DMD. To capture DMD progression, samples from 2-day- and 3-month-old animals were analyzed. Dystrophin was absent in all DMD samples, and components of the dystrophin-associated protein complex were decreased, suggesting destabilization of the cardiomyocyte plasma membrane and impaired cellular signaling. Furthermore, abundance alterations of proteins known to be associated with human cardiomyopathy were observed. Compared with data from skeletal muscle, we found clear evidence that DMD progression in myocardium is not only slower than in skeletal muscle but also involves different biological and biochemical pathways.



中文翻译:

杜氏肌营养不良猪模型心肌中蛋白质组的进展性变化。

杜氏肌营养不良症 (DMD) 由肌营养不良蛋白基因突变引起,其特征是进行性肌肉无力。尽管 DMD 首先出现在骨骼肌中,但心力衰竭是晚期 DMD 死亡的主要原因。为了深入了解 DMD 相关心肌病,我们对基因工程猪 DMD 模型的心肌进行了蛋白质组分析,该模型类似于人类 DMD 的临床和病理特征。为了了解 DMD 的进展情况,对 2 天和 3 个月大动物的样本进行了分析。所有 DMD 样本中均不存在肌营养不良蛋白,并且肌营养不良蛋白相关蛋白复合物的成分减少,表明心肌细胞质膜不稳定且细胞信号传导受损。此外,还观察到已知与人类心肌病相关的蛋白质的丰度变化。与骨骼肌的数据相比,我们发现明确的证据表明,心肌中的DMD进展不仅慢于骨骼肌,而且涉及不同的生物和生化途径。

更新日期:2020-09-12
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