Desmin is oxidized and nitrated in affected muscles in myotilinopathies and desminopathies
Desmin is oxidized and nitrated in affected muscles in myotilinopathies and desminopathies
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DOI：
10.1097/nen.0b013e3181256b4c
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发表时间：
2007-08-01
影响因子：
3.2
通讯作者：
Ferrer, Isidro
中科院分区：
文献类型：
--
作者：
Biol, Anna Janue;Odena, Maria Antonia;Ferrer, Isidro
具有异常蛋白质聚集体的退行性疾病的特征是具有可变翻译后修饰（包括磷酸化、糖氧化、氧化和硝化）的蛋白质的积累。肌原纤维性肌病，包括肌球蛋白病和结蛋白病，其特征在于肌细胞中不溶性聚集体中蛋白质的胞浆内局灶性积聚。通过使用单一的免疫组织化学，单向凝胶电泳和蛋白质印迹，双向凝胶电泳，凝胶内消化，和质谱，结蛋白被证明是一个主要的目标氧化和硝化的结蛋白病和肌球蛋白病。由于氧化和硝化蛋白质可能具有毒性作用，并可能损害泛素-蛋白酶体功能，修饰的结蛋白可以被认为是肌原纤维肌病发病机制中的附加元素。除了结蛋白，丙酮酸激酶肌肉剪接形式M1被氧化，从而支持补充线粒体损伤，至少在某些情况下的肌球蛋白病。
Degenerative diseases with abnormal protein aggregates are characterized by the accumulation of proteins with variable post-translational modifications including phosphorylation, glycoxidation, oxidation, and nitration. Myofibrillar myopathies, including myotilinopathies and desminopathies, are characterized by the intracytoplasmic focal accumulation of proteins in insoluble aggregates in muscle cells. By using single immunohistochemistry, monodimensional gel electrophoresis and Western blotting, and bidimensional gel electrophoresis, in-gel digestion, and mass spectometry, desmin was demonstrated to be a major target of oxidation and nitration in both desminopathies and myotilinopathies. Because oxidized and nitrated proteins may have toxic effects and may impair ubiquitin-proteasomal function, modified desmin can be considered to be an additional element in the pathogenesis of myofibrillar myopathies. In addition to desmin, pyruvate kinase muscle splice form M1 is oxidized, thus supporting complemental mitochondrial damage, at least in some cases of myotilinopathy.