Janué Anna, Odena Maria Antonia, Oliveira Eliandre, Olivé Montse, Ferrer Isidro
Institut de Neuropatologia, Servei Anatomia Patològica, Institut d'Investigacio de Bellvitge-Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Plataforma de Proteòmica, Barcelona Spain.
J Neuropathol Exp Neurol. 2007 Aug;66(8):711-23. doi: 10.1097/nen.0b013e3181256b4c.
Degenerative diseases with abnormal protein aggregates are characterized by the accumulation of proteins with variable posttranslational 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.
伴有异常蛋白质聚集体的退行性疾病的特征是蛋白质积累，这些蛋白质具有包括磷酸化、糖氧化、氧化和硝化在内的多种翻译后修饰。肌原纤维肌病，包括肌联蛋白病和结蛋白病，其特征是肌肉细胞内不溶性聚集体中的蛋白质在胞质内局部积累。通过使用单免疫组织化学、一维凝胶电泳和蛋白质印迹法，以及二维凝胶电泳、凝胶内消化和质谱分析，结蛋白被证明是结蛋白病和肌联蛋白病中氧化和硝化的主要靶点。由于氧化和硝化的蛋白质可能具有毒性作用，并可能损害泛素-蛋白酶体功能，因此修饰后的结蛋白可被视为肌原纤维肌病发病机制中的一个额外因素。除了结蛋白外，丙酮酸激酶肌肉剪接形式M1也被氧化，因此至少在某些肌联蛋白病病例中支持线粒体的补充性损伤。
