Fast-twitch sarcomeric and glycolytic enzyme protein loss in inclusion body myositis.
Fast-twitch sarcomeric and glycolytic enzyme protein loss in inclusion body myositis.
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DOI:
10.1002/mus.21230
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发表时间:
2009-06
期刊:
影响因子:
3.4
通讯作者:
Greenberg, Steven A.
中科院分区:
文献类型:
--
作者:
Parker, Kenneth C.;Kong, Sek Won;Walsh, Ronan J.;Salajegheh, Mohammad;Moghadaszadeh, Behzad;Amato, Anthony A.;Nazareno, Remedios;Lin, Yin Yin;Krastins, Bryan;Sarracino, David A.;Beggs, Alan H.;Pinkus, Jack L.;Greenberg, Steven A.
Inclusion body myositis (IBM) is an inflammatory disease of skeletal muscle of unknown cause. To further understand the nature of the tissue injury in this disease, we developed methods for large-scale detection and quantitation of proteins in muscle biopsy samples and analyzed proteomic data produced by these methods together with histochemical, immunohistochemical, and microarray data. Twenty muscle biopsy samples from patients with inflammatory myopathies (N=17) or elderly subjects without neuromuscular disease (N=3) were profiled by proteomic studies using liquid chromatographic separation of peptides followed by mass spectrometry. Thirteen of the diseased samples additionally underwent microarray studies. Seventy muscle specimens from patients with a range of neuromuscular disorders were examined by ATPase histochemical methods. Smaller numbers of samples underwent immunohistochemical and immunoblot studies. Mass spectrometric studies identified and quantified approximately 300 total distinct proteins in each muscle sample. In inclusion body myositis and to a lesser extent in polymyositis, proteomic studies confirmed by histochemical, immunohistochemical, and immunoblot studies loss of many fast-twitch specific structural proteins and glycolytic enzymes despite relative preservation of transcript levels. Increased abundance of a nuclear membrane protein, immunoglobulins, and two calpain-3 substrates were present. The atrophy present in inclusion body myositis muscle is accompanied by preferential loss of fast-twitch structural proteins and glycolytic enzymes, particularly glycogen debranching enzyme, with relative preservation of the abundance of their respective transcripts. Although muscle atrophy has long been recognized in IBM, these studies report the first specific proteins identified as reduced in quantity in IBM muscle.
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