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Fast‐twitch sarcomeric and glycolytic enzyme protein loss in inclusion body myositis
Author(s) -
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.
Publication year - 2009
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.21230
Subject(s) - inclusion body myositis , glycolysis , myositis , enzyme , medicine , biochemistry , endocrinology , chemistry
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 ≈300 total distinct proteins in each muscle sample. In IBM and to a lesser extent in polymyositis, proteomic studies confirmed by histochemical, immunohistochemical, and immunoblot studies showed 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 IBM 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 are the first to report specific proteins which are reduced in quantity in IBM muscle. Muscle Nerve, 2008