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- W1947806632 abstract "OBJECTIVE: To compare the muscle proteome in inclusion body myositis (sIBM) and healthy controls and to characterize proteome changes over time in longitudinal studies. BACKGROUND: sIBM is the most common acquired muscle disease of the elderly. Symptoms are progressive muscle weakness and atrophy often accompanied by dysphagia. Loss of ambulation and artificial nutrition are frequent. The cause of sIBM is unknown. The pathogenesis is complex and includes inflammatory-immunological and degenerative aspects. There is no treatment. DESIGN/METHODS: For accurate quantitation in our proteome analysis, we created a human muscle-specific Stable-isotope-labeling-by-amino-acids-in-cell-culture (SILAC)-reference. Frozen muscle specimens from sIBM (n=9) and healthy control (n=8) were subjected to urea extraction with Lys-C and trypsin-digestion followed by high-performance liquid chromatography coupled to tandem mass spectrometry. From two patients muscle biopsy specimens were analysed that were obtained at two different time points (time point A and B) seven years apart allowing insight into longitudinal changes. Data were analyzed with MaxQuant. RESULTS: Shotgun proteomics using human muscle-specific SILAC-reference resulted in identification of 2500 proteins, of which 2000 were quantified. Protein expression differed fundamentally between sIBM muscle and healthy muscle. Many pathways are affected, especially those which are associated with RNA processing, RNA metabolism, splicing and translation. The longitudinal study revealed that the proteomes were very similar between time point A and B, although, histologically, at time point A only features of polymyositis without increase in connective tissue, rimmed vacuoles or congophilic deposits were present. This applies in particular to the disruption in RNA metabolism, translation and mitochondrial abnormalities. CONCLUSIONS: sIBM implicates severe dysregulation of about 500 muscle proteins in particular widespread alterations of RNA metabolism. Proteome changes precede histopathology by years. Disclosure: Dr. Berger has nothing to disclose. Dr. Opialla has nothing to disclose. Dr. Marg has nothing to disclose. Dr. Kempa has nothing to disclose. Dr. Spuler has nothing to disclose." @default.
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- W1947806632 date "2015-04-06" @default.
- W1947806632 modified "2023-09-30" @default.
- W1947806632 title "Identification of widespread alterations in RNA metabolism in sporadic inclusion-body myositis using SILAC-based quantitative proteomics (P4.109)" @default.
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