Proteomforschung und molekulare Mechanismen bei Muskelanpassungen und Muskelerkrankungen

 

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Zusammenfassung

Biomedizinische Untersuchungen mit global ausgerichteten Forschungsansätzen haben erhebliche Erfolge bei der Erforschung der physiologischen Muskelanpassung und der molekularen Pathogenese von Muskelerkrankungen erzielt. Die Proteomanalyse mittels 2D-Gelelektrophorese, Flüssigkeitschromatografie und Massenspektrometrie wurde gezielt für die Erforschung pathobiochemischer Veränderungen bei der zeitlichen Abfolge der Proteinexpression und der posttranslationalen Modifizierung eingesetzt sowie zur Bestimmung von abnormalen Wechselwirkungen zwischen Muskelproteinen. Die differenzielle Proteomanalyse wurde erfolgreich angewendet zum Vergleich der Expressionsprofile von gesundem menschlichem Muskelgewebe und Muskelbiopsien von Patienten mit Einschlusskörpermyositis, Adipositas, Diabetes mellitus und Sarkopenie. Die zelluläre Plastizität von Muskelfasern wurde bestimmt bei der Muskelanpassung an Ausdauertraining und an Hypoxie. Weiterhin haben Proteomstudien an Modellorganismen mit Muskelerkrankungen zur Identifizierung von potenziell veränderten Reaktionskaskaden bei bestimmten Formen der Muskeldystrophie, Myotonie, Muskelatrophie und der amyotrophen Lateralsklerose geführt.

Summary

Global biomedical approaches have recently succeeded in the elucidation of physiological muscle adaptations and the molecular pathogenesis of various muscular disorders. Proteomic analyses using 2D gel electrophoresis, liquid chromatography and mass spectrometry were employed for the determination of pathobiochemical changes in protein expression patterns and post-translational modifications, as well as for the identification of abnormal protein-protein interactions in muscle. Differential proteomics was successfully applied for the comparison of expression profiles of normal human muscle tissues versus biopsy material from patients afflicted with inclusion body myositis, diabetes, obesity and sarcopenia. The degree of muscle plasticity was determined during adaptations to endurance training and chronic hypoxia. In addition, the proteomic profiling of animal models of muscle diseases has identified potential alterations in pathways relevant for certain types of muscular dystrophy, myotonia, muscular atrophy and amyotrophic lateral sclerosis.

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