Proteomic identification of elevated saliva kallikrein levels in the mdx-4cv mouse model of Duchenne muscular dystrophy |
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Authors: | Sandra Murphy Margit Zweyer Rustam R Mundegar Dieter Swandulla Kay Ohlendieck |
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Institution: | 1. Department of Biology, Maynooth University, National University of Ireland, Maynooth, Co. Kildare, Ireland;2. Institute of Physiology II, University of Bonn, D53115 Bonn, Germany |
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Abstract: | Dystrophinopathies are multi-system disorders that affect the skeletal musculature, the cardio-respiratory system and the central nervous system. The systematic screening of suitable biofluids for released or altered proteins promises new insights into the highly complex pathophysiology of X-linked muscular dystrophy. However, standard detection approaches using antibody-based assays often fail to reproducibly detect low-abundance protein isoforms in dilute biological fluids. In contrast, mass spectrometric screening approaches enable the proteome-wide identification of minor protein changes in biofluids. This report describes the findings from the comparative proteomic analysis of whole saliva samples from wild type versus the established mdx-4cv mouse model of highly progressive muscular dystrophy, focusing on the kallikrein protein family. Kallikrein-1 (Klk1) and 13 Klk1-related peptidases were identified in saliva and serum from normal mice. Comparative proteomics revealed elevated saliva levels of the Klk1-related peptidases Klk1-b1, Klk1-b5 and Klk-b22, as well as an increased Klk-1 concentration, which agrees with higher Klk-1 levels in serum from mdx-4cv mice. This indicates altered cellular signaling, extracellular matrix remodeling and an altered immune response in the mdx-4cv mouse, and establishes liquid biopsy procedures as suitable bioanalytical tools for the systematic survey of complex pathobiochemical changes in animal models of muscular dystrophy. |
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Keywords: | Dystrophinopathy Kallikrein-1 Kallikrein-related peptidase Klk Saliva proteomics X-linked muscular dystrophy |
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