Murphy, Sandra and Zweyer, Margit and Mundegar, Rustam R. and Swandulla, Dieter and Ohlendieck, Kay (2018) Comparative gel-based proteomic analysis of chemically crosslinked complexes in dystrophic skeletal muscle. Electrophoresis, 39. pp. 1735-1744. ISSN 0173-0835

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Abstract

Duchenne muscular dystrophy is a highly progressive muscle wasting disease with a complex pathophysiology that is based on primary abnormalities in the dystrophin gene. In order to study potential changes in the oligomerization of high-molecular-mass protein complexes in dystrophic skeletal muscle, chemical crosslinking was combined with mass spectrometric analysis. The biochemical stabilization of protein interactions was carried out with the homo-bifunctional and amine-reactive agent bis[sulfosuccinimidyl]suberate, followed by protein shift analysis in one-dimensional gels. The proteomic approach identified 11 and 15 protein species in wild type versus dystrophic microsomal fractions, respectively, as well as eight common proteins, with an electrophoretic mobility shift to very high molecular mass following chemical crosslinking. In dystrophin-deficient preparations, several protein species with an increased tendency of oligomerisation were identified as components of the sarcolemma and its associated intra- and extracellular structures, as well as mitochondria. This included the sarcolemmal proteins myoferlin and caveolin, the cytoskeletal components vimentin and tubulin, extracellular collagen alpha-1(XII) and the mitochondrial trifunctional enzyme and oxoglutarate dehydrogenase. These changes are probably related to structural and metabolic adaptations, especially cellular repair processes, which agrees with the increased oligomerisation of myosin-3, myosin-9 and actin, and their role in cellular regeneration and structural adjustments in dystrophinopathy.

Item Type:	Article
Additional Information:	© 2018 The Authors. Electrophoresis published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, www.electrophoresis-journal.com. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Cite as: Murphy, S., Zweyer, M., Mundegar, R.R., Swandulla, D. and Ohlendieck, K. (2018), Comparative gel‐based proteomic analysis of chemically crosslinked complexes in dystrophic skeletal muscle. ELECTROPHORESIS, 39: 1735-1744. doi:10.1002/elps.201800028
Keywords:	Caveolin; Crosslinking mass spectrometry; Dystrophinopathy; Myoferlin; Trifunctional enzyme;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	13141
Identification Number:	https://doi.org/10.1002/elps.201800028
Depositing User:	Prof. Kay Ohlendieck
Date Deposited:	22 Jul 2020 15:35
Journal or Publication Title:	Electrophoresis
Publisher:	Wiley-VCH Verlag
Refereed:	Yes
Funders:	Hume scholarship (Maynooth University), Muscular Dystrophy Ireland, Health Research Board (HRB), Science Foundation Ireland (SFI)
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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