Gargan, Stephen and Dowling, Paul and Zweyer, Margit and Reimann, Jens and Henry, Michael and Meleady, Paula and Swandulla, Dieter and Ohlendieck, Kay (2021) Mass Spectrometric Profiling of Extraocular Muscle and Proteomic Adaptations in the mdx-4cv Model of Duchenne Muscular Dystrophy. Life, 11 (7). p. 595. ISSN 2075-1729

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Abstract

Extraocular muscles (EOMs) represent a specialized type of contractile tissue with unique cellular, physiological, and biochemical properties. In Duchenne muscular dystrophy, EOMs stay functionally unaffected in the course of disease progression. Therefore, it was of interest to determine their proteomic profile in dystrophinopathy. The proteomic survey of wild type mice and the dystrophic mdx-4cv model revealed a broad spectrum of sarcomere-associated proteoforms, including components of the thick filament, thin filament, M-band and Z-disk, as well as a variety of muscle-specific markers. Interestingly, the mass spectrometric analysis revealed unusual expression levels of contractile proteins, especially isoforms of myosin heavy chain. As compared to diaphragm muscle, both proteomics and immunoblotting established isoform MyHC14 as a new potential marker in wild type EOMs, in addition to the previously identified isoforms MyHC13 and MyHC15. Comparative proteomics was employed to establish alterations in the protein expression profile between normal EOMs and dystrophin-lacking EOMs. The analysis of mdx-4cv EOMs identified elevated levels of glycolytic enzymes and molecular chaperones, as well as decreases in mitochondrial enzymes. These findings suggest a process of adaptation in dystrophin-deficient EOMs via a bioenergetic shift to more glycolytic metabolism, as well as an efficient cellular stress response in EOMs in dystrophinopathy.

Item Type:	Article
Additional Information:	Cite as: Gargan S, Dowling P, Zweyer M, Reimann J, Henry M, Meleady P, Swandulla D, Ohlendieck K. Mass Spectrometric Profiling of Extraocular Muscle and Proteomic Adaptations in the mdx-4cv Model of Duchenne Muscular Dystrophy. Life. 2021; 11(7):595. https://doi.org/10.3390/life11070595
Keywords:	Duchenne muscular dystrophy; dystrophinopathy; extraocular muscle; glyceraldehyde-3-phosphate dehydrogenase; myosin-14; myosin heavy chain
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	17270
Identification Number:	https://doi.org/10.3390/life11070595
Depositing User:	Paul Dowling
Date Deposited:	01 Jun 2023 14:18
Journal or Publication Title:	Life
Publisher:	MDPI
Refereed:	Yes
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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