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.
Highlights
IntroductionAs one of the most abundant cellular entities in the human body, the diverse types of skeletal muscle fibre form the contractile units of over 650 individual muscles
In order to elucidate the unique cell biological and biochemical status of extraocular muscles (EOMs) among other types of skeletal muscles [2], this study has focused on the refined proteomic analysis of this subtype of contractile tissue using an Orbitrap Fusion Tribrid mass spectrometer
The proteomic analysis presented in this report identified 2521 protein species in wild type
Summary
As one of the most abundant cellular entities in the human body, the diverse types of skeletal muscle fibre form the contractile units of over 650 individual muscles. Voluntary striated muscles differ considerably in their histological, anatomical, metabolic, biochemical, and physiological specialization between predominantly slow-twitching versus fast-twitching phenotypes [1]. A distinctly different subtype of skeletal muscles, as compared to non-craniofacial muscles, is presented by extraocular muscles (EOMs) [2,3], which control the movements of the eyes [4]. The finely tuned and highly coordinated actions of six EOMs, i.e., M. obliquus superior, M. obliquus inferior, M. rectus medialis, M
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