Next Article in Journal
Characterization and Pharmacokinetic Study of Aprepitant Solid Dispersions with Soluplus®
Next Article in Special Issue
Special Issue—Towards Understanding the Mechanisms and Curing of Muscular Dystrophy Diseases
Previous Article in Journal
Triel Bonds, π-Hole-π-Electrons Interactions in Complexes of Boron and Aluminium Trihalides and Trihydrides with Acetylene and Ethylene
Previous Article in Special Issue
Non-Invasive Biomarkers for Duchenne Muscular Dystrophy and Carrier Detection
Article Menu

Export Article

Open AccessArticle
Molecules 2015, 20(6), 11317-11344; doi:10.3390/molecules200611317

Comparative Label-Free Mass Spectrometric Analysis of Mildly versus Severely Affected mdx Mouse Skeletal Muscles Identifies Annexin, Lamin, and Vimentin as Universal Dystrophic Markers

1
Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland
2
National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland
3
Institute of Pathophysiology, University Medicine Greifswald, D-17495 Karlsburg, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Leonidas A. Phylactou
Received: 7 May 2015 / Revised: 10 June 2015 / Accepted: 12 June 2015 / Published: 19 June 2015
View Full-Text   |   Download PDF [3051 KB, uploaded 19 June 2015]   |  

Abstract

The primary deficiency in the membrane cytoskeletal protein dystrophin results in complex changes in dystrophic muscles. In order to compare the degree of secondary alterations in differently affected subtypes of skeletal muscles, we have conducted a global analysis of proteome-wide changes in various dystrophin-deficient muscles. In contrast to the highly degenerative mdx diaphragm muscle, which showed considerable alterations in 35 distinct proteins, the spectrum of mildly to moderately dystrophic skeletal muscles, including interosseus, flexor digitorum brevis, soleus, and extensor digitorum longus muscle, exhibited a smaller number of changed proteins. Compensatory mechanisms and/or cellular variances may be responsible for differing secondary changes in individual mdx muscles. Label-free mass spectrometry established altered expression levels for diaphragm proteins associated with contraction, energy metabolism, the cytoskeleton, the extracellular matrix and the cellular stress response. Comparative immunoblotting verified the differences in the degree of secondary changes in dystrophin-deficient muscles and showed that the up-regulation of molecular chaperones, the compensatory increase in proteins of the intermediate filaments, the fibrosis-related increase in collagen levels and the pathophysiological decrease in calcium binding proteins is more pronounced in mdx diaphragm as compared to the less severely affected mdx leg muscles. Annexin, lamin, and vimentin were identified as universal dystrophic markers. View Full-Text
Keywords: diaphragm; dystrophin; dystrophinopathy; Duchenne muscular dystrophy; extensor digitorum longus; flexor digitorum brevis; interosseus; muscle pathology; soleus; skeletal muscle proteome diaphragm; dystrophin; dystrophinopathy; Duchenne muscular dystrophy; extensor digitorum longus; flexor digitorum brevis; interosseus; muscle pathology; soleus; skeletal muscle proteome
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Holland, A.; Henry, M.; Meleady, P.; Winkler, C.K.; Krautwald, M.; Brinkmeier, H.; Ohlendieck, K. Comparative Label-Free Mass Spectrometric Analysis of Mildly versus Severely Affected mdx Mouse Skeletal Muscles Identifies Annexin, Lamin, and Vimentin as Universal Dystrophic Markers. Molecules 2015, 20, 11317-11344.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top