Proteomic Profiling of the Dystrophin-Deficient MDX Heart Reveals Drastically Altered Levels of Key Metabolic and Contractile Proteins
Open Access
- 1 January 2010
- journal article
- Published by Hindawi Limited in Journal of Biomedicine and Biotechnology
- Vol. 2010, 1-20
- https://doi.org/10.1155/2010/648501
Abstract
Although Duchenne muscular dystrophy is primarily classified as a neuromuscular disease, cardiac complications play an important role in the course of this X-linked inherited disorder. The pathobiochemical steps causing a progressive decline in the dystrophic heart are not well understood. We therefore carried out a fluorescence difference in-gel electrophoretic analysis of 9-month-old dystrophin-deficient versus age-matched normal heart, using the established MDX mouse model of muscular dystrophy-related cardiomyopathy. Out of 2,509 detectable protein spots, 79 2D-spots showed a drastic differential expression pattern, with the concentration of 3 proteins being increased, including nucleoside diphosphate kinase and lamin-A/C, and of 26 protein species being decreased, including ATP synthase, fatty acid binding-protein, isocitrate dehydrogenase, NADH dehydrogenase, porin, peroxiredoxin, adenylate kinase, tropomyosin, actin, and myosin light chains. Hence, the lack of cardiac dystrophin appears to trigger a generally perturbed protein expression pattern in the MDX heart, affecting especially energy metabolism and contractile proteins.Keywords
Funding Information
- Muscular Dystrophy Ireland (MDI-125437, HRB-EQ/2003/3, HEA-RERGS-07-NUIM, HRB-EQ/2004/2)
This publication has 78 references indexed in Scilit:
- Pathways of abnormal stress-induced Ca2+ influx into dystrophic mdx cardiomyocytesCell Calcium, 2009
- Proteomic profiling of antisense‐induced exon skipping reveals reversal of pathobiochemical abnormalities in dystrophic mdx diaphragmProteomics, 2009
- Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomerProceedings of the National Academy of Sciences of the United States of America, 2008
- The Iron−Sulfur Cluster of Electron Transfer Flavoprotein−Ubiquinone Oxidoreductase Is the Electron Acceptor for Electron Transfer FlavoproteinBiochemistry, 2008
- Towards developing standard operating procedures for pre-clinical testing in the mdx mouse model of Duchenne muscular dystrophyNeurobiology of Disease, 2008
- Long-term blinded placebo-controlled study of SNT-MC17/idebenone in the dystrophin deficient mdx mouse: cardiac protection and improved exercise performanceEuropean Heart Journal, 2008
- Characteristics and outcomes of cardiomyopathy in children with Duchenne or Becker muscular dystrophy: A comparative study from the Pediatric Cardiomyopathy RegistryAmerican Heart Journal, 2008
- Dystrophin-deficient cardiomyopathy in mouse: Expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heartNeuromuscular Disorders, 2008
- In-gel digestion for mass spectrometric characterization of proteins and proteomesNature Protocols, 2006
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976