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New pathobiochemical insights into dystrophinopathy from the proteomics of senescent mdx mouse muscle.

Holland A, Dowling P, Ohlendieck K - Front Aging Neurosci (2014)

Bottom Line: The idea that aging exacerbates the dystrophic mdx phenotype, as previously indicated by a large number of biochemical and cell biological studies, was clearly confirmed by comparative muscle proteomics.Here we outline recent findings of age-dependent changes in the dystrophin-deficient muscle proteome and contrast these results with the previously established proteomic profile of sarcopenic muscle.Besides comparable perturbations of various biochemical functions, especially striking are similarities in the cellular stress response associated with a drastic up-regulation of small αB-crystallin-like heat shock proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, National University of Ireland Maynooth, Ireland.

ABSTRACT
Primary abnormalities in the dystrophin gene cause X-linked muscular dystrophy, a highly progressive muscle wasting disorder of childhood. A spontaneous animal model of Duchenne muscular dystrophy is the mdx mouse, which presents a highly interesting phenotype that exhibits considerable variations in the degree of fiber degeneration in different subtypes of muscles. The idea that aging exacerbates the dystrophic mdx phenotype, as previously indicated by a large number of biochemical and cell biological studies, was clearly confirmed by comparative muscle proteomics. Here we outline recent findings of age-dependent changes in the dystrophin-deficient muscle proteome and contrast these results with the previously established proteomic profile of sarcopenic muscle. Besides comparable perturbations of various biochemical functions, especially striking are similarities in the cellular stress response associated with a drastic up-regulation of small αB-crystallin-like heat shock proteins. Hence, the comparison of large-scale proteomic data sets of natural muscle aging with dystrophic sarcopenia promises to shed light on the differential effect of sarcopenia of old age vs. senescent abnormalities on a mutant dystrophic background.

No MeSH data available.


Related in: MedlinePlus

Overview of proteome-wide alterations in the muscle tissue during sarcopenia of old age vs. dystrophic sarcopenia.
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Figure 2: Overview of proteome-wide alterations in the muscle tissue during sarcopenia of old age vs. dystrophic sarcopenia.

Mentions: Since both dystrophic sarcopenia and natural muscle senescence are characterized by a progressive loss of contractile tissue mass, elevated levels of fibrosis, a decline in the number of satellite cells, a drastically increased stress response and abnormal cellular signaling, it is interesting to determine whether these pathological similarities are reflected by analogous proteome-wide changes. The comparison of proteomic data sets from the analysis of muscular dystrophy vs. sarcopenia suggests that the pathobiochemical signature of certain damage or adaptation pathways is comparable, but that the molecular pathogenesis of both processes differs with respect to the degree of unilateral shifts in fiber types or energy metabolism. Both age-related processes show a disturbed abundance of proteins involved in excitation-contraction coupling, calcium homeostasis, cellular signaling cascades, the muscle contraction-relaxation cycle and the cellular stress response. For example, the expression of small heat shock proteins, such as αB-crystallin and some of its HSPB isoforms, is drastically increased in both natural muscle aging and dystrophic sarcopenia (Doran et al., 2006, 2007). Both types of skeletal muscle wasting are associated with altered levels of key enzymes involved in glycolysis, the citric acid cycle and oxidative phosphorylation (Piec et al., 2005; Doran et al., 2006, 2008). However, muscular dystrophy exhibits a generally perturbed abundance of metabolic enzymes, while the proteomic profiling of sarcopenia of old age clearly indicates a glycolytic-to-oxidative metabolic shift and concomitant fast-to-slow transformation on the level of the actomyosin apparatus (Ohlendieck, 2011). Figure 2 outlines the findings of the proteomic profiling of sarcopenia of old age vs. dystrophic sarcopenia.


New pathobiochemical insights into dystrophinopathy from the proteomics of senescent mdx mouse muscle.

Holland A, Dowling P, Ohlendieck K - Front Aging Neurosci (2014)

Overview of proteome-wide alterations in the muscle tissue during sarcopenia of old age vs. dystrophic sarcopenia.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4042888&req=5

Figure 2: Overview of proteome-wide alterations in the muscle tissue during sarcopenia of old age vs. dystrophic sarcopenia.
Mentions: Since both dystrophic sarcopenia and natural muscle senescence are characterized by a progressive loss of contractile tissue mass, elevated levels of fibrosis, a decline in the number of satellite cells, a drastically increased stress response and abnormal cellular signaling, it is interesting to determine whether these pathological similarities are reflected by analogous proteome-wide changes. The comparison of proteomic data sets from the analysis of muscular dystrophy vs. sarcopenia suggests that the pathobiochemical signature of certain damage or adaptation pathways is comparable, but that the molecular pathogenesis of both processes differs with respect to the degree of unilateral shifts in fiber types or energy metabolism. Both age-related processes show a disturbed abundance of proteins involved in excitation-contraction coupling, calcium homeostasis, cellular signaling cascades, the muscle contraction-relaxation cycle and the cellular stress response. For example, the expression of small heat shock proteins, such as αB-crystallin and some of its HSPB isoforms, is drastically increased in both natural muscle aging and dystrophic sarcopenia (Doran et al., 2006, 2007). Both types of skeletal muscle wasting are associated with altered levels of key enzymes involved in glycolysis, the citric acid cycle and oxidative phosphorylation (Piec et al., 2005; Doran et al., 2006, 2008). However, muscular dystrophy exhibits a generally perturbed abundance of metabolic enzymes, while the proteomic profiling of sarcopenia of old age clearly indicates a glycolytic-to-oxidative metabolic shift and concomitant fast-to-slow transformation on the level of the actomyosin apparatus (Ohlendieck, 2011). Figure 2 outlines the findings of the proteomic profiling of sarcopenia of old age vs. dystrophic sarcopenia.

Bottom Line: The idea that aging exacerbates the dystrophic mdx phenotype, as previously indicated by a large number of biochemical and cell biological studies, was clearly confirmed by comparative muscle proteomics.Here we outline recent findings of age-dependent changes in the dystrophin-deficient muscle proteome and contrast these results with the previously established proteomic profile of sarcopenic muscle.Besides comparable perturbations of various biochemical functions, especially striking are similarities in the cellular stress response associated with a drastic up-regulation of small αB-crystallin-like heat shock proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, National University of Ireland Maynooth, Ireland.

ABSTRACT
Primary abnormalities in the dystrophin gene cause X-linked muscular dystrophy, a highly progressive muscle wasting disorder of childhood. A spontaneous animal model of Duchenne muscular dystrophy is the mdx mouse, which presents a highly interesting phenotype that exhibits considerable variations in the degree of fiber degeneration in different subtypes of muscles. The idea that aging exacerbates the dystrophic mdx phenotype, as previously indicated by a large number of biochemical and cell biological studies, was clearly confirmed by comparative muscle proteomics. Here we outline recent findings of age-dependent changes in the dystrophin-deficient muscle proteome and contrast these results with the previously established proteomic profile of sarcopenic muscle. Besides comparable perturbations of various biochemical functions, especially striking are similarities in the cellular stress response associated with a drastic up-regulation of small αB-crystallin-like heat shock proteins. Hence, the comparison of large-scale proteomic data sets of natural muscle aging with dystrophic sarcopenia promises to shed light on the differential effect of sarcopenia of old age vs. senescent abnormalities on a mutant dystrophic background.

No MeSH data available.


Related in: MedlinePlus