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BMC Neurology

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Open Access 01-12-2013 | Research article

Cell stress molecules in the skeletal muscle of GNE myopathy

Authors: Charlotte Fischer, Konstanze Kleinschnitz, Arne Wrede, Ingrid Muth, Niels Kruse, Ichizo Nishino, Jens Schmidt

Published in: BMC Neurology | Issue 1/2013

Abstract

Background

Mutations of the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine-kinase (GNE)-gene are causally related to GNE myopathy. Yet, underlying pathomechanisms of muscle fibre damage have remained elusive. In sporadic inclusion body myositis (sIBM), the pro-inflammatory cell-stress mediators αB-crystallin and inducible nitric oxide synthase (iNOS) are crucial markers of the disease pathology.

Methods

10 muscle biopsies from GNE myopathy patients were analyzed for mRNA-expression of markers of cell-stress, inflammation and β-amyloid and compared to non-myopathic controls. Using double-labeling immunohistochemistry, serial sections of skeletal muscle biopsies were stained for amyloid precursor protein (APP), major histocompatibility complex (MHC)-I, αB-crystallin, neural cell adhesion molecule (NCAM), interleukin (IL)-1β, β-amyloid, iNOS, and phosphorylated neurofilament (P-neurofilament) as well as hematoxylin/eosin histochemistry. Corresponding areas of all biopsies with a total of 2,817 muscle fibres were quantitatively assessed for all markers.

Results

mRNA-expression of APP, NCAM, iNOS, TNF-α and TGF-β was higher in GNE myopathy compared to controls, yet this was not statistically significant. The mRNA-expression of APP and αB-crystallin significantly correlated with the expression of several pro-inflammatory and cell-stress-associated markers as NCAM, IL-1β, TGF-β, CCL-3, and CCL4. By immunohistochemistry, αB-crystallin and iNOS were co-upregulated and the number of fibres positive for αB-crystallin, NCAM, MHC-I and iNOS significantly correlated with each other. A large fraction of fibres positive for αB-crystallin were double positive for iNOS and vice-versa. Moreover, several fibres with structural abnormalities were positive for αB-crystallin and iNOS. Notably, particularly normal appearing fibres displayed an overexpression of these molecules.

Conclusions

The cell-stress molecules αB-crystallin and iNOS are overexpressed in GNE myopathy muscle and may identify early disease mechanisms. The data help to better understand the pathology of GNE myopathy.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2377/13/24/prepub

Title: Cell stress molecules in the skeletal muscle of GNE myopathy
Authors: Charlotte Fischer
Konstanze Kleinschnitz
Arne Wrede
Ingrid Muth
Niels Kruse
Ichizo Nishino
Jens Schmidt
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: BMC Neurology / Issue 1/2013
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/1471-2377-13-24

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Cell stress molecules in the skeletal muscle of GNE myopathy

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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