Abstract
To determine whether glutamine (Gln) reduces the ratio of oxidized to total glutathione (GSSG/GSH) and extracellular signal-regulated kinase (ERK1/2) activation in dystrophic muscle. Four-week old mdx mice, an animal model for Duchenne muscular dystrophy and control (C57BL/10) received daily intraperitoneal injections of l-Gln (500 mg/kg/d) or 0.9% NaCl for 3 d. GSH and GSSG concentrations in gastrocnemius were measured using a standard enzymatic recycling procedure. Free amino acid concentrations in gastrocnemius were determined by ion exchange chromatography. Phosphorylated protein levels of ERK1/2 in quadriceps were examined using Western Blot. l-Gln decreased GSSG and GSSG/GSH (an indicator of oxidative stress). This was associated with decreased ERK1/2 phosphorylation. Muscle free Gln, glutamate (Glu), and the sum (Gln + Glu) were higher in mdx versus C57BL/10, at the basal level. Exogenous Gln decreased muscle free Glu and Gln + Glu in mdx only, whereas Gln was not affected. In conclusion, exogenous Gln reduces GSSG/GSH and ERK1/2 activation in dystrophic skeletal muscle of young mdx mice, which is associated with decreased muscle free Glu and Gln + Glu. This antioxidant protective mechanism provides a molecular basis for Gln's antiproteolytic effect in Duchenne muscular dystrophy children.
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Abbreviations
- C57:
-
C57BL/10
- DMD:
-
Duchenne muscular dystrophy
- ERK1/2:
-
extracellular signal-regulated kinase1/2
- Gln:
-
glutamine
- Glu:
-
glutamate
- GSH:
-
total glutathione
- GSSG:
-
oxidized glutathione
- IκBα:
-
I-kappaB-alpha
- MAPK:
-
mitogen activated protein kinase
- NaCl:
-
sodium chloride
- NF-κB:
-
Nuclear factor-kappaB
- TNF-α:
-
Tumour necrosis factor-alpha
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Acknowledgements
We are grateful to Dr. C. Cognard and Dr. G. Raymond for providing the laboratory and animal facility where the majority of the work was performed. We thank Dr. N. Bourmeyster for his advice regarding biochemical analysis. We also thank the members of the Laboratoire Cytokines et Inflammation EA 3806, especially Dr. J-C. Lecron for ELISA advice.
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Supported by a grant from Institut National de la Santé et de la Recherche Médicale #33104700 (RAF 01005) (to R.H.) and the Association Française Contre les Myopathies (to R.H.), and by Les Fonds de la Recherche en Santé Québec (PhD Fellowship to E.M.) and Le Prix de Nutrition de la Fédération Association Nationale pour les Traitements A Domicile, les Innovations et la Recherche awarded by La Société Francophone de Nutrition Entérale et Parentérale (to E.M.).
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Mok, E., Constantin, B., Favreau, F. et al. L-Glutamine Administration Reduces Oxidized Glutathione and MAP Kinase Signaling in Dystrophic Muscle of mdx Mice. Pediatr Res 63, 268–273 (2008). https://doi.org/10.1203/PDR.0b013e318163a259
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DOI: https://doi.org/10.1203/PDR.0b013e318163a259
