1. L-Glutamine Administration Reduces Oxidized Glutathione and MAP Kinase Signaling in Dystrophic Muscle of mdx Mice
- Author
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Bruno Constantin, Régis Hankard, Elise Mok, Christophe Magaud, Frédéric Favreau, Adriana Delwail, Nathalie Neveux, Laboratoire des Adaptations Physiologiques aux Activités Physiques (LAPHAP), Université de Poitiers, Institut de physiologie et biologie cellulaires (IPBC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Laboratoire Ischémie-reperfusion en transplantation rénale, Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de biochimie et de génétique moléculaire [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Cytokines et Inflammation, Centre d' investigation clinique-plurithématique du CHU de Poitiers, INSERM, CNRS, AFM, Fonds de la Recherche en Santé Québec, Hôpital Hôtel-Dieu [Paris], Pediatrie Multidisciplinaire - Nutrition de l'Enfant, This work was supported by a grant from Institut National de la Santé et de la Recherche Médicale #33104700 (RAF 01005) (RH) and the Association Française Contre les Myopathies (RH). EM is supported by Les Fonds de la Recherche en Santé Québec PhD Fellowship 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., and Constantin, Bruno
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Time Factors ,Antioxidant ,[SDV]Life Sciences [q-bio] ,Glutamine ,medicine.medical_treatment ,Duchenne muscular dystrophy ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,medicine.disease_cause ,Antioxidants ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Nuclear factor-kappaB (NF-κB) ,Phosphorylation ,Muscular dystrophy ,[SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,Mitogen-Activated Protein Kinase 1 ,0303 health sciences ,Extracellular signal-regulated kinase (ERK1/2 p44/42) ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Mitogen-Activated Protein Kinase 3 ,Glutathione Disulfide ,Age Factors ,NF-kappa B ,Glutamate receptor ,Amino acid, Duchenne muscular dystrophy, Extracellular signal-regulated kinase (ERK1/2 p44/42), Nuclear factor-kappaB (NF-κB), Nutrition, Oxidative stress ,Glutathione ,Amino acid ,3. Good health ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,Injections, Intraperitoneal ,medicine.medical_specialty ,MAP Kinase Signaling System ,Down-Regulation ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,03 medical and health sciences ,[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics ,Internal medicine ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,[SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,medicine ,Animals ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,Muscle, Skeletal ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,Nutrition ,030304 developmental biology ,[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,Tumor Necrosis Factor-alpha ,Body Weight ,Skeletal muscle ,medicine.disease ,Mice, Inbred C57BL ,Muscular Dystrophy, Duchenne ,Disease Models, Animal ,Oxidative Stress ,Endocrinology ,chemistry ,Dietary Supplements ,Pediatrics, Perinatology and Child Health ,Mice, Inbred mdx ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,030217 neurology & neurosurgery ,Oxidative stress - Abstract
International audience; 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.
- Published
- 2008
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