Oral glutamine and amino acid supplementation inhibit whole-body protein degradation in children with Duchenne muscular dystrophy

Mok, Élise; Violante, Catherine Eléouet-Da; Daubrosse, Christel; Gottrand, Frédéric; Rigal, Odile; Fontan, Jean-Eudes; Cuisset, Jean‐Marie; Guilhot, Joëlle; Hankard, R.

doi:10.1093/ajcn/83.4.823

Cited by 51 publications

(43 citation statements)

References 26 publications

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“…decrease in GSSG/GSH was associated with a reduction in MAPK (ERK1/2) phosphorylation. The antioxidant mechanism may explain our previous findings in DMD children demonstrating decreased whole body protein degradation after 5 h and 10 d Gln supplementation (6,7). This study is novel in describing a molecular basis for Gln's antiproteolytic effect in dystrophic muscle.…”

Section: Discussionmentioning

confidence: 51%

“…Oxidative stress could contribute to muscle-wasting by regulating specific cell signaling pathways leading to increased proteolysis (5). We have shown that glutamine (Gln) supplementation decreases whole body protein breakdown in DMD children (6,7). However, the molecular basis for glutamine's antiproteolytic effect remains to be elucidated.…”

Section: Uchenne Muscular Dystrophy (Dmd) Is a Progressivementioning

confidence: 99%

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L-Glutamine Administration Reduces Oxidized Glutathione and MAP Kinase Signaling in Dystrophic Muscle of mdx Mice

et al. 2008

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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 ϩ Glu) were higher in mdx versus C57BL/10, at the basal level. Exogenous Gln decreased muscle free Glu and Gln ϩ 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 ϩ Glu. This antioxidant protective mechanism provides a molecular basis for Gln's antiproteolytic effect in Duchenne muscular dystrophy children.

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Section: Discussionmentioning

confidence: 51%

Section: Uchenne Muscular Dystrophy (Dmd) Is a Progressivementioning

confidence: 99%

L-Glutamine Administration Reduces Oxidized Glutathione and MAP Kinase Signaling in Dystrophic Muscle of mdx Mice

et al. 2008

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“…Glutamine has shown little benefit towards improving strength, muscle mass, or function in limited human studies despite evidence of it slowing down whole-body protein degradation [17][18][19].…”

Section: Nutritional Statusmentioning

confidence: 99%

Current Concepts in the Management of Duchenne Muscular Dystrophy

Rinaldi

Mayer

Dichiaro

2013

Curr Phys Med Rehabil Rep

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The management of Duchenne muscular dystrophy (DMD) has seen dramatic change over the past two decades. Improvements in clinical monitoring of disease progression, management of cardiac and pulmonary complications, and nutritional intervention have all led to decreases in co-morbidity commonly associated with DMD, and, as a consequence, quality of life and life expectancy of individuals with DMD have both continued to improve. This review will update the reader on current trends and recent advances in the diagnosis, management, and treatment of DMD, with a focus on reviewing pertinent current literature.

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“…As it is a precursor to glutathione, supplementation with glutamine has also been shown to protect against oxidative stress in the mdx [436]. Several clinical studies and multicentre randomized placebocontrolled trials have been performed with glutamine [437][438][439]. Nutritional supplements have often been found to be more effective when administered in combination in the mdx [440][441][442].…”

Section: Free Radicals/rosmentioning

confidence: 99%

“…A combination of creatine and glutamine has also been therapeutically assessed in a Cooperative International Neuromuscular Research Group (CINRG) randomized controlled trial in DMD patients [445]. Glutamine has been reported to delay protein breakdown [437,438], but functional benefits were not observed in either trial [439,445]. Furthermore, a small clinical study of creatine alone only yielded modest improvements [446].…”

Section: Free Radicals/rosmentioning

confidence: 99%

Pharmacologically Targeting the Primary Defect and Downstream Pathology in Duchenne Muscular Dystrophy

Fairclough

Perkins²,

Davies³

2012

CGT

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DMD is a devastatingly progressive muscle wasting disorder of childhood that significantly shortens life expectancy. Despite efforts to develop an effective therapy that dates back over a century, clinical interventions are still restricted to management of symptoms rather than a cure. The rationale to develop effective therapies changed in 1986 with the discovery of the dystrophin gene. Since then extensive research into both the molecular basis and pathophysiology of DMD has paved the way not only for development of strategies which aim to correct the primary defect, but also towards the identification of countless therapeutic targets with the potential to alleviate the downstream pathology. In addition to gene and cell-based therapies, which aim to deliver the missing gene and/or protein, an exciting spectrum of pharmacological approaches aimed at modulating therapeutic targets within DMD muscle cells through the use of small drugs are also being developed. This review presents promising pharmacological approaches aimed at targeting the primary defect, including suppression of nonsense mutations and functional compensation by upregulation of the dystrophin homologue, utrophin. Downstream of the primary membrane fragility, inflammation and fibrosis are reduced by blocking NF-κB, TGF-α and TGF-β, and free radical damage has been targeted using antioxidants and dietary/nutritional supplements. There are new hopes that ACE and PDE5 inhibitors can protect against skeletal as well as cardiac pathology, and modulating Ca2+ influx, NO, BMP, protein degradation and the mitochondrial permeability pore hold further promise in tackling the complex pathogenesis of this multifaceted disorder.

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Oral glutamine and amino acid supplementation inhibit whole-body protein degradation in children with Duchenne muscular dystrophy

Abstract: Oral glutamine or amino acid supplementation over 10 d equally inhibits whole-body protein degradation in DMD.

Cited by 51 publications

References 26 publications

L-Glutamine Administration Reduces Oxidized Glutathione and MAP Kinase Signaling in Dystrophic Muscle of mdx Mice

L-Glutamine Administration Reduces Oxidized Glutathione and MAP Kinase Signaling in Dystrophic Muscle of mdx Mice

Current Concepts in the Management of Duchenne Muscular Dystrophy

Pharmacologically Targeting the Primary Defect and Downstream Pathology in Duchenne Muscular Dystrophy

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