The NO way to increase muscular utrophin expression?

Chaubourt, Emmanuel; Voisin, Vincent; Fossier, Phillipe; Baux, Gérard; Israël, Maurice; Porte, Sabine de la

doi:10.1016/s0764-4469(00)01219-1

Cited by 17 publications

(12 citation statements)

References 24 publications

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“…In accordance with previous studies, 28,29 the morphological aspect of L-arginine-treated mdx diaphragm is significantly improved. The analyzed muscles share also a significant decrease in the number of infiltrated cells (macrophages and lymphocytes).…”

Section: L-arginine Improves Dystrophic Pattern and Promotes Regenerasupporting

confidence: 92%

l-Arginine Decreases Inflammation and Modulates the Nuclear Factor-κB/Matrix Metalloproteinase Cascade in Mdx Muscle Fibers

Hnia

Gayraud

Hugon

et al. 2008

The American Journal of Pathology

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156

107

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Duchenne muscular dystrophy (DMD) is a lethal, Xlinked disorder associated with dystrophin deficiency that results in chronic inflammation, sarcolemma damage, and severe skeletal muscle degeneration. Recently, the use of L-arginine , the substrate of nitric oxide synthase (nNOS), has been proposed as a pharmacological treatment to attenuate the dystrophic pattern of DMD. However, little is known about signaling events that occur in dystrophic muscle with L-arginine treatment. Considering the implication of inflammation in dystrophic processes, we asked whether L-arginine inhibits inflammatory signaling cascades. We demonstrate that L-arginine decreases inflammation and enhances muscle regeneration in the mdx mouse model. Classic stimulatory signals, such as proinflammatory cytokines interleukin-1␤, interleukin-6, and tumor necrosis factor-␣, are significantly decreased in mdx mouse muscle, resulting in lower nuclear factor (NF)-B levels and activity. NF-B serves as a pivotal transcription factor with multiple levels of regulation; previous studies have shown perturbation of NF-B signaling in both mdx and DMD muscle. Moreover, L-arginine decreases the activity of metalloproteinase (MMP)-2 and MMP-9, which are transcriptionally activated by NF-B. We show that the inhibitory effect of L-arginine on the NF-B/MMP cascade reduces ␤-dystroglycan cleavage and translocates utrophin and nNOS throughout the sarcolemma. Collectively, our results clarify the molecular events by which L-arginine promotes muscle membrane integrity in dystrophic muscle and suggest that NF-B-related signaling cascades could be potential therapeutic targets for DMD management. (Am J Pathol

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Section: L-arginine Improves Dystrophic Pattern and Promotes Regenerasupporting

confidence: 92%

l-Arginine Decreases Inflammation and Modulates the Nuclear Factor-κB/Matrix Metalloproteinase Cascade in Mdx Muscle Fibers

Hnia

Gayraud

Hugon

et al. 2008

The American Journal of Pathology

Self Cite

156

107

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“…NOS transgene expression significantly reduced the concentration of macrophages and ameliorated muscle damage, which indicated the possible benefits of an NO-based anti-inflammatory therapy for DMD (48). Another treatment strategy has used systemic administration of L-arginine, the substrate of nNOS, which was reported to reduce damage of mdx muscle by increasing expression of utrophin (114,115). However, this finding differs from another report that expression of a nNOS transgene in mdx muscle reduced utrophin concentration in muscle fibers (116).…”

Section: Tnf-␣ Tumor Necrosis Factor-␣ (Tnf-␣) Is a Cytokine That Ismentioning

confidence: 99%

Evolving Therapeutic Strategies for Duchenne Muscular Dystrophy: Targeting Downstream Events

Tidball¹,

Wehling‐Henricks

2004

Pediatr Res

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“…This is unlikely, since NOS knockout mice do not display overt dystrophy [79]. However, since increased NO production results in enhanced utrophin expression [80] and treatment of mdx mice with a nNOS substrate, l -arginine, also increases utrophin levels and its membrane localization [81], clinical manipulation of nNOS levels in the muscle is considered a potential starting point for therapeutic intervention [82]. …”

Section: Roles Of the Dgc At The Neuromuscular Junctionmentioning

confidence: 99%

The Roles of the Dystrophin-Associated Glycoprotein Complex at the Synapse

et al. 2009

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Duchenne muscular dystrophy is caused by mutations in the dystrophin gene and is characterized by progressive muscle wasting. A number of Duchenne patients also present with mental retardation. The dystrophin protein is part of the highly conserved dystrophin-associated glycoprotein complex (DGC) which accumulates at the neuromuscular junction (NMJ) and at a variety of synapses in the peripheral and central nervous systems. Many years of research into the roles of the DGC in muscle have revealed its structural function in stabilizing the sarcolemma. In addition, the DGC also acts as a scaffold for various signaling pathways. Here, we discuss recent advances in understanding DGC roles in the nervous system, gained from studies in both vertebrate and invertebrate model systems. From these studies, it has become clear that the DGC is important for the maturation of neurotransmitter receptor complexes and for the regulation of neurotransmitter release at the NMJ and central synapses. Furthermore, roles for the DGC have been established in consolidation of long-term spatial and recognition memory. The challenges ahead include the integration of the behavioral and mechanistic studies and the use of this information to identify therapeutic targets.

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The NO way to increase muscular utrophin expression?

Cited by 17 publications

References 24 publications

l-Arginine Decreases Inflammation and Modulates the Nuclear Factor-κB/Matrix Metalloproteinase Cascade in Mdx Muscle Fibers

l-Arginine Decreases Inflammation and Modulates the Nuclear Factor-κB/Matrix Metalloproteinase Cascade in Mdx Muscle Fibers

Evolving Therapeutic Strategies for Duchenne Muscular Dystrophy: Targeting Downstream Events

The Roles of the Dystrophin-Associated Glycoprotein Complex at the Synapse

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