ArticleHuman molecular genetics2016
Sarcolemmal targeting of nNOSμ improves contractile function of mdx muscle.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy.Neurology · 2017Trial
- Lipin1 restores nNOS sarcolemmal localization and improves fatigue resistance in Duchenne muscular dystrophy.American journal of physiology. Cell physiology · 2026Article
- Unveiling muscle fatigue: identifying key gene biomarkers and therapeutic targets.Molecular and cellular biochemistry · 2026Article
- Histone deacetylases in Duchenne muscular dystrophy: a role in the mechanism of disease and a target for inhibition.Clinical epigenetics · 2025Review
- Why is early-onset atrial fibrillation uncommon in patients with Duchenne muscular dystrophy? Insights from the mdx mouse.Cardiovascular research · 2024Article
- Modulating fast skeletal muscle contraction protects skeletal muscle in animal models of Duchenne muscular dystrophy.The Journal of clinical investigation · 2023Article
- Pathophysiology and Management of Fatigue in Neuromuscular Diseases.International journal of molecular sciences · 2023Review
- Episodic Binge-like Ethanol Reduces Skeletal Muscle Strength Associated with Atrophy, Fibrosis, and Inflammation in Young Rats.International journal of molecular sciences · 2023Article
- Promising therapeutic approaches of utrophin replacing dystrophin in the treatment of Duchenne muscular dystrophy.Fundamental research · 2022Review
- The Donnan-dominated resting state of skeletal muscle fibers contributes to resilience and longevity in dystrophic fibers.The Journal of general physiology · 2022Article
- Role of Matricellular CCN Proteins in Skeletal Muscle: Focus on CCN2/CTGF and Its Regulation by Vasoactive Peptides.International journal of molecular sciences · 2021Review
- Dose-Escalation Study of Systemically Delivered rAAVrh74.MHCK7.micro-dystrophin in theHuman gene therapy · 2021Article
- Review
- Dystrophin R16/17 protein therapy restores sarcolemmal nNOS in trans and improves muscle perfusion and function.Molecular medicine (Cambridge, Mass.) · 2019Article
- Mice lacking α-, β1- and β2-syntrophins exhibit diminished function and reduced dystrophin expression in both cardiac and skeletal muscle.Human molecular genetics · 2019Article
- Loss of peroxiredoxin-2 exacerbates eccentric contraction-induced force loss in dystrophin-deficient muscle.Nature communications · 2018Article
- Dystrophin R16/17-syntrophin PDZ fusion protein restores sarcolemmal nNOSμ.Skeletal muscle · 2018Article
- Blockade of Bradykinin receptors worsens the dystrophic phenotype of mdx mice: differential effects for B1 and B2 receptors.Journal of cell communication and signaling · 2018Article
- Syntrophin binds directly to multiple spectrin-like repeats in dystrophin and mediates binding of nNOS to repeats 16-17.Human molecular genetics · 2018Article
- Non-Glycanated Biglycan and LTBP4: Leveraging the extracellular matrix for Duchenne Muscular Dystrophy therapeutics.Matrix biology : journal of the International Society for Matrix Biology · 2018Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
Nitric oxide (NO) is a key regulator of skeletal muscle function and metabolism, including vasoregulation, mitochondrial function, glucose uptake, fatigue and excitation-contraction coupling. The main generator of NO in skeletal muscle is the muscle-specific form of neuronal nitric oxide synthase (nNOSμ) produced by the NOS1 gene. Skeletal muscle nNOSμ is predominantly localized at the sarcolemma by interaction with the dystrophin protein complex (DPC). In Duchenne muscular dystrophy (DMD), loss of dystrophin leads to the mislocalization of nNOSμ from the sarcolemma to the cytosol. This perturbation has been shown to impair contractile function and cause muscle fatigue in dystrophic (mdx) mice. Here, we investigated the effect of restoring sarcolemmal nNOSμ on muscle contractile function in mdx mice. To achieve this, we designed a modified form of nNOSμ (NOS-M) that is targeted to the sarcolemma by palmitoylation, even in the absence of the DPC. When expressed specifically in mdx skeletal muscle, NOS-M significantly attenuates force loss owing to damaging eccentric contractions and repetitive isometric contractions (fatigue), while also improving force recovery after fatigue. Expression of unmodified nNOSμ at similar levels does not lead to sarcolemmal association and fails to improve muscle function. Aside from the benefits of sarcolemmal-localized NO production, NOS-M also increased the surface membrane levels of utrophin and other DPC proteins, including β-dystroglycan, α-syntrophin and α-dystrobrevin in mdx muscle. These results suggest that the expression of NOS-M in skeletal muscle may be therapeutically beneficial in DMD and other muscle diseases characterized by the loss of nNOSμ from the sarcolemma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.