ArticleProceedings of the National Academy of Sciences of the United States of America2015
Dystrophin-glycoprotein complex regulates muscle nitric oxide production through mechanoregulation of AMPK signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 68 citations in OpenAlex.
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- Chamber-specific regulation of myofilament Ca2+ sensitivity by nNOSβ via troponin I phosphorylation: Predominance in the right ventricle.The Journal of general physiology · 2026Article
- Cardiac mechanotransduction from development to disease.APL bioengineering · 2026Review
- AAV microdystrophin gene replacement therapy for Duchenne muscular dystrophy: progress and prospects.Gene therapy · 2025Review
- Sinus Tachycardia and Unrelieved Wall Stress Precede Left Ventricular Systolic Dysfunction During Preclinical Cardiomyopathic Changes in Duchenne Muscular Dystrophy.Journal of cardiovascular development and disease · 2025Article
- Nitrate as Warden of Nitric Oxide Homeostasis in Mammals.Nutrients · 2025Review
- The Heart Is a Smart Pump: Mechanotransduction Mechanisms of the Frank-Starling Law and the Anrep Effect.Annual review of physiology · 2025Review
- L-Arginine Activates the Neuregulin-1/ErbB Receptor Signaling Pathway and Increases Utrophin mRNA Levels in C2C12 Cells.Biochemistry research international · 2025Article
- Dystroglycan-HSPG interactions provide synaptic plasticity and specificity.Glycobiology · 2024Review
- Focal Adhesion's Role in Cardiomyocytes Function: From Cardiomyogenesis to Mechanotransduction.Cells · 2024Review
- The BALB/c.mdx62 mouse exhibits a dystrophic muscle pathology and is a model of Duchenne muscular dystrophy.Disease models & mechanisms · 2024Article
- Molecular pathways involved in the control of contractile and metabolic properties of skeletal muscle fibers as potential therapeutic targets for Duchenne muscular dystrophy.Frontiers in physiology · 2024Review
- Curcumin Administration Improves Force ofAntioxidants (Basel, Switzerland) · 2023Article
- Pharmacological inhibition of HDAC6 improves muscle phenotypes in dystrophin-deficient mice by downregulating TGF-β via Smad3 acetylation.Nature communications · 2022Article
- The role of the dystrophin glycoprotein complex in muscle cell mechanotransduction.Communications biology · 2022Review
- Role of Muscle LIM Protein in Mechanotransduction Process.International journal of molecular sciences · 2022Review
- Determinants of epigenetic resistance to HDAC inhibitors in dystrophic fibro-adipogenic progenitors.EMBO reports · 2022Article
- Utrophin modulator drugs as potential therapies for Duchenne and Becker muscular dystrophies.Neuropathology and applied neurobiology · 2021Article
- Micro-dystrophin gene therapy prevents heart failure in an improved Duchenne muscular dystrophy cardiomyopathy mouse model.JCI insight · 2021Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Patients deficient in dystrophin, a protein that links the cytoskeleton to the extracellular matrix via the dystrophin-glycoprotein complex (DGC), exhibit muscular dystrophy, cardiomyopathy, and impaired muscle nitric oxide (NO) production. We used live-cell NO imaging and in vitro cyclic stretch of isolated adult mouse cardiomyocytes as a model system to investigate if and how the DGC directly regulates the mechanical activation of muscle NO signaling. Acute activation of NO synthesis by mechanical stretch was impaired in dystrophin-deficient mdx cardiomyocytes, accompanied by loss of stretch-induced neuronal NO synthase (nNOS) S1412 phosphorylation. Intriguingly, stretch induced the acute activation of AMP-activated protein kinase (AMPK) in normal cardiomyocytes but not in mdx cardiomyocytes, and specific inhibition of AMPK was sufficient to attenuate mechanoactivation of NO production. Therefore, we tested whether direct pharmacologic activation of AMPK could bypass defective mechanical signaling to restore nNOS activity in dystrophin-deficient cardiomyocytes. Indeed, activation of AMPK with 5-aminoimidazole-4-carboxamide riboside or salicylate increased nNOS S1412 phosphorylation and was sufficient to enhance NO production in mdx cardiomyocytes. We conclude that the DGC promotes the mechanical activation of cardiac nNOS by acting as a mechanosensor to regulate AMPK activity, and that pharmacologic AMPK activation may be a suitable therapeutic strategy for restoring nNOS activity in dystrophin-deficient hearts and muscle.
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