ArticleInternational journal of molecular sciences2020
Apocynin Treatment Prevents Cardiac Connexin 43 Hemichannels Hyperactivity by Reducing Nitroso-Redox Stress in Mdx Mice.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Reduced Cx43 S-nitrosylation protects against cardiac stress-induced arrhythmias and myocardial injury in Duchenne muscular dystrophy.Cardiovascular research · 2026Article
- S-Nitrosylation in Cardiovascular Disorders: The State of the Art.Biomolecules · 2025Review
- New NADPH Oxidase 2 Inhibitors Display Potent Activity against Oxidative Stress by Targeting p22Antioxidants (Basel, Switzerland) · 2023Article
- Remodeled connexin 43 hemichannels alter cardiac excitability and promote arrhythmias.The Journal of general physiology · 2023Article
- Tetrahydrobiopterin (BHBiomedicines · 2022Article
- Connexin and Pannexin Large-Pore Channels in Microcirculation and Neurovascular Coupling Function.International journal of molecular sciences · 2022Review
- Cardiovascular Disease in Duchenne Muscular Dystrophy: Overview and Insight Into Novel Therapeutic Targets.JACC. Basic to translational science · 2022Review
- Oxidative Stress, Inflammation and Connexin Hemichannels in Muscular Dystrophies.Biomedicines · 2022Review
- The mutual interplay of redox signaling and connexins.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Peptidic Connexin43 Therapeutics in Cardiac Reparative Medicine.Journal of cardiovascular development and disease · 2021Review
- Pharmacological Inhibition of S-Nitrosoglutathione Reductase Reduces Cardiac Damage Induced by Ischemia-Reperfusion.Antioxidants (Basel, Switzerland) · 2021Article
- Importance of Cx43 for Right Ventricular Function.International journal of molecular sciences · 2021Review
- Cardiac Connexin-43 Hemichannels and Pannexin1 Channels: Provocative Antiarrhythmic Targets.International journal of molecular sciences · 2020Review
- Anti-Fibrotic Effect of Human Wharton's Jelly-Derived Mesenchymal Stem Cells on Skeletal Muscle Cells, Mediated by Secretion of MMP-1.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Duchenne muscular dystrophy (DMD) is a fatal disease that causes cardiomyopathy and is associated with oxidative stress. In the heart, oxidative stress interferes with the location of connexin 43 (Cx43) to the intercalated discs causing its lateralization to the plasma membrane where Cx43 forms hemichannels. We tested the hypothesis that in DMD cardiomyopathy, increased oxidative stress is associated with the formation and activation of Cx43 hemichannels. For this, we used mdx mice as a DMD model and evaluated cardiac function, nitroso-redox changes and Cx43 hemichannels permeability. Mdx hearts presented increased NADPH oxidase-derived oxidative stress and increased Cx43 S-nitrosylation compared to controls. These redox changes were associated with increased Cx43 lateralization, decreased cardiac contractility and increased arrhythmic events. Pharmacological inhibition of NADPH oxidase using apocynin (one month) reduced systemic oxidative stress and reversed the aforementioned changes towards normal, except Cx43 lateralization. Opening of Cx43 hemichannels was blocked by apocynin treatment and by acute hemichannel blockade with carbenoxolone. NADPH oxidase inhibition also prevented the occurrence of apoptosis in mdx hearts and reversed the ventricular remodeling. These results show that NADPH oxidase activity in DMD is associated with S-nitrosylation and opening of Cx43 hemichannels. These changes lead to apoptosis and cardiac dysfunction and were prevented by NADPH oxidase inhibition.
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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.