ArticleCirculation research2012
Nitroxyl-mediated disulfide bond formation between cardiac myofilament cysteines enhances contractile function.
Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
62 citing papers in PubMed, 109 citations in OpenAlex.
- A Phase 1 Randomized Study of Single Intravenous Infusions of the Novel Nitroxyl Donor BMS-986231 in Healthy Volunteers.Journal of clinical pharmacology · 2019Trial
- A Phase 2a dose-escalation study of the safety, tolerability, pharmacokinetics and haemodynamic effects of BMS-986231 in hospitalized patients with heart failure with reduced ejection fraction.European journal of heart failure · 2017Trial
- Nitroxyl (HNO): A novel approach for the acute treatment of heart failure.Circulation. Heart failure · 2013Trial
- Experimental Detection Methods and Clinical Translational Challenges of Disulfidptosis in Cancer.Cells · 2026Review
- Research status and molecular mechanisms of disulfidptosis in cardiovascular diseases (Review).Molecular medicine reports · 2026Review
- GSNOR deletion differentially alters age-related cardiac function in a sex-dependent manner.American journal of physiology. Heart and circulatory physiology · 2026Article
- SCarP: Proteome Heterogeneity Characterization of Primary Mouse Cardiomyocytes.Circulation research · 2025Article
- Salivary-Gland-Mediated Nitrate Recirculation as a Modulator for Cardiovascular Diseases.Biomolecules · 2025Review
- The carbon monoxide prodrug oCOm-21 increases CaPhysiological reports · 2024Article
- From amino-acid to disease: the effects of oxidation on actin-myosin interactions in muscle.Journal of muscle research and cell motility · 2023Review
- The Chemical Biology of NO that Regulates Oncogenic Signaling and Metabolism: NOS2 and Its Role in Inflammatory Disease.Critical reviews in oncogenesis · 2023Review
- Association of free fatty acid binding protein with central aortic stiffness, myocardial dysfunction and preserved ejection fraction heart failure.Scientific reports · 2021Article
- The Interplay between S-Glutathionylation and Phosphorylation of Cardiac Troponin I and Myosin Binding Protein C in End-Stage Human Failing Hearts.Antioxidants (Basel, Switzerland) · 2021Article
- CoenzymeQ in cellular redox regulation and clinical heart failure.Free radical biology & medicine · 2021Review
- Regulation of Cardiac PKA Signaling by cAMP and Oxidants.Antioxidants (Basel, Switzerland) · 2021Review
- Cardiovascular Therapeutic Potential of the Redox Siblings, Nitric Oxide (NO•) and Nitroxyl (HNO), in the Setting of Reactive Oxygen Species Dysregulation.Handbook of experimental pharmacology · 2021Review
- Association Between Arterial Stiffness and Heart Failure With Preserved Ejection Fraction.Frontiers in cardiovascular medicine · 2021Article
- Interaction among Hydrogen Sulfide and Other Gasotransmitters in Mammalian Physiology and Pathophysiology.Advances in experimental medicine and biology · 2021Review
- Receptor-independent modulation of cAMP-dependent protein kinase and protein phosphatase signaling in cardiac myocytes by oxidizing agents.The Journal of biological chemistry · 2020Article
- Phosphorylated cofilin-2 is more prone to oxidative modifications on Cys39 and favors amyloid fibril formation.Redox biology · 2020Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
rationaleIn the myocardium, redox/cysteine modification of proteins regulating Ca(2+) cycling can affect contraction and may have therapeutic value. Nitroxyl (HNO), the one-electron-reduced form of nitric oxide, enhances cardiac function in a manner that suggests reversible cysteine modifications of the contractile machinery.
objectiveTo determine the effects of HNO modification in cardiac myofilament proteins. METHODS AND
resultsThe HNO-donor, 1-nitrosocyclohexyl acetate, was found to act directly on the myofilament proteins, increasing maximum force (F(max)) and reducing the concentration of Ca(2+) for 50% activation (Ca(50)) in intact and skinned cardiac muscles. The effects of 1-nitrosocyclohexyl acetate are reversible by reducing agents and distinct from those of another HNO donor, Angeli salt, which was previously reported to increase F(max) without affecting Ca50. Using a new mass spectrometry capture technique based on the biotin switch assay, we identified and characterized the formation by HNO of a disulfide-linked actin-tropomyosin and myosin heavy chain-myosin light chain 1. Comparison of the 1-nitrosocyclohexyl acetate and Angeli salt effects with the modifications induced by each donor indicated the actin-tropomyosin and myosin heavy chain-myosin light chain 1 interactions independently correlated with increased Ca(2+) sensitivity and force generation, respectively.
conclusionsHNO exerts a direct effect on cardiac myofilament proteins increasing myofilament Ca(2+) responsiveness by promoting disulfide bond formation between critical cysteine residues. These findings indicate a novel, redox-based modulation of the contractile apparatus, which positively impacts myocardial function, providing further mechanistic insight for HNO as a therapeutic agent.
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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.