ArticleAmerican journal of physiology. Heart and circulatory physiology2016
Reversible redox modifications of ryanodine receptor ameliorate ventricular arrhythmias in the ischemic-reperfused heart.
Article in American journal of physiology. Heart and circulatory physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Guidelines for experimental models of myocardial ischemia and infarction.American journal of physiology. Heart and circulatory physiology · 2018Guideline
- Sex differences in mitochondrial CaJournal of molecular and cellular cardiology · 2026Article
- The interaction between sarcoplasmic reticulum and mitochondria: a novel mechanism for cardiac arrhythmia.Frontiers in physiology · 2026Review
- Stress-Induced calcium mishandling in cardiac (Patho)physiology.Cellular and molecular life sciences : CMLS · 2025Review
- Involvement of Oxidative Stress and Antioxidants in Modification of Cardiac Dysfunction Due to Ischemia-Reperfusion Injury.Antioxidants (Basel, Switzerland) · 2025Review
- Unveiling the Role of Protein Posttranslational Modifications in Glioma Prognosis.CNS neuroscience & therapeutics · 2025Article
- Cysteines 1078 and 2991 cross-linking plays a critical role in redox regulation of cardiac ryanodine receptor (RyR).Nature communications · 2023Article
- Pharmacological Modulation by Low Molecular Weight Heparin of Purinergic Signaling in Cardiac Cells Prevents Arrhythmia and Lethality Induced by Myocardial Infarction.Journal of cardiovascular development and disease · 2023Article
- The Ryanodine Receptor as a Sensor for Intracellular Environments in Muscles.International journal of molecular sciences · 2021Review
- Irisin: A Promising Target for Ischemia-Reperfusion Injury Therapy.Oxidative medicine and cellular longevity · 2021Review
- ArrhythmoGenoPharmacoTherapy.Frontiers in pharmacology · 2020Review
- Inhibition of chymotrypsin-like activity of the proteasome by ixazomib prevents mitochondrial dysfunction during myocardial ischemia.PloS one · 2020Article
- Glutathione-related substances maintain cardiomyocyte contractile function in hypoxic conditions.Scientific reports · 2019Article
- Unbalance Between Sarcoplasmic Reticulum CaFrontiers in physiology · 2019Review
- Acute isoproterenol leads to age-dependent arrhythmogenesis in guinea pigs.American journal of physiology. Heart and circulatory physiology · 2018Article
- Oxidized CaMKII (CaCirculation. Arrhythmia and electrophysiology · 2018Article
- Simvastatin activates single skeletal RyR1 channels but exerts more complex regulation of the cardiac RyR2 isoform.British journal of pharmacology · 2018Article
- High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice.International journal of molecular sciences · 2018Article
- Redox Dependent Modifications of Ryanodine Receptor: Basic Mechanisms and Implications in Heart Diseases.Frontiers in physiology · 2018Review
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
Previous results from our laboratory showed that phosphorylation of ryanodine receptor 2 (RyR2) by Ca(2+) calmodulin-dependent kinase II (CaMKII) was a critical but not the unique event responsible for the production of reperfusion-induced arrhythmogenesis, suggesting the existence of other mechanisms cooperating in an additive way to produce these rhythm alterations. Oxidative stress is a prominent feature of ischemia/reperfusion injury. Both CaMKII and RyR2 are proteins susceptible to alteration by redox modifications. This study was designed to elucidate whether CaMKII and RyR2 redox changes occur during reperfusion and whether these changes are involved in the genesis of arrhythmias. Langendorff-perfused hearts from rats or transgenic mice with genetic ablation of CaMKII phosphorylation site on RyR2 (S2814A) were subjected to ischemia-reperfusion in the presence or absence of a free radical scavenger (mercaptopropionylglycine, MPG) or inhibitors of NADPH oxidase and nitric oxide synthase. Left ventricular contractile parameters and monophasic action potentials were recorded. Oxidation and phosphorylation of CaMKII and RyR2 were assessed. Increased oxidation of CaMKII during reperfusion had no consequences on the level of RyR2 phosphorylation. Avoiding the reperfusion-induced thiol oxidation of RyR2 with MPG produced a reduction in the number of arrhythmias and did not modify the contractile recovery. Conversely, selective prevention of S-nitrosylation and S-glutathionylation of RyR2 was associated with higher numbers of arrhythmias and impaired contractility. In S2814A mice, treatment with MPG further reduced the incidence of arrhythmias. Taken together, the results suggest that redox modification of RyR2 synergistically with CaMKII phosphorylation modulates reperfusion arrhythmias.
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