ArticleNitric oxide : biology and chemistry2009
Peroxynitrite Increases Protein Phosphatase Activity and Promotes the Interaction of Phospholamban with Protein Phosphatase 2a in the Myocardium.
Article in Nitric oxide : biology and chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Metabolic Dysfunction-Associated Steatotic Liver Disease as a Systemic Driver of Heart Failure With Preserved Ejection Fraction: Mechanistic Insights and Emerging Therapeutic Perspectives.Reviews in cardiovascular medicine · 2026Review
- SERCA2a dysfunction in the pathophysiology of heart failure with preserved ejection fraction: a direct role is yet to be established.Heart failure reviews · 2025Review
- Biochemical pathways of 8-aminoguanine production in Sprague-Dawley and Dahl salt-sensitive rats.Biochemical pharmacology · 2022Article
- Lipotoxicity: a driver of heart failure with preserved ejection fraction?Clinical science (London, England : 1979) · 2021Review
- Mechanisms underlying the pathophysiology of heart failure with preserved ejection fraction: the tip of the iceberg.Heart failure reviews · 2021Review
- Ischemic Heart Disease and Heart Failure: Role of Coronary Ion Channels.International journal of molecular sciences · 2020Review
- Alcohol drivesAmerican journal of physiology. Lung cellular and molecular physiology · 2017Article
- Targeting Endothelial Function to Treat Heart Failure with Preserved Ejection Fraction: The Promise of Exercise Training.Oxidative medicine and cellular longevity · 2017Review
- Nitric oxide signalling and neuronal nitric oxide synthase in the heart under stress.F1000Research · 2017Review
- Obligatory role of neuronal nitric oxide synthase in the heart's antioxidant adaptation with exercise.Journal of molecular and cellular cardiology · 2015Article
- Molecular mechanisms of neuronal nitric oxide synthase in cardiac function and pathophysiology.The Journal of physiology · 2014Review
- PR65A phosphorylation regulates PP2A complex signaling.PloS one · 2014Article
- Differential effects of the peroxynitrite donor, SIN-1, on atrial and ventricular myocyte electrophysiology.Journal of cardiovascular pharmacology · 2013Article
- Molecular mechanisms underlying cardiac protein phosphatase 2A regulation in heart.The Journal of biological chemistry · 2013Article
- Dietary inorganic nitrate alleviates doxorubicin cardiotoxicity: mechanisms and implications.Nitric oxide : biology and chemistry · 2012Review
- Modulation of myocardial contraction by peroxynitrite.Frontiers in physiology · 2012Article
- Peroxynitrite toxicity in Escherichia coli K12 elicits expression of oxidative stress responses and protein nitration and nitrosylation.The Journal of biological chemistry · 2010Article
- cAMP-independent activation of protein kinase A by the peroxynitrite generator SIN-1 elicits positive inotropic effects in cardiomyocytes.Journal of molecular and cellular cardiology · 2010Article
- Ascorbate protects endothelial barrier function during septic insult: Role of protein phosphatase type 2A.Free radical biology & medicine · 2010Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
High levels of peroxynitrite have been shown to decrease cardiomyocyte contraction through a reduction in phospholamban (PLB) phosphorylation. However, previous reports did not examine the direct effect of peroxynitrite on protein phosphatase activity in the myocardium or the role of specific phosphatases. Here we test the effect of the peroxynitrite donor SIN-1 on protein phosphatase activity in whole heart homogenates, as well as the interaction of PLB with protein phosphatase 1 (PP1) and 2a (PP2a). SIN-1 (200 μmol/L) induced a significant increase in protein phosphatase activity, which was alleviated with the specific PP1/PP2a inhibitor okadaic acid. Conversely, lower concentrations of SIN-1 and the nitric oxide donor spermine NONOate (300 μmol/L) were both without effect on phosphatase activity. We next examined the effect of SIN-1 on the interaction of PLB with PP1 and PP2a using co-immunoprecipitation, since okadaic acid inhibited the effects of SIN-1 in our current and previous studies. SIN-1 significantly increased the interaction of PLB with PP2a, but had no effect on the interaction between PLB and PP1. Urate, a peroxynitrite scavenger, inhibited the effects of SIN-1 on phosphatase activity and the interaction of PLB with PP2a, thus implicating peroxynitrite as the causal species. The results of this study provide further insight into the mechanism through which high levels of peroxynitrite serve to decrease PLB phosphorylation and myocardial contraction. Therefore, peroxynitrite signaling could play a key role in the contractile dysfunction manifested in heart failure where peroxynitrite production and protein phosphatase activity are increased and PLB phosphorylation is decreased.
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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.