ArticleJournal of molecular and cellular cardiology2010
cAMP-independent activation of protein kinase A by the peroxynitrite generator SIN-1 elicits positive inotropic effects in cardiomyocytes.
Article in Journal of molecular and cellular cardiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 39 citations in OpenAlex.
- Genome-wide RNAi screening in C. elegans reveals OXPHOS and pyrimidine synthesis pathways as PKA regulators.Communications biology · 2025Article
- Physiological and pathological roles of protein kinase A in the heart.Cardiovascular research · 2022Review
- Protein Kinase A in cellular migration-Niche signaling of a ubiquitous kinase.Frontiers in molecular biosciences · 2022Review
- Article
- Laminin 211 inhibits protein kinase A in Schwann cells to modulate neuregulin 1 type III-driven myelination.PLoS biology · 2017Article
- Mutual Regulation of Epicardial Adipose Tissue and Myocardial Redox State by PPAR-γ/Adiponectin Signalling.Circulation research · 2016Article
- Obligatory role of neuronal nitric oxide synthase in the heart's antioxidant adaptation with exercise.Journal of molecular and cellular cardiology · 2015Article
- Tri-modal regulation of cardiac muscle relaxation; intracellular calcium decline, thin filament deactivation, and cross-bridge cycling kinetics.Biophysical reviews · 2014Article
- Abnormal Ca(2+) cycling in failing ventricular myocytes: role of NOS1-mediated nitroso-redox balance.Antioxidants & redox signaling · 2014Review
- The NO/ONOO-cycle as the central cause of heart failure.International journal of molecular sciences · 2013Review
- Peroxynitrite mediates testosterone-induced vasodilation of microvascular resistance vessels.The Journal of pharmacology and experimental therapeutics · 2013Article
- Neuronal nitric oxide synthase is indispensable for the cardiac adaptive effects of exercise.Basic research in cardiology · 2013Article
- Oxidative stress induced mitochondrial protein kinase A mediates cytochrome c oxidase dysfunction.PloS one · 2013Article
- Diesterified nitrone rescues nitroso-redox levels and increases myocyte contraction via increased SR Ca(2+) handling.PloS one · 2012Article
- Modulation of myocardial contraction by peroxynitrite.Frontiers in physiology · 2012Article
- Effects of increased systolic Ca²⁺ and phospholamban phosphorylation during β-adrenergic stimulation on Ca²⁺ transient kinetics in cardiac myocytes.American journal of physiology. Heart and circulatory physiology · 2011Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The phosphatase vs. kinase equilibrium plays a critical role in the regulation of myocardial contractility. Previous studies have demonstrated that peroxynitrite exerts a biphasic effect on cardiomyocyte contraction, such that high peroxynitrite reduced beta-adrenergic-stimulated myocyte contraction by inducing the dephosphorylation of phospholamban (PLB) via phosphatase activation. Conversely, low peroxynitrite increased basal and beta-adrenergic-stimulated contraction also through a PLB-dependent mechanism. However, previous studies have not elucidated the mechanism underlying the positive effects of low peroxynitrite on myocyte contraction. In the current study, we examined the phosphatase vs. kinase equilibrium as a potential mechanism underlying the positive effects of peroxynitrite. SIN-1 (peroxynitrite donor, 10 mumol/L) increased myocyte Ca(2+) transient and shortening amplitude, accelerated myocyte relaxation, and enhanced PLB phosphorylation. Specific inhibition of PP1/PP2a with okadaic acid failed to inhibit this positive effect. However, inhibition of PKA with KT5720 completely abolished the effects of SIN-1 on myocyte contraction. Additionally, SIN-1 induced a significant increase in PKA activity in cardiac homogenates, which was inhibited with FeTPPS (peroxynitrite decomposition catalyst). Surprisingly, SIN-1 also increased activity in purified preparations (i.e., in the absence of cAMP) of PKA. Therefore, our data suggest that peroxynitrite directly activates PKA (independent from cAMP), resulting in the enhancement of myocyte contraction and relaxation through the phosphorylation of PLB.
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