ArticleBasic research in cardiology2010
Protein kinase C alpha and epsilon phosphorylation of troponin and myosin binding protein C reduce Ca2+ sensitivity in human myocardium.
Article in Basic research in cardiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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
47 citing papers in PubMed, 80 citations in OpenAlex.
- Genome-wide identification of expression quantitative trait loci (eQTLs) in human heart.PloS one · 2014Trial
- Metabolic-epigenetic axis in cardiovascular inflammatory injury: regulatory mechanisms and intervention strategies.Frontiers in cardiovascular medicine · 2026Review
- Abnormal phosphorylation / dephosphorylation and CaHeart failure reviews · 2024Review
- Cardioprotective Strategies After Ischemia-Reperfusion Injury.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2024Review
- Mechanosignaling pathways alter muscle structure and function by post-translational modification of existing sarcomeric proteins to optimize energy usage.Journal of muscle research and cell motility · 2021Article
- Heart Failure in Humans Reduces Contractile Force in Myocardium From Both Ventricles.JACC. Basic to translational science · 2020Article
- Slit2 Protects Hearts Against Ischemia-Reperfusion Injury by Inhibiting Inflammatory Responses and Maintaining Myofilament Contractile Properties.Frontiers in physiology · 2020Article
- Disease modeling of a mutation in α-actinin 2 guides clinical therapy in hypertrophic cardiomyopathy.EMBO molecular medicine · 2019Article
- Analysis of Contractile Function of Permeabilized Human Hypertrophic Cardiomyopathy Multicellular Heart Tissue.Frontiers in physiology · 2019Article
- Protein Kinase C Inhibition With Ruboxistaurin Increases Contractility and Reduces Heart Size in a Swine Model of Heart Failure With Reduced Ejection Fraction.JACC. Basic to translational science · 2017Article
- Is Protein Kinase C Inhibition the Tip of the Iceberg in New Therapeutics for Acutely Decompensated Heart Failure?JACC. Basic to translational science · 2017Article
- The continuing evolution of cardiac troponin I biomarker analysis: from protein to proteoform.Expert review of proteomics · 2017Review
- Sub-cellular localization specific SUMOylation in the heart.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- Role of Cardiolipin in Mitochondrial Signaling Pathways.Frontiers in cell and developmental biology · 2017Review
- Nebivolol Desensitizes Myofilaments of a Hypertrophic Cardiomyopathy Mouse Model.Frontiers in physiology · 2017Article
- Review
- A novel phosphorylation site, Serine 199, in the C-terminus of cardiac troponin I regulates calcium sensitivity and susceptibility to calpain-induced proteolysis.Journal of molecular and cellular cardiology · 2015Article
- Pathomechanisms in heart failure: the contractile connection.Journal of muscle research and cell motility · 2015Review
- Cardiac MyBP-C regulates the rate and force of contraction in mammalian myocardium.Circulation research · 2015Review
- Troponin I phosphorylation in human myocardium in health and disease.Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation · 2014Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previous studies indicated that the increase in protein kinase C (PKC)-mediated myofilament protein phosphorylation observed in failing myocardium might be detrimental for contractile function. This study was designed to reveal and compare the effects of PKCalpha- and PKCepsilon-mediated phosphorylation on myofilament function in human myocardium. Isometric force was measured at different [Ca2+] in single permeabilized cardiomyocytes from failing human left ventricular tissue. Activated PKCalpha and PKCepsilon equally reduced Ca2+ sensitivity in failing cardiomyocytes (DeltapCa50 = 0.08 +/- 0.01). Both PKC isoforms increased phosphorylation of troponin I- (cTnI) and myosin binding protein C (cMyBP-C) in failing cardiomyocytes. Subsequent incubation of failing cardiomyocytes with the catalytic subunit of protein kinase A (PKA) resulted in a further reduction in Ca2+ sensitivity, indicating that the effects of both PKC isoforms were not caused by cross-phosphorylation of PKA sites. Both isozymes showed no effects on maximal force and only PKCalpha resulted in a modest significant reduction in passive force. Effects of PKCalpha were only minor in donor cardiomyocytes, presumably because of already saturated cTnI and cMyBP-C phosphorylation levels. Donor tissue could therefore be used as a tool to reveal the functional effects of troponin T (cTnT) phosphorylation by PKCalpha. Massive dephosphorylation of cTnT with alkaline phosphatase increased Ca2+ sensitivity. Subsequently, PKCalpha treatment of donor cardiomyocytes reduced Ca2+ sensitivity (DeltapCa50 = 0.08 +/- 0.02) and solely increased phosphorylation of cTnT, but did not affect maximal and passive force. PKCalpha- and PKCepsilon-mediated phosphorylation of cMyBP-C and cTnI as well as cTnT decrease myofilament Ca2+ sensitivity and may thereby reduce contractility and enhance relaxation of human myocardium.
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