ArticleCardiovascular research2009
Protein phosphatase 2A contributes to the cardiac dysfunction induced by endotoxemia.
Article in Cardiovascular research, 2009. 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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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
16 citing papers in PubMed, 29 citations in OpenAlex.
- Protein Phosphatase 2A Improves Cardiac Functional Response to Ischemia and Sepsis.International journal of molecular sciences · 2022Article
- Role of type 2A phosphatase regulatory subunit B56α in regulating cardiac responses to β-adrenergic stimulation in vivo.Cardiovascular research · 2019Article
- Article
- β-Adrenergic regulation of cardiac type 2A protein phosphatase through phosphorylation of regulatory subunit B56δ at S573.Journal of molecular and cellular cardiology · 2018Article
- [Heart in sepsis : Molecular mechanisms, diagnosis and therapy of septic cardiomyopathy].Der Anaesthesist · 2017Review
- Protein phosphatase 2A activation attenuates inflammation in murine models of acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Inflammatory stimuli promote growth and invasion of pancreatic cancer cells through NF-κB pathway dependent repression of PP2Ac.Cell cycle (Georgetown, Tex.) · 2016Article
- Pathophysiology of sepsis-induced myocardial dysfunction.Military Medical Research · 2016Review
- Cardiac function is regulated by B56α-mediated targeting of protein phosphatase 2A (PP2A) to contractile relevant substrates.The Journal of biological chemistry · 2014Article
- Anthrax lethal toxin induces acute diastolic dysfunction in rats through disruption of the phospholamban signaling network.International journal of cardiology · 2013Article
- Molecular mechanisms underlying cardiac protein phosphatase 2A regulation in heart.The Journal of biological chemistry · 2013Article
- Urban air pollution produces up-regulation of myocardial inflammatory genes and dark chocolate provides cardioprotection.Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie · 2012Article
- Protein phosphatase 2A affects myofilament contractility in non-failing but not in failing human myocardium.Journal of muscle research and cell motility · 2011Article
- AKAP phosphatase complexes in the heart.Journal of cardiovascular pharmacology · 2011Review
- Nitrosative protein oxidation is modulated during early endotoxemia.Nitric oxide : biology and chemistry · 2011Article
- Protein phosphatase 2A catalytic subunit α (PP2Acα) maintains survival of committed erythroid cells in fetal liver erythropoiesis through the STAT5 pathway.The American journal of pathology · 2011Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
aimsSepsis-associated cardiac dysfunction represents an intrinsic impairment of cardiomyocyte function due in part to a decrease in myofilament Ca(2+) sensitivity associated with a sustained increase in cardiac troponin I (cTnI) phosphorylation at Ser23/24. Dephosphorylation of cTnI is under regulatory control. Thus, muscarinic and adenosine A(1)-receptor agonists antagonize beta-adrenergic stimulation via activation of protein phosphatase 2A (PP2A). The aim of this study was to determine whether modulation of PP2A and thus cTnI phosphorylation could improve sepsis-induced contractile dysfunction. METHODS AND
resultsCardiomyocytes were isolated from control or septic mice 16-18 h after an injection of vehicle or lipopolysaccharide (LPS; 9 mg/kg ip) respectively. Protein expression and phosphatase activity were determined in homogenates of control and septic hearts. Our data showed that LPS significantly increased cTnI phosphorylation at Ser23/24 in cardiomyocytes and reduced contraction amplitude without affecting Ca(2+)-transients. Treatment of cardiomyocytes with the A(1) agonist cyclopentyladenosine (CPA) or the protein kinase A inhibitor H89 significantly attenuated the LPS-induced contractile dysfunction without effect on Ca(2+)-transients. Co-treatment with CPA and H89 completely reversed the contractile dysfunction. Increased cTnI phosphorylation in septic hearts was associated with a significant reduction in the protein expression of both the catalytic and regulatory subunits (B56 alpha) of PP2A and a decrease in PP2A activity. CPA treatment of septic hearts increased PP2A activity. An increase in the protein expression of demethylated PP2A and a decrease in the PP2A-methyltransferase (PPMT; the methyltransferase that catalyses this reaction) were also observed.
conclusionThese data support the hypothesis that sustained cTnI phosphorylation underlies the contractile dysfunction seen in sepsis.
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Registered trials
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