ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2008
A human polymorphism of protein phosphatase-1 inhibitor-1 is associated with attenuated contractile response of cardiomyocytes to beta-adrenergic stimulation.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- Phospholamban interactome in cardiac contractility and survival: A new vision of an old friend.Journal of molecular and cellular cardiology · 2014Review
- AAV9.I-1c delivered via direct coronary infusion in a porcine model of heart failure improves contractility and mitigates adverse remodeling.Circulation. Heart failure · 2013Article
- Identification of a protein phosphatase-1/phospholamban complex that is regulated by cAMP-dependent phosphorylation.PloS one · 2013Article
- Modulation of cardiac contractility by the phospholamban/SERCA2a regulatome.Circulation research · 2012Review
- Expression of active protein phosphatase 1 inhibitor-1 attenuates chronic beta-agonist-induced cardiac apoptosis.Basic research in cardiology · 2010Article
- AFos inhibits phenylephrine-mediated contractile dysfunction by altering phospholamban phosphorylation.American journal of physiology. Heart and circulatory physiology · 2010Article
- Role of protein phosphatase-1 inhibitor-1 in cardiac physiology and pathophysiology.Journal of molecular and cellular cardiology · 2009Review
- The human G147D-protein phosphatase 1 inhibitor-1 polymorphism is not associated with altered clinical characteristics in heart failure.Cardiology · 2009Article
- Role of PP1 in the regulation of Ca cycling in cardiac physiology and pathophysiology.Frontiers in bioscience (Landmark edition) · 2009Article
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Aberrant beta-adrenergic signaling and depressed calcium homeostasis, associated with an imbalance of protein kinase A and phosphatase-1 activities, are hallmarks of heart failure. Phosphatase-1 is restrained by its endogenous inhibitor, protein phosphatase inhibitor-1 (PPI-1). We assessed 352 normal subjects, along with 959 patients with heart failure and identified a polymorphism in PPI-1 (G147D) exclusively in black subjects. To determine whether the G147D variant could affect cardiac function, we infected adult cardiomyocytes with adenoviruses expressing D147 or wild-type (G147) PPI-1. Under basal conditions, there were no significant differences in fractional shortening or contraction or relaxation rates. However, the enhancement of contractile parameters after isoproterenol stimulation was significantly blunted in D147 compared with G147 and control myocytes. Similar findings were observed in calcium kinetics. The attenuated beta-agonist response was associated with decreased (50%) phosphorylation of phospholamban (PLN) at serine 16, whereas phosphorylation of troponin I and ryanodine receptor was unaltered. These findings suggest that the human G147D PPI-1 can attenuate responses of cardiomyocytes to beta-adrenergic agonists by decreasing PLN phosphorylation and therefore may contribute to deteriorated function in heart failure.
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Registered trials
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