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PMID: 22679139 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Modulation of cardiac contractility by the phospholamban/SERCA2a regulatome.

Circulation research ·Vol. 110 ·No. 12 ·2012-06-08 ·Pages 1646-60

Kranias EG, Hajjar RJ

Abstract

Heart disease remains the leading cause of death and disability in the Western world. Current therapies aim at treating the symptoms rather than the subcellular mechanisms, underlying the etiology and pathological remodeling in heart failure. A universal characteristic, contributing to the decreased contractile performance in human and experimental failing hearts, is impaired calcium sequestration into the sarcoplasmic reticulum (SR). SR calcium uptake is mediated by a Ca(2+)-ATPase (SERCA2), whose activity is reversibly regulated by phospholamban (PLN). Dephosphorylated PLN is an inhibitor of SERCA and phosphorylation of PLN relieves this inhibition. However, the initial simple view of a PLN/SERCA regulatory complex has been modified by our recent identification of SUMO, S100 and the histidine-rich Ca-binding protein as regulators of SERCA activity. In addition, PLN activity is regulated by 2 phosphoproteins, the inhibitor-1 of protein phosphatase 1 and the small heat shock protein 20, which affect the overall SERCA-mediated Ca-transport. This review will highlight the regulatory mechanisms of cardiac contractility by the multimeric SERCA/PLN-ensemble and the potential for new therapeutic avenues targeting this complex by using small molecules and gene transfer methods.

MeSH Terms
Animals Calcium-Binding Proteins/physiology Humans Myocardial Contraction/physiology Protein Multimerization/physiology Sarcoplasmic Reticulum Calcium-Transporting ATPases/physiology
Chemicals
Calcium-Binding Proteins phospholamban Sarcoplasmic Reticulum Calcium-Transporting ATPases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kranias Evangelia G
Department of Pharmacology and Cell Biophysics, College of Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267-0575, USA. [email protected]
Hajjar Roger J
References (124)
124 references, click to expand
  1. Mutational screening of phospholamban gene in hypertrophic and idiopathic dilated cardiomyopathy and functional study of the PLN -42 C>G mutation.
    Eur J Heart Fail. 2007 Jan;9(1):37-43 PMID: 16829191
  2. Phospholamban and troponin I are substrates for protein kinase C in vitro but not in intact beating guinea pig hearts.
    Circ Res. 1990 Aug;67(2):394-400 PMID: 2165444
  3. Calcium upregulation by percutaneous administration of gene therapy in cardiac disease (CUPID Trial), a first-in-human phase 1/2 clinical trial.
    J Card Fail. 2009 Apr;15(3):171-81 PMID: 19327618
  4. SERCA2a gene transfer enhances eNOS expression and activity in endothelial cells.
    Mol Ther. 2010 Jul;18(7):1284-92 PMID: 20461063
  5. Maximal inhibition of SERCA2 Ca(2+) affinity by phospholamban in transgenic hearts overexpressing a non-phosphorylatable form of phospholamban.
    J Biol Chem. 2000 Apr 21;275(16):12129-35 PMID: 10766848
  6. Increased susceptibility to isoproterenol-induced cardiac hypertrophy and impaired weight gain in mice lacking the histidine-rich calcium-binding protein.
    Mol Cell Biol. 2006 Dec;26(24):9315-26 PMID: 17030629
  7. Role of phospholamban phosphorylation on Thr17 in cardiac physiological and pathological conditions.
    Cardiovasc Res. 2005 Dec 1;68(3):366-75 PMID: 16226237
  8. PKC-alpha regulates cardiac contractility and propensity toward heart failure.
    Nat Med. 2004 Mar;10(3):248-54 PMID: 14966518
  9. The human phospholamban Arg14-deletion mutant localizes to plasma membrane and interacts with the Na/K-ATPase.
    J Mol Cell Cardiol. 2012 Mar;52(3):773-82 PMID: 22155237
  10. Targeted overexpression of the sarcoplasmic reticulum Ca2+-ATPase increases cardiac contractility in transgenic mouse hearts.
    Circ Res. 1998 Dec 14-28;83(12):1205-14 PMID: 9851937
  11. Transgenic approaches to define the functional role of dual site phospholamban phosphorylation.
    J Biol Chem. 1998 Feb 20;273(8):4734-9 PMID: 9468536
  12. Calcium uptake by cardiac sarcoplasmic reticulum in human dilated cardiomyopathy.
    Cardiovasc Res. 1987 Aug;21(8):601-5 PMID: 3328648
  13. Prevention of ventricular arrhythmias with sarcoplasmic reticulum Ca2+ ATPase pump overexpression in a porcine model of ischemia reperfusion.
    Circulation. 2008 Aug 5;118(6):614-24 PMID: 18645052
  14. Regulation of myocardial function by histidine-rich, calcium-binding protein.
    Am J Physiol Heart Circ Physiol. 2004 Oct;287(4):H1705-11 PMID: 15191886
  15. Molecular mechanisms of S100-target protein interactions.
    Microsc Res Tech. 2003 Apr 15;60(6):552-9 PMID: 12645003
  16. S100ao (alpha alpha) protein is mainly located in the heart and striated muscles.
    Biochim Biophys Acta. 1985 Oct 17;842(2-3):146-50 PMID: 4052452
  17. Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban.
    Science. 2003 Feb 28;299(5611):1410-3 PMID: 12610310
  18. Increased expression of cardiac phosphatases in patients with end-stage heart failure.
    J Mol Cell Cardiol. 1997 Jan;29(1):265-72 PMID: 9040041
  19. Phosphorylation of protein phosphatase inhibitor-1 by Cdk5.
    J Biol Chem. 2001 Apr 27;276(17):14490-7 PMID: 11278334
  20. Functional reconstitution of the cardiac sarcoplasmic reticulum Ca2(+)-ATPase with phospholamban in phospholipid vesicles.
    J Biol Chem. 1990 Jan 25;265(3):1702-9 PMID: 2136856
  21. Type 1 phosphatase, a negative regulator of cardiac function.
    Mol Cell Biol. 2002 Jun;22(12):4124-35 PMID: 12024026
  22. Phosphorylation of human inhibitor-1 at Ser67 and/or Thr75 attenuates stimulatory effects of protein kinase A signaling in cardiac myocytes.
    Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H762-9 PMID: 17416610
  23. Network integration of the adrenergic system in cardiac hypertrophy.
    Cardiovasc Res. 2004 Aug 15;63(3):391-402 PMID: 15276464
  24. Impaired cardiac performance in heterozygous mice with a null mutation in the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 (SERCA2) gene.
    J Biol Chem. 1999 Jan 22;274(4):2556-62 PMID: 9891028
  25. Reversal of cardiac dysfunction after long-term expression of SERCA2a by gene transfer in a pre-clinical model of heart failure.
    J Am Coll Cardiol. 2008 Mar 18;51(11):1112-9 PMID: 18342232
  26. Phosphoproteome analysis of cardiomyocytes subjected to beta-adrenergic stimulation: identification and characterization of a cardiac heat shock protein p20.
    Circ Res. 2004 Feb 6;94(2):184-93 PMID: 14615292
  27. The anti-apoptotic protein HAX-1 is a regulator of cardiac function.
    Proc Natl Acad Sci U S A. 2009 Dec 8;106(49):20776-81 PMID: 19920172
  28. A single site (Ser16) phosphorylation in phospholamban is sufficient in mediating its maximal cardiac responses to beta -agonists.
    J Biol Chem. 2000 Dec 8;275(49):38938-43 PMID: 10988285
  29. Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling.
    Pharmacol Rev. 2001 Mar;53(1):1-24 PMID: 11171937
  30. The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy.
    Eur Heart J. 2008 Oct;29(20):2514-25 PMID: 18617481
  31. SUMO1-dependent modulation of SERCA2a in heart failure.
    Nature. 2011 Sep 07;477(7366):601-5 PMID: 21900893
  32. Constitutively active phosphatase inhibitor-1 improves cardiac contractility in young mice but is deleterious after catecholaminergic stress and with aging.
    J Clin Invest. 2010 Feb;120(2):617-26 PMID: 20071777
  33. Three-dimensional solution structure of the calcium-signaling protein apo-S100A1 as determined by NMR.
    Biochemistry. 2002 Jan 22;41(3):788-96 PMID: 11790100
  34. Targeted SERCA2a gene expression identifies molecular mechanism and therapeutic target for arrhythmogenic cardiac alternans.
    Circ Arrhythm Electrophysiol. 2009 Dec;2(6):686-94 PMID: 19948504
  35. Cardiac-specific overexpression of a superinhibitory pentameric phospholamban mutant enhances inhibition of cardiac function in vivo.
    J Biol Chem. 2000 Apr 7;275(14):10538-44 PMID: 10744747
  36. Effect of ablation of phospholamban on dynamics of cardiac myocyte contraction and intracellular Ca2+.
    Am J Physiol. 1996 Jul;271(1 Pt 1):C391-7 PMID: 8760070
  37. Cardiac-specific overexpression of mouse cardiac calsequestrin is associated with depressed cardiovascular function and hypertrophy in transgenic mice.
    J Biol Chem. 1998 Oct 23;273(43):28470-7 PMID: 9774476
  38. Solution structure of the cytoplasmic domain of phopholamban: phosphorylation leads to a local perturbation in secondary structure.
    Biochemistry. 1995 Jun 13;34(23):7603-13 PMID: 7779806
  39. Histidine-rich calcium binding protein: the new regulator of sarcoplasmic reticulum calcium cycling.
    J Mol Cell Cardiol. 2011 Jan;50(1):43-9 PMID: 20807542
  40. Small heat-shock protein Hsp20 phosphorylation inhibits beta-agonist-induced cardiac apoptosis.
    Circ Res. 2004 Jun 11;94(11):1474-82 PMID: 15105294
  41. The phospholamban phosphatase associated with cardiac sarcoplasmic reticulum is a type 1 enzyme.
    Arch Biochem Biophys. 1992 Feb 14;293(1):17-24 PMID: 1309982
  42. Abrogation of ventricular arrhythmias in a model of ischemia and reperfusion by targeting myocardial calcium cycling.
    Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5622-7 PMID: 15044708
  43. Novel cardioprotective role of a small heat-shock protein, Hsp20, against ischemia/reperfusion injury.
    Circulation. 2005 Apr 12;111(14):1792-9 PMID: 15809372
  44. Human phospholamban null results in lethal dilated cardiomyopathy revealing a critical difference between mouse and human.
    J Clin Invest. 2003 Mar;111(6):869-76 PMID: 12639993
  45. Evidence for protein phosphatase inhibitor-1 playing an amplifier role in beta-adrenergic signaling in cardiac myocytes.
    FASEB J. 2003 Mar;17(3):437-9 PMID: 12514122
  46. Enhanced cardiac function in mice overexpressing protein phosphatase Inhibitor-2.
    Cardiovasc Res. 2005 Oct 1;68(1):98-108 PMID: 15975567
  47. Sarcolipin and phospholamban as regulators of cardiac sarcoplasmic reticulum Ca2+ ATPase.
    J Mol Cell Cardiol. 2007 May;42(5):903-11 PMID: 17442337
  48. Domains of phosphatase inhibitor-2 involved in the control of the ATP-Mg-dependent protein phosphatase.
    J Biol Chem. 1994 Nov 18;269(46):28919-28 PMID: 7961854
  49. Disruption of a single copy of the SERCA2 gene results in altered Ca2+ homeostasis and cardiomyocyte function.
    J Biol Chem. 2000 Dec 1;275(48):38073-80 PMID: 10970890
  50. Phosphatase inhibitor-1-deficient mice are protected from catecholamine-induced arrhythmias and myocardial hypertrophy.
    Cardiovasc Res. 2008 Dec 1;80(3):396-406 PMID: 18689792
  51. Blockade of Hsp20 phosphorylation exacerbates cardiac ischemia/reperfusion injury by suppressed autophagy and increased cell death.
    Circ Res. 2009 Dec 4;105(12):1223-31 PMID: 19850943
  52. In vivo echocardiographic detection of enhanced left ventricular function in gene-targeted mice with phospholamban deficiency.
    Circ Res. 1995 Sep;77(3):632-7 PMID: 7641333
  53. Functional diversity of protein phosphatase-1, a cellular economizer and reset button.
    Physiol Rev. 2004 Jan;84(1):1-39 PMID: 14715909
  54. Human mutation in the anti-apoptotic heat shock protein 20 abrogates its cardioprotective effects.
    J Biol Chem. 2008 Nov 28;283(48):33465-71 PMID: 18790732
  55. Identification of the major protein phosphatases in mammalian cardiac muscle which dephosphorylate phospholamban.
    Eur J Biochem. 1991 Mar 28;196(3):725-34 PMID: 1849481
  56. Structure of the rabbit phospholamban gene, cloning of the human cDNA, and assignment of the gene to human chromosome 6.
    J Biol Chem. 1991 Jun 25;266(18):11669-75 PMID: 1828805
  57. A human polymorphism of protein phosphatase-1 inhibitor-1 is associated with attenuated contractile response of cardiomyocytes to beta-adrenergic stimulation.
    FASEB J. 2008 Jun;22(6):1790-6 PMID: 18192322
  58. Role of calcineurin and protein phosphatase-2A in the regulation of phosphatase inhibitor-1 in cardiac myocytes.
    Biochem Biophys Res Commun. 2006 Aug 4;346(3):700-6 PMID: 16774736
  59. Inducible expression of active protein phosphatase-1 inhibitor-1 enhances basal cardiac function and protects against ischemia/reperfusion injury.
    Circ Res. 2009 Apr 24;104(8):1012-20 PMID: 19299645
  60. Accelerated onset of heart failure in mice during pressure overload with chronically decreased SERCA2 calcium pump activity.
    Am J Physiol Heart Circ Physiol. 2004 Mar;286(3):H1146-53 PMID: 14630633
  61. Cardiac-specific overexpression of phospholamban alters calcium kinetics and resultant cardiomyocyte mechanics in transgenic mice.
    J Clin Invest. 1996 Jan 15;97(2):533-9 PMID: 8567978
  62. Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins.
    J Mol Cell Cardiol. 2007 Apr;42(4):852-61 PMID: 17300800
  63. Correlation between contraction and phosphorylation of the inhibitory subunit of troponin in perfused rat heart.
    FEBS Lett. 1975 Jan 15;50(1):57-60 PMID: 1109931
  64. Regulation of sarco(endo)plasmic reticulum Ca2+ adenosine triphosphatase by phospholamban and sarcolipin: implication for cardiac hypertrophy and failure.
    Trends Cardiovasc Med. 2003 May;13(4):152-7 PMID: 12732449
  65. Small heat shock protein 20 interacts with protein phosphatase-1 and enhances sarcoplasmic reticulum calcium cycling.
    Circ Res. 2011 Jun 10;108(12):1429-38 PMID: 21493896
  66. Threonine-17 phosphorylation of phospholamban: a key determinant of frequency-dependent increase of cardiac contractility.
    J Mol Cell Cardiol. 2004 Aug;37(2):607-12 PMID: 15276030
  67. Manipulating cardiac contractility in heart failure: data from mice and men.
    Circulation. 2004 Jan 20;109(2):150-8 PMID: 14734503
  68. Interaction of S100A1 with the Ca2+ release channel (ryanodine receptor) of skeletal muscle.
    Biochemistry. 1997 Sep 23;36(38):11496-503 PMID: 9298970
  69. Mutations in the human phospholamban gene in patients with heart failure.
    Am Heart J. 2011 Dec;162(6):1088-1095.e1 PMID: 22137083
  70. Sarcoplasmic reticulum Ca(2+) ATPase as a therapeutic target for heart failure.
    Expert Opin Biol Ther. 2010 Jan;10(1):29-41 PMID: 20078230
  71. Mutation of the phospholamban promoter associated with hypertrophic cardiomyopathy.
    Biochem Biophys Res Commun. 2003 Apr 25;304(1):1-4 PMID: 12705874
  72. Phospholamban is a good substrate for cyclic GMP-dependent protein kinase in vitro, but not in intact cardiac or smooth muscle.
    Biochem J. 1989 Jun 15;260(3):829-35 PMID: 2764906
  73. S100A1 is a novel molecular chaperone and a member of the Hsp70/Hsp90 multichaperone complex.
    J Biol Chem. 2004 Feb 6;279(6):4221-33 PMID: 14638689
  74. The transgenic expression of highly inhibitory monomeric forms of phospholamban in mouse heart impairs cardiac contractility.
    J Biol Chem. 2000 May 19;275(20):14985-91 PMID: 10809743
  75. Overexpression of calreticulin sensitizes SERCA2a to oxidative stress.
    Biochem Biophys Res Commun. 2005 Apr 22;329(4):1343-9 PMID: 15766574
  76. The role of phospholamban in the regulation of calcium transport by cardiac sarcoplasmic reticulum.
    Mol Cell Biochem. 1990 Dec 20;99(2):83-8 PMID: 1962847
  77. HAX-1: a multifaceted antiapoptotic protein localizing in the mitochondria and the sarcoplasmic reticulum of striated muscle cells.
    J Mol Cell Cardiol. 2010 Jun;48(6):1266-79 PMID: 19913549
  78. Plasticity of surface structures and β(2)-adrenergic receptor localization in failing ventricular cardiomyocytes during recovery from heart failure.
    Circ Heart Fail. 2012 May 1;5(3):357-65 PMID: 22456061
  79. Evidence for presence and hormonal regulation of protein phosphatase inhibitor-1 in ventricular cardiomyocyte.
    Am J Physiol. 1996 Apr;270(4 Pt 2):H1159-64 PMID: 8967352
  80. Structure-function relationships in Ca(2+) cycling proteins.
    J Mol Cell Cardiol. 2002 Aug;34(8):897-918 PMID: 12234762
  81. Phospholamban: protein structure, mechanism of action, and role in cardiac function.
    Physiol Rev. 1998 Oct;78(4):921-47 PMID: 9790566
  82. Cardiac AAV9-S100A1 gene therapy rescues post-ischemic heart failure in a preclinical large animal model.
    Sci Transl Med. 2011 Jul 20;3(92):92ra64 PMID: 21775667
  83. Inhibition of protein phosphatase 1 by inhibitor-2 gene delivery ameliorates heart failure progression in genetic cardiomyopathy.
    FASEB J. 2006 Jun;20(8):1197-9 PMID: 16627625
  84. Intracellular mechanisms mediating reversal of beta-adrenergic stimulation in intact beating hearts.
    Am J Physiol. 1993 Mar;264(3 Pt 2):H791-7 PMID: 8384422
  85. Stable myocardial-specific AAV6-S100A1 gene therapy results in chronic functional heart failure rescue.
    Circulation. 2007 May 15;115(19):2506-15 PMID: 17470693
  86. The anti-apoptotic protein HAX-1 interacts with SERCA2 and regulates its protein levels to promote cell survival.
    Mol Biol Cell. 2009 Jan;20(1):306-18 PMID: 18971376
  87. A human phospholamban promoter polymorphism in dilated cardiomyopathy alters transcriptional regulation by glucocorticoids.
    Hum Mutat. 2008 May;29(5):640-7 PMID: 18241046
  88. Regulatory effects of phospholamban on cardiac function in intact mice.
    Am J Physiol. 1997 Dec;273(6):H2826-31 PMID: 9435620
  89. Nature and site of phospholamban regulation of the Ca2+ pump of sarcoplasmic reticulum.
    Nature. 1989 Nov 2;342(6245):90-2 PMID: 2530454
  90. Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure.
    Circulation. 2011 Jul 19;124(3):304-13 PMID: 21709064
  91. A regulation of the level of phosphorylated phospholamban by inhibitor-1 in rat heart preparations in vitro.
    Mol Cell Endocrinol. 1988 Jan;55(1):1-6 PMID: 2834240
  92. Targeted ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of beta-agonist stimulation.
    Circ Res. 1994 Sep;75(3):401-9 PMID: 8062415
  93. Overexpression of the rat sarcoplasmic reticulum Ca2+ ATPase gene in the heart of transgenic mice accelerates calcium transients and cardiac relaxation.
    J Clin Invest. 1997 Jul 15;100(2):380-9 PMID: 9218515
  94. Phosphorylation of troponin I and phospholamban during catecholamine stimulation of rabbit heart.
    Nature. 1982 Jul 8;298(5870):182-4 PMID: 6211626
  95. Sites of regulatory interaction between calcium ATPases and phospholamban.
    Ann N Y Acad Sci. 1998 Sep 16;853:31-42 PMID: 10603934
  96. Design of a phase 1/2 trial of intracoronary administration of AAV1/SERCA2a in patients with heart failure.
    J Card Fail. 2008 Jun;14(5):355-67 PMID: 18514926
  97. Phosphorylation and functional modifications of sarcoplasmic reticulum and myofibrils in isolated rabbit hearts stimulated with isoprenaline.
    Biochem J. 1985 Feb 15;226(1):113-21 PMID: 3156585
  98. Phospholamban interacts with HAX-1, a mitochondrial protein with anti-apoptotic function.
    J Mol Biol. 2007 Mar 16;367(1):65-79 PMID: 17241641
  99. Altered stoichiometry of FKBP12.6 versus ryanodine receptor as a cause of abnormal Ca(2+) leak through ryanodine receptor in heart failure.
    Circulation. 2000 Oct 24;102(17):2131-6 PMID: 11044432
  100. Weighing in on heart failure: the role of SERCA2a SUMOylation.
    Circ Res. 2012 Jan 20;110(2):198-9 PMID: 22267837
  101. MicroRNA-320 is involved in the regulation of cardiac ischemia/reperfusion injury by targeting heat-shock protein 20.
    Circulation. 2009 May 5;119(17):2357-2366 PMID: 19380620
  102. Localization, macromolecular associations, and function of the small heat shock-related protein HSP20 in rat heart.
    Circulation. 2003 Jan 28;107(3):469-76 PMID: 12551873
  103. Regulation of calcium transport by protein phosphatase activity associated with cardiac sarcoplasmic reticulum.
    J Biol Chem. 1985 Sep 15;260(20):11006-10 PMID: 2993298
  104. Overexpression of HAX-1 protects cardiac myocytes from apoptosis through caspase-9 inhibition.
    Circ Res. 2006 Aug 18;99(4):415-23 PMID: 16857965
  105. Histidine-rich Ca-binding protein interacts with sarcoplasmic reticulum Ca-ATPase.
    Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1581-9 PMID: 17526652
  106. Enhancement of cardiac function and suppression of heart failure progression by inhibition of protein phosphatase 1.
    Circ Res. 2005 Apr 15;96(7):756-66 PMID: 15746443
  107. Discovery of phospholamban. A personal history.
    Ann N Y Acad Sci. 1998 Sep 16;853:9-19 PMID: 10603932
  108. Gender influences on sarcoplasmic reticulum Ca2+-handling in failing human myocardium.
    J Mol Cell Cardiol. 2001 Jul;33(7):1345-53 PMID: 11437540
  109. Ca2+ -dependent interaction of S100A1 with the sarcoplasmic reticulum Ca2+ -ATPase2a and phospholamban in the human heart.
    Biochem Biophys Res Commun. 2003 Jun 27;306(2):550-7 PMID: 12804600
  110. Catecholaminergic-induced arrhythmias in failing cardiomyocytes associated with human HRCS96A variant overexpression.
    Am J Physiol Heart Circ Physiol. 2011 Oct;301(4):H1588-95 PMID: 21742996
  111. Structural and functional implications of the phospholamban hinge domain: impaired SR Ca2+ uptake as a primary cause of heart failure.
    Cardiovasc Res. 2002 Nov;56(2):248-59 PMID: 12393095
  112. Evidence for isoproterenol-induced phosphorylation of phosphatase inhibitor-1 in the intact heart.
    Circ Res. 1991 Dec;69(6):1450-7 PMID: 1659500
  113. Identification of a novel phosphorylation site in protein phosphatase inhibitor-1 as a negative regulator of cardiac function.
    J Biol Chem. 2006 Dec 15;281(50):38599-608 PMID: 17046826
  114. Phospholamban gene dosage effects in the mammalian heart.
    Circ Res. 1996 May;78(5):839-47 PMID: 8620604
  115. Protection from cardiac arrhythmia through ryanodine receptor-stabilizing protein calstabin2.
    Science. 2004 Apr 9;304(5668):292-6 PMID: 15073377
  116. Histidine-rich Ca binding protein: a regulator of sarcoplasmic reticulum calcium sequestration and cardiac function.
    J Mol Cell Cardiol. 2006 May;40(5):653-65 PMID: 16600288
  117. Superinhibition of sarcoplasmic reticulum function by phospholamban induces cardiac contractile failure.
    J Biol Chem. 2001 Jun 29;276(26):24145-52 PMID: 11328820
  118. Protein phosphatase inhibitor-1 augments a protein kinase A-dependent increase in the Ca2+ loading of the sarcoplasmic reticulum without changing its Ca2+ release.
    Circ J. 2009 Jun;73(6):1133-40 PMID: 19377265
  119. Recirculating cardiac delivery of AAV2/1SERCA2a improves myocardial function in an experimental model of heart failure in large animals.
    Gene Ther. 2008 Dec;15(23):1550-7 PMID: 18650850
  120. Transgenic overexpression of the sarcoplasmic reticulum Ca2+ATPase improves reticular Ca2+ handling in normal and diabetic rat hearts.
    FASEB J. 2002 Oct;16(12):1657-9 PMID: 12206992
  121. Altered expression of the Ca(2+)-binding protein S100A1 in human cardiomyopathy.
    Biochim Biophys Acta. 1996 Oct 11;1313(3):253-7 PMID: 8898862
  122. beta-Adrenergic stimulation of phospholamban phosphorylation and Ca2+-ATPase activity in guinea pig ventricles.
    J Biol Chem. 1983 Jan 10;258(1):464-71 PMID: 6217205
  123. SERCA2a gene transfer decreases sarcoplasmic reticulum calcium leak and reduces ventricular arrhythmias in a model of chronic heart failure.
    Circ Arrhythm Electrophysiol. 2011 Jun;4(3):362-72 PMID: 21406682
  124. Cyclic adenosine 3',5'-monophosphate-dependent protein kinase stimulation of calcium uptake by canine cardiac microsomes.
    J Mol Cell Cardiol. 1972 Dec;4(6):673-80 PMID: 4347149
Article Info
Journal
Circulation research
Abbr.
Circ Res
ISSN
1524-4571
DOI
10.1161/CIRCRESAHA.111.259754
Email
[email protected]
Published
2012-06-08
Pages
1646-60
Language
English
Region
United States
NLM ID
0047103
PMCID
PMC3392125
Subset
IM
Grants
NHLBI NIH HHS · HL-26057 · United States
NHLBI NIH HHS · HL088434 · United States
NHLBI NIH HHS · HL093183 · United States
NHLBI NIH HHS · HL100396 · United States
NHLBI NIH HHS · R01 HL088434 · United States
NHLBI NIH HHS · R01 HL080498 · United States
NHLBI NIH HHS · HL080498 · United States
NHLBI NIH HHS · P20 HL100396 · United States
NHLBI NIH HHS · HL083156 · United States
NHLBI NIH HHS · R01 HL083156 · United States
NHLBI NIH HHS · R01 HL064018 · United States
NHLBI NIH HHS · R01 HL093183 · United States
NHLBI NIH HHS · R37 HL026057 · United States
NHLBI NIH HHS · HHSN268201000045C · United States
NHLBI NIH HHS · HL-64018 · United States
NHLBI NIH HHS · R01 HL026057 · United States
External Links
PubMed source DOI: 10.1161/CIRCRESAHA.111.259754 PMC Full Text View journal details
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