Cyclic GMP/Protein Kinase Localized Signaling and Disease Implications

Chapter
Part of the Cardiac and Vascular Biology book series (Abbreviated title: Card. vasc. biol.)

Abstract

Cyclic guanosine 3′,5′-monophosphate (cGMP) and its downstream target, protein kinase G (PKG or cGK), play central roles in cellular regulation and are important to cardiovascular homeostasis and disease pathophysiology. Cyclic GMP is synthesized via either nitric oxide (NO) or natriuretic peptide (NP) stimulation pathways, each coupled to corresponding cyclases, and catabolized by select members of the phosphodiesterase superfamily. Growing evidence now supports control of cGMP and PKG in distinct microdomains within the myocyte, which results in differential downstream targeting. This regional control stems from distinct localization of the relevant signaling components and their capacity to translocate in the cell under both physiological and pathophysiological conditions to further impact the net response. This chapter discusses current understanding of microdomain regulation of the cGMP/PKG pathway, as this information is important to optimally leverage their effects for the treatment of cardiovascular disease.

References

  1. Adams SR, Harootunian AT, Buechler YJ, Taylor SS, Tsien RY (1991) Fluorescence ratio imaging of cyclic AMP in single cells. Nature 349:694–697PubMedCrossRefGoogle Scholar
  2. Ahmad F, Shen W, Vandeput F, Szabo-Fresnais N, Krall J, Degerman E, Goetz F, Klussmann E, Movsesian M, Manganiello V (2015) Regulation of sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2) activity by phosphodiesterase 3A (PDE3A) in human myocardium: phosphorylation-dependent interaction of PDE3A1 with SERCA2. J Biol Chem 290:6763–6776PubMedPubMedCentralCrossRefGoogle Scholar
  3. Anand-Srivastava MB (2005) Natriuretic peptide receptor-C signaling and regulation. Peptides 26:1044–1059PubMedCrossRefGoogle Scholar
  4. Balligand JL (2013) Beta3-adrenoreceptors in cardiovascular diseases: new roles for an “old” receptor. Curr Drug Deliv 10:64–66PubMedCrossRefGoogle Scholar
  5. Blanton RM, Takimoto E, Lane AM, Aronovitz M, Piotrowski R, Karas RH, Kass DA, Mendelsohn ME (2012) Protein kinase G Ialpha inhibits pressure overload-induced cardiac remodeling and is required for the cardioprotective effect of sildenafil in vivo. J Am Heart Assoc 1:e003731PubMedPubMedCentralCrossRefGoogle Scholar
  6. Bubb KJ, Trinder SL, Baliga RS, Patel J, Clapp LH, Macallister RJ, Hobbs AJ (2014) Inhibition of phosphodiesterase 2 augments cGMP and cAMP signaling to ameliorate pulmonary hypertension. Circulation 130:496–507PubMedPubMedCentralCrossRefGoogle Scholar
  7. Burgoyne JR, Eaton P (2009) Transnitrosylating nitric oxide species directly activate type I protein kinase A, providing a novel adenylate cyclase-independent cross-talk to beta-adrenergic-like signaling. J Biol Chem 284:29260–29268PubMedPubMedCentralCrossRefGoogle Scholar
  8. Burgoyne JR, Madhani M, Cuello F, Charles RL, Brennan JP, Schroder E, Browning DD, Eaton P (2007) Cysteine redox sensor in PKGIa enables oxidant-induced activation. Science 317:1393–1397PubMedCrossRefGoogle Scholar
  9. Bush EW, Hood DB, Papst PJ, Chapo JA, Minobe W, Bristow MR, Olson EN, Mckinsey TA (2006) Canonical transient receptor potential channels promote cardiomyocyte hypertrophy through activation of calcineurin signaling. J Biol Chem 281:33487–33496PubMedCrossRefGoogle Scholar
  10. Buys ES, Cauwels A, Raher MJ, Passeri JJ, Hobai I, Cawley SM, Rauwerdink KM, Thibault H, Sips PY, Thoonen R, Scherrer-Crosbie M, Ichinose F, Brouckaert P, Bloch KD (2009) sGC(alpha)1(beta)1 attenuates cardiac dysfunction and mortality in murine inflammatory shock models. Am J Physiol Heart Circ Physiol 297:H654–H663PubMedPubMedCentralCrossRefGoogle Scholar
  11. Castro LR, Verde I, Cooper DM, Fischmeister R (2006) Cyclic guanosine monophosphate compartmentation in rat cardiac myocytes. Circulation 113:2221–2228PubMedPubMedCentralCrossRefGoogle Scholar
  12. Cayouette S, Lussier MP, Mathieu EL, Bousquet SM, Boulay G (2004) Exocytotic insertion of TRPC6 channel into the plasma membrane upon Gq protein-coupled receptor activation. J Biol Chem 279:7241–7246PubMedCrossRefGoogle Scholar
  13. Chaudhuri P, Rosenbaum MA, Sinharoy P, Damron DS, Birnbaumer L, Graham LM (2016) Membrane translocation of TRPC6 channels and endothelial migration are regulated by Calmodulin and PI3 kinase activation. Proc Natl Acad Sci U S A 113:2110–2115PubMedPubMedCentralCrossRefGoogle Scholar
  14. Chen W, Spitzl A, Mathes D, Nikolaev VO, Werner F, Weirather J, Spiranec K, Rock K, Fischer JW, Kammerer U, Stegner D, Baba HA, Hofmann U, Frantz S, Kuhn M (2016) Endothelial actions of ANP enhance myocardial inflammatory infiltration in the early phase after acute infarction. Circ Res 119:237–248PubMedCrossRefGoogle Scholar
  15. Cingolani HE, Perez NG, Cingolani OH, Ennis IL (2013) The Anrep effect: 100 years later. Am J Physiol Heart Circ Physiol 304:H175–H182PubMedCrossRefGoogle Scholar
  16. Conti M, Beavo J (2007) Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling. Annu Rev Biochem 76:481–511PubMedCrossRefGoogle Scholar
  17. Del Ry S (2013) C-type natriuretic peptide: a new cardiac mediator. Peptides 40:93–98PubMedCrossRefGoogle Scholar
  18. Del Ry S, Cabiati M, Vozzi F, Battolla B, Caselli C, Forini F, Segnani C, Prescimone T, Giannessi D, Mattii L (2011) Expression of C-type natriuretic peptide and its receptor NPR-B in cardiomyocytes. Peptides 32:1713–1718PubMedCrossRefGoogle Scholar
  19. Derbyshire ER, Marletta MA (2012) Structure and regulation of soluble guanylate cyclase. Annu Rev Biochem 81:533–559PubMedCrossRefGoogle Scholar
  20. Dietrich A, Gudermann T (2014) TRPC6: physiological function and pathophysiological relevance. Handb Exp Pharmacol 222:157–188PubMedCrossRefGoogle Scholar
  21. Dipilato LM, Cheng X, Zhang J (2004) Fluorescent indicators of cAMP and Epac activation reveal differential dynamics of cAMP signaling within discrete subcellular compartments. Proc Natl Acad Sci U S A 101:16513–16518PubMedPubMedCentralCrossRefGoogle Scholar
  22. Dou D, Zheng X, Liu J, Xu X, Ye L, Gao Y (2012) Hydrogen peroxide enhances vasodilatation by increasing dimerization of cGMP-dependent protein kinase type Ialpha. Circ J 76:1792–1798PubMedCrossRefGoogle Scholar
  23. Fisher DA, Smith JF, Pillar JS, St Denis SH, Cheng JB (1998) Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase. J Biol Chem 273:15559–15564PubMedCrossRefGoogle Scholar
  24. Forstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J 33:829–837. 837a–837dPubMedCrossRefGoogle Scholar
  25. Francis SH, Blount MA, Corbin JD (2011) Mammalian cyclic nucleotide phosphodiesterases: molecular mechanisms and physiological functions. Physiol Rev 91:651–690PubMedCrossRefGoogle Scholar
  26. Geiselhoringer A, Gaisa M, Hofmann F, Schlossmann J (2004) Distribution of Iraq and cGKI-isoforms in murine tissues. FEBS Lett 575:19–22PubMedCrossRefGoogle Scholar
  27. Gheorghiade M, Marti CN, Sabbah HN, Roessig L, Greene SJ, Bohm M, Burnett JC, Campia U, Cleland JG, Collins SP, Fonarow GC, Levy PD, Metra M, Pitt B, Ponikowski P, Sato N, Voors AA, Stasch JP, Butler J, Academic Research Team in Heart F (2013) Soluble guanylate cyclase: a potential therapeutic target for heart failure. Heart Fail Rev 18:123–134PubMedCrossRefGoogle Scholar
  28. Gisbert MP, Fischmeister R (1988) Atrial natriuretic factor regulates the calcium current in frog isolated cardiac cells. Circ Res 62:660–667PubMedCrossRefGoogle Scholar
  29. Gotz KR, Sprenger JU, Perera RK, Steinbrecher JH, Lehnart SE, Kuhn M, Gorelik J, Balligand JL, Nikolaev VO (2014) Transgenic mice for real-time visualization of cGMP in intact adult cardiomyocytes. Circ Res 114:1235–1245PubMedCrossRefGoogle Scholar
  30. Hao J, Michalek C, Zhang W, Zhu M, Xu X, Mende U (2006) Regulation of cardiomyocyte signaling by RGS proteins: differential selectivity towards G proteins and susceptibility to regulation. J Mol Cell Cardiol 41:51–61PubMedCrossRefGoogle Scholar
  31. Heximer SP, Watson N, Linder ME, Blumer KJ, Hepler JR (1997) RGS2/G0S8 is a selective inhibitor of Gqalpha function. Proc Natl Acad Sci U S A 94:14389–14393PubMedPubMedCentralCrossRefGoogle Scholar
  32. Honda A, Adams SR, Sawyer CL, Lev-Ram V, Tsien RY, Dostmann WR (2001) Spatiotemporal dynamics of guanosine 3',5'-cyclic monophosphate revealed by a genetically encoded, fluorescent indicator. Proc Natl Acad Sci U S A 98:2437–2442PubMedPubMedCentralCrossRefGoogle Scholar
  33. Horio T, Tokudome T, Maki T, Yoshihara F, Suga S, Nishikimi T, Kojima M, Kawano Y, Kangawa K (2003) Gene expression, secretion, and autocrine action of C-type natriuretic peptide in cultured adult rat cardiac fibroblasts. Endocrinology 144:2279–2284PubMedCrossRefGoogle Scholar
  34. Inserte J, Garcia-Dorado D (2015) The cGMP/PKG pathway as a common mediator of cardioprotection: translatability and mechanism. Br J Pharmacol 172:1996–2009PubMedPubMedCentralCrossRefGoogle Scholar
  35. Johnson WB, Katugampola S, Able S, Napier C, Harding SE (2012) Profiling of cAMP and cGMP phosphodiesterases in isolated ventricular cardiomyocytes from human hearts: comparison with rat and Guinea pig. Life Sci 90:328–336PubMedCrossRefGoogle Scholar
  36. Karbach S, Wenzel P, Waisman A, Munzel T, Daiber A (2014) eNOS uncoupling in cardiovascular diseases—the role of oxidative stress and inflammation. Curr Pharm Des 20:3579–3594PubMedCrossRefGoogle Scholar
  37. Kass DA (2012) Cardiac role of cyclic-GMP hydrolyzing phosphodiesterase type 5: from experimental models to clinical trials. Curr Heart Fail Rep 9:192–199PubMedPubMedCentralCrossRefGoogle Scholar
  38. Kim GE, Kass DA (2016) Cardiac phosphodiesterases and their modulation for treating heart disease. In: Handbook of experimental pharmacology. Springer, BerlinGoogle Scholar
  39. Kinugawa S, Huang H, Wang Z, Kaminski PM, Wolin MS, Hintze TH (2005) A defect of neuronal nitric oxide synthase increases xanthine oxidase-derived superoxide anion and attenuates the control of myocardial oxygen consumption by nitric oxide derived from endothelial nitric oxide synthase. Circ Res 96:355–362PubMedCrossRefGoogle Scholar
  40. Klaiber M, Kruse M, Volker K, Schroter J, Feil R, Freichel M, Gerling A, Feil S, Dietrich A, Londono JE, Baba HA, Abramowitz J, Birnbaumer L, Penninger JM, Pongs O, Kuhn M (2010) Novel insights into the mechanisms mediating the local antihypertrophic effects of cardiac atrial natriuretic peptide: role of cGMP-dependent protein kinase and RGS2. Basic Res Cardiol 105:583–595PubMedPubMedCentralCrossRefGoogle Scholar
  41. Knight WE, Chen S, Zhang Y, Oikawa M, Wu M, Zhou Q, Miller CL, Cai Y, Mickelsen DM, Moravec C, Small EM, Abe J, Yan C (2016) PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction. Proc Natl Acad Sci U S A 113(45):E7116–E7125PubMedCentralCrossRefGoogle Scholar
  42. Kockskamper J, Von Lewinski D, Khafaga M, Elgner A, Grimm M, Eschenhagen T, Gottlieb PA, Sachs F, Pieske B (2008) The slow force response to stretch in atrial and ventricular myocardium from human heart: functional relevance and subcellular mechanisms. Prog Biophys Mol Biol 97:250–267PubMedPubMedCentralCrossRefGoogle Scholar
  43. Koitabashi N, Aiba T, Hesketh GG, Rowell J, Zhang M, Takimoto E, Tomaselli GF, Kass DA (2010) Cyclic GMP/PKG-dependent inhibition of TRPC6 channel activity and expression negatively regulates cardiomyocyte NFAT activation novel mechanism of cardiac stress modulation by PDE5 inhibition. J Mol Cell Cardiol 48:713–724PubMedCrossRefGoogle Scholar
  44. Kokkonen K, Kass DA (2016) Nanodomain regulation of cardiac cyclic nucleotide signaling by phosphodiesterases. Annu Rev Pharmacol Toxicol 57:455–479PubMedCrossRefGoogle Scholar
  45. Koller KJ, Goeddel DV (1992) Molecular biology of the natriuretic peptides and their receptors. Circulation 86:1081–1088PubMedCrossRefGoogle Scholar
  46. Krawutschke C, Koesling D, Russwurm M (2015) Cyclic GMP in vascular relaxation: export is of similar importance as degradation. Arterioscler Thromb Vasc Biol 35:2011–2019PubMedCrossRefGoogle Scholar
  47. Kruger M, Kotter S, Grutzner A, Lang P, Andresen C, Redfield MM, Butt E, Dos Remedios CG, Linke WA (2009) Protein kinase G modulates human myocardial passive stiffness by phosphorylation of the titin springs. Circ Res 104:87–94PubMedCrossRefGoogle Scholar
  48. Kuhn M (2016) Molecular physiology of membrane guanylyl cyclase receptors. Physiol Rev 96:751–804PubMedCrossRefGoogle Scholar
  49. Kukreja RC, Salloum F, Das A, Ockaili R, Yin C, Bremer YA, Fisher PW, Wittkamp M, Hawkins J, Chou E, Kukreja AK, Wang X, Marwaha VR, Xi L (2005) Pharmacological preconditioning with sildenafil: basic mechanisms and clinical implications. Vasc Pharmacol 42:219–232CrossRefGoogle Scholar
  50. Kuwahara K, Wang Y, Mcanally J, Richardson JA, Bassel-Duby R, Hill JA, Olson EN (2006) TRPC6 fulfills a calcineurin signaling circuit during pathologic cardiac remodeling. J Clin Invest 116:3114–3126PubMedPubMedCentralCrossRefGoogle Scholar
  51. Langenickel TH, Buttgereit J, Pagel-Langenickel I, Lindner M, Monti J, Beuerlein K, Al-Saadi N, Plehm R, Popova E, Tank J, Dietz R, Willenbrock R, Bader M (2006) Cardiac hypertrophy in transgenic rats expressing a dominant-negative mutant of the natriuretic peptide receptor B. Proc Natl Acad Sci U S A 103:4735–4740PubMedPubMedCentralCrossRefGoogle Scholar
  52. Layland J, Li JM, Shah AM (2002) Role of cyclic GMP-dependent protein kinase in the contractile response to exogenous nitric oxide in rat cardiac myocytes. J Physiol 540:457–467PubMedPubMedCentralCrossRefGoogle Scholar
  53. Lee DI, Vahebi S, Tocchetti CG, Barouch LA, Solaro RJ, Takimoto E, Kass DA (2010) PDE5A suppression of acute beta-adrenergic activation requires modulation of myocyte beta-3 signaling coupled to PKG-mediated troponin I phosphorylation. Basic Res Cardiol 105:337–347PubMedPubMedCentralCrossRefGoogle Scholar
  54. Lee DI, Zhu G, Sasaki T, Cho GS, Hamdani N, Holewinski R, Jo SH, Danner T, Zhang M, Rainer PP, Bedja D, Kirk JA, Ranek MJ, Dostmann WR, Kwon C, Margulies KB, Van Eyk JE, Paulus WJ, Takimoto E, Kass DA (2015) Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease. Nature 519:472–476PubMedPubMedCentralCrossRefGoogle Scholar
  55. Li Y, Sarkar O, Brochu M, Anand-Srivastava MB (2014) Natriuretic peptide receptor-C attenuates hypertension in spontaneously hypertensive rats: role of nitroxidative stress and Gi proteins. Hypertension 63:846–855PubMedCrossRefGoogle Scholar
  56. Liu H, Maurice DH (1998) Expression of cyclic GMP-inhibited phosphodiesterases 3A and 3B (PDE3A and PDE3B) in rat tissues: differential subcellular localization and regulated expression by cyclic AMP. Br J Pharmacol 125:1501–1510PubMedPubMedCentralCrossRefGoogle Scholar
  57. Liu Y, Dillon AR, Tillson M, Makarewich C, Nguyen V, Dell’italia L, Sabri AK, Rizzo V, Tsai EJ (2013) Volume overload induces differential spatiotemporal regulation of myocardial soluble guanylyl cyclase in eccentric hypertrophy and heart failure. J Mol Cell Cardiol 60:72–83PubMedPubMedCentralCrossRefGoogle Scholar
  58. Logue JS, Scott JD (2010) Organizing signal transduction through A-kinase anchoring proteins (AKAPs). FEBS J 277:4370–4375PubMedPubMedCentralCrossRefGoogle Scholar
  59. Madhani M, Hall AR, Cuello F, Charles RL, Burgoyne JR, Fuller W, Hobbs AJ, Shattock MJ, Eaton P (2010) Phospholemman Ser69 phosphorylation contributes to sildenafil-induced cardioprotection against reperfusion injury. Am J Physiol Heart Circ Physiol 299:H827–H836PubMedPubMedCentralCrossRefGoogle Scholar
  60. Makarewich CA, Zhang H, Davis J, Correll RN, Trappanese DM, Hoffman NE, Troupes CD, Berretta RM, Kubo H, Madesh M, Chen X, Gao E, Molkentin JD, Houser SR (2014) Transient receptor potential channels contribute to pathological structural and functional remodeling after myocardial infarction. Circ Res 115:567–580PubMedPubMedCentralCrossRefGoogle Scholar
  61. Mattiazzi A, Mundina-Weilenmann C, Guoxiang C, Vittone L, Kranias E (2005) Role of phospholamban phosphorylation on Thr17 in cardiac physiological and pathological conditions. Cardiovasc Res 68:366–375PubMedCrossRefGoogle Scholar
  62. Mcmurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR, PARADIGM-HF Investigators & Committees (2014) Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 371:993–1004PubMedCrossRefGoogle Scholar
  63. Mehel H, Emons J, Vettel C, Wittkopper K, Seppelt D, Dewenter M, Lutz S, Sossalla S, Maier LS, Lechene P, Leroy J, Lefebvre F, Varin A, Eschenhagen T, Nattel S, Dobrev D, Zimmermann WH, Nikolaev VO, Vandecasteele G, Fischmeister R, El-Armouche A (2013) Phosphodiesterase-2 is up-regulated in human failing hearts and blunts beta-adrenergic responses in cardiomyocytes. J Am Coll Cardiol 62:1596–1606PubMedCrossRefGoogle Scholar
  64. Mery PF, Pavoine C, Belhassen L, Pecker F, Fischmeister R (1993) Nitric oxide regulates cardiac Ca2+ current. Involvement of cGMP-inhibited and cGMP-stimulated phosphodiesterases through guanylyl cyclase activation. J Biol Chem 268:26286–26295PubMedGoogle Scholar
  65. Miller CL, Oikawa M, Cai Y, Wojtovich AP, Nagel DJ, Xu X, Xu H, Florio V, Rybalkin SD, Beavo JA, Chen YF, Li JD, Blaxall BC, Abe J, Yan C (2009) Role of Ca2+/calmodulin-stimulated cyclic nucleotide phosphodiesterase 1 in mediating cardiomyocyte hypertrophy. Circ Res 105:956–964PubMedPubMedCentralCrossRefGoogle Scholar
  66. Miller CL, Cai Y, Oikawa M, Thomas T, Dostmann WR, Zaccolo M, Fujiwara K, Yan C (2011) Cyclic nucleotide phosphodiesterase 1A: a key regulator of cardiac fibroblast activation and extracellular matrix remodeling in the heart. Basic Res Cardiol 106:1023–1039PubMedPubMedCentralCrossRefGoogle Scholar
  67. Mittmann C, Chung CH, Hoppner G, Michalek C, Nose M, Schuler C, Schuh A, Eschenhagen T, Weil J, Pieske B, Hirt S, Wieland T (2002) Expression of ten RGS proteins in human myocardium: functional characterization of an upregulation of RGS4 in heart failure. Cardiovasc Res 55:778–786PubMedCrossRefGoogle Scholar
  68. Mongillo M, Tocchetti CG, Terrin A, Lissandron V, Cheung YF, Dostmann WR, Pozzan T, Kass DA, Paolocci N, Houslay MD, Zaccolo M (2006) Compartmentalized phosphodiesterase-2 activity blunts beta-adrenergic cardiac inotropy via an NO/cGMP-dependent pathway. Circ Res 98:226–234PubMedCrossRefGoogle Scholar
  69. Nagayama T, Zhang M, Hsu S, Takimoto E, Kass DA (2008) Sustained soluble guanylate cyclase stimulation offsets nitric-oxide synthase inhibition to restore acute cardiac modulation by sildenafil. J Pharmacol Exp Ther 326:380–387PubMedCrossRefGoogle Scholar
  70. Nakamura T, Ranek MJ, Lee DI, Shalkey Hahn V, Kim C, Eaton P, Kass DA (2015) Prevention of PKG1alpha oxidation augments cardioprotection in the stressed heart. J Clin Invest 125:2468–2472PubMedPubMedCentralCrossRefGoogle Scholar
  71. Nakayama H, Wilkin BJ, Bodi I, Molkentin JD (2006) Calcineurin-dependent cardiomyopathy is activated by TRPC in the adult mouse heart. FASEB J 20:1660–1670PubMedPubMedCentralCrossRefGoogle Scholar
  72. Nausch LW, Ledoux J, Bonev AD, Nelson MT, Dostmann WR (2008) Differential patterning of cGMP in vascular smooth muscle cells revealed by single GFP-linked biosensors. Proc Natl Acad Sci U S A 105:365–370PubMedCrossRefGoogle Scholar
  73. Nikolaev VO, Gambaryan S, Lohse MJ (2006) Fluorescent sensors for rapid monitoring of intracellular cGMP. Nat Methods 3:23–25PubMedCrossRefGoogle Scholar
  74. Onohara N, Nishida M, Inoue R, Kobayashi H, Sumimoto H, Sato Y, Mori Y, Nagao T, Kurose H (2006) TRPC3 and TRPC6 are essential for angiotensin II-induced cardiac hypertrophy. EMBO J 25:5305–5316PubMedPubMedCentralCrossRefGoogle Scholar
  75. Perera RK, Sprenger JU, Steinbrecher JH, Hubscher D, Lehnart SE, Abesser M, Schuh K, El-Armouche A, Nikolaev VO (2015) Microdomain switch of cGMP-regulated phosphodiesterases leads to ANP-induced augmentation of beta-adrenoceptor-stimulated contractility in early cardiac hypertrophy. Circ Res 116:1304–1311PubMedCrossRefGoogle Scholar
  76. Prysyazhna O, Eaton P (2015) Redox regulation of cGMP-dependent protein kinase Ialpha in the cardiovascular system. Front Pharmacol 6:139PubMedPubMedCentralCrossRefGoogle Scholar
  77. Prysyazhna O, Rudyk O, Eaton P (2012) Single atom substitution in mouse protein kinase G eliminates oxidant sensing to cause hypertension. Nat Med 18:286–290PubMedPubMedCentralCrossRefGoogle Scholar
  78. Prysyazhna O, Burgoyne JR, Scotcher J, Grover S, Kass D, Eaton P (2016) Phosphodiesterase 5 inhibition limits doxorubicin-induced heart failure by attenuating protein kinase G Ialpha oxidation. J Biol Chem 291:17427–17436PubMedPubMedCentralCrossRefGoogle Scholar
  79. Ranek MJ, Terpstra EJ, Li J, Kass DA, Wang X (2013) Protein kinase G positively regulates proteasome-mediated degradation of misfolded proteins. Circulation 128:365–376PubMedPubMedCentralCrossRefGoogle Scholar
  80. Ranek MJ, Kost CK Jr, Hu C, Martin DS, Wang X (2014) Muscarinic 2 receptors modulate cardiac proteasome function in a protein kinase G-dependent manner. J Mol Cell Cardiol 69:43–51PubMedPubMedCentralCrossRefGoogle Scholar
  81. Roy AA, Lemberg KE, Chidiac P (2003) Recruitment of RGS2 and RGS4 to the plasma membrane by G proteins and receptors reflects functional interactions. Mol Pharmacol 64:587–593PubMedCrossRefGoogle Scholar
  82. Rudyk O, Prysyazhna O, Burgoyne JR, Eaton P (2012) Nitroglycerin fails to lower blood pressure in redox-dead Cys42Ser PKG1alpha knock-in mouse. Circulation 126:287–295PubMedPubMedCentralCrossRefGoogle Scholar
  83. Rudyk O, Phinikaridou A, Prysyazhna O, Burgoyne JR, Botnar RM, Eaton P (2013) Protein kinase G oxidation is a major cause of injury during sepsis. Proc Natl Acad Sci U S A 110:9909–9913PubMedPubMedCentralCrossRefGoogle Scholar
  84. Scotcher J, Prysyazhna O, Boguslavskyi A, Kistamas K, Hadgraft N, Martin ED, Worthington J, Rudyk O, Rodriguez Cutillas P, Cuello F, Shattock MJ, Marber MS, Conte MR, Greenstein A, Greensmith DJ, Venetucci L, Timms JF, Eaton P (2016) Disulfide-activated protein kinase G Ialpha regulates cardiac diastolic relaxation and fine-tunes the Frank-Starling response. Nat Commun 7:13187PubMedPubMedCentralCrossRefGoogle Scholar
  85. Sears CE, Bryant SM, Ashley EA, Lygate CA, Rakovic S, Wallis HL, Neubauer S, Terrar DA, Casadei B (2003) Cardiac neuronal nitric oxide synthase isoform regulates myocardial contraction and calcium handling. Circ Res 92:e52–e59PubMedCrossRefGoogle Scholar
  86. Seddon M, Shah AM, Casadei B (2007) Cardiomyocytes as effectors of nitric oxide signalling. Cardiovasc Res 75:315–326PubMedCrossRefGoogle Scholar
  87. Senzaki H, Smith CJ, Juang GJ, Isoda T, Mayer SP, Ohler A, Paolocci N, Tomaselli GF, Hare JM, Kass DA (2001) Cardiac phosphodiesterase 5 (cGMP-specific) modulates beta-adrenergic signaling in vivo and is down-regulated in heart failure. FASEB J 15:1718–1726PubMedCrossRefGoogle Scholar
  88. Seo K, Rainer PP, Lee DI, Hao S, Bedja D, Birnbaumer L, Cingolani OH, Kass DA (2014a) Hyperactive adverse mechanical stress responses in dystrophic heart are coupled to transient receptor potential canonical 6 and blocked by cGMP-protein kinase G modulation. Circ Res 114:823–832PubMedPubMedCentralCrossRefGoogle Scholar
  89. Seo K, Rainer PP, Shalkey Hahn V, Lee DI, Jo SH, Andersen A, Liu T, Xu X, Willette RN, Lepore JJ, Marino JP Jr, Birnbaumer L, Schnackenberg CG, Kass DA (2014b) Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy. Proc Natl Acad Sci U S A 111:1551–1556PubMedPubMedCentralCrossRefGoogle Scholar
  90. Shi J, Geshi N, Takahashi S, Kiyonaka S, Ichikawa J, Hu Y, Mori Y, Ito Y, Inoue R (2013) Molecular determinants for cardiovascular TRPC6 channel regulation by Ca2+/calmodulin-dependent kinase II. J Physiol 591:2851–2866PubMedPubMedCentralCrossRefGoogle Scholar
  91. Simon JN, Duglan D, Casadei B, Carnicer R (2014) Nitric oxide synthase regulation of cardiac excitation-contraction coupling in health and disease. J Mol Cell Cardiol 73:80–91PubMedCrossRefGoogle Scholar
  92. Sonnenburg WK, Rybalkin SD, Bornfeldt KE, Kwak KS, Rybalkina IG, Beavo JA (1998) Identification, quantitation, and cellular localization of PDE1 calmodulin-stimulated cyclic nucleotide phosphodiesterases. Methods 14:3–19PubMedCrossRefGoogle Scholar
  93. Stangherlin A, Zaccolo M (2012) cGMP-cAMP interplay in cardiac myocytes: a local affair with far-reaching consequences for heart function. Biochem Soc Trans 40:11–14PubMedCrossRefGoogle Scholar
  94. Stangherlin A, Gesellchen F, Zoccarato A, Terrin A, Fields LA, Berrera M, Surdo NC, Craig MA, Smith G, Hamilton G, Zaccolo M (2011) cGMP signals modulate cAMP levels in a compartment-specific manner to regulate catecholamine-dependent signaling in cardiac myocytes. Circ Res 108:929–939PubMedPubMedCentralCrossRefGoogle Scholar
  95. Stubbert D, Prysyazhna O, Rudyk O, Scotcher J, Burgoyne JR, Eaton P (2014) Protein kinase G Ialpha oxidation paradoxically underlies blood pressure lowering by the reductant hydrogen sulfide. Hypertension 64:1344–1351PubMedCrossRefGoogle Scholar
  96. Su J, Scholz PM, Weiss HR (2005) Differential effects of cGMP produced by soluble and particulate guanylyl cyclase on mouse ventricular myocytes. Exp Biol Med (Maywood) 230:242–250CrossRefGoogle Scholar
  97. Sun J, Picht E, Ginsburg KS, Bers DM, Steenbergen C, Murphy E (2006) Hypercontractile female hearts exhibit increased S-nitrosylation of the L-type Ca2+ channel alpha1 subunit and reduced ischemia/reperfusion injury. Circ Res 98:403–411PubMedCrossRefGoogle Scholar
  98. Takahashi S, Lin H, Geshi N, Mori Y, Kawarabayashi Y, Takami N, Mori MX, Honda A, Inoue R (2008) Nitric oxide-cGMP-protein kinase G pathway negatively regulates vascular transient receptor potential channel TRPC6. J Physiol 586:4209–4223PubMedPubMedCentralCrossRefGoogle Scholar
  99. Takimoto E, Champion HC, Li M, Belardi D, Ren S, Rodriguez ER, Bedja D, Gabrielson KL, Wang Y, Kass DA (2005) Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med 11:214–222PubMedCrossRefGoogle Scholar
  100. Takimoto E, Belardi D, Tocchetti CG, Vahebi S, Cormaci G, Ketner EA, Moens AL, Champion HC, Kass DA (2007) Compartmentalization of cardiac beta-adrenergic inotropy modulation by phosphodiesterase type 5. Circulation 115:2159–2167PubMedCrossRefGoogle Scholar
  101. Takimoto E, Koitabashi N, Hsu S, Ketner EA, Zhang M, Nagayama T, Bedja D, Gabrielson KL, Blanton R, Siderovski DP, Mendelsohn ME, Kass DA (2009) Regulator of G protein signaling 2 mediates cardiac compensation to pressure overload and antihypertrophic effects of PDE5 inhibition in mice. J Clin Invest 119:408–420PubMedPubMedCentralGoogle Scholar
  102. Tamirisa P, Blumer KJ, Muslin AJ (1999) RGS4 inhibits G-protein signaling in cardiomyocytes. Circulation 99:441–447PubMedCrossRefGoogle Scholar
  103. Tang KM, Wang GR, Lu P, Karas RH, Aronovitz M, Heximer SP, Kaltenbronn KM, Blumer KJ, Siderovski DP, Zhu Y, Mendelsohn ME (2003) Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure. Nat Med 9:1506–1512PubMedCrossRefGoogle Scholar
  104. Thoonen R, Giovanni S, Govindan S, Lee DI, Wang GR, Calamaras TD, Takimoto E, Kass DA, Sadayappan S, Blanton RM (2015) Molecular screen identifies cardiac myosin-binding protein-C as a protein kinase G-Ialpha substrate. Circ Heart Fail 8:1115–1122PubMedPubMedCentralGoogle Scholar
  105. Tokudome T, Kishimoto I, Horio T, Arai Y, Schwenke DO, Hino J, Okano I, Kawano Y, Kohno M, Miyazato M, Nakao K, Kangawa K (2008) Regulator of G-protein signaling subtype 4 mediates antihypertrophic effect of locally secreted natriuretic peptides in the heart. Circulation 117:2329–2339PubMedCrossRefGoogle Scholar
  106. Tsai EJ, Liu Y, Koitabashi N, Bedja D, Danner T, Jasmin JF, Lisanti MP, Friebe A, Takimoto E, Kass DA (2012) Pressure-overload-induced subcellular relocalization/oxidation of soluble guanylyl cyclase in the heart modulates enzyme stimulation. Circ Res 110:295–303PubMedCrossRefGoogle Scholar
  107. Vandeput F, Wolda SL, Krall J, Hambleton R, Uher L, Mccaw KN, Radwanski PB, Florio V, Movsesian MA (2007) Cyclic nucleotide phosphodiesterase PDE1C1 in human cardiac myocytes. J Biol Chem 282:32749–32757PubMedCrossRefGoogle Scholar
  108. Vettel C, Lammle S, Ewens S, Cervirgen C, Emons J, Ongherth A, Dewenter M, Lindner D, Westermann D, Nikolaev VO, Lutz S, Zimmermann WH, El-Armouche A (2014) PDE2-mediated cAMP hydrolysis accelerates cardiac fibroblast to myofibroblast conversion and is antagonized by exogenous activation of cGMP signaling pathways. Am J Physiol Heart Circ Physiol 306:H1246–H1252PubMedCrossRefGoogle Scholar
  109. Vettel C, Lindner M, Dewenter M, Lorenz K, Schanbacher C, Riedel M, Lammle S, Meinecke S, Mason FE, Sossalla S, Geerts A, Hoffmann M, Wunder F, Brunner FJ, Wieland T, Mehel H, Karam S, Lechene P, Leroy J, Vandecasteele G, Wagner M, Fischmeister R, El-Armouche A (2016) Phosphodiesterase 2 protects against catecholamine-induced arrhythmia and preserves contractile function after myocardial infarction. Circ Res 120(1):120–132PubMedCrossRefGoogle Scholar
  110. Vila-Petroff MG, Younes A, Egan J, Lakatta EG, Sollott SJ (1999) Activation of distinct cAMP-dependent and cGMP-dependent pathways by nitric oxide in cardiac myocytes. Circ Res 84:1020–1031PubMedCrossRefGoogle Scholar
  111. Wang Y, De Waard MC, Sterner-Kock A, Stepan H, Schultheiss HP, Duncker DJ, Walther T (2007) Cardiomyocyte-restricted over-expression of C-type natriuretic peptide prevents cardiac hypertrophy induced by myocardial infarction in mice. Eur J Heart Fail 9:548–557PubMedCrossRefGoogle Scholar
  112. Wang H, Viatchenko-Karpinski S, Sun J, Gyorke I, Benkusky NA, Kohr MJ, Valdivia HH, Murphy E, Gyorke S, Ziolo MT (2010) Regulation of myocyte contraction via neuronal nitric oxide synthase: role of ryanodine receptor S-nitrosylation. J Physiol 588:2905–2917PubMedPubMedCentralCrossRefGoogle Scholar
  113. Wu X, Eder P, Chang B, Molkentin JD (2010) TRPC channels are necessary mediators of pathologic cardiac hypertrophy. Proc Natl Acad Sci U S A 107:7000–7005PubMedPubMedCentralCrossRefGoogle Scholar
  114. Yue ZJ, Xu PT, Jiao B, Chang H, Song Z, Xie MJ, Yu ZB (2015) Nitric oxide protects L-type calcium channel of cardiomyocyte during long-term isoproterenol stimulation in tail-suspended rats. Biomed Res Int 2015:780814PubMedPubMedCentralGoogle Scholar
  115. Zabel U, Kleinschnitz C, Oh P, Nedvetsky P, Smolenski A, Muller H, Kronich P, Kugler P, Walter U, Schnitzer JE, Schmidt HH (2002) Calcium-dependent membrane association sensitizes soluble guanylyl cyclase to nitric oxide. Nat Cell Biol 4:307–311PubMedCrossRefGoogle Scholar
  116. Zaccolo M, Movsesian MA (2007) cAMP and cGMP signaling cross-talk: role of phosphodiesterases and implications for cardiac pathophysiology. Circ Res 100:1569–1578PubMedCrossRefGoogle Scholar
  117. Zhang P, Mende U (2011) Regulators of G-protein signaling in the heart and their potential as therapeutic targets. Circ Res 109:320–333PubMedPubMedCentralCrossRefGoogle Scholar
  118. Zhang W, Anger T, Su J, Hao J, Xu X, Zhu M, Gach A, Cui L, Liao R, Mende U (2006) Selective loss of fine tuning of Gq/11 signaling by RGS2 protein exacerbates cardiomyocyte hypertrophy. J Biol Chem 281:5811–5820PubMedCrossRefGoogle Scholar
  119. Zhang M, Koitabashi N, Nagayama T, Rambaran R, Feng N, Takimoto E, Koenke T, O'Rourke B, Champion HC, Crow MT, Kass DA (2008) Expression, activity, and pro-hypertrophic effects of PDE5A in cardiac myocytes. Cell Signal 20:2231–2236PubMedPubMedCentralCrossRefGoogle Scholar
  120. Zhang DX, Borbouse L, Gebremedhin D, Mendoza SA, Zinkevich NS, Li R, Gutterman DD (2012) H2O2-induced dilation in human coronary arterioles: role of protein kinase G dimerization and large-conductance Ca2+-activated K+ channel activation. Circ Res 110:471–480PubMedCrossRefGoogle Scholar
  121. Zhang P, Ma Y, Wang Y, Ma X, Huang Y, Li RA, Wan S, Yao X (2014a) Nitric oxide and protein kinase G act on TRPC1 to inhibit 11,12-EET-induced vascular relaxation. Cardiovasc Res 104:138–146PubMedCrossRefGoogle Scholar
  122. Zhang YH, Jin CZ, Jang JH, Wang Y (2014b) Molecular mechanisms of neuronal nitric oxide synthase in cardiac function and pathophysiology. J Physiol 592:3189–3200PubMedPubMedCentralCrossRefGoogle Scholar
  123. Zoccarato A, Surdo NC, Aronsen JM, Fields LA, Mancuso L, Dodoni G, Stangherlin A, Livie C, Jiang H, Sin YY, Gesellchen F, Terrin A, Baillie GS, Nicklin SA, Graham D, Szabo-Fresnais N, Krall J, Vandeput F, Movsesian M, Furlan L, Corsetti V, Hamilton G, Lefkimmiatis K, Sjaastad I, Zaccolo M (2015) Cardiac hypertrophy is inhibited by a local pool of cAMP regulated by phosphodiesterase 2. Circ Res 117:707–719PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Division of Cardiology, Department of MedicineThe Johns Hopkins University Medical InstitutionsBaltimoreUSA
  2. 2.Department of Pharmacology and Molecular SciencesJohns Hopkins UniversityBaltimoreUSA

Personalised recommendations