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NO-cGMP Signaling and Regenerative Medicine Involving Stem Cells

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Abstract

Nitric oxide (NO) is a short lived diatomic free radical species synthesized by nitric oxide synthases (NOS). The physiological roles of NO depend on its local concentrations as well as availability and the nature of downstream target molecules. At low nanomolar concentrations, activation of soluble guanylyl cyclase (sGC) is the major event initiated by NO. The resulting elevation in the intracellular cyclic GMP (cGMP) levels serves as signals for regulating diverse cellular and physiological processes. The participation of NO and cGMP in diverse physiological processes is made possible through cell type specific spatio-temporal regulation of NO and cGMP synthesis and signal diversity downstream of cGMP achieved through specific target selection. Thus cyclic GMP directly regulates the activities of its downstream effectors such as Protein Kinase G (PKG), Cyclic Nucleotide Gated channels (CNG) and Cyclic nucleotide phosphodiesterases, which in turn regulate the activities of a number of proteins that are involved in regulating diverse cellular and physiological processes. Localization and activity of the NO-cGMP signaling pathway components are regulated by G-protein coupled receptors, receptor and non receptor tyrosine kinases, phosphatases and other signaling molecules. NO also serves as a powerful paracrine factor. At micromolar concentrations, NO reacts with superoxide anion to form reactive peroxinitrite, thereby leading to the oxidation of important cellular proteins. Extensive research efforts over the past two decades have shown that NO is an important modulator of axon outgrowth and guidance, synaptic plasticity, neural precursor proliferation as well as neuronal survival. Excessive NO production as that evoked by inflammatory signals has been identified as one of the major causative reasons for the pathogenesis of a number of neurodegenerative diseases such as ALS, Alzheimers and Parkinson diseases. Regenerative therapies involving transplantation of embryonic stem cells (ES cells) and ES cell derived lineage committed neural precursor cells have recently shown promising results in animal models of Parkinson disease (PD). Recent studies from our laboratory have shown that a functional NO-cGMP signaling system is operative early during the differentiation of embryonic stem cells. The cell type specific, spatio-temporally regulated NO-cGMP signaling pathways are well suited for inductive signals to use them for important cell fate decision making and lineage commitment processes. We believe that manipulating the NO-cGMP signaling system will be an important tool for large scale generation of lineage committed precursor cells to be used for regenerative therapies.

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References

  1. Alderton WK, Cooper CE, Knowles EG (2001) Nitric oxide synthases: structure, function and inhibition. Biochem J 357:593–615

    PubMed  CAS  Google Scholar 

  2. Armour KE, Ralston SH (1998) Estrogen upregulates endothelial constitutive nitric oxide synthase expression in human osteoblast-like cells. Endocrinology 139:799–802

    PubMed  CAS  Google Scholar 

  3. Arnold WP, Mittal CK, Katsuki S, Murad F (1977) Nitric oxide activates guanylate cyclase and increases guanosine 3′:5′-cyclic monophosphate levels in various tissue preparations. Proc Natl Acad Sci 74:3203–3207

    PubMed  CAS  Google Scholar 

  4. Ashe HL, Briscoe J (2006) Interpretation of morphogen gradients. Development 133:385–394

    PubMed  CAS  Google Scholar 

  5. Baltrons MA, Pedraza C, Sardon T, Navarra M, Garcia A (2003) Regulation of NO-dependent cyclic GMP formation by inflammatory agents in neural cells. Toxicol Lett 139:191–198

    PubMed  CAS  Google Scholar 

  6. Bellamy TC, Garthwaite J (2002) The receptor-like properties of nitric oxide-activated soluble guanylyl cyclase in intact cells. Mol Cell Biochem 230:165–176

    PubMed  CAS  Google Scholar 

  7. Bhoola KD, Figueroa CD, Worthy K (1992) Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev 44:1–80

    PubMed  CAS  Google Scholar 

  8. Bian K, Gao Z, Weisbrodt N, Muad F (2003) The nature of heme/iron-induced protein tyrosine nitration. Proc Natl Acad Sci USA 100:5712–5717

    Google Scholar 

  9. Bjorklund LM, Sanchez-Pernaute T, Chung S, Anderson T, Chen I, Chen Y, McNaught K, Brownell AL, Jenkins BG, Wahlestedt C, Kim KS, Isacson O (2002) Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci USA 99:2344–2349

    PubMed  CAS  Google Scholar 

  10. Bohme GA, Bon C, Stutzmann JM, Doble A, Blanchard JC (1991) Possible involvement of nitric oxide in long-term potentiation. Eur J Pharmacol 199:379–381

    PubMed  CAS  Google Scholar 

  11. Bonkale WL, Cowburn RF, Winblad B, Fastbom J (1997) Autoradiographic characterization of [3H] cGMP binding sites in rat brain. Brain Res 763:1–13

    Google Scholar 

  12. Boswell-Smith V, Spina D, Page CP (2006) Phosphodiesterase inhibitors. Brit J Pharmacol 147:S252–S257

    CAS  Google Scholar 

  13. Boulten CL, Southam E, Garthwaite J (1995) Nitric oxide-dependent long-term potentiation is blocked by a specific inhibitor of soluble guanylyl cyclase. Neuroscience 69:699–703

    Google Scholar 

  14. Bove J, Prou D, Perier C, Przedborski S (2005) Toxin-induced models of Parkinson’s disease. NeuroRx 2:484–494

    PubMed  Google Scholar 

  15. Brandish PE, Buchler W, Marletta MA (1998) Regeneration of the ferrous heme of soluble guanylate cyclase from the nitric oxide complex: acceleration by thiols and oxyhemoglobin. Biochemistry 37:16898–16907

    PubMed  CAS  Google Scholar 

  16. Casteel DE, Zhuang S, Gudi T, Tang J, Vuica M, Desiderio S, Pilz RB (2002) cGMP-dependent protein kinase 1 beta physically and functionally interacts with the transcriptional regulator TFII-I. J biol Chem 277:32003–32014

    PubMed  CAS  Google Scholar 

  17. Castegna A, Thongboonkerd V, Klein JB, Lynn B, Markesbery WR, Butterfield DA (2003) Proteomic identification of nitrated proteins in Alzheimer’s disease brain. J Neurochem 85:1394–1401

    PubMed  CAS  Google Scholar 

  18. Chalimoniuk M, Langfort J, Nadezda L, Marsala J (2004) Upregulation of guanylyl cyclase expression and activity in striatum of MPTP-induced parkinsonism in mice. Biochem Biophys Res Commun 324:118–126

    PubMed  CAS  Google Scholar 

  19. Chambliss KL, Shaul PW (2002) Estrogen modulation of endothelial nitric oxide synthase. Endocrine Rev 23:665–686

    CAS  Google Scholar 

  20. Chen Z, Yuhanna IS, Galcheva-Gargova Z, Karas RH Mendelsohn ME, Shaul PW (1999) Estrogen receptor alpha mediates the nongenomic activation of endothelial nitric oxide synthase by estrogen. J Clin Invest 103:401–406

    PubMed  CAS  Google Scholar 

  21. Chen ZJ, Che D, Vetter M, Liu S, Chang CH (2001) 17beta-estradiol inhibits soluble guanylate cyclase activity through a protein tyrosine phosphatase in PC12 cells. J Steroid Biochem Mol Biol 78:451

    PubMed  CAS  Google Scholar 

  22. Cheng A, Wang S, Rao MS, Mattson MP (2003) Nitric oxide acts in a positive feedback loop with BDNF to regulate neural progenitor cell proliferation and differentiation in the mammalian brain. Dev Biol 258:319–333

    PubMed  CAS  Google Scholar 

  23. Currie DA, de Vente J, Moody WJ (2006) Developmental appearance of cyclic guanosine monophosphate (cGMP) production and nitric oxide responsiveness in embryonic mouse cortex and striatum. Dev Dyn Online ahead of print, March 3

  24. Dehmer T, Lindenau J, Haid S, Dichgans J, Schulz JB (2000) Deficiency of inducible nitric oxide synthase protects against MPTP toxicity in vivo. J Neurochem 74:2213–2216

    PubMed  CAS  Google Scholar 

  25. Demyenenko GP, Halberstadt AI, Pryzwansky KB, Werner C, Hoffmann F, Maness PF (2005) Abnormal neocortical development in mice lacking cGMP dependent protein kinase I. Develop Br Res 160:1–8

    Google Scholar 

  26. Di Girolamo G, Farina M, Riberio ML, Ogando D, Aisemberg J, de los Santos AR, Marti ML, Franchi AM (2003) Effects of cyclooxygenase inhibitor pretreatment on nitric oxide production, nNOS and iNOS expression in rat cerebellum. Brit J Pharmacol 139:1164–1170

    CAS  Google Scholar 

  27. Dimmeler S, Fleming I, Fisslthaler B, Herman C, Busse R, Zeiher AM, (1999) Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 399:601–605

    PubMed  CAS  Google Scholar 

  28. Engert F, Bonhoeffer T (1999) Dendritic spine changes associated with hippocampal long-term synaptic plasticity. Nature 399:66–70

    PubMed  CAS  Google Scholar 

  29. El-Husseini AE, Bladen C, Vincent SR (1995) Molecular characterization of a type II cyclic GMP-dependent protein kinase expressed in the rat brain. J Neurochem 64:2814–2817

    Article  PubMed  CAS  Google Scholar 

  30. Eslamboli A (2005) Assessment of GDNF in primate models of Parkinson’s disease: comparison with human studies. Rev Neurosci 16:303–310

    PubMed  CAS  Google Scholar 

  31. Farrer MJ (2006) Genetics of Parkinson disease: paradigm shifts and future prospects. Nat Rev Genet 7:306–318

    PubMed  CAS  Google Scholar 

  32. Feng Z, Dongdong L, Fung PCW, Pei Z, Ramsden DB, Ho S-L (2003) COX-2-deficient mice are less prone to MPTP-neurotoxicity than wild-type mice. Mol Neurosci 14:1927–1929

    CAS  Google Scholar 

  33. Fesenko EE, Kolesnikov SS, Lyubarski AL (1985) Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment. Nature 313:310–313

    PubMed  CAS  Google Scholar 

  34. Fiscus RR, Murad F (1988) cGMP-dependent protein kinase activation in intact tissues. Methods Enzymol 159:150–159

    PubMed  CAS  Google Scholar 

  35. Fiscus RR, Rapoport RM, Murad F (1983–84) Endothelium-dependent and nitrovasodilator-induced activation of cyclic GMP-dependent protein kinase in rat aorta. J Cyclic Nucleotide Protein Phosphor Res 9:415–425

    Google Scholar 

  36. Förstermann U, Gorsky LD, Pollock JS, Schmidt HH, Heller M, Murad F (1990) Regional distribution of EDRF/NO-synthesizing enzyme(s) in rat brain. Biochem Biophys Res Commun 168:727–732

    PubMed  Google Scholar 

  37. Fryer BH, Wang C, Vedantam S, Zhou G-L, Jin S, Fletcher L, Simon MC, Field J (2006) PKG phosphorylates Pak1, inhibiting Pak/Nck binding and stimulating Pak/VASP association. J Biol Chem 281:11487–11495

    PubMed  CAS  Google Scholar 

  38. Fu Y-S, Cheng YC, Lin MA, Cheng H, Chu P-M, Chou SC, Shih YH, Ko M-H, Sung M-S (2006) Conversion of human umbilical cord mesenchymal stem cells in Wharton’s jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsonism. Stem Cells 24:115–124

    PubMed  Google Scholar 

  39. Fulton D, Gratton JP, McCabe TJ, Fontana J, Fujio Y, Walsh K, Franke TF, Papapetropoulos A, Sessa WC (1999) Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature 399:597–601

    PubMed  CAS  Google Scholar 

  40. Gamm DM, Francis SH, Angelotti TP, Corbin JD, Uhler MD (1995) The type II isoform of cGMP-dependent protein kinase is dimeric and possesses regulatory and catalytic properties distinct from the type I isoforms. J Biol Chem 270:27380–27388

    PubMed  CAS  Google Scholar 

  41. Garthwaite J (1991) Glutamate, nitric oxide and cell–cell signaling in the nervous system. Trends Neurosci 14:60–67

    PubMed  CAS  Google Scholar 

  42. Gibb BJ, Garthwaite J (2001) Subunits of the nitric oxide receptor, soluble guanylyl cyclase, expressed in rat brain. Eur J Neuroscience 13:539–544

    CAS  Google Scholar 

  43. Gudi T, Casteel DE, Vinson C, Boss GR, Pilz RB (2000) NO activation of fos promoter elements requires nuclear translocation of G-kinase I and CREB phosphorylation but is independent of MAP kinase activation. Oncogene 19:6324–6333

    PubMed  CAS  Google Scholar 

  44. Gudi T, Hing GK-P, Vaandrager AB, Lohmann SM, Pilz RB (1999) Nitric oxide and cGMP regulate gene expression in neuronal and glial cells by activating type II cGMP-dependent protein kinase. FASEB J 13:2143–2152

    PubMed  CAS  Google Scholar 

  45. Hanafy K, Martin E, Murad F (2004) CCTη, a novel soluble guanylyl cyclase-interacting protein. J Biol Chem 279:46946–46953

    PubMed  CAS  Google Scholar 

  46. Heikkila RE, Manzino L, Cabbat FS, Duvoisin RC (1984) Protection against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine by monoamine oxidase inhibitors. Nature 311:467–469

    PubMed  CAS  Google Scholar 

  47. Holtzman DM, Kilbridge J, Bredt DS, Black M, Li Y, Clary DO, Reichardt LF, Mobley WC (1994) NOS induction by NGF in basal forebrain cholinergic neurones: evidence for regulation of brain NOS by a neurotrophin. Neurobiol Diseases 1:51–60

    Google Scholar 

  48. Hunot S, Hirsch EC (2003) Neuroinflammatory processes in Parkinson’s disease. Ann Neurol 53:49–60

    Google Scholar 

  49. Hunot S, Vila M, Teismann P, Davis R, Hirsch E, Przedborski S, Rakic P, Flavel RA (2004) JNK-mediated induction of cyclooxygenase-2 is required for neurodegeneration in a mouse model of Parkinson’s disease. Proc Natl Acad Sci USA 101:665–670

    PubMed  CAS  Google Scholar 

  50. Ideda H, Osakada F, Watanabe K, Mizuseki K, Haraguchi T, Miyoshi H, Kamiya D, Honda Y, Sasai N, Yoshimura N, Takahashi M, Sasai Y (2005) Generation of Rx+/Pax6+ neural retinal precursors from embryonic stem cells. Proc Natl Acad Sci USA 102:11331–11336

    Google Scholar 

  51. Ishi K, Sheng H, Warner TD, Forstermann U, Murad F (1991) A simple and sensitive bioassay method for detection of EDRF with RFL-6 rat lung fibroblasts. Am J Physiol 26:H598–H603

    Google Scholar 

  52. Jin M, Guan CB, Jiang YA, Chen G, Zhao CT, Cui K, Song YQ, Wu CP, Poo MM, Yuan XB (2005) Ca2+-dependent regulation of rho GTPases triggers turning of nerve growth cones. J Neurosci 25:2338–2347

    PubMed  CAS  Google Scholar 

  53. Jouvert P, Revel MO, Lazaris A, Aunis D, Langley K, Zwiller J (2004) Activation of the cGMP pathway in dopaminergic structures reduces cocaine-induced EGR-1 expression and locomotor activity. J Neurosci 24:10716

    PubMed  CAS  Google Scholar 

  54. Kanno S, Kim PK, Sallam K, Li J, Biliiar TR, Shears LL (2004) Nitric oxide facilitates cardiomyogenesis in mouse embryonic stem cells. Proc Natl Acad Sci USA 101:12277–12281

    PubMed  CAS  Google Scholar 

  55. Katsuki S, Arnold W, Mittal C, Murad F (1977) Stimulation of guanylate cyclase by sodium nitroprusside, nitroglycerin and nitric oxide in various tissue preparations and comparison to the effects of sodium azide and hydroxylamine. J Cyclic Nucleotide Res 3:23–35

    PubMed  CAS  Google Scholar 

  56. Katsuki S, Murad F (1977) Regulation of adenosine cyclic 3′,5′-monophosphate and guanosine cyclic 3′,5′-monophosphate levels and contractility in bovine tracheal smooth muscle. Mol Pharmacol 13:330–341

    PubMed  CAS  Google Scholar 

  57. Kharitonov VG, Russwurm M, Magde D, Sharma VS, Koesling D (1997) Biochem Biophys Res Commun 239:284–286

    PubMed  CAS  Google Scholar 

  58. Kloss S, Furneaux H, Mulsch A (2003) Post-transcriptional regulation of soluble guanylyl cyclase expression in rat aorta. J Biol Chem 278:2377

    PubMed  Google Scholar 

  59. Kimura H, Murad F (1975) Two forms of guanylate cyclase in mammalian tissues and possible mechanisms for their regulation. Metabolism 24:439–445

    PubMed  CAS  Google Scholar 

  60. Kloss S, Srivastava R, Mulsch A (2004) Down-regulation of soluble guanylyl cyclase expression by cyclic AMP is mediated by mRNA-stabilizing protein HuR. Mol Pharmacol 65:1440–1451

    PubMed  Google Scholar 

  61. Koch K-W, Lambrecht H-G, Habercht M, Redburn D, Schmidt HH (1994) Functional coupling of a Ca2+/calmodulin-dependent nitric oxide synthase and a soluble guanylyl cyclase in vertebrate photoreceptor cells. EMBO J 13:3312–3320

    PubMed  CAS  Google Scholar 

  62. Krause M, Dent EW, Bear JE, Lourero JJ, Gertler FB (2003) Ena/VASP proteins: regulators of the actin cytoskeleton and cell migration. Ann Rev Cell Dev Biol 19:541–564

    CAS  Google Scholar 

  63. Krumenacker JS, Kots A, Murad F (2006) Differential expression of genes involved in cGMP-dependent nitric oxide signaling in murine embryonic stem (ES) cells and ES cell-derived cardiomyocytes. Nitric Oxide 14:1–11

    PubMed  CAS  Google Scholar 

  64. Kuan W-L, Barker RA (2005) New therapeutic approaches to Parkinson’s disease including neural transplants. Nerorehabil Neural Repair 19:155–181

    Google Scholar 

  65. Lam HHD, Bhardwaj A, O’Connel MT, Hanley DF, Traystman RJ, Sofroniew MV (1998) Nerve growth factor rapidly suppresses basal, NMDA-evoked, and AMPA-evoked nitric oxide synthase activity in rat hippocampus in vivo. Proc Natl Acad Sci USA 95:10926–10931

    PubMed  CAS  Google Scholar 

  66. Langston JW, Ballard PA (1983) Parkinson’s disease in a chemist working with 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. N Engl J Med 309:310

    PubMed  CAS  Google Scholar 

  67. Lee SH, Lumelsky N, Studer L, Auerbach JM, McKay RD (2000) Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nat Biotechnol 18:675–679

    PubMed  CAS  Google Scholar 

  68. Leeb-Lundberg LM, Marceau F, Muller-Esterl W, Pettibone DJ, Zuraw BL (2005) International union of pharmacology. XLV. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences. Pharmacol Rev 57:27–77

    PubMed  CAS  Google Scholar 

  69. Liberatore GT, Jackson-Lewis V, Vuskosavic S, Mandir AS, Vila M, McAuliffe WG, Dawson VL, Dawson TM, Przedborski S (1999) Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nat Med 5:1403–1409

    PubMed  CAS  Google Scholar 

  70. Liu J, Hughes TE, Sessa WC (1997) The first 35 amino acids and fatty acylation sites determine the molecular targeting of endothelial nitric oxide synthase into the Golgi region of cells: a green fluorescent protein study. J Cell Biol 137:1525–1535

    PubMed  CAS  Google Scholar 

  71. Lohmann SM, Walter U, Miller PE, Greengard P, DcCamilli P (1981) Immunohistochemical localization of cyclic GMP-dependent protein kinase in mammalian brain. PNAS 78: 653–657

    PubMed  CAS  Google Scholar 

  72. Lumelsky N, Lee S-H, Nguyen LJ, Sanchez-Pernaute R, Bankiewicz K, McKay R (2002) Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature 418:50–56

    PubMed  Google Scholar 

  73. Lu YF, Kandel ER, Hawkins RD (1999) Nitric oxide signaling contributes to late-phase LTP and CREB phosphorylation in the hippocampus. J Neurosci 19:10250–10261

    PubMed  CAS  Google Scholar 

  74. Malinow R, Malenka RC (2002) AMPA receptor trafficking and synaptic plasticity. Ann Rev Neurosci 25:103–126

    PubMed  CAS  Google Scholar 

  75. Mandir AS, Przedborski S, Jackson-Lewis V, Wang Z-Q, Simbulanrosenthal CM, Samuelson ME, Hoffman BE, Guastella DB, Dawson VL, Dawson TM (1999) Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. PNAS 96:5774–5779

    PubMed  CAS  Google Scholar 

  76. Margulis A, Sitaramaiah A (2000) Rate of deactivation of nitric oxide-stimulated soluble guanylate cyclase: influence of nitric oxide scavengers and calcium. Biochemistry 39:1034–1039

    PubMed  CAS  Google Scholar 

  77. Massion PB, Pelat M, Belge C, Balligand JL (2005) Regulation of mammalian heart function by nitric oxide. Comparative Biochem Physiol Part A 142:144–150

    Google Scholar 

  78. Matarredona ER, Murillo-Carretero M, Moreno-Lopez B, Estrada C (2004) Nitric oxide synthesis inhibition increases proliferation of neural precursors isolated from the postnatal mouse subventricular zone. Brain Res 995:274–284

    PubMed  CAS  Google Scholar 

  79. Messersmith EK, Leonardo ED, Shatz CJ, Tessier-Lavigne M, Goodman CS, Kolodkin AL (1995) Semaphorin III can function as a selective chemorepellent to pattern sensory projections in spinal chord. Neuron 14:949–959

    PubMed  CAS  Google Scholar 

  80. Meurer S, Pioch S, Gross S, Muller-Esterl W (2005) Reactive oxygen species induce tyrosine phosphorylation of and Src kinase recruitment to NO-sensitive guanylyl cyclase. J Biol Chem 280: 33149–33156

    PubMed  CAS  Google Scholar 

  81. Morishita T, Tsutsui M, Shimokawa H, Sabanai K, Tasaki H, Suda O, Nakata S, Tanimoto A, Wang K-Y, Ueta Y, Sasaguri Y, Nakashima Y, Yanagihara N (2005) Nephrogenic diabetes insipidus in mice lackingall nitric oxide synthase isoforms. Proc Natl Acad Sci USA 102:10616–10621

    PubMed  CAS  Google Scholar 

  82. Muerer S, Pioch S, Wagner K, Muller-Esterl W, Gross S (2004) AGAP1, a novel binding partner of nitric oxide sensitive guanylyl cyclase. J Biol Chem 279:49346–49354.

    Google Scholar 

  83. Murad F (1986) Cyclic guanosine monophosphate as a mediator of vasodilation. J Clin Invest 78:1–5

    Article  PubMed  CAS  Google Scholar 

  84. Nairn AC, Greengard P (1983) Cyclic GMP-dependent protein phosphorylation in mammalian brain. Fed Proc 42:3107–3113

    PubMed  CAS  Google Scholar 

  85. Nathan C, Calingasan N, Nezezon J, Ding A, Lucia MS, La Perle K, Fuortes M, Lin M, Ehrt S, Kwon NS, Chen J, Vodovotz Y, Kipiani K, Beal MF (2005) Protection from Alzheimer’s-like disease in the mouse by genetic ablation of inducible nitric oxide synthase. J Exp Med 202:1163–1169

    PubMed  CAS  Google Scholar 

  86. Nishiyama M, Hoshino A, Tsai L, Henley JR, Goshima Y, Lavigne T, Poo MM, Hong K (2003) Cyclic AMP/GMP-dependent modulation of Ca2+ channels sets the polarity of nerve growth-cone turning. Nature 423:990–995

    PubMed  CAS  Google Scholar 

  87. Nourry C, Grant SGN, Borg J-P (2003) PDZ domain proteins: plug and play. Sci STKE 179:re7

    Google Scholar 

  88. Nuelding S, Kahlert S, Loebbert K, Doevendans PA, Meyer R, Vetter H, Grohe C (1999) 17 Beta-estradiol stimulates expression of endothelial and inducible NO synthase in rat myocardium in-vitro and in-vivo. Cardiovascular Res 43:666–674

    Google Scholar 

  89. Pilz RB, Casteel DE (2003) Regulation of gene expression by cyclic GMP. Circ Res 93:1034–1046

    PubMed  CAS  Google Scholar 

  90. Pollock JS, Forstermann U, Mitchell JA, Warner TD, Schmidt HHH, Nakane M, Murad F (1991) Purification and characterization of particulate endothelium-derived relaxing factor synthase from cultured and native bovine aortic endothelial cells. Proc Natl Acad Sci USA 88:10480–10484

    PubMed  CAS  Google Scholar 

  91. Papapetropoulos A, Marczin N, Mora G, Milici A, Murad F, Catravas JD (1995) Regulation of vascular smooth muscle soluble guanylate cyclase activity, mRNA, and protein levels by cAMP-elevating agents. Hypertension 26:696–704

    PubMed  CAS  Google Scholar 

  92. Prabhakar P, Thatte HS, Goetz RM, Cho MR, Golan DE, Michel T (1998) Receptor-regulated translocation of endothelial nitric-oxide synthase. J Biol Chem 273:27383–27388

    PubMed  CAS  Google Scholar 

  93. Przedborski A, Jackson-Lewis V, Yokoyama R, Shibata T, Dawson VL, Dawson TM (1996) Role of neuronal nitric oxide in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity. PNAS 93:4565–4571

    PubMed  CAS  Google Scholar 

  94. Przybylkowski S, Kurkowska-Jastrzebska I, Joniec I, Ciesielska A, Czlonkowska A, Czlonkowski A (2004) Cyclooxygenases mRNA and protein expression in striata in the experimental mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration to mouse. Brain Res 1019:144–151

    PubMed  CAS  Google Scholar 

  95. Rathjen J, Haines BP, Hudson KM, Nesci A, Dunn S, Rathjen PD (2002) Directed differentiation of pluripotent cells to neural lineages: homogeneous formation and differentiation of a neurectoderm population. Development 129:2649–2661

    PubMed  CAS  Google Scholar 

  96. Raoul C, Buhler E, Sadeghi C, Jacquier A, Aebischer P, Pettmann B, Henderson CE, Haase G (2006) Chronic activation in presymptomatic amyotrophic lateral sclerosis (ALS) mice of a feedback loop involving Fas, Daxx, and FasL. Proc Natl Acad Sci USA 103:6007–6012

    PubMed  CAS  Google Scholar 

  97. Robertson CP, Gibbs SM, Roelink H (2001) cGMP enhances the sonic hedgehog responses in neural plate cells. Dev Biol 238:157–167

    PubMed  CAS  Google Scholar 

  98. Russwurm M, Wittau N, Koesling D (2001) Guanylyl cyclase/PSD-95 interaction: targeting of the nitric oxide-sensitive alpha2beta1 guanylyl cyclase to synaptic membranes. J Biol Chem 276:44647

    PubMed  CAS  Google Scholar 

  99. Rutten K, De Vente J, Şik A, Van Ittersum MM, Prickaerts J, Blokland A. (2005) The selective PDE5 inhibitor, sildenafil, improves object memory in Swiss mice and increases cGMP Levels in hippocampal slices. Behav Brain Res 164:11–16

    PubMed  CAS  Google Scholar 

  100. Saffer JD, Jackson SP, Annarella MB (1991) Developmental expression of Sp1 in mouse. Mol Cell Biol 11:2189–2199.

    PubMed  CAS  Google Scholar 

  101. Savchenko A, Barnes S, Kramer RH (1997) Cyclic-nucleotide-gated channels mediate synaptic feedback by nitric oxide. Nature 390:694–698

    PubMed  CAS  Google Scholar 

  102. Sauzeau V, Rolli-Derkinderen M, Marionneau C, Loirand G, Pacaud PJ (2003) RhoA expression is controlled by nitric oxide through cGMP-dependent protein kinase activation. J Biol Chem 278:9472–9480

    PubMed  CAS  Google Scholar 

  103. Scott JA, Shewan AM, den Elzen NR, Lourero JJ, Gertler FB, Yap AS. (2006) Ena/VASP proteins can regulate distinct modes of actin organization at cadherin-adhesive contacts. Mol Biol Cell 17:1085–1095

    PubMed  CAS  Google Scholar 

  104. Song H-J, Ming G-L, He Z, Lehmann M, McKeracher L, Tessier-Lavigne M, Poo MM (1998) Conversion of neuronal growth cone responses from repulsion to attraction by cyclic nucleotides. Science 281:1515–1518

    PubMed  CAS  Google Scholar 

  105. Suchowersky O, Gronseth G, Perlmutter J, Reich S, Zesiewicz T, Weiner WJ. (2006) Practice parameter: neuroprotective strategies and alternative therapies for Parkinson disease (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 66:976–982

    PubMed  CAS  Google Scholar 

  106. Sharina IG, Krumenacker JS, Martin E, Murad F (2000) Genomic organization of alpha1 and beta1 subunits of the mammalian soluble guanylyl cyclase genes. Proc Natl Acad Sci USA 97:10878

    PubMed  CAS  Google Scholar 

  107. Sharina IG, Martin E, Thomas A, Uray KL, Murad F (2003) CCAAT-binding factor regulates expression of the beta1 subunit of soluble guanylyl cyclase gene in the BE2 human neuroblastoma cell line. Proc Natl Acad Sci USA 100:11523–11528

    PubMed  CAS  Google Scholar 

  108. Simard JM, Chen M, Tarasov KV, Bhatta S, Ivanova S, Melnitchenko L, Tsymbalyuk N, West GA, Gerzanich V (2006) Newly expressed SUR1-regulated NC(Ca-ATP) channel mediates cerebral edema after ischemic stroke. Nat Med 12:433–440

    PubMed  CAS  Google Scholar 

  109. Skidgel RA, Stanisavljevic S, Erdos EG (2006) A phosphoinositide 3-kinase-AKT-nitric oxide-cGMP signaling pathway in stimulating platelet secretion and aggregation. Biol Chem 387:159–165

    PubMed  CAS  Google Scholar 

  110. Son H, Lu YF, Zhuo M, Arancio O, Kandel E, Hawkins RD (1998) The specific role of cGMP in hippocampal LTP. Learn Mem 5:231–245

    PubMed  CAS  Google Scholar 

  111. Tabar V, Panagiotakos G, Greenberg ED, Chan BK, Sadelain M, Gutin PH, Studer L. (2005) Migration and differentiation of neural precursors derived from human embryonic stem cells in the rat brain. Nat Biotechnol 23:601–606

    PubMed  CAS  Google Scholar 

  112. Takagi Y, Takahashi J, Morizane A, Hayashi T, Kishi Y, Fukuda H, Okamoto Y, Koyanagi M, Ideguchi M, Hayashi H, Imazato T, Kawasaki H, Suemori H, Omachi S, Iida H, Itoh N, Nakatsuji N, Sasai Y, Hashimoto N (2005) Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model. J Clin Invest 115:102–109

    PubMed  CAS  Google Scholar 

  113. Traister A, Abashidze S, Gold V, Yairi R, Plachta MN, McJinnell I, Patel K, Weil M (2004) BMP controls nitric oxide-mediated regulation of cell numbers in the developing neural tube. Cell Death Different 11:832–841

    CAS  Google Scholar 

  114. Tropepe V, Hitoshi S, Sirard C, Mak TW, Rossant J, van der Kooy D (2001) Direct neural fate specification from embryonic stem cells: a primitive mammalian neural stem cell stage acquired through a default mechanism. Neuron 30:65–78

    PubMed  CAS  Google Scholar 

  115. Uhler MD (1993) Cloning and expression of a novel cyclic GMP-dependent protein kinase from mouse brain. J Biol Chem 268:13586–13591

    PubMed  CAS  Google Scholar 

  116. Yamada RX, Matsuki N, Ikegaya Y (2006) Soluble guanylyl cyclase inhibitor prevents Sema3F-induced collapse of axonal and dendritic growth cones of dentate granule cells. Biol Pharm Bull 29:796–798

    PubMed  CAS  Google Scholar 

  117. Yamamoto T, Suzuki N (2002) Promoter activity of the 5′-flanking regions of medaka fish soluble guanylate cyclase α1 and β1 subunit genes. Biochem J 361:337

    PubMed  CAS  Google Scholar 

  118. Waldman R, Nieberding M, Walter U (1987) Vasodilator-stimulated protein phosphorylation in platelets is mediated by cAMP- and cGMP-dependent protein kinases. Eur J Biochem 167:441–448

    Google Scholar 

  119. Wang HG, Lu FM, Jin I, Udo H, Kandel ER, deVente J, Walter U, Lohmann SM, Hawkins RD, Antonova I (2005) Presynaptic and postsynaptic roles of NO, cGK, and RhoA in long-lasting potentiation and aggregation of synaptic proteins. Neuron 45:389–403

    PubMed  CAS  Google Scholar 

  120. Wang X, Robinson PJ (1995) Cyclic GMP-dependent protein kinase substrates in rat brain. J Neurochem 65:595–604

    Article  PubMed  CAS  Google Scholar 

  121. Weight FF, Petzold G, Greengard P (1974) Guanosine 3′,5′-monophosphate in sympathetic ganglia: increase assoicated with synaptic transmission. Science 186:942–944

    PubMed  CAS  Google Scholar 

  122. Welshhans K, Rehder V (2005) Local activation of the nitric oxide/cyclic guanosine monophosphate pathway in growth cones regulates filopodial length via protein kinase G, cyclic ADP ribose and intracellular Ca2+ release. Eur J Neurosci 22:3006–3016

    PubMed  Google Scholar 

  123. Wirdefeldt K, Gatz M, Pawitan Y, Pederson NL (2005) Risk and protective factors for Parkinson’s disease: a study in Swedish twins. Ann Neurol 57:27–33

    PubMed  Google Scholar 

  124. Wirdefeldt K, Gatz M, Schalling M, Pedersen NL (2004) No evidence for heritability of Parkinson disease in Swedish twins. Neurology 63:305–311

    PubMed  Google Scholar 

  125. Wyckoff MH, Chambliss KL, Mineo C, Yuhanna IS, Mendelsohn ME, Mumby SM, Shaul PW (2001) Plasma membrane estrogen receptors are coupled to endothelial nitric-oxide synthase through Galpha(i). J Biol Chem 276:27071–27076

    PubMed  CAS  Google Scholar 

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Acknowledgments

Our studies reported here were supported by multiple grants and awards from the following: The National Institute of Health, The John S. Dunn Foundation, The Welch Foundation, NASA, The U.S. Department of Defense and the University of Texas.

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Authors and Affiliations

  1. The Brown Foundation Institute of Molecular Medicine, University of Texas Houston Health Science Center, 1825 Pressler street, Houston, TX, 77030, USA

    K. S. Madhusoodanan & Ferid Murad

  2. Department of Integrative Biology and Pharmacology, University of Texas Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA

    Ferid Murad

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  1. K. S. Madhusoodanan
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  2. Ferid Murad
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Correspondence to Ferid Murad.

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Special issue dedicated to John P. Blass.

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Madhusoodanan, K.S., Murad, F. NO-cGMP Signaling and Regenerative Medicine Involving Stem Cells. Neurochem Res 32, 681–694 (2007). https://doi.org/10.1007/s11064-006-9167-y

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