Neuronal nitric oxide synthase: Structure, subcellular localization, regulation, and clinical implications

Nitric Oxide - Biology and Chemistry

Volumn 20, Issue 4, 2009, Pages 223-230

  Zhou, Li ^a   Zhu, Dong Ya ^a  

^a NANJING MEDICAL UNIVERSITY   (China)

Author keywords

Alzheimer's disease; Depression; Excitotoxicity; Learning and memory; Neurogenesis; Nitric oxide; nNOS; Parkinson's disease; PDZ domain

Indexed keywords

CAVEOLIN 3; HEAT SHOCK PROTEIN 90; NEURONAL NITRIC OXIDE SYNTHASE; PROTEIN; PROTEIN INHIBITOR;

ALZHEIMER DISEASE; BRAIN; CELLULAR DISTRIBUTION; DEPRESSION; DIMERIZATION; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; ENZYME REGULATION; ENZYME STRUCTURE; EXCITOTOXICITY; HUMAN; ISCHEMIA; LEARNING; MEMORY; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; PARKINSON DISEASE; PDZ DOMAIN; PHYSIOLOGY; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION;

ALZHEIMER DISEASE; ANIMALS; BRAIN; CALMODULIN; CAVEOLIN 3; DEPRESSION; HSP90 HEAT-SHOCK PROTEINS; HUMANS; ISCHEMIA; MODELS, BIOLOGICAL; NEUROGENESIS; NITRIC OXIDE SYNTHASE TYPE I; PARKINSON DISEASE; PHOSPHORYLATION;

EID: 67349230279     PISSN: 10898603     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.niox.2009.03.001     Document Type: Review

References (126)

1. Kang Y.C., Kim P.K., Choi B.M., Chung H.T., Ha K.S., Kwon Y.G., and Kim Y.M. Regulation of programmed cell death in neuronal cells by nitric oxide. In Vivo 18 (2004) 367-376
2. Moncada S., and Bolaños J.P. Nitric oxide, cell bioenergetics and neurodegeneration. J. Neurochem. 97 (2006) 1676-1689
3. Garthwaite J. Concepts of neural nitric oxide-mediated transmission. Eur. J. Neurosci. 27 (2008) 2783-2802
4. Bredt D.S. Endogenous nitric oxide synthesis: biological functions and pathophysiology. Free Radic. Res. 31 (1999) 577-596
5. Calabrese V., Mancuso C., Calvani M., Rizzarelli E., Butterfield D.A., and Stella A.M. Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat. Rev. Neurosci. 8 (2007) 766-775
6. Schwarz P.M., Kleinert H., and Forstermann U. Potential functional significance of brain-type and muscle-type nitric oxide synthase I expressed in adventitia and media of rat aorta. Arterioscler. Thromb. Vasc. Biol. 19 (1999) 2584-2590
7. Xu K.Y., Huso D.L., Dawson T.M., Bredt D.S., and Becker L.C. Nitric oxide synthase in cardiac sarcoplasmic reticulum. Proc. Natl. Acad. Sci. USA 96 (1999) 657-662
8. Rothe F., Langnaese K., and Wolf G. New aspects of the location of neuronal nitric oxide synthase in the skeletal muscle: a light and electron microscopic study. Nitric Oxide 13 (2005) 21-35
9. McConell G.K., Bradley S.J., Stephens T.J., Canny B.J., Kingwell B.A., and Lee-Young R.S. Skeletal muscle nNOS mu protein content is increased by exercise training in humans. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293 (2007) R821-R828
10. Stamler J.S., and Meissner G. Physiology of nitric oxide in skeletal muscle. Physiol. Rev. 81 (2001) 209-237
11. Lau K.S., Grange R.W., Isotani E., Sarelius I.H., Kamm K.E., Huang P.L., and Stull J.T. NNOS and eNOS modulate cGMP formation and vascular response in contracting fast-twitch skeletal muscle. Physiol. Genomics 2 (2000) 21-27
12. Santizo R., Baughman V.L., and Pelligrino D.A. Relative contributions from neuronal and endothelial nitric oxide synthases to regional cerebral blood flow changes during forebrain ischemia in rats. Neuroreport 11 (2000) 1549-1553
13. Boissel J.P., Schwarz P.M., and Förstermann U. Neuronal-type NO synthase: transcript diversity and expressional regulation. Nitric Oxide 2 (1998) 337-349
14. Reif A., Fröhlich L.G., Kotsonis P., Frey A., Bömmel H.M., Wink D.A., Pfleiderer W., and Schmidt H.H. Tetrahydrobiopterin inhibits monomerization and is consumed during catalysis in neuronal NO synthase. J. Biol. Chem. 274 (1999) 24921-24929
15. Sagami I., Daff S., and Shimizu T. Intra-subunit and inter-subunit electron transfer in neuronal nitric-oxide synthase: effect of calmodulin on heterodimer catalysis. J. Biol. Chem. 276 (2001) 30036-30042
16. Noguchi T., Sagami I., Daff S., and Shimizu T. Important role of tetrahydrobiopterin in no complex formation and interdomain electron transfer in neuronal nitric-oxide synthase. Biochem. Biophys. Res. Commun. 282 (2001) 1092-1097
17. Hemmens B., Goessler W., Schmidt K., and Mayer B. Role of bound zinc in dimer stabilization but not enzyme activity of neuronal nitric-oxide synthase. J. Biol. Chem. 275 (2000) 35786-35791
18. Roman L.J., and Masters B.S. Electron transfer by neuronal nitric-oxide synthase is regulated by concerted interaction of calmodulin and two intrinsic regulatory elements. J. Biol. Chem. 281 (2006) 23111-23118
19. Jiang X., Mu D., Manabat C., Koshy A.A., Christen S., Täuber M.G., Vexler Z.S., and Ferriero D.M. Differential vulnerability of immature murine neurons to oxygen-glucose deprivation. Exp. Neurol. 190 (2004) 224-232
20. Chen J., Tu Y., Moon C., Matarazzo V., Palmer A.M., and Ronnett G.V. The localization of neuronal nitric oxide synthase may influence its role in neuronal precursor proliferation and synaptic maintenance. Dev. Biol. 269 (2004) 165-182
21. Wang H., Kohr M.J., Traynham C.J., Wheeler D.G., Janssen P.M., and Ziolo M.T. Neuronal nitric oxide synthase signaling within cardiac myocytes targets phospholamban. Am. J. Physiol. Cell Physiol. 294 (2008) C1566-C1575
22. Yuan Z., Liu B., Yuan L., Zhang Y., Dong X., and Lu J. Evidence of nuclear localization of neuronal nitric oxide synthase in cultured astrocytes of rats. Life Sci. 74 (2004) 3199-3209
23. Hecker M., Mülsch A., and Busse R. Subcellular localization and characterization of neuronal nitric oxide synthase. J. Neurochem. 62 (1994) 1524-1529
24. Rothe F., Canzler U., and Wolf G. Subcellular localization of the neuronal isoform of nitric oxide synthase in the rat brain: a critical evaluation. Neuroscience 83 (1998) 259-269
25. Korzhevskiǐ D.E., Otellin V.A., Grigor'ev I.P., Petrova E.S., Gilerovich E.G., and Zin'kova N.N. Immunocytochemical demonstration of neuronal NO-synthase in rat brain cells. Morfologiia 132 (2007) 77-80
26. Brenman J.E., Christopherson K.S., Craven S.E., McGee A.W., and Bredt D.S. Cloning and characterization of postsynaptic density 93, a nitric oxide synthase interacting protein. J. Neurosci. 16 (1996) 7407-7415
27. Jaffrey S.R., Benfenati F., Snowman A.M., Czernik A.J., and Snyder S.H. Neuronal nitric-oxide synthase localization mediated by a ternary complex with synapsin and CAPON. Proc. Natl. Acad. Sci. USA 99 (2002) 3199-3204
28. Crane B.R., Arvai A.S., Ghosh D.K., Wu C., Getzoff E.D., Stuehr D.J., and Tainer J.A. Structure of nitric oxide synthase oxygenase dimer with pterin and substrate. Science 279 (1998) 2121-2126
29. Fischmann T.O., Hruza A., Niu X.D., Fossetta J.D., Lunn C.A., Dolphin E., Prongay A.J., Reichert P., Lundell D.J., Narula S.K., and Weber P.C. Structural characterization of nitric oxide synthase isoforms reveals striking active site conservation. Nat. Struct. Biol. 6 (1999) 233-242
30. Venema V.J., Ju H., Zou R., and Venema R.C. Interaction of neuronal nitric-oxide synthase with caveolin-3 in skeletal muscle. Identification of a novel caveolin scaffolding/inhibitory domain. J. Biol. Chem. 272 (1997) 28187-28190
31. Panda K., Adak S., Aulak K.S., Santolini J., McDonald J.F., and Stuehr D.J. Distinct influence of N-terminal elements on neuronal nitric-oxide synthase structure and catalysis. J. Biol. Chem. 278 (2003) 37122-37131
32. Kamada Y., Jenkins G.J., Lau M., Dunbar A.Y., Lowe E.R., and Osawa Y. Tetrahydrobiopterin depletion and ubiquitylation of neuronal nitric oxide synthase. Brain Res. Mol. Brain Res. 142 (2005) 19-27
33. Lajoix A.D., Pugnière M., Roquet F., Mani J.C., Dietz S., Linck N., Faurie F., Ribes G., Petit P., and Gross R. Changes in the dimeric state of neuronal nitric oxide synthase affect the kinetics of secretagogue-induced insulin response. Diabetes 53 (2004) 1467-1474
34. Dunbar A.Y., Kamada Y., Jenkins G.J., Lowe E.R., Billecke S.S., and Osawa Y. Ubiquitination and degradation of neuronal nitric-oxide synthase in vitro: dimer stabilization protects the enzyme from proteolysis. Mol. Pharmacol. 66 (2004) 964-969
35. Siddhanta U., Wu C., Abu-Soud H.M., Zhang J., Ghosh D.K., and Stuehr D.J. Heme iron reduction and catalysis by a nitric oxide synthase heterodimer containing one reductase and two oxygenase domains. J. Biol. Chem. 271 (1996) 7309-7312
36. Jaffrey S.R., and Snyder S.H. PIN: an associated protein inhibitor of neuronal nitric oxide synthase. Science 274 (1996) 774-777
37. El-Mlili N., Rodrigo R., Naghizadeh B., Cauli O., and Felipo V. Chronic hyperammonemia reduces the activity of neuronal nitric oxide synthase in cerebellum by altering its localization and increasing its phosphorylation by calcium-calmodulin kinase II. J. Neurochem. 106 (2008) 1440-1449
38. Rameau G.A., Chiu L.Y., and Ziff E.B. Bidirectional regulation of neuronal nitric oxide synthase phosphorylation at serine 847 by the N-methyl-d-aspartate receptor. J. Biol. Chem. 279 (2004) 4307-4314
39. Adak S., Santolini J., Tikunova S., Wang Q., Johnson J.D., and Stuehr D.J. Neuronal nitric-oxide synthase mutant (Ser-1412 → Asp) demonstrates surprising connections between heme reduction, NO complex formation, and catalysis. J. Biol. Chem. 276 (2001) 1244-1252
40. Rameau G.A., Tukey D.S., Garcin-Hosfield E.D., Titcombe R.F., Misra C., Khatri L., Getzoff E.D., and Ziff E.B. Biphasic coupling of neuronal nitric oxide synthase phosphorylation to the NMDA receptor regulates AMPA receptor trafficking and neuronal cell death. J. Neurosci. 27 (2007) 3445-3455
41. Song T., Hatano N., Horii M., Tokumitsu H., Yamaguchi F., Tokuda M., and Watanabe Y. Calcium/calmodulin-dependent protein kinase I inhibits neuronal nitric-oxide synthase activity through serine 741 phosphorylation. FEBS Lett. 570 (2004) 133-137
42. Matsuda H., and Iyanagi T. Calmodulin activates intramolecular electron transfer between the two flavins of neuronal nitric oxide synthase flavin domain. Biochim. Biophys. Acta 1473 (1999) 345-355
43. Roman L.J., and Masters B.S. Electron transfer by neuronal nitric-oxide synthase is regulated by concerted interaction of calmodulin and two intrinsic regulatory elements. J. Biol. Chem. 281 (2006) 23111-23118
44. Guan Z.W., and Iyanagi T. Electron transfer is activated by calmodulin in the flavin domain of human neuronal nitric oxide synthase. Arch. Biochem. Biophys. 412 (2003) 65-76
45. Dreyer J., Schleicher M., Tappe A., Schilling K., Kuner T., Kusumawidijaja G., Müller-Esterl W., Oess S., and Kuner R. Nitric oxide synthase (NOS)-interacting protein interacts with neuronal NOS and regulates its distribution and activity. J. Neurosci. 24 (2004) 10454-10465
46. Nathan C., and Xie Q.W. Nitric oxide synthases: roles, tolls, and controls. Cell 78 (1994) 915-918
47. 2+, calmodulin and phospholipids regulate nitric oxide synthase activity in the rabbit submandibular gland. J. Comp. Physiol. [B] 174 (2004) 593-599
48. Li H., and Poulos T.L. Structure-function studies on nitric oxide synthases. J. Inorg. Biochem. 99 (2005) 293-305
49. Cui H., Hayashi A., Sun H.S., Belmares M.P., Cobey C., Phan T., Schweizer J., Salter M.W., Wang Y.T., Tasker R.A., Garman D., Rabinowitz J., Lu P.S., and Tymianski M. PDZ protein interactions underlying NMDA receptor-mediated excitotoxicity and neuroprotection by PSD-95 inhibitors. J. Neurosci. 27 (2007) 9901-9915
50. Chen M., Cheng C., Yan M., Niu S., Gao S., Shi S., Liu H., Qin Y., and Shen A. Involvement of CAPON and nitric oxide synthases in rat muscle regeneration after peripheral nerve injury. J. Mol. Neurosci. 34 (2008) 89-100
51. Lemaire J.F., and McPherson P.S. Binding of Vac14 to neuronal nitric oxide synthase: characterisation of a new internal PDZ-recognition motif. FEBS Lett. 580 (2006) 6948-6954
52. Chanrion B., Mannoury la Cour C., Bertaso F., Lerner-Natoli M., Freissmuth M., Millan M.J., Bockaert J., and Marin P. Physical interaction between the serotonin transporter and neuronal nitric oxide synthase underlies reciprocal modulation of their activity. Proc. Natl. Acad. Sci. USA 104 (2007) 8119-8124
53. Saitoh F., Tian Q.B., Okano A., Sakagami H., Kondo H., and Suzuki T. NIDD, a novel DHHC-containing protein, targets neuronal nitric-oxide synthase (nNOS) to the synaptic membrane through a PDZ-dependent interaction and regulates nNOS activity. J. Biol. Chem. 279 (2004) 29461-29468
54. Riefler G.M., and Firestein B.L. Binding of neuronal nitric-oxide synthase (nNOS) to carboxyl-terminal-binding protein (CtBP) changes the localization of CtBP from the nucleus to the cytosol: a novel function for targeting by the PDZ domain of nNOS. J. Biol. Chem. 276 (2001) 48262-48268
55. Sattler R., Xiong Z., Lu W.Y., Hafner M., MacDonald J.F., and Tymianski M. Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein. Science 284 (1999) 1845-1848
56. Jaffrey S.R., Snowman A.M., Eliasson M.J., Cohen N.A., and Snyder S.H. CAPON: a protein associated with neuronal nitric oxide synthase that regulates its interactions with PSD95. Neuron 20 (1998) 115-124
57. Fang M., Jaffrey S.R., Sawa A., Ye K., Luo X., and Snyder S.H. Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON. Neuron 28 (2000) 183-19327
58. Cheah J.H., Kim S.F., Hester L.D., Clancy K.W., Patterson III S.E., Papadopoulos V., and Snyder S.H. NMDA receptor-nitric oxide transmission mediates neuronal iron homeostasis via the GTPase Dexras1. Neuron 51 (2006) 431-440
59. Moos T., and Morgan E.H. The metabolism of neuronal iron and its pathogenic role in neurological disease: review. Ann. NY Acad. Sci. 1012 (2004) 14-26
60. Firestein B.L., and Bredt D.S. Interaction of neuronal nitric-oxide synthase and phosphofructokinase-M. J. Biol. Chem. 274 (1999) 10545-10550
61. Tochio H., Mok Y.K., Zhang Q., Kan H.M., Bredt D.S., and Zhang M. Formation of nNOS/PSD-95 PDZ dimer requires a preformed beta-finger structure from the nNOS PDZ domain. J. Mol. Biol. 303 (2000) 359-370
62. Christopherson K.S., Hillier B.J., Lim W.A., and Bredt B.S. PSD-95 assembles a ternary complex with the N-methyl-d-aspartic acid receptor and a bivalent neuronal NO synthase PDZ domain. J. Biol. Chem. 274 (1999) 27467-27473
63. Rodríguez-Crespo I., Straub W., Gavilanes F., and Ortiz de Montellano P.R. Binding of dynein light chain (PIN) to neuronal nitric oxide synthase in the absence of inhibition. Arch. Biochem. Biophys. 359 (1998) 297-304
64. Xia Y., Berlowitz C.O., and Zweier J.L. PIN inhibits nitric oxide and superoxide production from purified neuronal nitric oxide synthase. Biochim. Biophys. Acta 1760 (2006) 1445-1449
65. Bender A.T., Silverstein A.M., Demady D.R., Kanelakis K.C., Noguchi S., Pratt W.B., and Osawa Y. Neuronal nitric-oxide synthase is regulated by the Hsp90-based chaperone system in vivo. J. Biol. Chem. 274 (1999) 1472-1478
66. Song Y., Zweier J.L., and Xia Y. Heat-shock protein 90 augments neuronal nitric oxide synthase activity by enhancing Ca2+/calmodulin binding. Biochem. J. 355 (2001) 357-360
67. Bruel-Jungerman E., Rampon C., and Laroche S. Adult hippocampal neurogenesis, synaptic plasticity and memory: facts and hypotheses. Rev. Neurosci. 18 (2007) 93-114
68. Parent J.M., Elliott R.C., Pleasure S.J., Barbaro N.M., and Lowenstein D.H. Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy. Ann. Neurol. 59 (2006) 81-91
69. Wiltrout C., Lang B., Yan Y., Dempsey R.J., and Vemuganti R. Repairing brain after stroke: a review on post-ischemic neurogenesis. Neurochem. Int. 50 (2007) 1028-1041
70. Ehninger D., and Kempermann G. Neurogenesis in the adult hippocampus. Cell Tissue Res. 331 (2008) 243-250
71. Romero-Grimaldi C., Moreno-López B., and Estrada C. Age-dependent effect of nitric oxide on subventricular zone and olfactory bulb neural precursor proliferation. J. Comp. Neurol. 506 (2008) 339-346
72. Islam A.T., Kuraoka A., and Kawabuchi M. Morphological basis of nitric oxide production and its correlation with the polysialylated precursor cells in the dentate gyrus of the adult guinea pig hippocampus. Anat. Sci. Int. 78 (2003) 98-103
73. Matarredona E.R., Murillo-Carretero M., Moreno-López B., and Estrada C. Nitric oxide synthesis inhibition increases proliferation of neural precursors isolated from the postnatal mouse subventricular zone. Brain Res. 995 (2004) 274-284
74. Zhu X.J., Hua Y., Jiang J., Zhou Q.G., Luo C.X., Han X., Lu Y.M., and Zhu D.Y. Neuronal nitric oxide synthase-derived nitric oxide inhibits neurogenesis in the adult dentate gyrus by down-regulating cyclic AMP response element binding protein phosphorylation. Neuroscience 141 (2006) 827-836
75. Packer M.A., Stasiv Y., Benraiss A., Chmielnicki E., Grinberg A., Westphal H., Goldman S.A., and Enikolopov G. Nitric oxide negatively regulates mammalian adult neurogenesis. Proc. Natl. Acad. Sci. USA 100 (2003) 9566-9571
76. Jin K., Minami M., Lan J.Q., Mao X.O., Batteur S., Simon R.P., and Greenberg D.A. Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc. Natl. Acad. Sci. USA 98 (2001) 4710-4715
77. Zhou Q.G., Hu Y., Hua Y., Hu M., Luo C.X., Han X., Zhu X.J., Wang B., Xu J.S., and Zhu D.Y. Neuronal nitric oxide synthase contributes to chronic stress-induced depression by suppressing hippocampal neurogenesis. J. Neurochem. 103 (2007) 1843-1854
78. Zhang R., Zhang L., Zhang Z., Wang Y., Lu M., Lapointe M., and Chopp M. A nitric oxide donor induces neurogenesis and reduces functional deficits after stroke in rats. Ann. Neurol. 50 (2001) 602-611
79. Hua Y., Huang X.Y., Zhou L., Zhou Q.G., Hu Y., Luo C.X., Li F., and Zhu D.Y. DETA/NONOate, a nitric oxide donor, produces antidepressant effects by promoting hippocampal neurogenesis. Psychopharmacology (Berlin) 200 (2008) 231-242
80. Blackshaw S., Eliasson M.J., Sawa A., Watkins C.C., Krug D., Gupta A., Arai T., Ferrante R.J., and Snyder S.H. Species, strain and developmental variations in hippocampal neuronal and endothelial nitric oxide synthase clarify discrepancies in nitric oxide-dependent synaptic plasticity. Neuroscience 119 (2003) 979-990
81. Bon C.L., and Garthwaite J. On the role of nitric oxide in hippocampal long-term potentiation. J. Neurosci. 23 (2003) 1941-1948
82. Böhme G.A., Bon C., Lemaire M., Reibaud M., Piot O., Stutzmann J.M., Doble A., and Blanchard J.C. Altered synaptic plasticity and memory formation in nitric oxide synthase inhibitor-treated rats. Proc. Natl. Acad. Sci. USA 90 (1993) 9191-9194
83. Rickard N.S., and Gibbs M.E. Effects of nitric oxide inhibition on avoidance learning in the chick are lateralized and localized. Neurobiol. Learn. Mem. 79 (2003) 252-256
84. Koylu E.O., Kanit L., Taskiran D., Dagci T., Balkan B., and Pogun S. Effects of nitric oxide synthase inhibition on spatial discrimination learning and central DA2 and mACh receptors. Pharmacol. Biochem. Behav. 81 (2005) 32-40
85. Bannerman D.M., Chapman P.F., Kelly P.A., Butcher S.P., and Morris R.G. Inhibition of nitric oxide synthase does not impair spatial learning. J. Neurosci. 14 (1994) 7404-7414
86. Rickard N.S., Gibbs M.E., and Ng K.T. Inhibition of the endothelial isoform of nitric oxide synthase impairs long-term memory formation in the chick. Learn. Mem. 6 (1999) 458-466
87. Hölscher C., McGlinchey L., Anwyl R., and Rowan M.J. 7-Nitroindazole, a selective neuronal nitric oxide synthase inhibitor in vivo, impairs spatial learning in the rat. Learn. Mem. 2 (1996) 267-278
88. Yildiz Akar F., Ulak G., Tanyeri P., Erden F., Utkan T., and Gacar N. 7-Nitroindazole, a neuronal nitric oxide synthase inhibitor, impairs passive-avoidance and elevated plus-maze memory performance in rats. Pharmacol. Biochem. Behav. 87 (2007) 434-443
89. Xu X.J., Russell T., Bazner J., and Hamilton J. NMDA receptor antagonist AP5 and nitric oxide synthase inhibitor 7-NI affect different phases of learning and memory in goldfish. Brain Res. 889 (2001) 274-277
90. Weitzdoerfer R., Hoeger H., Engidawork E., Engelmann M., Singewald N., Lubec G., and Lubec B. Neuronal nitric oxide synthase knock-out mice show impaired cognitive performance. Nitric oxide 10 (2004) 130-140
91. Kirchner L., Weitzdoerfer R., Hoeger H., Url A., Schmidt P., Engelmann M., Villar S.R., Fountoulakis M., Lubec G., and Lubec B. Impaired cognitive performance in neuronal nitric oxide synthase knockout mice is associated with hippocampal protein derangements. Nitric oxide 11 (2004) 316-330
92. Sattler R., and Tymianski M. Molecular mechanisms of calcium-dependent excitotoxicity. J. Mol. Med. 78 (2000) 3-13
93. Gardoni F., and Di Luca M. New targets for pharmacological intervention in the glutamatergic synapse. Eur. J. Pharmacol. 545 (2006) 2-10
94. Arundine M., and Tymianski M. Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity. Cell Calcium 34 (2003) 325-337
95. Eliasson M.J., Huang Z., Ferrante R.J., Sasamata M., Molliver M.E., Snyder S.H., and Moskowitz M.A. Neuronal nitric oxide synthase activation and peroxynitrite formation in ischemic stroke linked to neural damage. J. Neurosci. 19 (1999) 5910-5918
96. Oka M., Hirouchi M., Itoh Y., and Ukai Y. Involvement of peroxynitrite and hydroxyradical generated from nitric oxide in hypoxia/reoxygenation injury in rat cerebrocortical slices. Neuropharmacology 39 (2000) 1319-1330
97. Dawson V.L., Kizushi V.M., Huang P.L., Snyder S.H., and Dawson T.M. Resistance to neurotoxicity in cortical cultures from neuronal nitric oxide synthase deficient mice. J. Neurosci. 16 (1996) 2479-2487
98. Huang P.L. Neuronal and endothelial nitric oxide synthase gene knockout mice. Braz. J. Med. Biol. Res. 32 (1999) 1353-1359
99. Zhang Z.G., Reif D., Macdonald J., Tang W.X., Kamp D.K., Gentile R.J., Shakespeare W.C., Murray R.J., and Chopp M. ARL 17477, a potent and selective neuronal NOS inhibitor decreases infarct volume after transient middle cerebral artery occlusion in rats. J. Cereb. Blood Flow Metab. 16 (1996) 599-604
100. Nanri K., Montécot C., Springhetti V., Seylaz J., and Pinard E. The selective inhibitor of neuronal nitric oxide synthase, 7-nitroindazole, reduces the delayed neuronal damage due to forebrain ischemia in rats. Stroke 29 (1998) 1248-1253 discussion 1253-1254
101. Sun Y., Jin K., Childs J.T., Xie L., Mao X.O., and Greenberg D.A. Neuronal nitric oxide synthase and ischemia-induced neurogenesis. J. Cereb. Blood Flow Metab. 25 (2005) 485-492
102. Luo C.X., Zhu X.J., Zhou Q.G., Wang B., Wang W., Cai H.H., Sun Y.J., Hu M., Jiang J., Hua Y., Han X., and Zhu D.Y. Reduced neuronal nitric oxide synthase is involved in ischemia-induced hippocampal neurogenesis by up-regulating inducible nitric oxide synthase expression. J. Neurochem. 103 (2007) 1872-1882
103. Abulrob A., Tauskela J.S., Mealing G., Brunette E., Faid K., and Stanimirovic D. Protection by cholesterol-extracting cyclodextrins: a role for N-methyl-d-aspartate receptor redistribution. J. Neurochem. 92 (2005) 1477-1486
104. Takagi N., Logan R., Teves L., Wallace M.C., and Gurd J.W. Altered interaction between PSD-95 and the NMDA receptor following transient global ischemia. J. Neurochem. 74 (2000) 169-178
105. Yan X.B., Song B., and Zhang G.Y. Postsynaptic density protein 95 mediates Ca2+/calmodulin-dependent protein kinase II-activated serine phosphorylation of neuronal nitric oxide synthase during brain ischemia in rat hippocampus. Neurosci. Lett. 355 (2004) 197-200
106. Samdani A.F., Dawson T.M., and Dawson V.L. Nitric oxide synthase in models of focal ischemia. Stroke 28 (1997) 1283-1288
107. Manji H.K., Drevets W.C., and Charney D.S. The cellular neurobiology of depression. Nat. Med. 7 (2001) 541-547
108. Angulo J., Peiró C., Sanchez-Ferrer C.F., Gabancho S., Cuevas P., Gupta S., and Sáenz de Tejada I. Differential effects of serotonin reuptake inhibitors on erectile responses, NO-production, and neuronal NO synthase expression in rat corpus cavernosum tissue. Br. J. Pharmacol. 134 (2001) 1190-1194
109. Harvey B.H., Retief R., Korff A., and Wegener G. Increased hippocampal nitric oxide synthase activity and stress responsiveness after imipramine discontinuation: Role of 5HT2A/C-receptors. Metab. Brain Dis. 21 (2006) 211-220
110. Suzuki E., Yagi G., Nakaki T., Kanba S., and Asai M. Elevated plasma nitrate levels in depressive states. J. Affect Disord. 63 (2001) 221-224
111. F. Yildiz, B.F. Erden, G. Ulak, T. Utkan, N. Gacar, Antidepressant-like effect of 7-nitroindazole in the forced swimming test in rats, Psychopharmacology (Berlin) 149 (2000) 41-44.
112. Kishimoto J., Tsuchiya T., Emson P.C., and Nakayama Y. Immobilization-induced stress activates neuronal nitric oxide synthase (nNOS) mRNA and protein in hypothalamic-pituitary-adrenal axis in rats. Brain Res. 720 (1996) 159-171
113. Burns R.S., Chiueh C.C., Markey S.P., Ebert M.H., Jacobowitz D.M., and Kopin I.J. A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine. Proc. Natl. Acad. Sci. USA 80 (1983) 4546-4550
114. Kühn K., Wellen J., Link N., Maskri L., Lübbert H., and Stichel C.C. The mouse MPTP model: gene expression changes in dopaminergic neurons. Eur. J. Neurosci. 17 (2003) 1-12
115. Matthews R.T., Beal M.F., Fallon J., Fedorchak K., Huang P.L., Fishman M.C., and Hyman B.T. MPP+ induced substantia nigra degeneration is attenuated in nNOS knockout mice. Neurobiol. Dis. 4 (1997) 114-121
116. Kurosaki R., Muramatsu Y., Michimata M., Matsubara M., Kato H., Imai Y., Itoyama Y., and Araki T. Role of nitric oxide synthase against MPTP neurotoxicity in mice. Neurol. Res. 24 (2002) 655-662
117. Watanabe Y., Kato H., and Araki T. Protective action of neuronal nitric oxide synthase inhibitor in the MPTP mouse model of Parkinson's disease. Metab. Brain Dis. 23 (2008) 51-69
118. Gatto E.M., Riobó N.A., Carreras M.C., Cherñavsky A., Rubio A., Satz M.L., and Poderoso J.J. Overexpression of neutrophil neuronal nitric oxide synthase in Parkinson's disease. Nitric oxide 4 (2000) 534-539
119. Selkoe D.J. Alzheimer's disease: genes, proteins, and therapy. Physiol. Rev. 81 (2001) 741-766
120. Tran M.H., Yamada K., Nakajima A., Mizuno M., He J., Kamei H., and Nabeshima T. Tyrosine nitration of a synaptic protein synaptophysin contributes to amyloid beta-peptide-induced cholinergic dysfunction. Mol. Psychiatry 8 (2003) 407-412
121. Malinski T. Nitric oxide and nitroxidative stress in Alzheimer's disease. J. Alzheimer's Dis. 11 (2007) 207-218
122. Simic G., Lucassen P.J., Krsnik Z., Kruslin B., Kostovic I., and Winblad B. Bogdanovi, nNOS expression in reactive astrocytes correlates with increased cell death related DNA damage in the hippocampus and entorhinal cortex in Alzheimer's disease. Exp. Neurol. 165 (2000) 12-26
123. Sultana R., Poon H.F., Cai J., Pierce W.M., Merchant M., Klein J.B., Markesbery W.R., and Butterfield D.A. Identification of nitrated proteins in Alzheimer's disease brain using a redox proteomics approach. Neurobiol. Dis. 22 (2006) 76-87
124. Thorns V., Hansen L., and Masliah E. nNOS expressing neurons in the entorhinal cortex and hippocampus are affected in patients with Alzheimer's disease. Exp. Neurol. 150 (1998) 14-20
125. Lüth H.J., Holzer M., Gärtner U., Staufenbiel M., and Arendt T. Expression of endothelial and inducible NOS-isoforms is increased in Alzheimer's disease, in APP23 transgenic mice and after experimental brain lesion in rat: evidence for an induction by amyloid pathology. Brain Res. 913 (2001) 57-67
126. Cao J., Viholainen J.I., Dart C., Warwick H.K., Leyland M.L., and Courtney M.J. The PSD95-nNOS interface: a target for inhibition of excitotoxic p38 stress-activated protein kinase activation and cell death. J. Cell Biol. 168 (2005) 117-1126