Neurochemical Research

, Volume 43, Issue 1, pp 50–58 | Cite as

S-Nitrosylation Regulates Cell Survival and Death in the Central Nervous System

  • Yoshiki KoriyamaEmail author
  • Ayako Furukawa
Original Paper


Nitric oxide (NO), which is produced from nitric oxide synthase, is an important cell signaling molecule that is crucial for many physiological functions such as neuronal death, neuronal survival, synaptic plasticity, and vascular homeostasis. This diffusible gaseous compound functions as an effector or second messenger in many intercellular communications and/or cell signaling pathways. Protein S-nitrosylation is a posttranslational modification that involves the covalent attachment of an NO group to the thiol side chain of select cysteine residues on target proteins. This process is thought to be very important for the regulation of cell death, cell survival, and gene expression in the central nervous system (CNS). However, there have been few reports on the role of protein S-nitrosylation in CNS disorders. Here, we briefly review specific examples of S-nitrosylation, with particular emphasis on its functions in neuronal cell death and survival. An understanding of the role and mechanisms underlying the effects of protein S-nitrosylation on neurodegenerative/neuroprotective events may reveal a novel therapeutic strategy for rescuing neurons in neurodegenerative diseases.


Nitric oxide S-Nitrosylation CNS Death Survival 


  1. 1.
    Hara MR, Snyder SH (2007) Cell signaling and neuronal death. Annu Rev Pharmacol Toxicol 47:117–141PubMedCrossRefGoogle Scholar
  2. 2.
    Thippeswamy T, Jain RK, Mumtaz N, Morris R (2001) Inhibition of neuronal nitric oxide synthase results in neurodegenerative changes in the axotomised dorsal root ganglion neurons: evidence for a neuroprotective role of nitric oxide in vivo. Neurosci Res 40:37–44PubMedCrossRefGoogle Scholar
  3. 3.
    Ciani E, Guidi S, Della Valle G, Perini G, Bartesaghi R, Contestabile A (2002) Nitric oxide protects neuroblastoma cells from apoptosis induced by serum deprivation through cAMP-response element-binding protein (CREB) activation. J Biol Chem 277:49896–49902PubMedCrossRefGoogle Scholar
  4. 4.
    Estevez AG, Spear N, Thompson JA, Cornwell TL, Radi R, Barbeito L, Beckman JS (1998) Nitric oxide-dependent production of cGMP supports the survival of rat embryonic motor neurons cultured with brain-derived neurotrophic factor. J Neurosci 18:3708–3714PubMedCrossRefGoogle Scholar
  5. 5.
    Ha KS, Kim KM, Kwon YG, Bai SK, Nam WD, Yoo YM, Kim PK, Chung HT, Billiar TR, Kim YM (2003) Nitric oxide prevents 6-hydroxydopamine-induced apoptosis in PC12 cells through cGMP-dependent PI3 kinase/Akt activation. FASEB J 17:1036–1047PubMedCrossRefGoogle Scholar
  6. 6.
    Koriyama Y, Yasuda R, Homma K, Mawatari K, Nagashima M, Sugitani K, Matsukawa T, Kato S (2009) Nitric oxide-cGMP signaling regulates axonal elongation during optic nerve regeneration in the goldfish in vitro and in vivo. J Neurochem 110:890–901PubMedCrossRefGoogle Scholar
  7. 7.
    Yamazaki M, Chiba K, Mohri T, Hatanaka H (2001) Activation of the mitogen-activated protein kinase cascade through nitric oxide synthesis as a mechanism of neuritogenic effect of genipin in PC12h cells. J Neurochem 79:45–54PubMedCrossRefGoogle Scholar
  8. 8.
    Yamazaki M, Chiba K, Mohri T, Hatanaka H (2004) Cyclic GMP-dependent neurite outgrowth by genipin and nerve growth factor in PC12h cells. Eur J Pharmacol 488:35–43PubMedCrossRefGoogle Scholar
  9. 9.
    Zhao Y, Biermann T, Luther C, Unger T, Culman J, Gohlke P (2003) Contribution of bradykinin and nitric oxide to AT2 receptor-mediated differentiation in PC12 W cells. J Neurochem 85:759–767PubMedCrossRefGoogle Scholar
  10. 10.
    Audesirk T, Cabell L, Kern M, Audesirk G (2003) Enhancement of dendritic branching in cultured hippocampal neurons by 17β-estradiol is mediated by nitric oxide. Int J Dev Neurosci 21:225–233PubMedCrossRefGoogle Scholar
  11. 11.
    Catania MV, Giuffrida R, Seminara G, Barbagallo G, Aronica E, Gorter JA, Dell’Albani P, Ravagna A, Calabrese V, Giuffrida-Stella AM (2003) Upregulation of neuronal nitric oxide synthase in in vitro stellate astrocytes and in vivo reactive astrocytes after electrically induced status epilepticus. Neurochem Res 28:607–615PubMedCrossRefGoogle Scholar
  12. 12.
    Stewart VC, Heslegrave AJ, Brown GC, Clark JB, Heales SJ (2002) Nitric oxide-dependent damage to neuronal mitochondria involves the NMDA receptor. Eur J Neurosci 15:458–464PubMedCrossRefGoogle Scholar
  13. 13.
    Gatto EM, Riobo NA, Carreras MC, Chernavsky A, Rubio A, Satz ML, Poderoso JJ (2000) Overexpression of neutrophil neuronal nitric oxide synthase in Parkinson’s disease. Nitric Oxide 4:534–539PubMedCrossRefGoogle Scholar
  14. 14.
    Wallace MN, Geddes JG, Farquhar DA, Masson MR (1997) Nitric oxide synthase in reactive astrocytes adjacent to β-amyloid plaques. Exp Neurol 144:266–272PubMedCrossRefGoogle Scholar
  15. 15.
    Hunot S, Boissiere F, Faucheux B, Brugg B, Mouatt-Prigent A, Agid Y, Hirsch EC (1996) Nitric oxide synthase and neuronal vulnerability in Parkinson’s disease. Neuroscience 72:355–363PubMedCrossRefGoogle Scholar
  16. 16.
    Sattler R, Xiong Z, Lu WY, Hafner M, MacDonald JF, Tymianski M (1999) Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein. Science 284:1845–1848PubMedCrossRefGoogle Scholar
  17. 17.
    Bredt DS, Hwang PM, Glatt CE, Lowenstein C, Reed RR, Snyder SH (1991) Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. Nature 351:714–718PubMedCrossRefGoogle Scholar
  18. 18.
    Lipton SA, Choi YB, Pan ZH, Lei SZ, Chen HS, Sucher NJ, Loscalzo J, Singel DJ, Stamler JS (1993) A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature 364:626–632PubMedCrossRefGoogle Scholar
  19. 19.
    Forstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J 33:829–837PubMedCrossRefGoogle Scholar
  20. 20.
    Kuiper MA, Visser JJ, Bergmans PL, Scheltens P, Wolters EC (1994) Decreased cerebrospinal fluid nitrate levels in Parkinson’s disease, Alzheimer’s disease and multiple system atrophy patients. J Neurol Sci 121:46–49PubMedCrossRefGoogle Scholar
  21. 21.
    Chiou GC (2001) Review: effects of nitric oxide on eye diseases and their treatment. J Ocul Pharmacol Ther 17:189–198PubMedCrossRefGoogle Scholar
  22. 22.
    Cannon JG (1995) Cytokines in aging and muscle homeostasis. J Gerontol A 50:120–123Google Scholar
  23. 23.
    Zhu DY, Liu SH, Sun HS, Lu YM (2003) Expression of inducible nitric oxide synthase after focal cerebral ischemia stimulates neurogenesis in the adult rodent dentate gyrus. J Neurosci 23:223–229PubMedCrossRefGoogle Scholar
  24. 24.
    Stewart VC, Land JM, Clark JB, Heales SJ (1998) Pretreatment of astrocytes with interferon-α/β prevents neuronal mitochondrial respiratory chain damage. J Neurochem 70:432–434PubMedCrossRefGoogle Scholar
  25. 25.
    Borsani E, Giovannozzi S, Cocchi MA, Boninsegna R, Rezzani R, Rodella LF (2013) Endothelial nitric oxide synthase in dorsal root ganglia during chronic inflammatory nociception. Cells Tissues Org 197:159–168CrossRefGoogle Scholar
  26. 26.
    Garthwaite J (2008) Concepts of neural nitric oxide-mediated transmission. Eur J Neurosci 27:2783–2802PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87:1620–1624PubMedCrossRefGoogle Scholar
  28. 28.
    Schmidt HH, Lohmann SM, Walter U (1993) The nitric oxide and cGMP signal transduction system: regulation and mechanism of action. Biochim Biophys Acta 1178:153–175PubMedCrossRefGoogle Scholar
  29. 29.
    Jaffrey SR, Erdjument-Bromage H, Ferris CD, Tempst P, Snyder SH (2001) Protein S-nitrosylation: a physiological signal for neuronal nitric oxide. Nat Cell Biol 3:193–197PubMedCrossRefGoogle Scholar
  30. 30.
    Nakamura T, Lipton SA (2011) Redox modulation by S-nitrosylation contributes to protein misfolding, mitochondrial dynamics, and neuronal synaptic damage in neurodegenerative diseases. Cell Death Differ 18:1478–1486PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Coultrap SJ, Vest RS, Ashpole NM, Hudmon A, Bayer KU (2011) CaMKII in cerebral ischemia. Acta Pharmacol Sin 32:861–872PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Coultrap SJ, Bayer KU (2014) Nitric oxide induces Ca2+-independent activity of the Ca2+/calmodulin-dependent protein kinase II (CaMKII). J Biol Chem 289:19458–19465PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Eu JP, Sun J, Xu L, Stamler JS, Meissner G (2000) The skeletal muscle calcium release channel: coupled O2 sensor and NO signaling functions. Cell 102:499–509PubMedCrossRefGoogle Scholar
  34. 34.
    Mikami Y, Kanemaru K, Okubo Y, Nakaune T, Suzuki J, Shibata K, Sugiyama H, Koyama R, Murayama T, Ito A, Yamazawa T, Ikegaya Y, Sakurai T, Saito N, Kakizawa S, Iino M (2016) Nitric oxide-induced activation of the type 1 ryanodine receptor is critical for epileptic seizure-induced neuronal cell death. EBioMedicine 11:253–261PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Kundumani-Sridharan V, Subramani J, Das KC (2015) Thioredoxin activates MKK4-NFκB pathway in a redox-dependent manner to control manganese superoxide dismutase gene expression in endothelial cells. J Biol Chem 290:17505–17519PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Wei XW, Hao LY, Qi SH (2016) Inhibition on the S-nitrosylation of MKK4 can protect hippocampal CA1 neurons in rat cerebral ischemia/reperfusion. Brain Res Bull 124:123–128PubMedCrossRefGoogle Scholar
  37. 37.
    Shi ZQ, Yu DH, Park M, Marshall M, Feng GS (2000) Molecular mechanism for the Shp-2 tyrosine phosphatase function in promoting growth factor stimulation of Erk activity. Mol Cell Biol 20:1526–1536PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Shi ZQ, Sunico CR, McKercher SR, Cui J, Feng GS, Nakamura T, Lipton SA (2013) S-nitrosylated SHP-2 contributes to NMDA receptor-mediated excitotoxicity in acute ischemic stroke. Proc Natl Acad Sci USA 110:3137–3142PubMedCrossRefGoogle Scholar
  39. 39.
    Tian J, Kim SF, Hester L, Snyder SH (2008) S-nitrosylation/activation of COX-2 mediates NMDA neurotoxicity. Proc Natl Acad Sci USA 105:10537–10540PubMedCrossRefGoogle Scholar
  40. 40.
    Fang J, Nakamura T, Cho DH, Gu Z, Lipton SA (2007) S-nitrosylation of peroxiredoxin 2 promotes oxidative stress-induced neuronal cell death in Parkinson’s disease. Proc Natl Acad Sci USA 104:18742–18747PubMedCrossRefGoogle Scholar
  41. 41.
    Engelman R, Weisman-Shomer P, Ziv T, Xu J, Arner ES, Benhar M (2013) Multilevel regulation of 2-Cys peroxiredoxin reaction cycle by S-nitrosylation. J Biol Chem 288:11312–11324PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Azad N, Vallyathan V, Wang L, Tantishaiyakul V, Stehlik C, Leonard SS, Rojanasakul Y (2006) S-nitrosylation of Bcl-2 inhibits its ubiquitin-proteasomal degradation. A novel antiapoptotic mechanism that suppresses apoptosis. J Biol Chem 281:34124–34134PubMedCrossRefGoogle Scholar
  43. 43.
    Chanvorachote P, Nimmannit U, Wang L, Stehlik C, Lu B, Azad N, Rojanasakul Y (2005) Nitric oxide negatively regulates Fas CD95-induced apoptosis through inhibition of ubiquitin-proteasome-mediated degradation of FLICE inhibitory protein. J Biol Chem 280:42044–42050PubMedCrossRefGoogle Scholar
  44. 44.
    Yin L, Xie Y, Yin S, Lv X, Zhang J, Gu Z, Sun H, Liu S (2015) The S-nitrosylation status of PCNA localized in cytosol impacts the apoptotic pathway in a Parkinson’s disease paradigm. PLoS ONE 10:e0117546PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Zhang D, Zhao N, Ma B, Wang Y, Zhang G, Yan X, Hu S, Xu T (2016) Procaspase-9 induces its cleavage by transnitrosylating XIAP via the Thioredoxin system during cerebral ischemia-reperfusion in rats. Sci Rep 6:24203PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Nakamura T, Wang L, Wong CC, Scott FL, Eckelman BP, Han X, Tzitzilonis C, Meng F, Gu Z, Holland EA, Clemente AT, Okamoto S, Salvesen GS, Riek R, Yates JR 3rd, Lipton SA (2010) Transnitrosylation of XIAP regulates caspase-dependent neuronal cell death. Mol Cell 39:184–195PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Aleyasin H, Rousseaux MW, Marcogliese PC, Hewitt SJ, Irrcher I, Joselin AP, Parsanejad M, Kim RH, Rizzu P, Callaghan SM, Slack RS, Mak TW, Park DS (2010) DJ-1 protects the nigrostriatal axis from the neurotoxin MPTP by modulation of the AKT pathway. Proc Natl Acad Sci USA 107:3186–3191PubMedCrossRefGoogle Scholar
  48. 48.
    Numajiri N, Takasawa K, Nishiya T, Tanaka H, Ohno K, Hayakawa W, Asada M, Matsuda H, Azumi K, Kamata H, Nakamura T, Hara H, Minami M, Lipton SA, Uehara T (2011) On-off system for PI3-kinase-Akt signaling through S-nitrosylation of phosphatase with sequence homology to tensin (PTEN). Proc Natl Acad Sci USA 108:10349–10354PubMedCrossRefGoogle Scholar
  49. 49.
    Choi MS, Nakamura T, Cho SJ, Han X, Holland EA, Qu J, Petsko GA, Yates JR 3rd, Liddington RC, Lipton SA (2014) Transnitrosylation from DJ-1 to PTEN attenuates neuronal cell death in parkinson’s disease models. J Neurosci 34:15123–15131PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Hara MR, Agrawal N, Kim SF, Cascio MB, Fujimuro M, Ozeki Y, Takahashi M, Cheah JH, Tankou SK, Hester LD, Ferris CD, Hayward SD, Snyder SH, Sawa A (2005) S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding. Nat Cell Biol 7:665–674PubMedCrossRefGoogle Scholar
  51. 51.
    Hara MR, Cascio MB, Sawa A (2006) GAPDH as a sensor of NO stress. Biochim Biophys Acta 1762:502–509PubMedCrossRefGoogle Scholar
  52. 52.
    Tristan C, Shahani N, Sedlak TW, Sawa A (2011) The diverse functions of GAPDH: views from different subcellular compartments. Cell Signal 23:317–323PubMedCrossRefGoogle Scholar
  53. 53.
    Sen N, Hara MR, Ahmad AS, Cascio MB, Kamiya A, Ehmsen JT, Agrawal N, Hester L, Dore S, Snyder SH, Sawa A (2009) GOSPEL: a neuroprotective protein that binds to GAPDH upon S-nitrosylation. Neuron 63:81–91PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Colombo E, Alcalay M, Pelicci PG (2011) Nucleophosmin and its complex network: a possible therapeutic target in hematological diseases. Oncogene 30:2595–2609PubMedCrossRefGoogle Scholar
  55. 55.
    Lee SB, Kim CK, Lee KH, Ahn JY (2012) S-nitrosylation of B23/nucleophosmin by GAPDH protects cells from the SIAH1-GAPDH death cascade. J Cell Biol 199:65–76PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Perri ER, Thomas CJ, Parakh S, Spencer DM, Atkin JD (2015) The Unfolded Protein Response and the Role of Protein Disulfide Isomerase in Neurodegeneration. Front Cell Dev Biol 3:80PubMedGoogle Scholar
  57. 57.
    Uehara T, Nakamura T, Yao D, Shi ZQ, Gu Z, Ma Y, Masliah E, Nomura Y, Lipton SA (2006) S-nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration. Nature 441:513–517PubMedCrossRefGoogle Scholar
  58. 58.
    Nakato R, Ohkubo Y, Konishi A, Shibata M, Kaneko Y, Iwawaki T, Nakamura T, Lipton SA, Uehara T (2015) Regulation of the unfolded protein response via S-nitrosylation of sensors of endoplasmic reticulum stress. Sci Rep 5:14812PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Okuda K, Ito A, Uehara T (2015) Regulation of histone deacetylase 6 activity via S-nitrosylation. Biol Pharm Bull 38:1434–1437PubMedCrossRefGoogle Scholar
  60. 60.
    Chung KK, Thomas B, Li X, Pletnikova O, Troncoso JC, Marsh L, Dawson VL, Dawson TM (2004) S-nitrosylation of parkin regulates ubiquitination and compromises parkin’s protective function. Science 304:1328–1331PubMedCrossRefGoogle Scholar
  61. 61.
    Criollo A, Senovilla L, Authier H, Maiuri MC, Morselli E, Vitale I, Kepp O, Tasdemir E, Galluzzi L, Shen S, Tailler M, Delahaye N, Tesniere A, De Stefano D, Younes AB, Harper F, Pierron G, Lavandero S, Zitvogel L, Israel A, Baud V, Kroemer G (2010) The IKK complex contributes to the induction of autophagy. EMBO J 29:619–631PubMedCrossRefGoogle Scholar
  62. 62.
    Borsello T, Croquelois K, Hornung JP, Clarke PG (2003) N-methyl-d-aspartate-triggered neuronal death in organotypic hippocampal cultures is endocytic, autophagic and mediated by the c-Jun N-terminal kinase pathway. Eur J Neurosci 18:473–485PubMedCrossRefGoogle Scholar
  63. 63.
    Sarkar S, Korolchuk VI, Renna M, Imarisio S, Fleming A, Williams A, Garcia-Arencibia M, Rose C, Luo S, Underwood BR, Kroemer G, O’Kane CJ, Rubinsztein DC (2011) Complex inhibitory effects of nitric oxide on autophagy. Mol Cell 43:19–32PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Kurochkin IV, Goto S (1994) Alzheimer’s β-amyloid peptide specifically interacts with and is degraded by insulin degrading enzyme. FEBS Lett 345:33–37PubMedCrossRefGoogle Scholar
  65. 65.
    Ralat LA, Ren M, Schilling AB, Tang WJ (2009) Protective role of Cys-178 against the inactivation and oligomerization of human insulin-degrading enzyme by oxidation and nitrosylation. J Biol Chem 284:34005–34018PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Koriyama Y, Chiba K, Yamazaki M, Suzuki H, Muramoto K, Kato S (2010) Long-acting genipin derivative protects retinal ganglion cells from oxidative stress models in vitro and in vivo through the Nrf2/antioxidant response element signaling pathway. J Neurochem 115:79–91PubMedCrossRefGoogle Scholar
  67. 67.
    Koriyama Y, Kamiya M, Takadera T, Arai K, Sugitani K, Ogai K, Kato S (2012) Protective action of nipradilol mediated through S-nitrosylation of Keap1 and HO-1 induction in retinal ganglion cells. Neurochem Int 61:1242–1253PubMedCrossRefGoogle Scholar
  68. 68.
    Miller MR, Megson IL (2007) Recent developments in nitric oxide donor drugs. Br J Pharmacol 151:305–321PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Taguchi R, Shirakawa H, Yamaguchi T, Kume T, Katsuki H, Akaike A (2006) Nitric oxide-mediated effect of nipradilol, an α- and β-adrenergic blocker, on glutamate neurotoxicity in rat cortical cultures. Eur J Pharmacol 535:86–94PubMedCrossRefGoogle Scholar
  70. 70.
    Nakazawa T, Tomita H, Yamaguchi K, Sato Y, Shimura M, Kuwahara S, Tamai M (2002) Neuroprotective effect of nipradilol on axotomized rat retinal ganglion cells. Curr Eye Res 24:114–122PubMedCrossRefGoogle Scholar
  71. 71.
    Mizuno K, Koide T, Yoshimura M, Araie M (2001) Neuroprotective effect and intraocular penetration of nipradilol, a β-blocker with nitric oxide donative action. Invest Ophthalmol Vis Sci 42:688–694PubMedGoogle Scholar
  72. 72.
    Imai N, Tsuyama Y, Murayama K, Adachi-Usami E (1997) Protective effect of nitric oxide on ischemic retina. Nippon Ganka Gakkai Zasshi 101:639–643PubMedGoogle Scholar
  73. 73.
    Ando A, Yamazaki Y, Kaneko S, Miyake M, Nambu R, Taomoto M, Unezaki S, Okuda-Ashitaka E, Okumura T, Ito S, Matsumura M (2005) Cytoprotection by nipradilol, an anti-glaucomatous agent, via down-regulation of apoptosis related gene expression and activation of NF-kappaB. Exp Eye Res 80:501–507PubMedCrossRefGoogle Scholar
  74. 74.
    Tomita H, Nakazawa T, Sugano E, Abe T, Tamai M (2002) Nipradilol inhibits apoptosis by preventing the activation of caspase-3 via S-nitrosylation and the cGMP-dependent pathway. Eur J Pharmacol 452:263–268PubMedCrossRefGoogle Scholar
  75. 75.
    Naito A, Aniya Y, Sakanashi M (1994) Antioxidative action of the nitrovasodilator nicorandil: inhibition of oxidative activation of liver microsomal glutathione S-transferase and lipid peroxidation. Jpn J Pharmacol 65:209–213PubMedCrossRefGoogle Scholar
  76. 76.
    Baird L, Dinkova-Kostova AT (2011) The cytoprotective role of the Keap1-Nrf2 pathway. Arch Toxicol 85:241–272PubMedCrossRefGoogle Scholar
  77. 77.
    Himori N, Yamamoto K, Maruyama K, Ryu M, Taguchi K, Yamamoto M, Nakazawa T (2013) Critical role of Nrf2 in oxidative stress-induced retinal ganglion cell death. J Neurochem 127:669–680PubMedCrossRefGoogle Scholar
  78. 78.
    Li CQ, Kim MY, Godoy LC, Thiantanawat A, Trudel LJ, Wogan GN (2009) Nitric oxide activation of Keap1/Nrf2 signaling in human colon carcinoma cells. Proc Natl Acad Sci USA 106:14547–14551PubMedCrossRefGoogle Scholar
  79. 79.
    Buckley BJ, Li S, Whorton AR (2008) Keap1 modification and nuclear accumulation in response to S-nitrosocysteine. Free Radic Biol Med 44:692–698PubMedCrossRefGoogle Scholar
  80. 80.
    Calabrese V, Boyd-Kimball D, Scapagnini G, Butterfield DA (2004) Nitric oxide and cellular stress response in brain aging and neurodegenerative disorders: the role of vitagenes. In Vivo 18:245–267PubMedGoogle Scholar
  81. 81.
    Maines MD (1988) Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J 2:2557–2568PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Graduate School and Faculty of Pharmaceutical SciencesSuzuka University of Medical ScienceSuzukaJapan

Personalised recommendations