Cross-Talk between NO synthase isoforms in neuro-inflammation: Possible implications in HIV-associated neurocognitive disorders

Current Medicinal Chemistry

Volumn 23, Issue 24, 2016, Pages 2706-2714

  Persichini, Tiziana ^a   Mariotto, Sofia ^b   Suzuki, Hisanori ^b   Butturini, Elena ^b   Mastrantonio, Roberta ^a   Cantoni, Orazio ^c   Colasanti, Marco ^a  

^a ROMA TRE UNIVERSITY   (Italy)

^b UNIVERSITY OF VERONA   (Italy)

^c UNIVERSITY OF URBINO   (Italy)

Author keywords

Arachidonic acid; Astrocytes; Constitutive NOS; Cytosolic phospholipase A2; HAND; HIV; Inducible NOS; Nitric oxide

Indexed keywords

ARACHIDONIC ACID; CYTOSOLIC PHOSPHOLIPASE A2; INDUCIBLE NITRIC OXIDE SYNTHASE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; GLYCOPROTEIN GP 120; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; ISOPROTEIN; TRANSACTIVATOR PROTEIN;

CYTOTOXICITY; DISEASE ASSOCIATION; HIV ASSOCIATED DEMENTIA; HUMAN; NERVOUS SYSTEM INFLAMMATION; NEUROPATHOLOGY; NONHUMAN; REVIEW; SIGNAL TRANSDUCTION; COMPLICATION; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INFLAMMATION; METABOLISM; NEUROCOGNITIVE DISORDERS; VIROLOGY;

ARACHIDONIC ACID; HIV; HIV ENVELOPE PROTEIN GP120; HIV INFECTIONS; HUMANS; INFLAMMATION; NEUROCOGNITIVE DISORDERS; NF-KAPPA B; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; PROTEIN ISOFORMS; TAT GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS;

EID: 84989166234     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/0929867323666160809100452     Document Type: Review

References (71)

1. Mariotto, S.; Cuzzolin, L.; Adami, A.; Del Soldato, P.; Suzuki, H.; Benoni, G. Effect of a new non-steroidal antiinflammatory drug, nitroflurbiprofen, on the expression of inducible nitric oxide synthase in rat neutrophils. Br. J. Pharmacol., 1995, 115(2), 225-226.
2. Mariotto, S.; Cuzzolin, L.; Adami, A.; Del Soldato, P.; Suzuki, H.; Benoni, G. Inhibition by sodium nitroprusside of the expression of inducible nitric oxide synthase in rat neutrophils. Br. J. Pharmacol., 1995, 114(6), 1105-1106.
3. Colasanti, M.; Persichini, T.; Menegazzi, M.; Mariotto, S.; Giordano, E.; Caldarera, C. M.; Sogos, V.; Lauro, G. M.; Suzuki, H. Induction of nitric oxide synthase mRNA expression. Suppression by exogenous nitric oxide. J. Biol. Chem., 1995, 270(45), 26731-26733.
4. Colasanti, M.; Cavalieri, E.; Persichini, T.; Mollace, V.; Mariotto, S.; Suzuki, H.; Lauro, G. M. Bacterial lipopolysaccharide plus interferon-gamma elicit a very fast inhibition of a Ca2+-dependent nitric-oxide synthase activity in human astrocytoma cells. J. Biol. Chem., 1997, 272(12), 7582-7585.
5. Colasanti, M.; Persichini, T.; Cavalieri, E.; Fabrizi, C.; Mariotto, S.; Menegazzi, M.; Lauro, G. M.; Suzuki, H. Rapid inactivation of NOS-I by lipopolysaccharide plus interferon-gamma-induced tyrosine phosphorylation. J. Biol. Chem., 1999, 274(15), 9915-9917.
6. Katsuyama, K.; Shichiri, M.; Marumo, F.; Hirata, Y. NO inhibits cytokine-induced iNOS expression and NF-kappaB activation by interfering with phosphorylation and degradation of IkappaB-alpha. Arterioscler. Thromb. Vasc. Biol., 1998, 18(11), 1796-1802.
7. Lin, H. L.; Murphy, S. Regulation of astrocyte nitric oxide synthase type II expression by ATP and glutamate involves loss of transcription factor binding to DNA. J. Neurochem., 1997, 69(2), 612-616.
8. Koyanagi, M.; Egashira, K.; Kitamoto, S.; Ni, W.; Shimokawa, H.; Takeya, M.; Yoshimura, T.; Takeshita, A. Role of monocyte chemoattractant protein-1 in cardiovascular remodeling induced by chronic blockade of nitric oxide synthesis. Circulation, 2000, 102(18), 2243-2248.
9. Kanno, S.; Lee, P. C.; Zhang, Y.; Ho, C.; Griffith, B. P.; Shears, L. L., II; Billiar, T. R. Attenuation of myocardial ischemia/reperfusion injury by superinduction of inducible nitric oxide synthase. Circulation, 2000, 101(23), 2742-2748.
10. Paine, E.; Palmantier, R.; Akiyama, S. K.; Olden, K.; Roberts, J. D. Arachidonic acid activates mitogen-activated protein (MAP) kinase-activated protein kinase 2 and mediates adhesion of a human breast carcinoma cell line to collagen type IV through a p38 MAP kinase-dependent pathway. J. Biol. Chem., 2000, 275(15), 11284-11290.
11. Janda, E.; Visalli, V.; Colica, C.; Aprigliano, S.; Musolino, V.; Vadala, N.; Muscoli, C.; Sacco, I.; Iannone, M.; Rotiroti, D.; Spedding, M.; Mollace, V. The protective effect of tianeptine on Gp120-induced apoptosis in astroglial cells: role of GS and NOS, and NF-?B suppression. Br. J. Pharmacol., 2011, 164(6), 1590-1599.
12. Salvemini, D.; Kim, S. F.; Mollace, V. Reciprocal regulation of the nitric oxide and cyclooxygenase pathway in pathophysiology: relevance and clinical implications. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2013, 304(7), R473-R487.
13. Džolji?, E.; Grbatini?, I.; Kosti?, V. Why is nitric oxide important for our brain? Funct. Neurol., 2015, 30(3), 159-163.
14. Mollace, V.; Gliozzi, M.; Musolino, V.; Carresi, C.; Muscoli, S.; Mollace, R.; Tavernese, A.; Gratteri, S.; Palma, E.; Morabito, C.; Vitale, C.; Muscoli, C.; Fini, M.; Romeo, F. Oxidized LDL attenuates protective autophagy and induces apoptotic cell death of endothelial cells: Role of oxidative stress and LOX-1 receptor expression. Int. J. Cardiol., 2015, 184, 152-158.
15. Colasanti, M.; Suzuki, H. The dual personality of NO. Trends Pharmacol. Sci., 2000, 21(7), 249-252.
16. Suzuki, H.; Colasanti, M. NO: A molecule with two masks of 'NO-theatre. Biofactors, 2001, 15(2-4), 123-125.
17. Persichini, T.; Cantoni, O.; Suzuki, H.; Colasanti, M. Crosstalk between constitutive and inducible NO synthase: An update. Antioxid. Redox Signal., 2006, 8(5-6), 949-954.
18. Colasanti, M.; Persichini, T. Nitric oxide: An inhibitor of NF-kappaB/Rel system in glial cells. Brain Res. Bull., 2000, 52(3), 155-161.
19. Palomba, L.; Bianchi, M.; Persichini, T.; Magnani, M.; Colasanti, M.; Cantoni, O. Downregulation of nitric oxide formation by cytosolic phospholipase A2-released arachidonic acid. Free Radic. Biol. Med., 2004, 36(3), 319-329.
20. Palomba, L.; Persichini, T.; Mazzone, V.; Colasanti, M.; Cantoni, O. Inhibition of nitric-oxide synthase-I (NOS-I)-dependent nitric oxide production by lipopolysaccharide plus interferon-gamma is mediated by arachidonic acid. Effects on NFkappaB activation and late inducible NOS expression. J. Biol. Chem., 2004, 279(29), 29895-29901.
21. Brown, G. C. Nitric oxide and neuronal death. Nitric Oxide, 2010, 23(3), 153-165.
22. Ghasemi, M.; Fatemi, A. Pathologic role of glial nitric oxide in adult and pediatric neuroinflammatory diseases. Neurosci. Biobehav. Rev., 2014, 45, 168-182.
23. Bal-Price, A.; Moneer, Z.; Brown, G. C. Nitric oxide induces rapid, calcium-dependent release of vesicular glutamate and ATP from cultured rat astrocytes. Glia, 2002, 40(3), 312-323.
24. Yuste, J. E.; Tarragon, E.; Campuzano, C. M.; Ros-Bernal, F. Implications of glial nitric oxide in neurodegenerative diseases. Front. Cell. Neurosci., 2015, 9, 322.
25. Harry, G. J.; Sills, R.; Schlosser, M. J.; Maier, W. E. Neurodegeneration and glia response in rat hippocampus following nitro-L-arginine methyl ester (L-NAME). Neurotox. Res., 2001, 3(3), 307-319.
26. Mariotto, S.; Menegazzi, M.; Suzuki, H. Biochemical aspects of nitric oxide. Curr. Pharm. Des., 2004, 10(14), 1627-1645.
27. Ciampa, A. R.; de Prati, A. C.; Amelio, E.; Cavalieri, E.; Persichini, T.; Colasanti, M.; Musci, G.; Marlinghaus, E.; Suzuki, H.; Mariotto, S. Nitric oxide mediates antiinflammatory action of extracorporeal shock waves. FEBS Lett., 2005, 579(30), 6839-6845.
28. Mariotto, S.; de Prati, A. C.; Cavalieri, E.; Amelio, E.; Marlinghaus, E.; Suzuki, H. Extracorporeal shock wave therapy in inflammatory diseases: molecular mechanism that triggers anti-inflammatory action. Curr. Med. Chem., 2009, 16(19), 2366-2372.
29. de la Torre, J. C.; Stefano, G. B. Evidence that Alzheimer-s disease is a microvascular disorder: The role of constitutive nitric oxide. Brain Res. Brain Res. Rev., 2000, 34(3), 119-136.
30. McCarty, M. F. Vascular nitric oxide, sex hormone replacement, and fish oil may help to prevent Alzheimer-s disease by suppressing synthesis of acute-phase cytokines. Med. Hypotheses, 1999, 53(5), 369-374.
31. Lamoke, F.; Mazzone, V.; Persichini, T.; Maraschi, A.; Harris, M. B.; Venema, R. C.; Colasanti, M.; Gliozzi, M.; Muscoli, C.; Bartoli, M.; Mollace, V. Amyloid ? peptideinduced inhibition of endothelial nitric oxide production involves oxidative stress-mediated constitutive eNOS/HSP90 interaction and disruption of agonist-mediated Akt activation. J. Neuroinflammation, 2015, 12, 84.
32. Venturini, G.; Colasanti, M.; Persichini, T.; Fioravanti, E.; Ascenzi, P.; Palomba, L.; Cantoni, O.; Musci, G. Betaamyloid inhibits NOS activity by subtracting NADPH availability. FASEB J., 2002, 16(14), 1970-1972.
33. Sun, G. Y.; Chuang, D. Y.; Zong, Y.; Jiang, J.; Lee, J. C.; Gu, Z.; Simonyi, A. Role of cytosolic phospholipase A2 in oxidative and inflammatory signaling pathways in different cell types in the central nervous system. Mol. Neurobiol., 2014, 50(1), 6-14.
34. Xu, L.; Han, C.; Lim, K.; Wu, T. Activation of cytosolic phospholipase A2alpha through nitric oxide-induced Snitrosylation. Involvement of inducible nitric-oxide synthase and cyclooxygenase-2. J. Biol. Chem., 2008, 283(6), 3077-3087.
35. Florent-Bechard, S.; Desbene, C.; Garcia, P.; Allouche, A.; Youssef, I.; Escanye, M. C.; Koziel, V.; Hanse, M.; Malaplate-Armand, C.; Stenger, C.; Kriem, B.; Yen-Potin, F. T.; Olivier, J. L.; Pillot, T.; Oster, T. The essential role of lipids in Alzheimer-s disease. Biochimie, 2009, 91(6), 804-809.
36. Gentile, M. T.; Reccia, M. G.; Sorrentino, P. P.; Vitale, E.; Sorrentino, G.; Puca, A. A.; Colucci-D-Amato, L. Role of cytosolic calcium-dependent phospholipase A2 in Alzheimer-s disease pathogenesis. Mol. Neurobiol., 2012, 45(3), 596-604.
37. Kriem, B.; Sponne, I.; Fifre, A.; Malaplate-Armand, C.; Lozac-h-Pillot, K.; Koziel, V.; Yen-Potin, F. T.; Bihain, B.; Oster, T.; Olivier, J. L.; Pillot, T. Cytosolic phospholipase A2 mediates neuronal apoptosis induced by soluble oligomers of the amyloid-beta peptide. FASEB J., 2005, 19(1), 85-87.
38. Sanchez-Mejia, R. O.; Mucke, L. Phospholipase A2 and arachidonic acid in Alzheimer-s disease. Biochim. Biophys. Acta, 2010, 1801(8), 784-790.
39. Sanchez-Mejia, R. O.; Newman, J. W.; Toh, S.; Yu, G. Q.; Zhou, Y.; Halabisky, B.; Cisse, M.; Scearce-Levie, K.; Cheng, I. H.; Gan, L.; Palop, J. J.; Bonventre, J. V.; Mucke, L. Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer-s disease. Nat. Neurosci., 2008, 11(11), 1311-1318.
40. Solomonov, Y.; Hadad, N.; Levy, R. Reduction of cytosolic phospholipase A2? upregulation delays the onset of symptoms in SOD1G93A mouse model of amyotrophic lateral sclerosis. J. Neuroinflammation, 2016, 13(1), 134.
41. Williams, R. S.; Bate, C. An in vitro model for synaptic loss in neurodegenerative diseases suggests a neuroprotective role for valproic acid via inhibition of cPLA2 dependent signalling. Neuropharmacology, 2016, 101, 566-575.
42. Bate, C.; Williams, A. Amyloid-?(1-40) inhibits amyloid-?(1-42) induced activation of cytoplasmic phospholipase A2 and synapse degeneration. J. Alzheimers Dis., 2010, 21(3), 985-993.
43. Alfahad, T. B.; Nath, A. Update on HIV-associated neurocognitive disorders. Curr. Neurol. Neurosci. Rep., 2013, 13(10), 387.
44. Heaton, R. K.; Franklin, D. R.; Ellis, R. J.; McCutchan, J. A.; Letendre, S. L.; Leblanc, S.; Corkran, S. H.; Duarte, N. A.; Clifford, D. B.; Woods, S. P.; Collier, A. C.; Marra, C. M.; Morgello, S.; Mindt, M. R.; Taylor, M. J.; Marcotte, T. D.; Atkinson, J. H.; Wolfson, T.; Gelman, B. B.; McArthur, J. C.; Simpson, D. M.; Abramson, I.; Gamst, A.; Fennema-Notestine, C.; Jernigan, T. L.; Wong, J.; Grant, I.; Group, C.; Group, H. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J. Neurovirol., 2011, 17(1), 3-16.
45. Antinori, A.; Arendt, G.; Becker, J. T.; Brew, B. J.; Byrd, D. A.; Cherner, M.; Clifford, D. B.; Cinque, P.; Epstein, L. G.; Goodkin, K.; Gisslen, M.; Grant, I.; Heaton, R. K.; Joseph, J.; Marder, K.; Marra, C. M.; McArthur, J. C.; Nunn, M.; Price, R. W.; Pulliam, L.; Robertson, K. R.; Sacktor, N.; Valcour, V.; Wojna, V. E. Updated research nosology for HIV-associated neurocognitive disorders. Neurology, 2007, 69(18), 1789-1799.
46. Nath, A. Human immunodeficiency virus (HIV) proteins in neuropathogenesis of HIV dementia. J. Infect. Dis., 2002, 186(Suppl. 2), S193-S198.
47. Maldarelli, F.; Palmer, S.; King, M. S.; Wiegand, A.; Polis, M. A.; Mican, J.; Kovacs, J. A.; Davey, R. T.; Rock-Kress, D.; Dewar, R.; Liu, S.; Metcalf, J. A.; Rehm, C.; Brun, S. C.; Hanna, G. J.; Kempf, D. J.; Coffin, J. M.; Mellors, J. W. ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog., 2007, 3(4), e46.
48. Palmer, S.; Maldarelli, F.; Wiegand, A.; Bernstein, B.; Hanna, G. J.; Brun, S. C.; Kempf, D. J.; Mellors, J. W.; Coffin, J. M.; King, M. S. Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc. Natl. Acad. Sci. USA, 2008, 105(10), 3879-3884.
49. Johnson, T. P.; Patel, K.; Johnson, K. R.; Maric, D.; Calabresi, P. A.; Hasbun, R.; Nath, A. Induction of IL-17 and nonclassical T-cell activation by HIV-Tat protein. Proc. Natl. Acad. Sci. USA, 2013, 110(33), 13588-13593.
50. Capone, C.; Cervelli, M.; Angelucci, E.; Colasanti, M.; Macone, A.; Mariottini, P.; Persichini, T. A role for spermine oxidase as a mediator of reactive oxygen species production in HIV-Tat-induced neuronal toxicity. Free Radic. Biol. Med., 2013, 63, 99-107.
51. Mastrantonio, R.; Cervelli, M.; Pietropaoli, S.; Mariottini, P.; Colasanti, M.; Persichini, T. HIV-tat induces the Nrf2/ARE pathway through NMDA receptor-elicited spermine oxidase activation in human neuroblastoma cells. PLoS One, 2016, 11(2), e0149802.
52. Ancuta, P.; Kamat, A.; Kunstman, K. J.; Kim, E. Y.; Autissier, P.; Wurcel, A.; Zaman, T.; Stone, D.; Mefford, M.; Morgello, S.; Singer, E. J.; Wolinsky, S. M.; Gabuzda, D. Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients. PLoS One, 2008, 3(6), e2516.
53. Dohgu, S.; Fleegal-DeMotta, M. A.; Banks, W. A. Lipopolysaccharide-enhanced transcellular transport of HIV-1 across the blood-brain barrier is mediated by luminal microvessel IL-6 and GM-CSF. J. Neuroinflammation, 2011, 8, 167.
54. Codazzi, F.; Menegon, A.; Zacchetti, D.; Ciardo, A.; Grohovaz, F.; Meldolesi, J. HIV-1 gp120 glycoprotein induces Ca2+ i responses not only in type-2 but also type-1 astrocytes and oligodendrocytes of the rat cerebellum. Eur. J. Neurosci., 1995, 7(6), 1333-1341.
55. Lannuzel, A.; Lledo, P. M.; Lamghitnia, H. O.; Vincent, J. D.; Tardieu, M. HIV-1 envelope proteins gp120 and gp160 potentiate NMDA-induced [Ca2+]i increase, alterCa2+ i homeostasis and induce neurotoxicity in human embryonic neurons. Eur. J. Neurosci., 1995, 7(11), 2285-2293.
56. Medina, I.; Ghose, S.; Ben-Ari, Y. Mobilization of intracellular calcium stores participates in the rise of [Ca2+]i and the toxic actions of the HIV coat protein GP120. Eur. J. Neurosci., 1999, 11(4), 1167-1178.
57. Persichini, T.; Mastrantonio, R.; Del Matto, S.; Palomba, L.; Cantoni, O.; Colasanti, M. The role of arachidonic acid in the regulation of nitric oxide synthase isoforms by HIV gp120 protein in astroglial cells. Free Radic. Biol. Med., 2014, 74, 14-20.
58. Pandey, R.; Ghorpade, A. HIV-1 and alcohol abuse promote astrocyte inflammation: A mechanistic synergy via the cytosolic phospholipase A2 pathway. Cell Death Dis., 2015, 6, e2017.
59. Ramadan, E.; Basselin, M.; Chang, L.; Chen, M.; Ma, K.; Rapoport, S. I. Chronic lithium feeding reduces upregulated brain arachidonic acid metabolism in HIV-1 transgenic rat. J. Neuroimmune Pharmacol., 2012, 7(3), 701-713.
60. Rao, J. S.; Kim, H. W.; Kellom, M.; Greenstein, D.; Chen, M.; Kraft, A. D.; Harry, G. J.; Rapoport, S. I.; Basselin, M. Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats. J. Neuroinflammation, 2011, 8, 101.
61. Wikoff, W. R.; Pendyala, G.; Siuzdak, G.; Fox, H. S. Metabolomic analysis of the cerebrospinal fluid reveals changes in phospholipase expression in the CNS of SIVinfected macaques. J. Clin. Invest., 2008, 118(7), 2661-2669.
62. Cavet, M. E.; Vittitow, J. L.; Impagnatiello, F.; Ongini, E.; Bastia, E. Nitric oxide (NO): An emerging target for the treatment of glaucoma. Invest. Ophthalmol. Vis. Sci., 2014, 55(8), 5005-5015.
63. Ma, L.; Pei, H.; Lei, L.; He, L.; Chen, J.; Liang, X.; Peng, A.; Ye, H.; Xiang, M.; Chen, L. Structural exploration, synthesis and pharmacological evaluation of novel 5-benzylidenethiazolidine-2, 4-dione derivatives as iNOS inhibitors against inflammatory diseases. Eur. J. Med. Chem., 2015, 92, 178-190.
64. Nakajima, A.; Yamamoto, Y.; Yoshinaka, N.; Namba, M.; Matsuo, H.; Okuyama, T.; Yoshigai, E.; Okumura, T.; Nishizawa, M.; Ikeya, Y. A new flavanone and other flavonoids from green perilla leaf extract inhibit nitric oxide production in interleukin 1?-treated hepatocytes. Biosci. Biotechnol. Biochem., 2015, 79(1), 138-146.
65. Dehmer, T.; Lindenau, J.; Haid, S.; Dichgans, J.; Schulz, J. B. Deficiency of inducible nitric oxide synthase protects against MPTP toxicity in vivo. J. Neurochem., 2000, 74(5), 2213-2216.
66. Martin, L. J.; Liu, Z.; Chen, K.; Price, A. C.; Pan, Y.; Swaby, J. A.; Golden, W. C. Motor neuron degeneration in amyotrophic lateral sclerosis mutant superoxide dismutase-1 transgenic mice: mechanisms of mitochondriopathy and cell death. J. Comp. Neurol., 2007, 500(1), 20-46.
67. Nathan, C.; Calingasan, N.; Nezezon, J.; Ding, A.; Lucia, M. S.; La Perle, K.; Fuortes, M.; Lin, M.; Ehrt, S.; Kwon, N. S.; Chen, J.; Vodovotz, Y.; Kipiani, K.; Beal, M. F. Protection from Alzheimer-s-like disease in the mouse by genetic ablation of inducible nitric oxide synthase. J. Exp. Med., 2005, 202(9), 1163-1169.
68. Ono, K.; Suzuki, H.; Sawada, M. Delayed neural damage is induced by iNOS-expressing microglia in a brain injury model. Neurosci. Lett., 2010, 473(2), 146-150.
69. Vareniuk, I.; Pavlov, I. A.; Obrosova, I. G. Inducible nitric oxide synthase gene deficiency counteracts multiple manifestations of peripheral neuropathy in a streptozotocininduced mouse model of diabetes. Diabetologia, 2008, 51(11), 2126-2133.
70. Hernandez, M.; Bayon, Y.; Sanchez Crespo, M.; Nieto, M. L. Signaling mechanisms involved in the activation of arachidonic acid metabolism in human astrocytoma cells by tumor necrosis factor-alpha: phosphorylation of cytosolic phospholipase A2 and transactivation of cyclooxygenase-2. J. Neurochem., 1999, 73(4), 1641-1649.
71. Vana, A. C.; Li, S.; Ribeiro, R.; Tchantchou, F.; Zhang, Y. Arachidonyl trifluoromethyl ketone ameliorates experimental autoimmune encephalomyelitis via blocking peroxynitrite formation in mouse spinal cord white matter. Exp. Neurol., 2011, 231(1), 45-55.