Neuroglobin modification by reactive quinone species

Chemical Research in Toxicology

Volumn 26, Issue 12, 2013, Pages 1821-1831

  Nicolis, Stefania ^a   Monzani, Enrico ^a   Pezzella, Alessandro ^b   Ascenzi, Paolo ^c   Sbardella, Diego ^d,e   Casella, Luigi ^a,e  

^a UNIVERSITY OF PAVIA   (Italy)

^b UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^c ROMA TRE UNIVERSITY   (Italy)

^d UNIVERSITY OF ROME TOR VERGATA   (Italy)

^e Consorzio Interuniversitario per la Ricerca sulla Chimica Dei Metalli Nei Sistemi Biologici ^*  (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CATECHOL ESTROGEN; CATECHOLAMINE; HEMOPROTEIN; NEUROGLOBIN; QUINONE DERIVATIVE; SEMIQUINONE; CYSTEINE; GLOBIN; HYDROGEN PEROXIDE; NERVE PROTEIN;

ALZHEIMER DISEASE; ARTICLE; COVALENT BOND; CYTOTOXICITY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HOMEOSTASIS; HUMAN; NERVOUS TISSUE; NEUROPROTECTION; OXIDATION; OXIDATIVE STRESS; PARKINSON DISEASE; PHYSIOLOGY; PROTEIN STABILITY; PROTEIN UNFOLDING; TANDEM MASS SPECTROMETRY; CHEMICAL STRUCTURE; CHEMISTRY; KINETICS; METABOLISM; OXIDATION REDUCTION REACTION;

CATECHOLAMINES; CYSTEINE; GLOBINS; HUMANS; HYDROGEN PEROXIDE; KINETICS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; NERVE TISSUE PROTEINS; OXIDATION-REDUCTION; QUINONES; TANDEM MASS SPECTROMETRY;

EID: 84890497616     PISSN: 0893228X     EISSN: 15205010     Source Type: Journal    
DOI: 10.1021/tx4001896     Document Type: Article

References (91)

1. Burmester, T., Weich, B., Reinhardt, S., and Hankeln, T. (2000) A vertebrate globin expressed in the brain Nature 407, 520-523
2. Burmester, T. and Hankeln, T. (2004) Neuroglobin: A respiratory protein of the nervous system News Physiol. Sci. 19, 110-113
3. Pesce, A., Dewilde, S., Cardini, M., Moens, L., Ascenzi, P., Hankeln, T., Burmester, T., and Bolognesi, M. (2003) Human brain neuroglobin structure reveals a distinct mode of controlling oxygen affinity Structure 11, 1087-1095 (Pubitemid 37103070)
4. Vallone, B., Nienhaus, K., Brunori, M., and Nienhaus, G. U. (2004) The structure of murine neuroglobin: Novel pathways for ligand migration and binding Proteins 56, 85-92 (Pubitemid 38720840)
5. Hamdane, D., Kiger, L., Dewilde, S., Green, B. N., Pesce, A., Uzan, J., Burmester, T., Hankeln, T., Bolognesi, M., Moens, L., and Marden, M. C. (2004) Coupling of the heme and an internal disulfide bond in human neuroglobin Micron 35, 59-62 (Pubitemid 38214819)
6. Hamdane, D., Kiger, L., Dewilde, S., Green, B. N., Pesce, A., Uzan, J., Burmester, T., Hankeln, T., Bolognesi, M., Moens, L., and Marden, M. C. (2003) The redox state of the cell regulates the ligand binding affinity of human neuroglobin and cytoglobin J. Biol. Chem. 278, 51713-51721 (Pubitemid 38020417)
7. Nicolis, S., Monzani, E., Ciaccio, C., Ascenzi, P., Moens, L., and Casella, L. (2007) Reactivity and endogenous modification by nitrite and hydrogen peroxide: Does human neuroglobin act only as a scavenger? Biochem. J. 407, 89-99 (Pubitemid 47535584)
8. Burmester, T., Ebner, B., Weich, B., and Hankeln, T. (2002) Cytoglobin: A novel globin type ubiquitously expressed in vertebrate tissues Mol. Biol. Evol. 19, 416-421 (Pubitemid 34289416)
9. Kugelstadt, D., Haberkamp, M., Hankeln, T., and Burmester, T. (2004) Neuroglobin, cytoglobin, and a novel, eye-specific globin from chicken Biochem. Biophys. Res. Commun. 325, 719-725 (Pubitemid 39487931)
10. Roesner, A., Fuchs, C., Hankeln, T., and Burmester, T. (2005) A globin gene of ancient evolutionary origin in lower vertebrates: Evidence for two distinct globin families in animals Mol. Biol. Evol. 22, 12-22
11. Schelshorn, D. W., Schneider, A., Kuschinsky, W., Weber, D., Krüger, C., Dittgen, T., Bürgers, H. F., Sabouri, F., Gassler, N., Bach, A., and Maurer, M. H. (2009) Expression of hemoglobin in rodent neurons J. Cereb. Blood Flow Metab. 29, 585-595
12. Richter, F., Meurers, B. H., Zhu, C., Medvedeva, V. P., and Chesselet, M. F. (2009) Neurons express hemoglobin alpha- and beta-chains in rat and human brains J. Comp. Neurol. 515, 538-547
13. Duong, T. T., Witting, P. K., Antao, S. T., Parry, S. N., Kennerson, M., Lai, B., Vogt, S., Lay, P. A., and Harris, H. H. (2009) Multiple protective activities of neuroglobin in cultured neuronal cells exposed to hypoxia re-oxygenation injury J. Neurochem. 108, 1143-54
14. Dietz, G. P. (2011) Protection by neuroglobin and cell-penetrating peptide-mediated delivery in vivo: A decade of research. Comment on Cai et al.: TAT-mediated delivery of neuroglobin protects against focal cerebral ischemia in mice Exp. Neurol. 231, 1-10
15. Greenberg, D. A., Jin, K., and Khan, A. A. (2008) Neuroglobin: An endogenous neuroprotectant Curr. Opin. Pharmacol. 8, 20-24 (Pubitemid 351168689)
16. Sun, Y., Jin, K., Mao, X. O., Zhu, Y., and Greenberg, D. A. (2001) Neuroglobin is up-regulated by and protects neurons from hypoxic-ischemic injury Proc. Natl. Acad. Sci. U.S.A. 98, 15306-15311 (Pubitemid 34014010)
17. Sun, Y., Jin, K., Peel, A., Mao, X. O., Xie, L., and Greenberg, D. A. (2003) Neuroglobin protects the brain from experimental stroke in vivo Proc. Natl. Acad. Sci. U.S.A. 100, 3497-3500 (Pubitemid 36356612)
18. Nienhaus, K. and Nienhaus, G. U. (2007) Searching for neuroglobin's role in the brain IUBMB Life 59, 490-497 (Pubitemid 47265847)
19. Brunori, M., Giuffrè, A., Nienhaus, K., Nienhaus, G. U., Scandurra, F. M., and Vallone, B. (2005) Neuroglobin, nitric oxide, and oxygen: functional pathways and conformational changes Proc. Natl. Acad. Sci. U.S.A. 102, 8483-8488 (Pubitemid 40862762)
20. Brunori, M. and Vallone, B. (2006) A globin for the brain FASEB J. 20, 2192-2197 (Pubitemid 44953848)
21. Burmester, T. and Hankeln, T. (2009) What is the function of neuroglobin? J. Exp. Biol. 212, 1423-1428
22. Jin, K., Mao, X. O., Xie, L., Khan, A. A., and Greenberg, D. A. (2008) Neuroglobin protects against nitric oxide toxicity Neurosci. Lett. 430, 135-137
23. Li, R. C., Morris, M. W., Lee, S. K., Pouranfar, F., Wang, Y., and Gozal, D. (2008) Neuroglobin protects PC12 cells against oxidative stress Brain Res. 1190, 159-166
24. Fordel, E., Thijs, L., Moens, L., and Dewilde, S. (2007) Neuroglobin and cytoglobin expression in mice. Evidence for a correlation with reactive oxygen species scavenging FEBS J. 274, 1312-1317
25. Tansey, M. G., McCoy, M. K., and Frank-Cannon, T. C. (2007) Neuroinflammatory mechanisms in Parkinson's disease: Potential environmental triggers, pathways, and targets for early therapeutic intervention Exp. Neurol. 208, 1-25 (Pubitemid 47603240)
26. Rauk, A. (2009) The chemistry of Alzheimer's disease Chem. Soc. Rev. 38, 2698-715
27. Andersen, J. K. (2004) Oxidative stress in neurodegeneration: Cause or consequence? Nat. Med. 10, S18-S25
28. Szymanski, M., Wang, R., Fallin, M. D., Bassett, S. S., and Avramopoulos, D. (2010) Neuroglobin and Alzheimer's dementia: Genetic association and gene expression changes Neurobiol. Aging 31, 1835-1842
29. Khan, A. A., Mao, X. O., Banwait, S., Jin, K., and Greenberg, D. A. (2007) Neuroglobin attenuates beta-amyloid neurotoxicity in vitro and transgenic Alzheimer phenotype in vivo Proc. Natl. Acad. Sci. U.S.A. 104, 19114-19119
30. Chen, L.-M., Xiong, Y.-S., Kong, F.-L., Qu, M., Wang, Q., Chen, X.-Q., Wang, J.-Z., and Zhu, L.-Q. (2012) Neuroglobin attenuates Alzheimer-like tau hyperphosphorylation by activating Akt signaling J. Neurochem. 120, 157-164
31. Zucca, F. A., Bellei, C., Giannelli, S., Terreni, M. R., Gallorini, M., Rizzio, E., Pezzoli, G., Albertini, A., and Zecca, L. (2006) Neuromelanin and iron in human locus coeruleus and substantia nigra during aging: Consequences for neuronal vulnerability J. Neural Transm. 113, 757-767 (Pubitemid 43847169)
32. Manini, P., Panzella, L., Napolitano, A., and d'Ischia, M. (2007) Oxidation chemistry of norepinephrine: Partitioning of the O-quinone between competing cyclization and chain breakdown pathways and their roles in melanin formation Chem. Res. Toxicol. 20, 1549-1555 (Pubitemid 350057226)
33. Napolitano, A., Pezzella, A., and Prota, G. (1999) New reaction pathways of dopamine under oxidative stress conditions: Nonenzymatic iron-assisted conversion to norepinephrine and the neurotoxins 6-hydroxydopamine and 6, 7-dihydroxytetrahydroisoquinoline Chem. Res. Toxicol. 12, 1090-1097
34. Napolitano, A., Manini, P., and d'Ischia, M. (2011) Oxidation chemistry of catecholamines and neuronal degeneration: An update Curr. Med. Chem. 18, 1832-1845
35. Borta, A. and Höglinger, G. U. (2007) Dopamine and adult neurogenesis J. Neurochem. 100, 587-595 (Pubitemid 46095611)
36. Gesi, M., Soldani, P., Giorgi, F. S., Santinami, A., Bonaccorsi, I., and Fornai, F. (2000) The role of the locus coeruleus in the development of Parkinson's disease Neurosci. Biobehav. Rev. 24, 655-668 (Pubitemid 30625131)
37. Kalinin, S., Gavrilyuk, V., Polak, P. E., Heneka, M. T., and Feinstein, D. L. (2007) Noradrenaline deficiency in brain increases beta-amyloid plaque burden in an animal model of Alzheimer's disease Neurobiol. Aging 28, 1206-1214 (Pubitemid 46810064)
38. Shen, X.-M. and Dryhurst, G. (1996) Oxidation chemistry of (-)-norepinephrine in the presence of l -cysteine J. Med. Chem. 39, 2018-2029 (Pubitemid 26163252)
39. Xin, W., Shen, X.-M., Li, H., and Dryhurst, G. (2000) Oxidative metabolites of 5-S-cysteinylnorepinephrine are irreversible inhibitors of mitochondrial complex I and the alpha-ketoglutarate dehydrogenase and pyruvate dehydrogenase complexes: Possible implications for neurodegenerative brain disorders Chem. Res. Toxicol. 13, 749-760 (Pubitemid 30663453)
40. Tse, D. C. S., McCreery, R. L., and Adams, R. N. (1976) Potential oxidation pathways of brain catecholamines J. Med. Chem. 19, 37-40
41. Kato, T., Ito, S., and Fujita, K. (1986) Tyrosinase-catalyzed binding of 3,4-dihydroxyphenylalanine with proteins through the sulfhydryl group Biochim. Biophys. Acta 881, 415-421 (Pubitemid 16033458)
42. Ito, S., Kato, T., and Fujita, K. (1988) Covalent binding of catechols to proteins through the sulphydryl group Biochem. Pharmacol. 37, 1707-1710
43. Whitehead, R. E., Ferrer, J. V., Javitch, J. A., and Justice, J. B. (2001) Reaction of oxidized dopamine with endogenous cysteine residues in the human dopamine transporter J. Neurochem. 76, 1242-1251 (Pubitemid 32167397)
44. Xu, R., Huang, X., Morgan, T. D., and Prakash, O. (1996) Characterization of products from the reactions of N-acetyldopamine quinone with N-acetylhistidine Arch. Biochem. Biophys. 329, 56-64 (Pubitemid 26143397)
45. LaVoie, M. J., Ostaszewski, B. L., Weihofen, A., Schlossmacher, M. G., and Selkoe, D. J. (2005) Dopamine covalently modifies and functionally inactivates parkin Nat. Med. 11, 1214-1221 (Pubitemid 43093669)
46. Hastings, T. G., Lewis, D. A., and Zigmond, M. J. (1996) Role of oxidation in the neurotoxic effects of intrastriatal dopamine injections Proc. Natl. Acad. Sci. U.S.A. 93, 1956-1961 (Pubitemid 26079862)
47. Kuhn, D. M., Arthur, R. E., Jr., Thomas, D. M., and Elferink, L. A. (1999) Tyrosine hydroxylase is inactivated by catechol-quinones and converted to a redox-cycling quinoprotein: possible relevance to Parkinson's disease J. Neurochem. 73, 1309-1317 (Pubitemid 29395493)
48. Kuhn, D. M. and Arthur, R., Jr. (1998) Dopamine inactivates tryptophan hydroxylase and forms a redox-cycling quinoprotein: Possible endogenous toxin to serotonin neurons J. Neurosci. 18, 7111-7117 (Pubitemid 28425798)
49. Berman, S. B. and Hastings, T. G. (1997) Inhibition of glutamate transport in synaptosomes by dopamine oxidation and reactive oxygen species J. Neurochem. 69, 1185-1195 (Pubitemid 27364840)
50. Dauer, W. and Przedborski, S. (2003) Parkinson's disease: mechanisms and models Neuron 39, 889-909 (Pubitemid 37130207)
51. Robinson, P. A. (2008) Protein stability and aggregation in Parkinson's disease Biochem. J. 413, 1-13 (Pubitemid 351946857)
52. Nicolis, S., Zucchelli, M., Monzani, E., and Casella, L. (2008) Myoglobin modification by enzyme-generated dopamine reactive species Chem.-Eur. J. 14, 8661-8673
53. Cavalieri, E., Rogan, E., and Chakravarti, D. (2004) The role of endogenous catechol quinones in the initiation of cancer and neurodegenerative diseases Methods Enzymol. 382, 293-319 (Pubitemid 38240797)
54. Lippert, T. H., Seeger, H., and Mueck, A. O. (2000) The impact of endogenous estradiol metabolites on carcinogenesis Steroids 65, 357-369 (Pubitemid 30427333)
55. Bolton, J. L. and Thatcher, G. R. (2008) Potential mechanisms of estrogen quinone carcinogenesis Chem. Res. Toxicol. 21, 93-101 (Pubitemid 351219711)
56. Correia, S. C., Santos, R. X., Cardoso, S., Carvalho, C., Santos, M. S., Oliveira, C. R., and Moreira, P. I. (2010) Effects of estrogen in the brain: Is it a neuroprotective agent in Alzheimer's disease? Curr. Aging Sci. 3, 113-126
57. Sharpe, R. M. (1998) The roles of oestrogen in the male Trends Endocrinol. Metab. 371-377 (Pubitemid 28489836)
58. Gillies, G. E. and McArthur, S. (2010) Estrogen actions in the brain and the basis for differential action in men and women: a case for sex-specific medicines Pharmacol. Rev. 62, 155-198
59. De Marinis, E., Fiocchetti, M., Acconcia, F., Ascenzi, P., and Marino, M. (2013) Neuroglobin upregulation induced by 17β-estradiol sequesters cytocrome c in the mitochondria preventing H2O2-induced apoptosis of neuroblastoma cells Cell Death Dis. 4, e508
60. Fago, A., Mathews, A. J., and Brittain, T. (2008) A role for neuroglobin: Resetting the trigger level for apoptosis in neuronal and retinal cells IUBMB Life 60, 398-401
61. Raychaudhuri, S., Skommer, J., Henty, K., Birch, N., and Brittain, T. (2010) Neuroglobin protects nerve cells from apoptosis by inhibiting the intrinsic pathway of cell death Apoptosis 15, 401-411
62. Ito, S. (2003) The IFPCS presidential lecture: A chemist's view of melanogenesis Pigm. Cell Res. 16, 230-236 (Pubitemid 36597062)
63. Pezzella, A., Lista, L., Napolitano, A., and d'Ischia, M. (2005) An expedient one-pot entry to catecholestrogens and other catechol compounds via IBX-mediated phenolic oxygenation Tetrahedron Lett. 46, 3541-3544 (Pubitemid 40585589)
64. Gaitonde, M. K. (1967) A spectrophotometric method for the direct determination of cysteine in the presence of other naturally occurring amino acids Biochem. J. 104, 627-633
65. Monzani, E., Gatti, A. L., Profumo, A., Casella, L., and Gullotti, M. (1997) Oxidation of phenolic compounds by lactoperoxidase. Evidence for the presence of a low-potential compound II during catalytic turnover Biochemistry 36, 1918-1926 (Pubitemid 27086291)
66. Fago, A., Hundahl, C., Dewilde, S., Gilany, K., Moens, L., and Weber, R. E. (2004) Allosteric regulation and temperature dependence of oxygen binding in human neuroglobin and cytoglobin. Molecular mechanisms and physiological significance J. Biol. Chem. 279, 44417-44426 (Pubitemid 39430847)
67. Ros, J. R., Rodríguez-López, J. N., and García-Cánovas, F. (1994) Tyrosinase: Kinetic analysis of the transient phase and the steady state Biochim. Biophys. Acta, Protein Struct. Mol. Enzymol. 1204, 33-42 (Pubitemid 24034546)
68. Antonini, E. and Brunori, M. (1971) Hemoglobin and Myoglobin in Their Reactions with Ligands, North-Holland Publishing Company, Amsterdam, The Netherlands.
69. Roncone, R., Monzani, E., Labò, S., Sanangelantoni, A. M., and Casella, L. (2005) Catalytic activity, stability, unfolding, and degradation pathways of engineered and reconstituted myoglobins J. Biol. Inorg. Chem. 10, 11-24 (Pubitemid 40174304)
70. Dunford, H. B. and Stillmann, J. S. (1976) On the function and mechanism of action of peroxidases Coord. Chem. Rev. 19, 187-251
71. Fenoll, L. G., Rodriguez-Lopez, J. N., Garcia-Sevilla, F., Garcia-Ruiz, P. A., Varon, R., Garcia-Canovas, F., and Tudela, J. (2001) Analysis and interpretation of the action mechanism of mushroom tyrosinase on monophenols and diphenols generating highly unstable o-quinones Biochim. Biophys. Acta 1548, 1-22 (Pubitemid 32622815)
72. Everse, J. and Coates, P. W. (2009) Neurodegeneration and peroxidases Neurobiol. Aging 30, 1011-1025
73. Greggio, E., Bergantino, E., Carter, D., Ahmad, R., Costin, G. E., Hearing, V. J., Clarimon, J., Singleton, A., Eerola, J., Hellstrom, O., Tienari, P. J., Miller, D. W., Beilina, A., Bubacco, L., and Cookson, M. R. (2005) Tyrosinase exacerbates dopamine toxicity but is not genetically associated with Parkinson's disease J. Neurochem. 93, 246-256 (Pubitemid 40463533)
74. Nicolis, S., Monzani, E., Roncone, R., Gianelli, L., and Casella, L. (2004) Metmyoglobin-catalyzed exogenous and endogenous tyrosine nitration by nitrite and hydrogen peroxide Chem.-Eur. J. 10, 2281-2290
75. Roncone, R., Monzani, E., Nicolis, S., and Casella, L. (2004) Engineering and prosthetic-group modification of myoglobin: Peroxidase activity, chemical stability and unfolding properties Eur. J. Inorg. Chem. 2203-2213
76. Chapsal, J. M., Bourbigot, M. M., and Thomas, D. (1986) Oxidation of aromatic compounds by haemoglobin Water Res. 20, 709-713 (Pubitemid 16044713)
77. Ortiz de Montellano, P. R. and Catalano, C. E. (1985) Epoxidation of styrene by hemoglobin and myoglobin. Transfer of oxidizing equivalents to the protein surface J. Biol. Chem. 260, 9265-9271 (Pubitemid 16238308)
78. Monzani, E., Alzuet, G., Casella, L., Redaelli, C., Bassani, C., Sanangelantoni, A. M., Gullotti, M., De Gioiaạ, L., Santagostinị, L., and Chillemi, F. (2000) Properties and reactivity of myoglobin reconstituted with chemically modified protohemin complexes Biochemistry 39, 9571-9582 (Pubitemid 30627536)
79. Wardman, P. (1989) Reduction potentials of one-electron couples involving free radicals in aqueous solution J. Phys. Chem. Ref. Data 18, 1637-1755
80. Casella, L., Monzani, E., and Nicolis, S. (2010) Potential applications of peroxidases in the fine chemical industries. In Biocatalysis Based on Heme Peroxidases. Peroxidases as Potential Industrial Biocatalysts (Torres, E. and Ayala, M., Eds.) pp 111-153, Springer, Berlin.
81. Ferrari, E., Engelen, M., Monzani, E., Sturini, M., Girotto, S., Bubacco, L., Zecca, L., and Casella, L. (2013) Synthesis and structural characterization of soluble neuromelanin analogs provides important clues to its biosynthesis J. Biol. Inorg. Chem. 18, 81-93
82. Pezzella, A., Lista, L., Napoletano, A., and d'Ischia, M. (2005) Tyrosinase-catalyzed oxidation of 17beta-estradiol: Structure elucidation of the products formed beyond catechol estrogen quinones Chem. Res. Toxicol. 18, 1413-1419 (Pubitemid 41361714)
83. Cao, K., Devanesan, P. D., Ramanathan, R., Gross, M. L., Rogan, E. G., and Cavalieri, E. L. (1998) Covalent binding of catechol estrogens to glutathione catalyzed by horseradish peroxidase, lactoperoxidase, or rat liver microsomes Chem. Res. Toxicol. 11, 917-924 (Pubitemid 28390193)
84. Cao, K., Stack, D. E., Ramanathan, R., Gross, M. L., Rogan, E. G., and Cavalieri, E. L. (1998) Synthesis and structure elucidation of estrogen quinones conjugated with cysteine, N-acetylcysteine, and glutathione Chem. Res. Toxicol. 11, 909-916 (Pubitemid 28390192)
85. Dwivedy, I., Devanesan, P., Cremonesi, P., Rogan, E., and Cavalieri, E. L. (1992) Synthesis and characterization of estrogen 2,3- and 3,4-quinones. Comparison of DNA adducts formed by the quinones versus horseradish peroxidase-activated catechol estrogens Chem. Res. Toxicol. 5, 828-833 (Pubitemid 23004873)
86. Choi, J. and Terazima, M. (2002) Denaturation of a protein monitored by diffusion coefficients: Myoglobin J. Phys. Chem. B 106, 6587-6593 (Pubitemid 35281792)
87. Fiocchetti, M., Ascenzi, P., and Marino, M. (2012) Neuroprotective effects of 17β-estradiol rely on estrogen receptor membrane initiated signals Front. Physiol. 3, 73-79
88. Fiocchetti, M., De Marinis, E., Ascenzi, P., and Marino, M. (2013) Neuroglobin and neuronal cell survival Biochim. Biophys. Acta 1834, 1744-1749
89. Kemp, M., Go, Y. M., and Jones, D. P. (2008) Nonequilibrium thermodynamics of thiol/disulfide redox systems: a perspective on redox systems biology Free Radical Biol. Med. 44, 921-937
90. De Marinis, E., Marino, M., and Ascenzi, P. (2011) Neuroglobin, estrogens, and neuroprotection IUBMB Life 63, 140-145
91. De Marinis, E., Acaz-Fonseca, E., Arevalo, M. A., Ascenzi, P., Fiocchetti, M., Marino, M., and Garcia-Segura, L. M. (2013) 17β-Oestradiol anti-inflammatory effects in primary astrocytes require oestrogen receptor β-mediated neuroglobin up-regulation J. Neuroendocrinol. 25, 260-270