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Translational Stroke Research
Erschienen in: Translational Stroke Research 1/2013

01.02.2013 | Original Article

Nrf2 to Pre-condition the Brain Against Injury Caused by Products of Hemolysis After ICH

verfasst von: Xiurong Zhao, Jaroslaw Aronowski

Erschienen in: Translational Stroke Research | Ausgabe 1/2013

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Abstract

Brain damage caused by intracerebral hemorrhage is mediated in part by the toxicity of extravascular blood deposited in the brain parenchyma during the hematoma formation. In this paper, we discuss the therapeutic benefits and potential mechanisms associated with the activation of transcription factor Nrf2 regarding its role in defending the brain tissue against toxicity of the blood, a component of secondary injury. We emphasize the pleiotropic capacity of Nrf2 as it recruits multiple pathways aiming at reducing deleterious effects of blood lysis products.
Literatur
1.
Keep RF, Hua Y, Xi G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol. 2012;11(8):720–31.PubMedCrossRef
2.
Qureshi AI, Mendelow AD, Hanley DF. Intracerebral haemorrhage. Lancet. 2009;373(9675):1632–44.PubMedCrossRef
3.
Aronowski J, Zhao X. Molecular pathophysiology of cerebral hemorrhage: secondary brain injury. Stroke. 2011;42(6):1781–6.PubMedCrossRef
4.
Xi G, Fewel ME, Hua Y, Thompson Jr BG, Hoff JT, Keep RF. Intracerebral hemorrhage: pathophysiology and therapy. Neurocrit Care. 2004;1(1):5–18.PubMedCrossRef
5.
Wagner KR, Dwyer BE. Hematoma removal, heme, and heme oxygenase following hemorrhagic stroke. Ann N Y Acad Sci. 2004;1012:237–51.PubMedCrossRef
6.
Wagner KR, Sharp FR, Ardizzone TD, Lu A, Clark JF. Heme and iron metabolism: role in cerebral hemorrhage. J Cereb Blood Flow Metab. 2003;23(6):629–52.PubMedCrossRef
7.
Aronowski J, Hall CE. New horizons for primary intracerebral hemorrhage treatment: experience from preclinical studies. Neurol Res. 2005;27(3):268–79.PubMedCrossRef
8.
Huang FP, Xi G, Keep RF, Hua Y, Nemoianu A, Hoff JT. Brain edema after experimental intracerebral hemorrhage: role of hemoglobin degradation products. J Neurosurg. 2002;96(2):287–93.PubMedCrossRef
9.
Wu J, Hua Y, Keep RF, Schallert T, Hoff JT, Xi G. Oxidative brain injury from extravasated erythrocytes after intracerebral hemorrhage. Brain Res. 2002;953(1–2):45–52.PubMedCrossRef
10.
Ascenzi P, Bocedi A, Visca P, Altruda F, Tolosano E, Beringhelli T, et al. Hemoglobin and heme scavenging. IUBMB Life. 2005;57(11):749–59.PubMedCrossRef
11.
Schaer DJ, Alayash AI, Buehler PW. Gating the radical hemoglobin to macrophages: the anti-inflammatory role of CD163, a scavenger receptor. Antioxid Redox Signal. 2007;9(7):991–9.PubMedCrossRef
12.
Tolosano E, Altruda F. Hemopexin: structure, function, and regulation. DNA Cell Biol. 2002;21(4):297–306.PubMedCrossRef
13.
14.
Hvidberg V, Maniecki MB, Jacobsen C, Hojrup P, Moller HJ, Moestrup SK. Identification of the receptor scavenging hemopexin–heme complexes. Blood. 2005;106(7):2572–9.PubMedCrossRef
15.
Kirkby KA, Adin CA. Products of heme oxygenase and their potential therapeutic applications. Am J Physiol. 2006;290(3):F563–71.
16.
Roskams AJ, Connor JR. Iron, transferrin, and ferritin in the rat brain during development and aging. J Neurochem. 1994;63(2):709–16.PubMedCrossRef
17.
Rogers J, Munro H. Translation of ferritin light and heavy subunit mRNAs is regulated by intracellular chelatable iron levels in rat hepatoma cells. Proc Natl Acad Sci U S A. 1987;84(8):2277–81.PubMedCrossRef
18.
van Muiswinkel FL, Kuiperij HB. The Nrf2–ARE signalling pathway: promising drug target to combat oxidative stress in neurodegenerative disorders. Curr Drug Targets CNS Neurol Disord. 2005;4(3):267–81.PubMedCrossRef
19.
Kensler TW, Wakabayashi N, Biswal S. Cell survival responses to environmental stresses via the Keap1–Nrf2–ARE pathway. Annu Rev Pharmacol Toxicol. 2007;47:89–116.PubMedCrossRef
20.
Nguyen T, Sherratt PJ, Nioi P, Yang CS, Pickett CB. Nrf2 controls constitutive and inducible expression of ARE-driven genes through a dynamic pathway involving nucleocytoplasmic shuttling by Keap1. J Biol Chem. 2005;280(37):32485–92.PubMedCrossRef
21.
Zhao X, Sun G, Zhang J, Strong R, Dash PK, Kan YW, et al. Transcription factor Nrf2 protects the brain from damage produced by intracerebral hemorrhage. Stroke. 2007;38(12):3280–6.PubMedCrossRef
22.
Wang J, Fields J, Zhao C, Langer J, Thimmulappa RK, Kensler TW, et al. Role of Nrf2 in protection against intracerebral hemorrhage injury in mice. Free Radic Biol Med. 2007;43(3):408–14.PubMedCrossRef
23.
Lee JM, Shih AY, Murphy TH, Johnson JA. NF-E2-related factor-2 mediates neuroprotection against mitochondrial complex I inhibitors and increased concentrations of intracellular calcium in primary cortical neurons. J Biol Chem. 2003;278(39):37948–56.PubMedCrossRef
24.
Lee JM, Calkins MJ, Chan K, Kan YW, Johnson JA. Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis. J Biol Chem. 2003;278(14):12029–38.PubMedCrossRef
25.
Johnson DA, Amirahmadi S, Ward C, Fabry Z, Johnson JA. The absence of the pro-antioxidant transcription factor Nrf2 exacerbates experimental autoimmune encephalomyelitis. Toxicol Sci. 2010;114(2):237–46.PubMedCrossRef
26.
Wada T, Oara H, Watanabe K, Kinoshita H, Yachi A. Autoradiographic study on the site of uptake of the haptoglobin–hemoglobin complex. J Reticuloendothel Soc. 1970;8(2):185–93.PubMed
27.
Xi G, Keep RF, Hoff JT. Erythrocytes and delayed brain edema formation following intracerebral hemorrhage in rats. J Neurosurg. 1998;89(6):991–6.PubMedCrossRef
28.
Wang X, Mori T, Sumii T, Lo EH. Hemoglobin-induced cytotoxicity in rat cerebral cortical neurons: caspase activation and oxidative stress. Stroke. 2002;33(7):1882–8.PubMedCrossRef
29.
Sadrzadeh SM, Graf E, Panter SS, Hallaway PE, Eaton JW. Hemoglobin. A biologic fenton reagent. J Biol Chem. 1984;259(23):14354–6.PubMed
30.
Lee MY, Kim SY, Choi JS, Lee IH, Choi YS, Jin JY, et al. Upregulation of haptoglobin in reactive astrocytes after transient forebrain ischemia in rats. J Cereb Blood Flow Metab. 2002;22(10):1176–80.PubMedCrossRef
31.
Cid MC, Grant DS, Hoffman GS, Auerbach R, Fauci AS, Kleinman HK. Identification of haptoglobin as an angiogenic factor in sera from patients with systemic vasculitis. J Clin Invest. 1993;91(3):977–85.PubMedCrossRef
32.
Yang F, Haile DJ, Berger FG, Herbert DC, Van Beveren E, Ghio AJ. Haptoglobin reduces lung injury associated with exposure to blood. Am J Physiol Lung Cell Mol Physiol. 2003;284(2):L402–9.PubMed
33.
Chen W, Lu H, Dutt K, Smith A, Hunt DM, Hunt RC. Expression of the protective proteins hemopexin and haptoglobin by cells of the neural retina. Exp Eye Res. 1998;67(1):83–93.PubMedCrossRef
34.
Zhao X, Song S, Sun G, Strong R, Zhang J, Grotta JC, et al. Neuroprotective role of haptoglobin after intracerebral hemorrhage. J Neurosci. 2009;29(50):15819–27.PubMedCrossRef
35.
Panter SS, Sadrzadeh SM, Hallaway PE, Haines J, Anderson VE, Eaton JW. Hypohaptoglobinemia: a possible predisposition to epilepsy. Trans Assoc Am Physicians. 1984;97:56–62.PubMed
36.
Miller YI, Altamentova SM, Shaklai N. Oxidation of low-density lipoprotein by hemoglobin stems from a heme-initiated globin radical: antioxidant role of haptoglobin. Biochemistry. 1997;36(40):12189–98.PubMedCrossRef
37.
Goldstein L, Teng ZP, Zeserson E, Patel M, Regan RF. Hemin induces an iron-dependent, oxidative injury to human neuron-like cells. J Neurosci Res. 2003;73(1):113–21.PubMedCrossRef
38.
Camejo G, Halberg C, Manschik-Lundin A, Hurt-Camejo E, Rosengren B, Olsson H, et al. Hemin binding and oxidation of lipoproteins in serum: mechanisms and effect on the interaction of LDL with human macrophages. J Lipid Res. 1998;39(4):755–66.PubMed
39.
Balla J, Vercellotti GM, Jeney V, Yachie A, Varga Z, Eaton JW, et al. Heme, heme oxygenase and ferritin in vascular endothelial cell injury. Mol Nutr Food Res. 2005;49(11):1030–43.PubMedCrossRef
40.
Nikkila H, Gitlin JD, Muller-Eberhard U. Rat hemopexin. Molecular cloning, primary structural characterization, and analysis of gene expression. Biochemistry. 1991;30(3):823–9.PubMedCrossRef
41.
Grinberg LN, O’Brien PJ, Hrkal Z. The effects of heme-binding proteins on the peroxidative and catalatic activities of hemin. Free Radic Biol Med. 1999;27(1–2):214–9.PubMedCrossRef
42.
Hunt RC, Hunt DM, Gaur N, Smith A. Hemopexin in the human retina: protection of the retina against heme-mediated toxicity. J Cell Physiol. 1996;168(1):71–80.PubMedCrossRef
43.
Tolosano E, Cutufia MA, Hirsch E, Silengo L, Altruda F. Specific expression in brain and liver driven by the hemopexin promoter in transgenic mice. Biochem Biophys Res Commun. 1996;218(3):694–703.PubMedCrossRef
44.
Delanghe JR, Langlois MR. Hemopexin: a review of biological aspects and the role in laboratory medicine. Clin Chim Acta. 2001;312(1–2):13–23.PubMedCrossRef
45.
Tolosano E, Fagoonee S, Hirsch E, Berger FG, Baumann H, Silengo L, et al. Enhanced splenomegaly and severe liver inflammation in haptoglobin/hemopexin double-null mice after acute hemolysis. Blood. 2002;100(12):4201–8.PubMedCrossRef
46.
Kristiansson MH, Bhat VB, Babu IR, Wishnok JS, Tannenbaum SR. Comparative time-dependent analysis of potential inflammation biomarkers in lymphoma-bearing SJL mice. J Proteome Res. 2007;6(5):1735–44.PubMedCrossRef
47.
Shen G, Xu C, Hu R, Jain MR, Gopalkrishnan A, Nair S, et al. Modulation of nuclear factor E2-related factor 2-mediated gene expression in mice liver and small intestine by cancer chemopreventive agent curcumin. Mol Cancer Ther. 2006;5(1):39–51.PubMedCrossRef
48.
Li N, Venkatesan MI, Miguel A, Kaplan R, Gujuluva C, Alam J, et al. Induction of heme oxygenase-1 expression in macrophages by diesel exhaust particle chemicals and quinones via the antioxidant-responsive element. J Immunol. 2000;165(6):3393–401.PubMed
49.
Turner CP, Bergeron M, Matz P, Zegna A, Noble LJ, Panter SS, et al. Heme oxygenase-1 is induced in glia throughout brain by subarachnoid hemoglobin. J Cereb Blood Flow Metab. 1998;18(3):257–73.PubMedCrossRef
50.
Ewing JF, Haber SN, Maines MD. Normal and heat-induced patterns of expression of heme oxygenase-1 (HSP32) in rat brain: hyperthermia causes rapid induction of mRNA and protein. J Neurochem. 1992;58(3):1140–9.PubMedCrossRef
51.
Ryter SW, Alam J, Choi AM. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev. 2006;86(2):583–650.PubMedCrossRef
52.
Maines MD. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol. 1997;37:517–54.PubMedCrossRef
53.
Lin Y, Vreman HJ, Wong RJ, Tjoa T, Yamauchi T, Noble-Haeusslein LJ. Heme oxygenase-1 stabilizes the blood-spinal cord barrier and limits oxidative stress and white matter damage in the acutely injured murine spinal cord. J Cereb Blood Flow Metab. 2007;27(5):1010–21.PubMed
54.
Parfenova H, Basuroy S, Bhattacharya S, Tcheranova D, Qu Y, Regan RF, et al. Glutamate induces oxidative stress and apoptosis in cerebral vascular endothelial cells: contributions of HO-1 and HO-2 to cytoprotection. Am J Physiol Cell Physiol. 2006;290(5):C1399–410.PubMedCrossRef
55.
Ahmad AS, Zhuang H, Dore S. Heme oxygenase-1 protects brain from acute excitotoxicity. Neuroscience. 2006;141(4):1703–8.PubMedCrossRef
56.
Panahian N, Yoshiura M, Maines MD. Overexpression of heme oxygenase-1 is neuroprotective in a model of permanent middle cerebral artery occlusion in transgenic mice. J Neurochem. 1999;72(3):1187–203.PubMedCrossRef
57.
Wagener FA, van Beurden HE, von den Hoff JW, Adema GJ, Figdor CG. The heme–heme oxygenase system: a molecular switch in wound healing. Blood. 2003;102(2):521–8.PubMedCrossRef
58.
Gong Y, Tian H, Xi G, Keep RF, Hoff JT, Hua Y. Systemic zinc protoporphyrin administration reduces intracerebral hemorrhage-induced brain injury. Acta Neurochir Suppl. 2006;96:232–6.PubMedCrossRef
59.
Wagner KR, Hua Y, de Courten-Myers GM, Broderick JP, Nishimura RN, Lu SY, et al. Tin-mesoporphyrin, a potent heme oxygenase inhibitor, for treatment of intracerebral hemorrhage: in vivo and in vitro studies. Cell Mol Biol (Noisy-le-Grand). 2000;46(3):597–608.
60.
Koeppen AH, Dickson AC, Smith J. Heme oxygenase in experimental intracerebral hemorrhage: the benefit of tin-mesoporphyrin. J Neuropathol Exp Neurol. 2004;63(6):587–97.PubMed
61.
Gerlach M, Ben-Shachar D, Riederer P, Youdim MB. Altered brain metabolism of iron as a cause of neurodegenerative diseases? J Neurochem. 1994;63(3):793–807.PubMedCrossRef
62.
Chi SI, Wang CK, Chen JJ, Chau LY, Lin TN. Differential regulation of H- and L-ferritin messenger RNA subunits, ferritin protein and iron following focal cerebral ischemia–reperfusion. Neuroscience. 2000;100(3):475–84.PubMedCrossRef
63.
Yanagawa T, Itoh K, Uwayama J, Shibata Y, Yamaguchi A, Sano T, et al. Nrf2 deficiency causes tooth decolourization due to iron transport disorder in enamel organ. Genes Cells. 2004;9(7):641–51.PubMedCrossRef
64.
Pietsch EC, Chan JY, Torti FM, Torti SV. Nrf2 mediates the induction of ferritin H in response to xenobiotics and cancer chemopreventive dithiolethiones. J Biol Chem. 2003;278(4):2361–9.PubMedCrossRef
65.
Hua Y, Nakamura T, Keep RF, Wu J, Schallert T, Hoff JT, et al. Long-term effects of experimental intracerebral hemorrhage: the role of iron. J Neurosurg. 2006;104(2):305–12.PubMedCrossRef
66.
Nakamura T, Keep RF, Hua Y, Schallert T, Hoff JT, Xi G. Deferoxamine-induced attenuation of brain edema and neurological deficits in a rat model of intracerebral hemorrhage. J Neurosurg. 2004;100(4):672–8.PubMedCrossRef
67.
Wan S, Hua Y, Keep RF, Hoff JT, Xi G. Deferoxamine reduces CSF free iron levels following intracerebral hemorrhage. Acta Neurochir Suppl. 2006;96:199–202.PubMedCrossRef
68.
Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law SK, et al. Identification of the haemoglobin scavenger receptor. Nature. 2001;409(6817):198–201.PubMedCrossRef
69.
Hu R, Hebbar V, Kim BR, Chen C, Winnik B, Buckley B, et al. In vivo pharmacokinetics and regulation of gene expression profiles by isothiocyanate sulforaphane in the rat. J Pharmacol Exp Ther. 2004;310(1):263–71.PubMedCrossRef
Metadaten
Titel
Nrf2 to Pre-condition the Brain Against Injury Caused by Products of Hemolysis After ICH
verfasst von
Xiurong Zhao
Jaroslaw Aronowski
Publikationsdatum
01.02.2013
Verlag
Springer US
Erschienen in
Translational Stroke Research / Ausgabe 1/2013
Print ISSN: 1868-4483
Elektronische ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-012-0245-y

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