Abstract
The purpose of this study was to examine the expression of hemoglobin (Hb) in the brain after intracerebral hemorrhage (ICH) and the effects of hemin and iron on neuronal Hb.
For the in vivo studies, male Sprague-Dawley rats received either a sham operation or an ICH. The rats were killed 1, 4, 24 or 72 h later, and brains were used for real-time polymerase chain reaction (PCR) and immunohistochemistry. For the in vitro study, primary cultured neurons were exposed to either hemin or vehicle. Some neurons also received treatment with deferoxamine, an iron chelator. Neurons were collected 24 h later for real-time PCR.
We found that α-globin (HbA) and β-globin (HbB) mRNA levels in the ipsilateral basal ganglia are significantly increased after ICH, and Hb is localized in neurons and glia cells. Exposure of neurons to hemin also upregulated HbA and HbB mRNA levels. Hemin-induced HbA and HbB expression in cultured neurons was reduced by deferoxamine treatment.
These results indicate that ICH increases HbA and HbB expression in neurons and glia cells, and that heme and iron may be important factors in inducing endogenous Hb expression after ICH.
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References
Poyart C, Wajcman H, Kister J (1992) Molecular adaptation of hemoglobin function in mammals. Respir Physiol 90:3–17
Liu L, Zeng M, Stamler JS (1999) Hemoglobin induction in mouse macrophages. Proc Natl Acad Sci USA 96:6643–6647
Newton DA, Rao KM, Dluhy RA, Baatz JE (2006) Hemoglobin is expressed by alveolar epithelial cells. J Biol Chem 281:5668–5676
Nishi H, Inagi R, Kato H, Tanemoto M, Kojima I, Son D, Fujita T, Nangaku M (2008) Hemoglobin is expressed by mesangial cells and reduces oxidant stress. J Am Soc Nephrol 19:1500–1508
He Y, Hua Y, Liu W, Hu H, Keep RF, Xi G (2009) Effects of cerebral ischemia on neuronal hemoglobin. J Cereb Blood Flow Metab 29:596–605
Ohyagi Y, Yamada T, Goto I (1994) Hemoglobin as a novel protein developmentally regulated in neurons. Brain Res 635:323–327
Richter F, Meurers BH, Zhu C, Medvedeva VP, Chesselet MF (2009) Neurons express hemoglobin alpha- and beta-chains in rat and human brains. J Comp Neurol 515:538–547
Schelshorn DW, Schneider A, Kuschinsky W, Weber D, Kruger C, Dittgen T, Burgers HF, Sabouri F, Gassler N, Bach A, Maurer MH (2009) Expression of hemoglobin in rodent neurons. J Cereb Blood Flow Metab 29:585–595
Xi G, Keep RF, Hoff JT (1998) Erythrocytes and delayed brain edema formation following intracerebral hemorrhage in rats. J Neurosurg 89:991–996
Huang FP, Xi G, Keep RF, Hua Y, Nemoianu A, Hoff JT (2002) Brain edema after experimental intracerebral hemorrhage: role of hemoglobin degradation products. J Neurosurg 96:287–293
Sadrzadeh SM, Anderson DK, Panter SS, Hallaway PE, Eaton JW (1987) Hemoglobin potentiates central nervous system damage. J Clin Invest 79:662–664
Regan RF, Panter SS (1993) Neurotoxicity of hemoglobin in cortical cell culture. Neurosci Lett 153:219–222
Wang X, Mori T, Sumii T, Lo EH (2002) Hemoglobin-induced cytotoxicity in rat cerebral cortical neurons: caspase activation and oxidative stress. Stroke 33:1882–1888
Jiang Y, Wu J, Hua Y, Keep RF, Xiang J, Hoff JT, Xi G (2002) Thrombin-receptor activation and thrombin-induced brain tolerance. J Cereb Blood Flow Metab 22:404–410
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 25:402–408
Xi G, Keep RF, Hua Y, Xiang J, Hoff JT (1999) Attenuation of thrombin-induced brain edema by cerebral thrombin preconditioning. Stroke 30:1247–1255
Wagner KR, Sharp FR, Ardizzone TD, Lu A, Clark JF (2003) Heme and iron metabolism: role in cerebral hemorrhage. J Cereb Blood Flow Metab 23:629–652
Tahara T, Sun J, Igarashi K, Taketani S (2004) Heme-dependent up-regulation of the alpha-globin gene expression by transcriptional repressor Bach1 in erythroid cells. Biochem Biophys Res Commun 324:77–85
Tahara T, Sun J, Nakanishi K, Yamamoto M, Mori H, Saito T, Fujita H, Igarashi K, Taketani S (2004) Heme positively regulates the expression of beta-globin at the locus control region via the transcriptional factor Bach1 in erythroid cells. J Biol Chem 279:5480–5487
Fibach E, Kollia P, Schechter AN, Noguchi CT, Rodgers GP (1995) Hemin-induced acceleration of hemoglobin production in immature cultured erythroid cells: preferential enhancement of fetal hemoglobin. Blood 85:2967–2974
Rutherford TR, Clegg JB, Weatherall DJ (1979) K562 human leukaemic cells synthesise embryonic haemoglobin in response to haemin. Nature 280:164–165
Zhu Y, Sun Y, Jin K, Greenberg DA (2002) Hemin induces neuroglobin expression in neural cells. Blood 100:2494–2498
Wu J, Hua Y, Keep RF, Nakamura T, Hoff JT, Xi G (2003) Iron and iron-handling proteins in the brain after intracerebral hemorrhage. Stroke 34:2964–2969
Vincent SR, Das S, Maines MD (1994) Brain heme oxygenase isoenzymes and nitric oxide synthase are co-localized in select neurons. Neuroscience 63:223–231
Acknowledgements
This study was supported by grants NS-017760, NS-039866 and NS-057539 from the National Institutes of Health (NIH) and 0755717Z and 0840016N from the American Heart Association (AHA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH and AHA. MMW is supported by NS-062816 and NS-054724.
Conflict of interest statement We declare that we have no conflict of interest.
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He, Y., Hua, Y., Keep, R.F., Liu, W., Wang, M.M., Xi, G. (2011). Hemoglobin Expression in Neurons and Glia After Intracerebral Hemorrhage. In: Zhang, J., Colohan, A. (eds) Intracerebral Hemorrhage Research. Acta Neurochirurgica Supplementum, vol 111. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0693-8_22
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DOI: https://doi.org/10.1007/978-3-7091-0693-8_22
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