Neuroprotective effect of neuroglobin in hypoxia/ischemia
https://doi.org/10.18699/SSMJ20210205
Abstract
Neuroglobin is a representative of the globin group, an oxygen-binding protein which is predominantly expressed in the nervous system. Despite the large amount of conducted research, its role is still poorly understood. It’s assumed that neuroglobin is able to regulate cell activity in health and disease:in health it provides oxygen homeostasis of neurons, and in pathology it binds free radicals and nitrogen monoxide, blocks mitochondrial factors of apoptosis and suppresses oxidative stress. A clearer understanding of the role of neuroglobin in pathology can offer new approaches in the treatment of neurodegenerative diseases. Special attention in the literature is paid to the role of neuroglobin in cerebral ischemia, which among other cerebrovascular diseases is the cause of disability and mortality of the population all over the world. In the present article an overview of the literature data available to date on the study of the neuroprotective effect of neuroglobin in hypoxia/ischemia is provided: models used to study function in vitro and in vivo, the effects of its increased or decreased expression, neuroglobin-mediated neuroprotective action of hemin, estimated pathways of the induction of neuroglobin and views on the mechanisms of neuroprotection.
About the Authors
E. V. Uzlova
Grodno State Medical University
Belarus
Belarus
Elizaveta V. Uzlova
230009, Grodno, Gorky str., 80
S. M. Zimatkin
Grodno State Medical University
Belarus
Belarus
Sergey M. Zimatkin, doctor of biological sciences, professor
230009, Grodno, Gorky str., 80
References
1. Burmester T., Weich B., Reinhardt S., Hankeln T. A vertebrate globin expressed in the brain. Nature. 2000; 407 (6803): 520–523. doi:10.1038/35035093
2. Blank M., Burmester T. Widespread occurrence of N-terminal acylation in animal globins and possible origin of respiratory globins from a membrane-bound ancestor. Mol. Biol. Evol. 2012; 29 (11): 3553–3561. doi: 10.1093/molbev/mss164
3. Storz J.F., Opazo J.C., Hoffman F.G. Gene duplication, genome duplication, and the functional diversification of vertebrate globins. Mol. Phylogenet. Evol. 2013; 66 (2): 469–478. doi: 10.1016/j.ympev.2012.07.013
4. Узлова Е.В., Зиматкин С.М. Нейроглобин: строение, функции, локализация в мозге в норме и при патологии. Новости мед.-биол. наук. 2019; 19 (1): 91–96. Uzlova E.V., Zimatkin S.M. Neuroglobin: structure, function, localization in the brain in normal and pathological conditions. Novosti medikobiologicheskikh nauk = News of Biomedical Sciences. 2019; 19 (1): 91–96. [In Russian].
5. Burmester T., Hankeln T. What is the function of neuroglobin? J. Exp. Biol. 2009; 212 (10): 1423–1428. doi: 10.1242/jeb.000729
6. Wystub S., Ebner B., Fuchs C., Weich B., Burmester T., Hankeln T. Interspecies comparison of neuroglobin, cytoglobin and myoglobin: sequence evolution and candidate regulatory elements. Cytogenet. Genome Res. 2004; 105 (1): 65–78. doi: 10.1159/000078011
7. Зиматкин С.М., Бонь Е.И., Максимович Н.Е. Роль нейроглобина при церебральной ишемии/гипоксии и другой нейропатологии. Ж. Гродненск. гос. мед. ун-та. 2018; 16 (6): 643–647. doi: 10.25298/2221-8785-2018-16-6-643-647 Zimatkin S.M., Bon’ E.I., Maksimovich N.E. Role of neuroglobin in cerebral ischemia/hypoxia and other neuropathology. Zhurnal Grodnenskogo Gosudarstvennogo Meditsinskogo Universiteta = Journal of the Grodno State Medical University. 2018; 16 (6): 643–647. [In Russian]. doi: 10.25298/2221-8785-2018-16-6-643-647
8. Yu Z., Liu N., Liu J., Yang K., Wang X. Neuroglobin, a novel target for endogenous neuroprotection against stroke and neurodegenerative disorders. Int. J. Mol. Sci. 2012; 13 (6): 6995–7014. doi:10.3390/ijms13066995
9. Luyckx E., van Acker Z.P., Ponsaerts P., Dewilde S. Neuroglobin expression models as a tool to study its function. Oxid. Med. Cell. Longev. 2019; 2019: 5728129. doi: 10.1155/2019/5728129
10. Sun Y., Jin K., Mao X.O., Zhu Y., Greenberg D.A. Neuroglobin is up-regulated by and protects neurons from hypoxic-ischemic injury. Proc. Natl. Acad. Sci. USA. 2001; 98 (26): 15306–15311. doi: 10.1073/pnas.251466698
11. Sun Y., Jin K., Peel A., Mao X.O., Xie L., Greenberg D.A. Neuroglobin protects the brain from experimental stroke in vivo. Proc. Natl. Acad. Sci. USA. 2003; 100 (6): 3497–3500. doi: 10.1073/pnas.0637726100
12. Khan A.A., Wang Y., Sun Y., Mao X.O., Xie L., Miles E., Graboski J., Chen S., Ellerby L.M., Jin K., Greenberg D.A. Neuroglobin-overexpressing transgenic mice are resistant to cerebral and myocardial ischemia. Proc. Natl. Acad. Sci. USA. 2006; 103 (47): 17944–17948. doi: 10.1073/pnas.0607497103
13. Wang X., Liu J., Zhu H., Tejima E., Tsuji K., Murata Y., Atochin D.N., Huang P.L., Zhang C., Lo E.H. Effects of neuroglobin overexpression on acute brain injury and long-term outcomes after focal cerebral ischemia. Stroke. 2008; 39 (6): 1869–1874. doi: 10.1161/STROKEAHA.107.506022
14. Li R.C., Guo S.Z., Lee S.K., Gozal D. Neuroglobin protects neurons against oxidative stress in global ischemia. J. Cereb. Blood. Flow. Metab. 2010; 30 (11): 1874–1882. doi: 10.1038/jcbfm.2010.90
15. Raida Z., Hundahl C.A., Nyengaard J.R., HaySchmidt A. Neuroglobin over expressing mice: expression pattern and effect on brain ischemic infarct size. PLoS One. 2013; 8 (10): e76565. doi: 10.1371/journal.pone.0076565
16. Taylor J.M., Kelley B., Gregory E.J., Berman N.E. Neuroglobin overexpression improves sensorimotor outcomes in a mouse model of traumatic brain injury. Neurosci. Lett. 2014; 577: 125–129. doi: 10.1016/j.neulet.2014.03.012
17. Hundahl C.A., Luuk H., Ilmjärv S., Falktoft B., Raida Z., Vikesaa J., Friis-Hansen L., Hay-Schmidt A. Neuroglobin-deficiency exacerbates Hif1A and c-FOS response, but does not affect neuronal survival during severe hypoxia in vivo. PLoS One. 2011; 6 (12): e28160. doi: 10.1371/journal.pone.0028160
18. Raida Z., Hundahl C.A., Kelsen J., Nyengaard J.R., Hay-Schmidt A. Reduced infarct size in neuroglobin-null mice after experimental stroke in vivo. Exp. Transl. Stroke Med. 2012; 4 (1): 15. doi: 10.1186/2040-7378-4-15
19. Schmidt-Kastner R., Haberkamp M., Schmitz C., Hankeln T., Burmester T. Neuroglobin mRNA expression after transient global brain ischemia and prolonged hypoxia in cell culture. Brain Res. 2006; 1103 (1): 173–180. doi: 10.1016/j.brainres.2006.05.047
20. Гилерович Е.Г., Григорьев И.П., Кирик О.В., Алексеева О.С., Сухорукова Е.Г., Коржевский Д.Э. Распределение нейроглобина в структурах переднего мозга крыс после транзиторной ишемии. Морфология. 2014; 146 (4): 75–77. Gilerovich E.G., Grigor’ev I.P., Kirik O.V., Alekseeva O.S., Sukhorukova E.G., Korzhevskij D.J. Distribution of neuroglobin in the structures of the forebrain of rats after transient ischemia. Morfologiya = Morphology. 2014; 146 (4): 75–77. [In Russian].
21. Zhu Y., Sun Y., Jin K., Greenberg D.A. Hemin induces neuroglobin expression in neural cells. Blood. 2002; 100 (7): 2494–2498. doi: 10.1182/blood-2002-01-0280
22. Song X., Xu R., Xie F., Zhu H., Zhu J., Wang X. Hemin offers neuroprotection through inducing exogenous neuroglobin in focal cerebral hypoxic-ischemia in rats. Int. J. Clin. Exp. Pathol. 2014; 7 (5): 2163–2171.
23. Хie F., Xu R., Song X., Zhu H., Wang X., Zhu J. Joint protective effect of exogenous neuroglobin and hemin in rat focal ischemic brain tissues. Int. J. Clin. Exp. Med. 2014; 7 (8): 2009–2016.
24. Wen H., Liu L., Zhan L., Liang D., Li L., Liu D., Sun W., Xu E. Neuroglobin mediates neuroprotection of hypoxic postconditioning against transient global cerebral ischemia in rats through preserving the activity of Na+/K+ ATPases. Cell Death. Dis. 2018; 9 (6): 635. doi: 10.1038/s41419-018-0656-0
25. Conley K.E., Ordway G.A., Richardson R.S. Deciphering the mysteries of myoglobin in striated muscle. Acta Physiol. Scand. 2000; 168 (4): 623–634. doi: 10.1046/j.1365-201x.2000.00714.x
26. Schmidt M., Giessl A., Laufs T., Hankeln T., Wolfrum U., Burmester T. How does the eye breathe? Evidence for neuroglobin-mediated oxygen supply in the mammalian retina. J. Biol. Chem. 2003; 278 (3): 1932–1935. doi: 10.1074/jbc.M209909200
27. Hundahl C., Fago A., Dewilde S., Moens L., Hankeln T., Burmester T., Weber R.E. Oxygen binding properties of non-mammalian nerve globins. FEBS J. 2006; 273 (6): 1323–1329. doi: 10.1111/j.1742-4658.2006.05158.x
28. Trent J.T. 3rd, Watts R.A., Hargrove M.S. Human neuroglobin, a hexacoordinate hemoglobin that reversibly binds oxygen. J. Biol. Chem. 2001; 276 (32): 30106–30110. doi: 10.1074/jbc.C100300200
29. Brunori M., Giuffrè A., Nienhaus K., Nienhaus G.U., Scandurra F.M., Vallone B. Neuroglobin, nitric oxide, and oxygen: functional pathways and conformational changes. Proc. Natl. Acad. Sci. USA. 2005; 102 (24): 8483–8488. doi: 10.1073/pnas.0408766102
30. Tiso M., Tejero J., Basu S., Azarov I., Wang X., Simplaceanu V., Frizzell S., Jayaraman T., Geary L., Shapiro C., Ho C., Shiva S., Kim-Shapiro D.B. Gladwin M.T. Human neuroglobin functions as a redox-regulated nitrite reductase. J. Biol. Chem. 2011; 286 (20): 18277–18289. doi: 10.1074/jbc.M110.159541
31. Xiong X.X., Pan F., Chen R.Q., Hu D.X., Qiu X.Y., Li C.Y., Xie X.Q., Tian B., Chen X.Q. Neuroglobin boosts axon regeneration during ischemic reperfusion via p38 binding and activation depending on oxygen signal. Cell Death Dis. 2018; 9 (2): 163. doi: 10.1038/s41419-017-0260-8
32. Jin K., Mao X.O., Xie L., John V., Greenberg D.A. Pharmacological induction of neuroglobin expression. Pharmacology. 2011; 87 (1-2): 81–84. doi: 10.1159/000322998
Review
For citations:
Uzlova E.V., Zimatkin S.M. Neuroprotective effect of neuroglobin in hypoxia/ischemia. Сибирский научный медицинский журнал. 2021;41(2):33-39. (In Russ.) https://doi.org/10.18699/SSMJ20210205
Views:
606
Email this article 