Skip to main content

Cytoglobin Up-regulated by Hydrogen Peroxide Plays a Protective Role in Oxidative Stress

Neurochemical Research volume 32, pages 1375–1380 (2007)Cite this article

Abstract

Cytoglobin (Cygb) is a recently discovered intracellular respiratory globin, which exists in all types of cells. It has been suggested that Cygb has a role in protecting cells against oxidative stress. In the present study we have tested this hypothesis. The N2a neuroblastoma cells were exposed to various kinds of insults, including hydrogen peroxide (H2O2), hypoxia, kainic acid, high extracellular CaCl2, high osmolarity, UV irradiation and heat shock. Among them, only H2O2-treatment induced a significant up-regulation of cytoglobin mRNA level. We stably transfected N2a cells with Cygb-siRNA vectors and successfully knocked down Cygb. The Cygb-siRNA could exacerbate cell death upon H2O2-treatment, as demonstrated by MTT cell viability assay. Thus, Cygb in neuronal cells might be specifically induced under oxidative stress to protect them from death.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  1. Burmester T, Weich B, Reinhardt S et al (2000) A vertebrate globin expressed in the brain. Nature 407:520–523

    PubMed  Article  CAS  Google Scholar 

  2. Burmester T, Ebner B, Weich B et al (2002) Cytoglobin: a novel globin type ubiquitously expressed in vertebrate tissues. Mol Biol Evol 19:416–421

    PubMed  CAS  Google Scholar 

  3. Pesce A, Bolognesi M, Bocedi A et al (2002) Neuroglobin and cytoglobin: fresh blood for the vertebrate globin family. EMBO Rep 3:1146–1151

    PubMed  Article  CAS  Google Scholar 

  4. Hamdane D, Kiger L, Dewilde S et al (2003) The redox state of the cell regulates the ligand binding affinity of human neuroglobin and cytoglobin. J Biol Chem 278:51713–51721

    PubMed  Article  CAS  Google Scholar 

  5. Fago A, Hundahl C, Dewilde S et al (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

    PubMed  Article  CAS  Google Scholar 

  6. Hamdane D, Vasseur-Godbillon C, Baudin-Creuza V et al (2006) Reversible hexacoordination of AHSP/alpha -Hb vs pressure: evidence for protection of the alpha - chains by its chaperone. J Biol Chem, [Epub ahead of print]

  7. Fuchs C, Luckhardt A, Gerlach F et al (2003) Duplicated cytoglobin genes in teleost fishes. Biochem Biophys Res Commun 337:216–223

    Article  Google Scholar 

  8. Mammen PP, Shelton JM, Ye Q et al (2006) Cytoglobin is a stress-responsive hemoprotein that is expressed in the developing and adult brain. J Histochem Cytochem 54:1349–1361

    PubMed  Article  CAS  Google Scholar 

  9. Schmidt M, Gerlach F, Avivi A et al (2004) Cytoglobin is a respiratory protein in connective tissue and neurons, which is up-regulated by hypoxia. J Biol Chem 279:8063–8069

    PubMed  Article  CAS  Google Scholar 

  10. Geuens E, Brouns I, Flamez D et al (2003) A globin in the nucleus! J Biol Chem 278:30417–30420

    PubMed  Article  CAS  Google Scholar 

  11. Schmidt M, Gerlach F, Avivi A et al (2004) Cytoglobin is a respiratory protein in connective tissue and neurons, which is up-regulated by hypoxia. J Biol Chem 279:8063–8069

    PubMed  Article  CAS  Google Scholar 

  12. Fordel E, Geuens E, Dewilde S et al (2004) Cytoglobin expression is upregulated in all tissues upon hypoxia: an in vitro and in vivo study by quantitative real-time PCR. Biochem Biophys Res Commun 319:342–348

    PubMed  Article  CAS  Google Scholar 

  13. Li RC, Lee SK, Pouranfar F et al (2006) Hypoxia differentially regulates the expression of neuroglobin and cytoglobin in rat brain. Brain Res 1096:173–179

    PubMed  Article  CAS  Google Scholar 

  14. Stagner JI, Parthasarathy SN, Wyler K et al (2000) Protection from ischemic cell death by the induction of cytoglobin. Transplant Proc 37:3452–3453

    Article  Google Scholar 

  15. Xu R, Harrison PM, Chen M et al (2006) Cytoglobin overexpression protects against damage-induced fibrosis. Mol Ther 13:1093–1100

    PubMed  Article  CAS  Google Scholar 

  16. McRonald FE, Liloglou T, Xinarianos G et al (2006) Down-regulation of the cytoglobin gene, located on 17q25, in tylosis with oesophageal cancer (TOC): evidence for trans-allele repression. Hum Mol Genet 15:1271–1277

    PubMed  Article  CAS  Google Scholar 

  17. Xinarianos G, McRonald FE, Risk JM et al (2006) Frequent genetic and epigenetic abnormalities contribute to the deregulation of cytoglobin in non-small cell lung cancer. Hum Mol Genet 15:2038–2044

    PubMed  Article  CAS  Google Scholar 

  18. Klaunig JE, Kamendulis LM (2004) The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol Toxicol 44:239–267

    PubMed  Article  CAS  Google Scholar 

  19. Valko M, Izakovic M, Mazur M et al (2004) Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem 266:37–56

    PubMed  Article  CAS  Google Scholar 

  20. Paddison PJ, Caudy AA, Hannon GJ (2002) Stable suppression of gene expression by RNAi in mammalian cells. Proc Natl Acad Sci USA 99:1443–1448

    PubMed  Article  CAS  Google Scholar 

  21. Krichevsky AM, Kosik KS (2002) RNAi functions in cultured mammalian neurons. Proc Natl Acad Sci USA 99:11926–11929

    PubMed  Article  CAS  Google Scholar 

  22. Wang ZF, Li HL, Li XC et al (2006) Effects of endogenous beta-amyloid overproduction on tau phosphorylation in cell culture. J Neurochem 98:1167–1175

    PubMed  Article  CAS  Google Scholar 

  23. Ito D, Walker JR, Thompson CS et al (2004) Characterization of stanniocalcin 2, a novel target of the mammalian unfolded protein response with cytoprotective properties. Mol Cell Biol 24:9456–9469

    PubMed  Article  CAS  Google Scholar 

  24. Chen XQ, Liu S, Qin LY et al (2005). Selective regulation of 14-3-3eta in primary culture of cerebral cortical neurons and astrocytes during development. J Neurosci Res 79:114–118

    PubMed  Article  CAS  Google Scholar 

  25. Chen XQ, Qin LY, Zhang CG et al (2005) Presence of neuroglobin in cultured astrocytes. Glia 50:182–186

    PubMed  Article  Google Scholar 

  26. Fordel E, Thijs L, Martinet W et al (2006) Neuroglobin and cytoglobin overexpression protects human SH-SY5Y neuroblastoma cells against oxidative stress-induced cell death. Neurosci Lett 410:146–151

    PubMed  Article  CAS  Google Scholar 

  27. Moreira PI, Smith MA, Zhu X et al (2005) Oxidative stress and neurodegeneration. Ann N Y Acad Sci 1043:545–552

    PubMed  Article  CAS  Google Scholar 

  28. Chan PH (2005) Mitochondrial dysfunction and oxidative stress as determinants of cell death/survival in stroke. Ann N Y Acad Sci 1042:203–209

    PubMed  Article  CAS  Google Scholar 

  29. Guo X, Philipsen S, Tan-Un KC (2006) Characterization of human cytoglobin gene promoter region. Biochim Biophys Acta 1759:208–215

    PubMed  CAS  Google Scholar 

  30. Wystub S, Ebner B, Fuchs C et al (2004) Interspecies comparison of neuroglobin, cytoglobin and myoglobin: sequence evolution and candidate regulatory elements. Cytogenet Genome Res 105:65–78

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Miss Nelly Lam from Hong Kong DNA Chips Limited for assistance in preparation of this article. This work was supported by grants from the National Natural Science Foundation of China (30470539 and 30570555) and a grant of “Program for New Century Excellent Talents in University” to X.Q. Chen.

Author information

Affiliations

  1. Department of Pathophysiology and Hubei Provincial Key Laboratory of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Hang Kong Road 13, Wuhan, 430030, China

    Dan Li, Xiao Qian Chen, Wu-Jian Li, Yu-Hui Yang & Jian-Zhi Wang

  2. Neuroscience Research Institute, Peking University, Beijing, China

    Albert Cheung Hoi Yu

  3. Key Laboratory of Neuroscience (PKU), Ministry of Education, Beijing, China

    Albert Cheung Hoi Yu

  4. Department of Neurobiology, Peking University Health Science Center, Beijing, China

    Albert Cheung Hoi Yu

Authors
  1. Dan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao Qian Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wu-Jian Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu-Hui Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jian-Zhi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Albert Cheung Hoi Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiao Qian Chen.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Li, D., Chen, X.Q., Li, WJ. et al. Cytoglobin Up-regulated by Hydrogen Peroxide Plays a Protective Role in Oxidative Stress. Neurochem Res 32, 1375–1380 (2007). https://doi.org/10.1007/s11064-007-9317-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-007-9317-x

Keywords

  • Cytoglobin
  • Oxidative stress
  • N2a neuroblastoma cell
  • siRNA
  • Hydrogen peroxide