Skip to main content
Log in

SEPS1 Gene is Activated during Astrocyte Ischemia and Shows Prominent Antiapoptotic Effects

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Contrarily to neurons, astrocytes can survive short periods of ischemia. We have searched for genes implicated in astrocyte resistance to ischemia using oxygen and glucose deprivation (OGD) as a stroke model. A RNA differential display approach uncovered the OGD induction of selenoprotein-S-encoding gene SEPS1. This endoplasmic reticulum (ER) resident protein is known to promote cell survival regulating the ER stress as well as inflammation. We found that suppression of SEPS1 by small interfering RNA severely increases astrocyte injure caused by OGD, suggesting that selenoprotein S protects astrocytes against ischemia. Our data also support that modulation of ER stress is implicated in this effect.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3

Abbreviations

CHOP:

CEBP homologous protein

ER:

endoplasmic reticulum

GPx:

glutathione peroxidase

MTT:

3-[4,5-dimethylthiazol-2yl-2,5-diphenyltetrazolium bromide

OGD:

oxygen and glucose deprivation

ROS:

reactive oxygen species

SEPS1:

selenoprotein S

References

  • Alanne, M., Kristiansson, K., Auro, K., Silander, K., Kuulasmaa, K., Peltonen, L., et al. (2007). Variation in the selenoprotein S gene locus is associated with coronary heart disease and ischemic stroke in two independent Finnish cohorts. Human Genetics, 122, 355–365.

    Article  PubMed  CAS  Google Scholar 

  • Ansari, M. A., Ahmad, A. S., Ahmad, M., Salim, S., Yousuf, S., Ishrat, T., et al. (2004). Selenium protects cerebral ischemia in rat brain mitochondria. Biological Trace Element Research, 101, 73–86.

    Article  PubMed  CAS  Google Scholar 

  • Benavides, A., Pastor, D., Santos, P., Tranque, P., & Calvo, S. (2005). CHOP plays a pivotal role in the astrocyte death induced by oxygen and glucose deprivation. Glia, 52, 261–275.

    Article  PubMed  Google Scholar 

  • Chen, J., & Berry, M. J. (2003). Selenium and selenoproteins in the brain and brain diseases. Journal of Neurochemistry, 86, 1–12.

    Article  PubMed  CAS  Google Scholar 

  • Crack, P. J., Taylor, J. M., Flentjar, N. J., de, H. J., Hertzog, P., Iannello, R. C., et al. (2001). Increased infarct size and exacerbated apoptosis in the glutathione peroxidase-1 (Gpx-1) knockout mouse brain in response to ischemia/reperfusion injury. Journal of Neurochemistry, 78, 1389–1399.

    Article  PubMed  CAS  Google Scholar 

  • Curran, J. E., Jowett, J. B., Elliott, K. S., Gao, Y., Gluschenko, K., Wang, J., et al. (2005). Genetic variation in selenoprotein S influences inflammatory response. Nature Genetics, 37, 1234–1241.

    Article  PubMed  CAS  Google Scholar 

  • Gao, Y., Feng, H. C., Walder, K., Bolton, K., Sunderland, T., Bishara, N., et al. (2004). Regulation of the selenoprotein SelS by glucose deprivation and endoplasmic reticulum stress-SelS is a novel glucose-regulated protein. FEBS Letters, 563, 185–190.

    Article  PubMed  CAS  Google Scholar 

  • Gao, Y., Hannan, N. R., Wanyonyi, S., Konstantopolous, N., Pagnon, J., Feng, H. C., et al. (2006). Activation of the selenoprotein SEPS1 gene expression by pro-inflammatory cytokines in HepG2 cells. Cytokine, 33, 246–251.

    Article  PubMed  CAS  Google Scholar 

  • Giffard, R. G., & Swanson, R. A. (2005). Ischemia-induced programmed cell death in astrocytes. Glia, 50, 299–306.

    Article  PubMed  Google Scholar 

  • Hoffmann, P. R., Hoge, S. C., Li, P. A., Hoffmann, F. W., Hashimoto, A. C., & Berry, M. J. (2007). The selenoproteome exhibits widely varying, tissue-specific dependence on selenoprotein P for selenium supply. Nucleic Acids Research, 35, 3963–3973.

    Article  PubMed  CAS  Google Scholar 

  • Hyrenbach, S., Pezzini, A., del, Z. E., Giossi, A., Lichy, C., Kloss, M., et al. (2007). No association of the −105 promoter polymorphism of the selenoprotein S encoding gene SEPS1 with cerebrovascular disease. European Journal of Neurology, 14, 1173–1175.

    Article  PubMed  CAS  Google Scholar 

  • Kaufman, R. J. (2002). Orchestrating the unfolded protein response in health and disease. Journal of Clinical Investigation, 110, 1389–1398.

    PubMed  CAS  Google Scholar 

  • Kim, K. H., Gao, Y., Walder, K., Collier, G. R., Skelton, J., & Kissebah, A. H. (2007). SEPS1 protects RAW264.7 cells from pharmacological ER stress agent-induced apoptosis. Biochemical and Biophysical Research Communications, 354, 127–132.

    Article  PubMed  CAS  Google Scholar 

  • Kondo, S., Murakami, T., Tatsumi, K., Ogata, M., Kanemoto, S., Otori, K., et al. (2005). OASIS, a CREB/ATF-family member, modulates UPR signalling in astrocytes. Nature Cell Biology, 7, 186–194.

    Article  PubMed  CAS  Google Scholar 

  • Lindenau, J., Noack, H., Asayama, K., & Wolf, G. (1998). Enhanced cellular glutathione peroxidase immunoreactivity in activated astrocytes and in microglia during excitotoxin induced neurodegeneration. Glia, 24, 252–256.

    Article  PubMed  CAS  Google Scholar 

  • Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods, 25, 402–408.

    Article  PubMed  CAS  Google Scholar 

  • McCarthy, K. D., & de, V. J. (1980). Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. Journal of Cell Biology, 85, 890–902.

    Article  PubMed  CAS  Google Scholar 

  • Papp, L. V., Lu, J., Holmgren, A., & Khanna, K. K. (2007). From selenium to selenoproteins: Synthesis, identity, and their role in human health. Antioxidants & Redox Signalling, 9, 775–806.

    Article  CAS  Google Scholar 

  • Petito, C. K., Olarte, J. P., Roberts, B., Nowak Jr., T. S., & Pulsinelli, W. A. (1998). Selective glial vulnerability following transient global ischemia in rat brain. Journal of Neuropathology and Experimental Neurology, 57, 231–238.

    Article  PubMed  CAS  Google Scholar 

  • Ron, D. (2002). Translational control in the endoplasmic reticulum stress response. Journal of Clinical Investigation, 110, 1383–1388.

    PubMed  CAS  Google Scholar 

  • Savaskan, N. E., Borchert, A., Brauer, A. U., & Kuhn, H. (2007). Role for glutathione peroxidase-4 in brain development and neuronal apoptosis: specific induction of enzyme expression in reactive astrocytes following brain injury. Free Radical Biology & Medicine, 43, 191–201.

    Article  CAS  Google Scholar 

  • Schweizer, U., Brauer, A. U., Kohrle, J., Nitsch, R., & Savaskan, N. E. (2004). Selenium and brain function: A poorly recognized liaison. Brain Research. Brain Research Reviews, 45, 164–178.

    Article  PubMed  CAS  Google Scholar 

  • Steinbrenner, H., Alili, L., Bilgic, E., Sies, H., & Brenneisen, P. (2006). Involvement of selenoprotein P in protection of human astrocytes from oxidative damage. Free Radical Biology & Medicine, 40, 1513–1523.

    Article  CAS  Google Scholar 

  • Ye, Y., Shibata, Y., Kikkert, M., van, V. S., Wiertz, E., & Rapoport, T. A. (2005). Recruitment of the p97 ATPase and ubiquitin ligases to the site of retrotranslocation at the endoplasmic reticulum membrane. Proceedings of the National Academy of Sciences of the United States of America, 102, 14132–14138.

    Article  PubMed  CAS  Google Scholar 

  • Ye, Y., Shibata, Y., Yun, C., Ron, D., & Rapoport, T. A. (2004). A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol. Nature, 429, 841–847.

    Article  PubMed  CAS  Google Scholar 

  • Yousuf, S., Atif, F., Ahmad, M., Hoda, M. N., Khan, M. B., Ishrat, T., et al. (2007). Selenium plays a modulatory role against cerebral ischemia-induced neuronal damage in rat hippocampus. Brain Research, 1147, 218–225.

    Article  PubMed  CAS  Google Scholar 

  • Zawadzka, M., & Kaminska, B. (2005). A novel mechanism of FK506-mediated neuroprotection: Downregulation of cytokine expression in glial cells. Glia, 49, 36–51.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Gema Rodriguez, Vanessa Guijarro, and Juana Rozalen for their expert technical assistance. This work was supported by grants from Spanish Ministry of Education and Science (BFU2006-14267) and Junta de Comunidades de Castilla-La Mancha (PAI05-017 and PCI-08-0101-8639) to S.C.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Soledad Calvo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fradejas, N., Pastor, M.D., Mora-Lee, S. et al. SEPS1 Gene is Activated during Astrocyte Ischemia and Shows Prominent Antiapoptotic Effects. J Mol Neurosci 35, 259–265 (2008). https://doi.org/10.1007/s12031-008-9069-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-008-9069-3

Keywords

Navigation