Isolation of a Hypoxia/Reoxygenation Regulatory Factor in Rat Astrocytes

흰쥐 성상세포에서 산소농도의존성 유전자의 분리

  • Park Jeong-Ae (College of Pharmacy, Seoul National University) ;
  • Song Hyun-Seok (College of Pharmacy, Seoul National University) ;
  • Lee Hye-Shin (College of Pharmacy, Seoul National University) ;
  • Kim Kyu-Won (College of Pharmacy, Seoul National University)
  • Published : 2006.04.01

Abstract

Astrocyte has emerged as an active regulator of brain function, which connects between blood vessels and neurons as well as is a structural component of the blood-brain barrier, From its structural characteristics, astrocyte seems to sensitively respond to oxygen tension, and, in turn, generate diverse cellular cascades. Therefore, to reveal astrocytlc events by oxygen change, we screened genes whose expressions are upregulated under reoxygenation after hypoxic stress using cDNA representational difference analysis (RDA) technique. Meteorin that regulates glial differentiation was isolated from primary cultured rat astrocytes as a hypoxia/reoxygenation regulatory factor. We cloned rat version of Meteorin (rMe-teorin) and determined full-size sequences of rMeteorin. In addition, RT-PCR analysis revealed that Meteorin was increased under reoxygenation in astrocytes and highly expressed in the developing brain. Collectively, these results suggest that Meteorin may regulate astrocyte-mediated effects in response to the change of oxygen tension in the pathophysiological states.

Keywords

References

  1. Volterra, A. and Meldolesi, J. : Astrocytes, from brain glue to communication elements : the revolution continues. Nat. Rev. Neurosci. 6, 626 (2005) https://doi.org/10.1038/nrn1722
  2. Janzer, R. C. and Raff, M. C. : Astrocytes induce blood-brain barrier properties in endothelial cells. Nature 325, 253 (1987) https://doi.org/10.1038/325253a0
  3. Risau, W. and Wolburg, H. : Development of the blood-brain barrier. Trends Neurosci. 13, 174 (1990) https://doi.org/10.1016/0166-2236(90)90043-A
  4. Risau, W. : Differentiation of endothelium. FASEB J. 9, 926 (1995) https://doi.org/10.1096/fasebj.9.10.7615161
  5. Hackett, P. H. : High altitude cerebral edema and acute mountain sickness. A pathophysiology update. Adv. Exp. Med. Biol. 474, 23 (1999)
  6. Krasney J. A. : A neurogenic basis for acute altitude illness. Med. Sci. Sports Exerc. 26, 195 (1994) https://doi.org/10.1249/00005768-199402000-00010
  7. Plate, K. H. : Mechanisms of angiogenesis in the brain. J. Neuropathol. Exp. Neurol. 58, 313 (1999) https://doi.org/10.1097/00005072-199904000-00001
  8. Stone, J., Itin, A., Alon, T., Pe'er, J., Gnessin, H., Chan-Ling, T. and Keshet, E. : Development of retinal vasculature is mediated by hypoxia-induced vascular endothelial growth factor (VEGF) expression by neuroglia. J. Neurosci. 15, 4738 (1995)
  9. Lee, S. W., Kim, W. J., Choi, Y. K., Song, H. S., Son, M. J., Gelman I. H., Kim, Y. J. and Kim, K. W. : SSeCKS regulates angiogenesis and tight junction formation in blood-brain barrier. Nat. Med. 9, 900 (2003) https://doi.org/10.1038/nm889
  10. Morrison, S. J., Csete, M., Groves, A. K., Melega, W., Wold, B. and Anderson, D. J. : Culture in reduced levels of oxygen promotes clonogenic sympathoadrenal differentiation by isolated neural crest stem cells. J. Neurosci. 20, 7370 (2000)
  11. Studer, L., Csete, M., Lee, S. H., Kabbani, N., Walikonis, J., Wold, B. and McDay, R. : Enhanced proliferation, survival, and dopaminergic differentiation of CNS precursors in lowered oxygen. J. Neurosci. 20, 7377 (2000)
  12. Tanaka, Y., Kanno, H., Dezawa, M., Mimura, T., Kubo, A. and Yamamoto, I. : The role of von Hippel-Lindau protein in the differentiation of neural progenitor cells under normoxic and anoxic conditions. Neurosci. Lett. 383, 28 (2005) https://doi.org/10.1016/j.neulet.2005.03.056
  13. Hubank, M. and Schata, D. G. : cDNA representational difference analysis: a sensitive and flexible method for identification of differentially expressed genes. Methods Enzymol. 303, 325 (1999) https://doi.org/10.1016/S0076-6879(99)03021-9
  14. Nishino, J., Yamashita, K., Kashiguchi, H., Fujii, H., Shimazaki, T. and Hamada, H. : Meteorin: a secreted protein that regulates glial cell differentiation and promotes axonal extension. EMBO J. 23, 1998 (2004) https://doi.org/10.1038/sj.emboj.7600202