Advertisement

Doppel Protein Expression Correlates with Heme Oxygenase 1 and Nitric Oxide Synthase Induction

  • Boon-Seng Wong
  • Man-Sun Sy
  • David R. Brown

Abstract

In the early 1990’s discrepant phenotypes were observed in four reported prion protein gene (Prnp)-ablated transgenic mouse lines (Prnp 0/0 ) (Bueler et al., 1992; Manson et al., 1994; Moore et al., 1995; Sakaguchi et al., 1996). Two of them, Ngsk and Rcm0 Prnp 0/0 mice (Moore et al., 1999; Sakaguchi et al., 1996), displayed normal early development but revealed progressive ataxia accompanied by the degeneration of cerebellar Purkinje cells at ~70 weeks of age. This phenotype was not observed in the other mouse lines, Zrch1 and Npu Prnp 0/0 mice (Bueler et al., 1992; Manson et al., 1994). Further investigation on the Rcm0 Prnp 0/0 mice lead to the discovery of a prion protein (PrP)-like protein named Doppel (Dpl) (Moore et al., 1999).

Keywords

Nitric Oxide Prion Protein Heme Oxygenase Cerebellar Purkinje Cell Purkinje Cell Loss 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Baranano, D.E. and Snyder, S.H. (2001) Neural roles for heme oxygenase: Contrasts to nitric oxide synthase.Proc Natl Acad Sci USA,98, 10996–11002.PubMedCrossRefGoogle Scholar
  2. Beckman, J.S. (1996) Oxidative damage and tyrosine nitration from peroxynitrite.Chem Res Toxicol,9, 836–844.PubMedCrossRefGoogle Scholar
  3. Brown, D.R., Schulz-Schaeffer, W.J., Schmidt, B., and Kretzschmar, H.A. (1997) Prion protein-deficient cells show altered response to oxidative stress due to decreased SOD-1 activity.Exp Neurol,146, 104–112.PubMedCrossRefGoogle Scholar
  4. Brown, D.R., Wong, B.S., Hafiz, F., Clive, C., Haswell, S., and Jones, I.M. (1999) Normal prion protein has an activity like that of superoxide dismutase.Biochem J,344, 1–5.PubMedCrossRefGoogle Scholar
  5. Bueler, H., Fischer, M., Lang, Y., Bluethmann, H., Lipp, H.P., DeArmond, S.J., Prusiner, S.B., Aguet, M., and Weissmann, C. (1992) Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein.Nature,356, 577–582.PubMedCrossRefGoogle Scholar
  6. Butterfield, D.A. and Kanski, J. (2001) Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins.Mech Ageing Dev,122, 945–962.PubMedCrossRefGoogle Scholar
  7. Dawson, T.M. and Dawson, V.L. (1996) Nitric oxide synthase: role as a transmitter/mediator in the brain and endocrine system.Annu Rev Med,47, 219–227.PubMedCrossRefGoogle Scholar
  8. Dwyer, B.E., Lu, S.Y., and Nishimura, R.N. (1998) Heme oxygenase in the experimental ALS mouse.Exp Neural,150, 206–212.CrossRefGoogle Scholar
  9. Ju, W.K., Park, K.J., Choi, E.K., Kim, J., Carp, R.I., Wisniewski, H.M., and Kim, Y.S. (1998) Expression of inducible nitric oxide synthase in the brains of scrapie-infected mice.J Neurovirol,4, 445–450.PubMedCrossRefGoogle Scholar
  10. Keshet, G.I., Ovadia, H., Taraboulos, A., and Gabizon, R. (1999) Scrapie-infected mice and PrP knockout mice share abnormal localization and activity of neuronal nitric oxide synthase.J Neurochem,72, 1224–1231.PubMedCrossRefGoogle Scholar
  11. Li, A., Sakaguchi, S., Atarashi, R., Roy, B.C., Nakaoke, R., Arima, K., Okimura, N., Kopacek, J., and Shigematsu, K. (2000a) Identification of a novel gene encoding a PrP-like protein expressed as chimeric transcripts fused to PrP exon 1/2 in ataxic mouse line with a disrupted PrP gene.Cell Mol Neurobiol,20, 553–567.PubMedCrossRefGoogle Scholar
  12. Li, R., Liu, T., Wong, B.S., Pan, T., Morillas, M., Swietnicki, W., O’Rourke, K., Gambetti, P., Surewicz, W.K., and Sy, M.S. (2000b) Identification of an epitope in the C terminus of normal prion protein whose expression is modulated by binding events in the N terminus.J Mol Biol,301, 567–573.PubMedCrossRefGoogle Scholar
  13. Maines, M.D. (2000) The heme oxygenase system and its functions in the brain.Cell Mol Biol (Noisy-Le-Grand),46, 573–585.Google Scholar
  14. Manson, J.C., Clarke, A.R., Hooper, M.L., Aitchison, L., McConnell, I., and Hope, J. (1994) l29/Ola mice carrying a null mutation in PrP that abolishes mRNA production are developmentally normal.Mol Neurobiol,8, 121–127.PubMedCrossRefGoogle Scholar
  15. Mastrangelo, P. and Westaway, D. (2001) The prion gene complex encoding PrP(C) and Doppel: insights from mutational analysis.Gene,215, 1–18.CrossRefGoogle Scholar
  16. Mo, H., Moore, R.C., Cohen, F.E., Westaway, D., Prusiner, S.B., Wright, P.E., and Dyson, H.J. (2001) Two different neurodegenerative diseases caused by proteins with similar structures.Proc Natl Acad Sci USA,98, 2352–2357.PubMedCrossRefGoogle Scholar
  17. Moore, R.C., Lee, I.Y., Silverman, G.L., Harrison, P.M., Strome, R., Heinrich, C., Karunaratne, A., Pasternak, S.H., Chishti, M.A., Liang, Y., Mastrangelo, P., Wang, K., Smit, A.F., Katamine, S., Carlson, G.A., Cohen, F.E., Prusiner, S.B., Melton, D.W., Tremblay, P., Hood, L.E., and Westaway, D. (1999) Ataxia in prion protein (PrP)-deficient mice is associated with upregulation of the novel PrP-like protein doppel.J Mol Biol,292, 797–817.PubMedCrossRefGoogle Scholar
  18. Moore, R.C., Redhead, N.J., Selfridge, J., Hope, J., Manson, J.C., and Melton, D.W (1995) Double replacement gene targeting for the production of a series of mouse strains with different prion protein gene alterations.Biotechnology (NY),13, 999–1004.CrossRefGoogle Scholar
  19. Sakaguchi, S., Katamine, S., Nishida, N., Moriuchi, R., Shigematsu, K., Sugimoto, T., Nakatani, A., Kataoka, Y., Houtani, T., Shirabe, S., Okada, H., Hasegawa, S., Miyamoto, T., and Noda, T. (1996) Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene.Nature,380, 528–531.PubMedCrossRefGoogle Scholar
  20. Sayre, L.M., Perry, G., and Smith, M.A. (1999) In situ methods for detection and localization of markers of oxidative stress: application in neurodegenerative disorders.Methods Enzymol,309, 133–152.PubMedCrossRefGoogle Scholar
  21. Silverman, G.L., Qin, K., Moore, R.C., Yang, Y., Mastrangelo, P., Tremblay, P., Prusiner, S.B., Cohen, F.E., and Westaway, D. (2000) Doppel is an N-glycosylated, GPI-anchored protein: expression in testis and ectopic production in the brains of Prnpo/o mice predisposed to Purkinje cell loss.J Biol Chem,275, 26834–26841.PubMedGoogle Scholar
  22. Wong, B.S., Liu, T., Li, R.L., Pan, T., Petersen, R.B., Smith, M.A., Gambetti, P., Perry, G., Manson, J.C., Brown, D.R., and Sy, M.S. (2001a) Increased levels of oxidative stress markers detected in the brains of prion knock-out mice.J Neurochem,76, 565–572.PubMedCrossRefGoogle Scholar
  23. Wong, B.S., Liu, T., Paisley, D., Li, R.L., Pan, T., Gunaratne, R.S., Chen, S.G., Perry, G., Petersen, R.B., Smith, M.A., Melton, D.W., Gambetti, P., Brown, D.R., and Sy, M.S. (2001b) Induction of HO-1 and NOS in doppel-expressing mice devoid of prion protein: Implications for doppel function.Mol Cell Neurosci,17,768–775.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Boon-Seng Wong
    • 1
  • Man-Sun Sy
    • 1
  • David R. Brown
    • 2
  1. 1.Institute of PathologyCase Western Reserve UniversityClevelandUSA
  2. 2.Department of Biology and BiochemistryUniversity of BathBathUK

Personalised recommendations