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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Removal of the Glycosylation of Prion Protein Provokes Apoptosis in SF126

  • Chen, Lan (National Laboratory of Medical Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Sciences and Peking Union Medical College) ;
  • Yang, Yang (National Laboratory of Medical Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Sciences and Peking Union Medical College) ;
  • Han, Jun (State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention) ;
  • Zhang, Bao-Yun (State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention) ;
  • Zhao, Lin (National Laboratory of Medical Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Sciences and Peking Union Medical College) ;
  • Nie, Kai (State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention) ;
  • Wang, Xiao-Fan (State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention) ;
  • Li, Feng (State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention) ;
  • Gao, Chen (State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention) ;
  • Dong, Xiao-Ping (State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention) ;
  • Xu, Cai-Min (National Laboratory of Medical Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Sciences and Peking Union Medical College)
  • Published : 2007.09.30
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Abstract

Although the function of cellular prion protein (PrP$^C$) and the pathogenesis of prion diseases have been widely described, the mechanisms are not fully clarified. In this study, increases of the portion of non-glycosylated prion protein deposited in the hamster brains infected with scrapie strain 263K were described. To elucidate the pathological role of glycosylation profile of PrP, wild type human PrP (HuPrP) and two genetic engineering generated non-glycosylated PrP mutants (N181Q/N197Q and T183A/T199A) were transiently expressed in human astrocytoma cell line SF126. The results revealed that expressions of non-glycosylated PrP induced significantly more apoptosis cells than that of wild type PrP. It illustrated that Bcl-2 proteins might be involved in the apoptosis pathway of non-glycosylated PrPs. Our data highlights that removal of glycosylation of prion protein provokes cells apoptosis.

Keywords

References

  1. Bate C. and Williams A. (2004) Role of glycosylphosphatidylinositols in the activation of phospholipase A2 and the neurotoxicity of prions. J. Gen. Virol. 85, 3797-3804. https://doi.org/10.1099/vir.0.80366-0
  2. Bounhar Y., Zhang Y. and Goodyer C. G. (2001) Prion protein protects human neurons against Bax-mediated apoptosis. J. Biol. Chem. 276, 39145-39149. https://doi.org/10.1074/jbc.C100443200
  3. Chabry J., Ratsimanohatra C., Sponne I., Elena P. P., Vincent J. P. and Pillot T. (2003) In vivo and in vitro neurotoxicity of the human prion protein (PrP) fragment P118-135 independently of PrP expression. J. Neurosci. 23, 462-469. https://doi.org/10.1523/JNEUROSCI.23-02-00462.2003
  4. Ciesielski-Treska J., Grant N. J., Ulrich G., Corrotte M., Bailly Y., Haeberle A. M., Chasserot-Golaz S. and Bader M. F. (2004) Fibrillar prion peptide (106-126) and scrapie prion protein hamper phagocytosis in microglia. Glia. 46, 101-115. https://doi.org/10.1002/glia.10363
  5. Cronier S., Laude H. and Peyrin J. M. (2004) Prions can infect primary cultured neurons and astrocytes and promote neuronal cell death. Proc. Natl. Acad. Sci. USA 101, 12271-12276. https://doi.org/10.1073/pnas.0402725101
  6. Dricu A., Carlberg M., Wang M. and Larsson O. (1997) Inhibition of N-linked glycosylation using tunicamycin causes cell death in malignant cells: role of down-regulation of the insulin-like growth factor 1 receptor in induction of apoptosis. Cancer Res. 57, 543-548.
  7. Ermonval, M., Mouillet-Richard, S., Codogno, P., Kellermann, O. and Botti, J. (2003) Evolving views in prion glycosylation: functional and pathological implications. Biochimie. 85, 33-45. https://doi.org/10.1016/S0300-9084(03)00040-3
  8. Gao, J. M., Gao, C., Han, J., Zhou, X. B., Xiao, X. L., Zhang, J., Chen, L., Zhang B. Y., Hong, T. and Dong, X. P. (2004) Dynamic analyses of PrP and PrP(Sc) in brain tissues of golden hamsters infected with scrapie strain 263K revealed various PrP forms. Biomed. Environ. Sci. 17, 8-20.
  9. Katayama, T., Imaizumi, K., Manabe, T., Hitomi, J., Kudo, T. and Tohyama, M. (2004) Induction of neuronal death by ER stress in Alzheimer's disease. J. Chem. Neuroanat. 28, 67-78. https://doi.org/10.1016/j.jchemneu.2003.12.004
  10. Kuwahara, C., Takeuchi, A. M., Nishimura, T., Haraguchi, K., Kubosaki, A., Matsumoto, Y., Saeki, K., Matsumoto, Y., Yokoyama, T., Itohara, S. and Onodera, T. (1999) Prions prevent neuronal cell-line death. Nature 400, 225-226. https://doi.org/10.1038/22241
  11. Lehmann, S. and Harris, D. A. (1997) Blockade of glycosylation promotes acquisition of scrapie-like properties by the prion protein in cultured cells. J. Biol. Chem., 272, 21479-21487. https://doi.org/10.1074/jbc.272.34.21479
  12. Metrailler-Ruchonnet, I., Pagano, A., Carnesecchi, S., Ody, C., Donati, Y. and Barazzone, A. C. (2007) Bcl-2 protects against hyperoxia-induced apoptosis through inhibition of the mitochondria-dependent pathway. Free Radic. Biol. Med. 42, 1062-1074. https://doi.org/10.1016/j.freeradbiomed.2007.01.008
  13. Neuendorf, E., Weber, A., Saalmueller, A., Schatzl, H., Reifenberg, K., Pfaff, E. and Groschup, M. H. (2004) Glycosylation deficiency at either one of the two glycan attachment sites of cellular prion protein preserves susceptibility to bovine spongiform encephalopathy and scrapie infections. J. Biol. Chem. 279, 53306-53316. https://doi.org/10.1074/jbc.M410796200
  14. Niederer, K. E., Morrow, D. K., Gettings, J. L., Irick, M., Krawiecki, A. and Brewster, J. L. (2005) Cypermethrin blocks a mitochondria-dependent apoptotic signal initiated by deficient N-linked glycosylation within the endoplasmic reticulum. Cell Signal. 17, 177-186. https://doi.org/10.1016/j.cellsig.2004.06.009
  15. Nishimura, T., Sakudo, A., Nakamura, I., Lee, D. C., Taniuchi, Y., Saeki, K., Matsumoto, Y., Ogawa, M., Sakaguchi, S., Itohara, S. and Onodera, T. (2004) Cellular prion protein regulates intracellular hydrogen peroxide level and prevents copperinduced apoptosis. Biochem. Biophys. Res. Commun. 323, 218-222. https://doi.org/10.1016/j.bbrc.2004.08.087
  16. Park, S. K., Choi, S. I., Jin, J. K., Choi, E. K., Kim, J. I., Carp, R. I. and Kim, Y. S. (2000) Differential expression of Bax and Bcl-2 in the brains of hamsters infected with 263K scrapie agent. Neuroreport. 11, 1677-1682. https://doi.org/10.1097/00001756-200006050-00017
  17. Perovic, S., Schroder, H. C., Pergande, G., Ushijima, H. and Muller, W. E. (1997) Effect of flupirtine on Bcl-2 and glutathione level in neuronal cells treated in vitro with the prion protein fragment (PrP106-126). Exp. Neurol. 147, 518-524. https://doi.org/10.1006/exnr.1997.6559
  18. Prusiner, S. B. (1998) Prions. Proc. Natl. Acad. Sci. USA 95, 13363-13383. https://doi.org/10.1073/pnas.95.23.13363
  19. Roucou, X. and LeBlanc, A. C. (2005) Cellular prion protein neuroprotective function: implications in prion diseases. J. Mol. Med. 83, 3-11. https://doi.org/10.1007/s00109-004-0605-5
  20. Schroder, M. and Kaufman, R. J. (2005) ER stress and the unfolded protein response. Mutat. Res. 569, 29-63. https://doi.org/10.1016/j.mrfmmm.2004.06.056
  21. Zhang, J., Chen, L., Zhang, B. Y., Han, J., Xiao, X. L., Tian, H. Y., Li, B. L., Gao, C., Gao, J. M., Zhou, X. B., Ma, G. P., Liu, Y., Xu, C. M. and Dong, X. P. (2004) Comparison study on clinical and neuropathological characteristics of hamsters inoculated with scrapie strain 263K in different challenging pathways. Biomed. Environ. Sci. 17, 65-78.
  22. Yu, L. C., Flynn, A. N., Turner, J. R., Buret A. G. (2005) SGLT-1-mediated glucose uptake protects intestinal epithelial cells against LPS-induced apoptosis and barrier defects: a novel cellular rescue mechanism? FASEB J. 19, 1822-1835. https://doi.org/10.1096/fj.05-4226com
  23. Zuegg, J. and Gready, J. E. (2000) Molecular dynamics simulation of human prion protein including both N-linked oligosaccharides and the GPI anchor. Glycobiology. 10, 959-974. https://doi.org/10.1093/glycob/10.10.959

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