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Cytosolic prion protein induces apoptosis in human neuronal cell SH-SY5Y via mitochondrial disruption pathway

  • Wang, Xin (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, Chen-Fang (State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention) ;
  • Shi, Qi (State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention) ;
  • Shi, Song (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, Gui-Rong (State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention) ;
  • Lei, Yan-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) ;
  • Xu, Kun (State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention) ;
  • An, Run (State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention) ;
  • Chen, Jian-Ming (State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention) ;
  • Jiang, Hui-Ying (State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention) ;
  • Tian, Chan (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) ;
  • Zhao, Yu-Jun (College of Animal Husbandry and Veterinary Medicine, Shenyang Agricultural University) ;
  • 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) ;
  • 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)
  • Published : 2009.07.31

Abstract

Different neurodegenerative disorders like prion disease, is caused by protein misfolding conformers. Reverse-transfected cytosolic prion protein (PrP) and PrP expressed in the cytosol have been shown to be neurotoxic. To investigate the possible mechanism of neurotoxicity due to accumulation of PrP in cytosol, a PrP mutant lacking the signal and GPI (CytoPrP) was introduced into the SH-SY5Y cell. MTT and trypan blue assays indicated that the viability of cells expressing CytoPrP was remarkably reduced after treatment of MG-132. Obvious apoptosis phenomena were detected in the cells accumulated with CytoPrP, including loss of mitochondrial transmembrane potential, increase of caspase-3 activity, more annexin V/PI-double positive-stained cells and reduced Bcl-2 level. Moreover, DNA fragmentation and TUNEL assays also revealed clear evidences of late apoptosis in the cells accumulated CytoPrP. These data suggest that the accumulation of CytoPrP in cytoplasm may trigger cell apoptosis, in which mitochondrial relative apoptosis pathway seems to play critical role.

References

  1. Prusiner, S. B. (1998) Prions. Proc. Natl. Acad. Sci. U.S.A. 95, 13363-13383 https://doi.org/10.1073/pnas.95.23.13363
  2. Aguzzi, A. and Polymenidou, M. (2004) Mammalian prion biology: one century of evolving concepts. Cell 116, 313-327 https://doi.org/10.1016/S0092-8674(03)01031-6
  3. Ma, J., Wollmann, R. and Lindquist, S. (2002) Neurotoxicity and neurodegeneration when PrP accumulates in the cytosol. Science 298, 1781-1785 https://doi.org/10.1126/science.1073725
  4. Ma, J. and Lindquist, S. (2001) Wild-type PrP and a mutant associated with prion disease are subject to retrograde transport and proteasome degradation. Proc. Natl. Acad. Sci. U.S.A. 98, 14955-14960 https://doi.org/10.1073/pnas.011578098
  5. Keller, J. N., Gee, J. and Ding, Q. (2002) The proteasome in brain aging. Ageing Res. Rev. 1, 279-293 https://doi.org/10.1016/S1568-1637(01)00006-X
  6. Fioriti, L., Dossena, S., Stewart, L. R., Stewart, R. S., Harris, D. A., Forloni, G. and Chiesa, R. (2005) Cytosolic prion protein is not toxic in N2a cells and primary neurons expressing pathogenic PrP mutations. J. Biol. Chem. 280, 11320-11328 https://doi.org/10.1074/jbc.M412441200
  7. Carmody, R. J. and Cotter, T. G. (2001) Signaling apoptosis: a radical approach. Redox Report 6, 77 https://doi.org/10.1179/135100001101536085
  8. Rambold, A. S., Miesbauer, M., Rapaport, D., Barke, T., Baier, M., Winklhofer, K. F. and Tatzelt, J. (2006) Association of bcl-2 with misfolded prion protein is linked to the toxic potential of cytosolic PrP. Mol. Biol. Cell 17, 3356-3368 https://doi.org/10.1091/mbc.E06-01-0083
  9. Chen, L., Yang, Y., Han, J., Zhang, B. Y., Zhao, L., Nie, K., Wang, X. F., Li, F., Gao, C., Dong, X. P. and Xu C. M. (2007) Removal of the glycosylation of prion protein provokes apoptosis in SF126. J. Biochem. Mol. Biol. 41, 662-669
  10. Seo, Y. W., Park, S. Y., Yun, C. W. and Kim, T. H. (2006) Differential efflux of mitochondrial endonuclease G by hNoxa and tBid. J. Biochem. Mol. Biol. 39, 556-559 https://doi.org/10.5483/BMBRep.2006.39.5.556
  11. Adams, J. M. and Cory, S. (1998) The Bcl-2 protein family: Arbiters of cell survival. Science 281, 1322-1326 https://doi.org/10.1126/science.281.5381.1322
  12. Perovic, S., Schroder, H. C. and Pergande, G. (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
  13. Kopito, R. R. (1997) ER quality control: the cytoplasmic connection. Cell 88, 427-430 https://doi.org/10.1016/S0092-8674(00)81881-4
  14. Rane, N. S., Yonkovich, J. L. and Hedge, R. S. (2004) Protection from cytosolic prion protein toxicity by modulation of protein translocation. EMBO J. 23, 4550-4559 https://doi.org/10.1038/sj.emboj.7600462
  15. Zanusso, G., Petersen, R. B. and Jin, T. (1999) Proteasomal degradation and N-terminal protease resistance of the codon 145 mutant prion protein. J. Biol. Chem. 274, 23396-23404 https://doi.org/10.1074/jbc.274.33.23396
  16. Norstrom, E. M., Ciaccio, M. F., Rassbach, B., Wollmann, R. and Mastrianni, J. A. (2007) Cytosolic prion protein toxicity is independent of cellular prion protein expression and prion propagation. J. Virol. 81, 2831-2837 https://doi.org/10.1128/JVI.02157-06
  17. Dong, C. F., Wang, X. F., Wang, X., Shi, S., Wang, G. R., Shan, B., An, R., Li, X. L., Zhang, B. Y., Han, J. and Dong, X. P. (2008) Molecular interaction between prion protein and GFAP both in native and recombinant forms in vitro. Med. Microbiol. Immunol. 197, 361-368 https://doi.org/10.1007/s00430-007-0071-0
  18. Dong, C. F., Shi, S., Wang, X. F., An, R., Li, P., Chen, J. M., Wang, X., Wang, G. R., Shan, B., Zhang, B. Y., Han, J., and Dong, X. P. (2008) The N-terminus of PrP is responsible for interacting with tubulin and fCJD related PrP mutants possess stronger inhibitive effect on microtubule assembly in vitro. Arch. Biochem. Biophys. 480, 83-92

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