1887

Abstract

Prion diseases are characterized by the accumulation of an abnormal, proteinase K-resistant isoform of the prion protein, PrP, which is generated by a post-translational conversion of the protease-sensitive normal cell-surface glycoprotein PrP involving major conformational changes. The conversion is thought to occur at the plasma membrane or along the endocytic pathway towards the lysosome. PrP aggregates have been found to accumulate in secondary lysosomes. In our study, the activities of two major lysosomal cysteine proteases, cathepsins B and L, were found to be significantly increased in scrapie-infected Neuro2a cells compared with uninfected cells using biochemical and cytochemical methods. We hypothesize that lysosomal proteases may be involved in a ‘second autocatalytic loop’ of PrP formation, acting in concert with the well-known autocatalytic enhancement of PrP conversion in the presence of PrP.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.19153-0
2003-08-01
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/84/8/vir842279.html?itemId=/content/journal/jgv/10.1099/vir.0.19153-0&mimeType=html&fmt=ahah

References

  1. Aguzzi A., Montrasio F., Kaeser P. S. 2001; Prions: health scare and biological challenge. Nat Rev Mol Cell Biol 2:118–126
    [Google Scholar]
  2. Almeida P. C., Nantes I. L., Chagas J. R., Rizzi C. C., Faljoni-Alario A., Carmona E., Juliano L., Nader H. B., Tersariol I. L. 2001; Cathepsin B activity regulation. Heparin-like glycosaminoglycans protect human cathepsin B from alkaline pH-induced inactivation. J Biol Chem 276:944–951
    [Google Scholar]
  3. Barrett A. J., Kirschke H. 1981; Cathepsin B, cathepsin H and cathepsin L. In Methods in Enzymology pp  535–561 Edited by Colowick S. P., Kaplan N. O. New York: Academic Press;
    [Google Scholar]
  4. Bosque P. J., Prusiner S. B. 2000; Cultured cell sublines highly susceptible to prion infection. J Virol 74:4377–4386
    [Google Scholar]
  5. Caughey B. 1994; Scrapie-associated PrP accumulation and agent replication: effects of sulphated glycosaminoglycan analogues. Philos Trans R Soc Lond Ser B 343:399–404
    [Google Scholar]
  6. Caughey B., Chesebro B. 2001; Transmissible spongiform encephalopathies and prion protein interconversions. Adv Virus Res 56:277–311
    [Google Scholar]
  7. Caughey B., Raymond G. J. 1993; Sulfated polyanion inhibition of scrapie-associated PrP accumulation in cultured cells. J Virol 67:643–650
    [Google Scholar]
  8. Caughey B., Raymond G. J., Ernst D., Race R. E. 1991; N-terminal truncation of the scrapie-associated form of PrP by lysosomal protease(s): implications regarding the site of conversion of PrP to the protease-resistant state. J Virol 65:6597–6603
    [Google Scholar]
  9. Collinge J. 2001; Prion diseases of humans and animals: their causes and molecular basis. Annu Rev Neurosci 24:519–550
    [Google Scholar]
  10. Dandoy-Dron F., Guillo F., Benboudjema L., Deslys J. P., Lasmezas C., Dormont D., Tovey M. G., Dron M. 1998; Gene expression in scrapie: cloning of a new scrapie-responsive gene and the identification of increased levels of seven other mRNA transcripts. J Biol Chem 273:7691–7697
    [Google Scholar]
  11. Diedrich J. F., Minnigan H., Carp R. I., Whitaker J. N., Race R., Frey W., Haase A. T. 1991; Neuropathological changes in scrapie and Alzheimer's disease are associated with increased expression of apolipoprotein E and cathepsin D in astrocytes. J Virol 65:4759–4768
    [Google Scholar]
  12. Doh-ura K., Iwaki T., Caughey B. 2000; Lysosomotropic agents and cysteine protease inhibitors inhibit scrapie-associated prion protein accumulation. J Virol 74:4894–4897
    [Google Scholar]
  13. Dolbeare F. A., Smith R. E. 1977; Flow cytometric measurement of peptidases with use of 5-nitrosalicylaldehyde and 4-methoxy-beta-naphthylamine derivatives. Clin Chem 23:1485–1491
    [Google Scholar]
  14. Fairbairn D. W., Carnahan K. G., Thwaits R. N., Grigsby R. V., Holyoak G. R., O'Neill K. L. 1994; Detection of apoptosis induced DNA cleavage in scrapie-infected sheep brain. FEMS Microbiol Lett 115:341–346
    [Google Scholar]
  15. Forloni G., Angeretti N., Chiesa R., Monzani E., Salmona M., Bugiani O., Tagliavini F. 1993; Neurotoxicity of a prion protein fragment. Nature 362:543–546
    [Google Scholar]
  16. Giese A., Groschup M. H., Hess B., Kretzschmar H. A. 1995; Neuronal cell death in scrapie-infected mice is due to apoptosis. Brain Pathol 5:213–221
    [Google Scholar]
  17. Gray F., Chretien F., Adle-Biassette H., Dorandeu A., Ereau T., Delisle M. B., Kopp N., Ironside J. W., Vital C. 1999; Neuronal apoptosis in Creutzfeldt–Jakob disease. J Neuropathol Exp Neurol 58:321–328
    [Google Scholar]
  18. Guicciardi M. E., Deussing J., Miyoshi H., Bronk S. F., Svingen P. A., Peters C., Kaufmann S. H., Gores G. J. 2000; Cathepsin B contributes to TNF- α -mediated hepatocyte apoptosis by promoting mitochondrial release of cytochrome c . J Clin Invest 106:1127–1137
    [Google Scholar]
  19. Ishidoh K., Kominami E. 1995; Procathepsin L degrades extracellular matrix proteins in the presence of glycosaminoglycans in vitro. Biochem Biophys Res Commun 217:624–631
    [Google Scholar]
  20. Ishisaka R., Utsumi T., Kanno T., Arita K., Katunuma N., Akiyama J., Utsumi K. 1999; Participation of a cathepsin L-type protease in the activation of caspase-3. Cell Struct Funct 24:465–470
    [Google Scholar]
  21. Kegel K. B., Kim M., Sapp E., McIntyre C., Castano J. G., Aronin N., DiFiglia M. 2000; Huntingtin expression stimulates endosomal–lysosomal activity, endosome tubulation, and autophagy. J Neurosci 20:7268–7278
    [Google Scholar]
  22. Kingham P. J., Pocock J. M. 2001; Microglial secreted cathepsin B induces neuronal apoptosis. J Neurochem 76:1475–1484
    [Google Scholar]
  23. Kopacek J., Sakaguchi S., Shigematsu K., Nishida N., Atarashi R., Nakaoke R., Moriuchi R., Niwa M., Katamine S. 2000; Upregulation of the genes encoding lysosomal hydrolases, a perforin-like protein, and peroxidases in the brains of mice affected with an experimental prion disease. J Virol 74:411–417
    [Google Scholar]
  24. Lotem J., Sachs L. 1996; Differential suppression by protease inhibitors and cytokines of apoptosis induced by wild-type p53 and cytotoxic agents. Proc Natl Acad Sci U S A 93:12507–12512
    [Google Scholar]
  25. McKinley M. P., Taraboulos A., Kenaga L., Serban D., Stieber A., DeArmond S. J., Prusiner S. B., Gonatas N. 1991; Ultrastructural localization of scrapie prion proteins in cytoplasmic vesicles of infected cultured cells. Lab Invest 65:622–630
    [Google Scholar]
  26. Prusiner S. B. 2001; Shattuck lecture – neurodegenerative diseases and prions. N Engl J Med 344:1548–1551
    [Google Scholar]
  27. Rozman J., Stojan J., Kuhelj R., Turk V., Turk B. 1999; Autocatalytic processing of recombinant human procathepsin B is a bimolecular process. FEBS Lett 459:358–362
    [Google Scholar]
  28. Saborio G. P., Permanne B., Soto C. 2001; Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 411:810–813
    [Google Scholar]
  29. Snow A. D., Wight T. N., Nochlin D., Koike Y., Kimata K., DeArmond S. J., Prusiner S. B. 1990; Immunolocalization of heparan sulfate proteoglycans to the prion protein amyloid plaques of Gerstmann–Sträussler syndrome, Creutzfeldt–Jakob disease and scrapie. Lab Invest 63:601–611
    [Google Scholar]
  30. Ulbricht B., Spiess E., Schwartz-Albiez R., Ebert W. 1995; Quantification of intracellular cathepsin activities in human lung tumor cell lines by flow cytometry. Biol Chem Hoppe Seyler 376:407–414
    [Google Scholar]
  31. Vancompernolle K., Van Herreweghe F., Pynaert G. 7 other authors 1998; Atractyloside-induced release of cathepsin B, a protease with caspase-processing activity. FEBS Lett 438:150–158
    [Google Scholar]
  32. Wong C., Xiong L. W., Horiuchi M., Raymond L., Wehrly K., Chesebro B., Caughey B. 2001; Sulfated glycans and elevated temperature stimulate PrPSc-dependent cell-free formation of protease-resistant prion protein. EMBO J 20:377–386
    [Google Scholar]
  33. Yamashima T. 2000; Implication of cysteine proteases calpain, cathepsin and caspase in ischemic neuronal death of primates. Prog Neurobiol 62:273–295
    [Google Scholar]
  34. Zhang Y., Poirier G. G., Bürkle A. 2002; In situ analysis of cellular poly(ADP-ribose) production in scrapie-infected mouse neuroblastoma cells. Histochem J 34:357–363
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.19153-0
Loading
/content/journal/jgv/10.1099/vir.0.19153-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error