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Brain cathepsin B cleaves a caspase substrate

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Abstract

We show that an enzyme exists in rat brain capable of cleaving the caspase-3 specific peptide substrate Ac-DEVD-AMC at low pH. The enzyme shows properties of a cysteine protease and is localized, predominantly, in lysosomes. We have purified this enzyme from rat brain and identified it by MALDI-TOF MS. The enzyme possessing “acidic” DEVDase activity in rat brain appears to be cathepsin B. It remains obscure, whether cathepsin B participates in cleavage of caspase-3 substrates in vivo. We suggest that under certain conditions (e.g. in hypoxia) cathepsin B participates in cleavage of caspase-3 substrates in brain cells.

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Abbreviations

AMC:

7-amino-4-methylcoumarin

CA-074:

N-[L-3-trans-(propylcarbamoyl)oxirane-2-carbonyl]-L-isoleucyl-L-proline

DTT:

dithiothreitol

MALDI-TOF MS:

matrix-assisted laser desorption/ionization with time-of-flight mass spectrometry

References

  1. Samuilov, V. D., Oleskin, A. V., and Lagunova, E. M. (2000) Biochemistry (Moscow), 65, 873–887.

    CAS  Google Scholar 

  2. Hengartner, M. O. (2000) Nature, 407, 770–776.

    Article  PubMed  CAS  Google Scholar 

  3. Skulachev, V. P. (2002) Ann. N. Y. Acad. Sci., 959, 214–327.

    Article  PubMed  CAS  Google Scholar 

  4. Thompson, C. B. (1995) Science, 267, 1456–1462.

    Article  PubMed  CAS  Google Scholar 

  5. Thornberry, N. A., and Lazebnik, Y. (1998) Science, 281, 1312–1316.

    Article  PubMed  CAS  Google Scholar 

  6. Filchenkov, A. A. (2003) Biochemistry (Moscow), 68, 365–376.

    Article  Google Scholar 

  7. Oppenheim, R. W. (1991) Annu. Rev. Neurosci., 14, 453–501.

    Article  PubMed  CAS  Google Scholar 

  8. Salvesen, G. S. (2002) Cell Death Differ., 9, 3–5.

    Article  PubMed  Google Scholar 

  9. Troy, C. M., and Salvesen, G. S. (2002) J. Neurosci. Res., 69, 145–150.

    Article  PubMed  CAS  Google Scholar 

  10. Stennicke, H. R., and Salvesen, G. S. (2000) Meth. Enzymol., 322, 91–100.

    Article  PubMed  CAS  Google Scholar 

  11. Tewari, M., Quan, L. T., O’Rourke, K., Desnoyers, S., Zeng, Z., Beidler, D. R., Poirier, G. G., Salvesen, G. S., and Dixit, V. M. (1995) Cell, 81, 801–809.

    Article  PubMed  CAS  Google Scholar 

  12. Thornberry, N. A., Chapman, K. T., and Nicholson, D. W. (2000) Meth. Enzymol., 322, 100–110.

    Article  PubMed  CAS  Google Scholar 

  13. Stennicke, H. R., and Salvesen, G. S. (1997) J. Biol. Chem., 272, 25719–25723.

    Article  PubMed  CAS  Google Scholar 

  14. Bizat, N., Hermel, J. M., Humbert, S., Jacquard, C., Creminon, C., Escartin, C., Saudou, F., Krajewski, S., Hantraye, P., and Brouillet, E. (2003) J. Biol. Chem., 278, 43245–43253.

    Article  PubMed  CAS  Google Scholar 

  15. Blomgren, K., Zhu, C., Wang, X., Karlsson, J. O., Leverin, A. L., Bahr, B. A., Mallard, C., and Hagberg, H. (2001) J. Biol. Chem., 276, 10191–10198.

    Article  PubMed  CAS  Google Scholar 

  16. Benchoua, A., Braudeau, J., Reis, A., Couriaud, C., and Onteniente, B. (2004) J. Cerebr. Blood Flow Metab., 24, 1272–1279.

    CAS  Google Scholar 

  17. Canu, N., Tufi, R., Serafino, A. L., Amadoro, G., Ciotti, M. T., and Calissano, P. (2005) J. Neurochem., 92, 1228–1242.

    Article  PubMed  CAS  Google Scholar 

  18. Popovic, T., Puizdar, V., Ritonja, A., and Brzin, J. (1996) J. Chromatogr. B Biomed. Appl., 681, 251–262.

    Article  PubMed  CAS  Google Scholar 

  19. Laemmli, U. K. (1970) Nature, 227, 680–685.

    Article  PubMed  CAS  Google Scholar 

  20. Shevchenko, A., Wilm, M., Vorm, O., and Mann, M. (1996) Analyt. Chem., 68, 850–858.

    Article  CAS  Google Scholar 

  21. Yakovlev, A. A., Onufriev, M. V., Stepanichev, M. Yu., Braun, K., and Gulyaeva, N. V. (2001) Neirokhimiya, 18, 41–43.

    CAS  Google Scholar 

  22. Bradford, M. M. (1976) Analyt. Biochem., 72, 248–254.

    Article  PubMed  CAS  Google Scholar 

  23. Nyman, M., and Whittaker, V. P. (1963) Biochem. J., 87, 248–255.

    PubMed  CAS  Google Scholar 

  24. Lipton, P. (1999) Physiol. Rev., 79, 1431–1568.

    PubMed  CAS  Google Scholar 

  25. Robertson, G. S., Crocker, S. J., Nicholson, D. W., and Schulz, J. B. (2000) Brain Pathol., 10, 283–292.

    Article  PubMed  CAS  Google Scholar 

  26. Unal-Cevik, I., Kilinc, M., Can, A., Gursoy-Ozdemir, Y., and Dalkara, T. (2004) Stroke, 35, 2189–2194.

    Article  PubMed  Google Scholar 

  27. Castino, R., Bellio, N., Nicotra, G., Follo, C., Trincheri, N. F., and Isidoro, C. (2007) Free Radic. Biol. Med., 42, 1305–1316.

    Article  PubMed  CAS  Google Scholar 

  28. Blomgran, R., Zheng, L., and Stendahl, O. (2007) J. Leukoc. Biol., 81, 1213–1223.

    Article  PubMed  CAS  Google Scholar 

  29. Van Nierop, K., Muller, F. J., Stap, J., van Noorden, C. J., van Eijk, M., and de Groot, C. (2006) J. Histochem. Cytochem., 54, 1425–1435.

    Article  PubMed  Google Scholar 

  30. Clement, M. V., Ponton, A., and Pervaiz, S. (1998) FEBS Lett., 440, 13–18.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to N. V. Gulyaeva.

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Published in Russian in Biokhimiya, 2008, Vol. 73, No. 3, pp. 408–413.

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Yakovlev, A.A., Gorokhovatsky, A.Y., Onufriev, M.V. et al. Brain cathepsin B cleaves a caspase substrate. Biochemistry Moscow 73, 332–336 (2008). https://doi.org/10.1134/S0006297908030140

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  • DOI: https://doi.org/10.1134/S0006297908030140

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