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Influence of phospholipases A2 from snake venoms on survival and neurite outgrowth in pheochromocytoma cell line PC12

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Abstract

To determine whether the ability to induce neurite outgrowth in rat pheochromocytoma cell line PC12 is characteristic of phospholipases of different types, we have studied the influence of phospholipase A2 (PLA2) from cobra Naja kaouthia venom and two PLA2s from viper Vipera nikolskii venom on PC12 cells. Phospholipases from the viper venom are heterodimers in which only one of the subunits is enzymatically active, while PLA2 from the cobra venom is a monomer. It was found that all three PLA2s induce neurite outgrowth in PC12. The PLA2 from cobra venom exhibits this effect at higher concentrations as compared to the viper enzymes. We have not observed such an activity for isolated subunits of viper PLA2s, since the enzymatically active subunits have very high cytotoxicity, while the other subunits are not active at all. However, co-incubation of active and inactive subunits before addition to the cells leads to a marked decrease in cytotoxicity and to restoration of the neurite-inducing activity. It has also been shown that all enzymatically active PLA2s are cytotoxic, the PLA2 from cobra venom being the least active. Thus, for the first time we have shown that PLA2s from snake venoms can induce neurite outgrowth in PC12 cells.

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Abbreviations

PLA2:

phospholipase A2

HDP:

heterodimeric phospholipase

References

  1. Kudo, I., and Murakami, M. (2002) Prostaglandins Other Lipid Mediat., 68/69, 3–58.

    Article  Google Scholar 

  2. Murakami, M., and Kudo, I. (2004) Biol. Pharm. Bull., 27, 1158–1164.

    Article  PubMed  CAS  Google Scholar 

  3. Kini, R. M. (2003) Toxicon, 42, 827–840.

    Article  PubMed  CAS  Google Scholar 

  4. Fatehi, M., Rowan, E. G., Harvey, A. L., and Harris, J. B. (1994) Toxicon, 32, 1559–1572.

    Article  PubMed  CAS  Google Scholar 

  5. Fatehi, M., Harvey, A. L., and Rowan, E. G. (1998) Toxicon, 36, 115–129.

    Article  PubMed  CAS  Google Scholar 

  6. Balsinde, J., Winstead, M. V., and Dennis, E. A. (2002) FEBS Lett., 531, 2–6.

    Article  PubMed  CAS  Google Scholar 

  7. Rizzo, M. T., Nguyen, E., Aldo-Benson, M., and Lambeau, G. (2000) Blood, 96, 3809–3815.

    PubMed  CAS  Google Scholar 

  8. Traynor, A. E. (1984) Brain Res., 316, 205–210.

    PubMed  CAS  Google Scholar 

  9. Six, D. A., and Dennis, E. A. (2000) Biochim. Biophys. Acta, 1488, 1–19.

    PubMed  CAS  Google Scholar 

  10. Schiavo, G., Matteoli, M., and Montecucco, C. (2000) Physiol. Rev., 80, 717–766.

    PubMed  CAS  Google Scholar 

  11. Nakashima, S., Ikeno, Y., Yokoyama, T., Kuwana, M., Bolchi, A., Ottonello, S., Kitamoto, K., and Arioka, M. (2003) Biochem. J., 376, 655–666.

    Article  PubMed  CAS  Google Scholar 

  12. Nakashima, S., Kitamoto, K., and Arioka, M. (2004) Brain Res., 1015, 207–211.

    Article  PubMed  CAS  Google Scholar 

  13. Kalb, R. (2005) Trends Neurosci., 28, 5–11.

    Article  PubMed  CAS  Google Scholar 

  14. Van Kesteren, R. E., and Spencer, G. E. (2003) Rev. Neurosci., 14, 217–231.

    PubMed  Google Scholar 

  15. Gao, W., Starkov, V.G., Tsetlin, V.I., Utkin, Y.N., Lin, Z., and Bi, R. (2005) Acta Cryst., F61, 189–192.

    CAS  Google Scholar 

  16. Radvanyi, F., Jordan, L., Russo-Marie, F., and Bon, C. (1989) Analyt. Biochem., 177, 103–109.

    Article  PubMed  CAS  Google Scholar 

  17. Bligh, E. G., and Dyer, W. J. (1959) Can. J. Biochem. Physiol., 37, 911–917.

    PubMed  CAS  Google Scholar 

  18. Mancheva, I., Kleinschmidt, T., Aleksiev, B., and Braunitzer, G. (1987) Biol. Chem. Hoppe Seyler, 368, 343–352.

    PubMed  CAS  Google Scholar 

  19. Guillemin, I., Bouchier, C., Garrigues, T., Wisner, A., and Choumet, V. (2003) Eur. J. Biochem., 270, 2697–2706.

    Article  PubMed  CAS  Google Scholar 

  20. Faure, G., and Bon, C. (1988) Biochemistry, 27, 730–738.

    Article  PubMed  CAS  Google Scholar 

  21. Wang, Y. M., Lu, P. J., Ho, C. L., and Tsai, I. H. (1992) Eur. J. Biochem., 209, 635–641.

    Article  PubMed  CAS  Google Scholar 

  22. Joubert, F. J., and Taljaard, N. (1980) Eur. J. Biochem., 112, 493–499.

    Article  PubMed  CAS  Google Scholar 

  23. Gutierrez, J. M., and Ownby, C. L. (2003) Toxicon, 42, 915–931.

    Article  PubMed  CAS  Google Scholar 

  24. Andriao-Escarso, S. H., Soares, A. M., Rodrigues, V. M., Angulo, Y., Diaz, C., Lomonte, B., Gutierrez, J. M., and Giglio, J. R. (2000) Biochimie, 82, 755–763.

    Article  PubMed  CAS  Google Scholar 

  25. Soares, A. M., Andriao-Escarso, S. H., Bortoleto, R. K., Rodrigues-Simioni, L., Arni, R. K., Ward, R. J., Gutierrez, J. M., and Giglio, J. R. (2001) Arch. Biochem. Biophys., 387, 188–196.

    Article  PubMed  CAS  Google Scholar 

  26. Corin, R. T., Viskatis, L. J., Vidal, J. C., and Etcheverry, M. A. (1993) Invest. New Drugs, 11, 11–15.

    Article  PubMed  CAS  Google Scholar 

  27. Fletcher, J. E., and Jiang, M. S. (1998) Toxicon, 36, 1549–1555.

    Article  PubMed  CAS  Google Scholar 

  28. Mora, R., Valverde, B., Diaz, C., Lomonte, B., and Gutierrez, J. M. (2005) Toxicon, 45, 651–660.

    Article  PubMed  CAS  Google Scholar 

  29. Masuda, S., Murakami, M., Takanezawa, Y., Aoki, J., Arai, H., Ishikawa, Y., Ishii, T., Arioka, M., and Kudo, I. (2005) J. Biol. Chem., 280, 23203–23214.

    Article  PubMed  CAS  Google Scholar 

  30. Ikeno, Y., Konno, N., Cheon, S. H., Bolchi, A., Ottonello, S., Kitamoto, K., and Arioka, M. (2005) J. Biol. Chem., 280, 28044–28052.

    Article  PubMed  CAS  Google Scholar 

  31. Asaoka, Y., Yoshida, K., Sasaki, Y., and Nishizuka, Y. (1993) Proc. Natl. Acad. Sci. USA, 90, 4917–4921.

    Article  PubMed  CAS  Google Scholar 

  32. Ramoner, R., Putz, T., Gander, H., Rahm, A., Bartsch, G., Schaber, C., and Thurnher, M. (2005) Blood, 105, 3583–3587.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997, Moscow, Russia

    Ya. V. Makarova, A. V. Osipov, V. I. Tsetlin & Yu. N. Utkin

Authors
  1. Ya. V. Makarova
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  2. A. V. Osipov
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  3. V. I. Tsetlin
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  4. Yu. N. Utkin
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Correspondence to Yu. N. Utkin.

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Original Russian Text © Ya. V. Makarova, A. V. Osipov, V. I. Tsetlin, Yu. N. Utkin, 2006, published in Biokhimiya, 2006, Vol. 71, No. 6, pp. 838–846.

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Makarova, Y.V., Osipov, A.V., Tsetlin, V.I. et al. Influence of phospholipases A2 from snake venoms on survival and neurite outgrowth in pheochromocytoma cell line PC12. Biochemistry (Moscow) 71, 678–684 (2006). https://doi.org/10.1134/S0006297906060125

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  • DOI: https://doi.org/10.1134/S0006297906060125

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