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Effects of Reduced and Oxidized Glutathione on Sphingomyelinase Activity and Contents of Sphingomyelin and Lipid Peroxidation Products in Murine Liver

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Abstract

Like the phosphatidyl inositol cycle, the sphingomyelin cycle produces a series of the secondary messengers transmitting extracellular signals from the cytoplasmic membrane into the nucleus. Sphingomyelin, ceramide, sphingosine, sphingomyelinase, and ceramidase are the main components of the sphingomyelin cycle. In spite of numerous data on the functional properties of sphingomyelin cycle products, the activation mechanism for the key enzyme of the sphingomyelin cycle, sphingomyelinase (SMase), is not well understood. We have discovered effects of both reduced (GSH) and oxidized (GSSG) glutathione on the activity of neutral SMase in animals. GSH administration (18 mg per mouse) inhibits this enzymatic activity in liver for 2 h and increases the sphingomyelin level exactly as occurs in cell culture. The levels of diene conjugates and ketodienes decrease simultaneously during the experiment, thus indicating the ability of GSH to suppress oxidative processes in the cell. GSSG administration (18 mg per mouse) has no effect on the SMase activity during the first 15 min, but increases it twofold after 1 h. A short-term decrease in this activity after 30 min may depend on the conversion of excess GSSG into its reduced form by glutathione reductase. Unlike GSH, GSSG has no effect on the level of ketodienes after 1 h, but it induces the accumulation of diene conjugates. A strong correlation exists between the changes in SMase activity and in the level of oxidation products caused by either GSH or GSSG. These data indicate a relationship between SMase activity and the level of peroxidation products and possibly a relation between two signaling systems: the sphingomyelin cycle and the oxidative system.

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REFERENCES

  1. Hannun, Y. A., Loomis, C. R., Merrill, A. H., Jr., and Bell, R. M. (1986) J.Biol.Chem., 261, 12604–12609.

    PubMed  Google Scholar 

  2. Hannun, Y. A., and Bell, R. M. (1989) Science, 243, 500–506.

    Google Scholar 

  3. Mathias, S., Dressler, K. A., and Kolesnick, R. N. (1991) Proc.Natl.Acad.Sci.USA, 88, 10009–10013.

    PubMed  Google Scholar 

  4. Merrill, A. H., and Stevens, V. L. (1989) Biochim. Biophys.Acta, 1010, 131–139.

    PubMed  Google Scholar 

  5. Okazaki, T., Bell, R. M., and Hannun, Y. A. (1989) J.Biol.Chem., 264, 19076–19080.

    PubMed  Google Scholar 

  6. Schutze, S., Potthoff, K., Machleidt, T., Dorge, J., Berkovic, D., Wiegmann, K., and Kronke, M. (1992) Cell, 71, 765–776.

    Article  PubMed  Google Scholar 

  7. Alessenko, A. V., Korobko, V. G., Khrenov, A. V., Rozhnova, U. A., Soloviev, A. S., and Shingarova, L. N. (1997) Biochem.Mol.Biol.Int., 42, 143–154.

    PubMed  Google Scholar 

  8. Haimovitz Friedman, A., Cordon-Cardo, L., Bayoumy, S., Gardozotto, M., McLoughlin, M., and Gallily, R. (1997) J.Exp.Med., 186, 1831–1848.

    PubMed  Google Scholar 

  9. Okazaki, T., Bell, R. M., and Hannun, Y. A. (1989) J.Biol.Chem., 264, 18076–18090.

    PubMed  Google Scholar 

  10. Alessenko, A. V. (1999) Biol.Membr.(Moscow), 16, 242–255.

    Google Scholar 

  11. Hannun, Y. A., and Obeid, L. M. (1997) Adv.Exp.Med.Biol., 407, 145–149.

    PubMed  Google Scholar 

  12. Sakakura, C., Sweeney, E. A., Shirahama, T., Hakomori, S., and Igarashi, S. (1996) FEBS Lett., 379, 177–180.

    PubMed  Google Scholar 

  13. Chatterjee, S., and Ghosh, N. (1989) J.Biol.Chem., 264, 2554–2561.

    Google Scholar 

  14. Spence, M. W. (1993) Adv.Lipid Res., 26, 3–23.

    PubMed  Google Scholar 

  15. Okazaki, T., Bielawska, A., Domae, N., Bell, R. M., and Hannun, Y. A. (1994) J.Biol.Chem., 269, 4070–4077.

    PubMed  Google Scholar 

  16. Nyberg, L., Duan, R. D., Axelson, J., and Nilsson, A. (1996) Biochim.Biophys.Acta, 300, 42–48.

    Google Scholar 

  17. Takeda, Y., Tashima, M., Takahashi, A., Uchiyama, T., and Okazaki, T. (1999) J.Biol.Chem., 274, 10654–10660.

    Article  PubMed  Google Scholar 

  18. Lievremont, J. P., Sciorati, C., Paolucci, C., Bunone, G., Della Valle, G., Meldolesi, J., and Clementi, E. (1999) J.Biol.Chem., 274, 15466–15472.

    PubMed  Google Scholar 

  19. Huviler, A., Pfeilshifter, J., and van den Bosch, H. (1999) J.Biol.Chem., 274, 7190–7195.

    PubMed  Google Scholar 

  20. Garcia-Ruiz, C., Mari, M., Morales, A., Colell, A., Ardite, E., and Fernandez-Checa, J. C. (2000) Hepatology, 32, 56–65.

    Article  PubMed  Google Scholar 

  21. Denisova, N. A., Fische, R. D., Provost, M., and Joseph, J. A. (1999) Free Rad.Biol.Med., 27, 1292–12301.

    Google Scholar 

  22. Liu, B., Hassler, D. F., Smith, G. K., Weaver, K., and Hannun, Y. A. (1998) J.Biol.Chem., 273, 34472–34479.

    Article  PubMed  Google Scholar 

  23. Sies, H. (1999) Free Rad.Biol.Med., 27, 916–921.

    PubMed  Google Scholar 

  24. Evstigneeva, R. P., Volkov, I. M., and Chudinova, V. V. (1998) Biol.Membr.(Moscow), 15, 119–135.

    Google Scholar 

  25. Hostetler, K., and Yasaki, P. (1979) J.Lipid Res., 20, 456–463.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  27. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951) J.Biol.Chem., 193, 265–275.

    PubMed  Google Scholar 

  28. Stal'naya, I. D., and Garishvili, T. G. (1977) in Modern Methods in Biochemistry [in Russian], Nauka, Moscow, pp. 63–64.

    Google Scholar 

  29. Sies, H. (1985) in Oxidative Stress (Sies, H., ed.) Academic Press, London, pp. 73–90.

    Google Scholar 

  30. Kosower, N. S., and Kosower, E. M. (1978) Int.Rev.Cytol., 54, 109–160.

    PubMed  Google Scholar 

  31. Cotgreave, I. A., and Gerdes, R. G. (1998) Biochem.Biophys.Res.Commun., 242, 1–9.

    PubMed  Google Scholar 

  32. Liu, B., and Hannun, Y. A. (1997) J.Biol.Chem., 272, 16281–16287.

    PubMed  Google Scholar 

  33. Liu, B., Andrieu-Abadie, N., Levade, T., Zhang, P., Obeid, L. M., and Hannun, Y. A. (1998) J.Biol.Chem., 273, 11313–11320.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, ul. Kosygina 4, Moscow, 117977, Russia

    A. N. Tsyupko, L. B. Dudnik & A. V. Alessenko

  2. Lomonosov Moscow State Academy of Fine Chemical Technology, pr. Vernadskogo 86, Moscow, 117571, Russia

    R. P. Evstigneeva

Authors
  1. A. N. Tsyupko
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  2. L. B. Dudnik
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  3. R. P. Evstigneeva
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  4. A. V. Alessenko
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Tsyupko, A.N., Dudnik, L.B., Evstigneeva, R.P. et al. Effects of Reduced and Oxidized Glutathione on Sphingomyelinase Activity and Contents of Sphingomyelin and Lipid Peroxidation Products in Murine Liver. Biochemistry (Moscow) 66, 1028–1034 (2001). https://doi.org/10.1023/A:1012381928535

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