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Effect of Bilirubin on Lipid Peroxidation, Sphingomyelinase Activity, and Apoptosis Induced by Sphingosine and UV Irradiation

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Abstract

The effect of bilirubin (BR) on sphingomyelin cycle activity, lipid peroxidation (LPO), and apoptosis induced by sphingosine and UV irradiation has been studied in vivo. Neutral Mg2+-dependent sphingomyelinase (SMase) activity and LPO level were monitored in heart, kidney, and liver of mice after administration of BR. BR inhibited both LPO and SMase activities in heart and kidney. BR induced a mild increase in LPO level and moderate increase in lipid contents in liver, consistent with the functional role of liver in both BR and lipid metabolism. BR injected to mice causes simultaneous and unidirectional alterations in both LPO level and SMase activity with a significant (p < 0.05) positive linear correlation between these two parameters. Sphingosine administration results in increased lipid peroxidation in murine liver. Data on DNA fragmentation indicate that exogenous BR may effectively protect thymus cells against sphingosine- and UV-mediated apoptosis. These results have revealed a biochemical association between oxidative stress and BR on one hand and the sphingomyelin cycle and apoptotic cell death on the other hand. Our data show that BR as an antioxidant, due to its effect on the sphingomyelin cycle, can protect membrane lipids against peroxidation and cells against apoptosis induced by various factors.

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REFERENCES

  1. Leonarduzzi, G., Melek, C. A., Basaga, H., Chiarpotto, E., and Poli, G. (2000) Free Rad.Biol.Med., 28, 1370–1378.

    PubMed  Google Scholar 

  2. DeZwart, L. L., Meerman, J. H. N., Commandeur, J. N. M., and Vermeulen, N. P. E. (1999) Free Rad.Biol.Med., 26, 202–226.

    PubMed  Google Scholar 

  3. Hensley, K., Robinson, K. A., Gabbita, S. P., Salsman, S., and Floyd, R. A. (2000) Free Rad.Biol.Med., 28, 1456–1462.

    PubMed  Google Scholar 

  4. Shackelford, R. E., Kaufmann, W. K., and Paules, R. S. (2000) Free Rad.Biol.Med., 28, 1387–1404.

    PubMed  Google Scholar 

  5. Mansat-de Mas, V., Bezombes, C., Quillet-Mary, A., Bettaieb, A., D'O rgeix, A. D., Laurent, G., and Jaffrezou, J. P. (1999) Mol.Pharmacol., 56, 867–874.

    PubMed  Google Scholar 

  6. Hatanaka, Y., Fujii, J., Fukutomi, T., Watanabe, T., Che, W., Sanada, Y., Igarashi, Y., and Taniguchi, N. (1998) Biochim.Biophys.Acta, 1393, 203–210.

    PubMed  Google Scholar 

  7. Lopez-Lluch, G., Barroso, M. P., Martin, S. F., Fernandez-Ayala, D. J., Gomez-Diaz, C., Villalba, J. M., and Navas, P. (1999) Biofactors, 9, 171–177.

    PubMed  Google Scholar 

  8. Blyuger, A. F., Dudnik, L. B., Maiore, A. Ya., and Miyeze, I. E. (1985) Byull.Eksp.Biol.Med., 99, 166–168.

    Google Scholar 

  9. Stocker, R., Glazer, A. N., and Ames, B. N. (1987) Proc.Natl.Acad.Sci.USA, 84, 5918–5922.

  10. De Flora, S., Rosenkranz, H. S., and Klopman, G. (1994) Mutagenesis, 9, 39–45.

    PubMed  Google Scholar 

  11. Yamaguchi, T., Terakado, M., Horio, F., Aoki, K., Tanaka, M., and Nakajima, H. (1996) Biochem.Biophys.Res.Commun., 223, 129–135.

    PubMed  Google Scholar 

  12. Galbraith, R. (1999) Proc.Soc.Exp.Biol.Med., 222, 299–305.

    PubMed  Google Scholar 

  13. Dore, S., Takahashi, M., Ferris, C. D., Hester, L. D., Guastella, D., and Snyder, S. (1999) Proc.Natl.Acad.Sci.USA, 96, 2445–2450.

    PubMed  Google Scholar 

  14. Dudnik, L. B., and Khrapova, N. G. (1998) Membr.Cell.Biol., 12, 233–240.

    PubMed  Google Scholar 

  15. Levade, T., and Jaffrezou, J. P. (1999) Biochim.Biophys.Acta, 1438, 1–17.

    PubMed  Google Scholar 

  16. Zager, R. A., Conrad, D. S., and Burkhart, K. (1998) J.Am.Soc.Nephrol., 9, 1670–1680.

    PubMed  Google Scholar 

  17. Huwiler, A., Kolter, T., Pfeilschifter, J., and Sandho, K. (2000) Biochim.Biophys.Acta, 1485, 63–99.

    PubMed  Google Scholar 

  18. Harada-Shiba, M., Kinoshita, M., Kamido, H., and Shimokado, K. (1998) J.Biol.Chem., 273, 9681–9687.

    PubMed  Google Scholar 

  19. Denisova, N. A., Fisher, D., Provost, M., and Joseph, J. A. (1999) Free Rad.Biol.Med., 27, 1292–1301.

    PubMed  Google Scholar 

  20. Meldrum, D. R. (1998) Am.J.Physiol., 274, R577-R595.

    Google Scholar 

  21. Joseph, J. A., Denisova, N., Fisher, D., Shukitt-Hale, B., Bickford, P., Prior, R., and Cao, G. (1998) Ann.N.Y.Acad.Sci., 854, 268–276.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  23. 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 

  24. Yoshimura, S., Banno, Y., Nakashima, S., Hayashi, K., Yamakawa, H., Sawada, M., Sakai, N., and Nozawa, Y. (1999) J.Neurochem., 73, 675–683.

    PubMed  Google Scholar 

  25. 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 

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

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

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

    Google Scholar 

  30. Herrmann, M., Lorenz, H. M., Voll, R., Woith, W., Grunke, M., and Kalden, J. R. (1994) Nucleic Acids Res., 22, 5506–5507.

    PubMed  Google Scholar 

  31. Wu, T. W., Wu, J., Li, R. K., Mickle, D., and Carey, D. (1991) Biochem.Cell.Biol., 69, 683–688.

    PubMed  Google Scholar 

  32. Cuypers, H. T. M., Ter Hoar, E. M., and Jwuen, P. L. M. (1983) Biochim.Biophys.Acta, 758, 135–143.

    PubMed  Google Scholar 

  33. 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 

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

    Google Scholar 

  35. Garcia-Ruiz, C., Collel, A., Mari, M., Morales, A., and Fernandes-Cheka, J. C. (1997) J.Biol.Chem., 272, 11369–11377.

    PubMed  Google Scholar 

  36. Alessenko, A. V., and Khrenov, A. V. (1999) Lipids, 34S, 75–76.

    Google Scholar 

  37. Ossola, J. O., and Tomaro, M. L. (1998) Int.J.Biochem. Cell.Biol., 30, 285–292.

    PubMed  Google Scholar 

  38. Garcia-Ruiz, C., Mari, M., Morales, A., Collel, A., Ardite, E., and Fernandes-Cheka, J. C. (2000) Hepatology, 32, 56–65.

    Article  PubMed  Google Scholar 

  39. Krishna Murti, C. R. (1982) Proc.Ind.Nat.Acad.Sci., B48, 163–175.

    Google Scholar 

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Dudnik, L.B., Tsyupko, A.N., Khrenov, A.V. et al. Effect of Bilirubin on Lipid Peroxidation, Sphingomyelinase Activity, and Apoptosis Induced by Sphingosine and UV Irradiation. Biochemistry (Moscow) 66, 1019–1027 (2001). https://doi.org/10.1023/A:1012329911696

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  • DOI: https://doi.org/10.1023/A:1012329911696

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