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Cholesterol autoxidation in phospholipid membrane bilayers

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Lipid peroxidation in unilamellar liposomes of known cholesterol-phospholipid composition was monitored under conditions of autoxidation or as induced by a superoxide radical generating system, γ-irradiation or cumene hydroperoxide. Formation of cholesterol oxidation products was indexed to the level of lipid peroxidation. The major cholesterol oxidation products identified were 7-keto-cholesterol, isomeric cholesterol 5,6-epoxides, isomeric 7-hydroperoxides and isomeric 3,7-cholestane diols. Other commonly encountered products included 3,5-cholestadiene-7-one and cholestane-3β,5α,6β-triol. Superoxide-dependent peroxidation required iron and produced a gradual increase in 7-keto-cholesterol and cholesterol epoxides. Cholesterol oxidation was greatest in liposomes containing high proportions of unsaturated phospholipid to cholesterol (4∶1 molar ratio), intermediate with low phospholipid to cholesterol ratios (2∶1) and least in liposomes prepared with dipalmitoylphosphatidylcholine and cholesterol. This relationship held regardless of the oxidizing conditions used. Cumene hydroperoxide-dependent lipid peroxidation and/or more prolonge oxidations with other oxidizing systems yielded a variety of products where cholesterol-5β,6β-epoxide, 7-ketocholesterol and the 7-hydroperoxides were most consistently elevated. Oxyradical initiation of lipid peroxidation produced a pattern of cholesterol oxidation products distinguishable from the pattern derived by cumene hydroperoxide-dependent peroxidation. Our findings indicate that cholesterol autoxidation in biological membranes is modeled by the peroxide-induced oxidation of liposomes bearing unsaturated fatty acids and suggest that a number of cholesterol oxidation products are derived from peroxide-dependent propagation reactions occurring in biomembranes.

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  1. Scholan, N.A., and Boyd, G.S. (1968)Hoppe-Seyler's Z. Physiol. Chem. 349, 1628–1630.

    PubMed  CAS  Google Scholar 

  2. Teng, J.I., and Smith, L.L. (1976)Bioorganic Chem. 5, 99–119.

    Article  CAS  Google Scholar 

  3. Danielsson, H. (1973) inThe Bile Acids: Chemistry, Physiology and Metabolism. (Nair, P.P., and Kritchevsky, D., eds.), Vol. 2, pp. 22–50, Plenum Press, New York.

    Google Scholar 

  4. Mitton, J.R., Scholan, N.A., and Boyd, G.S. (1971)Eur. J. Biochem. 20, 569–579.

    Article  PubMed  CAS  Google Scholar 

  5. Johansson, G. (1971)Eur. J. Biochem. 21, 68–79.

    Article  PubMed  CAS  Google Scholar 

  6. Hochstein, P., and Ernster, L. (1963)Biochem. Biophys. Res. Commun. 12, 388–394.

    Article  PubMed  CAS  Google Scholar 

  7. Ansari, G.A.S., and Smith, L.L. (1979)Photochem. Photobiol. 30, 147–150.

    CAS  Google Scholar 

  8. Smith, L.L., Kulig, M.J., Miiller D., and Ansari, G.A.S. (1978)J. Am. Chem. Soc. 100, 6206–6211.

    Article  CAS  Google Scholar 

  9. Gowda, N.M., and Smith, L.L. (1984)J. Steroid Biochem. 20, 917–922.

    Article  CAS  Google Scholar 

  10. Terao, J., Sugino, K., and Matsushita, S. (1985)J. Nutr. Sci. Vitaminol. 31, 499–508.

    PubMed  CAS  Google Scholar 

  11. Muto, T., Tanaka, J., Miura, T., and Kimura, M., (1983)Chem. Pharm. Bull. 31, 1561–1566.

    CAS  Google Scholar 

  12. Floyd, R.A., and Lewis, C.A. (1983)Biochemistry 22, 2645–2649.

    Article  PubMed  CAS  Google Scholar 

  13. Estabrook, R.W., and Werringloer, J. (1977) inDrug Metabolism Concepts (Jerina, D.M., ed.), Series 44, pp. 1–25, American Chemical Society Symposium, Columbus, OH.

  14. Svingen, B.A., Buege, J.A., O'Neal, F.O., and Aust, S.D. (1979)J. Biol. Chem. 254, 5892–5899.

    PubMed  CAS  Google Scholar 

  15. Watabe, T., and Sawahata, T. (1979)J. Biol. Chem. 254, 3854–3860.

    PubMed  CAS  Google Scholar 

  16. Smith, L.L. (1981) inCholesterol Autoxidation, pp. 49–124, Plenum Press, New York, NY.

    Google Scholar 

  17. Lijana, R.C., McCracken, M.S., and Rudolph, C.J. (1986)Biochim. Biophys. Acta 879, 247–252.

    CAS  Google Scholar 

  18. Sevanian, A., and McLeod, L.L. (1986)J. Biol. Chem. 261, 54–59.

    PubMed  CAS  Google Scholar 

  19. Sevanian, A., Mead, J.F., and Stein, R.A. (1979)Lipids 14, 634–643.

    Article  PubMed  CAS  Google Scholar 

  20. Sevanian, A., and Peterson, A.R. (1984)Proc. Natl. Acad. Sci. USA 81, 4198–4202.

    Article  PubMed  CAS  Google Scholar 

  21. Bartlett, G.R. (1959)J. Biol. Chem. 234, 466–468.

    PubMed  CAS  Google Scholar 

  22. Touchstone, J.C., Chen, J.D., and Beaver, K.M. (1978)Lipids 15, 61–62.

    Article  Google Scholar 

  23. Mansour, A.N., Thompson, C., Theil, E.C., Chasteen, D., and Sayers, D.E. (1985)J. Biol. Chem. 260, 7975–7979.

    PubMed  CAS  Google Scholar 

  24. Floyd, R.A. (1983)Arch. Biochem. Biophys. 225, 263–270.

    Article  PubMed  CAS  Google Scholar 

  25. Schacter, L.P. (1985)Biochem. Biophys. Res. Commun. 127, 354–357.

    Article  PubMed  CAS  Google Scholar 

  26. Girotti, A.W. (1985)J. Free Rad. Biol. Med. 1, 87–95.

    Article  CAS  Google Scholar 

  27. Ursini, F., Maiorino, M., Ferri, L., Valente, M., and Gregolin, C. (1981)J. Inorg. Biochem. 15, 163–169.

    Article  PubMed  CAS  Google Scholar 

  28. Buege, J.A., and Aust, S.D. (1978) inMeth. Enzymol. 52, 302–310.

  29. Sevanian, A., Muakkassah-Kelly, S.F., and Montestruque, S. (1983)Arch. Biochem. Biophys. 223, 441–452.

    Article  PubMed  CAS  Google Scholar 

  30. Sevanian, A., and Kim, E. (1985)J. Free Rad. Biol. Med. 1, 263–271.

    Article  CAS  Google Scholar 

  31. Bielski, B.H.J., and Gebicki, J.M. (1977) inFree Radicals in Biology (Pryor, W.A., ed.), Vol. III, pp. 2–51, Academic Press, New York.

    Google Scholar 

  32. Arakawa, K., and Sagai, M. (1986)Lipids 21, 769–775.

    Article  PubMed  CAS  Google Scholar 

  33. Kimura, M., Jin, Y., and Sawaya, T. (1979)Chem. Pharm. Bull. 27, 710–714.

    CAS  Google Scholar 

  34. Cooper, R.A., and Strauss, J.F. (1984) inPhysiology of Membrane Fluidity (Shinitzky, M., ed.) Vol. I, pp. 74–97, CRC Press, Boca Raton, FL.

    Google Scholar 

  35. Zambrano, F., Fleisher, S., and Fleisher, B. (1978)Biochim. Biophys. Acta 380, 357–369.

    Google Scholar 

  36. Altman, P.L., and Katz, D.D. (1976) inCell Biology (Altman, P.L., and Katz, D.D., eds.) pp. 153–154, Federation of American Societies for Experimental Biology Handbook, Bethesda.

    Google Scholar 

  37. Touster, O., Aronson, N.N., Dulaney, J.T., and Hendrickson, H. (1970)J. Cell. Biol. 47, 604–618.

    Article  PubMed  CAS  Google Scholar 

  38. Smith, L.L., Kulig, M.J., and Teng, J.I. (1977)Chem. Phys. Lipids 20, 211–215.

    Article  PubMed  CAS  Google Scholar 

  39. Smith, L.L., and Kulig, M.J. (1975)Cancer Biochem. Biophys. 1, 79–84.

    CAS  Google Scholar 

  40. Aringer, L. (1980)Lipids 15, 563–571.

    Article  PubMed  CAS  Google Scholar 

  41. Gumulka, J., St. Pyrek, J., and Smith, L.L. (1982)Lipids 17, 197–203.

    Article  CAS  Google Scholar 

  42. Smith, L.L., and Kulig, M.J. (1976)J. Am. Chem. Soc. 98, 1027–1029.

    Article  CAS  Google Scholar 

  43. Watabe, T., Kanai, M., Isobe, M., and Ozawa, N. (1980)Biochim. Biophys. Acta 619, 414–419.

    PubMed  CAS  Google Scholar 

  44. Watabe, T., Isobe, M., and Tsubaki, A. (1982)Biochem. Biophys. Res. Commun. 108, 724–730.

    Article  PubMed  CAS  Google Scholar 

  45. Vandenheuvel, F.A. (1963)J. Am. Oil Chem. Soc. 40, 455–471.

    Google Scholar 

  46. Maerker, G., and Bunick, F.J. (1986)J. Am. Oil Chem. Soc. 63, 771–777.

    CAS  Google Scholar 

  47. Van Lier, J.E., and Smith, L.L. (1968)Anal. Biochem. 24, 419–430.

    Article  PubMed  Google Scholar 

  48. Brooks, C.J.W., McKenna, R.M., Cole, W.J., McLachlan, J., and Lawrie, T.D.V. (1983)Biochem. Soc. Trans. 11, 700–701.

    CAS  Google Scholar 

  49. Petrakis, N.L., Gruenke, L.D., and Craig, J.C. (1981)Cancer Res. 41, 2563–2565.

    PubMed  CAS  Google Scholar 

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Sevanian, A., McLeod, L.L. Cholesterol autoxidation in phospholipid membrane bilayers. Lipids 22, 627–636 (1987).

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