Abstract
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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Abbreviations
- PC:
-
phosphatidylcholine
- PE:
-
phosphatidylethanolamine
- TBAR:
-
thiobarbituric acid-reacting products
- CuOOH:
-
cumene hydroperoxide
- HX:
-
hypoxanthine
- ADP:
-
adenosine diphosphate
- XO:
-
xanthine oxidas
- SOD:
-
superoxide dismutase
- TLC:
-
thin layer chromatography
- 7-keto:
-
cholest-5-ene-3β-ol-7-one
- 3,5-diene:
-
3,5-cholestadiene-7-one
- α-CE:
-
cholestan-5α,6α-epoxy-3β-ol
- CT:
-
5α-6β-triol
- 7-OOH:
-
3β-hydroxycholest-5-ene-7α-hydroperoxide
- β-CE:
-
cholestan-5β,6β-epoxy-3β-ol
- HPLC:
-
high pressure liquid chromatography
- DPPC:
-
dipalmitoylphosphatidylcholine
- PI:
-
peroxidizability index
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Sevanian, A., McLeod, L.L. Cholesterol autoxidation in phospholipid membrane bilayers. Lipids 22, 627–636 (1987). https://doi.org/10.1007/BF02533940
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DOI: https://doi.org/10.1007/BF02533940