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Cholesterol autoxidation in phospholipid membrane bilayers

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Lipids

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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Authors and Affiliations

  1. Institute for Toxicology, University of Southern California, School of Pharmacy, 90033, Los Angeles, California

    Alex Sevanian & Laurie L. McLeod

  2. Department of Pathology, University of Southern California, School of Pharmacy, 1985 Zonal Ave., 90033, Los Angeles, California

    Alex Sevanian & Laurie L. McLeod

Authors
  1. Alex Sevanian
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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

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