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A more recent version of this article appeared on March 1, 2003
Papers In Press, published online ahead of print December 16, 2002
J. Lipid Res., doi:10.1194/jlr.M200407-JLR200
Submitted on October 16, 2002
Revised on December 16, 2002
Accepted on December 4, 2002
Prooxidant and antioxidant properties of human serum ultrafiltrates toward low density lipoprotein: Important role of uric acid
Rebecca A. Patterson, Elizabeth T.M. Horsley, and David S. Leake
Department of Cell and Molecular Biology, The University of Reading, Whiteknights, Reading, Berkshire RG6 6AJ
Corresponding Author: d.s.leake{at}reading.ac.uk
Oxidised low density lipoprotein (LDL) is present within atherosclerotic lesions, demonstrating a failure of antioxidant protection. A normal human serum ultrafiltrate of Mr below 500 was prepared as a model for the low Mr components of interstitial fluid and its effects on LDL oxidation were investigated. The ultrafiltrate (0.3%, v/v) was a potent antioxidant for native LDL, but was a strong prooxidant for mildly-oxidised LDL when copper, but not a water-soluble azo initiator, was used to oxidise LDL. Adding a lipid hydroperoxide to native LDL induced the antioxidant to prooxidant switch of the ultrafiltrate. Uric acid was identified, using uricase and add-back experiments, as both the major antioxidant and prooxidant within the ultrafiltrate for LDL. The ultrafiltrate or uric acid rapidly reduced Cu2+ to Cu+. The reduction of Cu2+ to Cu+ may help to explain both the antioxidant and pro-oxidant effects observed. The decreased concentration of Cu2+ would inhibit tocopherol-mediated peroxidation in native LDL and the generation of Cu+ would promote the rapid breakdown of lipid hydroperoxides in mildly-oxidised LDL into lipid radicals. The net effect of the low Mr serum components would therefore depend on the pre-existing levels of lipid hydroperoxides in LDL. These findings may help to explain why LDL oxidation occurs in atherosclerotic lesions in the presence of compounds that are usually considered to be antioxidants.

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