J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M200432-JLR200 on January 16, 2003

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Journal of Lipid Research, Vol. 44, 780-792, April 2003
Copyright © 2003 by Lipid Research, Inc.

Serum paraoxonase

: effect of the apolipoprotein composition of HDL and the acute phase response

Veneracion G. Cabana1, Catherine A. Reardon, Ning Feng, Sean Neath, John Lukens and Godfrey S. Getz

Department of Pathology, The University of Chicago, Chicago, IL 60637

1 To whom correspondence should be addressed. e-mail: vcabana{at}midway.uchicago.edu

Genetic variations of paraoxonase (PON) correlate with HDL cholesterol and apolipoprotein A-I (apoA-I), suggesting antiatherogenic properties. Atherosclerosis occurs naturally in humans and rabbits but not in mice. We compared variations of PON arylesterase activity (PON AEase, phenylacetate substrate) in humans, rabbits, and mice. In humans and rabbits, >95% of PON AEase is HDL associated. In mice, about 30% of PON AEase is lipid poor. In the absence of apoA-I in mice, total PON AEase is reduced and >60% is lipid poor. PON AEase level and distribution is restored in apoA-I-/- mice injected with adenoviruses encoding human apoA-I and in transgenic mice expressing human apoA-I at a steady-state level. Thus, while apoA-I is not required for the HDL association of PON AEase, induced variations in apoA-I correlate with changes in HDL-associated, but not lipid-poor, PON AEase. PON AEase associates only with apoA-I- or apoE-containing HDL but not VLDL. In the absence of both apoA-I and apoE, PON AEase is all-lipid-poor. PON AEase is displaced from HDL by ultracentrifugation and following incubation with serum amyloid A.

Variations in the PON distribution between HDL and lipid-poor fractions may have important consequences in its antioxidant activity and in atherogenesis.

Abbreviations: apoA-I-/-, apoA-I-deficient mice; apoE-/-, apoE-deficient mice; E-/-A-/-, mice deficient for both apoA-I and apoE; FPLC, fast-phase liquid chromatography; LPS, lipopolysaccharide; PON, paraoxonase; PON AEase, paraoxonase measured as an arylesterase by the rate of hydrolysis of phenylacetate; SAA, serum amyloid A

Supplementary key words apoA-I-deficient • apolipoprotein A-I transgenic • apoE-deficient • high-density lipoprotein • antioxidant enzyme • lipoproteins • serum amyloid A


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