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Journal of Lipid Research, Vol. 43, 732-741, May 2002
Copyright © 2002 by Lipid Research, Inc.

Antioxidant properties of HDL in transgenic mice overexpressing human apolipoprotein A-II

Elisabeth Boisfer*, Dominique Stengel{dagger}, Danièle Pastier*, P. Michel Laplaud§, Nicole Dousset{ddagger}, Ewa Ninio{dagger} and Athina-Despina Kalopissis1,*

* Inserm Unité 505 and Université Paris VI, Centre de Recherche des Cordeliers, Paris
{dagger} Inserm Unité 525, IFR 14 "C"ur Muscle et Vaisseaux" and Faculté de Médecine Pitié-Salpêtrière/Université Paris VI, Paris
§ Inserm Unité 551, Hôpital de la Pitié-Salpêtrière, Paris
{ddagger} FR 1744, ICMPS, 31062 Toulouse, France

1 To whom correspondence should be addressed at Unité 505 Inserm, Centre de Recherche des Cordeliers, 15, rue de l'Ecole de Médecine, 75006 Paris, France. e-mail: athina.kalopissis-u505{at}bhdc.jussieu.fr

Transgenic mice overexpressing human apolipoprotein A-II (huapoA-II) display high VLDL and low HDL levels. To evaluate the antioxidant potential of huapoA-II enriched HDL, we measured the activities of paraoxonase (PON) and platelet-activating factor acetylhydrolase (PAF-AH). Both activities decreased up to 43% in the serum of transgenic mice compared with controls, varied in parallel to HDL levels, but decreased less than HDL levels. The major part of PON and PAF-AH was associated with HDL, except in fed high huapoA-II-expressing mice, in which 20% of PAF-AH and 9% of PON activities were associated with VLDL. PON mRNA levels in the liver, its major site of synthesis, were similar in transgenic and control animals, indicating normal enzyme synthesis. In transgenic mice, the basal oxidation of lipoproteins was not increased, whereas their VLDL were more susceptible to oxidation than VLDL of controls. Interestingly, HDL of transgenic mice protected VLDL from oxidation more efficiently than HDL of controls. In conclusion, the decrease in both PON and PAF-AH activities in huapoA-II transgenic mice is best explained by their lower plasma HDL levels. However, the unchanged basal lipoprotein oxidation in transgenic mice suggests that huapoA-II-rich HDL may maintain adequate antioxidant potential.—Boisfer, E., D. Stengel, D. Pastier, P. M. Laplaud, N. Dousset, E. Ninio, and A-D. Kalopissis. Antioxidant properties of HDL in transgenic mice overexpressing human apolipoprotein A-II. J. Lipid Res. 2002. 43: 732–741.

Abbreviations: apo, apolipoprotein; huAIItg, human apolipoprotein A-II transgenic; huapoA-II, human apolipoprotein A-II; mapoA-II, mouse apolipoprotein A-II; GGE, gradient gel electrophoresis; FPLC, fast protein liquid chromatography; PON, paraoxonase; PAF-AH, platelet activating factor acetylhydrolase; TBARS, thiobarbituric acid reactive substances

Supplementary key words antioxidant enzymes associated with HDL • TBARS • lipid hydroperoxides • VLDL oxidation • VLDL susceptibility to oxidation


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