Volume 272, Number 47, Issue of November 21, 1997 pp. 29711-29720
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Effects of Reagent and Enzymatically Generated Hypochlorite on Physicochemical and Metabolic Properties of High Density Lipoproteins

(Received for publication, March 21, 1997, and in revised form, September 21, 1997)

Ute Panzenboeck , Sabine Raitmayer , Helga Reicher , Helmut Lindner , Otto Glatter , Ernst Malle and Wolfgang Sattler

From the University Graz, Department of Medical Biochemistry, Harrachgasse 21, and  Department of Physical Chemistry, Heinrichstrasse 28, A-8010 Graz, Austria

Myeloperoxidase (MPO), a protein secreted by activated phagocytes, may be a potential candidate for the generation of modified/oxidized lipoproteins in vivo via intermediate formation of HOCl, a powerful oxidant. During the present study, the effects of reagent NaOCl and OCl generated by the MPO/H₂O₂/Cl system on physicochemical and metabolic properties of high density lipoprotein (HDL) subclass 3 (HDL₃) were investigated. Up to a molar oxidant:lipoprotein ratio of approximately 30:1, apolipoprotein A-I (apoA-I), the major HDL₃ apolipoprotein component, represented the preferential target for OCl attack (consuming 35-76% of the oxidant), thereby protecting HDL₃ fatty acids (consuming between 17 and 30% of the oxidant) against OCl-mediated modification. At molar oxidant:HDL₃ ratios  60:1, we have observed pronounced consumption of HDL₃ unsaturated fatty acids with concomitant formation of fatty acid chlorohydrins. Modification of HDL₃ in the presence of the MPO/H₂O₂/Cl system resulted in amino acid oxidation in a manner comparable with that found with reagent NaOCl only. Treatment of HDL₃ with reagent NaOCl as well as modification by the MPO/H₂O₂/Cl system resulted in significantly enhanced turnover rates of HDL₃ by mouse peritoneal macrophages, an effect that was not a result of HDL₃ aggregation as judged by dynamic and static light-scattering experiments. In comparison with native HDL₃, the degradation by macrophages was enhanced by 4- and 15-fold when HDL₃ was modified with reagent NaOCl or the MPO/H₂O₂/Cl system. Finally, the ability of HDL₃ to promote cellular cholesterol efflux from macrophages was significantly diminished after modification with reagent NaOCl. Collectively, these results demonstrate that the modification of HDL₃ by hypochlorite (added as reagent or generated by the MPO/H₂O₂/Cl system) transformed an antiatherogenic lipoprotein particle into a modified lipoprotein with characteristics similar to lipoproteins commonly thought to initiate foam cell formation in vivo.

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