Impact of myeloperoxidase-LDL interactions on enzyme activity and subsequent posttranslational oxidative modifications of apoB-100
2014
Delporte, Cédric | Boudjeltia, Karim Zouaoui | Noyon, Caroline | Furtmüller, Paul G. | Nuyens, Vincent | Slomianny, Marie-Christine | Madhoun, Philippe | Desmet, Jean-Marc | Raynal, Pierre | Dufour, Damien | Koyani, Chintan N. | Reyé, Florence | Rousseau, Alexandre | Vanhaeverbeek, Michel | Ducobu, Jean | Michalski, Jean-Claude | Nève, Jean | Vanhamme, Luc | Obinger, Christian | Malle, Ernst | Van Antwerpen, Pierre
Oxidation of LDL by the myeloperoxidase (MPO)-H2O2-chloride system is a key event in the development of atherosclerosis. The present study aimed at investigating the interaction of MPO with native and modified LDL and at revealing posttranslational modifications on apoB-100 (the unique apolipoprotein of LDL) in vitro and in vivo. Using amperometry, we demonstrate that MPO activity increases up to 90% when it is adsorbed at the surface of LDL. This phenomenon is apparently reflected by local structural changes in MPO observed by circular dichroism. Using MS, we further analyzed in vitro modifications of apoB-100 by hypochlorous acid (HOCl) generated by the MPO-H2O2-chloride system or added as a reagent. A total of 97 peptides containing modified residues could be identified. Furthermore, differences were observed between LDL oxidized by reagent HOCl or HOCl generated by the MPO-H2O2-chloride system. Finally, LDL was isolated from patients with high cardiovascular risk to confirm that our in vitro findings are also relevant in vivo. We show that several HOCl-mediated modifications of apoB-100 identified in vitro were also present on LDL isolated from patients who have increased levels of plasma MPO and MPO-modified LDL. In conclusion, these data emphasize the specificity of MPO to oxidize LDL.
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