Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Delporte, C; Boudjeltia, KZ; Noyon, C; Furtmüller, PG; Nuyens, V; Slomianny, MC; Madhoun, P; Desmet, JM; Raynal, P; Dufour, D; Koyani, CN; Reyé, F; Rousseau, A; Vanhaeverbeek, M; Ducobu, J; Michalski, JC; Nève, J; Vanhamme, L; Obinger, C; Malle, E; Van Antwerpen, P.
Impact of myeloperoxidase-LDL interactions on enzyme activity and subsequent posttranslational oxidative modifications of apoB-100.
J Lipid Res. 2014; 55(4):747-757 Doi: 10.1194/jlr.M047449 [OPEN ACCESS]
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Co-authors Med Uni Graz

Koyani Chintan Navinchandra

Malle Ernst

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Abstract:

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.

Find related publications in this database (using NLM MeSH Indexing)

Amino Acid Sequence -

Apolipoprotein B-100 - chemistry

Apolipoprotein B-100 - metabolism

Case-Control Studies -

Humans -

Hydrogen Peroxide - chemistry

Hydrolysis -

Kidney Diseases - blood

Kidney Diseases - therapy

Lipoproteins, LDL - chemistry

Lipoproteins, LDL - metabolism

Molecular Sequence Data -

Oxidation-Reduction -

Peptide Fragments -

Peroxidase - chemistry

Peroxidase - metabolism

Protein Processing, Post-Translational -

Renal Dialysis -

Find related publications in this database (Keywords)

inflammation

myeloperoxidase activity

hypochlorous acid

3-chlorotyrosine

epitope mapping

low density lipoprotein

apolipoprotein B-100

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