@article{3089963,
    title = "trans Arachidonic acid isomers inhibit NADPH-oxidase activity by direct interaction with enzyme components",
    author = "Souabni, H. and Thoma, V. and Bizouarn, T. and Chatgilialoglu, C. and Siafaka-Kapadai, A. and Baciou, L. and Ferreri, C. and Houée-Levin, C. and Ostuni, M.A.",
    journal = "Biochimica et Biophysica Acta.  Biomembranes",
    year = "2012",
    volume = "1818",
    number = "9",
    pages = "2314-2324",
    issn = "0005-2736",
    doi = "10.1016/j.bbamem.2012.04.018",
    keywords = "arachidonic acid;  protein p40;  protein p47;  protein p67;  reduced nicotinamide adenine dinucleotide phosphate, animal cell;  article;  binding affinity;  binding site;  controlled study;  enzyme activation;  enzyme activity;  enzyme binding;  enzyme inhibition;  isomer;  lipid composition;  nonhuman;  Pichia pastoris;  priority journal;  protein function;  protein localization;  protein processing;  protein targeting;  protein translocation, Animals;  Arachidonic Acid;  Cattle;  Cell Membrane;  Cytochrome b Group;  Cytosol;  Dose-Response Relationship, Drug;  Fatty Acids;  Models, Biological;  NADPH Oxidase;  Neutrophils;  Phagocytes;  Phosphoproteins;  Pichia;  Protein Binding;  Protein Conformation;  Recombinant Proteins;  Time Factors;  Tryptophan",
    abstract = "NADPH-oxidase is an enzyme that represents, when activated, the major source of non-mitochondrial reactive oxygen species. In phagocytes, this production is an indispensable event for the destruction of engulfed pathogens. The functional NADPH-oxidase complex consists of a catalytic membrane flavocytochrome b (Cytb558) and four cytosolic proteins p47 phox, p67phox, Rac and p40phox. The NADPH-oxidase activity is finely regulated spatially and temporally by cellular signaling events that trigger the translocation of the cytosolic subunits to its membrane partner involving post-translational modifications and activation by second messengers such as arachidonic acid (AA). Arachidonic acid in its natural cis-poly unsaturated form (C20:4) has been described to be an efficient activator of the enzyme in vivo and in vitro. In this work, we examined in a cell-free system whether a change of the natural cis geometry to the trans configuration, which could occur either by diet or be produced by the action of free radicals, may have consequences on the functioning of NADPH-oxidase. We showed the inability of mono-trans AA isomers to activate the NADPH-oxidase complex and demonstrated the inhibitory effect on the cis-AA-induced NADPH oxidase activation. The inhibition is mediated by a direct effect of the mono-trans AA which targets both the membrane fraction containing the cytb 558 and the cytosolic p67phox. Our results suggest that the loss of the natural geometric feature (cis-AA) induces substantial structural modifications of p67phox that prevent its translocation to the complex. © 2012 Elsevier B.V. All rights reserved."
}