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NADPH Oxidases pp 75–101Cite as

A Close-Up View of the Impact of Arachidonic Acid on the Phagocyte NADPH Oxidase

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1982))

Abstract

The NADPH oxidase NOX2 complex consists of assembled cytosolic and redox membrane proteins. In mammalian cells, natural arachidonic acid (cis-AA), released by activated phospholipase-A2, plays an important role in the activation of the NADPH oxidase, but the mechanism of action of cis-AA is still a matter of debate. In cell-free systems, cis-AA is commonly used for activation although its structural effects are still unclear. Undoubtedly cis-AA participates in the synergistic multi-partner assembly that can be hardly studied at the molecular level in vivo due to cellular complexity. The capacity of this anionic amphiphilic fatty acid to activate the oxidase is mainly explained by its ability to disrupt intramolecular bonds, mimicking phosphorylation events in cell signaling and therefore allowing protein-protein interactions. Interestingly the geometric isomerism of the fatty acid and its purity are crucial for optimal superoxide production in cell-free assays. Indeed, optimal NADPH oxidase assembly was hampered by the substitution of the cis form by the trans forms of AA isomers (Souabni et al., BBA-Biomembranes 1818:2314–2324, 2012). Structural analysis of the changes induced by these two compounds, by circular dichroism and by biochemical methods, revealed differences in the interaction between subunits. We describe how the specific geometry of AA plays an important role in the activation of the NOX2 complex.

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Acknowledgments

Authors want to acknowledge Drs. M. Réfrégiers and F. Wien for SRCD measurements.

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Authors and Affiliations

  1. Laboratoire de Chimie Physique, UMR8000 CNRS, Université Paris-Sud, Université Paris-Saclay, Orsay, France

    Tania Bizouarn, Hager Souabni, Xavier Serfaty, Aicha Bouraoui, Rawand Masoud, Gilda Karimi, Chantal Houée-Levin & Laura Baciou

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  1. Tania Bizouarn
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  2. Hager Souabni
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  3. Xavier Serfaty
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  4. Aicha Bouraoui
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  6. Gilda Karimi
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  7. Chantal Houée-Levin
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  8. Laura Baciou
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Corresponding author

Correspondence to Laura Baciou .

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Editors and Affiliations

  1. Conway Institute, School of Medicine, University College Dublin, Dublin, Ireland

    Ulla G. Knaus

  2. Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Thomas L. Leto

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Bizouarn, T. et al. (2019). A Close-Up View of the Impact of Arachidonic Acid on the Phagocyte NADPH Oxidase. In: Knaus, U., Leto, T. (eds) NADPH Oxidases. Methods in Molecular Biology, vol 1982. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9424-3_5

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  • DOI: https://doi.org/10.1007/978-1-4939-9424-3_5

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9423-6

  • Online ISBN: 978-1-4939-9424-3

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