New insights in the molecular regulation of the NADPH oxidase 2 activity: Negative modulation by Poldip2.

Autor: Bouraoui A; Université Paris-Saclay, Institut de Chimie Physique UMR 8000, CNRS, 91405, Orsay Cedex, France., Louzada RA; Université Paris Saclay, UMR 9019 CNRS, Gustave Roussy, 94800, Villejuif, France., Aimeur S; Université Paris-Saclay, Institut de Chimie Physique UMR 8000, CNRS, 91405, Orsay Cedex, France., Waeytens J; Université Paris-Saclay, Institut de Chimie Physique UMR 8000, CNRS, 91405, Orsay Cedex, France; Structure et Fonction des Membranes Biologiques, Université libre de Bruxelles, Bruxelles, Belgium., Wien F; DISCO beamline, Synchrotron SOLEIL, Campus Paris-Saclay, 91192, Gif-sur-Yvette Cedex, France., My-Chan Dang P; INSERM U1149, CNRS ERL8252, Centre de Recherche sur l'Inflammation, Université de Paris, Laboratoire d'Excellence Inflamex, Faculté de Médecine, Site Xavier Bichat, Paris, F-75018, France., Bizouarn T; Université Paris-Saclay, Institut de Chimie Physique UMR 8000, CNRS, 91405, Orsay Cedex, France., Dupuy C; Université Paris Saclay, UMR 9019 CNRS, Gustave Roussy, 94800, Villejuif, France., Baciou L; Université Paris-Saclay, Institut de Chimie Physique UMR 8000, CNRS, 91405, Orsay Cedex, France. Electronic address: laura.baciou@universite-paris-saclay.fr.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2023 Apr; Vol. 199, pp. 113-125. Date of Electronic Publication: 2023 Feb 23.
DOI: 10.1016/j.freeradbiomed.2023.02.019
Abstrakt: Poldip2 was shown to be involved in oxidative signaling to ensure certain biological functions. It was proposed that, in VSMC, by interaction with the Nox4-associated membrane protein p22 phox , Poldip2 stimulates the level of reactive oxygen species (ROS) production. In vitro, with fractionated membranes from HEK393 cells over-expressing Nox4, we confirmed the up-regulation of NADPH oxidase 4 activity by the recombinant and purified Poldip2. Besides Nox4, the Nox1, Nox2, or Nox3 isoforms are also established partners of the p22 phox protein raising the question of their regulation by Poldip2 and of the effect in cells expressing simultaneously different Nox isoforms. In this study, we have addressed this issue by investigating the potential regulatory role of Poldip2 on NADPH oxidase 2, present in phagocyte cells. Unexpectedly, the effect of Poldip2 on phagocyte NADPH oxidase 2 was opposite to that observed on NADPH oxidase 4. Using membranes from circulating resting neutrophils, the ROS production rate of NADPH oxidase 2 was down-regulated by Poldip2 (2.5-fold). The down-regulation effect could not be correlated to the interaction of Poldip2 with p22 phox but rather, to the interaction of Poldip2 with the p47 phox protein, one of the regulatory proteins of the phagocyte NADPH oxidase. Our results show that the interaction of Poldip2 with p47 phox constitutes a novel regulatory mechanism that can negatively modulate the activity of NADPH oxidase 2 by trapping the so-called "adaptor" subunit of the complex. Poldip2 could act as a tunable switch capable of specifically regulating the activities of NADPH oxidases. This selective regulatory role of Poldip2, positive for Nox4 or negative for Nox2 could orchestrate the level and the type of ROS generated by Nox enzymes in the cells.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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