title: Titanium Dioxide Nanoparticles Increase Superoxide Anion Production by Acting on NADPH Oxidase.
abstract: Titanium dioxide (TiO2) anatase nanoparticles (NPs) are metal oxide NPs commercialized for several uses of everyday life. However their toxicity has been poorly investigated. Cellular internalization of NPs has been shown to activate macrophages and neutrophils that contribute to superoxide anion production by the NADPH oxidase complex. Transmission electron micrososcopy images showed that the membrane fractions were close to the NPs while fluorescence indicated an interaction between NPs and cytosolic proteins. Using a cell-free system, we have investigated the influence of TiO2 NPs on the behavior of the NADPH oxidase. In the absence of the classical activator molecules of the enzyme (arachidonic acid) but in the presence of TiO2 NPs, no production of superoxide ions could be detected indicating that TiO2 NPs were unable to activate by themselves the complex. However once the NADPH oxidase was activated (i.e., by arachidonic acid), the rate of superoxide anion production went up to 140% of its value without NPs, this effect being dependent on their concentration. In the presence of TiO2 nanoparticles, the NADPH oxidase produces more superoxide ions, hence induces higher oxidative stress. This hyper-activation and the subsequent increase in ROS production by TiO2 NPs could participate to the oxidative stress development.
authors.affiliation: Laboratoire de Chimie Physique, UMR 8000, Université Paris Sud Orsay France.|CNRS, UMR 8000, Orsay, France.
authors.forename: Rawand
authors.initials: R
authors.lastname: Masoud
authors.affiliation: Laboratoire de Chimie Physique, UMR 8000, Université Paris Sud Orsay France.|CNRS, UMR 8000, Orsay, France.
authors.forename: Tania
authors.initials: T
authors.lastname: Bizouarn
authors.affiliation: Institut Curie, Centre de Recherche, Centre Universitaire, Orsay, France.|INSERM U1196, Centre Universitaire, Orsay, France.|CNRS UMR9187, Centre Universitaire, Orsay, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Trepout
authors.affiliation: Synchrotron SOLEIL, L'Orme des Merisiers, Gif-sur-Yvette, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Wien
authors.affiliation: Laboratoire de Chimie Physique, UMR 8000, Université Paris Sud Orsay France.|CNRS, UMR 8000, Orsay, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Baciou
authors.affiliation: Institut Curie, Centre de Recherche, Centre Universitaire, Orsay, France.|INSERM U1196, Centre Universitaire, Orsay, France.|CNRS UMR9187, Centre Universitaire, Orsay, France.
authors.forename: Sergio
authors.initials: S
authors.lastname: Marco
authors.affiliation: Laboratoire de Chimie Physique, UMR 8000, Université Paris Sud Orsay France.|CNRS, UMR 8000, Orsay, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Houée Levin
mesh_terms: D000818:Animals; D002417:Cattle; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism*; D053758:Nanoparticles / Q000633:toxicity*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors; D014025:Titanium / Q000737:chemistry* / Q000633:toxicity*
chemical_list: D013481:Superoxides; C009495:titanium dioxide; D014025:Titanium; D019255:NADPH Oxidases