title: Unexpected function of the phagocyte NADPH oxidase in supporting hyperglycolysis in stimulated neutrophils: key role of 6-phosphofructo-2-kinase.
abstract: The phagocyte NADPH oxidase 2 (Nox2) is an enzymatic complex that is involved in innate immunity, notably via its capacity to produce toxic reactive oxygen species. Recently, a proteomic analysis of the constitutively active Nox2 complex, isolated from neutrophil fractions, highlighted the presence of 6-phosphofructo-2-kinase (PFK-2). The purpose of this work was to study the relationship between PFK-2 and NADPH oxidase in neutrophils. Data have underlined a specific association of the active phosphorylated form of PFK-2 with Nox2 complex in stimulated neutrophils. In its active form, PFK-2 catalyzes the production of fructose-2,6-bisphosphate, which is the main allosteric activator of phosphofructo-1-kinase, the limiting enzyme in glycolysis. Pharmacologic inhibition of PFK-2 phosphorylation and cell depletion in PFK-2 by a small interfering RNA strategy led to a decrease in the glycolysis rate and a reduction in NADPH oxidase activity in stimulated cells. Surprisingly, alteration of Nox2 activity impacted the glycolysis rate, which indicated that Nox2 in neutrophils was not only required for reactive oxygen species production but was also involved in supporting the energetic metabolism increase that was induced by inflammatory conditions. PFK-2 seems to be a strategic element that links NADPH oxidase activation and glycolysis modulation, and, as such, is proposed as a potential therapeutic target in inflammatory diseases.-Baillet, A., Hograindleur, M.-A., El Benna, J., Grichine, A., Berthier, S., Morel, F., Paclet, M.-H. Unexpected function of the phagocyte NADPH oxidase in supporting hyperglycolysis in stimulated neutrophils: key role of 6-phosphofructo-2-kinase.
authors: Groupe de Recherche et D'etude du Processus Inflammatoire (GREPI), EA 7408, Université Grenoble Alpes, Saint-Martin-d'Hères, France.|Rheumatology Department, Centre Hospitalier Universitaire Grenoble Alpes, La Tronche, France; and.
authors: Athan
authors: A
authors: Baillet
authors: Groupe de Recherche et D'etude du Processus Inflammatoire (GREPI), EA 7408, Université Grenoble Alpes, Saint-Martin-d'Hères, France.
authors: Marc-André
authors: MA
authors: Hograindleur
authors: INSERM, Unité 1149, Centre National de la Recherche Scientifique ERL8252, Centre de Recherche sur l'Inflammation, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence Inflamex, Départements Hospitalo-Universitaires Fibrosis, Inflammation, Remodeling in Cardiovascular, Respiratory and Renal Diseases (DHU FIRE), Faculté de Médecine, Site Xavier Bichat, Paris, France; and.
authors: Jamel
authors: J
authors: El Benna
authors: Platform Optical Microscopy-Cell Imaging, Université Joseph Fourier, INSERM Unité 823, Institut Albert Bonniot, La Tronche, France.
authors: Alexei
authors: A
authors: Grichine
authors: Groupe de Recherche et D'etude du Processus Inflammatoire (GREPI), EA 7408, Université Grenoble Alpes, Saint-Martin-d'Hères, France.|Pôle Biologie, Centre Hospitalier Universitaire Grenoble Alpes, La Tronche, France.
authors: Sylvie
authors: S
authors: Berthier
authors: Groupe de Recherche et D'etude du Processus Inflammatoire (GREPI), EA 7408, Université Grenoble Alpes, Saint-Martin-d'Hères, France.
authors: Françoise
authors: F
authors: Morel
authors: Groupe de Recherche et D'etude du Processus Inflammatoire (GREPI), EA 7408, Université Grenoble Alpes, Saint-Martin-d'Hères, France; mhpaclet@chu-grenoble.fr.|Pôle Biologie, Centre Hospitalier Universitaire Grenoble Alpes, La Tronche, France.
authors: Marie-Hélène
authors: MH
authors: Paclet
mesh_terms: D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000502:physiology*; D006801:Humans; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D010586:Phagocytes / Q000201:enzymology*; D025481:Phosphofructokinase-2 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D034741:RNA, Small Interfering; D019255:NADPH Oxidases; D025481:Phosphofructokinase-2; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate
keywords: Nox2; PFK-2; PMN; energetic metabolism; reactive oxygen species