Genetic Defects of Phagocyte Nadph Oxidase Activity and Activation

1989 ◽  
Vol 2 (2) ◽  
pp. 75-86
Author(s):  
P. Bellavite ◽  
Flavia Bazzoni ◽  
G. Scolaro ◽  
G. Poli ◽  
S. Dusi ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Protein A ◽  
Multicomponent System ◽  
Activation Mechanism ◽  
Molecular Entity ◽  
Genetic Defects ◽  
Phagocyte Nadph Oxidase ◽  
Key Enzyme ◽  
Molecular Nature

NADPH oxidase is the key enzyme of the free radical-generating oxidative matabolism of phagocytes. Work from our and other's laboratories has recently established that the oxidase is not a single molecular entity, but it is a multicomponent system including a NADPH-binding protein, a flavoprotein, a b-type cytochrome and other unidentified factors. A working model of the molecular nature and of the activation mechanism of phagocyte NADPH oxidase is here proposed. This model is suitable for the study and the classification of the molecular pathology of the oxidase system. The various genetic defects of the NADPH oxidase, that are the cause of chronic granulomatous disease, (CGD) are here presented and discussed.

scholarly journals Consequences of the constitutive NOX2 activity in living cells: cytosol acidification, apoptosis, and localized lipid peroxidation

2021 ◽  
Author(s):  
Hana Valenta ◽  
Sophie Dupré-Crochet ◽  
Tania Bizouarn ◽  
Laura Baciou ◽  
Oliver Nüsse ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Nadph Oxidase ◽  
Living Cells ◽  
Small Gtpase ◽  
Activation Mechanism ◽  
Cell Physiology ◽  
List Type ◽  
Catalytic Core ◽  
Cytosolic Proteins ◽  
Phagocyte Nadph Oxidase

ABSTRACTThe phagocyte NADPH oxidase (NOX2) is a key enzyme of the innate immune system generating superoxide anions (O2•−), precursors of reactive oxygen species. The NOX2 protein complex is composed of six subunits: two membrane proteins (gp91phox and p22phox) forming the catalytic core, three cytosolic proteins (p67phox, p47phox and p40phox) and a small GTPase Rac. The sophisticated activation mechanism of the NADPH oxidase relies on the assembly of cytosolic subunits with the membrane-bound components. A chimeric protein, called ‘Trimera’, composed of the essential domains of the cytosolic proteins p47phox (aa 1-286), p67phox (aa 1-212) and full-length Rac1Q61L, enables a constitutive and robust NOX2 activity in cells without the need of any stimulus. We employed Trimera as a single activating protein of the phagocyte NADPH oxidase in living cells and examined the consequences on the cell physiology of this continuous and long-term NOX activity. We showed that the sustained high level of NOX activity causes acidification of the intracellular pH, triggers apoptosis and leads to local peroxidation of lipids in the membrane. These local damages to the membrane correlate with the strong tendency of the Trimera to clusterize in the plasma membrane observed by FRET-FLIM microscopy.HighlightsTrimera is a tool to trigger a continuous ROS production in living cellsContinuous NOX2 activity causes cytosol acidification and apoptosisROS overproduction leads to localized oxidation of the membrane lipidsTrimera tends to clusterize in the plasma membrane of COSNOX and COS-7 cells

How Important are S100A8/S100A9 Calcium Binding Proteins for the Activation of Phagocyte NADPH Oxidase, Nox2

2009 ◽  
Vol 8 (4) ◽  
pp. 282-289 ◽  
Author(s):  
Sylvie Berthier ◽  
Athan Baillet ◽  
Marie-Helene Paclet ◽  
Philippe Gaudin ◽  
Francoise Morel
Keyword(s):  
Nadph Oxidase ◽  
Calcium Binding ◽  
Binding Proteins ◽  
Calcium Binding Proteins ◽  
Phagocyte Nadph Oxidase

scholarly journals Apocynin prevents GM-CSF-induced-ERK1/2 activation and -neutrophil survival independently of its inhibitory effect on the phagocyte NADPH oxidase NOX2

2020 ◽  
Vol 177 ◽  
pp. 113950
Author(s):  
Coralie Pintard ◽  
Marwa Ben Khemis ◽  
Dan Liu ◽  
Pham My-Chan Dang ◽  
Margarita Hurtado-Nedelec ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Inhibitory Effect ◽  
Gm Csf ◽  
Phagocyte Nadph Oxidase ◽  
Neutrophil Survival

scholarly journals STIM1 for stimulation of phagocyte NADPH oxidase

Blood ◽  
2014 ◽  
Vol 123 (14) ◽  
pp. 2129-2130
Author(s):  
Richard D. Ye
Keyword(s):  
Nadph Oxidase ◽  
Phagocyte Nadph Oxidase ◽  
Stimulation Of

scholarly journals Staphylococcus aureus, phagocyte NADPH oxidase and chronic granulomatous disease

2016 ◽  
pp. fuw042 ◽  
Author(s):  
Helene Buvelot ◽  
Klara M. Posfay-Barbe ◽  
Patrick Linder ◽  
Jacques Schrenzel ◽  
Karl-Heinz Krause
Keyword(s):  
Staphylococcus Aureus ◽  
Nadph Oxidase ◽  
Chronic Granulomatous Disease ◽  
Granulomatous Disease ◽  
Phagocyte Nadph Oxidase

scholarly journals The p47phox mouse knock-out model of chronic granulomatous disease.

1995 ◽  
Vol 182 (3) ◽  
pp. 751-758 ◽  
Author(s):  
S H Jackson ◽  
J I Gallin ◽  
S M Holland
Keyword(s):  
Nadph Oxidase ◽  
Chronic Granulomatous Disease ◽  
Fungal Infections ◽  
Critical Role ◽  
Granulomatous Inflammation ◽  
Mammalian Host ◽  
Granulomatous Disease ◽  
Knock Out ◽  
Phagocyte Nadph Oxidase ◽  
Life Threatening

Chronic granulomatous disease (CGD) is caused by a congenital defect in phagocyte reduced nicotinamide dinucleotide phosphate (NADPH) oxidase production of superoxide and related species. It is characterized by recurrent life-threatening bacterial and fungal infections and tissue granuloma formation. We have created a mouse model of CGD by targeted disruption of p47phox, one of the genes in which mutations cause human CGD. Identical to the case in human CGD, leukocytes from p47phox-/- mice produced no superoxide and killed staphylococci ineffectively. p47phox-/- mice developed lethal infections and granulomatous inflammation similar to those encountered in human CGD patients. This model mirrors human CGD and confirms a critical role for the phagocyte NADPH oxidase in mammalian host defense.

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