scholarly journals Impaired respiratory burst contributes to infections in PKCδ-deficient patients

2021 ◽  
Vol 218 (9) ◽  
Author(s):  
Anna-Lena Neehus ◽  
Kunihiko Moriya ◽  
Alejandro Nieto-Patlán ◽  
Tom Le Voyer ◽  
Romain Lévy ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Lupus Erythematosus ◽  
Autosomal Recessive ◽  
Neutrophil Extracellular Trap ◽  
Ros Production ◽  
Childhood Onset ◽  
Phagocyte Nadph Oxidase ◽  
Kinase C ◽  
Nadph Oxidase Complex ◽  
Low Levels

Patients with autosomal recessive protein kinase C δ (PKCδ) deficiency suffer from childhood-onset autoimmunity, including systemic lupus erythematosus. They also suffer from recurrent infections that overlap with those seen in patients with chronic granulomatous disease (CGD), a disease caused by defects of the phagocyte NADPH oxidase and a lack of reactive oxygen species (ROS) production. We studied an international cohort of 17 PKCδ-deficient patients and found that their EBV-B cells and monocyte-derived phagocytes produced only small amounts of ROS and did not phosphorylate p40phox normally after PMA or opsonized Staphylococcus aureus stimulation. Moreover, the patients’ circulating phagocytes displayed abnormally low levels of ROS production and markedly reduced neutrophil extracellular trap formation, altogether suggesting a role for PKCδ in activation of the NADPH oxidase complex. Our findings thus show that patients with PKCδ deficiency have impaired NADPH oxidase activity in various myeloid subsets, which may contribute to their CGD-like infectious phenotype.

scholarly journals p47phox siRNA-Loaded PLGA Nanoparticles Suppress ROS/Oxidative Stress-Induced Chondrocyte Damage in Osteoarthritis

Polymers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 443 ◽  
Author(s):  
Hyo Jung Shin ◽  
Hyewon Park ◽  
Nara Shin ◽  
Hyeok Hee Kwon ◽  
Yuhua Yin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Articular Chondrocytes ◽  
Cartilage Damage ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Plga Nanoparticles ◽  
Ros Production ◽  
Therapeutic Value ◽  
Joint Disorder ◽  
Low Levels

Osteoarthritis (OA) is the most common joint disorder that has had an increasing prevalence due to the aging of the population. Recent studies have concluded that OA progression is related to oxidative stress and reactive oxygen species (ROS). ROS are produced at low levels in articular chondrocytes, mainly by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and ROS production and oxidative stress have been found to be elevated in patients with OA. The cartilage of OA-affected rat exhibits a significant induction of p47phox, a cytosolic subunit of the NADPH oxidase, similarly to human osteoarthritis cartilage. Therefore, this study tested whether siRNA p47phox that is introduced with poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (p47phox si_NPs) can alleviate chondrocyte cell death by reducing ROS production. Here, we confirm that p47phox si_NPs significantly attenuated oxidative stress and decreased cartilage damage in mono-iodoacetate (MIA)-induced OA. In conclusion, these data suggest that p47phox si_NPs may be of therapeutic value in the treatment of osteoarthritis.

scholarly journals Functional modules and expression of mouse p40 phox and p67phox, SH3-domain-containing proteins involved in the phagocyte NADPH oxidase complex

1998 ◽  
Vol 251 (3) ◽  
pp. 573-582 ◽  
Author(s):  
Kazuhito Mizuki ◽  
Kenji Kadomatsu ◽  
Kenichiro Hata ◽  
Takashi Ito ◽  
Qi-Wen Fan ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Sh3 Domain ◽  
Functional Modules ◽  
Phagocyte Nadph Oxidase ◽  
Nadph Oxidase Complex

Cleaved N-terminal histone tails distinguish between NADPH oxidase (NOX)-dependent and NOX-independent pathways of neutrophil extracellular trap formation

2018 ◽  
Vol 77 (12) ◽  
pp. 1790-1798 ◽  
Author(s):  
Elmar Pieterse ◽  
Nils Rother ◽  
Cansu Yanginlar ◽  
Jelle Gerretsen ◽  
Sebastian Boeltz ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Nadph Oxidase ◽  
Lupus Erythematosus ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Neutrophil Extracellular Trap ◽  
Functional Responses ◽  
Serological Method ◽  
Independent Manner ◽  
Histone Tails

ObjectivesNeutrophil extracellular traps (NETs) act in various rheumatic diseases. Although NET formation was originally described as a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)-dependent pathway, it appears that there are also NOX-independent pathways of NET release. Currently, no tools are available that can discriminate between both NET-forming pathways. We aimed to develop a serological method allowing the discrimination between NETs generated through NOX-dependent or NOX-independent pathways.MethodsHistones from in vitro generated NOX-dependent and NOX-independent NETs were characterised with a panel of lupus-derived antibodies against N-terminal histone tails using immunofluorescence microscopy, western blot and ELISA. NETs in patients with NET-associated diseases, that is, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA) and sepsis, were characterised in sandwich ELISAs employing antibodies against myeloperoxidase (MPO) and N-terminal histone tails as detecting and capturing antibodies, respectively. Functional responses of endothelial cells to NOX-dependent and NOX-independent NETs were assessed as well.ResultsNeutrophil elastase cleaves the N-terminal tails of core histones during NOX-dependent, but not during NOX-independent NET formation. Consequently, the detection of MPO–histone complexes with antibodies against N-terminal histone tails allows discrimination between NETs formed through a NOX-dependent or NOX-independent manner. Characterisation of in vivo circulating NETs revealed the presence of NOX-independent NETs in RA, SLE and sepsis, but NOX-dependent NETs in PsA. NOX-independent NETs displayed an increased capacity to activate endothelial cells when compared with NOX-dependent NETs.ConclusionsThese results indicate heterogeneity in NET-forming pathways in vivo and highlight the need for disease-specific strategies to prevent NET-mediated pathology.

Correlation between NADPH Oxidase and Protein Kinase C in the ROS Production by Human Granulocytes Related to Age

Gerontology ◽  
2002 ◽  
Vol 48 (6) ◽  
pp. 354-359 ◽  
Author(s):  
Míriam Martins Chaves ◽  
Andreia Laura Prates Rodrigues ◽  
Ataualpa Pereira dos Reis ◽  
Nestor Carlos Gerzstein ◽  
José Augusto Nogueira-Machado
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Nadph Oxidase ◽  
Ros Production ◽  
Kinase C ◽  
Human Granulocytes

scholarly journals ROS production as a common mechanism of ENaC regulation by EGF, insulin, and IGF-1

2013 ◽  
Vol 304 (1) ◽  
pp. C102-C111 ◽  
Author(s):  
Daria V. Ilatovskaya ◽  
Tengis S. Pavlov ◽  
Vladislav Levchenko ◽  
Alexander Staruschenko
Keyword(s):  
Growth Factor ◽  
Nadph Oxidase ◽  
Collecting Duct ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Fine Tuning ◽  
Common Mechanism ◽  
Ros Production ◽  
Cortical Collecting Duct ◽  
Nadph Oxidase Complex

The epithelial Na+ channel (ENaC) is a key transporter participating in the fine tuning of Na+ reabsorption in the nephron. ENaC activity is acutely upregulated by epidermal growth factor (EGF), insulin, and insulin-like growth factor-1 (IGF-1). It was also proposed that reactive oxygen species (ROS) have a stimulatory effect on ENaC. Here we studied whether effects of EGF, insulin, and IGF-1 correlate with ROS production in the mouse cortical collecting duct (mpkCCDc14) cells. Western blotting confirmed the expression of the NADPH oxidase complex subunits in these cells. Treatment of mpkCCDc14 cells with EGF, insulin, or IGF-1 evoked an increase in ROS production as measured by CM-H2DCF-DA fluorescence. ROS production caused by a xanthine-xanthine oxidase reaction also resulted in a significant elevation in short-circuit current through the mpkCCDc14 monolayer. Transepithelial current measurements showed an acute increase of amiloride-sensitive current through the mpkCCDc14 monolayer in response to EGF, insulin, or IGF-1. Pretreatment with the nonselective NADPH oxidase activity inhibitor apocynin blunted both ROS production and increase in ENaC-mediated current in response to these drugs. To further test whether NADPH oxidase subunits are involved in the effect of EGF, we used a stable M-1 cell line with a knockdown of Rac1, which is one of the key subunits of the NADPH oxidase complex, and measured amiloride-sensitive currents in response to EGF. In contrast to control cells, EGF had no effect in Rac1 knockdown cells. We hypothesize that EGF, insulin, and IGF-1 have a common stimulatory effect on ENaC mediated by ROS production.

scholarly journals Regulation of the phagocyte NADPH oxidase activity: phosphorylation of gp91 phox /NOX2 by protein kinase C enhances its diaphorase activity and binding to Rac2, p67 phox , and p47 phox

2008 ◽  
Vol 23 (4) ◽  
pp. 1011-1022 ◽  
Author(s):  
Houssam Raad ◽  
Marie-Helene Paciet ◽  
Tarek Boussetta ◽  
Yolande Kroviarski ◽  
Françoise Morel ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Nadph Oxidase Activity ◽  
Phagocyte Nadph Oxidase ◽  
Diaphorase Activity ◽  
Kinase C
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