Immunostimulatory oligodeoxynucleotides induce dolphin neutrophil NADPH-oxidase activation in a CpG-independent but phosphorothioate backbone-dependent manner

Key Points Efferocytosis of ACs by inflammatory macrophages activates NADPH oxidase in a CD11b-TLR2/4-MyD88–dependent manner. ROS generated positively regulate acidification and proteolysis in efferosomes, and limit cross-presentation of AC-associated antigens.

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Differing structural requirements for GTPase-activating protein responsiveness and NADPH oxidase activation by Rac.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)31553-3 ◽

1994 ◽

Vol 269 (38) ◽

pp. 23569-23574

Author(s):

X. Xu ◽

D.C. Barry ◽

J. Settleman ◽

M.A. Schwartz ◽

G.M. Bokoch

Keyword(s):

Nadph Oxidase ◽

Gtpase Activating Protein ◽

Structural Requirements ◽

Nadph Oxidase Activation

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New Insights on NETosis Induced by Entamoeba histolytica: Dependence on ROS from Amoebas and Extracellular MPO Activity

Antioxidants ◽

10.3390/antiox10060974 ◽

2021 ◽

Vol 10 (6) ◽

pp. 974

Author(s):

César Díaz-Godínez ◽

Joshue Fabián Jorge-Rosas ◽

Mario Néquiz ◽

Santiago Martínez-Calvillo ◽

Juan P. Laclette ◽

...

Keyword(s):

Cell Surface ◽

Nadph Oxidase ◽

Entamoeba Histolytica ◽

Pathogen Detection ◽

Dependent Manner ◽

Antimicrobial Proteins ◽

Nadph Oxidase Activity ◽

Mitochondrial Ros ◽

Pre Treatment ◽

Dose Dependent

NETosis is a neutrophil process involving sequential steps from pathogen detection to the release of DNA harboring antimicrobial proteins, including the central generation of NADPH oxidase dependent or independent ROS. Previously, we reported that NETosis triggered by Entamoeba histolytica trophozoites is independent of NADPH oxidase activity in neutrophils, but dependent on the viability of the parasites and no ROS source was identified. Here, we explored the possibility that E. histolytica trophozoites serve as the ROS source for NETosis. NET quantitation was performed using SYTOX® Green assay in the presence of selective inhibitors and scavengers. We observed that respiratory burst in neutrophils was inhibited by trophozoites in a dose dependent manner. Mitochondrial ROS was not also necessary, as the mitochondrial scavenger mitoTEMPO did not affect the process. Surprisingly, ROS-deficient amoebas obtained by pre-treatment with pyrocatechol were less likely to induce NETs. Additionally, we detected the presence of MPO on the cell surface of trophozoites after the interaction with neutrophils and found that luminol and isoluminol, intracellular and extracellular scavengers for MPO derived ROS reduced the amount of NET triggered by amoebas. These data suggest that ROS generated by trophozoites and processed by the extracellular MPO during the contact with neutrophils are required for E. histolytica induced NETosis.

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Protein kinase C-α and -δ are required for NADPH oxidase activation in WKYMVm-stimulated IMR90 human fibroblasts

Archives of Biochemistry and Biophysics ◽

10.1016/j.abb.2006.11.009 ◽

2007 ◽

Vol 459 (2) ◽

pp. 288-294 ◽

Cited By ~ 18

Author(s):

Annalisa Iaccio ◽

Claudio Collinet ◽

Nicola Montesano Gesualdi ◽

Rosario Ammendola

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Nadph Oxidase ◽

Human Fibroblasts ◽

Kinase C ◽

Nadph Oxidase Activation

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Inositol-Requiring Enzyme 1-Dependent Activation of AMPK Promotes Brucella abortus Intracellular Growth

Journal of Bacteriology ◽

10.1128/jb.00868-15 ◽

2016 ◽

Vol 198 (6) ◽

pp. 986-993 ◽

Cited By ~ 7

Author(s):

Ning Liu ◽

Yingying Li ◽

Chunyan Dong ◽

Xiaohan Xu ◽

Pan Wei ◽

...

Keyword(s):

Nadph Oxidase ◽

Underlying Mechanism ◽

Peritoneal Macrophages ◽

Dependent Manner ◽

Ros Production ◽

Ampk Activation ◽

Intracellular Growth ◽

Serine Threonine Kinase ◽

Content Type ◽

Amp Activated Protein Kinase

ABSTRACTAMP-activated protein kinase (AMPK) is a serine/threonine kinase that is well conserved during evolution. AMPK activation inhibits production of reactive oxygen species (ROS) in cells via suppression of NADPH oxidase. However, the role of AMPK during the process ofBrucellainfection remains unknown. Our data demonstrate thatB. abortusinfection induces AMPK activation in HeLa cells in a time-dependent manner. The known AMPK kinases LKB1, CAMKKβ, and TAK1 are not required for the activation of AMPK byB. abortusinfection. Instead, this activation is dependent on the RNase activity of inositol-requiring enzyme 1 (IRE1). Moreover, we also found thatB. abortusinfection-induced IRE1-dependent activation of AMPK promotesB. abortusintracellular growth with peritoneal macrophages via suppression of NADPH-derived ROS production.IMPORTANCEPrevious studies showed thatB. abortusinfection does not promote any oxidative burst regulated by NADPH oxidase. However, the underlying mechanism remains elusive. We report for the first time that AMPK activation caused byB. abortusinfection plays important role in NADPH oxidase-derived ROS production.

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M1743 AKT and PKC Mediate NADPH Oxidase Activation, a Major Prosurvival Pathway in Pancreatic Cancer Cells, Through Transcriptional Up-Regulation of p22phox

Gastroenterology ◽

10.1016/s0016-5085(09)61943-0 ◽

2009 ◽

Vol 136 (5) ◽

pp. A-422

Author(s):

Mouad Edderkaoui ◽

Claudia J. Nitsche ◽

Guido Eibl ◽

Anna S. Gukovskaya

Keyword(s):

Pancreatic Cancer ◽

Nadph Oxidase ◽

Cancer Cells ◽

Pancreatic Cancer Cells ◽

Nadph Oxidase Activation

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Abstract 107: Apocynin Attenuates Isoproterenol-induced Myocardial Injury: Implications For Targeting Nadph Oxidase In Myocardial Fibrogenesis

Circulation Research ◽

10.1161/res.113.suppl_1.a107 ◽

2013 ◽

Vol 113 (suppl_1) ◽

Author(s):

Yu Chen ◽

Jingang Cui ◽

Qinbo Yang ◽

Chenglin Jia ◽

Minqi Xiong ◽

...

Keyword(s):

Oxidative Stress ◽

Nadph Oxidase ◽

Myocardial Fibrosis ◽

Myocardial Injury ◽

Oxidase Inhibitor ◽

Ros Generation ◽

Dependent Manner ◽

Expression Of Genes ◽

Therapeutic Development ◽

Myocardial Injuries

Myocardial fibrosis results from cardiac injuries caused by various pathophysiological mechanisms including myocardial infarction, leading to destruction of myocardial architecture and progressive cardiac dysfunction. Oxidative stress is likely involved in myocardial ischemic injury and the subsequent tissue remodeling mediated by myocardial fibrogenesis. Our current study aimed to evaluate the implication of NADPH oxidase in overproduction of reactive oxygen species and its contribution to the pathogenesis of myocardial fibrogenesis after ischemic injuries. The effects of Apocynin, a selective NADPH oxidase inhibitor, were evaluated in the mouse model of isoproterenol-induced myocardial injury by histopathological approaches and whole-genome gene expression profiling. The results demonstrated that Apocynin was able to inhibit the development of ISO-induced myocardial necrotic lesions and fibrogenesis in a dose-dependent manner. Moreover, the preventive effects of Apocynin on myocardial injuries were associated with suppressed expression of genes implicated in inflammation responses and extracellular matrix, which were remarkably upregulated by isoproterenol administration. In summary, o ur study provides proof-of-concept for the involvement of NADPH oxidase-mediated ROS generation in myocardial ischemic injuries and fibrogenesis, which will benefit the mechanism-based therapeutic development targeting NADPH oxidase and oxidative stress in treating myocardial fibrosis and related disorders.

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A Novel H+ Conductance in Eosinophils

Journal of Experimental Medicine ◽

10.1084/jem.190.2.183 ◽

1999 ◽

Vol 190 (2) ◽

pp. 183-194 ◽

Cited By ~ 106

Author(s):

Botond Bánfi ◽

Jacques Schrenzel ◽

Oliver Nüsse ◽

Daniel P. Lew ◽

Erzsébet Ligeti ◽

...

Keyword(s):

Nadph Oxidase ◽

The Novel ◽

Experimental Conditions ◽

Intact Cells ◽

Electrophysiological Studies ◽

Dependent Signal ◽

Low Threshold ◽

Nadph Oxidase Activation ◽

In Cells

Efficient mechanisms of H+ ion extrusion are crucial for normal NADPH oxidase function. However, whether the NADPH oxidase—in analogy with mitochondrial cytochromes—has an inherent H+ channel activity remains uncertain: electrophysiological studies did not find altered H+ currents in cells from patients with chronic granulomatous disease (CGD), challenging earlier reports in intact cells. In this study, we describe the presence of two different types of H+ currents in human eosinophils. The “classical” H+ current had properties similar to previously described H+ conductances and was present in CGD cells. In contrast, the “novel” type of H+ current had not been described previously and displayed unique properties: (a) it was absent in cells from gp91- or p47-deficient CGD patients; (b) it was only observed under experimental conditions that allowed NADPH oxidase activation; (c) because of its low threshold of voltage activation, it allowed proton influx and cytosolic acidification; (d) it activated faster and deactivated with slower and distinct kinetics than the classical H+ currents; and (e) it was ∼20-fold more sensitive to Zn2+ and was blocked by the histidine-reactive agent, diethylpyrocarbonate (DEPC). In summary, our results demonstrate that the NADPH oxidase or a closely associated protein provides a novel type of H+ conductance during phagocyte activation. The unique properties of this conductance suggest that its physiological function is not restricted to H+ extrusion and repolarization, but might include depolarization, pH-dependent signal termination, and determination of the phagosomal pH set point.

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Olfactomedin 4 contributes to hydrogen peroxide-induced NADPH oxidase activation and apoptosis in mouse neutrophils

AJP Cell Physiology ◽

10.1152/ajpcell.00336.2017 ◽

2018 ◽

Vol 315 (4) ◽

pp. C494-C501 ◽

Cited By ~ 3

Author(s):

Wenli Liu ◽

Yueqin Liu ◽

Hongzhen Li ◽

Griffin P. Rodgers

Keyword(s):

Hydrogen Peroxide ◽

Nadph Oxidase ◽

Molecular Mechanisms ◽

Oxidase Inhibitor ◽

Superoxide Production ◽

Wild Type ◽

Escherichia Coli Bacteria ◽

Induced Apoptosis ◽

Nadph Oxidase Activation ◽

Deficient Mice

Neutrophils increase production of reactive oxygen species, including superoxide, hydrogen peroxide (H2O2), and hydroxyl radical, to destroy invading microorganisms under pathological conditions. Conversely, oxidative stress conditions, such as the presence of H2O2, induce neutrophil apoptosis, which helps to remove neutrophils after inflammation. However, the detailed molecular mechanisms that are involved in the latter process have not been elucidated. In this study, we investigated the potential role of olfactomedin 4 (Olfm4) in H2O2-induced superoxide production and apoptosis in mouse neutrophils. We have demonstrated that Olfm4 is not required for maximal-dosage PMA- and Escherichia coli bacteria-induced superoxide production, but Olfm4 contributes to suboptimal-dosage PMA- and H2O2-induced superoxide production. Using an NADPH oxidase inhibitor and gp91phox-deficient mouse neutrophils, we found that NAPDH oxidase was required for PMA-stimulated superoxide production and that Olfm4 mediated H2O2-induced superoxide production through NADPH oxidase, in mouse neutrophils. We have shown that neutrophils from Olfm4-deficient mice exhibited reduced H2O2-induced apoptosis compared with neutrophils from wild-type mice. We also demonstrated that neutrophils from Olfm4-deficient mice exhibited reduced H2O2-stimulated mitochondrial damage and membrane permeability, and as well as reduced caspase-3 and caspase-9 activity, compared with neutrophils from wild-type mice. Moreover, the cytoplasmic translocation of the proapoptotic mitochondrial proteins Omi/HtrA2 and Smac/DIABLO in response to H2O2was reduced in neutrophils from Olfm4-deficient mice compared with neutrophils from wild-type mice. Our study demonstrates that Olfm4 contributes to H2O2-induced NADPH oxidase activation and apoptosis in mouse neutrophils. Olfactomedin 4 might prove to be a potential target for future studies on inflammatory neutrophil biology and for inflammatory disease treatment.

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