NADPH Oxidase Activity Research Articles

Microglial NOX2 as a therapeutic target in traumatic brain injury: Mechanisms, consequences, and potential for neuroprotection.

Microglial NOX2 as a therapeutic target in traumatic brain injury: Mechanisms, consequences, and potential for neuroprotection.

Sex- and age-dependent neurovascular abnormalities linked to neuroinflammation lead to exacerbated post-ischemic brain injury in Marfan syndrome mice.

Sex- and age-dependent neurovascular abnormalities linked to neuroinflammation lead to exacerbated post-ischemic brain injury in Marfan syndrome mice.

Activation and signaling characteristics of the hydroxy-carboxylic acid 3 receptor identified in human neutrophils through a microfluidic flow cell technique.

Activation and signaling characteristics of the hydroxy-carboxylic acid 3 receptor identified in human neutrophils through a microfluidic flow cell technique.

Effect of the probiotic Escherichia coli Nissle 1917 on serum levels of NADPH oxidase-2 and lipopolysaccharide in patients with Alzheimer's disease.

BackgroundIntestinal bacteria-derived molecules, such as lipopolysaccharide (LPS) produced by Gram-negative bacteria, can translocate into the bloodstream through the gut wall, contributing to inflammation and neurodegeneration via oxidative stress mechanisms. NADPH oxidase-2 activation and superoxide anion production play a key role in this process, particularly in conditions like Alzheimer's disease (AD), where gut permeability is often altered. This study hypothesized that modulating gut microbiota with the probiotic Escherichia coli Nissle 1917 (ECN) could mitigate LPS translocation and its associated inflammatory effects.ObjectiveTo evaluate the effect of daily ECN administration on serum LPS levels in elderly AD patients.MethodsA randomized, double-blind, placebo-controlled trial was conducted with 40 mild AD patients, with 39 completing the study (20 ECN, 19 placebo). Participants received ECN (2.5-25 × 10^9 CFU/capsule) or placebo for six weeks. The serum activity of soluble NOX2-dp (sNOX2-dp), hydrogen peroxide (H2O2) production, tumor necrosis factor (TNF)-α levels and LPS was evaluated, while serum zonulin levels were measured to assess gut permeability.ResultsThe ECN group showed significant reductions in sNOX2-dp (-21%), H2O2 (-27%), TNF-α (-18%), LPS (-15%), and zonulin (-35%), along with improved Mini-Mental State Examination (MMSE) scores. No significant changes were seen in the placebo group. Mixed ANOVA showed significant time-by-treatment interactions for zonulin (p = 0.04) and MMSE (p < 0.001). Changes in LPS correlated with changes in zonulin (Rs = 0.408, p = 0.011).ConclusionsECN may strengthen gut barrier function, reduce endotoxemia, and attenuate inflammation in AD, though larger studies are needed to confirm these findings.

Synthetic and Natural Red Food Dyes Affect Oxidative Metabolism and the Redox State in the Nauplii of Brine Shrimp Artemia franciscana

The food industry widely uses dyes from animal and plant sources, but their discharge into water bodies can harm aquatic animals. Red food dyes increase reactive oxygen species (ROS) production, disrupting redox homeostasis in Artemia franciscana nauplii, although the underlying mechanisms are unclear. In this study, we exposed Artemia franciscana cysts for 48 h to three different red dyes: E124 (synthetic), E120 (animal-based) or Vegan red (plant-based) and evaluated the oxidative metabolism and redox status in the hatched nauplii. Only E120 and VEG increased oxygen consumption. E124 and VEG increased mitochondrial Complex I activity, while all dyes enhanced the activity of Complex III. The levels of reactive oxygen species (ROS) and NADPH oxidase activity were increased by all red dyes. E120 and E124 increased antioxidant enzyme activity to a greater extent than VEG. Additionally, only E120 and E124 increased total antioxidant capacity. Nevertheless, E124 exposure induced redox imbalance (increased lipid and protein oxidative damage). Our data, as a whole, allow us to conclude that red dyes can influence the oxidative capacity and redox state of Artemia franciscana nauplii with more harmful effects in the presence of E124, thus drawing attention to their potentially severe influence on aquatic life.

Integrative multi-transcriptomic analysis uncovers core genes and potential defense mechanisms in rice-Magnoporthe oryzae interaction.

Multiple transcriptomic comprehensive analyses highlight key genes and cast new light on multifaceted pathways that may be important arenas in rice innate immunity against Magnoporthe oryzae blast disease. Magnaporthe oryzae (MOR) poses a significant threat to rice production worldwide. However, defense mechanisms in rice against MOR remain inadequately defined. In this study, a multi-transcriptomic integrative analysis on 441 samples from diverse microarrays and RNA-seq sets was conducted to reveal critical factors inrice defense against MOR infection. A robust pattern of 3534 upregulated genes and 2920 repressed genes was commonly identified across all MOR-infected arrays and RNA-seq profiles. Interestingly, enrichment analysis revealed a consistent triggering of endoplasmic reticulum (ER)-related mechanisms and citric acid cycle (TCA) influx in rice response to MOR infection across all the transcriptome profiles, suggesting their critical role in modulating rice immunity against the pathogen. By contrast, chloroplast and photosynthesis pathways were frequently repressed across all the profiles. Among ER-related mechanisms, the phagosome pathway involved in the activation of NADPH oxidase was highly triggered in early response to MOR infection. Moreover, WGCNA analysis highlighted four key co-expressed gene modules and 80 significant hub genes associated with MOR infection. Among the core genes, Sec61 gene involved in the ER-translocation process was identified along with OsMFP (peroxisomal oxidation gene) and OSAHH gene (involved in cyclic-trans-methylation). Furthermore, MPK6, WRKY24, NUP35, and NPR1 genes were observed as core co-expressed genes, suggesting their significance in regulating rice immunity against MOR. Our findings elucidate key genes and multifaceted mechanisms in rice-MOR interaction, proposing new informative clues that can be exploited to improve rice resistance against blast disease.

Alleviation of accelerated diabetic atherogenesis in STZ-treated apoE/NOX1 DKO mice, apoE-/-/tg-EC-DHFR mice, and by folic acid.

Alleviation of accelerated diabetic atherogenesis in STZ-treated apoE/NOX1 DKO mice, apoE-/-/tg-EC-DHFR mice, and by folic acid.

The brine shrimp Artemia franciscana as a model for astrobiological studies: Physiological adaptations to Mars-like atmospheric pressure conditions.

The brine shrimp Artemia franciscana as a model for astrobiological studies: Physiological adaptations to Mars-like atmospheric pressure conditions.

Human endogenous retrovirus W family envelope protein (ERVWE1) regulates macroautophagy activation and micromitophagy inhibition via NOXA1 in schizophrenia.

The human endogenous retrovirus type W envelope glycoprotein (ERVWE1), located at chromosome 7q21-22, has been implicated in the pathophysiology of schizophrenia. Our previous studies have shown elevated ERVWE1 expression in schizophrenia patients. Growing evidence suggests that autophagy dysfunction contributes to schizophrenia, yet the relationship between ERVWE1 and autophagy remains unclear. In this study, bioinformatics analysis of the human prefrontal cortex RNA microarray dataset (GSE53987) revealed that differentially expressed genes were predominantly enriched in autophagy-related pathways. Clinical data further demonstrated that serum levels of microtubule-associated protein 1 light chain 3β (LC3B), a key marker of macroautophagy, were significantly elevated in schizophrenia patients compared to controls, and positively correlated with ERVWE1 expression. Cellular and molecular experiments suggested that ERVWE1 promoted macroautophagy by increasing the LC3B II/I ratio, enhancing autophagosome formation, and reducing sequestosome 1 (SQSTM1) expression via upregulation of NADPH oxidase activator 1 (NOXA1). Concurrently, NOXA1 downregulated the expression of key micromitophagy-related genes, including PTEN-induced kinase 1 (PINK1), Parkin RBR E3 ubiquitin-protein ligase (Parkin), and the pyruvate dehydrogenase E1 subunit α 1 (PDHA1). As a result, ERVWE1, via NOXA1, inhibited micromitophagy by suppressing the expression of PINK1, Parkin, and PDHA1, thereby leading to impaired production of mitochondrial-derived vesicles (MDVs). Mechanistically, ERVWE1 enhanced NOXA1 transcription by upregulating upstream transcription factor 2 (USF2). In conclusion, ERVWE1 promotes macroautophagy and inhibits micromitophagy through USF2-NOXA1 axis, providing novel mechanistic insight into the role autophagy dysregulation in schizophrenia. These findings suggest that targeting autophagy pathways may offer novel therapeutic strategies for schizophrenia treatment.

Red light induced seed germination and seedling growth by modulating antioxidant defense system, Rubisco, and NADPH oxidase activities in Capsicum frutescens

In this study, the impact of light-emitting diodes (LEDs) in different spectrums was investigated on the seed germination and post-germinative performance of Capsicum frutescens seedlings. The seeds were exposed to different LED lights (full spectrum, white, red, blue, and red-blue) for 0, 1, 2, and 4 h (h). The seeds were placed for a week in darkness to investigate germination, and then the growth mechanisms were studied in four-week-old seedlings. Results indicated that germination percentage was promoted markedly under 2 h red and full lights and also in 1 h blue, which was accompanied by the regulation of H2O2 level and NADPH oxidase (NOX) activity. Sprout growth and height were more heightened under 2 h red light, but their contents decreased considerably under blue light with a rising incubation time. Red light induced more biomass yield, chlorophyll (Chl) pigments, Chl a/b ratio and florescence in four-week-old seedlings. Blue light also increased Chl pigments, but decreased biomass yield by enhancing malondialdehyde (MDA) level. Increased growth in seedlings treated to red light was associated with upregulating Rubisco gene expressions (rbcL and rbcS) and its activity. Red and red-blue lights promoted the activity of superoxide dismutase, glutathione reductase, and ascorbate peroxidase enzymes to increase ascorbic acid (ASA) production in the ascorbate–glutathione cycle. Total phenolic (0.22 mg DAG g− 1 DW), ASA (89.58 mg 100 g− 1 FW) and capsaicinoids (2.73 mg g− 1 DW) contents were heightened under red light, while carotenoid (11.78 µg g− 1 FW) content was more accumulated under blue light. The findings of this study suggest red light modulates NOX activity and H2O2 level for inducing seed germination and seedling quality in C. frutescens, which can create important implications for the production of antioxidant metabolites and increase the cultivation area of this plant.

High-mobility group protein B1 derived mutant peptide mB Box-97 inhibits the formation of neutrophil extracellular traps.

Neutrophil Extracellular Traps (NETs) are vital for innate immunity, playing a key role in controlling pathogen and biofilm proliferation. However, excessive NETosis is implicated in autoimmunity, inflammatory and neoplastic diseases, as well as thrombosis, stroke, and post-COVID-19 complications. Managing NETosis, therefore is a significant area of ongoing research. Herein, we have identified a peptide derived from HMGB1 that we have modified via a point mutation that is referred to as mB Box-97. In our recent study in a murine lung infection model, mB Box-97 was shown to be safe and effective at disrupting biofilms without eliciting an inflammatory response typically associated with HMGB1. Here we show that the lack of an inflammatory response of mB Box-97 is in part due to the inhibition of NETosis of which we investigated the mechanism of action. mB Box-97's anti-NETosis activity was assessed using human neutrophils with known NET inducers PMA, LPS, or Ionomycin. Additionally, mB Box-97's binding to Protein Kinase C (PKC), in addition to downstream effects on NADPH oxidase (NOX) activation, Reactive Oxygen Species (ROS) generation and thereby NETosis were assessed. mB Box-97 significantly inhibited NETosis regardless of the type of induction pathway. Mechanistically, mB Box-97 inhibits PKC activity likely through direct binding and thereby reduced downstream activities including NOX activation, ROS production and NETosis. mB Box-97 is a promising dual acting therapeutic candidate for managing NET-mediated pathologies and resolving biofilm infections. Our results reveal that PKC is a viable target for NETosis inhibition independent of NET inducer and worthy of further study. These findings pave the way for a novel class of therapeutics aimed at controlling excessive NETosis, potentially offering new treatments for a range of inflammatory and immune-related diseases.

Impairment of endothelial MerTK accelerates atherosclerosis development.

Atherosclerosis is a chronic inflammatory disease primarily affecting large arteries and is the leading cause of cardiovascular disease. MER proto-oncogene tyrosine kinase (MerTK) plays a key role in regulating efferocytosis, a process for the clearance of apoptotic cells. This study investigates the specific contribution of endothelial MerTK to atherosclerosis development. Big data analytics, human microarray analyses, proteomics, and a unique mouse model with MerTK deficiency in endothelial cells (MerTK flox/flox Tie2 Cre ) were utilized to elucidate the role of endothelial MerTK in atherosclerosis development. Our big data analytics, encompassing approximately 98881 cross analyses including 234 analyses for atherosclerosis in the aortic arch, along with human microarray data, reveal that inflammatory responses play a predominant role in atherosclerosis. In vivo, MerTK flox/flox Tie2 Cre mice and the littermate control MerTK flox/flox mice were used to establish an early stage of atherosclerosis model through a high-fat diet combined with AAV8-PCSK9 treatment. Consistent with big data analytics and human microarray analyses, our proteomics data showed that MerTK flox/flox Tie2 Cre mice demonstrated significantly enhanced proinflammatory signaling, mitochondrial dysfunction, and activated mitogen-activated protein kinase (MAPK) pathway compared to that of MerTK flox/flox mice. Endothelial MerTK deficiency induces endothelial dysfunction (enhanced endothelial inflammation, mitochondrial dysfunction, and activation of NADPH oxidases and MAPK signaling pathways) and subsequently causes smooth muscle cell (SMC) phenotypic alterations, ultimately promoting atherosclerosis development. Our findings provide strong evidence that endothelial MerTK impairment serves as a novel mechanism in promoting atherosclerosis development.

Hyperphosphataemia and NADPH Oxidase Regulation in Pathophysiological Processes: Implications for Oxidative Stress and Disease Progression.

Hyperphosphataemia is a key contributor to oxidative stress (OS) and cellular dysfunction across various pathological conditions. While numerous studies have associated phosphate overload with redox imbalances, the role of NADPH oxidase (NOX) in this process has received limited attention. NOX enzymes are major enzymatic sources of reactive oxygen species (ROS), and their activation has been implicated in the progression of chronic kidney disease, vascular calcification, metabolic disorders, and cancer development. Under hyperphosphataemic conditions, excessive ROS production exacerbates endothelial dysfunction, promotes vascular smooth muscle cell transdifferentiation, induces chronic inflammation, and facilitates tumour progression. Despite increasing evidence linking phosphate metabolism to NOX activation, the underlying molecular mechanisms remain poorly characterised. This review critically examines the relationship between hyperphosphataemia and NADPH oxidase-mediated OS and explores its impact on disease pathophysiology. By providing an integrated analysis of the current findings, this work aims to highlight the pathological consequences of phosphate-induced OS and identify potential therapeutic strategies to mitigate its effects.

Rod and spherical selenium nanoparticles: Physicochemical properties and effects on red blood cells and neutrophils.

Rod and spherical selenium nanoparticles: Physicochemical properties and effects on red blood cells and neutrophils.

Involvement of Oxidative Stress and Antioxidants in Modification of Cardiac Dysfunction Due to Ischemia-Reperfusion Injury.

Delayed reperfusion of the ischemic heart (I/R) is known to impair the recovery of cardiac function and produce a wide variety of myocardial defects, including ultrastructural damage, metabolic alterations, subcellular Ca2+-handling abnormalities, activation of proteases, and changes in cardiac gene expression. Although I/R injury has been reported to induce the formation of reactive oxygen species (ROS), inflammation, and intracellular Ca2+ overload, the generation of oxidative stress is considered to play a critical role in the development of cardiac dysfunction. Increases in the production of superoxide, hydroxyl radicals, and oxidants, such as hydrogen peroxide and hypochlorous acid, occur in hearts subjected to I/R injury. In fact, mitochondria are a major source of the excessive production of ROS in I/R hearts due to impairment in the electron transport system as well as activation of xanthine oxidase and NADPH oxidase. Nitric oxide synthase, mainly present in the endothelium, is also activated due to I/R injury, leading to the production of nitric oxide, which, upon combination with superoxide radicals, generates nitrosative stress. Alterations in cardiac function, sarcolemma, sarcoplasmic reticulum Ca2+-handling activities, mitochondrial oxidative phosphorylation, and protease activation due to I/R injury are simulated upon exposing the heart to the oxyradical-generating system (xanthine plus xanthine oxidase) or H2O2. On the other hand, the activation of endogenous antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, and the concentration of a transcription factor (Nrf2), which modulates the expression of various endogenous antioxidants, is depressed due to I/R injury in hearts. Furthermore, pretreatment of hearts with antioxidants such as catalase plus superoxide dismutase, N-acetylcysteine, and mercaptopropionylglycerine has been observed to attenuate I/R-induced subcellular Ca2+ handling and changes in Ca2+-regulatory activities; additionally, it has been found to depress protease activation and improve the recovery of cardiac function. These observations indicate that oxidative stress is intimately involved in the pathological effects of I/R injury and different antioxidants attenuate I/R-induced subcellular alterations and improve the recovery of cardiac function. Thus, we are faced with the task of developing safe and effective antioxidants as well as agents for upregulating the expression of endogenous antioxidants for the therapy of I/R injury.

Identification of hub genes and molecular mechanisms of association of PCOS, Breast and Ovarian Cancers using an Integrated Bioinformatics Analysis

Background: Oxidative stress plays a crucial role in various aspects of cancer and other diseases. While reactive oxygen species (ROS) serve as key signal molecules in physiological processes for normal functioning of the female reproductive system but have been implicated in pathological processes such as polycystic ovary syndrome (PCOS). Some studies have reported a significantly higher risk of endometrial cancer in women with PCOS, but the association of PCOS and common female cancers of breast and ovarian cancer has not been studied. Objective: The present study was undertaken to identify the hub genes and molecular pathways that are common amongst polycystic ovary syndrome and breast and ovarian cancers using bioinformatics based on the interactomes of these diseases. Methodology: Common differentially expressed genes (DEGs) of PCOS, breast and ovarian cancer were retrieved from GEO for analysis of datasets using R-software. An interactome of the common DEGs and their interacting partners was built in the STRING database, followed by analysis using different Cytoscape plugins to identify and validate the hub genes and their functional enrichment. Results: The identified hub proteins, namely CYBA, CYBB, DUOX1, NCF1, NCF2, NCF4, NOX1, NOX3, NOXA1, and NOXO1, are components or regulators of the NADPH oxidase, which catalyzes the production of ROS that could promote carcinogenesis and metastasis in patients suffering from PCOS. Conclusion: NOX-derived ROS are essential for normal cellular functions and host defense against pathogens; however, excessive ROS production can lead to oxidative stress and contribute to various diseases such as PCOS and cancers. Therefore, regulating NADPH oxidase activity could potentially serve as a therapeutic approach for PCOS management and prevent the initiation and progression of cancers in females suffering from PCOS.

GATA3 modulation of mitochondrial oxidative stress inhibits cerebrovascular remodeling-mediated ischemic stroke by suppressing MBVSMC phenotypic transformation.

GATA3 modulation of mitochondrial oxidative stress inhibits cerebrovascular remodeling-mediated ischemic stroke by suppressing MBVSMC phenotypic transformation.

Carbon monoxide alleviates endotoxin-induced acute lung injury via NADPH oxidase inhibition in macrophages and neutrophils.

Carbon monoxide alleviates endotoxin-induced acute lung injury via NADPH oxidase inhibition in macrophages and neutrophils.

Intranasal Zinc Oxide Nanoparticles Induce Neuronal PANoptosis via Microglial Pathway.

Recent data have revealed an increased risk of respiratory exposure during the manufacturing process and application of nanomaterials, resulting in an increased incidence of neurodegenerative diseases in the general population. Zinc oxide nanoparticles (ZNPs) are among the most used nanomaterials in biomedical and manufactured consumer products. In this study, neurological dysfunction after intranasal administration of ZNPs is observed, in which the ZNPs enter the brain via the nose-to-brain pathway and accumulate in microglia but not in astrocytes or neurons. By using a coculture system of microglia and neurons, the ZNPs are found that induce microglia-derived oxidative stress injury and lead to neuronal cell PANoptosis. In this context, ZNPs induced the generation of reactive oxygen species (ROS) originating from microglial NADPH oxidase 2 (NOX2), which further induced neuronal membrane lipid peroxidation and increased Ca2+ influx and mitochondrial DNA release. The leaked mitochondrial DNA subsequently initiates PANoptosis of neurons. Importantly, inhibition of microglial NOX2 activation can significantly alleviate brain oxidative injury and rescue neuronal PANoptosis. This study can advance the understanding of the mode of neuronal cell death while underscoring the importance of the interconnections among glial cells and neurons, which is beneficial for informing effective interventions for respiratory exposure to nanoparticles.

Non-Infectious Complications of Chronic Granulomatous Disease: Knowledge Gaps & Novel Treatment Considerations.

Non-Infectious Complications of Chronic Granulomatous Disease: Knowledge Gaps & Novel Treatment Considerations.