scholarly journals NADPH Oxidases (NOX): An Overview from Discovery, Molecular Mechanisms to Physiology and Pathology

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 890
Author(s):  
Annelise Vermot ◽  
Isabelle Petit-Härtlein ◽  
Susan M. E. Smith ◽  
Franck Fieschi
Keyword(s):  
Nadph Oxidase ◽  
Molecular Mechanisms ◽  
Structural Information ◽  
Regulation Of Gene Expression ◽  
Immune Defense ◽  
Ros Production ◽  
Phagocytic Cells ◽  
Nadph Oxidases ◽  
Phagocyte Nadph Oxidase ◽  
Wide Range

The reactive oxygen species (ROS)-producing enzyme NADPH oxidase (NOX) was first identified in the membrane of phagocytic cells. For many years, its only known role was in immune defense, where its ROS production leads to the destruction of pathogens by the immune cells. NOX from phagocytes catalyzes, via one-electron trans-membrane transfer to molecular oxygen, the production of the superoxide anion. Over the years, six human homologs of the catalytic subunit of the phagocyte NADPH oxidase were found: NOX1, NOX3, NOX4, NOX5, DUOX1, and DUOX2. Together with the NOX2/gp91phox component present in the phagocyte NADPH oxidase assembly itself, the homologs are now referred to as the NOX family of NADPH oxidases. NOX are complex multidomain proteins with varying requirements for assembly with combinations of other proteins for activity. The recent structural insights acquired on both prokaryotic and eukaryotic NOX open new perspectives for the understanding of the molecular mechanisms inherent to NOX regulation and ROS production (superoxide or hydrogen peroxide). This new structural information will certainly inform new investigations of human disease. As specialized ROS producers, NOX enzymes participate in numerous crucial physiological processes, including host defense, the post-translational processing of proteins, cellular signaling, regulation of gene expression, and cell differentiation. These diversities of physiological context will be discussed in this review. We also discuss NOX misregulation, which can contribute to a wide range of severe pathologies, such as atherosclerosis, hypertension, diabetic nephropathy, lung fibrosis, cancer, or neurodegenerative diseases, giving this family of membrane proteins a strong therapeutic interest.

scholarly journals The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

2007 ◽  
Vol 87 (1) ◽  
pp. 245-313 ◽  
Author(s):  
Karen Bedard ◽  
Karl-Heinz Krause
Keyword(s):  
Nadph Oxidase ◽  
Regulation Of Gene Expression ◽  
Nadph Oxidases ◽  
Phagocyte Nadph Oxidase ◽  
Current State ◽  
Wide Range ◽  
The Family ◽  
Activation Mechanisms ◽  
Long Time ◽  
Nox Family

For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phagocyte NADPH oxidase were found: NOX1, NOX3, NOX4, NOX5, DUOX1, and DUOX2. Together with the phagocyte NADPH oxidase itself (NOX2/gp91phox), the homologs are now referred to as the NOX family of NADPH oxidases. These enzymes share the capacity to transport electrons across the plasma membrane and to generate superoxide and other downstream reactive oxygen species (ROS). Activation mechanisms and tissue distribution of the different members of the family are markedly different. The physiological functions of NOX family enzymes include host defense, posttranlational processing of proteins, cellular signaling, regulation of gene expression, and cell differentiation. NOX enzymes also contribute to a wide range of pathological processes. NOX deficiency may lead to immunosuppresion, lack of otoconogenesis, or hypothyroidism. Increased NOX actvity also contributes to a large number or pathologies, in particular cardiovascular diseases and neurodegeneration. This review summarizes the current state of knowledge of the functions of NOX enzymes in physiology and pathology.

scholarly journals β-Aminobutyric Acid Primes an NADPH Oxidase–Dependent Reactive Oxygen Species Production During Grapevine-Triggered Immunity

2010 ◽  
Vol 23 (8) ◽  
pp. 1012-1021 ◽  
Author(s):  
Carole Dubreuil-Maurizi ◽  
Sophie Trouvelot ◽  
Patrick Frettinger ◽  
Alain Pugin ◽  
David Wendehenne ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Aminobutyric Acid ◽  
Ros Production ◽  
Oxygen Species ◽  
Defense Gene Expression ◽  
Diphenylene Iodonium ◽  
Signaling Events

The molecular mechanisms underlying the process of priming are poorly understood. In the present study, we investigated the early signaling events triggered by β-aminobutyric acid (BABA), a well-known priming-mediated plant resistance inducer. Our results indicate that, in contrast to oligogalacturonides (OG), BABA does not elicit typical defense-related early signaling events nor defense-gene expression in grapevine. However, in OG-elicited cells pretreated with BABA, production of reactive oxygen species (ROS) and expression of the respiratory-burst oxidase homolog RbohD gene were primed. In response to the causal agent of downy mildew Plasmopara viticola, a stronger ROS production was specifically observed in BABA-treated leaves. This process was correlated with an increased resistance. The NADPH oxidase inhibitor diphenylene iodonium (DPI) abolished this primed ROS production and reduced the BABA-induced resistance (BABA-IR). These results suggest that priming of an NADPH oxidase–dependent ROS production contributes to BABA-IR in the Vitis-Plasmopara pathosystem.

scholarly journals The biological characteristics of transcription factors AP-2α and AP-2γ and their importance in various types of cancers

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Damian Kołat ◽  
Żaneta Kałuzińska ◽  
Andrzej K. Bednarek ◽  
Elżbieta Płuciennik
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Cancer Tissue ◽  
Diagnostic Biomarkers ◽  
Oncological Patients ◽  
Wide Range ◽  
Non Coding Rnas

Abstract The Activator Protein 2 (AP-2) transcription factor (TF) family is vital for the regulation of gene expression during early development as well as carcinogenesis process. The review focusses on the AP-2α and AP-2γ proteins and their dualistic regulation of gene expression in the process of carcinogenesis. Both AP-2α and AP-2γ influence a wide range of physiological or pathological processes by regulating different pathways and interacting with diverse molecules, i.e. other proteins, long non-coding RNAs (lncRNA) or miRNAs. This review summarizes the newest information about the biology of two, AP-2α and AP-2γ, TFs in the carcinogenesis process. We emphasize that these two proteins could have either oncogenic or suppressive characteristics depending on the type of cancer tissue or their interaction with specific molecules. They have also been found to contribute to resistance and sensitivity to chemotherapy in oncological patients. A better understanding of molecular network of AP-2 factors and other molecules may clarify the atypical molecular mechanisms occurring during carcinogenesis, and may assist in the recognition of new diagnostic biomarkers.

scholarly journals Determinants shaping the nanoscale architecture of the mouse rod outer segment

2021 ◽  
Author(s):  
Matthias Pöge ◽  
Julia Mahamid ◽  
Sanae S Imanishi ◽  
Jürgen M Plitzko ◽  
Krzysztof Palczewski ◽  
...  
Keyword(s):  
Outer Segment ◽  
Molecular Mechanisms ◽  
Structural Information ◽  
Structural Basis ◽  
Radius Of Curvature ◽  
Rod Photoreceptor ◽  
Molecular Architecture ◽  
Structural Determinants ◽  
Rod Outer Segment ◽  
Wide Range

The unique membrane organization of the rod outer segment (ROS), the specialized sensory cilium of rod photoreceptor cells, provides the foundation for phototransduction, the initial step in vision. ROS architecture is characterized by a stack of identically shaped and tightly packed membrane disks loaded with the visual receptor rhodopsin. A wide range of genetic aberrations compromise ROS ultrastructure, impairing photoreceptor viability and function. Yet, the structural basis giving rise to the remarkable long range order of ROS membrane stacks and the molecular mechanisms underlying genetically inherited diseases remain elusive. Here, cryo-electron tomography (cryo-ET) performed on native ROS at molecular resolution provides insights into key structural determinants of ROS membrane architecture. Our data reveal the existence of two molecular connectors/spacers which likely contribute to the nanometer scale precise stacking of the ROS disks. We further show that the extreme radius of curvature at the disk rims is enforced by a continuous supramolecular assembly composed of peripherin-2 (PRPH2) and rod outer segment membrane protein 1 (ROM1) tetramers. We suggest that, together these molecular assemblies constitute the structural basis of the highly specialized ROS functional architecture. Cryo-ET therefore provides novel quantitative and structural information on the molecular architecture in ROS and insights into possible mechanisms underlying pathologies of certain PRPH2 mutations leading to blindness.

scholarly journals Unraveling the Molecular Pathophysiology of Myelodysplastic Syndromes

2011 ◽  
Vol 29 (5) ◽  
pp. 504-515 ◽  
Author(s):  
Rafael Bejar ◽  
Ross Levine ◽  
Benjamin L. Ebert
Keyword(s):  
Myelodysplastic Syndromes ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Response To Therapy ◽  
Predictors Of Response ◽  
Genetic Abnormalities ◽  
Wide Range ◽  
Risk Of Progression ◽  
Full Complement ◽  
Molecular Pathophysiology

Somatically acquired genetic abnormalities lead to the salient features that define myelodysplastic syndromes (MDS): clonal hematopoiesis, aberrant differentiation, peripheral cytopenias, and risk of progression to acute myeloid leukemia. Although specific karyotypic abnormalities have been linked to MDS for decades, more recent findings have demonstrated the importance of mutations within individual genes, focal alterations that are not apparent by standard cytogenetics, and aberrant epigenetic regulation of gene expression. The spectrum of genetic abnormalities in MDS implicates a wide range of molecular mechanisms in the pathogenesis of these disorders, including activation of tyrosine kinase signaling, genomic instability, impaired differentiation, altered ribosome function, and changes in the bone marrow microenvironment. Specific alterations present in individual patients with MDS may explain much of the heterogeneity in clinical phenotype associated with this disease and can predict prognosis and response to therapy. Elucidation of the full complement of genetic causes of MDS promises profound insight into the biology of the disease, improved classification and prognostic scoring schemes, and the potential for novel targeted therapies with molecular predictors of response.

scholarly journals Natural Compounds as Modulators of NADPH Oxidases

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Tullia Maraldi
Keyword(s):  
Mammalian Cells ◽  
Redox State ◽  
Regulation Of Gene Expression ◽  
Natural Compounds ◽  
Oxygen Species ◽  
Nadph Oxidases ◽  
Natural Extracts ◽  
Current State ◽  
Wide Range

Reactive oxygen species (ROS) are cellular signals generated ubiquitously by all mammalian cells, but their relative unbalance triggers also diseases through intracellular damage to DNA, RNA, proteins, and lipids. NADPH oxidases (NOX) are the only known enzyme family with the sole function to produce ROS. The NOX physiological functions concern host defence, cellular signaling, regulation of gene expression, and cell differentiation. On the other hand, increased NOX activity contributes to a wide range of pathological processes, including cardiovascular diseases, neurodegeneration, organ failure, and cancer. Therefore targeting these enzymatic ROS sources by natural compounds, without affecting the physiological redox state, may be an important tool. This review summarizes the current state of knowledge of the role of NOX enzymes in physiology and pathology and provides an overview of the currently available NADPH oxidase inhibitors derived from natural extracts such as polyphenols.

scholarly journals NADPH oxidase controls phagosomal pH and antigen cross-presentation in human dendritic cells

Blood ◽  
2008 ◽  
Vol 112 (12) ◽  
pp. 4712-4722 ◽  
Author(s):  
Adriana R. Mantegazza ◽  
Ariel Savina ◽  
Mónica Vermeulen ◽  
Laura Pérez ◽  
Jorge Geffner ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Nadph Oxidase ◽  
Tumor Antigens ◽  
Phagocytic Cells ◽  
Cross Presentation ◽  
Phagocyte Nadph Oxidase ◽  
Healthy Donors ◽  
Endosomal Ph ◽  
Human Dendritic Cells ◽  
Model Tumor

Abstract The phagocyte NADPH oxidase (NOX2) is critical for the bactericidal activity of phagocytic cells and plays a major role in innate immunity. We showed recently that NOX2 activity in mouse dendritic cells (DCs) prevents acidification of phagosomes, promoting antigen cross-presentation. Inorder to investigate the role of NOX2 in the regulation of the phagosomal pH in human DCs, we analyzed the production of reactive oxygen species (ROS) and the phagosomal/endosomal pH in monocyte-derived DCs and macrophages (MØs) from healthy donors or patients with chronic granulomatous disease (CGD). As expected, we found that human MØs acidify their phagosomes more efficiently than human DCs. Accordingly, the expression of the vacuolar proton ATPase (V-H+-ATPase) was higher in MØs than in DCs. Phagosomal ROS production, however, was also higher in MØs than in DCs, due to higher levels of gp91phox expression and recruitment to phagosomes. In contrast, in the absence of active NOX2, the phagosomal and endosomal pH decreased. Both in the presence of a NOX2 inhibitor and in DCs derived from patients with CGD, the cross-presentation of 2 model tumor antigens was impaired. We conclude that NOX2 activity participates in the regulation of the phagosomal and endosomal pH in human DCs, and is required for efficient antigen cross-presentation.

scholarly journals Accumulation of Cytochrome b558 at the Plasma Membrane: Hallmark of Oxidative Stress in Phagocytic Cells

2022 ◽  
Vol 23 (2) ◽  
pp. 767
Author(s):  
Stephenson B. Owusu ◽  
Sophie Dupré-Crochet ◽  
Tania Bizouarn ◽  
Chantal Houée-Levin ◽  
Laura Baciou
Keyword(s):  
Plasma Membrane ◽  
Nadph Oxidase ◽  
Irradiation Dose ◽  
Myeloid Cell ◽  
Good Alternative ◽  
Immune Defense ◽  
Cytotoxic Agents ◽  
Phagocytic Cells ◽  
Regulatory Subunits ◽  
Significant Difference

Neutrophils play a very key role in the human immune defense against pathogenic infections. The predominant players in this role during the activation of neutrophils are the release of cytotoxic agents stored in the granules and secretory vesicles and the massive production of reactive oxygen species (ROS) initiated by the enzyme NADPH oxidase. In addition, in living organisms, cells are continuously exposed to endogenous (inflammations, elevated neutrophil presence in the vicinity) and exogenous ROS at low and moderate levels (travels by plane, radiotherapy, space irradiation, blood banking, etc.). To study these effects, we used ROS induced by gamma radiation from low (0.2 Gy) to high (25 Gy) dose levels on PLB-985 cells from a myeloid cell line differentiated to neutrophil-like cells that are considered a good alternative to neutrophils. We determined a much longer lifetime of PLB-985 cells than that of neutrophils, which, as expected, decreased by increasing the irradiation dose. In the absence of any secondary stimulus, a very low production of ROS is detected with no significant difference between irradiated and non-irradiated cells. However, in phagocytosing cells, irradiation doses above 2 Gy enhanced oxidative burst in PLB-985 cells. Whatever the irradiation dose, NADPH oxidase devoid of its cytosolic regulatory units is observed at the plasma membrane in irradiated PLB-985 cells. This result is different from that observed for irradiated neutrophils in which irradiation also induced a translocation of regulatory subunits suggesting that the signal transduction mechanism or pathway operate differently in both cells.

scholarly journals The role of epigenetic regulation in adaptive phenotypic plasticity of plants

2021 ◽  
Vol 78 (5) ◽  
pp. 347-359
Author(s):  
E.L. Kordyum ◽  
◽  
D.V. Dubyna ◽  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Phenotypic Plasticity ◽  
Epigenetic Regulation ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Model Species ◽  
Wide Range ◽  
Adaptive Phenotypic Plasticity

In recent decades, knowledge about the role of epigenetic regulation of gene expression in plant responses to external stimuli and in adaptation of plants to adverse environmental fluctuations have extended significantly. DNA methylation is considered as the main molecular mechanism that provides genomic information and contributes to the understanding of the molecular basis of phenotypic variations based on epigenetic modifications. Unfortunately, the vast majority of research in this area has been performed on the model species Arabidopsis thaliana. The development of the methylation-sensitive amplified polymorphism (MSAP) method has made it possible to implement the large-scale detection of DNA methylation alterations in wild non-model and agricultural plants with large and highly repetitive genomes in natural and manipulated habitats. The article presents current information on DNA methylation in species of natural communities and crops and its importance in plant development and adaptive phenotypic plasticity, along with brief reviews of current ideas about adaptive phenotypic plasticity and epigenetic regulation of gene expression. The great potential of further studies of the epigenetic role in phenotypic plasticity of a wide range of non-model species in natural populations and agrocenoses for understanding the molecular mechanisms of plant existence in the changing environment in onto- and phylogeny, directly related to the key tasks of forecasting the effects of global warming and crop selection, is emphasized. Specific taxa of the Ukrainian flora, which, in authors’ opinion, are promising and interesting for this type of research, are recommended.

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