Academic literature on the topic 'NADPH oxidase (Nox) family'
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Journal articles on the topic "NADPH oxidase (Nox) family"
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Bedard, Karen, and Karl-Heinz Krause. "The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology." Physiological Reviews 87, no. 1 (January 2007): 245–313. http://dx.doi.org/10.1152/physrev.00044.2005.
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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.
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Maturana, Andrés, Karl-Heinz Krause, and Nicolas Demaurex. "NOX Family NADPH Oxidases." Journal of General Physiology 120, no. 6 (November 25, 2002): 781–86. http://dx.doi.org/10.1085/jgp.20028713.
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Donkó, Ágnes, Zalán Péterfi, Adrienn Sum, Thomas Leto, and Miklós Geiszt. "Dual oxidases." Philosophical Transactions of the Royal Society B: Biological Sciences 360, no. 1464 (November 4, 2005): 2301–8. http://dx.doi.org/10.1098/rstb.2005.1767.
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Reactive oxygen species (ROS) have an important role in various physiological processes including host defence, mitogenesis, hormone biosynthesis, apoptosis and fertilization. Currently, the most characterized ROS-producing system operates in phagocytic cells, where ROS generated during phagocytosis act in host defence. Recently, several novel homologues of the phagocytic oxidase have been discovered and this protein family is now designated as the NOX/DUOX family of NADPH oxidases. NOX/DUOX enzymes function in a variety of tissues, including colon, kidney, thyroid gland, testis, salivary glands, airways and lymphoid organs. Importantly, members of the enzyme family are also found in non-mammalian species, including Caenorhabditis elegans and sea urchin. The physiological functions of novel NADPH oxidase enzymes are currently largely unknown. This review focuses on our current knowledge about dual oxidases.
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Vermot, Annelise, Isabelle Petit-Härtlein, Susan M. E. Smith, and Franck Fieschi. "NADPH Oxidases (NOX): An Overview from Discovery, Molecular Mechanisms to Physiology and Pathology." Antioxidants 10, no. 6 (June 1, 2021): 890. http://dx.doi.org/10.3390/antiox10060890.
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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.
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Gray, Stephen P., Ajay M. Shah, and Ioannis Smyrnias. "NADPH oxidase 4 and its role in the cardiovascular system." Vascular Biology 1, no. 1 (August 12, 2019): H59—H66. http://dx.doi.org/10.1530/vb-19-0014.
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The heart relies on complex mechanisms that provide adequate myocardial oxygen supply in order to maintain its contractile function. At the cellular level, oxygen undergoes one electron reduction to superoxide through the action of different types of oxidases (e.g. xanthine oxidases, uncoupled nitric oxide synthases, NADPH oxidases or NOX). Locally generated oxygen-derived reactive species (ROS) are involved in various signaling pathways including cardiac adaptation to different types of physiological and pathophysiological stresses (e.g. hypoxia or overload). The specific effects of ROS and their regulation by oxidases are dependent on the amount of ROS generated and their specific subcellular localization. The NOX family of NADPH oxidases is a main source of ROS in the heart. Seven distinct Nox isoforms (NOX1–NOX5 and DUOX1 and 2) have been identified, of which NOX1, 2, 4 and 5 have been characterized in the cardiovascular system. For the purposes of this review, we will focus on the effects of NADPH oxidase 4 (NOX4) in the heart.
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Montezano, Augusto C., Dylan Burger, Graziela S. Ceravolo, Hiba Yusuf, Maria Montero, and Rhian M. Touyz. "Novel Nox homologues in the vasculature: focusing on Nox4 and Nox5." Clinical Science 120, no. 4 (November 2, 2010): 131–41. http://dx.doi.org/10.1042/cs20100384.
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The Noxes (NADPH oxidases) are a family of ROS (reactive oxygen species)-generating enzymes. Of the seven family members, four have been identified as important sources of ROS in the vasculature: Nox1, Nox2, Nox4 and Nox5. Although Nox isoforms can be influenced by the same stimulus and co-localize in cellular compartments, their tissue distribution, subcellular regulation, requirement for cofactors and NADPH oxidase subunits and ability to generate specific ROS differ, which may help to understand the multiplicity of biological functions of these oxidases. Nox4 and Nox5 are the newest isoforms identified in the vasculature. Nox4 is the major isoform expressed in renal cells and appear to produce primarily H2O2. The Nox5 isoform produces ROS in response to increased levels of intracellular Ca2+ and does not require the other NADPH oxidase subunits for its activation. The present review focuses on these unique Noxes, Nox4 and Nox5, and provides novel concepts related to the regulation and interaction in the vasculature, and discusses new potential roles for these isoforms in vascular biology.
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Bánfi, Botond, Brigitte Malgrange, Judit Knisz, Klaus Steger, Michel Dubois-Dauphin, and Karl-Heinz Krause. "NOX3, a Superoxide-generating NADPH Oxidase of the Inner Ear." Journal of Biological Chemistry 279, no. 44 (August 23, 2004): 46065–72. http://dx.doi.org/10.1074/jbc.m403046200.
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Reactive oxygen species (ROS) play a major role in drug-, noise-, and age-dependent hearing loss, but the source of ROS in the inner ear remains largely unknown. Herein, we demonstrate that NADPH oxidase (NOX) 3, a member of the NOX/dual domain oxidase family of NADPH oxidases, is highly expressed in specific portions of the inner ear. As assessed by real-time PCR, NOX3 mRNA expression in the inner ear is at least 50-fold higher than in any other tissues where its expression has been observed (e.g.fetal kidney, brain, skull). Microdissection andin situhybridization studies demonstrated that NOX3 is localized to the vestibular and cochlear sensory epithelia and to the spiral ganglions. Transfection of human embryonic kidney 293 cells with NOX3 revealed that it generates low levels of ROS on its own but produces high levels of ROS upon co-expression with cytoplasmic NOX subunits. NOX3-dependent superoxide production required a stimulus in the absence of subunits and upon co-expression with phagocyte NADPH oxidase subunits p47phoxand p67phox, but it was stimulus-independent upon co-expression with colon NADPH oxidase subunits NOX organizer 1 and NOX activator 1. Pre-incubation of NOX3-transfected human embryonic kidney 293 cells with the ototoxic drug cisplatin markedly enhanced superoxide production, in both the presence and the absence of subunits. Our data suggest that NOX3 is a relevant source of ROS generation in the cochlear and vestibular systems and that NOX3-dependent ROS generation might contribute to hearing loss and balance problems in response to ototoxic drugs.
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Maraldi, Tullia. "Natural Compounds as Modulators of NADPH Oxidases." Oxidative Medicine and Cellular Longevity 2013 (2013): 1–10. http://dx.doi.org/10.1155/2013/271602.
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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.
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Roy, Krishnendu, Yongzhong Wu, Jennifer L. Meitzler, Agnes Juhasz, Han Liu, Guojian Jiang, Jiamo Lu, Smitha Antony, and James H. Doroshow. "NADPH oxidases and cancer." Clinical Science 128, no. 12 (March 27, 2015): 863–75. http://dx.doi.org/10.1042/cs20140542.
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The mechanism by which reactive oxygen species (ROS) are produced by tumour cells remained incompletely understood until the discovery over the last 15 years of the family of NADPH oxidases (NOXs 1–5 and dual oxidases DUOX1/2) which are structural homologues of gp91phox, the major membrane-bound component of the respiratory burst oxidase of leucocytes. Knowledge of the roles of the NOX isoforms in cancer is rapidly expanding. Recent evidence suggests that both NOX1 and DUOX2 species produce ROS in the gastrointestinal tract as a result of chronic inflammatory stress; cytokine induction (by interferon-γ, tumour necrosis factor α, and interleukins IL-4 and IL-13) of NOX1 and DUOX2 may contribute to the development of colorectal and pancreatic carcinomas in patients with inflammatory bowel disease and chronic pancreatitis, respectively. NOX4 expression is increased in pre-malignant fibrotic states which may lead to carcinomas of the lung and liver. NOX5 is highly expressed in malignant melanomas, prostate cancer and Barrett's oesophagus-associated adenocarcinomas, and in the last it is related to chronic gastro-oesophageal reflux and inflammation. Over-expression of functional NOX proteins in many tissues helps to explain tissue injury and DNA damage from ROS that accompany pre-malignant conditions, as well as elucidating the potential mechanisms of NOX-related damage that contribute to both the initiation and the progression of a wide range of solid and haematopoietic malignancies.
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Matuz-Mares, Deyamira, Héctor Vázquez-Meza, and María Magdalena Vilchis-Landeros. "NOX as a Therapeutic Target in Liver Disease." Antioxidants 11, no. 10 (October 16, 2022): 2038. http://dx.doi.org/10.3390/antiox11102038.
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The nicotinamide adenine dinucleotide phosphate hydrogen oxidase (NADPH oxidase or NOX) plays a critical role in the inflammatory response and fibrosis in several organs such as the lungs, pancreas, kidney, liver, and heart. In the liver, NOXs contribute, through the generation of reactive oxygen species (ROS), to hepatic fibrosis by acting through multiple pathways, including hepatic stellate cell activation, proliferation, survival, and migration of hepatic stellate cells; hepatocyte apoptosis, enhancement of fibrogenic mediators, and mediation of an inflammatory cascade in both Kupffer cells and hepatic stellate cells. ROS are overwhelmingly produced during malignant transformation and hepatic carcinogenesis (HCC), creating an oxidative microenvironment that can cause different and various types of cellular stress, including DNA damage, ER stress, cell death of damaged hepatocytes, and oxidative stress. NOX1, NOX2, and NOX4, members of the NADPH oxidase family, have been linked to the production of ROS in the liver. This review will analyze some diseases related to an increase in oxidative stress and its relationship with the NOX family, as well as discuss some therapies proposed to slow down or control the disease’s progression.
Dissertations / Theses on the topic "NADPH oxidase (Nox) family"
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Okasha, Mohamed Elsir Elnabeeb. "Identification and quantification of regional expression of members of the NADPH oxidase (NOX) enzyme family during the estrous cycles in the bovine oviduct /." Berlin : Mbv, 2009. http://d-nb.info/994595913/04.
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Okasha, Mohamed Elsir Elnageeb [Verfasser]. "Identification and quantification of regional expression of members of the NADPH oxidase (NOX) enzyme family during the estrous cycles in the bovine oviduct / Mohamed Elsir Elnageeb Okasha." Berlin : Freie Universität Berlin, 2009. http://d-nb.info/1023582287/34.
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Cavallin, Lucas E. "The Role of PDGF AND Rac1-induced Oxidative Signaling in the Viral Oncogenesis of Kaposi's Sarcoma." Scholarly Repository, 2010. http://scholarlyrepository.miami.edu/oa_dissertations/441.
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Kaposi's sarcoma (KS), caused by the oncogenic Kaposi's sarcoma herpesvirus (KSHV), is an angiogenic tumor characterized by intense angiogenesis, inflammation and proliferation of KSHV-infected spindle cells. We describe the characterization of a mouse model of KS by transfection of a KSHV bacterial artificial chromosome (KSHVBac36) into mouse bone marrow endothelial-lineage cells which generated a cell (mECK36) that forms KS-like tumors in mice. Our results define mECK36 as a biologically sensitive animal model of KSHV-dependent KS with the following characteristics: (1) the pathological phenotype is a consequence of KSHV gene expression in normal progenitor cells subjected to in vivo growth conditions, (2) the histopathologic phenotype of the tumors resembles KS lesions, and (3) the model is suitable for analysis of vGPCR-driven tumorigenesis in the context of the whole KSHV genome. The mechanism by which vGPCR promotes tumorigenesis is not fully understood. The characterization of a Rac1 transgenic mouse model that produces KS-like lesions that highly resemble human KS has helped us to identify the potential role of Rac1, which is activated by vGPCR, in the pathogenesis of KS. The results from the RacCA transgenic mouse suggest that viral and host genes triggering Rac1 and ROS production may play an important role in KS tumorigenesis. We set out to determine how vGPCR physiologically activates Rac1 in KSHV-infected cells in the KS model mECK36. We found that KSHV oncogenesis in mECK36 is promoted by vGPCR activation of a paracrine oncogenic mechanism through PDGF-BB, which requires a Rac1- and ROS-mediated loop, leading to STAT3 transcriptional activation of c-Myc, VEGF and KSHV latent viral gene expression. We also found that the latency-associated nuclear antigen (LANA) upregulates the PDGFR in vivo, priming latently-infected cells to the PDGF signaling pathway. This oncogenic mechanism can be targeted with the antioxidant N-acetylcysteine (NAC) and FDA-approved PDGF receptor inhibitors to control KSHV-induced tumorigenesis. Our results highlight a ROS-dependent axis whereby Rac1 activating oncogenes and inflammatory signaling drive paracrine stimulation of neoplastic growth and angiogenesis in neighboring cells, defining this axis and its components as attractive anti-tumor targets in KS pathogenesis.
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Chen, Alpha Yan. "Role of Intracellular Oxidant Release in Oxidised Low Lipoprotein - Induced U937 Cell Death." Thesis, University of Canterbury. School of Biological Science, 2012. http://hdl.handle.net/10092/7006.
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Atherosclerosis is a complex inflammation condition involving the accumulation of lipid-filled macrophages within the artery wall. Progression of the initial fatty streak to an advanced atherosclerotic plaque is characterized by the development of a necrotic core region containing cholesterol and dead cells. The oxidation of low-density lipoprotein (LDL) to oxidized LDL (oxLDL) and its subsequent uptake by macrophages to form foam cells are the key process in plaque formation. OxLDL is found within atherosclerotic plaque, and it is cytotoxic to a range of cells including macrophages through the generation of reactive oxygen species (ROS) and induction of oxidative stress.
The aim of this study was to examine the cytotoxic effects of oxLDL to U937 human monocyte-like cells. OxLDL caused a rapid concentration-dependent cell viability loss in U937 cells within 6 hours. The progression of oxLDL-induced cell death was found to be strongly correlated with the intracellular ROS production and intracellular glutathione (GSH) loss. OxLDL also caused a rapid loss of intracellular aconitase activity, indicating the impairment of the cellular metabolic function. The cytosolic calcium ion (Ca²⁺) level was also elevated by oxLDL, which could be from both intra- and extra-cellular sources.
OxLDL also activated plasma membrane superoxide generation complex NADPH oxidase (NOX), and the progression of oxLDL-induced NOX activation was correlated with oxLDL-mediated ROS production, suggesting NOX is the major source of ROS. Further investigations using NOX inhibitors apocynin or diphenyleneiodonium (DPI) found that inhibition of NOX prevented oxLDL-induced cell viability loss, ROS production, GSH loss and aconitase activity decrease. The cytosolic Ca²⁺ elevation caused by oxLDL was also suppressed slightly by inhibiting NOX activity. These results clearly show that NOX is the major site of oxidative stress upon oxLDL activation, contributing to the oxLDL-induced cell death.
This study also examined the protective effect of 7,8-dihydroneopterin (7,8-NP) on oxLDL-induced oxidative stress. 7,8-NP dramatically protected cells from oxLDL-induced cell viability loss, ROS generation and aconitase activity loss. 7,8-NP also inhibited oxLDL-induced cytosolic Ca²⁺ influx particularly after 3 hours. 7,8-NP did not inhibited mitochondrial aconitase activity decrease caused by oxLDL, nor inhibited mitochondrial ROS production. This indicates the protective effect of 7,8-NP against oxLDL damage could primarily in cytoplasm. The failure of 7,8-NP protection from oxLDL activating NOX suggests that the protection of 7,8-NP against oxLDL-induced oxidative stress was not due to the inhibition of NOX activation, but by radical scavenging activity of the NOX products.
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Bednorz, Mariola [Verfasser]. "Die Rolle der NADPH-Oxidase (NOX)-Untereinheit, Nox Organizer 1 (NOXO1), in der Pathogenese des Zigarettenrauch-induzierten Lungenemphysem und der pulmonalen Hypertonie im Mausmodell / Mariola Bednorz." Gießen : Universitätsbibliothek, 2021. http://d-nb.info/1225774217/34.
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Lambeth, Elise. "Characterisation of a family of NADPH oxidase encoding genes in the roice blast Magnaporthe oryzae." Thesis, University of Exeter, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.529318.
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Karimi, Gilda. "Etude de l'assemblage de la NADPH oxydase du phagocyte." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA112025.
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La NADPH oxydase du phagocyte est une enzyme impliquée dans la défense immunitaire contre les pathogènes. Après activation du phagocyte, cette enzyme produit des ions superoxyde par réduction du dioxygène par le NADPH. Elle est constituée de quatre sous- unités cytosolubles (p47phox ; p67phox ; p40phox et Rac), et deux membranaires (gp91 ; p22phox). Son activation fait intervenir un processus complexe qui met en jeu des changements d’interaction entre les protéines la constituant et qui permet l’assemblage des six sous- unités. Afin d’obtenir des informations sur les processus d’assemblage et d’activation, j’ai reconstitué le complexe dans un système cell free à l’aide de protéines recombinantes pour pouvoir contrôler tous les paramètres. Dans ce travail nous avons comparé les modes d’activation de p47phox par phosphorylation, par mutation substitutionelle sérine - aspartate en position S303,S304 et S328 pour mimer la phosphorylation et enfin par addition d’acide arachidonique (AA) activateur connu de l’enzyme in vitro mais aussi in vivo. Bien qu’il ai été montré que ces trois méthodes ouvrent la protéine vers une conformation ayant des propriétés similaires, nous avons trouvé que les effets de ces méthodes d’activation sont significativement différents. Ainsi, les changement de conformation observés par dichroisme circulaire, sont dissemblables. Pour p47phox, l’addition de AA déstructure la protéine. La phosphorylation induit un déplacement bathochrome des bandes de CD qualitativement similaire, alors que les mutations S-D de p47phox provoquent un déplacement opposé. Pour le complexe p47phox-p67phox l’addition d’AA destructure le mélange tandis que la mutation induit relativement peu de changement. Nous avons mesuré les constantes de dissociation Kd du complexe p47phox-p67phox. Alors que pour les protéines « sauvages », le Kd est faible (4±2 nM), les mutations de p47phox ainsi que l’addition d’AA augmentent cette valeur jusqu’à environ 50 nM, montrant une diminution de l’affinité entre p47phox-p67phox. De même, sur le complexe entier, l’effet de la phosphorylation de p47phox est différent de la mutation. Nous avons mesuré les valeurs de EC50 relatives à p67phox pour les différentes formes de p47phox. L’activation de p47phox par phosphorylation diminue l’EC₅₀, alors que les doubles ou triple mutations augmentent sa valeur. Nous avons confirmé que la phosphorylation et la mutation sont insuffisantes pour activer l’enzyme. La présence de AA est indispensable pour le fonctionnement du complexe. L’ordre de fixation des sous unités cytosoliques semble indifférent mais il faut que tous les composants soient présents lors de l’ajout de AA. Enfin, la délétion de p47phox dans la partie C-terminale (aa 343 à 390, domaine d’interaction avec p67phox) il n’y a plus de formation du dimère mais l’enzyme fonctionne normalement. Ces résultats apportent des éléments nouveaux sur le rôle de la dimérisation p47 phox-p67 phox, non indispensable à l’activité du système et sur le rôle mineur de la phosphorylation dans l’activation de la NADPH oxydase in vitroThe NADPH oxidase of phagocytes is an enzyme involved in the innate defense of organisms against pathogens. After phagocyte activation, this enzyme produces superoxide ions by reduction of dioxygen by NADPH. It is constituted of four cytosolic sub-units (p47phox ; p67phox ; p40phox et Rac) and two membrane proteins (gp91 ; p22phox). Its activation takes place through a complex process that involves protein-protein interaction changes leading to assembly and functionning of the catalytic core. In order to obtain information on this process, I have reconstituted the enzyme in a cell free systeme using recombinant proteins, to be able to fully control all the measurement conditions. In this work, we have compared different activation modes of p47phox i) phosphorylation; ii) substitution serine - aspartate by mutations at positions S303, S304 and S328 to mimic phosphorylation; iii) addition of arachidonic acid (AA), a well known activator molecule in vitro. It has been shown that these three activating methods transform p47phox to an open configuration with similar characteristics. However, we have found that the effects of these methods are significantly different. Indeed, the conformational changes observed by circular dichroism are different. For p47phox, the addition of AA destructures the protein. Its phosphorylation induces a bathochromic displacement of the bands, whereas the mutations S-D lead to an opposite displacement. For the dimer p47phox-p67phox , the addition of AA destructures the proteins while mutations induce hardly no changes. We have measured the dissociation constant Kd of the complex p47phox-p67phox. For wild type proteins, Kd value is low (4±2 nM), while mutations of p47phox as well as addition of AA increase its value up to 50 nM, showing a decrease of affinity between p47phox and p67phox. Moreover, on the whole complex, the effect of phosphorylation of p47phox is different from mutations. We have shown that the EC50 values relative to p67phox are sensitive to the various modifications of p47phox. Phosphorylation of p47phox decreases EC₅₀, while double or triple mutations increase its value. We have confirmed that phosphorylation and mutation are not sufficient to activate the enzyme. The presence of AA is a prerequisite for the functionning of the complex, i.e. production of superoxide. The binding order of the cytosolic proteins seems random but it is necessary that all the components be present during the activation by AA. Finally, deletion of the C terminal part of p47phox (aa 343 to 390, interaction domain with p67phox) leads to the absence of dimer formation but does not affect the enzyme activity. These results bring new information on the role of dimerisation of p47-p67 and on that of phosphorylation in the activation of NADPH oxidase in vitro
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Debbabi, Maya. "Mécanismes de régulation de la NADPH Oxydase NOX1 : rôle de la phosphorylation de NOXA1 ( NOX Activator 1 ) et de NOXO1 ( NOX Organizer 1)." Phd thesis, Université Paris Sud - Paris XI, 2011. http://tel.archives-ouvertes.fr/tel-00769943.
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Les NADPH oxydases constituent une famille d'enzymes dont la fonction est dédiée à la production de formes réactives de l'oxygène. NOX1, un des membres de cette famille, est abondamment exprimée dans le colon et sa dérégulation pourrait être associée aux maladies inflammatoires chroniques de l'intestin. Les mécanismes qui modulent l'activation de NOX1 demeurent mal connus. Au cours de ma thèse je me suis donc intéressée à l'étude de la phosphorylation de NOXA1 et NOXO1, deux sous-unités régulatrices du complexe NOX1 et ai démontré 1) que la phosphorylation de NOXA1 constitue un mécanisme de régulation négative de l'activité de NOX1 en vue de maintenir l'activité constitutive du complexe à un niveau adéquat et non excessif. 2) pour la première fois, que NOXO1β est phosphorylée et que cette phosphorylation entraîne une hyperactivation de NOX1. L'ensemble de ces données montre que NOX1 est finement régulée. Par ce biais, NOX1 pourrait être impliquée dans la défense anti-infectieuse de l'intestin.
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Fan, Lampson Min. "The role of endothelial cells in the regulation of the vascular response to Angiotensin II." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:3723698f-11e4-456f-9988-4020ec94ae87.
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Aortic dissection is a detrimental disease with a high mortality. However, the mechanisms regulating the susceptibility to aortic dissection remain unknown. We hypothesize that endothelial oxidative stress due to the activation of the reactive oxygen species (ROS)-generating Nox2 enzyme may play an important role in the development of aortic dissection. To investigate this, we generated transgenic mice (C57BL/6J background) with endothelial specific over-expression of Nox2 (Nox2 Tg) under the control of a tie-2 promoter. Expression of the human Nox2 transgene was confirmed by qRT-PCR to be found only in endothelial cells (EC) isolated from transgenic mice, and not in Wt EC or vascular smooth muscle cells (VSMC) and macrophages isolated from either genotype. Wild-type (Wt) littermates and Nox2 Tg male mice (22-24 weeks old, n=11) were treated with saline or Ang II (1mg/kg/day) via subcutaneous mini-pump for 28 days. There was no significant difference in the pressor responses to Ang II between Wt and Nox2 Tg mice (Wt 121±7mmHg vs. Nox2-Tg 122±6mmHg). However, 5/11 Nox2 Tg mice developed aortic dissections compared to 0/11 Wt mice (P<0.05). Immunohistochemistry revealed significant increases in endothelial VCAM-1 expression, MMP activity and CD45+ inflammatory cell recruitment in the aortas of Nox2 Tg mice after 5 days of Ang II infusion. Inflammatory cell recruitment was confirmed by FACS analysis of cells from digested aortas (P<0.05). Explanted aortas from Nox2-Tg mice had significantly greater secreted pro-inflammatory cytokine, Cyclophilin A (CypA) both at baseline and after 5 days of Ang II infusion compared to Wt littermates. Compared to primary Wt EC and VSMC, Nox2-Tg primary EC, but not primary VSMC, had increased ROS production which was accompanied by increased endothelial CypA secretion and ERK1/2 activation. Furthermore, conditioned media from Nox2-Tg EC induced greater ERK1/2 phosphorylation compared to conditioned media from Wt controls. Knockdown of CypA from sEND.1 endothelial conditioned media by siRNA knockdown abolished VSMC Erk1/2 phosphorylation. In conclusion, we demonstrate for the first time that a specific increase in endothelial ROS through the over-expression of Nox2 was sufficient to induce aortic dissection in response to Ang II stimulation. Endothelial secreted CypA could be the signalling mechanism by which increased endothelial ROS regulates the inflammatory response and the susceptibility to aortic dissection.
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Hernandez, Isabelle. "Étude de l’expression, de l’activité et du rôle de la NADPH oxydase dans la villosité choriale au premier trimestre de la grossesse : implication dans la physiopathologie de la prééclampsie NADPH oxidase is the major source of placental superoxide in early pregnancy: association with MAPK pathway activation sFlt-1 secretion in early first trimester chorionic villi is associated with p38 MAPK pathway activation NADPH oxydase : enzyme potentiellement impliquée dans la physiopathologie de la prééclampsie." Thesis, Sorbonne Paris Cité, 2019. http://www.theses.fr/2019USPCB051.
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Le placenta est un organe transitoire permettant les échanges nutritionnel et gazeux entre la mère et le fœtus. Son unité structurale et fonctionnelle est la villosité choriale (VC), constituée en son centre d'un axe mésenchymateux bordé par une couche cellulaire de cytotrophoblastes villeux (CTV) fusionnant pour former la couche la plus externe : le syncytiotrophoblaste (ST), sécréteur d'hormones indispensables au maintien de la grossesse, notamment l'hCG. Au premier trimestre de la grossesse (T1), le placenta se développe dans un environnement pauvre en O2 dû à l'obstruction des artères utérines spiralées par des bouchons cytotrophoblastiques empêchant le sang maternel oxygéné de pénétrer dans la chambre intervilleuse (CIV). Dès 10 semaines d'aménorrhée (SA), ces bouchons se délitent, laissant entrer le flux sanguin dans la CIV au contact direct du placenta. La pO2 passe alors de 20 mmHg à 60 mmHg. En présence d'O2, la cellule produit des espèces réactives de l'oxygène (ERO) jouant le rôle de seconds messagers dans de multiples processus physiologiques (prolifération, différenciation, apoptose). Ils peuvent être cytotoxiques dans le cas du stress oxydant : la cellule possède un système de défense antioxydant permettant de maintenir le taux d'ERO intracellulaire à un niveau physiologique faible. L'équilibre des espèce pro- et anti-oxydantes est appelé homéostasie redox. Au T1, le placenta est soumis à une transition environnementale requérant l'adaptation de sa balance redox pour assurer le bon développement du placenta. Les objectifs de ce travail sont : (i) Déterminer la source principale d'anion superoxyde O2.- avant et après l'augmentation de la pO2 dans la CIV et étudier les défenses antioxydantes associées. (ii) Etudier l'impact de l'oxygéno-transition sur les voies redox-sensibles, notamment les MAPKs impliquées dans la prolifération et la différentiation trophoblastique. (iii) De déterminer au T1 l'influence de l'activité de la NADPH oxydase (Nox) placentaire sur la sécrétion du sFlt-1, facteur anti-angiogénique impliqué dans la physiopathologie de la prééclampsie (PE) afin de proposer de nouvelles réflexions concernant l'implication de la Nox dans la genèse de cette pathologie d'origine placentaire. Dans la VC (7-9 SA et 12-14 SA), la mesure de la production d'O2.- alliée à l'utilisation d'inhibiteurs spécifiques des différentes sources d'ERO montre que la Nox est la source principale d'O2.- au T1. Cette production est plus importante avant 10 SA et est associée à une modification de la localisation de la sous-unité organisatrice de Nox2, p47phox. Cette activation de la Nox placentaire est associée à une activation de la voie p38MAPK. p38 est localisée essentiellement dans le CTV au T1. L'expression génique et protéique des différentes isoformes de Nox révèle la présence de Nox2, Nox4 et Nox5 dans le trophoblaste au T1. Nox1 est cependant indétectable. L'activité des enzymes antioxydantes (SOD1, catalase, Gpx1) est augmentée à 12-14 SA, témoin de l'adaptation du système antioxydant à l'oxygéno-transition. L'exposition de VC à 7-9 SA au TGF-B1, activateur de Nox4 et de p38MAPK, associée à un inhibiteur de la voie p38 (SB203580), montre que l'activation de la voie p38 par le TGF-B1 entraine une augmentation de la sécrétion de sFlt-1. Cet effet est aboli par l'utilisation de SB203580. Dans notre modèle, l'exposition au TGF-B1 n'influence pas l'activation de la Nox. Cependant, l'utilisation d'un inhibiteur de Nox (DPI) permet de diminuer la sécrétion de sFlt-1. Ce travail a permis de montrer que la Nox est la source principale d'O2.- dans le placenta au premier trimestre en association avec l'activation de la voie p38MAPK. Nos résultats montrent que la sécrétion du sFlt-1 par la VC au premier trimestre est dépendante de la voie p38MAPK. Ce travail permettra une meilleure compréhension de l'implication des sources d'ERO dans le développement placentaire précoce et leur(s) rôle(s) dans la pathogenèse de la PEThe placenta is a transitory organ allowing gas and nutrients exchanges between mother and fetus. The structural and functional unit of the human placenta is the chorionic villi (CV). It is composed by a mesenchymal axis covered with a cellular layer called villous cytotrophoblast (VCT), which merges to form the syncytiotrophoblast (ST). The ST secretes hormones essential to maintain pregnancy, especially hCG. During the first trimester of pregnancy (T1), placenta develops itself in a poor oxygenated environment because of the obstruction of uterine spiraled arteries by cytotrophoblastic plugs which restrain the entry of the oxygenated maternal blood into the intervillous space (IVS). Between 10-12 gestational weeks (GW), the plugs will gradually disappear allowing blood to enter IVS in direct contact with CV. The pO2 will increase from 20 mmHg to 60 mmHg. Exposed to O2, the cell produces reactive oxygen species (ROS). ROS play a role as second messenger in redox-sensitive signaling pathways involved in physiological processes (proliferation, differentiation, apoptosis). They may become cytotoxic when oxidative stress occurs: the cell has an antioxidant defense system responsible for keeping low physiological levels of intracellular ROS, enough to ensure signal transduction. The balance between pro- and antioxidant systems is called redox homeostasis. The first trimester placenta is submitted to an environmental transition requiring redox balance adaptation to allow correct placental development in early pregnancy. The aim of this works are: (i) to determine the principal source of superoxide anion O2.- before and after the increase of pO2 in the intervillous space and the associated antioxidant defenses. (ii) To study the impact of the O2 transition on the activity of redox-sensitive pathways, specifically MAPKs involved in trophoblastic proliferation, differentiation. (iii) To determine, during T1, the placental NADPH oxidase (Nox) activity influence on the secretion of the antiangiogenic factor sFlt-1, which is involved in the pathophysiology of preeclampsia (PE), to offer new insight about Nox involvement in genesis of this pathology with placental origin. We measured the O2.- production in CV (7-9 GW vs. 12-14 GW). The O2.- assay was performed with specific inhibitors of ROS sources. The results show that NADPH oxidase (Nox) is the major source of O2.- in first trimester CV. Nox activity is significantly higher before 10 GW. This is confirmed by the modification of the Nox2 organizer subunit location, p47phox. This Nox activation in early stage of pregnancy is associated with p38 MAPK activation. p38 protein is mainly located within the villous cytotrophoblast in first trimester CV. Genic and protein expression study reveals the expression of Nox2, Nox4 and Nox5 isoforms in T1 trophoblast. Nox1 expression remains undetectable. The antioxidant enzymes (SOD1, catalase, and Gpx1) activities are increased at 12-14 GW, revealing an antioxidant system adaptation to the oxygen transition. We exposed CV from 7 to 9 GW to TGF-B1, described as an activator of Nox4 and p38MAPK, and to p38 inhibitor (SB203580). The results showed that the activation of p38MAPK pathway in first trimester CV by TGF-B1 increases the level of secreted sFlt-1. This effect is abolished using SB203580. TGF-B1 exposure does not influence the activation of placental Nox in our model, but the use of a Nox inhibitor (DPI) decreases the secretion of sFlt-1. To conclude, our work shows that Nox is the main source of O2.- in first trimester placenta and is associated with the activation of the p38MAPK pathway. Our results also demonstrate that first trimester CV sFlt-1 secretion relies on the p38MAPK activation. This work allows a better understanding of the cellular sources of ROS involvement in early placental development and their role in pathogenesis of preeclampsia
Book chapters on the topic "NADPH oxidase (Nox) family"
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Sumimoto, Hideki, Reiko Minakami, and Kei Miyano. "Soluble Regulatory Proteins for Activation of NOX Family NADPH Oxidases." In Methods in Molecular Biology, 121–37. New York, NY: Springer New York, 2019. http://dx.doi.org/10.1007/978-1-4939-9424-3_8.
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Rada, Balázs, and Thomas L. Leto. "Oxidative Innate Immune Defenses by Nox/Duox Family NADPH Oxidases." In Contributions to Microbiology, 164–87. Basel: KARGER, 2008. http://dx.doi.org/10.1159/000136357.
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Sumimoto, Hideki, Reiko Minakami, and Kei Miyano. "The Nox Family of NADPH Oxidases that Deliberately Produce Reactive Oxygen Species." In Frontiers of Gastrointestinal Research, 23–34. Basel: KARGER, 2010. http://dx.doi.org/10.1159/000319935.
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Miyano, Kei, and Hideki Sumimoto. "Assessment of the Role for Rho Family GTPases in NADPH Oxidase Activation." In Methods in Molecular Biology, 195–212. New York, NY: Springer New York, 2011. http://dx.doi.org/10.1007/978-1-61779-442-1_14.
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Abo, Arie, and Anthony W. Segal. "[29] Reconstitution of cell-free NADPH oxidase activity by purified components." In Small GTPases and Their Regulators Part B: Rho Family, 268–78. Elsevier, 1995. http://dx.doi.org/10.1016/0076-6879(95)56031-9.
Full textConference papers on the topic "NADPH oxidase (Nox) family"
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Zhao, Guiqing, Sherene Thomas, Gregory Kowalsky, John W. Christman, Feng Qian, Irena Levitan, Jing Deng, and Lei Xiao. "Lipopolysaccharide (LPS) Stimulation Up-regulates The Expression Of NADPH Oxidase (NOX) In Mouse Bone Marrow-derived Macrophages (BMDM)." In American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans. American Thoracic Society, 2010. http://dx.doi.org/10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a1277.
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Wang, Rong, Wan-Mohaiza Dashwood, Hui Nian, Naoto Tsuchiya, Hitoshi Nakagama, and Roderick Dashwood. "Abstract B84: NADPH oxidase 1 (NOX1) and related NOX isoforms as key mediators of NFκB signaling in colon cancer." In Abstracts: Frontiers in Cancer Prevention Research 2008. American Association for Cancer Research, 2008. http://dx.doi.org/10.1158/1940-6207.prev-08-b84.
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Lin, Yun, Nicholas Hoffman, Mark Aksoy, Madesh Muniswamy, and Steven Kelsen. "Cigarette Smoke-Induced Reactive Oxygen Species (ROS) Production In Human Airway Epithelial Cells Is Calcium And NADPH-Oxidase (NOX) Dependent." In American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California. American Thoracic Society, 2012. http://dx.doi.org/10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a4561.
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Thomas, Sherene, Guiqing Zhao, John W. Christman, and Lei Xiao. "Activation Of Toll-Like Receptor (TLR) 9 And TLR4 Differentially Regulate The Expression Of Nadph Oxidase (NOX) Enzyme Isoforms In Bone Marrow-Derived Macrophages (BMDM)." In American Thoracic Society 2011 International Conference, May 13-18, 2011 • Denver Colorado. American Thoracic Society, 2011. http://dx.doi.org/10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a2810.
Full textReports on the topic "NADPH oxidase (Nox) family"
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Dickman, Martin B., and Oded Yarden. Modulation of the Redox Climate and Phosphatase Signaling in a Necrotroph: an Axis for Inter- and Intra-cellular Communication that Regulates Development and Pathogenicity. United States Department of Agriculture, August 2011. http://dx.doi.org/10.32747/2011.7697112.bard.
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The long-term goals of our research are to understand the regulation of sclerotial development and pathogenicity in S. sclerotiorum. The focus in this project is on the elucidation of the signaling events and environmental cues that contribute to broad pathogenic success of S. sclerotiorum. In this proposal, we have taken advantage of the recent conceptual (ROS/PPs signaling) and technical (genome sequence availability and gene inactivation possibilities) developments to address the following questions, as appear in our research goals stated below, specifically concerning the involvement of REDOX signaling and protein dephosphorylation in the regulation of hyphal/sclerotial development and pathogenicity of S. sclerotiorum. Our stated specific objectives were to progress our understanding of the following questions: (i) Which ROS species affect S. sclerotiorum development and pathogenicity? (ii) In what manner do PPs affect S. sclerotiorum development and pathogenicity? (iii) Are PPs affected by ROS production and does PP activity affect ROS production and SMK1? (iv) How does Sclerotinia modulate the redox environment in both host and pathogen? While addressing these questions, our main findings include the identification and characterization the NADPH oxidase (NOX) family in S. sclerotiorum. Silencing of Ssnox1 indicated a central role for this enzyme in both virulence and pathogenic (sclerotial) development, while inactivation of Ssnox2 resulted in limited sclerotial development but remained fully pathogenic. Interestingly, we found a consistent correlation with Ssnox1(involved with pathogenicity) and oxalate levels. This same observation was also noted with Sssod1. Thus, fungal enzymes involved in oxidative stress tolerance,when inactivated, also exhibit reduced OA levels. We have also shown that protein phosphatases (specifically PP2A and PTP1) are involved in morphogenesis and pathogenesis of S. sclerotiorum, demonstrating the regulatory role of these key proteins in the mentioned processes. While probing the redox environment and host-pathogen interactions we determined that oxalic acid is an elicitor of plant programmed cell death during S. sclerotiorum disease development and that oxalic acid suppresses host defense via manipulation of the host redox environment. During the course of this project we also contributed to the progress of understanding S. sclerotiorum function and the manipulation of this fungus by establishing an efficient gene replacement and direct hyphal transformation protocols in S. sclerotiorum. Lastly, both PIs were involved in thegenomic analysis of this necrotrophic fungal pathogen (along with Botrytis cinerea). Our results have been published in 11 papers (including joint papers and refereed reviews) and have set the basis for a continuum towards a better understanding and eventual control of this important pathogen (with implications to other fungal-host systems as well).
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Horwitz, Benjamin A., and Barbara Gillian Turgeon. Fungal Iron Acquisition, Oxidative Stress and Virulence in the Cochliobolus-maize Interaction. United States Department of Agriculture, March 2012. http://dx.doi.org/10.32747/2012.7709885.bard.
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Our project focused on genes for high affinity iron acquisition in Cochliobolus heterostrophus, a necrotrophic pathogen of maize, and their intertwined relationship to oxidative stress status and virulence of the fungus on the host. An intriguing question was why mutants lacking the nonribosomal peptide synthetase (NRPS) gene (NPS6) responsible for synthesis of the extracellular siderophore, coprogen, are sensitive to oxidative stress. Our overall objective was to understand the mechanistic connection between iron stress and oxidative stress as related to virulence of a plant pathogen to its host. The first objective was to examine the interface where small molecule peptide and reactive oxygen species (ROS) mechanisms overlap. The second objective was to determine if the molecular explanation for common function is common signal transduction pathways. These pathways, built around sensor kinases, response regulators, and transcription factors may link sequestering of iron, production of antioxidants, resistance to oxidative stress, and virulence. We tested these hypotheses by genetic manipulation of the pathogen, virulence assays on the host plant, and by following the expression of key fungal genes. An addition to the original program, made in the first year, was to develop, for fungi, a genetically encoded indicator of redox state based on the commercially available Gfp-based probe pHyper, designed for animal cell biology. We implemented several tools including a genetically encoded indicator of redox state, a procedure to grow iron-depleted plants, and constructed a number of new mutants in regulatory genes. Lack of the major Fe acquisition pathways results in an almost completely avirulent phenotype, showing how critical Fe acquisition is for the pathogen to cause disease. Mutants in conserved signaling pathways have normal ability to regulate NPS6 in response to Fe levels, as do mutants in Lae1 and Vel1, two master regulators of gene expression. Vel1 mutants are sensitive to oxidative stress, and the reason may be underexpression of a catalase gene. In nps6 mutants, CAT3 is also underexpressed, perhaps explaining the sensitivity to oxidative stress. We constructed a deletion mutant for the Fe sensor-regulator SreA and found that it is required for down regulation of NPS6 under Fe-replete conditions. Lack of SreA, though, did not make the fungus over-sensitive to ROS, though the mutant had a slow growth rate. This suggests that overproduction of siderophore under Fe-replete conditions is not very damaging. On the other hand, increasing Fe levels protected nps6 mutants from inhibition by ROS, implying that Fe-catalyzed Fenton reactions are not the main factor in its sensitivity to ROS. We have made some progress in understanding why siderophore mutants are sensitive to oxidative stress, and in doing so, defined some novel regulatory relationships. Catalase genes, which are not directly related to siderophore biosynthesis, are underexpressed in nps6 mutants, suggesting that the siderophore product (with or without bound Fe) may act as a signal. Siderophores, therefore, could be a target for intervention in the field, either by supplying an incorrect signal or blocking a signal normally provided during infection. We already know that nps6 mutants cause smaller lesions and have difficulty establishing invasive growth in the host. Lae1 and Vel1 are the first factors shown to regulate both super virulence conferred by T-toxin, and basic pathogenicity, due to unknown factors. The mutants are also altered in oxidative stress responses, key to success in the infection court, asexual and sexual development, essential for fungal dissemination in the field, aerial hyphal growth, and pigment biosynthesis, essential for survival in the field. Mutants in genes encoding NADPH oxidase (Nox) are compromised in development and virulence. Indeed the triple mutant, which should lack all Nox activity, was nearly avirulent. Again, gene expression experiments provided us with initial evidence that superoxide produced by the fungus may be most important as a signal. Blocking oxidant production by the pathogen may be a way to protect the plant host, in interactions with necrotrophs such as C. heterostrophus which seem to thrive in an oxidant environment.