Myeloid-specific deletion of NOX2 prevents the metabolic and neurologic consequences of high fat diet.

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Jennifer K Pepping

Full Text Available High fat diet-induced obesity is associated with inflammatory and oxidative signaling in macrophages that likely participates in metabolic and physiologic impairment. One key factor that could drive pathologic changes in macrophages is the pro-inflammatory, pro-oxidant enzyme NADPH oxidase. However, NADPH oxidase is a pleiotropic enzyme with both pathologic and physiologic functions, ruling out indiscriminant NADPH oxidase inhibition as a viable therapy. To determine if targeted inhibition of monocyte/macrophage NADPH oxidase could mitigate obesity pathology, we generated mice that lack the NADPH oxidase catalytic subunit NOX2 in myeloid lineage cells. C57Bl/6 control (NOX2-FL and myeloid-deficient NOX2 (mNOX2-KO mice were given high fat diet for 16 weeks, and subject to comprehensive metabolic, behavioral, and biochemical analyses. Data show that mNOX2-KO mice had lower body weight, delayed adiposity, attenuated visceral inflammation, and decreased macrophage infiltration and cell injury in visceral adipose relative to control NOX2-FL mice. Moreover, the effects of high fat diet on glucose regulation and circulating lipids were attenuated in mNOX2-KO mice. Finally, memory was impaired and markers of brain injury increased in NOX2-FL, but not mNOX2-KO mice. Collectively, these data indicate that NOX2 signaling in macrophages participates in the pathogenesis of obesity, and reinforce a key role for macrophage inflammation in diet-induced metabolic and neurologic decline. Development of macrophage/immune-specific NOX-based therapies could thus potentially be used to preserve metabolic and neurologic function in the context of obesity.

NADPH oxidases as novel pharmacologic targets against influenza A virus infection.

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Vlahos, Ross; Selemidis, Stavros

2014-12-01

Influenza A viruses represent a major global health care challenge, with imminent pandemics, emerging antiviral resistance, and long lag times for vaccine development, raising a pressing need for novel pharmacologic strategies that ideally target the pathology irrespective of the infecting strain. Reactive oxygen species (ROS) pervade all facets of cell biology with both detrimental and protective properties. Indeed, there is compelling evidence that activation of the NADPH oxidase 2 (NOX2) isoform of the NADPH oxidase family of ROS-producing enzymes promotes lung oxidative stress, inflammation, injury, and dysfunction resulting from influenza A viruses of low to high pathogenicity, as well as impeding virus clearance. By contrast, the dual oxidase isoforms produce ROS that provide vital protective antiviral effects for the host. In this review, we propose that inhibitors of NOX2 are better alternatives than broad-spectrum antioxidant approaches for treatment of influenza pathologies, for which clinical efficacy may have been limited owing to poor bioavailability and inadvertent removal of beneficial ROS. Finally, we briefly describe the current suite of NADPH oxidase inhibitors and the molecular features of the NADPH oxidase enzymes that could be exploited by drug discovery for development of more specific and novel inhibitors to prevent or treat disease caused by influenza. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Functions and regulation of the Nox family in the filamentous fungus Podospora anserina: a new role in cellulose degradation.

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Brun, Sylvain; Malagnac, Fabienne; Bidard, Frédérique; Lalucque, Hervé; Silar, Philippe

2009-10-01

NADPH oxidases are enzymes that produce reactive oxygen species. Studies in mammals, plants and fungi have shown that they play important roles in differentiation, defence, host/pathogen interaction and mutualistic symbiosis. In this paper, we have identified a Podospora anserina mutant strain impaired for processes controlled by PaNox1 and PaNox2, the two Nox isoforms characterized in this model ascomycete. We show that the gene mutated is PaNoxR, the homologue of the gene encoding the regulatory subunit p67(phox), conserved in mammals and fungi, and that PaNoxR regulates both PaNox1 and PaNox2. Genome sequence analysis of P. anserina reveals that this fungus posses a third Nox isoform, PaNox3, related to human Nox5/Duox and plant Rboh. We have generated a knock-out mutant of PaNox3 and report that PaNox3 plays a minor role in P. anserina, if any. We show that PaNox1 and PaNox2 play antagonist roles in cellulose degradation. Finally, we report for the first time that a saprobic fungus, P. anserina, develops special cell structures dedicated to breach and to exploit a solid cellulosic substrate, cellophane. Importantly, as for similar structures present in some plant pathogens, their proper differentiation requires PaNox1, PaNox2, PaNoxR and the tetraspanin PaPls1.

Calcineurin Aβ regulates NADPH oxidase (Nox) expression and activity via nuclear factor of activated T cells (NFAT) in response to high glucose.

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Williams, Clintoria R; Gooch, Jennifer L

2014-02-21

Hypertrophy is an adaptive response that enables organs to appropriately meet increased functional demands. Previously, we reported that calcineurin (Cn) is required for glomerular and whole kidney hypertrophy in diabetic rodents (Gooch, J. L., Barnes, J. L., Garcia, S., and Abboud, H. E. (2003). Calcineurin is activated in diabetes and is required for glomerular hypertrophy and ECM accumulation. Am. J. Physiol. Renal Physiol. 284, F144-F154; Reddy, R. N., Knotts, T. L., Roberts, B. R., Molkentin, J. D., Price, S. R., and Gooch, J. L. (2011). Calcineurin Aβ is required for hypertrophy but not matrix expansion in the diabetic kidney. J. Cell Mol. Med. 15, 414-422). Because studies have also implicated the reactive oxygen species-generating enzymes NADPH oxidases (Nox) in diabetic kidney responses, we tested the hypothesis that Nox and Cn cooperate in a common signaling pathway. First, we examined the role of the two main isoforms of Cn in hypertrophic signaling. Using primary kidney cells lacking a catalytic subunit of Cn (CnAα(-/-) or CnAβ(-/-)), we found that high glucose selectively activates CnAβ, whereas CnAα is constitutively active. Furthermore, CnAβ but not CnAα mediates hypertrophy. Next, we found that chronic reactive oxygen species generation in response to high glucose is attenuated in CnAβ(-/-) cells, suggesting that Cn is upstream of Nox. Consistent with this, loss of CnAβ reduces basal expression and blocks high glucose induction of Nox2 and Nox4. Inhibition of nuclear factor of activated T cells (NFAT), a CnAβ-regulated transcription factor, decreases Nox2 and Nox4 expression, whereas NFAT overexpression increases Nox2 and Nox4, indicating that the CnAβ/NFAT pathway modulates Nox. These data reveal that the CnAβ/NFAT pathway regulates Nox and plays an important role in high glucose-mediated hypertrophic responses in the kidney.

Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX and Sirtuin1 (SIRT1

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Ming-Hung Lin

2016-06-01

Full Text Available Bladder cancer is one of the most frequent cancers among males, and its poor survival rate reflects problems with aggressiveness and chemo-resistance. Recent interest has focused on the use of chemopreventatives (nontoxic natural agents that may suppress cancer progression to induce targeted apoptosis for cancer therapy. Capsaicin, which has anti-cancer properties, is one such agent. It is known to preferentially inhibit a tumor-associated NADH oxidase (tNOX that is preferentially expressed in cancer/transformed cells. Here, we set out to elucidate the correlation between tNOX expression and the inhibitory effects of capsaicin in human bladder cancer cells. We showed that capsaicin downregulates tNOX expression and decreases bladder cancer cell growth by enhancing apoptosis. Moreover, capsaicin was found to reduce the expression levels of several proteins involved in cell cycle progression, in association with increases in the cell doubling time and enhanced cell cycle arrest. Capsaicin was also shown to inhibit the activation of ERK, thereby reducing the phosphorylation of paxillin and FAK, which leads to decreased cell migration. Finally, our results indicate that RNA interference-mediated tNOX depletion enhances spontaneous apoptosis, prolongs cell cycle progression, and reduces cell migration and the epithelial-mesenchymal transition. We also observed a downregulation of sirtuin 1 (SIRT1 in these tNOX-knockdown cells, a deacetylase that is important in multiple cellular functions. Taken together, our results indicate that capsaicin inhibits the growth of bladder cancer cells by inhibiting tNOX and SIRT1 and thereby reducing proliferation, attenuating migration, and prolonging cell cycle progression.

Effect of a heme oxygenase-1 inducer on NADPH oxidase ...

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Effect of a heme oxygenase-1 inducer on NADPH oxidase expression in ... and immunohistochemistry of hepatic NOX1 and NOX4 were investigated in week 4. ... (HO-1 inhibitor) administration caused upregulation of NOX gene expression ...

Peroxidasin-mediated crosslinking of collagen IV is independent of NADPH oxidases

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Gábor Sirokmány

2018-06-01

Full Text Available Collagen IV is a major component of the basement membrane in epithelial tissues. The NC1 domains of collagen IV protomers are covalently linked together through sulfilimine bonds, the formation of which is catalyzed by peroxidasin. Although hydrogen peroxide is essential for this reaction, the exact source of the oxidant remains elusive. Members of the NOX/DUOX NADPH oxidase family are specifically devoted to the production of superoxide and hydrogen peroxide. Our aim in this study was to find out if NADPH oxidases contribute in vivo to the formation of collagen IV sulfilimine crosslinks. We used multiple genetically modified in vivo model systems to provide a detailed assessment of this question. Our data indicate that in various peroxidasin-expressing tissues sulfilimine crosslinks between the NC1 domains of collagen IV can be readily detected in the absence of functioning NADPH oxidases. We also analyzed how subatmospheric oxygen levels influence the collagen IV network in collagen-producing cultured cells with rapid matrix turnover. We showed that collagen IV crosslinks remain intact even under strongly hypoxic conditions. Our hypothesis is that during collagen IV network formation PXDN cooperates with a NOX/DUOX-independent H2O2 source that is functional also at very low ambient oxygen levels. Keywords: Peroxidasin, NADPH oxidase, Hydrogen peroxide, Collagen IV, Sulfilimine

Unique role of NADPH oxidase 5 in oxidative stress in human renal proximal tubule cells

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Peiying Yu

2014-01-01

Full Text Available NADPH oxidases are the major sources of reactive oxygen species in cardiovascular, neural, and kidney cells. The NADPH oxidase 5 (NOX5 gene is present in humans but not rodents. Because Nox isoforms in renal proximal tubules (RPTs are involved in the pathogenesis of hypertension, we tested the hypothesis that NOX5 is differentially expressed in RPT cells from normotensive (NT and hypertensive subjects (HT. We found that NOX5 mRNA, total NOX5 protein, and apical membrane NOX5 protein were 4.2±0.7-fold, 5.2±0.7-fold, and 2.8±0.5-fold greater in HT than NT. Basal total NADPH oxidase activity was 4.5±0.2-fold and basal NOX5 activity in NOX5 immunoprecipitates was 6.2±0.2-fold greater in HT than NT (P=<0.001, n=6–14/group. Ionomycin increased total NOX and NOX5 activities in RPT cells from HT (P<0.01, n=4, ANOVA, effects that were abrogated by pre-treatment of the RPT cells with diphenylene-iodonium or superoxide dismutase. Silencing NOX5 using NOX5-siRNA decreased NADPH oxidase activity (−45.1±3.2% vs. mock-siRNA, n=6–8 in HT. D1-like receptor stimulation decreased NADPH oxidase activity to a greater extent in NT (−32.5±1.8% than HT (−14.8±1.8. In contrast to the marked increase in expression and activity of NOX5 in HT, NOX1 mRNA and protein were minimally increased in HT, relative to NT; total NOX2 and NOX4 proteins were not different between HT and NT, while the increase in apical RPT cell membrane NOX1, NOX2, and NOX4 proteins in HT, relative to NT, was much less than those observed with NOX5. Thus, we demonstrate, for the first time, that NOX5 is expressed in human RPT cells and to greater extent than the other Nox isoforms in HT than NT. We suggest that the increased expression of NOX5, which may be responsible for the increased oxidative stress in RPT cells in human essential hypertension, is caused, in part, by a defective renal dopaminergic system.

Molecular cloning and characterization of a tumor-associated, growth-related, and time-keeping hydroquinone (NADH) oxidase (tNOX) of the HeLa cell surface

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Chueh, Pin-Ju; Kim, Chinpal; Cho, NaMi; Morre, Dorothy M.; Morre, D. James

2002-01-01

NOX proteins are growth-related cell surface proteins that catalyze both hydroquinone or NADH oxidation and protein disulfide interchange and exhibit prion-like properties. The two enzymatic activities alternate to generate a regular period length of about 24 min. Here we report the expression, cloning, and characterization of a tumor-associated NADH oxidase (tNOX). The cDNA sequence of 1830 bp is located on gene Xq25-26 with an open reading frame encoding 610 amino acids. The activities of the bacterially expressed tNOX oscillate with a period length of 22 min as is characteristic of tNOX activities in situ. The activities are inhibited completely by capsaicin, which represents a defining characteristic of tNOX activity. Functional motifs identified by site-directed mutagenesis within the C-terminal portion of the tNOX protein corresponding to the processed plasma membrane-associated form include quinone (capsaicin), copper and adenine nucleotide binding domains, and two cysteines essential for catalytic activity. Four of the six cysteine to alanine replacements retained enzymatic activity, but the period lengths of the oscillations were increased. A single protein with two alternating enzymatic activities indicative of a time-keeping function is unprecedented in the biochemical literature.

Ionizing irradiation induces apoptotic damage of salivary gland acinar cells via NADPH oxidase 1-dependent superoxide generation

International Nuclear Information System (INIS)

Tateishi, Yoshihisa; Sasabe, Eri; Ueta, Eisaku; Yamamoto, Tetsuya

2008-01-01

Reactive oxygen species (ROS) have important roles in various physiological processes. Recently, several novel homologues of the phagocytic NADPH oxidase have been discovered and this protein family is now designated as the Nox family. We investigated the involvement of Nox family proteins in ionizing irradiation-induced ROS generation and impairment in immortalized salivary gland acinar cells (NS-SV-AC), which are radiosensitive, and immortalized ductal cells (NS-SV-DC), which are radioresistant. Nox1-mRNA was upregulated by γ-ray irradiation in NS-SV-AC, and the ROS level in NS-SV-AC was increased to approximately threefold of the control level after 10 Gy irradiation. The increase of ROS level in NS-SV-AC was suppressed by Nox1-siRNA-transfection. In parallel with the suppression of ROS generation and Nox1-mRNA expression by Nox1-siRNA, ionizing irradiation-induced apoptosis was strongly decreased in Nox1-siRNA-transfected NS-SV-AC. There were no large differences in total SOD or catalase activities between NS-SV-AC and NS-SV-DC although the post-irradiation ROS level in NS-SV-AC was higher than that in NS-SV-DC. In conclusion, these results indicate that Nox1 plays a crucial role in irradiation-induced ROS generation and ROS-associated impairment of salivary gland cells and that Nox1 gene may be targeted for preservation of the salivary gland function from radiation-induced impairment

Involvement of NADH Oxidase in Competition and Endocarditis Virulence in Streptococcus sanguinis.

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Ge, Xiuchun; Yu, Yang; Zhang, Min; Chen, Lei; Chen, Weihua; Elrami, Fadi; Kong, Fanxiang; Kitten, Todd; Xu, Ping

2016-05-01

Here, we report for the first time that the Streptococcus sanguinis nox gene encoding NADH oxidase is involved in both competition with Streptococcus mutans and virulence for infective endocarditis. An S. sanguinis nox mutant was found to fail to inhibit the growth of Streptococcus mutans under microaerobic conditions. In the presence of oxygen, the recombinant Nox protein of S. sanguinis could reduce oxygen to water and oxidize NADH to NAD(+) The oxidation of NADH to NAD(+) was diminished in the nox mutant. The nox mutant exhibited decreased levels of extracellular H2O2; however, the intracellular level of H2O2 in the mutant was increased. Furthermore, the virulence of the nox mutant was attenuated in a rabbit endocarditis model. The nox mutant also was shown to be more sensitive to blood killing, oxidative and acid stresses, and reduced growth in serum. Thus, NADH oxidase contributes to multiple phenotypes related to competitiveness in the oral cavity and systemic virulence. Copyright © 2016 Ge et al.

Nox regulation of smooth muscle contraction

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Ritsick, Darren R.; Edens, William A.; Finnerty, Victoria; Lambeth, J. David

2007-01-01

The catalytic subunit, gp91phox (a.k.a., Nox2) of the NADPH-oxidase of mammalian phagocytes is activated by microbes and immune mediators to produce large amounts of reactive oxygen species (ROS) which participate in microbial killing. Homologs of gp91phox, the Nox and Duox enzymes, were recently described in a range of organisms, including plants, vertebrates, and invertebrates such as Drosophila melanogaster. While their enzymology and cell biology is being extensively studied in many labor...

Tetraspanin is required for generation of reactive oxygen species by the dual oxidase system in Caenorhabditis elegans.

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Hiroki Moribe

2012-09-01

Full Text Available Reactive oxygen species (ROS are toxic but essential molecules responsible for host defense and cellular signaling. Conserved NADPH oxidase (NOX family enzymes direct the regulated production of ROS. Hydrogen peroxide (H(2O(2 generated by dual oxidases (DUOXs, a member of the NOX family, is crucial for innate mucosal immunity. In addition, H(2O(2 is required for cellular signaling mediated by protein modifications, such as the thyroid hormone biosynthetic pathway in mammals. In contrast to other NOX isozymes, the regulatory mechanisms of DUOX activity are less understood. Using Caenorhabditis elegans as a model, we demonstrate that the tetraspanin protein is required for induction of the DUOX signaling pathway in conjunction with the dual oxidase maturation factor (DUOXA. In the current study, we show that genetic mutation of DUOX (bli-3, DUOXA (doxa-1, and peroxidase (mlt-7 in C. elegans causes the same defects as a tetraspanin tsp-15 mutant, represented by exoskeletal deficiencies due to the failure of tyrosine cross-linking of collagen. The deficiency in the tsp-15 mutant was restored by co-expression of bli-3 and doxa-1, indicating the involvement of tsp-15 in the generation of ROS. H(2O(2 generation by BLI-3 was completely dependent on TSP-15 when reconstituted in mammalian cells. We also demonstrated that TSP-15, BLI-3, and DOXA-1 form complexes in vitro and in vivo. Cell-fusion-based analysis suggested that association with TSP-15 at the cell surface is crucial for BLI-3 activation to release H(2O(2. This study provides the first evidence for an essential role of tetraspanin in ROS generation.

Functional Analysis of the Trichoderma harzianum nox1 Gene, Encoding an NADPH Oxidase, Relates Production of Reactive Oxygen Species to Specific Biocontrol Activity against Pythium ultimum▿†

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Montero-Barrientos, M.; Hermosa, R.; Cardoza, R. E.; Gutiérrez, S.; Monte, E.

2011-01-01

The synthesis of reactive oxygen species (ROS) is one of the first events following pathogenic interactions in eukaryotic cells, and NADPH oxidases are involved in the formation of such ROS. The nox1 gene of Trichoderma harzianum was cloned, and its role in antagonism against phytopathogens was analyzed in nox1-overexpressed transformants. The increased levels of nox1 expression in these transformants were accompanied by an increase in ROS production during their direct confrontation with Pythium ultimum. The transformants displayed an increased hydrolytic pattern, as determined by comparing protease, cellulase, and chitinase activities with those for the wild type. In confrontation assays against P. ultimum the nox1-overexpressed transformants were more effective than the wild type, but not in assays against Botrytis cinerea or Rhizoctonia solani. A transcriptomic analysis using a Trichoderma high-density oligonucleotide (HDO) microarray also showed that, compared to gene expression for the interaction of wild-type T. harzianum and P. ultimum, genes related to protease, cellulase, and chitinase activities were differentially upregulated in the interaction of a nox1-overexpressed transformant with this pathogen. Our results show that nox1 is involved in T. harzianum ROS production and antagonism against P. ultimum. PMID:21421791

Constitutive NADPH-Dependent Electron Transferase Activity of the Nox4 Dehydrogenase Domain?

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Nisimoto, Yukio; Jackson, Heather M.; Ogawa, Hisamitsu; Kawahara, Tsukasa; Lambeth, J. David

2010-01-01

NADPH oxidase 4 (Nox4) is constitutively active, while Nox2 requires the cytosolic regulatory subunits p47 phox and p67 phox and activated Rac with activation by phorbol 12-myristate 13-acetate (PMA). This study was undertaken to identify the domain on Nox4 that confers constitutive activity. Lysates from Nox4-expressing cells exhibited constitutive NADPH- but not NADH-dependent hydrogen peroxide production with a K m for NADPH of 55 ? 10 ?M. The concentration of Nox4 in cell lysates was esti...

Decoding NADPH oxidase 4 expression in human tumors

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Jennifer L. Meitzler

2017-10-01

Full Text Available NADPH oxidase 4 (NOX4 is a redox active, membrane-associated protein that contributes to genomic instability, redox signaling, and radiation sensitivity in human cancers based on its capacity to generate H2O2 constitutively. Most studies of NOX4 in malignancy have focused on the evaluation of a small number of tumor cell lines and not on human tumor specimens themselves; furthermore, these studies have often employed immunological tools that have not been well characterized. To determine the prevalence of NOX4 expression across a broad range of solid tumors, we developed a novel monoclonal antibody that recognizes a specific extracellular region of the human NOX4 protein, and that does not cross-react with any of the other six members of the NOX gene family. Evaluation of 20 sets of epithelial tumors revealed, for the first time, high levels of NOX4 expression in carcinomas of the head and neck (15/19 patients, esophagus (12/18 patients, bladder (10/19 patients, ovary (6/17 patients, and prostate (7/19 patients, as well as malignant melanoma (7/15 patients when these tumors were compared to histologically-uninvolved specimens from the same organs. Detection of NOX4 protein upregulation by low levels of TGF-β1 demonstrated the sensitivity of this new probe; and immunofluorescence experiments found that high levels of endogenous NOX4 expression in ovarian cancer cells were only demonstrable associated with perinuclear membranes. These studies suggest that NOX4 expression is upregulated, compared to normal tissues, in a well-defined, and specific group of human carcinomas, and that its expression is localized on intracellular membranes in a fashion that could modulate oxidative DNA damage.

Regulation of Nox enzymes expression in vascular pathophysiology: Focusing on transcription factors and epigenetic mechanisms

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Simona-Adriana Manea

2015-08-01

Full Text Available NADPH oxidases (Nox represent a family of hetero-oligomeric enzymes whose exclusive biological function is the generation of reactive oxygen species (ROS. Nox-derived ROS are essential modulators of signal transduction pathways that control key physiological activities such as cell growth, proliferation, migration, differentiation, and apoptosis, immune responses, and biochemical pathways. Enhanced formation of Nox-derived ROS, which is generally associated with the up-regulation of different Nox subtypes, has been established in various pathologies, namely cardiovascular diseases, diabetes, obesity, cancer, and neurodegeneration. The detrimental effects of Nox-derived ROS are related to alterations in cell signalling and/or direct irreversible oxidative damage of nucleic acids, proteins, carbohydrates, and lipids. Thus, understanding of transcriptional regulation mechanisms of Nox enzymes have been extensively investigated in an attempt to find ways to counteract the excessive formation of Nox-derived ROS in various pathological states. Despite the numerous existing data, the molecular pathways responsible for Nox up-regulation are not completely understood. This review article summarizes some of the recent advances and concepts related to the regulation of Nox expression in the vascular pathophysiology. It highlights the role of transcription factors and epigenetic mechanisms in this process. Identification of the signalling molecules involved in Nox up-regulation, which is associated with the onset and development of cardiovascular dysfunction may contribute to the development of novel strategies for the treatment of cardiovascular diseases.

Role of Nox2 and p22phox in Persistent Postoperative Hypertension in Aldosterone-Producing Adenoma Patients after Adrenalectomy

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Xiaojing Geng

2016-01-01

Full Text Available Adrenal aldosterone-producing adenoma (APA, producing the salt-retaining hormone aldosterone, commonly causes secondary hypertension, which often persists after unilateral adrenalectomy. Although persistent hypertension was correlated with residual hormone aldosterone, the in vivo mechanism remains unclear. NADPH oxidase is the critical cause of aldosterone synthesis in vitro. Nox2 and p22phox comprise the NADPH oxidase catalytic core, serving to initiate a reactive oxygen species (ROS cascade that may participate in the pathology. mRNAs of seven NADPH oxidase isoforms in APA were evaluated by RT-PCR and Q-PCR and their proteins by immunohistochemistry and Western blotting. NADPH oxidase activity was also detected. Nox2 and p22phox were especially abundant in APA. Particularly higher Nox2 and p22phox gene and protein levels were seen in APA than controls. Significant correlations between Nox2 mRNA and aldosterone synthase (CYP11B2 mRNA (R=0.66, P<0.01 and Nox2 protein and baseline plasma aldosterone concentration (PAC (R=0.503, P<0.01 were detected in APA; however, none were found between p22phox mRNA, CYP11B2 mRNA, p22phox protein, and baseline PAC. Importantly, we found that Nox2 localized specifically in hyperplastic zona glomerulosa cells. In conclusion, our results highlight that Nox2 and p22phox may be directly involved in pathological aldosterone production and zona glomerulosa cell proliferation after APA resection.

Priming of the neutrophil NADPH oxidase activation: role of p47phox phosphorylation and NOX2 mobilization to the plasma membrane.

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El-Benna, Jamel; Dang, Pham My-Chan; Gougerot-Pocidalo, Marie-Anne

2008-07-01

Neutrophils play an essential role in host defense against microbial pathogens and in the inflammatory reaction. Upon activation, neutrophils produce superoxide anion (O*2), which generates other reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), hydroxyl radical (OH*) and hypochlorous acid (HOCl), together with microbicidal peptides and proteases. The enzyme responsible for O2* production is called the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two trans-membrane proteins (p22phox and gp91phox/NOX2, which form the cytochrome b558), three cytosolic proteins (p47phox, p67phox, p40phox) and a GTPase (Rac1 or Rac2), which assemble at membrane sites upon cell activation. NADPH oxidase activation in phagocytes can be induced by a large number of soluble and particulate factors. Three major events accompany NAPDH oxidase activation: (1) protein phosphorylation, (2) GTPase activation, and (3) translocation of cytosolic components to the plasma membrane to form the active enzyme. Actually, the neutrophil NADPH oxidase exists in different states: resting, primed, activated, or inactivated. The resting state is found in circulating blood neutrophils. The primed state can be induced by neutrophil adhesion, pro-inflammatory cytokines, lipopolysaccharide, and other agents and has been characterized as a "ready to go" state, which results in a faster and higher response upon exposure to a second stimulus. The active state is found at the inflammatory or infection site. Activation is induced by the pathogen itself or by pathogen-derived formylated peptides and other agents. Finally, inactivation of NADPH oxidase is induced by anti-inflammatory agents to limit inflammation. Priming is a "double-edged sword" process as it contributes to a rapid and efficient elimination of the pathogens but can also induce the generation of large quantities of toxic ROS by hyperactivation of

Nuclear Nox4-Derived Reactive Oxygen Species in Myelodysplastic Syndromes

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Marianna Guida

2014-01-01

Full Text Available A role for intracellular ROS production has been recently implicated in the pathogenesis and progression of a wide variety of neoplasias. ROS sources, such as NAD(PH oxidase (Nox complexes, are frequently activated in AML (acute myeloid leukemia blasts and strongly contribute to their proliferation, survival, and drug resistance. Myelodysplastic syndromes (MDS comprise a heterogeneous group of disorders characterized by ineffective hematopoiesis, with an increased propensity to develop AML. The molecular basis for MDS progression is unknown, but a key element in MDS disease progression is the genomic instability. NADPH oxidases are now recognized to have specific subcellular localizations, this targeting to specific compartments for localized ROS production. Local Nox-dependent ROS production in the nucleus may contribute to the regulation of redox-dependent cell growth, differentiation, senescence, DNA damage, and apoptosis. We observed that Nox1, 2, and 4 isoforms and p22phox and Rac1 subunits are expressed in MDS/AML cell lines and MDS samples, also in the nuclear fractions. Interestingly, Nox4 interacts with ERK and Akt1 within nuclear speckle domain, suggesting that Nox4 could be involved in regulating gene expression and splicing factor activity. These data contribute to the elucidation of the molecular mechanisms used by nuclear ROS to drive MDS evolution to AML.

Effects of dark chocolate on NOX-2-generated oxidative stress in patients with non-alcoholic steatohepatitis.

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Loffredo, L; Del Ben, M; Perri, L; Carnevale, R; Nocella, C; Catasca, E; Baratta, F; Ceci, F; Polimeni, L; Gozzo, P; Violi, F; Angelico, F

2016-08-01

Activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is considered a pathogenetic mechanism determining fibrosis and disease progression in non-alcoholic steatohepatitis (NASH). Polyphenols exert antioxidant action and inhibit NADPH oxidase in humans. To analyse the effect of cocoa polyphenols on NADPH oxidase isoform 2 (NOX2) activation, oxidative stress and hepatocyte apoptosis in a population affected by NASH. In a cross-sectional study comparing 19 NASH and 19 controls, oxidative stress, as assessed by serum NOX2 activity and F2-isoprostanes, and hepatocyte apoptosis, as assessed by serum cytokeratin-18 (CK-18) levels, were measured. Furthermore, the 19 NASH patients were randomly allocated in a crossover design to 40 g/day of dark chocolate (>85% cocoa) or 40 g/day of milk chocolate (chocolate intake. Compared to controls, NASH patients had higher sNOX2-dp, serum isoprostanes and CK-18 levels. A significant difference for treatments was found in subjects with respect to sNOX2-dp, serum isoprostanes and serum CK-18. The pairwise comparisons showed that, compared to baseline, after 14 days of dark chocolate intake, a significant reduction in sNOX2-dp serum isoprostanes and CK-18 M30 was found. No change was observed after milk chocolate ingestion. A simple linear regression analysis showed that ∆ of sNOX2-dp was associated with ∆ of serum isoprostanes. Cocoa polyphenols exert an antioxidant activity via NOX2 down-regulation in NASH patients. © 2016 John Wiley & Sons Ltd.

New insights into the roles of NADPH oxidases in sexual development and ascospore germination in Sordaria macrospora.

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Dirschnabel, Daniela Elisabeth; Nowrousian, Minou; Cano-Domínguez, Nallely; Aguirre, Jesus; Teichert, Ines; Kück, Ulrich

2014-03-01

NADPH oxidase (NOX)-derived reactive oxygen species (ROS) act as signaling determinants that induce different cellular processes. To characterize NOX function during fungal development, we utilized the genetically tractable ascomycete Sordaria macrospora. Genome sequencing of a sterile mutant led us to identify the NADPH oxidase encoding nox1 as a gene required for fruiting body formation, regular hyphal growth, and hyphal fusion. These phenotypes are shared by nor1, lacking the NOX regulator NOR1. Further phenotypic analyses revealed a high correlation between increased ROS production and hyphal fusion deficiencies in nox1 and other sterile mutants. A genome-wide transcriptional profiling analysis of mycelia and isolated protoperithecia from wild type and nox1 revealed that nox1 inactivation affects the expression of genes related to cytoskeleton remodeling, hyphal fusion, metabolism, and mitochondrial respiration. Genetic analysis of nox2, lacking the NADPH oxidase 2 gene, nor1, and transcription factor deletion mutant ste12, revealed a strict melanin-dependent ascospore germination defect, indicating a common genetic pathway for these three genes. We report that gsa3, encoding a G-protein α-subunit, and sac1, encoding cAMP-generating adenylate cyclase, act in a separate pathway during the germination process. The finding that cAMP inhibits ascospore germination in a melanin-dependent manner supports a model in which cAMP inhibits NOX2 activity, thus suggesting a link between both pathways. Our results expand the current knowledge on the role of NOX enzymes in fungal development and provide a frame to define upstream and downstream components of the NOX signaling pathways in fungi.

Nuclear Nox4 Role in Stemness Power of Human Amniotic Fluid Stem Cells

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Tullia Maraldi

2015-01-01

Full Text Available Human amniotic fluid stem cells (AFSC are an attractive source for cell therapy due to their multilineage differentiation potential and accessibility advantages. However the clinical application of human stem cells largely depends on their capacity to expand in vitro, since there is an extensive donor-to-donor heterogeneity. Reactive oxygen species (ROS and cellular oxidative stress are involved in many physiological and pathophysiological processes of stem cells, including pluripotency, proliferation, differentiation, and stress resistance. The mode of action of ROS is also dependent on the localization of their target molecules. Thus, the modifications induced by ROS can be separated depending on the cellular compartments they affect. NAD(PH oxidase family, particularly Nox4, has been known to produce ROS in the nucleus. In the present study we show that Nox4 nuclear expression (nNox4 depends on the donor and it correlates with the expression of transcription factors involved in stemness regulation, such as Oct4, SSEA-4, and Sox2. Moreover nNox4 is linked with the nuclear localization of redox sensitive transcription factors, as Nrf2 and NF-κB, and with the differentiation potential. Taken together, these results suggest that nNox4 regulation may have important effects in stem cell capability through modulation of transcription factors and DNA damage.

Advanced oxidation protein products sensitized the transient receptor potential vanilloid 1 via NADPH oxidase 1 and 4 to cause mechanical hyperalgesia

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Ruoting Ding

2016-12-01

Full Text Available Oxidative stress is a possible pathogenesis of hyperalgesia. Advanced oxidation protein products (AOPPs, a new family of oxidized protein compounds, have been considered as a novel marker of oxidative stress. However, the role of AOPPs in the mechanism of hyperalgesia remains unknown. Our study aims to investigate whether AOPPs have an effect on hyperalgesia and the possible underlying mechanisms. To identify the AOPPs involved, we induced hyperalgesia in rats by injecting complete Freund’s adjuvant (CFA in hindpaw. The level of plasma AOPPs in CFA-induced rats was 1.6-fold in comparison with what in normal rats (P<0.05. After intravenous injection of AOPPs-modified rat serum albumin (AOPPs-RSA in Sprague-Dawley rats, the paw mechanical thresholds, measured by the electronic von Frey system, significantly declined. Immunofluorescence staining indicated that AOPPs increased expressions of NADPH oxidase 1 (Nox1, NADPH oxidase 4 (Nox4, transient receptor potential vanilloid 1 (TRPV1 and calcitonin gene-related peptide (CGRP in the dorsal root ganglia (DRG tissues. In-vitro studies were performed on primary DRG neurons which were obtained from both thoracic and lumbar DRG of rats. Results indicated that AOPPs triggered reactive oxygen species (ROS production in DRG neurons, which were significantly abolished by ROS scavenger N-acetyl-l-cysteine (NAC and small-interfering RNA (siRNA silencing of Nox1 or Nox4. The expressions of Nox1, Nox4, TRPV1 and CGRP were significantly increased in AOPPs-induced DRG neurons. And relevant siRNA or inhibitors notably suppressed the expressions of these proteins and the calcium influxes in AOPPs-induced DRG neurons. In conclusion, AOPPs increased significantly in CFA-induced hyperalgesia rats and they activated Nox1/Nox4-ROS to sensitize TRPV1-dependent Ca2+ influx and CGRP release which led to inducing mechanical hyperalgesia.

Resveratrol protects vascular endothelial cells from high glucose-induced apoptosis through inhibition of NADPH oxidase activation-driven oxidative stress.

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Chen, Feng; Qian, Li-Hua; Deng, Bo; Liu, Zhi-Min; Zhao, Ying; Le, Ying-Ying

2013-09-01

Hyperglycemia-induced oxidative stress has been implicated in diabetic vascular complications in which NADPH oxidase is a major source of reactive oxygen species (ROS) generation. Resveratrol is a naturally occurring polyphenol, which has vasoprotective effects in diabetic animal models and inhibits high glucose (HG)-induced oxidative stress in endothelial cells. We aimed to examine whether HG-induced NADPH oxidase activation and ROS production contribute to glucotoxicity to endothelial cells and the effect of resveratrol on glucotoxicity. Using a murine brain microvascular endothelial cell line bEnd3, we found that NADPH oxidase inhibitor (apocynin) and resveratrol both inhibited HG-induced endothelial cell apoptosis. HG-induced elevation of NADPH oxidase activity and production of ROS were inhibited by apocynin, suggesting that HG induces endothelial cell apoptosis through NADPH oxidase-mediated ROS production. Mechanistic studies revealed that HG upregulated NADPH oxidase subunit Nox1 but not Nox2, Nox4, and p22(phox) expression through NF-κB activation, which resulted in elevation of NADPH oxidase activity and consequent ROS production. Resveratrol prevented HG-induced endothelial cell apoptosis through inhibiting HG-induced NF-κB activation, NADPH oxidase activity elevation, and ROS production. HG induces endothelial cell apoptosis through NF-κB/NADPH oxidase/ROS pathway, which was inhibited by resveratrol. Our findings provide new potential therapeutic targets against brain vascular complications of diabetes. © 2013 John Wiley & Sons Ltd.

Nox4 Is Dispensable for Exercise Induced Muscle Fibre Switch.

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Juri Vogel

Full Text Available By producing H2O2, the NADPH oxidase Nox4 is involved in differentiation of mesenchymal cells. Exercise alters the composition of slow and fast twitch fibres in skeletal. Here we hypothesized that Nox4 contributes to exercise-induced adaptation such as changes in muscle metabolism or muscle fibre specification and studied this in wildtype and Nox4-/- mice.Exercise, as induced by voluntary running in a running wheel or forced running on a treadmill induced a switch from fast twitch to intermediate fibres. However the induced muscle fibre switch was similar between Nox4-/- and wildtype mice. The same held true for exercise-induced expression of PGC1α or AMPK activation. Both are increased in response to exercise, but with no difference was observed between wildtype and Nox4-/- mice.Thus, exercise-induced muscle fibre switch is Nox4-independent.

Deficiency of NOX1 or NOX4 Prevents Liver Inflammation and Fibrosis in Mice through Inhibition of Hepatic Stellate Cell Activation.

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Tian Lan

Full Text Available Reactive oxygen species (ROS produced by nicotinamide adenine dinucleotide phosphate oxidase (NOX play a key role in liver injury and fibrosis. Previous studies demonstrated that GKT137831, a dual NOX1/4 inhibitor, attenuated liver fibrosis in mice as well as pro-fibrotic genes in hepatic stellate cells (HSCs as well as hepatocyte apoptosis. The effect of NOX1 and NOX4 deficiency in liver fibrosis is unclear, and has never been directly compared. HSCs are the primary myofibroblasts in the pathogenesis of liver fibrosis. Therefore, we aimed to determine the role of NOX1 and NOX4 in liver fibrosis, and investigated whether NOX1 and NOX4 signaling mediates liver fibrosis by regulating HSC activation. Mice were treated with carbon tetrachloride (CCl4 to induce liver fibrosis. Deficiency of either NOX1 or NOX4 attenuates liver injury, inflammation, and fibrosis after CCl4 compared to wild-type mice. NOX1 or NOX4 deficiency reduced lipid peroxidation and ROS production in mice with liver fibrosis. NOX1 and NOX4 deficiency are approximately equally effective in preventing liver injury in the mice. The NOX1/4 dual inhibitor GKT137831 suppressed ROS production as well as inflammatory and proliferative genes induced by lipopolysaccharide (LPS, platelet-derived growth factor (PDGF, or sonic hedgehog (Shh in primary mouse HSCs. Furthermore, the mRNAs of proliferative and pro-fibrotic genes were downregulated in NOX1 and NOX4 knock-out activated HSCs (cultured on plastic for 5 days. Finally, NOX1 and NOX4 protein levels were increased in human livers with cirrhosis compared with normal controls. Thus, NOX1 and NOX4 signaling mediates the pathogenesis of liver fibrosis, including the direct activation of HSC.

ROS-induced ROS release orchestrated by Nox4, Nox2, and mitochondria in VEGF signaling and angiogenesis.

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Kim, Young-Mee; Kim, Seok-Jo; Tatsunami, Ryosuke; Yamamura, Hisao; Fukai, Tohru; Ushio-Fukai, Masuko

2017-06-01

Reactive oxygen species (ROS) derived from NADPH oxidase (NOX) and mitochondria play a critical role in growth factor-induced switch from a quiescent to an angiogenic phenotype in endothelial cells (ECs). However, how highly diffusible ROS produced from different sources can coordinate to stimulate VEGF signaling and drive the angiogenic process remains unknown. Using the cytosol- and mitochondria-targeted redox-sensitive RoGFP biosensors with real-time imaging, here we show that VEGF stimulation in human ECs rapidly increases cytosolic RoGFP oxidation within 1 min, followed by mitochondrial RoGFP oxidation within 5 min, which continues at least for 60 min. Silencing of Nox4 or Nox2 or overexpression of mitochondria-targeted catalase significantly inhibits VEGF-induced tyrosine phosphorylation of VEGF receptor type 2 (VEGFR2-pY), EC migration and proliferation at the similar extent. Exogenous hydrogen peroxide (H 2 O 2 ) or overexpression of Nox4, which produces H 2 O 2 , increases mitochondrial ROS (mtROS), which is prevented by Nox2 siRNA, suggesting that Nox2 senses Nox4-derived H 2 O 2 to promote mtROS production. Mechanistically, H 2 O 2 increases S36 phosphorylation of p66Shc, a key mtROS regulator, which is inhibited by siNox2, but not by siNox4. Moreover, Nox2 or Nox4 knockdown or overexpression of S36 phosphorylation-defective mutant p66Shc(S36A) inhibits VEGF-induced mtROS, VEGFR2-pY, EC migration, and proliferation. In summary, Nox4-derived H 2 O 2 in part activates Nox2 to increase mtROS via pSer36-p66Shc, thereby enhancing VEGFR2 signaling and angiogenesis in ECs. This may represent a novel feed-forward mechanism of ROS-induced ROS release orchestrated by the Nox4/Nox2/pSer36-p66Shc/mtROS axis, which drives sustained activation of angiogenesis signaling program. Copyright © 2017 the American Physiological Society.

Activation of NADPH oxidase mediates increased endoplasmic reticulum stress and left ventricular remodeling after myocardial infarction in rabbits.

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Li, Bao; Tian, Jing; Sun, Yi; Xu, Tao-Rui; Chi, Rui-Fang; Zhang, Xiao-Li; Hu, Xin-Ling; Zhang, Yue-An; Qin, Fu-Zhong; Zhang, Wei-Fang

2015-05-01

Nicotinamide adenine dinucleotide 3-phosphate (NADPH) oxidase activity and endoplasmic reticulum (ER) stress are increased after myocardial infarction (MI). In this study, we proposed to test whether activation of the NADPH oxidase in the remote non-infarcted myocardium mediates ER stress and left ventricular (LV) remodeling after MI. Rabbits with MI or sham operation were randomly assigned to orally receive an NADPH oxidase inhibitor apocynin or placebo for 30 days. The agents were administered beginning at 1 week after surgery. MI rabbits exhibited decreases in LV fractional shortening, LV ejection fraction and the first derivative of the LV pressure rise, which were abolished by apocynin treatment. NADPH oxidase Nox2 protein and mRNA expressions were increased in the remote non-infarcted myocardium after MI. Immunolabeling further revealed that Nox2 was increased in cardiac myocytes in the remote myocardium. The apocynin treatment prevented increases in the Nox2 expression, NADPH oxidase activity, oxidative stress, myocyte apoptosis and GRP78, CHOP and cleaved caspase 12 protein expression in the remote myocardium. The apocynin treatment also attenuated increases in myocyte diameter and cardiac fibrosis. In cultured H9C2 cardiomyocytes exposed to angiotensin II, an important stimulus for post-MI remodeling, Nox2 knockdown with siRNA significantly inhibited angiotensin II-induced NADPH oxidase activation, reactive oxygen species and GRP78 and CHOP protein expression. We conclude that NADPH oxidase inhibition attenuates increased ER stress in the remote non-infarcted myocardium and LV remodeling late after MI in rabbits. These findings suggest that the activation of NADPH oxidase in the remote non-infarcted myocardium mediates increased ER stress, contributing to myocyte apoptosis and LV remodeling after MI. Copyright © 2015 Elsevier B.V. All rights reserved.

The role of oxidative stress and NADPH oxidase in the pathogenesis of atherosclerosis

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Dorota Bryk

2017-01-01

Full Text Available Reactive oxygen species (ROS play a key role in the pathogenesis of atherosclerosis. The main mechanisms which are involved are low-density lipoprotein oxidative modification, inactivation of nitric oxide and modulation of redox-sensitive signaling pathways. ROS contribute to several aspects of atherosclerosis including endothelial cell dysfunction, monocyte/macrophage recruitment and activation, stimulation of inflammation, and inducing smooth muscle cell migration and proliferation. NADPH oxidase is the main source of ROS in the vasculature. This enzyme consists of a membrane-bound heterodimer of gp91phox and p22phox, cytosolic regulatory subunits p47phox, p67phox and p40phox, and small GTP-binding proteins rac1 and rac 2. Seven distinct isoforms of this enzyme have been identified, of which four (NOX1, 2, 4 and 5 may have cardiovascular function. In this paper, we review the current state of knowledge concerning the role of oxidative stress and NOX enzymes in pathogenesis of atherosclerosis. Moreover, we analyze the experimental studies that explore the relationship between the NOX family and atherosclerosis.

Recombinant Nox4 cytosolic domain produced by a cell or cell-free base systems exhibits constitutive diaphorase activity

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Nguyen, Minh Vu Chuong, E-mail: mvchuong@yahoo.fr [GREPI AGIM FRE 3405 CNRS-UJF, Universite Joseph Fourier, Grenoble (France); Zhang, Leilei [GREPI AGIM FRE 3405 CNRS-UJF, Universite Joseph Fourier, Grenoble (France); Lhomme, Stanislas; Mouz, Nicolas [PX' Therapeutics, MINATEC/Batiment de Haute Technologie, Grenoble (France); Lenormand, Jean-Luc [HumProTher Laboratory, TheReX/TIMC-IMAG UMR 5525 CNRS UJF, Universite Joseph Fourier, UFR de Medecine, Domaine de la Merci, 38706 La Tronche (France); Lardy, Bernard; Morel, Francoise [GREPI AGIM FRE 3405 CNRS-UJF, Universite Joseph Fourier, Grenoble (France)

2012-03-16

Highlights: Black-Right-Pointing-Pointer A comparison of two bacterial cell and cell-free protein expression systems is presented. Black-Right-Pointing-Pointer Soluble and active truncated Nox4 proteins are produced. Black-Right-Pointing-Pointer Nox4 has a constitutive diaphorase activity which is independent of cytosolic factors. Black-Right-Pointing-Pointer Isoform Nox4B is unable to initiate the first electronic transfer step. Black-Right-Pointing-Pointer Findings contribute to the understanding of the mechanism of Nox4 oxidase activity. -- Abstract: The membrane protein NADPH (nicotinamide adenine dinucleotide phosphate) oxidase Nox4 constitutively generates reactive oxygen species differing from other NADPH oxidases activity, particularly in Nox2 which needs a stimulus to be active. Although the precise mechanism of production of reactive oxygen species by Nox2 is well characterized, the electronic transfer throughout Nox4 remains unclear. Our study aims to investigate the initial electronic transfer step (diaphorase activity) of the cytosolic tail of Nox4. For this purpose, we developed two different approaches to produce soluble and active truncated Nox4 proteins. We synthesized soluble recombinant proteins either by in vitro translation or by bacteria induction. While proteins obtained by bacteria induction demonstrate an activity of 4.4 {+-} 1.7 nmol/min/nmol when measured against iodonitro tetrazolium chloride and 20.5 {+-} 2.8 nmol/min/nmol with cytochrome c, the soluble proteins produced by cell-free expression system exhibit a diaphorase activity with a turn-over of 26 {+-} 2.6 nmol/min/nmol when measured against iodonitro tetrazolium chloride and 48 {+-} 20.2 nmol/min/nmol with cytochrome c. Furthermore, the activity of the soluble proteins is constitutive and does not need any stimulus. We also show that the cytosolic tail of the isoform Nox4B lacking the first NADPH binding site is unable to demonstrate any diaphorase activity pointing out the

Effect of different NADH oxidase levels on glucose metabolism by Lactococus lactis : kinetics of intracellular metabolite pools determined by in vivo nuclear magnetic resonance

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Neves, A.R.; Ramos, A.; Costa, H.; Swam, van I.I.; Hugenholtz, J.; Kleerebezem, M.; Vos, de W.M.; Santos, H.

2002-01-01

Three isogenic strains of Lactococcus lactis with different levels of H2O-forming NADH oxidase activity were used to study the effect of oxygen on glucose metabolism: the parent strain L. lactis MG1363, a NOX- strain harboring a deletion of the gene coding for H2O-forming NADH oxidase, and a NOX

Deficiency of Nox2 prevents angiotensin II-induced inward remodeling in cerebral arterioles

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Siu-Lung eChan

2013-06-01

Full Text Available Angiotensin II is an important determinant of inward remodeling in cerebral arterioles. Many of the vascular effects of angiotensin II are mediated by reactive oxygen species generated from homologues of NADPH oxidase with Nox2 predominating in small arteries and arterioles. Therefore, we tested the hypothesis that superoxide generated by Nox2 plays a role in angiotensin II-induced cerebral arteriolar remodeling. We examined Nox2-deficient and wild-type mice in which a pressor or a non-pressor dose of angiotensin II (1000 or 200 ng/kg/day or saline was infused for 4 weeks via osmotic minipumps. Systolic arterial pressure was measured by a tail-cuff method. Pressure and diameter of cerebral arterioles were measured through an open cranial window in anesthetized mice. Cross-sectional area (by histology and superoxide level (by hydroethidine staining of cerebral arterioles were determined ex vivo. The pressor, but not the non-pressor, dose of angiotensin II significantly increased systolic arterial pressure in both wild-type and Nox2-deficient mice. Both doses of angiotensin II increased superoxide levels and significantly reduced external diameter in maximally dilated cerebral arterioles in wild-type mice. Increased superoxide and inward remodeling were prevented in Nox2-deficient mice. Moreover, only the pressor dose of AngII increased cross-sectional area of arteriolar wall in wild-type mice and was prevented in Nox2-deficient mice. In conclusion, superoxide derived from Nox2-containing NADPH oxidase plays an important role in angiotensin II-mediated inward remodeling in cerebral arterioles. This effect appears to be independent of pressure and different from that of hypertrophy.

NADPH oxidase 4 attenuates cerebral artery changes during the progression of Marfan syndrome.

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Onetti, Yara; Meirelles, Thayna; Dantas, Ana P; Schröder, Katrin; Vila, Elisabet; Egea, Gustavo; Jiménez-Altayó, Francesc

2016-05-01

Marfan syndrome (MFS) is a connective tissue disorder that is often associated with the fibrillin-1 (Fbn1) gene mutation and characterized by cardiovascular alterations, predominantly ascending aortic aneurysms. Although neurovascular complications are uncommon in MFS, the improvement in Marfan patients' life expectancy is revealing other secondary alterations, potentially including neurovascular disorders. However, little is known about small-vessel pathophysiology in MFS. MFS is associated with hyperactivated transforming growth factor (TGF)-β signaling, which among numerous other downstream effectors, induces the NADPH oxidase 4 (Nox4) isoform of NADPH oxidase, a strong enzymatic source of H2O2 We hypothesized that MFS induces middle cerebral artery (MCA) alterations and that Nox4 contributes to them. MCA properties from 3-, 6-, or 9-mo-old Marfan (Fbn1(C1039G/+)) mice were compared with those from age/sex-matched wild-type littermates. At 6 mo, Marfan compared with wild-type mice developed higher MCA wall/lumen (wild-type: 0.081 ± 0.004; Marfan: 0.093 ± 0.002; 60 mmHg; P Marfan mice with Nox4 deficiency (Nox4(-/-)). Strikingly, Nox4 deletion in Marfan mice aggravated MCA wall thickening (cross-sectional area; Marfan: 6,660 ± 363 μm(2); Marfan Nox4(-/-): 8,795 ± 824 μm(2); 60 mmHg; P < 0.05), accompanied by decreased TGF-β expression and increased collagen deposition and Nox1 expression. These findings provide the first evidence that Nox4 mitigates cerebral artery structural changes in a murine model of MFS. Copyright © 2016 the American Physiological Society.

Overexpression of a water-forming NADH oxidase improves the metabolism and stress tolerance of Saccharmyces cerevisiae in aerobic fermenation

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Xinchi Shi

2016-09-01

Full Text Available Redox homeostasis is fundamental to the maintenance of metabolism. Redox imbalance can cause oxidative stress, which affects metabolism and growth. Water-forming NADH oxidase regulates the redox balance by oxidizing cytosolic NADH to NAD+, which relieves cytosolic NADH accumulation through rapid glucose consumption in Saccharomyces cerevisiae, thus decreasing the production of the byproduct glycerol in industrial ethanol production. Here, we studied the effects of overexpression of a water-forming NADH oxidase from Lactococcus lactis on the stress response of S. cerevisiae in aerobic batch fermentation, and we constructed an interaction network of transcriptional regulation and metabolic networks to study the effects of and mechanisms underlying NADH oxidase regulation. The oxidase-overexpressing strain (NOX showed increased glucose consumption, growth, and ethanol production, while glycerol production was remarkably lower. Glucose was exhausted by NOX at 26 h, while 18.92 ± 0.94 g/L residual glucose was left in the fermentation broth of the control strain (CON at this time point. At 29.5 h, the ethanol concentration for NOX peaked at 35.25 ± 1.76 g/L, which was 14.37 % higher than that for CON (30.82 ± 1.54 g/L. Gene expression involved in the synthesis of thiamine, which is associated with stress responses in various organisms, was increased in NOX. The transcription factor HAP4 was significantly upregulated in NOX at the late-exponential phase, indicating a diauxic shift in response to starvation. The apoptosis-inducing factor Nuc1 was downregulated while the transcription factor Sok2, which regulates the production of the small signaling molecule ammonia, was upregulated at the late-exponential phase, benefiting young cells on the rim. Reactive oxygen species production was decreased by 10% in NOX, supporting a decrease in apoptosis. The HOG pathway was not activated, although the osmotic stress was truly higher, indicating improved

NOX4-dependent neuronal autotoxicity and BBB breakdown explain the superior sensitivity of the brain to ischemic damage.

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Casas, Ana I; Geuss, Eva; Kleikers, Pamela W M; Mencl, Stine; Herrmann, Alexander M; Buendia, Izaskun; Egea, Javier; Meuth, Sven G; Lopez, Manuela G; Kleinschnitz, Christoph; Schmidt, Harald H H W

2017-11-14

Ischemic injury represents the most frequent cause of death and disability, and it remains unclear why, of all body organs, the brain is most sensitive to hypoxia. In many tissues, type 4 NADPH oxidase is induced upon ischemia or hypoxia, converting oxygen to reactive oxygen species. Here, we show in mouse models of ischemia in the heart, brain, and hindlimb that only in the brain does NADPH oxidase 4 (NOX4) lead to ischemic damage. We explain this distinct cellular distribution pattern through cell-specific knockouts. Endothelial NOX4 breaks down the BBB, while neuronal NOX4 leads to neuronal autotoxicity. Vascular smooth muscle NOX4, the common denominator of ischemia within all ischemic organs, played no apparent role. The direct neuroprotective potential of pharmacological NOX4 inhibition was confirmed in an ex vivo model, free of vascular and BBB components. Our results demonstrate that the heightened sensitivity of the brain to ischemic damage is due to an organ-specific role of NOX4 in blood-brain-barrier endothelial cells and neurons. This mechanism is conserved in at least two rodents and humans, making NOX4 a prime target for a first-in-class mechanism-based, cytoprotective therapy in the unmet high medical need indication of ischemic stroke. Copyright © 2017 the Author(s). Published by PNAS.

Congruence between PM H+-ATPase and NADPH oxidase during root growth: a necessary probability.

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Majumdar, Arkajo; Kar, Rup Kumar

2018-07-01

Plasma membrane (PM) H + -ATPase and NADPH oxidase (NOX) are two key enzymes responsible for cell wall relaxation during elongation growth through apoplastic acidification and production of ˙OH radical via O 2 ˙ - , respectively. Our experiments revealed a putative feed-forward loop between these enzymes in growing roots of Vigna radiata (L.) Wilczek seedlings. Thus, NOX activity was found to be dependent on proton gradient generated across PM by H + -ATPase as evident from pharmacological experiments using carbonyl cyanide m-chlorophenylhydrazone (CCCP; protonophore) and sodium ortho-vanadate (PM H + -ATPase inhibitor). Conversely, H + -ATPase activity retarded in response to different ROS scavengers [CuCl 2 , N, N' -dimethylthiourea (DMTU) and catalase] and NOX inhibitors [ZnCl 2 and diphenyleneiodonium (DPI)], while H 2 O 2 promoted PM H + -ATPase activity at lower concentrations. Repressing effects of Ca +2 antagonists (La +3 and EGTA) on the activity of both the enzymes indicate its possible mediation. Since, unlike animal NOX, the plant versions do not possess proton channel activity, harmonized functioning of PM H + -ATPase and NOX appears to be justified. Plasma membrane NADPH oxidase and H + -ATPase are functionally synchronized and they work cooperatively to maintain the membrane electrical balance while mediating plant cell growth through wall relaxation.

Involvement of NADH Oxidase in Biofilm Formation in Streptococcus sanguinis.

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Xiuchun Ge

Full Text Available Biofilms play important roles in microbial communities and are related to infectious diseases. Here, we report direct evidence that a bacterial nox gene encoding NADH oxidase is involved in biofilm formation. A dramatic reduction in biofilm formation was observed in a Streptococcus sanguinis nox mutant under anaerobic conditions without any decrease in growth. The membrane fluidity of the mutant bacterial cells was found to be decreased and the fatty acid composition altered, with increased palmitic acid and decreased stearic acid and vaccenic acid. Extracellular DNA of the mutant was reduced in abundance and bacterial competence was suppressed. Gene expression analysis in the mutant identified two genes with altered expression, gtfP and Idh, which were found to be related to biofilm formation through examination of their deletion mutants. NADH oxidase-related metabolic pathways were analyzed, further clarifying the function of this enzyme in biofilm formation.

Deciphering the role of NADPH oxidase in complex interactions between maize (Zea mays L.) genotypes and cereal aphids.

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Sytykiewicz, Hubert

2016-07-22

Plant NADPH oxidases (NOXs) encompass a group of membrane-bound enzymes participating in formation of reactive oxygen species (ROS) under physiological conditions as well as in response to environmental stressors. The purpose of the survey was to unveil the role of NADPH oxidase in pro-oxidative responses of maize (Zea mays L.) seedling leaves exposed to cereal aphids' infestation. The impact of apteral females of bird cherry-oat aphid (Rhopalosiphum padi L.) and grain aphid (Sitobion avenae F.) feeding on expression levels of all four NADPH oxidase genes (rbohA, rbohB, rbohC, rbohD) and total activity of NOX enzyme in maize plants were investigated. In addition, inhibitory effect of diphenylene iodonium (DPI) pre-treatment on NOX activity and hydrogen peroxide content in aphid-stressed maize seedlings was studied. Leaf infestation biotests were accomplished on 14-day-old seedlings representing two aphid-resistant varieties (Ambrozja and Waza) and two aphid-susceptible ones (Tasty Sweet and Złota Karłowa). Insects' attack led to profound upregulation of rbohA and rbohD genes in tested host plants, lower elevations were noted in level of rbohB mRNA, whereas abundance of rbohC transcript was not significantly altered. It was uncovered aphid-induced enhancement of NOX activity in examined plants. Higher increases in expression of all investigated rboh genes and activity of NADPH oxidase occurred in tissues of more resistant maize cultivars than in susceptible ones. Furthermore, DPI treatment resulted in strong reduction of NOX activity and H2O2 accumulation in aphid-infested Z. mays plants, thus evidencing circumstantial role of the enzyme in insect-elicited ROS generation. Copyright © 2016 Elsevier Inc. All rights reserved.

The Nox/Ferric reductase/Ferric reductase-like families of Eumycetes.

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Grissa, Ibtissem; Bidard, Frédérique; Grognet, Pierre; Grossetete, Sandrine; Silar, Philippe

2010-09-01

Reactive Oxygen Species (ROS) are involved in plant biomass degradation by fungi and development of fungal structures. While the ROS-generating NADPH oxidases from filamentous fungi are under strong scrutiny, much less is known about the related integral Membrane (or Ferric) Reductases (IMRs). Here, we present a survey of these enzymes in 29 fungal genomes covering the entire available range of fungal diversity. IMRs are present in all fungal genomes. They can be classified into at least 24 families, underscoring the high diversity of these enzymes. Some are differentially regulated during colony or fruiting body development, as well as by the nature of the carbon source of the growth medium. Importantly, functional characterization of IMRs has been made on proteins belonging to only two families, while nothing or very little is known about the proteins of the other 22 families. Copyright © 2010 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Involvement of NADPH oxidase isoforms in the production of O2- manipulated by ABA in the senescing leaves of early-senescence-leaf (esl) mutant rice (Oryza sativa).

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Li, Zhaowei; Wang, Fubiao; Zhao, Qian; Liu, Jianchao; Cheng, Fangmin

2018-01-01

In this study, the differences in reactive oxygen species (ROS) generation and abscisic acid (ABA) accumulation in senescing leaves were investigated by early-senescence-leaf (esl) mutant and its wild type, to clarify the relationship among ABA levels, ROS generation, and NADPH oxidase (Nox) in senescing leaves of rice (Oryza sativa). The temporal expression levels of OsNox isoforms in senescing leaves and their expression patterns in response to ABA treatment were determined through quantitative real-time reverse transcription PCR (qRT-PCR). Results showed that the flag leaf of the esl mutant generated more O2- concentrations and accumulated higher ABA levels than the wild-type cultivar did in the grain-filling stage. Exogenous ABA treatment induced O2- generation; however, it was depressed by diphenyleneiodonium chloride (DPI) pretreatment in the detached leaf segments. This finding suggested the involvement of NADPH oxidase in ABA-induced O2- generation. The esl mutant exhibited significantly higher expression of OsNox2, OsNox5, OsNox6, and OsNox7 in the initial of grain-filling stage, followed by sharply decrease. The transcriptional levels of OsNox1, OsNox3, and OsFR07 in the flag leaf of the esl mutant were significantly lower than those in the wild-type cultivar. The expression levels of OsNox2, OsNox5, OsNox6, and OsNox7 were significantly enhanced by exogenous ABA treatments. The enhanced expression levels of OsNox2 and OsNox6 were dependent on the duration of ABA treatment. The inducible expression levels of OsNox5 and OsNox7 were dependent on ABA concentrations. By contrast, exogenous ABA treatment severely repressed the transcripts of OsNox1, OsNox3, and OsFR07 in the detached leaf segments. Therefore, OsNox2, OsNox5, OsNox6, and OsNox7 were probably involved in the ABA-induced O2- generation in the initial stage of leaf senescence. Subsequently, other oxidases activated in deteriorating cells were associated with ROS generation and accumulation in the

Molecular evolution of the polyamine oxidase gene family in Metazoa

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Polticelli Fabio

2012-06-01

Full Text Available Abstract Background Polyamine oxidase enzymes catalyze the oxidation of polyamines and acetylpolyamines. Since polyamines are basic regulators of cell growth and proliferation, their homeostasis is crucial for cell life. Members of the polyamine oxidase gene family have been identified in a wide variety of animals, including vertebrates, arthropodes, nematodes, placozoa, as well as in plants and fungi. Polyamine oxidases (PAOs from yeast can oxidize spermine, N1-acetylspermine, and N1-acetylspermidine, however, in vertebrates two different enzymes, namely spermine oxidase (SMO and acetylpolyamine oxidase (APAO, specifically catalyze the oxidation of spermine, and N1-acetylspermine/N1-acetylspermidine, respectively. Little is known about the molecular evolutionary history of these enzymes. However, since the yeast PAO is able to catalyze the oxidation of both acetylated and non acetylated polyamines, and in vertebrates these functions are addressed by two specialized polyamine oxidase subfamilies (APAO and SMO, it can be hypothesized an ancestral reference for the former enzyme from which the latter would have been derived. Results We analysed 36 SMO, 26 APAO, and 14 PAO homologue protein sequences from 54 taxa including various vertebrates and invertebrates. The analysis of the full-length sequences and the principal domains of vertebrate and invertebrate PAOs yielded consensus primary protein sequences for vertebrate SMOs and APAOs, and invertebrate PAOs. This analysis, coupled to molecular modeling techniques, also unveiled sequence regions that confer specific structural and functional properties, including substrate specificity, by the different PAO subfamilies. Molecular phylogenetic trees revealed a basal position of all the invertebrates PAO enzymes relative to vertebrate SMOs and APAOs. PAOs from insects constitute a monophyletic clade. Two PAO variants sampled in the amphioxus are basal to the dichotomy between two well supported

Constitutive NADPH-dependent electron transferase activity of the Nox4 dehydrogenase domain.

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Nisimoto, Yukio; Jackson, Heather M; Ogawa, Hisamitsu; Kawahara, Tsukasa; Lambeth, J David

2010-03-23

NADPH oxidase 4 (Nox4) is constitutively active, while Nox2 requires the cytosolic regulatory subunits p47(phox) and p67(phox) and activated Rac with activation by phorbol 12-myristate 13-acetate (PMA). This study was undertaken to identify the domain on Nox4 that confers constitutive activity. Lysates from Nox4-expressing cells exhibited constitutive NADPH- but not NADH-dependent hydrogen peroxide production with a K(m) for NADPH of 55 +/- 10 microM. The concentration of Nox4 in cell lysates was estimated using Western blotting and allowed calculation of a turnover of approximately 200 mol of H(2)O(2) min(-1) (mol of Nox4)(-1). A chimeric protein (Nox2/4) consisting of the Nox2 transmembrane (TM) domain and the Nox4 dehydrogenase (DH) domain showed H(2)O(2) production in the absence of cytosolic regulatory subunits. In contrast, chimera Nox4/2, consisting of the Nox4 TM and Nox2 DH domains, exhibited PMA-dependent activation that required coexpression of regulatory subunits. Nox DH domains from several Nox isoforms were purified and evaluated for their electron transferase activities. Nox1 DH, Nox2 DH, and Nox5 DH domains exhibited barely detectable activities toward artificial electron acceptors, while the Nox4 DH domain exhibited significant rates of reduction of cytochrome c (160 min(-1), largely superoxide dismutase-independent), ferricyanide (470 min(-1)), and other electron acceptors (artificial dyes and cytochrome b(5)). Rates were similar to those observed for H(2)O(2) production by the Nox4 holoenzyme in cell lysates. The activity required added FAD and was seen with NADPH but not NADH. These results indicate that the Nox4 DH domain exists in an intrinsically activated state and that electron transfer from NADPH to FAD is likely to be rate-limiting in the NADPH-dependent reduction of oxygen by holo-Nox4.

Reactive Oxygen Species Generated by NADPH Oxidases Promote Radicle Protrusion and Root Elongation during Rice Seed Germination

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Wen-Yan Li

2017-01-01

Full Text Available Seed germination is a complicated biological process that requires regulation through various enzymatic and non-enzymatic mechanisms. Although it has been recognized that reactive oxygen species (ROS regulate radicle emergence and root elongation in a non-enzymatic manner during dicot seed germination, the role of ROS in monocot seed germination remains unknown. NADPH oxidases (NOXs are the major ROS producers in plants; however, whether and how NOXs regulate rice seed germination through ROS generation remains unclear. Here, we report that diphenyleneiodinium (DPI, a specific NOX inhibitor, potently inhibited embryo and seedling growth—especially that of the radicle and of root elongation—in a dose-dependent manner. Notably, the DPI-mediated inhibition of radicle and root growth could be eliminated by transferring seedlings from DPI to water. Furthermore, ROS production/accumulation during rice seed germination was quantified via histochemistry. Superoxide radicals (O2−, hydrogen peroxide (H2O2 and hydroxyl radicals (•OH accumulated steadily in the coleorhiza, radicle and seedling root of germinating rice seeds. Expression profiles of the nine typical NOX genes were also investigated. According to quantitative PCR, OsNOX5, 7 and 9 were expressed relatively higher. When seeds were incubated in water, OsNOX5 expression progressively increased in the embryo from 12 to 48 h, whereas OsNOX7 and 9 expressions increased from 12 to 24 h and decreased thereafter. As expected, DPI inhibits the expression at predetermined time points for each of these genes. Taken together, these results suggest that ROS produced by NOXs are involved in radicle and root elongation during rice seed germination, and OsNOX5, 7 and 9 could play crucial roles in rice seed germination. These findings will facilitate further studies of the roles of ROS generated by NOXs during seed germination and seedling establishment and also provide valuable information for the

STAT5A-mediated NOX5-L expression promotes the proliferation and metastasis of breast cancer cells

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Dho, So Hee [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Radioisotope Research Division, Department of Research Reactor Utilization, Korea Atomic Energy Research Institute, Daejeon 305-353 (Korea, Republic of); Kim, Ji Young; Lee, Kwang-Pyo; Kwon, Eun-Soo [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Lim, Jae Cheong [Radioisotope Research Division, Department of Research Reactor Utilization, Korea Atomic Energy Research Institute, Daejeon 305-353 (Korea, Republic of); Kim, Chang-Jin [Department of Pathology, Soonchunhyang Medical Science Research Institute, Chonan 330-090 (Korea, Republic of); Jeong, Dongjun, E-mail: juny1024@sch.ac.kr [Department of Pathology, Soonchunhyang Medical Science Research Institute, Chonan 330-090 (Korea, Republic of); Kwon, Ki-Sun, E-mail: kwonks@kribb.re.kr [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Department of Functional Genomics, Korea University of Science and Technology (UST), Daejeon 305-333 (Korea, Republic of)

2017-02-01

NADPH oxidase (NOX) generates reactive oxygen species (ROS) and has been suggested to mediate cell proliferation in some cancers. Here, we show that an increase in the expression of NOX5 long form (NOX5-L) is critical for tumor progression in breast tumor tissues. Immunostaining of clinical samples indicated that NOX5 was overexpressed in 41.1% of breast ductal carcinoma samples. NOX5-L depletion consistently suppressed cell proliferation, invasion, and migration in vitro. Antibody-mediated neutralization of NOX5-L attenuated tumor progression in a mouse xenograft model. Promoter analysis revealed that NOX5-L expression is regulated by STAT5A in breast cancer cells. Based on our novel findings, we suggest that inhibition of NOX5-L may be a promising therapeutic strategy that exerts anti-cancer effects via the modulation of ROS-mediated cell signaling. - Highlights: • The ROS-generating protein, NOX5-L, determines cellular proliferation and metastasis in subset of breast tumor. • Tumor growth was attenuated by the treatment of anti-NOX5-L antibody in a xenograft model. • NOX5-L expression is transcriptionally regulated by STAT5A in breast cancer cells.

Epigenetic regulation of vascular NADPH oxidase expression and reactive oxygen species production by histone deacetylase-dependent mechanisms in experimental diabetes

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Simona-Adriana Manea

2018-06-01

Full Text Available Reactive oxygen species (ROS generated by up-regulated NADPH oxidase (Nox contribute to structural-functional alterations of the vascular wall in diabetes. Epigenetic mechanisms, such as histone acetylation, emerged as important regulators of gene expression in cardiovascular disorders. Since their role in diabetes is still elusive we hypothesized that histone deacetylase (HDAC-dependent mechanisms could mediate vascular Nox overexpression in diabetic conditions. Non-diabetic and streptozotocin-induced diabetic C57BL/6J mice were randomized to receive vehicle or suberoylanilide hydroxamic acid (SAHA, a pan-HDAC inhibitor. In vitro studies were performed on a human aortic smooth muscle cell (SMC line. Aortic SMCs typically express Nox1, Nox4, and Nox5 subtypes. HDAC1 and HDAC2 proteins along with Nox1, Nox2, and Nox4 levels were found significantly elevated in the aortas of diabetic mice compared to non-diabetic animals. Treatment of diabetic mice with SAHA mitigated the aortic expression of Nox1, Nox2, and Nox4 subtypes and NADPH-stimulated ROS production. High concentrations of glucose increased HDAC1 and HDAC2 protein levels in cultured SMCs. SAHA significantly reduced the high glucose-induced Nox1/4/5 expression, ROS production, and the formation malondialdehyde-protein adducts in SMCs. Overexpression of HDAC2 up-regulated the Nox1/4/5 gene promoter activities in SMCs. Physical interactions of HDAC1/2 and p300 proteins with Nox1/4/5 promoters were detected at the sites of active transcription. High glucose induced histone H3K27 acetylation enrichment at the promoters of Nox1/4/5 genes in SMCs. The novel data of this study indicate that HDACs mediate vascular Nox up-regulation in diabetes. HDAC inhibition reduces vascular ROS production in experimental diabetes, possibly by a mechanism involving negative regulation of Nox expression. Keywords: NADPH oxidase, Epigenetics, HDAC, Histone acetylation, Diabetes

Involvement of NADPH oxidase isoforms in the production of O2− manipulated by ABA in the senescing leaves of early-senescence-leaf (esl) mutant rice (Oryza sativa)

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Wang, Fubiao; Zhao, Qian; Liu, Jianchao; Cheng, Fangmin

2018-01-01

In this study, the differences in reactive oxygen species (ROS) generation and abscisic acid (ABA) accumulation in senescing leaves were investigated by early-senescence-leaf (esl) mutant and its wild type, to clarify the relationship among ABA levels, ROS generation, and NADPH oxidase (Nox) in senescing leaves of rice (Oryza sativa). The temporal expression levels of OsNox isoforms in senescing leaves and their expression patterns in response to ABA treatment were determined through quantitative real-time reverse transcription PCR (qRT-PCR). Results showed that the flag leaf of the esl mutant generated more O2- concentrations and accumulated higher ABA levels than the wild-type cultivar did in the grain-filling stage. Exogenous ABA treatment induced O2- generation; however, it was depressed by diphenyleneiodonium chloride (DPI) pretreatment in the detached leaf segments. This finding suggested the involvement of NADPH oxidase in ABA-induced O2- generation. The esl mutant exhibited significantly higher expression of OsNox2, OsNox5, OsNox6, and OsNox7 in the initial of grain-filling stage, followed by sharply decrease. The transcriptional levels of OsNox1, OsNox3, and OsFR07 in the flag leaf of the esl mutant were significantly lower than those in the wild-type cultivar. The expression levels of OsNox2, OsNox5, OsNox6, and OsNox7 were significantly enhanced by exogenous ABA treatments. The enhanced expression levels of OsNox2 and OsNox6 were dependent on the duration of ABA treatment. The inducible expression levels of OsNox5 and OsNox7 were dependent on ABA concentrations. By contrast, exogenous ABA treatment severely repressed the transcripts of OsNox1, OsNox3, and OsFR07 in the detached leaf segments. Therefore, OsNox2, OsNox5, OsNox6, and OsNox7 were probably involved in the ABA-induced O2- generation in the initial stage of leaf senescence. Subsequently, other oxidases activated in deteriorating cells were associated with ROS generation and accumulation in the

NADPH Oxidases: Progress and Opportunities

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San Martin, Alejandra; Griendling, Kathy K.

2014-01-01

From the initial discovery in 1999 that NADPH oxidases comprise a family of enzymes to our current focus on drug development to treat multiple pathologies related to this enzyme family, progress has been swift and impressive. We have expanded our understanding of the extent of the family, the basic enzymatic biochemistry, the multiple cellular functions controlled by NADPH oxidases, and their varied roles in physiology and diseases. We have developed numerous cell culture tools, animal models...

Rho Kinase ROCK2 Mediates Acid-Induced NADPH Oxidase NOX5-S Expression in Human Esophageal Adenocarcinoma Cells.

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Jie Hong

Full Text Available Mechanisms of the progression from Barrett's esophagus (BE to esophageal adenocarcinoma (EA are not fully understood. We have shown that NOX5-S may be involved in this progression. However, how acid upregulates NOX5-S is not well known. We found that acid-induced increase in NOX5-S expression was significantly decreased by the Rho kinase (ROCK inhibitor Y27632 in BE mucosal biopsies and FLO-1 EA cells. In addition, acid treatment significantly increased the Rho kinase activity in FLO-1 cells. The acid-induced increase in NOX5-S expression and H2O2 production was significantly decreased by knockdown of Rho kinase ROCK2, but not by knockdown of ROCK1. Conversely, the overexpression of the constitutively active ROCK2, but not the constitutively active ROCK1, significantly enhanced the NOX5-S expression and H2O2 production. Moreover, the acid-induced increase in Rho kinase activity and in NOX5-S mRNA expression was blocked by the removal of calcium in both FLO-1 and OE33 cells. The calcium ionophore A23187 significantly increased the Rho kinase activity and NOX5-S mRNA expression. We conclude that acid-induced increase in NOX5-S expression and H2O2 production may depend on the activation of ROCK2, but not ROCK1, in EA cells. The acid-induced activation of Rho kinase may be mediated by the intracellular calcium increase. It is possible that persistent acid reflux present in BE patients may increase the intracellular calcium, activate ROCK2 and thereby upregulate NOX5-S. High levels of reactive oxygen species derived from NOX5-S may cause DNA damage and thereby contribute to the progression from BE to EA.

Both cardiomyocyte and endothelial cell Nox4 mediate protection against hemodynamic overload-induced remodelling.

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Zhang, Min; Mongue-Din, Heloise; Martin, Daniel; Catibog, Norman; Smyrnias, Ioannis; Zhang, Xiaohong; Yu, Bin; Wang, Minshu; Brandes, Ralf P; Schröder, Katrin; Shah, Ajay M

2018-03-01

NADPH oxidase-4 (Nox4) is an important reactive oxygen species (ROS) source that is upregulated in the haemodynamically overloaded heart. Our previous studies using global Nox4 knockout (Nox4KO) mice demonstrated a protective role of Nox4 during chronic abdominal aortic banding, involving a paracrine enhancement of myocardial capillary density. However, other authors who studied cardiac-specific Nox4KO mice reported detrimental effects of Nox4 in response to transverse aortic constriction (TAC). It has been speculated that these divergent results are due to cell-specific actions of Nox4 (i.e. cardiomyocyte Nox4 detrimental but endothelial Nox4 beneficial) and/or differences in the model of pressure overload (i.e. abdominal banding vs. TAC). This study aimed to (i) investigate whether the effects of Nox4 on pressure overload-induced cardiac remodelling vary according to the pressure overload model and (ii) compare the roles of cardiomyocyte vs. endothelial cell Nox4. Global Nox4KO mice subjected to TAC developed worse cardiac remodelling and contractile dysfunction than wild-type littermates, consistent with our previous results with abdominal aortic banding. Next, we generated inducible cardiomyocyte-specific Nox4 KO mice (Cardio-Nox4KO) and endothelial-specific Nox4 KO mice (Endo-Nox4KO) and studied their responses to pressure overload. Both Cardio-Nox4KO and Endo-Nox4KO developed worse pressure overload-induced cardiac remodelling and dysfunction than wild-type littermates, associated with significant decrease in protein levels of HIF1α and VEGF and impairment of myocardial capillarization. Cardiomyocyte as well as endothelial cell Nox4 contributes to protection against chronic hemodynamic overload-induced cardiac remodelling, at least in part through common effects on myocardial capillary density. © The Author 2017 Published by Oxford University Press on behalf of the European Society of Cardiology.

Identification of the NADPH Oxidase 4 Inhibiting Principle of Lycopus europaeus

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Silvia Revoltella

2018-03-01

Full Text Available NADPH oxidase 4 (Nox4 has recently been implicated as driving force in cellular senescence. Thus, there is growing interest to develop Nox4 inhibitors, which might be valuable agents for cosmeceutical applications. Alpine plants represent a valuable source for the identification of novel bioactive natural products with anti-ageing effects, especially substances that protect plants against UV radiation, which is also known to contribute to the ageing of human skin. Therefore, the aim of this study was to identify novel Nox4 inhibitors from alpine plants. Within an initial screening of extracts of alpine plants on their ability to inhibit Nox4 activity in HEK cells, the methanolic extract of the subaerial parts of Lycopus europaeus showed a strong inhibition of Nox4 (81% chemiluminescence quenching and a simultaneously high cell viability (91% vitality. Rosmarinic acid was isolated and identified as the major compound in this bioactive extract. It showed a dose dependent inhibitory activity on Nox4 with an IC50 of 1 µM. Moreover, it also showed a significant inhibitory activity on Nox2 in the low micromolar range, whereas no inhibition of Nox5 was detected. Further investigations confirmed that the observed effects of rosmarinic acid on Nox2 and Nox4 are real inhibitory activities, and not due to ROS scavenging effects. Therefore, L. europaeus, which we demonstrated to be a good source of rosmarinic acid, has great potential for usage in cosmeceutical products with anti-ageing activity.

Redox stress in Marfan syndrome: Dissecting the role of the NADPH oxidase NOX4 in aortic aneurysm.

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Jiménez-Altayó, Francesc; Meirelles, Thayna; Crosas-Molist, Eva; Sorolla, M Alba; Del Blanco, Darya Gorbenko; López-Luque, Judit; Mas-Stachurska, Aleksandra; Siegert, Ana-Maria; Bonorino, Fabio; Barberà, Laura; García, Carolina; Condom, Enric; Sitges, Marta; Rodríguez-Pascual, Fernando; Laurindo, Francisco; Schröder, Katrin; Ros, Joaquim; Fabregat, Isabel; Egea, Gustavo

2018-04-01

Marfan syndrome (MFS) is characterized by the formation of ascending aortic aneurysms resulting from altered assembly of extracellular matrix fibrillin-containing microfibrils and dysfunction of TGF-β signaling. Here we identify the molecular targets of redox stress in aortic aneurysms from MFS patients, and investigate the role of NOX4, whose expression is strongly induced by TGF-β, in aneurysm formation and progression in a murine model of MFS. Working models included aortae and cultured vascular smooth muscle cells (VSMC) from MFS patients, and a NOX4-deficient Marfan mouse model (Fbn1 C1039G/+ -Nox4 -/- ). Increased tyrosine nitration and reactive oxygen species levels were found in the tunica media of human aortic aneurysms and in cultured VSMC. Proteomic analysis identified nitrated and carbonylated proteins, which included smooth muscle α-actin (αSMA) and annexin A2. NOX4 immunostaining increased in the tunica media of human Marfan aorta and was transcriptionally overexpressed in VSMC. Fbn1 C1039G/+ -Nox4 -/- mice aortas showed a reduction of fragmented elastic fibers, which was accompanied by an amelioration in the Marfan-associated enlargement of the aortic root. Increase in the contractile phenotype marker calponin in the tunica media of MFS mice aortas was abrogated in Fbn1 C1039G/+ -Nox4 -/- mice. Endothelial dysfunction evaluated by myography in the Marfan ascending aorta was prevented by the absence of Nox4 or catalase-induced H 2 O 2 decomposition. We conclude that redox stress occurs in MFS, whose targets are actin-based cytoskeleton members and regulators of extracellular matrix homeostasis. Likewise, NOX4 have an impact in the progression of the aortic dilation in MFS and in the structural organization of the aortic tunica media, the VSMC phenotypic modulation, and endothelial function. Copyright © 2018 Elsevier Inc. All rights reserved.

QSYQ Attenuates Oxidative Stress and Apoptosis Induced Heart Remodeling Rats through Different Subtypes of NADPH-Oxidase

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Yong Wang

2013-01-01

Full Text Available We aim to investigate the therapeutic effects of QSYQ, a drug of heart failure (HF in clinical practice in China, on a rat heart failure (HF model. 3 groups were divided: HF model group (LAD ligation, QSYQ group (LAD ligation and treated with QSYQ, and sham-operated group. After 4 weeks, rats were sacrificed for cardiac injury measurements. Rats with HF showed obvious histological changes including necrosis and inflammation foci, elevated ventricular remodeling markers levels(matrix metalloproteinases-2, MMP-2, deregulated ejection fraction (EF value, increased formation of oxidative stress (Malondialdehyde, MDA, and up-regulated levels of apoptotic cells (caspase-3, p53 and tunnel in myocardial tissue. Treatment of QSYQ improved cardiac remodeling through counter-acting those events. The improvement of QSYQ was accompanied with a restoration of NADPH oxidase 4 (NOX4 and NADPH oxidase 2 (NOX2 pathways in different patterns. Administration of QSYQ could attenuate LAD-induced HF, and AngII-NOX2-ROS-MMPs pathway seemed to be the critical potential targets for QSYQ to reduce the remodeling. Moreover, NOX4 was another key targets to inhibit the p53 and Caspase3, thus to reduce the hypertrophy and apoptosis, and eventually provide a synergetic cardiac protective effect.

Correlation between total nitrite/nitrate concentrations and monoamine oxidase (types A and B) and semicarbazide-sensitive amine oxidase enzymatic activities in human mesenteric arteries from non-diabetic and type 2 diabetic patients

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Nunes, S.F.; Figueiredo, I.V. [Laboratório de Farmacologia, Faculdade de Farmácia, Universidade de Coimbra, Coimbra (Portugal); Pereira, J.S. [Instituto Português de Oncologia de Coimbra, Coimbra (Portugal); Lopes, M.C.; Caramona, M.M. [Laboratório de Farmacologia, Faculdade de Farmácia, Universidade de Coimbra, Coimbra (Portugal)

2011-11-25

The aim of this study was to determine the correlation between total nitrite/nitrate concentrations (NOx) and the kinetic parameters of monoamine oxidase enzymes (MAO-A and MAO-B) and semicarbazide-sensitive amine oxidase (SSAO) in human mesenteric arteries. Arteries were from non-diabetic and type 2 diabetic patients with sigmoid or rectum carcinoma for whom surgery was the first option and who were not exposed to neo-adjuvant therapy. Segments of human inferior mesenteric arteries from non-diabetic (61.1 ± 8.9 years old, 7 males and 5 females, N = 12) and type 2 diabetic patients (65.8 ± 6.2 years old, 8 males and 4 females, N = 12) were used to determine NOx concentrations and the kinetic parameters of MAO-A, MAO-B and SSAO by the Griess reaction and by radiochemical assay, respectively. The NOx concentrations in arteries from diabetic patients did not differ significantly from those of the non-diabetic group (10.28 ± 4.61 vs 10.71 ± 4.32 nmol/mg protein, respectively). In the non-diabetic group, there was a positive correlation between NOx concentrations and MAO-B parameters: K{sub m} (r = 0.612, P = 0.034) and V{sub max} (r = 0.593, P = 0.042), and a negative correlation with the SSAO parameters: K{sub m} (r = -0.625, P = 0.029) and V{sub max} (r = -0.754, P = 0.005). However, in the diabetic group no correlation was found between NOx concentrations and the three kinetic parameters of the enzymes. These results suggest an important function of sympathetic nerves and vascular NOx concentrations in arteries of non-diabetic patients. Thus, these results confirm the importance of a balance between oxidants and antioxidants in the maintenance of vascular homeostasis to prevent oxidative stress.

Nox-2-mediated phenotype loss of hippocampal parvalbumin interneurons might contribute to postoperative cognitive decline in aging mice

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lili qiu

2016-10-01

Full Text Available Postoperative cognitive decline (POCD is a common complication following anesthesia and surgery, especially in elderly patients; however, the precise mechanisms of POCD remain unclear. Here, we investigated whether nicotinamide adenine dinucleotide phosphate (NADPH oxidase mediated-abnormalities in parvalbumin (PV interneurons play an important role in the pathophysiology of POCD. The animal model was established using isoflurane anesthesia and exploratory laparotomy in sixteen-month-old male C57BL/6 mice. For interventional experiments, mice were chronically treated with the NADPH oxidase inhibitor apocynin (APO. Open field and fear conditioning behavioral tests were performed on day 6 and 7 post-surgery, respectively. In a separate experiment, brain tissue was harvested and subjected to biochemical analysis. Primary hippocampal neurons challenged with lipopolysaccharide in vitro were used to investigate the mechanisms underlying the oxidative stress-induced abnormalities in PV interneurons. Our results showed that anesthesia and surgery induced significant hippocampus-dependent memory impairment, which was accompanied by PV interneuron phenotype loss and increased expression of interleukin-1β, markers of oxidative stress, and NADPH oxidase 2 (Nox2 in the hippocampus. In addition, lipopolysaccharide exposure increased Nox2 level and decreased the expression of PV and the number of excitatory synapses onto PV interneurons in the primary hippocampal neurons. Notably, treatment with APO reversed these abnormalities. Our study suggests that Nox2-derived ROS production triggers, at least in part, anesthesia- and surgery-induced hippocampal PV interneuron phenotype loss and consequent cognitive impairment in aging mice.

Ebselen and congeners inhibit NADPH oxidase 2-dependent superoxide generation by interrupting the binding of regulatory subunits.

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Smith, Susan M E; Min, Jaeki; Ganesh, Thota; Diebold, Becky; Kawahara, Tsukasa; Zhu, Yerun; McCoy, James; Sun, Aiming; Snyder, James P; Fu, Haian; Du, Yuhong; Lewis, Iestyn; Lambeth, J David

2012-06-22

NADPH oxidases (Nox) are a primary source of reactive oxygen species (ROS), which function in normal physiology and, when overproduced, in pathophysiology. Recent studies using mice deficient in Nox2 identify this isoform as a novel target against Nox2-implicated inflammatory diseases. Nox2 activation depends on the binding of the proline-rich domain of its heterodimeric partner p22phox to p47phox. A high-throughput screen that monitored this interaction via fluorescence polarization identified ebselen and several of its analogs as inhibitors. Medicinal chemistry was performed to explore structure-activity relationships and to optimize potency. Ebselen and analogs potently inhibited Nox1 and Nox2 activity but were less effective against other isoforms. Ebselen also blocked translocation of p47phox to neutrophil membranes. Thus, ebselen and its analogs represent a class of compounds that inhibit ROS generation by interrupting the assembly of Nox2-activating regulatory subunits. Copyright © 2012 Elsevier Ltd. All rights reserved.

Nox2 and p47phox modulate compensatory growth of primary collateral arteries

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DiStasi, Matthew R.; Unthank, Joseph L.

2014-01-01

The role of NADPH oxidase (Nox) in both the promotion and impairment of compensatory collateral growth remains controversial because the specific Nox and reactive oxygen species involved are unclear. The aim of this study was to identify the primary Nox and reactive oxygen species associated with early stage compensatory collateral growth in young, healthy animals. Ligation of the feed arteries that form primary collateral pathways in rat mesentery and mouse hindlimb was used to assess the role of Nox during collateral growth. Changes in mesenteric collateral artery Nox mRNA expression determined by real-time PCR at 1, 3, and 7 days relative to same-animal control arteries suggested a role for Nox subunits Nox2 and p47phox. Administration of apocynin or Nox2ds-tat suppressed collateral growth in both rat and mouse models, suggesting the Nox2/p47phox interaction was involved. Functional significance of p47phox expression was assessed by evaluation of collateral growth in rats administered p47phox small interfering RNA and in p47phox−/− mice. Diameter measurements of collateral mesenteric and gracilis arteries at 7 and 14 days, respectively, indicated no significant collateral growth compared with control rats or C57BL/6 mice. Chronic polyethylene glycol-conjugated catalase administration significantly suppressed collateral development in rats and mice, implying a requirement for H2O2. Taken together, these results suggest that Nox2, modulated at least in part by p47phox, mediates early stage compensatory collateral development via a process dependent upon peroxide generation. These results have important implications for the use of antioxidants and the development of therapies for peripheral arterial disease. PMID:24633549

Neuroprotection of taurine against reactive oxygen species is associated with inhibiting NADPH oxidases.

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Han, Zhou; Gao, Li-Yan; Lin, Yu-Hui; Chang, Lei; Wu, Hai-Yin; Luo, Chun-Xia; Zhu, Dong-Ya

2016-04-15

It is well established that taurine shows potent protection against glutamate-induced injury to neurons in stroke. The neuroprotection may result from multiple mechanisms. Increasing evidences suggest that NADPH oxidases (Nox), the primary source of superoxide induced by N-methyl-d-aspartate (NMDA) receptor activation, are involved in the process of oxidative stress. We found that 100μM NMDA induced oxidative stress by increasing the reactive oxygen species level, which contributed to the cell death, in vitro. Neuron cultures pretreated with 25mM taurine showed lower percentage of death cells and declined reactive oxygen species level. Moreover, taurine attenuated Nox2/Nox4 protein expression and enzyme activity and declined intracellular calcium intensity during NMDA-induced neuron injury. Additionally, taurine also showed neuroprotection against H2O2-induced injury, accompanying with Nox inhibition. So, we suppose that protection of taurine against reactive oxygen species during NMDA-induced neuron injury is associated with Nox inhibition, probably in a calcium-dependent manner. Copyright © 2016 Elsevier B.V. All rights reserved.

Upregulation of NOX2 and NOX4 Mediated by TGF-β Signaling Pathway Exacerbates Cerebral Ischemia/Reperfusion Oxidative Stress Injury

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Zheng Lou

2018-04-01

Full Text Available Background/Aims: Ischemic stroke is still one of the leading debilitating diseases with high morbidity and mortality. NADPH oxidase (NOX-derived reactive oxygen species (ROS play an important role in cerebral ischemia/reperfusion (I/R injury. However, the mechanism underlying the regulation of ROS generation is still not fully elucidated. This study aims to explore the role of transforming growth beta (TGF-β signals in ROS generation. Methods: Sprague–Dawley rats were subjected to I/R injury, and PC-12 cells were challenged by hypoxia/reoxygenation (H/R and/or treated with activin receptor-like kinase (ALK5 inhibitor Sb505124 or siRNA against ALK5. Brain damage was evaluated using neurological scoring, triphenyl tetrazolium chloride staining, hematoxylin and eosin staining, infarct volume measurement, TUNEL staining, and caspase-3 activity measurement. Expression of TGF-β and oxidative stress-related genes was analyzed by real-time polymerase chain reaction and Western blot; NOX activity and ROS level were measured using spectrophotometry and fluorescence microscopy, respectively. Results: I/R contributed to severe brain damage (impaired neurological function, brain infarction, tissue edema, apoptosis, TGF-β signaling activation (upregulation of ALK5, phosphorylation of SMAD2/3 and oxidative stress (upregulation of NOX2/4, rapid release of ROS [oxidative burst]. However, Sb505124 significantly reversed these alterations and protected rats against I/R injury. As in the animal results, H/R also contributed to TGF-β signaling activation and oxidative stress. Likewise, the inhibition of ALK5 or ALK5 knockdown significantly reversed these alterations in PC-12 cells. Other than ALK5 knockdown, ALK5 inhibition had no effect on the expression of ALK5 in PC-12 cells. Conclusions: Our studies demonstrated that TGF-β signaling activation is involved in the regulation of NOX2/NOX4 expression and exacerbates cerebral I/R injury.

Cardiac and renal upregulation of Nox2 and NF-κB and repression of Nox4 and Nrf2 in season- and diabetes-mediated models of vascular oxidative stress in guinea-pig and rat.

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Gajos-Draus, Anna; Duda, Monika; Beręsewicz, Andrzej

2017-11-01

The superoxide-forming NADPH oxidase homologues, Nox1, Nox2, and Nox5, seem to mediate the pro-atherosclerotic vascular phenotype. The hydrogen peroxide-forming Nox4 afforded vascular protection, likely via NF-E2-related factor-2 (Nrf2) activation and/or Nox2 downregulation in transgenic mice. We hypothesized that oxidative stress in the intact vasculature involves, aside from the upregulation of the superoxide-forming Noxs, the downregulation of the Nox4/Nrf2 pathway. Guinea-pigs and rats were studied either in winter or in summer, and the streptozotocin diabetic rats in winter. Plasma nitrite, and superoxide production by isolated hearts were measured, while frozen tissues served in biochemical analyses. Summer in both species and diabetes in rats downregulated myocardial Nox4 while reciprocally upregulating Nox2 and Nox5 in guinea-pigs, and Nox2 in rats. Simultaneously, myocardial Nrf2 activity and the expression of the Nrf2-directed heme oxygenase-1 and endothelial NO synthase were reduced while activity of the nuclear factor κ B (NF- κ B) and the expression of NF- κ B-directed inducible NO synthase and the vascular cell adhesion molecule-1 were increased. Cardiac superoxide production was increased while plasma nitrite was decreased reciprocally. Analogous disregulation of Noxs, Nrf2, and NF- κ B, occurred in diabetic rat kidneys. Given the diversity of the experimental settings and the uniform pattern of the responses, we speculate that: (1) chronic vascular oxidative stress is a nonspecific (model-, species-, organ-independent) response involving the induction of Nox2 (and Nox5 in guinea-pigs) and the NF- κ B pathway, and the repression of Nox4 and the Nrf2 pathway; and (2) the systems Nox2-NF- κ B and Nox4-Nrf2 regulate each other negatively. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

TGF-β1-induced cell migration in pancreatic carcinoma cells is RAC1 and NOX4-dependent and requires RAC1 and NOX4-dependent activation of p38 MAPK.

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Witte, David; Bartscht, Tobias; Kaufmann, Roland; Pries, Ralph; Settmacher, Utz; Lehnert, Hendrik; Ungefroren, Hendrik

2017-12-01

Transforming growth factor (TGF)-β promotes epithelial-mesenchymal transition and cell invasion of cancer cells in part through the small GTPase RAC1. Since RAC1 can signal through reactive oxygen species (ROS), we probed the role of the ROS-producing NADPH oxidase (NOX) and p38 mitogen-activated protein kinase (MAPK) in mediating TGF-β1/RAC1-driven random cell migration (chemokinesis). Although the NOX isoforms NOX2, 4, 5, 6, and RAC1 were readily detectable by RT-PCR in pancreatic ductal adenocarcinoma (PDAC)-derived Panc1 and Colo357 cells, only NOX4 and RAC1 were expressed at higher levels comparable to those in peripheral blood monocytes. TGF-β1 treatment resulted in upregulation of NOX4 (and NOX2) and rapid intracellular production of ROS. To analyze whether RAC1 functions through NOX and ROS to promote cell motility, we performed real-time cell migration assays with xCELLigence® technology in the presence of the ROS scavenger N-acetyl-L-cysteine (NAC) and various NOX inhibitors. NAC, the NOX4 inhibitor diphenylene iodonium or small interfering RNA (siRNA) to NOX4, and the NOX2 inhibitor apocynin all suppressed TGF-β1-induced chemokinesis of Panc1 and Colo357 cells as did various inhibitors of RAC1 used as control. In addition, we showed that blocking NOX4 or RAC1 function abrogated phosphorylation of p38 MAPK signaling by TGF-β1 and that inhibition of p38 MAPK reduced TGF-β1-induced random cell migration, while ectopic expression of a kinase-active version of the p38 activating kinase MKK6 was able to partially rescue the decline in migration after RAC1 inhibition. Our data suggest that TGF-β1-induced chemokinesis in PDAC cells is mediated through a RAC1/NOX4/ROS/p38 MAPK cascade.

Arctigenin Induces an Activation Response in Porcine Alveolar Macrophage Through TLR6-NOX2-MAPKs Signaling Pathway

Science.gov (United States)

Lu, Zheng; Chang, Lingling; Du, Qian; Huang, Yong; Zhang, Xiujuan; Wu, Xingchen; Zhang, Jie; Li, Ruizhen; Zhang, Zelin; Zhang, Wenlong; Zhao, Xiaomin; Tong, Dewen

2018-01-01

Arctigenin (ARG), one of the most active ingredients abstracted from seeds of Arctium lappa L., has been proved to exert promising biological activities such as immunomodulatory, anti-viral, and anti-cancer etc. However, the mechanism behind its immunomodulatory function still remains elusive to be further investigated. In this study, we found that ARG had no significant effects on the cell proliferation in both porcine alveolar macrophage cell line (3D4/21) and primary porcine derived alveolar macrophage. It remarkably increased the expression and secretion of the two cytokines including tumor necrosis factor-alpha (TNF-α) and transforming growth factor beta1 (TGF-β1) in a dose-dependent manner with the concomitant enhancement of phagocytosis, which are the indicators of macrophage activation. ARG also elevated the intracellular reactive oxygen species (ROS) production by activating NOX2-based NADPH oxidase. Furthermore, inhibition of ROS generation by diphenyliodonium and apocynin significantly suppressed ARG-induced cytokine secretion and phagocytosis increase, indicating the requirement of ROS for the porcine alveolar macrophage activation. In addition, TLR6-My88 excitation, p38 MAPK and ERK1/2 phosphorylation were all involved in the process. As blocking TLR6 receptor dramatically attenuated the NOX2 oxidase activation, cytokine secretion and phagocytosis increase. Inhibiting ROS generation almost abolished p38 and ERK1/2 phosphorylation, and the cytokine secretion could also be remarkably reduced by p38 and ERK1/2 inhibitors (SB203580 and UO126). Our finding gave a new insight of understanding that ARG could improve the immune-function of porcine alveolar macrophages through TLR6-NOX2 oxidase-MAPKs signaling pathway.

Arctigenin Induces an Activation Response in Porcine Alveolar Macrophage Through TLR6-NOX2-MAPKs Signaling Pathway

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Zheng Lu

2018-05-01

Full Text Available Arctigenin (ARG, one of the most active ingredients abstracted from seeds of Arctium lappa L., has been proved to exert promising biological activities such as immunomodulatory, anti-viral, and anti-cancer etc. However, the mechanism behind its immunomodulatory function still remains elusive to be further investigated. In this study, we found that ARG had no significant effects on the cell proliferation in both porcine alveolar macrophage cell line (3D4/21 and primary porcine derived alveolar macrophage. It remarkably increased the expression and secretion of the two cytokines including tumor necrosis factor-alpha (TNF-α and transforming growth factor beta1 (TGF-β1 in a dose-dependent manner with the concomitant enhancement of phagocytosis, which are the indicators of macrophage activation. ARG also elevated the intracellular reactive oxygen species (ROS production by activating NOX2-based NADPH oxidase. Furthermore, inhibition of ROS generation by diphenyliodonium and apocynin significantly suppressed ARG-induced cytokine secretion and phagocytosis increase, indicating the requirement of ROS for the porcine alveolar macrophage activation. In addition, TLR6-My88 excitation, p38 MAPK and ERK1/2 phosphorylation were all involved in the process. As blocking TLR6 receptor dramatically attenuated the NOX2 oxidase activation, cytokine secretion and phagocytosis increase. Inhibiting ROS generation almost abolished p38 and ERK1/2 phosphorylation, and the cytokine secretion could also be remarkably reduced by p38 and ERK1/2 inhibitors (SB203580 and UO126. Our finding gave a new insight of understanding that ARG could improve the immune-function of porcine alveolar macrophages through TLR6-NOX2 oxidase-MAPKs signaling pathway.

Arctigenin Induces an Activation Response in Porcine Alveolar Macrophage Through TLR6-NOX2-MAPKs Signaling Pathway.

Science.gov (United States)

Lu, Zheng; Chang, Lingling; Du, Qian; Huang, Yong; Zhang, Xiujuan; Wu, Xingchen; Zhang, Jie; Li, Ruizhen; Zhang, Zelin; Zhang, Wenlong; Zhao, Xiaomin; Tong, Dewen

2018-01-01

Arctigenin (ARG), one of the most active ingredients abstracted from seeds of Arctium lappa L. , has been proved to exert promising biological activities such as immunomodulatory, anti-viral, and anti-cancer etc. However, the mechanism behind its immunomodulatory function still remains elusive to be further investigated. In this study, we found that ARG had no significant effects on the cell proliferation in both porcine alveolar macrophage cell line (3D4/21) and primary porcine derived alveolar macrophage. It remarkably increased the expression and secretion of the two cytokines including tumor necrosis factor-alpha (TNF-α) and transforming growth factor beta1 (TGF-β1) in a dose-dependent manner with the concomitant enhancement of phagocytosis, which are the indicators of macrophage activation. ARG also elevated the intracellular reactive oxygen species (ROS) production by activating NOX2-based NADPH oxidase. Furthermore, inhibition of ROS generation by diphenyliodonium and apocynin significantly suppressed ARG-induced cytokine secretion and phagocytosis increase, indicating the requirement of ROS for the porcine alveolar macrophage activation. In addition, TLR6-My88 excitation, p38 MAPK and ERK1/2 phosphorylation were all involved in the process. As blocking TLR6 receptor dramatically attenuated the NOX2 oxidase activation, cytokine secretion and phagocytosis increase. Inhibiting ROS generation almost abolished p38 and ERK1/2 phosphorylation, and the cytokine secretion could also be remarkably reduced by p38 and ERK1/2 inhibitors (SB203580 and UO126). Our finding gave a new insight of understanding that ARG could improve the immune-function of porcine alveolar macrophages through TLR6-NOX2 oxidase-MAPKs signaling pathway.

Crystallization and preliminary crystallographic analysis of a flavoprotein NADH oxidase from Lactobacillus brevis

International Nuclear Information System (INIS)

Kuzu, Mutlu; Niefind, Karsten; Hummel, Werner; Schomburg, Dietmar

2005-01-01

The water-forming flavoenzyme NADH oxidase was crystallized successfully for the first time. The crystals diffract X-rays to at least 4.0 Å resolution. NADH oxidase (NOX) from Lactobacillus brevis is a homotetrameric flavoenzyme composed of 450 amino acids per subunit. The molecular weight of each monomer is 48.8 kDa. The enzyme catalyzes the oxidation of two equivalents of NADH and reduces one equivalent of oxygen to yield two equivalents of water, without releasing hydrogen peroxide after the reduction of the first equivalent of NADH. Crystals of this protein were grown in the presence of 34% polyethylene glycol monomethyl ether 2000, 0.1 M sodium acetate and 0.2 M ammonium sulfate at pH 5.4. They belong to the tetragonal space group P4 3 2 1 2, with unit-cell parameters a = 74.8, b = 95.7, c = 116.9 Å, α = γ = 90, β = 103.8°. The current diffraction limit is 4.0 Å. The self-rotation function of the native data set is consistent with a NOX tetramer in the asymmetric unit

Diphenyleneiodonium, an inhibitor of NOXes and DUOXes, is also an iodide-specific transporter

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C. Massart

2014-01-01

Full Text Available NADPH oxidases (NOXes and dual oxidases (DUOXes generate O2.− and H2O2. Diphenyleneiodonium (DPI inhibits the activity of these enzymes and is often used as a specific inhibitor. It is shown here that DPI, at concentrations similar to those which inhibit the generation of O2 derivatives, activated the efflux of radioiodide but not of its analog 99mTcO4− nor of the K+ cation mimic 86Rb+ in thyroid cells, in the PCCl3 rat thyroid cell line and in COS cell lines expressing the iodide transporter NIS. Effects obtained with DPI, especially in thyroid cells, should therefore be interpreted with caution.

Regional up-regulation of NOX2 contributes to the differential vulnerability of outer hair cells to neomycin.

Science.gov (United States)

Qi, Meihao; Qiu, Yang; Zhou, Xueying; Tian, Keyong; Zhou, Ke; Sun, Fei; Yue, Bo; Chen, Fuquan; Zha, Dingjun; Qiu, Jianhua

2018-06-02

In hearing loss induced by aminoglycoside antibiotics, the outer hair cells (OHCs) in the basal turn are always more susceptible than OHCs in the apical turn, while the underlying mechanisms remain unknown. In this study, we reported that NAPDH oxidase 2 (NOX2) played an important role in the OHCs damage preferentially in the basal turn. Normally, NOX2 was evenly expressed in OHCs among different turns, at a relatively low level. However, after neomycin treatment, NOX2 was dominantly induced in OHCs in the basal turn. In vivo and in vitro studies demonstrated that inhibition of NOX2 significantly alleviated neomycin-induced OHCs damages, as seen from both the cleaved caspase-3 and TUNEL staining. Moreover, gp91 ds-tat delivery and DHE staining results showed that NOX2-derived ROS was responsible for neomycin ototoxicity. Taken together, our study shows that regional up-expression of NOX2 and subsequent increase of ROS in OHCs of the basal turn is an important factor contributing to the vulnerability of OHCs there, which should shed light on the prevention of hearing loss induced by aminoglycoside antibiotics. Copyright © 2018 Elsevier Inc. All rights reserved.

Nrf2 mediates redox adaptation in NOX4-overexpressed non-small cell lung cancer cells

Energy Technology Data Exchange (ETDEWEB)

Wu, Qipeng; Yao, Bei; Li, Ning; Ma, Lei; Deng, Yanchao; Yang, Yang; Zeng, Cheng; Yang, Zhicheng [Department of Clinical Pharmacy, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006 (China); Liu, Bing, E-mail: liubing520@gdpu.edu.cn [Department of Clinical Pharmacy, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006 (China); Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006 (China)

2017-03-15

The redox adaptation mechanisms in cancer cells are very complex and remain largely unclear. Our previous studies have confirmed that NADPH oxidase 4 (NOX4) is abundantly expressed in non-small cell lung cancer (NSCLC) and confers apoptosis resistance on NSCLC cells. However, the comprehensive mechanisms for NOX4-mediated oxidative resistance of cancer cells remain still undentified. The present study found that NOX4-derived H{sub 2}O{sub 2} enhanced the nuclear factor erythroid 2-related factor 2 (Nrf2) stability via disruption of redox-dependent proteasomal degradation and stimulated its activity through activation of PI3K signaling. Specifically, the results showed that ectopic NOX4 expression did not induce apoptosis of A549 cells; however, inhibition of Nrf2 resulted in obvious apoptotic death of NOX4-overexpressed A549 cells, accompanied by a significant increase in H{sub 2}O{sub 2} level and decrease in GSH content. Besides, inhibition of Nrf2 could suppress cell growth and efficiently reverse the enhancement effect of NOX4 on cell growth. The in vivo data confirmed that inhibition of Nrf2 could interfere apoptosis resistance in NOX4-overexpressed A549 tumors and led to cell growth inhibition. In conclusion, these results reveal that Nrf2 is critically involved in redox adaptation regulation in NOX4-overexpressed NSCLC cells. Therefore, NOX4 and Nrf2 may be promising combination targets against malignant progression of NSCLC. - Highlights: • NOX4-derived H{sub 2}O{sub 2} upregulates Nrf2 expression and activity in NSCLC. • Nrf2 confers apoptosis resistance in NOX4-overexpressed NSCLC cells. • Inhibition of Nrf2 reverses the enhancement effect of NOX4 on cell growth.

The plasma membrane-associated NADH oxidase of spinach leaves responds to blue light

Science.gov (United States)

Morre, D. James; Penel, Claude; Greppin, Hubert; Morre, Dorothy M.

2002-01-01

The plasma membrane-associated NADH oxidase (NOX) of spinach leaf disks is characterized by oscillations in activity with a regular period length of ca. 24 min. Within a single population of plants exposed to light at the same time, NOX activities of all plants function synchronously. Exposure of plants transferred from darkness to blue light (495 nm, 2 min, 50 micromoles m-2 s-1) resulted in a complex response pattern but with a new maximum in the rate of NOX activity 36 (24+12) min after illumination and then with maxima in the rate of NOX activity every 24 min thereafter. Transient maxima in NOX activity were observed as well after 9.3 + /- 1.4 and 20.7 +/- 2.1 min. The blue light response differed from the response to red (650 nm, 10 min, 50 micromoles m-2 s-1) or white light where activity maxima were initiated 12 min after the light exposure followed by maxima every 24 min thereafter. Green or yellow light was ineffective. The light response was independent of the time in the 24-min NOX cycle when the light was given. The net effects of blue and red light were ultimately the same with a new maximum in the rate of NOX activity at 12+24=36 min (and every 24 min thereafter), but the mechanisms appear to be distinct.

Resveratrol prevents high glucose-induced epithelial-mesenchymal transition in renal tubular epithelial cells by inhibiting NADPH oxidase/ROS/ERK pathway.

Science.gov (United States)

He, Ting; Guan, Xu; Wang, Song; Xiao, Tangli; Yang, Ke; Xu, Xinli; Wang, Junping; Zhao, Jinghong

2015-02-15

Resveratrol (RSV) is reported to have renoprotective activity against diabetic nephropathy, while the mechanisms underlying its function have not been fully elucidated. In this study, we investigate the effect and related mechanism of RSV against high glucose-induced epithelial to mesenchymal transition (EMT) in human tubular epithelial cells (HK-2). A typical EMT is induced by high glucose in HK-2 cells, accompanied by increased levels of reactive oxygen species (ROS). RSV exhibits a strong ability to inhibit high glucose-induced EMT by decreasing intracellular ROS levels via down-regulation of NADPH oxidase subunits NOX1 and NOX4. The activation of extracellular signal-regulated kinase (ERK1/2) is found to be involved in high glucose-induced EMT in HK-2 cells. RSV, like NADPH oxidase inhibitor diphenyleneiodonium, can block ERK1/2 activation induced by high glucose. Our results demonstrate that RSV is a potent agent against high glucose-induced EMT in renal tubular cells via inhibition of NADPH oxidase/ROS/ERK1/2 pathway. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

NADPH oxidase 1 deficiency alters caveolin phosphorylation and angiotensin II-receptor localization in vascular smooth muscle.

Science.gov (United States)

Basset, Olivier; Deffert, Christine; Foti, Michelangelo; Bedard, Karen; Jaquet, Vincent; Ogier-Denis, Eric; Krause, Karl-Heinz

2009-10-01

The superoxide-generating NADPH oxidase NOX1 is thought to be involved in signaling by the angiotensin II-receptor AT1R. However, underlying signaling steps are poorly understood. In this study, we investigated the effect of AngII on aortic smooth muscle from wild-type and NOX1-deficient mice. NOX1-deficient cells showed decreased basal ROS generation and did not produce ROS in response to AngII. Unexpectedly, AngII-dependent Ca(2+) signaling was markedly decreased in NOX1-deficient cells. Immunostaining demonstrated that AT1R was localized on the plasma membrane in wild-type, but intracellularly in NOX1-deficient cells. Immunohistochemistry and immunoblotting showed a decreased expression of AT1R in the aorta of NOX1-deficient mice. To investigate the basis of the abnormal AT1R targeting, we studied caveolin expression and phosphorylation. The amounts of total caveolin and of caveolae were not different in NOX1-deficient mice, but a marked decrease occurred in the phosphorylated form of caveolin. Exogenous H(2)O(2) or transfection of a NOX1 plasmid restored AngII responses in NOX1-deficient cells. Based on these findings, we propose that NOX1-derived reactive oxygen species regulate cell-surface expression of AT1R through mechanisms including caveolin phosphorylation. The lack cell-surface AT1R expression in smooth muscle could be involved in the decreased blood pressure in NOX1-deficient mice.

Fatal Chromobacterium violaceum septicaemia in northern Laos, a modified oxidase test and post-mortem forensic family G6PD analysis.

Science.gov (United States)

Slesak, Günther; Douangdala, Phouvieng; Inthalad, Saythong; Silisouk, Joy; Vongsouvath, Manivanh; Sengduangphachanh, Amphonesavanh; Moore, Catrin E; Mayxay, Mayfong; Matsuoka, Hiroyuki; Newton, Paul N

2009-07-29

Chromobacterium violaceum is a Gram negative facultative anaerobic bacillus, found in soil and stagnant water, that usually has a violet pigmented appearance on agar culture. It is rarely described as a human pathogen, mostly from tropical and subtropical areas. A 53 year-old farmer died with Chromobacterium violaceum septicemia in Laos. A modified oxidase method was used to demonstrate that this violacious organism was oxidase positive. Forensic analysis of the glucose-6-phosphate dehydrogenase genotypes of his family suggest that the deceased patient did not have this possible predisposing condition. C. violaceum infection should be included in the differential diagnosis in patients presenting with community-acquired septicaemia in tropical and subtropical areas. The apparently neglected but simple modified oxidase test may be useful in the oxidase assessment of other violet-pigmented organisms or of those growing on violet coloured agar.

Structure and activity of Aspergillus nidulans copper amine oxidase

DEFF Research Database (Denmark)

McGrath, Aaron P; Mithieux, Suzanne M; Collyer, Charles A

2011-01-01

Aspergillus nidulans amine oxidase (ANAO) has the unusual ability among the family of copper and trihydroxyphenylalanine quinone-containing amine oxidases of being able to oxidize the amine side chains of lysine residues in large peptides and proteins. We show here that in common with the related...... enzyme from the yeast Pichia pastoris, ANAO can promote the cross-linking of tropoelastin and oxidize the lysine residues in α-casein proteins and tropoelastin. The crystal structure of ANAO, the first for a fungal enzyme in this family, has been determined to a resolution of 2.4 Å. The enzyme is a dimer...... with the archetypal fold of a copper-containing amine oxidase. The active site is the most open of any of those of the structurally characterized enzymes in the family and provides a ready explanation for its lysine oxidase-like activity....

Characterization of water-forming NADH oxidases for co-factor regeneration

DEFF Research Database (Denmark)

Rehn, Gustav; Pedersen, Asbjørn Toftgaard; J. Charnock, Simon

an environmentaland economic perspective [1]. Alcohol dehydrogenases (ADH) offer one such alternative. However, the reaction requires the oxidized nicotinamide co-factor (NAD+) that must be recycled due to its high cost contribution. One regeneration method that offers certain advantages is the oxidation of NADH......Traditional chemical methods for alcohol oxidation are often associated with issues such as high consumption of expensive oxidizing agents, generation of metal waste and the use of environmentally undesirable organic solvents. Developing green, selective catalysts is therefore important from...... using water forming NADH oxidases (NOX-2). The implementation of the ADH/NOX system for alcohol oxidation, however, requires consideration of several different issues. Enzyme activity and stability at relevant pH and temperature conditions, but also the tolerance to the substrates and products present...

The Expression of NOX4 in Smooth Muscles of Small Airway Correlates with the Disease Severity of COPD.

Science.gov (United States)

Liu, Xianyan; Hao, Binwei; Ma, Ailing; He, Jinxi; Liu, Xiaoming; Chen, Juan

Airway smooth muscle (ASM) remodeling is a hallmark in chronic obstructive pulmonary disease (COPD), and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases (NOXs) produced reactive oxygen species (ROS) play a crucial role in COPD pathogenesis. In the present study, the expression of NOX4 and its correlation with the ASM hypertrophy/hyperplasia, clinical pulmonary functions, and the expression of transforming growth factor β (TGF- β ) in the ASM of COPD small airways were investigated by semiquantitative morphological and/or immunohistochemistry staining methods. The results showed that an elevated expression of NOX4 and TGF- β , along with an increased volume of ASM mass, was found in the ASM of small airways in COPD patients. The abundance of NOX4 protein in the ASM was increased with disease severity and inversely correlated with the pulmonary functions in COPD patients. In addition, the expression of NOX4 and ASM marker α -SMA was colocalized, and the increased NOX4 expression was found to accompany an upregulated expression of TGF- β in the ASM of small airways of COPD lung. These results indicate that NOX4 may be a key regulator in ASM remodeling of small airway, in part through a mechanism interacting with TGF- β signaling in the pathogenesis of COPD, which warrants further investigation.

Streptococcus mutans NADH oxidase lies at the intersection of overlapping regulons controlled by oxygen and NAD+ levels.

Science.gov (United States)

Baker, J L; Derr, A M; Karuppaiah, K; MacGilvray, M E; Kajfasz, J K; Faustoferri, R C; Rivera-Ramos, I; Bitoun, J P; Lemos, J A; Wen, Z T; Quivey, R G

2014-06-01

NADH oxidase (Nox, encoded by nox) is a flavin-containing enzyme used by the oral pathogen Streptococcus mutans to reduce diatomic oxygen to water while oxidizing NADH to NAD(+). The critical nature of Nox is 2-fold: it serves to regenerate NAD(+), a carbon cycle metabolite, and to reduce intracellular oxygen, preventing formation of destructive reactive oxygen species (ROS). As oxygen and NAD(+) have been shown to modulate the activity of the global transcription factors Spx and Rex, respectively, Nox is potentially poised at a critical junction of two stress regulons. In this study, microarray data showed that either addition of oxygen or loss of nox resulted in altered expression of genes involved in energy metabolism and transport and the upregulation of genes encoding ROS-metabolizing enzymes. Loss of nox also resulted in upregulation of several genes encoding transcription factors and signaling molecules, including the redox-sensing regulator gene rex. Characterization of the nox promoter revealed that nox was regulated by oxygen, through SpxA, and by Rex. These data suggest a regulatory loop in which the roles of nox in reduction of oxygen and regeneration of NAD(+) affect the activity levels of Spx and Rex, respectively, and their regulons, which control several genes, including nox, crucial to growth of S. mutans under conditions of oxidative stress. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Methylcholanthrene-Induced Sarcomas Develop Independently from NOX2-Derived ROS.

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Maarten A Ligtenberg

Full Text Available Reactive oxygen species (ROS produced by the inducible NADPH oxidase type 2 (NOX2 complex are essential for clearing certain infectious organisms but may also have a role in regulating inflammation and immune response. For example, ROS is involved in myeloid derived suppressor cell (MDSC- and regulatory T cell (T(reg mediated T- and NK-cell suppression. However, abundant ROS produced within the tumor microenvironment, or by the tumor itself may also yield oxidative stress, which can blunt anti-tumor immune responses as well as eventually leading to tumor toxicity. In this study we aimed to decipher the role of NOX2-derived ROS in a chemically (by methylcholanthrene (MCA induced sarcoma model. Superoxide production by NOX2 requires the p47(phox (NCF1 subunit to organize the formation of the NOX2 complex on the cell membrane. Homozygous mutant mice (NCF1*/* have a functional loss of their super oxide burst while heterozygous mice (NCF1*/+ retain this key function. Mice harboring either a homo- or a heterozygous mutation were injected intramuscularly with MCA to induce sarcoma formation. We found that NOX2 functionality does not determine tumor incidence in the tested MCA model. Comprehensive immune monitoring in tumor bearing mice showed that infiltrating immune cells experienced an increase in their oxidative state regardless of the NOX2 functionality. While MCA-induced sarcomas where characterized by a T(reg and MDSC accumulation, no significant differences could be found between NCF1*/* and NCF1*/+ mice. Furthermore, infiltrating T cells showed an increase in effector-memory cell phenotype markers in both NCF1*/* and NCF1*/+ mice. Tumors established from both NCF1*/* and NCF1*/+ mice were tested for their in vitro proliferative capacity as well as their resistance to cisplatin and radiation therapy, with no differences being recorded. Overall our findings indicate that NOX2 activity does not play a key role in tumor development or immune cell

Azithromycin attenuates myofibroblast differentiation and lung fibrosis development through proteasomal degradation of NOX4.

Science.gov (United States)

Tsubouchi, Kazuya; Araya, Jun; Minagawa, Shunsuke; Hara, Hiromichi; Ichikawa, Akihiro; Saito, Nayuta; Kadota, Tsukasa; Sato, Nahoko; Yoshida, Masahiro; Kurita, Yusuke; Kobayashi, Kenji; Ito, Saburo; Fujita, Yu; Utsumi, Hirofumi; Yanagisawa, Haruhiko; Hashimoto, Mitsuo; Wakui, Hiroshi; Yoshii, Yutaka; Ishikawa, Takeo; Numata, Takanori; Kaneko, Yumi; Asano, Hisatoshi; Yamashita, Makoto; Odaka, Makoto; Morikawa, Toshiaki; Nakayama, Katsutoshi; Nakanishi, Yoichi; Kuwano, Kazuyoshi

2017-08-03

Accumulation of profibrotic myofibroblasts is involved in the process of fibrosis development during idiopathic pulmonary fibrosis (IPF) pathogenesis. TGFB (transforming growth factor β) is one of the major profibrotic cytokines for myofibroblast differentiation and NOX4 (NADPH oxidase 4) has an essential role in TGFB-mediated cell signaling. Azithromycin (AZM), a second-generation antibacterial macrolide, has a pleiotropic effect on cellular processes including proteostasis. Hence, we hypothesized that AZM may regulate NOX4 levels by modulating proteostasis machineries, resulting in inhibition of TGFB-associated lung fibrosis development. Human lung fibroblasts (LF) were used to evaluate TGFB-induced myofibroblast differentiation. With respect to NOX4 regulation via proteostasis, assays for macroautophagy/autophagy, the unfolded protein response (UPR), and proteasome activity were performed. The potential anti-fibrotic property of AZM was examined by using bleomycin (BLM)-induced lung fibrosis mouse models. TGFB-induced NOX4 and myofibroblast differentiation were clearly inhibited by AZM treatment in LF. AZM-mediated NOX4 reduction was restored by treatment with MG132, a proteasome inhibitor. AZM inhibited autophagy and enhanced the UPR. Autophagy inhibition by AZM was linked to ubiquitination of NOX4 via increased protein levels of STUB1 (STIP1 homology and U-box containing protein 1), an E3 ubiquitin ligase. An increased UPR by AZM was associated with enhanced proteasome activity. AZM suppressed lung fibrosis development induced by BLM with concomitantly reduced NOX4 protein levels and enhanced proteasome activation. These results suggest that AZM suppresses NOX4 by promoting proteasomal degradation, resulting in inhibition of TGFB-induced myofibroblast differentiation and lung fibrosis development. AZM may be a candidate for the treatment of the fibrotic lung disease IPF.

Rac1-NADPH oxidase signaling promotes CD36 activation under glucotoxic conditions in pancreatic beta cells.

Science.gov (United States)

Elumalai, Suma; Karunakaran, Udayakumar; Lee, In Kyu; Moon, Jun Sung; Won, Kyu Chang

2017-04-01

We recently reported that cluster determinant 36 (CD36), a fatty acid transporter, plays a pivotal role in glucotoxicity-induced β-cell dysfunction. However, little is known about how glucotoxicity influences CD36 expression. Emerging evidence suggests that the small GTPase Rac1 is involved in the pathogenesis of beta cell dysfunction in type 2 diabetes (T2D). The primary objective of the current study was to determine the role of Rac1 in CD36 activation and its impact on β-cell dysfunction in diabetes mellitus. To address this question, we subjected INS-1 cells and human beta cells (1.1B4) to high glucose conditions (30mM) in the presence or absence of Rac1 inhibition either by NSC23766 (Rac1 GTPase inhibitor) or small interfering RNA. High glucose exposure in INS-1 and human beta cells (1.1b4) resulted in the activation of Rac1 and induced cell apoptosis. Rac1 activation mediates NADPH oxidase (NOX) activation leading to elevated ROS production in both cells. Activation of the Rac1-NOX complex by high glucose levels enhanced CD36 expression in INS-1 and human 1.1b4 beta cell membrane fractions. The inhibition of Rac1 by NSC23766 inhibited NADPH oxidase activity and ROS generation induced by high glucose concentrations in INS-1 & human 1.1b4 beta cells. Inhibition of Rac1-NOX complex activation by NSC23766 significantly reduced CD36 expression in INS-1 and human 1.1b4 beta cell membrane fractions. In addition, Rac1 inhibition by NSC23766 significantly reduced high glucose-induced mitochondrial dysfunction. Furthermore, NADPH oxidase inhibition by VAS2870 also attenuated high glucose-induced ROS generation and cell apoptosis. These results suggest that Rac1-NADPH oxidase dependent CD36 expression contributes to high glucose-induced beta cell dysfunction and cell death. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

40 CFR 52.2237 - NOX RACT and NOX conformity exemption.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 4 2010-07-01 2010-07-01 false NOX RACT and NOX conformity exemption... RACT and NOX conformity exemption. Approval. EPA is approving the section 182(f) oxides of nitrogen (NOX) reasonably available control technology (RACT) and NOX conformity exemption request submitted by...

Crystallization and preliminary X-ray analysis of formate oxidase, an enzyme of the glucose–methanol–choline oxidoreductase family

International Nuclear Information System (INIS)

Maeda, Yoshifumi; Doubayashi, Daiju; Ootake, Takumi; Oki, Masaya; Mikami, Bunzo; Uchida, Hiroyuki

2010-01-01

Formate oxidase from A. oryzae RIB40 was crystallized and diffraction data were collected to a resolution of 2.4 Å. Formate oxidase (FOD), which catalyzes the oxidation of formate to yield carbon dioxide and hydrogen peroxide, belongs to the glucose–methanol–choline oxidoreductase (GMCO) family. FOD from Aspergillus oryzae RIB40, which has a modified FAD as a cofactor, was crystallized at 293 K by the hanging-drop vapour-diffusion method. The crystal was orthorhombic and belonged to space group C222 1 . Diffraction data were collected from a single crystal to 2.4 Å resolution

Fatal Chromobacterium violaceum septicaemia in northern Laos, a modified oxidase test and post-mortem forensic family G6PD analysis

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Mayxay Mayfong

2009-07-01

Full Text Available Abstract Background Chromobacterium violaceum is a Gram negative facultative anaerobic bacillus, found in soil and stagnant water, that usually has a violet pigmented appearance on agar culture. It is rarely described as a human pathogen, mostly from tropical and subtropical areas. Case presentation A 53 year-old farmer died with Chromobacterium violaceum septicemia in Laos. A modified oxidase method was used to demonstrate that this violacious organism was oxidase positive. Forensic analysis of the glucose-6-phosphate dehydrogenase genotypes of his family suggest that the deceased patient did not have this possible predisposing condition. Conclusion C. violaceum infection should be included in the differential diagnosis in patients presenting with community-acquired septicaemia in tropical and subtropical areas. The apparently neglected but simple modified oxidase test may be useful in the oxidase assessment of other violet-pigmented organisms or of those growing on violet coloured agar.

NADH oxidase functions as an adhesin in Streptococcus pneumoniae and elicits a protective immune response in mice.

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Lena Muchnik

Full Text Available The initial event in disease caused by S. pneumoniae is adhesion of the bacterium to respiratory epithelial cells, mediated by surface expressed molecules including cell-wall proteins. NADH oxidase (NOX, which reduces free oxygen to water in the cytoplasm, was identified in a non-lectin enriched pneumococcal cell-wall fraction. Recombinant NOX (rNOX was screened with sera obtained longitudinally from children and demonstrated age-dependent immunogenicity. NOX ablation in S. pneumoniae significantly reduced bacterial adhesion to A549 epithelial cells in vitro and their virulence in the intranasal or intraperitoneal challenge models in mice, compared to the parental strain. Supplementation of Δnox WU2 with the nox gene restored its virulence. Saturation of A549 target cells with rNOX or neutralization of cell-wall residing NOX using anti-rNOX antiserum decreased adhesion to A549 cells. rNOX-binding phages inhibited bacterial adhesion. Moreover, peptides derived from the human proteins contactin 4, chondroitin 4 sulfotraferase and laminin5, homologous to the insert peptides in the neutralizing phages, inhibited bacterial adhesion to the A549 cells. Furthermore, rNOX immunization of mice elicited a protective immune response to intranasal or intraperitoneal S. pneumoniae challenge, whereas pneumococcal virulence was neutralized by anti-rNOX antiserum prior to intraperitoneal challenge. Our results suggest that in addition to its enzymatic activity, NOX contributes to S. pneumoniae virulence as a putative adhesin and thus peptides derived from its target molecules may be considered for the treatment of pneumococcal infections. Finally, rNOX elicited a protective immune response in both aerobic and anaerobic environments, which renders NOX a candidate for future pneumococcal vaccine.

NOX2-Induced Activation of Arginase and Diabetes-Induced Retinal Endothelial Cell Senescence

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Modesto Rojas

2017-06-01

Full Text Available Increases in reactive oxygen species (ROS and decreases in nitric oxide (NO have been linked to vascular dysfunction during diabetic retinopathy (DR. Diabetes can reduce NO by increasing ROS and by increasing activity of arginase, which competes with nitric oxide synthase (NOS for their commons substrate l-arginine. Increased ROS and decreased NO can cause premature endothelial cell (EC senescence leading to defective vascular repair. We have previously demonstrated the involvement of NADPH oxidase 2 (NOX2-derived ROS, decreased NO and overactive arginase in DR. Here, we investigated their impact on diabetes-induced EC senescence. Studies using diabetic mice and retinal ECs treated with high glucose or H2O2 showed that increases in ROS formation, elevated arginase expression and activity, and decreased NO formation led to premature EC senescence. NOX2 blockade or arginase inhibition prevented these effects. EC senescence was also increased by inhibition of NOS activity and this was prevented by treatment with a NO donor. These results indicate that diabetes/high glucose-induced activation of arginase and decreases in NO bioavailability accelerate EC senescence. NOX2-generated ROS contribute importantly to this process. Blockade of NOX2 or arginase represents a strategy to prevent diabetes-induced premature EC senescence by preserving NO bioavailability.

Oxidative stress caused by activation of NADPH oxidase 4 promotes contrast-induced acute kidney injury.

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Bo Young Jeong

Full Text Available Contrast-induced acute kidney injury (CIAKI is a leading cause of acute kidney injury following radiographic procedures. Intrarenal oxidative stress plays a critical role in CIAKI. Nicotinamide adenine dinucleotide 3-phosphate (NADPH oxidases (Noxs are important sources of reactive oxygen species (ROS. Among the various types of Noxs, Nox4 is expressed predominantly in the kidney in rodents. Here, we evaluated the role of Nox4 and benefit of Nox4 inhibition on CIAKI using in vivo and in vitro models. HK-2 cells were treated with iohexol, with or without Nox4 knockdown, or the most specific Nox1/4 inhibitor (GKT137831. Effects of Nox4 inhibition on CIAKI mice were examined. Expression of Nox4 in HK-2 cells was significantly increased following iohexol exposure. Silencing of Nox4 rescued the production of ROS, downregulated pro-inflammatory markers (particularly phospho-p38 implicated in CIAKI, and reduced Bax and caspase 3/7 activity, which resulted in increased cellular survival in iohexol-treated HK-2 cells. Pretreatment with GKT137831 replicated these effects by decreasing levels of phospho-p38. In a CIAKI mouse model, even though the improvement of plasma blood urea nitrogen was unclear, pretreatment with GKT137831 resulted in preserved structure, reduced expression of 8-hydroxy-2'-deoxyguanosine (8OHdG and kidney injury molecule-1 (KIM-1, and reduced number of TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. These results suggest Nox4 as a key source of reactive oxygen species responsible for CIAKI and provide a novel potential option for prevention of CIAKI.

NADPH Oxidase Isoform 2 (NOX2 Is Involved in Drug Addiction Vulnerability in Progeny Developmentally Exposed to Ethanol

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Marcela L. Contreras

2017-06-01

Full Text Available Ethanol exposure increases oxidative stress in developing organs, including the brain. Antioxidant treatment during maternal ethanol ingestion improves behavioral deficits in rodent models of fetal alcohol spectrum disorder (FASD. However, the impact of general antioxidant treatment in their adult offspring and the Specific Reactive Species (ROS-dependent mechanism, are not fully understood. We hypothesized that pre and early postnatal ethanol exposure (PEE modifies redox homeostasis, in particular NOX2 function during reward signaling in the mesocorticolimbic pathway, which reinforces the effects of alcohol. We developed a FASD rat model which was evaluated during adolescence (P21 and adulthood (P70. We first studied whether redox homeostasis is affected in PEE animals, by analyzing mRNA expression of SOD1, CAT, and Gpx1. We found that PEE reduced the mRNA levels of these three anti-oxidant enzymes in PFC and HIPP at P21 and in the VTA at P70. We also analyzed basal mRNA and protein expression of NOX2 subunits such as gp91phox, p22 phox, and p47 phox, in mesocorticolimbic brain areas of PEE rat brains. At P21, gp91 phox, and p47 phox levels in the VTA were decreased. At P70, gp91 phox mRNA levels was decreased in HIPP and both mRNA and protein levels were decreased in PFC. Since NOX2 is regulated by the N-methyl-D-aspartate Receptor (NMDAR, we analyzed NMDAR mRNA expression and found differential expression of NMDAR subunits (NR1 and NR2B in the PFC that was age dependent, with levels decreased at P21 and increased at P70. The analysis also revealed decreased NR2B mRNA expression in HIPP and VTA at P70. Offspring from maternal ethanol users consumed 25% more ethanol in a free choice alcohol consumption test than control rats, and showed place preference for an alcohol-paired compartment. In vivo inhibition of NOX2 using apocynin in drinking water, or infusion of blocked peptide gp91 phox ds in the VTA normalized alcohol place preference

NADPH Oxidase Isoform 2 (NOX2) Is Involved in Drug Addiction Vulnerability in Progeny Developmentally Exposed to Ethanol.

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Contreras, Marcela L; de la Fuente-Ortega, Erwin; Vargas-Roberts, Sofía; Muñoz, Daniela C; Goic, Carolina A; Haeger, Paola A

2017-01-01

Ethanol exposure increases oxidative stress in developing organs, including the brain. Antioxidant treatment during maternal ethanol ingestion improves behavioral deficits in rodent models of fetal alcohol spectrum disorder (FASD). However, the impact of general antioxidant treatment in their adult offspring and the Specific Reactive Species (ROS)-dependent mechanism, are not fully understood. We hypothesized that pre and early postnatal ethanol exposure (PEE) modifies redox homeostasis, in particular NOX2 function during reward signaling in the mesocorticolimbic pathway, which reinforces the effects of alcohol. We developed a FASD rat model which was evaluated during adolescence (P21) and adulthood (P70). We first studied whether redox homeostasis is affected in PEE animals, by analyzing mRNA expression of SOD1, CAT, and Gpx1. We found that PEE reduced the mRNA levels of these three anti-oxidant enzymes in PFC and HIPP at P21 and in the VTA at P70. We also analyzed basal mRNA and protein expression of NOX2 subunits such as gp91phox, p22 phox, and p47 phox, in mesocorticolimbic brain areas of PEE rat brains. At P21, gp91 phox, and p47 phox levels in the VTA were decreased. At P70, gp91 phox mRNA levels was decreased in HIPP and both mRNA and protein levels were decreased in PFC. Since NOX2 is regulated by the N-methyl-D-aspartate Receptor (NMDAR), we analyzed NMDAR mRNA expression and found differential expression of NMDAR subunits (NR1 and NR2B) in the PFC that was age dependent, with levels decreased at P21 and increased at P70. The analysis also revealed decreased NR2B mRNA expression in HIPP and VTA at P70. Offspring from maternal ethanol users consumed 25% more ethanol in a free choice alcohol consumption test than control rats, and showed place preference for an alcohol-paired compartment. In vivo inhibition of NOX2 using apocynin in drinking water, or infusion of blocked peptide gp91 phox ds in the VTA normalized alcohol place preference, suggesting that NOX

Association of a variant in the regulatory region of NADPH oxidase 4 gene and metabolic syndrome in patients with chronic hepatitis C.

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Siqueira, Erika Rabelo Forte de; Pereira, Luciano Beltrao; Stefano, Jose Tadeu; Patente, Thiago; Cavaleiro, Ana Mercedes; Silva Vasconcelos, Luydson Richardson; Carmo, Rodrigo Feliciano; Moreira Beltrao Pereira, Leila Maria; Carrilho, Flair Jose; Corrêa-Giannella, Maria Lucia; Oliveira, Claudia P

2015-03-28

Given the important contribution of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system to the generation of reactive oxygen species induced by hepatitis C virus (HCV), we investigated two single nucleotide polymorphisms (SNPs) in the putative regulatory region of the genes encoding NADPH oxidase 4 catalytic subunit (NOX4) and its regulatory subunit p22phox (CYBA) and their relation with metabolic and histological variables in patients with HCV. One hundred seventy eight naïve HCV patients (49.3% male; 65% HCV genotype 1) with positive HCV RNA were genotyped using specific primers and fluorescent-labeled probes for SNPs rs3017887 in NOX4 and -675 T → A in CYBA. No association was found between the genotype frequencies of NOX4 and CYBA SNPs and inflammation scores or fibrosis stages in the overall population. The presence of the CA + AA genotypes of the NOX4 SNP was nominally associated with a lower alanine aminotransferase (ALT) concentration in the male population (CA + AA = 72.23 ± 6.34 U/L versus CC = 100.22 ± 9.85; mean ± SEM; P = 0.05). The TT genotype of the CYBA SNP was also nominally associated with a lower ALT concentration in the male population (TT = 84.01 ± 6.77 U/L versus TA + AA = 109.67 ± 18.37 U/L; mean ± SEM; P = 0.047). The minor A-allele of the NOX4 SNP was inversely associated with the frequency of metabolic syndrome (MS) in the male population (odds ratio (OR): 0.15; 95% confidence interval (CI): 0.03 to 0.79; P = 0.025). The results suggest that the evaluated NOX4 and CYBA SNPs are not direct genetic determinants of fibrosis in HCV patients, but nevertheless NOX4 rs3017887 SNP could indirectly influence fibrosis susceptibility due to its inverse association with MS in male patients.

Inhibition of NAPDH Oxidase 2 (NOX2 Prevents Oxidative Stress and Mitochondrial Abnormalities Caused by Saturated Fat in Cardiomyocytes.

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Leroy C Joseph

Full Text Available Obesity and high saturated fat intake increase the risk of heart failure and arrhythmias. The molecular mechanisms are poorly understood. We hypothesized that physiologic levels of saturated fat could increase mitochondrial reactive oxygen species (ROS in cardiomyocytes, leading to abnormalities of calcium homeostasis and mitochondrial function. We investigated the effect of saturated fat on mitochondrial function and calcium homeostasis in isolated ventricular myocytes. The saturated fatty acid palmitate causes a decrease in mitochondrial respiration in cardiomyocytes. Palmitate, but not the monounsaturated fatty acid oleate, causes an increase in both total cellular ROS and mitochondrial ROS. Palmitate depolarizes the mitochondrial inner membrane and causes mitochondrial calcium overload by increasing sarcoplasmic reticulum calcium leak. Inhibitors of PKC or NOX2 prevent mitochondrial dysfunction and the increase in ROS, demonstrating that PKC-NOX2 activation is also required for amplification of palmitate induced-ROS. Cardiomyocytes from mice with genetic deletion of NOX2 do not have palmitate-induced ROS or mitochondrial dysfunction. We conclude that palmitate induces mitochondrial ROS that is amplified by NOX2, causing greater mitochondrial ROS generation and partial depolarization of the mitochondrial inner membrane. The abnormal sarcoplasmic reticulum calcium leak caused by palmitate could promote arrhythmia and heart failure. NOX2 inhibition is a potential therapy for heart disease caused by diabetes or obesity.

Serotonin Signaling Through the 5-HT1B Receptor and NADPH Oxidase 1 in Pulmonary Arterial Hypertension.

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Hood, Katie Y; Mair, Kirsty M; Harvey, Adam P; Montezano, Augusto C; Touyz, Rhian M; MacLean, Margaret R

2017-07-01

Serotonin can induce human pulmonary artery smooth muscle cell (hPASMC) proliferation through reactive oxygen species (ROS), influencing the development of pulmonary arterial hypertension (PAH). We hypothesize that in PASMCs, serotonin induces oxidative stress through NADPH-oxidase-derived ROS generation and reduced Nrf-2 (nuclear factor [erythroid-derived 2]-like 2) antioxidant systems, promoting vascular injury. HPASMCs from controls and PAH patients, and PASMCs from Nox1 -/- mice, were stimulated with serotonin in the absence/presence of inhibitors of Src kinase, the 5-HT 1B receptor, and NADPH oxidase 1 (Nox1). Markers of fibrosis were also determined. The pathophysiological significance of our findings was examined in vivo in serotonin transporter overexpressing female mice, a model of pulmonary hypertension. We confirmed thatserotonin increased superoxide and hydrogen peroxide production in these cells. For the first time, we show that serotonin increased oxidized protein tyrosine phosphatases and hyperoxidized peroxiredoxin and decreased Nrf-2 and catalase activity in hPASMCs. ROS generation was exaggerated and dependent on cellular Src-related kinase, 5-HT 1B receptor, and the serotonin transporter in human pulmonary artery smooth muscle cells from PAH subjects. Proliferation and extracellular matrix remodeling were exaggerated in human pulmonary artery smooth muscle cells from PAH subjects and dependent on 5-HT 1B receptor signaling and Nox1, confirmed in PASMCs from Nox1 -/- mice. In serotonin transporter overexpressing mice, SB216641, a 5-HT 1B receptor antagonist, prevented development of pulmonary hypertension in a ROS-dependent manner. Serotonin can induce cellular Src-related kinase-regulated Nox1-induced ROS and Nrf-2 dysregulation, contributing to increased post-translational oxidative modification of proteins and activation of redox-sensitive signaling pathways in hPASMCs, associated with mitogenic responses. 5-HT 1B receptors contribute to

NADPH Oxidase 1 Modulates WNT and NOTCH1 Signaling To Control the Fate of Proliferative Progenitor Cells in the Colon▿

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Coant, Nicolas; Ben Mkaddem, Sanae; Pedruzzi, Eric; Guichard, Cécile; Tréton, Xavier; Ducroc, Robert; Freund, Jean-Noel; Cazals-Hatem, Dominique; Bouhnik, Yoram; Woerther, Paul-Louis; Skurnik, David; Grodet, Alain; Fay, Michèle; Biard, Denis; Lesuffleur, Thécla; Deffert, Christine; Moreau, Richard; Groyer, André; Krause, Karl-Heinz; Daniel, Fanny; Ogier-Denis, Eric

2010-01-01

The homeostatic self-renewal of the colonic epithelium requires coordinated regulation of the canonical Wnt/β-catenin and Notch signaling pathways to control proliferation and lineage commitment of multipotent stem cells. However, the molecular mechanisms by which the Wnt/β-catenin and Notch1 pathways interplay in controlling cell proliferation and fate in the colon are poorly understood. Here we show that NADPH oxidase 1 (NOX1), a reactive oxygen species (ROS)-producing oxidase that is highly expressed in colonic epithelial cells, is a pivotal determinant of cell proliferation and fate that integrates Wnt/β-catenin and Notch1 signals. NOX1-deficient mice reveal a massive conversion of progenitor cells into postmitotic goblet cells at the cost of colonocytes due to the concerted repression of phosphatidylinositol 3-kinase (PI3K)/AKT/Wnt/β-catenin and Notch1 signaling. This conversion correlates with the following: (i) the redox-dependent activation of the dual phosphatase PTEN, causing the inactivation of the Wnt pathway effector β-catenin, and (ii) the downregulation of Notch1 signaling that provokes derepression of mouse atonal homolog 1 (Math1) expression. We conclude that NOX1 controls the balance between goblet and absorptive cell types in the colon by coordinately modulating PI3K/AKT/Wnt/β-catenin and Notch1 signaling. This finding provides the molecular basis for the role of NOX1 in cell proliferation and postmitotic differentiation. PMID:20351171

Adenosine A1 Receptor Protects Against Cisplatin Ototoxicity by Suppressing the NOX3/STAT1 Inflammatory Pathway in the Cochlea

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Kaur, Tejbeer; Borse, Vikrant; Sheth, Sandeep; Sheehan, Kelly; Ghosh, Sumana; Tupal, Srinivasan; Jajoo, Sarvesh; Mukherjea, Debashree; Rybak, Leonard P.

2016-01-01

Cisplatin is a commonly used antineoplastic agent that produces ototoxicity that is mediated in part by increasing levels of reactive oxygen species (ROS) via the NOX3 NADPH oxidase pathway in the cochlea. Recent studies implicate ROS generation in mediating inflammatory and apoptotic processes and hearing loss by activating signal transducer and activator of transcription (STAT1). In this study, we show that the adenosine A1 receptor (A1AR) protects against cisplatin ototoxicity by suppressing an inflammatory response initiated by ROS generation via NOX3 NADPH oxidase, leading to inhibition of STAT1. Trans-tympanic administration of the A1AR agonist R-phenylisopropyladenosine (R-PIA) inhibited cisplatin-induced ototoxicity, as measured by auditory brainstem responses and scanning electron microscopy in male Wistar rats. This was associated with reduced NOX3 expression, STAT1 activation, tumor necrosis factor-α (TNF-α) levels, and apoptosis in the cochlea. In vitro studies in UB/OC-1 cells, an organ of Corti immortalized cell line, showed that R-PIA reduced cisplatin-induced phosphorylation of STAT1 Ser727 (but not Tyr701) and STAT1 luciferase activity by suppressing the ERK1/2, p38, and JNK mitogen-activated protein kinase (MAPK) pathways. R-PIA also decreased the expression of STAT1 target genes, such as TNF-α, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and reduced cisplatin-mediated apoptosis. These data suggest that the A1AR provides otoprotection by suppressing NOX3 and inflammation in the cochlea and could serve as an ideal target for otoprotective drug therapy. SIGNIFICANCE STATEMENT Cisplatin is a widely used chemotherapeutic agent for the treatment of solid tumors. Its use results in significant and permanent hearing loss, for which no US Food and Drug Administration-approved treatment is currently available. In this study, we targeted the cochlear adenosine A1 receptor (A1AR) by trans-tympanic injections of the agonist R

Exercise training protects against atherosclerotic risk factors through vascular NADPH oxidase, extracellular signal-regulated kinase 1/2 and stress-activated protein kinase/c-Jun N-terminal kinase downregulation in obese rats.

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Touati, Sabeur; Montezano, Augusto C I; Meziri, Fayçal; Riva, Catherine; Touyz, Rhian M; Laurant, Pascal

2015-02-01

Exercise training reverses atherosclerotic risk factors associated with metabolic syndrome and obesity. The aim of the present study was to determine the molecular anti-inflammatory, anti-oxidative and anti-atherogenic effects in aorta from rats with high-fat diet-induced obesity. Male Sprague-Dawley rats were placed on a high-fat (HFD) or control (CD) diet for 12 weeks. The HFD rats were then divided into four groups: (i) sedentary HFD-fed rats (HFD-S); (ii) exercise trained (motor treadmill 5 days/week, 60 min/day, 12 weeks) HFD-fed rats (HFD-Ex); (iii) modified diet (HFD to CD) sedentary rats (HF/CD-S); and (iv) an exercise-trained modified diet group (HF/CD-Ex). Tissue levels of NADPH oxidase (activity and expression), NADPH oxidase (Nox) 1, Nox2, Nox4, p47(phox) , superoxide dismutase (SOD)-1, angiotensin AT1 and AT2 receptors, phosphorylated mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase (ERK) 1/2, stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK)) and vascular cell adhesion molecule-1 (VCAM-1) were determined in the aorta. Plasma cytokines (tumour necrosis factor (TNF)-α and interleukin (IL)-6) levels were also measured. Obesity was accompanied by increases in NADPH oxidase activity, p47(phox) translocation, Nox4 and VCAM-1 protein expression, MAPK (ERK1/2, SAPK/JNK) phosphorylation and plasma TNF-α and IL-6 levels. Exercise training and switching from the HFD to CD reversed almost all these molecular changes. In addition, training increased aortic SOD-1 protein expression and decreased ERK1/2 phosphorylation. These findings suggest that protective effects of exercise training on atherosclerotic risk factors induced by obesity are associated with downregulation of NADPH oxidase, ERK1/2 and SAPK/JNK activity and increased SOD-1 expression. © 2014 Wiley Publishing Asia Pty Ltd.

NOX2 Inhibition Impairs Early Muscle Gene Expression Induced by a Single Exercise Bout.

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Henríquez-Olguín, Carlos; Díaz-Vegas, Alexis; Utreras-Mendoza, Yildy; Campos, Cristian; Arias-Calderón, Manuel; Llanos, Paola; Contreras-Ferrat, Ariel; Espinosa, Alejandra; Altamirano, Francisco; Jaimovich, Enrique; Valladares, Denisse M

2016-01-01

Reactive oxygen species (ROS) participate as signaling molecules in response to exercise in skeletal muscle. However, the source of ROS and the molecular mechanisms involved in these phenomena are still not completely understood. The aim of this work was to study the role of skeletal muscle NADPH oxidase isoform 2 (NOX2) in the molecular response to physical exercise in skeletal muscle. BALB/c mice, pre-treated with a NOX2 inhibitor, apocynin, (3 mg/kg) or vehicle for 3 days, were swim-exercised for 60 min. Phospho-p47(phox) levels were significantly upregulated by exercise in flexor digitorum brevis (FDB). Moreover, exercise significantly increased NOX2 complex assembly (p47(phox)-gp91(phox) interaction) demonstrated by both proximity ligation assay and co-immunoprecipitation. Exercise-induced NOX2 activation was completely inhibited by apocynin treatment. As expected, exercise increased the mRNA levels of manganese superoxide dismutase (MnSOD), glutathione peroxidase (GPx), citrate synthase (CS), mitochondrial transcription factor A (tfam) and interleukin-6 (IL-I6) in FDB muscles. Moreover, the apocynin treatment was associated to a reduced activation of p38 MAP kinase, ERK 1/2, and NF-κB signaling pathways after a single bout of exercise. Additionally, the increase in plasma IL-6 elicited by exercise was decreased in apocynin-treated mice compared with the exercised vehicle-group (p < 0.001). These results were corroborated using gp91-dstat in an in vitro exercise model. In conclusion, NOX2 inhibition by both apocynin and gp91dstat, alters the intracellular signaling to exercise and electrical stimuli in skeletal muscle, suggesting that NOX2 plays a critical role in molecular response to an acute exercise.

Leonurine (SCM-198) attenuates myocardial fibrotic response via inhibition of NADPH oxidase 4.

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Liu, Xin-Hua; Pan, Li-Long; Deng, Hai-Yan; Xiong, Qing-Hui; Wu, Dan; Huang, Guo-Ying; Gong, Qi-Hai; Zhu, Yi-Zhun

2013-01-01

In our previous studies, we have reported that leonurine, a plant phenolic alkaloid in Herba leonuri, exerted cardioprotective properties in a number of preclinical experiments. Herein, we investigated the roles and the possible mechanisms of leonurine for reducing fibrotic responses in angiotensin II (Ang II)-stimulated primary neonatal rat cardiac fibroblasts and post-myocardial infarction (MI) rats. In in vitro experiments performed in neonatal rat cardiac fibroblasts, leonurine (10-20 μM) pretreatment attenuated Ang II-induced activation of extracellular signal-regulated kinase 1/2, production of intracellular reactive oxygen species (ROS), expression and activity of matrix metalloproteinase (MMP)-2/9, and expression of α-smooth muscle actin and types I and III collagen. A small interfering RNA-mediated knockdown strategy for NADPH oxidase 4 (Nox4) revealed that Nox4 was required for Ang II-induced activation of cardiac fibroblasts. In vivo studies using a post-MI model in rats indicated that administration of leonurine inhibited myocardial fibrosis while reducing cardiac Nox4 expression, ROS production, NF-κB activation, and plasma MMP-2 activity. In conclusion, our results provide the first evidence that leonurine could prevent cardiac fibrosis and the activation of cardiac fibroblasts partly through modulation of a Nox4-ROS pathway. Copyright © 2012 Elsevier Inc. All rights reserved.

Implication of NADPH Oxidases in the Early Inflammation Process Generated by Cystic Fibrosis Cells

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Pongnimitprasert, Nushjira; Hurtado, Margarita; Lamari, Foudil; El Benna, Jamel; Dupuy, Corinne; Fay, Michèle; Foglietti, Marie-José; Bernard, Maguy; Gougerot-Pocidalo, Marie-Anne; Braut-Boucher, Françoise

2012-01-01

In cystic fibrosis (CF) patients, pulmonary inflammation is a major cause of morbidity and mortality. The aim of this study was to further investigate whether oxidative stress could be involved in the early inflammatory process associated with CF pathogenesis. We used a model of CFTR defective epithelial cell line (IB3-1) and its reconstituted CFTR control (S9) cell line cultured in various ionic conditions. This study showed that IB3-1 and S9 cells expressed the NADPH oxidases (NOXs) DUOX1/2 and NOX2 at the same level. Nevertheless, several parameters participating in oxidative stress (increased ROS production and apoptosis, decreased total thiol content) were observed in IB3-1 cells cultured in hypertonic environment as compared to S9 cells and were inhibited by diphenyleneiodonium (DPI), a well-known inhibitor of NOXs; besides, increased production of the proinflammatory cytokines IL-6 and IL-8 by IB3-1 cells was also inhibited by DPI as compared to S9 cells. Furthermore, calcium ionophore (A23187), which upregulates DUOX and NOX2 activities, strongly induced oxidative stress and IL-8 and IL-6 overexpression in IB3-1 cells. All these events were suppressed by DPI, supporting the involvement of NOXs in the oxidative stress, which can upregulate proinflammatory cytokine production by the airway CFTR-deficient cells and trigger early pulmonary inflammation in CF patients. PMID:24049649

Leptin Induces Oxidative Stress Through Activation of NADPH Oxidase in Renal Tubular Cells: Antioxidant Effect of L-Carnitine.

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Blanca, Antonio J; Ruiz-Armenta, María V; Zambrano, Sonia; Salsoso, Rocío; Miguel-Carrasco, José L; Fortuño, Ana; Revilla, Elisa; Mate, Alfonso; Vázquez, Carmen M

2016-10-01

Leptin is a protein involved in the regulation of food intake and in the immune and inflammatory responses, among other functions. Evidences demonstrate that obesity is directly associated with high levels of leptin, suggesting that leptin may directly link obesity with the elevated cardiovascular and renal risk associated with increased body weight. Adverse effects of leptin include oxidative stress mediated by activation of NADPH oxidase. The aim of this study was to evaluate the effect of L-carnitine (LC) in rat renal epithelial cells (NRK-52E) exposed to leptin in order to generate a state of oxidative stress characteristic of obesity. Leptin increased superoxide anion (O2 (•) -) generation from NADPH oxidase (via PI3 K/Akt pathway), NOX2 expression and nitrotyrosine levels. On the other hand, NOX4 expression and hydrogen peroxide (H2 O2 ) levels diminished after leptin treatment. Furthermore, the expression of antioxidant enzymes, catalase, and superoxide dismutase, was altered by leptin, and an increase in the mRNA expression of pro-inflammatory factors was also found in leptin-treated cells. LC restored all changes induced by leptin to those levels found in untreated cells. In conclusion, stimulation of NRK-52E cells with leptin induced a state of oxidative stress and inflammation that could be reversed by preincubation with LC. Interestingly, LC induced an upregulation of NOX4 and restored the release of its product, hydrogen peroxide, which suggests a protective role of NOX4 against leptin-induced renal damage. J. Cell. Biochem. 117: 2281-2288, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The NADPH organizers NoxO1 and p47phox are both mediators of diabetes-induced vascular dysfunction in mice.

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Rezende, Flávia; Moll, Franziska; Walter, Maria; Helfinger, Valeska; Hahner, Fabian; Janetzko, Patrick; Ringel, Christian; Weigert, Andreas; Fleming, Ingrid; Weissmann, Norbert; Kuenne, Carsten; Looso, Mario; Rieger, Michael A; Nawroth, Peter; Fleming, Thomas; Brandes, Ralf P; Schröder, Katrin

2018-05-01

NADPH oxidases are important sources of reactive oxygen species (ROS). Several Nox homologues are present together in the vascular system but whether they exhibit crosstalk at the activity level is unknown. To address this, vessel function of knockout mice for the cytosolic Nox organizer proteins p47phox, NoxO1 and a p47phox-NoxO1-double knockout were studied under normal condition and during streptozotocin-induced diabetes. In the mouse aorta, mRNA expression for NoxO1 was predominant in smooth muscle and endothelial cells, whereas p47phox was markedly expressed in adventitial cells comprising leukocytes and tissue resident macrophages. Knockout of either NoxO1 or p47phox resulted in lower basal blood pressure. Deletion of any of the two subunits also prevented diabetes-induced vascular dysfunction. mRNA expression analysis by MACE (Massive Analysis of cDNA ends) identified substantial gene expression differences between the mouse lines and in response to diabetes. Deletion of p47phox induced inflammatory activation with increased markers of myeloid cells and cytokine and chemokine induction. In contrast, deletion of NoxO1 resulted in an attenuated interferon gamma signature and reduced expression of genes related to antigen presentation. This aspect was also reflected by a reduced number of circulating lymphocytes in NoxO1-/- mice. ROS production stimulated by NoxO1 and p47phox limit endothelium-dependent relaxation and maintain blood pressure in mice. However, NoxO1 and p47phox cannot substitute each other despite their similar effect on vascular function. Deletion of NoxO1 induced an anti-inflammatory phenotype, whereas p47phox deletion rather elicited a hyper-inflammatory response. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

NOX2 inhibition impairs early muscle gene expression induced by a single exercise bout

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Carlos Henríquez-Olguín

2016-07-01

Full Text Available Reactive oxygen species (ROS participate as signaling molecules in response to exercise in skeletal muscle. However, the source of ROS and the molecular mechanisms involved in these phenomena are still not completely understood. The aim of this work was to study the role of skeletal muscle NADPH oxidase isoform 2 (NOX2 in the molecular response to physical exercise in skeletal muscle. BALB/c mice, pre-treated with a NOX2 inhibitor, apocynin, (3 mg/kg or vehicle for 3 days, were swim-exercised for 60 min. Phospho-p47phox levels were significantly upregulated by exercise in flexor digitorum brevis (FDB. Moreover, exercise significantly increased NOX2 complex assembly (p47phox-gp91phox interaction demonstrated by both proximity ligation assay and co-immunoprecipitation. Exercise-induced NOX2 activation was completely inhibited by apocynin treatment. As expected, exercise increased the mRNA levels of manganese superoxide dismutase (MnSOD, glutathione peroxidase (GPx, citrate synthase (CS, mitochondrial transcription factor A (tfam and interleukin-6 (IL-6 in FDB muscles. Moreover, the apocynin treatment was associated to a reduced activation of p38 MAP kinase, ERK 1/2, and NF-κB signaling pathways after a single bout of exercise. Additionally, the increase in plasma IL-6 elicited by exercise was decreased in apocynin-treated mice compared with the exercised vehicle-group (p<0.001. These results were corroborated using gp91-dstat in an in-vitro exercise model. In conclusion, NOX2 inhibition by both apocynin and gp91dstat, alters the intracellular signaling to exercise and electrical stimuli in skeletal muscle, suggesting that NOX2 plays a critical role in molecular response to an acute exercise.

Adenosine A1 Receptor Protects Against Cisplatin Ototoxicity by Suppressing the NOX3/STAT1 Inflammatory Pathway in the Cochlea.

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Kaur, Tejbeer; Borse, Vikrant; Sheth, Sandeep; Sheehan, Kelly; Ghosh, Sumana; Tupal, Srinivasan; Jajoo, Sarvesh; Mukherjea, Debashree; Rybak, Leonard P; Ramkumar, Vickram

2016-04-06

Cisplatin is a commonly used antineoplastic agent that produces ototoxicity that is mediated in part by increasing levels of reactive oxygen species (ROS) via the NOX3 NADPH oxidase pathway in the cochlea. Recent studies implicate ROS generation in mediating inflammatory and apoptotic processes and hearing loss by activating signal transducer and activator of transcription (STAT1). In this study, we show that the adenosine A1 receptor (A1AR) protects against cisplatin ototoxicity by suppressing an inflammatory response initiated by ROS generation via NOX3 NADPH oxidase, leading to inhibition of STAT1. Trans-tympanic administration of the A1AR agonist R-phenylisopropyladenosine (R-PIA) inhibited cisplatin-induced ototoxicity, as measured by auditory brainstem responses and scanning electron microscopy in male Wistar rats. This was associated with reduced NOX3 expression, STAT1 activation, tumor necrosis factor-α (TNF-α) levels, and apoptosis in the cochlea. In vitro studies in UB/OC-1 cells, an organ of Corti immortalized cell line, showed that R-PIA reduced cisplatin-induced phosphorylation of STAT1 Ser(727) (but not Tyr(701)) and STAT1 luciferase activity by suppressing the ERK1/2, p38, and JNK mitogen-activated protein kinase (MAPK) pathways.R-PIA also decreased the expression of STAT1 target genes, such as TNF-α, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and reduced cisplatin-mediated apoptosis. These data suggest that the A1AR provides otoprotection by suppressing NOX3 and inflammation in the cochlea and could serve as an ideal target for otoprotective drug therapy. Cisplatin is a widely used chemotherapeutic agent for the treatment of solid tumors. Its use results in significant and permanent hearing loss, for which no US Food and Drug Administration-approved treatment is currently available. In this study, we targeted the cochlear adenosine A1 receptor (A1AR) by trans-tympanic injections of the agonist R

NADPH oxidase 1 supports proliferation of colon cancer cells by modulating reactive oxygen species-dependent signal transduction.

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Juhasz, Agnes; Markel, Susan; Gaur, Shikha; Liu, Han; Lu, Jiamo; Jiang, Guojian; Wu, Xiwei; Antony, Smitha; Wu, Yongzhong; Melillo, Giovanni; Meitzler, Jennifer L; Haines, Diana C; Butcher, Donna; Roy, Krishnendu; Doroshow, James H

2017-05-12

Reactive oxygen species (ROS) play a critical role in cell signaling and proliferation. NADPH oxidase 1 (NOX1), a membrane-bound flavin dehydrogenase that generates O 2 ̇̄ , is highly expressed in colon cancer. To investigate the role that NOX1 plays in colon cancer growth, we used shRNA to decrease NOX1 expression stably in HT-29 human colon cancer cells. The 80-90% decrease in NOX1 expression achieved by RNAi produced a significant decline in ROS production and a G 1 /S block that translated into a 2-3-fold increase in tumor cell doubling time without increased apoptosis. The block at the G 1 /S checkpoint was associated with a significant decrease in cyclin D 1 expression and profound inhibition of mitogen-activated protein kinase (MAPK) signaling. Decreased steady-state MAPK phosphorylation occurred concomitant with a significant increase in protein phosphatase activity for two colon cancer cell lines in which NOX1 expression was knocked down by RNAi. Diminished NOX1 expression also contributed to decreased growth, blood vessel density, and VEGF and hypoxia-inducible factor 1α (HIF-1α) expression in HT-29 xenografts initiated from NOX1 knockdown cells. Microarray analysis, supplemented by real-time PCR and Western blotting, revealed that the expression of critical regulators of cell proliferation and angiogenesis, including c-MYC, c-MYB, and VEGF, were down-regulated in association with a decline in hypoxic HIF-1α protein expression downstream of silenced NOX1 in both colon cancer cell lines and xenografts. These studies suggest a role for NOX1 in maintaining the proliferative phenotype of some colon cancers and the potential of NOX1 as a therapeutic target in this disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

NADPH oxidase 4 mediates insulin-stimulated HIF-1α and VEGF expression, and angiogenesis in vitro.

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Dan Meng

Full Text Available Acute intensive insulin therapy causes a transient worsening of diabetic retinopathy in type 1 diabetes patients and is related to VEGF expression. Reactive oxygen species (ROS have been shown to be involved in HIF-1α and VEGF expression induced by insulin, but the role of specific ROS sources has not been fully elucidated. In this study we examined the role of NADPH oxidase subunit 4 (Nox4 in insulin-stimulated HIF-1α and VEGF expression, and angiogenic responses in human microvascular endothelial cells (HMVECs. Here we demonstrate that knockdown of Nox4 by siRNA reduced insulin-stimulated ROS generation, the tyrosine phosphorylation of IR-β and IRS-1, but did not change the serine phosphorylation of IRS-1. Nox4 gene silencing had a much greater inhibitory effect on insulin-induced AKT activation than ERK1/2 activation, whereas it had little effect on the expression of the phosphatases such as MKP-1 and SHIP. Inhibition of Nox4 expression inhibited the transcriptional activity of VEGF through HIF-1. Overexpression of wild-type Nox4 was sufficient to increase VEGF transcriptional activity, and further enhanced insulin-stimulated the activation of VEGF. Downregulation of Nox4 expression decreased insulin-stimulated mRNA and protein expression of HIF-1α, but did not change the rate of HIF-1α degradation. Inhibition of Nox4 impaired insulin-stimulated VEGF expression, cell migration, cell proliferation, and tube formation in HMVECs. Our data indicate that Nox4-derived ROS are essential for HIF-1α-dependent VEGF expression, and angiogenesis in vitro induced by insulin. Nox4 may be an attractive therapeutic target for diabetic retinopathy caused by intensive insulin treatment.

Regulating NETosis: Increasing pH Promotes NADPH Oxidase-Dependent NETosis

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Khan, Meraj A.; Philip, Lijy M.; Cheung, Guillaume; Vadakepeedika, Shawn; Grasemann, Hartmut; Sweezey, Neil; Palaniyar, Nades

2018-01-01

Neutrophils migrating from the blood (pH 7.35–7.45) into the surrounding tissues encounter changes in extracellular pH (pHe) conditions. Upon activation of NADPH oxidase 2 (Nox), neutrophils generate large amounts of H+ ions reducing the intracellular pH (pHi). Nevertheless, how extracellular pH regulates neutrophil extracellular trap (NET) formation (NETosis) is not clearly established. We hypothesized that increasing pH increases Nox-mediated production of reactive oxygen species (ROS) and neutrophil protease activity, stimulating NETosis. Here, we found that raising pHe (ranging from 6.6 to 7.8; every 0.2 units) increased pHi of both activated and resting neutrophils within 10–20 min (Seminaphtharhodafluor dual fluorescence measurements). Since Nox activity generates H+ ions, pHi is lower in neutrophils that are activated compared to resting. We also found that higher pH stimulated Nox-dependent ROS production (R123 generation; flow cytometry, plate reader assay, and imaging) during spontaneous and phorbol myristate acetate-induced NETosis (Sytox Green assays, immunoconfocal microscopy, and quantifying NETs). In neutrophils that are activated and not resting, higher pH stimulated histone H4 cleavage (Western blots) and NETosis. Raising pH increased Escherichia coli lipopolysaccharide-, Pseudomonas aeruginosa (Gram-negative)-, and Staphylococcus aureus (Gram-positive)-induced NETosis. Thus, higher pHe promoted Nox-dependent ROS production, protease activity, and NETosis; lower pH has the opposite effect. These studies provided mechanistic steps of pHe-mediated regulation of Nox-dependent NETosis. Raising pH either by sodium bicarbonate or Tris base (clinically known as Tris hydroxymethyl aminomethane, tromethamine, or THAM) increases NETosis. Each Tris molecule can bind 3H+ ions, whereas each bicarbonate HCO3− ion binds 1H+ ion. Therefore, the amount of Tris solution required to cause the same increase in pH level is less than that of equimolar

Regulating NETosis: Increasing pH Promotes NADPH Oxidase-Dependent NETosis

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Meraj A. Khan

2018-02-01

Full Text Available Neutrophils migrating from the blood (pH 7.35–7.45 into the surrounding tissues encounter changes in extracellular pH (pHe conditions. Upon activation of NADPH oxidase 2 (Nox, neutrophils generate large amounts of H+ ions reducing the intracellular pH (pHi. Nevertheless, how extracellular pH regulates neutrophil extracellular trap (NET formation (NETosis is not clearly established. We hypothesized that increasing pH increases Nox-mediated production of reactive oxygen species (ROS and neutrophil protease activity, stimulating NETosis. Here, we found that raising pHe (ranging from 6.6 to 7.8; every 0.2 units increased pHi of both activated and resting neutrophils within 10–20 min (Seminaphtharhodafluor dual fluorescence measurements. Since Nox activity generates H+ ions, pHi is lower in neutrophils that are activated compared to resting. We also found that higher pH stimulated Nox-dependent ROS production (R123 generation; flow cytometry, plate reader assay, and imaging during spontaneous and phorbol myristate acetate-induced NETosis (Sytox Green assays, immunoconfocal microscopy, and quantifying NETs. In neutrophils that are activated and not resting, higher pH stimulated histone H4 cleavage (Western blots and NETosis. Raising pH increased Escherichia coli lipopolysaccharide-, Pseudomonas aeruginosa (Gram-negative-, and Staphylococcus aureus (Gram-positive-induced NETosis. Thus, higher pHe promoted Nox-dependent ROS production, protease activity, and NETosis; lower pH has the opposite effect. These studies provided mechanistic steps of pHe-mediated regulation of Nox-dependent NETosis. Raising pH either by sodium bicarbonate or Tris base (clinically known as Tris hydroxymethyl aminomethane, tromethamine, or THAM increases NETosis. Each Tris molecule can bind 3H+ ions, whereas each bicarbonate HCO3− ion binds 1H+ ion. Therefore, the amount of Tris solution required to cause the same increase in pH level is less than that of equimolar

Protocatechuic aldehyde attenuates cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation

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Li Gao

2016-12-01

Full Text Available Cisplatin is a classic chemotherapeutic agent widely used to treat different types of cancers including ovarian, head and neck, testicular and uterine cervical carcinomas. However, cisplatin induces acute kidney injury by directly triggering an excessive inflammatory response, oxidative stress and programmed cell death of renal tubular epithelial cells. All of which lead to higher mortality rates in patients. In this study we examined the protective effect of protocatechuic aldehyde (PA in vitro in cisplatin-treated tubular epithelial cells and in vivo in cisplatin nephropathy. PA is a monomer of Traditional Chinese Medicine isolated from the root of S. miltiorrhiza. Results show that PA prevented cisplatin-induced decline of renal function and histological damage, which was confirmed by attenuation of KIM1 in both mRNA and protein levels. Moreover, PA reduced renal inflammation by suppressing oxidative stress and programmed cell death in response to cisplatin, which was further evidenced by in vitro data. Of note, PA suppressed NAPDH oxidases, including Nox2 and Nox4, in a dosage-dependent manner. Moreover, silencing Nox4, but not Nox2, removed the inhibitory effect of PA on cisplatin-induced renal injury, indicating that Nox4 may play a pivotal role in mediating the protective effect of PA in cisplatin-induced acute kidney injury. Collectively, our data indicate that PA largely blocked cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation without compromising anti-tumor activity of cisplatin. These findings suggest that PA and its derivatives may serve as potential protective agents for cancer patients with cisplatin treatment.

Decreased neural precursor cell pool in NADPH oxidase 2-deficiency: From mouse brain to neural differentiation of patient derived iPSC

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Zeynab Nayernia

2017-10-01

Full Text Available There is emerging evidence for the involvement of reactive oxygen species (ROS in the regulation of stem cells and cellular differentiation. Absence of the ROS-generating NADPH oxidase NOX2 in chronic granulomatous disease (CGD patients, predominantly manifests as immune deficiency, but has also been associated with decreased cognition. Here, we investigate the role of NOX enzymes in neuronal homeostasis in adult mouse brain and in neural cells derived from human induced pluripotent stem cells (iPSC. High levels of NOX2 were found in mouse adult neurogenic regions. In NOX2-deficient mice, neurogenic regions showed diminished redox modifications, as well as decrease in neuroprecursor numbers and in expression of genes involved in neural differentiation including NES, BDNF and OTX2. iPSC from healthy subjects and patients with CGD were used to study the role of NOX2 in human in vitro neuronal development. Expression of NOX2 was low in undifferentiated iPSC, upregulated upon neural induction, and disappeared during neuronal differentiation. In human neurospheres, NOX2 protein and ROS generation were polarized within the inner cell layer of rosette structures. NOX2 deficiency in CGD-iPSCs resulted in an abnormal neural induction in vitro, as revealed by a reduced expression of neuroprogenitor markers (NES, BDNF, OTX2, NRSF/REST, and a decreased generation of mature neurons. Vector-mediated NOX2 expression in NOX2-deficient iPSCs rescued neurogenesis. Taken together, our study provides novel evidence for a regulatory role of NOX2 during early stages of neurogenesis in mouse and human.

Lycopene Inhibits Metastasis of Human Liver Adenocarcinoma SK-Hep-1 Cells by Downregulation of NADPH Oxidase 4 Protein Expression.

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Jhou, Bo-Yi; Song, Tuzz-Ying; Lee, Inn; Hu, Miao-Lin; Yang, Nae-Cherng

2017-08-16

NADPH oxidase 4 (NOX4), with the sole function to produce reactive oxygen species (ROS), can be a molecular target for disrupting cancer metastasis. Several studies have indicated that lycopene exhibited anti-metastatic actions in vitro and in vivo. However, the role of NOX4 in the anti-metastatic action of lycopene remains unknown. Herein, we first confirmed the anti-metastatic effect of lycopene (0.1-5 μM) on human liver adenocarcinoma SK-Hep-1 cells. We showed that lycopene significantly inhibited NOX4 protein expression, with the strongest inhibition of 64.3 ± 10.2% (P lycopene. Lycopene also significantly inhibited NOX4 mRNA expression, NOX activity, and intracellular ROS levels in SK-Hep-1 cells. We then determined the effects of lycopene on transforming growth factor β (TGF-β)-induced metastasis. We found that TGF-β (5 ng/mL) significantly increased migration, invasion, and adhesion activity, the intracellular ROS level, matrix metalloproteinase 9 (MMP-9) and MMP-2 activities, the level of NOX4 protein expression, and NOX activity. All these TGF-β-induced effects were antagonized by the incubation of SK-Hep-1 cells with lycopene (2.5 μM). Using transient transfection of siRNA against NOX4, we found that the downregulation of NOX4 could mimic lycopene by inhibiting cell migration and the activities of MMP-9 and MMP-2 during the incubation with or without TGF-β on SK-Hep-1 cells. The results demonstrate that the downregulation of NOX4 plays a crucial role in the anti-metastatic action of lycopene in SK-Hep-1 cells.

Identification of aldehyde oxidase 1 and aldehyde oxidase homologue 1 as dioxin-inducible genes

International Nuclear Information System (INIS)

Rivera, Steven P.; Choi, Hyun Ho; Chapman, Brett; Whitekus, Michael J.; Terao, Mineko; Garattini, Enrico; Hankinson, Oliver

2005-01-01

Aldehyde oxidases are a family of highly related molybdo-flavoenzymes acting upon a variety of compounds of industrial and medical importance. We have identified aldehyde oxidase 1 (AOX1) as a 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) inducible gene in the mouse hepatoma cell line Hepa-1. AOX1 mRNA levels were not increased by dioxin in mutant derivatives of the Hepa-1 cell line lacking either functional aryl hydrocarbon receptor (AHR) or aryl hydrocarbon receptor nuclear translocator (ARNT) proteins, thus demonstrating that transcriptional induction of AOX1 in response to dioxin occurs through the AHR pathway. Dioxin induction of AOX1 mRNA was also observed in mouse liver. In addition, levels of AOX1 protein as well as those of aldehyde oxidase homologue 1 (AOH1), a recently identified homolog of AOX1, were elevated in mouse liver in response to dioxin. Employing an aldehyde oxidase specific substrate, AOX1/AOH1 activity was shown to be induced by dioxin in mouse liver. This activity was inhibited by a known inhibitor of aldehyde oxidases, and eliminated by including tungstate in the mouse diet, which is known to lead to inactivation of molybdoflavoenzymes, thus confirming that the enzymatic activity was attributable to AOX1/AOH1. Our observations thus identify two additional xenobiotic metabolizing enzymes induced by dioxin

Kaempferol suppresses collagen-induced platelet activation by inhibiting NADPH oxidase and protecting SHP-2 from oxidative inactivation.

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Wang, Su Bin; Jang, Ji Yong; Chae, Yun Hee; Min, Ji Hyun; Baek, Jin Young; Kim, Myunghee; Park, Yunjeong; Hwang, Gwi Seo; Ryu, Jae-Sang; Chang, Tong-Shin

2015-06-01

Reactive oxygen species (ROS) generated upon collagen stimulation act as second messengers to propagate various platelet-activating events. Among the ROS-generating enzymes, NADPH oxidase (NOX) plays a prominent role in platelet activation. Thus, NOX has been suggested as a novel target for anti-platelet drug development. Although kaempferol has been identified as a NOX inhibitor, the influence of kaempferol on the activation of platelets and the underlying mechanism have never been investigated. Here, we studied the effects of kaempferol on NOX activation, ROS-dependent signaling pathways, and functional responses in collagen-stimulated platelets. Superoxide anion generation stimulated by collagen was significantly inhibited by kaempferol in a concentration-dependent manner. More importantly, kaempferol directly bound p47(phox), a major regulatory subunit of NOX, and significantly inhibited collagen-induced phosphorylation of p47(phox) and NOX activation. In accordance with the inhibition of NOX, ROS-dependent inactivation of SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2) was potently protected by kaempferol. Subsequently, the specific tyrosine phosphorylation of key components (Syk, Vav1, Btk, and PLCγ2) of collagen receptor signaling pathways was suppressed by kaempferol. Kaempferol also attenuated downstream responses, including cytosolic calcium elevation, P-selectin surface exposure, and integrin-αIIbβ3 activation. Ultimately, kaempferol inhibited platelet aggregation and adhesion in response to collagen in vitro and prolonged in vivo thrombotic response in carotid arteries of mice. This study shows that kaempferol impairs collagen-induced platelet activation through inhibition of NOX-derived ROS production and subsequent oxidative inactivation of SHP-2. This effect suggests that kaempferol has therapeutic potential for the prevention and treatment of thrombovascular diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Electrochemical reduction of NOx

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Traulsen, Marie Lund

NO and NO2 (collectively referred to as NOx) are air pollutants, and the largest single contributor to NOx pollution is automotive exhaust. This study investigates electrochemical deNOx, a technology which aims to remove NOx from automotive diesel exhaust by electrochemical reduction of NOx to N2...... and O2. The focus in this study is on improving the activity and selectivity of solid oxide electrodes for electrochemical deNOx by addition of NOx storage compounds to the electrodes. Two different composite electrodes, La0.85Sr0.15MnO3-δ-Ce0.9Gd0.1O1.95 (LSM15-CGO10) and La0.85Sr0.15FeO3-δ-Ce0.9Gd0.1O......1.95 (LSF15-CGO10), have been investigated in combination with three different NOx storage compounds: BaO, K2O and MnOx. The main focus in the investigation has been on conversion measurements and electrochemical characterization, the latter by means of electrochemical impedance spectroscopy...

Functional Assembly of Soluble and Membrane Recombinant Proteins of Mammalian NADPH Oxidase Complex.

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Souabni, Hajer; Ezzine, Aymen; Bizouarn, Tania; Baciou, Laura

2017-01-01

Activation of phagocyte cells from an innate immune system is associated with a massive consumption of molecular oxygen to generate highly reactive oxygen species (ROS) as microbial weapons. This is achieved by a multiprotein complex, the so-called NADPH oxidase. The activity of phagocyte NADPH oxidase relies on an assembly of more than five proteins, among them the membrane heterodimer named flavocytochrome b 558 (Cytb 558 ), constituted by the tight association of the gp91 phox (also named Nox2) and p22 phox proteins. The Cytb 558 is the membrane catalytic core of the NADPH oxidase complex, through which the reducing equivalent provided by NADPH is transferred via the associated prosthetic groups (one flavin and two hemes) to reduce dioxygen into superoxide anion. The other major proteins (p47 phox , p67 phox , p40 phox , Rac) requisite for the complex activity are cytosolic proteins. Thus, the NADPH oxidase functioning relies on a synergic multi-partner assembly that in vivo can be hardly studied at the molecular level due to the cell complexity. Thus, a cell-free assay method has been developed to study the NADPH oxidase activity that allows measuring and eventually quantifying the ROS generation based on optical techniques following reduction of cytochrome c. This setup is a valuable tool for the identification of protein interactions, of crucial components and additives for a functional enzyme. Recently, this method was improved by the engineering and the production of a complete recombinant NADPH oxidase complex using the combination of purified proteins expressed in bacterial and yeast host cells. The reconstitution into artificial membrane leads to a fully controllable system that permits fine functional studies.

Reduction of NADPH-oxidase activity ameliorates the cardiovascular phenotype in a mouse model of Williams-Beuren Syndrome.

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Victoria Campuzano

2012-02-01

Full Text Available A hallmark feature of Williams-Beuren Syndrome (WBS is a generalized arteriopathy due to elastin deficiency, presenting as stenoses of medium and large arteries and leading to hypertension and other cardiovascular complications. Deletion of a functional NCF1 gene copy has been shown to protect a proportion of WBS patients against hypertension, likely through reduced NADPH-oxidase (NOX-mediated oxidative stress. DD mice, carrying a 0.67 Mb heterozygous deletion including the Eln gene, presented with a generalized arteriopathy, hypertension, and cardiac hypertrophy, associated with elevated angiotensin II (angII, oxidative stress parameters, and Ncf1 expression. Genetic (by crossing with Ncf1 mutant and/or pharmacological (with ang II type 1 receptor blocker, losartan, or NOX inhibitor apocynin reduction of NOX activity controlled hormonal and biochemical parameters in DD mice, resulting in normalized blood pressure and improved cardiovascular histology. We provide strong evidence for implication of the redox system in the pathophysiology of the cardiovascular disease in a mouse model of WBS. The phenotype of these mice can be ameliorated by either genetic or pharmacological intervention reducing NOX activity, likely through reduced angII-mediated oxidative stress. Therefore, anti-NOX therapy merits evaluation to prevent the potentially serious cardiovascular complications of WBS, as well as in other cardiovascular disorders mediated by similar pathogenic mechanism.

The matricellular protein TSP1 promotes human and mouse endothelial cell senescence through CD47 and Nox1.

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Meijles, Daniel N; Sahoo, Sanghamitra; Al Ghouleh, Imad; Amaral, Jefferson H; Bienes-Martinez, Raquel; Knupp, Heather E; Attaran, Shireen; Sembrat, John C; Nouraie, Seyed M; Rojas, Mauricio M; Novelli, Enrico M; Gladwin, Mark T; Isenberg, Jeffrey S; Cifuentes-Pagano, Eugenia; Pagano, Patrick J

2017-10-17

Senescent cells withdraw from the cell cycle and do not proliferate. The prevalence of senescent compared to normally functioning parenchymal cells increases with age, impairing tissue and organ homeostasis. A contentious principle governing this process has been the redox theory of aging. We linked matricellular protein thrombospondin 1 (TSP1) and its receptor CD47 to the activation of NADPH oxidase 1 (Nox1), but not of the other closely related Nox isoforms, and associated oxidative stress, and to senescence in human cells and aged tissue. In human endothelial cells, TSP1 promoted senescence and attenuated cell cycle progression and proliferation. At the molecular level, TSP1 increased Nox1-dependent generation of reactive oxygen species (ROS), leading to the increased abundance of the transcription factor p53. p53 mediated a DNA damage response that led to senescence through Rb and p21 cip , both of which inhibit cell cycle progression. Nox1 inhibition blocked the ability of TSP1 to increase p53 nuclear localization and p21 cip abundance and its ability to promote senescence. Mice lacking TSP1 showed decreases in ROS production, p21 cip expression, p53 activity, and aging-induced senescence. Conversely, lung tissue from aging humans displayed increases in the abundance of vascular TSP1, Nox1, p53, and p21 cip Finally, genetic ablation or pharmacological blockade of Nox1 in human endothelial cells attenuated TSP1-mediated ROS generation, restored cell cycle progression, and protected against senescence. Together, our results provide insights into the functional interplay between TSP1 and Nox1 in the regulation of endothelial senescence and suggest potential targets for controlling the aging process at the molecular level. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Comparative analysis of lysyl oxidase (like) family members in pulmonary fibrosis.

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Aumiller, Verena; Strobel, Benjamin; Romeike, Merrit; Schuler, Michael; Stierstorfer, Birgit E; Kreuz, Sebastian

2017-03-10

Extracellular matrix (ECM) composition and stiffness are major driving forces for the development and persistence of fibrotic diseases. Lysyl oxidase (LOX) and LOX-like (LOXL) proteins play crucial roles in ECM remodeling due to their collagen crosslinking and intracellular functions. Here, we systematically investigated LOX/L expression in primary fibroblasts and epithelial cells under fibrotic conditions, Bleomycin (BLM) induced lung fibrosis and in human IPF tissue. Basal expression of all LOX/L family members was detected in epithelial cells and at higher levels in fibroblasts. Various pro-fibrotic stimuli broadly induced LOX/L expression in fibroblasts, whereas specific induction of LOXL2 and partially LOX was observed in epithelial cells. Immunohistochemical analysis of lung tissue from 14 IPF patients and healthy donors revealed strong induction of LOX and LOXL2 in bronchial and alveolar epithelium as well as fibroblastic foci. Using siRNA experiments we observed that LOXL2 and LOXL3 were crucial for fibroblast-to-myofibroblast transition (FMT). As FMT could only be reconstituted with an enzymatically active LOXL2 variant, we conclude that LOXL2 enzymatic function is crucial for fibroblast transdifferentiation. In summary, our study provides a comprehensive analysis of the LOX/L family in fibrotic lung disease and indicates prominent roles for LOXL2/3 in fibroblast activation and LOX/LOXL2 in IPF.

Studying neuroprotective effect of Atorvastatin as a small molecule drug on high glucose-induced neurotoxicity in undifferentiated PC12 cells: role of NADPH oxidase.

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Rayegan, Samira; Dehpour, Ahmad Reza; Sharifi, Ali Mohammad

2017-02-01

Overproduction of reactive oxygen species (ROS) by NADPH oxidase (NOX) activation has been considered the essential mechanism induced by hyperglycemia in various tissues. However, there is no comprehensive study on the role of NOXs in high glucose (HG)-induced toxic effect in neural tissues. Recently, a therapeutic strategy in oxidative related pathologies has been introduced by blocking the undesirable actions of NOX enzymes by small molecules. The protective roles of Statins in ameliorating oxidative stress by NOX inhibition have been shown in some tissues except neural. We hypothesized then, that different NOXs may have role in HG-induced neural cell injury. Furthermore, we postulate that Atorvastatin as a small molecule may modulate this NOXs activity to protect neural cells. Undifferentiated PC12 cells were treated with HG (140 mM/24 h) in the presence and absence of Atorvastatin (1 μM/96 h). The cell viability was measured by MTT assay and the gene and protein expressions profile of NOX (1-4) were determined by RT-PCR and western blotting, respectively. Levels of ROS and malondialdehyde (MDA) were also evaluated. Gene and protein expression levels of NOX (1-4) and consequently ROS and MDA levels were elevated in HG-treated PC12 cells. Atorvastatin could significantly decrease HG-induced NOXs, ROS and MDA elevation and improve impaired cell viability. It can be concluded that HG could elevate NOXs activity, ROS and MDA levels in neural tissues and Atorvastatin as a small molecule NOX inhibitor drug may prevent and delay diabetic complications, particularly neuropathy.

NOX4 mediates BMP4-induced upregulation of TRPC1 and 6 protein expressions in distal pulmonary arterial smooth muscle cells.

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Qian Jiang

Full Text Available Our previous studies demonstrated that bone morphogenetic protein 4 (BMP4 mediated, elevated expression of canonical transient receptor potential (TRPC largely accounts for the enhanced proliferation in pulmonary arterial smooth muscle cells (PASMCs. In the present study, we sought to determine the signaling pathway through which BMP4 up-regulates TRPC expression.We employed recombinant human BMP4 (rhBMP4 to determine the effects of BMP4 on NADPH oxidase 4 (NOX4 and reactive oxygen species (ROS production in rat distal PASMCs. We also designed small interfering RNA targeting NOX4 (siNOX4 and detected whether NOX4 knockdown affects rhBMP4-induced ROS, TRPC1 and 6 expression, cell proliferation and intracellular Ca2+ determination in PASMCs.In rhBMP4 treated rat distal PASMCs, NOX4 expression was (226.73±11.13 %, and the mean ROS level was (123.65±1.62 % of that in untreated control cell. siNOX4 transfection significantly reduced rhBMP4-induced elevation of the mean ROS level in PASMCs. Moreover, siNOX4 transfection markedly reduced rhBMP4-induced elevation of TRPC1 and 6 proteins, basal [Ca2+]i and SOCE. Furthermore, compared with control group (0.21±0.001, the proliferation of rhBMP4 treated cells was significantly enhanced (0.41±0.001 (P<0.01. However, such increase was attenuated by knockdown of NOX4. Moreover, external ROS (H2O2 100 µM, 24 h rescued the effects of NOX4 knockdown, which included the declining of TRPC1 and 6 expression, basal intracellular calcium concentration ([Ca2+]i and store-operated calcium entry (SOCE, suggesting that NOX4 plays as an important mediator in BMP4-induced proliferation and intracellular calcium homeostasis.These results suggest that BMP4 may increase ROS level, enhance TRPC1 and 6 expression and proliferation by up-regulating NOX4 expression in PASMCs.

Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis

DEFF Research Database (Denmark)

Peleli, Maria; Al-Mashhadi, Ammar; Yang, Ting

2016-01-01

Hydronephrosis is associated with development of salt-sensitive hypertension. Studies suggest that increased sympathetic nerve activity (SNA) and oxidative stress play important roles in renovascular hypertension. This study aimed to investigate the link between renal SNA and NADPH oxidase (NOX......) regulation in the development of hypertension in rats with hydronephrosis. Hydronephrosis was induced by partial unilateral ureteral obstruction (PUUO) in young rats. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high and low salt diets. Renal...

Contribution of NADPH Oxidase to Membrane CD38 Internalization and Activation in Coronary Arterial Myocytes

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Xu, Ming; Li, Xiao-Xue; Ritter, Joseph K.; Abais, Justine M.; Zhang, Yang; Li, Pin-Lan

2013-01-01

The CD38-ADP-ribosylcyclase-mediated Ca2+ signaling pathway importantly contributes to the vasomotor response in different arteries. Although there is evidence indicating that the activation of CD38-ADP-ribosylcyclase is associated with CD38 internalization, the molecular mechanism mediating CD38 internalization and consequent activation in response to a variety of physiological and pathological stimuli remains poorly understood. Recent studies have shown that CD38 may sense redox signals and is thereby activated to produce cellular response and that the NADPH oxidase isoform, NOX1, is a major resource to produce superoxide (O2 ·−) in coronary arterial myocytes (CAMs) in response to muscarinic receptor agonist, which uses CD38-ADP-ribosylcyclase signaling pathway to exert its action in these CAMs. These findings led us hypothesize that NOX1-derived O2 ·− serves in an autocrine fashion to enhance CD38 internalization, leading to redox activation of CD38-ADP-ribosylcyclase activity in mouse CAMs. To test this hypothesis, confocal microscopy, flow cytometry and a membrane protein biotinylation assay were used in the present study. We first demonstrated that CD38 internalization induced by endothelin-1 (ET-1) was inhibited by silencing of NOX1 gene, but not NOX4 gene. Correspondingly, NOX1 gene silencing abolished ET-1-induced O2 ·− production and increased CD38-ADP-ribosylcyclase activity in CAMs, while activation of NOX1 by overexpression of Rac1 or Vav2 or administration of exogenous O2 ·− significantly increased CD38 internalization in CAMs. Lastly, ET-1 was found to markedly increase membrane raft clustering as shown by increased colocalization of cholera toxin-B with CD38 and NOX1. Taken together, these results provide direct evidence that Rac1-NOX1-dependent O2 ·− production mediates CD38 internalization in CAMs, which may represent an important mechanism linking receptor activation with CD38 activity in these cells. PMID:23940720

NADH Oxidase of Streptococcus thermophilus 1131 is Required for the Effective Yogurt Fermentation with Lactobacillus delbrueckii subsp. bulgaricus 2038.

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Sasaki, Yasuko; Horiuchi, Hiroshi; Kawashima, Hiroko; Mukai, Takao; Yamamoto, Yuji

2014-01-01

We previously reported that dissolved oxygen (DO) suppresses yogurt fermentation with an industrial starter culture composed of Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus) 2038 and Streptococcus thermophilus 1131, and also found that reducing the DO in the medium prior to fermentation (deoxygenated fermentation) shortens the fermentation time. In this study, we found that deoxygenated fermentation primarily increased the cell number of S. thermophilus 1131 rather than that of L. bulgaricus 2038, resulting in earlier l-lactate and formate accumulation. Measurement of the DO concentration and hydrogen peroxide generation in the milk medium suggested that DO is mainly removed by S. thermophilus 1131. The results using an H2O-forming NADH oxidase (Nox)-defective mutant of S. thermophilus 1131 revealed that Nox is the major oxygen-consuming enzyme of the bacterium. Yogurt fermentation with the S. thermophilus Δnox mutant and L. bulgaricus 2038 was significantly slower than with S. thermophilus 1131 and L. bulgaricus 2038, and the DO concentrations of the mixed culture did not decrease to less than 2 mg/kg within 3 hr. These observations suggest that Nox of S. thermophilus 1131 contributes greatly to yogurt fermentation, presumably by removing the DO in milk.

NOX4-dependent Hydrogen peroxide promotes shear stress-induced SHP2 sulfenylation and eNOS activation.

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Sánchez-Gómez, Francisco J; Calvo, Enrique; Bretón-Romero, Rosa; Fierro-Fernández, Marta; Anilkumar, Narayana; Shah, Ajay M; Schröder, Katrin; Brandes, Ralf P; Vázquez, Jesús; Lamas, Santiago

2015-12-01

Laminar shear stress (LSS) triggers signals that ultimately result in atheroprotection and vasodilatation. Early responses are related to the activation of specific signaling cascades. We investigated the participation of redox-mediated modifications and in particular the role of hydrogen peroxide (H2O2) in the sulfenylation of redox-sensitive phosphatases. Exposure of vascular endothelial cells to short periods of LSS (12 dyn/cm(2)) resulted in the generation of superoxide radical anion as detected by the formation of 2-hydroxyethidium by HPLC and its subsequent conversion to H2O2, which was corroborated by the increase in the fluorescence of the specific peroxide sensor HyPer. By using biotinylated dimedone we detected increased total protein sulfenylation in the bovine proteome, which was dependent on NADPH oxidase 4 (NOX4)-mediated generation of peroxide. Mass spectrometry analysis allowed us to identify the phosphatase SHP2 as a protein susceptible to sulfenylation under LSS. Given the dependence of FAK activity on SHP2 function, we explored the role of FAK under LSS conditions. FAK activation and subsequent endothelial NO synthase (eNOS) phosphorylation were promoted by LSS and both processes were dependent on NOX4, as demonstrated in lung endothelial cells isolated from NOX4-null mice. These results support the idea that LSS elicits redox-sensitive signal transduction responses involving NOX4-dependent generation of hydrogen peroxide, SHP2 sulfenylation, and ulterior FAK-mediated eNOS activation. Copyright © 2015 Elsevier Inc. All rights reserved.

Molecular Basis for Converting (2S-Methylsuccinyl-CoA Dehydrogenase into an Oxidase

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Simon Burgener

2017-12-01

Full Text Available Although flavoenzymes have been studied in detail, the molecular basis of their dioxygen reactivity is only partially understood. The members of the flavin adenosine dinucleotide (FAD-dependent acyl-CoA dehydrogenase and acyl-CoA oxidase families catalyze similar reactions and share common structural features. However, both enzyme families feature opposing reaction specificities in respect to dioxygen. Dehydrogenases react with electron transfer flavoproteins as terminal electron acceptors and do not show a considerable reactivity with dioxygen, whereas dioxygen serves as a bona fide substrate for oxidases. We recently engineered (2S-methylsuccinyl-CoA dehydrogenase towards oxidase activity by rational mutagenesis. Here we characterized the (2S-methylsuccinyl-CoA dehydrogenase wild-type, as well as the engineered (2S-methylsuccinyl-CoA oxidase, in detail. Using stopped-flow UV-spectroscopy and liquid chromatography-mass spectrometry (LC-MS based assays, we explain the molecular base for dioxygen reactivity in the engineered oxidase and show that the increased oxidase function of the engineered enzyme comes at a decreased dehydrogenase activity. Our findings add to the common notion that an increased activity for a specific substrate is achieved at the expense of reaction promiscuity and provide guidelines for rational engineering efforts of acyl-CoA dehydrogenases and oxidases.

Hepatoprotective effects of curcumin in rats after bile duct ligation via downregulation of Rac1 and NOX1.

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Ghoreshi, Zohreh-Al-Sadat; Kabirifar, Razieh; Safari, Fatemeh; Karimollah, Alireza; Moradi, Ali; Eskandari-Nasab, Ebrahim

2017-04-01

New evidence has proven the hepatoprotective activity of curcumin; however, its underlying mechanisms remain to be elucidated. The aim of this study was to investigate the protective effect of curcumin on hepatic damage by measuring the antioxidant capacity and expression level of Rho-related C3 botulinum toxin substrate (Rac1), Rac1-Guanosine triphosphate (Rac1-GTP), and NADPH oxidase 1(NOX1) in biliary duct-ligated (BDL)-fibrotic rat model. Wistar rats weighing 200 to 250 g were divided into four groups (n = 8 for each): sham group, sham+Cur group (received curcumin 100 mg/kg daily), BDL+Cur group, and BDL group. The mRNA and protein expression levels of Rac1, Rac1-GTP, and NOX1 were measured by real-time polymerase chain reaction and Western blotting, respectively. Curcumin treatment of BDL rats reduced liver injury, as verified by improvement of hepatic cell histologic alterations, and by reduction of hepatic enzymes. Moreover, the increase in the expression of Rac1, Rac1-GTP, and NOX1 observed in BDL rats was precluded and reversed back toward normalcy by curcumin treatment (P Rac1, Rac1-GTP, and NOX1 as well as reduced oxidative stress in the serum and liver tissue of BDL rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Wear Particles Promote Reactive Oxygen Species-Mediated Inflammation via the Nicotinamide Adenine Dinucleotide Phosphate Oxidase Pathway in Macrophages Surrounding Loosened Implants

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Weishen Chen

2015-03-01

Full Text Available Background/Aims: Prosthesis loosening is closely associated with chronic inflammatory cytokine secretion by macrophages, which are activated by wear particles or inflammatory stimulants such as lipopolysaccharide (LPS. Reactive oxygen species (ROS are critical regulators of inflammation, but their enzymatic sources in response to wear particles and their effects on peri-implant LPS-tolerance remain unclear. Methods: Three ROS-related enzymes—nicotinamide adenine dinucleotide phosphate oxidase (NOX-1 and -2 and catalase—were investigated in interface membrane tissues and in titanium (Ti particle-stimulated macrophages in vitro. The generation of ROS and downstream inflammatory effects were measured with or without pre-incubation with apocynin, an NOX inhibitor. Results: Pre-exposure to Ti particles attenuated NF-κB activation in LPS-stimulated macrophages, indicating that wear particles suppress immune response, which may lead to chronic inflammation. NOX-1 and -2 were highly expressed in aseptically loosened interface membranes and in macrophages stimulated with Ti particles; the particles induced a moderate amount of ROS generation, NF-κB activation, and TNF-a secretion in macrophages, and these effects were suppressed by apocynin. Conclusion: Wear particles induce ROS generation through the NOX signaling pathway, resulting in persistent inflammation and delayed loosening. Thus, the suppression of NOX activity may be a useful strategy for preventing prosthesis loosening.

NecroX-7 prevents oxidative stress-induced cardiomyopathy by inhibition of NADPH oxidase activity in rats

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Park, Joonghoon; Park, Eok; Ahn, Bong-Hyun; Kim, Hyoung Jin [LG Life Sciences Ltd., R and D Park, Daejeon, 305-380 (Korea, Republic of); Park, Ji-hoon [Department of Biochemistry, School of Medicine, Chungnam National University, Daejeon, 301-747 (Korea, Republic of); Koo, Sun Young; Kwak, Hyo-Shin; Park, Heui Sul; Kim, Dong Wook; Song, Myoungsub; Yim, Hyeon Joo; Seo, Dong Ook [LG Life Sciences Ltd., R and D Park, Daejeon, 305-380 (Korea, Republic of); Kim, Soon Ha, E-mail: shakim@lgls.com [LG Life Sciences Ltd., R and D Park, Daejeon, 305-380 (Korea, Republic of)

2012-08-15

Oxidative stress is one of the causes of cardiomyopathy. In the present study, NecroXs, novel class of mitochondrial ROS/RNS scavengers, were evaluated for cardioprotection in in vitro and in vivo model, and the putative mechanism of the cardioprotection of NecroX-7 was investigated by global gene expression profiling and subsequent biochemical analysis. NecroX-7 prevented tert-butyl hydroperoxide (tBHP)-induced death of H9C2 rat cardiomyocytes at EC{sub 50} = 0.057 μM. In doxorubicin (DOX)-induced cardiomyopathy in rats, NecroX-7 significantly reduced the plasma levels of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) which were increased by DOX treatment (p < 0.05). Microarray analysis revealed that 21 genes differentially expressed in tBHP-treated H9C2 cells were involved in ‘Production of reactive oxygen species’ (p = 0.022), and they were resolved by concurrent NecroX-7 treatment. Gene-to-gene networking also identified that NecroX-7 relieved cell death through Ncf1/p47phox and Rac2 modulation. In subsequent biochemical analysis, NecroX-7 inhibited NADPH oxidase (NOX) activity by 53.3% (p < 0.001). These findings demonstrate that NecroX-7, in part, provides substantial protection of cardiomyopathy induced by tBHP or DOX via NOX-mediated cell death. -- Highlights: ► NecroX-7 prevented tert-butyl hydroperoxide-induced in vitro cardiac cell death. ► NecroX-7 ameliorated doxorubicin-induced in vivo cardiomyopathy. ► NecroX-7 prevented oxidative stress and necrosis-enriched transcriptional changes. ► NecroX-7 effectively inhibited NADPH oxidase activation. ► Cardioprotection of Necro-7 was brought on by modulation of NADPH oxidase activity.

Total Glucosides of Danggui Buxue Tang Attenuate BLM-Induced Pulmonary Fibrosis via Regulating Oxidative Stress by Inhibiting NOX4

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Zhao, Ping; Zhou, Wen-Cheng; Li, De-Lin; Mo, Xiao-Ting; Xu, Liang; Li, Liu-Cheng; Cui, Wen-Hui; Gao, Jian

2015-01-01

Pulmonary fibrosis (PF) is a serious chronic lung disease with unknown pathogenesis. Researches have confirmed that oxidative stress which is regulated by NADPH oxidase-4 (NOX4), a main source of reactive oxygen species (ROS), is an important molecular mechanism underlying PF. Previous studies showed that total glucosides of Danggui Buxue Tang (DBTG), an extract from a classical traditional Chinese herbal formula, Danggui Buxue Tang (DBT), attenuated bleomycin-induced PF in rats. However, the mechanisms of DBTG are still not clear. We hypothesize that DBTG attenuates PF through regulating the level of oxidative stress by inhibiting NOX4. And we found that fibrosis indexes hydroxyproline (HYP) and type I collagen (Col-I) were lower in DBTG groups compared with the model group. In addition, the expression of transforming growth factor-β1 (TGF-β1) and expression of alpha smooth muscle actin (α-SMA) were also much more decreased than the model group. For oxidative stress indicators, DBTG blunted the decrease of superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC), and the increase in malondialdehyde (MDA), 8-iso-prostaglandin in lung homogenates. Treatment with DBTG restrained the expression of NOX4 compared to the model group. Present study confirms that DBTG inhibits BLM-induced PF by modulating the level of oxidative stress via suppressing NOX4. PMID:26347805

Nitric oxide production and monoamine oxidase activity in cancer patients during interferon-alpha therapy.

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Fekkes, Durk; Van Gool, Arthur R; Bannink, Marjolein; Sleijfer, Stefan; Kruit, Wim H J; van der Holt, Bronno; Eggermont, Alexander M M; Hengeveld, Michiel W; Stoter, Gerrit

2009-10-01

Both increased and decreased nitric oxide (NO) synthesis have been reported in patients treated with interferon-alpha (IFN-alpha). Animal studies showed that IFN-alpha administration results in increased levels of biogenic amines, subsequent activation of monoamine oxidases (MAOs), and finally in a change in NO production due to the H(2)O(2) generated by MAOs. We examined the potential relationship between NO production in plasma and MAO-B activity in platelets of 43 cancer patients during 8 weeks of treatment with IFN-alpha. NO synthesis was quantitated by measuring both the ratio of citrulline and arginine (CIT/ARG-ratio) and total nitrite/nitrate (NOx) levels. Compared to baseline, MAO activity and NOx increased, while the CIT/ARG-ratio decreased. No associations were found between NOx, MAO and CIT/ARG-ratio. Only few associations were observed between changes in the biochemical parameters and changes in psychopathology induced by IFN-alpha, of which the association between changes in CIT and lassitude was the most consistent. The results suggest that peripheral NO production and MAO activity are unrelated to each other, and that peripheral changes in these biochemical parameters induced by IFN-alpha are unlikely to contribute to definite psychiatric disturbance.

New biotechnological perspectives of a NADH oxidase variant from Thermus thermophilus HB27 as NAD+-recycling enzyme

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Rocha-Martín Javier

2011-11-01

Full Text Available Abstract Background The number of biotransformations that use nicotinamide recycling systems is exponentially growing. For this reason one of the current challenges in biocatalysis is to develop and optimize more simple and efficient cofactor recycling systems. One promising approach to regenerate NAD+ pools is the use of NADH-oxidases that reduce oxygen to hydrogen peroxide while oxidizing NADH to NAD+. This class of enzymes may be applied to asymmetric reduction of prochiral substrates in order to obtain enantiopure compounds. Results The NADH-oxidase (NOX presented here is a flavoenzyme which needs exogenous FAD or FMN to reach its maximum velocity. Interestingly, this enzyme is 6-fold hyperactivated by incubation at high temperatures (80°C under limiting concentrations of flavin cofactor, a change that remains stable even at low temperatures (37°C. The hyperactivated form presented a high specific activity (37.5 U/mg at low temperatures despite isolation from a thermophile source. Immobilization of NOX onto agarose activated with glyoxyl groups yielded the most stable enzyme preparation (6-fold more stable than the hyperactivated soluble enzyme. The immobilized derivative was able to be reactivated under physiological conditions after inactivation by high solvent concentrations. The inactivation/reactivation cycle could be repeated at least three times, recovering full NOX activity in all cases after the reactivation step. This immobilized catalyst is presented as a recycling partner for a thermophile alcohol dehydrogenase in order to perform the kinetic resolution secondary alcohols. Conclusion We have designed, developed and characterized a heterogeneous and robust biocatalyst which has been used as recycling partner in the kinetic resolution of rac-1-phenylethanol. The high stability along with its capability to be reactivated makes this biocatalyst highly re-useable for cofactor recycling in redox biotransformations.

Bacillus calmette-guerin infection in NADPH oxidase deficiency: defective mycobacterial sequestration and granuloma formation.

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Christine Deffert

2014-09-01

Full Text Available Patients with chronic granulomatous disease (CGD lack generation of reactive oxygen species (ROS through the phagocyte NADPH oxidase NOX2. CGD is an immune deficiency that leads to frequent infections with certain pathogens; this is well documented for S. aureus and A. fumigatus, but less clear for mycobacteria. We therefore performed an extensive literature search which yielded 297 cases of CGD patients with mycobacterial infections; M. bovis BCG was most commonly described (74%. The relationship between NOX2 deficiency and BCG infection however has never been studied in a mouse model. We therefore investigated BCG infection in three different mouse models of CGD: Ncf1 mutants in two different genetic backgrounds and Cybb knock-out mice. In addition, we investigated a macrophage-specific rescue (transgenic expression of Ncf1 under the control of the CD68 promoter. Wild-type mice did not develop severe disease upon BCG injection. In contrast, all three types of CGD mice were highly susceptible to BCG, as witnessed by a severe weight loss, development of hemorrhagic pneumonia, and a high mortality (∼ 50%. Rescue of NOX2 activity in macrophages restored BCG resistance, similar as seen in wild-type mice. Granulomas from mycobacteria-infected wild-type mice generated ROS, while granulomas from CGD mice did not. Bacterial load in CGD mice was only moderately increased, suggesting that it was not crucial for the observed phenotype. CGD mice responded with massively enhanced cytokine release (TNF-α, IFN-γ, IL-17 and IL-12 early after BCG infection, which might account for severity of the disease. Finally, in wild-type mice, macrophages formed clusters and restricted mycobacteria to granulomas, while macrophages and mycobacteria were diffusely distributed in lung tissue from CGD mice. Our results demonstrate that lack of the NADPH oxidase leads to a markedly increased severity of BCG infection through mechanisms including increased cytokine

Hypertonic Saline Suppresses NADPH Oxidase-Dependent Neutrophil Extracellular Trap Formation and Promotes Apoptosis

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Ajantha Nadesalingam

2018-03-01

Full Text Available Tonicity of saline (NaCl is important in regulating cellular functions and homeostasis. Hypertonic saline is administered to treat many inflammatory diseases, including cystic fibrosis. Excess neutrophil extracellular trap (NET formation, or NETosis, is associated with many pathological conditions including chronic inflammation. Despite the known therapeutic benefits of hypertonic saline, its underlying mechanisms are not clearly understood. Therefore, we aimed to elucidate the effects of hypertonic saline in modulating NETosis. For this purpose, we purified human neutrophils and induced NETosis using agonists such as diacylglycerol mimetic phorbol myristate acetate (PMA, Gram-negative bacterial cell wall component lipopolysaccharide (LPS, calcium ionophores (A23187 and ionomycin from Streptomyces conglobatus, and bacteria (Pseudomonas aeruginosa and Staphylococcus aureus. We then analyzed neutrophils and NETs using Sytox green assay, immunostaining of NET components and apoptosis markers, confocal microscopy, and pH sensing reagents. This study found that hypertonic NaCl suppresses nicotinamide adenine dinucleotide phosphate oxidase (NADPH2 or NOX2-dependent NETosis induced by agonists PMA, Escherichia coli LPS (0111:B4 and O128:B12, and P. aeruginosa. Hypertonic saline also suppresses LPS- and PMA- induced reactive oxygen species production. It was determined that supplementing H2O2 reverses the suppressive effect of hypertonic saline on NOX2-dependent NETosis. Many of the aforementioned suppressive effects were observed in the presence of equimolar concentrations of choline chloride and osmolytes (d-mannitol and d-sorbitol. This suggests that the mechanism by which hypertonic saline suppresses NOX2-dependent NETosis is via neutrophil dehydration. Hypertonic NaCl does not significantly alter the intracellular pH of neutrophils. We found that hypertonic NaCl induces apoptosis while suppressing NOX2-dependent NETosis. In contrast, hypertonic

Nitro-oleic acid ameliorates oxygen and glucose deprivation/re-oxygenation triggered oxidative stress in renal tubular cells via activation of Nrf2 and suppression of NADPH oxidase.

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Nie, Huibin; Xue, Xia; Liu, Gang; Guan, Guangju; Liu, Haiying; Sun, Lina; Zhao, Long; Wang, Xueling; Chen, Zhixin

2016-01-01

Nitroalkene derivative of oleic acid (OA-NO 2 ), due to its ability to mediate revisable Michael addition, has been demonstrated to have various biological properties and become a therapeutic agent in various diseases. Though its antioxidant properties have been reported in different models of acute kidney injury (AKI), the mechanism by which OA-NO 2 attenuates intracellular oxidative stress is not well investigated. Here, we elucidated the anti-oxidative mechanism of OA-NO 2 in an in vitro model of renal ischemia/reperfusion (I/R) injury. Human tubular epithelial cells were subjected to oxygen and glucose deprivation/re-oxygenation (OGD/R) injury. Pretreatment with OA-NO 2 (1.25 μM, 45 min) attenuated OGD/R triggered reactive oxygen species (ROS) generation and subsequent mitochondrial membrane potential disruption. This action was mediated via up-regulating endogenous antioxidant defense components including superoxide dismutase (SOD1), heme oxygenase 1 (HO-1), and γ-glutamyl cysteine ligase modulatory subunits (GCLM). Moreover, subcellular fractionation analyses demonstrated that OA-NO 2 promoted nuclear translocation of nuclear factor-E2- related factor-2 (Nrf2) and Nrf2 siRNA partially abrogated these protective effects. In addition, OA-NO 2 inhibited NADPH oxidase activation and NADPH oxidase 4 (NOX4), NADPH oxidase 2 (NOX2) and p22 phox up-regulation after OGD/R injury, which was not relevant to Nrf2. These results contribute to clarify that the mechanism of OA-NO 2 reno-protection involves both inhibition of NADPH oxidase activity and induction of SOD1, Nrf2-dependent HO-1, and GCLM.

Rise and fall of the NOx emissions trade; Opkomst en ondergang van NOx-emissiehandel

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Van der Velde, R. [Royal Haskoning DHV, Amersfoort (Netherlands); Van der Kolk, J. [Van der Kolk Advies, Soest (Netherlands)

2013-04-15

In 2005, the Netherlands started NOx emission trading. In 2014 they are terminating these activities. Are they stopping because the targets have been realized? This article provides an overview of the developments and experiences that have ultimately led to the termination of the NOx emission trade in the Netherlands [Dutch] In 2005 is Nederland begonnen in NOx-emissiehandel. In 2014 stoppen we er weer mee. Stoppen we omdat de doelen zijn gehaald? Een overzicht wordt gegeven van de ontwikkelingen en ervaringen die uiteindelijk hebben geleid tot beeindiging van de NOx-emissiehandel in Nederland.

Qian Yang Yu Yin Granule-containing serum inhibits angiotensin II-induced proliferation, reactive oxygen species production, and inflammation in human mesangial cells via an NADPH oxidase 4-dependent pathway.

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Ding, Kang; Wang, Yan; Jiang, Weimin; Zhang, Yu; Yin, Hongping; Fang, Zhuyuan

2015-03-25

Qian Yang Yu Yin Granule (QYYYG), a traditional Chinese herbal medicine, has been indicated for renal damage in hypertension for decades in China, but little remains known regarding its underlying molecular mechanism. Therefore, we performed the current study in order to investigate the underlying molecular mechanism of QYYYG in the treatment of hypertensive renal damage. We hypothesize that QYYYG relieves hypertensive renal injury through an angiotensin II (Ang II)-nicotinamide adenine dinucleotide phosphate (NAPDH)-oxidase (NOX)-reactive oxygen species (ROS) pathway. In this study, we investigated the effects of QYYYG-containing serum (QYGS) in human mesangial cells (HMCs) against Ang II-induced cell proliferation, ROS production, and inflammation through the seropharmacological method. We found that QYGS could inhibit cell proliferation in Ang II-treated HMCs. In addition, QYGS considerably suppressed production of ROS, decreased mRNA and protein expression of NAPDH-oxidase 4 (NOX4), p22 (phox) , and activated Ras-related C3 botulinum toxin substrate 1 (GTP-Rac1); as well as counteracted the up-regulation of inflammatory markers including tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) p65, and interleukin 6 (IL-6). These effects were further confirmed in HMCs transfected with specific small interfering RNA (siRNA) targeting NOX4. Taken together, these results suggest that a NOX4-dependent pathway plays an important role in regulating the inhibitory effect of QYGS. Our findings provide new insights into the molecular mechanisms of QYYYG and their role in the treatment of hypertensive nephropathy.

Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1β-exposed Caco-2 cells.

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Tesoriere, L; Attanzio, A; Allegra, M; Gentile, C; Livrea, M A

2014-02-01

Dietary redox-active/antioxidant phytochemicals may help control or mitigate the inflammatory response in chronic inflammatory bowel disease (IBD). In the present study, the anti-inflammatory activity of indicaxanthin (Ind), a pigment from the edible fruit of cactus pear (Opuntia ficus-indica, L.), was shown in an IBD model consisting of a human intestinal epithelial cell line (Caco-2 cells) stimulated by IL-1β, a cytokine known to play a major role in the initiation and amplification of inflammatory activity in IBD. The exposure of Caco-2 cells to IL-1β brought about the activation of NADPH oxidase (NOX-1) and the generation of reactive oxygen species (ROS) to activate intracellular signalling leading to the activation of NF-κB, with the over-expression of inflammatory enzymes and release of pro-inflammatory mediators. The co-incubation of the cells with Ind, at a nutritionally relevant concentration (5-25 μM), and IL-1β prevented the release of the pro-inflammatory cytokines IL-6 and IL-8, PGE2 and NO, the formation of ROS and the loss of thiols in a dose-dependent manner. The co-incubation of the cells with Ind and IL-1β also prevented the IL-1β-induced increase of epithelial permeability. It was also shown that the activation of NOX-1 and NF-κB was prevented by Ind and the expression of COX-2 and inducible NO synthase was reduced. The uptake of Ind in Caco-2 cell monolayers appeared to be unaffected by the inflamed state of the cells. In conclusion, our findings suggest that the dietary pigment Ind may have the potential to modulate inflammatory processes at the intestinal level.

JNK and NADPH Oxidase Involved in Fluoride-Induced Oxidative Stress in BV-2 Microglia Cells

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Ling Yan

2013-01-01

Full Text Available Excessive fluoride may cause central nervous system (CNS dysfunction, and oxidative stress is a recognized mode of action of fluoride toxicity. In CNS, activated microglial cells can release more reactive oxygen species (ROS, and NADPH oxidase (NOX is the major enzyme for the production of extracellular superoxide in microglia. ROS have been characterized as an important secondary messenger and modulator for various mammalian intracellular signaling pathways, including the MAPK pathways. In this study we examined ROS production and TNF-α, IL-1β inflammatory cytokines releasing, and the expression of MAPKs in BV-2 microglia cells treated with fluoride. We found that fluoride increased JNK phosphorylation level of BV-2 cells and pretreatment with JNK inhibitor SP600125 markedly reduced the levels of intracellular and NO. NOX inhibitor apocynin and iNOS inhibitor SMT dramatically decreased NaF-induced ROS and NO generations, respectively. Antioxidant melatonin (MEL resulted in a reduction in JNK phosphorylation in fluoride-stimulated BV-2 microglia. The results confirmed that NOX and iNOS played an important role in fluoride inducing oxidative stress and NO production and JNK took part in the oxidative stress induced by fluoride and meanwhile also could be activated by ROS in fluoride-treated BV-2 cells.

JNK and NADPH Oxidase Involved in Fluoride-Induced Oxidative Stress in BV-2 Microglia Cells

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Yan, Ling; Liu, Shengnan; Wang, Chen; Wang, Fei; Song, Yingli; Yan, Nan; Xi, Shuhua; Liu, Ziyou; Sun, Guifan

2013-01-01

Excessive fluoride may cause central nervous system (CNS) dysfunction, and oxidative stress is a recognized mode of action of fluoride toxicity. In CNS, activated microglial cells can release more reactive oxygen species (ROS), and NADPH oxidase (NOX) is the major enzyme for the production of extracellular superoxide in microglia. ROS have been characterized as an important secondary messenger and modulator for various mammalian intracellular signaling pathways, including the MAPK pathways. In this study we examined ROS production and TNF-α, IL-1β inflammatory cytokines releasing, and the expression of MAPKs in BV-2 microglia cells treated with fluoride. We found that fluoride increased JNK phosphorylation level of BV-2 cells and pretreatment with JNK inhibitor SP600125 markedly reduced the levels of intracellular O2 ·− and NO. NOX inhibitor apocynin and iNOS inhibitor SMT dramatically decreased NaF-induced ROS and NO generations, respectively. Antioxidant melatonin (MEL) resulted in a reduction in JNK phosphorylation in fluoride-stimulated BV-2 microglia. The results confirmed that NOX and iNOS played an important role in fluoride inducing oxidative stress and NO production and JNK took part in the oxidative stress induced by fluoride and meanwhile also could be activated by ROS in fluoride-treated BV-2 cells. PMID:24072958

Escherichia coli LF82 differentially regulates ROS production and mucin expression in intestinal epithelial T84 cells: implication of NOX1.

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Elatrech, Imen; Marzaioli, Viviana; Boukemara, Hanane; Bournier, Odile; Neut, Christel; Darfeuille-Michaud, Arlette; Luis, José; Dubuquoy, Laurent; El-Benna, Jamel; My-Chan Dang, Pham; Marie, Jean-Claude

2015-05-01

Increased reactive oxygen species (ROS) production is associated with inflamed ileal lesions in Crohn's disease colonized by pathogenic adherent-invasive Escherichia coli LF82. We investigated whether such ileal bacteria can modulate ROS production by epithelial cells, thus impacting on inflammation and mucin expression. Ileal bacteria from patients with Crohn's disease were incubated with cultured epithelial T84 cells, and ROS production was assayed using the luminol-amplified chemiluminescence method. The gentamicin protection assay was used for bacterial invasion of T84 cell. The expression of NADPH oxidase (NOX) subunits, mucin, and IL-8 was analyzed by quantitative real-time PCR and Western blots. Involvement of NOX and ROS was analyzed using diphenyleneiodonium (DPI) and N-acetylcysteine (NAC). Among different bacteria tested, only LF82 induced an increase of ROS production by T84 cells in a dose-dependent manner. This response was inhibited by DPI and NAC. Heat- or ethanol-attenuated LF82 bacteria and the mutant LF82ΔFimA, which does not express pili type 1 and poorly adheres to epithelial cells, did not induce the oxidative response. The LF82-induced oxidative response coincides with its invasion in T84 cells, and both processes were inhibited by DPI. Also, we observed an increased expression of NOX1 and NOXO1 in response to LF82 bacteria versus the mutant LF82ΔFimA. Furthermore, LF82 inhibited mucin gene expression (MUC2 and MUC5AC) in T84 cells while increasing the chemotactic IL-8 expression, both in a DPI-sensitive manner. Adherent-invasive E. coli LF82 induced ROS production by intestinal NADPH oxidase and altered mucin and IL-8 expression, leading to perpetuation of inflammatory lesions in Crohn's disease.

Improvement of exopolysaccharide production in Lactobacillus casei LC2W by overexpression of NADH oxidase gene.

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Li, Nan; Wang, Yuanlong; Zhu, Ping; Liu, Zhenmin; Guo, Benheng; Ren, Jing

2015-02-01

Lactobacillus casei LC2W is an exopolysaccharide (EPS)-producing strain with probiotic effects. To investigate the regulation mechanism of EPS biosynthesis and to improve EPS production through cofactor engineering, a H₂O-forming NADH oxidase gene was cloned from Streptococcus mutans and overexpressed in L. casei LC2W under the control of constitutive promoter P₂₃. The recombinant strain LC-nox exhibited 0.854 U/mL of NADH oxidase activity, which was elevated by almost 20-fold in comparison with that of wild-type strain. As a result, overexpression of NADH oxidase resulted in a reduction in growth rate. In addition, lactate production was decreased by 22% in recombinant strain. It was proposed that more carbon source was saved and used for the biosynthesis of EPS, the production of which was reached at 219.4 mg/L, increased by 46% compared to that of wild-type strain. This work provided a novel and convenient genetic approach to manipulate metabolic flux and to increase EPS production. To the best of our knowledge, this is the first report which correlates cofactor engineering with EPS production. Copyright © 2015 Elsevier GmbH. All rights reserved.

Characterization of the polyphenol oxidase gene family reveals a novel microRNA involved in posttranscriptional regulation of PPOs in Salvia miltiorrhiza

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Li, Caili; Li, Dongqiao; Li, Jiang; Shao, Fenjuan; Lu, Shanfa

2017-01-01

Salvia miltiorrhiza is a well-known material of traditional Chinese medicine. Understanding the regulatory mechanisms of phenolic acid biosynthesis and metabolism are important for S. miltiorrhiza quality improvement. We report here that S. miltiorrhiza contains 19 polyphenol oxidases (PPOs), forming the largest PPO gene family in plant species to our knowledge. Analysis of gene structures and sequence features revealed the conservation and divergence of SmPPOs. SmPPOs were differentially exp...

ULTRA LOW NOx INTEGRATED SYSTEM FOR NOx EMISSION CONTROL FROM COAL-FIRED BOILERS

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Galen H. Richards; Charles Q. Maney; Richard W. Borio; Robert D. Lewis

2002-12-30

ALSTOM Power Inc.'s Power Plant Laboratories, working in concert with ALSTOM Power's Performance Projects Group, has teamed with the U.S. Department of Energy's National Energy Technology Laboratory (DOE NETL) to conduct a comprehensive study to develop/evaluate low-cost, efficient NOx control technologies for retrofit to pulverized coal fired utility boilers. The objective of this project was to develop retrofit NOx control technology to achieve less than 0.15 lb/MMBtu NOx (for bituminous coals) and 0.10 lb/MMBtu NOx (for subbituminous coals) from existing pulverized coal fired utility boilers at a cost which is at least 25% less than SCR technology. Efficient control of NOx is seen as an important, enabling step in keeping coal as a viable part of the national energy mix in this century, and beyond. Presently 57% of U.S. electrical generation is coal based, and the Energy Information Agency projects that coal will maintain a lead in U.S. power generation over all other fuel sources for decades (EIA 1998 Energy Forecast). Yet, coal-based power is being strongly challenged by society's ever-increasing desire for an improved environment and the resultant improvement in health and safety. The needs of the electric-utility industry are to improve environmental performance, while simultaneously improving overall plant economics. This means that emissions control technology is needed with very low capital and operating costs. This project has responded to the industry's need for low NOx emissions by evaluating ideas that can be adapted to present pulverized coal fired systems, be they conventional or low NOx firing systems. The TFS 2000{trademark} firing system has been the ALSTOM Power Inc. commercial offering producing the lowest NOx emission levels. In this project, the TFS 2000{trademark} firing system served as a basis for comparison to other low NOx systems evaluated and was the foundation upon which refinements were made to further

NADPH oxidase 4-derived superoxide mediates flow-stimulated NKCC2 activity in thick ascending limbs.

Science.gov (United States)

Saez, Fara; Hong, Nancy J; Garvin, Jeffrey L

2018-05-01

Luminal flow augments Na + reabsorption in the thick ascending limb more than can be explained by increased ion delivery. This segment reabsorbs 30% of the filtered load of Na + , playing a key role in its homeostasis. Whether flow elevations enhance Na + -K + -2Cl - cotransporter (NKCC2) activity and the second messenger involved are unknown. We hypothesized that raising luminal flow augments NKCC2 activity by enhancing superoxide ([Formula: see text]) production by NADPH oxidase 4 (NOX4). NKCC2 activity was measured in thick ascending limbs perfused at either 5 or 20 nl/min with and without inhibitors of [Formula: see text] production. Raising luminal flow from 5 to 20 nl/min enhanced NKCC2 activity from 4.8 ± 0.9 to 6.3 ± 1.2 arbitrary fluorescent units (AFU)/s. Maintaining flow at 5 nl/min did not alter NKCC2 activity. The superoxide dismutase mimetic manganese (III) tetrakis (4-benzoic acid) porphyrin chloride blunted NKCC2 activity from 3.5 ± 0.4 to 2.5 ± 0.2 AFU/s when flow was 20 nl/min but not 5 nl/min. When flow was 20 nl/min, NKCC2 activity showed no change with time. The selective NOX1/4 inhibitor GKT-137831 blunted NKCC2 activity when thick ascending limbs were perfused at 20 nl/min from 7.2 ± 1.1 to 4.5 ± 0.8 AFU/s but not at 5 nl/min. The inhibitor also prevented luminal flow from elevating [Formula: see text] production. Allopurinol, a xanthine oxidase inhibitor, had no effect on NKCC2 activity when flow was 20 nl/min. Tetanus toxin prevents flow-induced stimulation of NKCC2 activity. We conclude that elevations in luminal flow enhance NaCl reabsorption in thick ascending limbs by stimulating NKCC2 via NOX4 activation and increased [Formula: see text]. NKCC2 activation is primarily the result of insertion of new transporters in the membrane.

Geraniol improves endothelial function by inhibiting NOX-2 derived oxidative stress in high fat diet fed mice

International Nuclear Information System (INIS)

Wang, Xiaoyu; Zhao, Shiqi; Su, Mengqi; Sun, Li; Zhang, Song; Wang, Dingyu; Liu, Zhaorui; Yuan, Yue; Liu, Yang; Li, Yue

2016-01-01

Endothelial dysfunction occurs in obese patients and high-fat diet (HFD) fed experimental animals. While geraniol has been reported to ameliorate inflammation and oxidative stress, inhibit tumor cell proliferation, and improve atherosclerosis, its direct effect on endothelial function remains uncharacterized. The present study therefore investigated the effect of geraniol on endothelial function in HFD mice and its underlying mechanisms. C57 BL/6 mice were fed an HFD (n = 40) or a normal diet (n = 20) for 8 weeks. HFD fed mice then were randomized to intraperitoneal treatment with geraniol (n = 20) or vehicle (n = 20) for another 6 weeks. Acetylcholine (Ach)-induced endothelial dependent vasorelaxation was measured on wire myography; reactive oxygen species (ROS) generation was assessed by fluorescence imaging, and NADPH oxidases (NOXs) and adhesive molecules VCAM-1 and ICAM-1 protein expression by western blotting. Geraniol improved endothelial function in HFD fed mice, as evidenced by its: 1. restoring endothelial dependent vasorelaxation induced by Ach, and reversing increased VCAM-1 and ICAM-1 expression; 2. attenuating HFD induced increased serum TBARS and aortic ROS generation; and 3. downregulating aortic NOX-2 expression in both HFD fed mice and in palmitic acid treated endothelial cells. Geraniol therefore protects against endothelial dysfunction induced by HFD through reducing NOX-2 associated ROS generation. -- Highlights: •Geraniol improved endothelial dependent relaxation in high fat diet fed mice. •Geraniol alleviated vascular injury in high fat diet fed mice. •Geraniol inhibited ROS generation through downregulating NOX-2 expression.

Geraniol improves endothelial function by inhibiting NOX-2 derived oxidative stress in high fat diet fed mice

Energy Technology Data Exchange (ETDEWEB)

Wang, Xiaoyu; Zhao, Shiqi; Su, Mengqi; Sun, Li; Zhang, Song; Wang, Dingyu; Liu, Zhaorui; Yuan, Yue; Liu, Yang [Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province (China); Li, Yue, E-mail: ly99ly@vip.163.com [Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province (China); Key Laboratory of Cardiac Diseases and Heart Failure, Harbin Medical University, Harbin, 150001, Heilongjiang Province (China)

2016-05-20

Endothelial dysfunction occurs in obese patients and high-fat diet (HFD) fed experimental animals. While geraniol has been reported to ameliorate inflammation and oxidative stress, inhibit tumor cell proliferation, and improve atherosclerosis, its direct effect on endothelial function remains uncharacterized. The present study therefore investigated the effect of geraniol on endothelial function in HFD mice and its underlying mechanisms. C57 BL/6 mice were fed an HFD (n = 40) or a normal diet (n = 20) for 8 weeks. HFD fed mice then were randomized to intraperitoneal treatment with geraniol (n = 20) or vehicle (n = 20) for another 6 weeks. Acetylcholine (Ach)-induced endothelial dependent vasorelaxation was measured on wire myography; reactive oxygen species (ROS) generation was assessed by fluorescence imaging, and NADPH oxidases (NOXs) and adhesive molecules VCAM-1 and ICAM-1 protein expression by western blotting. Geraniol improved endothelial function in HFD fed mice, as evidenced by its: 1. restoring endothelial dependent vasorelaxation induced by Ach, and reversing increased VCAM-1 and ICAM-1 expression; 2. attenuating HFD induced increased serum TBARS and aortic ROS generation; and 3. downregulating aortic NOX-2 expression in both HFD fed mice and in palmitic acid treated endothelial cells. Geraniol therefore protects against endothelial dysfunction induced by HFD through reducing NOX-2 associated ROS generation. -- Highlights: •Geraniol improved endothelial dependent relaxation in high fat diet fed mice. •Geraniol alleviated vascular injury in high fat diet fed mice. •Geraniol inhibited ROS generation through downregulating NOX-2 expression.

Formation of fuel NOx during black-liquor combustion

International Nuclear Information System (INIS)

Nichols, K.M.; Lien, S.J.

1993-01-01

Fuel NOx and thermal NOx were measured in combustion gases from black liquors in two laboratory furnaces. Combustion at 950 C in air (8% O 2 ) produced NOx concentrations of 40-80ppm. Combustion at 950 C in synthetic air containing no nitrogen (21% 0 2 in Ar) produced the same result, demonstrating that all of the NOx produced during combustion at 950 C was fuel NOx. Formation of fuel NOx increased moderately with increasing temperature in the range of 800-1,000 C, but temperature sensitivity of fuel NOx was much less than that of thermal NOx. The results imply that the major source of NOx in recovery furnace emissions is the fuel NOx in recovery furnace formed by conversion of liquor-bound nitrogen during combustion. This is consistent with thermal NOx theory, which postulates that black-liquor combustion temperatures are too low to generate significant amounts of thermal NOx

NADPH Oxidase Contributes to Photoreceptor Degeneration in Constitutively Active RAC1 Mice

Science.gov (United States)

Song, Hongman; Vijayasarathy, Camasamudram; Zeng, Yong; Marangoni, Dario; Bush, Ronald A.; Wu, Zhijian; Sieving, Paul A.

2016-01-01

Purpose The active form of small GTPase RAC1 is required for activation of NADPH oxidase (NOX), which in turn generates reactive oxygen species (ROS) in nonphagocytic cells. We explored whether NOX-induced oxidative stress contributes to rod degeneration in retinas expressing constitutively active (CA) RAC1. Methods Transgenic (Tg)–CA-RAC1 mice were given apocynin (10 mg/kg, intraperitoneal), a NOX inhibitor, or vehicle daily for up to 13 weeks. Superoxide production and oxidative damage were assessed by dihydroethidium staining and by protein carbonyls and malondialdehyde levels, respectively. Outer nuclear layer (ONL) cells were counted and electroretinogram (ERG) amplitudes measured in Tg-CA-RAC1 mice. Outer nuclear layer cells were counted in wild-type (WT) mice after transfer of CA-Rac1 gene by subretinal injection of AAV8-pOpsin-CA Rac1-GFP. Results Transgenic-CA-RAC1 retinas had significantly fewer photoreceptor cells and more apoptotic ONL cells than WT controls from postnatal week (Pw) 3 to Pw13. Superoxide accumulation and protein and lipid oxidation were increased in Tg-CA-RAC1 retinas and were reduced in mice treated with apocynin. Apocynin reduced the loss of photoreceptors and increased the rod ERG a- and b-wave amplitudes when compared with vehicle-injected transgenic controls. Photoreceptor loss was also observed in regions of adult WT retina transduced with AAV8-pOpsin-CA Rac1-GFP but not in neighboring regions that were not transduced or in AAV8-pOpsin-GFP–transduced retinas. Conclusions Constitutively active RAC1 promotes photoreceptor cell death by oxidative damage that occurs, at least partially, through NOX-induced ROS. Reactive oxygen species are likely involved in multiple forms of retinal degenerations, and our results support investigating RAC1 inhibition as a therapeutic approach that targets this disease pathway. PMID:27233035

Independently recruited oxidases from the glucose-methanol-choline oxidoreductase family enabled chemical defences in leaf beetle larvae (subtribe Chrysomelina) to evolve

Science.gov (United States)

Rahfeld, Peter; Kirsch, Roy; Kugel, Susann; Wielsch, Natalie; Stock, Magdalena; Groth, Marco; Boland, Wilhelm; Burse, Antje

2014-01-01

Larvae of the leaf beetle subtribe Chrysomelina sensu stricto repel their enemies by displaying glandular secretions that contain defensive compounds. These repellents can be produced either de novo (iridoids) or by using plant-derived precursors (e.g. salicylaldehyde). The autonomous production of iridoids, as in Phaedon cochleariae, is the ancestral chrysomeline chemical defence and predates the evolution of salicylaldehyde-based defence. Both biosynthesis strategies include an oxidative step of an alcohol intermediate. In salicylaldehyde-producing species, this step is catalysed by salicyl alcohol oxidases (SAOs) of the glucose-methanol-choline (GMC) oxidoreductase superfamily, but the enzyme oxidizing the iridoid precursor is unknown. Here, we show by in vitro as well as in vivo experiments that P. cochleariae also uses an oxidase from the GMC superfamily for defensive purposes. However, our phylogenetic analysis of chrysomeline GMC oxidoreductases revealed that the oxidase of the iridoid pathway originated from a GMC clade different from that of the SAOs. Thus, the evolution of a host-independent chemical defence followed by a shift to a host-dependent chemical defence in chrysomeline beetles coincided with the utilization of genes from different GMC subfamilies. These findings illustrate the importance of the GMC multi-gene family for adaptive processes in plant–insect interactions. PMID:24943369

Zinc regulates Nox1 expression through a NF-κB and mitochondrial ROS dependent mechanism to induce senescence of vascular smooth muscle cells.

Science.gov (United States)

Salazar, G; Huang, J; Feresin, R G; Zhao, Y; Griendling, K K

2017-07-01

The role of oxidative stress and inflammation in the development and progression of cardiovascular diseases (CVD) is well established. Increases in oxidative stress can further exacerbate the inflammatory response and lead to cellular senescence. We previously reported that angiotensin II (Ang II) and zinc increase reactive oxygen species (ROS) and cause senescence of vascular smooth muscle cells (VSMCs) and that senescence induced by Ang II is a zinc-dependent process. Zinc stimulated NADPH oxidase (Nox) activity; however, the role of Nox isoforms in zinc effects was not determined. Here, we show that downregulation of Nox1, but not Nox4, by siRNA prevented both Ang II- and zinc-induced senescence in VSMCs. On the other hand, overexpression of Nox1 induced senescence, which was associated with reduced proliferation, reduced expression of telomerase and increased DNA damage. Zinc increased Nox1 protein expression, which was inhibited by chelation of zinc with TPEN and by overexpression of the zinc exporters ZnT3 and ZnT10. These transporters work to reduce cytosolic zinc, suggesting that increased cytosolic zinc mediates Nox1 upregulation. Other metals including copper, iron, cobalt and manganese failed to upregulate Nox1, suggesting that this pathway is zinc specific. Nox1 upregulation was inhibited by actinomycin D (ACD), an inhibitor of transcription, by inhibition of NF-κB, a known Nox1 transcriptional regulator and by N-acetyl cysteine (NAC) and MitoTEMPO, suggesting that NF-κB and mitochondrial ROS mediate zinc effects. Supporting this idea, we found that zinc increased NF-κB activation in the cytosol, stimulated the translocation of the p65 subunit to the nucleus, and that zinc accumulated in mitochondria increasing mitochondrial ROS, measured using MitoSox. Further, zinc-induced senescence was reduced by inhibition of NF-κB or reduction of mitochondrial ROS with MitoTEMPO. NF-κB activity was also reduced by MitoTEMPO, suggesting that mitochondrial ROS

Apocynin: Chemical and Biophysical Properties of a NADPH Oxidase Inhibitor

Directory of Open Access Journals (Sweden)

Valdecir F. Ximenes

2013-03-01

Full Text Available Apocynin is the most employed inhibitor of NADPH oxidase (NOX, a multienzymatic complex capable of catalyzing the one-electron reduction of molecular oxygen to the superoxide anion. Despite controversies about its selectivity, apocynin has been used as one of the most promising drugs in experimental models of inflammatory and neurodegenerative diseases. Here, we aimed to study the chemical and biophysical properties of apocynin. The oxidation potential was determined by cyclic voltammetry (Epa = 0.76V, the hydrophobicity index was calculated (logP = 0.83 and the molar absorption coefficient was determined (e275nm = 1.1 × 104 M−1 cm−1. Apocynin was a weak free radical scavenger (as measured using the DPPH, peroxyl radical and nitric oxide assays when compared to protocatechuic acid, used here as a reference antioxidant. On the other hand, apocynin was more effective than protocatechuic acid as scavenger of the non-radical species hypochlorous acid. Apocynin reacted promptly with the non-radical reactive species H2O2 only in the presence of peroxidase. This finding is relevant, since it represents a new pathway for depleting H2O2 in cellular experimental models, besides the direct inhibition of NADPH oxidase. This could be relevant for its application as an inhibitor of NOX4, since this isoform produces H2O2 and not superoxide anion. The binding parameters calculated by fluorescence quenching showed that apocynin binds to human serum albumin (HSA with a binding affinity of 2.19 × 104 M−1. The association did not alter the secondary and tertiary structure of HSA, as verified by synchronous fluorescence and circular dichroism. The displacement of fluorescent probes suggested that apocynin binds to site I and site II of HSA. Considering the current biomedical applications of this phytochemical, the dissemination of these chemical and biophysical properties can be very helpful for scientists and physicians interested in the use of apocynin.

Stimulus-dependent regulation of the phagocyte NADPH oxidase by a VAV1, Rac1, and PAK1 signaling axis

DEFF Research Database (Denmark)

Roepstorff, Kirstine; Rasmussen, Izabela Zorawska; Sawada, Makoto

2008-01-01

dominant-positive mutants enhanced, whereas dominant-negative mutants inhibited, NADPH oxidase-mediated superoxide generation following formyl-methionyl-leucylphenylalanine or phorbol 12-myristate 13-acetate stimulation. Both Rac1 and the GTP exchange factor VAV1 were required as upstream signaling......The p21-activated kinase-1 (PAK1) is best known for its role in the regulation of cytoskeletal and transcriptional signaling pathways. We show here in the microglia cell line Ra2 that PAK1 regulates NADPH oxidase (NOX-2) activity in a stimulus-specific manner. Thus, conditional expression of PAK1...... proteins in the formyl-methionyl-leucyl-phenylalanine-induced activation of endogenous PAK1. In contrast, PAK1 mutants had no effect on superoxide generation downstream of FcgammaR signaling during phagocytosis of IgG-immune complexes. We further present evidence that the effect of PAK1 on the respiratory...

Final Environmental Assessment for the Military Family Housing Privatization Initiative

Science.gov (United States)

2006-09-01

Year 2005 through 2009: VOCE = .016 * Trips NOxE = .015 * Trips PM10E = .0022 * Trips COE = .262 * Trips Appendix A Additional Materials Final...Environmental Assessment Page A-39 Military Family Housing Privatization Initiative Robins Air Force Base, Georgia Year 2010 and beyond: VOCE ...yr) = VOCE * DPYII/2000 NOx (tons/yr) = NOxE * DPYII/2000 PM10 (tons/yr) = PM10E * DPYII/2000 CO (tons/yr) = COE * DPYII/2000 Where: Area of

The Role of NADPH Oxidase in the Inhibition of Trichophyton rubrum by 420-nm Intense Pulsed Light

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Hao Huang

2018-01-01

Full Text Available Objectives: To evaluate the effect of intense pulsed light (IPL on Trichophyton rubrum and investigate its mechanism of action.Methods: The viability of fungi treated with IPL alone and with IPL combined with an NADPH oxidase inhibitor (DPI pretreatment was determined by MTT assays. The reactive oxygen species (ROS were quantified with a DCFH-DA fluorescent probe. Malondialdehyde (MDA content and superoxide dismutase (SOD and glutathione peroxidase (GSH-Px activities were determined by commercial kits. The transcription of the Nox gene was quantified using quantitative real-time PCR (qRT-PCR analysis, and micromorphology was observed using scanning electron microscopy (SEM. In addition, fungal keratinase activity was detected by measuring dye release from keratin azure.Results: The growth declined with statistical significance after 6 h of treatment (P < 0.001. The ROS and MDA content increased after IPL treatment, whereas the SOD and GSH-Px activity decreased. Nox gene expression was upregulated, and the micromorphology was damaged. Keratinase activity decreased. Fungi that received DPI pretreatment exhibited contrasting outcomes.Conclusion: We found that 420-nm IPL significantly inhibited the growth and pathogenicity of T. rubrum in vitro. A suggested mechanism involves Nox as a factor that mediates 420-nm IPL-induced oxidative damage of T. rubrum.

Critical role of NADPH oxidase in neuronal oxidative damage and microglia activation following traumatic brain injury.

Directory of Open Access Journals (Sweden)

Quan-Guang Zhang

Full Text Available BACKGROUND: Oxidative stress is known to play an important role in the pathology of traumatic brain injury. Mitochondria are thought to be the major source of the damaging reactive oxygen species (ROS following TBI. However, recent work has revealed that the membrane, via the enzyme NADPH oxidase can also generate the superoxide radical (O(2(-, and thereby potentially contribute to the oxidative stress following TBI. The current study thus addressed the potential role of NADPH oxidase in TBI. METHODOLOGY/PRINCIPAL FINDINGS: The results revealed that NADPH oxidase activity in the cerebral cortex and hippocampal CA1 region increases rapidly following controlled cortical impact in male mice, with an early peak at 1 h, followed by a secondary peak from 24-96 h after TBI. In situ localization using oxidized hydroethidine and the neuronal marker, NeuN, revealed that the O(2(- induction occurred in neurons at 1 h after TBI. Pre- or post-treatment with the NADPH oxidase inhibitor, apocynin markedly inhibited microglial activation and oxidative stress damage. Apocynin also attenuated TBI-induction of the Alzheimer's disease proteins β-amyloid and amyloid precursor protein. Finally, both pre- and post-treatment of apocynin was also shown to induce significant neuroprotection against TBI. In addition, a NOX2-specific inhibitor, gp91ds-tat was also shown to exert neuroprotection against TBI. CONCLUSIONS/SIGNIFICANCE: As a whole, the study demonstrates that NADPH oxidase activity and superoxide production exhibit a biphasic elevation in the hippocampus and cortex following TBI, which contributes significantly to the pathology of TBI via mediation of oxidative stress damage, microglial activation, and AD protein induction in the brain following TBI.

NADPH oxidase-2 derived ROS dictates murine DC cytokine-mediated cell fate decisions during CD4 T helper-cell commitment.

Directory of Open Access Journals (Sweden)

Meghan A Jendrysik

Full Text Available NADPH oxidase-2 (Nox2/gp91(phox and p47(phox deficient mice are prone to hyper-inflammatory responses suggesting a paradoxical role for Nox2-derived reactive oxygen species (ROS as anti-inflammatory mediators. The molecular basis for this mode of control remains unclear. Here we demonstrate that IFNγ/LPS matured p47(phox-/--ROS deficient mouse dendritic cells (DC secrete more IL-12p70 than similarly treated wild type DC, and in an in vitro co-culture model IFNγ/LPS matured p47(phox-/- DC bias more ovalbumin-specific CD4(+ T lymphocytes toward a Th1 phenotype than wild type (WT DC through a ROS-dependent mechanism linking IL-12p70 expression to regulation of p38-MAPK activation. The Nox2-dependent ROS production in DC negatively regulates proinflammatory IL-12 expression in DC by constraining p38-MAPK activity. Increasing endogenous H(2O(2 attenuates p38-MAPK activity in IFNγ/LPS stimulated WT and p47(phox-/- DC, which suggests that endogenous Nox 2-derived ROS functions as a secondary messenger in the activated p38-MAPK signaling pathway during IL-12 expression. These findings indicate that ROS, generated endogenously by innate and adaptive immune cells, can function as important secondary messengers that can regulate cytokine production and immune cell cross-talk to control during the inflammatory response.

NOx reduction using biomass as reburning fuel

Energy Technology Data Exchange (ETDEWEB)

Niu Sheng-li; Lu Chun-mei; Gao Pan; Han Kui-hua; Geng Ping; Cheng Zhong-jie [Shandong University, Jinan (China). School of Energy and Power Engineering

2008-10-15

A series of experiments were conducted in a multiple-functional combustion test bed with several kinds of biomass as reburning fuel to reduce NOx. The character and experimental parameters are, emphasized to examine the influences on NOx reduction. The results show that biomass could get about 55% to 70% NOx reduction. Within a certain range of the parameters tested, NOx reduction increases with the increasing temperature of reburning zone and initial concentration of NOx and with decreasing excess air ratio and diameter of fuel particle. Under the same test conditions, cornstalk gets the highest NOx reduction and wheat straw, peanut shell, wood chip follow in turn. 14 refs., 7 figs., 1 tab.

The substrate oxidation mechanism of pyranose 2-oxidase and other related enzymes in the glucose-methanol-choline superfamily.

Science.gov (United States)

Wongnate, Thanyaporn; Chaiyen, Pimchai

2013-07-01

Enzymes in the glucose-methanol-choline (GMC) oxidoreductase superfamily catalyze the oxidation of an alcohol moiety to the corresponding aldehyde. In this review, the current understanding of the sugar oxidation mechanism in the reaction of pyranose 2-oxidase (P2O) is highlighted and compared with that of other enzymes in the GMC family for which structural and mechanistic information is available, including glucose oxidase, choline oxidase, cholesterol oxidase, cellobiose dehydrogenase, aryl-alcohol oxidase, and pyridoxine 4-oxidase. Other enzymes in the family that have been newly discovered or for which less information is available are also discussed. A large primary kinetic isotope effect was observed for the flavin reduction when 2-d-D-glucose was used as a substrate, but no solvent kinetic isotope effect was detected for the flavin reduction step. The reaction of P2O is consistent with a hydride transfer mechanism in which there is stepwise formation of d-glucose alkoxide prior to the hydride transfer. Site-directed mutagenesis of P2O and pH-dependence studies indicated that His548 is a catalytic base that facilitates the deprotonation of C2-OH in D-glucose. This finding agrees with the current mechanistic model for aryl-alcohol oxidase, glucose oxidase, cellobiose dehydrogenase, methanol oxidase, and pyridoxine 4-oxidase, but is different from that of cholesterol oxidase and choline oxidase. Although all of the GMC enzymes share similar structural folding and use the hydride transfer mechanism for flavin reduction, they appear to have subtle differences in the fine-tuned details of how they catalyze substrate oxidation. © 2013 The Authors Journal compilation © 2013 FEBS.

Erv2p: characterization of the redox behavior of a yeast sulfhydryl oxidase

DEFF Research Database (Denmark)

Wang, Wenzhong; Winther, Jakob R; Thorpe, Colin

2007-01-01

centers that facilitate the transfer of reducing equivalents from the dithiol substrates of these oxidases to the isoalloxazine ring where the reaction with molecular oxygen occurs. The present study examines yeast Erv2p and compares the redox behavior of this ER luminal protein with the augmenter...... and with unfolded proteins. Rapid reaction studies confirm that reduction of the flavin center of Erv2p is rate-limiting during turnover with molecular oxygen. This comparison of the redox properties between members of the ERV/ALR family of sulfhydryl oxidases provides insights into their likely roles in oxidative......The FAD prosthetic group of the ERV/ALR family of sulfhydryl oxidases is housed at the mouth of a 4-helix bundle and communicates with a pair of juxtaposed cysteine residues that form the proximal redox active disulfide. Most of these enzymes have one or more additional distal disulfide redox...

Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis.

Science.gov (United States)

Peleli, Maria; Al-Mashhadi, Ammar; Yang, Ting; Larsson, Erik; Wåhlin, Nils; Jensen, Boye L; G Persson, A Erik; Carlström, Mattias

2016-01-01

Hydronephrosis is associated with the development of salt-sensitive hypertension. Studies have suggested that increased sympathetic nerve activity and oxidative stress play important roles in hypertension and the modulation of salt sensitivity. The present study primarily aimed to examine the role of renal sympathetic nerve activity in the development of hypertension in rats with hydronephrosis. In addition, we aimed to investigate if NADPH oxidase (NOX) function could be affected by renal denervation. Partial unilateral ureteral obstruction (PUUO) was created in 3-wk-old rats to induce hydronephrosis. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high-, and low-salt diets. The renal excretion pattern, NOX activity, and expression as well as components of the renin-angiotensin-aldosterone system were characterized after treatment with the normal salt diet. On the normal salt diet, rats in the PUUO group had elevated blood pressure compared with control rats (115 ± 3 vs. 87 ± 1 mmHg, P < 0.05) and displayed increased urine production and lower urine osmolality. The blood pressure change in response to salt loading (salt sensitivity) was more pronounced in the PUUO group compared with the control group (15 ± 2 vs. 5 ± 1 mmHg, P < 0.05). Renal denervation in PUUO rats attenuated both hypertension (97 ± 3 mmHg) and salt sensitivity (5 ± 1 mmHg, P < 0.05) and normalized the renal excretion pattern, whereas the degree of renal fibrosis and inflammation was not changed. NOX activity and expression as well as renin and ANG II type 1A receptor expression were increased in the renal cortex from PUUO rats and normalized by denervation. Plasma Na(+) and K(+) levels were elevated in PUUO rats and normalized after renal denervation. Finally, denervation in PUUO rats was also associated with reduced NOX expression, superoxide production, and fibrosis in the heart. In conclusion, renal denervation attenuates

NOx trade. Case studies

International Nuclear Information System (INIS)

Jantzen, J.

2002-01-01

Some of the questions with respect to the trade of nitrogen oxides that businesses in the Netherlands have to deal with are dealt with: should a business buy or sell rights for NOx emission; which measures must be taken to reduce NOx emission; how much must be invested; and how to deal with uncertainties with regard to prices. Simulations were carried out with the MOSES model to find the answers to those questions. Results of some case studies are presented, focusing on the chemical sector in the Netherlands. Finally, the financial (dis)advantages of NOx trade and the related uncertainties for a single enterprise are discussed [nl

The polyphenol oxidase gene family in land plants: Lineage-specific duplication and expansion

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Tran Lan T

2012-08-01

Full Text Available Abstract Background Plant polyphenol oxidases (PPOs are enzymes that typically use molecular oxygen to oxidize ortho-diphenols to ortho-quinones. These commonly cause browning reactions following tissue damage, and may be important in plant defense. Some PPOs function as hydroxylases or in cross-linking reactions, but in most plants their physiological roles are not known. To better understand the importance of PPOs in the plant kingdom, we surveyed PPO gene families in 25 sequenced genomes from chlorophytes, bryophytes, lycophytes, and flowering plants. The PPO genes were then analyzed in silico for gene structure, phylogenetic relationships, and targeting signals. Results Many previously uncharacterized PPO genes were uncovered. The moss, Physcomitrella patens, contained 13 PPO genes and Selaginella moellendorffii (spike moss and Glycine max (soybean each had 11 genes. Populus trichocarpa (poplar contained a highly diversified gene family with 11 PPO genes, but several flowering plants had only a single PPO gene. By contrast, no PPO-like sequences were identified in several chlorophyte (green algae genomes or Arabidopsis (A. lyrata and A. thaliana. We found that many PPOs contained one or two introns often near the 3’ terminus. Furthermore, N-terminal amino acid sequence analysis using ChloroP and TargetP 1.1 predicted that several putative PPOs are synthesized via the secretory pathway, a unique finding as most PPOs are predicted to be chloroplast proteins. Phylogenetic reconstruction of these sequences revealed that large PPO gene repertoires in some species are mostly a consequence of independent bursts of gene duplication, while the lineage leading to Arabidopsis must have lost all PPO genes. Conclusion Our survey identified PPOs in gene families of varying sizes in all land plants except in the genus Arabidopsis. While we found variation in intron numbers and positions, overall PPO gene structure is congruent with the phylogenetic

Extra virgin olive oil rich in polyphenols modulates VEGF-induced angiogenic responses by preventing NADPH oxidase activity and expression.

Science.gov (United States)

Calabriso, Nadia; Massaro, Marika; Scoditti, Egeria; D'Amore, Simona; Gnoni, Antonio; Pellegrino, Mariangela; Storelli, Carlo; De Caterina, Raffaele; Palasciano, Giuseppe; Carluccio, Maria Annunziata

2016-02-01

Previous studies have shown the antiinflammatory, antioxidant and antiangiogenic properties by pure olive oil polyphenols; however, the effects of olive oil phenolic fraction on the inflammatory angiogenesis are unknown. In this study, we investigated the effects of the phenolic fraction (olive oil polyphenolic extract, OOPE) from extra virgin olive oil and related circulating metabolites on the VEGF-induced angiogenic responses and NADPH oxidase activity and expression in human cultured endothelial cells. We found that OOPE (1-10 μg/ml), at concentrations achievable nutritionally, significantly reduced, in a concentration-dependent manner, the VEGF-induced cell migration, invasiveness and tube-like structure formation through the inhibition of MMP-2 and MMP-9. OOPE significantly (Pextra virgin olive oil, with high polyphenol content, decreased VEGF-induced NADPH oxidase activity and Nox4 expression, as well as, MMP-9 expression, as compared with fasting control serum. Overall, native polyphenols and serum metabolites of extra virgin olive oil rich in polyphenols are able to lower the VEGF-induced angiogenic responses by preventing endothelial NADPH oxidase activity and decreasing the expression of selective NADPH oxidase subunits. Our results provide an alternative mechanism by which the consumption of olive oil rich in polyphenols may account for a reduction of oxidative stress inflammatory-related sequelae associated with chronic degenerative diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Lysyl Oxidase and the Tumor Microenvironment

Directory of Open Access Journals (Sweden)

Tong-Hong Wang

2016-12-01

Full Text Available The lysyl oxidase (LOX family of oxidases contains a group of extracellular copper-dependent enzymes that catalyze the cross-linking of collagen and elastin by oxidation, thus maintaining the rigidity and structural stability of the extracellular matrix (ECM. Aberrant expression or activation of LOX alters the cellular microenvironment, leading to many diseases, including atherosclerosis, tissue fibrosis, and cancer. Recently, a number of studies have shown that LOX is overexpressed in most cancers and that it is involved in the regulation of tumor progression and metastasis. In contrast, a few reports have also indicated the tumor-suppressing role of LOX. In this short review, we discuss recent research on the correlations between LOX and cancer. Further, the role of LOX in tumor microenvironment remodeling, tumorigenesis, and metastasis and the underlying mechanisms have also been elucidated.

Construction of mutant glucose oxidases with increased dye-mediated dehydrogenase activity.

Science.gov (United States)

Horaguchi, Yohei; Saito, Shoko; Kojima, Katsuhiro; Tsugawa, Wakako; Ferri, Stefano; Sode, Koji

2012-11-02

Mutagenesis studies on glucose oxidases (GOxs) were conducted to construct GOxs with reduced oxidase activity and increased dehydrogenase activity. We focused on two representative GOxs, of which crystal structures have already been reported—Penicillium amagasakiense GOx (PDB ID; 1gpe) and Aspergillus niger GOx (PDB ID; 1cf3). We constructed oxygen-interacting structural models for GOxs, and predicted the residues responsible for oxidative half reaction with oxygen on the basis of the crystal structure of cholesterol oxidase as well as on the fact that both enzymes are members of the glucose/methanol/choline (GMC) oxidoreductase family. Rational amino acid substitution resulted in the construction of an engineered GOx with drastically decreased oxidase activity and increased dehydrogenase activity, which was higher than that of the wild-type enzyme. As a result, the dehydrogenase/oxidase ratio of the engineered enzyme was more than 11-fold greater than that of the wild-type enzyme. These results indicate that alteration of the dehydrogenase/oxidase activity ratio of GOxs is possible by introducing a mutation into the putative functional residues responsible for oxidative half reaction with oxygen of these enzymes, resulting in a further increased dehydrogenase activity. This is the first study reporting the alteration of GOx electron acceptor preference from oxygen to an artificial electron acceptor.

Construction of Mutant Glucose Oxidases with Increased Dye-Mediated Dehydrogenase Activity

Science.gov (United States)

Horaguchi, Yohei; Saito, Shoko; Kojima, Katsuhiro; Tsugawa, Wakako; Ferri, Stefano; Sode, Koji

2012-01-01

Mutagenesis studies on glucose oxidases (GOxs) were conducted to construct GOxs with reduced oxidase activity and increased dehydrogenase activity. We focused on two representative GOxs, of which crystal structures have already been reported—Penicillium amagasakiense GOx (PDB ID; 1gpe) and Aspergillus niger GOx (PDB ID; 1cf3). We constructed oxygen-interacting structural models for GOxs, and predicted the residues responsible for oxidative half reaction with oxygen on the basis of the crystal structure of cholesterol oxidase as well as on the fact that both enzymes are members of the glucose/methanol/choline (GMC) oxidoreductase family. Rational amino acid substitution resulted in the construction of an engineered GOx with drastically decreased oxidase activity and increased dehydrogenase activity, which was higher than that of the wild-type enzyme. As a result, the dehydrogenase/oxidase ratio of the engineered enzyme was more than 11-fold greater than that of the wild-type enzyme. These results indicate that alteration of the dehydrogenase/oxidase activity ratio of GOxs is possible by introducing a mutation into the putative functional residues responsible for oxidative half reaction with oxygen of these enzymes, resulting in a further increased dehydrogenase activity. This is the first study reporting the alteration of GOx electron acceptor preference from oxygen to an artificial electron acceptor. PMID:23203056

Impaired compensation to femoral artery ligation in diet-induced obese mice is primarily mediated via suppression of collateral growth by Nox2 and p47phox.

Science.gov (United States)

DiStasi, Matthew R; Mund, Julie A; Bohlen, H Glenn; Miller, Steven J; Ingram, David A; Dalsing, Michael C; Unthank, Joseph L

2015-10-01

The present study was undertaken to establish the role of NADPH oxidase (Nox) in impaired vascular compensation to arterial occlusion that occurs in the presence of risk factors associated with oxidative stress. Diet-induced obese (DIO) mice characterized by multiple comorbidities including diabetes and hyperlipidemia were used as a preclinical model. Arterial occlusion was induced by distal femoral artery ligation in lean and DIO mice. Proximal collateral arteries were identified as the site of major (∼70%) vascular resistance to calf perfusion by distal arterial pressures, which decreased from ∼80 to ∼30 mmHg with ligation in both lean and DIO mice. Two weeks after ligation, significant vascular compensation occurred in lean but not DIO mice as evidenced by increased perfusion (147 ± 48% vs. 49 ± 29%) and collateral diameter (151 ± 30% vs. 44 ± 17%). Vascular mRNA expression of p22(phox), Nox2, Nox4, and p47(phox) were all increased in DIO mice. Treatment of DIO mice with either apocynin or Nox2ds-tat or with whole body ablation of either Nox2 or p47(phox) ameliorated the impairment in both collateral growth and hindlimb perfusion. Multiparametric flow cytometry analysis demonstrated elevated levels of circulating monocytes in DIO mice without impaired mobilization and demargination after femoral artery ligation. These results establish collateral resistance as the major limitation to calf perfusion in this preclinical model, demonstrate than monocyte mobilization and demarginatin is not suppressed, implicate Nox2-p47(phox) interactions in the impairment of vascular compensation to arterial occlusion in DIO mice, and suggest that selective Nox component suppression/inhibition may be effective as either primary or adjuvant therapy for claudicants. Copyright © 2015 the American Physiological Society.

Native Alanine Substitution in the Glycine Hinge Modulates Conformational Flexibility of Heme Nitric Oxide/Oxygen (H-NOX) Sensing Proteins.

Science.gov (United States)

Hespen, Charles W; Bruegger, Joel J; Guo, Yirui; Marletta, Michael A

2018-06-15

Heme nitric oxide/oxygen sensing (H-NOX) domains are direct NO sensors that regulate a variety of biological functions in both bacteria and eukaryotes. Previous work on H-NOX proteins has shown that upon NO binding, a conformational change occurs along two glycine residues on adjacent helices (termed the glycine hinge). Despite the apparent importance of the glycine hinge, it is not fully conserved in all H-NOX domains. Several H-NOX sensors from the family Flavobacteriaceae contain a native alanine substitution in one of the hinge residues. In this work, the effect of the increased steric bulk within the Ala-Gly hinge on H-NOX function was investigated. The hinge in Kordia algicida OT-1 ( Ka H-NOX) is composed of A71 and G145. Ligand-binding properties and signaling function for this H-NOX were characterized. The variant A71G was designed to convert the hinge region of Ka H-NOX to the typical Gly-Gly motif. In activity assays with its cognate histidine kinase (HnoK), the wild type displayed increased signal specificity compared to A71G. Increasing titrations of unliganded A71G gradually inhibits HnoK autophosphorylation, while increasing titrations of unliganded wild type H-NOX does not inhibit HnoK. Crystal structures of both wild type and A71G Ka H-NOX were solved to 1.9 and 1.6 Å, respectively. Regions of H-NOX domains previously identified as involved in protein-protein interactions with HnoK display significantly higher b-factors in A71G compared to wild-type H-NOX. Both biochemical and structural data indicate that the hinge region controls overall conformational flexibility of the H-NOX, affecting NO complex formation and regulation of its HnoK.

Characterization of NOx emission in the suburbs of Tokyo based on simultaneous and real-time observations of atmospheric Ox and NOx

Science.gov (United States)

Matsumoto, J.

2013-12-01

Nitrogen oxides, NOx (NO, NO2), and volatile organic compounds, VOCs, are important as precursors of photochemical oxidants (tropospheric ozone, O3). To predict and control photochemical oxidants, NOx emission should be captured precisely. In addition, the ratio of NO2/NOx in the exhaust gas is also important as the initial balance between NO and NO2 in the atmosphere. Monitoring the NO2/NOx ratio in the exhaust gases is essential. Especially, the influence of the NOx emission on the real atmosphere should be explored. However, conversion reactions among NO, NO2 and O3 are typically in the time scale of minutes. The NO2/NOx ratio can change rapidly just after emission. Real-time observations of these compounds in the second time scale are essential. In view of photochemical oxidant, near emission sources of NO, ozone concentration can be easily perturbed by reaction with locally emitted NO. As an index of oxidant, the sum of O3 and NO2 (Ox = O3 + NO2) is useful. In this study, a simultaneous and real-time analyzer of atmospheric Ox and NOx has been developed utilizing the dual NO2 detectors based on laser-induced fluorescence technique (LIF), and characterization of NOx emission was explored through the observations of Ox and NOx in the suburbs of Tokyo. The dual LIF detectors consisted of one laser head, two LIF cells, and one common vacuum pump. As the Ox monitor, the excess NO was added to the sample and O3 was converted to NO2, and then the sum of O3 and NO2 in the sample was quantified at the 1st LIF cell. As the NOx monitor, the excess O3 was added to the sample and NO was converted to NO2, and then the sum of NO and NO2 in the sample was quantified at the 2nd LIF cell. Both the ';Ox' and ';NOx' channels in the dual LIF analyzer were simultaneously monitoring Ox and NOx in the sample air, respectively. The temporal resolution of observed data was 1 s. Typical conversion efficiencies of O3 and NO to NO2 were more than 0.98. The lower detection limits were 0

Hydrogen sulfide inhibits high glucose-induced NADPH oxidase 4 expression and matrix increase by recruiting inducible nitric oxide synthase in kidney proximal tubular epithelial cells.

Science.gov (United States)

Lee, Hak Joo; Lee, Doug Yoon; Mariappan, Meenalakshmi M; Feliers, Denis; Ghosh-Choudhury, Goutam; Abboud, Hanna E; Gorin, Yves; Kasinath, Balakuntalam S

2017-04-07

High-glucose increases NADPH oxidase 4 (NOX4) expression, reactive oxygen species generation, and matrix protein synthesis by inhibiting AMP-activated protein kinase (AMPK) in renal cells. Because hydrogen sulfide (H 2 S) inhibits high glucose-induced matrix protein increase by activating AMPK in renal cells, we examined whether H 2 S inhibits high glucose-induced expression of NOX4 and matrix protein and whether H 2 S and NO pathways are integrated. High glucose increased NOX4 expression and activity at 24 h in renal proximal tubular epithelial cells, which was inhibited by sodium hydrosulfide (NaHS), a source of H 2 S. High glucose decreased AMPK phosphorylation and activity, which was restored by NaHS. Compound C, an AMPK inhibitor, prevented NaHS inhibition of high glucose-induced NOX4 expression. NaHS inhibition of high glucose-induced NOX4 expression was abrogated by N (ω)-nitro-l-arginine methyl ester, an inhibitor of NOS. NaHS unexpectedly augmented the expression of inducible NOS (iNOS) but not endothelial NOS. iNOS siRNA and 1400W, a selective iNOS inhibitor, abolished the ameliorative effects of NaHS on high glucose-induced NOX4 expression, reactive oxygen species generation, and, matrix laminin expression. Thus, H 2 S recruits iNOS to generate NO to inhibit high glucose-induced NOX4 expression, oxidative stress, and matrix protein accumulation in renal epithelial cells; the two gasotransmitters H 2 S and NO and their interaction may serve as therapeutic targets in diabetic kidney disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Effects of NOX Storage Component on Ammonia Formation in TWC for Passive SCR NOX Control in Lean Gasoline Engines

Energy Technology Data Exchange (ETDEWEB)

Prikhodko, Vitaly Y. [ORNL; Pihl, Josh A. [ORNL; Toops, Todd J. [ORNL; Parks, II, James E. [ORNL

2018-04-01

A prototype three-way catalyst (TWC) with NOX storage component was evaluated for ammonia (NH3) generation on a 2.0-liter BMW lean burn gasoline direct injection engine as a component in a passive ammonia selective catalytic reduction (SCR) system. The passive NH3 SCR system is a potential approach for controlling nitrogen oxides (NOX) emissions from lean burn gasoline engines. In this system, NH3 is generated over a close-coupled TWC during periodic slightly-rich engine operation and subsequently stored on an underfloor SCR catalyst. Upon switching to lean, NOX passes through the TWC and is reduced by the stored NH3 on the SCR catalyst. Adding a NOX storage component to a TWC provides two benefits in the context of a passive SCR system: (1) enabling longer lean operation by storing NOX upstream and preserving NH3 inventory on the downstream SCR catalyst; and (2) increasing the quantity and rate of NH3 production during rich operation. Since the fuel penalty associated with passive SCR NOX control depends on the fraction of time that the engine is running rich rather than lean, both benefits (longer lean times and shorter rich times achieved via improved NH3 production) will decrease the passive SCR fuel penalty. However, these benefits are primarily realized at low to moderate temperatures (300-500 °C), where the NOX storage component is able to store NOX, with little to no benefit at higher temperatures (>500 °C), where NOX storage is no longer effective. This study discusses engine parameters and control strategies affecting the NH3 generation over a TWC with NOX storage component.

Commercial introduction of the Advanced NOxTECH system

Energy Technology Data Exchange (ETDEWEB)

Sudduth, B.C. [NOxTECH, Inc., Irvine, CA (United States)

1997-12-31

NOxTECH is BACT for diesel electric generators. Emissions of NO{sub x} are reduced 95% or more with substantial concurrent reductions in CO, particulates, and ROG`s. No engine modifications or other exhaust aftertreatments can remove all criteria pollutants as effectively as NOxTECH. The NOxTECH system reliably maintains NH{sub 3} slip below 2 ppm. Unlike other emissions controls, NOxTECH does not generate hazardous by-products. The Advanced NOxTECH system reduces the size, weight, and cost for BACT emissions reductions. Based on the operation of a 150 kW prototype, NOxTECH, Inc. is quoting commercial units for diesel electric generators. Advanced NOxTECH equipment costs about half as much as SCR systems, and NO{sub x} reduction can exceed 95% with guarantees for emissions compliance.

Myocardin-related transcription factor regulates Nox4 protein expression

DEFF Research Database (Denmark)

Rozycki, Matthew; Bialik, Janne Folke; Speight, Pam

2016-01-01

translocation of MRTF. Because the Nox4 promoter harbors a serum response factor/MRTF cis-element (CC(A/T)6GG box), we asked if MRTF (and thus cytoskeleton organization) could regulate Nox4 expression. We show that Nox4 protein is robustly induced in kidney tubular cells exclusively by combined application...... TGFβ/contact disruption-provoked Nox4 protein and mRNA expression, Nox4 promoter activation, and reactive oxygen species production. Mutation of the CC(A/T)6GG box eliminates the synergistic activation of the Nox4 promoter. Jasplakinolide-induced actin polymerization synergizes with TGFβ to facilitate...... MRTF-dependent Nox4 mRNA expression/promoter activation. Moreover, MRTF inhibition prevents Nox4 expression during TGFβ-induced fibroblast-myofibroblast transition as well. Although necessary, MRTF is insufficient; Nox4 expression also requires TGFβ-activated Smad3 and TAZ/YAP, two contact...

fMLP-Induced IL-8 Release Is Dependent on NADPH Oxidase in Human Neutrophils

Directory of Open Access Journals (Sweden)

María A. Hidalgo

2015-01-01

Full Text Available N-Formyl-methionyl-leucyl-phenylalanine (fMLP and platelet-activating factor (PAF induce similar intracellular signalling profiles; but only fMLP induces interleukin-8 (IL-8 release and nicotinamide adenine dinucleotide phosphate reduced (NADPH oxidase activity in neutrophils. Because the role of ROS on IL-8 release in neutrophils is until now controversial, we assessed if NADPH oxidase is involved in the IL-8 secretions and PI3K/Akt, MAPK, and NF-κB pathways activity induced by fMLP. Neutrophils were obtained from healthy volunteers. IL-8 was measured by ELISA, IL-8 mRNA by qPCR, and ROS production by luminol-amplified chemiluminescence, reduction of ferricytochrome c, and FACS. Intracellular pH changes were detected by spectrofluorescence. ERK1/2, p38 MAPK, and Akt phosphorylation were analysed by immunoblotting and NF-κB was analysed by immunocytochemistry. Hydroxy-3-methoxyaceto-phenone (HMAP, diphenyleneiodonium (DPI, and siRNA Nox2 reduced the ROS and IL-8 release in neutrophils treated with fMLP. HMAP, DPI, and amiloride (a Na+/H+ exchanger inhibitor inhibited the Akt phosphorylation and did not affect the p38 MAPK and ERK1/2 activity. DPI and HMAP reduced NF-κB translocation induced by fMLP. We showed that IL-8 release induced by fMLP is dependent on NADPH oxidase, and ROS could play a redundant role in cell signalling, ultimately activating the PI3K/Akt and NF-κB pathways in neutrophils.

Lysyl oxidases regulate fibrillar collagen remodelling in idiopathic pulmonary fibrosis

NARCIS (Netherlands)

Tjin, Gavin; White, Eric S; Faiz, Alen; Sicard, Delphine; Tschumperlin, Daniel J; Mahar, Annabelle; Kable, Eleanor P W; Burgess, Janette K

2017-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the lung with feweffective therapeutic options. Structural remodelling of the extracellular matrix [i.e. collagen cross-linkingmediated by the lysyl oxidase (LO) family of enzymes (LOX, LOXL1-4)] might contribute to disease

NOx from cement production - reduction by primary measures

DEFF Research Database (Denmark)

Jensen, Lars Skaarup

1999-01-01

cement production processes cement is typically produced by thermally treating a mixture of limestone and clay minerals in kiln systems consisting of a rotary kiln and a calciner. Clinker burning at a temperature of about 1450 °C takes place in the internally fired rotary kiln and calcination, which...... rotary kilns, while NOx formation from fuel-N and reduction of NOx take place in calciners. NOx formation in the rotary kiln is mainly governed by the necessary clinker burning temperature and is not very amenable to control, while net NOx formation in calciners depends strongly on calciner design......, calciner operation, fuel properties and on the NOx level from the rotary kiln. The low-NOx calciner types presently marketed are based on combinations of reburning, air staging and temperature control and seem equivalent in their ability to restrict NOx formation. If fuels with a significant volatile...

Construction of Mutant Glucose Oxidases with Increased Dye-Mediated Dehydrogenase Activity

Directory of Open Access Journals (Sweden)

Koji Sode

2012-11-01

Full Text Available Mutagenesis studies on glucose oxidases (GOxs were conducted to construct GOxs with reduced oxidase activity and increased dehydrogenase activity. We focused on two representative GOxs, of which crystal structures have already been reported—Penicillium amagasakiense GOx (PDB ID; 1gpe and Aspergillus niger GOx (PDB ID; 1cf3. We constructed oxygen-interacting structural models for GOxs, and predicted the residues responsible for oxidative half reaction with oxygen on the basis of the crystal structure of cholesterol oxidase as well as on the fact that both enzymes are members of the glucose/methanol/choline (GMC oxidoreductase family. Rational amino acid substitution resulted in the construction of an engineered GOx with drastically decreased oxidase activity and increased dehydrogenase activity, which was higher than that of the wild-type enzyme. As a result, the dehydrogenase/oxidase ratio of the engineered enzyme was more than 11-fold greater than that of the wild-type enzyme. These results indicate that alteration of the dehydrogenase/oxidase activity ratio of GOxs is possible by introducing a mutation into the putative functional residues responsible for oxidative half reaction with oxygen of these enzymes, resulting in a further increased dehydrogenase activity. This is the first study reporting the alteration of GOx electron acceptor preference from oxygen to an artificial electron acceptor.

Numerical simulation of flow in De-NOx catalyst honeycomb with NOx reduction reaction

Energy Technology Data Exchange (ETDEWEB)

Tanno, K.; Makino, H. [Electric Power Industry, Kanagawa (Japan). Energy Engineering Research Lab.; Kurose, R.; Komori, S. [Kyoto Univ. (Japan). Dept. of Mechanical Engineering and Science

2013-07-01

The effect of flow behavior in a De-NOx honeycomb with NOx reduction reaction is investigated by direct numerical simulation (DNS). As the inlet flow, fully developed turbulent or laminar flow is given. The results show that the surface reaction is strongly affected by inner flow behavior. The surface reaction rate for the turbulent flow is higher than that for the laminar flow. This is due to the difference of inner flow behavior that the diffusion of NOx in the vicinity of the wall is dominated only by molecular diffusion for the laminar flow, whereas it is enhanced by turbulent motions for the turbulent flow. Moreover, surface reaction is suppressed towards downstream even though inlet flow is turbulent. This is due to the flow transition from turbulent to laminar.

Delphinidin prevents high glucose-induced cell proliferation and collagen synthesis by inhibition of NOX-1 and mitochondrial superoxide in mesangial cells

Directory of Open Access Journals (Sweden)

Seung Eun Song

2016-04-01

Full Text Available This study examined the effect of delphinidin on high glucose-induced cell proliferation and collagen synthesis in mesangial cells. Glucose dose-dependently (5.6–25 mM increased cell proliferation and collagen I and IV mRNA levels, whereas pretreatment with delphinidin (50 μM prevented cell proliferation and the increased collagen mRNA levels induced by high glucose (25 mM. High glucose increased reactive oxygen species (ROS generation, and this was suppressed by pretreating delphinidin or the antioxidant N-acetyl cysteine. NADPH oxidase (NOX 1 was upregulated by high glucose, but pretreatment with delphinidin abrogated this upregulation. Increased mitochondrial superoxide by 25 mM glucose was also suppressed by delphinidin. The NOX inhibitor apocynin and mitochondria-targeted antioxidant Mito TEMPO inhibited ROS generation and cell proliferation induced by high glucose. Phosphorylation of extracellular signal regulated kinase (ERK1/2 was increased by high glucose, which was suppressed by delphinidin, apocynin or Mito TEMPO. Furthermore, PD98059 (an ERK1/2 inhibitor prevented the high glucose-induced cell proliferation and increased collagen mRNA levels. Transforming growth factor (TGF-β protein levels were elevated by high glucose, and pretreatment with delphinidin or PD98059 prevented this augmentation. These results suggest that delphinidin prevents high glucose-induced cell proliferation and collagen synthesis by inhibition of NOX-1 and mitochondrial superoxide in mesangial cells.

Microvascular Endothelial Dysfunction in Sedentary, Obese Humans is mediated by NADPH Oxidase; Influence of Exercise Training

Science.gov (United States)

La Favor, Justin D.; Dubis, Gabriel S.; Yan, Huimin; White, Joseph D.; Nelson, Margaret A.M.; Anderson, Ethan J.; Hickner, Robert C.

2016-01-01

Objective The objectives of this study were to determine the impact of in vivo reactive oxygen species (ROS) on microvascular endothelial function in obese human subjects and to determine the efficacy of an aerobic exercise intervention on alleviating obesity-associated dysfunctionality. Approach and Results Young, sedentary men and women were divided into lean (BMI 18–25; n=14), intermediate (BMI 28–32.5; n=13), and obese (BMI 33–40; n=15) groups. A novel microdialysis technique was utilized to detect elevated interstitial hydrogen peroxide (H2O2) and superoxide levels in the vastus lateralis of obese compared to both lean and intermediate subjects. Nutritive blood flow was monitored in the vastus lateralis via the microdialysis-ethanol technique. A decrement in acetylcholine-stimulated blood flow revealed impaired microvascular endothelial function in the obese subjects. Perfusion of apocynin, an NADPH oxidase (Nox) inhibitor, lowered (normalized) H2O2 and superoxide levels and reversed microvascular endothelial dysfunction in obese subjects. Following 8-weeks of exercise, H2O2 levels were decreased in the obese subjects and microvascular endothelial function in these subjects was restored to levels similar to lean subjects. Skeletal muscle protein expression of the Nox subunits p22phox, p47phox, and p67phox were increased in obese relative to lean subjects, where p22phox and p67phox expression was attenuated by exercise training in obese subjects. Conclusions This study implicates Nox as a source of excessive ROS production in skeletal muscle of obese individuals, and links excessive Nox derived ROS to microvascular endothelial dysfunction in obesity. Furthermore, aerobic exercise training proved to be an effective strategy for alleviating these maladies. PMID:27765769

Khz-cp (crude polysaccharide extract obtained from the fusion of Ganoderma lucidum and Polyporus umbellatus mycelia) induces apoptosis by increasing intracellular calcium levels and activating P38 and NADPH oxidase-dependent generation of reactive oxygen species in SNU-1 cells.

Science.gov (United States)

Kim, Tae Hwan; Kim, Ju Sung; Kim, Zoo Haye; Huang, Ren Bin; Chae, Young Lye; Wang, Ren Sheng

2014-07-10

Khz-cp is a crude polysaccharide extract that is obtained after nuclear fusion in Ganoderma lucidum and Polyporus umbellatus mycelia (Khz). It inhibits the growth of cancer cells. Khz-cp was extracted by solvent extraction. The anti-proliferative activity of Khz-cp was confirmed by using Annexin-V/PI-flow cytometry analysis. Intracellular calcium increase and measurement of intracellular reactive oxygen species (ROS) were performed by using flow cytometry and inverted microscope. SNU-1 cells were treated with p38, Bcl-2 and Nox family siRNA. siRNA transfected cells was employed to investigate the expression of apoptotic, growth and survival genes in SNU-1 cells. Western blot analysis was performed to confirm the expression of the genes. In the present study, Khz-cp induced apoptosis preferentially in transformed cells and had only minimal effects on non-transformed cells. Furthermore, Khz-cp was found to induce apoptosis by increasing the intracellular Ca2+ concentration ([Ca2+]i) and activating P38 to generate reactive oxygen species (ROS) via NADPH oxidase and the mitochondria. Khz-cp-induced apoptosis was caspase dependent and occurred via a mitochondrial pathway. ROS generation by NADPH oxidase was critical for Khz-cp-induced apoptosis, and although mitochondrial ROS production was also required, it appeared to occur secondary to ROS generation by NADPH oxidase. Activation of NADPH oxidase was shown by the translocation of the regulatory subunits p47phox and p67phox to the cell membrane and was necessary for ROS generation by Khz-cp. Khz-cp triggered a rapid and sustained increase in [Ca2+]i that activated P38. P38 was considered to play a key role in the activation of NADPH oxidase because inhibition of its expression or activity abrogated membrane translocation of the p47phox and p67phox subunits and ROS generation. In summary, these data indicate that Khz-cp preferentially induces apoptosis in cancer cells and that the signaling mechanisms involve an

Cambogin exerts anti-proliferative and pro-apoptotic effects on breast adenocarcinoma through the induction of NADPH oxidase 1 and the alteration of mitochondrial morphology and dynamics.

Science.gov (United States)

Shen, Kaikai; Lu, Fangfang; Xie, Jianling; Wu, Minfeng; Cai, Bo; Liu, Yurong; Zhang, Hong; Tan, Hongsheng; Pan, Yingyi; Xu, Hongxi

2016-08-02

Cambogin, a bioactive polycyclic polyprenylated acylphoroglucinol (PPAP) derived from the Garcinia genus, possesses proapoptotic effect in medulloblastoma and breast cancer cells. We have previously demonstrated that the proapoptotic effect of cambogin is driven by the production of reactive oxygen species (ROS). Here we have shown that the inhibitory effect of cambogin on cell proliferation is associated with the loss of mitochondrial transmembrane potential (ΔΨm) and mitochondrial fragmentation. Cambogin also promotes the mutual complex formation of the membrane-bound subunit p22phox of NADPH oxidase 1 (NOX1), as well as the phosphorylation of the cytosolic subunit p47phox, subsequently enhancing membrane-bound NOX1 activity, which leads to increases in intracellular and mitochondrial levels of O2.- and H2O2. Pharmacological inhibition of NOX1 using apocynin (pan-NOX inhibitor), ML171 (NOX1 inhibitor) or siRNA against NOX1 prevents the increases in O2.- and H2O2 levels and the anti-proliferative effect of cambogin. Antioxidants, including SOD (superoxide dismutase), CAT (catalase) and EUK-8, are also able to restore cell viability in the presence of cambogin. Besides, cambogin increases the dissociation of thioredoxin-1 (Trx1) from ASK1, switching the inactive form of ASK1 to the active kinase, subsequently leads to the phosphorylation of JNK/SAPK, which is abolished upon ML171 treatment. The proapoptotic effect of cambogin in breast cancer cells is also aggravated upon knocking down Trx1 in MCF-7 cells. Taken in conjunction, these data indicate that the anti-proliferative and pro-apoptotic effect of cambogin is mediated via inducing NOX1-dependent ROS production and the dissociation of ASK1 and Trx1.

Cannabidiol-induced apoptosis in human leukemia cells: A novel role of cannabidiol in the regulation of p22phox and Nox4 expression.

Science.gov (United States)

McKallip, Robert J; Jia, Wentao; Schlomer, Jerome; Warren, James W; Nagarkatti, Prakash S; Nagarkatti, Mitzi

2006-09-01

In the current study, we examined the effects of the nonpsychoactive cannabinoid, cannabidiol, on the induction of apoptosis in leukemia cells. Exposure of leukemia cells to cannabidiol led to cannabinoid receptor 2 (CB2)-mediated reduction in cell viability and induction in apoptosis. Furthermore, cannabidiol treatment led to a significant decrease in tumor burden and an increase in apoptotic tumors in vivo. From a mechanistic standpoint, cannabidiol exposure resulted in activation of caspase-8, caspase-9, and caspase-3, cleavage of poly(ADP-ribose) polymerase, and a decrease in full-length Bid, suggesting possible cross-talk between the intrinsic and extrinsic apoptotic pathways. The role of the mitochondria was further suggested as exposure to cannabidiol led to loss of mitochondrial membrane potential and release of cytochrome c. It is noteworthy that cannabidiol exposure led to an increase in reactive oxygen species (ROS) production as well as an increase in the expression of the NAD(P)H oxidases Nox4 and p22(phox). Furthermore, cannabidiol-induced apoptosis and reactive oxygen species (ROS) levels could be blocked by treatment with the ROS scavengers or the NAD(P)H oxidase inhibitors. Finally, cannabidiol exposure led to a decrease in the levels of p-p38 mitogen-activated protein kinase, which could be blocked by treatment with a CB2-selective antagonist or ROS scavenger. Together, the results from this study reveal that cannabidiol, acting through CB2 and regulation of Nox4 and p22(phox) expression, may be a novel and highly selective treatment for leukemia.

Sulfated Zirconia as Alkali-Resistant Support for Catalytic NOx Removal

DEFF Research Database (Denmark)

The use of bio-fuels as alternatives to traditional fossil fuels has attracted much attention recent years since bio-fuels belong to a family of renewable types of energy sources and do not contribute to the green-house effect. Selective catalytic reduction (SCR) of NOx with ammonia as reductant ...... interact with potassium stronger than active metal species. Among potential carriers, sulfated zirconia is of high interest because its acidic and textural properties can be modified by varying preparation conditions....

Gaseous ligand selectivity of the H-NOX sensor protein from Shewanella oneidensis and comparison to those of other bacterial H-NOXs and soluble guanylyl cyclase.

Science.gov (United States)

Wu, Gang; Liu, Wen; Berka, Vladimir; Tsai, Ah-Lim

2017-09-01

To delineate the commonalities and differences in gaseous ligand discrimination among the heme-based sensors with Heme Nitric oxide/OXygen binding protein (H-NOX) scaffold, the binding kinetic parameters for gaseous ligands NO, CO, and O 2 , including K D , k on , and k off , of Shewanella oneidensis H-NOX (So H-NOX) were characterized in detail in this study and compared to those of previously characterized H-NOXs from Clostridium botulinum (Cb H-NOX), Nostoc sp. (Ns H-NOX), Thermoanaerobacter tengcongensis (Tt H-NOX), Vibrio cholera (Vc H-NOX), and human soluble guanylyl cyclase (sGC), an H-NOX analogue. The K D (NO) and K D (CO) of each bacterial H-NOX or sGC follow the "sliding scale rule"; the affinities of the bacterial H-NOXs for NO and CO vary in a small range but stronger than those of sGC by at least two orders of magnitude. On the other hand, each bacterial H-NOX exhibits different characters in the stability of its 6c NO complex, reactivity with secondary NO, stability of oxyferrous heme and autoxidation to ferric heme. A facile access channel for gaseous ligands is also identified, implying that ligand access has only minimal effect on gaseous ligand selectivity of H-NOXs or sGC. This comparative study of the binding parameters of the bacterial H-NOXs and sGC provides a basis to guide future new structural and functional studies of each specific heme sensor with the H-NOX protein fold. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

NOx processing on Solar gas turbines; Turbines, traitement des nox sur les turbines a gaz solar

Energy Technology Data Exchange (ETDEWEB)

Chausse, X. [Spie Trindel, 95 - Cergy (France). Service TAG

1997-12-31

The Solar Company, in cooperation with Tuma Turbomach, has developed the SoLoNOx combustion system with a dry, lean, premixed compound, allowing for reduced NOx and CO emission levels (respectively 42 ppmv and 50 ppmv at 15 pc O{sub 2}). The combustor size is larger than a conventional combustor in order to maintain combustion efficiency and reduce carbon monoxide levels. Leaner combustion occurs at lower temperatures which produce less nitrogen oxides but require more volume to complete the combustion process. New developments should allow for a further reduction of NOx level at 25 ppmv

Effects of telmisartan on the expression of NADPH oxidase subunits in the myocardium of type 2 diabetic rats

Directory of Open Access Journals (Sweden)

Jia-wei LI

2011-10-01

Full Text Available Objective To explore the effect of telmisartan on the expression of NADPH oxidase subunits p22phox and NOX4 in the myocardiam of type 2 diabetic rats.Methods Thirty-six male Wistar rats were randomly divided into two groups: normal control group(group A,n=10,diabetic model group(n=26.Type 2 diabetic model was established by high-fat and high-sugar diet followed by intraperitoneal injection of a low dose of streptozotocin(STZ.After the model was reproduced successfully,20 diabetic rats were randomly divided into diabetic subgroup(group B,n=10 and telmisartan-treated subgroup(group C,n=10.Rats in group C were orally administered telmisartan(5mg/kg/d,and rats in group A and B were given equivalent volume of normal saline.All rats were sacrificed 12 weeks after treatment.The mRNA expressions of myocardial p22phox and NOX4 were detected by real-time fluorescence quantitative PCR,and the protein expressions of myocardial connective tissue growth factor(CTGF and copper-zinc-superoxide dismutase(Cu-Zn-SOD were detected by immunohistochemical staining.Results Compared with group A,the ratio of heart/body weight,the mRNA expression of myocardial p22phox and NOX4,and the protein expression of myocardial CTGF increased significantly in group B,and the protein expression of myocardial Cu-Zn-SOD decreased significantly(P 0.05.Conclusions Telmisartan can down-regulate the over-expression of myocardial NOX4 and p22phox mRNA in type 2 diabetic rats,lessen the myocardial damage induced by oxidative stress,thus plays a protective role in the myocardium of diabetic rats.

Alternative deNOx catalysts and technologies

DEFF Research Database (Denmark)

Due-Hansen, Johannes

The present thesis entitled Alternative deNOx Catalysts and technologies revolves around the topic of removal of nitrogen oxides. Nitrogen oxides, NOx, are unwanted byproducts formed during combustion (e.g. in engines or power plants). If emitted to the atmosphere, they are involved...... in the formation of acid rain and photochemical smog. Some basic concepts and reactions regarding the formation and removal of NOx are presented in chapter 1 and 2. Two approaches are undertaken in the present work to reduce the emission of NOx: by means of catalytic removal, and by NO absorption in ionic liquids....... The commercial catalyst used for the selective catalytic reduction (SCR) of nitrogen oxides exhibits high activity and selectivity towards N2. However, the vanadia-titania-based catalyst used is very sensitive to deactivation by alkali-species (primarily potassium), which are typically present in high amounts...

Enhanced Combustion Low NOx Pulverized Coal Burner

Energy Technology Data Exchange (ETDEWEB)

David Towle; Richard Donais; Todd Hellewell; Robert Lewis; Robert Schrecengost

2007-06-30

For more than two decades, Alstom Power Inc. (Alstom) has developed a range of low cost, infurnace technologies for NOx emissions control for the domestic U.S. pulverized coal fired boiler market. This includes Alstom's internally developed TFS 2000{trademark} firing system, and various enhancements to it developed in concert with the U.S. Department of Energy. As of the date of this report, more than 270 units representing approximately 80,000 MWe of domestic coal fired capacity have been retrofit with Alstom low NOx technology. Best of class emissions range from 0.18 lb/MMBtu for bituminous coal to 0.10 lb/MMBtu for subbituminous coal, with typical levels at 0.24 lb/MMBtu and 0.13 lb/MMBtu, respectively. Despite these gains, NOx emissions limits in the U.S. continue to ratchet down for new and existing boiler equipment. On March 10, 2005, the Environmental Protection Agency (EPA) announced the Clean Air Interstate Rule (CAIR). CAIR requires 25 Eastern states to reduce NOx emissions from the power generation sector by 1.7 million tons in 2009 and 2.0 million tons by 2015. Low cost solutions to meet such regulations, and in particular those that can avoid the need for a costly selective catalytic reduction system (SCR), provide a strong incentive to continue to improve low NOx firing system technology to meet current and anticipated NOx control regulations. The overall objective of the work is to develop an enhanced combustion, low NOx pulverized coal burner, which, when integrated with Alstom's state-of-the-art, globally air staged low NOx firing systems will provide a means to achieve: Less than 0.15 lb/MMBtu NOx emissions when firing a high volatile Eastern or Western bituminous coal, Less than 0.10 lb/MMBtu NOx emissions when firing a subbituminous coal, NOx reduction costs at least 25% lower than the costs of an SCR, Validation of the NOx control technology developed through large (15 MWt) pilot scale demonstration, and Documentation required for

40 CFR 96.85 - NOX Budget opt-in permit contents.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false NOX Budget opt-in permit contents. 96... (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS Individual Unit Opt-ins § 96.85 NOX Budget opt-in permit contents. (a) Each NOX Budget opt-in permit...

40 CFR 97.85 - NOX Budget opt-in permit contents.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false NOX Budget opt-in permit contents. 97... (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS Individual Unit Opt-ins. § 97.85 NOX Budget opt-in permit contents. (a) Each NOX Budget opt-in permit will contain all elements...

Tacrolimus increases Nox4 expression in human renal fibroblasts and induces fibrosis-related genes by aberrant TGF-beta receptor signalling.

Directory of Open Access Journals (Sweden)

Georg Kern

Full Text Available Chronic nephrotoxicity of immunosuppressives is one of the main limiting factors in the long-term outcome of kidney transplants, leading to tissue fibrosis and ultimate organ failure. The cytokine TGF-β is considered a key factor in this process. In the human renal fibroblast cell line TK-173, the macrolide calcineurin inhibitor tacrolimus (FK-506 induced TGF-β-like effects, manifested by increased expression of NAD(PH-oxidase 4 (Nox4, transgelin, tropomyosin 1, and procollagen α1(V mRNA after three days. The macrolide mTOR inhibitor rapamycin had similar effects, while cyclosporine A did not induce fibrose-related genes. Concentration dependence curves were sigmoid, where mRNA expression was induced already at low nanomolar levels of tacrolimus, and reached saturation at 100-300 nM. The effects were independent of extracellular TGF-β as confirmed by the use of neutralizing antibodies, and thus most likely caused by aberrant TGF-β receptor signaling, where binding of tacrolimus to the regulatory FKBP12 protein results in a "leaky" TGF-β receptor. The myofibroblast marker α-smooth muscle actin was neither induced by tacrolimus nor by TGF-β1, indicating an incomplete activation of TK-173 fibroblasts under culture conditions. Tacrolimus- and TGF-β1-induced Nox4 protein upregulation was confirmed by Western blotting, and was accompanied by a rise in intracellular H2O2 concentration. Si-RNA mediated knock-down of Nox4 expression prevented up-regulation of procollagen α1(V mRNA in tacrolimus-treated cells, but induced procollagen α1(V expression in control cells. Nox4 knock-down had no significant effect on the other genes tested. TGF-β is a key molecule in fibrosis, and the constant activation of aberrant receptor signaling by tacrolimus might contribute to the long-term development of interstitial kidney fibrosis in immunosuppressed patients. Nox4 levels possibly play a regulatory role in these processes.

Role of TLR4/NADPH oxidase/ROS-activated p38 MAPK in VCAM-1 expression induced by lipopolysaccharide in human renal mesangial cells

Directory of Open Access Journals (Sweden)

Lee I-Ta

2012-11-01

Full Text Available Abstract Background In bacteria-induced glomerulonephritis, Toll-like receptor 4 (TLR4 activation by lipopolysaccharide (LPS, a key component of the outer membranes of Gram-negative bacteria can increase oxidative stress and the expression of vascular cell adhesion molecule-1 (VCAM-1, which recruits leukocytes to the glomerular mesangium. However, the mechanisms underlying VCAM-1 expression induced by LPS are still unclear in human renal mesangial cells (HRMCs. Results We demonstrated that LPS induced VCAM-1 mRNA and protein levels associated with an increase in the promoter activity of VCAM-1, determined by Western blot, RT-PCR, and promoter assay. LPS-induced responses were inhibited by transfection with siRNAs of TLR4, myeloid differentiation factor 88 (MyD88, Nox2, Nox4, p47phox, c-Src, p38 MAPK, activating transcription factor 2 (ATF2, and p300 or pretreatment with the inhibitors of reactive oxygen species (ROS, edaravone, NADPH oxidase [apocynin (APO or diphenyleneiodonium chloride (DPI], c-Src (PP1, p38 MAPK (SB202190, and p300 (GR343. LPS induced NADPH oxidase activation, ROS production, and p47phox translocation from the cytosol to the membrane, which were reduced by PP1 or c-Src siRNA. We observed that LPS induced TLR4, MyD88, c-Src, and p47phox complex formation determined by co-immunoprecipitation and Western blot. We further demonstrated that LPS stimulated ATF2 and p300 phosphorylation and complex formation via a c-Src/NADPH oxidase/ROS/p38 MAPK pathway. Up-regulation of VCAM-1 led to enhancing monocyte adhesion to HRMCs challenged with LPS, which was inhibited by siRNAs of c-Src, p47phox, p38 MAPK, ATF2, and p300 or pretreatment with an anti-VCAM-1 neutralizing antibody. Conclusions In HRMCs, LPS-induced VCAM-1 expression was, at least in part, mediated through a TLR4/MyD88/ c-Src/NADPH oxidase/ROS/p38 MAPK-dependent p300 and ATF2 pathway associated with recruitment of monocyte adhesion to kidney. Blockade of these pathways may

Experience from performance testing of low NOx burners for refinery heaters; Tests de performance avec des bruleurs de raffinerie a basse emission de NOx

Energy Technology Data Exchange (ETDEWEB)

Boden, J.C. [Refining Technology, BP Oil International, Sunbury (United Kingdom)

2001-07-01

Developments in low NOx burner technology have resulted in major reductions in NOx emissions from refinery process heaters. However, the techniques used in low NOx burners to reduce NOx emissions can potentially affect other key aspects of burner performance, particularly flame stability and completeness of combustion. BP has evaluated many of the currently available low and ultra-low NOx burners, both natural and forced draught, in its purpose-built test furnace. This extensive test programme has shown that to be a reliable predictor of actual performance a test rig must recreate accurately the real furnace conditions, particularly with respect to furnace and hearth temperatures. The testing has demonstrated the NOx emissions to be expected in practice from different generic types of burner, conventional, low NOx and ultra-low NOx, and has highlighted the sets of conditions most likely to lead to combustion performance problems. (authors)

Characterization of Two VAO-Type Flavoprotein Oxidases from Myceliophthora thermophila

Directory of Open Access Journals (Sweden)

Alessandro R. Ferrari

2018-01-01

Full Text Available The VAO flavoprotein family consists mostly of oxidoreductases harboring a covalently linked flavin cofactor. The linkage can be either monocovalent at position 8 with a histidine or tyrosine or bicovalent at position 8 with a histidine and at position 6 with a cysteine. Bicovalently bound flavoproteins show a preference for bulkier substrates such as oligosaccharides or secondary metabolites. The genome of the thermophilic fungus Myceliophthora thermophila C1 was found to be rich in genes encoding putative covalent VAO-type flavoproteins. Enzymes from this fungus have the advantage of being rather thermostable and homologous overexpression in M. thermophila C1 is feasible. Recently we discovered a new and VAO-type carbohydrate oxidase from this fungus: xylooligosaccharide oxidase. In this study, two other putative VAO-type oxidases, protein sequence XP_003663615 (MtVAO615 and XP_003665713 (MtVAO713, were expressed in M. thermophila C1, purified and characterized. Enzyme MtVAO615 was found to contain a bicovalently bound FAD, while enzyme MtVAO713 contained a monocovalent histidyl-bound FAD. The crystal structures of both proteins were obtained which revealed atypical active site architectures. It could be experimentally verified that both proteins, when reduced, rapidly react with molecular oxygen, a hallmark of flavoprotein oxidases. A large panel of alcohols, including carbohydrates, steroids and secondary alcohols were tested as potential substrates. For enzyme MtVAO713 low oxidase activity was discovered towards ricinoleic acid.

NOX EMISSION CONTROL OPTIONS FOR COAL-FIRED ELECTRIC UTILITY BOILERS

Science.gov (United States)

The paper reviews NOx control options for coal-fired electric utility boilers. (NOTE: Acid Rain NOx regulations, the Ozone Transport Commission's NOx Budget Program, revision of the New Source Performance Standards (NSPS) for NOx emissions from utility sources, and Ozone Transpor...

Pro-inflammatory effects of interleukin-17A on vascular smooth muscle cells involve NAD(P)H- oxidase derived reactive oxygen species.

Science.gov (United States)

Pietrowski, Eweline; Bender, Bianca; Huppert, Jula; White, Robin; Luhmann, Heiko J; Kuhlmann, Christoph R W

2011-01-01

T cells are known for their contribution to the inflammatory element of atherosclerosis. Recently, it has been demonstrated that the Th17 derived cytokine IL-17 is involved in the pro-inflammatory response of vascular smooth muscle cells (VSMC). The aim of the present study was to examine whether reactive oxygen species (ROS) might be involved in this context. The effect of IL-17A on ROS generation was examined using the fluorescent dye 2'7'-dichlorodihydrofluorescein (H(2)DCF) in primary murine VSMC. IL-17A induced an increase in H(2)DCF fluorescence in VSMC, and this effect was blocked by the NAD(P)H-oxidase inhibitor apocynin and siRNA targeting Nox2. The p38-MAPK inhibitors SB203580 and SB202190 dose-dependently reduced the IL-17A induced ROS production. The IL-17A induced release of the pro-inflammatory cytokines IL-6, G-CSF, GM-CSF and MCP-1 from VSMC, as detected by the Luminex technology, was completely abolished by NAD(P)H-oxidase inhibition. Taken together, our data indicate that IL-17A causes the NAD(P)H-oxidase dependent generation of ROS leading to a pro-inflammatory activation of VSMC. Copyright © 2010 S. Karger AG, Basel.

40 CFR 97.86 - Withdrawal from NOX Budget Trading Program.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Withdrawal from NOX Budget Trading... PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS Individual Unit Opt-ins. § 97.86 Withdrawal from NOX Budget Trading Program. (a) Requesting withdrawal. To...

Peroxisome proliferator-activated receptor δ inhibits Porphyromonas gingivalis lipopolysaccharide-induced activation of matrix metalloproteinase-2 by downregulating NADPH oxidase 4 in human gingival fibroblasts.

Science.gov (United States)

Yoo, T; Ham, S A; Hwang, J S; Lee, W J; Paek, K S; Oh, J W; Kim, J H; Do, J T; Han, C W; Kim, J H; Seo, H G

2016-10-01

We investigated the roles of peroxisome proliferator-activated receptor δ (PPARδ) in Porphyromonas gingivalis-derived lipopolysaccharide (Pg-LPS)-induced activation of matrix metalloproteinase 2 (MMP-2). In human gingival fibroblasts (HGFs), activation of PPARδ by GW501516, a specific ligand of PPARδ, inhibited Pg-LPS-induced activation of MMP-2 and generation of reactive oxygen species (ROS), which was associated with reduced expression of NADPH oxidase 4 (Nox4). These effects were significantly smaller in the presence of small interfering RNA targeting PPARδ or the specific PPARδ inhibitor GSK0660, indicating that PPARδ is involved in these events. In addition, modulation of Nox4 expression by small interfering RNA influenced the effect of PPARδ on MMP-2 activity, suggesting a mechanism in which Nox4-derived ROS modulates MMP-2 activity. Furthermore, c-Jun N-terminal kinase and p38, but not extracellular signal-regulated kinase, mediated PPARδ-dependent inhibition of MMP-2 activity in HGFs treated with Pg-LPS. Concomitantly, PPARδ-mediated inhibition of MMP-2 activity was associated with the restoration of types I and III collagen to levels approaching those in HGFs not treated with Pg-LPS. These results indicate that PPARδ-mediated downregulation of Nox4 modulates cellular redox status, which in turn plays a critical role in extracellular matrix homeostasis through ROS-dependent regulation of MMP-2 activity. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

40 CFR 96.24 - Effective date of initial NOX Budget permit.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Effective date of initial NOX Budget... PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS Permits § 96.24 Effective date of initial NOX Budget permit. The initial NOX Budget permit...

40 CFR 96.86 - Withdrawal from NOX Budget Trading Program.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Withdrawal from NOX Budget Trading... PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS Individual Unit Opt-ins § 96.86 Withdrawal from NOX Budget Trading Program. (a) Requesting...

Glucose oxidase variants with improved properities

OpenAIRE

Fischer, Rainer; Ostafe, Raluca; Prodanovic, Radivoje

2014-01-01

Source: WO14173822A3 [EN] The technology provided herein relates to novel variants of microbial glucose oxidase with improved properties, more specifically to polypeptides having glucose oxidase activity as their major enzymatic activity; to nucleic acid molecules encoding said glucose oxidases; vectors and host cells containing the nucleic acids and methods for producing the glucose oxidase; compositions comprising said glucose oxidase; methods for the preparation and production of such enzy...

Plasma amine oxidase activities in Norrie disease patients with an X-chromosomal deletion affecting monoamine oxidase.

Science.gov (United States)

Murphy, D L; Sims, K B; Karoum, F; Garrick, N A; de la Chapelle, A; Sankila, E M; Norio, R; Breakefield, X O

1991-01-01

Two individuals with an X-chromosomal deletion were recently found to lack the genes encoding monoamine oxidase type A (MAO-A) and MAO-B. This abnormality was associated with almost total (90%) reductions in the oxidatively deaminated urinary metabolites of the MAO-A substrate, norepinephrine, and with marked (100-fold) increases in an MAO-B substrate, phenylethylamine, confirming systemic functional consequences of the genetic enzyme deficiency. However, urinary concentrations of the deaminated metabolites of dopamine and serotonin (5-HT) were essentially normal. To investigate other deaminating systems besides MAO-A and MAO-B that might produce these metabolites of dopamine and 5-HT, we examined plasma amine oxidase (AO) activity in these two patients and two additional patients with the same X-chromosomal deletion. Normal plasma AO activity was found in all four Norrie disease-deletion patients, in four patients with classic Norrie disease without a chromosomal deletion, and in family members of patients from both groups. Marked plasma amine metabolite abnormalities and essentially absent platelet MAO-B activity were found in all four Norrie disease-deletion patients, but in none of the other subjects in the two comparison groups. These results indicate that plasma AO is encoded by gene(s) independent of those for MAO-A and MAO-B, and raise the possibility that plasma AO, and perhaps the closely related tissue AO, benzylamine oxidase, as well as other atypical AOs or MAOs encoded independently from MAO-A and MAO-B may contribute to the oxidative deamination of dopamine and 5-HT in humans.

Copper radical oxidases and related extracellular oxidoreductases of wood-decay Agaricomycetes

Science.gov (United States)

Phil Kersten; Dan Cullen

2014-01-01

Extracellular peroxide generation, a key component of oxidative lignocellulose degradation, has been attributed to various enzymes including the copper radical oxidases. Encoded by a family of structurally related sequences, the genes are widely distributed among wood decay fungi including three recently completed polypore genomes. In all cases, core catalytic residues...

Inactivation of 1-aminocyclopropane-1-carboxylate oxidase involves oxidative modifications.

Science.gov (United States)

Barlow, J N; Zhang, Z; John, P; Baldwin, J E; Schofield, C J

1997-03-25

1-Aminocyclopropane-1-carboxylate (ACC) oxidase catalyzes the final step in the biosynthesis of the plant signaling molecule ethylene. It is a member of the ferrous iron dependent family of oxidases and dioxygenases and is unusual in that it displays a very short half-life under catalytic conditions, typically less than 20 min, and a requirement for CO2 as an activator. The rates of inactivation of purified, recombinant ACC oxidase from tomato under various combinations of substrates and cofactors were measured. Inactivation was relatively slow in the presence of buffer alone (t1/2 > 1 h), but fast in the presence of ferrous iron and ascorbate (t1/2 approximately 10 min). The rate of iron/ascorbate-mediated inactivation was increased by the addition of ACC, unaffected by the addition of CO2 at saturation (supplied as bicarbonate) but decreased by the addition of catalase or ACC + CO2 at saturation (supplied as bicarbonate). Iron/ascorbate-mediated inactivation was accompanied by partial proteolysis as observed by SDS-PAGE analysis. The fragmentation pattern was altered when ACC was also included, suggesting that ACC can bind to ACC oxidase in the absence of bicarbonate. N-terminal sequencing of fragments resulted in identification of an internal cleavage site which we propose is proximate to active-site bound iron. Thus, ACC oxidase inactivates via relatively slow partial unfolding of the catalytically active conformation, oxidative damage mediated via hydrogen peroxide which is catalase protectable and oxidative damage to the active site which results in partial proteolysis and is not catalase protectable.

β-Adrenergic receptors desensitization is not involved in exercise-induced cardiac fatigue: NADPH oxidase-induced oxidative stress as a new trigger.

Science.gov (United States)

Vitiello, Damien; Boissière, Julien; Doucende, Grégory; Gayrard, Sandrine; Polge, Anne; Faure, Patrice; Goux, Aurélie; Tanguy, Stéphane; Obert, Philippe; Reboul, Cyril; Nottin, Stéphane

2011-11-01

Prolonged strenuous exercise (PSE) induces transient left ventricular (LV) dysfunction. Previous studies suggest that β-adrenergic pathway desensitization could be involved in this phenomenon, but it remains to be confirmed. Moreover, other underlying mechanisms involving oxidative stress have been recently proposed. The present study aimed to evaluate the involvement of both the β-adrenergic pathway and NADPH oxidase (Nox) enzyme-induced oxidative stress in myocardial dysfunction in rats following PSE. Rats were divided into 4 groups: controls (Ctrl), 4-h exercised on treadmill (PSE), and 2 groups in which Nox enzyme was inhibited with apocynin treatment (Ctrl APO and PSE APO, respectively). We evaluated cardiac function in vivo and ex vivo during basal conditions and isoproterenol stress. GSH/GSSG ratio, cardiac troponin I (cTnI) release, and lipid peroxidation (MDA) were evaluated. PSE induced a decrease in LV developed pressure, intrinsic myocardial contractility, and relaxation associated with an increase in plasma cTnI release. Our in vivo and ex vivo results demonstrated no differences in myocardial response to isoproterenol and of effective dose 50 between control and PSE rats. Interestingly, the LV dysfunction was reversed by apocynin treatment. Moreover, apocynin prevented cellular oxidation [GSH/GSSG ratio: PSE APO rats vs. PSE rats in arbitrary units (au): 1.98 ± 0.07 vs. 1.35 ± 0.10; P stress from the Nox enzyme.

Valencene oxidase CYP706M1 from Alaska cedar (Callitropsis nootkatensis).

Science.gov (United States)

Cankar, Katarina; van Houwelingen, Adèle; Goedbloed, Miriam; Renirie, Rokus; de Jong, René M; Bouwmeester, Harro; Bosch, Dirk; Sonke, Theo; Beekwilder, Jules

2014-03-18

(+)-Nootkatone is a natural sesquiterpene ketone used in grapefruit and citrus flavour compositions. It occurs in small amounts in grapefruit and is a major component of Alaska cedar (Callitropsis nootkatensis) heartwood essential oil. Upon co-expression of candidate cytochrome P450 enzymes from Alaska cedar in yeast with a valencene synthase, a C. nootkatensis valencene oxidase (CnVO) was identified to produce trans-nootkatol and (+)-nootkatone. Formation of (+)-nootkatone was detected at 144±10μg/L yeast culture. CnVO belongs to a new subfamily of the CYP706 family of cytochrome P450 oxidases. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Direct comparison of gluco-oligosaccharide oxidase variants and glucose oxidase: substrate range and H2O2 stability.

Science.gov (United States)

Vuong, Thu V; Foumani, Maryam; MacCormick, Benjamin; Kwan, Rachel; Master, Emma R

2016-11-21

Glucose oxidase (GO) activity is generally restricted to glucose and is susceptible to inactivation by H 2 O 2 . By comparison, the Y300A variant of gluco-oligosaccharide oxidase (GOOX) from Sarocladium strictum showed broader substrate range and higher H 2 O 2 stability. Specifically, Y300A exhibited up to 40 times higher activity on all tested sugars except glucose, compared to GO. Moreover, fusion of the Y300A variant to a family 22 carbohydrate binding module from Clostridium thermocellum (CtCBM22A) nearly doubled its catalytic efficiency on glucose, while retaining significant activity on oligosaccharides. In the presence of 200 mM of H 2 O 2 , the recombinant CtCBM22A_Y300A retained 80% of activity on glucose and 100% of activity on cellobiose, the preferred substrate for this enzyme. By contrast, a commercial glucose oxidase reported to contain ≤0.1 units catalase/ mg protein, retained 60% activity on glucose under the same conditions. GOOX variants appear to undergo a different mechanism of inactivation, as a loss of histidine instead of methionine was observed after H 2 O 2 incubation. The addition of CtCBM22A also promoted functional binding of the fusion enzyme to xylan, facilitating its simultaneous purification and immobilization using edible oat spelt xylan, which might benefit the usage of this enzyme preparation in food and baking applications.

Evaluation of NOX emissions from TVA coal-fired power plants

International Nuclear Information System (INIS)

Jones, J.W.; Stamey-Hall, S.

1991-01-01

The paper gives results of a preliminary evaluation of nitrogen oxide (NOx) emissions from 11 Tennessee Valley Authority (TVA) coal-fired power plants. Current EPA AP-42 emission factors for NOx from coal-fired utility boilers do not account for variations either in these emissions as a function of generating unit load, or in designs of boilers of the same general type, particularly wall-fired boilers. The TVA has compiled short-term NOx emissions data from 30 units at 11 TVA coal-fired plants. These units include cyclone, cell burner, single wall, opposed wall, single tangential, and twin tangential boiler firing designs. Tests were conducted on 29 of the 30 units at high load; 18 were also tested at reduced load. NOx emissions rates were calculated for each test and compared to the calculated rate for each boiler type using AP-42. Preliminary analysis indicates that: (1) TVA cyclone-fired units emit more NOx than estimated using AP-42; (2) TVA cell burner units emit considerably more NOx than estimated; (3) most TVA single-wall-fired units emit slightly more NOx than estimated; (4) most TVA single-furnace tangentially fired units emit less NOx than estimated at high load, but the same as (or more than) estimated at reduced load; and (5) most TVA twin-furnace tangentially fired units, at high load, emit slightly more NOx than estimated using AP-42

Effect of GLP-1 on the expression of NADPH oxidase subunits in the kidney of type 1 diabetic rats

Directory of Open Access Journals (Sweden)

Jin-jin LIU

2013-09-01

Full Text Available Objective　To observe the effect of exenatide, a glucagon-like peptide-1 (GLP-1 receptor agonist, on the expression of NADPH oxidase subunits NOX4 and p22phox and connective tissue growth factor (CTGF in the kidney of streptozotocin (STZ-induced type 1 diabetic rats, and explore the protective effects and mechanisms of exenatide on the kidney of diabetic rats. Methods　Thirty male Sprague-Dawley (SD rats were divided into control group (group A, n=7 and diabetic model group (n=23. Type 1 diabetic model was reproduced by intraperitoneal injection of streptozotocin. It was successful in 19 rats. Diabetic rats were randomly divided into diabetic control group (group B, n=10 and diabetic with treatment of exenatide group (group C, n=9. Rats in group C were injected subcutaneously with exenatide in dose of 5μg/kg twice daily. Rats in group A and B were given equivalent volume of normal saline by subcutaneous injection. All rats were sacrificed after eight weeks. The mRNA expression of renal p22phox and NOX4 were detected by real-time fluorescence quantitative PCR. The protein expression of CTGF was detected by immunohistochemical staining. Results　The levels of blood glucose, lipids, creatinine, and urea nitrogen, the albumin excretion rate, kidney index, the mRNA expressions of renal NOX4 and p22phox, and the protein expression of renal CTGF were significantly increased in group B compared with that in group A (P0.05. Conclusion　Exenatide can decrease the expressions of renal NOX4, p22phox and CTGF, decline the index of urinary protein, and alleviate the kidney hypertrophy in type 1 diabetic rats, implying that exenatide exerted a protective effect on the kidney.

Sphingosine kinase 1 deficiency confers protection against hyperoxia-induced bronchopulmonary dysplasia in a murine model: role of S1P signaling and Nox proteins.

Science.gov (United States)

Harijith, Anantha; Pendyala, Srikanth; Reddy, Narsa M; Bai, Tao; Usatyuk, Peter V; Berdyshev, Evgeny; Gorshkova, Irina; Huang, Long Shuang; Mohan, Vijay; Garzon, Steve; Kanteti, Prasad; Reddy, Sekhar P; Raj, J Usha; Natarajan, Viswanathan

2013-10-01

Bronchopulmonary dysplasia of the premature newborn is characterized by lung injury, resulting in alveolar simplification and reduced pulmonary function. Exposure of neonatal mice to hyperoxia enhanced sphingosine-1-phosphate (S1P) levels in lung tissues; however, the role of increased S1P in the pathobiological characteristics of bronchopulmonary dysplasia has not been investigated. We hypothesized that an altered S1P signaling axis, in part, is responsible for neonatal lung injury leading to bronchopulmonary dysplasia. To validate this hypothesis, newborn wild-type, sphingosine kinase1(-/-) (Sphk1(-/-)), sphingosine kinase 2(-/-) (Sphk2(-/-)), and S1P lyase(+/-) (Sgpl1(+/-)) mice were exposed to hyperoxia (75%) from postnatal day 1 to 7. Sphk1(-/-), but not Sphk2(-/-) or Sgpl1(+/-), mice offered protection against hyperoxia-induced lung injury, with improved alveolarization and alveolar integrity compared with wild type. Furthermore, SphK1 deficiency attenuated hyperoxia-induced accumulation of IL-6 in bronchoalveolar lavage fluids and NADPH oxidase (NOX) 2 and NOX4 protein expression in lung tissue. In vitro experiments using human lung microvascular endothelial cells showed that exogenous S1P stimulated intracellular reactive oxygen species (ROS) generation, whereas SphK1 siRNA, or inhibitor against SphK1, attenuated hyperoxia-induced S1P generation. Knockdown of NOX2 and NOX4, using specific siRNA, reduced both basal and S1P-induced ROS formation. These results suggest an important role for SphK1-mediated S1P signaling-regulated ROS in the development of hyperoxia-induced lung injury in a murine neonatal model of bronchopulmonary dysplasia. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Determination of the NOx Loading of an Automotive Lean NOx Trap by Directly Monitoring the Electrical Properties of the Catalyst Material Itself

Directory of Open Access Journals (Sweden)

Ralf Moos

2011-08-01

Full Text Available Recently, it has been shown that the degree of loading of several types of automotive exhaust aftertreatment devices can be directly monitored in situ and in a contactless way by a microwave-based method. The goal of this study was to clarify whether this method can also be applied to NOx storage and reduction catalysts (lean NOx traps in order to obtain further knowledge about the reactions occurring in the catalyst and to compare the results with those obtained by wirebound NOx loading sensors. It is shown that both methods are able to detect the different catalyst loading states. However, the sensitivity of the microwave-based method turned out to be small compared to that previously observed for other exhaust aftertreatment devices. This may limit the practical applicability of the microwave-based NOx loading detection in lean NOx traps.

The conserved baculovirus protein p33 (Ac92) is a flavin adenine dinucleotide-linked sulfhydryl oxidase

International Nuclear Information System (INIS)

Long, C.M.; Rohrmann, G.F.; Merrill, G.F.

2009-01-01

Open reading frame 92 of the Autographa californica baculovirus (Ac92) is one of about 30 core genes present in all sequenced baculovirus genomes. Computer analyses predicted that the Ac92 encoded protein (called p33) and several of its baculovirus orthologs were related to a family of flavin adenine dinucleotide (FAD)-linked sulfhydryl oxidases. Alignment of these proteins indicated that, although they were highly diverse, a number of amino acids in common with the Erv1p/Alrp family of sulfhydryl oxidases are present. Some of these conserved amino acids are predicted to stack against the isoalloxazine and adenine components of FAD, whereas others are involved in electron transfer. To investigate this relationship, Ac92 was expressed in bacteria as a His-tagged fusion protein, purified, and characterized both spectrophotometrically and for its enzymatic activity. The purified protein was found to have the color (yellow) and absorption spectrum consistent with it being a FAD-containing protein. Furthermore, it was demonstrated to have sulfhydryl oxidase activity using dithiothreitol and thioredoxin as substrates.

Myocardial fibrosis induced by exposure to subclinical lipopolysaccharide is associated with decreased miR-29c and enhanced NOX2 expression in mice.

Directory of Open Access Journals (Sweden)

Wilbur Y W Lew

Full Text Available Exposure to subclinical levels of lipopolysaccharide (LPS occurs commonly and is seemingly well tolerated. However, recurrent LPS exposure induces cardiac fibrosis over 2 to 3 months in a murine model, not mediated by the renin-angiotensin system. Subclinical LPS induces cardiac fibrosis by unique mechanisms.In C57/Bl6 mice, LPS (10 mg/kg or saline (control were injected intraperitoneally once a week for 1-4 weeks. Mice showed no signs of distress, change in activity, appetite, or weight loss. Mice were euthanized after 3 days, 1, 2, or 4 weeks to measure cardiac expression of fibrosis-related genes and potential mediators (measured by QRT-PCR, including micro-RNA (miR and NADPH oxidase (NOX. Collagen fraction area of the left ventricle was measured with picrosirius red staining. Cardiac fibroblasts isolated from adult mouse hearts were incubated with 0, 0.1, 1.0 or 10 ng/ml LPS for 48 hours.Cardiac miR expression profiling demonstrated decreased miR-29c after 3 and 7 days following LPS, which were confirmed by QRT-PCR. The earliest changes in fibrosis-related genes and mediators that occurred 3 days after LPS were increased cardiac expression of TIMP-1 and NOX-2 (but not of NOX-4. This persisted at 1 and 2 weeks, with additional increases in collagen Iα1, collagen IIIα1, MMP2, MMP9, TIMP1, TIMP2, and periostin. There was no change in TGF-β or connective tissue growth factor. Collagen fraction area of the left ventricle increased after 2 and 4 weeks of LPS. LPS decreased miR-29c and increased NOX-2 in isolated cardiac fibroblasts.Recurrent exposure to subclinical LPS induces cardiac fibrosis after 2-4 weeks. Early changes 3 days after LPS were decreased miR-29c and increased NOX2 and TIMP1, which persisted at 1 and 2 weeks, along with widespread activation of fibrosis-related genes. Decreased miR-29c and increased NOX2, which induce cardiac fibrosis in other conditions, may uniquely mediate LPS-induced cardiac fibrosis.

40 CFR 96.186 - Withdrawal from CAIR NOX Annual Trading Program.

Science.gov (United States)

2010-07-01

... Trading Program. 96.186 Section 96.186 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR NOX Opt-in Units § 96.186 Withdrawal from CAIR NOX Annual Trading...

Neural networks prove effective at NOx reduction

Energy Technology Data Exchange (ETDEWEB)

Radl, B.J. [Pegasus Technologies, Mentor, OH (USA)

2000-05-01

The availability of low cost computer hardware and software is opening up possibilities for the use of artificial intelligence concepts, notably neural networks, in power plant control applications, delivering lower costs, greater efficiencies and reduced emissions. One example of a neural network system is the NeuSIGHT combustion optimisation system, developed by Pegasus Technologies, a subsidiary of KFx Inc. It can help reduce NOx emissions, improve heat rate and enable either deferral or elimination of capital expenditures. on other NOx control technologies, such as low NOx burners, SNCR and SCR. This paper illustrates these benefits using three recent case studies. 4 figs.

A review of NOx formation mechanisms in recovery furnaces

International Nuclear Information System (INIS)

Nichols, K.M.; Thompson, L.M.; Empie, H.J.

1993-01-01

Review of NOx formation studies shows that NO forms in recovery furnaces primarily by two independent mechanisms, thermal and fuel. Thermal NO formation is extremely temperature-sensitive. However, theoretical predictions indicate that recovery furnace temperatures are not high enough to form significant thermal NO. Fuel NO formation is less temperature-sensitive, and is related to fuel nitrogen content. Black liquors are shown to contain 0.05 to 0.24 weight percent fuel nitrogen. Conversion of just 20% of this would yield approximately 25-120 ppm NOx (at 8% 0 2 ) in the flue gas, enough to represent the majority of the total NOx. Data from operating recovery furnaces show NOx emissions ranging from near zero to over 100 ppm at 8% 0 2 . An apparent increase in recovery furnace NOx emissions was observed with increasing solids. This increase is much less than predicted by thermal NO formation theory, indicating that other NO formation/destruction mechanisms, such as fuel NO formation, are important. No data are available to show the relative importance of thermal and fuel NO to total NOx during black liquor combustion

40 CFR 97.186 - Withdrawal from CAIR NOX Annual Trading Program.

Science.gov (United States)

2010-07-01

... Trading Program. 97.186 Section 97.186 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS CAIR NOX Opt-In Units § 97.186 Withdrawal from CAIR NOX Annual Trading Program. Except as provided...

Characterization of LSM/CGO Symmetric Cells Modified by NOx Adsorbents for Electrochemical NOx Removal with Impedance Spectroscopy

DEFF Research Database (Denmark)

Shao, Jing; Kammer Hansen, Kent

2013-01-01

in the resistance of the low-frequency processes, which were ascribed to adsorption, diffusion, and transfer of O2 species and NOx species at or near the triple phase boundary (TPB) region and the formation of the reaction intermediate NO2. The BaO impregnation improved the adsorption of NOx on the LSM....../CGO electrode by selectively trapping NO2 in the form of nitrate over the BaO sites and provided availability for a direct reduction of the stored nitrate. The BaO-Pt-Al2O3 layer enhanced the NOx adsorption and promoted the formation of NO2 due to the NO oxidation ability of the Pt catalyst, but hindered...... the gas diffusion to the reaction sites....

Nitrogen Isotope Composition of Thermally Produced NOx from Various Fossil-Fuel Combustion Sources.

Science.gov (United States)

Walters, Wendell W; Tharp, Bruce D; Fang, Huan; Kozak, Brian J; Michalski, Greg

2015-10-06

The nitrogen stable isotope composition of NOx (δ(15)N-NOx) may be a useful indicator for NOx source partitioning, which would help constrain NOx source contributions in nitrogen deposition studies. However, there is large uncertainty in the δ(15)N-NOx values for anthropogenic sources other than on-road vehicles and coal-fired energy generating units. To this end, this study presents a broad analysis of δ(15)N-NOx from several fossil-fuel combustion sources that includes: airplanes, gasoline-powered vehicles not equipped with a three-way catalytic converter, lawn equipment, utility vehicles, urban buses, semitrucks, residential gas furnaces, and natural-gas-fired power plants. A relatively large range of δ(15)N-NOx values was measured from -28.1‰ to 8.5‰ for individual exhaust/flue samples that generally tended to be negative due to the kinetic isotope effect associated with thermal NOx production. A negative correlation between NOx concentrations and δ(15)N-NOx for fossil-fuel combustion sources equipped with selective catalytic reducers was observed, suggesting that the catalytic reduction of NOx increases δ(15)N-NOx values relative to the NOx produced through fossil-fuel combustion processes. Combining the δ(15)N-NOx measured in this study with previous published values, a δ(15)N-NOx regional and seasonal isoscape was constructed for the contiguous U.S., which demonstrates seasonal and regional importance of various NOx sources.

40 CFR 1065.670 - NOX intake-air humidity and temperature corrections.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 32 2010-07-01 2010-07-01 false NOX intake-air humidity and... NOX intake-air humidity and temperature corrections. See the standard-setting part to determine if you may correct NOX emissions for the effects of intake-air humidity or temperature. Use the NOX intake...

Selective NOx Recirculation for Stationary Lean-Burn Natural Gas Engines

Energy Technology Data Exchange (ETDEWEB)

Nigel Clark; Gregory Thompson; Richard Atkinson; Richard Turton; Chamila Tissera; Emre Tatli; Andy Zimmerman

2005-12-28

Selective NOx Recirculation (SNR) involves cooling the engine exhaust gas and then adsorbing the oxides of nitrogen (NOx) from the exhaust stream, followed by the periodic desorption of NOx. By returning the desorbed, concentrated NOx into the engine intake and through the combustion chamber, a percentage of the NOx is decomposed during the combustion process. An initial study of NOx decomposition during lean-burn combustion was concluded in 2004 using a 1993 Cummins L10G 240hp natural gas engine. It was observed that the air/fuel ratio, injected NO (nitric oxide) quantity and engine operating points affected NOx decomposition rates of the engine. Chemical kinetic modeling results were also used to determine optimum NOx decomposition operating points and were published in the 2004 annual report. A NOx decomposition rate of 27% was measured from this engine under lean-burn conditions while the software model predicted between 35-42% NOx decomposition for similar conditions. A later technology 1998 Cummins L10G 280hp natural gas engine was procured with the assistance of Cummins Inc. to replace the previous engine used for 2005 experimental research. The new engine was equipped with an electronic fuel management system with closed-loop control that provided a more stable air/fuel ratio control and improved the repeatability of the tests. The engine was instrumented with an in-cylinder pressure measurement system and electronic controls, and was adapted to operate over a range of air/fuel ratios. The engine was connected to a newly commissioned 300hp alternating current (AC) motoring dynamometer. The second experimental campaign was performed to acquire both stoichiometric and slightly rich (0.97 lambda ratio) burn NOx decomposition rates. Effects of engine load and speed on decomposition were quantified, but Exhaust Gas Recirculation (EGR) was not varied independently. Decomposition rates of up to 92% were demonstrated. Following recommendations at the 2004 ARES peer

40 CFR 96.83 - Applying for NOX Budget opt-in permit.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Applying for NOX Budget opt-in permit... PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS Individual Unit Opt-ins § 96.83 Applying for NOX Budget opt-in permit. (a) Applying for...

Characteristics of fundamental combustion and NOx emission using various rank coals.

Science.gov (United States)

Kim, Sung Su; Kang, Youn Suk; Lee, Hyun Dong; Kim, Jae-Kwan; Hong, Sung Chang

2011-03-01

Eight types of coals of different rank were selected and their fundamental combustion characteristics were examined along with the conversion of volatile nitrogen (N) to nitrogen oxides (NOx)/fuel N to NOx. The activation energy, onset temperature, and burnout temperature were obtained from the differential thermogravimetry curve and Arrhenius plot, which were derived through thermo-gravimetric analysis. In addition, to derive the combustion of volatile N to NOx/fuel N to NOx, the coal sample, which was pretreated at various temperatures, was burned, and the results were compared with previously derived fundamental combustion characteristics. The authors' experimental results confirmed that coal rank was highly correlated with the combustion of volatile N to NOx/fuel N to NOx.

40 CFR 97.83 - Applying for NOX Budget opt-in permit.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Applying for NOX Budget opt-in permit... PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS Individual Unit Opt-ins. § 97.83 Applying for NOX Budget opt-in permit. (a) Applying for initial NO X Budget opt...

ShenFu Preparation Protects AML12 Cells Against Palmitic Acid-Induced Injury Through Inhibition of Both JNK/Nox4 and JNK/NFκB Pathways

Directory of Open Access Journals (Sweden)

Jia-Fu Ji

2018-02-01

Full Text Available Background/Aims: Nonalcoholic steatohepatitis includes steatosis along with liver inflammation, hepatocyte injury and fibrosis. In this study, we investigated the protective role and the potential mechanisms of a traditional Chinese medicine ShenFu (SF preparation in an in vitro hepatic steatosis model. Methods: In palmitic acid (PA-induced murine hepatic AML12 cell injury, effects of SF preparation on cellular apoptosis and intracellular triglyceride (iTG level were assessed using TUNEL and TG Colorimetric Assay. Reactive oxygen species (ROS and mitochondrial membrane potential (MMP levels were measured using DCF and JC-1 assay. Cytokine levels were evaluated using ELISA assay. Immunoblot was used to compare the activation level of c-Jun N terminal kinase (JNK, NADPH oxidase (Nox4, and NFκB pathways. Results: Addition of SF preparation prevented PA-mediated increase of apoptosis and iTG as well as IL-8 and IL-6. In PA-treated cell, SF preparation reduced the level of Nox4 and ROS, while increasing the level of MMP and the expression of manganese superoxide dismutase (MnSOD and catalase, indicating emendation of mitochondrial dysfunction. Nox4 inhibitor GKT137381 prevented PA-induced increase of ROS and apoptosis, while decreasing iTG slightly and not influencing the level of IL-8 and IL-6. SF preparation prevented PA-induced upregulation of phospho-JNK. JNK inhibitor SP600125 prevented PA-mediated increase of Nox4, IL-8, IL-6 and iTG. Nuclear translocation of NFκB/p65 was detected in PA-treated cells, which was prevented by SF preparation. An IκB degradation inhibitor, BAY11-7082, prevented PA-induced increase of IL-8 and IL-6 as well as iTG, whereas it only decreased ROS levels slightly and showed no influence on cellular apoptosis. Conclusion: SF preparation shows a beneficial role in prevention of hepatocyte injury by attenuating oxidative stress and cytokines production at least partially through inhibition of JNK/Nox4 and JNK

Impact of FCC regenerator design in the NOx emissions

Energy Technology Data Exchange (ETDEWEB)

Pereira, Hugo Borges; Sandes, Emanuel Freire; Gilbert, William Richard; Roncolatto, Rodolfo Eugenio; Gobbo, Rodrigo; Casavechia, Luiz Carlos; Candido, William Victor Carlos [Petroleo Brasileiro S.A. (PETROBRAS), Rio de Janeiro, RJ (Brazil); Bridi, Patricia Elaine [Possebon Engenharia, Sao Mateus do Sul, PR (Brazil)

2012-07-01

Fluid Catalytic Cracking (FCC) is the main point source of NOx in the refinery and it is responsible for at least 20% of the total NOx emissions from the refineries. The thermal NOx formation in the FCC regenerator is negligible. However, half of the feed nitrogen is converted to coke, and is burned in the regenerator. The majority of coke nitrogen is reduced to N2 and less than 10% is converted to NOx. This number may vary significantly with the oxygen excess in the flue gas and other operational conditions. With the purpose of evaluating the impact of different regenerator designs in NOx formation, several tests were carried out in the PETROBRAS FCC prototype unit. The test unit is equipped with adiabatic insulation and a CO boiler, allowing it to reproduce the heat balance of a commercial FCC and to operate either in full combustion or partial combustion. Two different designs of FCC regenerators were evaluated: single stage regenerator (the existing configuration) and two stage regenerator, with the catalyst bed divided into two sections by a structured packing baffle. It was observed in the tests that the combustion regime had a very strong effect on NOx formation. In full combustion, the effect of the FCC operating variables: excess oxygen, combustion promoter content in catalyst and regenerator design could be identified. The two stage configuration was capable of decreasing NOx emissions by 30%. In partial combustion, the effect of the CO-boiler variables on NOx emissions was overwhelming, but the use of the structured packing baffle was able to improve the catalyst regeneration.(author)

Nox2 in regulatory T cells promotes angiotensin II-induced cardiovascular remodeling.

Science.gov (United States)

Emmerson, Amber; Trevelin, Silvia Cellone; Mongue-Din, Heloise; Becker, Pablo D; Ortiz, Carla; Smyth, Lesley A; Peng, Qi; Elgueta, Raul; Sawyer, Greta; Ivetic, Aleksandar; Lechler, Robert I; Lombardi, Giovanna; Shah, Ajay M

2018-04-24

The superoxide-generating enzyme Nox2 contributes to hypertension and cardiovascular remodeling triggered by activation of the renin-angiotensin system. Multiple Nox2-expressing cells are implicated in angiotensin II (AngII)-induced pathophysiology, but the importance of Nox2 in leukocyte subsets is poorly understood. Here, we investigated the role of Nox2 in T cells, particularly Tregs. Mice globally deficient in Nox2 displayed increased numbers of Tregs in the heart at baseline whereas AngII-induced T-effector cell (Teffs) infiltration was inhibited. To investigate the role of Treg Nox2, we generated a mouse line with CD4-targeted Nox2 deficiency (Nox2fl/flCD4Cre+). These animals showed inhibition of AngII-induced hypertension and cardiac remodeling related to increased tissue-resident Tregs and reduction in infiltrating Teffs, including Th17 cells. The protection in Nox2fl/flCD4Cre+ mice was reversed by anti-CD25 Ab-depletion of Tregs. Mechanistically, Nox2-/y Tregs showed higher in vitro suppression of Teffs proliferation than WT Tregs, increased nuclear levels of FoxP3 and NF-κB, and enhanced transcription of CD25, CD39, and CD73. Adoptive transfer of Tregs confirmed that Nox2-deficient cells had greater inhibitory effects on AngII-induced heart remodeling than WT cells. These results identify a previously unrecognized role of Nox2 in modulating suppression of Tregs, which acts to enhance hypertension and cardiac remodeling.

ERK1/2 pathway is involved in renal gluconeogenesis inhibition under conditions of lowered NADPH oxidase activity.

Science.gov (United States)

Winiarska, Katarzyna; Jarzyna, Robert; Dzik, Jolanta M; Jagielski, Adam K; Grabowski, Michal; Nowosielska, Agata; Focht, Dorota; Sierakowski, Bartosz

2015-04-01

The aim of this study was to elucidate the mechanisms involved in the inhibition of renal gluconeogenesis occurring under conditions of lowered activity of NADPH oxidase (Nox), the enzyme considered to be one of the main sources of reactive oxygen species in kidneys. The in vitro experiments were performed on primary cultures of rat renal proximal tubules, with the use of apocynin, a selective Nox inhibitor, and TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a potent superoxide radical scavenger. In the in vivo experiments, Zucker diabetic fatty (ZDF) rats, a well established model of diabetes type 2, were treated with apocynin solution in drinking water. The main in vitro findings are the following: (1) both apocynin and TEMPOL attenuate the rate of gluconeogenesis, inhibiting the step catalyzed by phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme of the process; (2) in the presence of the above-noted compounds the expression of PEPCK and the phosphorylation of transcription factor CREB and ERK1/2 kinases are lowered; (3) both U0126 (MEK inhibitor) and 3-(2-aminoethyl)-5-((4-ethoxyphenyl)methylene)-2,4-thiazolidinedione (ERK inhibitor) diminish the rate of glucose synthesis via mechanisms similar to those of apocynin and TEMPOL. The observed apocynin in vivo effects include: (1) slight attenuation of hyperglycemia; (2) inhibition of renal gluconeogenesis; (3) a decrease in renal PEPCK activity and content. In view of the results summarized above, it can be concluded that: (1) the lowered activity of the ERK1/2 pathway is of importance for the inhibition of renal gluconeogenesis found under conditions of lowered superoxide radical production by Nox; (2) the mechanism of this phenomenon includes decreased PEPCK expression, resulting from diminished activity of transcription factor CREB; (3) apocynin-evoked inhibition of renal gluconeogenesis contributes to the hypoglycemic action of this compound observed in diabetic animals. Thus, the study has

Serotonin disturbs colon epithelial tolerance of commensal E. coli by increasing NOX2-derived superoxide.

Science.gov (United States)

Banskota, Suhrid; Regmi, Sushil Chandra; Gautam, Jaya; Gurung, Pallavi; Lee, Yu-Jeong; Ku, Sae Kwang; Lee, Jin-Hyung; Lee, Jintae; Chang, Hyeun Wook; Park, Sang Joon; Kim, Jung-Ae

2017-05-01

Adherent-invasive E. coli colonization and Toll-like receptor (TLR) expression are increased in the gut of inflammatory bowel disease (IBD) patients. However, the underlying mechanism of such changes has not been determined. In the current study, it was examined whether gut serotonin (5-hydroxytryptamine, 5-HT) can induce adherent-invasive E. coli colonization and increase TLR expression. In a co-culture system, commensal E. coli strain (BW25113, BW) adhered minimally to colon epithelial cells, but this was significantly enhanced by 5-HT to the level of a pathogenic strain (EDL933). Without inducing bacterial virulence, such as, biofilm formation, 5-HT enhanced BW-induced signaling in colon epithelial cells, that is, NADPH oxidase (NOX)-dependent superoxide production, the up-regulations of IL-8, TLR2, TLR4, and ICAM-1, and the down-regulations of E-cadherin and claudin-2. In a manner commensurate with these gene modulations, BW induced an increase in NF-κB and a decrease in GATA reporter signals in colon epithelial cells. However, 5-HT-enhanced BW adhesion and colon epithelial responses were blocked by knock-down of NOX2, TLR2, or TLR4. In normal mice, 5-HT induced the invasion of BW into gut submucosa, and the observed molecular changes were similar to those observed in vitro, except for significant increases in TNFα and IL-1β, and resulted in death. In dextran sulfate sodium-induced colitis mice (an IBD disease model), in which colonic 5-HT levels were markedly elevated, BW administration induced death in along with large amount of BW invasion into colon submucosa, and time to death was negatively related to the amount of BW injected. Taken together, our results demonstrate that 5-HT induces the invasion of commensal E. coli into gut submucosa by amplifying commensal bacteria-induced epithelial signaling (superoxide production and the inductions of NOX2 and TLR2/TLR4). The authors suggest that these changes may constitute the molecular basis for the

Selective NOx Recirculation for Stationary Lean-Burn Natural Gas Engines

Energy Technology Data Exchange (ETDEWEB)

Nigel N. Clark

2006-12-31

Nitric oxide (NO) and nitrogen dioxide (NO2) generated by internal combustion (IC) engines are implicated in adverse environmental and health effects. Even though lean-burn natural gas engines have traditionally emitted lower oxides of nitrogen (NOx) emissions compared to their diesel counterparts, natural gas engines are being further challenged to reduce NOx emissions to 0.1 g/bhp-hr. The Selective NOx Recirculation (SNR) approach for NOx reduction involves cooling the engine exhaust gas and then adsorbing the NOx from the exhaust stream, followed by the periodic desorption of NOx. By sending the desorbed NOx back into the intake and through the engine, a percentage of the NOx can be decomposed during the combustion process. SNR technology has the support of the Department of Energy (DOE), under the Advanced Reciprocating Engine Systems (ARES) program to reduce NOx emissions to under 0.1 g/bhp-hr from stationary natural gas engines by 2010. The NO decomposition phenomenon was studied using two Cummins L10G natural gas fueled spark-ignited (SI) engines in three experimental campaigns. It was observed that the air/fuel ratio ({lambda}), injected NO quantity, added exhaust gas recirculation (EGR) percentage, and engine operating points affected NOx decomposition rates within the engine. Chemical kinetic model predictions using the software package CHEMKIN were performed to relate the experimental data with established rate and equilibrium models. The model was used to predict NO decomposition during lean-burn, stoichiometric burn, and slightly rich-burn cases with added EGR. NOx decomposition rates were estimated from the model to be from 35 to 42% for the lean-burn cases and from 50 to 70% for the rich-burn cases. The modeling results provided an insight as to how to maximize NOx decomposition rates for the experimental engine. Results from this experiment along with chemical kinetic modeling solutions prompted the investigation of rich-burn operating conditions

Reducing global NOx emissions: developing advanced energy and transportation technologies.

Science.gov (United States)

Bradley, Michael J; Jones, Brian M

2002-03-01

Globally, energy demand is projected to continue to increase well into the future. As a result, global NOx emissions are projected to continue on an upward trend for the foreseeable future as developing countries increase their standards of living. While the US has experienced improvements in reducing NOx emissions from stationary and mobile sources to reduce ozone, further progress is needed to reduce the health and ecosystem impacts associated with NOx emissions. In other parts of the world, (in developing countries in particular) NOx emissions have been increasing steadily with the growth in demand for electricity and transportation. Advancements in energy and transportation technologies may help avoid this increase in emissions if appropriate policies are implemented. This paper evaluates commercially available power generation and transportation technologies that produce fewer NOx emissions than conventional technologies, and advanced technologies that are on the 10-year commercialization horizon. Various policy approaches will be evaluated which can be implemented on the regional, national and international levels to promote these advanced technologies and ultimately reduce NOx emissions. The concept of the technology leap is offered as a possibility for the developing world to avoid the projected increases in NOx emissions.

Study on the Conversion of Fuel Nitrogen Into NOx

Directory of Open Access Journals (Sweden)

Raminta Plečkaitienė

2011-12-01

Full Text Available The aim of this work is to investigate NOx regularities combusting fuels having high concentration of nitrogen and to develop methods that will reduce the conversion of fuel nitrogen into NOx. There are three solutions to reducing NOx concentration: the combustion of fuel mixing it with other types of “clean” fuel containing small amounts of nitrogen, laundering fuel and the combustion of fuel using carbon additives. These solutions can help with reducing the amount of nitrogen in the wood waste of furniture by about 30% by washing fuel with water. Therefore, NOx value may decrease by about 35%.Article in Lithuanian

Effects space velocity and gas velocity on DeNOx catalyst with HC reductant; HC tenka NOx kangen shokubai no kukan sokudo oyobi gas ryusoku no eikyo

Energy Technology Data Exchange (ETDEWEB)

Niimura, K.; Tsujimura, K.

1995-04-20

Discussions were given on the hydrocarbon added reduction catalyst method to reduce NOx in diesel engine exhaust gas. An experiment was carried out with actual exhaust gas from a diesel engine by using a copper ion exchanged zeolite catalyst that has been coated on a honeycomb type substrate, and using propylene as a reductant. When the catalyst volume was changed with the exhaust gas space velocity kept constant, the NOx conversion ratio decreased as the catalyst length is decreased, and the activity shifted to the lower temperature side. The NOx reduction efficiency increased if the faster the gas flow velocity. On the other hand, if the gas flow velocity is slow, the NOx reduction can be carried out with relatively small amount of the reductant. When the catalyst volume was changed with the passing gas amount kept constant, the NOx conversion ratio decreased largely if the catalyst length is decreased. Further, the NOx reduction characteristics shift to the higher temperature side. In the catalyst length direction, the NOx reduction activity shows a relatively uniform action. However, a detailed observation reveals that the reaction heat in the catalyst is transmitted to the wake improving the activity, hence the further down the flow, the NOx conversion ratio gets higher in efficiency. 5 refs., 5 figs., 3 tabs.

Impact of NOx and OH on secondary organic aerosol formation from β-pinene photooxidation

Directory of Open Access Journals (Sweden)

M. Sarrafzadeh

2016-09-01

Full Text Available In this study, the NOx dependence of secondary organic aerosol (SOA formation from photooxidation of the biogenic volatile organic compound (BVOC β-pinene was comprehensively investigated in the Jülich Plant Atmosphere Chamber. Consistent with the results of previous NOx studies we found increases of SOA yields with increasing [NOx] at low-NOx conditions ([NOx]0  <  30 ppb, [BVOC]0 ∕ [NOx]0  >  10 ppbC ppb−1. Furthermore, increasing [NOx] at high-NOx conditions ([NOx]0  >  30 ppb, [BVOC]0 ∕ [NOx]0  ∼  10 to  ∼  2.6 ppbC ppb−1 suppressed the SOA yield. The increase of SOA yield at low-NOx conditions was attributed to an increase of OH concentration, most probably by OH recycling in NO + HO2  →  NO2 + OH reaction. Separate measurements without NOx addition but with different OH primary production rates confirmed the OH dependence of SOA yields. After removing the effect of OH concentration on SOA mass growth by keeping the OH concentration constant, SOA yields only decreased with increasing [NOx]. Measuring the NOx dependence of SOA yields at lower [NO] ∕ [NO2] ratio showed less pronounced increase in both OH concentration and SOA yield. This result was consistent with our assumption of OH recycling by NO and to SOA yields being dependent on OH concentrations. Our results furthermore indicated that NOx dependencies vary for different NOx compositions. A substantial fraction of the NOx-induced decrease of SOA yields at high-NOx conditions was caused by NOx-induced suppression of new particle formation (NPF, which subsequently limits the particle surface where low volatiles condense. This was shown by probing the NOx dependence of SOA formation in the presence of seed particles. After eliminating the effect of NOx-induced suppression of NPF and NOx-induced changes of OH concentrations, the remaining effect of NOx on the SOA yield from �

Suppression of new particle formation from monoterpene oxidation by NOx

Science.gov (United States)

Wildt, J.; Mentel, T. F.; Kiendler-Scharr, A.; Hoffmann, T.; Andres, S.; Ehn, M.; Kleist, E.; Müsgen, P.; Rohrer, F.; Rudich, Y.; Springer, M.; Tillmann, R.; Wahner, A.

2014-03-01

The impact of nitrogen oxides (NOx = NO + NO2) on new particle formation (NPF) and on photochemical ozone production from real plant volatile organic compound (BVOC) emissions was studied in a laboratory setup. At high NOx conditions ([BVOC] / [NOx] 23 ppb) new particle formation was suppressed. Instead, photochemical ozone formation was observed resulting in higher hydroxyl radical (OH) and lower nitrogen monoxide (NO) concentrations. When [NO] was reduced back to levels below 1 ppb by OH reactions, NPF was observed. Adding high amounts of NOx caused NPF to be slowed by orders of magnitude compared to analogous experiments at low NOx conditions ([NOx] ~300 ppt), although OH concentrations were higher. Varying NO2 photolysis enabled showing that NO was responsible for suppression of NPF. This suggests that peroxy radicals are involved in NPF. The rates of NPF and photochemical ozone production were related by power law dependence with an exponent approaching -2. This exponent indicated that the overall peroxy radical concentration must have been similar when NPF occurred. Thus, permutation reactions of first-generation peroxy radicals cannot be the rate limiting step in NPF from monoterpene oxidation. It was concluded that permutation reactions of higher generation peroxy-radical-like intermediates limit the rate of new particle formation. In contrast to the strong effects on the particle numbers, the formation of particle mass was substantially less sensitive to NOx concentrations. If at all, yields were reduced by about an order of magnitude only at very high NOx concentrations.

DESIGN REPORT: LOW-NOX BURNERS FOR PACKAGE BOILERS

Science.gov (United States)

The report describes a low-NOx burner design, presented for residual-oil-fired industrial boilers and boilers cofiring conventional fuels and nitrated hazardous wastes. The burner offers lower NOx emission levels for these applications than conventional commercial burners. The bu...

Low NOx combustion technologies for high-temperature natural gas combustion

International Nuclear Information System (INIS)

Flamme, Michael

1999-01-01

Because of the high process temperature which is required for some processes like glass melting and the high temperature to which the combustion air is preheated, NOx emission are extremely high. Even at these high temperatures, NOx emissions could be reduced drastically by using advanced combustion techniques such as staged combustion or flame-less oxidation, as experimental work has shown. In the case of oxy-fuel combustion, the NOx emission are also very high if conventional burners are used. The new combustion techniques achieve similar NOx reductions. (author)

NADPH Oxidase Activity in Cerebral Arterioles Is a Key Mediator of Cerebral Small Vessel Disease-Implications for Prevention.

Science.gov (United States)

McCarty, Mark F

2015-04-15

Cerebral small vessel disease (SVD), a common feature of brain aging, is characterized by lacunar infarcts, microbleeds, leukoaraiosis, and a leaky blood-brain barrier. Functionally, it is associated with cognitive decline, dementia, depression, gait abnormalities, and increased risk for stroke. Cerebral arterioles in this syndrome tend to hypertrophy and lose their capacity for adaptive vasodilation. Rodent studies strongly suggest that activation of Nox2-dependent NADPH oxidase activity is a crucial driver of these structural and functional derangements of cerebral arterioles, in part owing to impairment of endothelial nitric oxide synthase (eNOS) activity. This oxidative stress may also contribute to the breakdown of the blood-brain barrier seen in SVD. Hypertension, aging, metabolic syndrome, smoking, hyperglycemia, and elevated homocysteine may promote activation of NADPH oxidase in cerebral arterioles. Inhibition of NADPH oxidase with phycocyanobilin from spirulina, as well as high-dose statin therapy, may have potential for prevention and control of SVD, and high-potassium diets merit study in this regard. Measures which support effective eNOS activity in other ways-exercise training, supplemental citrulline, certain dietary flavonoids (as in cocoa and green tea), and capsaicin, may also improve the function of cerebral arterioles. Asian epidemiology suggests that increased protein intakes may decrease risk for SVD; conceivably, arginine and/or cysteine-which boosts tissue glutathione synthesis, and can be administered as N-acetylcysteine-mediate this benefit. Ameliorating the risk factors for SVD-including hypertension, metabolic syndrome, hyperglycemia, smoking, and elevated homocysteine-also may help to prevent and control this syndrome, although few clinical trials have addressed this issue to date.

40 CFR 97.386 - Withdrawal from CAIR NOX Ozone Season Trading Program.

Science.gov (United States)

2010-07-01

... Trading Program. 97.386 Section 97.386 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS CAIR NOX Ozone Season Opt-in Units § 97.386 Withdrawal from CAIR NOX Ozone Season Trading Program...

Genome-wide analysis and identification of cytokinin oxidase/dehydrogenase (CKX gene family in foxtail millet (Setaria italica

Directory of Open Access Journals (Sweden)

Yuange Wang

2014-08-01

Full Text Available Cytokinin oxidase/dehydrogenase (CKX; EC.1.5.99.12 regulates cytokinin (CK level in plants and plays an essential role in CK regulatory processes. CKX proteins are encoded by a small gene family with a varying number of members in different plants. In spite of their physiological importance, systematic analyses of SiCKX genes in foxtail millet have not yet been examined. In this paper, we report the genome wide isolation and characterization of SiCKXs using bioinformatic methods. A total of 11 members of the family were identified in the foxtail millet genome. SiCKX genes were distributed in seven chromosomes (chromosome 1, 3, 4, 5, 6, 7, and 11. The coding sequences of all the SiCKX genes were disrupted by introns, with numbers varying from one to four. These genes expanded in the genome mainly due to segmental duplication events. Multiple alignment and motif display results showed that all SiCKX proteins share FAD- and CK-binding domains. Putative cis-elements involved in Ca2 +-response, abiotic stress response, light and circadian rhythm regulation, disease resistance and seed development were present in the promoters of SiCKX genes. Expression data mining suggested that SiCKX genes have diverse expression patterns. Real-time PCR analysis indicated that all 11 SiCKX genes were up-regulated in embryos under 6-BA treatment, and some were NaCl or PEG inducible. Collectively, these results provide molecular insights into CKX research in plants.

Structure, organization, and transcriptional regulation of a family of copper radical oxidase genes in the lignin-degrading basidiomycete Phanerochaete chrysosporium

Science.gov (United States)

Amber Vanden Wymelenberg; Grzegorz Sabat; Michael Mozuch; Philip J. Kersten; Dan Cullen; Robert A. Blanchette

2006-01-01

The white rot basidiomycete Phanerochaete chrysosporium produces an array of nonspecific extracellular enzymes thought to be involved in lignin degradation, including lignin peroxidases, manganese peroxidases, and the H2O2-generating copper radical oxidase, glyoxal oxidase (GLX). Preliminary analysis of the P. chrysosporium draft genome had identified six sequences...

Oxidase-based biocatalytic processes

DEFF Research Database (Denmark)

Ramesh, Hemalata; Woodley, John; Krühne, Ulrich

interestingbiocatalystsbecause they use a mild oxidant (oxygen) as a substrateas opposed to their chemical counterparts which use strong oxidants such as permanganates. A class of oxidases calledmonoamine oxidases has been used as the central case study for the thesis. The rationale for choosing thissystemis that it has been...

TLR4-NOX4-AP-1 signaling mediates lipopolysaccharide-induced CXCR6 expression in human aortic smooth muscle cells

International Nuclear Information System (INIS)

Patel, Devang N.; Bailey, Steven R.; Gresham, John K.; Schuchman, David B.; Shelhamer, James H.; Goldstein, Barry J.; Foxwell, Brian M.; Stemerman, Michael B.; Maranchie, Jodi K.; Valente, Anthony J.; Mummidi, Srinivas; Chandrasekar, Bysani

2006-01-01

CXCL16 is a transmembrane non-ELR CXC chemokine that signals via CXCR6 to induce aortic smooth muscle cell (ASMC) proliferation. While bacterial lipopolysaccharide (LPS) has been shown to stimulate CXCL16 expression in SMC, its effects on CXCR6 are not known. Here, we demonstrate that LPS upregulates CXCR6 mRNA, protein, and surface expression in human ASMC. Inhibition of TLR4 with neutralizing antibodies or specific siRNA interference blocked LPS-mediated CXCR6 expression. LPS stimulated both AP-1 (c-Fos, c-Jun) and NF-κB (p50 and p65) activation, but only inhibition of AP-1 attenuated LPS-induced CXCR6 expression. Using dominant negative expression vectors and siRNA interference, we demonstrate that LPS induces AP-1 activation via MyD88, TRAF6, ERK1/2, and JNK signaling pathways. Furthermore, the flavoprotein inhibitor diphenyleniodonium chloride significantly attenuated LPS-mediated AP-1-dependent CXCR6 expression, as did inhibition of NOX4 NADPH oxidase by siRNA. Finally, CXCR6 knockdown inhibited CXCL16-induced ASMC proliferation. These results demonstrate that LPS-TLR4-NOX4-AP-1 signaling can induce CXCR6 expression in ASMC, and suggest that the CXCL16-CXCR6 axis may be an important proinflammatory pathway in the pathogenesis of atherosclerosis

Characterization of the 1st and 2nd EF-hands of NADPH oxidase 5 by fluorescence, isothermal titration calorimetry, and circular dichroism

Directory of Open Access Journals (Sweden)

Wei Chin-Chuan

2012-04-01

Full Text Available Abstract Background Superoxide generated by non-phagocytic NADPH oxidases (NOXs is of growing importance for physiology and pathobiology. The calcium binding domain (CaBD of NOX5 contains four EF-hands, each binding one calcium ion. To better understand the metal binding properties of the 1st and 2nd EF-hands, we characterized the N-terminal half of CaBD (NCaBD and its calcium-binding knockout mutants. Results The isothermal titration calorimetry measurement for NCaBD reveals that the calcium binding of two EF-hands are loosely associated with each other and can be treated as independent binding events. However, the Ca2+ binding studies on NCaBD(E31Q and NCaBD(E63Q showed their binding constants to be 6.5 × 105 and 5.0 × 102 M-1 with ΔHs of -14 and -4 kJ/mol, respectively, suggesting that intrinsic calcium binding for the 1st non-canonical EF-hand is largely enhanced by the binding of Ca2+ to the 2nd canonical EF-hand. The fluorescence quenching and CD spectra support a conformational change upon Ca2+ binding, which changes Trp residues toward a more non-polar and exposed environment and also increases its α-helix secondary structure content. All measurements exclude Mg2+-binding in NCaBD. Conclusions We demonstrated that the 1st non-canonical EF-hand of NOX5 has very weak Ca2+ binding affinity compared with the 2nd canonical EF-hand. Both EF-hands interact with each other in a cooperative manner to enhance their Ca2+ binding affinity. Our characterization reveals that the two EF-hands in the N-terminal NOX5 are Ca2+ specific. Graphical abstract

NOx Emissions Performance and Correlation Equations for a Multipoint LDI Injector

Science.gov (United States)

He, Zhuohui J.; Chang, Clarence T.; Follen, Caitlin E.

2015-01-01

Lean Direct Injection (LDI) is a combustor concept that reduces nitrogen oxides (NOx) emissions. This paper looks at a 3-zone multipoint LDI concept developed by Parker Hannifin Corporation. The concept was tested in a flame-tube test facility at NASA Glenn Research Center. Due to test facility limitations, such as inlet air temperature and pressure, the flame-tube test was not able to cover the full set of engine operation conditions. Three NOx correlation equations were developed based on assessing NOx emissions dependencies on inlet air pressure (P3), inlet air temperature (T3), and fuel air equivalence ratio (?) to estimate the NOx emissions at the unreachable high engine power conditions. As the results, the NOx emissions are found to be a strong function of combustion inlet air temperature and fuel air equivalence ratio but a weaker function of inlet air pressure. With these three equations, the NOx emissions performance of this injector concept is calculated as a 66% reduction relative to the ICAO CAEP-6 standard using a 55:1 pressure-ratio engine cycle. Uncertainty in the NOx emissions estimation increases as the extrapolation range departs from the experimental conditions. Since maximum inlet air pressure tested was less than 50% of the full power engine inlet air pressure, a future experiment at higher inlet air pressure conditions is needed to confirm the NOx emissions dependency on inlet air pressure.

Ships going slow in reducing their NOx emissions

NARCIS (Netherlands)

Boersma, K.F.; Vinken, G.C.M.; Tournadre, J.

2015-01-01

Weaddress the lack of temporal information on ship emissions, and report on rapid short-term variations of satellite-derived shipNOx emissions between 2005 and 2012 over European seas. Our inversion is based onOMI observed troposphericNO2 columns and GEOS-Chem simulations. Average European shipNOx

Isolated sulfite oxidase deficiency.

Science.gov (United States)

Rupar, C A; Gillett, J; Gordon, B A; Ramsay, D A; Johnson, J L; Garrett, R M; Rajagopalan, K V; Jung, J H; Bacheyie, G S; Sellers, A R

1996-12-01

Isolated sulfite oxidase (SO) deficiency is an autosomal recessively inherited inborn error of sulfur metabolism. In this report of a ninth patient the clinical history, laboratory results, neuropathological findings and a mutation in the sulfite oxidase gene are described. The data from this patient and previously published patients with isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are summarized to characterize this rare disorder. The patient presented neonatally with intractable seizures and did not progress developmentally beyond the neonatal stage. Dislocated lenses were apparent at 2 months. There was increased urine excretion of sulfite and S-sulfocysteine and a decreased concentration of plasma cystine. A lactic acidemia was present for 6 months. Liver sulfite oxidase activity was not detectable but xanthine dehydrogenase activity was normal. The boy died of respiratory failure at 32 months. Neuropathological findings of cortical necrosis and extensive cavitating leukoencephalopathy were reminiscent of those seen in severe perinatal asphyxia suggesting an etiology of energy deficiency. A point mutation that resulted in a truncated protein missing the molybdenum-binding site has been identified.

Effects of stevia on synaptic plasticity and NADPH oxidase level of CNS in conditions of metabolic disorders caused by fructose.

Science.gov (United States)

Chavushyan, V A; Simonyan, K V; Simonyan, R M; Isoyan, A S; Simonyan, G M; Babakhanyan, M A; Hovhannisyian, L E; Nahapetyan, Kh H; Avetisyan, L G; Simonyan, M A

2017-12-19

Excess dietary fructose intake associated with metabolic syndrome and insulin resistance and increased risk of developing type 2 diabetes. Previous animal studies have reported that diabetic animals have significantly impaired behavioural and cognitive functions, pathological synaptic function and impaired expression of glutamate receptors. Correction of the antioxidant status of laboratory rodents largely prevents the development of fructose-induced plurimetabolic changes in the nervous system. We suggest a novel concept of efficiency of Stevia leaves for treatment of central diabetic neuropathy. By in vivo extracellular studies induced spike activity of hippocampal neurons during high frequency stimulation of entorhinal cortex, as well as neurons of basolateral amygdala to high-frequency stimulation of the hippocampus effects of Stevia rebaudiana Bertoni plant evaluated in synaptic activity in the brain of fructose-enriched diet rats. In the conditions of metabolic disorders caused by fructose, antioxidant activity of Stevia rebaudiana was assessed by measuring the NOX activity of the hippocampus, amygdala and spinal cord. In this study, the characteristic features of the metabolic effects of dietary fructose on synaptic plasticity in hippocampal neurons and basolateral amygdala and the state of the NADPH oxidase (NOX) oxidative system of these brain formations are revealed, as well as the prospects for development of multitarget and polyfunctional phytopreparations (with adaptogenic, antioxidant, antidiabetic, nootropic activity) from native raw material of Stevia rebaudiana. Stevia modulates degree of expressiveness of potentiation/depression (approaches but fails to achieve the norm) by shifting the percentage balance in favor of depressor type of responses during high-frequency stimulation, indicating its adaptogenic role in plasticity of neural networks. Under the action of fructose an increase (3-5 times) in specific quantity of total fraction of NOX

Rac-1 as a new therapeutic target in cerebro- and cardio-vascular diseases.

Science.gov (United States)

Carrizzo, Albino; Forte, Maurizio; Lembo, Maria; Formisano, Luigi; Puca, Annibale A; Vecchione, Carmine

2014-01-01

Growing evidence indicates that overproduction of reactive oxygen species (ROS) plays a prominent role in the development of cardio- and cerebro-vascular diseases. Among the mechanisms identified to produce oxidative stress in the vascular wall, those mediated by membrane-bound NAD(P)H oxidases represent a major one. NAD(P)H oxidases are a family of enzymes that generate ROS both in phagocytic and non-phagocytic cell types. Vascular NAD(P)H oxidase contains the membrane-bound subunits Nox1, Nox2 (gp91phox), Nox4 and p22phox, the catalytic site of the oxidase, and the cytosolic components p47phox and p67phox. Rac1 (Ras-related C3 botulinum toxin substrate1) is a small GTPase essential for the assembly and activation of NADPH oxidase. Several molecular and cellular studies have reported the involvement of Rac1 in different cardiovascular pathologies, such as vascular smooth muscle proliferation, cardiomyocyte hypertrophy, endothelial cell shape change, atherosclerosis and endothelial dysfunction in hypertension. In addition, increased activation of NADPH oxidase by Rac1 has been reported in animals and humans after myocardial infarction and heart failure. The Rac1/NADPH pathway has also been found involved in different pathologies of the cerebral district, such as ischemic stroke, cognitive impairment, subaracnoid hemorrhage and neuronal oxidative damage typical of several neurodegenerative disorders. In addition, thrombotic events are an important step in the onset of cardio- and cerebrovascular diseases. Rac1 has been found involved also in platelet activation, inducing actin polymerization and lamellipodia formation, which are necessary steps for platelet aggregation. Taken together, the evidence candidates Rac1 as a new pharmacological target of cardiovascular and cerebrovascular diseases. Although the involvement of Rac1 in the beneficial pleiotropic effects of drugs such as statins is well known, and the onset of numerous side effects has raised concern for the

Astragaloside IV prevents damage to human mesangial cells through the inhibition of the NADPH oxidase/ROS/Akt/NF‑κB pathway under high glucose conditions.

Science.gov (United States)

Sun, Li; Li, Weiping; Li, Weizu; Xiong, Li; Li, Guiping; Ma, Rong

2014-07-01

Glomerular hypertrophy and hyperfiltration are the two major pathological characteristics of the early stages of diabetic nephropathy (DN), which are respectively related to mesangial cell (MC) proliferation and a decrease in calcium influx conducted by canonical transient receptor potential cation channel 6 (TRPC6). The marked increase in the production of reactive oxygen species (ROS) induced by hyperglycemia is the main sponsor of multiple pathological pathways in DN. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of ROS production in MCs. Astragaloside IV (AS‑IV) is an active ingredient of Radix Astragali which has a potent antioxidative effect. In this study, we aimed to investigate whether high glucose (HG)‑induced NADPH oxidase activation and ROS production contribute to MC proliferation and the downregulation of TRPC6 expression; we also wished to determine the effects of AS‑IV on MCs under HG conditions. Using a human glomerular mesangial cell line, we found that treatment with AS‑IV for 48 h markedly attenuated HG‑induced proliferation and the hypertrophy of MCs in a dose‑dependent manner. The intracellular ROS level was also markedly reduced following treatment with AS‑IV. In addition, the enhanced activity of NADPH oxidase and the expression level of NADPH oxidase 4 (Nox4) protein were decreased. Treatment with AS‑IV also inhibited the phosphorylation level of Akt and IκBα in the MCs. In addition, TRPC6 protein expression and the intracellular free calcium concentration were also markedly reduced following treatment with AS‑IV under HG conditions. These results suggest that AS‑IV inhibits HG‑induced mesangial cell proliferation and glomerular contractile dysfunction through the NADPH oxidase/ROS/Akt/nuclear factor‑κB (NF‑κB) pathway, providing a new perspective for the clinical treatment of DN.

Low-level NOx removal in ambient air by pulsed corona technology

NARCIS (Netherlands)

Beckers, F.J.C.M.; Hoeben, W.F.L.M.; Pemen, A.J.M.; Heesch, van E.J.M.

2013-01-01

Although removal of NOx by (pulsed) corona discharges has been thoroughly investigated for high concentrations of NOx in flue gas, removal of low levels in ambient air proves to be a difficult task. (Sub) ppm NOx levels exist in traffic tunnels due to accumulation of exhaust gases. The application

Salvianolic acid B protects against paraquat-induced pulmonary injury by mediating Nrf2/Nox4 redox balance and TGF-β1/Smad3 signaling

Energy Technology Data Exchange (ETDEWEB)

Liu, Bin, E-mail: iamicehe@163.com [Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Logistic University of Chinese People' s Armed Police Force, Tianjin 300162 (China); Cao, Bo, E-mail: caobo19814@126.com [Logistics University of Chinese People' s Armed Police Force, Tianjin 300162 (China); Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Tianjin, 300162 (China); Zhang, Di, E-mail: zhangdibad@163.com [Department of Otorhinolaryngology Head and Neck Surgery, Institute of Otorhinolaryngology, Tianjin First Center Hospital, Tianjin 300192 (China); Xiao, Na [Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Logistic University of Chinese People' s Armed Police Force, Tianjin 300162 (China); Chen, Hong [Logistics University of Chinese People' s Armed Police Force, Tianjin 300162 (China); Li, Guo-qiang; Peng, Shou-chun [Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Logistic University of Chinese People' s Armed Police Force, Tianjin 300162 (China); Wei, Lu-qing, E-mail: luqing-wei@163.com [Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Logistic University of Chinese People' s Armed Police Force, Tianjin 300162 (China)

2016-10-15

The present study was aimed at exploring the protective effects of Salvianolic acid B (SalB) against paraquat (PQ)-induced lung injury in mice. Lung fibrotic injuries were induced in mice by a single intragastrical administration of 300 mg/kg PQ, then the mice were administrated with 200 mg/kg, 400 mg/kg SalB, 100 mg/kg vitamin C (Vit C) and dexamethasone (DXM) for 14 days. PQ-triggered structure distortion, collagen overproduction, excessive inflammatory infiltration, pro-inflammatory cytokine release, and oxidative stress damages in lung tissues and mortality of mice were attenuated by SalB in a dose-dependent manner. Furthermore, SalB was noted to enhance the expression and nuclear translocation of nuclear factor erythroid 2–related factor 2 (Nrf2) and reduce expression of the reactive oxygen species-generating enzyme Nox4 [NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase-4]. SalB also inhibited the increasing expression of transforming growth factor (TGF)-β1 and the phosphorylation of its downstream target Smad3 which were enhanced by PQ. These results suggest that SalB may exert protective effects against PQ-induced lung injury and pulmonary fibrosis. Its mechanisms involve the mediation of Nrf2/Nox4 redox balance and TGF-β1/Smad3 signaling. - Highlights: • Salvianolic acid B (SalB) reduced Paraquat-induced mortality and pulmonary injury in mice. • SalB has anti-oxidation, anti-inflammatory and anti-fibrogenic effects simultaneously. • Its mechanisms were targeting Nrf2-Nox4 redox balance and TGF-β1/Smad3 signaling.

Salvianolic acid B protects against paraquat-induced pulmonary injury by mediating Nrf2/Nox4 redox balance and TGF-β1/Smad3 signaling

International Nuclear Information System (INIS)

Liu, Bin; Cao, Bo; Zhang, Di; Xiao, Na; Chen, Hong; Li, Guo-qiang; Peng, Shou-chun; Wei, Lu-qing

2016-01-01

The present study was aimed at exploring the protective effects of Salvianolic acid B (SalB) against paraquat (PQ)-induced lung injury in mice. Lung fibrotic injuries were induced in mice by a single intragastrical administration of 300 mg/kg PQ, then the mice were administrated with 200 mg/kg, 400 mg/kg SalB, 100 mg/kg vitamin C (Vit C) and dexamethasone (DXM) for 14 days. PQ-triggered structure distortion, collagen overproduction, excessive inflammatory infiltration, pro-inflammatory cytokine release, and oxidative stress damages in lung tissues and mortality of mice were attenuated by SalB in a dose-dependent manner. Furthermore, SalB was noted to enhance the expression and nuclear translocation of nuclear factor erythroid 2–related factor 2 (Nrf2) and reduce expression of the reactive oxygen species-generating enzyme Nox4 [NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase-4]. SalB also inhibited the increasing expression of transforming growth factor (TGF)-β1 and the phosphorylation of its downstream target Smad3 which were enhanced by PQ. These results suggest that SalB may exert protective effects against PQ-induced lung injury and pulmonary fibrosis. Its mechanisms involve the mediation of Nrf2/Nox4 redox balance and TGF-β1/Smad3 signaling. - Highlights: • Salvianolic acid B (SalB) reduced Paraquat-induced mortality and pulmonary injury in mice. • SalB has anti-oxidation, anti-inflammatory and anti-fibrogenic effects simultaneously. • Its mechanisms were targeting Nrf2-Nox4 redox balance and TGF-β1/Smad3 signaling.

40 CFR 96.142 - CAIR NOX allowance allocations.

Science.gov (United States)

2010-07-01

... the 3 highest amounts of the unit's adjusted control period heat input for 2000 through 2004, with the adjusted control period heat input for each year calculated as follows: (A) If the unit is coal-fired... CAIR NOX Allowance Allocations § 96.142 CAIR NOX allowance allocations. (a)(1) The baseline heat input...

Optical and Electronic NOx Sensors for Applications in Mechatronics

Directory of Open Access Journals (Sweden)

Scott D. Wolter

2009-05-01

Full Text Available Current production and emerging NOx sensors based on optical and nanomaterials technologies are reviewed. In view of their potential applications in mechatronics, we compared the performance of: i Quantum cascade lasers (QCL based photoacoustic (PA systems; ii gold nanoparticles as catalytically active materials in field-effect transistor (FET sensors, and iii functionalized III-V semiconductor based devices. QCL-based PA sensors for NOx show a detection limit in the sub part-per-million range and are characterized by high selectivity and compact set-up. Electrochemically synthesized gold-nanoparticle FET sensors are able to monitor NOx in a concentration range from 50 to 200 parts per million and are suitable for miniaturization. Porphyrin-functionalized III-V semiconductor materials can be used for the fabrication of a reliable NOx sensor platform characterized by high conductivity, corrosion resistance, and strong surface state coupling.

Optical and Electronic NOx Sensors for Applications in Mechatronics

Science.gov (United States)

Di Franco, Cinzia; Elia, Angela; Spagnolo, Vincenzo; Scamarcio, Gaetano; Lugarà, Pietro Mario; Ieva, Eliana; Cioffi, Nicola; Torsi, Luisa; Bruno, Giovanni; Losurdo, Maria; Garcia, Michael A.; Wolter, Scott D.; Brown, April; Ricco, Mario

2009-01-01

Current production and emerging NOx sensors based on optical and nanomaterials technologies are reviewed. In view of their potential applications in mechatronics, we compared the performance of: i) Quantum cascade lasers (QCL) based photoacoustic (PA) systems; ii) gold nanoparticles as catalytically active materials in field-effect transistor (FET) sensors, and iii) functionalized III-V semiconductor based devices. QCL-based PA sensors for NOx show a detection limit in the sub part-per-million range and are characterized by high selectivity and compact set-up. Electrochemically synthesized gold-nanoparticle FET sensors are able to monitor NOx in a concentration range from 50 to 200 parts per million and are suitable for miniaturization. Porphyrin-functionalized III-V semiconductor materials can be used for the fabrication of a reliable NOx sensor platform characterized by high conductivity, corrosion resistance, and strong surface state coupling. PMID:22412315

A hybrid plasma-chemical system for high-NOx flue gas treatment

Science.gov (United States)

Chmielewski, Andrzej G.; Zwolińska, Ewa; Licki, Janusz; Sun, Yongxia; Zimek, Zbigniew; Bułka, Sylwester

2018-03-01

The reduction of high concentrations of NOx and SO2 from simulated flue gas has been studied. Our aim was to optimise energy consumption for NOx and SO2 removal from off-gases from a diesel generator using heavy fuel oil. A hybrid process: electron beam (EB) plasma and wet scrubber has been applied. A much higher efficiency of NOx and SO2 removal was achieved in comparison to dry, ammonia free, electron beam flue gas treatment (EBFGT). A recorded removal from a concentration of 1500 ppm NOx reached 49% at a low dose of 6.5 kGy, while only 2% NOx was removed at the same dose if EB only was applied. For SO2, removal efficiency at a dose of 6.5 kGy increased from 15% (EB only) to 84% when sea water was used as a wet scrubber agent for 700 ppm SO2. The results of this study indicate that EB combined with wet scrubber is a very promising technology to be applied for removal of high concentrations of NOx and SO2 emitted from diesel engines operated e.g. on cargo ships, which are the main sources of SO2 and NOx pollution along their navigation routes.

Reburning technology - a means to reduce NOx emissions

International Nuclear Information System (INIS)

Kremer, H.; Lorra, M.

1999-01-01

Nitrogen oxide emission control technologies can be classified as either combustion modifications to minimize the NO production or post-combustion flue gas treatment to reduce the NO concentration afterwards. The techniques for minimizing NOx Production includes the use of low-NOx burners, overfire air (staged combustion) and boiler combustion optimization. Procedures for flue gas treatment can be subdivided into selective catalytic reduction (SCR) or selective non-catalytic reduction (SNCR). The re burning process is a selective non-catalytic technology which is applicable to a wide variety of boilers and can be implemented within a relatively short period of time. The NOx reduction potential of this technique is in the range of 50 % up to 70 %. (author)

Development of the Aqueous Processes for Removing NOx from Flue Gases.

Science.gov (United States)

Chappell, Gilford A.

A screening study was conducted to evaluate the capability of aqueous solutions to scrub NOx from the flue gases emitted by stationary power plants fired with fossil fuels. The report summarizes the findings of this laboratory program. The experimental program studied the following media for absorption of NOx from flue gases containing no NOx:…

Exploring flavin-containing carbohydrate oxidases

NARCIS (Netherlands)

Ferrari, Alessandro Renato

2017-01-01

Oxidases are enzymes capable of removing one or more electrons from their substrate and transfer them to molecular oxygen, forming hydrogen peroxide. Due to their high regio- and enantioselectivity, their use is preferred over traditional organic chemistry methods. Among the oxidases, flavoprotein

NADPH Oxidase Activity in Cerebral Arterioles Is a Key Mediator of Cerebral Small Vessel Disease—Implications for Prevention

Directory of Open Access Journals (Sweden)

Mark F. McCarty

2015-04-01

Full Text Available Cerebral small vessel disease (SVD, a common feature of brain aging, is characterized by lacunar infarcts, microbleeds, leukoaraiosis, and a leaky blood-brain barrier. Functionally, it is associated with cognitive decline, dementia, depression, gait abnormalities, and increased risk for stroke. Cerebral arterioles in this syndrome tend to hypertrophy and lose their capacity for adaptive vasodilation. Rodent studies strongly suggest that activation of Nox2-dependent NADPH oxidase activity is a crucial driver of these structural and functional derangements of cerebral arterioles, in part owing to impairment of endothelial nitric oxide synthase (eNOS activity. This oxidative stress may also contribute to the breakdown of the blood-brain barrier seen in SVD. Hypertension, aging, metabolic syndrome, smoking, hyperglycemia, and elevated homocysteine may promote activation of NADPH oxidase in cerebral arterioles. Inhibition of NADPH oxidase with phycocyanobilin from spirulina, as well as high-dose statin therapy, may have potential for prevention and control of SVD, and high-potassium diets merit study in this regard. Measures which support effective eNOS activity in other ways—exercise training, supplemental citrulline, certain dietary flavonoids (as in cocoa and green tea, and capsaicin, may also improve the function of cerebral arterioles. Asian epidemiology suggests that increased protein intakes may decrease risk for SVD; conceivably, arginine and/or cysteine—which boosts tissue glutathione synthesis, and can be administered as N-acetylcysteine—mediate this benefit. Ameliorating the risk factors for SVD—including hypertension, metabolic syndrome, hyperglycemia, smoking, and elevated homocysteine—also may help to prevent and control this syndrome, although few clinical trials have addressed this issue to date.

Quantifying the isotopic composition of NOx emission sources: An analysis of collection methods

Science.gov (United States)

Fibiger, D.; Hastings, M.

2012-04-01

We analyze various collection methods for nitrogen oxides, NOx (NO2 and NO), used to evaluate the nitrogen isotopic composition (δ15N). Atmospheric NOx is a major contributor to acid rain deposition upon its conversion to nitric acid; it also plays a significant role in determining air quality through the production of tropospheric ozone. NOx is released by both anthropogenic (fossil fuel combustion, biomass burning, aircraft emissions) and natural (lightning, biogenic production in soils) sources. Global concentrations of NOx are rising because of increased anthropogenic emissions, while natural source emissions also contribute significantly to the global NOx burden. The contributions of both natural and anthropogenic sources and their considerable variability in space and time make it difficult to attribute local NOx concentrations (and, thus, nitric acid) to a particular source. Several recent studies suggest that variability in the isotopic composition of nitric acid deposition is related to variability in the isotopic signatures of NOx emission sources. Nevertheless, the isotopic composition of most NOx sources has not been thoroughly constrained. Ultimately, the direct capture and quantification of the nitrogen isotopic signatures of NOx sources will allow for the tracing of NOx emissions sources and their impact on environmental quality. Moreover, this will provide a new means by which to verify emissions estimates and atmospheric models. We present laboratory results of methods used for capturing NOx from air into solution. A variety of methods have been used in field studies, but no independent laboratory verification of the efficiencies of these methods has been performed. When analyzing isotopic composition, it is important that NOx be collected quantitatively or the possibility of fractionation must be constrained. We have found that collection efficiency can vary widely under different conditions in the laboratory and fractionation does not vary

CONTROL OF NOX EMISSIONS FROM U.S. COAL-FIRED ELECTRIC UTILITY BOILERS

Science.gov (United States)

The paper discusses the control of nitrogen oxide (NOx) emissions from U.S. coal-fired electric utility boilers. (NOTE: In general, NOx control technologies are categorized as being either primary or secondary control technologies. Primary technologies reduce the amount of NOx pr...

Chloride Channel 3 Channels in the Activation and Migration of Human Blood Eosinophils in Allergic Asthma.

Science.gov (United States)

Gaurav, Rohit; Bewtra, Againdra K; Agrawal, Devendra K

2015-08-01

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is responsible for respiratory burst in immune cells. Chloride channel 3 (CLC3) has been linked to the respiratory burst in eosinophils and neutrophils. The effect of cytokines and the involvement of CLC3 in the regulation of NADPH-dependent oxidative stress and on cytokine-mediated migration of eosinophils are not known. Human peripheral blood eosinophils were isolated from healthy individuals and from individuals with asthma by negative selection. Real-time PCR was used to detect the expression of NADPH oxidases in eosinophils. Intracellular reactive oxygen species (ROS) measurement was done with flow cytometry. Superoxide generation was measured with transforming growth factor (TGF)-β, eotaxin, and CLC3 blockers. CLC3 dependence of eosinophils in TGF-β- and eotaxin-induced migration was also examined. The messenger RNA (mRNA) transcripts of NADPH oxidase (NOX) 2, dual oxidase (DUOX) 1, and DUOX2 were detected in blood eosinophils, with very low expression of NOX1, NOX3, and NOX5 and no NOX4 mRNA. The level of NOX2 mRNA transcripts increased with disease severity in the eosinophils of subjects with asthma compared with healthy nonatopic volunteers. Change in granularity and size in eosinophils, but no change in intracellular ROS, was observed with phorbol myristate acetate (PMA). PMA, TGF-β, and eotaxin used the CLC3-dependent pathway to increase superoxide radicals. TGF-β and eotaxin induced CLC3-dependent chemotaxis of eosinophils. These findings support the requirement of CLC3 in the activation and migration of human blood eosinophils and may provide a potential novel therapeutic target to regulate eosinophil hyperactivity in allergic airway inflammation in asthma.

Photocatalytic NO_x abatement. Theory, applications, current research, and limitations

International Nuclear Information System (INIS)

Bloh, Jonathan Z.

2017-01-01

Nitrogen oxides are one of the major air pollutants that threaten our air quality and health. As a consequence, increasingly stricter regulations are in place forcing action to reduce the concentration of these dangerous compounds. Conventional methods of reducing the NO_x pollution level are reducing the emission directly at the source or restrictive measures such as low emission zones. However, there are recent reports questioning the efficacy of the strategy to reduce ambient NO_x levels solely by reducing their emissions and existing threshold values are still frequently exceeded in many European cities. Semiconductor photocatalysis presents an appealing alternative capable of removing NO_x and other air pollutants from the air once they have already been released and dispersed. Recent field tests have shown that a reduction of a few percent in NO_x values is possible with available photocatalysts. Current research focuses on further increasing the catalysts' efficacy as well as their selectivity to suppress the formation of undesired by-products. Especially using these improved materials, photocatalytic NO_x abatement could prove a very valuable contributor to better air quality.

A role for NADPH oxidase in antigen presentation

Directory of Open Access Journals (Sweden)

Gail J Gardiner

2013-09-01

Full Text Available The nicotinamide adenine dinucleotide phosphate (NADPH oxidase expressed in phagocytes is a multi-subunit enzyme complex that generates superoxide (O2.-. This radical is an important precursor of hydrogen peroxide (H2O2 and other reactive oxygen species (ROS needed for microbicidal activity during innate immune responses. Inherited defects in NADPH oxidase give rise to chronic granulomatous disease (CGD, a primary immunodeficiency characterized by recurrent infections and granulomatous inflammation. Interestingly, CGD, CGD carrier status, and oxidase gene polymorphisms have all been associated with autoinflammatory and autoimmune disorders, suggesting a potential role for NADPH oxidase in regulating adaptive immune responses. Here, NADPH oxidase function in antigen processing and presentation is reviewed. NADPH oxidase influences dendritic cell (DC crosspresentation by major histocompatibility complex class I molecules (MHC-I through regulation of the phagosomal microenvironment, while in B lymphocytes, NADPH oxidase alters epitope selection by major histocompatibility complex class II molecules (MHC-II.

Multiphase catalysts for selective reduction of NOx with hydrocarbons

NARCIS (Netherlands)

Maisuls, S.E.

2000-01-01

The combustion of fuels, to meet the society demands for energy, result in the emissi of large quantities of nitrogen oxides (NOx) to the environment. These pollutants cause severe environmental problems and present a serious hazard to the health. Nowadays, two methods for the control of NOx

Single bank NOx adsorber for heavy duty diesel engines

NARCIS (Netherlands)

Genderen, M. van; Aken, M.G. van

2003-01-01

In a NOx adsorber programme the feasibility for applying this technology to heavy duty diesel engines was investigated. After modelling and simulations for realising best λ < 1 engine conditions a platform was build which was used to obtain good NOx adsorber regeneration settings in a number of

Role of pH in oxidase variability of Aeromonas hydrophila.

OpenAIRE

Hunt, L K; Overman, T L; Otero, R B

1981-01-01

Some strains of Aeromonas hydrophila may be oxidase negative or only weakly oxidase positive by the Kovacs method taken from the surface of a differential medium, such as MacConkey agar. Six strains of A. hydrophila, two oxidase variable, one oxidase constant, and three weakly oxidase positive on MacConkey agar, were studied to determine the cause of oxidase variability. The bacteriostatic dyes in MacConkey agar were considered possible inhibitors of the oxidase reaction. The concentration of...

The rationale for targeting the LOX family in cancer

DEFF Research Database (Denmark)

Barker, Holly E; Cox, Thomas R; Erler, Janine T

2012-01-01

The therapeutic targeting of extracellular proteins is becoming hugely attractive in light of evidence implicating the tumour microenvironment as pivotal in all aspects of tumour initiation and progression. Members of the lysyl oxidase (LOX) family of proteins are secreted by tumours and are the ......The therapeutic targeting of extracellular proteins is becoming hugely attractive in light of evidence implicating the tumour microenvironment as pivotal in all aspects of tumour initiation and progression. Members of the lysyl oxidase (LOX) family of proteins are secreted by tumours...... and are the subject of much effort to understand their roles in cancer. In this Review we discuss the roles of members of this family in the remodelling of the tumour microenvironment and their paradoxical roles in tumorigenesis and metastasis. We also discuss how targeting this family of proteins might lead to a new...... avenue of cancer therapeutics....

40 CFR 96.386 - Withdrawal from CAIR NOX Ozone Season Trading Program.

Science.gov (United States)

2010-07-01

... Trading Program. 96.386 Section 96.386 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR... Season Trading Program. Except as provided under paragraph (g) of this section, a CAIR NOX Ozone Season...

Modeling of NOx Destruction Options for INEEL Sodium-Bearing Waste Vitrification

Energy Technology Data Exchange (ETDEWEB)

Wood, Richard Arthur

2001-09-01

Off-gas NOx concentrations in the range of 1-5 mol% are expected as a result of the proposed vitrification of sodium-bearing waste at the Idaho National Engineering and Environmental Laboratory. An existing kinetic model for staged combustion (originally developed for NOx abatement from the calcination process) was updated for application to vitrification offgas. In addition, two new kinetic models were developed to assess the feasibility of using selective non-catalytic reduction (SNCR) or high-temperature alone for NOx abatement. Each of the models was developed using the Chemkin code. Results indicate that SNCR is a viable option, reducing NOx levels to below 1000 ppmv. In addition, SNCR may be capable of simultaneously reducing CO emissions to below 100 ppmv. Results for using high-temperature alone were not as promising, indicating that a minimum NOx concentration of 3950 ppmv is achievable at 3344°F.

Molecular, phylogenetic and comparative genomic analysis of the cytokinin oxidase/dehydrogenase gene family in the Poaceae.

Science.gov (United States)

Mameaux, Sabine; Cockram, James; Thiel, Thomas; Steuernagel, Burkhard; Stein, Nils; Taudien, Stefan; Jack, Peter; Werner, Peter; Gray, John C; Greenland, Andy J; Powell, Wayne

2012-01-01

The genomes of cereals such as wheat (Triticum aestivum) and barley (Hordeum vulgare) are large and therefore problematic for the map-based cloning of agronomicaly important traits. However, comparative approaches within the Poaceae permit transfer of molecular knowledge between species, despite their divergence from a common ancestor sixty million years ago. The finding that null variants of the rice gene cytokinin oxidase/dehydrogenase 2 (OsCKX2) result in large yield increases provides an opportunity to explore whether similar gains could be achieved in other Poaceae members. Here, phylogenetic, molecular and comparative analyses of CKX families in the sequenced grass species rice, brachypodium, sorghum, maize and foxtail millet, as well as members identified from the transcriptomes/genomes of wheat and barley, are presented. Phylogenetic analyses define four Poaceae CKX clades. Comparative analyses showed that CKX phylogenetic groupings can largely be explained by a combination of local gene duplication, and the whole-genome duplication event that predates their speciation. Full-length OsCKX2 homologues in barley (HvCKX2.1, HvCKX2.2) and wheat (TaCKX2.3, TaCKX2.4, TaCKX2.5) are characterized, with comparative analysis at the DNA, protein and genetic/physical map levels suggesting that true CKX2 orthologs have been identified. Furthermore, our analysis shows CKX2 genes in barley and wheat have undergone a Triticeae-specific gene-duplication event. Finally, by identifying ten of the eleven CKX genes predicted to be present in barley by comparative analyses, we show that next-generation sequencing approaches can efficiently determine the gene space of large-genome crops. Together, this work provides the foundation for future functional investigation of CKX family members within the Poaceae. © 2011 National Institute of Agricultural Botany (NIAB). Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell

OZONE PRODUCTION EFFICIENCY AND NOX DEPLETION IN AN URBAN PLUME: INTERPRETATION OF FIELD OBSERVATIONS AND IMPLICATIONS FOR EVALUATING O3-NOX-VOC SENSITIVITY

Science.gov (United States)

Ozone production efficiency (OPE) can be defined as the number of ozone (O3) molecules photochemically produced by a molecule of NOx (NO + NO2) before it is lost from the NOx - O3 cycle. Here, we consider observational and modeling techniques to evaluate various operational defi...

40 CFR 76.12 - Phase I NOX compliance extension.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Phase I NOX compliance extension. 76.12 Section 76.12 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.12 Phase I NOX compliance extension. (a...

NOx photocatalytic degradation employing concrete pavement containing titanium dioxide

NARCIS (Netherlands)

Ballari, M.M.; Hunger, Martin; Hüsken, Götz; Brouwers, Jos

2010-01-01

In the present work the degradation of nitrogen oxides (NOx) by concrete paving stones containing TiO2 to be applied in road construction is studied. A kinetic model is proposed to describe the photocatalytic reaction of NOx (combining the degradation of NO and the appearance and disappearance of

Reactive oxygen species produced by NADPH oxidase and mitochondrial dysfunction in lung after an acute exposure to Residual Oil Fly Ashes

Energy Technology Data Exchange (ETDEWEB)

Magnani, Natalia D.; Marchini, Timoteo; Vanasco, Virginia [Instituto de Bioquímica Medicina Molecular (IBIMOL-UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires (Argentina); Tasat, Deborah R. [CESyMA, Escuela de Ciencia y Tecnología, Universidad Nacional de San Martín, San Martín, Buenos Aires (Argentina); Alvarez, Silvia [Instituto de Bioquímica Medicina Molecular (IBIMOL-UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires (Argentina); Evelson, Pablo, E-mail: pevelson@ffyb.uba.ar [Instituto de Bioquímica Medicina Molecular (IBIMOL-UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires (Argentina)

2013-07-01

Reactive O{sub 2} species production triggered by particulate matter (PM) exposure is able to initiate oxidative damage mechanisms, which are postulated as responsible for increased morbidity along with the aggravation of respiratory diseases. The aim of this work was to quantitatively analyse the major sources of reactive O{sub 2} species involved in lung O{sub 2} metabolism after an acute exposure to Residual Oil Fly Ashes (ROFAs). Mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight), and lung samples were analysed 1 h after instillation. Tissue O{sub 2} consumption and NADPH oxidase (Nox) activity were evaluated in tissue homogenates. Mitochondrial respiration, respiratory chain complexes activity, H{sub 2}O{sub 2} and ATP production rates, mitochondrial membrane potential and oxidative damage markers were assessed in isolated mitochondria. ROFA exposure was found to be associated with 61% increased tissue O{sub 2} consumption, a 30% increase in Nox activity, a 33% increased state 3 mitochondrial O{sub 2} consumption and a mitochondrial complex II activity increased by 25%. During mitochondrial active respiration, mitochondrial depolarization and a 53% decreased ATP production rate were observed. Neither changes in H{sub 2}O{sub 2} production rate, nor oxidative damage in isolated mitochondria were observed after the instillation. After an acute ROFA exposure, increased tissue O{sub 2} consumption may account for an augmented Nox activity, causing an increased O{sub 2}{sup ·−} production. The mitochondrial function modifications found may prevent oxidative damage within the organelle. These findings provide new insights to the understanding of the mechanisms involving reactive O{sub 2} species production in the lung triggered by ROFA exposure. - Highlights: • Exposure to ROFA alters the oxidative metabolism in mice lung. • The augmented Nox activity contributes to the high tissue O{sub 2} consumption. • Exposure to ROFA

NOx PREDICTION FOR FBC BOILERS USING EMPIRICAL MODELS

Directory of Open Access Journals (Sweden)

Jiří Štefanica

2014-02-01

Full Text Available Reliable prediction of NOx emissions can provide useful information for boiler design and fuel selection. Recently used kinetic prediction models for FBC boilers are overly complex and require large computing capacity. Even so, there are many uncertainties in the case of FBC boilers. An empirical modeling approach for NOx prediction has been used exclusively for PCC boilers. No reference is available for modifying this method for FBC conditions. This paper presents possible advantages of empirical modeling based prediction of NOx emissions for FBC boilers, together with a discussion of its limitations. Empirical models are reviewed, and are applied to operation data from FBC boilers used for combusting Czech lignite coal or coal-biomass mixtures. Modifications to the model are proposed in accordance with theoretical knowledge and prediction accuracy.

Control strategies for vehicular NOx emissions in Guangzhou, China

International Nuclear Information System (INIS)

Shao Min; Zhang Yuanhang; Raufer, Roger

2001-01-01

Guangzhou is a city in southern China that has experienced very rapid economic development in recent years. The city's air has very high concentrations of various pollutants, including sulphur dioxide (SO 2 , oxides of nitrogen (NOx), ozone (O 3 ) and particulate. This paper reviews the changes in air quality in the city over the past 15 years, and notes that a serious vehicular-related emissions problem has been superimposed on the traditional coal-burning problem evident in most Chinese cities. As NOx concentrations have increased, oxidants and photochemical smog now interact with the traditional SO 2 and particulate pollutants, leading to increased health risks and other environmental concerns. Any responsible NOx control strategy for the city must include vehicle emission control measures. This paper reviews control strategies designed to abate vehicle emissions to fulfill the city's air quality improvement target in 2010. A cost-effectiveness analysis suggests that, while NOx emission control is expensive, vehicular emission standards could achieve a relatively sizable emissions reduction at reasonable cost. To achieve the 2010 air quality target of NOx, advanced implementation of EURO3 standards is recommended, substituting for the EURO2 currently envisioned in the national regulations Related technical options, including fuel quality improvements and inspection/maintenance (I/M) upgrades (ASM or IM240) are assessed as well. (author)

Fundamental limits on gas-phase chemical reduction of NOx in a plasma

Energy Technology Data Exchange (ETDEWEB)

Penetrante, B.M.; Hsiao, M.C.; Merritt, B.T.; Vogtlin, G.E. [Lawrence Livermore National Lab., CA (United States)

1997-12-31

In the plasma, the electrons do not react directly with the NOx molecules. The electrons collide mainly with the background gas molecules like N{sub 2}, O{sub 2} and H{sub 2}O. Electron impact on these molecules result partly in dissociation reactions that produce reactive species like N, O and OH. The NOx in the engine exhaust gas initially consist mostly of NO. The ground state nitrogen atom, N, is the only species that could lead to the chemical reduction of NO to N{sub 2}. The O radical oxidizes NO to NO{sub 2} leaving the same amount of NOx. The OH radical converts NO{sub 2} to nitric acid. Acid products in the plasma can easily get adsorbed on surfaces in the plasma reactor and in the pipes. When undetected, the absence of these oxidation products can often be mistaken for chemical reduction of NOx. In this paper the authors will examine the gas-phase chemical reduction of NOx. They will show that under the best conditions, the plasma can chemically reduce 1.6 grams of NOx per brake-horsepower-hour [g(NOx)/bhp-hr] when 5% of the engine output energy is delivered to the plasma.

Modeling of nitrogen oxides (NO(x)) concentrations resulting from ships at berth.

Science.gov (United States)

Abdul-Wahab, Sabah A; Elkamel, Ali; Al Balushi, Abdullah S; Al-Damkhi, Ali M; Siddiqui, Rafiq A

2008-12-01

Oxides of nitrogen (NO(x)) emissions from ships (marine vessels) contribute to poor air quality that negatively impacts public health and communities in coastal areas and far inland. These emissions often excessively harm human health, environment, wildlife habituates, and quality of life of communities and indigenous of people who live near ports. This study was conducted to assess the impact of NO(x) emissions origination from ships at berth on a nearby community. It was undertaken at Said Bin Sultan Naval base in Wullayat Al-Mussana (Sultanate of Oman) during the year 2005. The Industrial Source Complex Short Term (ISCST) model was adopted to determine the dispersion of NO(x) into port and beyond into surrounding urban areas. The hourly and monthly contours (isopleths) of NO(x) concentrations in and around the port were plotted. The results were analyzed to determine the affected area and the level of NO(x) concentrations. The highest concentration points in the studied area were also identified. The isopleths of NO(x) indicated that most shipping emissions of NO(x) occur at the port can be transported over land. The output results can help to derive advice of recommendations ships operators and environmentalists to take the correct decision to prevent workers and surrounded environment from pollution.

NOx emission trade. What is the state-of-the-art?

International Nuclear Information System (INIS)

Witkamp, J.

2003-01-01

In Leiden, Netherlands, 28 November 2002, a symposium was organized on the subject of NOx emission trade in preparation of a NOx emission trade system. In this article an overview is given of the developments so far [nl

A water-forming NADH oxidase from Lactobacillus pentosus and its potential application in the regeneration of synthetic biomimetic cofactors

Directory of Open Access Journals (Sweden)

Claudia eNowak

2015-09-01

Full Text Available The cell-free biocatalytic production of fine chemicals by oxidoreductases has continuously grown over the past years. Since especially dehydrogenases depend on the stoichiometric use of nicotinamide pyridine cofactors, an integrated efficient recycling system is crucial to allow process operation under economic conditions. Lately, the variety of cofactors for biocatalysis was broadened by the utilization of totally synthetic and cheap biomimetics. Though, to date the regeneration has been limited to chemical or electrochemical methods. Here, we report an enzymatic recycling by the flavoprotein NADH-oxidase from Lactobacillus pentosus (LpNox. Since this enzyme has not been described before, we first characterized it in regard to its optimal reaction parameters. We found that the heterologously overexpressed enzyme only contained 13 % FAD. In vitro loading of the enzyme with FAD, resulted in a higher specific activity towards its natural cofactor NADH as well as different nicotinamide derived biomimetics. Apart from the enzymatic recycling, which gives water as a by-product by transferring four electrons onto oxygen, unbound FAD can also catalyse the oxidation of biomimetic cofactors. Here a two electron process takes place yielding H2O2 instead. The enzymatic and chemical recycling was compared in regard to reaction kinetics for the natural and biomimetic cofactors. With LpNox and FAD, two recycling strategies for biomimetic cofactors are described with either water or hydrogen peroxide as a by-product.

Heteropoly acid promoted catalyst for SCR of NOx with ammonia

DEFF Research Database (Denmark)

2012-01-01

The present invention concerns the selective removal of nitrogen oxides (NOx) from gases. In particular, the invention concerns a process, a highly alkali metal resistant heteropoly acid promoted catalyst and the use of said catalyst for removal of NOx from exhaust or flue gases, said gases...... comprising alkali or earth alkali metals. Such gases comprise for example flue gases arising from the burning of biomass, combined biomass and fossil fuel, and from waste incineration units. The process comprises the selective catalytic reduction (SCR) of NOx, such as nitrogen dioxide (NO2) and nitrogen...

Ambient NOx concentrations in the UK, 1976-84: a summary

Energy Technology Data Exchange (ETDEWEB)

Williams, M.L.; Broughton, G.F.J.; Bower, J.S.; Drury, V.J.; Lilley, K.

1987-01-01

This report summarizes NOx concentration data obtained at Warren Spring Laboratory (WSL) sites up to and including 1984. The statistics of NO and NO/sub 2/ concentrations are discussed, and an extreme value analysis of upper-percentile NO/sub 2/ concentrations is presented. The seasonal behavior, diurnal averages, and weekday/weekend differences of NO and NO/sub 2/ concentrations are discussed in terms of the more-important sources of NOx and the mechanisms for the production and loss of NO/sub 2/. An investigation of the NO/sub 2//NOx relationship is presented.

Nighttime NOx Chemistry in Coal-Fired Power Plant Plumes

Science.gov (United States)

Fibiger, D. L.; McDuffie, E. E.; Dube, W. P.; Veres, P. R.; Lopez-Hilfiker, F.; Lee, B. H.; Green, J. R.; Fiddler, M. N.; Ebben, C. J.; Sparks, T.; Weinheimer, A. J.; Montzka, D.; Campos, T. L.; Cohen, R. C.; Bililign, S.; Holloway, J. S.; Thornton, J. A.; Brown, S. S.

2015-12-01

Nitrogen oxides (NOx = NO + NO2) play a key role in atmospheric chemistry. During the day, they catalyze ozone (O3) production, while at night they can react to form nitric acid (HNO3) and nitryl chloride (ClNO2) and remove O3 from the atmosphere. These processes are well studied in the summer, but winter measurements are more limited. Coal-fired power plants are a major source of NOx to the atmosphere, making up approximately 30% of emissions in the US (epa.gov). NOx emissions can vary seasonally, as well as plant-to-plant, with important impacts on the details of the plume chemistry. In particular, due to inefficient plume dispersion, nighttime NOx emissions from power plants are held in concentrated plumes, where rates of mixing with ambient O3 have a strong influence on plume evolution. We will show results from the aircraft-based WINTER campaign over the northeastern United States, where several nighttime intercepts of power plant plumes were made. Several of these intercepts show complete O3 titration, which can have a large influence on NOx lifetime, and thus O3 production, in the plume. When power plant NO emissions exceed background O3 levels, O3 is completely consumed converting NO to NO2. In the presence of O3, NO2 will be oxidized to NO3, which will then react with NO2 to form N2O5, which can then form HNO3 and/or ClNO2 and, ultimately, remove NOx from the atmosphere or provide next-day oxidant sources. If there is no O3 present, however, no further chemistry can occur and NO and NO2 will be transported until mixing with sufficient O3 for higher oxidation products. Modeling results of plume development and mixing, which can tell us more about this transport, will also be presented.

Identification and characterization of aldehyde oxidases (AOXs) in the cotton bollworm

Science.gov (United States)

Xu, Wei; Liao, Yalin

2017-12-01

Aldehyde oxidases (AOXs) are a family of metabolic enzymes that oxidize aldehydes into carboxylic acids; therefore, they play critical roles in detoxification and degradation of chemicals. By using transcriptomic and genomic approaches, we successfully identified six putative AOX genes (HarmAOX1-6) from cotton bollworm, Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae). In silico expression profile, reverse transcription (RT)-PCR, and quantitative PCR (qPCR) analyses showed that HarmAOX1 is highly expressed in adult antennae, tarsi, and larval mouthparts, so they may play an important role in degrading plant-derived compounds. HarmAOX2 is highly and specifically expressed in adult antennae, suggesting a candidate pheromone-degrading enzyme (PDE) to inactivate the sex pheromone components (Z)-11-hexadecenal and (Z)-9-hexadecenal. RNA sequencing data further demonstrated that a number of host plants they feed on could significantly upregulate the expression levels of HarmAOX1 in larvae. This study improves our understanding of insect aldehyde oxidases and insect-plant interactions.

Plasma and catalyst for the oxidation of NOx

DEFF Research Database (Denmark)

Jögi, I.; Erme, K.; Levoll, E.

2017-01-01

The removal of NOx from the exhaust gases requires the oxidation of most abundant NO to NO2 or N2O5. The oxidation can be done by non-thermal plasma but the efficiency is limited due to the back-reaction of NO2 to NO by O radicals. Present contribution investigates the role of catalysts in the im......The removal of NOx from the exhaust gases requires the oxidation of most abundant NO to NO2 or N2O5. The oxidation can be done by non-thermal plasma but the efficiency is limited due to the back-reaction of NO2 to NO by O radicals. Present contribution investigates the role of catalysts...... in the improvement of oxidation efficiency based on the stationary and time-dependent studies of the NOx oxidation at different reactor configurations and experimental conditions. The plasma produced active oxygen species (O, O3) were shown to play an important role in the reactions taking place on the catalyst...... surfaces while the exact mechanism and extent of the effect depended on the reactor configuration. The effect of catalyst at different experimental conditions was quantitatively described with the aid of analytical lumped kinetic models derived for the NOx oxidation when the catalyst was directly...

NOx reduction and NO2 emission characteristics in rich-lean combustion of hydrogen

OpenAIRE

Shudo, Toshio; Omori, Kento; Hiyama, Osamu

2008-01-01

Hydrogen is a clean alternative to conventional hydrocarbon fuels, but it is very important to reduce the nitrogen oxides (NOx) emissions generated by hydrogen combustion. The rich-lean combustion or staged combustion is known to reduce NOx emissions from continuous combustion burners such as gas turbines and boilers, and NOx reduction effects have been demonstrated for hydrocarbon fuels. The authors applied rich-lean combustion to a hydrogen gas turbine and showed its NOx reduction effect in...

Regulation of the NADPH Oxidase RBOHD During Plant Immunity.

Science.gov (United States)

Kadota, Yasuhiro; Shirasu, Ken; Zipfel, Cyril

2015-08-01

Pathogen recognition induces the production of reactive oxygen species (ROS) by NADPH oxidases in both plants and animals. ROS have direct antimicrobial properties, but also serve as signaling molecules to activate further immune outputs. However, ROS production has to be tightly controlled to avoid detrimental effects on host cells, but yet must be produced in the right amount, at the right place and at the right time upon pathogen perception. Plant NADPH oxidases belong to the respiratory burst oxidase homolog (RBOH) family, which contains 10 members in the model plant Arabidopsis thaliana. The perception of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) leads to a rapid, specific and strong production of ROS, which is dependent on RBOHD. RBOHD is mainly controlled by Ca(2+) via direct binding to EF-hand motifs and phosphorylation by Ca(2+)-dependent protein kinases. Recent studies have, however, revealed a critical role for a Ca(2+)-independent regulation of RBOHD. The plasma membrane-associated cytoplasmic kinase BIK1 (BOTRYTIS-INDUCED KINASE1), which is a direct substrate of the PRR complex, directly interacts with and phosphorylates RBOHD upon PAMP perception. Impairment of these phosphorylation events completely abolishes the function of RBOHD in immunity. These results suggest that RBOHD activity is tightly controlled by multilayered regulations. In this review, we summarize recent advances in our understanding of the regulatory mechanisms controlling RBOHD activation. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Dosimeter-Type NOx Sensing Properties of KMnO4 and Its Electrical Conductivity during Temperature Programmed Desorption

Directory of Open Access Journals (Sweden)

Ralf Moos

2013-04-01

Full Text Available An impedimetric NOx dosimeter based on the NOx sorption material KMnO4 is proposed. In addition to its application as a low level NOx dosimeter, KMnO4 shows potential as a precious metal free lean NOx trap material (LNT for NOx storage catalysts (NSC enabling electrical in-situ diagnostics. With this dosimeter, low levels of NO and NO2 exposure can be detected electrically as instantaneous values at 380 °C by progressive NOx accumulation in the KMnO4 based sensitive layer. The linear NOx sensing characteristics are recovered periodically by heating to 650 °C or switching to rich atmospheres. Further insight into the NOx sorption-dependent conductivity of the KMnO4-based material is obtained by the novel eTPD method that combines electrical characterization with classical temperature programmed desorption (TPD. The NOx loading amount increases proportionally to the NOx exposure time at sorption temperature. The cumulated NOx exposure, as well as the corresponding NOx loading state, can be detected linearly by electrical means in two modes: (1 time-continuously during the sorption interval including NOx concentration information from the signal derivative or (2 during the short-term thermal NOx release.

Optical and Electronic NO(x) Sensors for Applications in Mechatronics.

Science.gov (United States)

Di Franco, Cinzia; Elia, Angela; Spagnolo, Vincenzo; Scamarcio, Gaetano; Lugarà, Pietro Mario; Ieva, Eliana; Cioffi, Nicola; Torsi, Luisa; Bruno, Giovanni; Losurdo, Maria; Garcia, Michael A; Wolter, Scott D; Brown, April; Ricco, Mario

2009-01-01

Current production and emerging NO(x) sensors based on optical and nanomaterials technologies are reviewed. In view of their potential applications in mechatronics, we compared the performance of: i) Quantum cascade lasers (QCL) based photoacoustic (PA) systems; ii) gold nanoparticles as catalytically active materials in field-effect transistor (FET) sensors, and iii) functionalized III-V semiconductor based devices. QCL-based PA sensors for NO(x) show a detection limit in the sub part-per-million range and are characterized by high selectivity and compact set-up. Electrochemically synthesized gold-nanoparticle FET sensors are able to monitor NO(x) in a concentration range from 50 to 200 parts per million and are suitable for miniaturization. Porphyrin-functionalized III-V semiconductor materials can be used for the fabrication of a reliable NO(x) sensor platform characterized by high conductivity, corrosion resistance, and strong surface state coupling.

Composite TiO{sub 2}/clays materials for photocatalytic NOx oxidation

Energy Technology Data Exchange (ETDEWEB)

Todorova, N.; Giannakopoulou, T.; Karapati, S.; Petridis, D. [Institute of Nanoscience and Nanotechnology, NCSR “Demokritos”, P.O. Box 60037, 153 10, Ag. Paraskevi, Attiki (Greece); Vaimakis, T. [Department of Chemistry, University of Ioannina, P.O. Box 1186, 451 10, Ioannina (Greece); Trapalis, C., E-mail: trapalis@ims.demokritos.gr [Institute of Nanoscience and Nanotechnology, NCSR “Demokritos”, P.O. Box 60037, 153 10, Ag. Paraskevi, Attiki (Greece)

2014-11-15

Graphical abstract: - Highlights: • Clays-supported TiO{sub 2} photocatalysts are prepared by simple, scalable method. • Visible light active TiO{sub 2} is incorporated in hydrotalcite, talk and kunipia clays. • The alkali substrates facilitate the NOx adsorption to the photocatalytic surface. • Low-content TiO{sub 2} photocatalysts demonstrated high NOx oxidation activity. • Titania/hydrotalcite photocatalyst exhibited remarkable NOx removal activity. - Abstract: TiO{sub 2} photocatalyst received much attention for air purification applications especially for removal of air pollutants like NOx, VOCs etc. It has been established that the activity of the photocatalyst can be significantly enhanced by its immobilization onto suitable substrates like inorganic minerals, porous silica, hydroxyapatite, adsorbent materials like activated carbon, various co-catalysts such as semiconductors, graphene, reduced graphite oxide, etc. In the present work, photocatalytic composite materials consisted of mineral substrate and TiO{sub 2} in weight ratio 1:1 were manufactured and examined for oxidation and removal of nitric oxides NOx (NO and NO{sub 2}). Commercial titania P25 (Evonik-Degussa) and urea-modified P25 were used as photocatalytically active components. Inorganic minerals, namely kunipia, talk and hydrotalcite were selected as supporting materials due to their layered structure and expected high NOx adsorption capability. Al{sup 3+} and Ca{sup 2+} intercalation was applied in order to improve the dispersion of TiO{sub 2} and its loading into the supporting matrix. The X-ray diffraction analysis and Scanning Electron Microscopy revealed the binary structure of the composites and homogeneous dispersion of the photocatalyst into the substrates. The photocatalytic behavior of the materials in NOx oxidation and removal was investigated under UV and visible light irradiation. The composite materials exhibited superior photocatalytic activity than the bare titania

Assessment and identification of some novel NOx reducing reagents for SNCR process

International Nuclear Information System (INIS)

Mahmood, A.; Javed, M.T.; Irfan, N.; Hamid, A. and K.; Waheed, K.

2009-01-01

Nitrogen oxides (NOx) are one of the most hazardous air pollutants arising from the combustion processes. Because of the implementation of strict emission limits many NOx removal technologies have been developed. In the present work post combustion NOx removal technique that is Selective Non-Catalytic Reduction (SNCR) has been investigated in a pilot scale 150 kW combustion rig facility. Investigation has been performed using some novel NOx reducing reagents like urea, ammonium carbonate and mixture of their 50%-50% aqueous solution within the temperature range of 700 to 1200 deg. C., at 1.1% excess oxygen and background NOx level of 500 ppm. The effects of these reagents were determined in term of their temperature characteristics and molar ratio. Among the reducing reagents used urea solution gave the highest NOx removal efficiency (81%) and was attractive due to its superior high temperature (1000 to 1150 deg. C) performance, ammonium carbonate was more effective at lower temperature range (850 to 950 deg. C) though its efficiency (32%) was lower than urea, while 50-50% solution of urea and ammonium carbonate gave higher efficiency than ammonium carbonate but slightly lesser than urea within a wide temperature range (875 to 1125 deg. C). It was also observed that the NOx removal efficiency was increased with increasing the molar ratio. (author)

Targeting vascular NADPH oxidase 1 blocks tumor angiogenesis through a PPARα mediated mechanism.

Directory of Open Access Journals (Sweden)

Sarah Garrido-Urbani

Full Text Available Reactive oxygen species, ROS, are regulators of endothelial cell migration, proliferation and survival, events critically involved in angiogenesis. Different isoforms of ROS-generating NOX enzymes are expressed in the vasculature and provide distinct signaling cues through differential localization and activation. We show that mice deficient in NOX1, but not NOX2 or NOX4, have impaired angiogenesis. NOX1 expression and activity is increased in primary mouse and human endothelial cells upon angiogenic stimulation. NOX1 silencing decreases endothelial cell migration and tube-like structure formation, through the inhibition of PPARα, a regulator of NF-κB. Administration of a novel NOX-specific inhibitor reduced angiogenesis and tumor growth in vivo in a PPARα dependent manner. In conclusion, vascular NOX1 is a critical mediator of angiogenesis and an attractive target for anti-angiogenic therapies.

ACRATA: a novel electron transfer domain associated to apoptosis and cancer

International Nuclear Information System (INIS)

Sanchez-Pulido, Luis; Rojas, Ana M; Valencia, Alfonso; Martinez-A, Carlos; Andrade, Miguel A

2004-01-01

Recently, several members of a vertebrate protein family containing a six trans-membrane (6TM) domain and involved in apoptosis and cancer (e.g. STEAP, STAMP1, TSAP6), have been identified in Golgi and cytoplasmic membranes. The exact function of these proteins remains unknown. We related this 6TM domain to distant protein families using intermediate sequences and methods of iterative profile sequence similarity search. Here we show for the first time that this 6TM domain is homolog to the 6TM heme binding domain of both the NADPH oxidase (Nox) family and the YedZ family of bacterial oxidoreductases. This finding gives novel insights about the existence of a previously undetected electron transfer system involved in apoptosis and cancer, and suggests further steps in the experimental characterization of these evolutionarily related families

Covalently bound phosphate residues in bovine milk xanthine oxidase and in glucose oxidase from Aspergillus niger: A reevaluation

Energy Technology Data Exchange (ETDEWEB)

Johnson, J.L.; Rajagopalan, K.V. (Duke Univ. Medical Center, Durham, NC (USA)); London, R.E. (National Institute of Environmental Health Science, Research Triangle Park, NC (USA))

1989-09-01

The reported presence of covalently bound phosphate residues in flavoproteins has significant implications with regard to the catalytic mechanisms and structural stability of the specific enzymes themselves and in terms of general cellular metabolic regulation. These considerations have led to a reevaluation of the presence of covalently bound phosphorus in the flavoproteins xanthine oxidase and glucose oxidase. Milk xanthine oxidase purified by a procedure that includes anion-exchange chromatography is shown to contain three phosphate residues. All three are noncovalently associated with the protein, two with the FAD cofactor, and one with the molybdenum cofactor. Results of chemical analysis and {sup 31}P NMR spectroscopy indicate that enzyme purified by this method contains no phosphoserine residues. Xanthine oxidase preparations purified by chromatography on calcium phosphate gel in place of DEAE-Sephadex yielded higher phosphate-to-protein ratios, which could be reduced to the expected values by additional purification on a folate affinity column. Highly active, highly purified preparations of glucose oxidase are shown to contain only the two phosphate residues of the FAD cofactor. The covalently bound bridging phosphate reported by others may arise in aged or degraded preparations of the enzyme but appears not to be a constituent of functional glucose oxidase. These results suggest that the presence of covalent phosphate residues in other flavoproteins should be rigorously reevaluated as well.

Covalently bound phosphate residues in bovine milk xanthine oxidase and in glucose oxidase from Aspergillus niger: A reevaluation

International Nuclear Information System (INIS)

Johnson, J.L.; Rajagopalan, K.V.; London, R.E.

1989-01-01

The reported presence of covalently bound phosphate residues in flavoproteins has significant implications with regard to the catalytic mechanisms and structural stability of the specific enzymes themselves and in terms of general cellular metabolic regulation. These considerations have led to a reevaluation of the presence of covalently bound phosphorus in the flavoproteins xanthine oxidase and glucose oxidase. Milk xanthine oxidase purified by a procedure that includes anion-exchange chromatography is shown to contain three phosphate residues. All three are noncovalently associated with the protein, two with the FAD cofactor, and one with the molybdenum cofactor. Results of chemical analysis and 31 P NMR spectroscopy indicate that enzyme purified by this method contains no phosphoserine residues. Xanthine oxidase preparations purified by chromatography on calcium phosphate gel in place of DEAE-Sephadex yielded higher phosphate-to-protein ratios, which could be reduced to the expected values by additional purification on a folate affinity column. Highly active, highly purified preparations of glucose oxidase are shown to contain only the two phosphate residues of the FAD cofactor. The covalently bound bridging phosphate reported by others may arise in aged or degraded preparations of the enzyme but appears not to be a constituent of functional glucose oxidase. These results suggest that the presence of covalent phosphate residues in other flavoproteins should be rigorously reevaluated as well

ASCR{trademark}: lower NOx removal costs without sacrificing performance

Energy Technology Data Exchange (ETDEWEB)

Bible, S.; Rummenhohl, V.; Siebeking, M.; Thomas, R.; Triece, C. [Fuel Tech (United States)

2011-05-15

With recent regulatory initiatives, the new Industrial Emissions Directive in Europe, and new rules being proposed by EPA in the USA, the question for power plants is now whether they will be required to reduce NOx emissions in the future to stay in operation, but when. What is needed is a low-capital-cost but high-performance NOx removal technology. 7 figs.

Experiments and simulations of NOx formation in the combustion of hydroxylated fuels

KAUST Repository

Bohon, Myles

2015-06-01

This work investigates the influence of molecular structure in hydroxylated fuels (i.e. fuels with one or more hydroxyl groups), such as alcohols and polyols, on NOx formation. The fuels studied are three lower alcohols (methanol, ethanol, and n-propanol), two diols (1,2-ethanediol and 1,2-propanediol), and one triol (1,2,3-propanetriol); all of which are liquids at room temperature and span a wide range of thermophysical properties. Experimental stack emissions measurements of NO/NO2, CO, and CO2 and flame temperature profiles utilizing a rake of thermocouples were obtained in globally lean, swirling, liquid atomized spray flames inside a refractory-lined combustion chamber as a function of the atomizing air flow rate and swirl number. These experiments show significantly lower NOx formation with increasing fuel oxygen content despite similarities in the flame temperature profiles. By controlling the temperature profiles, the contribution to NOx formation through the thermal mechanism were matched, and variations in the contribution through non-thermal NOx formation pathways are observed. Simulations in a perfectly stirred reactor, at conditions representative of those measured within the combustion region, were conducted as a function of temperature and equivalence ratio. The simulations employed a detailed high temperature chemical kinetic model for NOx formation from hydroxylated fuels developed based on recent alcohol combustion models and extended to include polyol combustion chemistry. These simulations provide a qualitative comparison to the range of temperatures and equivalence ratios observed in complex swirling flows and provide insight into the influence of variations in the fuel decomposition pathways on NOx formation. It is observed that increasing the fuel bound oxygen concentration ultimately reduces the formation of NOx by increasing the proportion of fuel oxidized through formaldehyde, as opposed to acetylene or acetaldehyde. The subsequent

Polyphenol Oxidase Enzyme and Inactivation Methods

Directory of Open Access Journals (Sweden)

Leman Yılmaz

2018-03-01

Full Text Available Polyphenol oxidase enzyme is found in vegetables and fruits, as well as in some animal organs and microorganisms. Polyphenol oxidase enzyme responsible for enzymatic browning is a group of copper proteins that catalyses the oxidation of phenolic compounds to quinones, which produce brown pigments, commonly found in fruits and vegetables. During the industrial preparation of fruits and vegetables, results of catalytic effect of polyphenol oxidase causes enzymatic browning. Enzymatic browning impairs the appearance of products containing phenolic compounds along with undesirable colour, odor and taste formation and significant loss of nutritional value of the products. This affects the acceptability of the products by the consumers and causes economic losses. In this review, some characteristics of polyphenol oxidase enzyme in different fruits and vegetables have been reviewed and information about chemical antibrowning agents, thermal applications, irradiation applications and alternative methods such as high pressure processing, pulse electric field, supercritical carbon dioxide and ultrasound applications to inactivate this enzyme has been presented.

Biodiesel unsaturation degree effects on diesel engine NOx emissions and cotton wick flame temperature

OpenAIRE

Abdullah Mohd Fareez Edzuan; Zhing Sim Shu; Bilong Bugik Clarence

2017-01-01

As compared with conventional diesel fuel, biodiesel has better lubricity and lower particulate matter (PM) emissions however nitrogen oxides (NOx) emissions generally increase in biodiesel-fuelled diesel engine. Strict regulation on NOx emissions is being implemented in current Euro 6 standard and it is expected to be tighter in next standard, thus increase of NOx cannot be accepted. In this study, biodiesel unsaturation degree effects on NOx emissions are investigated. Canola, palm and coco...

The terminal oxidases of Paracoccus denitrificans

NARCIS (Netherlands)

de Gier, J.-W.; Lübben, M; Reijnders, W N; Tipker, C A; Slotboom, D.J.; van Spanning, R J; Stouthamer, A.H.; van der Oost, J.

Three distinct types of terminal oxidases participate in the aerobic respiratory pathways of Paracoccus denitrificans. Two alternative genes encoding subunit I of the aa3-type cytochrome c oxidase have been isolated before, namely ctaDI and ctaDII. Each of these genes can be expressed separately to

Quantitation of immunoadsorbed flavoprotein oxidases by luminol-mediated chemiluminescence.

Science.gov (United States)

Hinkkanen, A; Maly, F E; Decker, K

1983-04-01

The detection of the flavoenzymes 6-hydroxy-L-nicotine oxidase and 6-hydroxy-D-nicotine oxidase at the sub-femtomol level was achieved by coupling the reaction of the immunoadsorbed proteins to the peroxidase-catalysed oxidation of luminol. The H2O2-producing oxidases retained their full activity when bound to the respective immobilized antibodies. This fact allowed the concentration of the enzymes from very dilute solutions and the quantitative assay of their activities in the microU range. Due to strict stereoselectivity and the absence of immunological cross-reactivity, the two flavoproteins could be determined in the same solution. This method was used to measure the 6-hydroxy-D-nicotine oxidase and 6-hydroxy-L-nicotine oxidase activities in Escherichia coli RR1 and different Arthrobacter strains cultured under non-inducing conditions. The same activity ratio of 6-hydroxy-L-nicotine oxidase/6-hydroxy-D-nicotine oxidase as in D L-nicotine-induced cells of A. oxidans was observed in non-induced wild type and in riboflavin-requiring (rf-) mutant cells of this aerob.

Less stress, more success? Oncological implications of surgery-induced oxidative stress.

LENUS (Irish Health Repository)

O'Leary, D P

2013-03-01

Reactive oxygen species (ROS) possess important cell signalling properties. This contradicts traditional thought which associated ROS activity with cell death. Emerging evidence clearly demonstrates that ROS signalling acts as a key regulator in tumour cell survival and in the cellular processes required for tumour cells to successfully metastasise and proliferate. The discovery of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) family of enzymes in the last decade has unravelled much of the mystery surrounding how ROS are generated. Tumour cells are now known to express Nox enzymes which produce ROS required for cellular signalling. Activation of Nox enzymes occurs via interaction with proinflammatory cytokines and growth factors, all of which are released following surgical trauma. As our understanding of the signalling capabilities of ROS grows, the oncological implications of ROS activity are gradually being revealed. Nox-derived ROS are known to play a central role in each step of the metastatic cascade including invasion, adhesion, angiogenesis and proliferation. This article describes how surgery creates a ROS-rich environment, which facilitates redox signalling, and also examines the role played by Nox enzymes in this process. The authors then explore current knowledge of the oncological implications of surgery-induced redox signalling, and discuss current and future therapeutic strategies targeted at ROS and Nox enzymes in cancer patients.

Composite TiO2/clays materials for photocatalytic NOx oxidation

Science.gov (United States)

Todorova, N.; Giannakopoulou, T.; Karapati, S.; Petridis, D.; Vaimakis, T.; Trapalis, C.

2014-11-01

TiO2 photocatalyst received much attention for air purification applications especially for removal of air pollutants like NOx, VOCs etc. It has been established that the activity of the photocatalyst can be significantly enhanced by its immobilization onto suitable substrates like inorganic minerals, porous silica, hydroxyapatite, adsorbent materials like activated carbon, various co-catalysts such as semiconductors, graphene, reduced graphite oxide, etc. In the present work, photocatalytic composite materials consisted of mineral substrate and TiO2 in weight ratio 1:1 were manufactured and examined for oxidation and removal of nitric oxides NOx (NO and NO2). Commercial titania P25 (Evonik-Degussa) and urea-modified P25 were used as photocatalytically active components. Inorganic minerals, namely kunipia, talk and hydrotalcite were selected as supporting materials due to their layered structure and expected high NOx adsorption capability. Al3+ and Ca2+ intercalation was applied in order to improve the dispersion of TiO2 and its loading into the supporting matrix. The X-ray diffraction analysis and Scanning Electron Microscopy revealed the binary structure of the composites and homogeneous dispersion of the photocatalyst into the substrates. The photocatalytic behavior of the materials in NOx oxidation and removal was investigated under UV and visible light irradiation. The composite materials exhibited superior photocatalytic activity than the bare titania under both types of irradiation. Significant visible light activity was recorded for the composites containing urea-modified titania that was accredited to the N-doping of the semiconductor. Among the different substrates, the hydrotalcite caused highest increase in the NOx removal, while among the intercalation ions the Ca2+ was more efficient. The results were related to the improved dispersion of the TiO2 and the synergetic activity of the substrates as NOx adsorbers.

Prediction of the production of nitrogen oxide (NOx) in turbojet engines

Science.gov (United States)

Tsague, Louis; Tsogo, Joseph; Tatietse, Thomas Tamo

Gaseous nitrogen oxides (NO+NO2=NOx) are known as atmospheric trace constituent. These gases remain a big concern despite the advances in low NOx emission technology because they play a critical role in regulating the oxidization capacity of the atmosphere according to Crutzen [1995. My life with O 3, NO x and other YZO x S; Nobel Lecture; Chemistry 1995; pp 195; December 8, 1995] . Aircraft emissions of nitrogen oxides ( NOx) are regulated by the International Civil Aviation Organization. The prediction of NOx emission in turbojet engines by combining combustion operational data produced information showing correlation between the analytical and empirical results. There is close similarity between the calculated emission index and experimental data. The correlation shows improved accuracy when the 2124 experimental data from 11 gas turbine engines are evaluated than a previous semi empirical correlation approach proposed by Pearce et al. [1993. The prediction of thermal NOx in gas turbine exhausts. Eleventh International Symposium on Air Breathing Engines, Tokyo, 1993, pp. 6-9]. The new method we propose predict the production of NOx with far more improved accuracy than previous methods. Since a turbojet engine works in an atmosphere where temperature, pressure and humidity change frequently, a correction factor is developed with standard atmospheric laws and some correlations taken from scientific literature [Swartwelder, M., 2000. Aerospace engineering 410 Term Project performance analysis, November 17, 2000, pp. 2-5; Reed, J.A. Java Gas Turbine Simulator Documentation. pp. 4-5]. The new correction factor is validated with experimental observations from 19 turbojet engines cruising at altitudes of 9 and 13 km given in the ICAO repertory [Middleton, D., 1992. Appendix K (FAA/SETA). Section 1: Boeing Method Two Indices, 1992, pp. 2-3]. This correction factor will enable the prediction of cruise NOx emissions of turbojet engines at cruising speeds. The ICAO

Effect of NOx level on secondary organic aerosol (SOA formation from the photooxidation of terpenes

Directory of Open Access Journals (Sweden)

R. C. Flagan

2007-10-01

Full Text Available Secondary organic aerosol (SOA formation from the photooxidation of one monoterpene (α-pinene and two sesquiterpenes (longifolene and aromadendrene is investigated in the Caltech environmental chambers. The effect of NOx on SOA formation for these biogenic hydrocarbons is evaluated by performing photooxidation experiments under varying NOx conditions. The NOx dependence of α-pinene SOA formation follows the same trend as that observed previously for a number of SOA precursors, including isoprene, in which SOA yield (defined as the ratio of the mass of organic aerosol formed to the mass of parent hydrocarbon reacted decreases as NOx level increases. The NOx dependence of SOA yield for the sesquiterpenes, longifolene and aromadendrene, however, differs from that determined for isoprene and α-pinene; the aerosol yield under high-NOx conditions substantially exceeds that under low-NOx conditions. The reversal of the NOx dependence of SOA formation for the sesquiterpenes is consistent with formation of relatively low-volatility organic nitrates, and/or the isomerization of large alkoxy radicals leading to less volatile products. Analysis of the aerosol chemical composition for longifolene confirms the presence of organic nitrates under high-NOx conditions. Consequently the formation of SOA from certain biogenic hydrocarbons such as sesquiterpenes (and possibly large anthropogenic hydrocarbons as well may be more efficient in polluted air.

miR-9-5p suppresses pro-fibrogenic transformation of fibroblasts and prevents organ fibrosis by targeting NOX4 and TGFBR2.

Science.gov (United States)

Fierro-Fernández, Marta; Busnadiego, Óscar; Sandoval, Pilar; Espinosa-Díez, Cristina; Blanco-Ruiz, Eva; Rodríguez, Macarena; Pian, Héctor; Ramos, Ricardo; López-Cabrera, Manuel; García-Bermejo, Maria Laura; Lamas, Santiago

2015-10-01

Uncontrolled extracellular matrix (ECM) production by fibroblasts in response to injury contributes to fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). Reactive oxygen species (ROS) generation is involved in the pathogenesis of IPF. Transforming growth factor-β1 (TGF-β1) stimulates the production of NADPH oxidase 4 (NOX4)-dependent ROS, promoting lung fibrosis (LF). Dysregulation of microRNAs (miRNAs) has been shown to contribute to LF. To identify miRNAs involved in redox regulation relevant for IPF, we performed arrays in human lung fibroblasts exposed to ROS. miR-9-5p was selected as the best candidate and we demonstrate its inhibitory effect on TGF-β receptor type II (TGFBR2) and NOX4 expression. Increased expression of miR-9-5p abrogates TGF-β1-dependent myofibroblast phenotypic transformation. In the mouse model of bleomycin-induced LF, miR-9-5p dramatically reduces fibrogenesis and inhibition of miR-9-5p and prevents its anti-fibrotic effect both in vitro and in vivo. In lung specimens from patients with IPF, high levels of miR-9-5p are found. In omentum-derived mesothelial cells (MCs) from patients subjected to peritoneal dialysis (PD), miR-9-5p also inhibits mesothelial to myofibroblast transformation. We propose that TGF-β1 induces miR-9-5p expression as a self-limiting homeostatic response. © 2015 The Authors.

A rate based reactor model for BiodeNOx absorber units

NARCIS (Netherlands)

Winkelman, J. G. M.; Gambardella, F.; Heeres, H. J.

2007-01-01

The reactive absorption of NO in aqueous solutions of Fe-II(EDTA), resulting in the formation of a nitrosyl complex, Fe-II(EDTA)(NO), is a key step of the BiodeNOx process for the removal of NOx from industrial flue gas. Oxygen present in the flue gas will also absorb and oxidize Fe-II(EDTA). This

NOx Emissions from Diesel Passenger Cars Worsen with Age.

Science.gov (United States)

Chen, Yuche; Borken-Kleefeld, Jens

2016-04-05

Commonly, the NOx emissions rates of diesel vehicles have been assumed to remain stable over the vehicle's lifetime. However, there have been hardly any representative long-term emission measurements. Here we present real-driving emissions of diesel cars and light commercial vehicles sampled on-road over 15 years in Zurich/Switzerland. Results suggest deterioration of NOx unit emissions for Euro 2 and Euro 3 diesel technologies, while Euro 1 and Euro 4 technologies seem to be stable. We can exclude a significant influence of high-emitting vehicles. NOx emissions from all cars and light commercial vehicles in European emission inventories increase by 5-10% accounting for the observed deterioration, depending on the country and its share of diesel cars. We suggest monitoring the stability of emission controls particularly for high-mileage light commercial as well as heavy-duty vehicles.

Pilot test and optimization of plasma based deNOx

DEFF Research Database (Denmark)

Stamate, Eugen; Chen, Weifeng; Michelsen, Poul

. Experiments are in good agreement with numerical simulations. An optimized oxidation scheme for NOx reduction processes with time dependent combustion, such as the biomass power plants, was developed. Ozone production by micro-hollow and capillary discharges at atmospheric pressures was investigated......The NOx reduction of flue gas by plasma generated ozone was investigated in pilot test experiments at two industrial power plants running on natural gas (Ringsted) and biomass (Haslev). Reduction rates higher than 95% have been achieved for a molar ratio O3:NOx of 1.56. Fourier transform infrared...... and ultraviolet absorption spectroscopy were used for spatial measurements of stable molecules and radicals along the reduction reactor. Reactions of O3 injected in the flue gas in the reduction reactor were also modeled including the influence of the flue gas temperature, water droplets and SOx and HCl content...

Genome-wide association study identifies nox3 as a critical gene for susceptibility to noise-induced hearing loss.

Directory of Open Access Journals (Sweden)

Joel Lavinsky

2015-04-01

Full Text Available In the United States, roughly 10% of the population is exposed daily to hazardous levels of noise in the workplace. Twin studies estimate heritability for noise-induced hearing loss (NIHL of approximately 36%, and strain specific variation in sensitivity has been demonstrated in mice. Based upon the difficulties inherent to the study of NIHL in humans, we have turned to the study of this complex trait in mice. We exposed 5 week-old mice from the Hybrid Mouse Diversity Panel (HMDP to a 10 kHz octave band noise at 108 dB for 2 hours and assessed the permanent threshold shift 2 weeks post exposure using frequency specific stimuli. These data were then used in a genome-wide association study (GWAS using the Efficient Mixed Model Analysis (EMMA to control for population structure. In this manuscript we describe our GWAS, with an emphasis on a significant peak for susceptibility to NIHL on chromosome 17 within a haplotype block containing NADPH oxidase-3 (Nox3. Our peak was detected after an 8 kHz tone burst stimulus. Nox3 mutants and heterozygotes were then tested to validate our GWAS. The mutants and heterozygotes demonstrated a greater susceptibility to NIHL specifically at 8 kHz both on measures of distortion product otoacoustic emissions (DPOAE and on auditory brainstem response (ABR. We demonstrate that this sensitivity resides within the synaptic ribbons of the cochlea in the mutant animals specifically at 8 kHz. Our work is the first GWAS for NIHL in mice and elucidates the power of our approach to identify tonotopic genetic susceptibility to NIHL.

Post combustion methods for control of NOx emission

Energy Technology Data Exchange (ETDEWEB)

Rosenberg, H S; Curran, L M; Slack, A V; Ando, J; Oxley, J H

1980-01-01

Review of stack gas treatment methods for the control of NOx emissions. Particular emphasis is placed on status of development and factors affecting the performance of the processes. Catalytic, noncatalytic, and scrubbing processes are compared on a uniform engineering basis. Most of the active process development work is taking place in Japan. The three leading stack gas treatment techniques for NOx control are catalytic reduction with ammonia, noncatalytic reduction with ammonia, and direct scrubbing of NO with simultaneous absorption of SO2. The wet processes are much less developed than the dry processes.

O3 and NOx Exchange

NARCIS (Netherlands)

Loubet, B.; Castell, J.F.; Laville, P.; Personne, E.; Tuzet, A.; Ammann, C.; Emberson, L.; Ganzeveld, L.; Kowalski, A.S.; Merbold, L.; Stella, P.; Tuovinen, J.P.

2015-01-01

This discussion was based on the background document “Review on modelling atmosphere-biosphere exchange of Ozone and Nitrogen oxides”, which reviews the processes contributing to biosphere-atmosphere exchange of O3 and NOx, including stomatal and non-stomatal exchange of O3 and NO, NO2.

Confirmation of a blocked amino terminus of sulfhydryl oxidase

International Nuclear Information System (INIS)

Janolino, V.G.; Morrison-Rowe, S.J.; Swaisgood, H.E.

1990-01-01

The isolation of sulfhydryl oxidase from bovine milk in a suitably pure form for sequencing was carried out by transient covalent affinity chromatography of diafiltered whey using cysteinylsuccinamidopropyl-glass as matrix. The glutathione-eluted proteins were separated by SDS-PAGE. By radiolabeling the affinity chromatography-purified enzyme with [ 14 C]iodoacetate before subjecting to SDS-PAGE, the sulfhydryl oxidase band was identified, because sulfhydryl oxidase is known to be inactivated by alkylation of one sulfhydryl group per mole. The results confirmed that sulfhydryl oxidase corresponds to the 85 (± 5)-kDa band observed on SDS-PAGE. The protein band corresponding to radiolabeled sulfhydryl oxidase was recovered from SDS-PAGE gels by electrophoretic elution and by electroblotting on polyvinylidene difluoride membrane and subjected to gas phase sequencing. Precautions were taken during electrophoretic elution to prevent reactions that result in N-terminal blocking. Both methods of protein recovery yielded negative results when subjected to sequence analysis indicating that the N-terminus of sulfhydryl oxidase is blocked

Toluene decomposition performance and NOx by-product formation during a DBD-catalyst process.

Science.gov (United States)

Guo, Yufang; Liao, Xiaobin; Fu, Mingli; Huang, Haibao; Ye, Daiqi

2015-02-01

Characteristics of toluene decomposition and formation of nitrogen oxide (NOx) by-products were investigated in a dielectric barrier discharge (DBD) reactor with/without catalyst at room temperature and atmospheric pressure. Four kinds of metal oxides, i.e., manganese oxide (MnOx), iron oxide (FeOx), cobalt oxide (CoOx) and copper oxide (CuO), supported on Al2O3/nickel foam, were used as catalysts. It was found that introducing catalysts could improve toluene removal efficiency, promote decomposition of by-product ozone and enhance CO2 selectivity. In addition, NOx was suppressed with the decrease of specific energy density (SED) and the increase of humidity, gas flow rate and toluene concentration, or catalyst introduction. Among the four kinds of catalysts, the CuO catalyst showed the best performance in NOx suppression. The MnOx catalyst exhibited the lowest concentration of O3 and highest CO2 selectivity but the highest concentration of NOx. A possible pathway for NOx production in DBD was discussed. The contributions of oxygen active species and hydroxyl radicals are dominant in NOx suppression. Copyright © 2014. Published by Elsevier B.V.

Immobilization of oxidases and their analytical applications

International Nuclear Information System (INIS)

Yasinzai, M.

2007-01-01

Immobilized enzymes are replacing their soluble counter-parts in nearly every field of application. These enzyme modifications have evolved from a research curiosity into an entire branch of Biotechnology. An immobilization method for flavin containing oxidases and their use in flow injection system is described. An electrochemical detector for H/sub 2/O/sub 2/ is assembled which is used effectively for the determination of glucose using more common glucose oxidase and the simultaneous determination of sugars. The combination of oxidases with hydrolases have been used for the determination of maltose and starch. (author)

Urea-SCR Temperature Investigation for NOx Control of Diesel Engine

Directory of Open Access Journals (Sweden)

Asif Muhammad

2015-01-01

Full Text Available SCR (selective catalytic reduction system is continuously being analyzed by many researchers worldwide on various concerns due to the stringent nitrogen oxides (NOx emissions legislation for heavy-duty diesel engines. Urea-SCR includes AdBlue as urea source, which subsequently decomposes to NH3 (ammonia being the reducing agent. Reaction temperature is a key factor for the performance of urea-SCR system, as urea decomposition rate is sensitive to a specific temperature range. This particular study was directed to investigate the temperature of the SCR system in diesel engine with the objective to confirm that whether the appropriate temperature is attained for occurrence of urea based catalytic reduction or otherwise and how the system performs on the prescribed temperature range. Diesel engine fitted with urea-SCR exhaust system has been operated on European standard cycle for emission testing to monitor the temperature and corresponding nitrogen oxides (NOx values on specified points. Moreover, mathematical expressions for approximation of reaction temperature are also proposed which are derived by applying energy conservation principal and gas laws. Results of the investigation have shown that during the whole testing cycle system temperature has remained in the range where urea-SCR can take place with best optimum rate and the system performance on account of NOx reduction was exemplary as excellent NOx conversion rate is achieved. It has also been confirmed that selective catalytic reduction (SCR is the best suitable technology for automotive engine-out NOx control.

Sensitizing effects of NOx on CH4 oxidation at high pressure

DEFF Research Database (Denmark)

Rasmussen, Christian Lund; Rasmussen, Anja Egede; Glarborg, Peter

2008-01-01

The CH4/O2/NOx system is investigated in a laboratory-scale high pressure laminar flow reactor with the purpose of elucidating the sensitizing effects of NOx on CH4 oxidation at high pressures and medium temperatures. Experiments are conducted at 100, 50, and 20 bar, 600-900 K, and stoichiometric...... ratios ranging from highly reducing to oxidizing conditions. The experimental results are interpreted in terms of a detailed kinetic model drawn from previous work of the authors, including an updated reaction subset for the direct interactions of NOx and C1-2 hydrocarbon species relevant...

Feasibility of plasma aftertreatment for simultaneous control of NOx and particulates

International Nuclear Information System (INIS)

Brusasco, R M; Merritt, B T; Penetrante, B; Pitz, W J; Vogtlin, G E

1999-01-01

Plasma reactors can be operated as a particulate trap or as a NOx converter. Particulate trapping in a plasma reactor can be accomplished by electrostatic precipitation. The soluble organic fraction of the trapped particulates can be utilized for the hydrocarbon-enhanced oxidation of NO to NO2 . The NO2 can then be used to non-thermally oxidize the carbon fraction of the particulates. The oxidation of the carbon fraction by NO2 can lead to reduction of NOx or backconversion of NO2 to NO. This paper examines the hydrocarbon and electrical energy density requirements in a plasma for maximum NOx conversion in both heavy-duty and light-duty diesel engine exhaust. The energy density required for complete oxidation of hydrocarbons is also examined and shown to be much greater than that required for maximum NOx conversion. The reaction of NO2 with carbon is shown to lead mainly to backconversion of NO2 to NO. These results suggest that the combination of the plasma with a catalyst will be required to reduce the NOx and oxidize the hydrocarbons. The plasma reactor can be operated occasionally in the arc mode to thermally oxidize the carbon fraction of the particulates

Pre-treatment with cardamonin protects against cisplatin-induced nephrotoxicity in rats: Impact on NOX-1, inflammation and apoptosis

International Nuclear Information System (INIS)

El-Naga, Reem N.

2014-01-01

partially involved in the pathogenesis of cispaltin-induced nephrotoxicity. - Highlights: • Pre-treatment with cardamonin showed a promising nephroprotection against cisplatin. • Cardamonin attenuated cisplatin-induced oxidative stress and inflammation. • Cardamonin reduced apoptotic cell death in kidneys of cisplatin treated rats. • Cardamonin enhanced survival factors in cisplatin treated rats. • Cardamonin was shown to be NADPH oxidase (NOX-1) inhibitor

Pre-treatment with cardamonin protects against cisplatin-induced nephrotoxicity in rats: Impact on NOX-1, inflammation and apoptosis

Energy Technology Data Exchange (ETDEWEB)

El-Naga, Reem N., E-mail: reemelnaga@hotmail.com

2014-01-01

partially involved in the pathogenesis of cispaltin-induced nephrotoxicity. - Highlights: • Pre-treatment with cardamonin showed a promising nephroprotection against cisplatin. • Cardamonin attenuated cisplatin-induced oxidative stress and inflammation. • Cardamonin reduced apoptotic cell death in kidneys of cisplatin treated rats. • Cardamonin enhanced survival factors in cisplatin treated rats. • Cardamonin was shown to be NADPH oxidase (NOX-1) inhibitor.

Fructose suppresses uric acid excretion to the intestinal lumen as a result of the induction of oxidative stress by NADPH oxidase activation.

Science.gov (United States)

Kaneko, Chihiro; Ogura, Jiro; Sasaki, Shunichi; Okamoto, Keisuke; Kobayashi, Masaki; Kuwayama, Kaori; Narumi, Katsuya; Iseki, Ken

2017-03-01

A high intake of fructose increases the risk for hyperuricemia. It has been reported that long-term fructose consumption suppressed renal uric acid excretion and increased serum uric acid level. However, the effect of single administration of fructose on excretion of uric acid has not been clarified. We used male Wistar rats, which were orally administered fructose (5g/kg). Those rats were used in each experiment at 12h after administration. Single administration of fructose suppressed the function of ileal uric acid excretion and had no effect on the function of renal uric acid excretion. Breast cancer resistance protein (BCRP) predominantly contributes to intestinal excretion of uric acid as an active homodimer. Single administration of fructose decreased BCRP homodimer level in the ileum. Moreover, diphenyleneiodonium (DPI), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), recovered the suppression of the function of ileal uric acid excretion and the Bcrp homodimer level in the ileum of rats that received single administration of fructose. Single administration of fructose decreases in BCRP homodimer level, resulting in the suppression the function of ileal uric acid excretion. The suppression of the function of ileal uric acid excretion by single administration of fructose is caused by the activation of Nox. The results of our study provide a new insight into the mechanism of fructose-induced hyperuricemia. Copyright © 2016 Elsevier B.V. All rights reserved.

40 CFR 76.5 - NOX emission limitations for Group 1 boilers.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false NOX emission limitations for Group 1 boilers. 76.5 Section 76.5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.5 NOX emission limitations...

40 CFR 76.6 - NOX emission limitations for Group 2 boilers.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false NOX emission limitations for Group 2 boilers. 76.6 Section 76.6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.6 NOX emission limitations...

Retrofit SCR system for NOx control from heavy-duty mining equipment

International Nuclear Information System (INIS)

Mannan, M.A.

2009-01-01

Diesel engines are used extensively in the mining industry and offer many advantages. However, particulate matter (PM) emissions and nitrogen oxide emissions (NOx) are among its disadvantages. A significant concern related to PM and NOx in an underground mine involves the use of diesel exhaust after treatment systems such as diesel particulate filters and selective catalytic reduction (SCR). This presentation discussed NOx and PM control and provided a description of an SCR system and examples of SCR retrofits. Options for NOx control were discussed and a case study involving the installation of an SCR retrofit system in an underground mine operated by Sifto Salt was also presented. The purpose of the case study was to identify cost effective retrofit solutions to lower nitrogen dioxide emissions from heavy-duty trucks operating in underground mines. The case study illustrated and presented the candidate vehicle, baseline emissions, a BlueMax SCR retrofit solution, and BlueMax installation. 1 tab., 6 figs.

ACRATA: a novel electron transfer domain associated to apoptosis and cancer

Directory of Open Access Journals (Sweden)

Martinez-A Carlos

2004-12-01

Full Text Available Abstract Background Recently, several members of a vertebrate protein family containing a six trans-membrane (6TM domain and involved in apoptosis and cancer (e.g. STEAP, STAMP1, TSAP6, have been identified in Golgi and cytoplasmic membranes. The exact function of these proteins remains unknown. Methods We related this 6TM domain to distant protein families using intermediate sequences and methods of iterative profile sequence similarity search. Results Here we show for the first time that this 6TM domain is homolog to the 6TM heme binding domain of both the NADPH oxidase (Nox family and the YedZ family of bacterial oxidoreductases. Conclusions This finding gives novel insights about the existence of a previously undetected electron transfer system involved in apoptosis and cancer, and suggests further steps in the experimental characterization of these evolutionarily related families.

40 CFR 60.4320 - What emission limits must I meet for nitrogen oxides (NOX)?

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 6 2010-07-01 2010-07-01 false What emission limits must I meet for nitrogen oxides (NOX)? 60.4320 Section 60.4320 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... nitrogen oxides (NOX)? (a) You must meet the emission limits for NOX specified in Table 1 to this subpart...

Federal NOx Budget Trading Program and CAIR NOx and SO2 Trading Programs (40 CFR Part 97)

Science.gov (United States)

This part establishes general provisions and the applicability, permitting, allowance, excess emissions, monitoring, and opt-in provisions for the federal NOx Budget Trading Program as a means of mitigating interstate transport of ozone and nitrogen oxides

Modulation of NADPH oxidase activity by known uraemic retention solutes

DEFF Research Database (Denmark)

Schulz, Anna Marta; Terne, Cindy; Jankowski, Vera

2014-01-01

chloride (DPI), an inhibitor of NADPH oxidase. The effect on enzymatic activity of NADPH oxidase was quantified within an incubation time of 120 min. RESULTS: Thirty-nine of the 48 uraemic retention solutes tested had a significant decreasing effect on NADPH oxidase activity. Oxalate has been characterized......BACKGROUND: Uraemia and cardiovascular disease appear to be associated with an increased oxidative burden. One of the key players in the genesis of reactive oxygen species (ROS) is nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Based on initial experiments demonstrating a decreased...... inhibitory effect on NADPH oxidase activity in the presence of plasma from patients with CKD-5D after dialysis compared with before dialysis, we investigated the effect of 48 known and commercially available uraemic retention solutes on the enzymatic activity of NADPH oxidase. METHODS: Mononuclear leucocytes...

Gravity Responsive NADH Oxidase of the Plasma Membrane

Science.gov (United States)

Morre, D. James (Inventor)

2002-01-01

A method and apparatus for sensing gravity using an NADH oxidase of the plasma membrane which has been found to respond to unit gravity and low centrifugal g forces. The oxidation rate of NADH supplied to the NADH oxidase is measured and translated to represent the relative gravitational force exerted on the protein. The NADH oxidase of the plasma membrane may be obtained from plant or animal sources or may be produced recombinantly.

Regional Marginal Abatement Cost Curves for NOx

Data.gov (United States)

U.S. Environmental Protection Agency — Data underlying the figures included in the manuscript "Marginal abatement cost curve for NOx incorporating controls, renewable electricity, energy efficiency and...

Modeling lightning-NOx chemistry on a sub-grid scale in a global chemical transport model

Directory of Open Access Journals (Sweden)

A. Gressent

2016-05-01

Full Text Available For the first time, a plume-in-grid approach is implemented in a chemical transport model (CTM to parameterize the effects of the nonlinear reactions occurring within high concentrated NOx plumes from lightning NOx emissions (LNOx in the upper troposphere. It is characterized by a set of parameters including the plume lifetime, the effective reaction rate constant related to NOx–O3 chemical interactions, and the fractions of NOx conversion into HNO3 within the plume. Parameter estimates were made using the Dynamical Simple Model of Atmospheric Chemical Complexity (DSMACC box model, simple plume dispersion simulations, and the 3-D Meso-NH (non-hydrostatic mesoscale atmospheric model. In order to assess the impact of the LNOx plume approach on the NOx and O3 distributions on a large scale, simulations for the year 2006 were performed using the GEOS-Chem global model with a horizontal resolution of 2° × 2.5°. The implementation of the LNOx parameterization implies an NOx and O3 decrease on a large scale over the region characterized by a strong lightning activity (up to 25 and 8 %, respectively, over central Africa in July and a relative increase downwind of LNOx emissions (up to 18 and 2 % for NOx and O3, respectively, in July. The calculated variability in NOx and O3 mixing ratios around the mean value according to the known uncertainties in the parameter estimates is at a maximum over continental tropical regions with ΔNOx [−33.1, +29.7] ppt and ΔO3 [−1.56, +2.16] ppb, in January, and ΔNOx [−14.3, +21] ppt and ΔO3 [−1.18, +1.93] ppb, in July, mainly depending on the determination of the diffusion properties of the atmosphere and the initial NO mixing ratio injected by lightning. This approach allows us (i to reproduce a more realistic lightning NOx chemistry leading to better NOx and O3 distributions on the large scale and (ii to focus on other improvements to reduce remaining uncertainties from processes

NOx and SO2 emission factors for Serbian lignite Kolubara

Directory of Open Access Journals (Sweden)

Jovanović Vladimir V.

2012-01-01

Full Text Available Emission factors are widely accepted tool for estimation of various pollutants emissions in USA and EU. Validity of emission factors is strongly related to experimental data on which they are based. This paper is a result of an effort to establish reliable NOx and SO2 emission factors for Serbian coals. The results of NOx and SO2 emissions estimations based on USA and EU emission factors from thermal power plants Nikola Tesla Obrenovac A and B utilizing the Serbian lignite Kolubara are compared with experimental data obtained during almost one decade (2000-2008 of emissions measurements. Experimental data are provided from regular annual emissions measurement along with operational parameters of the boiler and coal (lignite Kolubara ultimate and proximate analysis. Significant deviations of estimated from experimental data were observed for NOx, while the results for SO2 were satisfactory. Afterwards, the estimated and experimental data were plotted and linear regression between them established. Single parameter optimization was performed targeting the ideal slope of the regression line. Results of this optimization provided original NOx and SO2 emission factors for Kolubara lignite.

Solid State Electrochemical DeNOx

DEFF Research Database (Denmark)

Kammer Hansen, Kent

2010-01-01

The literature on direct electrochemical reduction of NOx in a solid state cell has been reviewed. It is shown that that the reduction of nitric oxide either occurs on the electrode or on the electrolyte if F-centers are formed. It is also shown that some oxide based electrodes has a high apparent...

Worldwide biogenic soil NOx emissions inferred from OMI NO2 observations

NARCIS (Netherlands)

Vinken, G.C.M.; Boersma, K.F.; Maasakkers, J.D.; Adon, M.; Martin, R.V.

2014-01-01

Biogenic NOx emissions from soils are a large natural source with substantial uncertainties in global bottom-up estimates (ranging from 4 to 15 Tg N yr-1). We reduce this range in emission estimates, and present a top-down soil NOx emission inventory for 2005 based on retrieved tropospheric NO2

Worldwide biogenic soil NOx emissions inferred from OMI NO2 observations.

NARCIS (Netherlands)

Vinken, G.C.M.; Boersma, K.F.; Maasakkers, J.D.; Adon, M.; Martin, R.V.

2014-01-01

Biogenic NOx emissions from soils are a large natural source with substantial uncertainties in global bottom-up estimates (ranging from 4 to 15 Tg N yr-1). We reduce this range in emission estimates, and present a top-down soil NOx emission inventory for 2005 based on retrieved tropospheric NO2

Analysis of NOx Budget Trading Program Units Brought into the CAIR NOx Ozone Season Trading Program

Science.gov (United States)

EPA analyzed the effect of having the large non-EGU units in the NBP and the CAIR NOX ozone season trading program and evaluated whether or not emissions from this group of units were reduced as a result of their inclusion in those trading programs.

INF-γ Enhances Nox2 Activity by Upregulating phox Proteins When Applied to Differentiating PLB-985 Cells but Does Not Induce Nox2 Activity by Itself.

Directory of Open Access Journals (Sweden)

Michael A Ellison

Full Text Available The cytokine and drug interferon-γ enhances superoxide anion production by the antimicrobicidal Nox2 enzyme of neutrophils. Because mature neutrophils have a short lifespan, we hypothesized that the effects of interferon-γ on these cells might be mediated by its prolonged exposure to differentiating neutrophil precursors in the bone marrow rather than its brief exposure to mature circulating neutrophils. Effects of INF-Γ on NOX2 activity: To address this possibility we exposed the myeloid PLB-985 cell line to interferon-γ for 3 days in the presence of dimethyl sulfoxide which induces terminal differentiation of these cells. Interferon-γ was found to enhance superoxide production by Nox2 in a concentration dependent manner. In contrast, application of interferon-γ alone for 3 days failed to induce detectible Nox2 activity. Additionally, application of interferon-γ for 3 hours to pre-differentiated PLB-985 cells, which models studies using isolated neutrophils, was much less effective at enhancing superoxide anion production. Effects of INF-Γ on phox protein levels: Addition of interferon-γ during differentiation was found to upregulate the Nox2 proteins gp91phox and p47phox in concert with elevated transcription of their genes. The p22phox protein was upregulated in the absence of increased transcription presumably reflecting stabilization resulting from binding to the elevated gp91phox. Thus, increased levels of gp91phox, p47phox and p22phox likely account for the interferon-γ mediated enhancement of dimethyl sulfoxide-induced Nox2 activity. In contrast, although interferon-γ alone also increased various phox proteins and their mRNAs, the pattern was very different to that seen with interferon-γ plus dimethyl sulfoxide. In particular, p47phox was not induced thus explaining the inability of interferon -γ alone to enhance Nox2 activity. Short application of interferon-γ to already differentiated cells failed to increase any phox

Wintertime Overnight NOx Removal in a Southeastern United States Coal-fired Power Plant Plume: A Model for Understanding Winter NOx Processing and its Implications

Science.gov (United States)

Fibiger, Dorothy L.; McDuffie, Erin E.; Dubé, William P.; Aikin, Kenneth C.; Lopez-Hilfiker, Felipe D.; Lee, Ben H.; Green, Jaime R.; Fiddler, Marc N.; Holloway, John S.; Ebben, Carlena; Sparks, Tamara L.; Wooldridge, Paul; Weinheimer, Andrew J.; Montzka, Denise D.; Apel, Eric C.; Hornbrook, Rebecca S.; Hills, Alan J.; Blake, Nicola J.; DiGangi, Josh P.; Wolfe, Glenn M.; Bililign, Solomon; Cohen, Ronald C.; Thornton, Joel A.; Brown, Steven S.

2018-01-01

Nitric oxide (NO) is emitted in large quantities from coal-burning power plants. During the day, the plumes from these sources are efficiently mixed into the boundary layer, while at night, they may remain concentrated due to limited vertical mixing during which they undergo horizontal fanning. At night, the degree to which NO is converted to HNO3 and therefore unable to participate in next-day ozone (O3) formation depends on the mixing rate of the plume, the composition of power plant emissions, and the composition of the background atmosphere. In this study, we use observed plume intercepts from the Wintertime INvestigation of Transport, Emissions and Reactivity campaign to test sensitivity of overnight NOx removal to the N2O5 loss rate constant, plume mixing rate, background O3, and background levels of volatile organic compounds using a 2-D box model of power plant plume transport and chemistry. The factor that exerted the greatest control over NOx removal was the loss rate constant of N2O5. At the lowest observed N2O5 loss rate constant, no other combination of conditions converts more than 10% of the initial NOx to HNO3. The other factors did not influence NOx removal to the same degree.

Wintertime Overnight NOx Removal in a Southeastern United States Coal-Fired Power Plant Plume: A Model for Understanding Winter NOx Processing and Its Implications

Science.gov (United States)

Fibiger, Dorothy L.; McDuffie, Erin E.; Dube, William P.; Aikin, Kenneth C.; Lopez-Hilifiker, Felipe D.; Lee, Ben H.; Green, Jaime R.; Fiddler, Marc N.; Holloway, John S.; Ebben, Carlena;

Calcium transport in vesicles energized by cytochrome oxidase

Energy Technology Data Exchange (ETDEWEB)

Rosier, Randy N. [Univ. of Rochester, NY (United States)

1979-01-01

Experiments on the reconstitution of cytochrome oxidase into phospholipid vesicles were carried out using techniques of selectivity energizing the suspensions with ascorbate and cytochrome c or ascorbate, PMS, and internally trapped cytochrome c. It was found that the K⁺ selective ionophore valinomycin stimulated the rate of respiration of cytochrome oxidase vesicles regardless of the direction of the K⁺ flux across the vesicle membranes. The stimulation occurred in the presence of protonophoric uncouplers and in the complete absence of potassium or in detergent-lysed suspensions. Gramicidin had similar effects and it was determined that the ionophores acted by specific interaction with cytochrome oxidase rather than by the previously assumed collapse of membrane potentials. When hydrophobic proteins and appropriate coupling factors were incorporated into the cytochrome oxidase, vesicles phosphorylation of ADP could be coupled to the oxidation reaction of cytochrome oxidase. Relatively low P:O, representing poor coupling of the system, were problematical and precluded measurements of protonmotive force. However the system was used to study ion translocation.

Mechanistic Investigation of the Reduction of NOx over Pt- and Rh-Based LNT Catalysts

Directory of Open Access Journals (Sweden)

Lukasz Kubiak

2016-03-01

Full Text Available The influence of the noble metals (Pt vs. Rh on the NOx storage reduction performances of lean NOx trap catalysts is here investigated by transient micro-reactor flow experiments. The study indicates a different behavior during the storage in that the Rh-based catalyst showed higher storage capacity at high temperature as compared to the Pt-containing sample, while the opposite is seen at low temperatures. It is suggested that the higher storage capacity of the Rh-containing sample at high temperature is related to the higher dispersion of Rh as compared to Pt, while the lower storage capacity of Rh-Ba/Al2O3 at low temperature is related to its poor oxidizing properties. The noble metals also affect the catalyst behavior upon reduction of the stored NOx, by decreasing the threshold temperature for the reduction of the stored NOx. The Pt-based catalyst promotes the reduction of the adsorbed NOx at lower temperatures if compared to the Rh-containing sample, due to its superior reducibility. However, Rh-based material shows higher reactivity in the NH3 decomposition significantly enhancing N2 selectivity. Moreover, formation of small amounts of N2O is observed on both Pt- and Rh-based catalyst samples only during the reduction of highly reactive NOx stored at 150 °C, where NOx is likely in the form of nitrites.

Peroxisomal Polyamine Oxidase and NADPH-Oxidase cross-talk for ROS homeostasis which affects respiration rate in Arabidopsis thaliana

Directory of Open Access Journals (Sweden)

Efthimios A. Andronis

2014-04-01

Full Text Available Homeostasis of reactive oxygen species (ROS in the intracellular compartments is of critical importance as ROS have been linked with nearly all cellular processes and more importantly with diseases and aging. PAs are nitrogenous molecules with an evolutionary conserved role in the regulation of metabolic and energetic status of cells. Recent evidence also suggests that polyamines (PA are major regulators of ROS homeostasis. In Arabidopsis the backconversion of the PAs spermidine (Spd and spermine (Spm to putrescine (Put and Spd, respectively is catalyzed by two peroxisomal PA oxidases (AtPAO. However, the physiological role of this pathway remains largely elusive. Here we explore the role of peroxisomal PA backconversion and in particular that catalyzed by the highly expressed AtPAO3 in the regulation of ROS homeostasis and mitochondrial respiratory burst. Exogenous PAs exert an NADPH-oxidase dependent stimulation of oxygen consumption, with Spd exerting the strongest effect. This increase is attenuated by treatment with the NADPH-oxidase blocker diphenyleneiodonium iodide (DPI. Loss-of-function of AtPAO3 gene results to increased NADPH-oxidase-dependent production of superoxide anions (O2.-, but not H2O2, which activate the mitochondrial alternative oxidase pathway (AOX. On the contrary, overexpression of AtPAO3 results to an increased but balanced production of both H2O2 and O2.-. These results suggest that the ratio of O2.-/H2O2 regulates respiratory chain in mitochondria, with PA-dependent production of O2.- by NADPH-oxidase tilting the balance of electron transfer chain in favor of the AOX pathway. In addition, AtPAO3 seems to be an important component in the regulating module of ROS homeostasis, while a conserved role for PA backconversion and ROS across kingdoms is discussed.

Influence of satellite-derived photolysis rates and NOx emissions on Texas ozone modeling

Science.gov (United States)

Tang, W.; Cohan, D. S.; Pour-Biazar, A.; Lamsal, L. N.; White, A. T.; Xiao, X.; Zhou, W.; Henderson, B. H.; Lash, B. F.

2015-02-01

Uncertain photolysis rates and emission inventory impair the accuracy of state-level ozone (O3) regulatory modeling. Past studies have separately used satellite-observed clouds to correct the model-predicted photolysis rates, or satellite-constrained top-down NOx emissions to identify and reduce uncertainties in bottom-up NOx emissions. However, the joint application of multiple satellite-derived model inputs to improve O3 state implementation plan (SIP) modeling has rarely been explored. In this study, Geostationary Operational Environmental Satellite (GOES) observations of clouds are applied to derive the photolysis rates, replacing those used in Texas SIP modeling. This changes modeled O3 concentrations by up to 80 ppb and improves O3 simulations by reducing modeled normalized mean bias (NMB) and normalized mean error (NME) by up to 0.1. A sector-based discrete Kalman filter (DKF) inversion approach is incorporated with the Comprehensive Air Quality Model with extensions (CAMx)-decoupled direct method (DDM) model to adjust Texas NOx emissions using a high-resolution Ozone Monitoring Instrument (OMI) NO2 product. The discrepancy between OMI and CAMx NO2 vertical column densities (VCDs) is further reduced by increasing modeled NOx lifetime and adding an artificial amount of NO2 in the upper troposphere. The region-based DKF inversion suggests increasing NOx emissions by 10-50% in most regions, deteriorating the model performance in predicting ground NO2 and O3, while the sector-based DKF inversion tends to scale down area and nonroad NOx emissions by 50%, leading to a 2-5 ppb decrease in ground 8 h O3 predictions. Model performance in simulating ground NO2 and O3 are improved using sector-based inversion-constrained NOx emissions, with 0.25 and 0.04 reductions in NMBs and 0.13 and 0.04 reductions in NMEs, respectively. Using both GOES-derived photolysis rates and OMI-constrained NOx emissions together reduces modeled NMB and NME by 0.05, increases the model

Modulation of NADPH oxidase activity by known uraemic retention solutes.

Science.gov (United States)

Schulz, Anna Marta; Terne, Cindy; Jankowski, Vera; Cohen, Gerald; Schaefer, Mandy; Boehringer, Falko; Tepel, Martin; Kunkel, Desiree; Zidek, Walter; Jankowski, Joachim

2014-08-01

Uraemia and cardiovascular disease appear to be associated with an increased oxidative burden. One of the key players in the genesis of reactive oxygen species (ROS) is nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Based on initial experiments demonstrating a decreased inhibitory effect on NADPH oxidase activity in the presence of plasma from patients with CKD-5D after dialysis compared with before dialysis, we investigated the effect of 48 known and commercially available uraemic retention solutes on the enzymatic activity of NADPH oxidase. Mononuclear leucocytes isolated from buffy coats of healthy volunteers were isolated, lysed and incubated with NADH in the presence of plasma from healthy controls and patients with CKD-5D. Furthermore, the leucocytes were lysed and incubated in the presence of uraemic retention solute of interest and diphenyleneiodonium chloride (DPI), an inhibitor of NADPH oxidase. The effect on enzymatic activity of NADPH oxidase was quantified within an incubation time of 120 min. Thirty-nine of the 48 uraemic retention solutes tested had a significant decreasing effect on NADPH oxidase activity. Oxalate has been characterized as the strongest inhibitor of NADPH oxidase (90% of DPI inhibition). Surprisingly, none of the uraemic retention solutes we investigated was found to increase NADPH oxidase activity. Furthermore, plasma from patients with CKD-5D before dialysis caused significantly higher inhibitory effect on NADPH oxidase activity compared with plasma from healthy subjects. However, this effect was significantly decreased in plasma from patients with CKD-5D after dialysis. The results of this study show that uraemic retention solutes modulated the activity of the NADPH oxidase. The results of this study might be the basis for the development of inhibitors applicable as drug in the situation of increased oxidative stress. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

Supported Metal Zeolites as Environmental Catalysts for Reduction of NOx Molecules

International Nuclear Information System (INIS)

May Nwe Win; Tin Tin Aye; Kyaw Myo Naing; Nyunt Wynn; Maung Maung Htay

2005-09-01

The NOx contamination of air is a major pollutant due to its reaction with the volatile organic compounds, which give rise to ground level (tropospheric) ozone. It is a conventional fact that NOx are one of the major components of car exhaust. In view of that fact, to sustain the tropospheric ozone is to reduce the amount of NOx in the air. Therefore, this paper is concerned with the catalytic activity of Fe-loaded zeolite and Cu-loaded zeolite used to decompose NIOx by SCR (selective catalytic reduction) reaction with very high activity have been studied. Their preparations, characterization by XRD, FT-IR and SEM were also studied. Fe and Cu containig were prepared by soild state ion-exchange method under ambient presure and at the temperature of 600C for 4 hours. From this study, selective catalytic reduction rection was observed, showing about 87% conversion of the NOx molecule with the corresponding optimum amount of catalyst (1.0+-0.5)g working under the reactor space volume of 30cm3 at ambient temperature (30-32)C

Microwave catalytic NOx and SO{sub 2} removal using FeCu/zeolite as catalyst

Energy Technology Data Exchange (ETDEWEB)

Z.S. Wei; G.H. Zeng; Z.R. Xie; C.Y. Ma; X.H. Liu; J.L. Sun; L.H. Liu [Sun Yat-sen University, Guangzhou (China). School of Environmental Science and Engineering

2011-04-15

Non-thermal plasma technology is a promising process for flue gas treatment. Microwave catalytic NOx and SO{sub 2} removal simultaneously has been investigated using FeCu/zeolite as catalyst. The experimental results showed that a microwave reactor with FeCu/zeolite only could be used to microwave catalytic oxidative 91.7% NOx to nitrates and 79.6% SO{sub 2} to sulfate; the reaction efficiencies of microwave catalytic reduction of NOx and SO{sub 2} in a microwave reactor with FeCu/zeolite and ammonium bicarbonate (NH{sub 4}HCO{sub 3}) as a reducing agent could be up to 95.8% and 93.4% respectively. Microwave irradiation accentuates catalytic reduction of SO{sub 2} and NOx treatment, and microwave addition can increases SO{sub 2} removal efficiency from 14.5% to 18.7%, and NOx removal efficiency from 13.4% to 18.7%, separately. FeCu/zeolite catalyst was characterized by X-ray diffraction (XRD), X-ray photoelectron spectrum analysis (XPS), scanning electron microscopy (SEM) and the Brunauer Emmett Teller (BET) method. Microwave catalytic NOx and SO{sub 2} removal follows Langmuir-Hinshelwood (L-H) kinetics. 25 refs., 7 figs., 1 tab.

Lysyl oxidase in colorectal cancer

DEFF Research Database (Denmark)

Cox, Thomas R; Erler, Janine T

2013-01-01

Colorectal cancer is the third most prevalent form of cancer worldwide and fourth-leading cause of cancer-related mortality, leading to ~600,000 deaths annually, predominantly affecting the developed world. Lysyl oxidase is a secreted, extracellular matrix-modifying enzyme previously suggested...... to act as a tumor suppressor in colorectal cancer. However, emerging evidence has rapidly implicated lysyl oxidase in promoting metastasis of solid tumors and in particular colorectal cancer at multiple stages, affecting tumor cell proliferation, invasion, and angiogenesis. This emerging research has...... advancements in the field of colorectal cancer....

Characterization of the cydAB-Encoded Cytochrome bd Oxidase from Mycobacterium smegmatis

Science.gov (United States)

Kana, Bavesh D.; Weinstein, Edward A.; Avarbock, David; Dawes, Stephanie S.; Rubin, Harvey; Mizrahi, Valerie

2001-01-01

The cydAB genes from Mycobacterium smegmatis have been cloned and characterized. The cydA and cydB genes encode the two subunits of a cytochrome bd oxidase belonging to the widely distributed family of quinol oxidases found in prokaryotes. The cydD and cydC genes located immediately downstream of cydB encode a putative ATP-binding cassette-type transporter. At room temperature, reduced minus oxidized difference spectra of membranes purified from wild-type M. smegmatis displayed spectral features that are characteristic of the γ-proteobacterial type cytochrome bd oxidase. Inactivation of cydA or cydB by insertion of a kanamycin resistance marker resulted in loss of d-heme absorbance at 631 nm. The d-heme could be restored by transformation of the M. smegmatis cyd mutants with a replicating plasmid carrying the highly homologous cydABDC gene cluster from Mycobacterium tuberculosis. Inactivation of cydA had no effect on the ability of M. smegmatis to exit from stationary phase at 37 or 42°C. The growth rate of the cydA mutant was tested under oxystatic conditions. Although no discernible growth defect was observed under moderately aerobic conditions (9.2 to 37.5 × 102 Pa of pO2 or 5 to 21% air saturation), the mutant displayed a significant growth disadvantage when cocultured with the wild type under extreme microaerophilia (0.8 to 1.7 × 102 Pa of pO2 or 0.5 to 1% air saturation). These observations were in accordance with the two- to threefold increase in cydAB gene expression observed upon reduction of the pO2 of the growth medium from 21 to 0.5% air saturation and with the concomitant increase in d-heme absorbance in spectra of membranes isolated from wild-type M. smegmatis cultured at 1% air saturation. Finally, the cydA mutant displayed a competitive growth disadvantage in the presence of the terminal oxidase inhibitor, cyanide, when cocultured with wild type at 21% air saturation in an oxystat. In conjunction with these findings, our results suggest that

Effects of NOx and SO2 on the secondary organic aerosol formation from photooxidation of α-pinene and limonene

Science.gov (United States)

Zhao, Defeng; Schmitt, Sebastian H.; Wang, Mingjin; Acir, Ismail-Hakki; Tillmann, Ralf; Tan, Zhaofeng; Novelli, Anna; Fuchs, Hendrik; Pullinen, Iida; Wegener, Robert; Rohrer, Franz; Wildt, Jürgen; Kiendler-Scharr, Astrid; Wahner, Andreas; Mentel, Thomas F.

2018-02-01

Anthropogenic emissions such as NOx and SO2 influence the biogenic secondary organic aerosol (SOA) formation, but detailed mechanisms and effects are still elusive. We studied the effects of NOx and SO2 on the SOA formation from the photooxidation of α-pinene and limonene at ambient relevant NOx and SO2 concentrations (NOx: leading to a lack of particle surface for the organics to condense on and thus a significant influence of vapor wall loss on SOA mass yield. By compensating for the suppressing effect on nucleation of NOx, SO2 also compensated for the suppressing effect on SOA yield. Aerosol mass spectrometer data show that increasing NOx enhanced nitrate formation. The majority of the nitrate was organic nitrate (57-77 %), even in low-NOx conditions (nitrate contributed 7-26 % of total organics assuming a molecular weight of 200 g mol-1. SOA from α-pinene photooxidation at high NOx had a generally lower hydrogen to carbon ratio (H / C), compared to low NOx. The NOx dependence of the chemical composition can be attributed to the NOx dependence of the branching ratio of the RO2 loss reactions, leading to a lower fraction of organic hydroperoxides and higher fractions of organic nitrates at high NOx. While NOx suppressed new particle formation and SOA mass formation, SO2 can compensate for such effects, and the combining effect of SO2 and NOx may have an important influence on SOA formation affected by interactions of biogenic volatile organic compounds (VOCs) with anthropogenic emissions.

The Gothenburg Protocol: NOx emissions problematic for Norway

International Nuclear Information System (INIS)

Lind, Oddvar

2000-01-01

The Gothenburg Protocol concerns long-range air pollution and is a continuation of earlier protocols and agreements. Its recommendations are based on calculations of where the greatest possible health- and environmental impact is obtained per dollar invested. European countries have done much to reduce the emission of sulphur dioxide. Norway and most other countries, however, have difficulties reducing their emissions of nitrogen oxides. In Norway, the emission of sulphur dioxide must also be substantially reduced, as the tolerance limit for SO2 in nature is low. It is socio-economically profitable for Norway to conform to the Gothenburg Protocol. One of the largest environmental problems in Norway is acid rain and death of fish. Although it is difficult to calculate the exact values of fishing-lakes and of reduced health injuries when the emissions of harmful waste gases are reduced, the profit is very high. 90% of the SO2 pollution in Norway is long-range transported from abroad. Yet Norway must reduce the domestic emissions from 30 000 to 22 000 tonnes the next 10 years. Most of the present emission of SO2 in Norway comes from the production of metals. The reduction goal can be achieved by a combination of improving industrial processes, SO2 cleaning, and reducing the sulphur content of oil. In many European countries, the greatest problem is the increasing emission of NOx and formation of ozone at the ground, which is largely due to the rapidly increasing motor traffic. In Norway, most of the NOx emission comes from the coastal traffic and the fishing fleet, followed by the motor traffic, the petroleum industry and the processing industry. The most cost-effective NOx reductions can be obtained in the North Sea by installing low-NOx gas turbines. In ships, catalytic cleaning of NOx and engine improvements will contribute. On land, the goods traffic can be made more efficient. Most of the emission of ammonia comes from agriculture, where special measures are

Evaluation of oxalate decarboxylase and oxalate oxidase for industrial applications.

Science.gov (United States)

Cassland, Pierre; Sjöde, Anders; Winestrand, Sandra; Jönsson, Leif J; Nilvebrant, Nils-Olof

2010-05-01

Increased recirculation of process water has given rise to problems with formation of calcium oxalate incrusts (scaling) in the pulp and paper industry and in forest biorefineries. The potential in using oxalate decarboxylase from Aspergillus niger for oxalic acid removal in industrial bleaching plant filtrates containing oxalic acid was examined and compared with barley oxalate oxidase. Ten different filtrates from chemical pulping were selected for the evaluation. Oxalate decarboxylase degraded oxalic acid faster than oxalate oxidase in eight of the filtrates, while oxalate oxidase performed better in one filtrate. One of the filtrates inhibited both enzymes. The potential inhibitory effect of selected compounds on the enzymatic activity was tested. Oxalate decarboxylase was more sensitive than oxalate oxidase to hydrogen peroxide. Oxalate decarboxylase was not as sensitive to chlorate and chlorite as oxalate oxidase. Up to 4 mM chlorate ions, the highest concentration tested, had no inhibitory effect on oxalate decarboxylase. Analysis of the filtrates suggests that high concentrations of chlorate present in some of the filtrates were responsible for the higher sensitivity of oxalate oxidase in these filtrates. Oxalate decarboxylase was thus a better choice than oxalate oxidase for treatment of filtrates from chlorine dioxide bleaching.

Source apportionment and health effect of NO_x over the Pearl River Delta region in southern China

International Nuclear Information System (INIS)

Lu, Xingcheng; Yao, Teng; Li, Ying; Fung, Jimmy C.H.; Lau, Alexis K.H.

2016-01-01

As one of the most notorious atmospheric pollutants, NO_x not only promotes the formation of ozone but also has adverse health effects on humans. It is therefore of great importance to study the sources of NO_x and its effects on human health. The Comprehensive Air Quality Model (CAMx) modeling system and ozone source apportionment technology (OSAT) were used to study the contribution of NO_x from different emission sources over southern China. The results indicate that heavy duty diesel vehicles (HDDVs) and industrial point sources are the two major local NO_x sources, accounting for 30.8% and 18.5% of local NO_x sources, respectively. In Hong Kong, marine emissions contributed around 43.4% of local NO_x in 2011. Regional transport is another important source of this pollutant, especially in February and November, and it can contribute over 30% of ambient NO_x on average. Power plant point emission is an significant regional source in Zhuhai, Zhongshan and Foshan. The total emission sources are estimated to cause 2119 (0–4405) respiratory deaths and 991 (0–2281) lung cancer deaths due to long-term exposure to NO_x in the Pearl River Delta region. Our results suggest that local governments should combine their efforts and vigorously promote further reduction of NO_x emissions, especially for those sources that make a substantial contribution to NO_x emissions and affect human health: HDDV, LDGV, industrial point sources and marine sources. - Highlights: • WRF-CAMx modeling system with OSAT was used to study the source of NO_x over Pearl River Delta region in China. • The results indicated that local emission and regional transportation are important contributors for NO_x in this region. • Heavy duty diesel vehicle, marine emission and industrial point source are three important contribution sectors. • Long-term exposure to NO_x is estimated to cause 2119 respiratory deaths and 991 lung cancer deaths in PRD during 2011. - Result indicated that heavy duty

Sulfur Deactivation of NOx Storage Catalysts: A Multiscale Modeling Approach

Directory of Open Access Journals (Sweden)

Rankovic N.

2013-09-01

Full Text Available Lean NOx Trap (LNT catalysts, a promising solution for reducing the noxious nitrogen oxide emissions from the lean burn and Diesel engines, are technologically limited by the presence of sulfur in the exhaust gas stream. Sulfur stemming from both fuels and lubricating oils is oxidized during the combustion event and mainly exists as SOx (SO2 and SO3 in the exhaust. Sulfur oxides interact strongly with the NOx trapping material of a LNT to form thermodynamically favored sulfate species, consequently leading to the blockage of NOx sorption sites and altering the catalyst operation. Molecular and kinetic modeling represent a valuable tool for predicting system behavior and evaluating catalytic performances. The present paper demonstrates how fundamental ab initio calculations can be used as a valuable source for designing kinetic models developed in the IFP Exhaust library, intended for vehicle simulations. The concrete example we chose to illustrate our approach was SO3 adsorption on the model NOx storage material, BaO. SO3 adsorption was described for various sites (terraces, surface steps and kinks and bulk for a closer description of a real storage material. Additional rate and sensitivity analyses provided a deeper understanding of the poisoning phenomena.

Lagrangian Hotspots of In-Use NOX Emissions from Transit Buses.

Science.gov (United States)

Kotz, Andrew J; Kittelson, David B; Northrop, William F

2016-06-07

In-use, spatiotemporal NOX emissions were measured from a conventional powertrain transit bus and a series electric hybrid bus over gradients of route kinetic intensity and ambient temperature. This paper introduces a new method for identifying NOX emissions hotspots along a bus route using high fidelity Lagrangian vehicle data to explore spatial interactions that may influence emissions production. Our study shows that the studied transit buses emit higher than regulated emissions because on-route operation does not accurately represent the range of engine operation tested according to regulatory standards. Using the Lagrangian hotspot detection, we demonstrate that NOX hotspots occurred at bus stops, during cold starts, on inclines, and for accelerations. On the selected routes, bus stops resulted in 3.3 times the route averaged emissions factor in grams/km without significant dependence on bus type or climate. The buses also emitted 2.3 times the route averaged NOX emissions factor at the beginning of each route due to cold selective catalytic reduction aftertreatment temperature. The Lagrangian hotspot detection technique demonstrated here could be employed in future connected vehicles empowered by advances in computational power, data storage capability, and improved sensor technology to optimize emissions as a function of spatial location.

Low cost combustion tuning and fuel nozzles modification to reduce NOx emission in large coal-fired boilers

Energy Technology Data Exchange (ETDEWEB)

B. Chudnovsky; L. Levin; A. Talanker; E. Bar-Ziv; A. Vikhansky; A.F. Sarofim [Israel Electric Corporation (IEC), Haifa (Israel)

2003-07-01

This work focuses on low-cost combustion tuning to reduce NOx emission in coal-fired tangential boilers, testing the furnace in various operation modes. We have also experimented different coal nozzle types. The measurements were accompanied by computer simulations of the combustion process. We also used an on-line supervision system. The data obtained from 575 MW boilers show that with tuning and modified nozzles NOx was considerably reduced. The emission of NOx was reduced from 1200 to 570 mg/dNm{sup 3} at 6% O{sub 2} for South African coal at full load. At partial load NOx emission dropped from 1400 to 750-850 mg/dNm{sup 3} at 6% O{sub 2}. High volatile coal firing led to additional NOx reduction. A series of tests were performed with Colombian and Indonesian coals as well, dropping NOx emission to 400-450 mg/dNm{sup 3} at6% O{sub 2} at full load. Sootblowing optimization using the supervision system enabled us to further reduce NOx emission by approximately 10%. The boiler and unit performance was not influenced by any of the techniques used for NOx reduction. In such a manner, the results presented in this work clearly show that technological methods for reduction NOx are available and capable of obtaining the required NOx emission. We believe that the conclusions of the present study are general and may be applied to other utility boilers as well. 13 refs., 12 figs., 7 tabs.

Biodiesel unsaturation degree effects on diesel engine NOx emissions and cotton wick flame temperature

Directory of Open Access Journals (Sweden)

Abdullah Mohd Fareez Edzuan

2017-01-01

Full Text Available As compared with conventional diesel fuel, biodiesel has better lubricity and lower particulate matter (PM emissions however nitrogen oxides (NOx emissions generally increase in biodiesel-fuelled diesel engine. Strict regulation on NOx emissions is being implemented in current Euro 6 standard and it is expected to be tighter in next standard, thus increase of NOx cannot be accepted. In this study, biodiesel unsaturation degree effects on NOx emissions are investigated. Canola, palm and coconut oils are selected as the feedstock based on their unsaturation degree. Biodiesel blends of B20 were used to fuel a single cylinder diesel engine and exhaust emissions were sampled directly at exhaust tailpipe with a flue gas analyser. Biodiesel flame temperature was measured from a cotton wick burned in simple atmospheric conditions using a thermocouple. Fourier transform infrared (FTIR spectrometer was also used to identify the functional groups presence in the biodiesel blends. Oxygen content in biodiesel may promote complete combustion as the NOx emissions and flame temperatures were increased while the carbon monoxide (CO emissions were decreased for all biodiesel blends. It is interesting to note that the NOx emissions and flame temperatures were directly proportional with biodiesel unsaturation degree. It might be suggested that apart from excess oxygen and free radical formation, higher NOx emissions can also be caused by the elevated flame temperatures due to the presence of double bonds in unsaturated biodiesel.

Production of rabbit antibodies against purified Glucose oxidase

Directory of Open Access Journals (Sweden)

Muhammad Anjum Zia

2012-02-01

Full Text Available Glucose oxidase is an active oxygen species generating enzyme produced from Aspergillus niger grown in submerged fermentation. Disintegration of the mycelium resulted in high glucose oxidase activity that was subjected to ammonium sulfate precipitation at 60-85% saturation rates that resulted to 6.14 U mg -1 specific activity. Purification of enzyme by anion exchange column (DEAE-Cellulose resulted into 22.53 U mg-1 specific activity and 10.27 fold purification. This was applied to sephadex G-200 column for gel filtration chromatography. It was observed that enzyme achieved 59.37 U mg-1of specific activity with 27.08 fold purity and 64.36% recovery. Purified glucose oxidase was injected into rabbits through intravenous route, to raise the glucose oxidase antibodies. After 30 days incubation period, the rabbits were slaughtered and serum was separated from blood. The antibodies were isolated by ammonium sulfate precipitation and confirmed by agar gel precipitation test. This could be a convenient and low cost alternate assay for the estimation of glucose oxidase in biological fluids. Moreover, such antibodies against the said enzyme could be used in various therapeutic and diagnostic applications.

Highly selective NOx reduction for diesel engine exhaust via an electrochemical system

DEFF Research Database (Denmark)

Shao, Jing; Tao, Youkun; Kammer Hansen, Kent

2016-01-01

It is challenging to reduce the nitrogen oxides (NOx) in diesel engine exhaust due to the inhibiting effect of excess oxygen. In this study, a novel electrochemical deNOx system was developed, which eliminated the need for additional reducing materials or a sophisticated controlling system as used...

State Estimation in the Automotive SCR DeNOx Process

DEFF Research Database (Denmark)

Zhou, Guofeng; Jørgensen, John Bagterp; Duwig, Christophe

2012-01-01

on exhaust gas emissions. For advanced control, e.g. Model Predictive Control (MPC), of the SCR process, accurate state estimates are needed. We investigate the performance of the ordinary and the extended Kalman filters based on a simple first principle system model. The performance is tested through......Selective catalytic reduction (SCR) of nitrogen oxides (NOx) is a widely applied diesel engine exhaust gas after-treatment technology. For effective NOx removal in a transient operating automotive application, controlled dosing of urea can be used to meet the increasingly restrictive legislations...

Chemoenzymatic combination of glucose oxidase with titanium silicalite -1

DEFF Research Database (Denmark)

Vennestrøm, Peter Nicolai Ravnborg; Taarning, Esben; Christensen, Claus H.

2010-01-01

Zeozymes: A proof-of-concept is presented for the chemoenzymatic combination of titanium silicalite-1 zeolite with glucose oxidase. In this combination, glucose is oxidized to gluconic acid and the H2O2 byproduct formed in situ is used for the simultaneous oxidation of chemical substrates. Both...... a soluble glucose oxidase and a truly integrated heterogeneous combination whereby the oxidase enzyme is anchored onto the zeolite surface are reported....

Crystal structure of human lysyl oxidase-like 2 (hLOXL2) in a precursor state.

Science.gov (United States)

Zhang, Xi; Wang, Qifan; Wu, Jianping; Wang, Jiawei; Shi, Yigong; Liu, Minhao

2018-04-10

Lysyl oxidases (LOXs), a type of copper- and lysyl tyrosylquinone (LTQ) -dependent amine oxidase, catalyze the oxidative deamination of lysine residues of extracellular matrix (ECM) proteins such as elastins and collagens and generate aldehyde groups. The oxidative deamination of lysine represents the foundational step for the cross-linking of elastin and collagen and thus is crucial for ECM modeling. Despite their physiological significance, the structure of this important family of enzymes remains elusive. Here we report the crystal structure of human lysyl oxidase-like 2 (hLOXL2) at 2.4-Å resolution. Unexpectedly, the copper-binding site of hLOXL2 is occupied by zinc, which blocks LTQ generation and the enzymatic activity of hLOXL2 in our in vitro assay. Biochemical analysis confirms that copper loading robustly activates hLOXL2 and supports LTQ formation. Furthermore, the LTQ precursor residues in the structure are distanced by 16.6 Å, corroborating the notion that the present structure may represent a precursor state and that pronounced conformational rearrangements would be required for protein activation. The structure presented here establishes an important foundation for understanding the structure-function relationship of LOX proteins and will facilitate LOX-targeting drug discovery. Copyright © 2018 the Author(s). Published by PNAS.

Diffusion-controlled oxygen reduction on multi-copper oxidase-adsorbed carbon aerogel electrodes without mediator

Energy Technology Data Exchange (ETDEWEB)

Tsujimura, S.; Kamitaka, Y.; Kano, K. [Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto (Japan)

2007-12-15

Bioelectrocatalytic reduction of O{sub 2} into water was archived at diffusion-controlled rate by using enzymes (laccase from Trametes sp. and bilirubin oxidase from Myrothecium verrucaria, which belong to the family of multi-copper oxidase) adsorbed on mesoporous carbon aerogel particle without a mediator. The current density was predominantly controlled by the diffusion of dissolved O{sub 2} in rotating-disk electrode experiments, and reached a value as large as 10 mA cm{sup -2} at 1 atm O{sub 2}, 25 C, and 8,000 rpm on the laccase-adsorbed electrode. The overpotential of the bioelectrocatalytic reduction of O{sub 2} was 0.4-0.55 V smaller than that observed on a Pt disk electrode. Without any optimization, the laccase-adsorbed biocathode showed stable current intensity of the O{sub 2} reduction in an air-saturated buffer at least for 10 days under continuous flow system. (Abstract Copyright [2007], Wiley Periodicals, Inc.)

Comparison of wintertime CO to NOx ratios to MOVES and MOBILE6.2 on-road emissions inventories

Science.gov (United States)

Wallace, H. W.; Jobson, B. T.; Erickson, M. H.; McCoskey, J. K.; VanReken, T. M.; Lamb, B. K.; Vaughan, J. K.; Hardy, R. J.; Cole, J. L.; Strachan, S. M.; Zhang, W.

2012-12-01

The CO-to-NOx molar emission ratios from the US EPA vehicle emissions models MOVES and MOBILE6.2 were compared to urban wintertime measurements of CO and NOx. Measurements of CO, NOx, and volatile organic compounds were made at a regional air monitoring site in Boise, Idaho for 2 months from December 2008 to January 2009. The site is impacted by roadway emissions from a nearby busy urban arterial roads and highway. The measured CO-to-NOx ratio for morning rush hour periods was 4.2 ± 0.6. The average CO-to-NOx ratio during weekdays between the hours of 08:00 and 18:00 when vehicle miles travelled were highest was 5.2 ± 0.5. For this time period, MOVES yields an average hourly CO-to-NOx ratio of 9.1 compared to 20.2 for MOBILE6.2. Off-network emissions are a significant fraction of the CO and NOx emissions in MOVES, accounting for 65% of total CO emissions, and significantly increase the CO-to-NOx molar ratio. Observed ratios were more similar to the average hourly running emissions for urban roads determined by MOVES to be 4.3.

NOx from lightning: 1. Global distribution based on lightning physics

Science.gov (United States)

Price, Colin; Penner, Joyce; Prather, Michael

1997-03-01

This paper begins a study on the role of lightning in maintaining the global distribution of nitrogen oxides (NOx) in the troposphere. It presents the first global and seasonal distributions of lightning-produced NOx (LNOx) based on the observed distribution of electrical storms and the physical properties of lightning strokes. We derive a global rate for cloud-to-ground (CG) flashes of 20-30 flashes/s with a mean energy per flash of 6.7×109 J. Intracloud (IC) flashes are more frequent, 50-70 flashes/s but have 10% of the energy of CG strokes and, consequently, produce significantly less NOx. It appears to us that the majority of previous studies have mistakenly assumed that all lightning flashes produce the same amount of NOx, thus overestimating the NOx production by a factor of 3. On the other hand, we feel these same studies have underestimated the energy released in CG flashes, resulting in two negating assumptions. For CG energies we adopt a production rate of 10×1016 molecules NO/J based on the current literature. Using a method to simulate global lightning frequencies from satellite-observed cloud data, we have calculated the LNOx on various spatial (regional, zonal, meridional, and global) and temporal scales (daily, monthly, seasonal, and interannual). Regionally, the production of LNOx is concentrated over tropical continental regions, predominantly in the summer hemisphere. The annual mean production rate is calculated to be 12.2 Tg N/yr, and we believe it extremely unlikely that this number is less than 5 or more than 20 Tg N/yr. Although most of LNOx, is produced in the lowest 5 km by CG lightning, convective mixing in the thunderstorms is likely to deposit large amounts of NOx, in the upper troposphere where it is important in ozone production. On an annual basis, 64% of the LNOx, is produced in the northern hemisphere, implying that the northern hemisphere should have natural ozone levels as much as 2 times greater than the southern hemisphere

Reducing NOx emissions from a biodiesel-fueled engine by use of low-temperature combustion.

Science.gov (United States)

Fang, Tiegang; Lin, Yuan-Chung; Foong, Tien Mun; Lee, Chia-Fon

2008-12-01

Biodiesel is popularly discussed in many countries due to increased environmental awareness and the limited supply of petroleum. One of the main factors impacting general replacement of diesel by biodiesel is NOx (nitrogen oxides) emissions. Previous studies have shown higher NOx emissions relative to petroleum diesel in traditional direct-injection (DI) diesel engines. In this study, effects of injection timing and different biodiesel blends are studied for low load [2 bar IMEP (indicated mean effective pressure)] conditions. The results show that maximum heat release rate can be reduced by retarding fuel injection. Ignition and peak heat release rate are both delayed for fuels containing more biodiesel. Retarding the injection to post-TDC (top dead center) lowers the peak heat release and flattens the heat release curve. It is observed that low-temperature combustion effectively reduces NOx emissions because less thermal NOx is formed. Although biodiesel combustion produces more NOx for both conventional and late-injection strategies, with the latter leading to a low-temperature combustion mode, the levels of NOx of B20 (20 vol % soy biodiesel and 80 vol % European low-sulfur diesel), B50, and B100 all with post-TDC injection are 68.1%, 66.7%, and 64.4%, respectively, lower than pure European low-sulfur diesel in the conventional injection scenario.

Amine oxidases as important agents of pathological processes of rhabdomyolysis in rats.

Science.gov (United States)

Gudkova, O O; Latyshko, N V; Shandrenko, S G

2016-01-01

In this study we have tested an idea on the important role of amine oxidases (semicarbazide-sensitive amine oxidase, diamine oxidase, polyamine oxidase) as an additional source of oxidative/carbonyl stress under glycerol-induced rhabdomyolysis, since the enhanced formation of reactive oxygen species and reactive carbonyl species in a variety of tissues is linked to various diseases. In our experiments we used the sensitive fluorescent method devised for estimation of amine oxidases activity in the rat kidney and thymus as targeted organs under rhabdomyolysis. We have found in vivo the multiple rises in activity of semicarbazide-sensitive amine oxidase, diamine oxidase, polyamine oxidase (2-4.5 times) in the corresponding cell fractions, whole cells or their lysates at the 3-6th day after glycerol injection. Aberrant antioxidant activities depended on rhabdomyolysis stage and had organ specificity. Additional treatment of animals with metal chelator ‘Unithiol’ adjusted only the activity of antioxidant enzymes but not amine oxidases in both organs. Furthermore the in vitro experiment showed that Fenton reaction (hydrogen peroxide in the presence of iron) products alone had no effect on semicarbazide-sensitive amine oxidase activity in rat liver cell fraction whereas supplementation with methylglyoxal resulted in its significant 2.5-fold enhancement. Combined action of the both agents had additive effect on semicarbazide-sensitive amine oxidase activity. We can assume that biogenic amine and polyamine catabolism by amine oxidases is upregulated by oxidative and carbonyl stress factors directly under rhabdomyolysis progression, and the increase in catabolic products concentration contributes to tissue damage in glycerol-induced acute renal failure and apoptosis stimulation in thymus.

Experimental and Modeling Investigation of the Effect of Air Preheat on the Formation of NOx in an RQL Combustor

Science.gov (United States)

Samuelsen, G. S.; Brouwer, J.; Vardakas, M. A.; Holderman, J. D.

2012-01-01

The Rich-burn/Quick-mix/Lean-burn (RQL) combustor concept has been proposed to minimize the formation of oxides of nitrogen (NOx) in gas turbine systems. The success of this low-NOx combustor strategy is dependent upon the links between the formation of NOx, inlet air preheat temperature, and the mixing of the jet air and fuel-rich streams. Chemical equilibrium and kinetics modeling calculations and experiments were performed to further understand NOx emissions in an RQL combustor. The results indicate that as the temperature at the inlet to the mixing zone increases (due to preheating and/or operating conditions) the fuel-rich zone equivalence ratio must be increased to achieve minimum NOx formation in the primary zone of the combustor. The chemical kinetics model illustrates that there is sufficient residence time to produce NOx at concentrations that agree well with the NOx measurements. Air preheat was found to have very little effect on mixing, but preheating the air did increase NOx emissions significantly. By understanding the mechanisms governing NOx formation and the temperature dependence of key reactions in the RQL combustor, a strategy can be devised to further reduce NOx emissions using the RQL concept.

Laboratory-evolved vanillyl-alcohol oxidase produces natural vanillin

NARCIS (Netherlands)

Heuvel, van den R.H.H.; Berg, van den W.A.M.; Rovida, S.; Berkel, van W.J.H.

2004-01-01

The flavoenzyme vanillyl-alcohol oxidase was subjected to random mutagenesis to generate mutants with enhanced reactivity to creosol (2-methoxy-4-methylphenol). The vanillyl-alcohol oxidase-mediated conversion of creosol proceeds via a two-step process in which the initially formed vanillyl alcohol

Maritime NOx Emissions Over Chinese Seas Derived From Satellite Observations

Science.gov (United States)

Ding, J.; van der A, R. J.; Mijling, B.; Jalkanen, J.-P.; Johansson, L.; Levelt, P. F.

2018-02-01

By applying an inversion algorithm to NOx satellite observations from Ozone Monitoring Instrument, monthly NOx emissions for a 10 year period (2007 to 2016) over Chinese seas are presented for the first time. No effective regulations on NOx emissions have been implemented for ships in China, which is reflected in the trend analysis of maritime emissions. The maritime emissions display a continuous increase rate of about 20% per year until 2012 and slow down to 3% after that. The seasonal cycle of shipping emissions has regional variations, but all regions show lower emissions during winter. Simulations by an atmospheric chemistry transport model show a notable influence of maritime emissions on air pollution over coastal areas, especially in summer. The satellite-derived spatial distribution and the magnitude of maritime emissions over Chinese seas are in good agreement with bottom-up studies based on the Automatic Identification System of ships.

Benfotiamine increases glucose oxidation and downregulates NADPH oxidase 4 expression in cultured human myotubes exposed to both normal and high glucose concentrations.

Science.gov (United States)

Fraser, D A; Hessvik, N P; Nikolić, N; Aas, V; Hanssen, K F; Bøhn, S K; Thoresen, G H; Rustan, A C

2012-07-01

The aim of the present work was to study the effects of benfotiamine (S-benzoylthiamine O-monophosphate) on glucose and lipid metabolism and gene expression in differentiated human skeletal muscle cells (myotubes) incubated for 4 days under normal (5.5 mM glucose) and hyperglycemic (20 mM glucose) conditions. Myotubes established from lean, healthy volunteers were treated with benfotiamine for 4 days. Glucose and lipid metabolism were studied with labeled precursors. Gene expression was measured using real-time polymerase chain reaction (qPCR) and microarray technology. Benfotiamine significantly increased glucose oxidation under normoglycemic (35 and 49% increase at 100 and 200 μM benfotiamine, respectively) as well as hyperglycemic conditions (70% increase at 200 μM benfotiamine). Benfotiamine also increased glucose uptake. In comparison, thiamine (200 μM) increased overall glucose metabolism but did not change glucose oxidation. In contrast to glucose, mitochondrial lipid oxidation and overall lipid metabolism were unchanged by benfotiamine. The expression of NADPH oxidase 4 (NOX4) was significantly downregulated by benfotiamine treatment under both normo- and hyperglycemic conditions. Gene set enrichment analysis (GSEA) showed that befotiamine increased peroxisomal lipid oxidation and organelle (mitochondrial) membrane function. In conclusion, benfotiamine increases mitochondrial glucose oxidation in myotubes and downregulates NOX4 expression. These findings may be of relevance to type 2 diabetes where reversal of reduced glucose oxidation and mitochondrial capacity is a desirable goal.

Putting together a plasma membrane NADH oxidase: a tale of three laboratories.

Science.gov (United States)

Löw, Hans; Crane, Frederick L; Morré, D James

2012-11-01

The observation that high cellular concentrations of NADH were associated with low adenylate cyclase activity led to a search for the mechanism of the effect. Since cyclase is in the plasma membrane, we considered the membrane might have a site for NADH action, and that NADH might be oxidized at that site. A test for NADH oxidase showed very low activity, which could be increased by adding growth factors. The plasma membrane oxidase was not inhibited by inhibitors of mitochondrial NADH oxidase such as cyanide, rotenone or antimycin. Stimulation of the plasma membrane oxidase by iso-proterenol or triiodothyronine was different from lack of stimulation in endoplasmic reticulum. After 25 years of research, three components of a trans membrane NADH oxidase have been discovered. Flavoprotein NADH coenzyme Q reductases (NADH cytochrome b reductase) on the inside, coenzyme Q in the middle, and a coenzyme Q oxidase on the outside as a terminal oxidase. The external oxidase segment is a copper protein with unique properties in timekeeping, protein disulfide isomerase and endogenous NADH oxidase activity, which affords a mechanism for control of cell growth by the overall NADH oxidase and the remarkable inhibition of oxidase activity and growth of cancer cells by a wide range of anti-tumor drugs. A second trans plasma membrane electron transport system has been found in voltage dependent anion channel (VDAC), which has NADH ferricyanide reductase activity. This activity must be considered in relation to ferricyanide stimulation of growth and increased VDAC antibodies in patients with autism. Copyright © 2012 Elsevier Ltd. All rights reserved.

In Situ Enzymatically Generated Photoswitchable Oxidase Mimetics and Their Application for Colorimetric Detection of Glucose Oxidase.

Science.gov (United States)

Cao, Gen-Xia; Wu, Xiu-Ming; Dong, Yu-Ming; Li, Zai-Jun; Wang, Guang-Li

2016-07-09

In this study, a simple and amplified colorimetric assay is developed for the detection of the enzymatic activity of glucose oxidase (GOx) based on in situ formation of a photoswitchable oxidase mimetic of PO₄(3-)-capped CdS quantum dots (QDs). GOx catalyzes the oxidation of 1-thio-β-d-glucose to give 1-thio-β-d-gluconic acid which spontaneously hydrolyzes to β-d-gluconic acid and H₂S; the generated H₂S instantly reacts with Cd(2+) in the presence of Na₃PO₄ to give PO₄(3-)-stabilized CdS QDs in situ. Under visible-light (λ ≥ 400 nm) stimulation, the PO₄(3-)-capped CdS QDs are a new style of oxidase mimic derived by producing some active species, such as h⁺, (•)OH, O₂(•-) and a little H₂O₂, which can oxidize the typical substrate (3,3,5,5-tetramethylbenzydine (TMB)) with a color change. Based on the GOx-triggered growth of the oxidase mimetics of PO₄(3-)-capped CdS QDs in situ, we developed a simple and amplified colorimetric assay to probe the enzymatic activity of GOx. The proposed method allowed the detection of the enzymatic activity of GOx over the range from 25 μg/L to 50 mg/L with a low detection limit of 6.6 μg/L. We believe the PO₄(3-)-capped CdS QDs generated in situ with photo-stimulated enzyme-mimicking activity may find wide potential applications in biosensors.

Effects of NOx and SO2 on the secondary organic aerosol formation from photooxidation of α-pinene and limonene

Directory of Open Access Journals (Sweden)

D. Zhao

2018-02-01

Full Text Available Anthropogenic emissions such as NOx and SO2 influence the biogenic secondary organic aerosol (SOA formation, but detailed mechanisms and effects are still elusive. We studied the effects of NOx and SO2 on the SOA formation from the photooxidation of α-pinene and limonene at ambient relevant NOx and SO2 concentrations (NOx: < 1to 20 ppb, SO2: < 0.05 to 15 ppb. In these experiments, monoterpene oxidation was dominated by OH oxidation. We found that SO2 induced nucleation and enhanced SOA mass formation. NOx strongly suppressed not only new particle formation but also SOA mass yield. However, in the presence of SO2 which induced a high number concentration of particles after oxidation to H2SO4, the suppression of the mass yield of SOA by NOx was completely or partly compensated for. This indicates that the suppression of SOA yield by NOx was largely due to the suppressed new particle formation, leading to a lack of particle surface for the organics to condense on and thus a significant influence of vapor wall loss on SOA mass yield. By compensating for the suppressing effect on nucleation of NOx, SO2 also compensated for the suppressing effect on SOA yield. Aerosol mass spectrometer data show that increasing NOx enhanced nitrate formation. The majority of the nitrate was organic nitrate (57–77 %, even in low-NOx conditions (<  ∼  1 ppb. Organic nitrate contributed 7–26 % of total organics assuming a molecular weight of 200 g mol−1. SOA from α-pinene photooxidation at high NOx had a generally lower hydrogen to carbon ratio (H ∕ C, compared to low NOx. The NOx dependence of the chemical composition can be attributed to the NOx dependence of the branching ratio of the RO2 loss reactions, leading to a lower fraction of organic hydroperoxides and higher fractions of organic nitrates at high NOx. While NOx suppressed new particle formation and SOA mass formation, SO2 can compensate for such effects, and the

On-road NOx and CO2 investigations of Euro 5 Light commercial vehicles

NARCIS (Netherlands)

Kadijk, G.; Ligterink, N.E.; Spreen, J.S.

2015-01-01

NOx emissions of vehicles contribute to the ambient NO2 concentration. To gain insight into those NOx emissions, TNO, commissioned by the Dutch Ministry of Infrastructure and the Environment, regularly performs real-world emission measurements on vehicles. The measurements mainly focus on vehicles

Monoamine Oxidase Inhibitors (MAOIs)

Science.gov (United States)

... health-medications/index.shtml. Accessed May 16, 2016. Hirsch M, et al. Monoamine oxidase inhibitors (MAOIs) for ... www.uptodate.com/home. Accessed May 16, 2016. Hirsch M, et al. Discontinuing antidepressant medications in adults. ...

Gas Turbines: ''low NOx'' technologies at EGT

International Nuclear Information System (INIS)

Anon.

1996-01-01

For more than 15 years, European Gas Turbines (EGT - GEC Alsthom Group) has gained an important know-how culture and can use its rich feedback experience in the domain of gas turbine emissions. The EGT gas turbine units equipped with denitrogenation technologies cover the 4 to 226 MW power range and cumulate more than 1.7 hours of functioning in the different existing installations in the world. This paper describes the economical and environmental interests of gas turbines for power production and the combustion technologies developed by EGT to reduce the NOx emissions. The selective catalytic reduction technique is the only available secondary technique with can allow NOx and CO emissions lower than 10 ppm. Other technologies involving diluent injection (water, water-fuel mixture, vapor..) are also described and were developed in several countries to reduce the emission of these pollutants. (J.S.)

Reduce NOx Emissions by Adsorber-Reduction Catalyst on Lean Burn Gasoline Engine

Directory of Open Access Journals (Sweden)

Dongpeng Yue

2013-09-01

Full Text Available The effect of a new catalyst system composed of traditional three way catalyst converter and adsorber-reduction catalysis converter on the emission characteristics and BSFC (Breake Specific Fuel Consumption- BSFCof a lean burn gasoline engine operated were investigated in this paper under different schemes of catalyst converter arrangement and different speeds and loads. The results show that the position of Three Way Catalyst is before the NOx adsorber Catalyst was the best scheme of catalyst converter arrangement. Which has the highest converter efficiency of reduction NOx emission in lean burn gasoline engine. The effects of speed on the exhaust emission and BSFC were also related to the ratio of lean burn time to rich burn time and the absolute value of both time of the adsorber-reduction catalyst converter. The load of the engine was the main influential factor to the exhaust emission characteristics and BSFC of lean burn gasoline engine, and the more load of the engine was, the more NOx emission , the less NOx conversion rate (CNOx and the better BSFC were.

Influence of Co or Ce addition on the NOx storage and sulfur-resistance performance of the lean-burn NOx trap catalyst Pt/K/TiO{sub 2}-ZrO{sub 2}

Energy Technology Data Exchange (ETDEWEB)

Zou Zhiqiang [Tianjin Key Laboratory of Applied Catalysis Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Meng, Ming, E-mail: mengm@tju.edu.cn [Tianjin Key Laboratory of Applied Catalysis Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Tsubaki, Noritatsu [Department of Applied Chemistry, School of Engineering, University of Toyama, Gofuku 3190, Toyama city, Toyama 930 8555 (Japan); He Junjun; Wang Gang; Li Xingang; Zhou Xiaoyan [Tianjin Key Laboratory of Applied Catalysis Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China)

2009-10-15

The Pt/K/TiO{sub 2}-ZrO{sub 2} catalysts promoted by Co or Ce were prepared by successive impregnation or mechanically mixing method. The influence of Co or Ce addition on the NOx storage and sulfur-resistance performance of the catalyst was investigated carefully. The techniques of XRD, FT-IR, in-situ DRIFTS, H{sub 2}-TPR and XPS were employed for catalyst characterization. The Co or Ce addition can greatly improve the NOx storage capacity of Pt/K/TiO{sub 2}-ZrO{sub 2} due to the enhanced oxidation ability and the release of more K sites. Ce addition induces higher K/Ti atomic ratio and larger NOx storage capacity as compared with Co addition. After sulfation and regeneration, the promoted catalysts shows more or less decreased NSC than Pt/K/TiO{sub 2}-ZrO{sub 2} due to the formation of more sulfates, especially for the Co-promoted catalysts, which possess better oxidation ability and facilitate the formation of large sulfates. The effect of Ce addition on Pt/K/TiO{sub 2}-ZrO{sub 2} largely depends on the addition mode. The high oxidation ability and the high K/Ti ratio of the mechanically prepared Ce-promoted catalyst make it still possess considerable NOx storage capacity (NSC) of 142 {mu}mol/g after sulfation and regeneration. With the decrease of sulfur content in fuels, the Co- and Ce-promoted catalysts possessing large NOx storage capacity, will be applicable to the purification of lean-burn NOx.

Enhancement of removal of SO2 and NOx by powdery materials in radiation treatment of exhaust gases

International Nuclear Information System (INIS)

Tokunaga, Okihiro; Namba, Hideki; Suzuki, Nobutake

1985-01-01

We studied the effect of powdery silica on radiation removal of SO 2 and NOx from mixtures of SO 2 , NOx, water vapour, oxygen and nitrogen under irradiation by electron beams of 1.5 MeV at 120 0 C. The SO 2 and NOx concentrations decreased when powdery silica was fed without irradiation. Decrements of SO 2 and NOx concentrations were markedly enhanced when powdery silica was fed together with the irradiation. The enhancement of SO 2 - and NOx-removal is attributed to the adsorption of SO 2 and NO on the water-covered surface of powdery silica, and the effective removal of NO 2 due to the reaction with water adsorbed on the surface of powdery silica. The results obtained show that the addition of powdery silica under irradiation is an effective method of enhancing the removal of SO 2 and NOx. (author)

Understanding NOx SCR Mechanism and Activity on Cu/Chabazite Structures throughout the Catalyst Life Cycle

Energy Technology Data Exchange (ETDEWEB)

Ribeiro, Fabio; Delgass, Nick; Gounder, Rajmani; Schneider, William F.; Miller, Jeff; Yezerets, Aleksey; McEwen, Jean-Sabin; Peden, Charles HF; Howden, Ken

2014-12-09

Oxides of nitrogen (NOx) compounds contribute to acid rain and photochemical smog and have been linked to respiratory ailments. NOx emissions regulations continue to tighten, driving the need for high performance, robust control strategies. The goal of this project is to develop a deep, molecular level understanding of the function of Cu-SSZ-13 and Cu-SAPO-34 materials that catalyze the SCR of NOx with NH3.

Optimization of glucose oxidase production by Aspergillus niger

African Journals Online (AJOL)

user

2011-02-28

Feb 28, 2011 ... manganese, cobalt, thioglycolic acid, and gluconic acid according to (Liu et al., .... In this experiment duplicate media of glucose 10% were adjusted at different ... Glucose oxidase as a pharmaceutical anti oxidant Drug. Devt. ... Plush KS, Hellmuth K, Rinas U (1996). kinetics of glucose oxidase excretion by ...

Matrix cross-linking lysyl oxidases are induced in response to myocardial infarction and promote cardiac dysfunction

DEFF Research Database (Denmark)

González-Santamaría, José; Villalba, María; Busnadiego, Oscar

2016-01-01

arrhythmias, and sudden cardiac death. Cardiac fibrosis is characterized by extensive deposition of collagen and also by increased stiffness as a consequence of enhanced collagen cross-linking. Members of the lysyl oxidase (LOX) family of enzymes are responsible for the formation of collagen cross......-links. This study investigates the contribution of LOX family members to the heart response to MI. METHODS AND RESULTS: Experimental MI was induced in C57BL/6 mice by permanent ligation of the left anterior descending coronary artery. The expression of LOX isoforms (LOX and LOXL1-4) was strongly increased upon MI...... resulted in reduced ventricular dilatation and improved cardiac function. CONCLUSION: LOX family members contribute significantly to the detrimental effects of cardiac remodelling, highlighting LOX inhibition as a potential therapeutic strategy for post-infarction recovery....

Experimental Validation of a Virtual Engine-Out NOx Sensor for Diesel Emission Control

NARCIS (Netherlands)

Escobar Valdivieso, D.; Mentink, P.; Külah, S.; Forrai, A.; Willems, F.P.T.

2017-01-01

Motivated by automotive emissions legislations, a Virtual NOx sensor is developed. This virtual sensor consists of a real-time, phenomenological model that computes engine-out NOx by using the measured in-cylinder pressure signal from a single cylinder as its main input. The implementation is made

Cytochrome cbb3 of Thioalkalivibrio is a Na+-pumping cytochrome oxidase

NARCIS (Netherlands)

Muntyan, M.S.; Cherepanov, D.A.; Malinen, A.M.; Bloch, D.A.; Sorokin, D.Y.; Severina, I.I.; Ivashina, T.V.; Lahti, R.; Muyzer, G.; Skulachev, V.P.

2015-01-01

Cytochrome c oxidases (Coxs) are the basic energy transducers in the respiratory chain of the majority of aerobic organisms. Coxs studied to date are redox-driven proton-pumping enzymes belonging to one of three subfamilies: A-, B-, and C-type oxidases. The C-type oxidases (cbb3 cytochromes), which

NOx Reduction Technology in Diesel Engine Exhaust by the Plasmatron

International Nuclear Information System (INIS)

Joa, Sang Beom

2008-02-01

The diesel vehicle is relatively superior to gasoline vehicle on the fuel consumption, durability and combustion efficiency. However, exhaust emissions from diesel vehicles are known to be harmful to human health and environment. An experimental study of the diesel fuel reformation by a plasmatron and diesel engine exhaust cleaning by means of plasma chemical pretreatment of fuel is described. Plasma chemical reformation of fuel was carried by a DC arc plasmatron that was fabricated to increase an ability of the gas activation. Some portion of the fuel was activated in an arc discharge and turned into the hydrogen-rich synthesis gas. The yield of reformation for the diesel fuel showed 80 % ∼ 100 % when the small quantities of fuel (flow rate up to about 6 cc/min) were reformed. The regulation for an emission from the diesel vehicle is getting more stringent, the research in the field of the in-cylinder processing technologies (pretreatment) becomes more important issue as well as the catalyst after-treatment. The used high durability plasmatron has the characteristics of low contamination level, low anode erosion rate, low plasma temperature, and effective activation of the process gas. The developed fuel reformation system with the plasmatron was connected to the air feeding inlet sleeve of the diesel engine Kookje 3T90LT-AC (Korea) in order to study the reduction of NOx content in the engine's emission. Tubular reformation chamber was connected to the engine through the heat exchanger DOVER B10Hx20/1P-SC-S. Its cooling jacket was connected in series with the cooling system of the plasmatron. At the exit of this device gas temperature did not exceed ∼40 .deg. C at plasmatron power up to 1.5 kW which seemed quite acceptable. Gas composition was studied here using RBR-Ecom KD gas analyzer. The design of the DC arc plasmatron applied for the plasma chemical fuel reformation was improved boosting the degree of fuel-air mixture activation that provided the

NOx Emission Reduction by Oscillating Combustion

Energy Technology Data Exchange (ETDEWEB)

None

2005-09-01

This project focuses on a new technology that reduces NOx emissions while increasing furnace efficiency for both air- and oxygen-fired furnaces. Oscillating combustion is a retrofit technology that involves the forced oscillation of the fuel flow rate to a furnace. These oscillations create successive, fuel-rich and fuel-lean zones within the furnace.

Estimates of lightning NOx production from GOME satellite observations

Directory of Open Access Journals (Sweden)

K. F. Boersma

2005-01-01

Full Text Available Tropospheric NO2 column retrievals from the Global Ozone Monitoring Experiment (GOME satellite spectrometer are used to quantify the source strength and 3-D distribution of lightning produced nitrogen oxides (NOx=NO+NO2. A sharp increase of NO2 is observed at convective cloud tops with increasing cloud top height, consistent with a power-law behaviour with power 5±2. Convective production of clouds with the same cloud height are found to produce NO2 with a ratio 1.6/1 for continents compared to oceans. This relation between cloud properties and NO2 is used to construct a 10:30 local time global lightning NO2 production map for 1997. An extensive statistical comparison is conducted to investigate the capability of the TM3 chemistry transport model to reproduce observed patterns of lightning NO2 in time and space. This comparison uses the averaging kernel to relate modelled profiles of NO2 to observed NO2 columns. It exploits a masking scheme to minimise the interference of other NOx sources on the observed total columns. Simulations are performed with two lightning parameterizations, one relating convective preciptation (CP scheme to lightning flash distributions, and the other relating the fifth power of the cloud top height (H5 scheme to lightning distributions. The satellite-retrieved NO2 fields show significant correlations with the simulated lightning contribution to the NO2 concentrations for both parameterizations. Over tropical continents modelled lightning NO2 shows remarkable quantitative agreement with observations. Over the oceans however, the two model lightning parameterizations overestimate the retrieved NO2 attributed to lightning. Possible explanations for these overestimations are discussed. The ratio between satellite-retrieved NO2 and modelled lightning NO2 is used to rescale the original modelled lightning NOx production. Eight estimates of the lightning NOx production in 1997 are obtained from spatial and temporal

Serum diamine oxidase activity in patients with histamine intolerance.

Science.gov (United States)

Manzotti, G; Breda, D; Di Gioacchino, M; Burastero, S E

2016-03-01

Intolerance to various foods, excluding bona fide coeliac disease and lactose intolerance, represents a growing cause of patient visits to allergy clinics.Histamine intolerance is a long-known, multifaceted clinical condition triggered by histamine-rich foods and alcohol and/or by drugs that liberate histamine or block diamine oxidase (DAO), the main enzyme involved in the metabolism of ingested histamine. Histamine limitation diets impose complex, non-standardized restrictions that may severely impact the quality of life of patients. We retrospectively evaluated 14 patients who visited allergy outpatient facilities in northern Italy with a negative diagnosis for IgE-mediated food hypersensitivity, coeliac disease, conditions related to gastric hypersecretion, and systemic nickel hypersensitivity, and who previously underwent a histamine limitation diet with benefits for their main symptoms. Serum diamine oxidase levels and the clinical response to diamine oxidase supplementation were investigated. We found that 10 out of 14 patients had serum DAO activityintolerance. Moreover, 13 out of 14 patients subjectively reported a benefit in at least one of the disturbances related to food intolerances following diamine oxidase supplementation. The mean value (±SD) of diamine oxidase activity in the cohort of patients with histamine intolerance symptoms was 7.04±6.90 U/mL compared to 39.50±18.16 U/mL in 34 healthy controls (P=0.0031). In patients with symptoms triggered by histamine-rich food, measuring the serum diamine oxidase activity can help identify subjects who can benefit from a histamine limitation diet and/or diamine oxidase supplementation.Properly designed, controlled studies investigating histamine intolerance that include histamine provocation are indispensable for providing insights into the area of food intolerances, which are currently primarily managed with non-scientific approaches in Italy. © The Author(s) 2015.

Cyclone Boiler Field Testing of Advanced Layered NOx Control Technology in Sioux Unit 1

Energy Technology Data Exchange (ETDEWEB)

Marc A. Cremer; Bradley R. Adams

2006-06-30

A four week testing program was completed during this project to assess the ability of the combination of deep staging, Rich Reagent Injection (RRI), and Selective Non-Catalytic Reduction (SNCR) to reduce NOx emissions below 0.15 lb/MBtu in a cyclone fired boiler. The host site for the tests was AmerenUE's Sioux Unit 1, a 500 MW cyclone fired boiler located near St. Louis, MO. Reaction Engineering International (REI) led the project team including AmerenUE, FuelTech Inc., and the Electric Power Research Institute (EPRI). This layered approach to NOx reduction is termed the Advanced Layered Technology Approach (ALTA). Installed RRI and SNCR port locations were guided by computational fluid dynamics (CFD) based modeling conducted by REI. During the parametric testing, NOx emissions of 0.12 lb/MBtu were achieved consistently from overfire air (OFA)-only baseline NOx emissions of 0.25 lb/MBtu or less, when firing the typical 80/20 fuel blend of Powder River Basin (PRB) and Illinois No.6 coals. From OFA-only baseline levels of 0.20 lb/MBtu, NOx emissions of 0.12 lb/MBtu were also achieved, but at significantly reduced urea flow rates. Under the deeply staged conditions that were tested, RRI performance was observed to degrade as higher blends of Illinois No.6 were used. NOx emissions achieved with ALTA while firing a 60/40 blend were approximately 0.15 lb/MBtu. NOx emissions while firing 100% Illinois No.6 were approximately 0.165 lb/MBtu. Based on the performance results of these tests, economics analyses of the application of ALTA to a nominal 500 MW cyclone unit show that the levelized cost to achieve 0.15 lb/MBtu is well below 75% of the cost of a state of the art SCR.

Hydrogen Peroxide Enhances Removal of NOx from Flue Gases

Science.gov (United States)

Collins, Michelle M.

2005-01-01

Pilot scale experiments have demonstrated a method of reducing the amounts of oxides of nitrogen (NOx) emitted by industrial boilers and powerplant combustors that involves (1) injection of H2O2 into flue gases and (2) treatment of the flue gases by caustic wet scrubbing like that commonly used to remove SO2 from combustion flue gases. Heretofore, the method most commonly used for removing NOx from flue gases has been selective catalytic reduction (SCR), in which the costs of both installation and operation are very high. After further development, the present method may prove to be an economically attractive alternative to SCR.

COST OF SELECTIVE CATALYTIC REDUCTION (SCR) APPLICATION FOR NOX CONTROL ON COAL-FIRED BOILERS

Science.gov (United States)

The report provides a methodology for estimating budgetary costs associated with retrofit applications of selective catalytic reduction (SCR) technology on coal-fired boilers. SCR is a postcombustion nitrogen oxides (NOx) control technology capable of providing NOx reductions >90...

LOW NOX BURNER DEVELOPMENT

Energy Technology Data Exchange (ETDEWEB)

KRISHNA,C.R.; BUTCHER,T.

2004-09-30

The objective of the task is to develop concepts for ultra low NOx burners. One approach that has been tested previously uses internal recirculation of hot gases and the objective was to how to implement variable recirculation rates during burner operation. The second approach was to use fuel oil aerosolization (vaporization) and combustion in a porous medium in a manner similar to gas-fired radiant burners. This task is trying the second approach with the use of a somewhat novel, prototype system for aerosolization of the liquid fuel.

Top-down NOX Emissions of European Cities Derived from Modelled and Spaceborne Tropospheric NO2 Columns

Science.gov (United States)

Verstraeten, W. W.; Boersma, K. F.; Douros, J.; Williams, J. E.; Eskes, H.; Delcloo, A. W.

2017-12-01

High nitrogen oxides (NOX = NO + NO2) concentrations near the surface impact humans and ecosystems badly and play a key role in tropospheric chemistry. NO2 is an important precursor of tropospheric ozone (O3) which in turn affects the production of the hydroxyl radical controlling the chemical lifetime of key atmospheric pollutants and reactive greenhouse gases. Combustion from industrial, traffic and household activities in large and densely populated urban areas result in high NOX emissions. Accurate mapping of these emissions is essential but hard to do since reported emissions factors may differ from real-time emissions in order of magnitude. Modelled NO2 levels and lifetimes also have large associated uncertainties and overestimation in the chemical lifetime which may mask missing NOX chemistry in current chemistry transport models (CTM's). The simultaneously estimation of both the NO2 lifetime and as well as the concentrations by applying the Exponentially Modified Gaussian (EMG) method on tropospheric NO2 columns lines densities should improve the surface NOX emission estimates. Here we evaluate if the EMG methodology applied on the tropospheric NO2 columns simulated by the LOTOS-EUROS (Long Term Ozone Simulation-European Ozone Simulation) CTM can reproduce the NOX emissions used as model input. First we process both the modelled tropospheric NO2 columns for the period April-September 2013 for 21 selected European urban areas under windy conditions (averaged vertical wind speeds between surface and 500 m from ECMWF > 2 m s-1) as well as the accompanying OMI (Ozone Monitoring Instrument) data providing us with real-time observation-based estimates of midday NO2 columns. Then we compare the top-down derived surface NOX emissions with the 2011 MACC-III emission inventory, used in the CTM as input to simulate the NO2 columns. For cities where NOX emissions can be assumed as originating from one large source good agreement is found between the top-down derived

The NOx Budget. Market-based control of tropospheric ozone in the northeastern United States

International Nuclear Information System (INIS)

Farrell, Alex; Carter, Robert; Raufer, Roger

1999-01-01

The NOx Budget is a marketable emissions allowance system currently being adopted by states in the Northeastern US to reduce tropospheric ozone concentrations to healthful levels in a cost-effective manner. Oxides of nitrogen (NOx) are currently regulated within the existing Command and Control (CAC) framework. The introduction of a market-based approach will further reduce emissions, but will not resolve all regulatory uncertainties. These implementation concerns are identified and discussed. Cost savings and emissions reductions patterns which will arise under several different scenarios are determined through the use of a dynamic, relaxed mixed-integer linear programming model of the NOx allowance market. Like other market-based pollution control programs, the NOx Budget is found to be more efficient than CAC options. Restrictions on the market designed to address perceived flaws are found to be expensive but ineffectual

Stereodynamics in NO(X) + Ar inelastic collisions

Energy Technology Data Exchange (ETDEWEB)

Brouard, M., E-mail: mark.brouard@chem.ox.ac.uk; Chadwick, H.; Gordon, S. D. S.; Hornung, B.; Nichols, B. [The Department of Chemistry, University of Oxford, The Chemistry Research Laboratory, 12 Mansfield Road, Oxford, OX1 3TA (United Kingdom); Aoiz, F. J., E-mail: aoiz@quim.ucm.es [Departamento de Química Física, Facultad de Química, Universidad Complutense, 28040 Madrid (Spain); Stolte, S., E-mail: s.stolte@vu.nl [Institute of Atomic and Molecular Physics, Jilin University, Changchun 130012 (China)

2016-06-14

The effect of orientation of the NO(X) bond axis prior to rotationally inelastic collisions with Ar has been investigated experimentally and theoretically. A modification to conventional velocity-map imaging ion optics is described, which allows the orientation of hexapole state-selected NO(X) using a static electric field, followed by velocity map imaging of the resonantly ionized scattered products. Bond orientation resolved differential cross sections are measured experimentally for a series of spin-orbit conserving transitions and compared with quantum mechanical calculations. The agreement between experimental results and those from quantum mechanical calculations is generally good. Parity pairs, which have previously been observed in collisions of unpolarized NO with various rare gases, are not observed due to the coherent superposition of the two j = 1/2, Ω = 1/2 Λ-doublet levels in the orienting field. The normalized difference differential cross sections are found to depend predominantly on the final rotational state, and are not very sensitive to the final Λ-doublet level. The differential steric effect has also been investigated theoretically, by means of quantum mechanical and classical calculations. Classically, the differential steric effect can be understood by considering the steric requirement for different types of trajectories that contribute to different regions of the differential cross section. However, classical effects cannot account quantitatively for the differential steric asymmetry observed in NO(X) + Ar collisions, which reflects quantum interference from scattering at either end of the molecule. This quantum interference effect is dominated by the repulsive region of the potential.

Observations of the temperature dependent response of ozone to NOx reductions in the Sacramento, CA urban plume

Science.gov (United States)

Lafranchi, B. W.; Goldstein, A. H.; Cohen, R. C.

2011-07-01

Observations of NOx in the Sacramento, CA region show that mixing ratios decreased by 30 % between 2001 and 2008. Here we use an observation-based method to quantify net ozone (O3) production rates in the outflow from the Sacramento metropolitan region and examine the O3 decrease resulting from reductions in NOx emissions. This observational method does not rely on assumptions about detailed chemistry of ozone production, rather it is an independent means to verify and test these assumptions. We use an instantaneous steady-state model as well as a detailed 1-D plume model to aid in interpretation of the ozone production inferred from observations. In agreement with the models, the observations show that early in the plume, the NOx dependence for Ox (Ox = O3 + NO2) production is strongly coupled with temperature, suggesting that temperature-dependent biogenic VOC emissions and other temperature-related effects can drive Ox production between NOx-limited and NOx-suppressed regimes. As a result, NOx reductions were found to be most effective at higher temperatures over the 7 year period. We show that violations of the California 1-h O3 standard (90 ppb) in the region have been decreasing linearly with decreases in NOx (at a given temperature) and predict that reductions of NOx concentrations (and presumably emissions) by an additional 30 % (relative to 2007 levels) will eliminate violations of the state 1 h standard in the region. If current trends continue, a 30 % decrease in NOx is expected by 2012, and an end to violations of the 1 h standard in the Sacramento region appears to be imminent.

Atmospheric emission of NOx from mining explosives: A critical review

Science.gov (United States)

Oluwoye, Ibukun; Dlugogorski, Bogdan Z.; Gore, Jeff; Oskierski, Hans C.; Altarawneh, Mohammednoor

2017-10-01

High-energy materials such as emulsions, slurries and ammonium-nitrate fuel-oil (ANFO) explosives play crucial roles in mining, quarrying, tunnelling and many other infrastructure activities, because of their excellent transport and blasting properties. These explosives engender environmental concerns, due to atmospheric pollution caused by emission of dust and nitrogen oxides (NOx) from blasts, the latter characterised by the average emission factor of 5 kg (t AN explosive)-1. This first-of-its-kind review provides a concise literature account of the formation of NOx during blasting of AN-based explosives, employed in surface operations. We estimate the total NOx emission rate from AN-based explosives as 0.05 Tg (i.e., 5 × 104 t) N per annum, compared to the total global annual anthropogenic NOx emissions of 41.3 × 106 t N y-1. Although minor in the global sense, the large localised plumes from blasting exhibit high NOx concentration (500 ppm) exceeding up to 3000 times the international standards. This emission has profound consequences at mining sites and for adjacent atmospheric environment, necessitating expensive management of exclusion zones. The review describes different types of AN energetic materials for civilian applications, and summarises the essential properties and terminologies pertaining to their use. Furthermore, we recapitulate the mechanisms that lead to the formation of the reactive nitrogen species in blasting of AN-based explosives, review their implications to atmospheric air pollution, and compare the mechanisms with those experienced in other thermal and combustion operations. We also examine the mitigation approaches, including guidelines and operational-control measures. The review discusses the abatement technologies such as the formulation of new explosive mixtures, comprising secondary fuels, spin traps and other additives, in light of their effectiveness and efficiency. We conclude the review with a summary of unresolved problems

Expression and Chloroplast Targeting of Cholesterol Oxidase in Transgenic Tobacco Plants

Science.gov (United States)

Corbin, David R.; Grebenok, Robert J.; Ohnmeiss, Thomas E.; Greenplate, John T.; Purcell, John P.

2001-01-01

Cholesterol oxidase represents a novel type of insecticidal protein with potent activity against the cotton boll weevil (Anthonomus grandis grandis Boheman). We transformed tobacco (Nicotiana tabacum) plants with the cholesterol oxidase choM gene and expressed cytosolic and chloroplast-targeted versions of the ChoM protein. Transgenic leaf tissues expressing cholesterol oxidase exerted insecticidal activity against boll weevil larvae. Our results indicate that cholesterol oxidase can metabolize phytosterols in vivo when produced cytosolically or when targeted to chloroplasts. The transgenic plants exhibiting cytosolic expression accumulated low levels of saturated sterols known as stanols, and displayed severe developmental aberrations. In contrast, the transgenic plants expressing chloroplast-targeted cholesterol oxidase maintained a greater accumulation of stanols, and appeared phenotypically and developmentally normal. These results are discussed within the context of plant sterol distribution and metabolism. PMID:11457962

Exploring the roles of temperature and NOx on ozone production in the Sacramento urban plume

Science.gov (United States)

Lafranchi, B. W.; Cohen, R. C.

2009-12-01

We investigate the role of temperature and NOx (NOx = NO+NO2) on ozone (O3) production in the Sacramento urban plume over a stretch of seven years (2001-2007) using data collected at UC Blodgett Forest Research Station (a forested site in the Sierra Nevadas about 80 km downwind of Sacramento, CA) and at a series of California Air Resources Board (CARB) sites along the Sacramento-Blodgett transect. The consistent daytime wind patterns between the Central Valley of California and the foothills of the Sierra Nevada mountains permits the assumption of plume transport from downtown Sacramento, over the CARB monitoring sites in the eastern suburbs, and past the Blodgett Forest research site. While NOx emissions are limited primarily to the urban and suburban regions of the transect, biogenic volatile organic compound (VOC) emissions are significant throughout the transect, thus there is a fast transition from VOC-limited to NOx-limited as the plume travels away from the urban center, and we have the opportunity to analyze the differences in ozone production across these two chemical regimes. For this analysis, the Sacramento-Blodgett transect is separated into three segments: urban, suburban, and rural, defined by the locations of selected monitoring sites. Ozone concentrations across each segment are controlled by chemical production (Pchem) and loss (Lchem), deposition to surfaces (Ldep), and mixing with background air (Lmix). At an assumed deposition rate, mixing rate, and background O3 concentration, the net chemical flux of ozone (Pchem - Lchem) can be inferred from differences in ozone concentrations between adjacent monitoring sites. We show that ozone production rates, in general, increase with temperature. We also show that decreases in NOx emissions over the period from 2001-2007 have been effective at reducing ozone production at all points along the transect, but only on days where temperatures are highest. At low temperatures, this decrease is less apparent

Heterotrophic nitrogen removal in Bacillus sp. K5: involvement of a novel hydroxylamine oxidase.

Science.gov (United States)

Yang, Yunlong; Lin, Ershu; Huang, Shaobin

2017-12-01

An aerobic denitrifying bacterium isolated from a bio-trickling filter treating NOx, Bacillus sp. K5, is able to convert ammonium to nitrite, in which hydroxylamine oxidase (HAO) plays a critical role. In the present study, the performance for simultaneous nitrification and denitrification was investigated with batch experiments and an HAO was purified by an anion-exchange and gel-filtration chromatography from strain K5. The purified HAO's molecular mass was determined by SDS-PAGE and its activity by measuring the change in the concentration of ferricyanide, the electron acceptor. Results showed that as much as 87.8 mg L -1 ammonium-N was removed without nitrite accumulation within 24 hours in the sodium citrate medium at C/N of 15. The HAO isolated from the strain K5 was approximately 71 KDa. With hydroxylamine (NH 2 OH) as a substrate and potassium ferricyanide as an electron acceptor, the enzyme was capable of oxidizing NH 2 OH to nitrite in vitro when the pH varied from 7 to 9 and temperature ranged from 25 °C to 40 °C. This is the first time that an HAO has been purified from the Bacillus genus, and the findings revealed that it is distinctive in its molecular mass and enzyme properties.

Glucose impairs aspirin inhibition in platelets through a NAD(P)H oxidase signaling pathway.

Science.gov (United States)

Kobzar, Gennadi; Mardla, Vilja; Samel, Nigulas

2017-07-01

Hyperglycemia has been suggested to play a role in the increased platelet resistance to antiplatelet therapy in patients with diabetes mellitus. Exposure to high glucose impairs platelet inhibition by aspirin. It has been found that antioxidant agents reduce the effect of glucose, confirming the involvement of reactive oxygen species (ROS) in the effect of glucose. The aim of the study was to examine the mechanism of ROS increase by high glucose in aspirin-treated platelets. Platelet aggregation was measured by the optical method, and the production of ROS was detected using luminol-dependent horseradish peroxidase-enhanced chemiluminescence. We found that glucose did not affect ADP-induced platelet aggregation. However, it reduced the effect of aspirin on platelet aggregation, which was accompanied by an increase in ROS generation. The inhibition of NAD(P)H oxidase (NOX) prevented the glucose effect and ROS generation. The same result was recorded after the inhibition of p38 mitogen-activated protein kinases (p38 MAPK), phospholipase A 2 (PLA 2 ) or 12-lipoxygenase (12-LOX). The inhibition of TxA 2 receptor did not decrease the effect of glucose indicating that the effect was not caused by activation of TxA 2 receptors. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of Ca-Fe oxides additives on NOx reduction in iron ore sintering

Institute of Scientific and Technical Information of China (English)

Zhi-yuan Yu; Xiao-hui Fan; Min Gan; Xu-ling Chen

2017-01-01

As the emission control regulations get stricter, the NOx reduction in the sintering process becomes an important environmental concern owing to its role in the formation of photochemical smog and acid rain. The NOx emissions from the sintering machine account for 48% of total amount from the iron and steel industry.Thus, it is essential to reduce NOx emissions from the sintering machine, for the achievement of clean production of sinter.Ca-Fe oxides, serving as the main binding phase in the sinter, are therefore used as additives into the sintering mixture to reduce NOx emissions.The results show that the NOx re-duction ratio achieves 27.76% with 8% Ca-Fe oxides additives since the Ca-Fe oxides can advance the ig-nition and inhibit the nitrogen oxidation compared with the conventional condition.Meanwhile, the exist-ence of Ca-Fe oxides was beneficial to the sinter quality since they were typical low melting point com-pounds.The optimal mass fraction of Ca-Fe oxides additives should be less than 8% since the permeability of sintering bed was significantly decreased with a further increase of the Ca-Fe oxides fines, inhibiting the mineralization reaction of sintering mixture.Additionally, the appropriate particle size can be obtained when mixing an equal amount of Ca-Fe oxides additives of -0.5 mm and 0.5-3.0 mm in size.

NOx removal characteristics of corona radical shower with ammonia and methylamine radical injections

Energy Technology Data Exchange (ETDEWEB)

Urashima, K.; Ara, M.; Chang, J.S. [McMaster Univ., Hamilton, ON (Canada). Dept. of Engineering Physics; Uchida, Y. [Aichi Inst. of Technology, (Japan). Dept. of Engineering

2010-07-01

Air pollutants such as nitrogen oxides (NOx) and sulfur oxides (SOx) are the major cause of acid rain. There are different types of NOx and SOx conversion techniques such as wet scrubber, selective catalytic reactor, sorbent injection, and low NOx burner. Non-thermal plasma techniques have also been utilized in commercial plants, but the energy efficiency of the non-thermal plasma reactors have not yet been optimized. The direct plasma treatments of flue gases including, the electron beam, barrier discharge and pulsed corona reactors, may lose input energy to activate unwanted components of flue gases such as carbon dioxide (CO{sub 2}) and nitrogen (N{sub 2}). The corona discharge ammonia radical shower system has demonstrated significant NOx removal with higher energy efficiency for large bench scale and pilot plant tests for combustion exhausts. An experiment has also demonstrated that methane can replace ammonia as an injection gas with less NOx removal efficiency. This paper presented an experimental investigation that compared methylamine radical injection with traditional ammonia and methane radical injections. The paper discussed the bench scale test facilities and corona radical shower plasma reactor. It was concluded that the processes to form ammonium nitrate could be observed from trace white solid particles deposited on the reactor wall as observed by scanning electron microscopy pictures. 10 refs., 5 figs., 2 appendices.

Plasma diamine oxidase levels in pregnancy complicated by threatened abortion.

OpenAIRE

Legge, M; Duff, G B

1981-01-01

Plasma diamine oxidase levels were assayed in 66 patients who presented with pregnancy complicated by threatened abortion. Levels within the normal range were associated with continuing pregnancies, whereas levels below the normal range were associated with subsequent abortion. Among those patients in whom gestation was greater than eight weeks, 66.6% of diamine oxidase levels correctly predicted the pregnancy outcome. Assay of the diamine oxidase levels at eight weeks of gestation or less ga...

NOx Binding and Dissociation: Enhanced Ferroelectric Surface Chemistry by Catalytic Monolayers

Science.gov (United States)

Kakekhani, Arvin; Ismail-Beigi, Sohrab

2013-03-01

NOx molecules are regulated air pollutants produced during automotive combustion. As part of an effort to design viable catalysts for NOx decomposition operating at higher temperatures that would allow for improved fuel efficiency, we examine NOx chemistry on ferroelectric perovskite surfaces. Changing the direction of ferroelectric polarization can modify surface electronic properties and may lead to switchable surface chemistry. Here, we describe our recent work on potentially enhanced surface chemistry using catalytic RuO2 monolayers on perovskite ferroelectric substrates. In addition to thermodynamic stabilization of the RuO2 layer, we present results on the polarization-dependent binding of NO, O2, N2, and atomic O and N. We present results showing that one key problem with current catalysts, involving the difficulty of releasing dissociation products (especially oxygen), can be ameliorated by this method. Primary support from Toyota Motor Engineering and Manufacturing, North America, Inc.

40 CFR 75.19 - Optional SO2, NOX, and CO2 emissions calculation for low mass emissions (LME) units.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Optional SO2, NOX, and CO2 emissions... § 75.19 Optional SO2, NOX, and CO2 emissions calculation for low mass emissions (LME) units. (a... input, NOX, SO2, and CO2 mass emissions, and NOX emission rate under this part. If the owner or operator...

Metavanadate causes cellular accumulation of copper and decreased lysyl oxidase activity

International Nuclear Information System (INIS)

Cui, Changtai T.; Uriu-Adams, Janet Y.; Tchaparian, Eskouhie H.; Keen, Carl L.; Rucker, Robert B.

2004-01-01

Selected indices of copper metabolism in weanling rats and fibroblast cultures were progressively altered in response to increased levels of sodium metavanadate. In diets, vanadium was added in amounts ranging from 0 to 80 μg V/g of diet, that is, 0-1.6 μmol V/g of diet. In fibroblast cultures, vanadium ranged from 0 to 400 nmol V/ml. The inhibition of P-ATPase-7A activity by metavanadate, important to copper egress from cells, was a primary focus. In skin, and tendon, the copper concentration was increased in response to increased dietary levels of metavanadate, whereas lysyl oxidase activity, a secreted cuproprotein, was reduced. The reduction in lysyl oxidase activity was also accompanied by reduced redox cycling potential of isolated fractions of lysyl oxidase, presumably due to reduced lysyltyrosyl quinone (LTQ) formation at the active site of lysyl oxidase. In contrast, liver copper concentrations and plasma ceruloplasmin activity were not affected by metavanadate exposure. However, semicarbazide-sensitive benzylamine oxidase (SCBO) activity, which was taken as an indirect measure of vascular adhesive protein-1 (VAP-1), was increased. In cultured fibroblasts, cellular copper was also increased and lysyl oxidase decreased in response to metavanadate. Moreover, the steady-state levels of atp7a and lysyl oxidase mRNAs were not affected by addition of metavanadate to culture medium up to 200 nmol/ml. Taken together, these data suggest that pathways involving copper egress and lysyl oxidase activation are particularly sensitive to metavanadate exposure through processes that are predominately posttranslational

Measurement of NOx and CO Fluxes from a Tall Tower in Beijing.

Science.gov (United States)

Squires, F. A.; Drysdale, W. S.; Hamilton, J.; Lee, J. D.; Vaughan, A. R.; Wild, O.; Mullinger, N.; Nemitz, E.; Metzger, S.; Zhang, Q.

2017-12-01

China's air quality problems are well publicised; in 2010, 1.2 million premature deaths were attributed to outdoor air pollution in China. One of the major air quality issues is high concentrations of nitrogen oxides (NOx). China is the largest NOx emitter, contributing an estimated 18 % to global NOx emissions. Beijing itself is reported to have NO2 concentrations 42 % higher than the annual national standard. Given the high levels of pollution, increased focus has been placed on improving emissions estimates which are typically developed using a `bottom-up' approach where emissions are predicted from their sources. Emission inventories in China have large uncertainties and are rapidly changing with time in response to economic development, environmental regulation and new technologies. In fact, China is the largest contributor to the uncertainty in the source and the magnitude of air pollutants in air quality models. Recent studies have shown a discrepancy between NOx inventories and measured NOx emissions for UK cities, highlighting the limitations of bottom-up emissions inventories and the importance of accurate measurement data to improve the estimates. 5 Hz measurements of NOx and CO concentration were made as part of the Air Pollutants in Beijing (AIRPOLL-Beijing) project during two field campaigns in Nov-Dec 2016 and May-June 2017. Sampling took place from an inlet co-located with a sonic anemometer at 102 m on a meteorological tower in central Beijing. Analysis of the covariance between vertical wind speed and concentration enabled the calculation of emission flux, with an estimated footprint of between 2 - 5 km from the tower (which typically included some major ring roads and expressways). Fluxes were quantified using the continuous wavelet transformation (CWT) method, which enabled one minute resolved fluxes to be calculated. These data were compared to existing emissions estimates from the Multi-resolution Emission Inventory for China (MEIC). It is

Amperometric biosensor based on prussian blue and nafion modified screen-printed electrode for screening of potential xanthine oxidase inhibitors from medicinal plants.

Science.gov (United States)