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Sample records for oxidative defence regulation

  1. Glutamate ameliorates copper-induced oxidative injury by regulating antioxidant defences in fish intestine.

    PubMed

    Jiang, Jun; Wu, Xiao-Yun; Zhou, Xiao-Qiu; Feng, Lin; Liu, Yang; Jiang, Wei-Dan; Wu, Pei; Zhao, Ye

    2016-07-01

    The objective of this study was to determine the protective effect of glutamate (Glu) in Cu-induced oxidative injury in fish intestine in vivo and enterocytes in vitro. The results indicated that exposure to 6 mg/l Cu for 72 h induced the production of reactive oxygen species, thereby increasing protein oxidation and lipid peroxidation in enterocytes of grass carp in vitro. Cells exposed to Cu alone resulted in a significant increase in lactate dehydrogenase release, which is accompanied by depletions of antioxidants, including total superoxide dismutase (T-SOD), glutathione S-transferase (GST), glutathione reductase (GR), anti-superoxide anion (ASA), anti-hydroxy radical (AHR) activities and GSH content. Pre-treatment with Glu remarkably prevented the toxic effects of Cu on the T-SOD, GST, GR, AHR, and ASA activities and GSH content in enterocytes. However, Cu induced an adaptive increase in the activities of catalase and glutathione peroxidase (GPx). Glu supplementation further increased GPx activity in enterocytes. Interestingly, the experiment in vivo showed that Glu pre-supplementation significantly elevated SOD, GPx, GST, GR, ASA and AHR activities, as well as GSH content. Further results showed that pre-treatment with Glu could alleviate Cu-induced oxidative injury by elevating antioxidant enzyme activities through regulating the expression of NF-E2-related nuclear factor 2 (Nrf2) mRNA. Together, these results indicated that Glu could attenuate Cu-induced cellular oxidative damage in fish intestine, likely mediated through Nrf2 signalling pathways regulating mRNA expressions of antioxidant enzyme genes and synthesis of GSH. PMID:27184647

  2. Identification of plant defence regulators through transcriptional profiling of Arabidopsis thaliana cdd1 mutant.

    PubMed

    Swain, Swadhin; Singh, Nidhi; Nandi, Ashis Kumar

    2015-03-01

    A sustainable balance between defence and growth is essential for optimal fitness under pathogen stress. Plants activate immune response at the cost of normal metabolic requirements. Thus, plants that constitutively activate defence are deprived of growth. Arabidopsis thaliana mutant constitutive defence without defect in growth and development1 (cdd1) is an exception. The cdd1 mutant is constitutive for salicylic acid accumulation, signalling, and defence against biotrophic and hemibiotrophic pathogens, without having much impact on growth. Thus, cdd1 offers an ideal genetic background to identify novel regulators of plant defence. Here we report the differential gene expression profile between cdd1 and wild-type plants as obtained by microarray hybridization. Expression of several defence-related genes also supports constitutive activation of defence in cdd1. We screened T-DNA insertion mutant lines of selected genes, for resistance against virulent bacterial pathogen Pseudomonas syringae pv. tomato DC3000 (Pst DC3000). Through bacterial resistance, callose deposition and pathogenesis-associated expression analyses, we identified four novel regulators of plant defence. Resistance levels in the mutants suggest that At2g19810 and [rom] At5g05790 are positive regulators, whereas At1g61370 and At3g42790 are negative regulators of plant defence against bacterial pathogens. PMID:25740148

  3. AhR sensing of bacterial pigments regulates antibacterial defence.

    PubMed

    Moura-Alves, Pedro; Faé, Kellen; Houthuys, Erica; Dorhoi, Anca; Kreuchwig, Annika; Furkert, Jens; Barison, Nicola; Diehl, Anne; Munder, Antje; Constant, Patricia; Skrahina, Tatsiana; Guhlich-Bornhof, Ute; Klemm, Marion; Koehler, Anne-Britta; Bandermann, Silke; Goosmann, Christian; Mollenkopf, Hans-Joachim; Hurwitz, Robert; Brinkmann, Volker; Fillatreau, Simon; Daffe, Mamadou; Tümmler, Burkhard; Kolbe, Michael; Oschkinat, Hartmut; Krause, Gerd; Kaufmann, Stefan H E

    2014-08-28

    The aryl hydrocarbon receptor (AhR) is a highly conserved ligand-dependent transcription factor that senses environmental toxins and endogenous ligands, thereby inducing detoxifying enzymes and modulating immune cell differentiation and responses. We hypothesized that AhR evolved to sense not only environmental pollutants but also microbial insults. We characterized bacterial pigmented virulence factors, namely the phenazines from Pseudomonas aeruginosa and the naphthoquinone phthiocol from Mycobacterium tuberculosis, as ligands of AhR. Upon ligand binding, AhR activation leads to virulence factor degradation and regulated cytokine and chemokine production. The relevance of AhR to host defence is underlined by heightened susceptibility of AhR-deficient mice to both P. aeruginosa and M. tuberculosis. Thus, we demonstrate that AhR senses distinct bacterial virulence factors and controls antibacterial responses, supporting a previously unidentified role for AhR as an intracellular pattern recognition receptor, and identify bacterial pigments as a new class of pathogen-associated molecular patterns. PMID:25119038

  4. An Overview of Seasonal Changes in Oxidative Stress and Antioxidant Defence Parameters in Some Invertebrate and Vertebrate Species

    PubMed Central

    Chainy, Gagan Bihari Nityananda; Paital, Biswaranjan; Dandapat, Jagneswar

    2016-01-01

    Antioxidant defence system, a highly conserved biochemical mechanism, protects organisms from harmful effects of reactive oxygen species (ROS), a by-product of metabolism. Both invertebrates and vertebrates are unable to modify environmental physical factors such as photoperiod, temperature, salinity, humidity, oxygen content, and food availability as per their requirement. Therefore, they have evolved mechanisms to modulate their metabolic pathways to cope their physiology with changing environmental challenges for survival. Antioxidant defences are one of such biochemical mechanisms. At low concentration, ROS regulates several physiological processes, whereas at higher concentration they are toxic to organisms because they impair cellular functions by oxidizing biomolecules. Seasonal changes in antioxidant defences make species able to maintain their correct ROS titre to take various physiological functions such as hibernation, aestivation, migration, and reproduction against changing environmental physical parameters. In this paper, we have compiled information available in the literature on seasonal variation in antioxidant defence system in various species of invertebrates and vertebrates. The primary objective was to understand the relationship between varied biological phenomena seen in different animal species and conserved antioxidant defence system with respect to seasons. PMID:27127682

  5. An Overview of Seasonal Changes in Oxidative Stress and Antioxidant Defence Parameters in Some Invertebrate and Vertebrate Species.

    PubMed

    Chainy, Gagan Bihari Nityananda; Paital, Biswaranjan; Dandapat, Jagneswar

    2016-01-01

    Antioxidant defence system, a highly conserved biochemical mechanism, protects organisms from harmful effects of reactive oxygen species (ROS), a by-product of metabolism. Both invertebrates and vertebrates are unable to modify environmental physical factors such as photoperiod, temperature, salinity, humidity, oxygen content, and food availability as per their requirement. Therefore, they have evolved mechanisms to modulate their metabolic pathways to cope their physiology with changing environmental challenges for survival. Antioxidant defences are one of such biochemical mechanisms. At low concentration, ROS regulates several physiological processes, whereas at higher concentration they are toxic to organisms because they impair cellular functions by oxidizing biomolecules. Seasonal changes in antioxidant defences make species able to maintain their correct ROS titre to take various physiological functions such as hibernation, aestivation, migration, and reproduction against changing environmental physical parameters. In this paper, we have compiled information available in the literature on seasonal variation in antioxidant defence system in various species of invertebrates and vertebrates. The primary objective was to understand the relationship between varied biological phenomena seen in different animal species and conserved antioxidant defence system with respect to seasons. PMID:27127682

  6. Hexanoic acid protects tomato plants against Botrytis cinerea by priming defence responses and reducing oxidative stress.

    PubMed

    Finiti, Ivan; de la O Leyva, María; Vicedo, Begonya; Gómez-Pastor, Rocío; López-Cruz, Jaime; García-Agustín, Pilar; Real, Maria Dolores; González-Bosch, Carmen

    2014-08-01

    Treatment with the resistance priming inducer hexanoic acid (Hx) protects tomato plants from Botrytis cinerea by activating defence responses. To investigate the molecular mechanisms underlying hexanoic acid-induced resistance (Hx-IR), we compared the expression profiles of three different conditions: Botrytis-infected plants (Inf), Hx-treated plants (Hx) and Hx-treated + infected plants (Hx+Inf). The microarray analysis at 24 h post-inoculation showed that Hx and Hx+Inf plants exhibited the differential expression and priming of many Botrytis-induced genes. Interestingly, we found that the activation by Hx of other genes was not altered by the fungus at this time point. These genes may be considered to be specific targets of the Hx priming effect and may help to elucidate its mechanisms of action. It is noteworthy that, in Hx and Hx+Inf plants, there was up-regulation of proteinase inhibitor genes, DNA-binding factors, enzymes involved in plant hormone signalling and synthesis, and, remarkably, the genes involved in oxidative stress. Given the relevance of the oxidative burst occurring in plant-pathogen interactions, the effect of Hx on this process was studied in depth. We showed by specific staining that reactive oxygen species (ROS) accumulation in Hx+Inf plants was reduced and more restricted around infection sites. In addition, these plants showed higher ratios of reduced to oxidized glutathione and ascorbate, and normal levels of antioxidant activities. The results obtained indicate that Hx protects tomato plants from B. cinerea by regulating and priming Botrytis-specific and non-specific genes, preventing the harmful effects of oxidative stress produced by infection. PMID:24320938

  7. Sulphur dioxide evokes a large scale reprogramming of the grape berry transcriptome associated with oxidative signalling and biotic defence responses.

    PubMed

    Giraud, Estelle; Ivanova, Aneta; Gordon, Colin S; Whelan, James; Considine, Michael J

    2012-02-01

    The grape and wine industries are heavily reliant on sulphite preservatives. However, the view that sulphites act directly on bacterial and fungal pathogens may be simplistic. Mechanisms of sulphur-enhanced defences are largely unknown; many sulphur-rich compounds enhance plant defences and sulphite can also have oxidative consequences via production of H(2)O(2) or sulphitolysis. To investigate the effects of sulphur dioxide (SO(2) ) on fresh table grapes (Vitis vinifera L. 'Crimson Seedless'), transcriptome analysis was carried out on berries treated with SO(2) under commercial conditions for 21 d. We found a broad perturbation of metabolic processes, consistent with a large-scale stress response. Transcripts encoding putative sulphur-metabolizing enzymes indicated that sulphite was directed towards chelation and conjugation, and away from oxidation to sulphate. The results indicated that redox poise was altered dramatically by SO(2) treatment, evidenced by alterations in plastid and mitochondrial alternative electron transfer pathways, up-regulation of fermentation transcripts and numerous glutathione S-transferases, along with a down-regulation of components involved in redox homeostasis. Features of biotic stress were up-regulated, notably signalling via auxin, ethylene and jasmonates. Taken together, this inventory of transcriptional responses is consistent with a long-term cellular response to oxidative stress, similar to the effects of reactive oxygen species. PMID:21689113

  8. Nitric oxide, antioxidants and prooxidants in plant defence responses

    PubMed Central

    Groß, Felicitas; Durner, Jörg; Gaupels, Frank

    2013-01-01

    In plant cells the free radical nitric oxide (NO) interacts both with anti- as well as prooxidants. This review provides a short survey of the central roles of ascorbate and glutathione—the latter alone or in conjunction with S-nitrosoglutathione reductase—in controlling NO bioavailability. Other major topics include the regulation of antioxidant enzymes by NO and the interplay between NO and reactive oxygen species (ROS). Under stress conditions NO regulates antioxidant enzymes at the level of activity and gene expression, which can cause either enhancement or reduction of the cellular redox status. For instance chronic NO production during salt stress induced the antioxidant system thereby increasing salt tolerance in various plants. In contrast, rapid NO accumulation in response to strong stress stimuli was occasionally linked to inhibition of antioxidant enzymes and a subsequent rise in hydrogen peroxide levels. Moreover, during incompatible Arabidopsis thaliana-Pseudomonas syringae interactions ROS burst and cell death progression were shown to be terminated by S-nitrosylation-triggered inhibition of NADPH oxidases, further highlighting the multiple roles of NO during redox-signaling. In chemical reactions between NO and ROS reactive nitrogen species (RNS) arise with characteristics different from their precursors. Recently, peroxynitrite formed by the reaction of NO with superoxide has attracted much attention. We will describe putative functions of this molecule and other NO derivatives in plant cells. Non-symbiotic hemoglobins (nsHb) were proposed to act in NO degradation. Additionally, like other oxidases nsHb is also capable of catalyzing protein nitration through a nitrite- and hydrogen peroxide-dependent process. The physiological significance of the described findings under abiotic and biotic stress conditions will be discussed with a special emphasis on pathogen-induced programmed cell death (PCD). PMID:24198820

  9. Dopamine is a key regulator in the signalling pathway underlying predator-induced defences in Daphnia.

    PubMed

    Weiss, Linda C; Leese, Florian; Laforsch, Christian; Tollrian, Ralph

    2015-10-01

    The waterflea Daphnia is a model to investigate the genetic basis of phenotypic plasticity resulting from one differentially expressed genome. Daphnia develops adaptive phenotypes (e.g. morphological defences) thwarting predators, based on chemical predator cue perception. To understand the genomic basis of phenotypic plasticity, the description of the precedent cellular and neuronal mechanisms is fundamental. However, key regulators remain unknown. All neuronal and endocrine stimulants were able to modulate but not induce defences, indicating a pathway of interlinked steps. A candidate able to link neuronal with endocrine responses is the multi-functional amine dopamine. We here tested its involvement in trait formation in Daphnia pulex and Daphnia longicephala using an induction assay composed of predator cues combined with dopaminergic and cholinergic stimulants. The mere application of both stimulants was sufficient to induce morphological defences. We determined dopamine localization in cells found in close association with the defensive trait. These cells serve as centres controlling divergent morphologies. As a mitogen and sclerotization agent, we anticipate that dopamine is involved in proliferation and structural formation of morphological defences. Furthermore, dopamine pathways appear to be interconnected with endocrine pathways, and control juvenile hormone and ecdysone levels. In conclusion, dopamine is suggested as a key regulator of phenotypic plasticity. PMID:26423840

  10. Endoplasmic reticulum stress triggers ROS signalling, changes the redox state, and regulates the antioxidant defence of Arabidopsis thaliana

    PubMed Central

    Turkan, Ismail

    2014-01-01

    Inefficient chaperone activity in endoplasmic reticulum (ER) causes accumulation of unfolded proteins and is called ER stress, which triggers the unfolded protein response. For proper oxidative protein folding, reactive oxygen species (ROS) such as H2O2 are produced in the ER. Although the role of ROS during abiotic stresses such as salinity is well documented, the role of ER-related ROS production and its signalling is not yet known. Moreover, how H2O2 production, redox regulation, and antioxidant defence are affected in salt-treated plants when ER protein-folding machinery is impaired needs to be elucidated. For this aim, changes in NADPH-oxidase-dependent ROS signalling and H2O2 content at sequential time intervals and after 48h of ER stress, induced by tunicamycin (Tm), salinity, and their combination were determined in Arabidopsis thaliana. The main root growth was inhibited by ER stress, while low levels of Tm caused an increase in lateral root density. Salt stress and Tm induced the expression of ER-stress-related genes (bZIP17, bZIP28, bZIP60, TIN1, BiP1, BiP3) and ERO1. Tm induced expression of RBOHD and RBOHF, which led to an early increase in H2O2 and triggered ROS signalling. This study is the first report that ER stress induces the antioxidant system and the Asada–Halliwell pathway of A. thaliana in a similar way to salinity. ER stress caused oxidative damage, as evident by increased H2O2 accumulation, lipid peroxidation, and protein oxidation. As a result, this study shows that ER stress triggers ROS signalling, changes the redox state, and regulates the antioxidant defence of A. thaliana. PMID:24558072

  11. Prioritizing plant defence over growth through WRKY regulation facilitates infestation by non-target herbivores

    PubMed Central

    Li, Ran; Zhang, Jin; Li, Jiancai; Zhou, Guoxin; Wang, Qi; Bian, Wenbo; Erb, Matthias; Lou, Yonggen

    2015-01-01

    Plants generally respond to herbivore attack by increasing resistance and decreasing growth. This prioritization is achieved through the regulation of phytohormonal signaling networks. However, it remains unknown how this prioritization affects resistance against non-target herbivores. In this study, we identify WRKY70 as a specific herbivore-induced, mitogen-activated protein kinase-regulated rice transcription factor that physically interacts with W-box motifs and prioritizes defence over growth by positively regulating jasmonic acid (JA) and negatively regulating gibberellin (GA) biosynthesis upon attack by the chewing herbivore Chilo suppressalis. WRKY70-dependent JA biosynthesis is required for proteinase inhibitor activation and resistance against C. suppressalis. In contrast, WRKY70 induction increases plant susceptibility against the rice brown planthopper Nilaparvata lugens. Experiments with GA-deficient rice lines identify WRKY70-dependent GA signaling as the causal factor in N. lugens susceptibility. Our study shows that prioritizing defence over growth leads to a significant resistance trade-off with important implications for the evolution and agricultural exploitation of plant immunity. DOI: http://dx.doi.org/10.7554/eLife.04805.001 PMID:26083713

  12. Polyphenol Stilbenes: Molecular Mechanisms of Defence against Oxidative Stress and Aging-Related Diseases

    PubMed Central

    Reinisalo, Mika; Kårlund, Anna; Koskela, Ali; Kaarniranta, Kai; Karjalainen, Reijo O.

    2015-01-01

    Numerous studies have highlighted the key roles of oxidative stress and inflammation in aging-related diseases such as obesity, type 2 diabetes, age-related macular degeneration (AMD), and Alzheimer's disease (AD). In aging cells, the natural antioxidant capacity decreases and the overall efficiency of reparative systems against cell damage becomes impaired. There is convincing data that stilbene compounds, a diverse group of natural defence phenolics, abundant in grapes, berries, and conifer bark waste, may confer a protective effect against aging-related diseases. This review highlights recent data helping to clarify the molecular mechanisms involved in the stilbene-mediated protection against oxidative stress. The impact of stilbenes on the nuclear factor-erythroid-2-related factor-2 (Nrf2) mediated cellular defence against oxidative stress as well as the potential roles of SQSTM1/p62 protein in Nrf2/Keap1 signaling and autophagy will be summarized. The therapeutic potential of stilbene compounds against the most common aging-related diseases is discussed. PMID:26180583

  13. Polyphenol Stilbenes: Molecular Mechanisms of Defence against Oxidative Stress and Aging-Related Diseases.

    PubMed

    Reinisalo, Mika; Kårlund, Anna; Koskela, Ali; Kaarniranta, Kai; Karjalainen, Reijo O

    2015-01-01

    Numerous studies have highlighted the key roles of oxidative stress and inflammation in aging-related diseases such as obesity, type 2 diabetes, age-related macular degeneration (AMD), and Alzheimer's disease (AD). In aging cells, the natural antioxidant capacity decreases and the overall efficiency of reparative systems against cell damage becomes impaired. There is convincing data that stilbene compounds, a diverse group of natural defence phenolics, abundant in grapes, berries, and conifer bark waste, may confer a protective effect against aging-related diseases. This review highlights recent data helping to clarify the molecular mechanisms involved in the stilbene-mediated protection against oxidative stress. The impact of stilbenes on the nuclear factor-erythroid-2-related factor-2 (Nrf2) mediated cellular defence against oxidative stress as well as the potential roles of SQSTM1/p62 protein in Nrf2/Keap1 signaling and autophagy will be summarized. The therapeutic potential of stilbene compounds against the most common aging-related diseases is discussed. PMID:26180583

  14. Influence of strict regulations on the use of hearing protectors in the Finnish Defence Forces.

    PubMed

    Savolainen, S; Kuokkanen, J T; Lehtomäki, K M

    1999-11-01

    The regulations concerning hearing protection during military training in the Finnish Defence Forces were renewed in 1989. The material of this prospective study concerns 912 consecutive conscripts (463 before and 449 after the new regulations) who were referred to the Central Military Hospital for acute acoustic trauma (AAT). We focused on three issues: (1) general habits regarding the use of hearing protection during shooting drills and combat training; (2) hearing protection at the moment of AAT; and (3) the cause of AAT. In combat training, the use of any hearing protectors was only 50% before the new regulations, but after they came into force the proportion was greater than 90%, and more effective protectors were used. However, at the time of AAT the hearing protection was absent in more than 80% of cases in both groups. The most common cause of AAT was small arms in both groups (83%). PMID:10578597

  15. Glycine metabolism and anti-oxidative defence mechanisms in Pseudomonas fluorescens.

    PubMed

    Alhasawi, Azhar; Castonguay, Zachary; Appanna, Nishma D; Auger, Christopher; Appanna, Vasu D

    2015-02-01

    The role of metabolism in anti-oxidative defence is only now beginning to emerge. Here, we show that the nutritionally-versatile microbe, Pseudomonas fluorescens, reconfigures its metabolism in an effort to generate NADPH, ATP and glyoxylate in order to fend off oxidative stress. Glyoxylate was produced predominantly via the enhanced activities of glycine dehydrogenase-NADP(+) (GDH), glycine transaminase (GTA) and isocitrate lyase (ICL) in a medium exposed to hydrogen peroxide (H₂O₂). This ketoacid was utilized to produce ATP by substrate-level phosphorylation and to neutralize reactive oxygen species with the concomitant formation of formate. The latter was also a source of NADPH, a process mediated by formate dehydrogenase-NADP(+) (FDH). The increased activities of phosphoenolpyruvate carboxylase (PEPC) and pyruvate orthophosphate dikinase (PPDK) worked in tandem to synthesize ATP in the H₂O₂-challenged cells that had markedly diminished capacity for oxidative phosphorylation. These metabolic networks provide an effective means of combating ROS and reveal therapeutic targets against microbes resistant to oxidative stress. PMID:25644949

  16. Pella vilya: Near earth objects—Planetary defence through the regulation of resource utilisation

    NASA Astrophysics Data System (ADS)

    Goh, Gérardine Meishan

    2010-07-01

    Reactions to near earth objects (NEOs) in the past decade have run the gamut from expectations of Armageddon-type scenarios to Eureka moments of revolutionary scientific ideas. Concerns over the potentially devastating effects of an unmitigated collision jostle with forecasts of untold economic returns from the utilisation of NEO resources. Drawing from recent analogies and examples from the field of international environmental law, this paper proposes the development of a legal framework for the regulation of NEO resource utilisation. The proposed legal framework also includes a mechanism to ensure the political will and economic investment necessary for technological advances in planetary defence. By twinning the threats and opportunities presented by NEOs, this paper also analyses the position of theme-specific space law development in the overall legal framework of space exploration and traffic management.

  17. Anti-Oxidative Defences Are Modulated Differentially in Three Freshwater Teleosts in Response to Ammonia-Induced Oxidative Stress

    PubMed Central

    Giblen, Terri; Zinta, Gaurav; De Rop, Michelle; Asard, Han; Blust, Ronny; De Boeck, Gudrun

    2014-01-01

    Oxidative stress and the antioxidant response induced by high environmental ammonia (HEA) were investigated in the liver and gills of three freshwater teleosts differing in their sensitivities to ammonia. The highly ammonia-sensitive salmonid Oncorhynchus mykiss (rainbow trout), the less ammonia sensitive cyprinid Cyprinus carpio (common carp) and the highly ammonia-resistant cyprinid Carassius auratus (goldfish) were exposed to 1 mM ammonia (as NH4HCO3) for 0 h (control), 3 h, 12 h, 24 h, 48 h, 84 h and 180 h. Results show that HEA exposure increased ammonia accumulation significantly in the liver of all the three fish species from 24 h–48 h onwards which was associated with an increment in oxidative stress, evidenced by elevation of xanthine oxidase activity and levels of hydrogen peroxide (H2O2) and malondialdehyde (MDA). Unlike in trout, H2O2 and MDA accumulation in carp and goldfish liver was restored to control levels (84 h–180 h); which was accompanied by a concomitant increase in superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase activity and reduced ascorbate content. Many of these defence parameters remained unaffected in trout liver, while components of the glutathione redox cycle (reduced glutathione, glutathione peroxidase and glutathione reductase) enhanced to a greater extent. The present findings suggest that trout rely mainly on glutathione dependent defensive mechanism while carp utilize SOD, CAT and ascorbate as anti-oxidative sentinels. Hepatic cells of goldfish appear to utilize each of these protective systems, and showed more effective anti-oxidative compensatory responses towards HEA than carp, while trout were least effective. The present work also indicates that HEA exposure resulted in a relatively mild oxidative stress in the gills of all three species. This probably explains the almost complete lack of anti-oxidative responses in branchial tissue. This research suggests that oxidative stress, as well as the antioxidant

  18. Effects of depleted uranium on oxidative stress, detoxification, and defence parameters of zebrafish Danio rerio.

    PubMed

    Gagnaire, Beatrice; Cavalie, Isabelle; Camilleri, Virginie; Adam-Guillermin, Christelle

    2013-01-01

    In this study, we investigated the effects of depleted uranium (DU), the by-product of nuclear enrichment of uranium, on several parameters related to oxidative stress, detoxification, and the defence system in the zebrafish Danio rerio. Several parameters were recorded: phenoloxidase-like (PO) activity, reactive oxygen species (ROS) production, and 7-ethoxyresrufin-O-deethylase (EROD) activity. Experiments were performed on adult and larvae D. rerio. Adult fish were exposed for 28 days at 20 μg U/L followed by a 27-day depuration period. Eggs of D. rerio were exposed for 4 days at 0, 20, 100, 250, 500, and 1,000 μg U/L. Results showed that DU increased ROS production both in adult and in larvae even at the low concentrations tested and even during the depuration period for adult D. rerio. DU also modified PO-like activity, both in the D. rerio adult and larvae experiments, but in a more transient manner. EROD activity was not modified by DU, but sex effects were shown. Results are discussed by way of comparison with other known effects of uranium in fish. Overall, these results show that the mechanisms of action of DU in fish tend to be similar to the ones existing for mammals. These results encourage the development and use of innate immune biomarkers to understand the effects of uranium and, more generally, radionuclides on the fish immune system. PMID:23052361

  19. Effect of probiotic Pediococcus acidilactici on antioxidant defences and oxidative stress of Litopenaeus stylirostris under Vibrio nigripulchritudo challenge.

    PubMed

    Castex, Mathieu; Lemaire, Pierrette; Wabete, Nelly; Chim, Liet

    2010-04-01

    Antioxidant defences and induced oxidative stress tissue damage of the blue shrimp Litopenaeus stylirostris, under challenge with Vibrio nigripulchritudo, were investigated for a 72-h period. For this purpose, L. stylirostris were first infected by immersion with pathogenic V. nigripulchritudo strain SFn1 and then antioxidant defences: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx), Total antioxidant status (TAS), glutathiones and induced tissue damage (MDA and carbonyl proteins) were determined in the digestive gland at 0, 12, 24, 48 and 72 h post-infection (h.p.i.). In the meantime, TAS was also measured in the blood. Infection level of the shrimps during the challenge was followed by determining V. nigripulchritudo prevalence and load in the haemolymph of the shrimps. Changes in all these parameters during the 72-h.p.i. period were recorded for control shrimps and shrimps previously fed for one month with probiotic Pediococcus acidilactici MA18/5M at 10(7) CFU g(-1) of feed. Our results showed that immersion with V. nigripulchritudo led to maximal infection level in the haemolymph at 24 h.p.i. preceding the mortality peak recorded at 48 h.p.i. Significant decreases in the antioxidant defences were detected from 24 h.p.i. and beyond that time infection leaded to increases in oxidative stress level and tissue damage. Compared to control group, shrimps fed the probiotic diet showed lower infection (20% instead of 45% at 24 h.p.i. in the control group) and mortality (25% instead of 41.7% in the control group) levels. Moreover, infected shrimp fed the probiotic compared to uninfected control shrimps exhibited very similar antioxidant status and oxidative stress level. Compared to the infected control group, shrimps fed the probiotic sustained higher antioxidant defences and lower oxidative stress level. This study shows that bacterial infection leads to oxidative stress in L. stylirostris and highlighted a beneficial effect of P

  20. Functional analysis of Arabidopsis immune-related MAPKs uncovers a role for MPK3 as negative regulator of inducible defences

    PubMed Central

    2014-01-01

    Background Mitogen-activated protein kinases (MAPKs) are key regulators of immune responses in animals and plants. In Arabidopsis, perception of microbe-associated molecular patterns (MAMPs) activates the MAPKs MPK3, MPK4 and MPK6. Increasing information depicts the molecular events activated by MAMPs in plants, but the specific and cooperative contributions of the MAPKs in these signalling events are largely unclear. Results In this work, we analyse the behaviour of MPK3, MPK4 and MPK6 mutants in early and late immune responses triggered by the MAMP flg22 from bacterial flagellin. A genome-wide transcriptome analysis reveals that 36% of the flg22-upregulated genes and 68% of the flg22-downregulated genes are affected in at least one MAPK mutant. So far MPK4 was considered as a negative regulator of immunity, whereas MPK3 and MPK6 were believed to play partially redundant positive functions in defence. Our work reveals that MPK4 is required for the regulation of approximately 50% of flg22-induced genes and we identify a negative role for MPK3 in regulating defence gene expression, flg22-induced salicylic acid accumulation and disease resistance to Pseudomonas syringae. Among the MAPK-dependent genes, 27% of flg22-upregulated genes and 76% of flg22-downregulated genes require two or three MAPKs for their regulation. The flg22-induced MAPK activities are differentially regulated in MPK3 and MPK6 mutants, both in amplitude and duration, revealing a highly interdependent network. Conclusions These data reveal a new set of distinct functions for MPK3, MPK4 and MPK6 and indicate that the plant immune signalling network is choreographed through the interplay of these three interwoven MAPK pathways. PMID:24980080

  1. Are diverse signalling pathways integrated in the regulation of arabidopsis antioxidant defence gene expression in response to excess excitation energy?

    PubMed Central

    Mullineaux, P; Ball, L; Escobar, C; Karpinska, B; Creissen, G; Karpinski, S

    2000-01-01

    When low-light-grown Arabidopsis rosettes are partially exposed to excess light (EL), the unexposed leaves become acclimated to excess excitation energy (EEE) and consequent photo-oxidative stress. This phenomenon, termed systemic acquired acclimation (SAA), is associated with redox changes in the proximity of photosystem II, changes in foliar H2O2 content and induction of antioxidant defences. The induction of extra-plastidial antioxidant systems is important in the protection of the chloroplast under EL conditions. A larger range of transcripts encoding different antioxidant defence enzymes may be induced in the systemically acclimated leaves and these include those encoded by the glutathione peroxidase (GPX2) and glutathione-S-transferase (GST) genes, which are also highly induced in the hypersensitive response and associated systemic acquired resistance (SAR) in incompatible plant-pathogen interactions. Furthermore, the expression of the SAR-inducible pathogenesis-related protein gene, PR2, is enhanced in SAA leaves. Wounded leaf tissue also shows enhanced systemic induction of a cytosolic ascorbate peroxidase gene (APX2) under EL conditions. These and other considerations, suggest H2O2 and other reactive oxygen species (ROS) could be the common factor in signalling pathways for diverse environmental stresses. These effects may be mediated by changes in the level and redox state of the cellular glutathione pool. Mutants with constitutive expression of a normally EL-inducible APX2 gene have much reduced levels of foliar glutathione. The expression of APX1 and APX3, encoding cytosolic and peroxisome-associated isoforms, respectively, are also under phytochrome-A-mediated control. The expression of these genes is tightly linked to the greening of plastids in etiolated seedlings. These data suggest that part of the developmental processes that bring about the acclimation of leaves to high light includes the configuration of antioxidant defences. Therefore, the

  2. Gene coevolution and regulation lock cyclic plant defence peptides to their targets.

    PubMed

    Gilding, Edward K; Jackson, Mark A; Poth, Aaron G; Henriques, Sónia Troeira; Prentis, Peter J; Mahatmanto, Tunjung; Craik, David J

    2016-04-01

    Plants have evolved many strategies to protect themselves from attack, including peptide toxins that are ribosomally synthesized and thus adaptable directly by genetic polymorphisms. Certain toxins in Clitoria ternatea (butterfly pea) are cyclic cystine-knot peptides of c. 30 residues, called cyclotides, which have co-opted the plant's albumin-1 gene family for their production. How butterfly pea albumin-1 genes were commandeered and how these cyclotides are utilized in defence remain unclear. The role of cyclotides in host plant ecology and biotechnological applications requires exploration. We characterized the sequence diversity and expression dynamics of precursor and processing proteins implicated in butterfly pea cyclotide biosynthesis by expression profiling through RNA-sequencing (RNA-seq). Peptide-enriched extracts from various organs were tested for activity against insect-like membranes and the model nematode Caenorhabditis elegans. We found that the evolution and deployment of cyclotides involved their diversification to exhibit different chemical properties and expression between organs facing different defensive challenges. Cyclotide-enriched fractions from soil-contacting organs were effective at killing nematodes, whereas similar enriched fractions from aerial organs contained cyclotides that exhibited stronger interactions with insect-like membrane lipids. Cyclotides are employed as versatile and combinatorial mediators of defence in C. ternatea and have specialized to affect different classes of attacking organisms. PMID:26668107

  3. The Arabidopsis immune regulator SRFR1 dampens defences against herbivory by Spodoptera exigua and parasitism by Heterodera schachtii.

    PubMed

    Nguyen, Phuong Dung T; Pike, Sharon; Wang, Jianying; Nepal Poudel, Arati; Heinz, Robert; Schultz, Jack C; Koo, Abraham J; Mitchum, Melissa G; Appel, Heidi M; Gassmann, Walter

    2016-05-01

    Plants have developed diverse mechanisms to fine tune defence responses to different types of enemy. Cross-regulation between signalling pathways may allow the prioritization of one response over another. Previously, we identified SUPPRESSOR OF rps4-RLD1 (SRFR1) as a negative regulator of ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1)-dependent effector-triggered immunity against the bacterial pathogen Pseudomonas syringae pv. tomato strain DC3000 expressing avrRps4. The use of multiple stresses is a powerful tool to further define gene function. Here, we examined whether SRFR1 also impacts resistance to a herbivorous insect in leaves and to a cyst nematode in roots. Interestingly, srfr1-1 plants showed increased resistance to herbivory by the beet army worm Spodoptera exigua and to parasitism by the cyst nematode Heterodera schachtii compared with the corresponding wild-type Arabidopsis accession RLD. Using quantitative real-time PCR (qRT-PCR) to measure the transcript levels of salicylic acid (SA) and jasmonate/ethylene (JA/ET) pathway genes, we found that enhanced resistance of srfr1-1 plants to S. exigua correlated with specific upregulation of the MYC2 branch of the JA pathway concurrent with suppression of the SA pathway. In contrast, the greater susceptibility of RLD was accompanied by simultaneously increased transcript levels of SA, JA and JA/ET signalling pathway genes. Surprisingly, mutation of either SRFR1 or EDS1 increased resistance to H. schachtii, indicating that the concurrent presence of both wild-type genes promotes susceptibility. This finding suggests a novel form of resistance in Arabidopsis to the biotrophic pathogen H. schachtii or a root-specific regulation of the SA pathway by EDS1, and places SRFR1 at an intersection between multiple defence pathways. PMID:26310916

  4. Real-time electrochemical detection of extracellular nitric oxide in tobacco cells exposed to cryptogein, an elicitor of defence responses

    PubMed Central

    Besson-Bard, Angélique; Griveau, Sophie; Bedioui, Fethi; Wendehenne, David

    2008-01-01

    It was previously reported that cryptogein, an elicitor of defence responses, induces an intracellular production of nitric oxide (NO) in tobacco. Here, the possibility was explored that cryptogein might also trigger an increase of NO extracellular content through two distinct approaches, an indirect method using the NO probe 4,5-diaminofluorescein (DAF-2) and an electrochemical method involving a chemically modified microelectrode probing free NO in biological media. While the chemical nature of DAF-2-reactive compound(s) is still uncertain, the electrochemical modified microelectrodes provide real-time evidence that cryptogein induces an increase of extracellular NO. Direct measurement of free extracellular NO might offer important new insights into its role in plants challenged by biotic stresses. PMID:18653691

  5. CYP94-mediated jasmonoyl-isoleucine hormone oxidation shapes jasmonate profiles and attenuates defence responses to Botrytis cinerea infection

    PubMed Central

    Aubert, Yann; Widemann, Emilie; Miesch, Laurence; Pinot, Franck; Heitz, Thierry

    2015-01-01

    Induced resistance to the necrotrophic pathogen Botrytis cinerea depends on jasmonate metabolism and signalling in Arabidopsis. We have presented here extensive jasmonate profiling in this pathosystem and investigated the impact of the recently reported jasmonoyl-isoleucine (JA-Ile) catabolic pathway mediated by cytochrome P450 (CYP94) enzymes. Using a series of mutant and overexpressing (OE) plant lines, we showed that CYP94B3 and CYP94C1 are integral components of the fungus-induced jasmonate metabolic pathway and control the abundance of oxidized conjugated but also some unconjugated derivatives, such as sulfated 12-HSO4-JA. Despite causing JA-Ile overaccumulation due to impaired oxidation, CYP94 deficiency had negligible impacts on resistance, associated with enhanced JAZ repressor transcript levels. In contrast, plants overexpressing (OE) CYP94B3 or CYP94C1 were enriched in 12-OH-JA-Ile or 12-COOH-JA-Ile respectively. This shift towards oxidized JA-Ile derivatives was concomitant with strongly impaired defence gene induction and reduced disease resistance. CYP94B3-OE, but unexpectedly not CYP94C1-OE, plants displayed reduced JA-Ile levels compared with the wild type, suggesting that increased susceptibility in CYP94C1-OE plants may result from changes in the hormone oxidation ratio rather than absolute changes in JA-Ile levels. Consistently, while feeding JA-Ile to seedlings triggered strong induction of JA pathway genes, induction was largely reduced or abolished after feeding with the CYP94 products 12-OH-JA-Ile and 12-COOH-JA-Ile, respectively. This trend paralleled in vitro pull-down assays where 12-COOH-JA-Ile was unable to promote COI1–JAZ9 co-receptor assembly. Our results highlight the dual function of CYP94B3/C1 in antimicrobial defence: by controlling hormone oxidation status for signal attenuation, these enzymes also define JA-Ile as a metabolic hub directing jasmonate profile complexity. PMID:25903915

  6. CYP94-mediated jasmonoyl-isoleucine hormone oxidation shapes jasmonate profiles and attenuates defence responses to Botrytis cinerea infection.

    PubMed

    Aubert, Yann; Widemann, Emilie; Miesch, Laurence; Pinot, Franck; Heitz, Thierry

    2015-07-01

    Induced resistance to the necrotrophic pathogen Botrytis cinerea depends on jasmonate metabolism and signalling in Arabidopsis. We have presented here extensive jasmonate profiling in this pathosystem and investigated the impact of the recently reported jasmonoyl-isoleucine (JA-Ile) catabolic pathway mediated by cytochrome P450 (CYP94) enzymes. Using a series of mutant and overexpressing (OE) plant lines, we showed that CYP94B3 and CYP94C1 are integral components of the fungus-induced jasmonate metabolic pathway and control the abundance of oxidized conjugated but also some unconjugated derivatives, such as sulfated 12-HSO4-JA. Despite causing JA-Ile overaccumulation due to impaired oxidation, CYP94 deficiency had negligible impacts on resistance, associated with enhanced JAZ repressor transcript levels. In contrast, plants overexpressing (OE) CYP94B3 or CYP94C1 were enriched in 12-OH-JA-Ile or 12-COOH-JA-Ile respectively. This shift towards oxidized JA-Ile derivatives was concomitant with strongly impaired defence gene induction and reduced disease resistance. CYP94B3-OE, but unexpectedly not CYP94C1-OE, plants displayed reduced JA-Ile levels compared with the wild type, suggesting that increased susceptibility in CYP94C1-OE plants may result from changes in the hormone oxidation ratio rather than absolute changes in JA-Ile levels. Consistently, while feeding JA-Ile to seedlings triggered strong induction of JA pathway genes, induction was largely reduced or abolished after feeding with the CYP94 products 12-OH-JA-Ile and 12-COOH-JA-Ile, respectively. This trend paralleled in vitro pull-down assays where 12-COOH-JA-Ile was unable to promote COI1-JAZ9 co-receptor assembly. Our results highlight the dual function of CYP94B3/C1 in antimicrobial defence: by controlling hormone oxidation status for signal attenuation, these enzymes also define JA-Ile as a metabolic hub directing jasmonate profile complexity. PMID:25903915

  7. Crucial Roles of Systemic and Tissue Lipid Peroxidation Levels and Anti-Oxidant Defences Following Contrast Agent Application

    PubMed Central

    Sitar, Gungor; Kucuk, Mehmet; Erinc Sitar, Mustafa; Yasar, Ozgur; Aydin, Seval; Yanar, Karolin; Cakatay, Ufuk; Buyukpınarbasili, Nur

    2016-01-01

    Background One of the most important side effects of contrast pharmaceutical agents, which are used very common in routine radiology practice, is contrast induced nephropathy. Even ischemia, oxidative stress and osmolality related cytotoxic effects are considered, the molecular mechanisms underlying this pathology have not been identified completely yet. Objectives The aim of the current study was to reveal the role of oxidative stress and antioxidant enzymatic defence mechanisms in the aetiopathogenesis of contrast-induced nephropathy. We also studied possible alleviating effects of N-acetylcysteine (NAC), a potent antioxidant, to obtain extra information regarding the molecular mechanisms underlying this pathology. Materials and Methods This is an clinical-experimental study, This study was conducted of Istanbul/Turkey between September 15, 2012 and April 15, 2013. Three groups of male rats were randomly set up as a control group (C), a 100 mg/kg intraperitoneal NAC + 7 mL/kg contrast agent group (N + CIN) and a 7 mL/kg intraperitoneal contrast agent group (CIN). They were placed in individual metabolic cages 48 hours after agent administration to obtain 24-hour urine samples. Renal function tests (albumin, urea, creatinine, total protein) were conducted, oxidative stress parameters (Cu, Zn superoxide dismutase activity - Cu, Zn-SOD; advanced oxidation protein products - AOPP; protein carbonyls - PCO; total thiol groups - T-SH; and lipid hydroperoxides -LHP) were measured and tissues were analysed histopathologically. Results Compared with the control group, groups CIN and N + CIN had significantly higher urea and LHP levels (P < 0.05 and P < 0.001, respectively) and significantly lower Cu, Zn-SOD activity and creatinine clearance (P < 0.05). There was no statistically significant difference between the groups in PCO or AOPP levels despite differences in descriptive statistics. Conclusions Contrast-agent-induced nephropathic changes are more closely related to

  8. First line of defence: the role of sloughing in the regulation of cutaneous microbes in frogs

    PubMed Central

    Cramp, Rebecca L.; McPhee, Rebecca K.; Meyer, Edward A.; Ohmer, Michel E.; Franklin, Craig E.

    2014-01-01

    Amphibian populations worldwide are currently experiencing unprecedented declines due to the combined effects of emerging infectious disease and climate change. The skin is the first line of defence in preventing establishment of pathogens and associated infections. Although amphibians undergo regular sloughing of the outer layer of the skin, the potential for regular sloughing to play a role in influencing cutaneous microbial populations and pathogens has been largely overlooked. In the present study, we assessed the effect of skin sloughing on cultivable cutaneous bacterial abundance in the green tree frog (Litoria caerulea). We also examined the effects of temperature and hydric environment on sloughing frequency and microbial re-establishment rates. Our data showed that cultivable cutaneous bacterial abundance was significantly reduced by sloughing events, and frogs kept at ‘summer’ temperatures (23–33°C) sloughed almost twice as frequently as those maintained at ‘winter’ temperatures (13–23°C). No effect of hydric environment on sloughing frequency was observed, but we did find that sloughing in L. caerulea appeared to be linked to ambient light cycles. Examination of the effect of sloughing on microbial recolonization indicated that at cool temperatures, an extended intermoult interval allowed microbial abundance to reach higher levels than at warmer ‘summer’ temperatures (when the intermoult interval was significantly reduced). Our data suggest that sloughing may significantly influence the establishment and/or maintenance of cutaneous bacterial populations (pathogenic, mutualistic and/or commensal) and this, in turn, may be affected by environmental factors, such as ambient light and temperature. These findings are likely to be important for our understanding of the ecology of skin-based pathogens, such as the amphibian chytrid fungus, Batrachochytrium dendrobatidis. PMID:27293633

  9. Comparative analyses of genotoxicity, oxidative stress and antioxidative defence system under exposure of methyl parathion and hexaconazole in barley (Hordeum vulgare L.).

    PubMed

    Dubey, Pragyan; Mishra, Amit Kumar; Singh, Ashok Kumar

    2015-12-01

    The present study aims to evaluate the comparative effects of methyl parathion and hexaconazole on genotoxicity, oxidative stress, antioxidative defence system and photosynthetic pigments in barley (Hordeum vulgare L. variety karan-16). The seeds were exposed with three different concentrations, i.e. 0.05, 0.1 and 0.5 % for 6 h after three pre-soaking durations 7, 17 and 27 h which represents G1, S and G2 phases of the cell cycle, respectively. Ethyl methane sulphonate, a well-known mutagenic agent and double distilled water, was used as positive and negative controls, respectively. The results indicate significant decrease in mitotic index with increasing concentrations of pesticides, and the extent was higher in methyl parathion. Chromosomal aberrations were found more frequent in methyl parathion than hexaconazole as compared to their respective controls. Treatment with the pesticides induced oxidative stress which was evident with higher contents of H2O2 and lipid peroxidation, and the increase was more prominent in methyl parathion. Contents of total phenolics were increased; however, soluble protein content showed a reverse trend. Among the enzymatic antioxidants, activities of superoxide dismutase and peroxidase were significantly up-regulated, and more increase was noticed in hexaconazole. Increments in total chlorophyll and carotenoid contents were observed up to 0.1 % but decreased at higher concentration (0.5 %), and the reductions were more prominent in methyl parathion than hexaconazole as compared to their respective controls. Methyl parathion treatment caused more damage in the plant cells of barley as compared to hexaconazole, which may be closely related to higher genotoxicity and oxidative stress. PMID:26286802

  10. The in vitro manipulation of carbohydrate metabolism: a new strategy for deciphering the cellular defence mechanisms against nitric oxide attack.

    PubMed Central

    Le Goffe, C; Vallette, G; Jarry, A; Bou-Hanna, C; Laboisse, C L

    1999-01-01

    This study was aimed at examining the effects of manipulating the carbohydrate source of the culture medium on the cellular sensitivity of epithelial cells to an oxidative attack. Our rationale was that substituting galactose for glucose in culture media would remove the protection afforded by glucose utilization in two major metabolic pathways, i.e. anaerobic glycolysis and/or the pentose phosphate pathway (PPP), which builds up cellular reducing power. Indeed, we show that the polarized human colonic epithelial cell line HT29-Cl.16E was sensitive to the deleterious effects of the NO donor PAPANONOate [3-(2-hydroxy-2-nitroso-1-propylhydrazino)-1-propanamine] only in galactose-containing medium. In such medium NO attack led to cytotoxic and apoptotic cell death, associated with formation of derivatives of NO auto-oxidation (collectively termed NOx) and peroxynitrite, leading to intracellular GSH depletion and nitrotyrosine formation. The addition of 2-deoxyglucose, a non-glycolytic substrate, to galactose-fed cells protected HT29-Cl. 16E cells from NO attack and maintained control GSH levels through its metabolic utilization in the PPP, as shown by (14)CO(2) production from 2-deoxy[1-(14)C]glucose. Therefore, increasing the availability of reducing equivalents without interfering with energy metabolism is able to prevent NO-induced cell injury. Finally, this background provides the conceptual framework for establishing nutritional manipulation of cellular metabolic pathways that could provide new means for (i) deciphering the mechanisms of cell injury by reactive nitrogen species and reactive oxygen species at the whole-cell level and (ii) establishing the hierarchy of intracellular defence mechanisms against these attacks. PMID:10585850

  11. A single blueberry (Vaccinium corymbosum) portion does not affect markers of antioxidant defence and oxidative stress in healthy volunteers following cigarette smoking.

    PubMed

    Del Bo', Cristian; Porrini, Marisa; Campolo, Jonica; Parolini, Marina; Lanti, Claudia; Klimis-Zacas, Dorothy; Riso, Patrizia

    2016-03-01

    We previously reported that a portion of blueberries reversed endothelial dysfunction induced by acute cigarette smoking. Since smoking-induced endothelial dysfunction is associated with a condition of oxidative stress, we evaluated whether the observed effect was mediated by modulation of markers of oxidative stress and antioxidant defence. Fourteen out of 16 male healthy smokers previously enrolled, participated in a three-armed randomized controlled study with the following experimental conditions: smoking treatment (one cigarette); blueberry treatment (300g of blueberries) + smoking (one cigarette); control treatment (300ml of water with sugar) + smoking (one cigarette). The cigarette was smoked 100min after blueberry/control/water consumption. Each treatment was separated by 1 week of washout period. Plasma vitamin (C, B12 and folate) and aminothiol concentrations, endogenous [formamidopyrimidine-DNA glycosylase (FPG)-sensitive sites] and oxidatively induced DNA damage (resistance to H2O2-induced DNA damage) in peripheral blood mononuclear cells (PBMCs) were measured at baseline and 20, 60, 90, 120min and 24h after smoking. On the whole, analysis of variance did not show a significant effect of treatment on the modulation of markers of oxidative stress and antioxidant defence but revealed an effect of time for plasma concentrations of vitamin C (P = 0.003), B12 (P < 0.001), folate (P < 0.001), total cysteine (P = 0.007) and cysteine-glycine (P = 0.010) that increased following the three treatments after smoking. No significant effect of treatment was observed for the levels of FPG-sensitive sites (P > 0.05) and H2O2-induced DNA damage (P > 0.05) in PBMCs. In conclusion, the consumption of a single blueberry portion failed to modulate markers of oxidative stress and antioxidant defence investigated in our experimental conditions. Further studies are necessary to elucidate this finding and help clarifying the mechanisms of protection of blueberries against

  12. Role of antioxidant enzymatic defences against oxidative stress H(2)O(2) and the acquisition of oxidative tolerance in Candida albicans.

    PubMed

    González-Párraga, Pilar; Hernández, José A; Argüelles, Juan Carlos

    2003-10-30

    In Candida albicans, trehalose plays an essential role as a protector of cell integrity against oxidative challenge. A double homozygous mutant, tps1/tps1, deficient in trehalose synthesis, displayed severe cell mortality when exposed to high H(2)O(2) concentrations, compared with its congenic parental (CAI-4) strain (Alvarez-Peral et al., 2002). We have examined the putative role of a set of well-known antioxidant enzymes as components of the defence mechanism against oxidative challenges. When exposed to mild non-lethal oxidative treatment (0.5 mM H(2)O(2)), a significant induction of catalase, glutathione reductase (GR), and Cu,Zn-superoxide dismutase (SOD) was recorded in tps1/tps1 exponential cultures. However, in CAI-4 cells, subjected to the same conditions, there was only a clear activation of catalase, Mn-SOD and Cu,Zn-SOD activities. The degree of activation was always much more pronounced in the trehalose-deficient mutant than in its wild-type counterpart, except for Mn-SOD activity. After exposure to severe oxidative stress (50 mM H(2)O(2)) only GR and catalase activities increased in tps1/tps1 cultures, whereas in CAI-4 cells GR but not catalase was induced. In both cell strains, 50 mM H(2)O(2) caused inhibition of the Mn- and Cu,Zn-SOD isozymes, this inhibition being more pronounced in tps1/tps1 cells. C. albicans is able to acquire adaptive oxidative tolerance by pretreatment with a low non-stressing concentration of H(2)O(2) before exposure to a drastic oxidative challenge. When these antioxidant activities were measured during the adaptive response, a greater degree of enzymatic antioxidant induction was consistently observed in the tps1/tps1 mutant with respect to the CAI-4 strain. Together with a higher intrinsic sensitivity of tps1/tps1 cells, we suggest that this unexpected increase might be explained in terms of a compensatory mechanism to overcome the lack of endogenous trehalose upon drastic oxidative exposure, although this induction was

  13. A newly discovered oxidant defence system and its involvement in the development of Aurelia aurita (Scyphozoa, Cnidaria): reactive oxygen species and elemental iodine control medusa formation.

    PubMed

    Berking, Stefan; Czech, Nicole; Gerharz, Melanie; Herrmann, Klaus; Hoffmann, Uwe; Raifer, Hartmann; Sekul, Guy; Siefker, Barbara; Sommerei, Andrea; Vedder, Fritz

    2005-01-01

    In Aurelia aurita, applied iodine induces medusa formation (strobilation). This process also occurs when the temperature is lowered. This was found to increase oxidative stress resulting in an increased production of iodine from iodide. One polyp produces several medusae (initially termed ephyrae) starting at the polyp's oral end. The spreading of strobilation down the body column is controlled by a feedback loop: ephyra anlagen decrease the tyrosine content in adjacent polyp tissue by producing melanin from tyrosine. Endogenous tyrosine is able to remove iodine by forming iodiferous tyrosine compounds. The reduced level of tyrosine causes the ephyra-polyp-border to move towards the basal end of the former polyp. We argue that an oxidant defence system may exist which makes use of iodide and tyrosine. Like other marine invertebrates, polyps of Aurelia contain iodide ions. Inevitably produced peroxides oxidise iodide into iodine. The danger to be harmed by iodine is strongly decreased by endogenous tyrosine which reacts with iodine to form iodiferous tyrosine compounds including thyroxin. Both substances together, iodide and tyrosine, form an efficient oxidant defence system which shields the tissue against damage by reactive oxygen species. In the course of evolution (from a species at the basis of the animal kingdom like Aurelia to a highly evolved species like man) the waste product thyroxin (indicating a high metabolic rate) has developed into a hormone which controls the metabolic rate. PMID:16281174

  14. A novel rice C2H2-type zinc finger protein, ZFP36, is a key player involved in abscisic acid-induced antioxidant defence and oxidative stress tolerance in rice

    PubMed Central

    Zhang, Hong; Liu, Yanpei; Wen, Feng; Yao, Dongmei; Wang, Lu; Guo, Jin; Ni, Lan; Zhang, Aying; Tan, Mingpu; Jiang, Mingyi

    2014-01-01

    C2H2-type zinc finger proteins (ZFPs) have been shown to play important roles in the responses of plants to oxidative and abiotic stresses, and different members of this family might have different roles during stresses. Here a novel abscisic acid (ABA)- and hydrogen peroxide (H2O2)-responsive C2H2-type ZFP gene, ZFP36, is identified in rice. The analyses of ZFP36-overexpressing and silenced transgenic rice plants showed that ZFP36 is involved in ABA-induced up-regulation of the expression and the activities of superoxide dismutase (SOD) and ascorbate peroxidase (APX). Overexpression of ZFP36 in rice plants was found to elevate the activities of antioxidant enzymes and to enhance the tolerance of rice plants to water stress and oxidative stress. In contrast, an RNA interference (RNAi) mutant of ZFP36 had lower activities of antioxidant enzymes and was more sensitive to water stress and oxidative stress. ABA-induced H2O2 production and ABA-activated mitogen-activated protein kinases (MAPKs) were shown to regulate the expression of ZFP36 in ABA signalling. On the other hand, ZFP36 also regulated the expression of NADPH oxidase genes, the production of H2O2, and the expression of OsMPK genes in ABA signalling. These results indicate that ZFP36 is required for ABA-induced antioxidant defence, for the tolerance of rice plants to water stress and oxidative stress, and for the regulation of the cross-talk between NADPH oxidase, H2O2, and MAPK in ABA signalling. PMID:25071223

  15. Host defence versus intraspecific competition in the regulation of infrapopulations of the flea Xenopsylla conformis on its rodent host Meriones crassus.

    PubMed

    Hawlena, Hadas; Abramsky, Zvika; Krasnov, Boris R; Saltz, David

    2007-07-01

    Mechanisms that regulate parasite populations may influence the evolution of hosts and parasites, as well as the stability of host-parasite dynamics but are still poorly understood. A manipulation experiment on the grooming ability of rodent hosts (Meriones crassus) and flea (Xenopsylla conformis) densities on these hosts successfully disentangled two possible regulating mechanisms: (i) behavioural defence of the host and (ii) intraspecific competition among parasites, and revealed their importance in suppressing the feeding of fleas. Moreover, the results suggest that flea competition is direct and is not mediated by host grooming, immune response, or parasite-induced damage to the host. These mechanisms, together with interspecific competition and density-dependent parasite-induced host damage, may limit the parasite burden on an individual host and may prevent parasites from overexploiting their host population. PMID:17362966

  16. Rapid evolution of antioxidant defence in a natural population of Daphnia magna.

    PubMed

    Oexle, S; Jansen, M; Pauwels, K; Sommaruga, R; De Meester, L; Stoks, R

    2016-07-01

    Natural populations can cope with rapid changes in stressors by relying on sets of physiological defence mechanisms. Little is known onto what extent these physiological responses reflect plasticity and/or genetic adaptation, evolve in the same direction and result in an increased defence ability. Using resurrection ecology, we studied how a natural Daphnia magna population adjusted its antioxidant defence to ultraviolet radiation (UVR) during a period with increasing incident UVR reaching the water surface. We demonstrate a rapid evolution of the induction patterns of key antioxidant enzymes under UVR exposure in the laboratory. Notably, evolutionary changes strongly differed among enzymes and mainly involved the evolution of UV-induced plasticity. Whereas D. magna evolved a strong plastic up-regulation of glutathione peroxidase under UVR, it evolved a lower plastic up-regulation of glutathione S-transferase and superoxide dismutase and a plastic down-regulation of catalase. The differentially evolved antioxidant strategies were collectively equally effective in dealing with oxidative stress because they resulted in the same high levels of oxidative damage (to lipids, proteins and DNA) and lowered fitness (intrinsic growth rate) under UVR exposure. The lack of better protection against UVR may suggest that the UVR exposure did not increase between both periods. Predator-induced evolution to migrate to lower depths that occurred during the same period may have contributed to the evolved defence strategy. Our results highlight the need for a multiple trait approach when focusing on the evolution of defence mechanisms. PMID:27018861

  17. Enhancement of Cellular Antioxidant-Defence Preserves Diastolic Dysfunction via Regulation of Both Diastolic Zn2+ and Ca2+ and Prevention of RyR2-Leak in Hyperglycemic Cardiomyocytes

    PubMed Central

    Tuncay, Erkan; Okatan, Esma N.; Toy, Aysegul; Turan, Belma

    2014-01-01

    We examined whether cellular antioxidant-defence enhancement preserves diastolic dysfunction via regulation of both diastolic intracellular free Zn2+ and Ca2+ levels ([Zn2+]i and [Ca2+]i) levels N-acetyl cysteine (NAC) treatment (4 weeks) of diabetic rats preserved altered cellular redox state and also prevented diabetes-induced tissue damage and diastolic dysfunction with marked normalizations in the resting [Zn2+]i and [Ca2+]i. The kinetic parameters of transient changes in Zn2+ and Ca2+ under electrical stimulation and the spatiotemporal properties of Zn2+ and Ca2+ sparks in resting cells are found to be normal in the treated diabetic group. Biochemical analysis demonstrated that the NAC treatment also antagonized hyperphosphorylation of cardiac ryanodine receptors (RyR2) and significantly restored depleted protein levels of both RyR2 and calstabin2. Incubation of cardiomyocytes with 10 µM ZnCl2 exerted hyperphosphorylation in RyR2 as well as higher phosphorphorylations in both PKA and CaMKII in a concentration-dependent manner, similar to hyperglycemia. Our present data also showed that a subcellular oxidative stress marker, NF-κB, can be activated if the cells are exposed directly to Zn2+. We thus for the first time report that an enhancement of antioxidant defence in diabetics via directly targeting heart seems to prevent diastolic dysfunction due to modulation of RyR2 macromolecular-complex thereby leading to normalized [Ca2+]i and [Zn2+]i in cardiomyocytes. PMID:24693334

  18. Phytoagents for cancer management: regulation of nucleic acid oxidation, ROS, and related mechanisms.

    PubMed

    Lee, Wai-Leng; Huang, Jing-Ying; Shyur, Lie-Fen

    2013-01-01

    Accumulation of oxidized nucleic acids causes genomic instability leading to senescence, apoptosis, and tumorigenesis. Phytoagents are known to reduce the risk of cancer development; whether such effects are through regulating the extent of nucleic acid oxidation remains unclear. Here, we outlined the role of reactive oxygen species in nucleic acid oxidation as a driving force in cancer progression. The consequential relationship between genome instability and cancer progression highlights the importance of modulation of cellular redox level in cancer management. Current epidemiological and experimental evidence demonstrate the effects and modes of action of phytoagents in nucleic acid oxidation and provide rationales for the use of phytoagents as chemopreventive or therapeutic agents. Vitamins and various phytoagents antagonize carcinogen-triggered oxidative stress by scavenging free radicals and/or activating endogenous defence systems such as Nrf2-regulated antioxidant genes or pathways. Moreover, metal ion chelation by phytoagents helps to attenuate oxidative DNA damage caused by transition metal ions. Besides, the prooxidant effects of some phytoagents pose selective cytotoxicity on cancer cells and shed light on a new strategy of cancer therapy. The "double-edged sword" role of phytoagents as redox regulators in nucleic acid oxidation and their possible roles in cancer prevention or therapy are discussed in this review. PMID:24454991

  19. Phytoagents for Cancer Management: Regulation of Nucleic Acid Oxidation, ROS, and Related Mechanisms

    PubMed Central

    Shyur, Lie-Fen

    2013-01-01

    Accumulation of oxidized nucleic acids causes genomic instability leading to senescence, apoptosis, and tumorigenesis. Phytoagents are known to reduce the risk of cancer development; whether such effects are through regulating the extent of nucleic acid oxidation remains unclear. Here, we outlined the role of reactive oxygen species in nucleic acid oxidation as a driving force in cancer progression. The consequential relationship between genome instability and cancer progression highlights the importance of modulation of cellular redox level in cancer management. Current epidemiological and experimental evidence demonstrate the effects and modes of action of phytoagents in nucleic acid oxidation and provide rationales for the use of phytoagents as chemopreventive or therapeutic agents. Vitamins and various phytoagents antagonize carcinogen-triggered oxidative stress by scavenging free radicals and/or activating endogenous defence systems such as Nrf2-regulated antioxidant genes or pathways. Moreover, metal ion chelation by phytoagents helps to attenuate oxidative DNA damage caused by transition metal ions. Besides, the prooxidant effects of some phytoagents pose selective cytotoxicity on cancer cells and shed light on a new strategy of cancer therapy. The “double-edged sword” role of phytoagents as redox regulators in nucleic acid oxidation and their possible roles in cancer prevention or therapy are discussed in this review. PMID:24454991

  20. Host defences against Giardia lamblia.

    PubMed

    Lopez-Romero, G; Quintero, J; Astiazarán-García, H; Velazquez, C

    2015-08-01

    Giardia spp. is a protozoan parasite that inhabits the upper small intestine of mammals and other species and is the aetiological agent of giardiasis. It has been demonstrated that nitric oxide, mast cells and dendritic cells are the first line of defence against Giardia. IL-6 and IL-17 play an important role during infection. Several cytokines possess overlapping functions in regulating innate and adaptive immune responses. IgA and CD4(+) T cells are fundamental to the process of Giardia clearance. It has been suggested that CD4(+) T cells play a double role during the anti-Giardia immune response. First, they activate and stimulate the differentiation of B cells to generate Giardia-specific antibodies. Second, they act through a B-cell-independent mechanism that is probably mediated by Th17 cells. Several Giardia proteins that stimulate humoral and cellular immune responses have been described. Variant surface proteins, α-1 giardin, and cyst wall protein 2 can induce host protective responses to future Giardia challenges. The characterization and evaluation of the protective potential of the immunogenic proteins that are associated with Giardia will offer new insights into host-parasite interactions and may aid in the development of an effective vaccine against the parasite. PMID:26072999

  1. Manganese regulation of virulence factors and oxidative stress resistance in Neisseria gonorrhoeae

    PubMed Central

    Wu, Hsing-Ju; Seib, Kate L.; Srikhanta, Yogitha N.; Edwards, Jennifer; Kidd, Stephen P.; Maguire, Tina L .; Hamilton, Amanda; Pan, Kuan-Tin; Hsiao, He-Hsuan; Yao, Chen-Wen; Grimmond, Sean M.; Apicella, Michael A.; McEwan, Alastair G.; Wang, Andrew H-J.; Jennings, Michael P.

    2014-01-01

    Neisseria gonorrhoeae has evolved a complex and novel network of oxidative stress responses, including defense mechanisms that are dependent on manganese (Mn). We performed systematic analyses at the transcriptomic and proteomic (1D SDS-PAGE and Isotope-Coded Affinity Tag [ICAT]) levels to investigate the global expression changes that take place in a high Mn environment, which results in a Mn-dependent oxidative stress resistance phenotype. These studies revealed that 97 proteins are regulated at the post-transcriptional level under conditions of increased Mn concentration, including proteins involved in virulence (eg. Pilin, a key adhesin), oxidative stress defence (eg. superoxide dismutase), cellular metabolism, protein synthesis, RNA processing and cell division. Mn regulation of inorganic pyrophosphatase (Ppa) indicated the potential involvement of phosphate metabolism in the Mn-dependent oxidative stress defense. A detailed analysis of the role of Ppa and polyphosphate kinase (Ppk) in the gonococcal oxidative stress response revealed that ppk and ppa mutant strains showed increased resistance to oxidative stress. Investigation of these mutants grown with high Mn suggests that phosphate and pyrophosphate are involved in Mn-dependent oxidative stress resistance. PMID:20004262

  2. Functional and toxicological consequences of metabolic bioactivation of methapyrilene via thiophene S-oxidation: Induction of cell defence, apoptosis and hepatic necrosis

    SciTech Connect

    Mercer, Amy E.; Regan, Sophie L.; Hirst, Charlotte M.; Graham, Emma E.; Antoine, Daniel J.; Benson, Craig A.; Williams, Dominic P. Foster, John; Kenna, J. Gerry; Park, B. Kevin

    2009-09-15

    Methapyrilene, [N,N-dimethyl-N'-pyridyl-N'(2-thienylmethyl)-1,2-ethanediamine] (MP) was withdrawn from, clinical use due to reported periportal hepatic necrosis and hepatocarcinogenicity in the rat, via S-oxidation of the thiophene group. In this study MP is used as a model hepatotoxin to further characterise the functional consequences of S-oxidation of the thiophene group in vivo, in rat models and in vitro, in freshly isolated rat hepatocyte suspensions. In vivo histological studies revealed the early depletion of glutathione (GSH), which was confined to the damaged periportal area, in contrast to an increase in GSH levels in the centrilobular region. Additionally, the induction of cell defence was demonstrated by an increase in the protein levels of heme-oxygenase 1 (HO-1) and glutamate cysteine ligase, catalytic subunit (GCLC) in vivo. Histological examination demonstrated that cytotoxicity progresses initially via apoptosis before an increase in necrosis over the 3-day administration. An apoptotic-like mechanism was observed in vitro via the measurement of cytochrome c release and caspase activation. Conclusion: This study provides evidence for a complex pathway of MP-induced hepatotoxicity which progresses through early adaptation, apoptosis, necrosis and inflammation, all underpinned by the zonal induction and depletion of GSH within the liver.

  3. Virus-induced gene silencing of Withania somnifera squalene synthase negatively regulates sterol and defence-related genes resulting in reduced withanolides and biotic stress tolerance.

    PubMed

    Singh, Anup Kumar; Dwivedi, Varun; Rai, Avanish; Pal, Shaifali; Reddy, Sajjalavarahalli Gangireddy Eswara; Rao, Dodaghatta Krishnarao Venkata; Shasany, Ajit Kumar; Nagegowda, Dinesh A

    2015-12-01

    Withania somnifera (L.) Dunal is an important Indian medicinal plant that produces withanolides, which are triterpenoid steroidal lactones having diverse biological activities. To enable fast and efficient functional characterization of genes in this slow-growing and difficult-to-transform plant, a virus-induced gene silencing (VIGS) was established by silencing phytoene desaturase (PDS) and squalene synthase (SQS). VIGS of the gene encoding SQS, which provides precursors for triterpenoids, resulted in significant reduction of squalene and withanolides, demonstrating its application in studying withanolides biosynthesis in W. somnifera leaves. A comprehensive analysis of gene expression and sterol pathway intermediates in WsSQS-vigs plants revealed transcriptional modulation with positive feedback regulation of mevalonate pathway genes, and negative feed-forward regulation of downstream sterol pathway genes including DWF1 (delta-24-sterol reductase) and CYP710A1 (C-22-sterol desaturase), resulting in significant reduction of sitosterol, campesterol and stigmasterol. However, there was little effect of SQS silencing on cholesterol, indicating the contribution of sitosterol, campesterol and stigmasterol, but not of cholesterol, towards withanolides formation. Branch-point oxidosqualene synthases in WsSQS-vigs plants exhibited differential regulation with reduced CAS (cycloartenol synthase) and cycloartenol, and induced BAS (β-amyrin synthase) and β-amyrin. Moreover, SQS silencing also led to the down-regulation of brassinosteroid-6-oxidase-2 (BR6OX2), pathogenesis-related (PR) and nonexpressor of PR (NPR) genes, resulting in reduced tolerance to bacterial and fungal infection as well as to insect feeding. Taken together, SQS silencing negatively regulated sterol and defence-related genes leading to reduced phytosterols, withanolides and biotic stress tolerance, thus implicating the application of VIGS for functional analysis of genes related to withanolides

  4. Effect of acetaminophen exposure in Oncorhynchus mykiss gills and liver: detoxification mechanisms, oxidative defence system and peroxidative damage.

    PubMed

    Ramos, A S; Correia, A T; Antunes, S C; Gonçalves, F; Nunes, B

    2014-05-01

    The increasing presence of pharmaceutical drugs in nature is cause of concern due to the occurrence of oxidative stress in non-target species. Acetaminophen is widely used in human medicine as an analgesic and antipyretic drug, and it is one of the most sold non-prescription drugs. The present study aimed to assess the toxic effects of acetaminophen (APAP) in Oncorhynchus mykiss following acute and chronic exposures in realistic levels. In order to evaluate the APAP effects in the rainbow trout, gills and liver were analyzed with biochemical biomarkers, such as catalase (CAT), total and selenium-dependent glutathione peroxidase (GPx), glutathione reductase (GRed) and glutathione-S-transferases (GSTs) activity and also lipid peroxidation levels (TBARS). The results obtained in all tests indicate that a significant response of oxidative stress was established, along with the increase of APAP concentrations. The establishment of an oxidative stress scenario occurred with the involvement of all tested biomarkers, sustaining a generalized set of pro-oxidative effects elicited by APAP. Additionally, the occurrence of oxidative damage strongly suggests the impairment of the antioxidant defense mechanism of O. mykiss. It is important to note that the occurrence of oxidative deleterious effects and peroxidative damages occurred for concentrations similar to those already reported for several freshwater ecosystems. The importance of these assumptions is further discussed under the scope of ecological relevance of the assessment of effects caused by pharmaceuticals in non-target organisms. PMID:24816177

  5. Nitric oxide and hydrogen peroxide: two players in the defence response of tomato plants to root-knot nematodes.

    PubMed

    Leonetti, P; Melillo, M T; Bleve-Zacheo, T

    2011-01-01

    Nitric oxide (NO) has been postulated to be required, together with reactive oxygen species (ROS) for activation of disease resistance reaction of plants to pathogen infection. Here, we investigated NO, superoxide (O(*-)2), and hydrogen peroxide (H2O2) in tomato-root-knot nematode interactions to answer the question of whether they are produced during the early stages of nematode infection. NO detection was carried out using diaminofluorescein diacetate (DAF-2DA) by means of confocal laser microscopy and spectrophotometric analyses, and production of NO was estimated by monitoring the conversion of L-[U14C]arginine into L-[U14C]citrulline. O(*-)2 production was determined by using the tetrazolium salt, sodium,3'-{1-[phenylamino-carbonyl]-3,4-tetrazolium}-bis(4-methoxy-6-nitro) benzene-sulfonic acid hydrate (XTT) and H2O2 was measured by using the Amplex Red H2O2/peroxidase assay. Results showed i) the highest NO production in tissues challenged by avr pathotype, 12h after nematode inoculation, ii) NO production by nitric oxide synthase (NOS-like activity), iii) ROSbalance dependent control of NO. Our data evidenced, for the first time, that NO-generated signal, its spatiotemporal expression, and its cross-communication with other pro-oxidants or anti-oxidants critically influence compatible and incompatible tomato-Meloidogyne incognito interactions. PMID:22696948

  6. The transcriptional coregulator PGC-1β controls mitochondrial function and anti-oxidant defence in skeletal muscles.

    PubMed

    Gali Ramamoorthy, Thanuja; Laverny, Gilles; Schlagowski, Anna-Isabel; Zoll, Joffrey; Messaddeq, Nadia; Bornert, Jean-Marc; Panza, Salvatore; Ferry, Arnaud; Geny, Bernard; Metzger, Daniel

    2015-01-01

    The transcriptional coregulators PGC-1α and PGC-1β modulate the expression of numerous partially overlapping genes involved in mitochondrial biogenesis and energetic metabolism. The physiological role of PGC-1β is poorly understood in skeletal muscle, a tissue of high mitochondrial content to produce ATP levels required for sustained contractions. Here we determine the physiological role of PGC-1β in skeletal muscle using mice, in which PGC-1β is selectively ablated in skeletal myofibres at adulthood (PGC-1β((i)skm-/-) mice). We show that myofibre myosin heavy chain composition and mitochondrial number, muscle strength and glucose homeostasis are unaffected in PGC-1β((i)skm-/-) mice. However, decreased expression of genes controlling mitochondrial protein import, translational machinery and energy metabolism in PGC-1β((i)skm-/-) muscles leads to mitochondrial structural and functional abnormalities, impaired muscle oxidative capacity and reduced exercise performance. Moreover, enhanced free-radical leak and reduced expression of the mitochondrial anti-oxidant enzyme Sod2 increase muscle oxidative stress. PGC-1β is therefore instrumental for skeletal muscles to cope with high energetic demands. PMID:26674215

  7. The transcriptional coregulator PGC-1β controls mitochondrial function and anti-oxidant defence in skeletal muscles

    PubMed Central

    Gali Ramamoorthy, Thanuja; Laverny, Gilles; Schlagowski, Anna-Isabel; Zoll, Joffrey; Messaddeq, Nadia; Bornert, Jean-Marc; Panza, Salvatore; Ferry, Arnaud; Geny, Bernard; Metzger, Daniel

    2015-01-01

    The transcriptional coregulators PGC-1α and PGC-1β modulate the expression of numerous partially overlapping genes involved in mitochondrial biogenesis and energetic metabolism. The physiological role of PGC-1β is poorly understood in skeletal muscle, a tissue of high mitochondrial content to produce ATP levels required for sustained contractions. Here we determine the physiological role of PGC-1β in skeletal muscle using mice, in which PGC-1β is selectively ablated in skeletal myofibres at adulthood (PGC-1β(i)skm−/− mice). We show that myofibre myosin heavy chain composition and mitochondrial number, muscle strength and glucose homeostasis are unaffected in PGC-1β(i)skm−/− mice. However, decreased expression of genes controlling mitochondrial protein import, translational machinery and energy metabolism in PGC-1β(i)skm−/− muscles leads to mitochondrial structural and functional abnormalities, impaired muscle oxidative capacity and reduced exercise performance. Moreover, enhanced free-radical leak and reduced expression of the mitochondrial anti-oxidant enzyme Sod2 increase muscle oxidative stress. PGC-1β is therefore instrumental for skeletal muscles to cope with high energetic demands. PMID:26674215

  8. The regulation of methane oxidation in soil

    NASA Technical Reports Server (NTRS)

    Mancinelli, R. L.

    1995-01-01

    The atmospheric concentration of methane, a greenhouse gas, has more than doubled during the past 200 years. Consequently, identifying the factors influencing the flux of methane into the atmosphere is becoming increasingly important. Methanotrophs, microaerophilic organisms widespread in aerobic soils and sediments, oxidize methane to derive energy and carbon for biomass. In so doing, they play an important role in mitigating the flux of methane into the atmosphere. Several physico-chemical factors influence rates of methane oxidation in soil, including soil diffusivity; water potential; and levels of oxygen, methane, ammonium, nitrate, nitrite, and copper. Most of these factors exert their influence through interactions with methane monooxygenase (MMO), the enzyme that catalyzes the reaction converting methane to methanol, the first step in methane oxidation. Although biological factors such as competition and predation undoubtedly play a role in regulating the methanotroph population in soils, and thereby limit the amount of methane consumed by methanotrophs, the significance of these factors is unknown. Obtaining a better understanding of the ecology of methanotrophs will help elucidate the mechanisms that regulate soil methane oxidation.

  9. The organophosphate insecticide Coumaphos induces oxidative stress and increases antioxidant and detoxification defences in the green macroalgae Ulva pertusa.

    PubMed

    Schweikert, Katja; Burritt, David J

    2012-10-15

    It is well established that many pesticides used in the farming and horticultural industries are harmful to not only the target species they were developed for, but also other organisms. Organophosphates were introduced as a replacement for the organochlorines and are generally considered non-toxic to plants and algae. This study investigated the impact of Coumaphos, a commonly used organophosphate, on the estuarine macrophyte Ulva pertusa. In a seven-day experiment U. pertusa cultures were exposed to four environmentally relevant concentrations of Coumaphos (0.01 mg/L, 0.05 mg/L, 0.1mg/L, 0.5 mg/L), well below the aqueous solubility maximum of the insecticide. The impact of Coumaphos was determined at a cellular level by assessing oxidative damage in the form of protein carbonyl and lipid hydroperoxide levels. Furthermore, non-enzymatic antioxidant levels and changes in the levels of enzymatic antioxidants and the enzyme GST were measured. Concentrations of Coumaphos above 0.01 mg/L caused rapid increases in the levels of protein carbonyls and lipid hydroperoxides peaking after 2-3 days of exposure, followed by a rapid decline in both markers of oxidative stress. Glutathione levels and the activities SOD, CAT, GR, APOX and GST all increased in response to the higher concentrations of Coumaphos tested and remained elevated for the duration of the experiment. These results demonstrate that environmentally relevant levels of the insecticide Coumaphos can cause oxidative damage and increase the antioxidant scavenging capacity, and GST activity in U. pertusa. This could potentially alter resource allocation within this alga, impacting algal growth and development, with possible indirect ecological consequences. PMID:22728208

  10. Nitric oxide regulates vascular adaptive mitochondrial dynamics.

    PubMed

    Miller, Matthew W; Knaub, Leslie A; Olivera-Fragoso, Luis F; Keller, Amy C; Balasubramaniam, Vivek; Watson, Peter A; Reusch, Jane E B

    2013-06-15

    Cardiovascular disease risk factors, such as diabetes, hypertension, dyslipidemia, obesity, and physical inactivity, are all correlated with impaired endothelial nitric oxide synthase (eNOS) function and decreased nitric oxide (NO) production. NO-mediated regulation of mitochondrial biogenesis has been established in many tissues, yet the role of eNOS in vascular mitochondrial biogenesis and dynamics is unclear. We hypothesized that genetic eNOS deletion and 3-day nitric oxide synthase (NOS) inhibition in rodents would result in impaired mitochondrial biogenesis and defunct fission/fusion and autophagy profiles within the aorta. We observed a significant, eNOS expression-dependent decrease in mitochondrial electron transport chain (ETC) protein subunits from complexes I, II, III, and V in eNOS heterozygotes and eNOS null mice compared with age-matched controls. In response to NOS inhibition with NG-nitro-L-arginine methyl ester (L-NAME) treatment in Sprague Dawley rats, significant decreases were observed in ETC protein subunits from complexes I, III, and IV as well as voltage-dependent anion channel 1. Decreased protein content of upstream regulators of mitochondrial biogenesis, cAMP response element-binding protein and peroxisome proliferator-activated receptor-γ coactivator-1α, were observed in response to 3-day L-NAME treatment. Both genetic eNOS deletion and NOS inhibition resulted in decreased manganese superoxide dismutase protein. L-NAME treatment resulted in significant changes to mitochondrial dynamic protein profiles with decreased fusion, increased fission, and minimally perturbed autophagy. In addition, L-NAME treatment blocked mitochondrial adaptation to an exercise intervention in the aorta. These results suggest that eNOS/NO play a role in basal and adaptive mitochondrial biogenesis in the vasculature and regulation of mitochondrial turnover. PMID:23585138

  11. Do strigolactones contribute to plant defence?

    PubMed

    Torres-Vera, Rocío; García, Juan M; Pozo, María J; López-Ráez, Juan A

    2014-02-01

    Strigolactones are multifunctional molecules involved in several processes outside and within the plant. As signalling molecules in the rhizosphere, they favour the establishment of arbuscular mycorrhizal symbiosis, but they also act as host detection cues for root parasitic plants. As phytohormones, they are involved in the regulation of plant architecture, adventitious rooting, secondary growth and reproductive development, and novel roles are emerging continuously. In the present study, the possible involvement of strigolactones in plant defence responses was investigated. For this purpose, the resistance/susceptibility of the strigolactone-deficient tomato mutant Slccd8 against the foliar fungal pathogens Botrytis cinerea and Alternaria alternata was assessed. Slccd8 was more susceptible to both pathogens, pointing to a new role for strigolactones in plant defence. A reduction in the content of the defence-related hormones jasmonic acid, salicylic acid and abscisic acid was detected by high-performance liquid chromatography coupled to tandem mass spectrometry in the Slccd8 mutant, suggesting that hormone homeostasis is altered in the mutant. Moreover, the expression level of the jasmonate-dependent gene PinII, involved in the resistance of tomato to B. cinerea, was lower than in the corresponding wild-type. We propose here that strigolactones play a role in the regulation of plant defences through their interaction with other defence-related hormones, especially with the jasmonic acid signalling pathway. PMID:24112811

  12. Nitric oxide negatively regulates mammalian adult neurogenesis

    NASA Astrophysics Data System (ADS)

    Packer, Michael A.; Stasiv, Yuri; Benraiss, Abdellatif; Chmielnicki, Eva; Grinberg, Alexander; Westphal, Heiner; Goldman, Steven A.; Enikolopov, Grigori

    2003-08-01

    Neural progenitor cells are widespread throughout the adult central nervous system but only give rise to neurons in specific loci. Negative regulators of neurogenesis have therefore been postulated, but none have yet been identified as subserving a significant role in the adult brain. Here we report that nitric oxide (NO) acts as an important negative regulator of cell proliferation in the adult mammalian brain. We used two independent approaches to examine the function of NO in adult neurogenesis. In a pharmacological approach, we suppressed NO production in the rat brain by intraventricular infusion of an NO synthase inhibitor. In a genetic approach, we generated a null mutant neuronal NO synthase knockout mouse line by targeting the exon encoding active center of the enzyme. In both models, the number of new cells generated in neurogenic areas of the adult brain, the olfactory subependyma and the dentate gyrus, was strongly augmented, which indicates that division of neural stem cells in the adult brain is controlled by NO and suggests a strategy for enhancing neurogenesis in the adult central nervous system.

  13. Cellular mechanisms of redox cell signalling: role of cysteine modification in controlling antioxidant defences in response to electrophilic lipid oxidation products.

    PubMed Central

    Levonen, Anna-Liisa; Landar, Aimee; Ramachandran, Anup; Ceaser, Erin K; Dickinson, Dale A; Zanoni, Giuseppe; Morrow, Jason D; Darley-Usmar, Victor M

    2004-01-01

    The molecular mechanisms through which oxidized lipids and their electrophilic decomposition products mediate redox cell signalling is not well understood and may involve direct modification of signal-transduction proteins or the secondary production of reactive oxygen or nitrogen species in the cell. Critical in the adaptation of cells to oxidative stress, including exposure to subtoxic concentrations of oxidized lipids, is the transcriptional regulation of antioxidant enzymes, many of which are controlled by antioxidant-responsive elements (AREs), also known as electrophile-responsive elements. The central regulator of the ARE response is the transcription factor Nrf2 (NF-E2-related factor 2), which on stimulation dissociates from its cytoplasmic inhibitor Keap1, translocates to the nucleus and transactivates ARE-dependent genes. We hypothesized that electrophilic lipids are capable of activating ARE through thiol modification of Keap1 and we have tested this concept in an intact cell system using induction of glutathione synthesis by the cyclopentenone prostaglandin, 15-deoxy-Delta12,14-prostaglandin J2. On exposure to 15-deoxy-Delta12,14-prostaglandin J2, the dissociation of Nrf2 from Keap1 occurred and this was dependent on the modification of thiols in Keap1. This mechanism appears to encompass other electrophilic lipids, since 15-A(2t)-isoprostane and the lipid aldehyde 4-hydroxynonenal were also shown to modify Keap1 and activate ARE. We propose that activation of ARE through this mechanism will have a major impact on inflammatory situations such as atherosclerosis, in which both enzymic as well as non-enzymic formation of electrophilic lipid oxidation products are increased. PMID:14616092

  14. Only an early nitric oxide burst and the following wave of secondary nitric oxide generation enhanced effective defence responses of pelargonium to a necrotrophic pathogen.

    PubMed

    Floryszak-Wieczorek, Jolanta; Arasimowicz, Magdalena; Milczarek, Grzegorz; Jelen, Henryk; Jackowiak, Hanna

    2007-01-01

    Participation of nitric oxide (NO) in cross-talk between ivy pelargonium (Pelargonium peltatum) leaves and Botrytis cinerea was investigated using electrochemical and biochemical approaches. In response to the necrotroph, leaves initiated a near-immediate NO burst, but the specificity of its generation was dependent on the genetic makeup of the host plant. In the resistant cultivar, a strong NO burst was followed by a wave of secondary NO generation, shown by bio-imaging with DAF-2DA. The epicentre of NO synthesis was located in targeted cells, which exhibited a TUNEL-positive reaction. Soon after the challenge, an elevated concentration of hydrogen peroxide (H(2)O(2)) was correlated with a reversible inhibition of catalase (CAT), ascorbate peroxidase (APX), and suppression of ethylene synthesis. The induced NO generation initially expanded and then gradually disappeared on successive days, provoking noncell-death-associated resistance with an enhanced pool of antioxidants, which finally favoured the maintenance of homeostasis of surrounding cells. By contrast, in the susceptible pelargonium, a weak NO burst was recorded and further NO generation increased only as the disease progressed, which was accompanied by very intensive H(2)O(2) and ethylene synthesis. The pathogen colonizing susceptible cells also acquired the ability to produce considerable amounts of NO and enhanced nitrosative and oxidative stress in host tissues. PMID:17688587

  15. Allergic host defences.

    PubMed

    Palm, Noah W; Rosenstein, Rachel K; Medzhitov, Ruslan

    2012-04-26

    Allergies are generally thought to be a detrimental outcome of a mistargeted immune response that evolved to provide immunity to macroparasites. Here we present arguments to suggest that allergic immunity has an important role in host defence against noxious environmental substances, including venoms, haematophagous fluids, environmental xenobiotics and irritants. We argue that appropriately targeted allergic reactions are beneficial, although they can become detrimental when excessive. Furthermore, we suggest that allergic hypersensitivity evolved to elicit anticipatory responses and to promote avoidance of suboptimal environments. PMID:22538607

  16. Processes regulating nitric oxide emissions from soils.

    PubMed

    Pilegaard, Kim

    2013-07-01

    Nitric oxide (NO) is a reactive gas that plays an important role in atmospheric chemistry by influencing the production and destruction of ozone and thereby the oxidizing capacity of the atmosphere. NO also contributes by its oxidation products to the formation of acid rain. The major sources of NO in the atmosphere are anthropogenic emissions (from combustion of fossil fuels) and biogenic emission from soils. NO is both produced and consumed in soils as a result of biotic and abiotic processes. The main processes involved are microbial nitrification and denitrification, and chemodenitrification. Thus, the net result is complex and dependent on several factors such as nitrogen availability, organic matter content, oxygen status, soil moisture, pH and temperature. This paper reviews recent knowledge on processes forming NO in soils and the factors controlling its emission to the atmosphere. Schemes for simulating these processes are described, and the results are discussed with the purpose of scaling up to global emission. PMID:23713124

  17. Coordinated defence and the liver.

    PubMed

    Elias, Elwyn; Mills, Charles O

    2007-04-01

    The liver is strategically placed to protect the body against a vast array of potentially harmful compounds. The steps involved include phase I metabolism which makes molecules more reactive and phase II reactions which generally enhance solubility in bile or urine. Recent discoveries have shown how regulation of these reactions is also closely allied to expression of membrane transporters which excrete the products of biotransformation into bile and prevent their reabsorption via the intestine. The coordinated activity of these various functions is orchestrated by orphan nuclear receptors which, in response to an encounter with a potential toxin, are able to induce expression of the genes involved in its biotransformation and excretion. Lithocholic acid (LCA) is routinely produced in our intestine by bacterial deconjugation of chenodeoxycholic acid a major bile acid in humans. In human liver the presence of LCA is sensed by the pregnane X receptor (PXR) which has the potential to switch on all the genes required for safe metabolism and elimination of LCA from the body. These include cytochrome P450 3A which hydroxylates LCA to more soluble forms and sulfotransferase (SULT2A1) which by sulphation of LCA makes it more readily solublein bile and enhances its faecal excretion. Similarly, PXR exposure to LCA produces up-regulated expression of the membrane transporters MDR1 and MRP2 which excrete metabolites of LCA. Evidence is accumulating in support of the hypothesis that deficiencies in these defence mechanisms underlie susceptibility to primary sclerosing cholangitis and ulcerative colitis. PMID:17491508

  18. Iron homeostasis in host defence and inflammation

    PubMed Central

    Ganz, Tomas; Nemeth, Elizabeta

    2016-01-01

    Iron is an essential trace element for multicellular organisms and nearly all microorganisms. Although iron is abundant in the environment, common forms of iron are minimally soluble and therefore poorly accessible to biological organisms. Microorganisms entering a mammalian host face multiple mechanisms that further restrict their ability to obtain iron and thereby limit their pathogenicity. Iron levels also modulate host defence, as iron content in macrophages regulates their cytokine production. Here, we review recent advances that highlight the role of systemic and cellular iron-regulating mechanisms in protecting hosts from infection, emphasizing aspects that are applicable to human health and disease. PMID:26160612

  19. Oxidative Regulation of Large Conductance Calcium-Activated Potassium Channels

    PubMed Central

    Tang, Xiang D.; Daggett, Heather; Hanner, Markus; Garcia, Maria L.; McManus, Owen B.; Brot, Nathan; Weissbach, Herbert; Heinemann, Stefan H.; Hoshi, Toshinori

    2001-01-01

    Reactive oxygen/nitrogen species are readily generated in vivo, playing roles in many physiological and pathological conditions, such as Alzheimer's disease and Parkinson's disease, by oxidatively modifying various proteins. Previous studies indicate that large conductance Ca2+-activated K+ channels (BKCa or Slo) are subject to redox regulation. However, conflicting results exist whether oxidation increases or decreases the channel activity. We used chloramine-T, which preferentially oxidizes methionine, to examine the functional consequences of methionine oxidation in the cloned human Slo (hSlo) channel expressed in mammalian cells. In the virtual absence of Ca2+, the oxidant shifted the steady-state macroscopic conductance to a more negative direction and slowed deactivation. The results obtained suggest that oxidation enhances specific voltage-dependent opening transitions and slows the rate-limiting closing transition. Enhancement of the hSlo activity was partially reversed by the enzyme peptide methionine sulfoxide reductase, suggesting that the upregulation is mediated by methionine oxidation. In contrast, hydrogen peroxide and cysteine-specific reagents, DTNB, MTSEA, and PCMB, decreased the channel activity. Chloramine-T was much less effective when concurrently applied with the K+ channel blocker TEA, which is consistent with the possibility that the target methionine lies within the channel pore. Regulation of the Slo channel by methionine oxidation may represent an important link between cellular electrical excitability and metabolism. PMID:11222629

  20. Oxidative Stress-Mediated Regulation of Proteasome Complexes*

    PubMed Central

    Aiken, Charity T.; Kaake, Robyn M.; Wang, Xiaorong; Huang, Lan

    2011-01-01

    Oxidative stress has been implicated in aging and many human diseases, notably neurodegenerative disorders and various cancers. The reactive oxygen species that are generated by aerobic metabolism and environmental stressors can chemically modify proteins and alter their biological functions. Cells possess protein repair pathways to rescue oxidized proteins and restore their functions. If these repair processes fail, oxidized proteins may become cytotoxic. Cell homeostasis and viability are therefore dependent on the removal of oxidatively damaged proteins. Numerous studies have demonstrated that the proteasome plays a pivotal role in the selective recognition and degradation of oxidized proteins. Despite extensive research, oxidative stress-triggered regulation of proteasome complexes remains poorly defined. Better understanding of molecular mechanisms underlying proteasome function in response to oxidative stress will provide a basis for developing new strategies aimed at improving cell viability and recovery as well as attenuating oxidation-induced cytotoxicity associated with aging and disease. Here we highlight recent advances in the understanding of proteasome structure and function during oxidative stress and describe how cells cope with oxidative stress through proteasome-dependent degradation pathways. PMID:21543789

  1. Nitric oxide regulates blastocyst hatching in mice

    PubMed Central

    Pan, Xiaoyan; Wang, Xuenan; Wang, Xiyan; Sun, Zhanxuan; Zhang, Xue; Liang, Xuanxuan; Li, Zhixin; Dou, Zhaohua

    2015-01-01

    Objective: This study is to determine the regulatory role of nitric oxide in mouse blastocyst hatching. Methods: Kunming female mice were superovulated and then mated with mature male mice. On day 2.5 of their pregnancy, the pregnant mice were killed and morulae were flushed from their uterine horns with culture media. Morulae were cultured in media with different concentrations of N-nitro-L arginine methyl ester (L-NAME), sodium nitroprusside (SNP), 8-Br-3’-5’-cyclic guanosine monophosphate (8-Br-cGMP) or the combination of L-NAME with SNP or 8-Br-cGMP for 48 h. The hatched blastocysts were examined on day 5 and the expressions of epithelial nitric oxide synthase (eNOS) and active cysteinyl aspartate specific proteinase 3 (caspase 3) were observed under confocal laser scanning microscope. Results: L-NAME significantly reduced the expression of eNOS in blastocyst cells. With the increase of the concentrations of L-NAME, SNP or 8-Br-cGMP, blastocyst hatching rate was significantly lowered. In addition, 5 mM L-NAME, 2 μM SNP and 2 μM 8-Br-cGMP completely inhibited blastocyst hatching. Low concentrations of SNP or 8-Br-cGMP in culture media containing 5 mM L-NAME significantly reversed the inhibition of blastocyst hatching and promoted hatching development. Moreover, 5 mM L-NAME and 2 μM 8-Br-cGMP had no significant influence on the expression of active caspase 3 in blastocyst cells. SNP (> 500 nM) significantly increased the expression of active caspase 3 in blastocyst cells. Conclusions: NO/cGMP pathway plays an important role in mouse blastocyst hatching. Excessive or depleted NO can interrupt blastocyst hatching. Excessive NO leads to apoptosis of blastocyst cells. PMID:26221236

  2. Regulation of thrombosis and vascular function by protein methionine oxidation

    PubMed Central

    Gu, Sean X.; Stevens, Jeff W.

    2015-01-01

    Redox biology is fundamental to both normal cellular homeostasis and pathological states associated with excessive oxidative stress. Reactive oxygen species function not only as signaling molecules but also as redox regulators of protein function. In the vascular system, redox reactions help regulate key physiologic responses such as cell adhesion, vasoconstriction, platelet aggregation, angiogenesis, inflammatory gene expression, and apoptosis. During pathologic states, altered redox balance can cause vascular cell dysfunction and affect the equilibrium between procoagulant and anticoagulant systems, contributing to thrombotic vascular disease. This review focuses on the emerging role of a specific reversible redox reaction, protein methionine oxidation, in vascular disease and thrombosis. A growing number of cardiovascular and hemostatic proteins are recognized to undergo reversible methionine oxidation, in which methionine residues are posttranslationally oxidized to methionine sulfoxide. Protein methionine oxidation can be reversed by the action of stereospecific enzymes known as methionine sulfoxide reductases. Calcium/calmodulin-dependent protein kinase II is a prototypical methionine redox sensor that responds to changes in the intracellular redox state via reversible oxidation of tandem methionine residues in its regulatory domain. Several other proteins with oxidation-sensitive methionine residues, including apolipoprotein A-I, thrombomodulin, and von Willebrand factor, may contribute to vascular disease and thrombosis. PMID:25900980

  3. Regulation of thrombosis and vascular function by protein methionine oxidation.

    PubMed

    Gu, Sean X; Stevens, Jeff W; Lentz, Steven R

    2015-06-18

    Redox biology is fundamental to both normal cellular homeostasis and pathological states associated with excessive oxidative stress. Reactive oxygen species function not only as signaling molecules but also as redox regulators of protein function. In the vascular system, redox reactions help regulate key physiologic responses such as cell adhesion, vasoconstriction, platelet aggregation, angiogenesis, inflammatory gene expression, and apoptosis. During pathologic states, altered redox balance can cause vascular cell dysfunction and affect the equilibrium between procoagulant and anticoagulant systems, contributing to thrombotic vascular disease. This review focuses on the emerging role of a specific reversible redox reaction, protein methionine oxidation, in vascular disease and thrombosis. A growing number of cardiovascular and hemostatic proteins are recognized to undergo reversible methionine oxidation, in which methionine residues are posttranslationally oxidized to methionine sulfoxide. Protein methionine oxidation can be reversed by the action of stereospecific enzymes known as methionine sulfoxide reductases. Calcium/calmodulin-dependent protein kinase II is a prototypical methionine redox sensor that responds to changes in the intracellular redox state via reversible oxidation of tandem methionine residues in its regulatory domain. Several other proteins with oxidation-sensitive methionine residues, including apolipoprotein A-I, thrombomodulin, and von Willebrand factor, may contribute to vascular disease and thrombosis. PMID:25900980

  4. Argininosuccinate lyase is an essential regulator of nictric oxide homeostatis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The regulation of nitric oxide synthesis is a complex mechanism, depending on the availability of substrates and the activity of the enzymes involved. Here we describe in a mouse model the channeling of urea cycle intermediates for the recycling of citrulline and the transport of extracellular argin...

  5. NRF2 Regulates PINK1 Expression under Oxidative Stress Conditions

    PubMed Central

    Murata, Hitoshi; Takamatsu, Hitoshi; Liu, Sulai; Kataoka, Ken; Huh, Nam-ho; Sakaguchi, Masakiyo

    2015-01-01

    Mutations of the PTEN-induced putative kinase 1 (PINK1) gene are a cause of autosomal recessive forms of Parkinson’s disease. Recent studies have revealed that PINK1 is an essential factor for controlling mitochondrial quality, and that it protects cells from oxidative stresses. Although there has been considerable progress in the elucidation of various aspects of PINK1 protein regulation such as activation, stability and degradation, the transcriptional regulation of PINK1 mRNA under stress conditions remains unclear. In this study, we found that nuclear factor (erythroid-derived 2)-like 2 (NRF2), an antioxidant transcription factor, regulates PINK1 expression under oxidative stress conditions. Damaged mitochondria arising from stress conditions induced NRF2-dependent transcription of the PINK1 gene through production of reactive oxygen species (ROS). Either an ROS scavenger or forced expression of KEAP1, a potent inhibitory partner to NRF2, restricted PINK1 expression induced by activated NRF2. Transcriptionally up-regulated PINK1 diminished oxidative stress-associated cell death. The results indicate that PINK1 expression is positively regulated by NRF2 and that the NRF2-PINK1 signaling axis is deeply involved in cell survival. PMID:26555609

  6. Oxidant-specific regulation of protein synthesis in Candida albicans.

    PubMed

    Sundaram, Arunkumar; Grant, Chris M

    2014-06-01

    Eukaryotic cells typically respond to stress conditions by inhibiting global protein synthesis. The initiation phase is the main target of regulation and represents a key control point for eukaryotic gene expression. In Saccharomyces cerevisiae and mammalian cells this is achieved by phosphorylation of eukaryotic initiation factor 2 (eIF2α). We have examined how the fungal pathogen Candida albicans responds to oxidative stress conditions and show that oxidants including hydrogen peroxide, the heavy metal cadmium and the thiol oxidant diamide inhibit translation initiation. The inhibition in response to hydrogen peroxide and cadmium largely depends on phosphorylation of eIF2α since minimal inhibition is observed in a gcn2 mutant. In contrast, translation initiation is inhibited in a Gcn2-independent manner in response to diamide. Our data indicate that all three oxidants inhibit growth of C. albicans in a dose-dependent manner, however, loss of GCN2 does not improve growth in the presence of hydrogen peroxide or cadmium. Examination of translational activity indicates that these oxidants inhibit translation at a post-initiation phase which may account for the growth inhibition in a gcn2 mutant. As well as inhibiting global translation initiation, phosphorylation of eIF2α also enhances expression of the GCN4 mRNA in yeast via a well-known translational control mechanism. We show that C. albicans GCN4 is similarly induced in response to oxidative stress conditions and Gcn4 is specifically required for hydrogen peroxide tolerance. Thus, the response of C. albicans to oxidative stress is mediated by oxidant-specific regulation of translation initiation and we discuss our findings in comparison to other eukaryotes including the yeast S. cerevisiae. PMID:24699161

  7. Epigenetic Regulation of Oxidative Stress in Ischemic Stroke

    PubMed Central

    Zhao, Haiping; Han, Ziping; Ji, Xunming; Luo, Yumin

    2016-01-01

    The prevalence and incidence of stroke rises with life expectancy. However, except for the use of recombinant tissue-type plasminogen activator, the translation of new therapies for acute stroke from animal models into humans has been relatively unsuccessful. Oxidative DNA and protein damage following stroke is typically associated with cell death. Cause-effect relationships between reactive oxygen species and epigenetic modifications have been established in aging, cancer, acute pancreatitis, and fatty liver disease. In addition, epigenetic regulatory mechanisms during stroke recovery have been reviewed, with focuses mainly on neural apoptosis, necrosis, and neuroplasticity. However, oxidative stress-induced epigenetic regulation in vascular neural networks following stroke has not been sufficiently explored. Improved understanding of the epigenetic regulatory network upon oxidative stress may provide effective antioxidant approaches for treating stroke. In this review, we summarize the epigenetic events, including DNA methylation, histone modification, and microRNAs, that result from oxidative stress following experimental stroke in animal and cell models, and the ways in which epigenetic changes and their crosstalk influence the redox state in neurons, glia, and vascular endothelial cells, helping us to understand the foregone and vicious epigenetic regulation of oxidative stress in the vascular neural network following stroke. PMID:27330844

  8. Nitric oxide regulates synaptic transmission between spiny projection neurons

    PubMed Central

    Sagi, Yotam; Heiman, Myriam; Peterson, Jayms D.; Musatov, Sergei; Scarduzio, Mariangela; Logan, Stephen M.; Kaplitt, Michael G.; Surmeier, Dalton J.; Heintz, Nathaniel; Greengard, Paul

    2014-01-01

    Recurrent axon collaterals are a major means of communication between spiny projection neurons (SPNs) in the striatum and profoundly affect the function of the basal ganglia. However, little is known about the molecular and cellular mechanisms that underlie this communication. We show that intrastriatal nitric oxide (NO) signaling elevates the expression of the vesicular GABA transporter (VGAT) within recurrent collaterals of SPNs. Down-regulation of striatal NO signaling resulted in an attenuation of GABAergic signaling in SPN local collaterals, down-regulation of VGAT expression in local processes of SPNs, and impaired motor behavior. PKG1 and cAMP response element-binding protein are involved in the signal transduction that transcriptionally regulates VGAT by NO. These data suggest that transcriptional control of the vesicular GABA transporter by NO regulates GABA transmission and action selection. PMID:25413364

  9. H2S regulation of nitric oxide metabolism

    PubMed Central

    Kolluru, Gopi K.; Yuan, Shuai; Shen, Xinggui; Kevil, Christopher G.

    2015-01-01

    Nitric oxide (NO) and hydrogen sulfide (H2S) are two major gaseous signaling molecules that regulate diverse physiological functions. Recent publications indicate the regulatory role of H2S on NO metabolism. In this chapter, we discuss the latest findings on H2S-NO interactions through formation of novel chemical derivatives, and experimental approaches to study these adducts. This chapter also addresses potential H2S interference on various NO detection techniques, along with precautions for analyzing biological samples from various sources. This information will facilitate critical evaluation and clearer insight into H2S regulation of NO signaling and its influence on various physiological functions. PMID:25725527

  10. Nitric oxide: a regulator of eukaryotic initiation factor 2 kinases.

    PubMed

    Tong, Lingying; Heim, Rachel A; Wu, Shiyong

    2011-06-15

    Generation of nitric oxide (NO(•)) can upstream induce and downstream mediate the kinases that phosphorylate the α subunit of eukaryotic initiation factor 2 (eIF2α), which plays a critical role in regulating gene expression. There are four known eIF2α kinases (EIF2AKs), and NO(•) affects each one uniquely. Whereas NO(•) directly activates EIF2AK1 (HRI), it indirectly activates EIF2AK3 (PERK). EIF2AK4 (GCN2) is activated by depletion of l-arginine, which is used by nitric oxide synthase (NOS) during the production of NO(•). Finally EIF2AK2 (PKR), which can mediate inducible NOS expression and therefore NO(•) production, can also be activated by NO(•). The production of NO(•) and activation of EIF2AKs coordinately regulate physiological and pathological events such as innate immune response and cell apoptosis. PMID:21463677

  11. Nitrogen oxide cycle regulates nitric oxide levels and bacterial cell signaling

    PubMed Central

    Sasaki, Yasuyuki; Oguchi, Haruka; Kobayashi, Takuya; Kusama, Shinichiro; Sugiura, Ryo; Moriya, Kenta; Hirata, Takuya; Yukioka, Yuriya; Takaya, Naoki; Yajima, Shunsuke; Ito, Shinsaku; Okada, Kiyoshi; Ohsawa, Kanju; Ikeda, Haruo; Takano, Hideaki; Ueda, Kenji; Shoun, Hirofumi

    2016-01-01

    Nitric oxide (NO) signaling controls various metabolic pathways in bacteria and higher eukaryotes. Cellular enzymes synthesize and detoxify NO; however, a mechanism that controls its cellular homeostasis has not been identified. Here, we found a nitrogen oxide cycle involving nitrate reductase (Nar) and the NO dioxygenase flavohemoglobin (Fhb), that facilitate inter-conversion of nitrate, nitrite, and NO in the actinobacterium Streptomyces coelicolor. This cycle regulates cellular NO levels, bacterial antibiotic production, and morphological differentiation. NO down-regulates Nar and up-regulates Fhb gene expression via the NO-dependent transcriptional factors DevSR and NsrR, respectively, which are involved in the auto-regulation mechanism of intracellular NO levels. Nitrite generated by the NO cycles induces gene expression in neighboring cells, indicating an additional role of the cycle as a producer of a transmittable inter-cellular communication molecule. PMID:26912114

  12. Nitrogen oxide cycle regulates nitric oxide levels and bacterial cell signaling.

    PubMed

    Sasaki, Yasuyuki; Oguchi, Haruka; Kobayashi, Takuya; Kusama, Shinichiro; Sugiura, Ryo; Moriya, Kenta; Hirata, Takuya; Yukioka, Yuriya; Takaya, Naoki; Yajima, Shunsuke; Ito, Shinsaku; Okada, Kiyoshi; Ohsawa, Kanju; Ikeda, Haruo; Takano, Hideaki; Ueda, Kenji; Shoun, Hirofumi

    2016-01-01

    Nitric oxide (NO) signaling controls various metabolic pathways in bacteria and higher eukaryotes. Cellular enzymes synthesize and detoxify NO; however, a mechanism that controls its cellular homeostasis has not been identified. Here, we found a nitrogen oxide cycle involving nitrate reductase (Nar) and the NO dioxygenase flavohemoglobin (Fhb), that facilitate inter-conversion of nitrate, nitrite, and NO in the actinobacterium Streptomyces coelicolor. This cycle regulates cellular NO levels, bacterial antibiotic production, and morphological differentiation. NO down-regulates Nar and up-regulates Fhb gene expression via the NO-dependent transcriptional factors DevSR and NsrR, respectively, which are involved in the auto-regulation mechanism of intracellular NO levels. Nitrite generated by the NO cycles induces gene expression in neighboring cells, indicating an additional role of the cycle as a producer of a transmittable inter-cellular communication molecule. PMID:26912114

  13. Regulation of properties of oxidized asphalt from heavy crude

    SciTech Connect

    Yudina, E.E.; Bam, V.Ya.; Antoshkin, A.S.

    1988-03-01

    The commercial properties of the Karazhanbas crude asphalts obtained by oxidation were regulated by adding asphalt-resin and wax deposits (ARWD) to the crude. The liquid-phase oxidation was performed in a laboratory unit using the method of R. B. Gun. Control of the physiocochemical properties of oxidized asphalt was obtained by varying the dimensions of the complex structural units of the petroleum disperse system, on the basis of a theory by Z. I. Syunyaev. The effects of varying the crude oil/ARWD ratio in the mixture on certain physiocochemical properties of the starting material and the final asphalt were established. It was possible to control the asphalt properties by changing the complex structural unit dimensions to obtain the required structural-mechanical properties.

  14. The Oxidation Status of Mic19 Regulates MICOS Assembly.

    PubMed

    Sakowska, Paulina; Jans, Daniel C; Mohanraj, Karthik; Riedel, Dietmar; Jakobs, Stefan; Chacinska, Agnieszka

    2015-12-01

    The function of mitochondria depends on the proper organization of mitochondrial membranes. The morphology of the inner membrane is regulated by the recently identified mitochondrial contact site and crista organizing system (MICOS) complex. MICOS mutants exhibit alterations in crista formation, leading to mitochondrial dysfunction. However, the mechanisms that underlie MICOS regulation remain poorly understood. MIC19, a peripheral protein of the inner membrane and component of the MICOS complex, was previously reported to be required for the proper function of MICOS in maintaining the architecture of the inner membrane. Here, we show that human and Saccharomyces cerevisiae MIC19 proteins undergo oxidation in mitochondria and require the mitochondrial intermembrane space assembly (MIA) pathway, which couples the oxidation and import of mitochondrial intermembrane space proteins for mitochondrial localization. Detailed analyses identified yeast Mic19 in two different redox forms. The form that contains an intramolecular disulfide bond is bound to Mic60 of the MICOS complex. Mic19 oxidation is not essential for its integration into the MICOS complex but plays a role in MICOS assembly and the maintenance of the proper inner membrane morphology. These findings suggest that Mic19 is a redox-dependent regulator of MICOS function. PMID:26416881

  15. The Oxidation Status of Mic19 Regulates MICOS Assembly

    PubMed Central

    Sakowska, Paulina; Jans, Daniel C.; Mohanraj, Karthik; Riedel, Dietmar; Jakobs, Stefan

    2015-01-01

    The function of mitochondria depends on the proper organization of mitochondrial membranes. The morphology of the inner membrane is regulated by the recently identified mitochondrial contact site and crista organizing system (MICOS) complex. MICOS mutants exhibit alterations in crista formation, leading to mitochondrial dysfunction. However, the mechanisms that underlie MICOS regulation remain poorly understood. MIC19, a peripheral protein of the inner membrane and component of the MICOS complex, was previously reported to be required for the proper function of MICOS in maintaining the architecture of the inner membrane. Here, we show that human and Saccharomyces cerevisiae MIC19 proteins undergo oxidation in mitochondria and require the mitochondrial intermembrane space assembly (MIA) pathway, which couples the oxidation and import of mitochondrial intermembrane space proteins for mitochondrial localization. Detailed analyses identified yeast Mic19 in two different redox forms. The form that contains an intramolecular disulfide bond is bound to Mic60 of the MICOS complex. Mic19 oxidation is not essential for its integration into the MICOS complex but plays a role in MICOS assembly and the maintenance of the proper inner membrane morphology. These findings suggest that Mic19 is a redox-dependent regulator of MICOS function. PMID:26416881

  16. Nitric Oxide Regulation of Mitochondrial Processes: Commonality in Medical Disorders.

    PubMed

    Stefano, George B; Kream, Richard M

    2015-01-01

    The vital status of diverse classes of eukaryotic mitochondria is reflected by the high degree of evolutionary modification functionally linked to ongoing multifaceted organelle development. From this teleological perspective, a logistical enhancement of eukaryotic cellular energy requirements indicates a convergence of metabolic processes within the mitochondrial matrix for optimal synthesis of ATP from ADP and inorganic phosphate and necessitates an evolutionarily driven retrofit of the primordial endosymbiont bacterial plasma membrane into the inner mitochondrial membrane. The biochemical complexity of eukaryotic inner membrane electron transport complexes linked to temporally-defined, state-dependent, fluctuations in mitochondrial oxygen utilization is capable of generating deleterious reactive oxygen species. Within this functional context, an extensive neurochemical literature supports the role of the free radical gas nitric oxide (NO) as a key signaling molecule involved in the regulation of multiple aspects of mitochondrial respiration/oxidative phosphorylation. Importantly, the unique chemical properties of NO underlie its rapid metabolism in vivo within a mechanistic spectrum of small oxidative molecules, free and protein-bound thiol adducts, and reversible binding to ferrous heme iron centers. Recent compelling work has identified a medically relevant dual regulation pathway for mitochondrial NO expression mediated by traditionally characterized NO synthases (NOS) and by enzymatic reduction of available cellular nitrite pools by a diverse class of cytosolic and mitochondrial nitrite reductases. Accordingly, our short review presents selected medically-based discussion topics relating to multi-faceted NO regulation of mitochondrial functions in human health and disease states. PMID:26177568

  17. In Defence of the Lecture

    ERIC Educational Resources Information Center

    Webster, R. Scott

    2015-01-01

    In response to the lecture format coming under "attack" and being replaced by online materials and smaller tutorials, this paper attempts to offer not only a defence but also to assert that the potential value of the lecture is difficult to replicate through other learning formats. Some of the criticisms against lectures will be…

  18. Endothelial cell expression of haemoglobin α regulates nitric oxide signalling.

    PubMed

    Straub, Adam C; Lohman, Alexander W; Billaud, Marie; Johnstone, Scott R; Dwyer, Scott T; Lee, Monica Y; Bortz, Pamela Schoppee; Best, Angela K; Columbus, Linda; Gaston, Benjamin; Isakson, Brant E

    2012-11-15

    Models of unregulated nitric oxide (NO) diffusion do not consistently account for the biochemistry of NO synthase (NOS)-dependent signalling in many cell systems. For example, endothelial NOS controls blood pressure, blood flow and oxygen delivery through its effect on vascular smooth muscle tone, but the regulation of these processes is not adequately explained by simple NO diffusion from endothelium to smooth muscle. Here we report a new model for the regulation of NO signalling by demonstrating that haemoglobin (Hb) α (encoded by the HBA1 and HBA2 genes in humans) is expressed in human and mouse arterial endothelial cells and enriched at the myoendothelial junction, where it regulates the effects of NO on vascular reactivity. Notably, this function is unique to Hb α and is abrogated by its genetic depletion. Mechanistically, endothelial Hb α haem iron in the Fe(3+) state permits NO signalling, and this signalling is shut off when Hb α is reduced to the Fe(2+) state by endothelial cytochrome b5 reductase 3 (CYB5R3, also known as diaphorase 1). Genetic and pharmacological inhibition of CYB5R3 increases NO bioactivity in small arteries. These data reveal a new mechanism by which the regulation of the intracellular Hb α oxidation state controls NOS signalling in non-erythroid cells. This model may be relevant to haem-containing globins in a broad range of NOS-containing somatic cells. PMID:23123858

  19. Redox regulation of Rac1 by thiol oxidation.

    PubMed

    Hobbs, G Aaron; Mitchell, Lauren E; Arrington, Megan E; Gunawardena, Harsha P; DeCristo, Molly J; Loeser, Richard F; Chen, Xian; Cox, Adrienne D; Campbell, Sharon L

    2015-02-01

    The Rac1 GTPase is an essential and ubiquitous protein that signals through numerous pathways to control critical cellular processes, including cell growth, morphology, and motility. Rac1 deletion is embryonic lethal, and its dysregulation or mutation can promote cancer, arthritis, cardiovascular disease, and neurological disorders. Rac1 activity is highly regulated by modulatory proteins and posttranslational modifications. Whereas much attention has been devoted to guanine nucleotide exchange factors that act on Rac1 to promote GTP loading and Rac1 activation, cellular oxidants may also regulate Rac1 activation by promoting guanine nucleotide exchange. Herein, we show that Rac1 contains a redox-sensitive cysteine (Cys(18)) that can be selectively oxidized at physiological pH because of its lowered pKa. Consistent with these observations, we show that Rac1 is glutathiolated in primary chondrocytes. Oxidation of Cys(18) by glutathione greatly perturbs Rac1 guanine nucleotide binding and promotes nucleotide exchange. As aspartate substitutions have been previously used to mimic cysteine oxidation, we characterized the biochemical properties of Rac1(C18D). We also evaluated Rac1(C18S) as a redox-insensitive variant and found that it retains structural and biochemical properties similar to those of Rac1(WT) but is resistant to thiol oxidation. In addition, Rac1(C18D), but not Rac1(C18S), shows greatly enhanced nucleotide exchange, similar to that observed for Rac1 oxidation by glutathione. We employed Rac1(C18D) in cell-based studies to assess whether this fast-cycling variant, which mimics Rac1 oxidation by glutathione, affects Rac1 activity and function. Expression of Rac1(C18D) in Swiss 3T3 cells showed greatly enhanced GTP-bound Rac1 relative to Rac1(WT) and the redox-insensitive Rac1(C18S) variant. Moreover, expression of Rac1(C18D) in HEK-293T cells greatly promoted lamellipodia formation. Our results suggest that Rac1 oxidation at Cys(18) is a novel

  20. Oxide for valve-regulated lead-acid batteries

    NASA Astrophysics Data System (ADS)

    Lam, L. T.; Lim, O. V.; Haigh, N. P.; Rand, D. A. J.; Manders, J. E.; Rice, D. M.

    In order to meet the increasing demand for valve-regulated lead-acid (VRLA) batteries, a new soft lead has been produced by Pasminco Metals. In this material, bismuth is increased to a level that produces a significant improvement in battery cycle life. By contrast, other common impurities, such as arsenic, cobalt, chromium, nickel, antimony and tellurium, that are known to be harmful to VRLA batteries are controlled to very low levels. A bismuth (Bi)-bearing oxide has been manufactured (Barton-pot method) from this soft lead and is characterized in terms of phase composition, particle size distribution, BET surface area, and reactivity. An investigation is also made of the rates of oxygen and hydrogen evolution on pasted electrodes prepared from the Bi-bearing oxide. For comparison, the characteristics and performance of a Bi-free (Barton-pot) oxide, which is manufactured in the USA, are also examined. Increasing the level of bismuth and lowering those of the other impurities in soft lead produces no unusual changes in either the physical or the chemical properties of the resulting Bi-bearing oxide compared with Bi-free oxide. This is very important because there is no need for battery manufacturers to change their paste formulae and paste-mixing procedures on switching to the new Bi-bearing oxide. There is little difference in the rates of oxygen and hydrogen evolution on pasted electrodes prepared from Bi-bearing or Bi-free oxides. On the other hand, these rates increase on the former electrodes when the levels of all the other impurities are made to exceed (by deliberately adding the impurities as oxide powders) the corresponding, specified values for the Bi-bearing oxide. The latter behaviour is particularly noticeable for hydrogen evolution, which is enhanced even further when a negative electrode prepared from Bi-bearing oxide is contaminated through the deposition of impurities added to the sulfuric acid solution. The effects of impurities in the positive

  1. Air pollution and epigenetics: effects on SP-A and innate host defence in the lung.

    PubMed

    Silveyra, Patricia; Floros, Joanna

    2012-01-01

    An appropriate immune and inflammatory response is key to defend against harmful agents present in the environment, such as pathogens, allergens and inhaled pollutants, including ozone and particulate matter. Air pollution is a serious public health concern worldwide, and cumulative evidence has revealed that air pollutants contribute to epigenetic variation in several genes, and this in turn can contribute to disease susceptibility. Several groups of experts have recently reviewed findings on epigenetics and air pollution [1-6]. Surfactant proteins play a central role in pulmonary host defence by mediating pathogen clearance, modulating allergic responses and facilitating the resolution of lung inflammation. Recent evidence indicates that surfactant proteins are subject to epigenetic regulation under hypoxia and other conditions. Oxidative stress caused by ozone, and exposure to particulate matter have been shown to affect the expression of surfactant protein A (SP-A), an important lung host defence molecule, as well as alter its functions. In this review, we discuss recent findings in the fields of epigenetics and air pollution effects on innate immunity, with the focus on SP-A, and the human SP-A variants in particular. Their function may be differentially affected by pollutants and specifically by ozone-induced oxidative stress, and this in turn may differentially affect susceptibility to lung disease. PMID:22553125

  2. The cysteine desulfurase IscS of Mycobacterium tuberculosis is involved in iron-sulfur cluster biogenesis and oxidative stress defence.

    PubMed

    Rybniker, Jan; Pojer, Florence; Marienhagen, Jan; Kolly, Gaëlle S; Chen, Jeffrey M; van Gumpel, Edeltraud; Hartmann, Pia; Cole, Stewart T

    2014-05-01

    The complex multiprotein systems for the assembly of protein-bound iron-sulfur (Fe-S) clusters are well defined in Gram-negative model organisms. However, little is known about Fe-S cluster biogenesis in other bacterial species. The ISC (iron-sulfur cluster) operon of Mycobacterium tuberculosis lacks several genes known to be essential for the function of this system in other organisms. However, the cysteine desulfurase IscSMtb (Rv number Rv3025c; Mtb denotes M. tuberculosis) is conserved in this important pathogen. The present study demonstrates that deleting iscSMtb renders the cells microaerophilic and hypersensitive to oxidative stress. Moreover, the ∆iscSMtb mutant shows impaired Fe-S cluster-dependent enzyme activity, clearly indicating that IscSMtb is associated with Fe-S cluster assembly. An extensive interaction network of IscSMtb with Fe-S proteins was identified, suggesting a novel mechanism of sulfur transfer by direct interaction with apoproteins. Interestingly, the highly homologous IscS of Escherichia coli failed to complement the ∆iscSMtb mutant and showed a less diverse protein-interaction profile. To identify a structural basis for these observations we determined the crystal structure of IscSMtb, which mirrors adaptations made in response to an ISC operon devoid of IscU-like Fe-S cluster scaffold proteins. We conclude that in M. tuberculosis IscS has been redesigned during evolution to compensate for the deletion of large parts of the ISC operon. PMID:24548275

  3. Endothelial nitric oxide synthase regulates microvascular hyperpermeability in vivo

    PubMed Central

    Hatakeyama, Takuya; Pappas, Peter J; Hobson, Robert W; Boric, Mauricio P; Sessa, William C; Durán, Walter N

    2006-01-01

    Nitric oxide (NO) is an important regulator of blood flow, but its role in permeability is still challenged. We tested in vivo the hypotheses that: (a) endothelial nitric oxide synthase (eNOS) is not essential for regulation of baseline permeability; (b) eNOS is essential for hyperpermeability responses in inflammation; and (c) molecular inhibition of eNOS with caveolin-1 scaffolding domain (AP-Cav) reduces eNOS-regulated hyperpermeability. We used eNOS-deficient (eNOS−/−) mice and their wild-type control as experimental animals, platelet-activating factor (PAF) at 10−7 m as the test pro-inflammatory agent, and integrated optical intensity (IOI) as an index of microvascular permeability. PAF increased permeability in wild-type cremaster muscle from a baseline of 2.4 ± 2.2 to a peak net value of 84.4 ± 2.7 units, while the corresponding values in cremaster muscle of eNOS−/− mice were 1.0 ± 0.3 and 15.6 ± 7.7 units (P < 0.05). Similarly, PAF increased IOI in the mesentery of wild-type mice but much less in the mesentery of eNOS−/− mice. PAF increased IOI to comparable values in the mesenteries of wild-type mice and those lacking the gene for inducible NOS (iNOS). Administration of AP-Cav blocked the microvascular hyperpermeability responses to 10−7 m PAF. We conclude that: (1) baseline permeability does not depend on eNOS; (2) eNOS and NO are integral elements of the signalling pathway for the hyperpermeability response to PAF; (3) iNOS does not affect either baseline permeability or hyperpermeability responses to PAF; and (4) caveolin-1 inhibits eNOS regulation of microvascular permeability in vivo. Our results establish eNOS as an important regulator of microvascular permeability in inflammation. PMID:16675496

  4. Differential regulation of cytokine production by nitric oxide.

    PubMed Central

    Marcinkiewicz, J; Chain, B M

    1993-01-01

    Nitric oxide (NO) has recently been identified as a potent and pleiotropic intracellular mediator produced by and acting on many cells of the body. Although considerable attention has been devoted to the regulation of NO by inflammatory cytokines, and also to the role of NO as an important effector molecule in immune function, there is very little information on the role of this mediator in modulating T-cell-dependent cytokine production. In this study we show that physiological levels of NO (either produced by activated macrophages or by the addition of exogenous NO donors) can selectively down-regulate interleukin-3 (IL-3) production by spleen cells from contact-sensitized mice, while leaving IL-2 activity unaffected. Thus NO may have an important role as an immunomodulatory as well as effector molecule in the immune system. PMID:8244457

  5. REGULATION OF OBESITY AND INSULIN RESISTANCE BY NITRIC OXIDE

    PubMed Central

    Sansbury, Brian E.; Hill, Bradford G.

    2014-01-01

    Obesity is a risk factor for developing type 2 diabetes and cardiovascular disease and has quickly become a world-wide pandemic with few tangible and safe treatment options. While it is generally accepted that the primary cause of obesity is energy imbalance, i.e., the calories consumed are greater than are utilized, understanding how caloric balance is regulated has proven a challenge. Many “distal” causes of obesity, such as the structural environment, occupation, and social influences, are exceedingly difficult to change or manipulate. Hence, molecular processes and pathways more proximal to the origins of obesity—those that directly regulate energy metabolism or caloric intake—appear to be more feasible targets for therapy. In particular, nitric oxide (NO) is emerging as a central regulator of energy metabolism and body composition. NO bioavailability is decreased in animal models of diet-induced obesity and in obese and insulin resistant patients, and increasing NO output has remarkable effects on obesity and insulin resistance. This review discusses the role of NO in regulating adiposity and insulin sensitivity and places its modes of action into context with the known causes and consequences of metabolic disease. PMID:24878261

  6. Salmonella Rapidly Regulates Membrane Permeability To Survive Oxidative Stress

    PubMed Central

    van der Heijden, Joris; Reynolds, Lisa A.; Deng, Wanyin; Mills, Allan; Scholz, Roland; Imami, Koshi; Foster, Leonard J.; Duong, Franck

    2016-01-01

    ABSTRACT The outer membrane (OM) of Gram-negative bacteria provides protection against toxic molecules, including reactive oxygen species (ROS). Decreased OM permeability can promote bacterial survival under harsh circumstances and protects against antibiotics. To better understand the regulation of OM permeability, we studied the real-time influx of hydrogen peroxide in Salmonella bacteria and discovered two novel mechanisms by which they rapidly control OM permeability. We found that pores in two major OM proteins, OmpA and OmpC, could be rapidly opened or closed when oxidative stress is encountered and that the underlying mechanisms rely on the formation of disulfide bonds in the periplasmic domain of OmpA and TrxA, respectively. Additionally, we found that a Salmonella mutant showing increased OM permeability was killed more effectively by treatment with antibiotics. Together, these results demonstrate that Gram-negative bacteria regulate the influx of ROS for defense against oxidative stress and reveal novel targets that can be therapeutically targeted to increase bacterial killing by conventional antibiotics. PMID:27507830

  7. Nitric oxide as a regulator of B. anthracis pathogenicity

    PubMed Central

    Popova, Taissia G.; Teunis, Allison; Vaseghi, Haley; Zhou, Weidong; Espina, Virginia; Liotta, Lance A.; Popov, Serguei G.

    2015-01-01

    Nitric oxide (NO) is a key physiological regulator in eukaryotic and prokaryotic organisms. It can cause a variety of biological effects by reacting with its targets or/and indirectly inducing oxidative stress. NO can also be produced by bacteria including the pathogenic Bacillus anthracis; however, its role in the infectious process only begins to emerge. NO incapacitates macrophages by S-nitrosylating the intracellular proteins and protects B. anthracis from oxidative stress. It is also implicated in the formation of toxic peroxynitrite. In this study we further assessed the effects of B. anthracis NO produced by the NO synthase (bNOS) on bacterial metabolism and host cells in experiments with the bNOS knockout Sterne strain. The mutation abrogated accumulation of nitrite and nitrate as tracer products of NO in the culture medium and markedly attenuated growth in both aerobic and microaerobic conditions. The regulatory role of NO was also suggested by the abnormally high rate of nitrate denitrification by the mutant in the presence of oxygen. Anaerobic regulation mediated by NO was reflected in reduced fermentation of glucose by the mutant correlating with the reduced toxicity of bacteria toward host cells in culture. The toxic effect of NO required permeabilization of the target cells as well as the activity of fermentation-derived metabolite in the conditions of reduced pH. The host cells demonstrated increased phosphorylation of major survivor protein kinase AKT correlating with reduced toxicity of the mutant in comparison with Sterne. Our global proteomic analysis of lymph from the lymph nodes of infected mice harboring bacteria revealed numerous changes in the pattern and levels of proteins associated with the activity of bNOS influencing key cell physiological processes relevant to energy metabolism, growth, signal transduction, stress response, septic shock, and homeostasis. This is the first in vivo observation of the bacterial NO effect on the lymphatic

  8. Nitric oxide as a regulator of B. anthracis pathogenicity.

    PubMed

    Popova, Taissia G; Teunis, Allison; Vaseghi, Haley; Zhou, Weidong; Espina, Virginia; Liotta, Lance A; Popov, Serguei G

    2015-01-01

    Nitric oxide (NO) is a key physiological regulator in eukaryotic and prokaryotic organisms. It can cause a variety of biological effects by reacting with its targets or/and indirectly inducing oxidative stress. NO can also be produced by bacteria including the pathogenic Bacillus anthracis; however, its role in the infectious process only begins to emerge. NO incapacitates macrophages by S-nitrosylating the intracellular proteins and protects B. anthracis from oxidative stress. It is also implicated in the formation of toxic peroxynitrite. In this study we further assessed the effects of B. anthracis NO produced by the NO synthase (bNOS) on bacterial metabolism and host cells in experiments with the bNOS knockout Sterne strain. The mutation abrogated accumulation of nitrite and nitrate as tracer products of NO in the culture medium and markedly attenuated growth in both aerobic and microaerobic conditions. The regulatory role of NO was also suggested by the abnormally high rate of nitrate denitrification by the mutant in the presence of oxygen. Anaerobic regulation mediated by NO was reflected in reduced fermentation of glucose by the mutant correlating with the reduced toxicity of bacteria toward host cells in culture. The toxic effect of NO required permeabilization of the target cells as well as the activity of fermentation-derived metabolite in the conditions of reduced pH. The host cells demonstrated increased phosphorylation of major survivor protein kinase AKT correlating with reduced toxicity of the mutant in comparison with Sterne. Our global proteomic analysis of lymph from the lymph nodes of infected mice harboring bacteria revealed numerous changes in the pattern and levels of proteins associated with the activity of bNOS influencing key cell physiological processes relevant to energy metabolism, growth, signal transduction, stress response, septic shock, and homeostasis. This is the first in vivo observation of the bacterial NO effect on the lymphatic

  9. Mincle-mediated translational regulation is required for strong nitric oxide production and inflammation resolution

    PubMed Central

    Lee, Wook-Bin; Kang, Ji-Seon; Choi, Won Young; Zhang, Quanri; Kim, Chul Han; Choi, Un Yung; Kim-Ha, Jeongsil; Kim, Young-Joon

    2016-01-01

    In response to persistent mycobacteria infection, the host induces a granuloma, which often fails to eradicate bacteria and results in tissue damage. Diverse host receptors are required to control the formation and resolution of granuloma, but little is known concerning their regulatory interactions. Here we show that Mincle, the inducible receptor for mycobacterial cord factor, is the key switch for the transition of macrophages from cytokine expression to high nitric oxide production. In addition to its stimulatory role on TLR-mediated transcription, Mincle enhanced the translation of key genes required for nitric oxide synthesis through p38 and eIF5A hypusination, leading to granuloma resolution. Thus, Mincle has dual functions in the promotion and subsequent resolution of inflammation during anti-mycobacterial defence using both transcriptional and translational controls. PMID:27089465

  10. Nitric oxide destabilizes Pias3 and regulates sumoylation.

    PubMed

    Qu, Jing; Liu, Guang-Hui; Wu, Kaiyuan; Han, Peiwei; Wang, Peng; Li, Jiangmei; Zhang, Xu; Chen, Chang

    2007-01-01

    Small ubiquitin-related protein modifiers (SUMO) modification is an important mechanism for posttranslational regulation of protein function. However, it is largely unknown how the sumoylation pathway is regulated. Here, we report that nitric oxide (NO) causes global hyposumoylation in mammalian cells. Both SUMO E2 conjugating enzyme Ubc9 and E3 ligase protein inhibitor of activated STAT3 (Pias3) were targets for S-nitrosation. S-nitrosation did not interfere with the SUMO conjugating activity of Ubc9, but promoted Pias3 degradation by facilitating its interaction with tripartite motif-containing 32 (Trim32), a ubiquitin E3 ligase. On the one hand, NO promoted Trim32-mediated Pias3 ubiquitination. On the other hand, NO enhanced the stimulatory effect of Pias3 on Trim32 autoubiquitination. The residue Cys459 of Pias3 was identified as a target site for S-nitrosation. Mutation of Cys459 abolished the stimulatory effect of NO on the Pias3-Trim32 interaction, indicating a requirement of S-nitrosation at Cys459 for positive regulation of the Pias3-Trim32 interplay. This study reveals a novel crosstalk between S-nitrosation, ubiquitination, and sumoylation, which may be crucial for NO-related physiological and pathological processes. PMID:17987106

  11. Regulation of Injury-Induced Neurogenesis by Nitric Oxide

    PubMed Central

    Carreira, Bruno P.; Carvalho, Caetana M.; Araújo, Inês M.

    2012-01-01

    The finding that neural stem cells (NSCs) are able to divide, migrate, and differentiate into several cellular types in the adult brain raised a new hope for restorative neurology. Nitric oxide (NO), a pleiotropic signaling molecule in the central nervous system (CNS), has been described to be able to modulate neurogenesis, acting as a pro- or antineurogenic agent. Some authors suggest that NO is a physiological inhibitor of neurogenesis, while others described NO to favor neurogenesis, particularly under inflammatory conditions. Thus, targeting the NO system may be a powerful strategy to control the formation of new neurons. However, the exact mechanisms by which NO regulates neural proliferation and differentiation are not yet completely clarified. In this paper we will discuss the potential interest of the modulation of the NO system for the treatment of neurodegenerative diseases or other pathological conditions that may affect the CNS. PMID:22997523

  12. Nitric Oxide Regulates Neurogenesis in the Hippocampus following Seizures

    PubMed Central

    Carreira, Bruno P.; Santos, Daniela F.; Santos, Ana I.; Carvalho, Caetana M.; Araújo, Inês M.

    2015-01-01

    Hippocampal neurogenesis is changed by brain injury. When neuroinflammation accompanies injury, activation of resident microglial cells promotes the release of inflammatory cytokines and reactive oxygen/nitrogen species like nitric oxide (NO). In these conditions, NO promotes proliferation of neural stem cells (NSC) in the hippocampus. However, little is known about the role of NO in the survival and differentiation of newborn cells in the injured dentate gyrus. Here we investigated the role of NO following seizures in the regulation of proliferation, migration, differentiation, and survival of NSC in the hippocampus using the kainic acid (KA) induced seizure mouse model. We show that NO increased the proliferation of NSC and the number of neuroblasts following seizures but was detrimental to the survival of newborn neurons. NO was also required for the maintenance of long-term neuroinflammation. Taken together, our data show that NO positively contributes to the initial stages of neurogenesis following seizures but compromises survival of newborn neurons. PMID:26587180

  13. Metabolomic Assessment of Induced and Activated Chemical Defence in the Invasive Red Alga Gracilaria vermiculophylla

    PubMed Central

    Nylund, Göran M.; Weinberger, Florian; Rempt, Martin; Pohnert, Georg

    2011-01-01

    In comparison with terrestrial plants the mechanistic knowledge of chemical defences is poor for marine macroalgae. This restricts our understanding in the chemically mediated interactions that take place between algae and other organisms. Technical advances such as metabolomics, however, enable new approaches towards the characterisation of the chemically mediated interactions of organisms with their environment. We address defence responses in the red alga Gracilaria vermiculophylla using mass spectrometry based metabolomics in combination with bioassays. Being invasive in the north Atlantic this alga is likely to possess chemical defences according to the prediction that well-defended exotics are most likely to become successful invaders in systems dominated by generalist grazers, such as marine macroalgal communities. We investigated the effect of intense herbivore feeding and simulated herbivory by mechanical wounding of the algae. Both processes led to similar changes in the metabolic profile. Feeding experiments with the generalist isopod grazer Idotea baltica showed that mechanical wounding caused a significant increase in grazer resistance. Structure elucidation of the metabolites of which some were up-regulated more than 100 times in the wounded tissue, revealed known and novel eicosanoids as major components. Among these were prostaglandins, hydroxylated fatty acids and arachidonic acid derived conjugated lactones. Bioassays with pure metabolites showed that these eicosanoids are part of the innate defence system of macroalgae, similarly to animal systems. In accordance with an induced defence mechanism application of extracts from wounded tissue caused a significant increase in grazer resistance and the up-regulation of other pathways than in the activated defence. Thus, this study suggests that G. vermiculophylla chemically deters herbivory by two lines of defence, a rapid wound-activated process followed by a slower inducible defence. By unravelling

  14. The protein quality control system manages plant defence compound synthesis.

    PubMed

    Pollier, Jacob; Moses, Tessa; González-Guzmán, Miguel; De Geyter, Nathan; Lippens, Saskia; Vanden Bossche, Robin; Marhavý, Peter; Kremer, Anna; Morreel, Kris; Guérin, Christopher J; Tava, Aldo; Oleszek, Wieslaw; Thevelein, Johan M; Campos, Narciso; Goormachtig, Sofie; Goossens, Alain

    2013-12-01

    Jasmonates are ubiquitous oxylipin-derived phytohormones that are essential in the regulation of many development, growth and defence processes. Across the plant kingdom, jasmonates act as elicitors of the production of bioactive secondary metabolites that serve in defence against attackers. Knowledge of the conserved jasmonate perception and early signalling machineries is increasing, but the downstream mechanisms that regulate defence metabolism remain largely unknown. Here we show that, in the legume Medicago truncatula, jasmonate recruits the endoplasmic-reticulum-associated degradation (ERAD) quality control system to manage the production of triterpene saponins, widespread bioactive compounds that share a biogenic origin with sterols. An ERAD-type RING membrane-anchor E3 ubiquitin ligase is co-expressed with saponin synthesis enzymes to control the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the rate-limiting enzyme in the supply of the ubiquitous terpene precursor isopentenyl diphosphate. Thus, unrestrained bioactive saponin accumulation is prevented and plant development and integrity secured. This control apparatus is equivalent to the ERAD system that regulates sterol synthesis in yeasts and mammals but that uses distinct E3 ubiquitin ligases, of the HMGR degradation 1 (HRD1) type, to direct destruction of HMGR. Hence, the general principles for the management of sterol and triterpene saponin biosynthesis are conserved across eukaryotes but can be controlled by divergent regulatory cues. PMID:24213631

  15. Plant defences against herbivore and insect attack

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plants deploy a number of defences against attack by insects and other herbivores. Direct defence is conferred by plant products and structures that deter or kill the herbivores. Chemical toxins and deterrents vary widely among plant species, and some typical toxins include alkaloids, terpenoids, st...

  16. Defence electro-optics: European perspective

    NASA Astrophysics Data System (ADS)

    Hartikainen, Jari

    2011-11-01

    In 2009 the United States invested in defence R&T 3,6 times and in defence research and development 6,8 times as much as all member states of the European Defence Agency (EDA) combined while the ratio in the total defence expenditure was 2,6 in the US' favour. The European lack of investments in defence research and development has a negative impact on the competitiveness of European defence industry and on the European non-dependence. In addition, the efficiency of investment is reduced due to duplication of work in different member states. The Lisbon Treaty tasks EDA to support defence technology research, and coordinate and plan joint research activities and the study of technical solutions meeting future operational needs. This paper gives an overview how EDA meets the challenge of improving the efficiency of European defence R&T investment with an emphasis on electro-optics and describes shortly the ways that governmental and industrial partners can participate in the EDA cooperation. Examples of joint R&T projects addressing electro-optics are presented.

  17. Nitric oxide regulates neutrophil migration through microparticle formation.

    PubMed

    Nolan, Sarah; Dixon, Rachel; Norman, Keith; Hellewell, Paul; Ridger, Victoria

    2008-01-01

    The role of nitric oxide (NO) in regulating neutrophil migration has been investigated. Human neutrophil migration to interleukin (IL)-8 (1 nmol/L) was measured after a 1-hour incubation using a 96-well chemotaxis plate assay. The NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME) significantly (P < 0.001) enhanced IL-8-induced migration by up to 45%. Anti-CD18 significantly (P < 0.001) inhibited both IL-8-induced and L-NAME enhanced migration. Antibodies to L-selectin or PSGL-1 had no effect on IL-8-induced migration but prevented the increased migration to IL-8 induced by L-NAME. L-NAME induced generation of neutrophil-derived microparticles that was significantly (P < 0.01) greater than untreated neutrophils or D-NAME. This microparticle formation was dependent on calpain activity and superoxide production. Only microparticles from L-NAME and not untreated or D-NAME-treated neutrophils induced a significant (P < 0.01) increase in IL-8-induced migration and transendothelial migration. Pretreatment of microparticles with antibodies to L-selectin (DREG-200) or PSGL-1 (PL-1) significantly (P < 0.001) inhibited this effect. The ability of L-NAME-induced microparticles to enhance migration was found to be dependent on the number of microparticles produced and not an increase in microparticle surface L-selectin or PSGL-1 expression. These data show that NO can modulate neutrophil migration by regulating microparticle formation. PMID:18079439

  18. 40 CFR 52.125 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control strategy and regulations: Sulfur oxides. 52.125 Section 52.125 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Arizona § 52.125 Control strategy and regulations: Sulfur oxides....

  19. 40 CFR 52.2731 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...: Sulfur oxides. 52.2731 Section 52.2731 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Rico § 52.2731 Control strategy and regulations: Sulfur oxides. (a) The requirements of subpart G of... the national standards for sulfur oxides in the areas of Aguirre, Barceloneta, Trujillo...

  20. 40 CFR 52.1475 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...: Sulfur oxides. 52.1475 Section 52.1475 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... § 52.1475 Control strategy and regulations: Sulfur oxides. (a) The requirements of subpart G of this... National Ambient Air Quality Standards for sulfur oxides in the Nevada Intrastate Region. (b) Article...

  1. 40 CFR 52.1475 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...: Sulfur oxides. 52.1475 Section 52.1475 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... § 52.1475 Control strategy and regulations: Sulfur oxides. (a) The requirements of subpart G of this... National Ambient Air Quality Standards for sulfur oxides in the Nevada Intrastate Region. (b) Article...

  2. 40 CFR 52.2731 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...: Sulfur oxides. 52.2731 Section 52.2731 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Rico § 52.2731 Control strategy and regulations: Sulfur oxides. (a) The requirements of subpart G of... the national standards for sulfur oxides in the areas of Aguirre, Barceloneta, Trujillo...

  3. 40 CFR 52.2731 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...: Sulfur oxides. 52.2731 Section 52.2731 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Rico § 52.2731 Control strategy and regulations: Sulfur oxides. (a) The requirements of subpart G of... the national standards for sulfur oxides in the areas of Aguirre, Barceloneta, Trujillo...

  4. 40 CFR 52.1475 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...: Sulfur oxides. 52.1475 Section 52.1475 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... § 52.1475 Control strategy and regulations: Sulfur oxides. (a) The requirements of subpart G of this... National Ambient Air Quality Standards for sulfur oxides in the Nevada Intrastate Region. (b) Article...

  5. 40 CFR 52.2731 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...: Sulfur oxides. 52.2731 Section 52.2731 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Rico § 52.2731 Control strategy and regulations: Sulfur oxides. (a) The requirements of subpart G of... the national standards for sulfur oxides in the areas of Aguirre, Barceloneta, Trujillo...

  6. 40 CFR 52.1475 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...: Sulfur oxides. 52.1475 Section 52.1475 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... § 52.1475 Control strategy and regulations: Sulfur oxides. (a) The requirements of subpart G of this... National Ambient Air Quality Standards for sulfur oxides in the Nevada Intrastate Region. (b) Article...

  7. Nitric oxide and the autonomic regulation of cardiac excitability. The G.L. Brown Prize Lecture.

    PubMed

    Paterson, D

    2001-01-01

    Cardiac sympathetic imbalance and arrhythmia; Nitric oxide-cGMP pathway and the cholinergic modulation of cardiac excitability; Nitric oxide-cGMP pathway and the sympathetic modulation of cardiac excitability; Functional significance of nitric oxide in the autonomic regulation of cardiac excitability; Summary; References. Experimental Physiology (2001) 86.1, 1-12. PMID:11429613

  8. 40 CFR 52.2731 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...: Sulfur oxides. 52.2731 Section 52.2731 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Rico § 52.2731 Control strategy and regulations: Sulfur oxides. (a) The requirements of subpart G of... the national standards for sulfur oxides in the areas of Aguirre, Barceloneta, Trujillo...

  9. 40 CFR 52.1475 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...: Sulfur oxides. 52.1475 Section 52.1475 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... § 52.1475 Control strategy and regulations: Sulfur oxides. (a) The requirements of subpart G of this... National Ambient Air Quality Standards for sulfur oxides in the Nevada Intrastate Region. (b) Article...

  10. Transcriptional responses to exposure to the brassicaceous defence metabolites camalexin and allyl-isothiocyanate in the necrotrophic fungus Alternaria brassicicola.

    PubMed

    Sellam, Adnane; Dongo, Anita; Guillemette, Thomas; Hudhomme, Piétrick; Simoneau, Philippe

    2007-03-01

    SUMMARY Alternaria brassicicola is the causative agent of black spot disease of Brassicaceae belonging to the genera Brassica and Raphanus. During host infection, A. brassicicola is exposed to high levels of antimicrobial defence compounds such as indolic phytoalexins and glucosinolate breakdown products. To investigate the transcriptomic response of A. brassicicola when challenged with brassicaceous defence metabolites, suppression subtractive hybridization (SSH) was performed to generate two cDNA libraries from germinated conidia treated either with allyl isothiocyanate (Al-ITC) or with camalexin. Following exposure to Al-ITC, A. brassicicola displayed a response similar to that experienced during oxidative stress. Indeed, a substantial subset of differentially expressed genes was related to cell protection against oxidative damage. Treatment of A. brassicicola conidia with the phytoalexin camalexin appeared to activate a compensatory mechanism to preserve cell membrane integrity and, among the camalexin-elicited genes, several were involved in sterol and sphingolipid biosynthesis. The transcriptomic analysis suggested that protection against the two tested compounds also involved mechanisms aimed at limiting their intracellular accumulation, such as melanin biosynthesis (in the case of camalexin exposure only) and drug efflux. From the Al-ITC and the camalexin differentially expressed genes identified here, 25 were selected to perform time-course studies during interactions with brassicaceous hosts. In planta, up-regulation of all the selected genes was observed during infection of Raphanus sativus whereas only a subset were over-expressed during the incompatible interaction with Arabidopsis thaliana ecotype Columbia. PMID:20507491

  11. Mitochondrial Thioredoxin in Regulation of Oxidant-Induced Cell Death

    PubMed Central

    Chen, Yan; Cai, Jiyang; Jones, Dean P

    2006-01-01

    Mitochondrial thioredoxin (mtTrx) can be oxidized in response to inducers of oxidative stress; yet the functional consequences of the oxidation have not been determined. This study evaluated the redox status of mtTrx and its association to oxidant-induced apoptosis. Results showed that mtTrx was oxidized after exposure to peroxides and diamide. Overexpression of mtTrx protected against diamide-induced oxidation and cytotoxicity. Oxidation of mtTrx was also achieved by knocking down its reductase; and lead to increased susceptibility to cell death. The data indicate that the redox status of mtTrx is a regulatory mechanism underlying the vulnerability of mitochondria to oxidative injury. PMID:17113580

  12. Regulation of neuronal nitric oxide synthase and identification of novel nitric oxide signaling pathways.

    PubMed

    Dawson, T M; Sasaki, M; Gonzalez-Zulueta, M; Dawson, V L

    1998-01-01

    Neuronal nitric oxide synthase (nNOS) participate in a variety of physiologic and pathologic processes in the nervous system. nNOS was originally felt to be a constitutively expressed enzyme, but recent observations suggest that its levels are dynamically controlled in response to neuronal development, plasticity and injury. nNOS expression is regulated through alternative promoter usage through alternative mRNA splicing and it is likely that this plays an important role in the inducibility of gene expression in response to extracellular stimuli. Emerging data also suggests that NO may be the key mediator linking activity to gene expression and long-lasting neuronal responses through NO activating p21Ras through redox-sensitive modulation. PMID:9932430

  13. Uncoupling of reactive oxygen species accumulation and defence signalling in the metal hyperaccumulator plant Noccaea caerulescens.

    PubMed

    Fones, Helen N; Eyles, Chris J; Bennett, Mark H; Smith, J Andrew C; Preston, Gail M

    2013-09-01

    The metal hyperaccumulator plant Noccaea caerulescens is protected from disease by the accumulation of high concentrations of metals in its aerial tissues, which are toxic to many pathogens. As these metals can lead to the production of damaging reactive oxygen species (ROS), metal hyperaccumulator plants have developed highly effective ROS tolerance mechanisms, which might quench ROS-based signals. We therefore investigated whether metal accumulation alters defence signalling via ROS in this plant. We studied the effect of zinc (Zn) accumulation by N. caerulescens on pathogen-induced ROS production, salicylic acid accumulation and downstream defence responses, such as callose deposition and pathogenesis-related (PR) gene expression, to the bacterial pathogen Pseudomonas syringae pv. maculicola. The accumulation of Zn caused increased superoxide production in N. caerulescens, but inoculation with P. syringae did not elicit the defensive oxidative burst typical of most plants. Defences dependent on signalling through ROS (callose and PR gene expression) were also modified or absent in N. caerulescens, whereas salicylic acid production in response to infection was retained. These observations suggest that metal hyperaccumulation is incompatible with defence signalling through ROS and that, as metal hyperaccumulation became effective as a form of elemental defence, normal defence responses became progressively uncoupled from ROS signalling in N. caerulescens. PMID:23758201

  14. Thyroid hormone regulation of heme oxidation in the liver.

    PubMed Central

    Smith, T J; Drummond, G S; Kourides, I A; Kappas, A

    1982-01-01

    The effects of 3,5,3'-triiodothyronine (T3) on heme oxygenase (EC 1.14.99.3) activity and cytochrome P-450 content in liver were examined in thyroidectomized rats. T3, when administered for 5 days at a dose of 6 micrograms/100 g of body weight, stimulated basal heme oxygenase activity approximately equal to 2-fold compared to diluent-treated animals. The induction of heme oxygenase by cobalt heme also was enhanced approximately equal to 3-fold in T3-treated animals. T3 treatment lowered cytochrome P-450 content by approximately equal to 50% and potentiated the depletion of this heme protein after cobalt heme administration. Reverse T3 had no effect either on cytochrome P-450 content or on heme oxygenase activity in liver. The time course of response to a single dose of T3 (50 micrograms/100 g of body weight) revealed that both basal and cobalt heme-induced heme oxygenase activity peaked at 48 hr and that cytochrome P-450 content declined to approximately equal to 40% of controls at 96 hr. Examination of microsomal proteins by polyacrylamide gel electrophoresis after T3 treatment disclosed that major bands in the Mr approximately equal to 50,000-55,000 region were diminished. The administration of T3 together with SKF-525A, a compound known to complex with the heme prosthetic group of cytochrome P-450, resulted in partial preservation of these proteins. These data indicate that thyroid hormone can regulate heme oxygenase activity and concomitantly can lower cytochrome P-450 content in liver. The hormone also can act in a synergistic fashion to enhance the response of hepatic heme oxygenase to a chemical inducer of the enzyme. Thyroid status thus may be a potentially significant determinant of the rate of heme oxidation in the liver. Images PMID:6961431

  15. Sexual misbehaviour in the Australian Defence Force.

    PubMed

    Williams, Angela; Ranson, David

    2013-12-01

    It is clear from recent media reporting that serious issues have come to light regarding sexual misbehaviour matters within the Australian Defence Force. Subsequent reviews have indicated that these behaviours appear to have been more widespread than the initial media reports suggested and a number of reviews have been undertaken to better understand the problem and address the concerns of victims, Defence command, government and the community. If these problems are not addressed, there is a risk that recruitment to the Defence Forces may become problematic. The strong command structures within the Defence Forces can both exacerbate these misbehaviours through entrenching secrecy and at the same time have the capacity to provide a powerful leadership message that can change attitudes and reduce such misbehaviours. PMID:24597372

  16. The mechanical defence advantage of small seeds.

    PubMed

    Fricke, Evan C; Wright, S Joseph

    2016-08-01

    Seed size and toughness affect seed predators, and size-dependent investment in mechanical defence could affect relationships between seed size and predation. We tested how seed toughness and mechanical defence traits (tissue density and protective tissue content) are related to seed size among tropical forest species. Absolute toughness increased with seed size. However, smaller seeds had higher specific toughness both within and among species, with the smallest seeds requiring over 2000 times more energy per gram to break than the largest seeds. Investment in mechanical defence traits varied widely but independently of the toughness-mass allometry. Instead, a physical scaling relationship confers a toughness advantage on small seeds independent of selection on defence traits and without a direct cost. This scaling relationship may contribute to seed size diversity by decreasing fitness differences among large and small seeds. Allometric scaling of toughness reconciles predictions and conflicting empirical relationships between seed size and predation. PMID:27324185

  17. Light acclimation, retrograde signalling, cell death and immune defences in plants.

    PubMed

    Karpiński, Stanisław; Szechyńska-Hebda, Magdalena; Wituszyńska, Weronika; Burdiak, Paweł

    2013-04-01

    This review confronts the classical view of plant immune defence and light acclimation with recently published data. Earlier findings have linked plant immune defences to nucleotide-binding site leucine-rich repeat (NBS-LRR)-dependent recognition of pathogen effectors and to the role of plasma membrane-localized NADPH-dependent oxidoreductase (AtRbohD), reactive oxygen species (ROS) and salicylic acid (SA). However, recent results suggest that plant immune defence also depends on the absorption of excessive light energy and photorespiration. Rapid changes in light intensity and quality often cause the absorption of energy, which is in excess of that required for photosynthesis. Such excessive light energy is considered to be a factor triggering photoinhibition and disturbance in ROS/hormonal homeostasis, which leads to cell death in foliar tissues. We highlight here the tight crosstalk between ROS- and SA-dependent pathways leading to light acclimation, and defence responses leading to pathogen resistance. We also show that LESION SIMULATING DISEASE 1 (LSD1) regulates and integrates these processes. Moreover, we discuss the role of plastid-nucleus signal transduction, photorespiration, photoelectrochemical signalling and 'light memory' in the regulation of acclimation and immune defence responses. All of these results suggest that plants have evolved a genetic system that simultaneously regulates systemic acquired resistance (SAR), cell death and systemic acquired acclimation (SAA). PMID:23046215

  18. Hydrogen sulfide induces systemic tolerance to salinity and non-ionic osmotic stress in strawberry plants through modification of reactive species biosynthesis and transcriptional regulation of multiple defence pathways.

    PubMed

    Christou, Anastasis; Manganaris, George A; Papadopoulos, Ioannis; Fotopoulos, Vasileios

    2013-04-01

    Hydrogen sulfide (H2S) has been recently found to act as a potent priming agent. This study explored the hypothesis that hydroponic pretreatment of strawberry (Fragaria × ananassa cv. Camarosa) roots with a H2S donor, sodium hydrosulfide (NaHS; 100 μM for 48 h), could induce long-lasting priming effects and tolerance to subsequent exposure to 100mM NaCI or 10% (w/v) PEG-6000 for 7 d. Hydrogen sulfide pretreatment of roots resulted in increased leaf chlorophyll fluorescence, stomatal conductance and leaf relative water content as well as lower lipid peroxidation levels in comparison with plants directly subjected to salt and non-ionic osmotic stress, thus suggesting a systemic mitigating effect of H2S pretreatment to cellular damage derived from abiotic stress factors. In addition, root pretreatment with NaHS resulted in the minimization of oxidative and nitrosative stress in strawberry plants, manifested via lower levels of synthesis of NO and H(2)O(2) in leaves and the maintenance of high ascorbate and glutathione redox states, following subsequent salt and non-ionic osmotic stresses. Quantitative real-time RT-PCR gene expression analysis of key antioxidant (cAPX, CAT, MnSOD, GR), ascorbate and glutathione biosynthesis (GCS, GDH, GS), transcription factor (DREB), and salt overly sensitive (SOS) pathway (SOS2-like, SOS3-like, SOS4) genes suggests that H2S plays a pivotal role in the coordinated regulation of multiple transcriptional pathways. The ameliorative effects of H2S were more pronounced in strawberry plants subjected to both stress conditions immediately after NaHS root pretreatment, rather than in plants subjected to stress conditions 3 d after root pretreatment. Overall, H2S-pretreated plants managed to overcome the deleterious effects of salt and non-ionic osmotic stress by controlling oxidative and nitrosative cellular damage through increased performance of antioxidant mechanisms and the coordinated regulation of the SOS pathway, thus proposing a

  19. Hydrogen sulfide induces systemic tolerance to salinity and non-ionic osmotic stress in strawberry plants through modification of reactive species biosynthesis and transcriptional regulation of multiple defence pathways

    PubMed Central

    Christou, Anastasis; Manganaris, George A.; Papadopoulos, Ioannis; Fotopoulos, Vasileios

    2013-01-01

    Hydrogen sulfide (H2S) has been recently found to act as a potent priming agent. This study explored the hypothesis that hydroponic pretreatment of strawberry (Fragaria × ananassa cv. Camarosa) roots with a H2S donor, sodium hydrosulfide (NaHS; 100 μM for 48h), could induce long-lasting priming effects and tolerance to subsequent exposure to 100mM NaCI or 10% (w/v) PEG-6000 for 7 d. Hydrogen sulfide pretreatment of roots resulted in increased leaf chlorophyll fluorescence, stomatal conductance and leaf relative water content as well as lower lipid peroxidation levels in comparison with plants directly subjected to salt and non-ionic osmotic stress, thus suggesting a systemic mitigating effect of H2S pretreatment to cellular damage derived from abiotic stress factors. In addition, root pretreatment with NaHS resulted in the minimization of oxidative and nitrosative stress in strawberry plants, manifested via lower levels of synthesis of NO and H2O2 in leaves and the maintenance of high ascorbate and glutathione redox states, following subsequent salt and non-ionic osmotic stresses. Quantitative real-time RT-PCR gene expression analysis of key antioxidant (cAPX, CAT, MnSOD, GR), ascorbate and glutathione biosynthesis (GCS, GDH, GS), transcription factor (DREB), and salt overly sensitive (SOS) pathway (SOS2-like, SOS3-like, SOS4) genes suggests that H2S plays a pivotal role in the coordinated regulation of multiple transcriptional pathways. The ameliorative effects of H2S were more pronounced in strawberry plants subjected to both stress conditions immediately after NaHS root pretreatment, rather than in plants subjected to stress conditions 3 d after root pretreatment. Overall, H2S-pretreated plants managed to overcome the deleterious effects of salt and non-ionic osmotic stress by controlling oxidative and nitrosative cellular damage through increased performance of antioxidant mechanisms and the coordinated regulation of the SOS pathway, thus proposing a novel

  20. 40 CFR 52.231 - Regulations: Sulfur oxides.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Ambient Air Quality Standard for Sulfur Oxides. (1) Lake County Intrastate Region. (i) Lake County, APCD... previously approved under 40 CFR 52.223, is retained as applicable to sources other than sulfur...

  1. 40 CFR 52.231 - Regulations: Sulfur oxides.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Ambient Air Quality Standard for Sulfur Oxides. (1) Lake County Intrastate Region. (i) Lake County, APCD... previously approved under 40 CFR 52.223, is retained as applicable to sources other than sulfur...

  2. 40 CFR 52.231 - Regulations: Sulfur oxides.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Ambient Air Quality Standard for Sulfur Oxides. (1) Lake County Intrastate Region. (i) Lake County, APCD... previously approved under 40 CFR 52.223, is retained as applicable to sources other than sulfur...

  3. 40 CFR 52.231 - Regulations: Sulfur oxides.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Ambient Air Quality Standard for Sulfur Oxides. (1) Lake County Intrastate Region. (i) Lake County, APCD... previously approved under 40 CFR 52.223, is retained as applicable to sources other than sulfur...

  4. 40 CFR 52.231 - Regulations: Sulfur oxides.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Ambient Air Quality Standard for Sulfur Oxides. (1) Lake County Intrastate Region. (i) Lake County, APCD... previously approved under 40 CFR 52.223, is retained as applicable to sources other than sulfur...

  5. Capability engineering: transforming defence acquisition in Canada

    NASA Astrophysics Data System (ADS)

    Pagotto, Jack; Walker, Robert S.

    2004-07-01

    Capability engineering, a new methodology with the potential to transform defence planning and acquisition, is described. The impact of capability engineering on existing defence business processes and organizations is being explored in Canada during the course of a four-year Technology Demonstration Project called Collaborative Capability Definition, Engineering and Management (CapDEM). Having completed the first of three experimentation spirals within this project, a high-level capability engineering process model has been defined. The process begins by mapping strategic defence guidance onto defence capabilities, using architectural models that articulate the people, process and materiel requirements of each capability when viewed as a system-of-systems. For a selected capability, metrics are rigorously applied to these models to assess their ability to deliver the military capability outcomes required by a set of predefined tasks and force planning scenarios. By programming the modification of these tasks and planning scenarios over time according to evolving capability objectives, quantifiable capability gaps are identified, that in turn drive the process towards options to close these gaps. The implementation plan for these options constitutes a capability evolution roadmap to support defence-investment decisions. Capability engineering is viewed as an essential enabler to meeting the objective of improved capability management, subsuming the functions of capability generation, sustainment and employment.

  6. Regulation of antioxidant enzymes in lung after oxidant injury.

    PubMed Central

    Quinlan, T; Spivack, S; Mossman, B T

    1994-01-01

    Studies have implicated active oxygen species (AOS) in the pathogenesis of various lung diseases. Many chemical and physical agents in the environment are potent generators of AOS, including ozone, hyperoxia, mineral dusts, paraquat, etc. These agents produce AOS by different mechanisms, but frequently the lung is the primary target of toxicity, and exposure results in damage to lung tissue to varying degrees. The lung has developed defenses to AOS-mediated damage, which include antioxidant enzymes, the superoxide dismutases [copper-zinc (CuZnSOD) and manganese-containing (MnSOD)], catalase, and glutathione peroxidase (GPX). In this review, antioxidant defenses to environmental stresses in the lung as well as in isolated pulmonary cells following exposure to a number of different oxidants, are summarized. Each oxidant appears to induce a different pattern of antioxidant enzyme response in the lung, although some common trends, i.e., induction of MnSOD following oxidants inducing inflammation or pulmonary fibrosis, in responses to oxidants occur. Responses may vary between the different cell types in the lung as a function of cell-cycle or other factors. Increases in MnSOD mRNA or immunoreactive protein in response to certain oxidants may serve as a biomarker of AOS-mediated damage in the lung. Images Figure 3. PMID:7523104

  7. Nitric oxide synthase in macula densa regulates glomerular capillary pressure.

    PubMed Central

    Wilcox, C S; Welch, W J; Murad, F; Gross, S S; Taylor, G; Levi, R; Schmidt, H H

    1992-01-01

    Tubular-fluid reabsorption by specialized cells of the nephron at the junction of the ascending limb of the loop of Henle and the distal convoluted tubule, termed the macula densa, releases compounds causing vasoconstriction of the adjacent afferent arteriole. Activation of this tubuloglomerular feedback response reduces glomerular capillary pressure of the nephron and, hence, the glomerular filtration rate. The tubuloglomerular feedback response functions in a negative-feedback mode to relate glomerular capillary pressure to tubular-fluid delivery and reabsorption. This system has been implicated in renal autoregulation, renin release, and longterm body fluid and blood-pressure homeostasis. Here we report that arginine-derived nitric oxide, generated in the macula densa, is an additional intercellular signaling molecule that is released during tubular-fluid reabsorption and counters the vasoconstriction of the afferent arteriole. Antibody to rat cerebellar constitutive nitric oxide synthase stained rat macula densa cells specifically. Microperfusion of the macula densa segment of single nephrons with N omega-methyl-L-arginine (an inhibitor of nitric oxide synthase) or with pyocyanin (a lipid-soluble inhibitor of endothelium-derived relaxation factor) showed that generation of nitric oxide can vasodilate the afferent arteriole and increase glomerular capillary pressure; this effect was blocked by drugs that prevent tubular-fluid reabsorption. We conclude that nitric oxide synthase in macula densa cells is activated by tubular-fluid reabsorption and mediates a vasodilating component to the tubuloglomerular feedback response. These findings imply a role for arginine-derived nitric oxide in body fluid-volume and blood-pressure homeostasis, in addition to its established roles in modulation of vascular tone by the endothelium and in neurotransmission. Images PMID:1281548

  8. Interleukin-12 gene-expression of macrophages is regulated by nitric oxide.

    PubMed

    Rothe, H; Hartmann, B; Geerlings, P; Kolb, H

    1996-07-01

    Interleukin-12 is a heterodimeric cytokine, mainly produced by macrophages. In our present study we demonstrate that interleukin-12 expression is regulated by nitric oxide. Incubation of the macrophage cell line IC 21 with interferon-gamma gave rise to both interleukin-12 p40 mRNA and nitric oxide production. The concurrent addition of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine inhibited nitrite production and in parallel completely suppressed interleukin-12 p40 mRNA formation. This indicated that endogenous nitric oxide synthase activity was required for IL-12 p40 gene expression. Exposure of the cells towards the nitric oxide generating compounds nitroprusside or S-nitroso-N-acetyl-penicillamine induced interleukin-12 p40 mRNA. Maximal mRNA levels were induced with nitric oxide donors at 1 microM concentration. We conclude that nitric oxide may exert an autoregulatory and paracrine control of interleukin-12 gene expression. PMID:8694804

  9. The Pseudomonas aeruginosa oxidative stress regulator OxyR influences production of pyocyanin and rhamnolipids: protective role of pyocyanin.

    PubMed

    Vinckx, Tiffany; Wei, Qing; Matthijs, Sandra; Cornelis, Pierre

    2010-03-01

    The LysR-type transcriptional regulator (LTTR) OxyR orchestrates the defence of the opportunistic pathogen Pseudomonas aeruginosa against reactive oxygen species. In previous work we also demonstrated that OxyR is needed for the utilization of the ferrisiderophore pyoverdine, stressing the importance of this regulator. Here, we show that an oxyR mutant is unable to swarm on agar plates, probably as a consequence of absence of production of rhamnolipid surfactant molecules. Another obvious phenotypic change was the increased production of the phenazine redox-active molecule pyocyanin in the oxyR mutant. As already described, the oxyR mutant could not grow in LB medium, unless high numbers of cells (>10( 8) ml(-1)) were inoculated. However, its growth in Pseudomonas P agar (King's A), a medium inducing pyocyanin production, was like that of the wild-type, suggesting a protective action of this redox-active phenazine compound. This was confirmed by the restoration of the capacity to grow in LB medium upon addition of pure pyocyanin. Although both rhamnolipid and pyocyanin production are controlled by quorum sensing, no obvious changes were observed in the production of N-acylhomoserine lactones or the Pseudomonas quinolone signal (PQS). Complementation of rhamnolipid production and motility, and restoration of normal pyocyanin levels, was only possible when the oxyR gene was in single copy, while pyocyanin levels were increased when oxyR was present in a multicopy vector. Conversely, plating efficiency was increased only when the oxyR gene was present in multicopy, but not when in single copy in the chromosome, due to lower expression of oxyR compared with the wild-type, suggesting that some phenotypes are differently affected in function to the levels of OxyR molecules in the cell. Analysis of transcripts of oxidative stress-response enzymes showed a strong decrease of katB, ahpC and ahpB expression in the oxyR mutant grown in LB, but this was not the case when the

  10. 40 CFR 52.1675 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) of the Act, and 40 CFR part 51 (relating to approval of and revisions to State implementation plans... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Control strategy and regulations... § 52.1675 Control strategy and regulations: Sulfur oxides. (a)-(c) (d) Section 225.3(e) of Subchapter...

  11. 40 CFR 52.1601 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Control strategy and regulations... § 52.1601 Control strategy and regulations: Sulfur oxides. (a) The applicable limitation on the sulfur... Deepwaters Deepwaters 5/7, 7/9, 3/5, 4/6. Public Service Electric & Gas Essex Newark All. Do...

  12. 40 CFR 52.1601 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 4 2012-07-01 2012-07-01 false Control strategy and regulations... § 52.1601 Control strategy and regulations: Sulfur oxides. (a) The applicable limitation on the sulfur... Deepwaters Deepwaters 5/7, 7/9, 3/5, 4/6. Public Service Electric & Gas Essex Newark All. Do...

  13. 40 CFR 52.1601 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy and regulations... § 52.1601 Control strategy and regulations: Sulfur oxides. (a) The applicable limitation on the sulfur... Deepwaters Deepwaters 5/7, 7/9, 3/5, 4/6. Public Service Electric & Gas Essex Newark All. Do...

  14. 40 CFR 52.1601 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 4 2014-07-01 2014-07-01 false Control strategy and regulations... § 52.1601 Control strategy and regulations: Sulfur oxides. (a) The applicable limitation on the sulfur... Deepwaters Deepwaters 5/7, 7/9, 3/5, 4/6. Public Service Electric & Gas Essex Newark All. Do...

  15. Protein kinase Cδ regulates endothelial nitric oxide synthase expression via Akt activation and nitric oxide generation

    PubMed Central

    Sud, Neetu; Wedgwood, Stephen; Black, Stephen M.

    2008-01-01

    In this study, we explore the roles of the delta isoform of PKC (PKCδ) in the regulation of endothelial nitric oxide synthase (eNOS) activity in pulmonary arterial endothelial cells isolated from fetal lambs (FPAECs). Pharmacological inhibition of PKCδ with either rottlerin or with the peptide, δV1-1, acutely attenuated NO production, and this was associated with a decrease in phosphorylation of eNOS at Ser1177 (S1177). The chronic effects of PKCδ inhibition using either rottlerin or the overexpression of a dominant negative PKCδ mutant included the downregulation of eNOS gene expression that was manifested by a decrease in both eNOS promoter activity and protein expression after 24 h of treatment. We also found that PKCδ inhibition blunted Akt activation as observed by a reduction in phosphorylated Akt at position Ser473. Thus, we conclude that PKCδ is actively involved in the activation of Akt. To determine the effect of Akt on eNOS signaling, we overexpressed a dominant negative mutant of Akt and determined its effect of NO generation, eNOS expression, and phosphorylation of eNOS at S1177. Our results demonstrated that Akt inhibition was associated with decreased NO production that correlated with reduced phosphorylation of eNOS at S1177, and decreased eNOS promoter activity. We next evaluated the effect of endogenously produced NO on eNOS expression by incubating FPAECs with the eNOS inhibitor 2-ethyl-2-thiopseudourea (ETU). ETU significantly inhibited NO production, eNOS promoter activity, and eNOS protein levels. Together, our data indicate involvement of PKCδ-mediated Akt activation and NO generation in maintaining eNOS expression. PMID:18192589

  16. Nitric Oxide Regulates Mitochondrial Fatty Acid Metabolism through Reversible Protein S-Nitrosylation **

    PubMed Central

    Doulias, Paschalis-Thomas; Tenopoulou, Margarita; Greene, Jennifer L.; Raju, Karthik; Ischiropoulos, Harry

    2014-01-01

    Cysteine S-nitrosylation is a posttranslational modification by which nitric oxide regulates protein function and signaling. Studies of individual proteins have elucidated specific functional roles for S-nitrosylation, but knowledge of the extent of endogenous S-nitrosylation, the sites that are nitrosylated, and the regulatory consequences of S-nitrosylation remains limited. We used mass spectrometry-based methodologies to identify 1011 S-nitrosocysteine residues in 647 proteins in various mouse tissues. We uncovered selective S-nitrosylation of enzymes participating in glycolysis, gluconeogenesis, tricarboxylic acid cycle, and oxidative phosphorylation, indicating that this posttranslational modification may regulate metabolism and mitochondrial bioenergetics. S-nitrosylation of the liver enzyme VLCAD (very long acyl-CoA dehydrogenase) at Cys238, which was absent in mice lacking endothelial nitric oxide synthase, improved its catalytic efficiency. These data implicate protein S-nitrosylation in the regulation of β-oxidation of fatty acids in mitochondria. PMID:23281369

  17. Relationships between isotopic values and oxidative status: insights from populations of gentoo penguins.

    PubMed

    Beaulieu, Michaël; González-Acuña, Daniel; Thierry, Anne-Mathilde; Polito, Michael J

    2015-04-01

    Feeding strategies can affect the balance between the production of reactive oxygen species and antioxidant defences (i.e. oxidative status). This is ecologically relevant, as variation in oxidative status can in turn strongly affect fitness. However, how animals regulate their oxidative status through their feeding behaviour under natural conditions remains poorly understood. Thus, relating the isotopic values of free-ranging animals to their oxidative status may prove useful. Here, we considered three colonies of gentoo penguins (Pygoscelis papua) in which we measured (1) δ(13)C and δ(15)N values, and (2) antioxidant defences and oxidative damage. We found that colonies with the highest δ(13)C and δ(15)N values also had the highest levels of antioxidant defences and oxidative damage, resulting in positive relationships between isotopic values and markers of oxidative status. As a result, colony segregation in terms of isotopic values was reflected by segregation in terms of oxidative markers (although more markedly for oxidative damage than for antioxidant defences). Interestingly, variation in the estimated contribution of krill in the diet of penguins followed an opposite pattern to that observed for markers of oxidative status, providing evidence that inter-population differences in terms of foraging strategies can result in inter-population differences in terms of oxidative status. More studies examining simultaneously oxidative status, isotopic signature, foraging behaviour and food allocation between parents and young are, however, needed to understand better the interplay between the foraging strategies adopted by animals in their natural habitat and their oxidative status. PMID:25698143

  18. Protein oxidation mediated by heme-induced active site conversion specific for heme-regulated transcription factor, iron response regulator

    PubMed Central

    Kitatsuji, Chihiro; Izumi, Kozue; Nambu, Shusuke; Kurogochi, Masaki; Uchida, Takeshi; Nishimura, Shin-Ichiro; Iwai, Kazuhiro; O’Brian, Mark R.; Ikeda-Saito, Masao; Ishimori, Koichiro

    2016-01-01

    The Bradyrhizobium japonicum transcriptional regulator Irr (iron response regulator) is a key regulator of the iron homeostasis, which is degraded in response to heme binding via a mechanism that involves oxidative modification of the protein. Here, we show that heme-bound Irr activates O2 to form highly reactive oxygen species (ROS) with the “active site conversion” from heme iron to non-heme iron to degrade itself. In the presence of heme and reductant, the ROS scavenging experiments show that Irr generates H2O2 from O2 as found for other hemoproteins, but H2O2 is less effective in oxidizing the peptide, and further activation of H2O2 is suggested. Interestingly, we find a time-dependent decrease of the intensity of the Soret band and appearance of the characteristic EPR signal at g = 4.3 during the oxidation, showing the heme degradation and the successive formation of a non-heme iron site. Together with the mutational studies, we here propose a novel “two-step self-oxidative modification” mechanism, during which O2 is activated to form H2O2 at the heme regulatory motif (HRM) site and the generated H2O2 is further converted into more reactive species such as ·OH at the non-heme iron site in the His-cluster region formed by the active site conversion. PMID:26729068

  19. A Dirofilaria immitis Polyprotein Up-Regulates Nitric Oxide Production

    PubMed Central

    Tezuka, Hiroyuki; Imai, Shinjiro; Tsukidate, Setsuko; Fujita, Koichiro

    2002-01-01

    We investigated the effect of recombinant Dirofilaria immitis polyprotein (rDiAg) on nitric oxide (NO) production by peritoneal macrophages. rDiAg induced NO production by macrophages from wild-type and lipopolysaccharide-hyporesponsive C3H/HeJ, but not CD40−/−, mice. These results suggest that CD40 is involved in rDiAg-driven NO production by murine macrophages. PMID:12183583

  20. Role of Nitric Oxide in the Regulation of Renin and Vasopressin Secretion

    NASA Technical Reports Server (NTRS)

    Reid, Ian A.

    1994-01-01

    Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, immune, and other systems. Nitric oxide has also been implicated in the control of the secretion of hormones by the pancreas, hypothalamus, and anterior pituitary gland, and evidence is accumulating that it contributes to the regulation of the secretion of renin and vasopressin, hormones that play key roles in the control of sodium and water balance. Several lines of evidence have implicated nitric oxide in the control of renin secretion. The enzyme nitric oxide synthase is present in vascular and tubular elements of the kidney, particularly in cells of the macula densa, a structure that plays an important role in the control of renin secretion. Guanylyl cyclase, a major target for nitric oxide, is also present in the kidney. Drugs that inhibit nitric oxide synthesis generally suppress renin release in vivo and in vitro, suggesting a stimulatory role for the L-arginine/nitric oxide pathway in the control of renin secretion. Under some conditions, however, blockade of nitric oxide synthesis increases renin secretion. Recent studies indicate that nitric oxide not only contributes to the regulation of basal renin secretion, but also participates in the renin secretory responses to activation of the renal baroreceptor, macula densa, and beta adrenoceptor mechanisms that regulate renin secretion. Histochemical and immunocytochemical studies have revealed the presence of nitric oxide synthase in the supraoptic and paraventricular nuclei of the hypothalamus and in the posterior pituitary gland. Colocalization of nitric oxide synthase and vasopressin has been demonstrated in some hypothalamic neurons. Nitric oxide synthase activity in the hypothalamus and pituitary is increased by maneuvers known to stimulate vasopressin secretion, including salt loading and dehydration, Administration of L-arginine and nitric

  1. Aloin Protects Skin Fibroblasts from Heat Stress-Induced Oxidative Stress Damage by Regulating the Oxidative Defense System.

    PubMed

    Liu, Fu-Wei; Liu, Fu-Chao; Wang, Yu-Ren; Tsai, Hsin-I; Yu, Huang-Ping

    2015-01-01

    Oxidative stress is commonly involved in the pathogenesis of skin damage induced by environmental factors, such as heat stress. Skin fibroblasts are responsible for the connective tissue regeneration and the skin recovery from injury. Aloin, a bioactive compound in Aloe vera, has been reported to have various pharmacological activities, such as anti-inflammatory effects. The aim of this study was to investigate the protective effect of aloin against heat stress-mediated oxidative stress in human skin fibroblast Hs68 cells. Hs68 cells were first incubated at 43°C for 30 min to mimic heat stress. The study was further examined if aloin has any effect on heat stress-induced oxidative stress. We found that aloin protected Hs68 cells against heat stress-induced damage, as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assay. Aloin protected Hs68 cells by regulating reactive oxygen species production and increasing the levels of glutathione, cytosolic and mitochondrial superoxide dismutase. Aloin also prevented the elevation of thiobarbituric acid reactive substances and the reduction of 8-OH-dG induced by heat stress. These results indicated that aloin protected human skin fibroblasts from heat stress-induced oxidative stress damage by regulating the oxidative defense system. PMID:26637174

  2. Aloin Protects Skin Fibroblasts from Heat Stress-Induced Oxidative Stress Damage by Regulating the Oxidative Defense System

    PubMed Central

    Wang, Yu-Ren; Tsai, Hsin-I; Yu, Huang-Ping

    2015-01-01

    Oxidative stress is commonly involved in the pathogenesis of skin damage induced by environmental factors, such as heat stress. Skin fibroblasts are responsible for the connective tissue regeneration and the skin recovery from injury. Aloin, a bioactive compound in Aloe vera, has been reported to have various pharmacological activities, such as anti-inflammatory effects. The aim of this study was to investigate the protective effect of aloin against heat stress-mediated oxidative stress in human skin fibroblast Hs68 cells. Hs68 cells were first incubated at 43°C for 30 min to mimic heat stress. The study was further examined if aloin has any effect on heat stress-induced oxidative stress. We found that aloin protected Hs68 cells against heat stress-induced damage, as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assay. Aloin protected Hs68 cells by regulating reactive oxygen species production and increasing the levels of glutathione, cytosolic and mitochondrial superoxide dismutase. Aloin also prevented the elevation of thiobarbituric acid reactive substances and the reduction of 8-OH-dG induced by heat stress. These results indicated that aloin protected human skin fibroblasts from heat stress-induced oxidative stress damage by regulating the oxidative defense system. PMID:26637174

  3. Mitochondrial oxidant stress in locus coeruleus is regulated by activity and nitric oxide synthase.

    PubMed

    Sanchez-Padilla, Javier; Guzman, Jaime N; Ilijic, Ema; Kondapalli, Jyothisri; Galtieri, Daniel J; Yang, Ben; Schieber, Simon; Oertel, Wolfgang; Wokosin, David; Schumacker, Paul T; Surmeier, D James

    2014-06-01

    Loss of noradrenergic locus coeruleus (LC) neurons is a prominent feature of aging-related neurodegenerative diseases, such as Parkinson's disease (PD). The basis of this vulnerability is not understood. To explore possible physiological determinants, we studied LC neurons using electrophysiological and optical approaches in ex vivo mouse brain slices. We found that autonomous activity in LC neurons was accompanied by oscillations in dendritic Ca(2+) concentration that were attributable to the opening of L-type Ca(2+) channels. This oscillation elevated mitochondrial oxidant stress and was attenuated by inhibition of nitric oxide synthase. The relationship between activity and stress was malleable, as arousal and carbon dioxide increased the spike rate but differentially affected mitochondrial oxidant stress. Oxidant stress was also increased in an animal model of PD. Thus, our results point to activity-dependent Ca(2+) entry and a resulting mitochondrial oxidant stress as factors contributing to the vulnerability of LC neurons. PMID:24816140

  4. Mitochondrial oxidant stress in locus coeruleus is regulated by activity and nitric oxide synthase

    PubMed Central

    Sanchez–Padilla, J.; Guzman, J.N.; Ilijic, E.; Kondapalli, J.; Galtieri, D.J.; Yang, B.; Schieber, S.; Oertel, W.; Wokosin, D.; Schumacker, P. T.; Surmeier, D. J.

    2014-01-01

    Summary Loss of noradrenergic locus coeruleus (LC) neurons is a prominent feature of aging–related neurodegenerative diseases, like Parkinson’s disease (PD). The basis of this vulnerability is not understood. To explore possible physiological determinants, LC neurons were studied using electrophysiological and optical approaches in ex vivo mouse brain slices. These studies revealed that autonomous activity in LC neurons was accompanied by oscillations in dendritic Ca2+ concentration attributable to opening of L–type Ca2+ channels. This oscillation elevated mitochondrial oxidant stress and was attenuated by inhibition of nitric oxide synthase. The relationship between activity and stress was malleable, as arousal and carbon dioxide, each increased the spike rate, but differentially affected mitochondrial oxidant stress. Oxidant stress also was increased in an animal model of PD. Thus, our results point to activity–dependent Ca2+ entry and a resulting mitochondrial oxidant stress as factors contributing to the vulnerability of LC neurons. PMID:24816140

  5. Does dissolved organic carbon regulate biological methane oxidation in semiarid soils?

    PubMed

    Sullivan, Benjamin W; Selmants, Paul C; Hart, Stephen C

    2013-07-01

    In humid ecosystems, the rate of methane (CH4 ) oxidation by soil-dwelling methane-oxidizing bacteria (MOB) is controlled by soil texture and soil water holding capacity, both of which limit the diffusion of atmospheric CH4 into the soil. However, it remains unclear whether these same mechanisms control CH4 oxidation in more arid soils. This study was designed to measure the proximate controls of potential CH4 oxidation in semiarid soils during different seasons. Using a unique and well-constrained 3-million-year-old semiarid substrate age gradient, we were able to hold state factors constant while exploring the relationship between seasonal potential CH4 oxidation rates and soil texture, soil water holding capacity, and dissolved organic carbon (DOC). We measured unexpectedly higher rates of potential CH4 oxidation in the wet season than the dry season. Although other studies have attributed low CH4 oxidation rates in dry soils to desiccation of MOB, we present several lines of evidence that this may be inaccurate. We found that soil DOC concentration explained CH4 oxidation rates better than soil physical factors that regulate the diffusion of CH4 from the atmosphere into the soil. We show evidence that MOB facultatively incorporated isotopically labeled glucose into their cells, and MOB utilized glucose in a pattern among our study sites that was similar to wet-season CH4 oxidation rates. This evidence suggests that DOC, which is utilized by MOB in other environments with varying effects on CH4 oxidation rates, may be an important regulator of CH4 oxidation rates in semiarid soils. Our collective understanding of the facultative use of DOC by MOB is still in its infancy, but our results suggest it may be an important factor controlling CH4 oxidation in soils from dry ecosystems. PMID:23526765

  6. In Defence of the Classroom Science Demonstration

    ERIC Educational Resources Information Center

    McCrory, Paul

    2013-01-01

    Science demonstrations are often criticised for their passive nature, their gratuitous exploitation and their limited ability to develop scientific knowledge and understanding. This article is intended to present a robust defence of the use of demonstrations in the classroom by identifying some of their unique and powerful benefits--practical,…

  7. The Man-in-the-Middle Defence

    NASA Astrophysics Data System (ADS)

    Anderson, Ross

    The man-in-the-middle defence is all about rehabilitating Charlie. For 20 years we’ve worried about this guy in the middle, Charlie, who’s forever intercalating himself into the communications between Alice and Bob, and people have been very judgemental about poor Charlie, saying that Charlie is a wicked person. Well, we’re not entirely convinced.

  8. Malaysian Defence and E-Learning

    ERIC Educational Resources Information Center

    Juhary, Jowati binti

    2005-01-01

    This paper begins with an analysis of the changing security scenario in the Asian region, with special focus on Malaysian defence strategies and foreign policies. Beginning in the mid 1990s, the Malaysian government shifted its attention away from the counter insurgency strategies of the early decades of independence to focus on wider questions of…

  9. Host defence mediates interspecific competition in ectoparasites.

    PubMed

    Bush, Sarah E; Malenke, Jael R

    2008-05-01

    1. Interspecific competition influences which, how many and where species coexist in biological communities. Interactions between species in different trophic levels can mediate interspecific competition; e.g. predators are known to reduce competition between prey species by suppressing their population sizes. A parallel phenomenon may take place in host-parasite systems, with host defence mediating competition between parasite species. 2. We experimentally investigated the impact of host defence (preening) on competitive interactions between two species of feather-feeding lice: 'wing' lice Columbicola columbae and 'body' lice Campanulotes compar. Both species are host-specific parasites that co-occur on rock pigeons Columba livia. 3. We show that wing lice and body lice compete and that host defence mediates the magnitude of this competitive interaction. 4. Competition is asymmetrical; wing louse populations are negatively impacted by body lice, but not vice versa. This competitive asymmetry is consistent with the fact that body lice predominate in microhabitats on the host's body that offer the most food and the most space. 5. Our results indicate that host-defence-mediated competition can influence the structure of parasite communities and may play a part in the evolution of parasite diversity. PMID:18194262

  10. Testing the optimal defence hypothesis for two indirect defences: extrafloral nectar and volatile organic compounds

    PubMed Central

    Radhika, Venkatesan; Kost, Christian; Bartram, Stefan; Heil, Martin

    2008-01-01

    Many plants respond to herbivory with an increased production of extrafloral nectar (EFN) and/or volatile organic compounds (VOCs) to attract predatory arthropods as an indirect defensive strategy. In this study, we tested whether these two indirect defences fit the optimal defence hypothesis (ODH), which predicts the within-plant allocation of anti-herbivore defences according to trade-offs between growth and defence. Using jasmonic acid-induced plants of Phaseolus lunatus and Ricinus communis, we tested whether the within-plant distribution pattern of these two indirect defences reflects the fitness value of the respective plant parts. Furthermore, we quantified photosynthetic rates and followed the within-plant transport of assimilates with 13C labelling experiments. EFN secretion and VOC emission were highest in younger leaves. Moreover, the photosynthetic rate increased with leaf age, and pulse-labelling experiments suggested transport of carbon to younger leaves. Our results demonstrate that the ODH can explain the within-plant allocation pattern of both indirect defences studied. PMID:18493790

  11. Responses of foliar antioxidative and photoprotective defence systems of trees to drought: a meta-analysis.

    PubMed

    Wujeska, Agnieszka; Bossinger, Gerd; Tausz, Michael

    2013-10-01

    Current climate change predictions hint to more frequent extreme weather events, including extended droughts, making better understanding of the impacts of water stress on trees even more important. At the individual plant level, stomatal closure as a result of water deficit leads to reduced CO2 availability in the leaf, which can lead to photo-oxidative stress. Photorespiration and the Mehler reaction can maintain electron transport rates under low internal CO2, but result in production of reactive oxygen species (ROS). If electron consumption is decreased, upstream photochemical processes can be affected and light energy is absorbed in excess of photochemical requirements. Trees evolved to cope with excess energy and elevated concentration of ROS by activating photoprotective and antioxidative defence systems. The meta-analysis we present here assessed responses of these defence systems reported in 50 studies. We found responses to vary depending on stress intensity, foliage type and habitat, and on whether experiments were done in the field or in controlled environments. In general, drought increased concentrations of antioxidants and photoprotective pigments. However, severe stress caused degradation of antioxidant concentrations and oxidation of antioxidant pools. Evergreen trees seemed to preferentially reinforce membrane-bound protection systems zeaxanthin and tocopherol, whereas deciduous species showed greater responses in water-soluble antioxidants ascorbic acid and glutathione. Trees and shrubs from arid versus humid habitats vary in their antioxidative and photoprotective defence responses. In field experiments, drought had greater effects on some defence compounds than under controlled conditions. PMID:24178981

  12. Regulation of Methane Oxidation in a Freshwater Wetland by Water Table Changes and Anoxia

    NASA Technical Reports Server (NTRS)

    Roslev, Peter; King, Gary M.

    1996-01-01

    The effects of water table fluctuations and anoxia on methane emission and methane oxidation were studied in a freshwater marsh. Seasonal aerobic methane oxidation rates varied between 15% and 76% of the potential diffusive methane flux (diffusive flux in the absence of aerobic oxidation). On an annual basis, approximately 43% of the methane diffusing into the oxic zone was oxidized before reaching the atmosphere. The highest methane oxidation was observed when the water table was below the peat surface. This was confirmed in laboratory experiments where short-term decreases in water table levels increased methane oxidation but also net methane emission. Although methane emission was generally not observed during the winter, stems of soft rush (Juncus effusus) emitted methane when the marsh was ice covered. Indigenous methanotrophic bacteria from the wetiand studied were relatively anoxia tolerant. Surface peat incubated under anoxic conditions maintained 30% of the initial methane oxidation capacity after 32 days of anoxia. Methanotrophs from anoxic peat initiated aerobic methane oxidation relatively quickly after oxygen addition (1-7 hours). These results were supported by culture experiments with the methanotroph Methylosinus trichosporium OB3b. This organism maintained a greater capacity for aerobic methane oxidation when starved under anoxic compared to oxic conditions. Anoxic incubation of M. trichosporium OB3b in the presence of sulfide (2 mM) and a low redox potential (-110 mV) did not decrease the capacity for methane oxidation relative to anoxic cultures incubated without sulfide. The results suggest that aerobic methane oxidation was a major regulator of seasonal methane emission front the investigated wetland. The observed water table fluctuations affected net methane oxidation presumably due to associated changes in oxygen gradients. However, changes from oxic to anoxic conditions in situ had relatively little effect on survival of the methanotrophic

  13. Rusi/Brassey's defence yearbook 1987 97th edition

    SciTech Connect

    Not Available

    1987-01-01

    This annual review of defence and strategic affairs provides an up-to-date survey of international strategic affairs, contemporary weapons and developments and future trends. For all those involved in defence studies, university and public libraries and the general public. Contents: The Year Ahead; The Middle East; NATO; The Soviet Union and Eastern Europe; UK defence policy; The Issues: What is SDI.; Will SDI help. A military view; SDI-the industrial implications; Conventional defence, a military view; An alternative view; European armaments cooperation; Terrorism; Sri Lanka: the Tamils; Israel 1986; The Iran/Iraq war; Arab view; South Africa; Chronology of conflict; Defence literature; Arms control; Nuclear weapons; Characteristics.

  14. Oxidative stress in the haematopoietic niche regulates the cellular immune response in Drosophila.

    PubMed

    Sinenko, Sergey A; Shim, Jiwon; Banerjee, Utpal

    2012-01-01

    Oxidative stress induced by high levels of reactive oxygen species (ROS) is associated with the development of different pathological conditions, including cancers and autoimmune diseases. We analysed whether oxidatively challenged tissue can have systemic effects on the development of cellular immune responses using Drosophila as a model system. Indeed, the haematopoietic niche that normally maintains blood progenitors can sense oxidative stress and regulate the cellular immune response. Pathogen infection induces ROS in the niche cells, resulting in the secretion of an epidermal growth factor-like cytokine signal that leads to the differentiation of specialized cells involved in innate immune responses. PMID:22134547

  15. Regulation of A20 and other OTU deubiquitinases by reversible oxidation

    PubMed Central

    Kulathu, Yogesh; Garcia, Francisco J.; Mevissen, Tycho E.T.; Busch, Martin; Arnaudo, Nadia; Carroll, Kate S.; Barford, David; Komander, David

    2013-01-01

    Protein ubiquitination is a highly versatile posttranslational modification that regulates as diverse processes as protein degradation and kinase activation. Deubiquitinases hydrolyse ubiquitin modifications from proteins and are hence key regulators of the ubiquitin system. Ovarian Tumour (OTU) deubiquitinases comprise a family of fourteen human enzymes, many of which regulate cellular signalling pathways. OTU deubiquitinases are cysteine proteases that cleave polyubiquitin (polyUb) chains in vitro and in cells, but little is currently known about their regulation. Here we show that OTU deubiquitinases are susceptible to reversible oxidation of the catalytic cysteine residue. High-resolution crystal structures of the catalytic domain of A20 in four different oxidation states reveal that the reversible form of A20 oxidation is a cysteine sulphenic acid intermediate, which is stabilised by the architecture of the catalytic centre. Using chemical tools to detect sulphenic acid intermediates, we show that many OTU deubiquitinases undergo reversible oxidation upon treatment with H2O2, revealing a new mechanism to regulate deubiquitinase activity. PMID:23463012

  16. The Capsicum annuum class IV chitinase ChitIV interacts with receptor-like cytoplasmic protein kinase PIK1 to accelerate PIK1-triggered cell death and defence responses

    PubMed Central

    Kim, Dae Sung; Kim, Nak Hyun; Hwang, Byung Kook

    2015-01-01

    The pepper receptor-like cytoplasmic protein kinase, CaPIK1, which mediates signalling of plant cell death and defence responses was previously identified. Here, the identification of a class IV chitinase, CaChitIV, from pepper plants (Capsicum annuum), which interacts with CaPIK1 and promotes CaPIK1-triggered cell death and defence responses, is reported. CaChitIV contains a signal peptide, chitin-binding domain, and glycol hydrolase domain. CaChitIV expression was up-regulated by Xanthomonas campestris pv. vesicatoria (Xcv) infection. Notably, avirulent Xcv infection rapidly induced CaChitIV expression in pepper leaves. Bimolecular fluorescence complementation and co-immunoprecipitation revealed that CaPIK1 interacts with CaChitIV in planta, and that the CaPIK1–CaChitIV complex is localized mainly in the cytoplasm and plasma membrane. CaChitIV is also localized in the endoplasmic reticulum. Transient co-expression of CaChitIV with CaPIK1 enhanced CaPIK1-triggered cell death response and reactive oxygen species (ROS) and nitric oxide (NO) bursts. Co-silencing of both CaChitIV and CaPIK1 in pepper plants conferred enhanced susceptibility to Xcv infection, which was accompanied by a reduced induction of cell death response, ROS and NO bursts, and defence response genes. Ectopic expression of CaPIK1 in Arabidopsis enhanced basal resistance to Hyaloperonospora arabidopsidis infection. Together, the results suggest that CaChitIV positively regulates CaPIK1-triggered cell death and defence responses through its interaction with CaPIK1. PMID:25694549

  17. Nitric oxide-mediated blood flow regulation as affected by smoking and nicotine.

    PubMed

    Toda, Noboru; Toda, Hiroshi

    2010-12-15

    Cigarette smoking is a major risk factor for atherosclerosis, cerebral and coronary vascular diseases, hypertension, and diabetes mellitus. Chronic smoking impairs endothelial function by decreasing the formation of nitric oxide and increasing the degradation of nitric oxide via generation of oxygen free radicals. Nitric oxide liberated from efferent nitrergic nerves is also involved in vasodilatation, increased regional blood flow, and hypotension that are impaired through nitric oxide sequestering by smoking-induced factors. Influence of smoking on nitric oxide-induced blood flow regulation is not necessarily the same in all organs and tissues. However, human studies are limited mainly to the forearm blood flow measurement that assesses endothelial function under basal and stimulated conditions and also determination of penile tumescence and erection in response to endothelial and neuronal nitric oxide. Therefore, information about blood flow regulation in other organs, such as the brain and placenta, has been provided mainly from studies on experimental animals. Nicotine, a major constituent of cigarette smoke, acutely dilates cerebral arteries and arterioles through nitric oxide liberated from nitrergic neurons, but chronically interferes with endothelial function in various vasculatures, both being noted in studies on experimental animals. Cigarette smoke constituents other than nicotine also have some vascular actions. Not only active but also passive smoking is undoubtedly harmful for both the smokers themselves and their neighbors, who should bear in mind that they can face serious diseases in the future, which may result in lengthy hospitalization, and a shortened lifespan. PMID:20868673

  18. Soil formate regulates the fungal nitrous oxide emission pathway.

    PubMed

    Ma, W K; Farrell, R E; Siciliano, S D

    2008-11-01

    Fungal activity is a major driver in the global nitrogen cycle, and mounting evidence suggests that fungal denitrification activity contributes significantly to soil emissions of the greenhouse gas nitrous oxide (N(2)O). The metabolic pathway and oxygen requirement for fungal denitrification are different from those for bacterial denitrification. We hypothesized that the soil N(2)O emission from fungi is formate and O(2) dependent and that land use and landforms could influence the proportion of N(2)O coming from fungi. Using substrate-induced respiration inhibition under anaerobic and aerobic conditions in combination with (15)N gas analysis, we found that formate and hypoxia (versus anaerobiosis) were essential for the fungal reduction of (15)N-labeled nitrate to (15)N(2)O. As much as 65% of soil-emitted N(2)O was attributable to fungi; however, this was found only in soils from water-accumulating landforms. From these results, we hypothesize that plant root exudates could affect N(2)O production from fungi via the proposed formate-dependent pathway. PMID:18791019

  19. Oxidative Stress, Redox Regulation and Diseases of Cellular Differentiation

    PubMed Central

    Ye, Zhi-Wei; Zhang, Jie; Townsend, Danyelle M.; Tew, Kenneth D.

    2015-01-01

    Background Within cells, there is a narrow concentration threshold that governs whether reactive oxygen species (ROS) induce toxicity or act as second messengers. Scope of review We discuss current understanding of how ROS arise, facilitate cell signaling, cause toxicities and disease related to abnormal cell differentiation and those (primarily) sulfur based pathways that provide nucleophilicity to offset these effects. Primary conclusions Cellular redox homeostasis mediates a plethora of cellular pathways that determine life and death events. For example, ROS intersect with GSH based enzyme pathways to influence cell differentiation, a process integral to normal hematopoiesis, but also affecting a number of diverse cell differentiation related human diseases. Recent attempts to manage such pathologies have focused on intervening in some of these pathways, with the consequence that differentiation therapy targeting redox homeostasis has provided a platform for drug discovery and development. General Significance The balance between electrophilic oxidative stress and protective biomolecular nucleophiles predisposes the evolution of modern life forms. Imbalances of the two can produce aberrant redox homeostasis with resultant pathologies. Understanding the pathways involved provides opportunities to consider interventional strategies. PMID:25445706

  20. Nitric oxide directly regulates gene expression during Drosophila development: need some gas to drive into metamorphosis?

    PubMed

    Yamanaka, Naoki; O'Connor, Michael B

    2011-07-15

    Nitric oxide (NO) is an important second messenger involved in numerous biological processes, but how it regulates gene expression is not well understood. In this issue of Genes & Development, Cáceres and colleagues (pp. 1476-1485) report a critical requirement of NO as a direct regulator of gene expression through its binding to a heme-containing nuclear receptor in Drosophila. This may be an anciently evolved mechanism to coordinate behavior and metabolism during animal development. PMID:21764850

  1. Antioxidant defence systems in the protozoan pathogen Giardia intestinalis.

    PubMed

    Mastronicola, Daniela; Falabella, Micol; Forte, Elena; Testa, Fabrizio; Sarti, Paolo; Giuffrè, Alessandro

    2016-01-01

    The microaerophilic protist Giardia intestinalis is the causative agent of giardiasis, one of the most common intestinal infectious diseases worldwide. The pathogen lacks not only respiratory terminal oxidases (being amitochondriate), but also several conventional antioxidant enzymes, including catalase, superoxide dismutase and glutathione peroxidase. In spite of this, since living attached to the mucosa of the proximal small intestine, the parasite should rely on an efficient antioxidant system to survive the oxidative and nitrosative stress conditions found in this tract of the human gut. Here, we review current knowledge on the antioxidant defence systems in G. intestinalis, focusing on the progress made over the last decade in the field. The relevance of this research and future perspectives are discussed. PMID:26672398

  2. Overexpression of Protochlorophyllide Oxidoreductase C Regulates Oxidative Stress in Arabidopsis

    PubMed Central

    Pattanayak, Gopal K.; Tripathy, Baishnab C.

    2011-01-01

    Light absorbed by colored intermediates of chlorophyll biosynthesis is not utilized in photosynthesis; instead, it is transferred to molecular oxygen, generating singlet oxygen (1O2). As there is no enzymatic detoxification mechanism available in plants to destroy 1O2, its generation should be minimized. We manipulated the concentration of a major chlorophyll biosynthetic intermediate i.e., protochlorophyllide in Arabidopsis by overexpressing the light-inducible protochlorophyllide oxidoreductase C (PORC) that effectively phototransforms endogenous protochlorophyllide to chlorophyllide leading to minimal accumulation of the photosensitizer protochlorophyllide in light-grown plants. In PORC overexpressing (PORCx) plants exposed to high-light, the 1O2 generation and consequent malonedialdehyde production was minimal and the maximum quantum efficiency of photosystem II remained unaffected demonstrating that their photosynthetic apparatus and cellular organization were intact. Further, PORCx plants treated with 5-aminolevulinicacid when exposed to light, photo-converted over-accumulated protochlorophyllide to chlorophyllide, reduced the generation of 1O2 and malonedialdehyde production and reduced plasma membrane damage. So PORCx plants survived and bolted whereas, the 5-aminolevulinicacid-treated wild-type plants perished. Thus, overexpression of PORC could be biotechnologically exploited in crop plants for tolerance to 1O2-induced oxidative stress, paving the use of 5-aminolevulinicacid as a selective commercial light-activated biodegradable herbicide. Reduced protochlorophyllide content in PORCx plants released the protochlorophyllide-mediated feed-back inhibition of 5-aminolevulinicacid biosynthesis that resulted in higher 5-aminolevulinicacid production. Increase of 5-aminolevulinicacid synthesis upregulated the gene and protein expression of several downstream chlorophyll biosynthetic enzymes elucidating a regulatory net work of expression of genes involved in 5

  3. Immune defence under extreme ambient temperature

    PubMed Central

    Seppälä, Otto; Jokela, Jukka

    2011-01-01

    Owing to global climate change, the extreme weather conditions are predicted to become more frequent, which is suggested to have an even greater impact on ecological interactions than the gradual increase in average temperatures. Here, we examined whether exposure to high ambient temperature affects immune function of the great pond snail (Lymnaea stagnalis). We quantified the levels of several immune traits from snails maintained in a non-stressful temperature (15°C) and in an extreme temperature (30°C) that occurs in small ponds during hot summers. We found that snails exposed to high temperature had weaker immune defence, which potentially predisposes them to infections. However, while phenoloxidase and antibacterial activity of snail haemolymph were reduced at high temperature, haemocyte concentration was not affected. This suggests that the effect of high temperature on snail susceptibility to infections may vary across different pathogens because different components of invertebrate immune defence have different roles in resistance. PMID:20610417

  4. AMP-Activated Protein Kinase Regulates Oxidative Metabolism in Caenorhabditis elegans through the NHR-49 and MDT-15 Transcriptional Regulators

    PubMed Central

    Moreno-Arriola, Elizabeth; EL Hafidi, Mohammed; Ortega-Cuéllar, Daniel; Carvajal, Karla

    2016-01-01

    Cellular energy regulation relies on complex signaling pathways that respond to fuel availability and metabolic demands. Dysregulation of these networks is implicated in the development of human metabolic diseases such as obesity and metabolic syndrome. In Caenorhabditis elegans the AMP-activated protein kinase, AAK, has been associated with longevity and stress resistance; nevertheless its precise role in energy metabolism remains elusive. In the present study, we find an evolutionary conserved role of AAK in oxidative metabolism. Similar to mammals, AAK is activated by AICAR and metformin and leads to increased glycolytic and oxidative metabolic fluxes evidenced by an increase in lactate levels and mitochondrial oxygen consumption and a decrease in total fatty acids and lipid storage, whereas augmented glucose availability has the opposite effects. We found that these changes were largely dependent on the catalytic subunit AAK-2, since the aak-2 null strain lost the observed metabolic actions. Further results demonstrate that the effects due to AAK activation are associated to SBP-1 and NHR-49 transcriptional factors and MDT-15 transcriptional co-activator, suggesting a regulatory pathway that controls oxidative metabolism. Our findings establish C. elegans as a tractable model system to dissect the relationship between distinct molecules that play a critical role in the regulation of energy metabolism in human metabolic diseases. PMID:26824904

  5. A cocaine-regulated and amphetamine-regulated transcript inhibits oxidative stress in neurons deprived of oxygen and glucose.

    PubMed

    Sha, Dujuan; Wang, Zhongyuan; Qian, Lai; Han, Yong; Zhang, Jun; Gu, Shuangshuang; Wang, Luna; Li, Jie; Chen, Cong; Xu, Yun

    2013-09-11

    Stroke, of which about 87% is ischemic stroke, constitutes one of the main causes of morbidity, disability, and mortality worldwide. Ischemic brain injury has complex pathological mechanisms. Considerable evidence has been collected over the last few years suggesting that oxidative stress associated with excessive production of reactive oxygen species is a fundamental mechanism of brain damage in stroke and reperfusion after stroke. Oxidative stress is an important trigger of neuronal apoptosis in ischemic stroke. In this current study, it was found that cocaine-regulated and amphetamine-regulated transcript 55-102 (CART55-102) inhibited oxygen-induced and glucose deprivation (OGD)-induced neurotoxicity in a dose-dependent manner. The peak dose of CART55-102 was 0.4 nmol/l. In addition, the level of intracellular reactive oxygen species was decreased in OGD-treated neurons in the presence of 0.4 nmol/l CART55-102. Mitochondrial membrane potential (ΔΨm) and mtDNA mRNA expressions were increased in OGD-treated neurons in the presence of 0.4 nmol/l CART55-102. The current study suggests that CART55-102, by inhibiting oxidative stress, may be developed into therapeutic agents for ischemic stroke. PMID:23884173

  6. The Man-in-the-Middle Defence

    NASA Astrophysics Data System (ADS)

    Anderson, Ross; Bond, Mike

    Eliminating middlemen from security protocols helps less than one would think. EMV electronic payments, for example, can be made fairer by adding an electronic attorney - a middleman which mediates access to a customer’s card. We compare middlemen in crypto protocols and APIs with those in the real world, and show that a man-in-the-middle defence is helpful in many circumstances. We suggest that the middleman has been unfairly demonised.

  7. 40 CFR 52.1675 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...: Converted; North Campus Science and Physical Education Building: October 1, 1980. (b) Harlem Hospital, 135th... 40 Protection of Environment 4 2012-07-01 2012-07-01 false Control strategy and regulations: Sulfur oxides. 52.1675 Section 52.1675 Protection of Environment ENVIRONMENTAL PROTECTION...

  8. 40 CFR 52.1675 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...: Converted; North Campus Science and Physical Education Building: October 1, 1980. (b) Harlem Hospital, 135th... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy and regulations: Sulfur oxides. 52.1675 Section 52.1675 Protection of Environment ENVIRONMENTAL PROTECTION...

  9. 40 CFR 52.1675 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...: Converted; North Campus Science and Physical Education Building: October 1, 1980. (b) Harlem Hospital, 135th... 40 Protection of Environment 4 2013-07-01 2013-07-01 false Control strategy and regulations: Sulfur oxides. 52.1675 Section 52.1675 Protection of Environment ENVIRONMENTAL PROTECTION...

  10. 40 CFR 52.1601 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 4 2013-07-01 2013-07-01 false Control strategy and regulations: Sulfur oxides. 52.1601 Section 52.1601 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) New Jersey § 52.1601 Control strategy and...

  11. Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF

    PubMed Central

    Haq, Rizwan; Shoag, Jonathan; Andreu-Perez, Pedro; Yokoyama, Satoru; Edelman, Hannah; Rowe, Glenn C.; Frederick, Dennie T.; Hurley, Aeron D.; Nellore, Abhinav; Kung, Andrew L.; Wargo, Jennifer A.; Song, Jun S.; Fisher, David E.; Arany, Zolt; Widlund, Hans R.

    2013-01-01

    Summary Activating mutations in BRAF are the most common genetic alterations in melanoma. Inhibition of BRAF by small molecule inhibitors leads to cell cycle arrest and apoptosis. We show here that BRAF inhibition also induces an oxidative phosphorylation gene program, mitochondrial biogenesis, and the increased expression of the mitochondrial master regulator, PGC1α. We further show that a target of BRAF, the melanocyte lineage factor MITF, directly regulates the expression of PGC1α. Melanomas with activation of the BRAF/MAPK pathway have suppressed levels of MITF and PGC1α, and decreased oxidative metabolism. Conversely, treatment of BRAF mutated melanomas with BRAF inhibitors renders them addicted to oxidative phosphorylation. Our data thus identify an adaptive metabolic program that limits the efficacy of BRAF inhibitors. PMID:23477830

  12. Apolipoprotein D is involved in the mechanisms regulating protection from oxidative stress

    PubMed Central

    Ganfornina, Maria D.; Do Carmo, Sonia; Lora, Jose M.; Torres-Schumann, Sonia; Vogel, Marci; Allhorn, Maria; González, Constancio; Bastiani, Michael J.; Rassart, Eric; Sanchez, Diego

    2008-01-01

    Summary Many nervous system pathologies are associated with increased levels of Apolipoprotein D (ApoD), a lipocalin also expressed during normal development and aging. An ApoD homologous gene in Drosophila, Glial Lazarillo, regulates resistance to stress, and neurodegeneration in the aging brain. Here we study for the first time the protecting potential of ApoD in a vertebrate model organism. Loss of mouse ApoD function increases the sensitivity to oxidative stress and the levels of brain lipid peroxidation, and impairs locomotor and learning abilities. Human ApoD over-expression in the mouse brain produces opposite effects, increasing survival and preventing the raise of brain lipid peroxides after oxidant treatment. These observations, together with its transcriptional up-regulation in the brain upon oxidative insult, identify ApoD as an acute response protein with a protective and therefore beneficial function mediated by the control of peroxidated lipids. PMID:18419796

  13. A Chloroplast Light-Regulated Oxidative Sensor for Moderate Light Intensity in Arabidopsis[C][W

    PubMed Central

    Dangoor, Inbal; Peled-Zehavi, Hadas; Wittenberg, Gal; Danon, Avihai

    2012-01-01

    The transition from dark to light involves marked changes in the redox reactions of photosynthetic electron transport and in chloroplast stromal enzyme activity even under mild light and growth conditions. Thus, it is not surprising that redox regulation is used to dynamically adjust and coordinate the stromal and thylakoid compartments. While oxidation of regulatory proteins is necessary for the regulation, the identity and the mechanism of action of the oxidizing pathway are still unresolved. Here, we studied the oxidation of a thylakoid-associated atypical thioredoxin-type protein, ACHT1, in the Arabidopsis thaliana chloroplast. We found that after a brief period of net reduction in plants illuminated with moderate light intensity, a significant oxidation reaction of ACHT1 arises and counterbalances its reduction. Interestingly, ACHT1 oxidation is driven by 2-Cys peroxiredoxin (Prx), which in turn eliminates peroxides. The ACHT1 and 2-Cys Prx reaction characteristics in plants further indicated that ACHT1 oxidation is linked with changes in the photosynthetic production of peroxides. Our findings that plants with altered redox poise of the ACHT1 and 2-Cys Prx pathway show higher nonphotochemical quenching and lower photosynthetic electron transport infer a feedback regulatory role for this pathway. PMID:22570442

  14. Regulation of skeletal muscle lipolysis and oxidative metabolism by the co-lipase CGI-58.

    PubMed

    Badin, Pierre-Marie; Loubière, Camille; Coonen, Maarten; Louche, Katie; Tavernier, Geneviève; Bourlier, Virginie; Mairal, Aline; Rustan, Arild C; Smith, Steven R; Langin, Dominique; Moro, Cedric

    2012-05-01

    We investigated here the specific role of CGI-58 in the regulation of energy metabolism in skeletal muscle. We first examined CGI-58 protein expression in various muscle types in mice, and next modulated CGI-58 expression during overexpression and knockdown studies in human primary myotubes and evaluated the consequences on oxidative metabolism. We observed a preferential expression of CGI-58 in oxidative muscles in mice consistent with triacylglycerol hydrolase activity. We next showed by pulse-chase that CGI-58 overexpression increased by more than 2-fold the rate of triacylglycerol (TAG) hydrolysis, as well as TAG-derived fatty acid (FA) release and oxidation. Oppositely, CGI-58 silencing reduced TAG hydrolysis and TAG-derived FA release and oxidation (-77%, P < 0.001), whereas it increased glucose oxidation and glycogen synthesis. Interestingly, modulations of CGI-58 expression and FA release are reflected by changes in pyruvate dehydrogenase kinase 4 gene expression. This regulation involves the activation of the peroxisome proliferator activating receptor-δ (PPARδ) by lipolysis products. Altogether, these data reveal that CGI-58 plays a limiting role in the control of oxidative metabolism by modulating FA availability and the expression of PPARδ-target genes, and highlight an important metabolic function of CGI-58 in skeletal muscle. PMID:22383684

  15. Regulation of skeletal muscle lipolysis and oxidative metabolism by the co-lipase CGI-58[S

    PubMed Central

    Badin, Pierre-Marie; Loubière, Camille; Coonen, Maarten; Louche, Katie; Tavernier, Geneviève; Bourlier, Virginie; Mairal, Aline; Rustan, Arild C.; Smith, Steven R.; Langin, Dominique; Moro, Cedric

    2012-01-01

    We investigated here the specific role of CGI-58 in the regulation of energy metabolism in skeletal muscle. We first examined CGI-58 protein expression in various muscle types in mice, and next modulated CGI-58 expression during overexpression and knockdown studies in human primary myotubes and evaluated the consequences on oxidative metabolism. We observed a preferential expression of CGI-58 in oxidative muscles in mice consistent with triacylglycerol hydrolase activity. We next showed by pulse-chase that CGI-58 overexpression increased by more than 2-fold the rate of triacylglycerol (TAG) hydrolysis, as well as TAG-derived fatty acid (FA) release and oxidation. Oppositely, CGI-58 silencing reduced TAG hydrolysis and TAG-derived FA release and oxidation (−77%, P < 0.001), whereas it increased glucose oxidation and glycogen synthesis. Interestingly, modulations of CGI-58 expression and FA release are reflected by changes in pyruvate dehydrogenase kinase 4 gene expression. This regulation involves the activation of the peroxisome proliferator activating receptor-δ (PPARδ) by lipolysis products. Altogether, these data reveal that CGI-58 plays a limiting role in the control of oxidative metabolism by modulating FA availability and the expression of PPARδ-target genes, and highlight an important metabolic function of CGI-58 in skeletal muscle. PMID:22383684

  16. The role of glutathione in the regulation of nucleotide excision repair during oxidative stress.

    PubMed

    Langie, Sabine A S; Knaapen, Ad M; Houben, Joyce M J; van Kempen, Frederik C; de Hoon, Joep P J; Gottschalk, Ralph W H; Godschalk, Roger W L; van Schooten, Frederik J

    2007-02-01

    Nucleotide excision repair (NER) mainly repairs bulky DNA adducts and helix distorting lesions, but is additionally considered to be a back-up system for base excision repair to remove oxidative stress induced DNA damage. Therefore, it can be speculated that NER is up-regulated or primed by oxidative stress. Exposure of human pulmonary epithelial cells (A549) to non-toxic doses of 100muM H(2)O(2) indeed showed a 2 to 4.5-fold increase in expression of XPA, XPC, ERCC4, and ERCC5, whereas the expression of ERCC1 was 5-fold decreased. Phenotypical assessment of NER capacity (i.e. recognition and incision of benzo[a]pyrene-DNA adducts) showed a significant decrease to less than 50% after H(2)O(2) exposure, which paralleled the effects of H(2)O(2) on ERCC1 expression. To study the possible involvement of glutathione (GSH) in the regulation of NER, cells were pre-incubated with 0.5mM BSO, resulting in total GSH depletion and increased intracellular oxidative stress. In GSH-depleted cells, the down-regulation of ERCC1 expression by H(2)O(2) was completely abolished and the up-regulation of ERCC4 expression was potentiated from 2.5-fold to >10-fold. Similarly, the H(2)O(2)-induced decrease in NER capacity was absent in GSH-depleted cells. Overall, our data suggest that NER capacity as well as the expression of NER related genes can be modulated by oxidative stress. ERCC1 expression and NER capacity correlated strongly (R(2)=0.85, P<0.01) after oxidant exposure, indicating ERCC1 as a specific target for oxidative stress induced modification of NER. PMID:17207589

  17. Roles of Chinese herbal medicines in ischemic heart diseases (IHD) by regulating oxidative stress.

    PubMed

    Wang, Dawei; Wang, Jin; Liu, Yuntao; Zhao, Zhen; Liu, Qing

    2016-10-01

    Ischemic heart disease (IHD) basing on atherosclerosis (AS) is known as a top killer for decades. Oxidative stress, representing excessive oxidation and insufficient elimination, has been proved to be a critical molecular mechanism of IHD and accompanying myocardium dysfunction. Therefore, anti-oxidation therapy may be efficient. Chinese herbal medicine, including extractive compounds, decoctions, patent drugs, and injections, has shown its enormous potential in prevention and treatment of IHD as an effective antioxidant in experimental studies. The aim of this review is to highlight recent studies of Chinese herbal medicine in regulating oxidative stress in IHD. These studies represent recent progress of IHD treatment and indicate the possible pathways and target spots of Chinese herbal medicine. PMID:27390948

  18. Oxidative stress and redox regulation of phospholipase D in myocardial disease.

    PubMed

    Tappia, Paramjit S; Dent, Melissa R; Dhalla, Naranjan S

    2006-08-01

    Oxidative stress may be viewed as an imbalance between reactive oxygen species (ROS) and oxidant production and the state of glutathione redox buffer and antioxidant defense system. Recently, a new paradigm of redox signaling has emerged whereby ROS and oxidants can function as intracellular signaling molecules, where ROS- and oxidant-induced death signal is converted into a survival signal. It is now known that oxidative stress is involved in cardiac hypertrophy and in the pathogenesis of cardiomyopathies, ischemic heart disease and congestive heart failure. Phospholipase D (PLD) is an important signaling enzyme in mammalian cells, including cardiomyocytes. PLD catalyzes the hydrolysis of phosphatidylcholine to produce phosphatidic acid (PA). Two mammalian PLD isozymes, PLD1 and PLD2 have been identified, characterized and cloned. The importance of PA in heart function is evident from its ability to stimulate cardiac sarcolemmal membrane and sarcoplasmic reticular Ca2+-related transport systems and to increase the intracellular concentration of free Ca2+ in adult cardiomyocytes and augment cardiac contractile activity of the normal heart. In addition, PA is also considered an important signal transducer in cardiac hypertrophy. Accordingly, this review discusses a role for redox signaling mediated via PLD in ischemic preconditioning and examines how oxidative stress affects PLD in normal hearts and during different myocardial diseases. In addition, the review provides a comparative account on the regulation of PLD activities in vascular smooth muscle cells under conditions of oxidative stress. PMID:16843818

  19. A New Oxidative Sensing and Regulation Pathway Mediated by the MgrA Homologue SarZ in Staphylococcus aureus

    PubMed Central

    Chen, Peng, R.; Nishida, Satoshi; Poor, Catherine B.; Cheng, Alice; Bae, Taeok; Kuechenmeister, Lisa; Dunman, Paul M.; Missiakas, Dominique; He, Chuan

    2009-01-01

    Summary Oxidative stress serves as an important host/environmental signal that triggers a wide range of responses from the human pathogen Staphylococcus aureus. Among these, a thiol-based oxidation sensing pathway through a global regulator MgrA controls the virulence and antibiotic resistance of the bacterium. Herein, we report a new thiol-based oxidation sensing and regulation system that is mediated through a parallel global regulator SarZ. SarZ is a functional homologue of MgrA and is shown to affect the expression of ~87 genes in S. aureus. It uses a key Cys residue, Cys13, to sense oxidative stress and to coordinate the expression of genes involved in metabolic switching, antibiotic resistance, peroxide stress defense, virulence, and cell wall properties. The discovery of this SarZ-mediated regulation, mostly independent from the MgrA-based regulation, fills a missing gap of oxidation sensing and response in S. aureus. PMID:19007410

  20. Diacylglycerol kinase regulation of protein kinase D during oxidative stress-induced intestinal cell injury

    SciTech Connect

    Song Jun; Li Jing; Mourot, Joshua M.; Mark Evers, B.; Chung, Dai H.

    2008-10-17

    We recently demonstrated that protein kinase D (PKD) exerts a protective function during oxidative stress-induced intestinal epithelial cell injury; however, the exact role of DAG kinase (DGK){zeta}, an isoform expressed in intestine, during this process is unknown. We sought to determine the role of DGK during oxidative stress-induced intestinal cell injury and whether DGK acts as an upstream regulator of PKD. Inhibition of DGK with R59022 compound or DGK{zeta} siRNA transfection decreased H{sub 2}O{sub 2}-induced RIE-1 cell apoptosis as measured by DNA fragmentation and increased PKD phosphorylation. Overexpression of kinase-dead DGK{zeta} also significantly increased PKD phosphorylation. Additionally, endogenous nuclear DGK{zeta} rapidly translocated to the cytoplasm following H{sub 2}O{sub 2} treatment. Our findings demonstrate that DGK is involved in the regulation of oxidative stress-induced intestinal cell injury. PKD activation is induced by DGK{zeta}, suggesting DGK is an upstream regulator of oxidative stress-induced activation of the PKD signaling pathway in intestinal epithelial cells.

  1. Regulation of oxidative stress resistance in Campylobacter jejuni, a microaerophilic foodborne pathogen

    PubMed Central

    Kim, Jong-Chul; Oh, Euna; Kim, Jinyong; Jeon, Byeonghwa

    2015-01-01

    Campylobacter jejuni is one of the leading bacterial causes of human gastroenteritis. Due to the increasing rates of human campylobacteriosis, C. jejuni is considered as a serious public health concern worldwide. C. jejuni is a microaerophilic, fastidious bacterium. C. jejuni must overcome a wide range of stress conditions during foodborne transmission to humans, such as food preservation and processing conditions, and even in infection of the gastrointestinal tracts of humans. Particularly, this microaerophilic foodborne pathogen must survive in the atmospheric conditions prior to the initiation of infection. C. jejuni possesses unique regulatory mechanisms for oxidative stress resistance. Lacking OxyR and SoxRS that are highly conserved in other Gram-negative foodborne pathogens, C. jejuni modulates the expression of genes involved in oxidative stress resistance mainly via the peroxide resistance regulator and Campylobacter oxidative stress regulator. Based on recent findings of ours and others, in this review, we described how C. jejuni regulates the expression of oxidative stress defense. PMID:26284041

  2. Regulation of transcription factors by nitric oxide in neurons and in neural-derived tumor cells.

    PubMed

    Contestabile, Antonio

    2008-04-01

    Nitric oxide (NO), a diffusible molecule acting as an intercellular and intracellular messenger in many tissues, plays multiple roles in the nervous system. In addition to regulating proliferation, survival and differentiation of neurons, NO is also involved in synaptic activity, neural plasticity and memory formation. Long-lasting effects of NO, a simple and unstable molecule, occur through regulation of transcription factors and modulation of gene expression. cAMP-response-element-binding (CREB) protein is an important transcription factor that regulates the expression of several genes involved in survival and neuroprotection as well as in synaptic plasticity and memory formation. Nitric oxide promotes survival and differentiation of neural cells, both activating through cGMP signaling CREB phosphorylation-dependent transcriptional activity and promoting S-nitrosylation of nuclear proteins that favor CREB binding to its promoters on target genes. Among oncogenic transcription factors, N-Myc is important in neurogenesis and in regulating proliferation of neural-derived tumor cells, such as neuroblastomas and medulloblastomas. Nitric oxide negatively regulates the proliferation of neuronal precursors, as well as the proliferation of neuroblastoma cells, by downregulating N-Myc expression through cGMP signaling. Other oncogenic transcription factors, such as c-fos and c-jun, zinc-finger transcription factors, such as egr-1, and NF-kappaB are regulated by NO signaling in cGMP-dependent way or through nitrosative conformational changes. The present survey of how NO signaling influences neural cells through regulation of transcription factors allows us to predict that better knowledge of these interactions will provide a better understanding of the physiological role of NO in the nervous system in order to conceive novel therapies for neural-derived tumors. PMID:18308460

  3. Influence of Trichobilharzia regenti (Digenea: Schistosomatidae) on the Defence Activity of Radix lagotis (Lymnaeidae) Haemocytes

    PubMed Central

    Skála, Vladimír; Černíková, Alena; Jindrová, Zuzana; Kašný, Martin; Vostrý, Martin; Walker, Anthony J.; Horák, Petr

    2014-01-01

    Radix lagotis is an intermediate snail host of the nasal bird schistosome Trichobilharzia regenti. Changes in defence responses in infected snails that might be related to host-parasite compatibility are not known. This study therefore aimed to characterize R. lagotis haemocyte defence mechanisms and determine the extent to which they are modulated by T. regenti. Histological observations of R. lagotis infected with T. regenti revealed that early phases of infection were accompanied by haemocyte accumulation around the developing larvae 2–36 h post exposure (p.e.) to the parasite. At later time points, 44–92 h p.e., no haemocytes were observed around T. regenti. Additionally, microtubular aggregates likely corresponding to phagocytosed ciliary plates of T. regenti miracidia were observed within haemocytes by use of transmission electron microscopy. When the infection was in the patent phase, haemocyte phagocytic activity and hydrogen peroxide production were significantly reduced in infected R. lagotis when compared to uninfected counterparts, whereas haemocyte abundance increased in infected snails. At a molecular level, protein kinase C (PKC) and extracellular-signal regulated kinase (ERK) were found to play an important role in regulating these defence reactions in R. lagotis. Moreover, haemocytes from snails with patent infection displayed lower PKC and ERK activity in cell adhesion assays when compared to those from uninfected snails, which may therefore be related to the reduced defence activities of these cells. These data provide the first integrated insight into the immunobiology of R. lagotis and demonstrate modulation of haemocyte-mediated responses in patent T. regenti infected snails. Given that immunomodulation occurs during patency, interference of snail-host defence by T. regenti might be important for the sustained production and/or release of infective cercariae. PMID:25372492

  4. FABP4 reversed the regulation of leptin on mitochondrial fatty acid oxidation in mice adipocytes

    PubMed Central

    Gan, Lu; Liu, Zhenjiang; Cao, Weina; Zhang, Zhenzhen; Sun, Chao

    2015-01-01

    Fatty acid binding protein 4 (FABP4), plays key role in fatty acid transportation and oxidation, and increases with leptin synergistically during adipose inflammation process. However, the regulation mechanism between FABP4 and leptin on mitochondrial fatty acid oxidation remains unclear. In this study, we found that FABP4 reduced the expression of leptin, CPT-1 and AOX1 in mice adipocytes. Conversely, FABP4 was down-regulated in a time-dependent manner by leptin treatment. Additionally, forced expression of FABP4 attenuated the expression of PGC1-α, UCP2, CPT-1, AOX1 and COX2 compared with leptin incubation. Moreover, mitochondrial membrane potential, fatty acid oxidation enzyme medium-chain acyl-CoA dehydrogenase (MCAD), long-chain acyl-CoA dehydrogenase (LCAD) and Cyt C levels were reduced in response to the overexpression of FABP4. These reductions correspond well with the reduced release of free fatty acid and the inactivation of mitochondrial complexes I and III by FABP4 overexpression. Furthermore, addition of the Akt/mTOR pathway-specific inhibitor (MK2206) blocked the mitochondrial fatty acid oxidation and respiration factors, whereas interference of FABP4 overcame these effects. Taken together, FABP4 could reverse the activation of the leptin-induced mitochondrial fatty acid oxidation, and the inhibition of Akt/mTOR signal pathway played a key role in this process. PMID:26310911

  5. Vasomotor Regulation of Coronary Microcirculation by Oxidative Stress: Role of Arginase

    PubMed Central

    Kuo, Lih; Hein, Travis W.

    2013-01-01

    Overproduction of reactive oxygen species, i.e., oxidative stress, is associated with the activation of redox signaling pathways linking to inflammatory insults and cardiovascular diseases by impairing endothelial function and consequently blood flow dysregulation due to microvascular dysfunction. This review focuses on the regulation of vasomotor function in the coronary microcirculation by endothelial nitric oxide (NO) during oxidative stress and inflammation related to the activation of L-arginine consuming enzyme arginase. Superoxide produced in the vascular wall compromises vasomotor function by not only scavenging endothelium-derived NO but also inhibiting prostacyclin synthesis due to formation of peroxynitrite. The upregulation of arginase contributes to the deficiency of endothelial NO and microvascular dysfunction in various vascular diseases by initiating or following oxidative stress and inflammation. Hydrogen peroxide, a diffusible and stable oxidizing agent, exerts vasodilator function and plays important roles in the physiological regulation of coronary blood flow. In occlusive coronary ischemia, the release of hydrogen peroxide from the microvasculature helps to restore vasomotor function of coronary collateral microvessels with exercise training. However, excessive production and prolonged exposure of microvessels to hydrogen peroxide impairs NO-mediated endothelial function by reducing L-arginine availability through hydroxyl radical-dependent upregulation of arginase. The redox signaling can be a double-edged sword in the microcirculation, which helps tissue survival in one way by improving vasomotor regulation and elicits oxidative stress and tissue injury in the other way by causing vascular dysfunction. The impact of vascular arginase on the development of vasomotor dysfunction associated with angiotensin II receptor activation, hypertension, ischemia-reperfusion, hypercholesterolemia, and inflammatory insults is discussed. PMID:23966996

  6. Comparative genomics tools applied to bioterrorism defence.

    PubMed

    Slezak, Tom; Kuczmarski, Tom; Ott, Linda; Torres, Clinton; Medeiros, Dan; Smith, Jason; Truitt, Brian; Mulakken, Nisha; Lam, Marisa; Vitalis, Elizabeth; Zemla, Adam; Zhou, Carol Ecale; Gardner, Shea

    2003-06-01

    Rapid advances in the genomic sequencing of bacteria and viruses over the past few years have made it possible to consider sequencing the genomes of all pathogens that affect humans and the crops and livestock upon which our lives depend. Recent events make it imperative that full genome sequencing be accomplished as soon as possible for pathogens that could be used as weapons of mass destruction or disruption. This sequence information must be exploited to provide rapid and accurate diagnostics to identify pathogens and distinguish them from harmless near-neighbours and hoaxes. The Chem-Bio Non-Proliferation (CBNP) programme of the US Department of Energy (DOE) began a large-scale effort of pathogen detection in early 2000 when it was announced that the DOE would be providing bio-security at the 2002 Winter Olympic Games in Salt Lake City, Utah. Our team at the Lawrence Livermore National Lab (LLNL) was given the task of developing reliable and validated assays for a number of the most likely bioterrorist agents. The short timeline led us to devise a novel system that utilised whole-genome comparison methods to rapidly focus on parts of the pathogen genomes that had a high probability of being unique. Assays developed with this approach have been validated by the Centers for Disease Control (CDC). They were used at the 2002 Winter Olympics, have entered the public health system, and have been in continual use for non-publicised aspects of homeland defence since autumn 2001. Assays have been developed for all major threat list agents for which adequate genomic sequence is available, as well as for other pathogens requested by various government agencies. Collaborations with comparative genomics algorithm developers have enabled our LLNL team to make major advances in pathogen detection, since many of the existing tools simply did not scale well enough to be of practical use for this application. It is hoped that a discussion of a real-life practical application of

  7. Pknox1/Prep1 regulates mitochondrial oxidative phosphorylation components in skeletal muscle.

    PubMed

    Kanzleiter, Timo; Rath, Michaela; Penkov, Dmitry; Puchkov, Dmytro; Schulz, Nadja; Blasi, Francesco; Schürmann, Annette

    2014-01-01

    The homeodomain transcription factor Prep1 was previously shown to regulate insulin sensitivity. Our aim was to study the specific role of Prep1 for the regulation of energy metabolism in skeletal muscle. Muscle-specific ablation of Prep1 resulted in increased expression of respiratory chain subunits. This finding was consistent with an increase in mitochondrial enzyme activity without affecting mitochondrial volume fraction as assessed by electron microscopy. Metabolic phenotyping revealed no differences in daily energy expenditure or body composition. However, during treadmill exercise challenge, Prep1 ablation resulted in a higher maximal oxidative capacity and better endurance. Elevated PGC-1α expression was identified as a cause for increased mitochondrial capacity in Prep1 ablated mice. Prep1 stabilizes p160 Mybbp1a, a known inhibitor of PGC-1α activity. Thereby, p160 protein levels were significantly lower in the muscle of Prep1 ablated mice. By a chromatin immunoprecipitation-sequencing (ChIP-seq) approach, PREP1 binding sites in genes encoding mitochondrial components (e.g., Ndufs2) were identified that might be responsible for elevated proteins involved in oxidative phosphorylation (OXPHOS) in the muscle of Prep1 null mutants. These results suggest that Prep1 exhibits additional direct effects on regulation of mitochondrial proteins. We therefore conclude that Prep1 is a regulator of oxidative phosphorylation components via direct and indirect mechanisms. PMID:24216763

  8. Pknox1/Prep1 Regulates Mitochondrial Oxidative Phosphorylation Components in Skeletal Muscle

    PubMed Central

    Rath, Michaela; Penkov, Dmitry; Puchkov, Dmytro; Schulz, Nadja; Blasi, Francesco; Schürmann, Annette

    2014-01-01

    The homeodomain transcription factor Prep1 was previously shown to regulate insulin sensitivity. Our aim was to study the specific role of Prep1 for the regulation of energy metabolism in skeletal muscle. Muscle-specific ablation of Prep1 resulted in increased expression of respiratory chain subunits. This finding was consistent with an increase in mitochondrial enzyme activity without affecting mitochondrial volume fraction as assessed by electron microscopy. Metabolic phenotyping revealed no differences in daily energy expenditure or body composition. However, during treadmill exercise challenge, Prep1 ablation resulted in a higher maximal oxidative capacity and better endurance. Elevated PGC-1α expression was identified as a cause for increased mitochondrial capacity in Prep1 ablated mice. Prep1 stabilizes p160 Mybbp1a, a known inhibitor of PGC-1α activity. Thereby, p160 protein levels were significantly lower in the muscle of Prep1 ablated mice. By a chromatin immunoprecipitation-sequencing (ChIP-seq) approach, PREP1 binding sites in genes encoding mitochondrial components (e.g., Ndufs2) were identified that might be responsible for elevated proteins involved in oxidative phosphorylation (OXPHOS) in the muscle of Prep1 null mutants. These results suggest that Prep1 exhibits additional direct effects on regulation of mitochondrial proteins. We therefore conclude that Prep1 is a regulator of oxidative phosphorylation components via direct and indirect mechanisms. PMID:24216763

  9. CIRCADIAN CLOCK-ASSOCIATED 1 regulates ROS homeostasis and oxidative stress responses

    PubMed Central

    Lai, Alvina Grace; Doherty, Colleen J.; Mueller-Roeber, Bernd; Kay, Steve A.; Schippers, Jos H. M.; Dijkwel, Paul P.

    2012-01-01

    Organisms have evolved endogenous biological clocks as internal timekeepers to coordinate metabolic processes with the external environment. Here, we seek to understand the mechanism of synchrony between the oscillator and products of metabolism known as Reactive Oxygen Species (ROS) in Arabidopsis thaliana. ROS-responsive genes exhibit a time-of-day–specific phase of expression under diurnal and circadian conditions, implying a role of the circadian clock in transcriptional regulation of these genes. Hydrogen peroxide production and scavenging also display time-of-day phases. Mutations in the core-clock regulator, CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), affect the transcriptional regulation of ROS-responsive genes, ROS homeostasis, and tolerance to oxidative stress. Mis-expression of EARLY FLOWERING 3, LUX ARRHYTHMO, and TIMING OF CAB EXPRESSION 1 affect ROS production and transcription, indicating a global effect of the clock on the ROS network. We propose CCA1 as a master regulator of ROS homeostasis through association with the Evening Element in promoters of ROS genes in vivo to coordinate time-dependent responses to oxidative stress. We also find that ROS functions as an input signal that affects the transcriptional output of the clock, revealing an important link between ROS signaling and circadian output. Temporal coordination of ROS signaling by CCA1 and the reciprocal control of circadian output by ROS reveal a mechanistic link that allows plants to master oxidative stress responses. PMID:23027948

  10. Redox-dependent regulation, redox control and oxidative damage in plant cells subjected to abiotic stress.

    PubMed

    Dietz, Karl-Josef

    2010-01-01

    Stress development intricately involves uncontrolled redox reactions and oxidative damage to functional macromolecules. Three phases characterize progressing abiotic stress and the stress strength; in the first phase redox-dependent deregulation in metabolism, in the second phase detectable development of oxidative damage and in the third phase cell death. Each phase is characterized by traceable biochemical features and specific molecular responses that reflect on the one hand cell damage but on the other hand indicate specific regulation and redox signalling aiming at compensation of stress impact. PMID:20387040

  11. The Bacterial Response Regulator ArcA Uses a Diverse Binding Site Architecture to Regulate Carbon Oxidation Globally

    PubMed Central

    Park, Dan M.; Akhtar, Md. Sohail; Ansari, Aseem Z.; Landick, Robert; Kiley, Patricia J.

    2013-01-01

    Despite the importance of maintaining redox homeostasis for cellular viability, how cells control redox balance globally is poorly understood. Here we provide new mechanistic insight into how the balance between reduced and oxidized electron carriers is regulated at the level of gene expression by mapping the regulon of the response regulator ArcA from Escherichia coli, which responds to the quinone/quinol redox couple via its membrane-bound sensor kinase, ArcB. Our genome-wide analysis reveals that ArcA reprograms metabolism under anaerobic conditions such that carbon oxidation pathways that recycle redox carriers via respiration are transcriptionally repressed by ArcA. We propose that this strategy favors use of catabolic pathways that recycle redox carriers via fermentation akin to lactate production in mammalian cells. Unexpectedly, bioinformatic analysis of the sequences bound by ArcA in ChIP-seq revealed that most ArcA binding sites contain additional direct repeat elements beyond the two required for binding an ArcA dimer. DNase I footprinting assays suggest that non-canonical arrangements of cis-regulatory modules dictate both the length and concentration-sensitive occupancy of DNA sites. We propose that this plasticity in ArcA binding site architecture provides both an efficient means of encoding binding sites for ArcA, σ70-RNAP and perhaps other transcription factors within the same narrow sequence space and an effective mechanism for global control of carbon metabolism to maintain redox homeostasis. PMID:24146625

  12. Potato skin proteome is enriched with plant defence components

    PubMed Central

    Barel, Gilli; Ginzberg, Idit

    2008-01-01

    Periderm is a tissue of secondary origin that replaces damaged epidermis. It can be found in underground plant organs, as an above-ground tissue of woody species (cork), and as a wound-healing tissue. Its outer layers are composed of phellem cells with suberized walls that constitute a protective barrier, preventing pathogen invasion and fluid loss. In potato, a model for periderm studies, periderm tissue replaces the epidermis early in tuber development and the suberized phellems constitute the tuber's skin. To identify factors involved in phellem/skin development and that play a role in its defensive characteristics, two-dimensional gel electrophoresis was used to compare the skin and parenchymatic flesh proteomes of young developing tubers. Proteins exhibiting differentially high signal intensity in the skin were sorted by functional categories. As expected, the differential skin proteome was enriched in proteins whose activity is characteristic of actively dividing tissues such as cell proliferation, C1 metabolism, and the oxidative respiratory chain. Interestingly, the major functional category consisted of proteins (63%) involved in plant defence responses to biotic and abiotic stresses. This group included three isozymes of caffeoyl-CoA O-methyltransferase and five isozymes of peroxidase that may play a role in suberization processes. The differential expression of these proteins in the skin was further verified by RT-PCR of their corresponding transcripts in skin and tuber flesh samples. The results presented here shed light on the early events in skin development and further expand the concept of the periderm as a protective tissue containing an array of plant defence components. PMID:18653692

  13. The single functional blast resistance gene Pi54 activates a complex defence mechanism in rice.

    PubMed

    Gupta, Santosh Kumar; Rai, Amit Kumar; Kanwar, Shamsher Singh; Chand, Duni; Singh, Nagendera Kumar; Sharma, Tilak Raj

    2012-01-01

    The Pi54 gene (Pi-k(h)) confers a high degree of resistance to diverse strains of the fungus Magnaporthe oryzae. In order to understand the genome-wide co-expression of genes in the transgenic rice plant Taipei 309 (TP) containing the Pi54 gene, microarray analysis was performed at 72 h post-inoculation of the M. oryzae strain PLP-1. A total of 1154 differentially expressing genes were identified in TP-Pi54 plants. Of these, 587 were up-regulated, whereas 567 genes were found to be down-regulated. 107 genes were found that were exclusively up-regulated and 58 genes that were down- regulated in the case of TP-Pi54. Various defence response genes, such as callose, laccase, PAL, and peroxidase, and genes related to transcription factors like NAC6, Dof zinc finger, MAD box, bZIP, and WRKY were found to be up-regulated in the transgenic line. The enzymatic activities of six plant defence response enzymes, such as peroxidase, polyphenol oxidase, phenylalanine ammonia lyase, β-glucosidase, β-1,3-glucanase, and chitinase, were found to be significantly high in TP-Pi54 at different stages of inoculation by M. oryzae. The total phenol content also increased significantly in resistant transgenic plants after pathogen inoculation. This study suggests the activation of defence response and transcription factor-related genes and a higher expression of key enzymes involved in the defence response pathway in the rice line TP-Pi54, thus leading to incompatible host-pathogen interaction. PMID:22058403

  14. Mechanism of H₂O₂-induced oxidative stress regulating viability and biocontrol ability of Rhodotorula glutinis.

    PubMed

    Chen, Jian; Li, Boqiang; Qin, Guozheng; Tian, Shiping

    2015-01-16

    The use of antagonistic yeasts to control postharvest pathogens is a promising alternative to fungicides. The effectiveness of the antagonists against fungal pathogens is greatly dependent on their viability, which is usually mediated by reactive oxygen species (ROS). Here, we investigated the effects of H₂O₂-induced oxidative stress on the viability and biocontrol efficacy of Rhodotorula glutinis and, using flow cytometric analysis, observed the changes of ROS accumulation and apoptosis in the yeast cells with or without H₂O₂ treatment. We found that the viability of R. glutinis decreased in a time- and dose-dependent manner under H₂O₂-induced oxidative stress. Compared to the control, yeast cells exposed to oxidative stress exhibited more accumulation of ROS and higher levels of protein oxidative damage, but showed lower efficacy for biocontrol of Penicillium expansum causing blue mold rot on peach fruit. The results indicate that apoptosis is a main cause of the cell viability loss in R. glutinis, which is attributed to ROS accumulation under oxidative stress. These findings offer a plausible explanation that oxidative stress affects biocontrol efficacy of R. glutinis via regulating its viability and cell apoptosis. PMID:25462935

  15. Nitric Oxide Acts as a Positive Regulator to Induce Metamorphosis of the Ascidian Herdmania momus

    PubMed Central

    Ueda, Nobuo; Degnan, Sandie M.

    2013-01-01

    Marine invertebrates commonly have a biphasic life cycle in which the metamorphic transition from a pelagic larva to a benthic post-larva is mediated by the nitric oxide signalling pathway. Nitric oxide (NO) is synthesised by nitric oxide synthase (NOS), which is a client protein of the molecular chaperon heat shock protein 90 (HSP90). It is notable, then, that both NO and HSP90 have been implicated in regulating metamorphosis in marine invertebrates as diverse as urochordates, echinoderms, molluscs, annelids, and crustaceans. Specifically, the suppression of NOS activity by the application of either NOS- or HSP90-inhibiting pharmacological agents has been shown consistently to induce the initiation of metamorphosis, leading to the hypothesis that a negative regulatory role of NO is widely conserved in biphasic life cycles. Further, the induction of metamorphosis by heat-shock has been demonstrated for multiple species. Here, we investigate the regulatory role of NO in induction of metamorphosis of the solitary tropical ascidian, Herdmania momus. By coupling pharmacological treatments with analysis of HmNOS and HmHSP90 gene expression, we present compelling evidence of a positive regulatory role for NO in metamorphosis of this species, in contrast to all existing ascidian data that supports the hypothesis of NO as a conserved negative regulator of metamorphosis. The exposure of competent H. momus larvae to a NOS inhibitor or an NO donor results in an up-regulation of NOS and HSP90 genes. Heat shock of competent larvae induces metamorphosis in a temperature dependent manner, up to a thermal tolerance that approaches 35°C. Both larval/post-larval survival and the appearance of abnormal morphologies in H. momus post-larvae reflect the magnitude of up-regulation of the HSP90 gene in response to heat-shock. The demonstrated role of NO as a positive metamorphic regulator in H. momus suggests the existence of inter-specific adaptations of NO regulation in ascidian

  16. Bacterial strategies to overcome insect defences.

    PubMed

    Vallet-Gely, Isabelle; Lemaitre, Bruno; Boccard, Frédéric

    2008-04-01

    Recent genetic and molecular analyses have revealed how several strategies enable bacteria to persist and overcome insect immune defences. Genetic and genomic tools that can be used with Drosophila melanogaster have enabled the characterization of the pathways that are used by insects to detect bacterial invaders and combat infection. Conservation of bacterial virulence factors and insect immune repertoires indicates that there are common strategies of host invasion and pathogen eradication. Long-term interactions of bacteria with insects might ensure efficient dissemination of pathogens to other hosts, including humans. PMID:18327270

  17. Herbivory: Caterpillar saliva beats plant defences

    NASA Astrophysics Data System (ADS)

    Musser, Richard O.; Hum-Musser, Sue M.; Eichenseer, Herb; Peiffer, Michelle; Ervin, Gary; Murphy, J. Brad; Felton, Gary W.

    2002-04-01

    Blood-feeding arthropods secrete special salivary proteins that suppress the defensive reaction they induce in their hosts. This is in contrast to herbivores, which are thought to be helpless victims of plant defences elicited by their oral secretions. On the basis of the finding that caterpillar regurgitant can reduce the amount of toxic nicotine released by the tobacco plant Nicotiana tabacum, we investigate here whether specific salivary components from the caterpillar Helicoverpa zea might be responsible for this suppression. We find that the enzyme glucose oxidase counteracts the production of nicotine induced by the caterpillar feeding on the plant.

  18. Clostridium difficile colitis: pathogenesis and host defence.

    PubMed

    Abt, Michael C; McKenney, Peter T; Pamer, Eric G

    2016-10-01

    Clostridium difficile is a major cause of intestinal infection and diarrhoea in individuals following antibiotic treatment. Recent studies have begun to elucidate the mechanisms that induce spore formation and germination and have determined the roles of C. difficile toxins in disease pathogenesis. Exciting progress has also been made in defining the role of the microbiome, specific commensal bacterial species and host immunity in defence against infection with C. difficile. This Review will summarize the recent discoveries and developments in our understanding of C. difficile infection and pathogenesis. PMID:27573580

  19. In Defence of Multimodal Re-Signification: A Response to Havard Skaar's "In Defence of Writing"

    ERIC Educational Resources Information Center

    Adami, Elisabetta

    2011-01-01

    Responding to "In defence of writing" by Havard Skaar, published in issue 43.1 of this journal (April 2009), the present article argues that (1) compared with text production "from scratch," producing texts through copy-and-paste requires a different type of--rather than less--semiotic work, and that (2) digitally produced writing may involve the…

  20. Regulated spatial organization and sensitivity of cytosolic protein oxidation in Caenorhabditis elegans

    PubMed Central

    Romero-Aristizabal, Catalina; Marks, Debora S.; Fontana, Walter; Apfeld, Javier

    2014-01-01

    Cells adjust their behavior in response to redox events by regulating protein activity through the reversible formation of disulfide bridges between cysteine thiols. However, the spatial and temporal control of these modifications remains poorly understood in multicellular organisms. Here, we measured the protein thiol-disulfide balance in live C. elegans using a genetically-encoded redox sensor and found that it is specific to tissues and patterned spatially within a tissue. Insulin signaling regulates the sensor's oxidation at both of these levels. Unexpectedly, we found that isogenic individuals exhibit large differences in the sensor's thiol-disulfide balance. This variation contrasts with the general view that glutathione acts as the main cellular redox buffer. Indeed, our work suggests that glutathione converts small changes in its oxidation level into large changes in its redox potential. We therefore propose that glutathione facilitates the sensitive control of the thioldisulfide balance of target proteins in response to cellular redox events. PMID:25262602

  1. Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance

    PubMed Central

    Tsang, Chi Kwan; Liu, Yuan; Thomas, Janice; Zhang, Yanjie; Zheng, X. F. Steven

    2015-01-01

    Summary Superoxide dismutase 1 (Sod1) has been known for nearly half a century for catalysis of superoxide to hydrogen peroxide. Here we report a new Sod1 function in oxidative signaling: in response to elevated endogenous and exogenous reactive oxygen species (ROS), Sod1 rapidly relocates into the nucleus, which is important for maintaining genomic stability. Interestingly, H2O2 is sufficient to promote Sod1 nuclear localization, indicating that it is responding to general ROS rather than Sod1 substrate superoxide. ROS signaling is mediated by Mec1/ATM and its effector Dun1/Cds1 kinase, through Dun1 interaction with Sod1 and regulation of Sod1 by phosphorylation at S60, 99. In the nucleus, Sod1 binds to the promoters and regulates the expression of oxidative resistance and repair genes. Altogether, our study unravels an unorthodox function of Sod1 as a transcription factor and elucidates the regulatory mechanism for its localization. PMID:24647101

  2. Post-translational regulation of endothelial nitric oxide synthase in vascular endothelium

    PubMed Central

    Qian, Jin; Fulton, David

    2013-01-01

    Nitric oxide (NO) is a short-lived gaseous signaling molecule. In blood vessels, it is synthesized in a dynamic fashion by endothelial nitric oxide synthase (eNOS) and influences vascular function via two distinct mechanisms, the activation of soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP)-dependent signaling and the S-nitrosylation of proteins with reactive thiols (S-nitrosylation). The regulation of eNOS activity and NO bioavailability is critical to maintain blood vessel function. The activity of eNOS and ability to generate NO is regulated at the transcriptional, posttranscriptional, and posttranslational levels. Post-translational modifications acutely impact eNOS activity and dysregulation of these mechanisms compromise eNOS activity and foster the development of cardiovascular diseases (CVDs). This review will intergrate past and current literature on the post-translational modifications of eNOS in both health and disease. PMID:24379783

  3. Oxidative burst: an early plant response to pathogen infection.

    PubMed Central

    Wojtaszek, P

    1997-01-01

    As plants are confined to the place where they grow, they have to develop a broad range of defence responses to cope with pathogenic infections. The oxidative burst, a rapid, transient, production of huge amounts of reactive oxygen species (ROS), is one of the earliest observable aspects of a plant's defence strategy. First this Review describes the chemistry of ROS (superoxide radical, hydrogen peroxide and hydroxyl radical). Secondly, the role of ROS in defence responses is demonstrated, and some important issues are considered, such as: (1) which of the ROS is a major building element of the oxidative burst; (2) the spatial and temporal regulation of the oxidative burst; and (3) differences in the plant's responses to biotic and abiotic elicitation. Thirdly, the relationships between the oxidative burst and other plant defence responses are indicated. These include: (1) an oxygen consumption, (2) the production of phytoalexins, (3) systemic acquired resistance, (4) immobilization of plant cell wall proteins, (5) changes in membrane permeability and ion fluxes and (6) a putative role in hypersensitive cell death. Wherever possible, the comparisons with models applicable to animal systems are presented. Finally, the question of the origin of ROS in the oxidative burst is considered, and two major hypotheses, (1) the action of NADPH oxidase system analogous to that of animal phagocytes, and (2) the pH-dependent generation of hydrogen peroxide by a cell wall peroxidase, are presented. On the basis of this material, a third 'unifying' hypothesis is presented, where transient changes in the pH of the cell wall compartment are indicated as a core phenomenon in evoking ROS production. Additionally, a germin/oxalate oxidase system which generates H2O2 in response to pathogenic infection is also described. PMID:9148737

  4. Staphylococcus aureus CymR Is a New Thiol-based Oxidation-sensing Regulator of Stress Resistance and Oxidative Response

    SciTech Connect

    Ji, Quanjiang; Zhang, Liang; Sun, Fei; Deng, Xin; Liang, Haihua; Bae, Taeok; He, Chuan

    2014-10-02

    As a human pathogen, Staphylococcus aureus must cope with oxidative stress generated by the human immune system. Here, we report that CymR utilizes its sole Cys-25 to sense oxidative stress. Oxidation followed by thiolation of this cysteine residue leads to dissociation of CymR from its cognate promoter DNA. In contrast, the DNA binding of the CymRC25S mutant was insensitive to oxidation and thiolation, suggesting that CymR senses oxidative stress through oxidation of its sole cysteine to form a mixed disulfide with low molecular weight thiols. The determined crystal structures of the reduced and oxidized forms of CymR revealed that Cys-25 is oxidized to Cys-25-SOH in the presence of H{sub 2}O{sub 2}. Deletion of cymR reduced the resistance of S. aureus to oxidative stresses, and the resistance was restored by expressing a C25S mutant copy of cymR. In a C25S substitution mutant, the expression of two genes, tcyP and mccB, was constitutively repressed and did not respond to hydrogen peroxide stress, whereas the expression of the genes were highly induced under oxidative stress in a wild-type strain, indicating the critical role of Cys-25 in redox signaling in vivo. Thus, CymR is another master regulator that senses oxidative stress and connects stress responses to virulence regulation in S. aureus.

  5. Keap1 redox-dependent regulation of doxorubicin-induced oxidative stress response in cardiac myoblasts.

    PubMed

    Nordgren, Kendra K S; Wallace, Kendall B

    2014-01-01

    Doxorubicin (DOX) is a widely prescribed treatment for a broad scope of cancers, but clinical utility is limited by the cumulative, dose-dependent cardiomyopathy that occurs with repeated administration. DOX-induced cardiotoxicity is associated with the production of reactive oxygen species (ROS) and oxidation of lipids, DNA and proteins. A major cellular defense mechanism against such oxidative stress is activation of the Keap1/Nrf2-antioxidant response element (ARE) signaling pathway, which transcriptionally regulates expression of antioxidant genes such as Nqo1 and Gstp1. In the present study, we address the hypothesis that an initial event associated with DOX-induced oxidative stress is activation of the Keap1/Nrf2-dependent expression of antioxidant genes and that this is regulated through drug-induced changes in redox status of the Keap1 protein. Incubation of H9c2 rat cardiac myoblasts with DOX resulted in a time- and dose-dependent decrease in non-protein sulfhydryl groups. Associated with this was a near 2-fold increase in Nrf2 protein content and enhanced transcription of several of the Nrf2-regulated down-stream genes, including Gstp1, Ugt1a1, and Nqo1; the expression of Nfe2l2 (Nrf2) itself was unaltered. Furthermore, both the redox status and the total amount of Keap1 protein were significantly decreased by DOX, with the loss of Keap1 being due to both inhibited gene expression and increased autophagic, but not proteasomal, degradation. These findings identify the Keap1/Nrf2 pathway as a potentially important initial response to acute DOX-induced oxidative injury, with the primary regulatory events being the oxidation and autophagic degradation of the redox sensor Keap1 protein. PMID:24211725

  6. microRNAs: Emerging Targets Regulating Oxidative Stress in the Models of Parkinson's Disease

    PubMed Central

    Xie, Yangmei; Chen, Yinghui

    2016-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder. This chronic, progressive disease is characterized by loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and the presence of cytoplasmic inclusions called Lewy bodies (LBs) in surviving neurons. PD is attributed to a combination of environment and genetic factors, but the precise underlying molecular mechanisms remain elusive. Oxidative stress is generally recognized as one of the main causes of PD, and excessive reactive oxygen species (ROS) can lead to DA neuron vulnerability and eventual death. Several studies have demonstrated that small non-coding RNAs termed microRNAs (miRNAs) can regulate oxidative stress in vitro and in vivo models of PD. Relevant miRNAs involved in oxidative stress can prevent ROS-mediated damage to DA neurons, suggesting that specific miRNAs may be putative targets for novel therapeutic targets in PD. PMID:27445669

  7. Conservation of thiol-oxidative stress responses regulated by SigR orthologues in actinomycetes

    PubMed Central

    Kim, Min-Sik; Dufour, Yann S.; Yoo, Ji Sun; Cho, Yoo-Bok; Park, Joo-Hong; Nam, Gi-Baeg; Kim, Hae Min; Lee, Kang-Lok; Donohue, Timothy J.; Roe, Jung-Hye

    2015-01-01

    Summary Numerous thiol-reactive compounds cause oxidative stress where cells counteract by activation of survival strategies regulated by thiol-based sensors. In Streptomyces coelicolor, a model actinomycete, a sigma/antisigma pair SigR/RsrA controls the response to thiol-oxidative stress. To unravel its full physiological functions, chromatin immuno-precipitation combined with sequence and transcript analyses were employed to identify 108 SigR target genes in S. coelicolor and to predict orthologous regulons across actinomycetes. In addition to reported genes for thiol homeostasis, protein degradation and ribosome modulation, 64 additional operons were identified suggesting new functions of this global regulator. We demonstrate that SigR maintains the level and activity of the housekeeping sigma factor HrdB during thiol-oxidative stress, a novel strategy for stress responses. We also found that SigR defends cells against UV and thiol-reactive damages, in which repair UvrA takes a part. Using a refined SigR-binding sequence model, SigR orthologues and their targets were predicted in 42 actinomycetes. This revealed a conserved core set of SigR targets to function for thiol homeostasis, protein quality control, possible modulation of transcription and translation, flavin-mediated redox reactions, and Fe-S delivery. The composition of the SigR regulon reveals a robust conserved physiological mechanism to deal with thiol-oxidative stress from bacteria to human. PMID:22651816

  8. Regulation of cytoskeletal dynamics by redox signaling and oxidative stress: implications for neuronal development and trafficking

    PubMed Central

    Wilson, Carlos; González-Billault, Christian

    2015-01-01

    A proper balance between chemical reduction and oxidation (known as redox balance) is essential for normal cellular physiology. Deregulation in the production of oxidative species leads to DNA damage, lipid peroxidation and aberrant post-translational modification of proteins, which in most cases induces injury, cell death and disease. However, physiological concentrations of oxidative species are necessary to support important cell functions, such as chemotaxis, hormone synthesis, immune response, cytoskeletal remodeling, Ca2+ homeostasis and others. Recent evidence suggests that redox balance regulates actin and microtubule dynamics in both physiological and pathological contexts. Microtubules and actin microfilaments contain certain amino acid residues that are susceptible to oxidation, which reduces the ability of microtubules to polymerize and causes severing of actin microfilaments in neuronal and non-neuronal cells. In contrast, inhibited production of reactive oxygen species (ROS; e.g., due to NOXs) leads to aberrant actin polymerization, decreases neurite outgrowth and affects the normal development and polarization of neurons. In this review, we summarize emerging evidence suggesting that both general and specific enzymatic sources of redox species exert diverse effects on cytoskeletal dynamics. Considering the intimate relationship between cytoskeletal dynamics and trafficking, we also discuss the potential effects of redox balance on intracellular transport via regulation of the components of the microtubule and actin cytoskeleton as well as cytoskeleton-associated proteins, which may directly impact localization of proteins and vesicles across the soma, dendrites and axon of neurons. PMID:26483635

  9. Redox signalling directly regulates TDP-43 via cysteine oxidation and disulphide cross-linking.

    PubMed

    Cohen, Todd J; Hwang, Andrew W; Unger, Travis; Trojanowski, John Q; Lee, Virginia M Y

    2012-03-01

    TDP-43 is the major disease protein in ubiquitin-positive inclusions of amyotrophic lateral sclerosis and frontotemporal lobar degeneration (FTLD) characterized by TDP-43 pathology (FTLD-TDP). Accumulation of insoluble TDP-43 aggregates could impair normal TDP-43 functions and initiate disease progression. Thus, it is critical to define the signalling mechanisms regulating TDP-43 since this could open up new avenues for therapeutic interventions. Here, we have identified a redox-mediated signalling mechanism directly regulating TDP-43. Using in vitro and cell-based studies, we demonstrate that oxidative stress promotes TDP-43 cross-linking via cysteine oxidation and disulphide bond formation leading to decreased TDP-43 solubility. Biochemical analysis identified several cysteine residues located within and adjacent to the second RNA-recognition motif that contribute to both intra- and inter-molecular interactions, supporting TDP-43 as a target of redox signalling. Moreover, increased levels of cross-linked TDP-43 species are found in FTLD-TDP brains, indicating that aberrant TDP-43 cross-linking is a prominent pathological feature of this disease. Thus, TDP-43 is dynamically regulated by a redox regulatory switch that links oxidative stress to the modulation of TDP-43 and its downstream targets. PMID:22193716

  10. Redox signalling directly regulates TDP-43 via cysteine oxidation and disulphide cross-linking

    PubMed Central

    Cohen, Todd J; Hwang, Andrew W; Unger, Travis; Trojanowski, John Q; Lee, Virginia M Y

    2012-01-01

    TDP-43 is the major disease protein in ubiquitin-positive inclusions of amyotrophic lateral sclerosis and frontotemporal lobar degeneration (FTLD) characterized by TDP-43 pathology (FTLD-TDP). Accumulation of insoluble TDP-43 aggregates could impair normal TDP-43 functions and initiate disease progression. Thus, it is critical to define the signalling mechanisms regulating TDP-43 since this could open up new avenues for therapeutic interventions. Here, we have identified a redox-mediated signalling mechanism directly regulating TDP-43. Using in vitro and cell-based studies, we demonstrate that oxidative stress promotes TDP-43 cross-linking via cysteine oxidation and disulphide bond formation leading to decreased TDP-43 solubility. Biochemical analysis identified several cysteine residues located within and adjacent to the second RNA-recognition motif that contribute to both intra- and inter-molecular interactions, supporting TDP-43 as a target of redox signalling. Moreover, increased levels of cross-linked TDP-43 species are found in FTLD-TDP brains, indicating that aberrant TDP-43 cross-linking is a prominent pathological feature of this disease. Thus, TDP-43 is dynamically regulated by a redox regulatory switch that links oxidative stress to the modulation of TDP-43 and its downstream targets. PMID:22193716

  11. Science and outreach for planetary defence

    NASA Astrophysics Data System (ADS)

    Stavinschi, M.

    2011-10-01

    The recent IAA Planetary Defence Conference held in Romania, focused on a hot topic: from Threat to Action. It is true that we ought to protect the planet but also educate the population in this direction. Increasing rumours about pseudo-scientific issues, such as the impact with asteroids, comets or debris of spatial missions, the effects of the growing solar activity, the displacement of the terrestrial rotation axis following major earthquakes, let alone spreading news about the end-of-the-world, show how crucial it is to prepare people to understand what is going on in the universe and, in particular, on our planet, and how to deal with inevitable events. Another central question is in order: who should be in charge of this education? Perhaps the journalists, but they lack the necessary preparation to present correct and updated information to the public. Or the scientists, but they are extremely busy and concentrated on their projects aimed at defending the planet and at answering the vast array of questions that their research stirs up. Our goal is to answer the following question: to what extent is it the scientist's responsibility and to what extent the journalist's to educate people for the planetary defence? In addition, we shall suggest how they can effectively co-ordinate efforts to solve the current problems of a society submerged in increasingly sophisticated but decreasingly informed technologies.

  12. Actin as Deathly Switch? How Auxin Can Suppress Cell-Death Related Defence

    PubMed Central

    Chang, Xiaoli; Riemann, Michael; Liu, Qiong; Nick, Peter

    2015-01-01

    Plant innate immunity is composed of two layers – a basal immunity, and a specific effector-triggered immunity, which is often accompanied by hypersensitive cell death. Initiation of cell death depends on a complex network of signalling pathways. The phytohormone auxin as central regulator of plant growth and development represents an important component for the modulation of plant defence. In our previous work, we showed that cell death is heralded by detachment of actin from the membrane. Both, actin response and cell death, are triggered by the bacterial elicitor harpin in grapevine cells. In this study we investigated, whether harpin-triggered actin bundling is necessary for harpin-triggered cell death. Since actin organisation is dependent upon auxin, we used different auxins to suppress actin bundling. Extracellular alkalinisation and transcription of defence genes as the basal immunity were examined as well as cell death. Furthermore, organisation of actin was observed in response to pharmacological manipulation of reactive oxygen species and phospholipase D. We find that induction of defence genes is independent of auxin. However, auxin can suppress harpin-induced cell death and also counteract actin bundling. We integrate our findings into a model, where harpin interferes with an auxin dependent pathway that sustains dynamic cortical actin through the activity of phospholipase D. The antagonism between growth and defence is explained by mutual competition for signal molecules such as superoxide and phosphatidic acid. Perturbations of the auxin-actin pathway might be used to detect disturbed integrity of the plasma membrane and channel defence signalling towards programmed cell death. PMID:25933033

  13. Keap1 redox-dependent regulation of doxorubicin-induced oxidative stress response in cardiac myoblasts

    SciTech Connect

    Nordgren, Kendra K.S. Wallace, Kendall B.

    2014-01-01

    Doxorubicin (DOX) is a widely prescribed treatment for a broad scope of cancers, but clinical utility is limited by the cumulative, dose-dependent cardiomyopathy that occurs with repeated administration. DOX-induced cardiotoxicity is associated with the production of reactive oxygen species (ROS) and oxidation of lipids, DNA and proteins. A major cellular defense mechanism against such oxidative stress is activation of the Keap1/Nrf2-antioxidant response element (ARE) signaling pathway, which transcriptionally regulates expression of antioxidant genes such as Nqo1 and Gstp1. In the present study, we address the hypothesis that an initial event associated with DOX-induced oxidative stress is activation of the Keap1/Nrf2-dependent expression of antioxidant genes and that this is regulated through drug-induced changes in redox status of the Keap1 protein. Incubation of H9c2 rat cardiac myoblasts with DOX resulted in a time- and dose-dependent decrease in non-protein sulfhydryl groups. Associated with this was a near 2-fold increase in Nrf2 protein content and enhanced transcription of several of the Nrf2-regulated down-stream genes, including Gstp1, Ugt1a1, and Nqo1; the expression of Nfe2l2 (Nrf2) itself was unaltered. Furthermore, both the redox status and the total amount of Keap1 protein were significantly decreased by DOX, with the loss of Keap1 being due to both inhibited gene expression and increased autophagic, but not proteasomal, degradation. These findings identify the Keap1/Nrf2 pathway as a potentially important initial response to acute DOX-induced oxidative injury, with the primary regulatory events being the oxidation and autophagic degradation of the redox sensor Keap1 protein. - Highlights: • DOX caused a ∼2-fold increase in Nrf2 protein content. • DOX enhanced transcription of several Nrf2-regulated down-stream genes. • Redox status and total amount of Keap1 protein were significantly decreased by DOX. • Loss of Keap1 protein was due to

  14. Redox regulation of mitochondrial function with emphasis on cysteine oxidation reactions☆

    PubMed Central

    Mailloux, Ryan J.; Jin, Xiaolei; Willmore, William G.

    2013-01-01

    Mitochondria have a myriad of essential functions including metabolism and apoptosis. These chief functions are reliant on electron transfer reactions and the production of ATP and reactive oxygen species (ROS). The production of ATP and ROS are intimately linked to the electron transport chain (ETC). Electrons from nutrients are passed through the ETC via a series of acceptor and donor molecules to the terminal electron acceptor molecular oxygen (O2) which ultimately drives the synthesis of ATP. Electron transfer through the respiratory chain and nutrient oxidation also produces ROS. At high enough concentrations ROS can activate mitochondrial apoptotic machinery which ultimately leads to cell death. However, if maintained at low enough concentrations ROS can serve as important signaling molecules. Various regulatory mechanisms converge upon mitochondria to modulate ATP synthesis and ROS production. Given that mitochondrial function depends on redox reactions, it is important to consider how redox signals modulate mitochondrial processes. Here, we provide the first comprehensive review on how redox signals mediated through cysteine oxidation, namely S-oxidation (sulfenylation, sulfinylation), S-glutathionylation, and S-nitrosylation, regulate key mitochondrial functions including nutrient oxidation, oxidative phosphorylation, ROS production, mitochondrial permeability transition (MPT), apoptosis, and mitochondrial fission and fusion. We also consider the chemistry behind these reactions and how they are modulated in mitochondria. In addition, we also discuss emerging knowledge on disorders and disease states that are associated with deregulated redox signaling in mitochondria and how mitochondria-targeted medicines can be utilized to restore mitochondrial redox signaling. PMID:24455476

  15. ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion

    PubMed Central

    Chen, Wei-Ta; Ebelt, Nancy D; Stracker, Travis H; Xhemalce, Blerta; Van Den Berg, Carla L; Miller, Kyle M

    2015-01-01

    Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression. Here we report a cancer-promoting role for ATM. ATM depletion in metastatic cancer cells reduced cell migration and invasion. Transcription analyses identified a gene network, including the chemokine IL-8, regulated by ATM. IL-8 expression required ATM and was regulated by oxidative stress. IL-8 was validated as an ATM target by its ability to rescue cell migration and invasion defects in ATM-depleted cells. Finally, ATM-depletion in human breast cancer cells reduced lung tumors in a mouse xenograft model and clinical data validated IL-8 in lung metastasis. These findings provide insights into how ATM activation by oxidative stress regulates IL-8 to sustain cell migration and invasion in cancer cells to promote metastatic potential. Thus, in addition to well-established roles in tumor suppression, these findings identify a role for ATM in tumor progression. DOI: http://dx.doi.org/10.7554/eLife.07270.001 PMID:26030852

  16. FurA contributes to the oxidative stress response regulation of Mycobacterium avium ssp. paratuberculosis

    PubMed Central

    Eckelt, Elke; Meißner, Thorsten; Meens, Jochen; Laarmann, Kristin; Nerlich, Andreas; Jarek, Michael; Weiss, Siegfried; Gerlach, Gerald-F.; Goethe, Ralph

    2015-01-01

    The ferric uptake regulator A (FurA) is known to be involved in iron homeostasis and stress response in many bacteria. In mycobacteria the precise role of FurA is still unclear. In the presented study, we addressed the functional role of FurA in the ruminant pathogen Mycobacterium avium ssp. paratuberculosis (MAP) by construction of a furA deletion strain (MAPΔfurA). RNA deep sequencing revealed that the FurA regulon consists of repressed and activated genes associated to stress response or intracellular survival. Not a single gene related to metal homeostasis was affected by furA deletion. A decisive role of FurA during intracellular survival in macrophages was shown by significantly enhanced survival of MAPΔfurA compared to the wildtype, indicating that a principal task of mycobacterial FurA is oxidative stress response regulation in macrophages. This resistance was not associated with altered survival of mice after long term infection with MAP. Our results demonstrate for the first time, that mycobacterial FurA is not involved in the regulation of iron homeostasis. However, they provide strong evidence that FurA contributes to intracellular survival as an oxidative stress sensing regulator. PMID:25705205

  17. KLF15 and PPARα Cooperate to Regulate Cardiomyocyte Lipid Gene Expression and Oxidation

    PubMed Central

    Prosdocimo, Domenick A.; John, Jenine E.; Zhang, Lilei; Efraim, Elizabeth S.; Zhang, Rongli; Liao, Xudong; Jain, Mukesh K.

    2015-01-01

    The metabolic myocardium is an omnivore and utilizes various carbon substrates to meet its energetic demand. While the adult heart preferentially consumes fatty acids (FAs) over carbohydrates, myocardial fuel plasticity is essential for organismal survival. This metabolic plasticity governing fuel utilization is under robust transcriptional control and studies over the past decade have illuminated members of the nuclear receptor family of factors (e.g., PPARα) as important regulators of myocardial lipid metabolism. However, given the complexity of myocardial metabolism in health and disease, it is likely that other molecular pathways are likely operative and elucidation of such pathways may provide the foundation for novel therapeutic approaches. We previously demonstrated that Kruppel-like factor 15 (KLF15) is an independent regulator of cardiac lipid metabolism thus raising the possibility that KLF15 and PPARα operate in a coordinated fashion to regulate myocardial gene expression requisite for lipid oxidation. In the current study, we show that KLF15 binds to, cooperates with, and is required for the induction of canonical PPARα-mediated gene expression and lipid oxidation in cardiomyocytes. As such, this study establishes a molecular module involving KLF15 and PPARα and provides fundamental insights into the molecular regulation of cardiac lipid metabolism. PMID:25815008

  18. Oleic acid-dependent modulation of Nitric oxide associated 1 protein levels regulates nitric oxide-mediated defense signaling in Arabidopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The conserved cellular metabolites nitric oxide (NO) and oleic acid (18:1) are well-known regulators of disease physiologies in diverse organism. We show that NO production in plants is regulated via 18:1. Reduction in 18:1 levels, via a genetic mutation in the 18:1-synthesizing gene SUPPRESSOR OF S...

  19. PPARs in Regulation of Paraoxonases: Control of Oxidative Stress and Inflammation Pathways

    PubMed Central

    Camps, Jordi; García-Heredia, Anabel; Rull, Anna; Alonso-Villaverde, Carlos; Aragonès, Gerard; Beltrán-Debón, Raúl; Rodríguez-Gallego, Esther; Joven, Jorge

    2012-01-01

    The paraoxonase (PON) group of enzymes, composed of PON1, PON2, and PON3, play an important role in decreasing oxidative stress by degrading lipid peroxides. PON1 synthesis is upregulated by PPAR. Several pharmacological compounds (acting as antioxidants and, hence, atheroprotective) stimulate both PPAR activity and PON1 expression. Recent evidence suggests that PON1 and the monocyte chemoattractant protein-1 (MCP-1) are involved in coordinating the inflammatory response in damaged tissues; PPAR may be central in the regulation of these biochemical pathways. This article reviews the state of knowledge on PON1 biochemistry and function, the influence of genetic variation, and the regulation of PON1 expression by pharmaceutical compounds that increase PPAR activity. We also describe recent lines of evidence suggesting links between PON1 and MCP-1 and how their production may be regulated by PPAR. PMID:22315585

  20. Costs of inducible defence along a resource gradient.

    PubMed

    Brönmark, Christer; Lakowitz, Thomas; Nilsson, P Anders; Ahlgren, Johan; Lennartsdotter, Charlotte; Hollander, Johan

    2012-01-01

    In addition to having constitutive defence traits, many organisms also respond to predation by phenotypic plasticity. In order for plasticity to be adaptive, induced defences should incur a benefit to the organism in, for example, decreased risk of predation. However, the production of defence traits may include costs in fitness components such as growth, time to reproduction, or fecundity. To test the hypothesis that the expression of phenotypic plasticity incurs costs, we performed a common garden experiment with a freshwater snail, Radix balthica, a species known to change morphology in the presence of molluscivorous fish. We measured a number of predator-induced morphological and behavioural defence traits in snails that we reared in the presence or absence of chemical cues from fish. Further, we quantified the costs of plasticity in fitness characters related to fecundity and growth. Since plastic responses may be inhibited under limited resource conditions, we reared snails in different densities and thereby levels of competition. Snails exposed to predator cues grew rounder and thicker shells, traits confirmed to be adaptive in environments with fish. Defence traits were consistently expressed independent of density, suggesting strong selection from predatory molluscivorous fish. However, the expression of defence traits resulted in reduced growth rate and fecundity, particularly with limited resources. Our results suggest full defence in predator related traits regardless of resource availability, and costs of defence consequently paid in traits related to fitness. PMID:22291961

  1. Costs of Inducible Defence along a Resource Gradient

    PubMed Central

    Brönmark, Christer; Lakowitz, Thomas; Nilsson, P. Anders; Ahlgren, Johan; Lennartsdotter, Charlotte; Hollander, Johan

    2012-01-01

    In addition to having constitutive defence traits, many organisms also respond to predation by phenotypic plasticity. In order for plasticity to be adaptive, induced defences should incur a benefit to the organism in, for example, decreased risk of predation. However, the production of defence traits may include costs in fitness components such as growth, time to reproduction, or fecundity. To test the hypothesis that the expression of phenotypic plasticity incurs costs, we performed a common garden experiment with a freshwater snail, Radix balthica, a species known to change morphology in the presence of molluscivorous fish. We measured a number of predator-induced morphological and behavioural defence traits in snails that we reared in the presence or absence of chemical cues from fish. Further, we quantified the costs of plasticity in fitness characters related to fecundity and growth. Since plastic responses may be inhibited under limited resource conditions, we reared snails in different densities and thereby levels of competition. Snails exposed to predator cues grew rounder and thicker shells, traits confirmed to be adaptive in environments with fish. Defence traits were consistently expressed independent of density, suggesting strong selection from predatory molluscivorous fish. However, the expression of defence traits resulted in reduced growth rate and fecundity, particularly with limited resources. Our results suggest full defence in predator related traits regardless of resource availability, and costs of defence consequently paid in traits related to fitness. PMID:22291961

  2. Computed Tomography Technology: Development and Applications for Defence

    NASA Astrophysics Data System (ADS)

    Baheti, G. L.; Saxena, Nisheet; Tripathi, D. K.; Songara, K. C.; Meghwal, L. R.; Meena, V. L.

    2008-09-01

    Computed Tomography(CT) has revolutionized the field of Non-Destructive Testing and Evaluation (NDT&E). Tomography for industrial applications warrants design and development of customized solutions catering to specific visualization requirements. Present paper highlights Tomography Technology Solutions implemented at Defence Laboratory, Jodhpur (DLJ). Details on the technological developments carried out and their utilization for various Defence applications has been covered.

  3. Regulation of mitochondrial oxidative stress by β-arrestins in cultured human cardiac fibroblasts

    PubMed Central

    Philip, Jennifer L.; Razzaque, Md. Abdur; Han, Mei; Li, Jinju; Theccanat, Tiju; Xu, Xianyao; Akhter, Shahab A.

    2015-01-01

    ABSTRACT Oxidative stress in cardiac fibroblasts (CFs) promotes transformation to myofibroblasts and collagen synthesis leading to myocardial fibrosis, a precursor to heart failure (HF). NADPH oxidase 4 (Nox4) is a major source of cardiac reactive oxygen species (ROS); however, mechanisms of Nox4 regulation are unclear. β-arrestins are scaffold proteins that signal in G-protein-dependent and -independent pathways; for example, in ERK activation. We hypothesize that β-arrestins regulate oxidative stress in a Nox4-dependent manner and increase fibrosis in HF. CFs were isolated from normal and failing adult human left ventricles. Mitochondrial ROS/superoxide production was quantitated using MitoSox. β-arrestin and Nox4 expressions were manipulated using adenoviral overexpression or short interfering RNA (siRNA)-mediated knockdown. Mitochondrial oxidative stress and Nox4 expression in CFs were significantly increased in HF. Nox4 knockdown resulted in inhibition of mitochondrial superoxide production and decreased basal and TGF-β-stimulated collagen and α-SMA expression. CF β-arrestin expression was upregulated fourfold in HF. β-arrestin knockdown in failing CFs decreased ROS and Nox4 expression by 50%. β-arrestin overexpression in normal CFs increased mitochondrial superoxide production twofold. These effects were prevented by inhibition of either Nox or ERK. Upregulation of Nox4 seemed to be a primary mechanism for increased ROS production in failing CFs, which stimulates collagen deposition. β-arrestin expression was upregulated in HF and plays an important and newly identified role in regulating mitochondrial superoxide production via Nox4. The mechanism for this effect seems to be ERK-mediated. Targeted inhibition of β-arrestins in CFs might decrease oxidative stress as well as pathological cardiac fibrosis. PMID:26449263

  4. A Universally Conserved ATPase Regulates the Oxidative Stress Response in Escherichia coli*

    PubMed Central

    Wenk, Meike; Ba, Qiaorui; Erichsen, Veronika; MacInnes, Katherine; Wiese, Heike; Warscheid, Bettina; Koch, Hans-Georg

    2012-01-01

    YchF is an evolutionarily conserved ATPase of unknown function. In humans, the YchF homologue hOla1 appears to influence cell proliferation and was found to be up-regulated in many tumors. A possible involvement in regulating the oxidative stress response was also suggested, but details on the underlying mechanism are lacking. For gaining insight into YchF function, we used Escherichia coli as a model organism and found that YchF overexpression resulted in H2O2 hypersensitivity. This was not caused by transcriptional or translational down-regulation of H2O2-scavenging enzymes. Instead, we observed YchF-dependent inhibition of catalase activity and a direct interaction with the major E. coli catalase KatG. KatG inhibition was dependent on the ATPase activity of YchF and was regulated by post-translational modifications, most likely including an H2O2-dependent dephosphorylation. We furthermore showed that YchF expression is repressed by the transcription factor OxyR and further post-translationally modified in response to H2O2. In summary, our data show that YchF functions as a novel negative regulator of the oxidative stress response in E. coli. Considering the available data on hOla1, YchF/Ola1 most likely execute similar functions in bacteria and humans, and their up-regulation inhibits the ability of the cells to scavenge damaging reactive oxygen species. PMID:23139412

  5. TXNIP regulates myocardial fatty acid oxidation via miR-33a signaling.

    PubMed

    Chen, Junqin; Young, Martin E; Chatham, John C; Crossman, David K; Dell'Italia, Louis J; Shalev, Anath

    2016-07-01

    Myocardial fatty acid β-oxidation is critical for the maintenance of energy homeostasis and contractile function in the heart, but its regulation is still not fully understood. While thioredoxin-interacting protein (TXNIP) has recently been implicated in cardiac metabolism and mitochondrial function, its effects on β-oxidation have remained unexplored. Using a new cardiomyocyte-specific TXNIP knockout mouse and working heart perfusion studies, as well as loss- and gain-of-function experiments in rat H9C2 and human AC16 cardiomyocytes, we discovered that TXNIP deficiency promotes myocardial β-oxidation via signaling through a specific microRNA, miR-33a. TXNIP deficiency leads to increased binding of nuclear factor Y (NFYA) to the sterol regulatory element binding protein 2 (SREBP2) promoter, resulting in transcriptional inhibition of SREBP2 and its intronic miR-33a. This allows for increased translation of the miR-33a target genes and β-oxidation-promoting enzymes, carnitine octanoyl transferase (CROT), carnitine palmitoyl transferase 1 (CPT1), hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase-β (HADHB), and AMPKα and is associated with an increase in phospho-AMPKα and phosphorylation/inactivation of acetyl-CoA-carboxylase. Thus, we have identified a novel TXNIP-NFYA-SREBP2/miR-33a-AMPKα/CROT/CPT1/HADHB pathway that is conserved in mouse, rat, and human cardiomyocytes and regulates myocardial β-oxidation. PMID:27199118

  6. The Physiological Regulation of Skeletal Muscle Fatty Acid Supply and Oxidation During Moderate-Intensity Exercise.

    PubMed

    van Hall, Gerrit

    2015-11-01

    Energy substrates that are important to the working muscle at moderate intensities are the non-esterified fatty acids (NEFAs) taken up from the circulation and NEFAs originating from lipolysis of the intramuscular triacylglycerol (IMTAG). Moreover, NEFA from lipolysis via lipoprotein lipase (LPL) in the muscle of the very-low-density lipoproteins and in the (semi) post-prandial state chylomicrons may also contribute. In this review, the NEFA fluxes and oxidation by skeletal muscle during prolonged moderate-intensity exercise are described in terms of the integration of physiological systems. Steps involved in the regulation of the active muscle NEFA uptake include (1) increased energy demand; (2) delivery of NEFA to the muscle; (3) transport of NEFA into the muscle by NEFA transporters; and (4) activation of the NEFAs and either oxidation or re-esterification into IMTAG. The increased metabolic demand of the exercising muscle is the main driving force for all physiological regulatory processes. It elicits functional hyperemia, increasing the recruitment of capillaries and muscle blood flow resulting in increased NEFA delivery and accessibility to NEFA transporters and LPL. It also releases epinephrine that augments adipose tissue NEFA release and thereby NEFA delivery to the active muscle. Moreover, NEFA transporters translocate to the plasma membrane, further increasing the NEFA uptake. The majority of the NEFAs taken up by the active muscle is oxidized and a minor portion is re-esterified to IMTAG. Net IMTAG lipolysis occurs; however, the IMTAG contribution to total fat oxidation is rather limited compared to plasma-derived NEFA oxidation, suggesting a complex role and regulation of IMTAG utilization. PMID:26553490

  7. A saponin-detoxifying enzyme mediates suppression of plant defences

    NASA Astrophysics Data System (ADS)

    Bouarab, K.; Melton, R.; Peart, J.; Baulcombe, D.; Osbourn, A.

    2002-08-01

    Plant disease resistance can be conferred by constitutive features such as structural barriers or preformed antimicrobial secondary metabolites. Additional defence mechanisms are activated in response to pathogen attack and include localized cell death (the hypersensitive response). Pathogens use different strategies to counter constitutive and induced plant defences, including degradation of preformed antimicrobial compounds and the production of molecules that suppress induced plant defences. Here we present evidence for a two-component process in which a fungal pathogen subverts the preformed antimicrobial compounds of its host and uses them to interfere with induced defence responses. Antimicrobial saponins are first hydrolysed by a fungal saponin-detoxifying enzyme. The degradation product of this hydrolysis then suppresses induced defence responses by interfering with fundamental signal transduction processes leading to disease resistance.

  8. Functional inactivation of UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1) induces early leaf senescence and defence responses in rice.

    PubMed

    Wang, Zhaohai; Wang, Ya; Hong, Xiao; Hu, Daoheng; Liu, Caixiang; Yang, Jing; Li, Yang; Huang, Yunqing; Feng, Yuqi; Gong, Hanyu; Li, Yang; Fang, Gen; Tang, Huiru; Li, Yangsheng

    2015-02-01

    Plant leaf senescence and defence responses are important biological processes, but the molecular mechanisms involved are not well understood. This study identified a new rice mutant, spotted leaf 29 (spl29). The SPL29 gene was identified by map-based cloning, and SPL29 was confirmed as UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1) by enzymatic analysis. The mutant spl29 lacks UAP activity. The biological phenotypes for which UAP is responsible have not previously been reported in plants. The spl29 mutant displayed early leaf senescence, confirmed by chlorophyll loss and photosystem II decline as physiological indicators, chloroplast degradation as a cellular characteristic, and both upregulation of senescence transcription factors and senescence-associated genes, and downregulation of photosynthesis-related genes, as molecular evidence. Defence responses were induced in the spl29 mutant, shown by enhanced resistance to bacterial blight inoculation and upregulation of defence response genes. Reactive oxygen species, including O2 (-) and H2O2, accumulated in spl29 plants; there was also increased malondialdehyde content. Enhanced superoxide dismutase activity combined with normal catalase activity in spl29 could be responsible for H2O2 accumulation. The plant hormones jasmonic acid and abscisic acid also accumulated in spl29 plants. ROS and plant hormones probably play important roles in early leaf senescence and defence responses in the spl29 mutant. Based on these findings, it is suggested that UAP1 is involved in regulating leaf senescence and defence responses in rice. PMID:25399020

  9. [Hi-tech health care: modern status and prospects of development in medical facilities of the Ministry of Defence].

    PubMed

    Fisun, A Ia; Kuvshinov, K É; Makiev, R G; Pastukhov, A G

    2014-02-01

    The article is devoted to the current issues of providing hi-tech medical care in hospitals of the Ministry of Defence. Since the beginning of 2013 the executive body of the Russian Ministry of Defense pays special attention to improvement of the quality and accessibility of health care contingent of the Ministry of Defence. Thus, according to decision of the Minister of Defense of the Russian Federation, General of the Army Sergei Shoigu in 2013 more than 1.1 billion rubles (in 2012, targeted funding of high-tech medical care in the Ministry of Defence did not materialize) was allocated for military medical institutions of the Ministry of Defense of the Russian Federation to provide high-tech medical care. As a result, in 7 months in 2013 the volume of medical care has increased by 32% in comparison with the same period in 2012. Currently the main military medical department of the Ministry of Defense is working to resolve the order of delivery and financing hi-tech medical care in the Armed Forces in the following areas: inclusion of military medical institutions of the Ministry of Defence in the list of health organizations, providing high-tech medical care, approved by Order of the Ministry of Health of the Russian Federation, legal regulation of the provision of high-tech medical care in military medical establishments of the Ministry of defense of the Russian Federation within the budget appropriation allocated to the Ministry of Defence. PMID:25046918

  10. Role of stress-related hormones in plant defence during early infection of the cyst nematode Heterodera schachtii in Arabidopsis

    PubMed Central

    Kammerhofer, Nina; Radakovic, Zoran; Regis, Jully M A; Dobrev, Petre; Vankova, Radomira; Grundler, Florian M W; Siddique, Shahid; Hofmann, Julia; Wieczorek, Krzysztof

    2015-01-01

    Heterodera schachtii, a plant-parasitic cyst nematode, invades host roots and induces a specific syncytial feeding structure, from which it withdraws all required nutrients, causing severe yield losses. The system H. schachtii–Arabidopsis is an excellent research model for investigating plant defence mechanisms. Such responses are suppressed in well-established syncytia, whereas they are induced during early parasitism. However, the mechanisms by which the defence responses are modulated and the role of phytohormones are largely unknown. The aim of this study was to elucidate the role of hormone-based defence responses at the onset of nematode infection. First, concentrations of main phytohormones were quantified and the expression of several hormone-related genes was analysed using quantitative real-time (qRT)-PCR or GeneChip. Further, the effects of individual hormones were evaluated via nematode attraction and infection assays using plants with altered endogenous hormone concentrations. Our results suggest a pivotal and positive role for ethylene during nematode attraction, whereas jasmonic acid triggers early defence responses against H. schachtii. Salicylic acid seems to be a negative regulator during later syncytium and female development. We conclude that nematodes are able to impose specific changes in hormone pools, thus modulating hormone-based defence and signal transduction in strict dependence on their parasitism stage. PMID:25825039

  11. The proteasome and the degradation of oxidized proteins: Part III—Redox regulation of the proteasomal system

    PubMed Central

    Höhn, Tobias Jung Annika; Grune, Tilman

    2014-01-01

    Here, we review shortly the current knowledge on the regulation of the proteasomal system during and after oxidative stress. After addressing the components of the proteasomal system and the degradation of oxidatively damaged proteins in part I and II of this series, we address here which changes in activity undergo the proteasome and the ubiquitin-proteasomal system itself under oxidative conditions. While several components of the proteasomal system undergo direct oxidative modification, a number of redox-regulated events are modulating the proteasomal activity in a way it can address the major tasks in an oxidative stress situation: the removal of oxidized proteins and the adaptation of the cellular metabolism to the stress situation. PMID:24563857

  12. Chemical Diversity and Defence Metabolism: How Plants Cope with Pathogens and Ozone Pollution

    PubMed Central

    Iriti, Marcello; Faoro, Franco

    2009-01-01

    Chemical defences represent a main trait of the plant innate immune system. Besides regulating the relationship between plants and their ecosystems, phytochemicals are involved both in resistance against pathogens and in tolerance towards abiotic stresses, such as atmospheric pollution. Plant defence metabolites arise from the main secondary metabolic routes, the phenylpropanoid, the isoprenoid and the alkaloid pathways. In plants, antibiotic compounds can be both preformed (phytoanticipins) and inducible (phytoalexins), the former including saponins, cyanogenic glycosides and glucosinolates. Chronic exposure to tropospheric ozone (O3) stimulates the carbon fluxes from the primary to the secondary metabolic pathways to a great extent, inducing a shift of the available resources in favour of the synthesis of secondary products. In some cases, the plant defence responses against pathogens and environmental pollutants may overlap, leading to the unspecific synthesis of similar molecules, such as phenylpropanoids. Exposure to ozone can also modify the pattern of biogenic volatile organic compounds (BVOC), emitted from plant in response to herbivore feeding, thus altering the tritrophic interaction among plant, phytophagy and their natural enemies. Finally, the synthesis of ethylene and polyamines can be regulated by ozone at level of S-adenosylmethionine (SAM), the biosynthetic precursor of both classes of hormones, which can, therefore, mutually inhibit their own biosynthesis with consequence on plant phenotype. PMID:20111684

  13. Neutrophil oxidative burst activates ATM to regulate cytokine production and apoptosis

    PubMed Central

    Harbort, C. J.; Soeiro-Pereira, Paulo Vitor; von Bernuth, Horst; Kaindl, Angela M.; Costa-Carvalho, Beatriz Tavares; Condino-Neto, Antonio; Reichenbach, Janine; Roesler, Joachim; Zychlinsky, Arturo

    2015-01-01

    Neutrophils play an essential role in the initial stages of inflammation by balancing pro- and antiinflammatory signals. Among these signals are the production of proinflammatory cytokines and the timely initiation of antiinflammatory cell death via constitutive apoptosis. Here we identify ataxia-telangiectasia mutated (ATM) kinase as a modulator of these neutrophil functions. Ataxia-telangiectasia (AT) is a pleiotropic multisystem disorder caused by mutations in the gene-encoding ATM, a master regulator of the DNA damage response. In addition to progressive neurodegeneration and high rates of cancer, AT patients have numerous symptoms that can be linked to chronic inflammation. We report that neutrophils isolated from patients with AT overproduce proinflammatory cytokines and have a prolonged lifespan compared with healthy controls. This effect is partly mediated by increases in activation of p38 MAP kinase. Furthermore, we show that the oxidative burst, catalyzed by nicotinamide adenine dinucleotide phosphate oxidase, can activate ATM in neutrophils. Finally, activation of ATM and DNA damage signaling suppress cytokine production and can abrogate the overproduction of IL-8 in ROS-deficient cells. This reveals a novel mechanism for the regulation of cytokine production and apoptosis, establishing DNA damage as a downstream mediator of immune regulation by reactive oxygen species. We propose that deficiencies in the DNA damage response, like deficiencies in the oxidative burst seen in chronic granulomatous disease, could lead to pathologic inflammation. PMID:26491069

  14. Flow-dependent regulation of endothelial nitric oxide synthase: role of protein kinases

    NASA Technical Reports Server (NTRS)

    Boo, Yong Chool; Jo, Hanjoong

    2003-01-01

    Vascular endothelial cells are directly and continuously exposed to fluid shear stress generated by blood flow. Shear stress regulates endothelial structure and function by controlling expression of mechanosensitive genes and production of vasoactive factors such as nitric oxide (NO). Though it is well known that shear stress stimulates NO production from endothelial nitric oxide synthase (eNOS), the underlying molecular mechanisms remain unclear and controversial. Shear-induced production of NO involves Ca2+/calmodulin-independent mechanisms, including phosphorylation of eNOS at several sites and its interaction with other proteins, including caveolin and heat shock protein-90. There have been conflicting results as to which protein kinases-protein kinase A, protein kinase B (Akt), other Ser/Thr protein kinases, or tyrosine kinases-are responsible for shear-dependent eNOS regulation. The functional significance of each phosphorylation site is still unclear. We have attempted to summarize the current status of understanding in shear-dependent eNOS regulation.

  15. Neutrophil oxidative burst activates ATM to regulate cytokine production and apoptosis.

    PubMed

    Harbort, C J; Soeiro-Pereira, Paulo Vitor; von Bernuth, Horst; Kaindl, Angela M; Costa-Carvalho, Beatriz Tavares; Condino-Neto, Antonio; Reichenbach, Janine; Roesler, Joachim; Zychlinsky, Arturo; Amulic, Borko

    2015-12-24

    Neutrophils play an essential role in the initial stages of inflammation by balancing pro- and antiinflammatory signals. Among these signals are the production of proinflammatory cytokines and the timely initiation of antiinflammatory cell death via constitutive apoptosis. Here we identify ataxia-telangiectasia mutated (ATM) kinase as a modulator of these neutrophil functions. Ataxia-telangiectasia (AT) is a pleiotropic multisystem disorder caused by mutations in the gene-encoding ATM, a master regulator of the DNA damage response. In addition to progressive neurodegeneration and high rates of cancer, AT patients have numerous symptoms that can be linked to chronic inflammation. We report that neutrophils isolated from patients with AT overproduce proinflammatory cytokines and have a prolonged lifespan compared with healthy controls. This effect is partly mediated by increases in activation of p38 MAP kinase. Furthermore, we show that the oxidative burst, catalyzed by nicotinamide adenine dinucleotide phosphate oxidase, can activate ATM in neutrophils. Finally, activation of ATM and DNA damage signaling suppress cytokine production and can abrogate the overproduction of IL-8 in ROS-deficient cells. This reveals a novel mechanism for the regulation of cytokine production and apoptosis, establishing DNA damage as a downstream mediator of immune regulation by reactive oxygen species. We propose that deficiencies in the DNA damage response, like deficiencies in the oxidative burst seen in chronic granulomatous disease, could lead to pathologic inflammation. PMID:26491069

  16. RNA splicing in regulation of Nitric Oxide receptor Soluble Guanylyl Cyclase

    PubMed Central

    Sharina, Iraida G.; Cote, Gilbert J.; Martin, Emil; Doursout, Marie-Francoise; Murad, Ferid

    2011-01-01

    Soluble guanylyl cyclase (sGC) is a key protein in the nitric oxide (NO)/-cGMP signaling pathway. sGC activity is involved in a number of important physiological processes including smooth muscle relaxation, neurotransmission and platelet aggregation and adhesion. Regulation of sGC expression and activity emerges as a crucial factor in control of sGC function in normal and pathological conditions. Recently accumulated evidence strongly indicates that the regulation of sGC expression is a complex process modulated on several levels including transcription, post-transcriptional regulation, translation and protein stability. Presently our understanding of mechanisms governing regulation of sGC expression remains very limited and awaits systematic investigation. Among other ways, the expression of sGC subunits is modulated at the levels of mRNA abundance and transcript diversity. In this review we summarize available information on different mechanisms (including transcriptional activation, mRNA stability and alternative splicing) involved in the modulation of mRNA levels of sGC subunits in response to various environmental clues. We also summarize and cross-reference the information on human sGC splice forms available in the literature and in genomic databases. This review highlights the fact that the study of the biological role and regulation of sGC splicing will bring new insights to our understanding of NO/cGMP biology. PMID:21867767

  17. Lipopolysaccharide augments the uptake of oxidized LDL by up-regulating lectin-like oxidized LDL receptor-1 in macrophages.

    PubMed

    Hossain, Ekhtear; Ota, Akinobu; Karnan, Sivasundaram; Takahashi, Miyuki; Mannan, Shahnewaj B; Konishi, Hiroyuki; Hosokawa, Yoshitaka

    2015-02-01

    There is a growing body of evidence supporting an intimate association of immune activation with the pathogenesis of cardiovascular diseases, including atherosclerosis. Uptake of oxidized low-density lipoprotein (oxLDL) through scavenging receptors promotes the formation of mature lipid-laden macrophages, which subsequently leads to exacerbation of regional inflammation and atherosclerotic plaque formation. In this study, we first examined changes in the mRNA level of the lectin-like oxLDL receptor-1 (LOX-1) in the mouse macrophage cell line RAW264.7 and the human PMA-induced macrophage cell line THP-1 after LPS stimulation. LPS significantly up-regulated LOX-1 mRNA in RAW264.7 cells; LOX-1 cell-surface protein expression was also increased. Flow cytometry and fluorescence microscopy analyses showed that cellular uptake of fluorescence (Dil)-labeled oxLDL was significantly augmented with LPS stimulation. The augmented uptake of Dil-oxLDL was almost completely abrogated by treatment with an anti-LOX-1 antibody. Of note, knockdown of Erk1/2 resulted in a significant reduction of LPS-induced LOX-1 up-regulation. Treatment with U0126, a specific inhibitor of MEK, significantly suppressed LPS-induced expression of LOX-1 at both the mRNA and protein levels. Furthermore, LOX-1 promoter activity was significantly augmented by LPS stimulation; this augmentation was prevented by U0126 treatment. Similar results were also observed in human PMA-induced THP-1 macrophages. Taken together, our results indicate that LPS up-regulates LOX-1, at least in part through activation of the Erk1/2 signaling pathway, followed by augmented cellular oxLDL uptake, thus highlighting a critical role of TLR4-mediated aberrant LOX-1 signaling in the pathogenesis of atherosclerosis. PMID:25348362

  18. Rev-erb-α modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy

    PubMed Central

    Woldt, Estelle; Sebti, Yasmine; Solt, Laura A.; Duhem, Christian; Lancel, Steve; Eeckhoute, Jérôme; Hesselink, Matthijs K.C.; Paquet, Charlotte; Delhaye, Stéphane; Shin, Youseung; Kamenecka, Theodore M.; Schaart, Gert; Lefebvre, Philippe; Nevière, Rémi; Burris, Thomas P.; Schrauwen, Patrick; Staels, Bart; Duez, Hélène

    2013-01-01

    The nuclear receptor Rev-erb-α modulates hepatic lipid and glucose metabolism, adipogenesis and the inflammatory response in macrophages. We show here that Rev-erb-α is highly expressed in oxidative skeletal muscle and plays a role in mitochondrial biogenesis and oxidative function, in gain- and loss-of function studies. Rev-erb-α-deficiency in skeletal muscle leads to reduced mitochondrial content and oxidative function, resulting in compromised exercise capacity. This phenotype was recapitulated in isolated fibers and in muscle cells upon Rev-erbα knock-down, while Rev-erb-α over-expression increased the number of mitochondria with improved respiratory capacity. Rev-erb-α-deficiency resulted in deactivation of the Stk11–Ampk–Sirt1–Ppargc1-α signaling pathway, whereas autophagy was up-regulated, resulting in both impaired mitochondrial biogenesis and increased clearance. Muscle over-expression or pharmacological activation of Rev-erb-α increased respiration and exercise capacity. This study identifies Rev-erb-α as a pharmacological target which improves muscle oxidative function by modulating gene networks controlling mitochondrial number and function. PMID:23852339

  19. CUEDC2 modulates cardiomyocyte oxidative capacity by regulating GPX1 stability.

    PubMed

    Jian, Zhao; Liang, Bing; Pan, Xin; Xu, Guang; Guo, Sai-Sai; Li, Ting; Zhou, Tao; Xiao, Ying-Bin; Li, Ai-Ling

    2016-01-01

    The irreversible loss of cardiomyocytes due to oxidative stress is the main cause of heart dysfunction following ischemia/reperfusion (I/R) injury and ageing-induced cardiomyopathy. Here, we report that CUEDC2, a CUE domain-containing protein, plays a critical role in oxidative stress-induced cardiac injury. Cuedc2(-/-) cardiomyocytes exhibited a greater resistance to oxidative stress-induced cell death. Loss of CUEDC2 enhanced the antioxidant capacity of cardiomyocytes, promoted reactive oxygen species (ROS) scavenging, and subsequently inhibited the redox-dependent activation of signaling pathways. Notably, CUEDC2 promoted E3 ubiquitin ligases tripartite motif-containing 33 (TRIM33)-mediated the antioxidant enzyme, glutathione peroxidase 1 (GPX1) ubiquitination, and proteasome-dependent degradation. Ablation of CUEDC2 upregulated the protein level of GPX1 in the heart significantly. Strikingly, in vivo, the infarct size of Cuedc2(-/-) heart was significantly decreased after I/R injury, and aged Cuedc2(-/-) mice preserved better heart function as the overall ROS levels in their hearts were significantly lower. Our results demonstrated a novel role of CUEDC2 in cardiomyocyte death regulation. Manipulating CUEDC2 level might be an attractive therapeutic strategy for promoting cardiomyocyte survival following oxidative stress-induced cardiac injury. PMID:27286733

  20. Regulation of Ca2+ release from mitochondria by the oxidation-reduction state of pyridine nucleotides.

    PubMed

    Lehninger, A L; Vercesi, A; Bababunmi, E A

    1978-04-01

    Mitochondria from normal rat liver and heart, and also Ehrlich tumor cells, respiring on succinate as energy source in the presence of rotenone (to prevent net electron flow to oxygen from the endogenous pyridine nucleotides), rapidly take up Ca(2+) and retain it so long as the pyridine nucleotides are kept in the reduced state. When acetoacetate is added to bring the pyridine nucleotides into a more oxidized state, Ca(2+) is released to the medium. A subsequent addition of a reductant of the pyridine nucleotides such as beta-hydroxybutyrate, glutamate, or isocitrate causes reuptake of the released Ca(2+). Successive cycles of Ca(2+) release and uptake can be induced by shifting the redox state of the pyridine nucleotides to more oxidized and more reduced states, respectively. Similar observations were made when succinate oxidation was replaced as energy source by ascorbate oxidation or by the hydrolysis of ATP. These and other observations form the basis of a hypothesis for feedback regulation of Ca(2+)-dependent substrate- or energy-mobilizing enzymatic reactions by the uptake or release of mitochondrial Ca(2+), mediated by the cytosolic phosphate potential and the ATP-dependent reduction of mitochondrial pyridine nucleotides by reversal of electron transport. PMID:25436

  1. Anr, the anaerobic global regulator, modulates the redox state and oxidative stress resistance in Pseudomonas extremaustralis.

    PubMed

    Tribelli, Paula M; Nikel, Pablo I; Oppezzo, Oscar J; López, Nancy I

    2013-02-01

    The role of Anr in oxidative stress resistance was investigated in Pseudomonas extremaustralis, a polyhydroxybutyrate-producing Antarctic bacterium. The absence of Anr caused increased sensitivity to hydrogen peroxide under low oxygen tension. This phenomenon was associated with a decrease in the redox ratio, higher oxygen consumption and higher reactive oxygen species production. Physiological responses of the mutant to the oxidized state included an increase in NADP(H) content, catalase activity and exopolysaccharide production. The wild-type strain showed a sharp decrease in the reduced thiol pool when exposed to hydrogen peroxide, not observed in the mutant strain. In silico analysis of the genome sequence of P. extremaustralis revealed putative Anr binding sites upstream from genes related to oxidative stress. Genes encoding several chaperones and cold shock proteins, a glutathione synthase, a sulfate transporter and a thiol peroxidase were identified as potential targets for Anr regulation. Our results suggest a novel role for Anr in oxidative stress resistance and in redox balance maintenance under conditions of restricted oxygen supply. PMID:23223440

  2. Estrogen-related receptor gamma is a key regulator of muscle mitochondrial activity and oxidative capacity.

    PubMed

    Rangwala, Shamina M; Wang, Xiaomei; Calvo, Jennifer A; Lindsley, Loren; Zhang, Yunyu; Deyneko, Galina; Beaulieu, Valerie; Gao, Jiaping; Turner, Gordon; Markovits, Judit

    2010-07-16

    Estrogen-related receptor gamma (ERRgamma) regulates the perinatal switch to oxidative metabolism in the myocardium. We wanted to understand the significance of induction of ERRgamma expression in skeletal muscle by exercise. Muscle-specific VP16ERRgamma transgenic mice demonstrated an increase in exercise capacity, mitochondrial enzyme activity, and enlarged mitochondria despite lower muscle weights. Furthermore, peak oxidative capacity was higher in the transgenics as compared with control littermates. In contrast, mice lacking one copy of ERRgamma exhibited decreased exercise capacity and muscle mitochondrial function. Interestingly, we observed that increased ERRgamma in muscle generates a gene expression profile that closely overlays that of red oxidative fiber-type muscle. We further demonstrated that a small molecule agonist of ERRbeta/gamma can increase mitochondrial function in mouse myotubes. Our data indicate that ERRgamma plays an important role in causing a shift toward slow twitch muscle type and, concomitantly, a greater capacity for endurance exercise. Thus, the activation of this nuclear receptor provides a potential node for therapeutic intervention for diseases such as obesity, which is associated with reduced oxidative metabolism and a lower type I fiber content in skeletal muscle. PMID:20418374

  3. Estrogen-related Receptor γ Is a Key Regulator of Muscle Mitochondrial Activity and Oxidative Capacity

    PubMed Central

    Rangwala, Shamina M.; Wang, Xiaomei; Calvo, Jennifer A.; Lindsley, Loren; Zhang, Yunyu; Deyneko, Galina; Beaulieu, Valerie; Gao, Jiaping; Turner, Gordon; Markovits, Judit

    2010-01-01

    Estrogen-related receptor γ (ERRγ) regulates the perinatal switch to oxidative metabolism in the myocardium. We wanted to understand the significance of induction of ERRγ expression in skeletal muscle by exercise. Muscle-specific VP16ERRγ transgenic mice demonstrated an increase in exercise capacity, mitochondrial enzyme activity, and enlarged mitochondria despite lower muscle weights. Furthermore, peak oxidative capacity was higher in the transgenics as compared with control littermates. In contrast, mice lacking one copy of ERRγ exhibited decreased exercise capacity and muscle mitochondrial function. Interestingly, we observed that increased ERRγ in muscle generates a gene expression profile that closely overlays that of red oxidative fiber-type muscle. We further demonstrated that a small molecule agonist of ERRβ/γ can increase mitochondrial function in mouse myotubes. Our data indicate that ERRγ plays an important role in causing a shift toward slow twitch muscle type and, concomitantly, a greater capacity for endurance exercise. Thus, the activation of this nuclear receptor provides a potential node for therapeutic intervention for diseases such as obesity, which is associated with reduced oxidative metabolism and a lower type I fiber content in skeletal muscle. PMID:20418374

  4. Regulation of Ca2+ release from mitochondria by the oxidation-reduction state of pyridine nucleotides

    PubMed Central

    Lehninger, Albert L.; Vercesi, Anibal; Bababunmi, Enitan A.

    1978-01-01

    Mitochondria from normal rat liver and heart, and also Ehrlich tumor cells, respiring on succinate as energy source in the presence of rotenone (to prevent net electron flow to oxygen from the endogenous pyridine nucleotides), rapidly take up Ca2+ and retain it so long as the pyridine nucleotides are kept in the reduced state. When acetoacetate is added to bring the pyridine nucleotides into a more oxidized state, Ca2+ is released to the medium. A subsequent addition of a reductant of the pyridine nucleotides such as β-hydroxybutyrate, glutamate, or isocitrate causes reuptake of the released Ca2+. Successive cycles of Ca2+ release and uptake can be induced by shifting the redox state of the pyridine nucleotides to more oxidized and more reduced states, respectively. Similar observations were made when succinate oxidation was replaced as energy source by ascorbate oxidation or by the hydrolysis of ATP. These and other observations form the basis of a hypothesis for feedback regulation of Ca2+-dependent substrate- or energy-mobilizing enzymatic reactions by the uptake or release of mitochondrial Ca2+, mediated by the cytosolic phosphate potential and the ATP-dependent reduction of mitochondrial pyridine nucleotides by reversal of electron transport. Images PMID:25436

  5. A Cytokine Signalling Network for the Regulation of Inducible Nitric Oxide Synthase Expression in Rheumatoid Arthritis.

    PubMed

    Dey, Poulami; Panga, Venugopal; Raghunathan, Srivatsan

    2016-01-01

    In rheumatoid arthritis (RA), nitric oxide (NO) is implicated in inflammation, angiogenesis and tissue destruction. The enzyme inducible nitric oxide synthase (iNOS) is responsible for the localised over-production of NO in the synovial joints affected by RA. The pro- and anti-inflammatory cytokines stimulate the synovial macrophages and the fibroblast-like synoviocytes to express iNOS. Therefore, the cytokine signalling network underlying the regulation of iNOS is essential to understand the pathophysiology of the disease. By using information from the literature, we have constructed, for the first time, the cytokine signalling network involved in the regulation of iNOS expression. Using the differential expression patterns obtained by re-analysing the microarray data on the RA synovium and the synovial macrophages available in the Gene Expression Omnibus (GEO) database, we aimed to establish the role played by the network genes towards iNOS regulation in the RA synovium. Our analysis reveals that the network genes belonging to interferon (IFN) and interleukin-10 (IL-10) pathways are always up-regulated in the RA synovium whereas the genes which are part of the anti-inflammatory transforming growth factor-beta (TGF-β) signalling pathway are mostly down-regulated. We observed a consistent up-regulation of the transcription factor signal transducers and activators of transcription 1 (STAT1) in the RA synovium and the macrophages. Interestingly, we found a consistent up-regulation of the iNOS interacting protein ras-related C3 botulinum toxin substrate 2 (RAC2) in the RA synovium as well as the macrophages. Importantly, we have constructed a model to explain the impact of IFN and IL-10 pathways on Rac2-iNOS interaction leading to over-production of NO and thereby causing chronic inflammation in the RA synovium. The interplay between STAT1 and RAC2 in the regulation of NO could have implications for the identification of therapeutic targets for RA. PMID:27626941

  6. Regulation of cardiac nitric oxide signaling by nuclear β-adrenergic and endothelin receptors*

    PubMed Central

    Vaniotis, George; Glazkova, Irina; Merlen, Clémence; Smith, Carter; Villeneuve, Louis R.; Chatenet, David; Therien, Michel; Fournier, Alain; Tadevosyan, Artavazd; Trieu, Phan; Nattel, Stanley; Hébert, Terence E.; Allen, Bruce G.

    2013-01-01

    At the cell surface, βARs and endothelin receptors can regulate nitric oxide (NO) production. β-adrenergic receptors (βARs) and type B endothelin receptors (ETB) are present in cardiac nuclear membranes and regulate transcription. The present study investigated the role of the NO pathway in the regulation of gene transcription by these nuclear G protein-coupled receptors. Nitric oxide production and transcription initiation were measured in nuclei isolated from adult rat heart. The cell-permeable fluorescent dye 4,5-diaminofluorescein diacetate (DAF2 DA) was used to provide a direct assessment of nitric oxide release. Both isoproterenol and endothelin increased NO production in isolated nuclei. Furthermore, a β3AR-selective agonist, BRL 37344, increased NO synthesis whereas the β1AR-selective agonist xamoterol did not. Isoproterenol increased, whereas ET-1 reduced, de novo transcription. The NO synthase inhibitor L-NAME prevented isoproterenol from increasing either NO production or de novo transcription. L-NAME also blocked ET-1-induced NO-production but did not alter the suppression of transcription initiation by ET-1. Inhibition of the cGMP-dependent protein kinase (PKG) using KT5823 also blocked the ability of isoproterenol to increase transcription initiation. Furthermore, immunoblotting revealed eNOS, but not nNOS, in isolated nuclei. Finally, caged, cell-permeable isoproterenol and endothelin-1 analogs were used to selectively activate intracellular β-adrenergic and endothelin receptors in intact adult cardiomyocytes. Intracellular release of caged ET-1 or isoproterenol analogs increased NO production in intact adult cardiomyocytes. Hence, activation of the NO synthase/guanylyl cyclase/PKG pathway is necessary for nuclear β3ARs to increase de novo transcription. Furthermore, we have demonstrated the potential utility of caged receptor ligands in selectively modulating signaling via endogenous intracellular G protein-coupled receptors. PMID:23684854

  7. The Campylobacter jejuni Ferric Uptake Regulator Promotes Acid Survival and Cross-Protection against Oxidative Stress.

    PubMed

    Askoura, Momen; Sarvan, Sabina; Couture, Jean-François; Stintzi, Alain

    2016-05-01

    Campylobacter jejuni is a prevalent cause of bacterial gastroenteritis in humans worldwide. The mechanisms by which C. jejuni survives stomach acidity remain undefined. In the present study, we demonstrated that the C. jejuni ferric uptake regulator (Fur) plays an important role in C. jejuni acid survival and acid-induced cross-protection against oxidative stress. A C. jejuni Δfur mutant was more sensitive to acid than the wild-type strain. Profiling of the acid stimulon of the C. jejuni Δfur mutant allowed us to uncover Fur-regulated genes under acidic conditions. In particular, Fur was found to upregulate genes involved in flagellar and cell envelope biogenesis upon acid stress, and mutants with deletions of these genes were found to be defective in surviving acid stress. Interestingly, prior acid exposure of C. jejuni cross-protected against oxidative stress in a catalase (KatA)- and Fur-dependent manner. Western blotting and reverse transcription-quantitative PCR revealed increased expression of KatA upon acid stress. Electrophoretic mobility shift assays (EMSAs) demonstrated that the binding affinity between Fur and the katA promoter is reduced in vitro under conditions of low pH, rationalizing the higher levels of expression of katA under acidic conditions. Strikingly, the Δfur mutant exhibited reduced virulence in both human epithelial cells and the Galleria mellonella infection model. Altogether, this is the first study showing that, in addition to its role in iron metabolism, Fur is an important regulator of C. jejuni acid responses and this function cross-protects against oxidative stress. Moreover, our results clearly demonstrate Fur's important role in C. jejuni pathogenesis. PMID:26883589

  8. DELLA proteins modulate Arabidopsis defences induced in response to caterpillar herbivory

    PubMed Central

    Bede, Jacqueline C.

    2014-01-01

    Upon insect herbivory, many plant species change the direction of metabolic flux from growth into defence. Two key pathways modulating these processes are the gibberellin (GA)/DELLA pathway and the jasmonate pathway. In this study, the effect of caterpillar herbivory on plant-induced responses was compared between wild-type Arabidopsis thaliana (L.) Heynh. and quad-della mutants that have constitutively elevated GA responses. The labial saliva (LS) of caterpillars of the beet armyworm, Spodoptera exigua, is known to influence induced plant defence responses. To determine the role of this herbivore cue in determining metabolic shifts, plants were subject to herbivory by caterpillars with intact or impaired LS secretions. In both wild-type and quad-della plants, a jasmonate burst is an early response to caterpillar herbivory. Negative growth regulator DELLA proteins are required for the LS-mediated suppression of hormone levels. Jasmonate-dependent marker genes are induced in response to herbivory independently of LS, with the exception of AtPDF1.2 that showed LS-dependent expression in the quad-della mutant. Early expression of the salicylic acid (SA)-marker gene, AtPR1, was not affected by herbivory which also reflected SA hormone levels; however, this gene showed LS-dependent expression in the quad-della mutant. DELLA proteins may positively regulate glucosinolate levels and suppress laccase-like multicopper oxidase activity in response to herbivory. The present results show a link between DELLA proteins and early, induced plant defences in response to insect herbivory; in particular, these proteins are necessary for caterpillar LS-associated attenuation of defence hormones. PMID:24399173

  9. Effect of 28-homobrassinolide on antioxidant defence system in Raphanus sativus L. under chromium toxicity.

    PubMed

    Sharma, Indu; Pati, Pratap Kumar; Bhardwaj, Renu

    2011-06-01

    Heavy metals have emerged as major environmental contaminants due to rapid industrialization and urbanization. The genotoxic, mutagenic and carcinogenic effects of heavy metal like chromium (Cr) on man, animals and plants have been documented. In plants, accumulation of heavy metals beyond critical levels generates oxidative stress. This stress is generally overcome by antioxidant defence system and stress shielding phytohormones. Thus, the present study has been focused to analyze the effect of one of imperative group of plant hormones, i.e., brassinosteroids (BRs) which have been reported for its protective properties for wide array of environmental stresses. Raphanus sativus L. (Pusa Chetaki) seeds pre-treated with different concentrations of 28-homobrassinolide (28-HBL) were raised under various concentrations of Cr(VI). It was observed that 28-HBL treatment considerably reduced the impact of Cr-stress on seedlings which was evinced upon analysis of morphological and biochemical parameters of 7-days old radish seedlings. The toxic effects of Cr in terms of reduced growth, lowered contents of chlorophyll (Chl), protein, proline; increased malondialdehyde (MDA) content and elevated metal uptake were ameliorated by applications of 28-HBL. Also, the activities of all the antioxidant enzymes except guaiacol peroxidase (POD), increased significantly when subjected to Cr stress in combination with 28-HBL. Overall, seed pre-soaking treatment of 28-HBL at 10(-7) M was most effective in ameliorating Cr stress. The present work emphasizes the protective role of 28-HBL on regulation of antioxidant enzymes and its possible link in amelioration of stress in plants. PMID:21448625

  10. Oxidative folding in the mitochondrial intermembrane space: A regulated process important for cell physiology and disease.

    PubMed

    Chatzi, Afroditi; Manganas, Phanee; Tokatlidis, Kostas

    2016-06-01

    Mitochondria are fundamental organelles with a complex internal architecture that fulfill important diverse functions including iron-sulfur cluster assembly and cell respiration. Intense work for more than 30 years has identified the key protein import components and the pathways involved in protein targeting and assembly. More recently, oxidative folding has been discovered as one important mechanism for mitochondrial proteostasis whilst several human disorders have been linked to this pathway. We describe the molecular components of this pathway in view of their putative redox regulation and we summarize available evidence on the connections of these pathways to human disorders. PMID:27033519