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Sample records for oxidative defence regulation

  1. Nitric oxide-activated calcium/calmodulin-dependent protein kinase regulates the abscisic acid-induced antioxidant defence in maize.

    PubMed

    Ma, Fangfang; Lu, Rui; Liu, Huiying; Shi, Ben; Zhang, Jianhua; Tan, Mingpu; Zhang, Aying; Jiang, Mingyi

    2012-08-01

    Nitric oxide (NO), hydrogen peroxide (H2O2), and calcium (Ca2+)/calmodulin (CaM) are all required for abscisic acid (ABA)-induced antioxidant defence. Ca2+/CaM-dependent protein kinase (CCaMK) is a strong candidate for the decoder of Ca2+ signals. However, whether CCaMK is involved in ABA-induced antioxidant defence is unknown. The results of the present study show that exogenous and endogenous ABA induced increases in the activity of ZmCCaMK and the expression of ZmCCaMK in leaves of maize. Subcellular localization analysis showed that ZmCCaMK is located in the nucleus, the cytoplasm, and the plasma membrane. The transient expression of ZmCCaMK and the RNA interference (RNAi) silencing of ZmCCaMK analysis in maize protoplasts revealed that ZmCCaMK is required for ABA-induced antioxidant defence. Moreover, treatment with the NO donor sodium nitroprusside (SNP) induced the activation of ZmCCaMK and the expression of ZmCCaMK. Pre-treatments with an NO scavenger and inhibitor blocked the ABA-induced increases in the activity and the transcript level of ZmCCaMK. Conversely, RNAi silencing of ZmCCaMK in maize protoplasts did not affect the ABA-induced NO production, which was further confirmed using a mutant of OsCCaMK, the homologous gene of ZmCCaMK in rice. Moreover, H2O2 was also required for the ABA activation of ZmCCaMK, and pre-treatments with an NO scavenger and inhibitor inhibited the H2O2-induced increase in the activity of ZmCCaMK. Taken together, the data clearly suggest that ZmCCaMK is required for ABA-induced antioxidant defence, and H2O2-dependent NO production plays an important role in the ABA-induced activation of ZmCCaMK.

  2. Nitric oxide-activated calcium/calmodulin-dependent protein kinase regulates the abscisic acid-induced antioxidant defence in maize

    PubMed Central

    Zhang, Aying; Jiang, Mingyi

    2012-01-01

    Nitric oxide (NO), hydrogen peroxide (H2O2), and calcium (Ca2+)/calmodulin (CaM) are all required for abscisic acid (ABA)-induced antioxidant defence. Ca2+/CaM-dependent protein kinase (CCaMK) is a strong candidate for the decoder of Ca2+ signals. However, whether CCaMK is involved in ABA-induced antioxidant defence is unknown. The results of the present study show that exogenous and endogenous ABA induced increases in the activity of ZmCCaMK and the expression of ZmCCaMK in leaves of maize. Subcellular localization analysis showed that ZmCCaMK is located in the nucleus, the cytoplasm, and the plasma membrane. The transient expression of ZmCCaMK and the RNA interference (RNAi) silencing of ZmCCaMK analysis in maize protoplasts revealed that ZmCCaMK is required for ABA-induced antioxidant defence. Moreover, treatment with the NO donor sodium nitroprusside (SNP) induced the activation of ZmCCaMK and the expression of ZmCCaMK. Pre-treatments with an NO scavenger and inhibitor blocked the ABA-induced increases in the activity and the transcript level of ZmCCaMK. Conversely, RNAi silencing of ZmCCaMK in maize protoplasts did not affect the ABA-induced NO production, which was further confirmed using a mutant of OsCCaMK, the homologous gene of ZmCCaMK in rice. Moreover, H2O2 was also required for the ABA activation of ZmCCaMK, and pre-treatments with an NO scavenger and inhibitor inhibited the H2O2-induced increase in the activity of ZmCCaMK. Taken together, the data clearly suggest that ZmCCaMK is required for ABA-induced antioxidant defence, and H2O2-dependent NO production plays an important role in the ABA-induced activation of ZmCCaMK. PMID:22865912

  3. Pathogenic infection and the oxidative defences in plant apoplast.

    PubMed

    Bolwell, P P; Page, A; Piślewska, M; Wojtaszek, P

    2001-01-01

    The structural and functional continuum of the plant apoplast is the first site of contact with a pathogen and plays a crucial role in initiation and coordination of many defence responses. In this paper, we present an overview of the involvement of the plant apoplast in plant-pathogen interactions. The process of infection of French bean (Phaseolus vulgaris L.) plants by Colletotrichum lindemuthianum is analysed. The ultrastructural features of plant defence responses to fungal infection are then compared with those observed in plants or cell suspensions treated with various elicitors. Changes in cell walls and in whole plant cells responding to infection seem to be highly similar in all systems used. Model systems of French bean and white lupin (Lupinus albus L.) are then utilised to provide some biochemical characteristics of oxidative reactions in the apoplast evoked by elicitor treatment. The species specificity of various mechanisms generating reactive oxygen species is discussed, and some details of pH-dependent H2O2-generating activity of peroxidases are demonstrated. As its exocellular nature is an important feature of the oxidative burst, the major consequence of this event, i.e., the oxidative cross-linking of wall components during the papilla formation and strengthening of the walls, is analysed. Finally, the possible involvement of other wall-associated and developmentally regulated H2O2-generating mechanisms, like amine and oxalate oxidases, in plant defence is demonstrated. It is concluded that under stress conditions, such apoplastic mechanisms might be employed to increase plants' chances of survival.

  4. Upstream and downstream signals of nitric oxide in pathogen defence.

    PubMed

    Gaupels, Frank; Kuruthukulangarakoola, Gitto Thomas; Durner, Jörg

    2011-12-01

    Nitric oxide (NO) is now recognised as a crucial player in plant defence against pathogens. Considerable progress has been made in defining upstream and downstream signals of NO. Recently, MAP kinases, cyclic nucleotide phosphates, calcium and phosphatidic acid were demonstrated to be involved in pathogen-induced NO-production. However, the search for inducers of NO synthesis is difficult because of the still ambiguous enzymatic source of NO. Accumulation of NO triggers signal transduction by other second messengers. Here we depict NON-EXPRESSOR OF PATHOGENESIS-RELATED 1 and glyceraldehyde-3-phosphate dehydrogenase as central redox switches translating NO redox signalling into cellular responses. Although the exact position of NO in defence signal networks is unresolved at last some NO-related signal cascades are emerging.

  5. Carbon monoxide enhances salt tolerance by nitric oxide-mediated maintenance of ion homeostasis and up-regulation of antioxidant defence in wheat seedling roots.

    PubMed

    Xie, Yanjie; Ling, Tengfang; Han, Yi; Liu, Kaili; Zheng, Qingsong; Huang, Liqin; Yuan, Xingxing; He, Ziyi; Hu, Bing; Fang, Lei; Shen, Zhenguo; Yang, Qing; Shen, Wenbiao

    2008-12-01

    Salt stress induced an increase in endogenous carbon monoxide (CO) production and the activity of the CO synthetic enzyme haem oxygenase (HO) in wheat seedling roots. In addition, a 50% CO aqueous solution, applied daily, not only resulted in the enhancement of CO release, but led to a significant reversal in dry weight (DW) and water loss caused by 150 mm NaCl treatment, which was mimicked by the application of two nitric oxide (NO) donors sodium nitroprusside (SNP) and diethylenetriamine NO adduct (DETA/NO). Further analyses showed that CO, as well as SNP, apparently up-regulated H(+)-pump and antioxidant enzyme activities or related transcripts, thus resulting in the increase of K/Na ratio and the alleviation of oxidative damage. Whereas, the CO/NO scavenger haemoglobin (Hb), NO scavenger or synthetic inhibitor methylene blue (MB) or N(G)-nitro-l-arginine methyl ester hydrochloride (l-NAME) differentially blocked these effects. Furthermore, CO was able to mimic the effect of SNP by strongly increasing NO release in the root tips, whereas the CO-induced NO signal was quenched by the addition of l-NAME or cPTIO, the specific scavenger of NO. The results suggested that CO might confer an increased tolerance to salinity stress by maintaining ion homeostasis and enhancing antioxidant system parameters in wheat seedling roots, both of which were partially mediated by NO signal.

  6. Establishment of chronic hepatitis C virus infection: Translational evasion of oxidative defence

    PubMed Central

    Chan, Shiu-Wan

    2014-01-01

    Hepatitis C virus (HCV) causes a clinically important disease affecting 3% of the world population. HCV is a single-stranded, positive-sense RNA virus belonging to the genus Hepacivirus within the Flaviviridae family. The virus establishes a chronic infection in the face of an active host oxidative defence, thus adaptation to oxidative stress is key to virus survival. Being a small RNA virus with a limited genomic capacity, we speculate that HCV deploys a different strategy to evade host oxidative defence. Instead of counteracting oxidative stress, it utilizes oxidative stress to facilitate its own survival. Translation is the first step in the replication of a plus strand RNA virus so it would make sense if the virus can exploit the host oxidative defence in facilitating this very first step. This is particularly true when HCV utilizes an internal ribosome entry site element in translation, which is distinctive from that of cap-dependent translation of the vast majority of cellular genes, thus allowing selective translation of genes under conditions when global protein synthesis is compromised. Indeed, we were the first to show that HCV translation was stimulated by an important pro-oxidant-hydrogen peroxide in hepatocytes, suggesting that HCV is able to adapt to and utilize the host anti-viral response to facilitate its own translation thus allowing the virus to thrive under oxidative stress condition to establish chronicity. Understanding how HCV translation is regulated under oxidative stress condition will advance our knowledge on how HCV establishes chronicity. As chronicity is the initiator step in disease progression this will eventually lead to a better understanding of pathogenicity, which is particularly relevant to the development of anti-virals and improved treatments of HCV patients using anti-oxidants. PMID:24659872

  7. Sensory neuron regulation of gastrointestinal inflammation and bacterial host defence.

    PubMed

    Lai, N Y; Mills, K; Chiu, I M

    2017-07-01

    Sensory neurons in the gastrointestinal tract have multifaceted roles in maintaining homeostasis, detecting danger and initiating protective responses. The gastrointestinal tract is innervated by three types of sensory neurons: dorsal root ganglia, nodose/jugular ganglia and intrinsic primary afferent neurons. Here, we examine how these distinct sensory neurons and their signal transducers participate in regulating gastrointestinal inflammation and host defence. Sensory neurons are equipped with molecular sensors that enable neuronal detection of diverse environmental signals including thermal and mechanical stimuli, inflammatory mediators and tissue damage. Emerging evidence shows that sensory neurons participate in host-microbe interactions. Sensory neurons are able to detect pathogenic and commensal bacteria through specific metabolites, cell-wall components, and toxins. Here, we review recent work on the mechanisms of bacterial detection by distinct subtypes of gut-innervating sensory neurons. Upon activation, sensory neurons communicate to the immune system to modulate tissue inflammation through antidromic signalling and efferent neural circuits. We discuss how this neuro-immune regulation is orchestrated through transient receptor potential ion channels and sensory neuropeptides including substance P, calcitonin gene-related peptide, vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Recent studies also highlight a role for sensory neurons in regulating host defence against enteric bacterial pathogens including Salmonella typhimurium, Citrobacter rodentium and enterotoxigenic Escherichia coli. Understanding how sensory neurons respond to gastrointestinal flora and communicate with immune cells to regulate host defence enhances our knowledge of host physiology and may form the basis for new approaches to treat gastrointestinal diseases. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  8. Cold defence responses: the role of oxidative stress.

    PubMed

    Blagojevic, Dusko P; Grubor-Lajsic, Gordana N; Spasic, Mihajlo B

    2011-01-01

    Low temperatures provoke increased production of heat accompanied by increased respiration, oxygen consumption and the production of partially reduced oxygen species called ROS. ROS induce different forms of cellular oxidative damage, disturb the redox state and can change the activity of several metabolic enzymes. Organisms have developed a functionally connected set of anti-oxidant enzymes and low molecular mass compounds (together termed the ADS) that metabolise primary ROS. If ROS production within cells overwhelms the ADS, oxidative damage arises and oxidative stress can occur. Short-term cold exposure in endotherms leads to oxidative stress. As cold exposure persists organisms develop adaptive changes toward reducing ROS production and increasing the ADS. In contrast, heterotherms and ectotherms as a normal part of their over-wintering strategy slow down metabolism, oxygen consumption and subsequently cause ROS production. Increased baseline activity of key anti-oxidant enzymes as well as 'secondary' enzymatic defence and/or glutathione levels in preparation for a putative oxidative stressful situation arising from tissue re-oxygenation seems to be the preferred evolutionary adaptation of such animals exposed to low environmental temperatures.

  9. 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.

  10. The regulation of host defences to infection by the microbiota.

    PubMed

    Brown, Rebecca L; Clarke, Thomas B

    2017-01-01

    The skin and mucosal epithelia of humans and other mammals are permanently colonized by large microbial communities (the microbiota). Due to this life-long association with the microbiota, these microbes have an extensive influence over the physiology of their host organism. It is now becoming apparent that nearly all tissues and organ systems, whether in direct contact with the microbiota or in deeper host sites, are under microbial influence. The immune system is perhaps the most profoundly affected, with the microbiota programming both its innate and adaptive arms. The regulation of immunity by the microbiota helps to protect the host against intestinal and extra-intestinal infection by many classes of pathogen. In this review, we will discuss the experimental evidence supporting a role for the microbiota in regulating host defences to extra-intestinal infection, draw together common mechanistic themes, including the central role of pattern recognition receptors, and outline outstanding questions that need to be answered. © 2016 The Authors. Immunology Published by John Wiley & Sons Ltd.

  11. 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.

  12. 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

  13. Exploring the neutral invertase–oxidative stress defence connection in Arabidopsis thaliana

    PubMed Central

    Xiang, Li; Le Roy, Katrien; Bolouri-Moghaddam, Mohammad-Reza; Vanhaecke, Mieke; Lammens, Willem; Rolland, Filip; Van den Ende, Wim

    2011-01-01

    Over the past decades, considerable advances have been made in understanding the crucial role and the regulation of sucrose metabolism in plants. Among the various sucrose-catabolizing enzymes, alkaline/neutral invertases (A/N-Invs) have long remained poorly studied. However, recent findings have demonstrated the presence of A/N-Invs in various organelles in addition to the cytosol, and their importance for plant development and stress tolerance. A cytosolic (At-A/N-InvG, At1g35580) and a mitochondrial (At-A/N-InvA, At1g56560) member of the A/N-Invs have been analysed in more detail in Arabidopsis and it was found that At-A/N-InvA knockout plants show an even more severe growth phenotype than At-A/N-InvG knockout plants. The absence of either A/N-Inv was associated with higher oxidative stress defence gene expression, while transient overexpression of At-A/N-InvA and At-A/N-InvG in leaf mesophyll protoplasts down-regulated the oxidative stress-responsive ascorbate peroxidase 2 (APX2) promoter. Moreover, up-regulation of the APX2 promoter by hydrogen peroxide or abscisic acid could be blocked by adding metabolizable sugars or ascorbate. A hypothetical model is proposed in which both mitochondrial and cytosolic A/N-Invs can generate glucose as a substrate for mitochondria-associated hexokinase, contributing to mitochondrial reactive oxygen species homeostasis. PMID:21441406

  14. PM2.5, oxidant defence and cardiorespiratory health: a review

    PubMed Central

    2013-01-01

    Airborne fine particle mass concentrations (PM2.5) are used for ambient air quality management worldwide based in part on known cardiorespiratory health effects. While oxidative stress is generally thought to be an important mechanism in determining these effects, relatively few studies have specifically examined how oxidant defence may impact susceptibility to particulate air pollution. Here we review studies that explore the impact of polymorphisms in anti-oxidant related genes or anti-oxidant supplementation on PM2.5-induced cardiorespiratory outcomes in an effort to summarize existing evidence related to oxidative stress defence and the health effects of PM2.5. Recent studies of PM-oxidative burden were also examined. In total, nine studies were identified and reviewed and existing evidence generally suggests that oxidant defence may modify the impact of PM2.5 exposure on various health outcomes, particularly heart rate variability (a measure of autonomic function) which was the most common outcome examined in the studies reviewed. Few studies examined interactions between PM2.5 and oxidant defence for respiratory outcomes, and in general studies focused primarily on acute health effects. Therefore, further evaluation of the potential modifying role of oxidant defence in PM2.5-induced health effects is required, particularly for chronic outcomes. Similarly, while an exposure metric that captures the ability of PM2.5 to cause oxidative stress may offer advantages over traditional mass concentration measurements, little epidemiological evidence is currently available to evaluate the potential benefits of such an approach. Therefore, further evaluation is required to determine how this metric may be incorporated in ambient air quality management. PMID:23641908

  15. A Herbivorous Mite Down-Regulates Plant Defence and Produces Web to Exclude Competitors

    PubMed Central

    Sarmento, Renato A.; Lemos, Felipe; Dias, Cleide R.; Kikuchi, Wagner T.; Rodrigues, Jean C. P.; Pallini, Angelo; Sabelis, Maurice W.; Janssen, Arne

    2011-01-01

    Herbivores may interact with each other through resource competition, but also through their impact on plant defence. We recently found that the spider mite Tetranychus evansi down-regulates plant defences in tomato plants, resulting in higher rates of oviposition and population growth on previously attacked than on unattacked leaves. The danger of such down-regulation is that attacked plants could become a more profitable resource for heterospecific competitors, such as the two-spotted spider mite Tetranychus urticae. Indeed, T. urticae had an almost 2-fold higher rate of oviposition on leaf discs on which T. evansi had fed previously. In contrast, induction of direct plant defences by T. urticae resulted in decreased oviposition by T. evansi. Hence, both herbivores affect each other through induced plant responses. However, when populations of T. evansi and T. urticae competed on the same plants, populations of the latter invariably went extinct, whereas T. evansi was not significantly affected by the presence of its competitor. This suggests that T. evansi can somehow prevent its competitor from benefiting from the down-regulated plant defence, perhaps by covering it with a profuse web. Indeed, we found that T. urticae had difficulties reaching the leaf surface to feed when the leaf was covered with web produced by T. evansi. Furthermore, T. evansi produced more web when exposed to damage or other cues associated with T. urticae. We suggest that the silken web produced by T. evansi serves to prevent competitors from profiting from down-regulated plant defences. PMID:21887311

  16. 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. © 2013 BSPP AND JOHN WILEY & SONS LTD.

  17. 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

  18. Osmotic stress-induced polyamine oxidation mediates defence responses and reduces stress-enhanced grapevine susceptibility to Botrytis cinerea.

    PubMed

    Hatmi, Saloua; Trotel-Aziz, Patricia; Villaume, Sandra; Couderchet, Michel; Clément, Christophe; Aziz, Aziz

    2014-01-01

    Abiotic factors inducing osmotic stress can influence the plant immune response and resistance to pathogen infections. In this study, the effect of polyethylene glycol (PEG)- and sucrose-induced osmotic stress on polyamine (PA) homeostasis and the basal immune response in grapevine plantlets before and after Botrytis cinerea infection was determined. Pharmacological approaches were also addressed to assess the contribution of osmotic stress-induced PA oxidation to the regulation of defence responses and the susceptibility of grapevine to B. cinerea. Following osmotic stress or pathogen infection, PA homeostasis was linked to enhanced activity of diamine oxidases (CuAO) and PA oxidases (PAO) and the production of 1,3-diaminopropane. These responses paralleled the accumulation of the main stilbenic phytoalexins, resveratrol and ε-viniferin and upregulation of gene transcripts including STS (a stilbene synthase), PR-2 (a β-1,3-glucanase), PR3-4c (acidic chitinase IV), and PR-5 (a thaumatin-like protein), as well as NCED2 involved in abscisic acid biosynthesis. It was also demonstrated that leaves pre-exposed to osmotic stress and later inoculated with B. cinerea showed enhanced PA accumulation and attenuation of CuAO and PAO activities. This was consistent with the impaired production of phytoalexins and transcript levels of defence- and stress-related genes following infection, and the enhanced susceptibility to B. cinerea. Pharmacological experiments revealed that, under osmotic stress conditions, CuAO and PAO were involved in PA homeostasis and in the regulation of defence responses. Specific inhibition of CuAO and PAO in osmotically stressed leaves strongly attenuated the induction of defence responses triggered by B. cinerea infection and enhanced susceptibility to the pathogen. Taken together, this study reveals a contribution of PA catabolism to the resistance state through modulation of immune response in grapevine following osmotic stress and/or after B

  19. Oxidative stress and antioxidant defence in a healthy nonagenarian population.

    PubMed

    Balbis, Emanuela; Patriarca, Stefania; Furfaro, Anna Lisa; Cottalasso, Damiano; Pronzato, Maria Adelaide; Carlier, Paolo; Botta, Federica; Marinari, Umberto Maria; Fontana, Luigi; Traverso, Nicola

    2007-01-01

    Results on oxidative markers during ageing are not consistent throughout the scientific literature; however, successful ageing may depend on better ability to cope with oxidative stress. A previous study of ours showed that successful ageing could actually be related to enhanced response to oxidatively modified proteins. In this study, a healthy nonagenarian population (OVER-90) was examined for various blood oxidative biomarkers and compared with a healthy population of blood donors (age range, 23-66 years). Blood glutathione, both total (tGSH) and oxidised (GSSG), and total plasmatic antioxidant status were maintained in the OVER-90 at a level similar to the control population. Sulphydryl (sulfhydryl) groups and glutathione peroxidase (GPx) were instead decreased. The results are discussed in a possible unifying view: the OVER-90 population could possess a globally preserved antioxidant ability, though some signs of oxidative damage are present and some structures could be 'sacrificed' in order to keep the redox equilibrium.

  20. 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

    2015-10-07

    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. © 2015 The Author(s).

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

    PubMed Central

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

    2015-01-01

    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

  2. [Research of antioxidant defence system under alimentary induced oxidative stress].

    PubMed

    Kravchenko, Iu V; Mal'tsev, G Iu; Vasil'ev, A V

    2004-01-01

    Alimentary induced oxidative stress and its corrections in children and adults with homocysteine metabolism disorder are urgent problems for arteriosclerosis and cardiovascular disease prophylactics. For determination antioxidant status GSH-Px, SOD, GSH-reductase, catalase activities were detected. Effectiveness of Se-contained antioxidant complex "Selenec" was determined in experimental model with pubertal male Wistar rats. Including high value of methionine to semipurified diet with pyridoxine and folate deficiency induced oxidative stress. Lipid peroxidation substances were increased in blood, liver, intestine mucous tunic, aortal endothelium and myocardium. GSH-Px, SOD, GSH-reductase, catalase activities decreased significant compared to control. "Selenec" supplementation caused a decrease of thiobarbituric-reactive substances level, increasing SOD and catalase activity and decreasing GSH-Px and GSH-reductase activity in blood, liver, intestine mucous tunic, aorta and myocardium.

  3. Arabidopsis clade I TGA factors regulate apoplastic defences against the bacterial pathogen Pseudomonas syringae through endoplasmic reticulum-based processes.

    PubMed

    Wang, Lipu; Fobert, Pierre R

    2013-01-01

    During the plant immune response, large-scale transcriptional reprogramming is modulated by numerous transcription (co) factors. The Arabidopsis basic leucine zipper transcription factors TGA1 and TGA4, which comprise the clade I TGA factors, have been shown to positively contribute to disease resistance against virulent strains of the bacterial pathogen Pseudomonas syringae. Despite physically interacting with the key immune regulator, NON-EXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1), following elicitation with salicylic acid (SA), clade I function was shown to be largely independent of NPR1. Unlike mutants in NPR1, tga1-1 tga4-1 plants do not display reductions in steady-state levels of SA-pathway marker genes following treatment with this phenolic signaling metabolite or after challenge with virulent or avirulent P. syringae. By exploiting bacterial strains that have limited capacity to suppress Arabidopsis defence responses, the present study demonstrates that tga1-1 tga4-1 plants are compromised in basal resistance and defective in several apoplastic defence responses, including the oxidative burst of reactive oxygen species, callose deposition, as well as total and apoplastic PATHOGENESIS-RELATED 1 (PR-1) protein accumulation. Furthermore, analysis of npr1-1 and the tga1-1 tga4-1 npr1-1 triple mutant indicates that clade I TGA factors act substantially independent of NPR1 in mediating disease resistance against these strains of P. syringae. Increased sensitivity to the N-glycosylation inhibitor tunicamycin and elevated levels of endoplasmic reticulum (ER) stress marker genes encoding ER-resident chaperones in mutant seedlings suggest that loss of apoplastic defence responses is associated with aberrant protein secretion and implicate clade I TGA factors as positive regulators of one or more ER-related secretion pathways.

  4. Arabidopsis Clade I TGA Factors Regulate Apoplastic Defences against the Bacterial Pathogen Pseudomonas syringae through Endoplasmic Reticulum-Based Processes

    PubMed Central

    Wang, Lipu; Fobert, Pierre R.

    2013-01-01

    During the plant immune response, large-scale transcriptional reprogramming is modulated by numerous transcription (co) factors. The Arabidopsis basic leucine zipper transcription factors TGA1 and TGA4, which comprise the clade I TGA factors, have been shown to positively contribute to disease resistance against virulent strains of the bacterial pathogen Pseudomonas syringae. Despite physically interacting with the key immune regulator, NON-EXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1), following elicitation with salicylic acid (SA), clade I function was shown to be largely independent of NPR1. Unlike mutants in NPR1, tga1-1 tga4-1 plants do not display reductions in steady-state levels of SA-pathway marker genes following treatment with this phenolic signaling metabolite or after challenge with virulent or avirulent P. syringae. By exploiting bacterial strains that have limited capacity to suppress Arabidopsis defence responses, the present study demonstrates that tga1-1 tga4-1 plants are compromised in basal resistance and defective in several apoplastic defence responses, including the oxidative burst of reactive oxygen species, callose deposition, as well as total and apoplastic PATHOGENESIS-RELATED 1 (PR-1) protein accumulation. Furthermore, analysis of npr1-1 and the tga1-1 tga4-1 npr1-1 triple mutant indicates that clade I TGA factors act substantially independent of NPR1 in mediating disease resistance against these strains of P. syringae. Increased sensitivity to the N-glycosylation inhibitor tunicamycin and elevated levels of endoplasmic reticulum (ER) stress marker genes encoding ER-resident chaperones in mutant seedlings suggest that loss of apoplastic defence responses is associated with aberrant protein secretion and implicate clade I TGA factors as positive regulators of one or more ER-related secretion pathways. PMID:24086773

  5. Respiratory nitrogen metabolism and nitrosative stress defence in ϵ-proteobacteria: the role of NssR-type transcription regulators.

    PubMed

    Kern, Melanie; Winkler, Christine; Simon, Jörg

    2011-01-01

    ϵ-Proteobacteria form a globally ubiquitous group of ecologically significant organisms and comprise a diverse range of host-associated and free-living species. To grow by anaerobic respiration, many ϵ-proteobacteria reduce nitrate to nitrite followed by either nitrite ammonification or denitrification. Using the ammonifying model organisms Wolinella succinogenes and Campylobacter jejuni, the electron transport chains of nitrate respiration, respiratory nitrite ammonification and even N2O (nitrous oxide) respiration have been characterized in recent years, but knowledge on nitrosative stress defence, nitrogen compound-sensing and corresponding signal transduction pathways is limited. The potentially dominant role of NssR (nitrosative stress-sensing regulator)-type transcription regulators in ϵ-proteobacterial nitrogen metabolism is discussed.

  6. Enterococcus faecalis zinc-responsive proteins mediate bacterial defence against zinc overload, lysozyme and oxidative stress.

    PubMed

    Abrantes, Marta C; Kok, Jan; Silva Lopes, Maria de Fátima

    2014-12-01

    Two Enterococcus faecalis genes encoding the P-type ATPase EF1400 and the putative SapB protein EF0759 were previously shown to be strongly upregulated in the presence of high concentrations of zinc. In the present work, we showed that a Zn(2+)-responsive DNA-binding motif (zim) is present in the promoter regions of these genes. Both proteins were further studied with respect to their involvement in zinc homeostasis and invasion of the host. EF0759 contributed to intramacrophage survival by an as-yet unknown mechanism(s). EF1400, here renamed ZntAEf, is an ATPase with specificity for zinc and plays a role in dealing with several host defences, i.e. zinc overload, oxidative stress and lysozyme; it provides E. faecalis cells with the ability to survive inside macrophages. As these three host defence mechanisms are important at several sites in the host, i.e. inside macrophages and in saliva, this work suggested that ZntAEf constitutes a crucial E. faecalis defence mechanism that is likely to contribute to the ability of this bacterium to endure life inside its host.

  7. How Trypanosoma cruzi deals with oxidative stress: Antioxidant defence and DNA repair pathways.

    PubMed

    Machado-Silva, Alice; Cerqueira, Paula Gonçalves; Grazielle-Silva, Viviane; Gadelha, Fernanda Ramos; Peloso, Eduardo de Figueiredo; Teixeira, Santuza Maria Ribeiro; Machado, Carlos Renato

    2016-01-01

    Trypanosoma cruzi, the causative agent of Chagas disease, is an obligatory intracellular parasite with a digenetic life cycle. Due to the variety of host environments, it faces several sources of oxidative stress. In addition to reactive oxygen species (ROS) produced by its own metabolism, T. cruzi must deal with high ROS levels generated as part of the host's immune responses. Hence, the conclusion that T. cruzi has limited ability to deal with ROS (based on the lack of a few enzymes involved with oxidative stress responses) seems somewhat paradoxical. Actually, to withstand such variable sources of oxidative stress, T. cruzi has developed complex defence mechanisms. This includes ROS detoxification pathways that are distinct from the ones in the mammalian host, DNA repair pathways and specialized polymerases, which not only protect its genome from the resulting oxidative damage but also contribute to the generation of genetic diversity within the parasite population. Recent studies on T. cruzi's DNA repair pathways as mismatch repair (MMR) and GO system suggested that, besides a role associated with DNA repair, some proteins of these pathways may also be involved in signalling oxidative damage. Recent data also suggested that an oxidative environment might be beneficial for parasite survival within the host cell as it contributes to iron mobilization from the host's intracellular storages. Besides contributing to the understanding of basic aspects of T. cruzi biology, these studies are highly relevant since oxidative stress pathways are part of the poorly understood mechanisms behind the mode of action of drugs currently used against this parasite. By unveiling new peculiar aspects of T. cruzi biology, emerging data on DNA repair pathways and other antioxidant defences from this parasite have revealed potential new targets for a much needed boost in drug development efforts towards a better treatment for Chagas disease. Copyright © 2015. Published by Elsevier B.V.

  8. 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

  9. The ubiquitin conjugating enzyme, TaU4 regulates wheat defence against the phytopathogen Zymoseptoria tritici

    PubMed Central

    Millyard, Linda; Lee, Jack; Zhang, Cunjin; Yates, Gary; Sadanandom, Ari

    2016-01-01

    Mycosphaerella graminicola (Zymoseptoria tritici commonly known as Septoria), the causal agent of Septoria Leaf Blotch (STB), is considered one of the major threats to European wheat production. Previous studies have shown the importance of ubiquitination in plant defence against a multitude of pathogens. However the ubiquitination machinery in wheat is under studied, particularly E2 enzymes that have the ability to control the ubiquitination and thereby the fate of many different target proteins. In this study we identify an E2 enzyme, Triticum aestivum Ubiquitin conjugating enzyme 4 (TaU4) that functions in wheat defence against Septoria. We demonstrate TaU4 to be a bona fide E2 enzyme through an E2 charging assay. TaU4 localises in both the cytoplasm and nucleus, therefore potentially interacting with E3 ligases and substrate proteins in multiple compartments. Virus Induced Gene Silencing of TaU4 in wheat leaves resulted in delayed development of disease symptoms, reduced Septoria growth and reproduction. We conclude that TaU4 is a novel negative regulator of defence against Septoria. PMID:27759089

  10. 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

  11. Antioxidant defences and oxidative damage in salt-treated olive plants under contrasting sunlight irradiance.

    PubMed

    Melgar, Juan Carlos; Guidi, Lucia; Remorini, Damiano; Agati, Giovanni; Degl'innocenti, Elena; Castelli, Silvana; Camilla Baratto, Maria; Faraloni, Cecilia; Tattini, Massimiliano

    2009-09-01

    The interactive effects of root-zone salinity and sunlight on leaf biochemistry, with special emphasis on antioxidant defences, were analysed in Olea europaea L. cv. Allora, during the summer period. Plants were grown outside under 15% (shade plants) or 100% sunlight (sun plants) and supplied with 0 or 125 mM NaCl. The following measurements were performed: (1) the contribution of ions and soluble carbohydrates to osmotic potentials; (2) the photosystem II (PSII) photochemistry and the photosynthetic pigment concentration; (3) the concentration and the tissue-specific distribution of leaf flavonoids; (4) the activity of antioxidant enzymes; and (5) the leaf oxidative damage. The concentrations of Na(+) and Cl(-) were significantly greater in sun than in shade leaves, as also observed for the concentration of the 'antioxidant' sugar-alcohol mannitol. The de-epoxidation state of violaxanthin-cycle pigments increased in response to salinity stress in sun leaves. This finding agrees with a greater maximal PSII photochemistry (F(v)/F(m)) at midday, detected in salt-treated than in control plants, growing in full sunshine. By contrast, salt-treated plants in the shade suffered from midday depression in F(v)/F(m) to a greater degree than that observed in control plants. The high concentration of violaxanthin-cycle pigments in sun leaves suggests that zeaxanthin may protect the chloroplast from photo-oxidative damage, rather than dissipating excess excitation energy via non-photochemical quenching mechanisms. Dihydroxy B-ring-substituted flavonoid glycosides accumulate greatly in the mesophyll, not only in the epidermal cells, in response to high sunlight. The activity of antioxidant enzymes varied little because of sunlight irradiance, but declined sharply in response to high salinity in shade leaves. Interestingly, control and particularly salt-treated plants in the shade underwent greater oxidative damage than their sunny counterparts. These findings, which conform to

  12. Cyclo(His-Pro) promotes cytoprotection by activating Nrf2-mediated up-regulation of antioxidant defence

    PubMed Central

    Minelli, Alba; Conte, Carmela; Grottelli, Silvia; Bellezza, Maria; Cacciatore, Ivana; Bolaños, Juan P

    2009-01-01

    Hystidyl-proline [cyclo(His-Pro)] is an endogenous cyclic dipeptide produced by the cleavage of thyrotropin releasing hormone. Previous studies have shown that cyclo(His-Pro) protects against oxidative stress, although the underlying mechanism has remained elusive. Here, we addressed this issue and found that cyclo(His-Pro) triggered nuclear accumulation of NF-E2-related factor-2 (Nrf2), a transcription factor that up-regulates antioxidant-/electrophile-responsive element (ARE-EpRE)-related genes, in PC12 cells. Cyclo(His-Pro) attenuated reactive oxygen species production, and prevented glutathione depletion caused by glutamate, rotenone, paraquat and β-amyloid treatment. Moreover, real-time PCR analyses revealed that cyclo(His-Pro) induced the expression of a number of ARE-related genes and protected cells against hydrogen peroxide-mediated apoptotic death. Furthermore, these effects were abolished by RNA interference-mediated Nrf2 knockdown. Finally, pharmacological inhibition of p-38 MAPK partially prevented both cyclo(His-Pro)-mediated Nrf2 activation and cellular protection. These results suggest that the signalling mechanism responsible for the cytoprotective actions of cyclo(His-Pro) would involve p-38 MAPK activation leading to Nrf2-mediated up-regulation of antioxidant cellular defence. PMID:18373731

  13. 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

  14. Negative regulation of defence and stress genes by EAR-motif-containing repressors.

    PubMed

    Kazan, Kemal

    2006-03-01

    Although positive control or activation mechanism(s) involved in plant defence- and stress-related gene expression is relatively well studied, little is known about what keeps defensive armoury under control when not needed. Recent reports suggest that transcriptional repression of gene expression by EAR-motif-containing repressor proteins plays a key role in modulating plant defence and stress responses.

  15. Defence Responses of Arabidopsis thaliana to Infection by Pseudomonas syringae Are Regulated by the Circadian Clock

    PubMed Central

    Bhardwaj, Vaibhav; Meier, Stuart; Petersen, Lindsay N.; Ingle, Robert A.; Roden, Laura C.

    2011-01-01

    The circadian clock allows plants to anticipate predictable daily changes in abiotic stimuli, such as light; however, whether the clock similarly allows plants to anticipate interactions with other organisms is unknown. Here we show that Arabidopsis thaliana (Arabidopsis) has circadian clock-mediated variation in resistance to the virulent bacterial pathogen Pseudomonas syringae pv. tomato DC3000 (Pst DC3000), with plants being least susceptible to infection in the subjective morning. We suggest that the increased resistance to Pst DC3000 observed in the morning in Col-0 plants results from clock-mediated modulation of pathogen associated molecular pattern (PAMP)-triggered immunity. Analysis of publicly available microarray data revealed that a large number of Arabidopsis defence-related genes showed both diurnal- and circadian-regulation, including genes involved in the perception of the PAMP flagellin which exhibit a peak in expression in the morning. Accordingly, we observed that PAMP-triggered callose deposition was significantly higher in wild-type plants inoculated with Pst DC3000 hrpA in the subjective morning than in the evening, while no such temporal difference was evident in arrhythmic plants. Our results suggest that PAMP-triggered immune responses are modulated by the circadian clock and that temporal regulation allows plants to anticipate and respond more effectively to pathogen challenges in the daytime. PMID:22066021

  16. Defence responses of Arabidopsis thaliana to infection by Pseudomonas syringae are regulated by the circadian clock.

    PubMed

    Bhardwaj, Vaibhav; Meier, Stuart; Petersen, Lindsay N; Ingle, Robert A; Roden, Laura C

    2011-01-01

    The circadian clock allows plants to anticipate predictable daily changes in abiotic stimuli, such as light; however, whether the clock similarly allows plants to anticipate interactions with other organisms is unknown. Here we show that Arabidopsis thaliana (Arabidopsis) has circadian clock-mediated variation in resistance to the virulent bacterial pathogen Pseudomonas syringae pv. tomato DC3000 (Pst DC3000), with plants being least susceptible to infection in the subjective morning. We suggest that the increased resistance to Pst DC3000 observed in the morning in Col-0 plants results from clock-mediated modulation of pathogen associated molecular pattern (PAMP)-triggered immunity. Analysis of publicly available microarray data revealed that a large number of Arabidopsis defence-related genes showed both diurnal- and circadian-regulation, including genes involved in the perception of the PAMP flagellin which exhibit a peak in expression in the morning. Accordingly, we observed that PAMP-triggered callose deposition was significantly higher in wild-type plants inoculated with Pst DC3000 hrpA in the subjective morning than in the evening, while no such temporal difference was evident in arrhythmic plants. Our results suggest that PAMP-triggered immune responses are modulated by the circadian clock and that temporal regulation allows plants to anticipate and respond more effectively to pathogen challenges in the daytime.

  17. 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.

  18. Mitochondrial function and antioxidative defence in human muscle: effects of endurance training and oxidative stress

    PubMed Central

    Tonkonogi, Michail; Walsh, Brandon; Svensson, Michael; Sahlin, Kent

    2000-01-01

    -term training on mitochondrial oxygen consumption has for the first time been investigated in human skeletal muscle. The results showed that maximal mitochondrial oxidative power is increased after endurance training but that the efficiency of energy transfer (P/O ratio) remained unchanged. Antioxidative defence was unchanged after training when expressed relative to muscle weight. Although this corresponds to a reduced antioxidant protection per individual mitochondrion, the sensitivity of aerobic energy transfer to ROS was unchanged. However, the augmented ROS-induced non-coupled respiration after training indicates an increased susceptibility of mitochondrial membrane proton conductance to oxidative stress. PMID:11034627

  19. Mutation of Arabidopsis HY1 causes UV-C hypersensitivity by impairing carotenoid and flavonoid biosynthesis and the down-regulation of antioxidant defence

    PubMed Central

    Xie, Yanjie; Xu, Daokun; Cui, Weiti; Shen, Wenbiao

    2012-01-01

    Previous pharmacological results confirmed that haem oxygenase-1 (HO-1) is involved in protection of cells against ultraviolet (UV)-induced oxidative damage in soybean [Glycine max (L.) Merr.] seedlings, but there remains a lack of genetic evidence. In this study, the link between Arabidopsis thaliana HO-1 (HY1) and UV-C tolerance was investigated at the genetic and molecular levels. The maximum inducible expression of HY1 in wild-type Arabidopsis was observed following UV-C irradiation. UV-C sensitivity was not observed in ho2, ho3, and ho4 single and double mutants. However, the HY1 mutant exhibited UV-C hypersensitivity, consistent with the observed decreases in chlorophyll content, and carotenoid and flavonoid metabolism, as well as the down-regulation of antioxidant defences, thereby resulting in severe oxidative damage. The addition of the carbon monoxide donor carbon monoxide-releasing molecule-2 (CORM-2), in particular, and bilirubin (BR), two catalytic by-products of HY1, partially rescued the UV-C hypersensitivity, and other responses appeared in the hy1 mutant. Transcription factors involved in the synthesis of flavonoid or UV responses were induced by UV-C, but reduced in the hy1 mutant. Overall, the findings showed that mutation of HY1 triggered UV-C hypersensitivity, by impairing carotenoid and flavonoid synthesis and antioxidant defences. PMID:22419743

  20. Cortical microtubule as a sensor and target of nitric oxide signal during the defence responses to Verticillium dahliae toxins in Arabidopsis.

    PubMed

    Shi, Fu-Mei; Yao, Lin-Lin; Pei, Bao-Lei; Zhou, Qun; Li, Xiu-Li; Li, Yun; Li, Ying-Zhang

    2009-04-01

    The molecular mechanisms of signal transduction of plants in response to Verticillium dahliae (VD) are not known. Here, we show that Arabidopsis reacts to VD-toxins with a rapid burst of nitric oxide (NO) and cortical microtubule destabilization. VD-toxins treatment triggered a disruption of cortical microtubules network. This disruption can be influenced by NO production. However, cortical microtubule disruptions were not involved in regulating the NO production. The results indicated that NO may act as an upstream signalling molecule to trigger the depolymerization of cortical microtubule. Cortical microtubules may act as a target of NO signal and as a sensor to mediate the activation of PR-1 gene expression. These results suggested that NO production and cortical microtubule dynamics appeared to be parts of the important signalling system and are involved in the defence mechanisms to VD-toxins in Arabidopsis.

  1. Shifting from priming of salicylic acid- to jasmonic acid-regulated defences by Trichoderma protects tomato against the root knot nematode Meloidogyne incognita.

    PubMed

    Martínez-Medina, Ainhoa; Fernandez, Ivan; Lok, Gerrit B; Pozo, María J; Pieterse, Corné M J; Van Wees, Saskia C M

    2017-02-01

    Beneficial root endophytes such as Trichoderma spp. can reduce infections by parasitic nematodes through triggering host defences. Little is currently known about the complex hormone signalling underlying the induction of resistance. In this study, we investigated whether Trichoderma modulates the hormone signalling network in the host to induce resistance to nematodes. We investigated the role and the timing of the jasmonic acid (JA)- and salicylic acid (SA)-regulated defensive pathways in Trichoderma-induced resistance to the root knot nematode Meloidogyne incognita. A split-root system of tomato (Solanum lycopersicum) was used to study local and systemic induced defences by analysing nematode performance, defence gene expression, responsiveness to exogenous hormone application, and dependence on SA and JA signalling of Trichoderma-induced resistance. Root colonization by Trichoderma impeded nematode performance both locally and systemically at multiple stages of the parasitism, that is, invasion, galling and reproduction. First, Trichoderma primed SA-regulated defences, which limited nematode root invasion. Then, Trichoderma enhanced JA-regulated defences, thereby antagonizing the deregulation of JA-dependent immunity by the nematodes, which compromised galling and fecundity. Our results show that Trichoderma primes SA- and JA-dependent defences in roots, and that the priming of responsiveness to these hormones upon nematode attack is plastic and adaptive to the parasitism stage. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  2. Antioxidant defence system during exponential and stationary growth phases of Phycomyces blakesleeanus: response to oxidative stress by hydrogen peroxide.

    PubMed

    de Castro, Cristina; del Valle, Pilar; Rúa, Javier; García-Armesto, María Rosario; Gutiérrez-Larraínzar, Marta; Busto, Félix; de Arriaga, Dolores

    2013-04-01

    An analysis of the components of the antioxidant defence system in exponential and stationary growth phases of filamentous fungus Phycomyces blakesleeanus and the response to the oxidative stress hydrogen peroxide were performed. There is a strong positive correlation between mycelial antioxidant capacity and the contents of gallic acid, d-erythroascorbate (d-EAA) or d-erythroascorbate monoglucoside (d-EAAG). These secondary metabolites are specifically synthesized by this fungus and reach maximal values in the stationary growth phase, suggesting that they can play some role in the antioxidant defence system of this fungus. There is a differential expression of the two more notable antioxidant activities, catalase (CAT) and superoxide dismutase (SOD), depending of the growth stage of P. blakesleeanus, CAT being expressed in the exponential and SOD in the stationary phase. Phycomyces blakesleeanus showed a high resistance to the oxidative stress caused by H2O2 (50 and 200 mM) which was higher in exponential phase. This higher resistance can be explained by the presence of CAT, glutathione peroxidase (GPx), and the probable contribution of glutathione-S-transferase (GST) and high levels of reduced form of glutathione (GSH). The transition to stationary phase was accompanied with a higher physiological oxidative damage illustrated by the higher protein carbonylation. In this growth stage the resistance of the fungus to the oxidative stress caused by H2O2 could be explained by the presence of SOD, GPx, and the probable contribution of GST as well as of secondary metabolites, mainly d-EAA and d-EAAG. These results highlight a specific response to oxidative stress by H2O2 depending on the growth phase of P. blakesleeanus.

  3. 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

  4. Defence against oxidative stress in two species of land snails (Helix pomatia and Helix aspersa) subjected to estivation.

    PubMed

    Nowakowska, Anna; Caputa, Michał; Rogalska, Justyna

    2011-12-01

    During summer, land snails are exposed to estivation/arousal cycles that imposes oxidative stress, but they exhibit different patterns of antioxidant defence. To test the ability of two related species, Helix pomatia and Helix aspersa, to modulate their antioxidant defence mechanism during estivation/arousal cycles, we examined activities of catalase and glutathione-related enzymes and concentrations of glutathione and thiobarbituric acid reactive substances (TBARS; as products of lipid peroxidation). In both species, estivation evoked changes in activity of total and selenium-dependent glutathione peroxidase (GPx), but did not affect activity of catalase, glutathione reductase, and glutathione transferase, and had no effect on concentration of glutathione. Activity of catalase in estivating snails, instead of the expected increase, showed a tendency to diminish. Extremely low activities of catalase in the foot were usually associated with extremely high activities of both forms of GPx. In conclusion, maintenance of relatively high activities of the antioxidant enzymes and accumulation of glutathione, resulting in a low and stable concentration of TBARS, plays an important role in scavenging oxygen free radicals from the organism of both species.

  5. Transcriptional regulation of defence genes and involvement of the WRKY transcription factor in arbuscular mycorrhizal potato root colonization.

    PubMed

    Gallou, Adrien; Declerck, Stéphane; Cranenbrouck, Sylvie

    2012-03-01

    The establishment of arbuscular mycorrhizal associations causes major changes in plant roots and affects significantly the host in term of plant nutrition and resistance against biotic and abiotic stresses. As a consequence, major changes in root transcriptome, especially in plant genes related to biotic stresses, are expected. Potato microarray analysis, followed by real-time quantitative PCR, was performed to detect the wide transcriptome changes induced during the pre-, early and late stages of potato root colonization by Glomus sp. MUCL 41833. The microarray analysis revealed 526 up-regulated and 132 down-regulated genes during the pre-stage, 272 up-regulated and 109 down-regulated genes during the early stage and 734 up-regulated and 122 down-regulated genes during the late stage of root colonization. The most important class of regulated genes was associated to plant stress and in particular to the WRKY transcription factors genes during the pre-stage of root colonization. The expression profiling clearly demonstrated a wide transcriptional change during the pre-, early and late stages of root colonization. It further suggested that the WRKY transcription factor genes are involved in the mechanisms controlling the arbuscular mycorrhizal establishment by the regulation of plant defence genes.

  6. 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

  7. 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.

  8. Defence on demand: mechanisms behind optimal defence patterns

    PubMed Central

    Meldau, Stefan; Erb, Matthias; Baldwin, Ian T.

    2012-01-01

    Background The optimal defence hypothesis (ODH) predicts that tissues that contribute most to a plant's fitness and have the highest probability of being attacked will be the parts best defended against biotic threats, including herbivores. In general, young sink tissues and reproductive structures show stronger induced defence responses after attack from pathogens and herbivores and contain higher basal levels of specialized defensive metabolites than other plant parts. However, the underlying physiological mechanisms responsible for these developmentally regulated defence patterns remain unknown. Scope This review summarizes current knowledge about optimal defence patterns in above- and below-ground plant tissues, including information on basal and induced defence metabolite accumulation, defensive structures and their regulation by jasmonic acid (JA). Physiological regulations underlying developmental differences of tissues with contrasting defence patterns are highlighted, with a special focus on the role of classical plant growth hormones, including auxins, cytokinins, gibberellins and brassinosteroids, and their interactions with the JA pathway. By synthesizing recent findings about the dual roles of these growth hormones in plant development and defence responses, this review aims to provide a framework for new discoveries on the molecular basis of patterns predicted by the ODH. Conclusions Almost four decades after its formulation, we are just beginning to understand the underlying molecular mechanisms responsible for the patterns of defence allocation predicted by the ODH. A requirement for future advances will be to understand how developmental and defence processes are integrated. PMID:23022676

  9. 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

  10. 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

  11. Baicalein acts as a nephroprotectant that ameliorates colistin-induced nephrotoxicity by activating the antioxidant defence mechanism of the kidneys and down-regulating the inflammatory response.

    PubMed

    Dai, Chongshan; Tang, Shusheng; Wang, Yang; Velkov, Tony; Xiao, Xilong

    2017-09-01

    Nephrotoxicity is the major adverse effect patients experience during colistin therapy. The development of effective nephroprotective agents that can be co-administered during polymyxin therapy remains a priority area in antimicrobial chemotherapy. To investigate the nephroprotective effect of baicalein, a component of the root of Scutellaria baicalensis, against colistin-induced nephrotoxicity using a mouse model. C57BL/6 mice were randomly divided into the following groups: control, baicalein 100 mg/kg/day (administered orally), colistin (18 mg/kg/day administered intraperitoneally) and colistin (18 mg/kg/day) plus baicalein (25, 50 and 100 mg/kg/day). After 7 day treatments, histopathological damage, the markers of renal functions, oxidative stress and inflammation were examined. The expressions of Nrf2, HO-1 and NF-κB mRNAs were also further examined using quantitative RT-PCR examination. Baicalein co-administration markedly attenuated colistin-induced oxidative and nitrative stress, apoptosis, the infiltration of inflammatory cells, and caused decreases in IL-1β and TNF-α levels (all P < 0.05 or 0.01) in the kidney tissues. Baicalein co-administration up-regulated expression of Nrf2 and HO-1 mRNAs and down-regulated the expression of NF-κB mRNA, compared with those in the colistin alone group. To the best of our knowledge, this is the first study demonstrating the protective effect of baicalein on colistin-induced nephrotoxicity and apoptosis by activating the antioxidant defence mechanism in kidneys and down-regulating the inflammatory response. Our study highlights that oral baicalein could potentially ameliorate nephrotoxicity in patients undergoing polymyxin therapy.

  12. 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.

  13. 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

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

    PubMed

    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.

  15. Reactive oxygen species and anti-oxidant defences in swine follicular fluids.

    PubMed

    Basini, Giuseppina; Simona, Bussolati; Santini, Sujen Eleonora; Grasselli, Francesca

    2008-01-01

    A growing body of evidence indicates that the pro-oxidant/anti-oxidant balance inside the ovarian follicle plays an important role in folliculogenesis. Therefore, the aim of the present study was to assess the redox status of follicular fluids collected from different-sized swine follicles. We quantified the most important reactive oxygen species (ROS), namely superoxide anion (O(2)(-)), hydrogen peroxide and hydroperoxides (ROOH); in addition, we examined the activity of the detoxifying enzymes superoxide dismutase, catalase (CAT) and glutathione peroxidase and the total non-enzymatic antioxidant capacity as determined by the ferric-reducing anti-oxidant power assay. Our data demonstrate that oxidative stress does not affect follicle growth because O(2)(-) levels do not change during follicle development, whereas concentrations of H2O2 and ROOH are reduced (P < 0.05). Surprisingly, all non-enzymatic and enzymatic scavengers examined in the present study, except for CAT, demonstrated reduced activity during follicle development (P < 0.05). Taken together, these results suggest that other factors could be involved in ROS detoxification during follicle development.

  16. Oxidative stress and glycemic regulation.

    PubMed

    Ceriello, A

    2000-02-01

    Oxidative stress is an acknowledged pathogenetic mechanism in diabetic complications. Hyperglycemia is a widely known cause of enhanced free radical concentration, whereas oxidative stress involvement in glycemic regulation is still debated. Glucose transport is a cascade of events starting from the interaction of insulin with its own receptor at the plasma membrane and ending with intracellular glucose metabolism. In this complex series of events, each step plays an important role and can be inhibited by a negative effect of oxidative stress. Several studies show that an acute increase in the blood glucose level may impair the physiological homeostasis of many systems in living organisms. The mechanisms through which acute hyperglycemia exerts these effects may be identified in the production of free radicals. It has been suggested that insulin resistance may be accompanied by intracellular production of free radicals. In adipocytes cultured in vitro, insulin increases the production of hydrogen peroxide, which has been shown to mimic the action of insulin. These data allow us to hypothesize that a vicious circle between hyperinsulinemia and free radicals could be operating: insulin resistance might cause elevated plasma free radical concentrations, which, in turn, might be responsible for a deterioration of insulin action, with hyperglycemia being a contributory factor. Data supporting this hypothesis are available. Vitamin E improves insulin action in healthy, elderly, and non-insulin-dependent diabetic subjects. Similar results can be obtained by vitamin C administration.

  17. Detrimental role of endogenous nitric oxide in host defence against Sporothrix schenckii

    PubMed Central

    Fernandes, Karla Simone S; Neto, Edward Helal; Brito, Marcelly M S; Silva, João S; Cunha, Fernando Q; Barja-Fidalgo, Christina

    2008-01-01

    We earlier demonstrated that nitric oxide (NO) is a fungicidal molecule against Sporothrix schenckii in vitro. In the present study we used mice deficient in inducible nitric oxide synthase (iNOS–/–) and C57BL/6 wild-type (WT) mice treated with Nω-nitro-arginine (Nitro-Arg-treated mice), an NOS inhibitor, both defective in the production of reactive nitrogen intermediates, to investigate the role of endogenous NO during systemic sporotrichosis. When inoculated with yeast cells of S. schenckii, WT mice presented T-cell suppression and high tissue fungal dissemination, succumbing to infection. Furthermore, susceptibility of mice seems to be related to apoptosis and high interleukin-10 and tumour necrosis factor-α production by spleen cells. In addition, fungicidal activity and NO production by interferon-γ (IFN-γ) and lipopolysaccharide-activated macrophages from WT mice were abolished after fungal infection. Strikingly, iNOS–/– and Nitro-Arg-treated mice presented fungal resistance, controlling fungal load in tissues and restoring T-cell activity, as well as producing high amounts of IFN-γ Interestingly, macrophages from these groups of mice presented fungicidal activity after in vitro stimulation with higher doses of IFN-γ. Herein, these results suggest that although NO was an essential mediator to the in vitro killing of S. schenckii by macrophages, the activation of NO system in vivo contributes to the immunosuppression and cytokine balance during early phases of infection with S. schenckii. PMID:18194265

  18. Normalization of Explosives Safety Regulations Between U.S. Navy and Australian Defence Force

    DTIC Science & Technology

    2010-07-01

    of the host nation, unless the U.S. has control of the real estate, as under a Status of Forces Agreement (SOFA); in the later case, the Navy...past two years to reach a consensus on the normalization of explosives safety regulations. This effort has demonstrated that the Australian...Operations (CNO) submitted a request to the DDESB in December 2009, for USN ships, as well as USN and USMC aircraft, to operate in Australia under

  19. 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

  20. Correlation between oxidative stress and antioxidant defence in South Indian urban vegetarians and non-vegetarians.

    PubMed

    Somannavar, M S; Kodliwadmath, M V

    2012-03-01

    The diet is a key environmental factor implicated in health and disease. Oxidative stress, antioxidant status and their relation to diet is a subject of interest in recent years. The objective of the study was to compare lipid peroxidation and antioxidant status in healthy vegetarians and non-vegetarians. The present study comprises 100 healthy individuals (50 vegetarians and 50 non-vegetarians) residing in Belgaum urban area. All the participants were in the age group of 40-60 years of both sexes. This cross-sectional study was done in one year period from April 2007 to March 2008. Malondialdehyde (MDA) (lipid peroxidation product) was estimated by thiobarbituric acid method, glutathione peroxidase by Beutler's method, Vitamin A and Vitamin E by Bessay et al and Quife et al methods respectively. Our study revealed that the blood MDA level was significantly increased (p value < 0.001) in non-vegetarians compared to lactovegetarians and lacto-ovo-vegetarians. There was significant decrease in the level of enzymatic antioxidant glutathione peroxidase and non-enzymatic antioxidants Vitamin A and Vitamin E in non-vegetarians compared to lactovegetarians and lacto-ovo-vegetarians (p value < 0.001). Results of this investigation present study indicate that there was an increased lipid peroxidation and a low antioxidant status in non-vegetarians compared to vegetarians. Vegetarian nutrition provides adequate antioxidants which effectively prevent free radicals generation.

  1. Antioxidant properties of grape seed extract on human lymphocyte oxidative defence.

    PubMed

    Stanković, Miroslava; Tesević, Vele; Vajs, Vlatka; Todorović, Nina; Milosavljević, Slobodan; Godevac, Dejan

    2008-06-01

    The distribution of polyphenolic compounds in a grape (Vitis vinifera) seed extract (GSE) was determined using LC/ESI-TOF MS, HPLC/DAD, and (13)C-NMR. The 17 identified compounds comprised gallic and protocatechuic acid, catechin and epicatechin monomers, procyanidin oligomers, and procyanidin gallates. This study addresses the in vitro effects of grape seed extract (GSE) on the frequency of micronuclei with reference to the antioxidant status in human lymphocytes. To establish the most effective protective support, we used four different concentrations of GSE, in the range 1-6 microg/mL. Treatment of lymphocytes with GSE at a concentration of 2.5 microg/mL induced a significant decrease in the frequency of micronuclei by 40%, reduction of malonyldialdehyde production by 30%, while a concentration of 5 microg/mL increased catalase and glutathione S-transferase activity by 10% and 15%, respectively. These results demonstrate that GSE may be effective in the prevention of oxidative lymphocyte damage by ROS.

  2. Filamin acts as a key regulator in epithelial defence against transformed cells.

    PubMed

    Kajita, Mihoko; Sugimura, Kaoru; Ohoka, Atsuko; Burden, Jemima; Suganuma, Hitomi; Ikegawa, Masaya; Shimada, Takashi; Kitamura, Tetsuya; Shindoh, Masanobu; Ishikawa, Susumu; Yamamoto, Sayaka; Saitoh, Sayaka; Yako, Yuta; Takahashi, Ryosuke; Okajima, Takaharu; Kikuta, Junichi; Maijima, Yumiko; Ishii, Masaru; Tada, Masazumi; Fujita, Yasuyuki

    2014-07-31

    Recent studies have shown that certain types of transformed cells are extruded from an epithelial monolayer. However, it is not known whether and how neighbouring normal cells play an active role in this process. In this study, we demonstrate that filamin A and vimentin accumulate in normal cells specifically at the interface with Src- or RasV12-transformed cells. Knockdown of filamin A or vimentin in normal cells profoundly suppresses apical extrusion of the neighbouring transformed cells. In addition, we show in zebrafish embryos that filamin plays a positive role in the elimination of the transformed cells. Furthermore, the Rho/Rho kinase pathway regulates filamin accumulation and filamin acts upstream of vimentin in the apical extrusion. This is the first report demonstrating that normal epithelial cells recognize and actively eliminate neighbouring transformed cells and that filamin is a key mediator in the interaction between normal and transformed epithelial cells.

  3. Molecular regulation of sucrose catabolism and sugar transport for development, defence and phloem function.

    PubMed

    Li, Jun; Wu, Limin; Foster, Ryan; Ruan, Yong-Ling

    2017-05-01

    Sucrose (Suc) is the major end product of photosynthesis in mesophyll cells of most vascular plants. It is loaded into phloem of mature leaves for long-distance translocation to non-photosynthetic organs where it is unloaded for diverse uses. Clearly, Suc transport and metabolism is central to plant growth and development and the functionality of the entire vascular system. Despite vast information in the literature about the physiological roles of individual sugar metabolic enzymes and transporters, there is a lack of systematic evaluation about their molecular regulation from transcriptional to post-translational levels. Knowledge on this topic is essential for understanding and improving plant development, optimizing resource distribution and increasing crop productivity. We therefore focused our analyses on molecular control of key players in Suc metabolism and transport, including: (i) the identification of promoter elements responsive to sugars and hormones or targeted by transcription factors and microRNAs degrading transcripts of target genes; and (ii) modulation of enzyme and transporter activities through protein-protein interactions and other post-translational modifications. We have highlighted major remaining questions and discussed opportunities to exploit current understanding to gain new insights into molecular control of carbon partitioning for improving plant performance. © 2017 Institute of Botany, Chinese Academy of Sciences.

  4. Expression of coordinately regulated defence response genes and analysis of their role in disease resistance in Medicago truncatula.

    PubMed

    Samac, Deborah A; Peñuela, Silvia; Schnurr, Judy A; Hunt, E Nicole; Foster-Hartnett, Dawn; Vandenbosch, Kathryn A; Gantt, J Stephen

    2011-10-01

    Microarray technology was used to identify the genes associated with disease defence responses in the model legume Medicago truncatula. Transcript profiles from M. truncatula cv. Jemalong genotype A17 leaves inoculated with Colletotrichum trifolii and Erysiphe pisi and roots infected with Phytophthora medicaginis were compared to identify the genes expressed in response to all three pathogens and genes unique to an interaction. The A17 genotype is resistant to C. trifolii and E. pisi, exhibiting a hypersensitive response after inoculation, and is moderately susceptible to P. medicaginis. Among the most strongly up-regulated genes in all three interactions were those encoding a hevein-like protein, thaumatin-like protein (TLP) and members of the pathogenesis response (PR)10 family. Transcripts of genes for enzymes in the phenylpropanoid pathway leading to the production of isoflavonoid phytoalexins increased dramatically in response to inoculation with the foliar pathogens. In P. medicaginis-inoculated roots, transcripts of genes in the phenylpropanoid pathway peaked at 5 days post-inoculation, when symptoms became visible. Transcript accumulation of three PR10 family members, a TLP and chalcone synthase (CHS) was assessed in M. truncatula genotype R108 plants. The R108 plants are resistant to C. trifolii and moderately susceptible to E. pisi and P. medicaginis. Transcript accumulation paralleled the stages of pathogen development. To evaluate the role of a TLP, a PR10 family member and CHS in disease resistance, transgenic R108 plants containing interfering RNA (RNAi) constructs were produced. Reduced expression of PR10 and TLP had no effect on the disease phenotype, whereas reduced expression of CHS resulted in increased susceptibility to necrotrophic pathogens. MOLECULAR PLANT PATHOLOGY © 2011 BSPP AND BLACKWELL PUBLISHING LTD. NO CLAIM TO ORIGINAL US GOVERNMENT WORKS.

  5. 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

  6. 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.

  7. MAP65-1a positively regulates H2O2 amplification and enhances brassinosteroid-induced antioxidant defence in maize.

    PubMed

    Zhu, Yuan; Zuo, Mingxing; Liang, Yali; Jiang, Mingyi; Zhang, Jianhua; Scheller, Henrik Vibe; Tan, Mingpu; Zhang, Aying

    2013-09-01

    Brassinosteroid (BR)-induced antioxidant defence has been shown to enhance stress tolerance. In this study, the role of the maize 65 kDa microtubule-associated protein (MAP65), ZmMAP65-1a, in BR-induced antioxidant defence was investigated. Treatment with BR increased the expression of ZmMAP65-1a in maize (Zea mays) leaves and mesophyll protoplasts. Transient expression and RNA interference silencing of ZmMAP65-1a in mesophyll protoplasts further revealed that ZmMAP65-1a is required for the BR-induced increase in expression and activity of superoxide dismutase (SOD) and ascorbate peroxidase (APX). Both exogenous and BR-induced endogenous H2O2 increased the expression of ZmMAP65-1a. Conversely, transient expression of ZmMAP65-1a in maize mesophyll protoplasts enhanced BR-induced H2O2 accumulation, while transient silencing of ZmMAP65-1a blocked the BR-induced expression of NADPH oxidase genes and inhibited BR-induced H2O2 accumulation. Inhibiting the activity and gene expression of ZmMPK5 significantly prevented the BR-induced expression of ZmMAP65-1a. Likewise, transient expression of ZmMPK5 enhanced BR-induced activities of the antioxidant defence enzymes SOD and APX in a ZmMAP65- 1a-dependent manner. ZmMPK5 directly interacted with ZmMAP65-1a in vivo and phosphorylated ZmMAP65-1a in vitro. These results suggest that BR-induced antioxidant defence in maize operates through the interaction of ZmMPK5 with ZmMAP65-1a. Furthermore, ZmMAP65-1a functions in H2O2 self-propagation via regulation of the expression of NADPH oxidase genes in BR signalling.

  8. Oxidative Stress: A Master Regulator of Plant Trade-Offs?

    PubMed

    Morales, Melanie; Munné-Bosch, Sergi

    2016-12-01

    Trade-offs between growth, reproduction, and defence have been documented. Oxidative stress is one of the physiological mechanisms that underlie trade-offs at the cellular and organ levels. The diversity of plant life forms and the complexity of scaling up limit our knowledge of oxidative stress as a universal mediator of life-history trade-offs at the organism level. Joint efforts by plant physiologists and ecologists will undoubtedly provide novel insights into this topic in the near future.

  9. Physiological adaptations to reproduction. I. Experimentally increasing litter size enhances aspects of antioxidant defence but does not cause oxidative damage in mice.

    PubMed

    Garratt, Michael; Pichaud, Nicolas; King, Edith D Aloise; Brooks, Robert C

    2013-08-01

    Life history theory suggests that investment in reproduction can trade off against growth, longevity and both reproduction and performance later in life. One possible reason for this trade-off is that reproduction directly causes somatic damage. Oxidative stress, an overproduction of reactive oxygen species in relation to cellular defences, can correlate with reproductive investment and has been implicated as a pathway leading to senescence. This has led to the suggestion that this aspect of physiology could be an important mechanism underlying the trade-off between reproduction and lifespan. We manipulated female reproductive investment to test whether oxidative stress increases with reproduction in mice. Each female's pups were cross-fostered to produce litters of either two or eight, representing low and high levels of reproductive investment for wild mice. No differences were observed between reproductive groups at peak lactation for several markers of oxidative stress in the heart and gastrocnemius muscle. Surprisingly, oxidative damage to proteins was lower in the livers of females with a litter size of eight than in females with two pups or non-reproductive control females. While protein oxidation decreased, activity levels of the antioxidant enzyme superoxide dismutase increased in the liver, suggesting this may be one pathway used to protect against oxidative stress. Our results highlight the need for caution when interpreting correlative relationships and suggest that oxidative stress does not increase with enhanced reproductive effort during lactation.

  10. Defence White Paper 2013

    DTIC Science & Technology

    2013-01-01

    Asia, the Middle East, and Africa 65 The United Kingdom 66 Spain 66 Canada and Latin America 67 Defence White Paper 2013 v Europe and the North...Defence and National Security 111 CHAPTER TWELVE: INDUSTRY AND INNOVATION POLICY 115 Global Defence and Broader Industry Trends 116 The...Relationship between Defence and Industry 117 Priorities for Industry Capability 118 Defence Industry and Innovation Policy Priorities 119 Enhancing Innovation

  11. Statin-induced inhibition of breast cancer proliferation and invasion involves attenuation of iron transport: intermediacy of nitric oxide and antioxidant defence mechanisms.

    PubMed

    Kanugula, Anantha Koteswararao; Gollavilli, Paradesi Naidu; Vasamsetti, Sathish Babu; Karnewar, Santosh; Gopoju, Raja; Ummanni, Ramesh; Kotamraju, Srigiridhar

    2014-08-01

    Accumulating evidence from in vitro, in vivo, clinical and epidemiological studies shows promising results for the use of statins against many cancers including breast carcinoma. However, the molecular mechanisms responsible for the anti-proliferative and anti-invasive properties of statins still remain elusive. In this study, we investigated the involvement of nitric oxide, iron homeostasis and antioxidant defence mechanisms in mediating the anti-proliferative and anti-invasive properties of hydrophobic statins in MDA-MB-231, MDA-MB-453 and BT-549 metastatic triple negative breast cancer cells. Fluvastatin and simvastatin significantly increased cytotoxicity which was reversed with mevalonate. Interestingly, fluvastatin downregulated transferrin receptor (TfR1), with a concomitant depletion of intracellular iron levels in these cells. Statin-induced effects were mimicked by geranylgeranyl transferase inhibitor (GGTI-298) but not farnesyl transferase inhibitor (FTI-277). Further, it was observed that TfR1 downregulation is mediated by increased nitric oxide levels via inducible nitric oxide synthase (iNOS) expression. NOS inhibitors (asymmetric dimethylarginine and 1400W) counteracted and sepiapterin, a precursor of tetrahydrobiopterin, exacerbated statin-induced depletion of intracellular iron levels. Notably, fluvastatin increased manganese superoxide dismutase (by repressing the transcription factor DNA damage-binding protein 2), catalase and glutathione which, in turn, diminished H2 O2 levels. Fluvastatin-induced downregulation of TfR1, matrix metalloproteinase-2, -9 and inhibition of invasion were reversed in the presence of aminotriazole, a specific inhibitor of catalase. Finally, we conclude that fluvastatin, by altering iron homeostasis, nitric oxide generation and antioxidant defence mechanisms, induces triple negative breast cancer cell death. © 2014 FEBS.

  12. Transcriptional control of plant defence responses.

    PubMed

    Buscaill, Pierre; Rivas, Susana

    2014-08-01

    Mounting of efficient plant defence responses depends on the ability to trigger a rapid defence reaction after recognition of the invading microbe. Activation of plant resistance is achieved by modulation of the activity of multiple transcriptional regulators, both DNA-binding transcription factors and their regulatory proteins, that are able to reprogram transcription in the plant cell towards the activation of defence signalling. Here we provide an overview of recent developments on the transcriptional control of plant defence responses and discuss defence-related hormone signalling, the role of WRKY transcription factors during the regulation of plant responses to pathogens, nuclear functions of plant immune receptor proteins, as well as varied ways by which microbial effectors subvert plant transcriptional reprogramming to promote disease.

  13. NADP-Dependent Isocitrate Dehydrogenase from Arabidopsis Roots Contributes in the Mechanism of Defence against the Nitro-Oxidative Stress Induced by Salinity

    PubMed Central

    Leterrier, Marina; Barroso, Juan B.; Valderrama, Raquel; Palma, José M.; Corpas, Francisco J.

    2012-01-01

    NADPH regeneration appears to be essential in the mechanism of plant defence against oxidative stress. Plants contain several NADPH-generating dehydrogenases including isocitrate dehydrogenase (NADP-ICDH), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), and malic enzyme (ME). In Arabidopsis seedlings grown under salinity conditions (100 mM NaCl) the analysis of physiological parameters, antioxidant enzymes (catalase and superoxide dismutase) and content of superoxide radical (O2   ∙−), nitric oxide (NO), and peroxynitrite (ONOO−) indicates a process of nitro-oxidative stress induced by NaCl. Among the analysed NADPH-generating dehydrogenases under salinity conditions, the NADP-ICDH showed the maximum activity mainly attributable to the root NADP-ICDH. Thus, these data provide new insights on the relevance of the NADP-ICDH which could be considered as a second barrier in the mechanism of response against the nitro-oxidative stress generated by salinity. PMID:22649311

  14. Regulation of basal and oxidative stress-triggered jasmonic acid-related gene expression by glutathione.

    PubMed

    Han, Yi; Mhamdi, Amna; Chaouch, Sejir; Noctor, Graham

    2013-06-01

    Glutathione is a determinant of cellular redox state with roles in defence and detoxification. Emerging concepts suggest that this compound also has functions in cellular signalling. Here, we report evidence that glutathione plays potentially important roles in setting signalling strength through the jasmonic acid (JA) pathway. Firstly, we show that basal expression of JA-related genes is correlated with leaf glutathione content when the latter is manipulated either genetically or pharmacologically. Secondly, analyses of an oxidative stress signalling mutant, cat2, reveal that up-regulation of the JA pathway triggered by intracellular oxidation requires accompanying glutathione accumulation. Genetically blocking this accumulation in a cat2 cad2 line largely annuls H2 O2 -induced expression of JA-linked genes, and this effect can be rescued by exogenously supplying glutathione. While most attention on glutathione functions in biotic stress responses has been focused on the thiol-regulated protein NPR1, a comparison of JA-linked gene expression in cat2 cad2 and cat2 npr1 double mutants provides evidence that glutathione acts through other components to regulate the response of this pathway to oxidative stress. Our study provides new information implicating glutathione as a factor determining basal JA gene expression and suggests novel glutathione-dependent control points that regulate JA signalling in response to intracellular oxidation.

  15. 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. © 2015 John Wiley & Sons Ltd.

  16. 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.

  17. AtMYB44 regulates resistance to the green peach aphid and diamondback moth by activating EIN2-affected defences in Arabidopsis.

    PubMed

    Lü, B-B; Li, X-J; Sun, W-W; Li, L; Gao, R; Zhu, Q; Tian, S-M; Fu, M-Q; Yu, H-L; Tang, X-M; Zhang, C-L; Dong, H-S

    2013-09-01

    Recently we showed that the transcription activator AtMYB44 regulates expression of EIN2, a gene essential for ethylene signalling and insect resistance, in Arabidopsis thaliana (Arabidopsis). To link the transactivation with insect resistance, we investigated the wild-type and atmyb44 mutant plants, genetically Complemented atmyb44 (Catmyb44) and AtMYB44-Overexpression Transgenic Arabidopsis (MYB44OTA). We found that AtMYB44 played a critical role in Arabidopsis resistance to the phloem-feeding generalist green peach aphid (Myzus persicae Sulzer) and leaf-chewing specialist caterpillar diamondback moth (Plutella xylostella L.). AtMYB44 was required not only for the development of constitutive resistance but also for the induction of resistance by both herbivorous insects. Levels of constitutive and herbivore-induced resistance were consistent with corresponding amounts of the AtMYB44 protein constitutively produced in MYB44OTA and induced by herbivory in Catmyb44. In both cases, AtMYB44 promoted EIN2 expression to a greater extent in MYB44OTA than in Catmyb44. However, AtMYB44-promoted EIN2 expression was arrested with reduced resistance levels in the EIN2-deficient Arabidopsis mutant ein2-1 and the MYB44OTA ein2-1 hybrid. In the different plant genotypes, only MYB44OTA constitutively displayed phloem-based defences, which are specific to phloem-feeding insects, and robust expression of genes involved in the biosynthesis of glucosinolates, which are the secondary plant metabolites known as deterrents to generalist herbivores. Phloem-based defences and glucosinolate-related gene expression were not detected in ein2-1 and MYB44OTA ein2-1. These results establish a genetic connection between the regulatory role of AtMYB44 in EIN2 expression and the development of Arabidopsis resistance to insects.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. Defence response of tomato seedlings to oxidative stress induced by phenolic compounds from dry olive mill residue.

    PubMed

    García-Sánchez, Mercedes; Garrido, Inmaculada; Casimiro, Ilda de Jesús; Casero, Pedro Joaquín; Espinosa, Francisco; García-Romera, Inmaculada; Aranda, Elisabet

    2012-10-01

    ADOR is an aqueous extract obtained from the dry olive mill residue (DOR) which contains the majority of its soluble phenolic compounds, which are responsible for its phytotoxic properties. Some studies have shown that ADOR negatively affects seed germination. However, to date, few studies have been carried out on the effect of ADOR on the oxidative stress of the plant. It is well known that saprobe fungi can detoxify these phenolic compounds and reduce the potential negative effects of ADOR on plants. To gain a better understanding of the phytotoxic effects and oxidative stress caused by this residue, tomato seeds were germinated in the presence of ADOR, treated and untreated with Coriolopsis rigida, Trametes versicolor, Pycnoporus cinnabarinus and Penicillium chrysogenum-10 saprobe fungi. ADOR sharply reduced tomato seed germination and also generated high levels of malondialdehyde (MDA), O(2)(-) and H(2)O(2). However, bioremediated ADOR did not negatively affect germination and reduced MDA, O(2)(-) and H(2)O(2) content in different ways depending on the fungus used. In addition, the induced defense response was studied by analyzing the activity of both antioxidant enzymes (superoxide dismutase (SOD), catalase, ascorbate peroxidasa, glutathione reductase (GR), peroxidases and coniferil alcohol peroxidasa) and detoxification enzymes (glutathione-S-transferase (GST)). Our findings suggest that, because ADOR is capable of inducing oxidative stress, tomato seedlings trigger a defense response through SOD, GR, and GST activity and through antioxidant and lignification processes. On the other hand, the bioremediation of ADOR plays an important role in counteracting the oxidative stress induced by the untreated residue.

  4. 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

  5. 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

    2015-12-17

    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.

  6. Abscisic acid-regulated responses of aba2-1 under osmotic stress: the abscisic acid-inducible antioxidant defence system and reactive oxygen species production.

    PubMed

    Ozfidan, C; Turkan, I; Sekmen, A H; Seckin, B

    2012-03-01

    We investigated the interaction among abscisic acid (ABA), reactive oxygen species (ROS) and antioxidant defence system in the transduction of osmotic stress signalling using Arabidopsis thaliana WT (Columbia ecotype, WT) and an ABA-deficient mutant (aba2-1). For this, 50 μm ABA and osmotic stress, induced with 40% (w/v) polyethylene glycol (PEG8000; -0.7 MPa), were applied to WT and aba2-1 for 6, 12 or 24 h. Time course analysis was undertaken for determination of total/isoenzyme activity of the antioxidant enzymes, superoxide dismutase (SOD; EC 1.15.1.1), catalase (CAT; EC 1.11.1.6), ascorbate peroxidase (APX; EC 1.11.1.11), NADPH oxidase (NOX; EC 1.6.3.1) activity; scavenging activity of the hydroxyl radical (OH˙), hydrogen peroxide (H(2) O(2) ); endogenous ABA and malondialdehyde (MDA). The highest H(2) O(2) and MDA content was found in PEG-treated groups of both genotypes, but with more in aba2-1. ABA treatment under stress reduced the accumulation of H(2) O(2) and MDA, while it promoted activity of SOD, CAT and APX. APX activity was higher than CAT activity in ABA-treated WT and aba2-1, indicating a protective role of APX rather than CAT during osmotic stress-induced oxidative damage. Treatment with ABA also significantly induced increased NOX activity. Oxidative damage was lower in ABA-treated seedlings of both genotypes, which was associated with greater activity of SOD (Mn-SOD1 and 2 and Fe-SOD isoenzymes), CAT and APX in these seedlings after 24 h of stress. These results suggest that osmotic stress effects were overcome by ABA treatment because of increased SOD, CAT, APX and NOX.

  7. Obesity and oxidative stress: potential roles of melatonin as antioxidant and metabolic regulator.

    PubMed

    Bonnefont-Rousselot, Dominique

    2014-01-01

    Obesity is associated with an oxidative stress status, defined as an excessive production of reactive oxygen species (ROS) compared to the level of antioxidants acting in the natural defence systems. Several sources of ROS can be identified in obesity (e.g., mitochondrial respiratory chain, or NADPH oxidase) and could contribute to the pathogenesis of obesity. Indeed, these conditions favour the development of insulin resistance and metabolic syndrome through deregulation of adipokines and pro-inflammatory cytokines, so that it could be of interest to associate antioxidant therapeutic strategies with strategies of weight loss. Among antioxidants, melatonin holds a special place, on the one hand for its antioxidant and anti-inflammatory properties, and on the other hand for its role as a metabolic regulator. As melatonin modulates several processes involved in obesity and its related metabolic alterations, it could have a therapeutic interest in the treatment of obesity.

  8. Ability of innate defence regulator peptides IDR-1002, IDR-HH2 and IDR-1018 to protect against Mycobacterium tuberculosis infections in animal models.

    PubMed

    Rivas-Santiago, Bruno; Castañeda-Delgado, Julio E; Rivas Santiago, Cesar E; Waldbrook, Matt; González-Curiel, Irma; León-Contreras, Juan C; Enciso-Moreno, Jose Antonio; del Villar, Victor; Mendez-Ramos, Jazmin; Hancock, Robert E W; Hernandez-Pando, Rogelio

    2013-01-01

    Tuberculosis is an ongoing threat to global health, especially with the emergence of multi drug-resistant (MDR) and extremely drug-resistant strains that are motivating the search for new treatment strategies. One potential strategy is immunotherapy using Innate Defence Regulator (IDR) peptides that selectively modulate innate immunity, enhancing chemokine induction and cell recruitment while suppressing potentially harmful inflammatory responses. IDR peptides possess only modest antimicrobial activity but have profound immunomodulatory functions that appear to be influential in resolving animal model infections. The IDR peptides HH2, 1018 and 1002 were tested for their activity against two M. tuberculosis strains, one drug-sensitive and the other MDR in both in vitro and in vivo models. All peptides showed no cytotoxic activity and only modest direct antimicrobial activity versus M. tuberculosis (MIC of 15-30 µg/ml). Nevertheless peptides HH2 and 1018 reduced bacillary loads in animal models with both the virulent drug susceptible H37Rv strain and an MDR isolate and, especially 1018 led to a considerable reduction in lung inflammation as revealed by decreased pneumonia. These results indicate that IDR peptides have potential as a novel immunotherapy against TB.

  9. The effects of temperature and dissolved oxygen on antioxidant defences and oxidative damage in the fathead minnow Pimephales promelas.

    PubMed

    Clotfelter, E D; Lapidus, S J H; Brown, A C

    2013-03-01

    Fathead minnows Pimephales promelas maintained at 25° C for 6 h had significantly higher superoxide dismutase (SOD) activity than fish maintained at 7 or 32° C, but hypoxic conditions (3 mg l(-1) O2 ) over the same time period did not affect SOD activity. Fish in better body condition (length-adjusted mass) had higher SOD activity. In a separate experiment, P. promelas maintained at three water temperatures (7, 23 and 32° C) for 31 days did not differ in liver acrolein, a biomarker of oxidative stress.

  10. Class III peroxidases in plant defence reactions.

    PubMed

    Almagro, L; Gómez Ros, L V; Belchi-Navarro, S; Bru, R; Ros Barceló, A; Pedreño, M A

    2009-01-01

    When plants are attacked by pathogens, they defend themselves with an arsenal of defence mechanisms, both passive and active. The active defence responses, which require de novo protein synthesis, are regulated through a complex and interconnected network of signalling pathways that mainly involve three molecules, salicylic acid (SA), jasmonic acid (JA), and ethylene (ET), and which results in the synthesis of pathogenesis-related (PR) proteins. Microbe or elicitor-induced signal transduction pathways lead to (i) the reinforcement of cell walls and lignification, (ii) the production of antimicrobial metabolites (phytoalexins), and (iii) the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Among the proteins induced during the host plant defence, class III plant peroxidases (EC 1.11.1.7; hydrogen donor: H(2)O(2) oxidoreductase, Prxs) are well known. They belong to a large multigene family, and participate in a broad range of physiological processes, such as lignin and suberin formation, cross-linking of cell wall components, and synthesis of phytoalexins, or participate in the metabolism of ROS and RNS, both switching on the hypersensitive response (HR), a form of programmed host cell death at the infection site associated with limited pathogen development. The present review focuses on these plant defence reactions in which Prxs are directly or indirectly involved, and ends with the signalling pathways, which regulate Prx gene expression during plant defence. How they are integrated within the complex network of defence responses of any host plant cell will be the cornerstone of future research.

  11. 40 CFR 52.231 - Regulations: Sulfur oxides.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Regulations: Sulfur oxides. 52.231... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS California § 52.231 Regulations: Sulfur oxides... Ambient Air Quality Standard for Sulfur Oxides. (1) Lake County Intrastate Region. (i) Lake County,...

  12. 40 CFR 52.231 - Regulations: Sulfur oxides.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Regulations: Sulfur oxides. 52.231... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS California § 52.231 Regulations: Sulfur oxides... Ambient Air Quality Standard for Sulfur Oxides. (1) Lake County Intrastate Region. (i) Lake County,...

  13. 40 CFR 52.231 - Regulations: Sulfur oxides.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Regulations: Sulfur oxides. 52.231... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS California § 52.231 Regulations: Sulfur oxides... Ambient Air Quality Standard for Sulfur Oxides. (1) Lake County Intrastate Region. (i) Lake County,...

  14. 40 CFR 52.231 - Regulations: Sulfur oxides.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Regulations: Sulfur oxides. 52.231... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS California § 52.231 Regulations: Sulfur oxides... Ambient Air Quality Standard for Sulfur Oxides. (1) Lake County Intrastate Region. (i) Lake County,...

  15. 40 CFR 52.231 - Regulations: Sulfur oxides.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Regulations: Sulfur oxides. 52.231... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS California § 52.231 Regulations: Sulfur oxides... Ambient Air Quality Standard for Sulfur Oxides. (1) Lake County Intrastate Region. (i) Lake County,...

  16. RNA silencing suppression by plant pathogens: defence, counter-defence and counter-counter-defence.

    PubMed

    Pumplin, Nathan; Voinnet, Olivier

    2013-11-01

    RNA silencing is a central regulator of gene expression in most eukaryotes and acts both at the transcriptional level through DNA methylation and at the post-transcriptional level through direct mRNA interference mediated by small RNAs. In plants and invertebrates, the same pathways also function directly in host defence against viruses by targeting viral RNA for degradation. Successful viruses have consequently evolved diverse mechanisms to avoid silencing, most notably through the expression of viral suppressors of RNA silencing. RNA silencing suppressors have also been recently identified in plant pathogenic bacteria and oomycetes, suggesting that disruption of host silencing is a general virulence strategy across several kingdoms of plant pathogens. There is also increasing evidence that plants have evolved specific defences against RNA-silencing suppression by pathogens, providing yet another illustration of the never-ending molecular arms race between plant pathogens and their hosts.

  17. Membrane-bound oxygen reductases of the anaerobic sulfate-reducing Desulfovibrio vulgaris Hildenborough: roles in oxygen defence and electron link with periplasmic hydrogen oxidation.

    PubMed

    Ramel, F; Amrani, A; Pieulle, L; Lamrabet, O; Voordouw, G; Seddiki, N; Brèthes, D; Company, M; Dolla, A; Brasseur, G

    2013-12-01

    Cytoplasmic membranes of the strictly anaerobic sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough contain two terminal oxygen reductases, a bd quinol oxidase and a cc(b/o)o3 cytochrome oxidase (Cox). Viability assays pointed out that single Δbd, Δcox and double ΔbdΔcox deletion mutant strains were more sensitive to oxygen exposure than the WT strain, showing the involvement of these oxygen reductases in the detoxification of oxygen. The Δcox strain was slightly more sensitive than the Δbd strain, pointing to the importance of the cc(b/o)o3 cytochrome oxidase in oxygen protection. Decreased O2 reduction rates were measured in mutant cells and membranes using lactate, NADH, ubiquinol and menadiol as substrates. The affinity for oxygen measured with the bd quinol oxidase (Km, 300 nM) was higher than that of the cc(b/o)o3 cytochrome oxidase (Km, 620 nM). The total membrane activity of the bd quinol oxidase was higher than that of the cytochrome oxidase activity in line with the higher expression of the bd oxidase genes. In addition, analysis of the ΔbdΔcox mutant strain indicated the presence of at least one O2-scavenging membrane-bound system able to reduce O2 with menaquinol as electron donor with an O2 affinity that was two orders of magnitude lower than that of the bd quinol oxidase. The lower O2 reductase activity in mutant cells with hydrogen as electron donor and the use of specific inhibitors indicated an electron transfer link between periplasmic H2 oxidation and membrane-bound oxygen reduction via the menaquinol pool. This linkage is crucial in defence of the strictly anaerobic bacterium Desulfovibrio against oxygen stress.

  18. Thioredoxin 2 is involved in oxidative stress defence and redox-dependent expression of photosynthesis genes in Rhodobacter capsulatus.

    PubMed

    Li, Kuanyu; Härtig, Elisabeth; Klug, Gabriele

    2003-02-01

    Thioredoxins are small ubiquitous proteins that display different functions mainly via redox-mediated processes. The facultatively photosynthetic bacterium Rhodobacter capsulatus harbours at least two genes for thioredoxin 1 and 2, trxA and trxC. It is demonstrated that thioredoxin 2 of R. capsulatus can partially replace the thioredoxin 1 function as a hydrogen donor for methionine sulfoxide reductase but cannot replace thioredoxin 1 as a subunit of phage T7 DNA polymerase. By inactivating the trxC gene in R. capsulatus, it is shown that thioredoxin 2 is involved in resistance against oxidative stress. As thioredoxin 1 of Rhodobacter sphaeroides, R. capsulatus thioredoxin 2 affects the oxygen-dependent expression of photosynthesis genes, albeit in an opposite way. The trxC mutant of R. capsulatus shows a stronger increase in photosynthesis gene expression after a decrease in oxygen tension than the isogenic wild-type strain. The expression of the trxC gene is downregulated by oxygen.

  19. Diverse opportunities in defence

    NASA Astrophysics Data System (ADS)

    Brown, Gareth

    2016-08-01

    Working at the UK's defence laboratory gives Gareth Brown the ability to apply his physics and mathematics knowledge to real-world applications - and not necessarily in the ways you might expect. This article is Crown copyright

  20. Impact of salicylic acid- and jasmonic acid-regulated defences on root colonization by Trichoderma harzianum T-78.

    PubMed

    Martínez-Medina, Ainhoa; Appels, Freek V W; van Wees, Saskia C M

    2017-07-10

    We recently found that the beneficial fungus Trichoderma harzianum T-78 primes tomato plants for salicylic acid (SA)- and jasmonic acid (JA)-regulated defenses, resulting in enhanced resistance against the root knot nematode Meloidogyne incognita. By using SA- and JA-impaired mutant lines and exogenous hormonal application, here we investigated whether the SA- and JA-pathways also have a role in T-78 root colonization of Arabidopsis thaliana. Endophytic colonization by T-78 was faster in the SA-impaired mutant sid2 than in the wild type. Moreover, elicitation of SA-dependent defenses by SA application reduced T-78 colonization, indicating that the SA-pathway affects T-78 endophytism. In contrast, elicitation of the JA-pathway, which antagonized SA-dependent defenses, resulted in enhanced endophytic colonization by T-78. These findings are in line with our previous observation that SA-dependent defenses are repressed by T-78, which likely aids colonization by the endophytic fungus.

  1. Defence Reporter. Spring 2011

    DTIC Science & Technology

    2011-01-01

    of a series of services and products produced by ATHENA to keep readers up -to- date with the latest developments in key areas of defence science...the MOD’s ATHENA Collection. Defence Reporter is available by subscription. To sign up for this free service, please send an e-mail with your full...for the oral route. This study was set up lo enable some confirmation of published LD50 information of orally dosed ricin but also to enable some

  2. Defence Industrial Strategy

    DTIC Science & Technology

    2005-12-01

    make clear which industrial capabilities we need to have onshore (and this includes those maintained by foreign- owned defence companies), industry...industry to deliver the complex system of systems that will make up the Future Rapid Effects System (FRES) fleet. xxi. It is questionable whether... make clear which industrial capabilities we need to have onshore (and this includes those maintained by foreign- owned defence companies), industry may

  3. 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. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  4. 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.

  5. 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.

  6. The lack of alternative oxidase at low temperature leads to a disruption of the balance in carbon and nitrogen metabolism, and to an up-regulation of antioxidant defence systems in Arabidopsis thaliana leaves.

    PubMed

    Watanabe, Chihiro K; Hachiya, Takushi; Terashima, Ichiro; Noguchi, Ko

    2008-08-01

    Alternative oxidase (AOX) catalyses the ATP-uncoupling cyanide (CN)-resistant pathway. In this study, our aim was to clarify the physiological role of AOX at low temperature. We examined the effect of low-temperature treatment on CN-resistant respiration (CN-resistant R) and on the transcription of respiratory components in wild-type (WT) and aox1a knock-out transgenic (aox1a) Arabidopsis thaliana plants. In WT leaves, the expression of AOX1a mRNA was strongly induced by the low-temperature treatment, and thus CN-resistant R increased during low-temperature treatment. In aox1a, the CN-sensitive respiration, and the expression of NDB2 and UCP1 were increased compared with WT. We compared several physiological parameters between WT and aox1a. Low-temperature treatment did not result in a visible phenotype to distinguish aox1a from WT. In aox1a, several antioxidant defence genes were induced, and the malondialdehyde content was lower than in WT. Starch content and a ratio of carbon to nitrogen were higher in aox1a than in WT. Our results indicate that a lack of AOX was linked to a difference in the carbon and nitrogen balance, and an up-regulation of the transcription of antioxidant defence system at low temperature. It is likely that AOX is a necessary component in antioxidant defence mechanisms and for the control of a balanced metabolism.

  7. Air Defence Alerting Device

    NASA Astrophysics Data System (ADS)

    Trapmore, Clive

    1990-04-01

    The Air Defence Alerting Device, otherwise known as ADAD, is a passive infra-red system which detects the presence of a potentially hostile airborne threat and relays its bearings to a Close Air Defence Weapon System (CADWS). The equipment is therefore a cueing device which directs a weapon system operator (or his sight) to the bearing of the threat. From an overall weapon system point of view, use of ADAD realises a very significant increase in weapon effectiveness which is greatly welcomed in these times of constrained defence budgets. The ADAD system is believed to be the first of its kind in the world to be procured in production quantities - it will go into service with the UK Army in the early 1990's.

  8. Lack of Clinical Manifestations in Asymptomatic Dengue Infection Is Attributed to Broad Down-Regulation and Selective Up-Regulation of Host Defence Response Genes

    PubMed Central

    Yeo, Adeline S. L.; Azhar, Nur Atiqah; Yeow, Wanyi; Talbot, C. Conover; Khan, Mohammad Asif; Shankar, Esaki M.; Rathakrishnan, Anusyah; Azizan, Azliyati; Wang, Seok Mui; Lee, Siew Kim; Fong, Mun Yik; Manikam, Rishya; Sekaran, Shamala Devi

    2014-01-01

    Objectives Dengue represents one of the most serious life-threatening vector-borne infectious diseases that afflicts approximately 50 million people across the globe annually. Whilst symptomatic infections are frequently reported, asymptomatic dengue remains largely unnoticed. Therefore, we sought to investigate the immune correlates conferring protection to individuals that remain clinically asymptomatic. Methods We determined the levels of neutralizing antibodies (nAbs) and gene expression profiles of host immune factors in individuals with asymptomatic infections, and whose cognate household members showed symptoms consistent to clinical dengue infection. Results We observed broad down-regulation of host defense response (innate, adaptive and matrix metalloprotease) genes in asymptomatic individuals as against symptomatic patients, with selective up-regulation of distinct genes that have been associated with protection. Selected down-regulated genes include: TNF α (TNF), IL8, C1S, factor B (CFB), IL2, IL3, IL4, IL5, IL8, IL9, IL10 and IL13, CD80, CD28, and IL18, MMP8, MMP10, MMP12, MMP15, MMP16, and MMP24. Selected up-regulated genes include: RANTES (CCL5), MIP-1α (CCL3L1/CCL3L3), MIP-1β (CCL4L1), TGFβ (TGFB), and TIMP1. Conclusion Our findings highlight the potential association of certain host genes conferring protection against clinical dengue. These data are valuable to better explore the mysteries behind the hitherto poorly understood immunopathogenesis of subclinical dengue infection. PMID:24727912

  9. The response of L5178Y lymphoma sublines to oxidative stress: antioxidant defence, iron content and nuclear translocation of the p65 subunit of NF-kappaB.

    PubMed

    Bouzyk, E; Gradzka, I; Iwaneńko, T; Kruszewski, M; Sochanowicz, B; Szumiel, I

    2000-01-01

    We examined the response to hydrogen peroxide of two L5178Y (LY) sublines which are inversely cross-sensitive to hydrogen peroxide and X-rays: LY-R cells are radio-resistant and hydrogen peroxide-sensitive, whereas LY-S cells are radiosensitive and hydrogen peroxide-resistant. Higher initial DNA breaks and higher iron content (potentially active in the Fenton reaction) were found in the hydrogen peroxide sensitive LY-R cells than in the hydrogen peroxide resistant LY-S cells, whereas the antioxidant defence of LY-R cells was weaker. In particular, catalase activity is twofold higher in LY-S than in LY-R cells. The content of monobromobimane-reactive thiols is 54% higher in LY-S than in LY-R cells. In contrast, the activity of glutathione peroxidase (GPx) is about two times higher in LY-R than in LY-S cells; however, upon induction with selenium the activity increases 15.6-fold in LY-R cells and 50.3-fold in LY-S cells. Altogether, the sensitivity difference is related to the iron content, the amount of the initial DNA damage, as well as to the efficiency of the antioxidant defence system. Differential nuclear translocation of p65-NF-kappaB in LY sublines is due to the more efficient antioxidant defence in LY-S than in LY-R cells.

  10. Functional analysis reveals effects of tobacco alternative oxidase gene (NtAOX1a) on regulation of defence responses against abiotic and biotic stresses.

    PubMed

    Zhang, Yi; Xi, Dongmei; Wang, Jian; Zhu, Dongfang; Guo, Xingqi

    2009-07-22

    Mitochondrial AOX (alternative oxidase) is the terminal oxidase of the CN (cyanide)-resistant alternative respiratory pathway in plants. To investigate the role of the tobacco AOX gene (NtAOX1a) (where Nt is Nicotiana tabacum) under deleterious conditions which could induce ROS (reactive oxygen species) accumulation, we generated and characterized a number of independent transgenic tobacco (N. tabacum) lines with altered NtAOX1a gene expression and AP (alternative pathway) capacity. AOX efficiently inhibited the production of low-temperature-induced H2O2 and might be a major enzyme for scavenging H2O2 at low temperature. Furthermore, NtAOX1a may act as a regulator of KCN-induced resistance to TMV (tobacco mosaic virus) through the regulation of H2O2. Notably, a moderate accumulation of H2O2 under the control of NtAOX1a was crucial in viral resistance. Analysis of seed germination indicated an important role for NtAOX1a in germination under H2O2-induced oxidative stress when the CP (cytochrome pathway) was inhibited. These results demonstrate that NtAOX1a is necessary for plants to survive low temperature, pathogen attack and oxidative stress by scavenging ROS under these adverse conditions when the CP is restricted.

  11. The regulation of superoxide generation and nitric oxide synthesis by C-reactive protein.

    PubMed Central

    Ratnam, S; Mookerjea, S

    1998-01-01

    Activated macrophages utilize both reactive oxygen intermediates and reactive oxynitrogen intermediates for defence against microbes. However, simultaneous generation of superoxide (O- 2;) and nitric oxide (NO) could be harmful to host cells due to the production of peroxynitrite, nitrogen dioxide and hydroxyl radicals. Therefore, the regulation of the production of these molecules is critical to host survival. During periods of inflammation or infection, the level of serum C-reactive protein (CRP) increases in many species. Human and rat CRP have been shown to bind and interact with phagocytic cells. Since many of the interactions of CRP involve the binding to the phosphocholine ligand, we studied the role of CRP in O- 2; and NO generation through the modulation of phosphatidylcholine (PC) metabolism in macrophages. This study has shown that, while rat CRP inhibited phorbol myristate acetate- (PMA) induced release of O- 2; by rat macrophages, CRP-treated macrophages released NO in a time- and dose-dependent manner. CRP increased inducible nitric oxide synthase (iNOS) enzyme as well as iNOS mRNA levels in rat macrophages. Tricyclodecan-9-yl-xanthogenate (D609), an inhibitor to PC phospholipase C (PC-PLC), suppressed iNOS induction but enhanced PMA-induced release of O- 2;. These data indicate that an increased level of CRP during periods of inflammation may result in differential regulation of macrophage NADPH oxidase and iNOS activity. Increased hepatic synthesis of CRP may contribute to the mechanism by which phagocytic cells avoid simultaneous O- 2; and NO synthesis, and this could possibly be mediated through the regulation of PC-PLC. Images Figure 4 Figure 5 PMID:9767445

  12. Alternative defence policy

    SciTech Connect

    Burt, G.

    1987-01-01

    This book considers key questions connected with the present crisis, questions such as Would conventional deterrence really be effective. Just what is the Labour Party's policy. How precisely might Britain be transformed into a non-aligned, non-military state. The future of British defence policy is an issue of major concern not just in Britain but throughout the world, especially in the United States where there are major anxieties in the Pentagon about what will happen if the Labour Party wins an election outright. British defence policy is currently in a state of crisis. The former position where a reasonably united establishment on one hand confronted nuclear disarmers on the other has been replaced by a position where a wide spectrum of different opinions is held not just by the peace movement and the opposition parties but by many people in the Conservative party and the military also.

  13. Processes regulating nitric oxide emissions from soils.

    PubMed

    Pilegaard, Kim

    2013-07-05

    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.

  14. Processes regulating nitric oxide emissions from soils

    PubMed Central

    Pilegaard, Kim

    2013-01-01

    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

  15. Regulation of alkane oxidation in Pseudomonas putida.

    PubMed Central

    Grund, A; Shapiro, J; Fennewald, M; Bacha, P; Leahy, J; Markbreiter, K; Nieder, M; Toepfer, M

    1975-01-01

    We have studied the appearance of whole-cell oxidizing activity for n-alkanes and their oxidation products in strains of Pseudomonas putida carrying the OCT plasmid. Our results indicate that the OCT plasmid codes for inducible alkane-hydroxylating and primary alcohol-dehydrogenating activities and that the chromosome codes for constitutive oxidizing activities for primary alcohols, aliphatic aldehydes, and fatty acids. Mutant isolation confirms the presence of an alcohol dehydrogenase locus on the OCT plasmid and indicated the presence of multiple alcohol and aldehyde dehydrogenase loci on the P. putida chromosome. Induction tests with various compounds indicate that inducer recognition has specificity for chain length and can be affected by the degree of oxidation of the carbon chain. Some inducers are neither growth nor respiration substrates. Growth tests with and without a gratuitous inducer indicate that undecane is not a growth substrate because it does not induce alkane hydroxylase activity. Using a growth test for determining induction of the plasmid alcohol dehydrogenase it is possible to show that heptane induces this activity in hydroxylase-negative mutants. This suggests that unoxidized alkane molecules are the physiological inducers of both plasmid activities. PMID:1150626

  16. LKB1 regulates lipid oxidation during exercise independently of AMPK.

    PubMed

    Jeppesen, Jacob; Maarbjerg, Stine J; Jordy, Andreas B; Fritzen, Andreas M; Pehmøller, Christian; Sylow, Lykke; Serup, Annette Karen; Jessen, Niels; Thorsen, Kasper; Prats, Clara; Qvortrup, Klaus; Dyck, Jason R B; Hunter, Roger W; Sakamoto, Kei; Thomson, David M; Schjerling, Peter; Wojtaszewski, Jørgen F P; Richter, Erik A; Kiens, Bente

    2013-05-01

    Lipid metabolism is important for health and insulin action, yet the fundamental process of regulating lipid metabolism during muscle contraction is incompletely understood. Here, we show that liver kinase B1 (LKB1) muscle-specific knockout (LKB1 MKO) mice display decreased fatty acid (FA) oxidation during treadmill exercise. LKB1 MKO mice also show decreased muscle SIK3 activity, increased histone deacetylase 4 expression, decreased NAD⁺ concentration and SIRT1 activity, and decreased expression of genes involved in FA oxidation. In AMP-activated protein kinase (AMPK)α2 KO mice, substrate use was similar to that in WT mice, which excluded that decreased FA oxidation in LKB1 MKO mice was due to decreased AMPKα2 activity. Additionally, LKB1 MKO muscle demonstrated decreased FA oxidation in vitro. A markedly decreased phosphorylation of TBC1D1, a proposed regulator of FA transport, and a low CoA content could contribute to the low FA oxidation in LKB1 MKO. LKB1 deficiency did not reduce muscle glucose uptake or oxidation during exercise in vivo, excluding a general impairment of substrate use during exercise in LKB1 MKO mice. Our findings demonstrate that LKB1 is a novel molecular regulator of major importance for FA oxidation but not glucose uptake in muscle during exercise.

  17. LKB1 Regulates Lipid Oxidation During Exercise Independently of AMPK

    PubMed Central

    Jeppesen, Jacob; Maarbjerg, Stine J.; Jordy, Andreas B.; Fritzen, Andreas M.; Pehmøller, Christian; Sylow, Lykke; Serup, Annette Karen; Jessen, Niels; Thorsen, Kasper; Prats, Clara; Qvortrup, Klaus; Dyck, Jason R.B.; Hunter, Roger W.; Sakamoto, Kei; Thomson, David M.; Schjerling, Peter; Wojtaszewski, Jørgen F.P.; Richter, Erik A.; Kiens, Bente

    2013-01-01

    Lipid metabolism is important for health and insulin action, yet the fundamental process of regulating lipid metabolism during muscle contraction is incompletely understood. Here, we show that liver kinase B1 (LKB1) muscle-specific knockout (LKB1 MKO) mice display decreased fatty acid (FA) oxidation during treadmill exercise. LKB1 MKO mice also show decreased muscle SIK3 activity, increased histone deacetylase 4 expression, decreased NAD+ concentration and SIRT1 activity, and decreased expression of genes involved in FA oxidation. In AMP-activated protein kinase (AMPK)α2 KO mice, substrate use was similar to that in WT mice, which excluded that decreased FA oxidation in LKB1 MKO mice was due to decreased AMPKα2 activity. Additionally, LKB1 MKO muscle demonstrated decreased FA oxidation in vitro. A markedly decreased phosphorylation of TBC1D1, a proposed regulator of FA transport, and a low CoA content could contribute to the low FA oxidation in LKB1 MKO. LKB1 deficiency did not reduce muscle glucose uptake or oxidation during exercise in vivo, excluding a general impairment of substrate use during exercise in LKB1 MKO mice. Our findings demonstrate that LKB1 is a novel molecular regulator of major importance for FA oxidation but not glucose uptake in muscle during exercise. PMID:23349504

  18. The role of thionins in rice defence against root pathogens.

    PubMed

    Ji, Hongli; Gheysen, Godelieve; Ullah, Chhana; Verbeek, Ruben; Shang, Chenjing; De Vleesschauwer, David; Höfte, Monica; Kyndt, Tina

    2015-10-01

    Thionins are antimicrobial peptides that are involved in plant defence. Here, we present an in-depth analysis of the role of rice thionin genes in defence responses against two root pathogens: the root-knot nematode Meloidogyne graminicola and the oomycete Pythium graminicola. The expression of rice thionin genes was observed to be differentially regulated by defence-related hormones, whereas all analysed genes were consistently down-regulated in M. graminicola-induced galls, at least until 7 days post-inoculation (dpi). Transgenic lines of Oryza sativa cv. Nipponbare overproducing OsTHI7 revealed decreased susceptibility to M. graminicola infection and P. graminicola colonization. Taken together, these results demonstrate the role of rice thionin genes in defence against two of the most damaging root pathogens attacking rice.

  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. Defence Reporter. Autumn 2013

    DTIC Science & Technology

    2013-01-01

    Reporter is one part of a series of services and products produced by ATHENA to keep readers up -to- date with the latest developments in key areas...ATHENA Collection. Defence Reporter is available by subscription. To sign up for this free service, please send an e-mail with your full name and...here is that in a joined- up coalition environment our allies will not be able to discover UK data and if they do have it, they may not treat it

  1. Anti-carcinogenic action of curcumin by activation of antioxidant defence system and inhibition of NF-κB signalling in lymphoma-bearing mice.

    PubMed

    Das, Laxmidhar; Vinayak, Manjula

    2012-04-01

    NF-κB (nuclear factor κB) plays a significant role in inflammation, immunity, cell proliferation, apoptosis and malignancy. ROS (reactive oxygen species) are among the most important regulating factors of NF-κB. Intracellular ROS are mainly regulated by an endogenous antioxidant defence system. Any disruption of redox balance leads to oxidative stress, which causes a number of pathological conditions including inflammation and malignancy. Increased metabolic activity in cancerous cells leads to oxidative stress, which is further enhanced due to depletion of the endogenous antioxidant defence system. However, the activation and signalling of NF-κB are reported to be inhibited by overexpression and induced activity of antioxidant enzymes. Therefore the present study focuses on the correlation between the endogenous antioxidant defence system, ROS and NF-κB activation during lymphoma growth in mice. The study highlights the anti-carcinogenic role of curcumin by modulation of NF-κB activation and oxidative stress via the endogenous antioxidant defence system. Oxidative stress was monitored by lipid peroxidation, protein carbonylation and antioxidant enzyme activity. NF-κB-mediated signalling was tested by DNA-binding activity. The results reflect that intracellular production of H2O2 in oxidative tumour micro-environment regulates NF-κB activation. Curcumin inhibits oxidative state in the liver of lymphoma-bearing mice by enhancing the transcription and activities of antioxidant enzymes, which in turn modulate activation of NF-κB, leading to a decrease in lymphoma growth. Morphological changes as well as cell proliferation and cell survival assays confirmed reduced lymphoma growth. Thus curcumin contributes to cancer prevention by disrupting the vicious cycle of constant ROS production, responsible for a high oxidative micro-environment for tumour growth.

  2. Biphasic regulation of lysosomal exocytosis by oxidative stress.

    PubMed

    Ravi, Sreeram; Peña, Karina A; Chu, Charleen T; Kiselyov, Kirill

    2016-11-01

    Oxidative stress drives cell death in a number of diseases including ischemic stroke and neurodegenerative diseases. A better understanding of how cells recover from oxidative stress is likely to lead to better treatments for stroke and other diseases. The recent evidence obtained in several models ties the process of lysosomal exocytosis to the clearance of protein aggregates and toxic metals. The mechanisms that regulate lysosomal exocytosis, under normal or pathological conditions, are only beginning to emerge. Here we provide evidence for the biphasic effect of oxidative stress on lysosomal exocytosis. Lysosomal exocytosis was measured using the extracellular levels of the lysosomal enzyme beta-hexosaminidase (ß-hex). Low levels or oxidative stress stimulated lysosomal exocytosis, but inhibited it at high levels. Deletion of the lysosomal ion channel TRPML1 eliminated the stimulatory effect of low levels of oxidative stress. The inhibitory effects of oxidative stress appear to target the component of lysosomal exocytosis that is driven by extracellular Ca(2+). We propose that while moderate oxidative stress promotes cellular repair by stimulating lysosomal exocytosis, at high levels oxidative stress has a dual pathological effect: it directly causes cell damage and impairs damage repair by inhibiting lysosomal exocytosis. Harnessing these adaptive mechanisms may point to pharmacological interventions for diseases involving oxidative proteotoxicity or metal toxicity.

  3. Regulation and Function of Lactate Oxidation in Streptococcus faecium

    PubMed Central

    London, Jack

    1968-01-01

    Regulation of the synthesis and function of an l(+)-specific lactate-oxidizing enzyme system found in a homofermentative Streptococcus was investigated. With the exception of fructose, aerobic growth at the expense of a variety of substrates resulted in the formation of a lactate oxidation system; anaerobic growth resulted in a marked reduction or complete loss of lactate-oxidizing activity. Growth on fructose, under aerobic and anaerobic conditions, invariably produced a decrease in the activity of the lactate oxidation system. A negative control, activated by an early intermediate product of glycolysis, appeared to be responsible for repression of the lactate-oxidizing enzyme(s). The enzyme system confers upon the organism the ability to grow aerobically at the expense of l(+)-lactic acid. PMID:5646625

  4. 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.

  5. 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

  6. [The changes of processes of free radical oxidation of lipids and proteins, antioxidant defence in rats with hypofunction of the thyroid gland in conditions of iodine and copper deficiency].

    PubMed

    Voronych-Semchenko, N M; Huranych, T V

    2014-01-01

    Thyroid status, copper balance, correlation of processes of peroxide oxidation of lipids (POL), proteins (POP), antioxidant defence (AOD) were examined in experiments on rats with hypofunction of thyroid gland under iodine monodeficit (HTGI) and combined iodine and copper deficit (HTGI+Cu). It was determined that a combined deficit of microelements is accompanied by a distribution of copper content between different tissues (increase in red blood cell mass and cerebrum, decrease in myocardium), essential changes of indexes of hypotalamo-hypophysis-thyroid axis, oxygen-dependent metabolism, antiradical defense, exacerbating the effects of negative influence of each of them on organism. It was established that HTGI+Cu causes a suppression of oxygen-dependent processes. In thyroid gland, it is shown a decrease of content of dyenic conjugates (DC) by 69,70% , of TBA-reacting products (TBA-RP) by 47,72% in diencephalon, the volume of modified proteins (VMP) - by 37,10-98,98% in the tissues of diencephalons. The results obtained let us to suggest a pivotal role ofmicroelement dysbalance and metabolic mechanisms in pathogenesis of cardiological pathology under thyroid dysfunction. The development of HTGI +Cu exhausts the resources of AOD: decreases the activity of catalase (on 47,05%), superoxide dismutase (on 33,13%), ceruloplasmine (on 33,93%) and saturation of transferrin with iron (on 56,76%) against the background of selective rise in the activity of glu-tationreductase (in 2,8 time) in comparison with the control data. The long-term disturbances ofantyoxidative defence can be the reason of manifestation of oxygendependent processes and the development of pathological changes in separate physiological systems of organism.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  8. Nanothermites for space and defence applications

    NASA Astrophysics Data System (ADS)

    Comet, Marc; Spitzer, Denis; Moeglin, Jean-Pierre

    2009-05-01

    Thermites are energetic materials which are made of a metallic oxide mixed with a reducing metal1. The reactivity of classical thermites is moderate but it can be substantially improved when micron-sized particles are replaced by nanoparticles. In this paper, three examples of nanothermites are given in order to illustrate the contribution of these nanomaterials in the future spatial and defence applications: - the incidence of the size of the metallic oxide particles on the reactivity was illustrated by the case of WO3/Al nanothermites, - the correlation between the composition/structure of the oxide phase and the reactivity was achieved on AlxMoyOz/Al nanothermites, - the fabrication of Gas Generating Nanothermites was performed by adding military explosives in porous mineral oxides (Cr2O3; MnO2) used to fabricate nanothermites.

  9. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. 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

  11. 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

  12. Antioxidant defences in hydrated and desiccated states of the tardigrade Paramacrobiotus richtersi.

    PubMed

    Rizzo, Angela M; Negroni, Manuela; Altiero, Tiziana; Montorfano, Gigliola; Corsetto, Paola; Berselli, Patrizia; Berra, Bruno; Guidetti, Roberto; Rebecchi, Lorena

    2010-06-01

    Reactive oxygen species (ROS) are formed in all aerobic organisms, potentially leading to oxidative damage of all biological molecules. A number of defence mechanisms have developed to protect the organism from attack by ROS. Desiccation tolerance is correlated with an increase in the antioxidant potential in several organisms, but the regulation of the antioxidant defence system is complex and its role in desiccation-tolerant organisms is not yet firmly established. To determine if anhydrobiotic tardigrades have an antioxidant defence system, capable of counteracting ROS, we compared the activity of several antioxidant enzymes, the fatty acid composition and Heat shock protein expression in two physiological states (desiccated vs. hydrated) of the tardigrade Paramacrobiotus richtersi. In hydrated tardigrades, superoxide dismutase and catalase show comparable activities, while in desiccated specimens the activity of superoxide dismutase increases. Both glutathione peroxidase and glutathione were induced by desiccation. The percentage of fatty acid composition of polyunsaturated fatty acids and the amount of thiobarbituric acid reactive substances are higher in desiccated animals than in hydrated ones. Lastly, desiccated tardigrades did not differ significantly from the hydrated ones in the relative levels of Hsp70 and Hsp90. These results indicate that the possession of antioxidant metabolism could represent a crucial strategy to avoid damages during desiccation in anhydrobiotic tardigrades.

  13. Nitric oxide regulates synaptic transmission between spiny projection neurons.

    PubMed

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

    2014-12-09

    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.

  14. 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

  15. 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

  16. Defence Food Research Activities Report.

    DTIC Science & Technology

    1983-01-01

    7 7115618 DEFENCE FOOD RESEARCH ACTIVITES REPORTWU ARMED)FORCES 1/ FOOD SCIENCE ESTARLISHMENT SCOTTSDALE (ADSTRA L A 1983 DLASFIED F/G6/8 *EEL A...681 1)epartment of I)efence I)efence Science and Technology Organization Armed Forces Food Science Establishment Scottsdale, Tasmania AFFSE REPORT 2/83...DEFENCE FOOD RESEARCH ACTIVITIES REPORTI [UI C) COMMONWEALTH OF AUSTRALIA, 1983 DTICELECTE Approved For Public Release 1978-83 ItC FILE COPY 83 .9 o

  17. 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.

  18. 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

  19. Oxidative stress in aspic vipers facing pregnancy and water constraints.

    PubMed

    Stier, Antoine; Dupoué, Andréaz; Picard, Damien; Angelier, Frédéric; Brischoux, François; Lourdais, Olivier

    2017-03-14

    The physiological mechanisms underlying the 'cost of reproduction' remain under debate, though oxidative stress has emerged as a potential candidate. The 'oxidative cost of reproduction' has received considerable attention with regards to food and antioxidant availability, however the limitation of water availability has thus far been neglected. In this study we experimentally examined the combined effect of pregnancy and water-deprivation on oxidative status in a viviparous snake (Vipera aspis), a species naturally exposed to periods of water and food deprivation. We predicted a cumulative effect of pregnancy and dehydration on oxidative stress levels. Our results support the occurrence of an oxidative cost of reproduction since we found higher oxidative damage levels in pregnant females than in non-reproductive individuals, despite an up-regulation of antioxidant defences. Surprisingly, water-deprivation was associated with an up-regulation of antioxidant defences, and did not increase oxidative damage, either alone or in combination with reproduction.

  20. Oxidative guanine base damage regulates human telomerase activity

    PubMed Central

    Fouquerel, Elise; Lormand, Justin; Bose, Arindam; Lee, Hui-Ting; Kim, Grace S.; Li, Jianfeng; Sobol, Robert W.; Freudenthal, Bret D.; Myong, Sua; Opresko, Patricia L.

    2016-01-01

    Changes in telomere length are associated with degenerative diseases and cancer. Oxidative stress and DNA damage have been linked to both positive and negative alterations in telomere length and integrity. Here we examined how the common oxidative lesion 8-oxo-7,8-dihydro-2′-deoxyguanine (8-oxoG) regulates telomere elongation by telomerase. When present in the deoxynucleoside triphosphate pool as 8-oxodGTP, telomerase utilization of the oxidized nucleotide during telomere extension is mutagenic and terminates further elongation. Depletion of the enzyme that removes oxidized dNTPs, MTH1, increases telomere dysfunction and cell death in telomerase positive cancer cells harboring shortened telomeres. In contrast, a pre-existing 8-oxoG within the telomeric DNA sequence promotes telomerase activity by destabilizing G-quadruplex structure in the DNA. We show that the mechanism by which 8-oxoG arises in the telomere, either by insertion of oxidized nucleotides or by direct reaction with free radicals, dictates whether telomerase is inhibited or stimulated and thereby, mediates the biological outcome. PMID:27820808

  1. Cold-stress-induced modulation of antioxidant defence: role of stressed conditions in tissue injury followed by protein oxidation and lipid peroxidation

    NASA Astrophysics Data System (ADS)

    Şahin, E.; Gümüşlü, S.

    The aim of this study was to determine the effects of cold stress on antioxidant enzyme activities and examine protein oxidation and lipid peroxidation in various tissues (brain, liver, kidney, heart and stomach). Twenty male Wistar rats (3 months old) weighing 220 +/- 20 g were used. The rats were randomly divided into two groups of ten: the control group and the cold stress group. Cold stress was applied to the animals by maintaining them in a cold room (5 °C) for 15 min/day for 15 days. Blood samples were taken for measuring plasma corticosterone levels. Tissues were obtained from each rat for measuring the antioxidant enzyme activities, protein oxidation and lipid peroxidation. Corticosterone levels were increased in the cold stress group. Copper, zinc superoxide dismutase activities were increased in the brains, livers and kidneys, whereas they decreased in the hearts and stomachs of rats in the cold stress group. Catalase activities were increased in the brains, livers, kidneys and hearts, whereas they decreased in the stomachs of rats in the cold stress group. Selenium-dependent glutathione peroxidase activities were increased in the brain, liver, heart and stomach. Reduced glutathione levels were decreased, while levels of protein carbonyl, conjugated diene and thiobarbituric-acid-reactive substances were increased in all tissues of the cold stress group. These results lead us to conclude that cold stress can disrupt the balance in an oxidant/antioxidant system and cause oxidative damage to several tissues by altering the enzymatic and non-enzymatic antioxidant status, protein oxidation and lipid peroxidation.

  2. Redox regulation of Rac1 by thiol oxidation

    PubMed Central

    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.

    2016-01-01

    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 (Cys18) 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 Cys18 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 Rac1C18D. We also evaluated Rac1C18S as a redox-insensitive variant and found that it retains structural and biochemical properties similar to those of Rac1WT but is resistant to thiol oxidation. In addition, Rac1C18D, but not Rac1C18S, shows greatly enhanced nucleotide exchange, similar to that observed for Rac1 oxidation by glutathione. We employed Rac1C18D in cell-based studies to assess whether this fast-cycling variant, which mimics Rac1 oxidation by glutathione, affects Rac1 activity and function. Expression of Rac1C18D in Swiss 3T3 cells showed greatly enhanced GTP-bound Rac1 relative to Rac1WT and the redox-insensitive Rac1C18S variant. Moreover, expression of Rac1C18D in HEK-293T cells greatly promoted lamellipodia formation. Our results suggest that Rac1 oxidation at Cys18 is a novel posttranslational modification that

  3. Inhibition of in vivo leishmanicidal mechanisms by tempol: nitric oxide down-regulation and oxidant scavenging.

    PubMed

    Linares, Edlaine; Giorgio, Selma; Augusto, Ohara

    2008-04-15

    Tempol (4-hydroxy-2,2,6,6-tetramethyl-1-piperidinyloxy) has long been known to protect experimental animals from the injury associated with oxidative and inflammatory conditions. In the latter case, a parallel decrease in tissue protein nitration levels has been observed. Protein nitration represents a shift in nitric oxide actions from physiological to pathophysiological and potentially damaging pathways involving its derived oxidants such as nitrogen dioxide and peroxynitrite. In infectious diseases, protein tyrosine nitration of tissues and cells has been taken as evidence for the involvement of nitric oxide-derived oxidants in microbicidal mechanisms. To examine whether tempol inhibits the microbicidal action of macrophages, we investigated its effects on Leishmania amazonensis infection in vitro (RAW 264.7 murine macrophages) and in vivo (C57Bl/6 mice). Tempol was administered in the drinking water at 2 mM throughout the experiments and shown to reach infected footpads as the nitroxide plus the hydroxylamine derivative by EPR analysis. At the time of maximum infection (6 weeks), tempol increased footpad lesion size (120%) and parasite burden (150%). In lesion extracts, tempol decreased overall nitric oxide products and expression of inducible nitric oxide synthase to about 80% of the levels in control animals. Nitric oxide-derived products produced by radical mechanisms, such as 3-nitrotyrosine and nitrosothiol, decreased to about 40% of the levels in control mice. The results indicate that tempol worsened L. amazonensis infection by a dual mechanism involving down-regulation of iNOS expression and scavenging of nitric oxide-derived oxidants. Thus, the development of therapeutic strategies based on nitroxides should take into account the potential risk of altering host resistance to parasite infection.

  4. 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.

  5. Mitochondrial nitric oxide synthase regulates mitochondrial matrix pH.

    PubMed

    Ghafourifar, P; Richter, C

    1999-01-01

    Nitric oxide (nitrogen monoxide, NO) exerts a wide profile of its biological activities via regulation of respiration and respiration-dependent functions. The presence of nitric oxide synthase (NOS) in mitochondria (mtNOS) was recently reported by us (Ghafourifar and Richter, FEBS Lett. 418, 291-296, 1997) and others (Giulivi et al., J. Biol. Chem. 273, 11038-11043, 1998). Here we report that NO, provided by an NO donor as well as by mtNOS stimulation, regulates mitochondrial matrix pH, transmembrane potential and Ca2+ buffering capacity. Exogenously-added NO causes a dose-dependent matrix acidification. Also mtNOS stimulation, induced by loading mitochondria with Ca2+, causes mitochondrial matrix acidification and a drop in mitochondrial transmembrane potential. Inhibition of mtNOS's basal activity causes mitochondrial matrix alkalinization and provides a resistance to the sudden drop of mitochondrial transmembrane potential induced by mitochondrial Ca2+ uptake. We conclude that mtNOS plays a critical role in regulating mitochondrial delta(pH).

  6. Pathological neoangiogenesis depends on oxidative stress regulation by ATM.

    PubMed

    Okuno, Yuji; Nakamura-Ishizu, Ayako; Otsu, Kinya; Suda, Toshio; Kubota, Yoshiaki

    2012-08-01

    The ataxia telangiectasia mutated (ATM) kinase, a master regulator of the DNA damage response (DDR), acts as a barrier to cellular senescence and tumorigenesis. Aside from DDR signaling, ATM also functions in oxidative defense. Here we show that Atm in mice is activated specifically in immature vessels in response to the accumulation of reactive oxygen species (ROS). Global or endothelial-specific Atm deficiency in mice blocked pathological neoangiogenesis in the retina. This block resulted from increased amounts of ROS and excessive activation of the mitogen activated kinase p38α rather than from defects in the canonical DDR pathway. Atm deficiency also lowered tumor angiogenesis and enhanced the antiangiogenic action of vascular endothelial growth factor (Vegf) blockade. These data suggest that pathological neoangiogenesis requires ATM-mediated oxidative defense and that agents that promote excessive ROS generation may have beneficial effects in the treatment of neovascular disease.

  7. Exogenous N-acyl-homoserine lactones enhance the expression of flagella of Pseudomonas syringae and activate defence responses in plants.

    PubMed

    Cheng, Feifei; Ma, Anzhou; Zhuang, Guoqiang; Fray, Rupert G

    2016-10-18

    In order to cope with pathogens, plants have evolved sophisticated mechanisms to sense pathogenic attacks and to induce defence responses. The N-acyl-homoserine lactone (AHL)-mediated quorum sensing in bacteria regulates diverse physiological processes, including those involved in pathogenicity. In this work, we study the interactions between AHL-producing transgenic tobacco plants and Pseudomonas syringae pv. tabaci 11528 (P. syringae 11528). Both a reduced incidence of disease and decrease in the growth of P. syringae 11528 were observed in AHL-producing plants compared with wild-type plants. The present data indicate that plant-produced AHLs enhance disease resistance against this pathogen. Subsequent RNA-sequencing analysis showed that the exogenous addition of AHLs up-regulated the expression of P. syringae 11528 genes for flagella production. Expression levels of plant defence genes in AHL-producing and wild-type plants were determined by quantitative real-time polymerase chain reaction. These data showed that plant-produced AHLs activated a wide spectrum of defence responses in plants following inoculation, including the oxidative burst, hypersensitive response, cell wall strengthening, and the production of certain metabolites. These results demonstrate that exogenous AHLs alter the gene expression patterns of pathogens, and plant-produced AHLs either directly or indirectly enhance plant local immunity during the early stage of plant infection.

  8. Salmonella Rapidly Regulates Membrane Permeability To Survive Oxidative Stress.

    PubMed

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

    2016-08-09

    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. Pathogenic bacteria have evolved ways to circumvent inflammatory immune responses. A decrease in bacterial outer membrane permeability during infection helps protect bacteria from toxic molecules produced by the host immune system and allows for effective colonization of the host. In this report, we reveal molecular mechanisms that rapidly alter outer membrane pores and their permeability in response to hydrogen peroxide and oxidative stress. These mechanisms are the first examples of pores that are rapidly opened or closed in response to reactive oxygen species. Moreover, one of these mechanisms can be targeted to artificially increase membrane permeability and thereby increase bacterial killing by the antibiotic cefotaxime during in vitro experiments and in a mouse model of infection. We envision that a better understanding of the regulation of membrane

  9. Moving nitrogen to the centre of plant defence against pathogens.

    PubMed

    Mur, Luis A J; Simpson, Catherine; Kumari, Aprajita; Gupta, Alok Kumar; Gupta, Kapuganti Jagadis

    2017-03-01

    Plants require nitrogen (N) for growth, development and defence against abiotic and biotic stresses. The extensive use of artificial N fertilizers has played an important role in the Green Revolution. N assimilation can involve a reductase series ( NO3- → NO2- → NH4+ ) followed by transamination to form amino acids. Given its widespread use, the agricultural impact of N nutrition on disease development has been extensively examined. When a pathogen first comes into contact with a host, it is usually nutrient starved such that rapid assimilation of host nutrients is essential for successful pathogenesis. Equally, the host may reallocate its nutrients to defence responses or away from the site of attempted infection. Exogenous application of N fertilizer can, therefore, shift the balance in favour of the host or pathogen. In line with this, increasing N has been reported either to increase or to decrease plant resistance to pathogens, which reflects differences in the infection strategies of discrete pathogens. Beyond considering only N content, the use of NO3- or NH4+ fertilizers affects the outcome of plant-pathogen interactions. NO3- feeding augments hypersensitive response- (HR) mediated resistance, while ammonium nutrition can compromise defence. Metabolically, NO3- enhances production of polyamines such as spermine and spermidine, which are established defence signals, with NH4+ nutrition leading to increased γ-aminobutyric acid (GABA) levels which may be a nutrient source for the pathogen. Within the defensive N economy, the roles of nitric oxide must also be considered. This is mostly generated from NO2- by nitrate reductase and is elicited by both pathogen-associated microbial patterns and gene-for-gene-mediated defences. Nitric oxide (NO) production and associated defences are therefore NO3- dependent and are compromised by NH4+ . This review demonstrates how N content and form plays an essential role in defensive primary and secondary metabolism and

  10. 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

  11. The effects of two common edible herbs, Ipomoea aquatica and Enhydra fluctuans, on cadmium-induced pathophysiology: a focus on oxidative defence and anti-apoptotic mechanism.

    PubMed

    Dua, Tarun K; Dewanjee, Saikat; Khanra, Ritu; Bhattacharya, Niloy; Bhaskar, Bhuvan; Zia-Ul-Haq, Muhammad; De Feo, Vincenzo

    2015-07-28

    Ipomoea aquatica (Convolvulaceae) and Enhydra fluctuans (Asteraceae), two aquatic vegetables, are traditionally used against heavy metal toxicity in traditional medicines in India. The present study aimed to explore the protective role of edible (aqueous) extracts of I. aquatica (AEIA) and E. fluctuans (AEEF) against Cd-intoxication. The extracts were chemically standardized by spectroscopic and HPLC analysis. The cytoprotective roles of AEIA and AEEF were measured on mouse hepatocytes. The effect on redox status were measured after incubating the hepatocytes with CdCl2 (30 μM) along with AEIA or AEEF (400 μg/ml). The effects on the expressions of apoptotic signal proteins were estimated. The protective roles of AEIA or AEEF were measured by in vivo assay in mice. Haematological, serum biochemical, tissue redox status, Cd bioaccumulation and histological parameters were evaluated to estimate the protective role of AEIA or AEEF (100 mg/kg) against CdCl2 (4 mg/kg) intoxication. Phytochemical analysis revealed presence of substantial quantities of phenolics, flavonoids, saponins, carbohydrates and ascorbic acid in AEIA or AEEF. CdCl2 treated murine hepatocytes showed a gradual reduction of cell viability in a concentration dependent manner with an IC50 of ~30 μM. CdCl2 treated hepatocytes exhibited significantly enhanced levels (p < 0.01) of ROS production, lipid peroxidation, protein carbonylation and NADPH oxidase with concomitant depletion (p < 0.01) of antioxidant enzymes and GSH. However, AEIA or AEEF treatment along with CdCl2 significantly restored the aforementioned parameters in murine hepatocytes near to normalcy. Besides, AEIA or AEEF significantly counteracted (p < 0.05-0.01) with ROS mediated alteration of transcription levels of signal proteins viz. Bcl-2, BAD, Cyt-C, Caspases, Fas and Bid. In in vivo bioassay, CdCl2 treatment caused significantly high Cd bioaccumulation and oxidative stress in the liver, kidney, heart, brain and testes in mice. In

  12. 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

  13. 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

  14. 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.

  15. 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…

  16. An IFIH1 gene polymorphism associated with risk for autoimmunity regulates canonical antiviral defence pathways in Coxsackievirus infected human pancreatic islets

    PubMed Central

    Domsgen, Erna; Lind, Katharina; Kong, Lingjia; Hühn, Michael H.; Rasool, Omid; van Kuppeveld, Frank; Korsgren, Olle; Lahesmaa, Riitta; Flodström-Tullberg, Malin

    2016-01-01

    The IFIH1 gene encodes the pattern recognition receptor MDA5. A common polymorphism in IFIH1 (rs1990760, A946T) confers increased risk for autoimmune disease, including type 1-diabetes (T1D). Coxsackievirus infections are linked to T1D and cause beta-cell damage in vitro. Here we demonstrate that the rs1990760 polymorphism regulates the interferon (IFN) signature expressed by human pancreatic islets following Coxsackievirus infection. A strong IFN signature was associated with high expression of IFNλ1 and IFNλ2, linking rs1990760 to the expression of type III IFNs. In the high-responding genotype, IRF-1 expression correlated with that of type III IFN, suggesting a positive-feedback on type III IFN transcription. In summary, our study uncovers an influence of rs1990760 on the canonical effector function of MDA5 in response to an acute infection of primary human parenchymal cells with a clinically relevant virus linked to human T1D. It also highlights a previously unrecognized connection between the rs1990760 polymorphism and the expression level of type III IFNs. PMID:28000722

  17. Arsenite oxidation regulator AioR regulates bacterial chemotaxis towards arsenite in Agrobacterium tumefaciens GW4

    PubMed Central

    Shi, Kaixiang; Fan, Xia; Qiao, Zixu; Han, Yushan; McDermott, Timothy R.; Wang, Qian; Wang, Gejiao

    2017-01-01

    Some arsenite [As(III)]-oxidizing bacteria exhibit positive chemotaxis towards As(III), however, the related As(III) chemoreceptor and regulatory mechanism remain unknown. The As(III)-oxidizing bacterium Agrobacterium tumefaciens GW4 displays positive chemotaxis towards 0.5–2 mM As(III). Genomic analyses revealed a putative chemoreceptor-encoding gene, mcp, located in the arsenic gene island and having a predicted promoter binding site for the As(III) oxidation regulator AioR. Expression of mcp and other chemotaxis related genes (cheA, cheY2 and fliG) was inducible by As(III), but not in the aioR mutant. Using capillary assays and intrinsic tryptophan fluorescence spectra analysis, Mcp was confirmed to be responsible for chemotaxis towards As(III) and to bind As(III) (but not As(V) nor phosphate) as part of the sensing mechanism. A bacterial one-hybrid system technique and electrophoretic mobility shift assays showed that AioR interacts with the mcp regulatory region in vivo and in vitro, and the precise AioR binding site was confirmed using DNase I foot-printing. Taken together, these results indicate that this Mcp is responsible for the chemotactic response towards As(III) and is regulated by AioR. Additionally, disrupting the mcp gene affected bacterial As(III) oxidation and growth, inferring that Mcp may exert some sort of functional connection between As(III) oxidation and As(III) chemotaxis. PMID:28256605

  18. Dopamine in the ink defence system of Sepia officinalis: biosynthesis, vesicular compartmentation in mature ink gland cells, nitric oxide (NO)/cGMP-induced depletion and fate in secreted ink.

    PubMed Central

    Fiore, Gabriella; Poli, Annarita; Di Cosmo, Anna; d'Ischia, Marco; Palumbo, Anna

    2004-01-01

    The biosynthesis, localization and fate of catecholamines in the ink gland of the cuttlefish Sepia officinalis were investigated by combined biochemical and immunohistocytochemical methodologies. HPLC analysis of crude ink gland extracts indicated the presence of dopa (2.18+/-0.82 nmol/mg of protein) and DA (dopamine, 0.06+/-0.02 nmol/mg of protein), but no detectable noradrenaline or adrenaline. DA was shown to derive from L-tyrosine, according to experiments performed by incubating intact ink glands with [L-14C]tyrosine. The biosynthetic process involves a tyrosine hydroxylase and a dopa decarboxylase pathway and is independent of tyrosinase. The tyrosine hydroxylase activity was detected under conditions of tyrosinase suppression in the cytosolic fraction, but not in the melanosomal fraction, of ink gland extracts, and the presence of the enzyme was confirmed by Western-blot analysis. Dopa and DA were found to be released from the ink glands by processes controlled through the NMDA-nitric oxide-cGMP (where NMDA stands for N -methyl-D-aspartate) signalling pathway, as apparent from incubation experiments performed with [L-14C]tyrosine in the presence of NMDA, diethylamine NONOate (diethylamine diazeniumdiolate), a nitric oxide donor, 8-bromo-cGMP or a guanylyl cyclase inhibitor. Immunohistochemical results coupled with electron microscopy indicated that DA was concentrated in vesicles specifically localized in the mature melanin-producing cells of the ink gland proximal to the lumen and separated from the melanin-containing melanosomes. NMDA receptor stimulation or exposure to an NO donor caused a marked loss of DA immunoreactivity in mature cells, consistent with a release process. In the lumen of the ink gland, where mature exhausted cells pour their contents, DA immunoreactivity was found to be associated with the melanin granules, due apparently to physical adsorption. Overall, these results point to DA as a marker of cell maturation in Sepia ink gland

  19. 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

  20. 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

  1. Limiting immunopathology: Interaction between carotenoids and enzymatic antioxidant defences.

    PubMed

    Babin, A; Saciat, C; Teixeira, M; Troussard, J-P; Motreuil, S; Moreau, J; Moret, Y

    2015-04-01

    The release of reactive oxygen and nitrogen species (ROS and RNS) during the inflammatory response generates damages to host tissues, referred to as immunopathology, and is an important factor in ecological immunology. The integrated antioxidant system, comprising endogenous antioxidant enzymes (e.g. superoxide dismutase SOD, and catalase CAT) and dietary antioxidants (e.g. carotenoids), helps to cope with immune-mediated oxidative stress. Crustaceans store large amounts of dietary carotenoids for yet unclear reasons. While being immunostimulants and antioxidants, the interaction of these pigments with antioxidant enzymes remains unclear. Here, we tested the interaction between dietary supplementation with carotenoids and immune challenge on immune defences and the activity of the antioxidant enzymes SOD and CAT, in the amphipod crustacean Gammarus pulex. Dietary supplementation increased the concentrations of circulating carotenoids and haemocytes in the haemolymph, while the immune response induced the consumption of circulating carotenoids and a drop of haemocyte density. Interestingly, supplemented gammarids exhibited down-regulated SOD activity but high CAT activity compared to control ones. Our study reveals specific interactions of dietary carotenoids with endogenous antioxidant enzymes, and further underlines the potential importance of carotenoids in the evolution of immunity and/or of antioxidant mechanisms in crustaceans. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Microglial self-defence mediated through GLT-1 and glutathione.

    PubMed

    Persson, Mikael; Rönnbäck, Lars

    2012-01-01

    Glutamate is stored in synaptic vesicles in presynaptic neurons. It is released into the synaptic cleft to provide signalling to postsynaptic neurons. Normally, the astroglial glutamate transporters GLT-1 and GLAST take up glutamate to mediate a high signal-to-noise ratio in the synaptic signalling, and also to prevent excitotoxic effects by glutamate. In astrocytes, glutamate is transformed into glutamine, which is safely transported back to neurons. However, in pathological conditions, such as an ischemia or virus infection, astroglial transporters are down-regulated which could lead to excitotoxicity. Lately, it was shown that even microglia can express glutamate transporters during pathological events. Microglia have two systems for glutamate transport: GLT-1 for transport into the cells and the x (c) (-) system for transport out of the cells. We here review results from our work and others, which demonstrate that microglia in culture express GLT-1, but not GLAST, and transport glutamate from the extracellular space. We also show that TNF-α can induce increased microglial GLT-1 expression, possibly associating the expression with inflammatory systems. Furthermore, glutamate taken up through GLT-1 may be used for direct incorporation into glutathione and to fuel the intracellular glutamate pool to allow cystine uptake through the x (c) (-) system. This can lead to a defence against oxidative stress and have an antiviral function.

  3. Defence Capability Plan 2009 (Australian Department of Defence). Public Version

    DTIC Science & Technology

    2009-01-24

    2017 to 2019 Points of Contact Phase: Capability Staff: Defence Materiel Organisation: Phase 2A/2B Program Manager New Air Combat Capability (02...radio backbone for the Battlefield Command Support System already in service and Battlefield Management Systems intended to be procured under LAND 75...the acquisition contract proposed for the common service, and are to be managed regionally. Through-life Support A PSI is to be engaged under the

  4. Pregnane X receptor regulates drug metabolism and transport in the vasculature and protects from oxidative stress

    PubMed Central

    Swales, Karen E.; Moore, Rick; Truss, Nicola J.; Tucker, Arthur; Warner, Timothy D.; Negishi, Masahiko; Bishop-Bailey, David

    2012-01-01

    Aims Circulating endogenous, dietary, and foreign chemicals can contribute to vascular dysfunction. The mechanism by which the vasculature protects itself from these chemicals is unknown. This study investigates whether the pregnane X receptor (PXR), the major transcriptional regulator of hepatic drug metabolism and transport that responds to such xenobiotics, mediates vascular protection by co-ordinating a defence gene programme in the vasculature. Methods and results PXR was detected in primary human and rat aortic endothelial and smooth muscle cells (SMC) and blood vessels including the human and rat aorta. Metabolic PXR target genes cytochrome P450 3A, 2B, 2C, and glutathione S-transferase mRNA and activity were induced by PXR ligands in rodent and human vascular cells and absent in the aortas from PXR-null mice stimulated in vivo or in rat aortic SMC expressing dominant-negative PXR. Activation of aortic PXR by classical agonists had several protective effects: increased xenobiotic metabolism demonstrated by bioactivation of the pro-drug clopidogrel, which reduced adenosine diphosphate-induced platelet aggregation; increased expression of multidrug resistance protein 1, mediating chemical efflux from the vasculature; and protection from reactive oxygen species-mediated cell death. Conclusion PXR co-ordinately up-regulates drug metabolism, transport, and antioxidant genes to protect the vasculature from endogenous and exogenous insults, thus representing a novel gatekeeper for vascular defence. PMID:22166712

  5. Metabolic regulation of aldose reductase activity by nitric oxide donors.

    PubMed

    Dixit, B L; Ramana, K V; Chandra, D; Jackson, E B; Srivastava, S; Bhatnagar, A; Srivastava, S K

    2001-01-30

    Regulation of aldose reductase (AR), a member of the aldo-keto reductase superfamily, by nitric oxide (NO) donors was examined. Incubation of human recombinant AR with S-nitrosoglutathione (GSNO) led to inactivation of the enzyme and the formation of an AR-glutathione adduct. In contrast, incubation with S-nitroso-N-acetyl penicillamine (SNAP) or N-(beta-D-glucopyranosyl)-SNAP (GlycoSNAP) led to an increase in enzyme activity which was accompanied by the direct nitrosation of the enzyme and the formation of a mixed disulfide with the NO-donor. To examine in vivo modification, red blood cells (RBC) and rat aortic vascular smooth muscle cells (VSMC) were incubated with 1 mM GSNO or SNAP. Exposure of VSMC to SNAP and GSNO for 2 h at 37 degrees C led to approximately 71% decrease in the enzyme activity with DL-glyceraldehyde as the substrate. Similarly, exposure of RBC in 5 mM glucose to NO-donors for 30 min at room temperature, followed by increasing the glucose concentration to 40 mM, resulted in >75% decrease in the formation of sorbitol. These investigations indicate that NO and/or its bioactive metabolites can regulate cellular AR, leading to either activation (by nitrosation) or inactivation (by S-thiolation).

  6. 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.

  7. Molecular regulation of tumour angiogenesis by nitric oxide.

    PubMed

    Ziche, Marina; Morbidelli, Lucia

    2009-12-01

    As tumors grow, their original vasculature can be insufficient to supply the growing tissue mass, and consequently local hypoxia develops. Thus neovascularisation is a key feature determining growth and metastasis of malignant tumors. This is, at least in part, mediated by humoral factors known to stimulate angiogenesis, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2). Among the multiple angiogenic modulators released by tumor and stromal cells, a key role is played by nitric oxide (NO). Beside its capacity to regulate permeability and blood flow, NO has been reported to exert angiogenic properties in various tumor models. The focus of this review will be the proangiogenic role of NO in the tumor microenvironment and its multiple mechanism of action on vascular endothelium. Particular attention will be devoted to the role of NO in regulating metalloproteinase activity on cultured microvascular endothelium and in the in vivo rabbit cornea assay. Finally, the potential clinical outcomes and expectations related to this topic will be discussed.

  8. Defence Science and Technology Organisation.

    DTIC Science & Technology

    1983-01-01

    develops new food forms with defence significance and monitors commercial innovations. It operates many types of food dehydration equipment and has developed...umergenc.i water packs that are resealable and con iithstand pilot ejection forces as Lcell as lou" pressures of unpr’ ssunsed aircraft. These pictures show...Dr G. Driver conducts food acceptability studies for servicemen in various situations, develops special ration packs for combat and surival situations

  9. Nrf2 and regulation of the antioxidant system in the Antarctic silverfish, Pleuragramma antarctica: Adaptation to environmental changes of pro-oxidant pressure.

    PubMed

    Giuliani, Maria Elisa; Benedetti, Maura; Nigro, Marco; Regoli, Francesco

    2017-08-01

    Despite the key importance of Nrf2-Keap1 in regulating antioxidant system in vertebrates, this system is still poorly investigated in marine species. The present study focused on the Antarctic silverfish Pleuragramma antarctica which, during the final phases of embryo development in platelet ice, is challenged by a sudden enhancement of environmental oxidative conditions associated to ice melting. Partial coding sequences were identified for Nrf2, its repressor Keap1 and for typical Nrf2-target antioxidant genes, like catalase, glutathione peroxidase isoform 1 and Cu/Zn-dependent superoxide dismutase. Compared to temperate homologues, the protein sequences showed an elevated conservation of amino acids essential for catalytic functions, while a few specific substitutions in non-essential regions may represent a molecular adaptation to improve flexibility and accessibility to active site at cold temperatures. The role of the Nrf2-Keap1 pathway in modulating the activation of antioxidant defences was demonstrated at both transcriptional and functional levels with a clear temporal increase of antioxidant protection in embryos before the hatching. Such findings confirm the importance of Nrf2 and highlight regulation of antioxidants as an adaptive strategy in P. antarctica to protect the early life stages toward the environmental changes of pro-oxidant pressure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Genetic dissection of basal defence responsiveness in accessions of Arabidopsis thaliana.

    PubMed

    Ahmad, Shakoor; Van Hulten, Marieke; Martin, Janet; Pieterse, Corné M J; Van Wees, Saskia C M; Ton, Jurriaan

    2011-07-01

    Basal resistance involves a multitude of pathogen- and herbivore-inducible defence mechanisms, ranging from localized callose deposition to systemic defence gene induction by salicylic acid (SA) and jasmonic acid (JA). In this study, we have explored and dissected genetic variation in the responsiveness of basal defence mechanisms within a selection of Arabidopsis accessions. Responsiveness of JA-induced PDF1.2 gene expression was associated with enhanced basal resistance against the necrotrophic fungus Plectosphaerella cucumerina and the herbivore Spodoptera littoralis. Conversely, accessions showing augmented PR-1 induction upon SA treatment were more resistant to the hemi-biotrophic pathogen Pseudomonas syringae, and constitutively expressed defence-related transcription factor (TF) genes. Unexpectedly, accessions with primed responsiveness to SA deposited comparatively little callose after treatment with microbe-associated molecular patterns. A quantitative trait locus (QTL) analysis identified two loci regulating flagellin-induced callose and one locus regulating SA-induced PR-1 expression. The latter QTL was found to contribute to basal resistance against P. syringae. None of the defence regulatory QTLs influenced plant growth, suggesting that the constitutive defence priming conferred by these loci is not associated with major costs on plant growth. Our study demonstrates that natural variation in basal resistance can be exploited to identify genetic loci that prime the plant's basal defence arsenal.

  11. α-Tocopherol prevents lymphoma by improving antioxidant defence system of mice.

    PubMed

    Sharma, Renu; Vinayak, Manjula

    2013-02-01

    Increased level of ROS causes oxidative stress and leads to various pathological conditions including cancer. Therefore antioxidants should contribute to cancer prevention by improving antioxidant defense system and thereby protecting the cell from oxidative damage. In the present study we have validated the hypothesis by evaluating the antioxidant action of α-tocopherol. The effect of α-tocopherol is analyzed on oxidative stress as well as its regulation on antioxidant defense system. Oxidative stress is measured in terms of reduced glutathione and protein carbonylation. To evaluate the role of α-tocopherol on antioxidant defense system, the activities and expressions of antioxidant enzymes like glutathione peroxidase, catalase and superoxide dismutase are analyzed by activity gel assay and by RT-PCR respectively. These enzyme activities and/or expressions are found to be improved by α-tocopherol in lymphoma bearing mice which brings down the oxidative stress as reflected by increased level of reduced glutathione as well as decreased protein carbonylation. The effect of α-tocopherol is further analyzed on general characteristics of lymphoma growth like body weight, longevity, accumulation of ascites fluid, angiogenesis in peritoneum, morphology of liver and abundance of lymphocytes. The antioxidant α-tocopherol is found to check lymphoma growth. The results suggest that α-tocopherol contributes to lymphoma prevention by improving antioxidant defence system of mice.

  12. 40 CFR 52.269 - Control strategy and regulations: Photochemical oxidants (hydrocarbons) and carbon monoxide.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...: Photochemical oxidants (hydrocarbons) and carbon monoxide. 52.269 Section 52.269 Protection of Environment... PLANS California § 52.269 Control strategy and regulations: Photochemical oxidants (hydrocarbons) and... provide for attainment and maintenance of the national standards for photochemical oxidants (hydrocarbons...

  13. 40 CFR 52.269 - Control strategy and regulations: Photochemical oxidants (hydrocarbons) and carbon monoxide.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...: Photochemical oxidants (hydrocarbons) and carbon monoxide. 52.269 Section 52.269 Protection of Environment... PLANS California § 52.269 Control strategy and regulations: Photochemical oxidants (hydrocarbons) and... provide for attainment and maintenance of the national standards for photochemical oxidants (hydrocarbons...

  14. 40 CFR 52.269 - Control strategy and regulations: Photochemical oxidants (hydrocarbons) and carbon monoxide.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...: Photochemical oxidants (hydrocarbons) and carbon monoxide. 52.269 Section 52.269 Protection of Environment... PLANS California § 52.269 Control strategy and regulations: Photochemical oxidants (hydrocarbons) and... provide for attainment and maintenance of the national standards for photochemical oxidants (hydrocarbons...

  15. 40 CFR 52.269 - Control strategy and regulations: Photochemical oxidants (hydrocarbons) and carbon monoxide.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...: Photochemical oxidants (hydrocarbons) and carbon monoxide. 52.269 Section 52.269 Protection of Environment... PLANS California § 52.269 Control strategy and regulations: Photochemical oxidants (hydrocarbons) and... provide for attainment and maintenance of the national standards for photochemical oxidants (hydrocarbons...

  16. 40 CFR 52.269 - Control strategy and regulations: Photochemical oxidants (hydrocarbons) and carbon monoxide.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...: Photochemical oxidants (hydrocarbons) and carbon monoxide. 52.269 Section 52.269 Protection of Environment... PLANS California § 52.269 Control strategy and regulations: Photochemical oxidants (hydrocarbons) and... provide for attainment and maintenance of the national standards for photochemical oxidants (hydrocarbons...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. The psychiatric defence and international criminal law.

    PubMed

    Tobin, John

    2007-01-01

    Following the development of the International Criminal Court (ICC) the mental state of the perpetrators of genocide, crimes against humanity and war crimes will become a more important issue in regard to defence and mitigating factors. This article examines how the International Criminal Tribunal for the Former Yugoslavia (ICTY) in particular has dealt with the mental illness defence to date, and how its judgements can serve as guidance for the ICC as it becomes the major international court of the future. The absence of a mental health defence in the Statutes of the ICTY and the International Criminal Tribunal for Rwanda has led to a reliance on the Rules of Procedure and Evidence of the two tribunals. There are major difficulties in using the mental health defence as it is defined in the Statutes of the ICC because of a requirement for the destruction of mental capacity as a valid defence. Fitness to plead and the defence of intoxication are also examined.

  8. Superparamagnetic iron oxide nanoparticles regulate smooth muscle cell phenotype

    PubMed Central

    Angelopoulos, Ioannis; Southern, Paul; Pankhurst, Quentin A.

    2016-01-01

    Abstract Superparamagnetic iron oxide nanoparticles (SPION) are used for an increasing range of biomedical applications, from imaging to mechanical actuation of cells and tissue. The aim of this study was to investigate the loading of smooth muscle cells (SMC) with SPION and to explore what effect this has on the phenotype of the cells. Adherent human SMC were loaded with ∼17 pg of unconjugated, negatively charged, 50 nm SPION. Clusters of the internalized SPION particles were held in discrete cytoplasmic vesicles. Internalized SPION did not cause any change in cell morphology, proliferation, metabolic activity, or staining pattern of actin and calponin, two of the muscle contractile proteins involved in force generation. However, internalized SPION inhibited the increased gene expression of actin and calponin normally observed when cells are incubated under differentiation conditions. The observed change in the control of gene expression of muscle contractile apparatus by SPION has not previously been described. This finding could offer novel approaches for regulating the phenotype of SMC and warrants further investigation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2412–2419, 2016. PMID:27176658

  9. Defence Reporter. Summer/Autumn 2011

    DTIC Science & Technology

    2011-01-01

    defence science and technology literature. Defence Reporter is one part of a series of services and products produced by ATHENA to keep readers up ...To sign up for this free service, please send an e-mail with your full name and address details to: DefenceReporter@dstl.gov.uk. © Crown Copyright...methodological limitations. An alternative approach based on ‘bottom up ’ comparisons with existing platforms of similar capabilities is also described. In

  10. Australian Defence Force Demographic Data and Challenges

    DTIC Science & Technology

    2001-10-01

    AUSTRALIAN DEFENCE FORCE DEMOGRAPHIC DATA AND CHALLENGES Directorate of Strategic Personnel Planning and Research DSPPR Technical Note 10/2001...DATE 00 OCT 2001 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Australian Defence Force Demographic Data and Challenges 5a...Prescribed by ANSI Std Z39-18 AUSTRALIAN DEFENCE FORCE DEMOGRAPHIC DATA AND CHALLENGES The findings and views expressed in this report are the results

  11. Defence Capability Plan 2006-2016

    DTIC Science & Technology

    2006-06-14

    Version Points of Contact Phase 8B Capability Staff: Defence Materiel Organisation: Squadron Leader Greg Trott Ms Katrina Burzynski (02) 6265...Capability Plan 2006 – 2016 Public Version 0 Points of Contact Phase 7 Capability Staff: Defence Materiel Organisation: Major Paul Randall Mr Ross...Staff: Defence Materiel Organisation: Major Paul Randall Lieutenant Colonel Duncan Roach (02) 6265 4441 (03) 9282 5380 LAND 58 Phase 3 Weapon

  12. Aspects of the regulation of long-chain fatty acid oxidation in bovine liver

    SciTech Connect

    Jesse, B.W.; Emery, R.S.; Thomas, J.W.

    1986-09-01

    Factors involved in regulation of bovine hepatic fatty acid oxidation were examined using liver slices. Fatty acid oxidation was measured as the conversion of l-(/sup 14/C) palmitate to /sup 14/CO/sub 2/ and total (/sup 14/C) acid-soluble metabolites. Extended (5 to 7 d) fasting of Holstein cows had relatively little effect on palmitate oxidation to acid-soluble metabolites by liver slices, although oxidation to CO/sup 2/ was decreased. Feeding a restricted roughage, high concentrate ration to lactating cows resulted in inhibition of palmitate oxidation. Insulin, glucose, and acetate inhibited palmitate oxidation by bovine liver slices. The authors suggest the regulation of bovine hepatic fatty acid oxidation may be less dependent on hormonally induced alterations in enzyme activity as observed in rat liver and more dependent upon action of rumen fermentation products or their metabolites on enzyme systems involved in fatty acid oxidation.

  13. Metabolomic assessment of induced and activated chemical defence in the invasive red alga Gracilaria vermiculophylla.

    PubMed

    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. 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

  15. Involvement of protein kinases and calcium in the NO-signalling cascade for defence-gene induction in ozonated tobacco plants.

    PubMed

    Pasqualini, S; Reale, L; Calderini, O; Pagiotti, R; Ederli, L

    2012-07-01

    This study analyses the signalling pathways triggered by nitric oxide (NO) in response to ozone (O(3)) fumigation of tobacco plants, with particular attention to protein kinase cascades and free cytosolic Ca(2+) in defence-gene activation. NO was visualized with the NO probe DAF-FM. Using a pharmacological approach, the effects of different inhibitors on the expression profiles of NO-dependent defence genes were monitored using RT-PCR. The assay of the kinase activity of the immunoprecipitates complexes shows that O(3) stimulates a 48 kDa salicylic acid (SA)-induced protein kinase (SIPK) in an NO-dependent manner. The O(3)-induced alternative oxidase 1a (AOX1a) and phenylalanine ammonia lyase a (PALa) genes are modulated by phosphorylation by protein kinases, and SIPK might have a role in this up-regulation. By contrast, protein dephosphorylation mediates pathogenesis-related protein 1a (PR1a) expression in O(3)-treated tobacco plants. Ca(2+) is essential, but not sufficient, to promote NO accumulation in ozonated tobacco plants. Intracellular Ca(2+) transients are also essential for PALa up-regulation and cGMP-induced PR1a expression. Partial dependence on intracellular Ca(2+) suggests two different pathways of SA accumulation and PR1a induction. A model summarizing the signalling networks involving NO, SA, and the cellular messengers in this O(3)-induced defence gene activation is proposed.

  16. HIF and reactive oxygen species regulate oxidative phosphorylation in cancer.

    PubMed

    Hervouet, Eric; Cízková, Alena; Demont, Jocelyne; Vojtísková, Alena; Pecina, Petr; Franssen-van Hal, Nicole L W; Keijer, Jaap; Simonnet, Hélène; Ivánek, Robert; Kmoch, Stanislav; Godinot, Catherine; Houstek, Josef

    2008-08-01

    A decrease in oxidative phosphorylation (OXPHOS) is characteristic of many cancer types and, in particular, of clear cell renal carcinoma (CCRC) deficient in von Hippel-Lindau (vhl) gene. In the absence of functional pVHL, hypoxia-inducible factor (HIF) 1-alpha and HIF2-alpha subunits are stabilized, which induces the transcription of many genes including those involved in glycolysis and reactive oxygen species (ROS) metabolism. Transfection of these cells with vhl is known to restore HIF-alpha subunit degradation and to reduce glycolytic genes transcription. We show that such transfection with vhl of 786-0 CCRC (which are devoid of HIF1-alpha) also increased the content of respiratory chain subunits. However, the levels of most transcripts encoding OXPHOS subunits were not modified. Inhibition of HIF2-alpha synthesis by RNA interference in pVHL-deficient 786-0 CCRC also restored respiratory chain subunit content and clearly demonstrated a key role of HIF in OXPHOS regulation. In agreement with these observations, stabilization of HIF-alpha subunit by CoCl(2) decreased respiratory chain subunit levels in CCRC cells expressing pVHL. In addition, HIF stimulated ROS production and mitochondrial manganese superoxide dismutase content. OXPHOS subunit content was also decreased by added H(2)O(2.) Interestingly, desferrioxamine (DFO) that also stabilized HIF did not decrease respiratory chain subunit level. While CoCl(2) significantly stimulates ROS production, DFO is known to prevent hydroxyl radical production by inhibiting Fenton reactions. This indicates that the HIF-induced decrease in OXPHOS is at least in part mediated by hydroxyl radical production.

  17. Sex-based differential regulation of oxidative stress in the vasculature by nitric oxide

    PubMed Central

    Morales, Rommel C.; Bahnson, Edward S.M.; Havelka, George E.; Cantu-Medellin, Nadiezhda; Kelley, Eric E.; Kibbe, Melina R.

    2015-01-01

    Background Nitric oxide (•NO) is more effective at inhibiting neointimal hyperplasia following arterial injury in male versus female rodents, though the etiology is unclear. Given that superoxide (O2•−) regulates cellular proliferation, and •NO regulates superoxide dismutase-1 (SOD-1) in the vasculature, we hypothesized that •NO differentially regulates SOD-1 based on sex. Materials and methods Male and female vascular smooth muscle cells (VSMC) were harvested from the aortae of Sprague-Dawley rats. O2•− levels were quantified by electron paramagnetic resonance (EPR) and HPLC. sod-1 gene expression was assayed by qPCR. SOD-1, SOD-2, and catalase protein levels were detected by Western blot. SOD-1 activity was measured via colorimetric assay. The rat carotid artery injury model was performed on Sprague-Dawley rats ±•NO treatment and SOD-1 protein levels were examined by Western blot. Results In vitro, male VSMC have higher O2•− levels and lower SOD − 1 activity at baseline compared to female VSMC (P < 0.05). •NO decreased O2•− levels and increased SOD − 1 activity in male (P<0.05) but not female VSMC. •NO also increased sod− 1 gene expression and SOD − 1 protein levels in male (P<0.05) but not female VSMC. In vivo, SOD-1 levels were 3.7-fold higher in female versus male carotid arteries at baseline. After injury, SOD-1 levels decreased in both sexes, but •NO increased SOD-1 levels 3-fold above controls in males, but returned to baseline in females. Conclusions Our results provide evidence that regulation of the redox environment at baseline and following exposure to •NO is sex-dependent in the vasculature. These data suggest that sex-based differential redox regulation may be one mechanism by which •NO is more effective at inhibiting neointimal hyperplasia in male versus female rodents. PMID:25617803

  18. Plant defences against herbivore and insect attack

    USDA-ARS?s Scientific Manuscript database

    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...

  19. Evolutionarily stable defence and signalling of that defence.

    PubMed

    Broom, M; Speed, M P; Ruxton, G D

    2006-09-07

    We examine the evolution and maintenance of defence and conspicuousness in prey species using a game theoretic model. In contrast to previous works, predators can raise as well as lower their attack probabilities as a consequence of encountering moderately defended prey. Our model predicts four distinct possibilities for evolutionarily stable strategies (ESSs) featuring maximum crypsis. Namely that such a solution can exist with (1) zero toxicity, (2) a non-zero but non-aversive level of toxicity, (3) a high, aversive level of toxicity or (4) that no such maximally cryptic solution exists. Maximally cryptic prey may still invest in toxins, because of the increased chance of surviving an attack (should they be discovered) that comes from having toxins. The toxin load of maximally cryptic prey may be sufficiently strong that the predators will find them aversive, and seek to avoid similar looking prey in future. However, this aversiveness does not always necessarily trigger aposematic signalling, and highly toxic prey can still be maximally cryptic, because the increased initial rate of attack from becoming more conspicuous is not necessarily always compensated for by increased avoidance of aversive prey by predators. In other circumstances, the optimal toxin load may be insufficient to generate aversion but still be non-zero (because it increases survival), and in yet other circumstances, it is optimal to make no investment in toxins at all. The model also predicts ESSs where the prey are highly defended and aversive and where this defence is advertised at a cost of increased conspicuousness to predators. In many circumstances there is an infinite array of these aposematic ESSs, where the precise appearance is unimportant as long as it is highly visible and shared by all members of the population. Yet another class of solutions is possible where there is strong between-individual variation in appearance between conspicuous, poorly defended prey.

  20. Role for Mitochondrial Oxidants as Regulators of Cellular Metabolism

    PubMed Central

    Nemoto, Shino; Takeda, Kazuyo; Yu, Zu-Xi; Ferrans, Victor J.; Finkel, Toren

    2000-01-01

    Leakage of mitochondrial oxidants contributes to a variety of harmful conditions ranging from neurodegenerative diseases to cellular senescence. We describe here, however, a physiological and heretofore unrecognized role for mitochondrial oxidant release. Mitochondrial metabolism of pyruvate is demonstrated to activate the c-Jun N-terminal kinase (JNK). This metabolite-induced rise in cytosolic JNK1 activity is shown to be triggered by increased release of mitochondrial H2O2. We further demonstrate that in turn, the redox-dependent activation of JNK1 feeds back and inhibits the activity of the metabolic enzymes glycogen synthase kinase 3β and glycogen synthase. As such, these results demonstrate a novel metabolic regulatory pathway activated by mitochondrial oxidants. In addition, they suggest that although chronic oxidant production may have deleterious effects, mitochondrial oxidants can also function acutely as signaling molecules to provide communication between the mitochondria and the cytosol. PMID:10982848

  1. RNA silencing is required for Arabidopsis defence against Verticillium wilt disease.

    PubMed

    Ellendorff, Ursula; Fradin, Emilie F; de Jonge, Ronnie; Thomma, Bart P H J

    2009-01-01

    RNA silencing is a conserved mechanism in eukaryotes that plays an important role in various biological processes including regulation of gene expression. RNA silencing also plays a role in genome stability and protects plants against invading nucleic acids such as transgenes and viruses. Recently, RNA silencing has been found to play a role in defence against bacterial plant pathogens in Arabidopsis through modulating host defence responses. In this study, it is shown that gene silencing plays a role in plant defence against multicellular microbial pathogens; vascular fungi belonging to the Verticillium genus. Several components of RNA silencing pathways were tested, of which many were found to affect Verticillium defence. Remarkably, no altered defence towards other fungal pathogens that include Alternaria brassicicola, Botrytis cinerea, and Plectosphaerella cucumerina, but also the vascular pathogen Fusarium oxysporum, was recorded. Since the observed differences in Verticillium susceptibility cannot be explained by notable differences in root architecture, it is speculated that the gene silencing mechanisms affect regulation of Verticillium-specific defence responses.

  2. RNA silencing is required for Arabidopsis defence against Verticillium wilt disease

    PubMed Central

    Ellendorff, Ursula; Fradin, Emilie F.; de Jonge, Ronnie; Thomma, Bart P. H. J.

    2009-01-01

    RNA silencing is a conserved mechanism in eukaryotes that plays an important role in various biological processes including regulation of gene expression. RNA silencing also plays a role in genome stability and protects plants against invading nucleic acids such as transgenes and viruses. Recently, RNA silencing has been found to play a role in defence against bacterial plant pathogens in Arabidopsis through modulating host defence responses. In this study, it is shown that gene silencing plays a role in plant defence against multicellular microbial pathogens; vascular fungi belonging to the Verticillium genus. Several components of RNA silencing pathways were tested, of which many were found to affect Verticillium defence. Remarkably, no altered defence towards other fungal pathogens that include Alternaria brassicicola, Botrytis cinerea, and Plectosphaerella cucumerina, but also the vascular pathogen Fusarium oxysporum, was recorded. Since the observed differences in Verticillium susceptibility cannot be explained by notable differences in root architecture, it is speculated that the gene silencing mechanisms affect regulation of Verticillium-specific defence responses. PMID:19098131

  3. Products of lipid, protein and RNA oxidation as signals and regulators of gene expression in plants

    PubMed Central

    Chmielowska-Bąk, Jagna; Izbiańska, Karolina; Deckert, Joanna

    2015-01-01

    Reactive oxygen species (ROS) are engaged in several processes essential for normal cell functioning, such as differentiation, anti-microbial defense, stimulus sensing and signaling. Interestingly, recent studies imply that cellular signal transduction and gene regulation are mediated not only directly by ROS but also by the molecules derived from ROS-mediated oxidation. Lipid peroxidation leads to non-enzymatic formation of oxylipins. These molecules were shown to modulate expression of signaling associated genes including genes encoding phosphatases, kinases and transcription factors. Oxidized peptides derived from protein oxidation might be engaged in organelle-specific ROS signaling. In turn, oxidation of particular mRNAs leads to decrease in the level of encoded proteins and thus, contributes to the post-transcriptional regulation of gene expression. Present mini review summarizes latest findings concerning involvement of products of lipid, protein and RNA oxidation in signal transduction and gene regulation. PMID:26082792

  4. Coastal modelling for flood defence.

    PubMed

    Battjes, Jurjen A; Gerritsen, Herman

    2002-07-15

    This paper reviews practices and trends in hydrodynamic and statistical analyses and modelling in the Netherlands with regard to the risk of coastal flooding. We restrict ourselves to the physical phenomena of tides, storm surges and wind waves. We first give a brief outline of established policy in the Netherlands regarding accepted levels of risk of flooding, and current changes therein. This is followed by a summary of a statistical reanalysis of historical storm-surge data combined with numerical hydrodynamic modelling, aimed at improved estimates of probabilities of occurrence of extreme water levels along the Dutch coast. Recent developments concerning the physical and numerical modelling of inundation of low-lying areas are presented. State-of-the-art modelling of wind waves in coastal areas is also reviewed. Research issues in the area of coastal modelling for flood defence are indicated.

  5. Emerging importance of oxidative stress in regulating striated muscle elasticity.

    PubMed

    Beckendorf, Lisa; Linke, Wolfgang A

    2015-02-01

    The contractile function of striated muscle cells is altered by oxidative/nitrosative stress, which can be observed under physiological conditions but also in diseases like heart failure or muscular dystrophy. Oxidative stress causes oxidative modifications of myofilament proteins and can impair myocyte contractility. Recent evidence also suggests an important effect of oxidative stress on muscle elasticity and passive stiffness via modifications of the giant protein titin. In this review we provide a short overview of known oxidative modifications in thin and thick filament proteins and then discuss in more detail those oxidative stress-related modifications altering titin stiffness directly or indirectly. Direct modifications of titin include reversible disulfide bonding within the cardiac-specific N2-Bus domain, which increases titin stiffness, and reversible S-glutathionylation of cryptic cysteines in immunoglobulin-like domains, which only takes place after the domains have unfolded and which reduces titin stiffness in cardiac and skeletal muscle. Indirect effects of oxidative stress on titin can occur via reversible modifications of protein kinase signalling pathways (especially the NO-cGMP-PKG axis), which alter the phosphorylation level of certain disordered titin domains and thereby modulate titin stiffness. Oxidative stress also activates proteases such as matrix-metalloproteinase-2 and (indirectly via increasing the intracellular calcium level) calpain-1, both of which cleave titin to irreversibly reduce titin-based stiffness. Although some of these mechanisms require confirmation in the in vivo setting, there is evidence that oxidative stress-related modifications of titin are relevant in the context of biomarker design and represent potential targets for therapeutic intervention in some forms of muscle and heart disease.

  6. Hepatic oleate regulates adipose tissue lipogenesis and fatty acid oxidation[S

    PubMed Central

    Burhans, Maggie S.; Flowers, Matthew T.; Harrington, Kristin R.; Bond, Laura M.; Guo, Chang-An; Anderson, Rozalyn M.; Ntambi, James M.

    2015-01-01

    Hepatic steatosis is associated with detrimental metabolic phenotypes including enhanced risk for diabetes. Stearoyl-CoA desaturases (SCDs) catalyze the synthesis of MUFAs. In mice, genetic ablation of SCDs reduces hepatic de novo lipogenesis (DNL) and protects against diet-induced hepatic steatosis and adiposity. To understand the mechanism by which hepatic MUFA production influences adipose tissue stores, we created two liver-specific transgenic mouse models in the SCD1 knockout that express either human SCD5 or mouse SCD3, that synthesize oleate and palmitoleate, respectively. We demonstrate that hepatic de novo synthesized oleate, but not palmitoleate, stimulate hepatic lipid accumulation and adiposity, reversing the protective effect of the global SCD1 knockout under lipogenic conditions. Unexpectedly, the accumulation of hepatic lipid occurred without induction of the hepatic DNL program. Changes in hepatic lipid composition were reflected in plasma and in adipose tissue. Importantly, endogenously synthesized hepatic oleate was associated with suppressed DNL and fatty acid oxidation in white adipose tissue. Regression analysis revealed a strong correlation between adipose tissue lipid fuel utilization and hepatic and adipose tissue lipid storage. These data suggest an extrahepatic mechanism where endogenous hepatic oleate regulates lipid homeostasis in adipose tissues. PMID:25555387

  7. 40 CFR 52.1601 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...: Sulfur oxides. 52.1601 Section 52.1601 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... § 52.1601 Control strategy and regulations: Sulfur oxides. (a) The applicable limitation on the sulfur... permit applied for that would authorize a relaxation in the sulfur-in-coal limitation at any...

  8. 40 CFR 52.1601 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...: Sulfur oxides. 52.1601 Section 52.1601 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... § 52.1601 Control strategy and regulations: Sulfur oxides. (a) The applicable limitation on the sulfur... permit applied for that would authorize a relaxation in the sulfur-in-coal limitation at any...

  9. 40 CFR 52.1601 - Control strategy and regulations: Sulfur oxides.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...: Sulfur oxides. 52.1601 Section 52.1601 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... § 52.1601 Control strategy and regulations: Sulfur oxides. (a) The applicable limitation on the sulfur... permit applied for that would authorize a relaxation in the sulfur-in-coal limitation at any...

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...: Sulfur oxides. 52.1601 Section 52.1601 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... § 52.1601 Control strategy and regulations: Sulfur oxides. (a) The applicable limitation on the sulfur... permit applied for that would authorize a relaxation in the sulfur-in-coal limitation at any...

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

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...: Sulfur oxides. 52.1601 Section 52.1601 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... § 52.1601 Control strategy and regulations: Sulfur oxides. (a) The applicable limitation on the sulfur... permit applied for that would authorize a relaxation in the sulfur-in-coal limitation at any...

  12. 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. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  13. Oxidative stress and DNA methylation regulation in the metabolic syndrome.

    PubMed

    Yara, Sabrina; Lavoie, Jean-Claude; Levy, Emile

    2015-01-01

    DNA methylation is implicated in tissue-specific gene expression and genomic imprinting. It is modulated by environmental factors, especially nutrition. Modified DNA methylation patterns may contribute to health problems and susceptibility to complex diseases. Current advances have suggested that the metabolic syndrome (MS) is a programmable disease, which is characterized by epigenetic modifications of vital genes when exposed to oxidative stress. Therefore, the main objective of this paper is to critically review the central context of MS while presenting the most recent knowledge related to epigenetic alterations that are promoted by oxidative stress. Potential pro-oxidant mechanisms that orchestrate changes in methylation profiling and are related to obesity, diabetes and hypertension are discussed. It is anticipated that the identification and understanding of the role of DNA methylation marks could be used to uncover early predictors and define drugs or diet-related treatments able to delay or reverse epigenetic changes, thereby combating MS burden.

  14. Two thiadiazole compounds promote rice defence against Xanthomonas oryzae pv. oryzae by suppressing the bacterium's production of extracellular polysaccharides.

    PubMed

    Liang, Xiaoyu; Yu, Xiaoyue; Dong, Wenxia; Guo, Shijian; Xu, Shu; Wang, Jianxin; Zhou, Mingguo

    2015-10-01

    Thiazole, isothiazole, thiadiazole, and their derivatives are used to control various human, animal and plant diseases. In addition to having direct anti-microbial and anti-fungal properties, these compounds are thought to induce host defences, but the mechanism of defence induction remains poorly understood. This article reports that the thiadiazoles of zinc thiazole and bismerthiazol induce H2 O2 accumulation, up-regulation of defence-related genes, callose deposition and hypersensitive response-like cell death in rice leaves infected with Xanthomonas oryaze pv. oryzae (Xoo) strain ZJ173, but not in non-infected leaves. These defence responses in Xoo-infected leaves were suppressed by the exogenous application of catalase, which reduces H2 O2 accumulation. The application of extracellular polysaccharides (EPSs) extracted from strain ZJ173 significantly compromised rice defence against ZJ173 with or without thiadiazole treatment. The EPS-deficient Xoo mutant ∆gumH triggered a stronger defence than its parent strain ZJ173. The thiadiazole treatments reduced EPS production by strain ZJ173, but not by the thiadiazole-resistant strain 2-1-1, which is thiadiazole resistant in vivo, but not in vitro; moreover, enhanced defence was not detected in thiadiazole-treated rice inoculated with 2-1-1. Based on these data, we infer that zinc thiazole and bismerthiazol promote rice defence against Xoo by inhibiting the production of bacterial EPS.

  15. Anosognosia as motivated unawareness: the 'defence' hypothesis revisited.

    PubMed

    Turnbull, Oliver H; Fotopoulou, Aikaterini; Solms, Mark

    2014-12-01

    Anosognosia for hemiplegia has seen a century of almost continuous research, yet a definitive understanding of its mechanism remains elusive. Essentially, anosognosic patients hold quasi-delusional beliefs about their paralysed limbs, in spite of all the contrary evidence, repeated questioning, and logical argument. We review a range of findings suggesting that emotion and motivation play an important role in anosognosia. We conclude that anosognosia involves (amongst other things) a process of psychological defence. This conclusion stems from a wide variety of clinical and experimental investigations, including data on implicit awareness of deficit, fluctuations in awareness over time, and dramatic effects upon awareness of psychological interventions such as psychotherapy, reframing of the emotional consequences of the paralysis, and first versus third person perspectival manipulations. In addition, we review and refute the (eight) arguments historically raised against the 'defence' hypothesis, including the claim that a defence-based account cannot explain the lateralised nature of the disorder. We argue that damage to a well-established right-lateralised emotion regulation system, with links to psychological processes that appear to underpin allocentric spatial cognition, plays a key role in anosognosia (at least in some patients). We conclude with a discussion of implications for clinical practice.

  16. Creatine-induced activation of antioxidative defence in myotube cultures revealed by explorative NMR-based metabonomics and proteomics

    PubMed Central

    2010-01-01

    Background Creatine is a key intermediate in energy metabolism and supplementation of creatine has been used for increasing muscle mass, strength and endurance. Creatine supplementation has also been reported to trigger the skeletal muscle expression of insulin like growth factor I, to increase the fat-free mass and improve cognition in elderly, and more explorative approaches like transcriptomics has revealed additional information. The aim of the present study was to reveal additional insight into the biochemical effects of creatine supplementation at the protein and metabolite level by integrating the explorative techniques, proteomics and NMR metabonomics, in a systems biology approach. Methods Differentiated mouse myotube cultures (C2C12) were exposed to 5 mM creatine monohydrate (CMH) for 24 hours. For proteomics studies, lysed myotubes were analyzed in single 2-DGE gels where the first dimension of protein separation was pI 5-8 and second dimension was a 12.5% Criterion gel. Differentially expressed protein spots of significance were excised from the gel, desalted and identified by peptide mass fingerprinting using MALDI-TOF MS. For NMR metabonomic studies, chloroform/methanol extractions of the myotubes were subjected to one-dimensional 1H NMR spectroscopy and the intracellular oxidative status of myotubes was assessed by intracellular DCFH2 oxidation after 24 h pre-incubation with CMH. Results The identified differentially expressed proteins included vimentin, malate dehydrogenase, peroxiredoxin, thioredoxin dependent peroxide reductase, and 75 kDa and 78 kDa glucose regulated protein precursors. After CMH exposure, up-regulated proteomic spots correlated positively with the NMR signals from creatine, while down-regulated proteomic spots were negatively correlated with these NMR signals. The identified differentially regulated proteins were related to energy metabolism, glucose regulated stress, cellular structure and the antioxidative defence system. The

  17. Transcriptional regulators of oxidative stress-inducible genes in prokaryotes and eukaryotes.

    PubMed

    Storz, G; Polla, B S

    1996-01-01

    It appears that redox regulation is an important mechanism for the control of transcription factor activation. The role of oxidation-reduction is probably determined in part by the structure of the transcription factors. For example, the presence of cysteine residues within the DNA binding sites may sensitize a transcription factor to ROS. The ROS-mediated regulation of transcription factors is specific, some ROS are more efficient than other ROS in activating defined regulators. While the protective antioxidant responses induced by ROS in prokaryotes and eukaryotes are rather conserved (for example, SOD, HSP...), the regulators for these genes do not appear to be conserved. Further studies designed to fully characterize these regulators and understand the subtle mechanisms involved in redox gene regulation are ongoing, and should provide the theoretical basis for clinical approaches using antioxidant therapies in human diseases in which oxidative stress is implicated.

  18. Comparing systemic defence-related gene expression changes upon migratory and sedentary nematode attack in rice.

    PubMed

    Kyndt, T; Nahar, K; Haegeman, A; De Vleesschauwer, D; Höfte, M; Gheysen, G

    2012-03-01

    Complex defence signalling pathways, controlled by different hormones, are known to be involved in the reaction of plants to a wide range of biotic and abiotic stress factors. Here, we studied the differential expression of genes involved in stress and defence responses in systemic tissue of rice infected with the root knot nematode (RKN) Meloidogyne graminicola and the migratory root rot nematode Hirschmanniella oryzae, two agronomically important rice pathogens with very different lifestyles. qRT-PCR revealed that all investigated systemic tissues had significantly lower expression of isochorismate synthase, a key enzyme for salicylic acid production involved in basal defence and systemic acquired resistance. The systemic defence response upon migratory nematode infection was remarkably similar to fungal rice blast infection. Almost all investigated defence-related genes were up-regulated in rice shoots 3 days after root rot nematode attack, including the phenylpropanoid pathway, ethylene pathway and PR genes, but many of which were suppressed at 7 dpi. Systemic shoot tissue of RKN-infected plants showed similar attenuation of expression of almost all studied genes already at 3 dpi, with clear attenuation of the ethylene pathway and methyl jasmonate biosynthesis. These results provide an interesting starting point for further studies to elucidate how nematodes are able to suppress systemic plant defence mechanisms and the effect in multitrophic interactions.

  19. 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.

  20. Iron oxides, dissolved silica, and regulation of marine phosphate concentration

    NASA Astrophysics Data System (ADS)

    Planavsky, N.; Reinhard, C.; Lyons, T.

    2008-12-01

    Phosphorous concentrations in iron oxide-rich sediments reflect orthophosphate levels in the water column from which iron oxides precipitated. Sediment P/Fe ratios are also strongly influenced by the concentrations of dissolved species that inhibit orthophosphate-to-ferrihydrite sorption, most notably silica. It may, therefore, be possible to use P/Fe ratios in iron oxide-rich sediments to estimate past dissolved P concentrations, if one considers the evolution of the silica cycle. A compilation of Fe and P data in iron oxide-rich sediments through time reveals an increase in P/Fe ratios after the Jurassic. We propose that this trend indicates evolution of the iron-oxide phosphate removal mechanism caused by decreasing levels of sorption inhibition by dissolved silica. The large difference in P/Fe ratios in Cenozoic versus older iron-oxide rich sediments can be linked with Si drawdown caused by the proliferation of siliceous plankton in the Cretaceous. There is also a late Mesozoic or Cenozoic increase in V/Fe ratios, which provides additional evidence for lower ferrihydrite anion sorption efficiency prior to diatom radiation. P/Fe ratios in iron oxide-rich sediments from the early and middle Phanerozoic are comparable to the ratios in iron formations previously presented as evidence for an early Precambrian phosphate crisis (Bjerrum and Canfield, 2002, Nature, 417:159-162). Given the compelling evidence for higher Si concentrations in the Precambrian compared to the Phanerozoic and dissolved P concentrations comparable to modern levels throughout the Phanerozoic, the presented trend of P/Fe ratios suggests dissolved P concentrations were higher in Precambrian than Phanerozoic oceans. High dissolved P levels in the Precambrian may have been linked to inhibited carbonate fluorapatite (CFA) formation as a result of persistently high levels of carbonate supersaturation. Carbonate ion substitution into CFA scales with the ambient carbonate ion activity and increases

  1. Calcium in plant defence-signalling pathways.

    PubMed

    Lecourieux, David; Ranjeva, Raoul; Pugin, Alain

    2006-01-01

    In plant cells, the calcium ion is a ubiquitous intracellular second messenger involved in numerous signalling pathways. Variations in the cytosolic concentration of Ca2+ ([Ca2+]cyt) couple a large array of signals and responses. Here we concentrate on calcium signalling in plant defence responses, particularly on the generation of the calcium signal and downstream calcium-dependent events participating in the establishment of defence responses with special reference to calcium-binding proteins.

  2. The Harbour Defence IKC2 Experience

    DTIC Science & Technology

    2005-06-01

    Choon Kiat, Tan Defence Science and Technolgy Agency 1 Depot Road #22-01 DefenceTechnology Tower A Singapore 109679 Phone : +65 63732338 Fax...Command Post (Desktop) Mobile Units (PDA) Radar 1 Web Service Radar 2 Web Service Radar 1 Tracks Msg Radar 2 Tracks Msg Web Service Abstraction...was found to be adequate for the mobile forces, providing a relatively constant throughput of 8 kbps throughout the base, though minor service

  3. Public Private Partnerships Applicability to Defence Procurement

    DTIC Science & Technology

    2001-09-01

    Public Private Partnerships Applicability to Defence Procurement Jonathan Barnes KPMG Corporate Finance Report Documentation Page Report Date...25SEP2001 Report Type N/A Dates Covered (from... to) 25SEP2001 - 27SEP2001 Title and Subtitle Public Private Partnerships Applicability to Defence...unclassified Classification of Abstract unclassified Limitation of Abstract UU Number of Pages 6 kpmg Aim Provide an appreciation of: n Public Private Partnerships

  4. 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).

  5. UK photonics in defence and security

    NASA Astrophysics Data System (ADS)

    Gracie, C.; Tooley, I.; Wilson, A.

    2008-10-01

    The UK is globally recognised as strong in Photonics. However its Photonics sector is fragmented and the size and sectors of interest have not previously been established. The UK government has instigated the formation of the Photonics Knowledge Transfer Network (PKTN) to bring the Photonics community together. The UK features in Defence & Security; Communications; Measurement; Medical Technology; Lighting; Solar Energy; Information Technology and Flat Panels. This expertise is scattered through out the UK in geographic areas each with a breadth of Photonic interests. The PKTN has mapped the UK capability in all Photonics sectors. This paper will present the capability of the Companies, Research Institutions and Infrastructure making up the Defence & Security Photonics scene in the UK. Large Defence companies in the UK are well known throughout the world. However, there are a large number of SMEs, which may not be as well known in the supply chain. These are being actively encouraged by the UK MoD to engage with the Defence & Security Market and shall be discussed here. The presentation will reference a number of organisations which help to fund and network the community, such as the Defence Technology Centres. In addition the Roadmap for Defence & Security in the UK, produced for the UK Photonics Strategy (July 2006) by the Scottish Optoelectronics Association will be described and the plans in taking it forward under the PKTN will be revealed.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

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

    PubMed

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

    2016-01-05

    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.

  12. Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase.

    PubMed Central

    MacAllister, R. J.; Parry, H.; Kimoto, M.; Ogawa, T.; Russell, R. J.; Hodson, H.; Whitley, G. S.; Vallance, P.

    1996-01-01

    1. Dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that metabolizes the endogenous nitric oxide synthase inhibitors NG-monomethyl-arginine and NG,NG-dimethy-L-arginine to citrulline, was identified by Western blotting in rat and human tissue homogenates. 2. S-2-amino-4(3-methylguanidino)butanoic acid (4124W) inhibited the metabolism of [14C]-NG-monomethyl-L-arginine to [14C]-citrulline by rat liver homogenates (IC50 416 +/- 66 microM; n = 9), human cultured endothelial cells (IC50 250 +/- 34 microM; n = 9) and isolated purified dimethylarginine dimethylaminohydrolase. 3. Addition of 4124W to culture medium increased the accumulation of endogenously-generated NG,NG-dimethy-L-arginine in the supernatant of human cultured endothelial cells from 3.1 +/- 0.3 to 5 +/- 0.7 microM (n = 15; P < 0.005). 4. 4124W (1 microM - 1 mM) had no direct effect on endothelial nitric oxide synthase activity but caused endothelium-dependent contraction of rat aortic rings (1 mM 4124W increased tone by 81.5 +/- 9.6% of that caused by phenylephrine 100 nM). This effect was reversed by L-arginine (100 microM). 4124W reversed endothelium-dependent relaxation of human saphenous vein (19.2 +/- 6.7% reversal of bradykinin-induced relaxation at 1 mM 4124W). 5. These data suggest that inhibition of dimethylarginine dimethylaminohydrolase increases the intracellular contraction of NG,NG-dimethyl-L-arginine sufficiently to inhibit nitric oxide synthesis. Inhibiting the activity of DDAH may provide an alternative mechanism for inhibition of nitric oxide synthases and changes in the activity of DDAH could contribute to pathophysiological alterations in NO generation. Images Figure 1 Figure 2 Figure 3 PMID:8982498

  13. 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

  14. 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.

  15. Coriandrum sativum L. protects human keratinocytes from oxidative stress by regulating oxidative defense systems.

    PubMed

    Park, G; Kim, H G; Kim, Y O; Park, S H; Kim, S Y; Oh, M S

    2012-01-01

    Oxidative radicals are major environmental causes of human skin damage. Oxidative defense factors, including nuclear factor erythroid-derived 2-related factor 2 (Nrf2), are centrally involved in repairing skin cells or protecting them from oxidative damage. Coriandrum sativum L. (coriander; CS) is a commonly consumed food and a traditional phytomedicine in Asia and Europe. In this study, we examined the protective effects of a standardized CS leaf extract against oxidative stress in human HaCaT keratinocytes. CS significantly and dose-dependently protected cells against reduced cell viability caused by H2O2-induced damage, as assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Other assays demonstrated that CS protected HaCaT cells by increasing the levels of glutathione and activities of oxidative defense enzymes, such as superoxide dismutase and catalase. Moreover, it increased the expression of activated Nrf2, which plays a crucial role in protecting skin cells against oxidative stress. These results suggest that CS protects human keratinocytes from H2O2-induced oxidative stress through antioxidant effects. Copyright © 2012 S. Karger AG, Basel.

  16. Glucose oxidation positively regulates glucose uptake and improves cardiac function recovery after myocardial reperfusion.

    PubMed

    Li, Tingting; Xu, Jie; Qin, Xinghua; Hou, Zuoxu; Guo, Yongzheng; Liu, Zhenhua; Wu, Jianjiang; Zheng, Hong; Zhang, Xing; Gao, Feng

    2017-03-21

    Myocardial reperfusion decreases glucose oxidation and uncouples glucose oxidation from glycolysis. Therapies that increase glucose oxidation lessen myocardial ischemia/reperfusion injury. However, the regulation of glucose uptake during reperfusion remains poorly understood. Here we found that glucose uptake was remarkably diminished in myocardium following reperfusion in Sprague-Dawley rats as detected by 18F-labeled and fluorescent-labeled glucose analogs, even though GLUT1 was upregulated by 3 folds and GLUT4 translocation remained unchanged compared with those of sham rats. The decreased glucose uptake was accompanied by suppressed glucose oxidation. Interestingly, stimulating glucose oxidation by inhibition of pyruvate dehydrogenase kinase 4 (PDK4), a rate-limiting enzyme for glucose oxidation, increased glucose uptake and alleviated ischemia/reperfusion injury. In vitro data in neonatal myocytes showed that PDK4 overexpression decreased glucose uptake, while its knockdown increased glucose uptake, suggesting a role of PDK4 in regulating glucose uptake. Moreover, inhibition of PDK4 increased myocardial glucose uptake with concomitant enhancement of cardiac insulin sensitivity following myocardial ischemia/reperfusion. These results showed that the suppressed glucose oxidation mediated by PDK4 contributes to the reduced glucose uptake in myocardium following reperfusion, and enhancement of glucose uptake exerts cardioprotection. The findings suggest that stimulating glucose oxidation via PDK4 could be an efficient approach to improve recovery from myocardial ischemia/reperfusion injury.

  17. Oxidation of calmodulin alters activation and regulation of CaMKII.

    PubMed

    Robison, A J; Winder, Danny G; Colbran, Roger J; Bartlett, Ryan K

    2007-04-27

    Increases in reactive oxygen species and mis-regulation of calcium homeostasis are associated with various physiological conditions and disease states including aging, ischemia, exposure to drugs of abuse, and neurodegenerative diseases. In aged animals, this is accompanied by a reduction in oxidative repair mechanisms resulting in increased methionine oxidation of the calcium signaling protein calmodulin in the brain. Here, we show that oxidation of calmodulin results in an inability to: (1) activate CaMKII; (2) support Thr(286) autophosphorylation of CaMKII; (3) prevent Thr(305/6) autophosphorylation of CaMKII; (4) support binding of CaMKII to the NR2B subunit of the NMDA receptor; and (5) compete with alpha-actinin for binding to CaMKII. Moreover, oxidized calmodulin does not efficiently bind calcium/calmodulin-dependent protein kinase II (CaMKII) in rat brain lysates or in vitro. These observations contrast from past experiments performed with oxidized calmodulin and the plasma membrane calcium ATPase, where oxidized calmodulin binds to, and partially activates the PMCA. When taken together, these data suggest that oxidative stress may perturb neuronal and cardiac function via a decreased ability of oxidized calmodulin to bind, activate, and regulate the interactions of CaMKII.

  18. Graphene Oxide Regulated Tin Oxide Nanostructures: Engineering Composition, Morphology, Band Structure, and Photocatalytic Properties.

    PubMed

    Pan, Xiaoyang; Yi, Zhiguo

    2015-12-16

    A facile, one-step hydrothermal method has been developed to fabricate tin oxide-reduced graphene oxide (Sn-RGO) nanocomposites with tunable composition, morphology, and energy band structure by utilizing graphene oxide (GO) as a multifunctional two-dimensional scaffold. By adjusting the GO concentration during synthesis, a variety of tin oxide nanomaterials with diverse composition and morphology are obtained. Simultaneously, the varying of GO concentration can also narrow the bandgap and tune the band edge positions of the Sn-RGO nanocomposites. As a result, the Sn-RGO nanocomposites with controllable composition, morphology, and energy band structure are obtained, which exhibit efficient photoactivities toward methyl orange (MO) degradation under visible-light irradiation. It is expected that our work would point to the new possibility of using GO for directing synthesis of semiconductor nanomaterials with tailored structure and physicochemical properties.

  19. Growth-defence balance in grass biomass production: the role of jasmonates.

    PubMed

    Shyu, Christine; Brutnell, Thomas P

    2015-07-01

    Growth-defence balance is the selective partitioning of resources between biomass accumulation and defence responses. Although it is generally postulated that reallocation of limited carbon pools drives the antagonism between growth and defence, little is known about the mechanisms underlying this regulation. Jasmonates (JAs) are a group of oxylipins that are required for a broad range of responses from defence against insects to reproductive growth. Application of JAs to seedlings also leads to inhibited growth and repression of photosynthesis, suggesting a role for JAs in regulating growth-defence balance. The majority of JA research uses dicot models such as Arabidopsis and tomato, while understanding of JA biology in monocot grasses, which comprise most bioenergy feedstocks, food for human consumption, and animal feed, is limited. Interestingly, JA mutants of grasses exhibit unique phenotypes compared with well-studied dicot models. Gene expression analyses in bioenergy grasses also suggest roles for JA in rhizome development, which has not been demonstrated in Arabidopsis. In this review we summarize current knowledge of JA biology in panicoid grasses-the group that consists of the world's emerging bioenergy grasses such as switchgrass, sugarcane, Miscanthus, and sorghum. We discuss outstanding questions regarding the role of JAs in panicoid grasses, and highlight the importance of utilizing emerging grass models for molecular studies to provide a basis for engineering bioenergy grasses that can maximize biomass accumulation while efficiently defending against stress.

  20. Photosynthesis, photorespiration, and light signalling in defence responses.

    PubMed

    Kangasjärvi, Saijaliisa; Neukermans, Jenny; Li, Shengchun; Aro, Eva-Mari; Noctor, Graham

    2012-02-01

    Visible light is the basic energetic driver of plant biomass production through photosynthesis. The constantly fluctuating availability of light and other environmental factors means that the photosynthetic apparatus must be able to operate in a dynamic fashion appropriate to the prevailing conditions. Dynamic regulation is achieved through an array of homeostatic control mechanisms that both respond to and influence cellular energy and reductant status. In addition, light availability and quality are continuously monitored by plants through photoreceptors. Outside the laboratory growth room, it is within the context of complex changes in energy and signalling status that plants must regulate pathways to deal with biotic challenges, and this can be influenced by changes in the highly energetic photosynthetic pathways and in the turnover of the photosynthetic machinery. Because of this, defence responses are neither simple nor easily predictable, but rather conditioned by the nutritional and signalling status of the plant cell. This review discusses recent data and emerging concepts of how recognized defence pathways interact with and are influenced by light-dependent processes. Particular emphasis is placed on the potential roles of the chloroplast, photorespiration, and photoreceptor-associated pathways in regulating the outcome of interactions between plants and pathogenic organisms.

  1. 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

  2. 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

  3. Glial β-Oxidation regulates Drosophila Energy Metabolism

    PubMed Central

    Schulz, Joachim G.; Laranjeira, Antonio; Van Huffel, Leen; Gärtner, Annette; Vilain, Sven; Bastianen, Jarl; Van Veldhoven, Paul P.; Dotti, Carlos G.

    2015-01-01

    The brain's impotence to utilize long-chain fatty acids as fuel, one of the dogmas in neuroscience, is surprising, since the nervous system is the tissue most energy consuming and most vulnerable to a lack of energy. Challenging this view, we here show in vivo that loss of the Drosophila carnitine palmitoyltransferase 2 (CPT2), an enzyme required for mitochondrial β-oxidation of long-chain fatty acids as substrates for energy production, results in the accumulation of triacylglyceride-filled lipid droplets in adult Drosophila brain but not in obesity. CPT2 rescue in glial cells alone is sufficient to restore triacylglyceride homeostasis, and we suggest that this is mediated by the release of ketone bodies from the rescued glial cells. These results demonstrate that the adult brain is able to catabolize fatty acids for cellular energy production. PMID:25588812

  4. Glial β-oxidation regulates Drosophila energy metabolism.

    PubMed

    Schulz, Joachim G; Laranjeira, Antonio; Van Huffel, Leen; Gärtner, Annette; Vilain, Sven; Bastianen, Jarl; Van Veldhoven, Paul P; Dotti, Carlos G

    2015-01-15

    The brain's impotence to utilize long-chain fatty acids as fuel, one of the dogmas in neuroscience, is surprising, since the nervous system is the tissue most energy consuming and most vulnerable to a lack of energy. Challenging this view, we here show in vivo that loss of the Drosophila carnitine palmitoyltransferase 2 (CPT2), an enzyme required for mitochondrial β-oxidation of long-chain fatty acids as substrates for energy production, results in the accumulation of triacylglyceride-filled lipid droplets in adult Drosophila brain but not in obesity. CPT2 rescue in glial cells alone is sufficient to restore triacylglyceride homeostasis, and we suggest that this is mediated by the release of ketone bodies from the rescued glial cells. These results demonstrate that the adult brain is able to catabolize fatty acids for cellular energy production.

  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. Linoleic acid participates in the response to ischemic brain injury through oxidized metabolites that regulate neurotransmission.

    PubMed

    Hennebelle, Marie; Zhang, Zhichao; Metherel, Adam H; Kitson, Alex P; Otoki, Yurika; Richardson, Christine E; Yang, Jun; Lee, Kin Sing Stephen; Hammock, Bruce D; Zhang, Liang; Bazinet, Richard P; Taha, Ameer Y

    2017-06-28

    Linoleic acid (LA; 18:2 n-6), the most abundant polyunsaturated fatty acid in the US diet, is a precursor to oxidized metabolites that have unknown roles in the brain. Here, we show that oxidized LA-derived metabolites accumulate in several rat brain regions during CO2-induced ischemia and that LA-derived 13-hydroxyoctadecadienoic acid, but not LA, increase somatic paired-pulse facilitation in rat hippocampus by 80%, suggesting bioactivity. This study provides new evidence that LA participates in the response to ischemia-induced brain injury through oxidized metabolites that regulate neurotransmission. Targeting this pathway may be therapeutically relevant for ischemia-related conditions such as stroke.

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

    PubMed

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

    2015-06-01

    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.

  8. Dietary Phytochemicals Promote Health by Enhancing Antioxidant Defence in a Pig Model

    PubMed Central

    Selby-Pham, Sophie N. B.; Cottrell, Jeremy J.; Ng, Ken

    2017-01-01

    Phytochemical-rich diets are protective against chronic diseases and mediate their protective effect by regulation of oxidative stress (OS). However, it is proposed that under some circumstances, phytochemicals can promote production of reactive oxygen species (ROS) in vitro, which might drive OS-mediated signalling. Here, we investigated the effects of administering single doses of extracts of red cabbage and grape skin to pigs. Blood samples taken at baseline and 30 min intervals for 4 hours following intake were analyzed by measures of antioxidant status in plasma, including Trolox equivalent antioxidant capacity (TEAC) and glutathione peroxidase (GPx) activity. In addition, dose-dependent production of hydrogen peroxide (H2O2) by the same extracts was measured in untreated commercial pig plasma in vitro. Plasma from treated pigs showed extract dose-dependent increases in non-enzymatic (plasma TEAC) and enzymatic (GPx) antioxidant capacities. Similarly, extract dose-dependent increases in H2O2 were observed in commercial pig plasma in vitro. The antioxidant responses to extracts by treated pigs were highly correlated with their respective yields of H2O2 production in vitro. These results support that dietary phytochemicals regulate OS via direct and indirect antioxidant mechanisms. The latter may be attributed to the ability to produce H2O2 and to thereby stimulate cellular antioxidant defence systems. PMID:28708113

  9. Quorum Quenching of Nitrobacter winogradskyi Suggests that Quorum Sensing Regulates Fluxes of Nitrogen Oxide(s) during Nitrification.

    PubMed

    Mellbye, Brett L; Giguere, Andrew T; Bottomley, Peter J; Sayavedra-Soto, Luis A

    2016-10-25

    Quorum sensing (QS) is a widespread process in bacteria used to coordinate gene expression with cell density, diffusion dynamics, and spatial distribution through the production of diffusible chemical signals. To date, most studies on QS have focused on model bacteria that are amenable to genetic manipulation and capable of high growth rates, but many environmentally important bacteria have been overlooked. For example, representatives of proteobacteria that participate in nitrification, the aerobic oxidation of ammonia to nitrate via nitrite, produce QS signals called acyl-homoserine lactones (AHLs). Nitrification emits nitrogen oxide gases (NO, NO2, and N2O), which are potentially hazardous compounds that contribute to global warming. Despite considerable interest in nitrification, the purpose of QS in the physiology/ecology of nitrifying bacteria is poorly understood. Through a quorum quenching approach, we investigated the role of QS in a well-studied AHL-producing nitrite oxidizer, Nitrobacter winogradskyi We added a recombinant AiiA lactonase to N. winogradskyi cultures to degrade AHLs to prevent their accumulation and to induce a QS-negative phenotype and then used mRNA sequencing (mRNA-Seq) to identify putative QS-controlled genes. Our transcriptome analysis showed that expression of nirK and nirK cluster genes (ncgABC) increased up to 19.9-fold under QS-proficient conditions (minus active lactonase). These data led to us to query if QS influenced nitrogen oxide gas fluxes in N. winogradskyi Production and consumption of NOx increased and production of N2O decreased under QS-proficient conditions. Quorum quenching transcriptome approaches have broad potential to identify QS-controlled genes and phenotypes in organisms that are not genetically tractable. Bacterial cell-cell signaling, or quorum sensing (QS), is a method of bacterial communication and gene regulation that is well studied in bacteria. However, little is known about the purpose of QS in many

  10. Soil Formate Regulates the Fungal Nitrous Oxide Emission Pathway▿

    PubMed Central

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

    2008-01-01

    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 (N2O). The metabolic pathway and oxygen requirement for fungal denitrification are different from those for bacterial denitrification. We hypothesized that the soil N2O emission from fungi is formate and O2 dependent and that land use and landforms could influence the proportion of N2O coming from fungi. Using substrate-induced respiration inhibition under anaerobic and aerobic conditions in combination with 15N gas analysis, we found that formate and hypoxia (versus anaerobiosis) were essential for the fungal reduction of 15N-labeled nitrate to 15N2O. As much as 65% of soil-emitted N2O 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 N2O production from fungi via the proposed formate-dependent pathway. PMID:18791019

  11. 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.

  12. 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

  13. [Nitric oxide and reflectory regulation of blood circulation in rats].

    PubMed

    Shapoval, L M; Moĭbenko, O O; Sahach, V F; Pobihaĭlo, L S; Dmytrenko, O V

    2003-01-01

    In acute experiments on anaesthetized with urethane normotensive rats we studied the ways of participation of nitric oxide (NO) in reflector control of the cardiovascular system by the medullary neurons within n.tractus solitarii (NTS), dorsal nucleus of the vagus nerve (DNV), n. ambiguus (AMB), and the lateral reticular nucleus (LRN). Modulations of the activities of neuronal NO-synthase (nNOS) in the populations of the cardiovascular neurons within the medullary nuclei which are involved in the reflector cardiovascular control were induced by intramedullary injections of sodium nitroprusside as NO donor, L-arginine as NO precursor, L-NNA as an inhibitor of NOS, as well as by intraperetoneal injections of 7-nitroindazol (nNOS inhibitor). We have determined that stimulation of nNOS activity in the populations of the medullary neurons resulted in both remarkable shifts in the SAP level and in inhibiting the chemoreceptor reflector responses. After preliminary inhibiting nNOS chemoreceptor reflexes induced by epinephrine were found to be enhanced in most experiments.

  14. Plant RNA silencing in viral defence.

    PubMed

    Pantaleo, Vitantonio

    2011-01-01

    RNA silencing is described in plants and insects as a defence mechanism against foreign nucleic acids, such as invading viruses. The RNA silencing-based antiviral defence involves the production of virus-derived small interfering RNAs and their association to effector proteins, which together drive the sequence specific inactivation of viruses. The entire process of antiviral defence 'borrows' several plant factors involved in other specialized RNA silencing endogenous pathways. Different viruses use variable strategies to infect different host plants, which render the antiviral RNA silencing a complex phenomenon far to be completely clarified. This chapter reports current advances in understanding the main steps of the plant's RNA-silencing response to viral invasion and discusses some of the key questions still to be answered.

  15. Skeletal Muscle Growth Hormone Receptor Signaling Regulates Basal, but Not Fasting-Induced, Lipid Oxidation

    PubMed Central

    Vijayakumar, Archana; Wu, YingJie; Buffin, Nicholas J.; Li, Xiaosong; Sun, Hui; Gordon, Ronald E.; Yakar, Shoshana; LeRoith, Derek

    2012-01-01

    Background Growth hormone (GH) stimulates whole-body lipid oxidation, but its regulation of muscle lipid oxidation is not clearly defined. Mice with a skeletal muscle-specific knockout of the GH receptor (mGHRKO model) are protected from high fat diet (HFD)–induced insulin resistance and display increased whole-body carbohydrate utilization. In this study we used the mGRHKO mice to investigate the role of muscle GHR signaling on lipid oxidation under regular chow (RC)- and HFD- fed conditions, and in response to fasting. Methodology/Principal Findings Expression of lipid oxidation genes was analyzed by real-time PCR in the muscles of RC- and HFD- fed mice, and after 24 h fasting in the HFD-fed mice. Expression of lipid oxidation genes was lower in the muscles of the mGHRKO mice relative to the controls, irrespective of diet. However, in response to 24 h fasting, the HFD-fed mGHRKO mice displayed up-regulation of lipid oxidation genes similar to the fasted controls. When subjected to treadmill running challenge, the HFD-fed mGHRKO mice demonstrated increased whole-body lipid utilization. Additionally, under fasted conditions, the adipose tissue of the mGHRKO mice displayed increased lipolysis as compared to both the fed mGHRKO as well as the fasted control mice. Conclusions/Significance Our data show that muscle GHR signaling regulates basal lipid oxidation, but not the induction of lipid oxidation in response to fasting. We further demonstrate that muscle GHR signaling is involved in muscle-adipose tissue cross-talk; however the mechanisms mediating this remain to be elucidated. PMID:23024761

  16. Prophage-mediated defence against viral attack and viral counter-defence.

    PubMed

    Dedrick, Rebekah M; Jacobs-Sera, Deborah; Bustamante, Carlos A Guerrero; Garlena, Rebecca A; Mavrich, Travis N; Pope, Welkin H; Reyes, Juan C Cervantes; Russell, Daniel A; Adair, Tamarah; Alvey, Richard; Bonilla, J Alfred; Bricker, Jerald S; Brown, Bryony R; Byrnes, Deanna; Cresawn, Steven G; Davis, William B; Dickson, Leon A; Edgington, Nicholas P; Findley, Ann M; Golebiewska, Urszula; Grose, Julianne H; Hayes, Cory F; Hughes, Lee E; Hutchison, Keith W; Isern, Sharon; Johnson, Allison A; Kenna, Margaret A; Klyczek, Karen K; Mageeney, Catherine M; Michael, Scott F; Molloy, Sally D; Montgomery, Matthew T; Neitzel, James; Page, Shallee T; Pizzorno, Marie C; Poxleitner, Marianne K; Rinehart, Claire A; Robinson, Courtney J; Rubin, Michael R; Teyim, Joseph N; Vazquez, Edwin; Ware, Vassie C; Washington, Jacqueline; Hatfull, Graham F

    2017-01-09

    Temperate phages are common, and prophages are abundant residents of sequenced bacterial genomes. Mycobacteriophages are viruses that infect mycobacterial hosts including Mycobacterium tuberculosis and Mycobacterium smegmatis, encompass substantial genetic diversity and are commonly temperate. Characterization of ten Cluster N temperate mycobacteriophages revealed at least five distinct prophage-expressed viral defence systems that interfere with the infection of lytic and temperate phages that are either closely related (homotypic defence) or unrelated (heterotypic defence) to the prophage. Target specificity is unpredictable, ranging from a single target phage to one-third of those tested. The defence systems include a single-subunit restriction system, a heterotypic exclusion system and a predicted (p)ppGpp synthetase, which blocks lytic phage growth, promotes bacterial survival and enables efficient lysogeny. The predicted (p)ppGpp synthetase coded by the Phrann prophage defends against phage Tweety infection, but Tweety codes for a tetrapeptide repeat protein, gp54, which acts as a highly effective counter-defence system. Prophage-mediated viral defence offers an efficient mechanism for bacterial success in host-virus dynamics, and counter-defence promotes phage co-evolution.

  17. Regulation of cytochrome c oxidase by adenylic nucleotides. Is oxidative phosphorylation feedback regulated by its end-products?

    PubMed

    Beauvoit, B; Rigoulet, M

    2001-01-01

    Cytochrome c oxidase, which catalyzes an irreversible step of the respiratory chain, is one of the rate-controlling steps of oxidative phosphorylation on isolated mitochondria. The rate of electron transfer through the complex is primarily controlled by the associated thermodynamic forces, i.e., the span in redox potential between oxygen and cytochrome c and the protonmotive force. However, the electron flux also depends on the various kinetic effectors, including adenylic nucleotides. Although the number of binding sites for ATP and ADP on cytochrome oxidase is still a matter of debate, experiments performed on the solubilized and reconstituted enzyme provide strong functional evidence that the mammalian cytochrome c oxidase binds adenylic nucleotides on both sides of the inner membrane. These effects include modification in cytochrome c affinity, allosteric inhibition and changes in proton pumping efficiency. Immunological studies have pointed out the role of subunit IV and that of an ATP-binding protein, subunit VIa, in these kinetic regulations. In yeast, the role of the nuclear-encoded subunits in assembly and regulation of the cytochrome c oxidase has been further substantiated by using gene-disruption analysis. Using a subunit VIa-null mutant, the consequences of the ATP regulation on oxidative phosphorylation have been further investigated on isolated mitochondria. Taken together, the data demonstrate that there are multiple regulating sites for ATP on the yeast cytochrome oxidase with respect to the location (matrix versus cytosolic side), kinetic effect (activation versus inhibition) and consequence on the flow-force relationships. The question is therefore raised as to the physiological meaning of such feedback regulation of the respiratory chain by ATP in the control and regulation of cellular energy metabolism.

  18. Grp94 acts as a mediator of curcumin-induced antioxidant defence in myogenic cells.

    PubMed

    Pizzo, Paola; Scapin, Cristina; Vitadello, Maurizio; Florean, Cristina; Gorza, Luisa

    2010-04-01

    Curcumin is a non-toxic polyphenol with pleiotropic activities and limited bioavailability. We investigated whether a brief exposure to low doses of curcumin would induce in the myogenic C2C12 cell line an endoplasmic reticulum (ER) stress response and protect against oxidative stress. A 3-hr curcumin administration (5-10 microM) increased protein levels of the ER chaperone Grp94, without affecting those of Grp78, calreticulin and haeme-oxygenase-1 (HO-1). Exposure of cells to hydrogen peroxide 24 hrs after the curcumin treatment decreased caspase-12 activation, total protein oxidation and translocation of NF-kappaB to the nucleus, compared with untreated cells. Grp94 overexpression, achieved by means of either stable or transient trasfection, induced comparable cytoprotective effects to hydrogen peroxide. The delayed cytoprotection induced by curcumin acted through Grp94, because the curcumin-induced increase in Grp94 expression was hampered by either stable or transient transfection with antisense cDNA; in these latter cells, the extent of total protein oxidation, as well as the translocation of NF-kappaB to the nucleus, and the percentage of apoptotic cells were comparable to those observed in both curcumin-untreated wild-type and empty vector transfected cells. Defining the mechanism(s) by which Grp94 exerts its antioxidant defence, the determination of cytosolic calcium levels in C2C12 cells by fura-2 showed a significantly reduced amount of releasable calcium from intracellular stores, both in conditions of Grp94 overexpression and after curcumin pre-treatment. Therefore, a brief exposure to curcumin induces a delayed cytoprotection against oxidative stress in myogenic cells by increasing Grp94 protein level, which acts as a regulator of calcium homeostasis.

  19. ROS accumulation and antiviral defence control by microRNA528 in rice.

    PubMed

    Wu, Jianguo; Yang, Rongxin; Yang, Zhirui; Yao, Shengze; Zhao, Shanshan; Wang, Yu; Li, Pingchuan; Song, Xianwei; Jin, Lian; Zhou, Tong; Lan, Ying; Xie, Lianhui; Zhou, Xueping; Chu, Chengcai; Qi, Yijun; Cao, Xiaofeng; Li, Yi

    2017-01-06

    MicroRNAs (miRNAs) are key regulators of plant-pathogen interactions. Modulating miRNA function has emerged as a new strategy to produce virus resistance traits(1-5). However, the miRNAs involved in antiviral defence and the underlying mechanisms remain largely elusive. We previously demonstrated that sequestration by Argonaute (AGO) proteins plays an important role in regulating miRNA function in antiviral defence pathways(6). Here we reveal that cleavage-defective AGO18 complexes sequester microRNA528 (miR528) upon viral infection. We show that miR528 negatively regulates viral resistance in rice by cleaving L-ascorbate oxidase (AO) messenger RNA, thereby reducing AO-mediated accumulation of reactive oxygen species. Upon viral infection, miR528 becomes preferentially associated with AGO18, leading to elevated AO activity, higher basal reactive oxygen species accumulation and enhanced antiviral defence. Our findings reveal a mechanism in which antiviral defence is boosted through suppression of an miRNA that negatively regulates viral resistance. This mechanism could be manipulated to engineer virus-resistant crop plants.

  20. Regulation of neuronal growth cone filopodia by nitric oxide.

    PubMed

    Van Wagenen, S; Rehder, V

    1999-05-01

    Nitric oxide (NO) has been proposed to play an important role during neuronal development. Since many of its effects occur during the time of growth cone pathfinding and target interaction, we here test the hypothesis that part of NO's effects might be exerted at the growth cone. We found that low concentrations of the NO-donors DEA/NO, SIN-1, and SNP caused a rapid and transient elongation of filopodia as well as a reduction in filopodial number. These effects resulted from distinct changes in filopodial extension and retraction rates. Our novel findings suggest that NO could play a physiological role by temporarily changing a growth cone's morphology and switching its behavior from a close-range to a long-range exploratory mode. We subsequently dissected the pathway by which NO acted on growth cones. The effect of NO donors on filopodial length could be blocked by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of soluble guanylyl cyclase (sGC), indicating that NO acted via sGC. Supporting this idea, injection of cyclic GMP (cGMP) mimicked the effect of NO donors on growth cone filopodia. Moreover, application of NO-donors as well as injection of cGMP elicited a rapid and transient rise in intracellular calcium in growth cones, indicating that NO acted via cGMP to elevate calcium. This calcium rise, as well as the morphological effects of SIN-1 on filopodia, were blocked by preventing calcium entry. Given the role of filopodia in axonal guidance, our new data suggest that NO could function at the neuronal growth cone as an intracellular and/or intercellular signaling molecule by affecting steering decisions during neuronal pathfinding.

  1. Nitric oxide regulates retinal vascular tone in humans.

    PubMed

    Dorner, Guido T; Garhofer, Gerhard; Kiss, Barbara; Polska, Elzbieta; Polak, Kaija; Riva, Charles E; Schmetterer, Leopold

    2003-08-01

    The purpose of the present study was to investigate the contribution of basal nitric oxide (NO) on retinal vascular tone in humans. In addition, we set out to elucidate the role of NO in flicker-induced retinal vasodilation in humans. Twelve healthy young subjects were studied in a three-way crossover design. Subjects received an intravenous infusion of either placebo or NG-monomethyl-L-arginine (L-NMMA; 3 or 6 mg/kg over 5 min), an inhibitor of NO synthase. Thereafter, diffuse luminance flicker was consecutively performed for 16, 32, and 64 s at a frequency of 8 Hz. The effect of L-NMMA on retinal arterial and venous diameter was assessed under resting conditions and during the hyperemic flicker response. Retinal vessel diameter was measured with a Zeiss retinal vessel analyzer. L-NMMA significantly reduced arterial diameter (3 mg/kg: -2%; 6 mg/kg: -4%, P < 0.001) and venous diameter (3 mg/kg: -5%; 6 mg/kg: -8%, P < 0.001). After placebo infusion, flicker induced a significant increase in retinal vessel diameter (P < 0.001). At a flicker duration of 64 s, arterial diameter increased by 4% and venous diameter increased by 3%. L-NMMA did not abolish these hyperemic responses but blunted venous vasodilation (P = 0.017) and arterial vasodilation (P = 0.02) in response to flicker stimulation. Our data indicate that NO contributes to basal retinal vascular tone in humans. In addition, NO appears to play a role in flicker-induced vasodilation of the human retinal vasculature.

  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. New insights into the regulation of plant immunity by amino acid metabolic pathways.

    PubMed

    Zeier, Jürgen

    2013-12-01

    Besides defence pathways regulated by classical stress hormones, distinct amino acid metabolic pathways constitute integral parts of the plant immune system. Mutations in several genes involved in Asp-derived amino acid biosynthetic pathways can have profound impact on plant resistance to specific pathogen types. For instance, amino acid imbalances associated with homoserine or threonine accumulation elevate plant immunity to oomycete pathogens but not to pathogenic fungi or bacteria. The catabolism of Lys produces the immune signal pipecolic acid (Pip), a cyclic, non-protein amino acid. Pip amplifies plant defence responses and acts as a critical regulator of plant systemic acquired resistance, defence priming and local resistance to bacterial pathogens. Asp-derived pyridine nucleotides influence both pre- and post-invasion immunity, and the catabolism of branched chain amino acids appears to affect plant resistance to distinct pathogen classes by modulating crosstalk of salicylic acid- and jasmonic acid-regulated defence pathways. It also emerges that, besides polyamine oxidation and NADPH oxidase, Pro metabolism is involved in the oxidative burst and the hypersensitive response associated with avirulent pathogen recognition. Moreover, the acylation of amino acids can control plant resistance to pathogens and pests by the formation of protective plant metabolites or by the modulation of plant hormone activity.

  4. Ascorbic Acid (Vitamin C) in Defence Feeding,

    DTIC Science & Technology

    1982-09-01

    k ARD-Ai25 944 ASCORBIC ACID ( VITAMIN C) IN DEFENCE FEEDING(U) ARMED I/i I FORCES FOOD SCIENCE ESTABLISHMENT SCOTTSDALE I NOSFE (AUSTRALIA) C H4...1963 A . , r ’ . - -~ . * u ,. l m -, -’ W - -r n UNCLASSIFIED l. ~kc 3 27 3 ’" * ASCORBIC ACID ( VITAMIN C) IN DEFENCE FEEDING by C. H. FORBES-EWAN...fresh vegetables could prevent and cure scurvy, it was not until the early 20th Century that the factor involved, vitamin C, was purified. Vitamin C

  5. Oxidative stress activates a specific p53 transcriptional response that regulates cellular senescence and aging

    PubMed Central

    Gambino, Valentina; De Michele, Giulia; Venezia, Oriella; Migliaccio, Pierluigi; Dall'Olio, Valentina; Bernard, Loris; Minardi, Simone Paolo; Fazia, Maria Agnese Della; Bartoli, Daniela; Servillo, Giuseppe; Alcalay, Myriam; Luzi, Lucilla; Giorgio, Marco; Scrable, Heidi; Pelicci, Pier Giuseppe; Migliaccio, Enrica

    2013-01-01

    Oxidative stress is a determining factor of cellular senescence and aging and a potent inducer of the tumour-suppressor p53. Resistance to oxidative stress correlates with delayed aging in mammals, in the absence of accelerated tumorigenesis, suggesting inactivation of selected p53-downstream pathways. We investigated p53 regulation in mice carrying deletion of p66, a mutation that retards aging and confers cellular resistance and systemic resistance to oxidative stress. We identified a transcriptional network of ∼200 genes that are repressed by p53 and encode for determinants of progression through mitosis or suppression of senescence. They are selectively down-regulated in cultured fibroblasts after oxidative stress, and, in vivo, in proliferating tissues and during physiological aging. Selectivity is imposed by p66 expression and activation of p44/p53 (also named Delta40p53), a p53 isoform that accelerates aging and prevents mitosis after protein damage. p66 deletion retards aging and increases longevity of p44/p53 transgenic mice. Thus, oxidative stress activates a specific p53 transcriptional response, mediated by p44/p53 and p66, which regulates cellular senescence and aging. PMID:23448364

  6. Oxidants Positively or Negatively Regulate Nuclear Factor κB in a Context-dependent Manner*

    PubMed Central

    Loukili, Noureddine; Rosenblatt-Velin, Nathalie; Rolli, Joëlle; Levrand, Sandra; Feihl, François; Waeber, Bernard; Pacher, Pal; Liaudet, Lucas

    2010-01-01

    Redox-based mechanisms play critical roles in the regulation of multiple cellular functions. NF-κB, a master regulator of inflammation, is an inducible transcription factor generally considered to be redox-sensitive, but the modes of interactions between oxidant stress and NF-κB are incompletely defined. Here, we show that oxidants can either amplify or suppress NF-κB activation in vitro by interfering both with positive and negative signals in the NF-κB pathway. NF-κB activation was evaluated in lung A549 epithelial cells stimulated with tumor necrosis factor α (TNFα), either alone or in combination with various oxidant species, including hydrogen peroxide or peroxynitrite. Exposure to oxidants after TNFα stimulation produced a robust and long lasting hyperactivation of NF-κB by preventing resynthesis of the NF-κB inhibitor IκB, thereby abrogating the major negative feedback loop of NF-κB. This effect was related to continuous activation of inhibitor of κB kinase (IKK), due to persistent IKK phosphorylation consecutive to oxidant-mediated inactivation of protein phosphatase 2A. In contrast, exposure to oxidants before TNFα stimulation impaired IKK phosphorylation and activation, leading to complete prevention of NF-κB activation. Comparable effects were obtained when interleukin-1β was used instead of TNFα as the NF-κB activator. This study demonstrates that the influence of oxidants on NF-κB is entirely context-dependent, and that the final outcome (activation versus inhibition) depends on a balanced inhibition of protein phosphatase 2A and IKK by oxidant species. Our findings provide a new conceptual framework to understand the role of oxidant stress during inflammatory processes. PMID:20299457

  7. 50 years of biological research--from oxidative phosphorylation to energy requiring transport regulation.

    PubMed

    Kalckar, H M

    1991-01-01

    In 1930 adenosine triphosphate appeared in the literature from W. A. Engelhardt's work on avian erythrocytes. This was an early example of oxidative phosphorylation in intact cells, and it required methylene blue and oxygen. Both Belitser and I realized that the use of Warburg manometers for aeration was critical in order to generate oxidative phosphorylation of glucose in tissue preparations. Test tube techniques did not work. In 1956 we were able to describe a human type of diabetes called "galactose diabetes," in which consumption of human or cows' milk provokes mental retardation. Replacement of human or cows' milk products with "vegetable milk" formula in early infancy can prevent retardation. We determined that the disease results from a defect of galactose-one-phosphate uridylyl-transferase, a hereditary enzyme. This type of enzyme defect, if discovered and treated in early infancy, is a benign molecular disease. Regulation of transport systems in mammalian cell cultures are frequently complex energized systems. Perhaps my greatest surprise in this regard was the mere fact that an all-cis "odd" hexose-D-allose turned out to be a highly intense down-regulator of the hexose transport system. Additions of inhibitors of oxidative phosphorylation (such as oligomycin or di-nitrophenol) arrested the allose-mediated down-regulation. We have reason to suspect that the strong down-regulator is a phosphorylated form of D-allose. Thus ends my story about oxidative energized biological phosphorylation systems.

  8. 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

  9. S-Nitrosation and regulation of inducible nitric oxide synthase.

    PubMed

    Mitchell, Douglas A; Erwin, Phillip A; Michel, Thomas; Marletta, Michael A

    2005-03-29

    The inducible isoform of nitric oxide synthase (iNOS) and three zinc tetrathiolate mutants (C104A, C109A, and C104A/C109A) were expressed in Escherichia coli and purified. The mutants were found by ICP-AES and the zinc-specific PAR colorimetric assay to be zinc free, whereas the wild-type iNOS zinc content was 0.38 +/- 0.01 mol of Zn/mol of iNOS dimer. The cysteine mutants (C104A and C109A) had an activity within error of wild-type iNOS (2.24 +/- 0.12 micromol of NO min(-1) mg(-1)), but the double cysteine mutant had a modestly decreased activity (1.75 +/- 0.14 micromol of NO min(-1) mg(-1)). To determine if NO could stimulate release of zinc and dimer dissociation, wild-type protein was allowed to react with an NO donor, DEA/NO, followed by buffer exchange. ICP-AES of samples treated with 10 microM DEA/NO showed a decrease in zinc content (0.23 +/- 0.01 to 0.09 +/- 0.01 mol of Zn/mol of iNOS dimer) with no loss of heme iron. Gel filtration of wild-type iNOS treated similarly resulted in approximately 20% more monomeric iNOS compared to a DEA-treated sample. Only wild-type iNOS had decreased activity (42 +/- 2%) after reaction with 50 microM DEA/NO compared to a control sample. Using the biotin switch method under the same conditions, only wild-type iNOS had increased levels of S-biotinylation. S-Biotinylation was mapped to C104 and C109 on wild-type iNOS using LysC digestion and MALDI-TOF/TOF MS. Immunoprecipitation of iNOS from the mouse macrophage cell line, RAW-264.7, and the biotin switch method were used to confirm endogenous S-nitrosation of iNOS. The data show that S-nitrosation of the zinc tetrathiolate cysteine results in zinc release from the dimer interface and formation of inactive monomers, suggesting that this mode of inhibition might occur in vivo.

  10. 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

  11. Future directions in the ontogeny of plant defence: understanding the evolutionary causes and consequences.

    PubMed

    Barton, Kasey E; Boege, Karina

    2017-04-01

    Plant defence often varies by orders of magnitude as plants develop from the seedling to juvenile to mature and senescent stages. Ontogenetic trajectories can involve switches among defence traits, leading to complex shifting phenotypes across plant lifetimes. While considerable research has characterised ontogenetic trajectories for now hundreds of plant species, we still lack a clear understanding of the molecular, ecological and evolutionary factors driving these patterns. In this study, we identify several non-mutually exclusive factors that may have led to the evolution of ontogenetic trajectories in plant defence, including developmental constraints, resource allocation costs, multi-functionality of defence traits, and herbivore selection pressure. Evidence from recent physiological studies is highlighted to shed light on the underlying molecular mechanisms involved in the regulation and activation of these developmental changes. Overall, our goal is to promote new research avenues that would provide evidence for the factors that have promoted the evolution of this complex lifetime phenotype. Future research focusing on the questions and approaches identified here will advance the field and shed light on why defence traits shift so dramatically across plant ontogeny, a widespread but poorly understood ecological pattern.

  12. Plant defence suppression is mediated by a fungal sirtuin during rice infection by Magnaporthe oryzae.

    PubMed

    Fernandez, Jessie; Marroquin-Guzman, Margarita; Nandakumar, Renu; Shijo, Sara; Cornwell, Kathryn M; Li, Gang; Wilson, Richard A

    2014-10-01

    Crop destruction by the hemibiotrophic rice pathogen Magnaporthe oryzae requires plant defence suppression to facilitate extensive biotrophic growth in host cells before the onset of necrosis. How this is achieved at the genetic level is not well understood. Here, we report that a M. oryzae sirtuin, MoSir2, plays an essential role in rice defence suppression and colonization by controlling superoxide dismutase (SOD) gene expression. Loss of MoSir2 function in Δsir2 strains did not affect appressorial function, but biotrophic growth in rice cells was attenuated. Compared to wild type, Δsir2 strains failed to neutralize plant-derived reactive oxygen species (ROS) and elicited robust defence responses in rice epidermal cells that included elevated pathogenesis-related gene expression and granular depositions. Deletion of a SOD-encoding gene under MoSir2 control generated Δsod1 deletion strains that mimicked Δsir2 for impaired rice defence suppression, confirming SOD activity as a downstream output of MoSir2. In addition, comparative protein acetylation studies and forward genetic analyses identified a JmjC domain-containing protein as a likely target of MoSir2, and a Δsir2 Δjmjc double mutant was restored for MoSOD1 expression and defence suppression in rice epidermal cells. Together, this work reveals MoSir2 and MoJmjC as novel regulators of early rice cell infection.

  13. The nexus between growth and defence signalling: auxin and cytokinin modulate plant immune response pathways.

    PubMed

    Naseem, Muhammad; Kaltdorf, Martin; Dandekar, Thomas

    2015-08-01

    Plants deploy a finely tuned balance between growth and defence responses for better fitness. Crosstalk between defence signalling hormones such as salicylic acid (SA) and jasmonates (JAs) as well as growth regulators plays a significant role in mediating the trade-off between growth and defence in plants. Here, we specifically discuss how the mutual antagonism between the signalling of auxin and SA impacts on plant growth and defence. Furthermore, the synergism between auxin and JA benefits a class of plant pathogens. JA signalling also poses growth cuts through auxin. We discuss how the effect of cytokinins (CKs) is multifaceted and is effective against a broad range of pathogens in mediating immunity. The synergism between CKs and SA promotes defence against biotrophs. Reciprocally, SA inhibits CK-mediated growth responses. Recent reports show that CKs promote JA responses; however, in a feedback loop, JA suppresses CK responses. We also highlight crosstalk between auxin and CKs and discuss their antagonistic effects on plant immunity. Efforts to minimize the negative effects of auxin on immunity and a reduction in SA- and JA-mediated growth losses should lead to better sustainable plant protection strategies.

  14. Myzus persicae (green peach aphid) salivary components induce defence responses in Arabidopsis thaliana.

    PubMed

    De Vos, Martin; Jander, Georg

    2009-11-01

    Myzus persicae (green peach aphid) feeding on Arabidopsis thaliana induces a defence response, quantified as reduced aphid progeny production, in infested leaves but not in other parts of the plant. Similarly, infiltration of aphid saliva into Arabidopsis leaves causes only a local increase in aphid resistance. Further characterization of the defence-eliciting salivary components indicates that Arabidopsis recognizes a proteinaceous elicitor with a size between 3 and 10 kD. Genetic analysis using well-characterized Arabidopsis mutants shows that saliva-induced resistance against M. persicae is independent of the known defence signalling pathways involving salicylic acid, jasmonate and ethylene. Among 78 Arabidopsis genes that were induced by aphid saliva infiltration, 52 had been identified previously as aphid-induced, but few are responsive to the well-known plant defence signalling molecules salicylic acid and jasmonate. Quantitative PCR analyses confirm expression of saliva-induced genes. In particular, expression of a set of O-methyltransferases, which may be involved in the synthesis of aphid-repellent glucosinolates, was significantly up-regulated by both M. persicae feeding and treatment with aphid saliva. However, this did not correlate with increased production of 4-methoxyindol-3-ylmethylglucosinolate, suggesting that aphid salivary components trigger an Arabidopsis defence response that is independent of this aphid-deterrent glucosinolate.

  15. Cellular bioenergetics is regulated by PARP1 under resting conditions and during oxidative stress

    PubMed Central

    Módis, Katalin; Gerő, Domokos; Erdélyi, Katalin; Szoleczky, Petra; DeWitt, Douglas; Szabo, Csaba

    2012-01-01

    Purpose The goal of the current studies was to elucidate the role of the principal poly(ADP-ribose)polymerase isoform, PARP1 in the regulation of cellular energetics in endothelial cells under resting conditions and during oxidative stress. Methods We utilized bEnd.3 endothelial cells and A549 human transformed epithelial cells. PARP1 was inhibited either by pharmacological inhibitors or by siRNA silencing. The Seahorse XF24 Extracellular Flux Analyzer was used to measure indices of mitochondrial respiration (oxygen consumption rate) and of glycolysis (extracellular acidification rate). Cell viability, cellular and mitochondrial NAD+ levels and mitochondrial biogenesis were also measured. Results Silencing of PARP1 increased basal cellular parameters of oxidative phosphorylation, providing direct evidence that PARP1 is a regulator of mitochondrial function in resting cells. Pharmacological inhibitors of PARP1 and siRNA silencing of PARP1 protected against the development of mitochondrial dysfunction and elevated the respiratory reserve capacity in endothelial cells exposed to oxidative stress. The observed effects were unrelated to an effect on mitochondrial biogenesis. Isolated mitochondria of A549 human transformed epithelial cells exhibited an improved resting bioenergetic status after stable lentiviral silencing of PARP1; these effects were associated with elevated resting mitochondrial NAD+ levels in PARP1 silenced cells. Conclusions PARP1 is a regulator of basal cellular energetics in resting endothelial and epithelial cells. Furthermore, endothelial cells respond with a decrease in their mitochondrial reserve capacity during low-level oxidative stress, an effect, which is attenuated by PARP1 inhibition. While PARP1 is a regulator of oxidative phosphorylation in resting and oxidatively stressed cells, it only exerts a minor effect on glycolysis. PMID:22198485

  16. Regulation of dissimilatory sulfur oxidation in the purple sulfur bacterium allochromatium vinosum.

    PubMed

    Grimm, Frauke; Franz, Bettina; Dahl, Christiane

    2011-01-01

    In the purple sulfur bacterium Allochromatium vinosum, thiosulfate oxidation is strictly dependent on the presence of three periplasmic Sox proteins encoded by the soxBXAK and soxYZ genes. It is also well documented that proteins encoded in the dissimilatory sulfite reductase (dsr) operon, dsrABEFHCMKLJOPNRS, are essential for the oxidation of sulfur that is stored intracellularly as an obligatory intermediate during the oxidation of thiosulfate and sulfide. Until recently, detailed knowledge about the regulation of the sox genes was not available. We started to fill this gap and show that these genes are expressed on a low constitutive level in A. vinosum in the absence of reduced sulfur compounds. Thiosulfate and possibly sulfide lead to an induction of sox gene transcription. Additional translational regulation was not apparent. Regulation of soxXAK is probably performed by a two-component system consisting of a multi-sensor histidine kinase and a regulator with proposed di-guanylate cyclase activity. Previous work already provided some information about regulation of the dsr genes encoding the second important sulfur-oxidizing enzyme system in the purple sulfur bacterium. The expression of most dsr genes was found to be at a low basal level in the absence of reduced sulfur compounds and enhanced in the presence of sulfide. In the present work, we focused on the role of DsrS, a protein encoded by the last gene of the dsr locus in A. vinosum. Transcriptional and translational gene fusion experiments suggest a participation of DsrS in the post-transcriptional control of the dsr operon. Characterization of an A. vinosum ΔdsrS mutant showed that the monomeric cytoplasmic 41.1-kDa protein DsrS is important though not essential for the oxidation of sulfur stored in the intracellular sulfur globules.

  17. Oxidative regulation of the Na(+)-K(+) pump in the cardiovascular system.

    PubMed

    Figtree, Gemma A; Keyvan Karimi, Galougahi; Liu, Chia-Chi; Rasmussen, Helge H

    2012-12-15

    The Na(+)-K(+) pump is an essential heterodimeric membrane protein, which maintains electrochemical gradients for Na(+) and K(+) across cell membranes in all tissues. We have identified glutathionylation, a reversible posttranslational redox modification, of the Na(+)-K(+) pump's β1 subunit as a regulatory mechanism of pump activity. Oxidative inhibition of the Na(+)-K(+) pump by angiotensin II- and β1-adrenergic receptor-coupled signaling via NADPH oxidase activation demonstrates the relevance of this regulatory mechanism in cardiovascular physiology and pathophysiology. This has implications for dysregulation of intracellular Na(+) and Ca(2+) as well as increased oxidative stress in heart failure, myocardial ischemia-reperfusion, and regulation of vascular tone under conditions of elevated oxidative stress. Treatment strategies that are able to reverse this oxidative inhibition of the Na(+)-K(+) pump have the potential for cardiovascular-protective effects. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Biological methane oxidation: regulation, biochemistry, and active site structure of particulate methane monooxygenase.

    PubMed

    Lieberman, Raquel L; Rosenzweig, Amy C

    2004-01-01

    Particulate methane monooxygenase (pMMO) is a three-subunit integral membrane enzyme that catalyzes the oxidation of methane to methanol. Although pMMO is the predominant methane oxidation catalyst in nature, it has proved difficult to isolate, and most questions regarding its molecular structure, active site composition, chemical mechanism, and genetic regulation remain unanswered. Copper ions are believed to play a key role in both pMMO regulation and catalysis, and there is some evidence that the enzyme contains iron as well. A number of research groups have solubilized and purified or partially purified pMMO. These preparations have been characterized by biochemical and biophysical methods. In addition, aspects of methane monooxygenase gene regulation and copper accumulation in methanotrophs have been studied. This review summarizes for the first time the often controversial pMMO literature, focusing on recent progress and highlighting unresolved issues.

  19. Oxidative stress-responsive microRNA-320 regulates glycolysis in diverse biological systems

    PubMed Central

    Tang, Huibin; Lee, Myung; Sharpe, Orr; Salamone, Louis; Noonan, Emily J.; Hoang, Chuong D.; Levine, Sanford; Robinson, William H.; Shrager, Joseph B.

    2012-01-01

    Glycolysis is the initial step of glucose catabolism and is up-regulated in cancer cells (the Warburg Effect). Such shifts toward a glycolytic phenotype have not been explored widely in other biological systems, and the molecular mechanisms underlying the shifts remain unknown. With proteomics, we observed increased glycolysis in disused human diaphragm muscle. In disused muscle, lung cancer, and H2O2-treated myotubes, we show up-regulation of the rate-limiting glycolytic enzyme muscle-type phosphofructokinase (PFKm, >2 fold, P<0.05) and accumulation of lactate (>150%, P<0.05). Using microRNA profiling, we identify miR-320a as a regulator of PFKm expression. Reduced miR-320a levels (to ∼50% of control, P<0.05) are associated with the increased PFKm in each of these diverse systems. Manipulation of miR-320a levels both in vitro and in vivo alters PFKm and lactate levels in the expected directions. Further, miR-320a appears to regulate oxidative stress-induced PFKm expression, and reduced miR-320a allows greater induction of glycolysis in response to H2O2 treatment. We show that this microRNA-mediated regulation occurs through PFKm's 3′ untranslated region and that Ets proteins are involved in the regulation of PFKm via miR-320a. These findings suggest that oxidative stress-responsive microRNA-320a may regulate glycolysis broadly within nature.—Tang, H., Lee, M., Sharpe, O., Salamone, L., Noonan, E. J., Hoang, C. D., Levine, S., Robinson, W. H., Shrager, J. B. Oxidative stress-responsive microRNA-320 regulates glycolysis in diverse biological systems. PMID:22767230

  20. Dopamine signaling regulates fat content through β-oxidation in Caenorhabditis elegans.

    PubMed

    Barros, Alexandre Guimarães de Almeida; Bridi, Jessika Cristina; de Souza, Bruno Rezende; de Castro Júnior, Célio; de Lima Torres, Karen Cecília; Malard, Leandro; Jorio, Ado; de Miranda, Débora Marques; Ashrafi, Kaveh; Romano-Silva, Marco Aurélio

    2014-01-01

    The regulation of energy balance involves an intricate interplay between neural mechanisms that respond to internal and external cues of energy demand and food availability. Compelling data have implicated the neurotransmitter dopamine as an important part of body weight regulation. However, the precise mechanisms through which dopamine regulates energy homeostasis remain poorly understood. Here, we investigate mechanisms through which dopamine modulates energy storage. We showed that dopamine signaling regulates fat reservoirs in Caenorhabditis elegans. We found that the fat reducing effects of dopamine were dependent on dopaminergic receptors and a set of fat oxidation enzymes. Our findings reveal an ancient role for dopaminergic regulation of fat and suggest that dopamine signaling elicits this outcome through cascades that ultimately mobilize peripheral fat depots.

  1. Dopamine Signaling Regulates Fat Content through β-Oxidation in Caenorhabditis elegans

    PubMed Central

    Barros, Alexandre Guimarães de Almeida; Bridi, Jessika Cristina; de Souza, Bruno Rezende; de Castro Júnior, Célio; de Lima Torres, Karen Cecília; Malard, Leandro; Jorio, Ado; de Miranda, Débora Marques; Ashrafi, Kaveh; Romano-Silva, Marco Aurélio

    2014-01-01

    The regulation of energy balance involves an intricate interplay between neural mechanisms that respond to internal and external cues of energy demand and food availability. Compelling data have implicated the neurotransmitter dopamine as an important part of body weight regulation. However, the precise mechanisms through which dopamine regulates energy homeostasis remain poorly understood. Here, we investigate mechanisms through which dopamine modulates energy storage. We showed that dopamine signaling regulates fat reservoirs in Caenorhabditis elegans. We found that the fat reducing effects of dopamine were dependent on dopaminergic receptors and a set of fat oxidation enzymes. Our findings reveal an ancient role for dopaminergic regulation of fat and suggest that dopamine signaling elicits this outcome through cascades that ultimately mobilize peripheral fat depots. PMID:24465759

  2. [Defects in antioxidant defence enhance glyoxal toxicity in the yeast Saccharomyces cerevisiae].

    PubMed

    Semchyshyn, H M

    2013-01-01

    Glyoxal being either exogenous or endogenous compound belongs to reactive carbonyl species. In particular, its level increases under disturbance of the balance of glucose intracellular metabolism as well as of other reductive carbohydrates. Having two carbonyl reactive groups, glyoxal readily enters glycation reaction that results in carbonyl stress development. Investigations of different model systems demonstrate a strong relationship between carbonyl and oxidative stress. However, a possible role of antioxidant system in the organisms' defence against carbonyl stress is poor understood. In addition, the influence of glyoxal on living organisms is less studied than the effect of such carbonyl reactive species as malonic aldehyde or methylglyoxal. To study a potential role of antioxidant system in organisms' defence against carbonyl stress induced by glyoxal, the baker's yeast Saccharomyces cerevisiae was used. It has been found that strains with different defects in the antioxidant defence were more sensitive to glyoxal as compared with parental wild strain. Therefore, the data obtained in the present study confirm the relationship between carbonyl and oxidative stress and reveal the important role of antioxidant system in baker's yeast defence against carbonyl stress induced by glyoxal.

  3. 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.

  4. Brain stem oxidative stress and its associated signaling in the regulation of sympathetic vasomotor tone.

    PubMed

    Chan, Samuel H H; Chan, Julie Y H

    2012-12-15

    There is now compelling evidence from studies in humans and animals that overexcitation of the sympathetic nervous system plays an important role in the pathogenesis of cardiovascular diseases. An excellent example is neurogenic hypertension, in which central sympathetic overactivation is involved in the development, staging, and progression of the disease, and one of the underlying mechanisms involves oxidative stress in key brain stem sites that are engaged in the regulation of sympathetic vasomotor tone. Using the rostral ventrolateral medulla (RVLM) and nucleus tractus solitarii (NTS) as two illustrative brain stem neural substrates, this article provides an overview of the impact of reactive oxygen species and antioxidants on RVLM and NTS in the pathogenesis of neurogenic hypertension. This is followed by a discussion of the redox-sensitive signaling pathways, including several kinases, ion channels, and transcription factors that underpin the augmentation in sympathetic vasomotor tone. In addition, the emerging view that brain stem oxidative stress is also causally related to a reduction in sympathetic vasomotor tone and hypotension during brain stem death, methamphetamine intoxication, and temporal lobe status epilepticus will be presented, along with the causal contribution of the oxidant peroxynitrite formed by a reaction between nitric oxide synthase II (NOS II)-derived nitric oxide and superoxide. Also discussed as a reasonable future research direction is dissection of the cellular mechanisms and signaling cascades that may underlie the contributory role of nitric oxide generated by different NOS isoforms in the differential effects of oxidative stress in the RVLM or NTS on sympathetic vasomotor tone.

  5. 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…

  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. Swedish Defence Acquisition Transformation: A Research Agenda

    DTIC Science & Technology

    2015-05-13

    presentation • A small country perspective • The swinging pendulum : “From preparedness to deployment to preparedness?” – or “from national defence to PSOs to...history of war The swinging (political) pendulum • A. 200 years of peace – Standing in preparedness • B. Post Cold War – Deployed on PSOs • C

  8. Driving Danish Defence Towards Political Goals

    DTIC Science & Technology

    2016-06-10

    everything from research methodology to English grammar . Your patience and understanding throughout the year have been admirable. My research committee... essential messages. The communication perspective focuses on how it was used in this particular change process, for enforcing leadership and the efficiency...structure of the analysis will be based on qualitative research, identifying essential communications from the Defence Senior Leadership and comparing

  9. Defence Output Measures: An Economics Perspective

    DTIC Science & Technology

    2011-11-01

    Des budgets de la comptabilité des intrants, des extrants, de la gestion et des ressources ont été utilisés comme mesures relatives aux résultats...This Report focused on financial management information (e.g. management of stocks and assets)) and made no mention of defence output measures. At

  10. Superconductivity: Recent Developments and Defence Applications

    DTIC Science & Technology

    1988-03-11

    particular interest to the defence community include: batteries , bearings, electromagnetic guns and launchers, energy storage, free electron lasers...has looked at muon spin rotation measurements of the penetration depth of magnetic fields into the superconductors. Basic research is under way at Chalk...and batteries (3) High density magnetic field transducers (4) Magnetic levitation (5) Magnetic, frictionless be arings (6) Magnetic separation (7

  11. 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,…

  12. Towards an internet civil defence against bioterrorism.

    PubMed

    LaPorte, R E; Sauer, F; Dearwater, S; Sekikawa, A; Sa, E R; Aaron, D; Shubnikov, E

    2001-09-01

    Approaches towards the public-health prevention of bioterrorism are too little, and too late. New information-based approaches could yield better homeland protection. An internet civil defence is presented where millions of eyes could help to identify suspected cases of bioterrorism, with the internet used to report, confirm, and prevent outbreaks.

  13. Probiotics: beneficial factors of the defence system.

    PubMed

    Antoine, Jean Michel

    2010-08-01

    Probiotics, defined as living micro-organisms that provide a health benefit to the host when ingested in adequate amounts, have been used traditionally as food components to help the body to recover from diarrhoea. They are commonly ingested as part of fermented foods, mostly in fresh fermented dairy products. They can interact with the host through different components of the gut defence systems. There is mounting clinical evidence that some probiotics, but not all, help the defence of the host as demonstrated by either a shorter duration of infections or a decrease in the host's susceptibility to pathogens. Different components of the gut barrier can be involved in the strengthening of the body's defences: the gut microbiota, the gut epithelial barrier and the immune system. Many studies have been conducted in normal free-living subjects or in subjects during common infections like the common cold and show that some probiotic-containing foods can improve the functioning of or strengthen the body's defence. Specific probiotic foods can be included in the usual balanced diet of consumers to help them to better cope with the daily challenges of their environment.

  14. 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

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

    2015-04-01

    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. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  15. 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

  16. 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.

  17. Regulation of Skeletal Muscle Oxidative Capacity and Muscle Mass by SIRT3

    PubMed Central

    Khalek, Waed Abdel; Ward, Jack Lee; Yang, Henry; Chabi, Béatrice; Wrutniak-Cabello, Chantal; Tong, Qiang

    2014-01-01

    We have previously reported that the expression of mitochondrial deacetylase SIRT3 is high in the slow oxidative muscle and that the expression of muscle SIRT3 level is increased by dietary restriction or exercise training. To explore the function of SIRT3 in skeletal muscle, we report here the establishment of a transgenic mouse model with muscle-specific expression of the murine SIRT3 short isoform (SIRT3M3). Calorimetry study revealed that the transgenic mice had increased energy expenditure and lower respiratory exchange rate (RER), indicating a shift towards lipid oxidation for fuel usage, compared to control mice. The transgenic mice exhibited better exercise performance on treadmills, running 45% further than control animals. Moreover, the transgenic mice displayed higher proportion of slow oxidative muscle fibers, with increased muscle AMPK activation and PPARδ expression, both of which are known regulators promoting type I muscle fiber specification. Surprisingly, transgenic expression of SIRT3M3 reduced muscle mass up to 30%, likely through an up-regulation of FOXO1 transcription factor and its downstream atrophy gene MuRF-1. In summary, these results suggest that SIRT3 regulates the formation of oxidative muscle fiber, improves muscle metabolic function, and reduces muscle mass, changes that mimic the effects of caloric restriction. PMID:24454908

  18. 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

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

    PubMed

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

    2015-08-27

    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.

  20. 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

  1. 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

  2. Histidine Regulates Seed Oil Deposition through Abscisic Acid Biosynthesis and β-Oxidation.

    PubMed

    Ma, Huimin; Wang, Shui

    2016-10-01

    The storage compounds are deposited into plant seeds during maturation. As the model oilseed species, Arabidopsis (Arabidopsis thaliana) has long been studied for seed oil deposition. However, the regulation of this process remains unclear. Through genetic screen with a seed oil body-specific reporter, we isolated low oil1 (loo1) mutant. LOO1 was mapped to HISTIDINE BIOSYNTHESIS NUMBER 1A (HISN1A). HISN1A catalyzes the first step of His biosynthesis. Oil significantly decreased, and conversely proteins markedly increased in hisn1a mutants, indicating that HISN1A regulates both oil accumulation and the oil-protein balance. HISN1A was predominantly expressed in embryos and root tips. Accordingly, the hisn1a mutants exhibited developmental phenotype especially of seeds and roots. Transcriptional profiling displayed that β-oxidation was the major metabolic pathway downstream of HISN1A β-Oxidation was induced in hisn1a mutants, whereas it was reduced in 35S:HISN1A-transgenic plants. In plants, seed storage oil is broken-down by β-oxidation, which is controlled by abscisic acid (ABA). We found that His activated genes of ABA biosynthesis and correspondingly advanced ABA accumulation. Exogenous ABA rescued the defects of hisn1a mutants, whereas mutation of ABA DEFICIENT2, a key enzyme in ABA biosynthesis, blocked the effect of His on β-oxidation, indicating that ABA mediates His regulation in β-oxidation. Intriguingly, structural analysis showed that a potential His-binding domain was present in the general amino acid sensors GENERAL CONTROL NON-DEREPRESSIBLE2 and PII, suggesting that His may serve as a signal molecule. Taken together, our study reveals that His promotes plant seed oil deposition through ABA biosynthesis and β-oxidation.

  3. 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

  4. Chromatin remodeling regulates catalase expression during cancer cells adaptation to chronic oxidative stress.

    PubMed

    Glorieux, Christophe; Sandoval, Juan Marcelo; Fattaccioli, Antoine; Dejeans, Nicolas; Garbe, James C; Dieu, Marc; Verrax, Julien; Renard, Patricia; Huang, Peng; Calderon, Pedro Buc

    2016-10-01

    Regulation of ROS metabolism plays a major role in cellular adaptation to oxidative stress in cancer cells, but the molecular mechanism that regulates catalase, a key antioxidant enzyme responsible for conversion of hydrogen peroxide to water and oxygen, remains to be elucidated. Therefore, we investigated the transcriptional regulatory mechanism controlling catalase expression in three human mammary cell lines: the normal mammary epithelial 250MK primary cells, the breast adenocarcinoma MCF-7 cells and an experimental model of MCF-7 cells resistant against oxidative stress resulting from chronic exposure to H2O2 (Resox), in which catalase was overexpressed. Here we identify a novel promoter region responsible for the regulation of catalase expression at -1518/-1226 locus and the key molecules that interact with this promoter and affect catalase transcription. We show that the AP-1 family member JunB and retinoic acid receptor alpha (RARα) mediate catalase transcriptional activation and repression, respectively, by controlling chromatin remodeling through a histone deacetylases-dependent mechanism. This regulatory mechanism plays an important role in redox adaptation to chronic exposure to H2O2 in breast cancer cells. Our study suggests that cancer adaptation to oxidative stress may be regulated by transcriptional factors through chromatin remodeling, and reveals a potential new mechanism to target cancer cells.

  5. Selective Up-regulation of Human Selenoproteins in Response to Oxidative Stress*

    PubMed Central

    Touat-Hamici, Zahia; Legrain, Yona; Bulteau, Anne-Laure; Chavatte, Laurent

    2014-01-01

    Selenocysteine is inserted into selenoproteins via the translational recoding of a UGA codon, normally used as a stop signal. This process depends on the nature of the selenocysteine insertion sequence element located in the 3′ UTR of selenoprotein mRNAs, selenium bioavailability, and, possibly, exogenous stimuli. To further understand the function and regulation of selenoproteins in antioxidant defense and redox homeostasis, we investigated how oxidative stress influences selenoprotein expression as a function of different selenium concentrations. We found that selenium supplementation of the culture media, which resulted in a hierarchical up-regulation of selenoproteins, protected HEK293 cells from reactive oxygen species formation. Furthermore, in response to oxidative stress, we identified a selective up-regulation of several selenoproteins involved in antioxidant defense (Gpx1, Gpx4, TR1, SelS, SelK, and Sps2). Interestingly, the response was more efficient when selenium was limiting. Although a modest change in mRNA levels was noted, we identified a novel translational control mechanism stimulated by oxidative stress that is characterized by up-regulation of UGA-selenocysteine recoding efficiency and relocalization of SBP2, selenocysteine-specific elongation factor, and L30 recoding factors from the cytoplasm to the nucleus. PMID:24706762

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

    PubMed

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

    2012-10-16

    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.

  7. 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

  8. Arginase regulates red blood cell nitric oxide synthase and export of cardioprotective nitric oxide bioactivity.

    PubMed

    Yang, Jiangning; Gonon, Adrian T; Sjöquist, Per-Ove; Lundberg, Jon O; Pernow, John

    2013-09-10

    The theory that red blood cells (RBCs) generate and release nitric oxide (NO)-like bioactivity has gained considerable interest. However, it remains unclear whether it can be produced by endothelial NO synthase (eNOS), which is present in RBCs, and whether NO can escape scavenging by hemoglobin. The aim of this study was to test the hypothesis that arginase reciprocally controls NO formation in RBCs by competition with eNOS for their common substrate arginine and that RBC-derived NO is functionally active following arginase blockade. We show that rodent and human RBCs contain functional arginase 1 and that pharmacological inhibition of arginase increases export of eNOS-derived nitrogen oxides from RBCs under basal conditions. The functional importance was tested in an ex vivo model of myocardial ischemia-reperfusion injury. Inhibitors of arginase significantly improved postischemic functional recovery in rat hearts if administered in whole blood or with RBCs in plasma. By contrast, arginase inhibition did not improve postischemic recovery when administered with buffer solution or plasma alone. The protective effect of arginase inhibition was lost in the presence of a NOS inhibitor. Moreover, hearts from eNOS(-/-) mice were protected when the arginase inhibitor was given with blood from wild-type donors. In contrast, when hearts from wild-type mice were given blood from eNOS(-/-) mice, the arginase inhibitor failed to protect against ischemia-reperfusion. These results strongly support the notion that RBCs contain functional eNOS and release NO-like bioactivity. This process is under tight control by arginase 1 and is of functional importance during ischemia-reperfusion.

  9. 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.

  10. The role of oxidized ATM in the regulation of oxidative stress-induced energy metabolism reprogramming of CAFs.

    PubMed

    Tang, Shifu; Yang, Li; Tang, Xi; Liu, Manran

    2014-10-28

    Cancer-associated fibroblasts (CAFs) are the predominant cell type in tumor microenvironment (TM) and featured with the distinct energy metabolism reprogramming (EMR) phenotype caused by many factors such as hypoxia and growth factors. The EMR of CAFs plays a key role in biological behaviors of cancer cells including proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Recently, accumulative evidence indicates that oxidative stress (OS) mediates the EMR of CAFs under conditions of various stimuli. However, the precise mechanism by which OS causes the EMR of CAFs is not clear. Interestingly, our previous work suggested that ataxia-telangiectasia mutated (ATM) signaling is activated independent of DNA double strand breaks (DSBs) in CAFs derived from human breast cancers compared with paired normal fibroblasts (NFs). Recent studies have shown that ATM protein kinase, as a redox sensor, is closely associated with cellular energy metabolism. Thus, it is very possible that ATM protein kinase regulates the EMR of CAFs. So, it is necessary to perform an integral study on how oxidized ATM regulates the EMR of CAFs in response to various stimuli evoking OS. This will facilitate to develop a new powerful strategy of preventing and treating cancers. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Monophosphoryl lipid A stimulated up-regulation of nitric oxide synthase and nitric oxide release by human monocytes in vitro.

    PubMed

    Saha, D C; Astiz, M E; Lin, R Y; Rackow, E C; Eales, L J

    1997-10-01

    Monophosphoryl lipid A (MPL) is a derivative of lipopolysaccharide (LPS) with reduced toxicity which has been shown to modulate various immune functions in monocytes. We examined whether human monocytes can be stimulated to produce nitric oxide (NO) and its catalytic enzyme nitric oxide synthase (NOS). Monocytes were stimulated with LPS or MPL and both NOS and NO (as nitrite) production were measured. MPL at high doses (> 100 micrograms/ml) stimulated monocytes to release NO that was significantly greater than both the control and LPS-treated monocytes (p < 0.05). NO release by control cells and the LPS treated cells was not significantly different. Both arginase and N-monomethyl arginine (NMLA) inhibited the MPL stimulated release of NO (p < 0.01). MPL significantly increased inducible NOS (iNOS) expression as measured by both fluorescent microscopy and flow cytometry (p < 0.05). Similarly, both soluble NOS (sNOS) and particulate NOS (pNOS) activity were significantly up-regulated by MPL (p < 0.05). Significant correlations were found between pNOS expression and sNOS release (r = 0.72, p < 0.0001) and between 12 h NO release and sNOS production (r = 0.44, p < 0.005). These experiments confirm that human monocytes can be stimulated with MPL to produce NO in vitro and suggest that up-regulation of pNOS does not preclude NO release.

  12. 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

  13. The bacterial response regulator ArcA uses a diverse binding site architecture to regulate carbon oxidation globally.

    PubMed

    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, σ(70)-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.

  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. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Subunit dependent oxidative stress sensitivity of LRRC8 volume regulated anion channels.

    PubMed

    Gradogna, Antonella; Gavazzo, Paola; Boccaccio, Anna; Pusch, Michael

    2017-08-25

    The volume-regulated anion channel (VRAC) is formed by heteromers of LRRC8 proteins containing the essential LRRC8A subunit and at least one among the LRRC8B-E subunits. Reactive oxygen species (ROS) play physiological and pathophysiological roles and VRAC channels are highly ROS sensitive. However, it is unclear if ROS act directly on the channels or on molecules involved in the activation pathway. We used fluorescently tagged LRRC8 proteins that yield large constitutive currents to test direct effects of oxidation. We found that 8A/8E heteromers are dramatically potentiated (more than 10-fold) by oxidation of intracellular cysteine residues by chloramine-T or tert-butyl hydroperoxide. Oxidation was, however, not necessary for hypotonicity induced activation. In contrast, 8A/8C and 8A/8D heteromers were strongly inhibited by oxidation. Endogenous VRAC currents in Jurkat T lymphocytes were similarly inhibited by oxidation, in agreement with the finding that LRRC8C and LRRC8D subunits were more abundantly expressed than LRRC8E in Jurkat cells. Our results show that LRRC8 channels are directly modulated by oxidation in a subunit dependent manner. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Cytoglobin regulates blood pressure and vascular tone through nitric oxide metabolism in the vascular wall

    NASA Astrophysics Data System (ADS)

    Liu, Xiaoping; El-Mahdy, Mohamed A.; Boslett, James; Varadharaj, Saradhadevi; Hemann, Craig; Abdelghany, Tamer M.; Ismail, Raed S.; Little, Sean C.; Zhou, Danlei; Thuy, Le Thi Thanh; Kawada, Norifumi; Zweier, Jay L.

    2017-04-01

    The identity of the specific nitric oxide dioxygenase (NOD) that serves as the main in vivo regulator of O2-dependent NO degradation in smooth muscle remains elusive. Cytoglobin (Cygb) is a recently discovered globin expressed in fibroblasts and smooth muscle cells with unknown function. Cygb, coupled with a cellular reducing system, efficiently regulates the rate of NO consumption by metabolizing NO in an O2-dependent manner with decreased NO consumption in physiological hypoxia. Here we show that Cygb is a major regulator of NO degradation and cardiovascular tone. Knockout of Cygb greatly prolongs NO decay, increases vascular relaxation, and lowers blood pressure and systemic vascular resistance. We further demonstrate that downregulation of Cygb prevents angiotensin-mediated hypertension. Thus, Cygb has a critical role in the regulation of vascular tone and disease. We suggest that modulation of the expression and NOD activity of Cygb represents a strategy for the treatment of cardiovascular disease.

  17. Cytoglobin regulates blood pressure and vascular tone through nitric oxide metabolism in the vascular wall

    PubMed Central

    Liu, Xiaoping; El-Mahdy, Mohamed A.; Boslett, James; Varadharaj, Saradhadevi; Hemann, Craig; Abdelghany, Tamer M.; Ismail, Raed S.; Little, Sean C.; Zhou, Danlei; Thuy, Le Thi Thanh; Kawada, Norifumi; Zweier, Jay L.

    2017-01-01

    The identity of the specific nitric oxide dioxygenase (NOD) that serves as the main in vivo regulator of O2-dependent NO degradation in smooth muscle remains elusive. Cytoglobin (Cygb) is a recently discovered globin expressed in fibroblasts and smooth muscle cells with unknown function. Cygb, coupled with a cellular reducing system, efficiently regulates the rate of NO consumption by metabolizing NO in an O2-dependent manner with decreased NO consumption in physiological hypoxia. Here we show that Cygb is a major regulator of NO degradation and cardiovascular tone. Knockout of Cygb greatly prolongs NO decay, increases vascular relaxation, and lowers blood pressure and systemic vascular resistance. We further demonstrate that downregulation of Cygb prevents angiotensin-mediated hypertension. Thus, Cygb has a critical role in the regulation of vascular tone and disease. We suggest that modulation of the expression and NOD activity of Cygb represents a strategy for the treatment of cardiovascular disease. PMID:28393874

  18. 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.

  19. 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

  20. Nitric oxide acts as a positive regulator to induce metamorphosis of the ascidian Herdmania momus.

    PubMed

    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

  1. Effect of gestation length on the levels of five innate defence proteins in human milk.

    PubMed

    Broadhurst, Marita; Beddis, Keryn; Black, Janet; Henderson, Harold; Nair, Arun; Wheeler, Thomas

    2015-01-01

    Human milk contains a range of host defence proteins that appear to contribute to health and wellbeing, but their variability in abundance among individuals has not been very well characterised. Milk from mothers of premature infants has altered composition, but the effect of gestation length on the host-defence properties of milk is not known. A study was therefore undertaken to determine the variability and effect of gestation length on the abundance of five host-defence proteins in milk; lactoferrin, secretory IgA, IgG, secretory component, and complement C3. Milk was obtained from 30 mothers at their second and fifth week of lactation. These were from three groups of ten mothers having had very premature (V; 28-32 weeks gestation), premature (P; 33-36 weeks) or full term deliveries (T; 37-41 weeks). The concentration of each of the five proteins was measured in each milk sample by either ELISA or quantitative western blotting. The concentration of IgG, and complement C3 ranged 22- and 17-fold respectively between mothers, while lactoferrin, secretory IgA, and secretory component ranged 7-, 9-, and 4-fold, respectively. The V group had significantly lower concentrations of four of the five proteins, the exception being IgG. Levels of these four proteins also decreased between weeks 2 and 5 of lactation in the P and T groups. Significant correlation was found between the concentrations of the host defence proteins within individual mothers, indicating some degree of co-ordinate regulation. Mothers vary widely in the levels of host defence proteins in milk. Very short gestation length results in decreased abundance of host-defence proteins in milk. This may have functional implications for very premature infants. Copyright © 2014 Elsevier Ltd. All rights reserved.

  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. 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

  4. Thiol switches in redox regulation of chloroplasts: balancing redox state, metabolism and oxidative stress.

    PubMed

    Dietz, Karl-Josef; Hell, Rüdiger

    2015-05-01

    In photosynthesizing chloroplasts, rapidly changing energy input, intermediate generation of strong reductants as well as oxidants and multiple participating physicochemical processes and pathways, call for efficient regulation. Coupling redox information to protein function via thiol modifications offers a powerful mechanism to activate, down-regulate and coordinate interdependent processes. Efficient thiol switching of target proteins involves the thiol-disulfide redox regulatory network, which is highly elaborated in chloroplasts. This review addresses the features of this network. Its conditional function depends on specificity of reduction and oxidation reactions and pathways, thiol redox buffering, but also formation of heterogeneous milieus by microdomains, metabolite gradients and macromolecular assemblies. One major player is glutathione. Its synthesis and function is under feedback redox control. The number of thiol-controlled processes and involved thiol switched proteins is steadily increasing, e.g., in tetrapyrrole biosynthesis, plastid transcription and plastid translation. Thus chloroplasts utilize an intricate and versatile redox regulatory network for intraorganellar and retrograde communication.

  5. Regulation of protein function by S-glutathiolation in response to oxidative and nitrosative stress.

    PubMed

    Klatt, P; Lamas, S

    2000-08-01

    Protein S-glutathiolation, the reversible covalent addition of glutathione to cysteine residues on target proteins, is emerging as a candidate mechanism by which both changes in the intracellular redox state and the generation of reactive oxygen and nitrogen species may be transduced into a functional response. This review will provide an introduction to the concepts of oxidative and nitrosative stress and outline the molecular mechanisms of protein regulation by oxidative and nitrosative thiol-group modifications. Special attention will be paid to recently published work supporting a role for S-glutathiolation in stress signalling pathways and in the adaptive cellular response to oxidative and nitrosative stress. Finally, novel insights into the molecular mechanisms of S-glutathiolation as well as methodological problems related to the interpretation of the biological relevance of this post-translational protein modification will be discussed.

  6. 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

  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. Trade-offs between constitutive and induced defences drive geographical and climatic clines in pine chemical defences.

    PubMed

    Moreira, Xoaquín; Mooney, Kailen A; Rasmann, Sergio; Petry, William K; Carrillo-Gavilán, Amparo; Zas, Rafael; Sampedro, Luis

    2014-05-01

    There is increasing evidence that geographic and climatic clines drive the patterns of plant defence allocation and defensive strategies. We quantified early growth rate and both constitutive and inducible chemical defences of 18 Pinaceae species in a common greenhouse environment and assessed their defensive allocation with respect to each species' range across climatic gradients spanning 31° latitude and 2300 m elevation. Constitutive defences traded-off with induced defences, and these defensive strategies were associated with growth rate such that slow-growing species invested more in constitutive defence, whereas fast-growing species invested more in inducible defence. The position of each pine species along this trade-off axis was in turn associated with geography; moving poleward and to higher elevations, growth rate and inducible defences decreased, while constitutive defence increased. These geographic patterns in plant defence were most strongly associated with variation in temperature. Climatic and geographical clines thus act as drivers of defence profiles by mediating the constraints imposed by trade-offs, and this dynamic underlays global patterns of defence allocation.

  9. Are natural antibodies involved in tumour defence?

    PubMed

    Bohn, J

    1999-09-01

    Natural antibodies (NAb) are found in the serum of healthy individuals. These antibodies are produced without any apparent specific antigenic stimulation. They are one part of the circulating immunoglobulins and are found in virtually all vertebrate species. NAb react to various self- and non-self antigens. A protective function in different infection models could be demonstrated. Several groups have reported the ability of NAb to bind to tumour cells. Their possible role in tumour defence is documented in mice. The present status of attempts to characterise the role of NAb in tumour defence is discussed, particularly as regards the human immune system. This paper focuses on antibody cell interactions and discusses the genetic background of the Nab-producing B-cells.

  10. 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.

  11. Autonomous Systems: Issues for Defence Policymakers

    DTIC Science & Technology

    2015-09-30

    this provision, but bullets tipped with poison or specifically designed to cause untreatable wounds would be. There is no reason why autonomous weapon...During the Cold War, defence planners faced a similar problem of ‘fragile stability’, whereby vulnerable nuclear arsenals incentivized an enemy to...in ways that are conducive to the cause of peace. An accelerated tempo of operations may lead to combat that is more chaotic, but not more

  12. Doubts about a classic defence of abortion.

    PubMed

    Difford, Jo

    2011-01-01

    Professor Judith Jarvis Thomson's seminal paper "A defence of abortion" published in 1971 has formed part of higher education syllabi for decades. In the paper Thomson criticizes one of the fundamental arguments against abortion, that is, the right of the foetus to life by denying that the foetus is a person. This article argues that her thought experiments do not compare to the reality of abortion and focuses on the influence of the paper on arguments concerning personhood.

  13. Neurons of self-defence: neuronal innervation of the exocrine defence glands in stick insects.

    PubMed

    Stolz, Konrad; von Bredow, Christoph-Rüdiger; von Bredow, Yvette M; Lakes-Harlan, Reinhard; Trenczek, Tina E; Strauß, Johannes

    2015-01-01

    Stick insects (Phasmatodea) use repellent chemical substances (allomones) for defence which are released from so-called defence glands in the prothorax. These glands differ in size between species, and are under neuronal control from the CNS. The detailed neural innervation and possible differences between species are not studied so far. Using axonal tracing, the neuronal innervation is investigated comparing four species. The aim is to document the complexity of defence gland innervation in peripheral nerves and central motoneurons in stick insects. In the species studied here, the defence gland is innervated by the intersegmental nerve complex (ISN) which is formed by three nerves from the prothoracic (T1) and suboesophageal ganglion (SOG), as well as a distinct suboesophageal nerve (Nervus anterior of the suboesophageal ganglion). In Carausius morosus and Sipyloidea sipylus, axonal tracing confirmed an innervation of the defence glands by this N. anterior SOG as well as N. anterior T1 and N. posterior SOG from the intersegmental nerve complex. In Peruphasma schultei, which has rather large defence glands, only the innervation by the N. anterior SOG was documented by axonal tracing. In the central nervous system of all species, 3-4 neuron types are identified by axonal tracing which send axons in the N. anterior SOG likely innervating the defence gland as well as adjacent muscles. These neurons are mainly suboesophageal neurons with one intersegmental neuron located in the prothoracic ganglion. The neuron types are conserved in the species studied, but the combination of neuron types is not identical. In addition, the central nervous system in S. sipylus contains one suboesophageal and one prothoracic neuron type with axons in the intersegmental nerve complex contacting the defence gland. Axonal tracing shows a very complex innervation pattern of the defence glands of Phasmatodea which contains different neurons in different nerves from two adjacent body segments

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

    USDA-ARS?s Scientific Manuscript database

    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...

  15. 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

  16. Copper-inducible transcription: regulation by metal- and oxidative stress-responsive pathways.

    PubMed

    Mattie, Michael D; Freedman, Jonathan H

    2004-02-01

    Although copper is an essential metal, it is capable of catalyzing the formation of reactive oxygen species that can cause intracellular oxidative damage. We investigated the hypothesis that metal- and oxidative stress-responsive signal transduction pathways mediate the cellular and molecular responses associated with copper exposure. Transient transfection assays using COS-7 cells and mouse metallothionein-I (MT-I) or rat NAD(P)H:oxidoreductase 1-based reporter genes demonstrate that copper activates transcription via metal and antioxidant response elements. Concomitant with copper exposures is a decrease in the level of total glutathione and an increase in oxidized glutathione. Depletion of glutathione, before copper exposure, increases metal- and oxidative stress-inducible transcription and cytotoxicity. Pretreatment with the reactive oxygen scavengers aspirin or vitamin E provides partial protection against copper toxicity and reduces inducible transcription. Experiments using signal transduction inhibitors and a metal transcription factor (MTF)-1 null cell line demonstrate that copper-inducible MT-I transcription is regulated by protein kinase C and mitogen-activated protein kinase signaling pathways and requires MTF-1. The results of these studies indicate that copper activates transcription through both metal- and oxidative stress-responsive signal transduction pathways.

  17. Kouksundo, a traditional Korean mind-body practice, regulates oxidative stress profiles and stress hormones.

    PubMed

    Im, Hwi-Jin; Kim, Yoon-Jung; Kim, Hyeong-Geug; Kim, Hyo-Seon; Son, Chang-Gue

    2015-03-15

    Kouksundo is a traditional Korean mind-body practice that has been practiced for thousands of years. We investigated the effects of Kouksundo on oxidative stress-related biomarkers and stress hormones. A single-arm observational study was conducted on 57 Kouksundo trainees (34 males and 23 females). Blood samples were collected 30 min before and after Kouksundo practice (25 min for warm-up, 45 min for breathing meditation, and 20 min for cool-down). Kouksundo significantly reduced serum levels of oxidant markers, including reactive oxygen species (p<0.01), nitric oxide (p<0.01), and malondialdehyde (p<0.05), induced elevation of superoxide dismutase (p<0.01), and reduction of catalase (p<0.001). No significant changes were observed in total antioxidant capacity or total glutathione content levels (p>0.05). Kouksundo practice also significantly reduced the serum level of cortisol (p<0.001), norepinephrine (p<0.001), and dopamine (p<0.05), and significantly increased serum epinephrine concentrations (p<0.05). The traditional Korean mind-body practice Kouksundo provided health benefits by regulating oxidative stress and levels of stress hormones. This study is the first investigation of the changes in oxidative stress and stress hormones induced by mind-body therapy, producing reference data for mechanistic studies on these practices. Copyright © 2015. Published by Elsevier Inc.

  18. Influence of oxidized biodiesel blends on regulated and unregulated emissions from a diesel passenger car.

    PubMed

    Karavalakis, Georgios; Bakeas, Evangelos; Stournas, Stamos

    2010-07-01

    This paper investigates the effects of biodiesel blends on regulated and unregulated emissions from a Euro 4 diesel passenger car, fitted with a diesel oxidation catalyst and a diesel particle filter (DPF). Emission and fuel consumption measurements were conducted for the New European Driving Cycle (NEDC) and the Artemis driving cycles. Criteria pollutants, along with carbonyl, polycyclic aromatic hydrocarbon (PAH) and nitrate PAH and oxygenate PAH emissions, were measured and recorded. A soy-based biodiesel and an oxidized biodiesel, obtained from used frying oils, were blended with an ultra low sulfur diesel at proportions of 20, 30, and 50% by volume. The results showed that the DPF had the ability to significantly reduce particulate matter (PM) emissions over all driving conditions. Carbon monoxide (CO) and hydrocarbon (HC) emissions were also reduced with biodiesel; however, a notable increase in nitrogen oxide (NO(x)) emissions was observed with biodiesel blends. Carbon dioxide (CO(2)) emissions and fuel consumption followed similar patterns and increased with biodiesel. The influence of fuel type and properties was particularly noticeable on the unregulated pollutants. The use of the oxidized biodiesel blends led to significant increases in carbonyl emissions, especially in compounds which are associated with potential health risks such as formaldehyde, acetaldehyde, and acrolein. Sharp increases in most PAH compounds and especially those which are known for their toxic and carcinogenic potency were observed with the oxidized blends. The presence of polymerization products and cyclic acids were the main factors that influenced the PAH emissions profile.

  19. Regulation of oxidized base damage repair by chromatin assembly factor 1 subunit A

    PubMed Central

    Yang, Chunying; Sengupta, Shiladitya; Hegde, Pavana M.; Mitra, Joy; Jiang, Shuai; Holey, Brooke; Sarker, Altaf H.; Tsai, Miaw-Sheue; Hegde, Muralidhar L.; Mitra, Sankar

    2017-01-01

    Reactive oxygen species (ROS), generated both endogenously and in response to exogenous stress, induce point mutations by mis-replication of oxidized bases and other lesions in the genome. Repair of these lesions via base excision repair (BER) pathway maintains genomic fidelity. Regulation of the BER pathway for mutagenic oxidized bases, initiated by NEIL1 and other DNA glycosylases at the chromatin level remains unexplored. Whether single nucleotide (SN)-BER of a damaged base requires histone deposition or nucleosome remodeling is unknown, unlike nucleosome reassembly which is shown to be required for other DNA repair processes. Here we show that chromatin assembly factor (CAF)-1 subunit A (CHAF1A), the p150 subunit of the histone H3/H4 chaperone, and its partner anti-silencing function protein 1A (ASF1A), which we identified in human NEIL1 immunoprecipitation complex, transiently dissociate from chromatin bound NEIL1 complex in G1 cells after induction of oxidative base damage. CHAF1A inhibits NEIL1 initiated repair in vitro. Subsequent restoration of the chaperone-BER complex in cell, presumably after completion of repair, suggests that histone chaperones sequester the repair complex for oxidized bases in non-replicating chromatin, and allow repair when oxidized bases are induced in the genome. PMID:27794043

  20. 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

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

    PubMed

    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.

  2. 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

  3. Nitric oxide regulates dark-induced leaf senescence through EIN2 in Arabidopsis.

    PubMed

    Niu, Yun-Han; Guo, Fang-Qing

    2012-08-01

    The nitric oxide (NO)-deficient mutant nos1/noa1 exhibited an early leaf senescence phenotype. ETHYLENE INSENSITIVE 2 (EIN2) was previously reported to function as a positive regulator of ethylene-induced senescence. The aim of this study was to address the question of how NO interacts with ethylene to regulate leaf senescence by characterizing the double mutant ein2-1 nos1/noa1 (Arabidopsis thaliana). Double mutant analysis revealed that the nos1/noa1-mediated, dark-induced early senescence phenotype was suppressed by mutations in EIN2, suggesting that EIN2 is involved in nitric oxide signaling in the regulation of leaf senescence. The results showed that chlorophyll degradation in the double mutant leaves was significantly delayed. In addition, nos1/noa1-mediated impairment in photochemical efficiency and integrity of thylakoid membranes was reverted by EIN2 mutations. The rapid upregulation of the known senescence marker genes in the nos1/noa1 mutant was severely inhibited in the double mutant during leaf senescence. Interestingly, the response of dark-grown nos1/noa1 mutant seedlings to ethylene was similar to that of wild type seedlings. Taken together, our findings suggest that EIN2 is involved in the regulation of early leaf senescence caused by NO deficiency, but NO deficiency caused by NOS1/NOA1 mutations does not affect ethylene signaling. © 2012 Institute of Botany, Chinese Academy of Sciences.

  4. Platelet aggregation responses are critically regulated in vivo by endogenous nitric oxide but not by endothelial nitric oxide synthase.

    PubMed

    Tymvios, C; Moore, C; Jones, S; Solomon, A; Sanz-Rosa, D; Emerson, M

    2009-12-01

    Although exogenous nitric oxide (NO) clearly modifies platelet function, the role and the source of endogenous NO in vivo remain undefined. In addition, endothelial NO synthase (NOS-3) critically regulates vessel tone but its role in modulating platelet function is unclear. In this paper we have investigated the roles of endogenous NO and NOS-3 in regulating platelet function in vivo and determined the functional contribution made by platelet-derived NO. We used a mouse model for directly assessing platelet functional responses in situ in the presence of an intact vascular endothelium with supporting in vitro and molecular studies. Acute NOS inhibition by N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME) enhanced platelet aggregatory responses to thrombin and platelets were shown to be regulated primarily by NO sources external to the platelet. Elevation of endogenous NOS inhibitors to mimic effects reported in patients with cardiovascular diseases did not enhance platelet responses. Platelet responsiveness following agonist stimulation was not modified in male or female NOS-3(-/-) mice but responses in NOS-3(-/-) mice were enhanced by L-NAME. Platelets are regulated by endogenous NO in vivo, primarily by NO originating from the environment external to the platelet with a negligible or undetectable role of platelet-derived NO. Raised levels of endogenous NOS inhibitors, as reported in a range of diseases were not, in isolation, sufficient to enhance platelet activity and NOS-3 is not essential for normal platelet function in vivo due to the presence of bioactive NO following deletion of NOS-3.

  5. Comparative analysis of defence responses induced by the endophytic plant growth-promoting rhizobacterium Burkholderia phytofirmans strain PsJN and the non-host bacterium Pseudomonas syringae pv. pisi in grapevine cell suspensions.

    PubMed

    Bordiec, Sophie; Paquis, Sandra; Lacroix, Hélène; Dhondt, Sandrine; Ait Barka, Essaïd; Kauffmann, Serge; Jeandet, Philippe; Mazeyrat-Gourbeyre, Florence; Clément, Christophe; Baillieul, Fabienne; Dorey, Stéphan

    2011-01-01

    Plant growth-promoting rhizobacteria (PGPR) are beneficial microorganisms that colonize the rhizosphere of many plant species and confer beneficial effects, such as an increase in plant growth. PGPR are also well known as inducers of systemic resistance to pathogens in plants. However, the molecular mechanisms involved locally after direct perception of these bacteria by plant cells still remain largely unknown. Burkholderia phytofirmans strain PsJN is an endophytic PGPR that colonizes grapevine and protects the plant against the grey mould disease caused by Botrytis cinerea. This report focuses on local defence events induced by B. phytofirmans PsJN after perception by the grapevine cells. It is demonstrated that, after addition to cell suspension cultures, the bacteria were tightly attaching to plant cells in a way similar to the grapevine non-host bacteria Pseudomonas syringae pv. pisi. B. phytofirmans PsJN perception led to a transient and monophasic extracellular alkalinization but no accumulation of reactive oxygen species or cell death were detected. By contrast, challenge with P. syringae pv. pisi induced a sustained and biphasic extracellular alkalinization, a two phases oxidative burst, and a HR-like response. Perception of the PGPR also led to the production of salicylic acid (SA) and the expression of a battery of defence genes that was, however, weaker in intensity compared with defence gene expression triggered by the non-host bacteria. Some defence genes up-regulated after B. phytofirmans PsJN challenge are specifically induced by exogenous treatment with SA or jasmonic acid, suggesting that both signalling pathways are activated by the PGPR in grapevine.

  6. Cortisol regulates nitric oxide synthase in freshwater and seawater acclimated rainbow trout, Oncorhynchus mykiss.

    PubMed

    Gerber, Lucie; Madsen, Steffen S; Jensen, Frank B

    2017-02-01

    Cortisol and nitric oxide (NO) are regulators of ion transport and metabolic functions in fish. In the gill, they show opposite effects on Na(+)/K(+)-ATPase (NKA) activity: cortisol stimulates NKA activity while NO inhibits NKA activity. We hypothesized that cortisol may impact NO production in osmoregulatory tissues by regulating NO synthase (NOS) expression. We evaluated the influence of cortisol treatment on mRNA expression of Nos1 and Nos2 in gill, kidney and middle intestine of both freshwater (FW) and seawater (SW) acclimated rainbow trout and found both tissue- and salinity-dependent effects. Nos2 expression was down-regulated in the gill by cortisol injection in both FW and SW trout. This was substantiated by incubating gill tissue with cortisol ex vivo. Similarly, cortisol injection significantly down-regulated Nos2 expression in kidney of SW fish but not in FW fish. In the middle intestine, Nos2 expression was up-regulated by cortisol injection in FW but unchanged in SW fish. Nos1 expression was up-regulated by cortisol injection in FW kidney and down-regulated in SW kidney, whereas it was unaffected in gill and middle intestine of FW and SW fish. Our data provide the first evidence that cortisol may influence NO production in fish by regulating Nos expression. Indeed, the down-regulation of Nos2 expression by cortisol in the gill may prevent the inhibitory effect of NO on NKA activity thereby furthering the stimulatory effect of cortisol on ion-transport. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. 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

  8. CRP Regulates D-Lactate Oxidation in Shewanella oneidensis MR-1.

    PubMed

    Kasai, Takuya; Kouzuma, Atsushi; Watanabe, Kazuya

    2017-01-01

    Shewanella oneidensis MR-1 is a heterotrophic facultative anaerobe that respires using various organic and inorganic compounds. This organism has served as a model to study bacterial metabolic and regulatory systems that facilitate their survival in redox-stratified environments. The expression of many anaerobic respiratory genes in MR-1, including those for the reduction of fumarate, dimethyl sulfoxide, and metal oxides, is regulated by cyclic AMP receptor protein (CRP). However, relatively little is known about how this organism regulates the expression of catabolic enzymes catalyzing the oxidation of organic compounds, including lactate. Here, we investigated transcriptional mechanisms for the lldP (SO_1522) and dld (SO_1521) genes, which encode putative lactate permease and D-lactate dehydrogenase, respectively, and demonstrate that CRP regulates their expression in MR-1. We found that a crp-deletion mutant of MR-1 (Δcrp) showed impaired growth on D-lactate. Complementary expression of dld in Δcrp restored the ability to grow on D-lactate, indicating that the deficient growth of Δcrp on D-lactate is attributable to decreased expression of dld. In vivo transcription and in vitro electrophoretic mobility shift assays reveal that CRP positively regulates the expression of the lldP and dld genes by directly binding to an upstream region of lldP. Taken together, these results indicate that CRP is a global transcriptional regulator that coordinately regulates the expression of catabolic and respiratory pathways in MR-1, including D-lactate dehydrogenase and anaerobic terminal reductases.

  9. 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.

  10. PHLPP2 down regulation influences nuclear Nrf2 stability via Akt-1/Gsk3β/Fyn kinase axis in acetaminophen induced oxidative renal toxicity: Protection accorded by morin.

    PubMed

    Mathur, Alpana; Rizvi, Fatima; Kakkar, Poonam

    2016-03-01

    NF-E2 p45-related factor 2 (Nrf2) is a cap 'n' collar (CNC) basic region-leucine zipper (bZIP) transcription factor that imparts cellular defence against xenobiotic and oxidative stress evoked responses by inducing an array of cytoprotective genes. Essential factors that regulate Nrf2 activity and stability during analgesic nephropathy are incompletely understood. In this study, we demonstrate that acetaminophen (a classic analgesic) posit nephrotoxicity both in vitro and in vivo via PHLPP2 activation. Enhanced PHLPP2 levels down regulate p-Akt by dephosphorylating it at Ser 473 residue leading to Gsk3β activation. APAP subsided Nrf2 nuclear accumulation by activating Gsk3β which phosphorylates Fyn kinase. p-Fyn kinase translocates into the nucleus and phosphorylates Nrf2 (Tyr 568) leading to its nuclear export, ubiquitination and degradation. Therefore, poor prognosis prevails during analgesic nephrotoxicity because of the defects in Akt-1/Gsk3β/Fyn-Nrf2 signaling pathway. Morin, a bioflavonoid given as co- and pre-treatment with acetaminophen significantly prevented the toxicity induced damage by constitutively stabilizing Nrf2 nuclear retention. Diminished Nrf2 levels by APAP overdose imposed severe proximal tubular damage leading to apoptotic cell death. Morin, as a potent Nrf2 inducer accorded protection against acetaminophen induced renal damages by its molecular intervention with Akt-1/Gsk3β/Fyn kinase pathway via PHLPP2 de-activation.

  11. 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

  12. Influence of Trichobilharzia regenti (Digenea: Schistosomatidae) on the defence activity of Radix lagotis (Lymnaeidae) Haemocytes.

    PubMed

    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.

  13. 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

  14. Up-regulation of cardiac nitric oxide synthase 1-derived nitric oxide after myocardial infarction in senescent rats.

    PubMed

    Damy, Thibaud; Ratajczak, Philippe; Robidel, Estelle; Bendall, Jennifer K; Oliviéro, Patricia; Boczkowski, Jorge; Ebrahimian, Talin; Marotte, Françoise; Samuel, Jane-Lise; Heymes, Christophe

    2003-10-01

    Nitric oxide (NO) has been implicated in the development of heart failure, although the source, significance, and functional role of the different NO synthase (NOS) isoforms in this pathology are controversial. The presence of a neuronal-type NOS isoform (NOS1) in the cardiac sarcoplasmic reticulum has been recently discovered, leading to the hypothesis that NOS1-derived NO may notably alter myocardial inotropy. However, the regulation and role(s) of NOS1 in cardiac diseases remain to be determined. Using an experimental model of myocardial infarction (MI) in senescent rats, we demonstrated a significant increase in cardiac NOS1 expression and activity in MI, coupled with the translocation of this enzyme to the sarcolemma through interactions with caveolin-3. The enhanced NOS1 activity counteracts the decrease in cardiac NOS3 expression and activity observed in heart failure. We demonstrated an increased interaction between NOS1 and its regulatory protein HSP90 in post-MI hearts, a potential mechanism for the higher NOS1 activity in this setting. Finally, preferential in vivo inhibition of NOS1 activity enhanced basal post-MI left ventricular dysfunction in senescent rats. These results provide the first evidence that increased NOS1-derived NO production may play a significant role in the autocrine regulation of myocardial contractility after MI in aging rats.

  15. Nitric oxide production and NO synthase gene expression contribute to vascular regulation during exercise.

    PubMed

    Shen, W; Zhang, X; Zhao, G; Wolin, M S; Sessa, W; Hintze, T H

    1995-08-01

    Nitric oxide (NO) is a vasodilator produced under normal physiologic conditions primarily by the vascular endothelium lining all blood vessels. The primary stimulus for the production of nitric oxide by the constitutive endothelial nitric oxide synthase (ECNOS, Type II) found in blood vessels is most likely the shear stress, the frictional force, caused by blood flowing through blood vessels. During exercise there is an increase in cardiac output and redistribution of blood flow to increase blood flow in skeletal muscle and in the coronary circulation. These adjustments provide increased oxygen delivery to support aerobic energy production and to sustain the exercise response. NO may be involved in the regulation of vascular tone in exercising skeletal and cardiac muscle by promoting, enhancing the metabolic vasodilation. In addition, the production of NO by capillary endothelium may regulate oxygen consumption by mitochondria through chemical interactions between NO and the iron-sulfur center of these enzymes. Finally, brief exercise training may alter the gene expression for the enzyme, the constitutive endothelial NO synthase, which forms NO and may be part of the vascular adaptation seen after aerobic exercise training. Furthermore, if there is a genetic predisposition to produce NO, as in world class athletes or animals bred to race, NO may contribute to spectacular exercise performance. These three potential roles of NO will be discussed and data presented to support each of these in our review.

  16. The oxidative molecular regulation mechanism of NOX in children with phenylketonuria.

    PubMed

    He, Ying-Zhong; Gu, Xue-Fan; Lu, Li-Hua; Liang, Li-Li

    2014-11-01

    Phenylketonuria (PKU) is the most frequent inherited disorder of amino acid metabolism. In our previous work, we investigated the role of NADPH oxidase (NOX) in a Pahenu2-BTBR PKU mouse model, and an in vitro cell culture model of PKU. In the current study, we evaluated various oxidative stress parameters, namely total antioxidant capacity (T-AOC), glutathione (GSH) and maleic dialdehyde (MDA) in the plasma of 40 PKU children, for further investigating the oxidative molecular regulation mechanism of NOX in PKU. It was observed that T-AOC and GSH markedly decreased in PKU as compared with the control group (P<0.01), and seemed to correlate negatively with Phe level. However, there was no statistical difference in MDA level among the three groups. And 8-isoprostane in the blood samples of PKU2 groups was slightly higher than control group (P<0.05). Additionally, mRNA levels of subunits of NOX included p47(phox) and p67(phox) significantly increased in PKU group (P<0.01). These results reflected that NOX is the important source of reactive oxygen species and is involved in the oxidative molecular regulation mechanism in PKU, which shows a new perspective toward understanding the biological underpinnings of PKU. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

  17. DAPK2 regulates oxidative stress in cancer cells by preserving mitochondrial function

    PubMed Central

    Schlegel, C R; Georgiou, M L; Misterek, M B; Stöcker, S; Chater, E R; Munro, C E; Pardo, O E; Seckl, M J; Costa-Pereira, A P

    2015-01-01

    Death-associated protein kinase (DAPK) 2 is a serine/threonine kinase that belongs to the DAPK family. Although it shows significant structural differences from DAPK1, the founding member of this protein family, DAPK2 is also thought to be a putative tumour suppressor. Like DAPK1, it has been implicated in programmed cell death, the regulation of autophagy and diverse developmental processes. In contrast to DAPK1, however, few mechanistic studies have been carried out on DAPK2 and the majority of these have made use of tagged DAPK2, which almost invariably leads to overexpression of the protein. As a consequence, physiological roles of this kinase are still poorly understood. Using two genetically distinct cancer cell lines as models, we have identified a new role for DAPK2 in the regulation of mitochondrial integrity. RNA interference-mediated depletion of DAPK2 leads to fundamental metabolic changes, including significantly decreased rate of oxidative phosphorylation in combination with overall destabilised mitochondrial membrane potential. This phenotype is further corroborated by an increase in the production of mitochondrial superoxide anions and increased oxidative stress. This then leads to the activation of classical stress-activated kinases such as ERK, JNK and p38, which is observed on DAPK2 genetic ablation. Interestingly, the generation of oxidative stress is further enhanced on overexpression of a kinase-dead DAPK2 mutant indicating that it is the kinase domain of DAPK2 that is important to maintain mitochondrial integrity and, by inference, for cellular metabolism. PMID:25741596

  18. Artemis Is a Negative Regulator of p53 in Response to Oxidative Stress

    PubMed Central

    Zhang, Xiaoshan; Zhu, Yaqin; Geng, Liyi; Wang, Haiyong; Legerski, Randy J.

    2009-01-01

    Artemis is a multifunctional phospho-protein with roles in V(D)J recombination, repair of double-strand breaks by nonhomologous end-joining, and regulation of cell cycle checkpoints after DNA damage. Here, we describe a novel function of Artemis as a negative regulator of p53 in response to oxidative stress in both primary cells and cancer cell lines. We show that depletion of Artemis under typical culture conditions (21% oxygen) leads to a spontaneous phosphorylation and stabilization of p53, and resulting cellular G1 arrest and apoptosis. These effects are suppressed by co-depletion of DNA-PKcs, but not ATM, indicating that Artemis is an inhibitor of DNA-PKcs-mediated stabilization of p53. Culturing of cells at 3% oxygen or treatment with an antioxidant abrogated p53 stabilization indicating that oxidative stress is the responsible cellular stimulus. Treatment with IR or hydrogen peroxide did not cause activation of this signaling pathway, while inhibitors of mitochondrial electron transport were effective in reducing its activation. In addition, we show that p53-inducible genes involved in reducing reactive oxygen species (ROS) are upregulated by Artemis depletion. These findings indicate that Artemis and DNA-PKcs participate in a novel, signaling pathway to modulate p53 function in response to oxidative stress produced by mitochondrial respiration. PMID:19398950

  19. Artemis is a negative regulator of p53 in response to oxidative stress.

    PubMed

    Zhang, X; Zhu, Y; Geng, L; Wang, H; Legerski, R J

    2009-06-04

    Artemis is a multifunctional phospho-protein with roles in V(D)J recombination, repair of double-strand breaks by nonhomologous end-joining and regulation of cell-cycle checkpoints after DNA damage. Here, we describe a new function of Artemis as a negative regulator of p53 in response to oxidative stress in both primary cells and cancer cell lines. We show that depletion of Artemis under typical culture conditions (21% oxygen) leads to a spontaneous phosphorylation and stabilization of p53, and resulting cellular G1 arrest and apoptosis. These effects are suppressed by co-depletion of DNA-PKcs, but not ATM, indicating that Artemis is an inhibitor of DNA-PKcs-mediated stabilization of p53. Culturing of cellsat 3% oxygen or treatment with an antioxidant abrogated p53 stabilization, indicating that oxidative stress is the responsible cellular stimulus. Treatment with ionizing radiation or hydrogen peroxide did not cause activation of this signaling pathway, whereas inhibitors of mitochondrial electron transport were effective in reducing its activation. In addition, we show that p53-inducible genes involved in reducing reactive oxygen species are upregulated by Artemis depletion. These findings indicate that Artemis and DNA-PKcs participate in a new, signaling pathway to modulate p53 function in response to oxidative stress produced by mitochondrial respiration.

  20. Involvement of putative glutamate receptors in plant defence signaling and NO production.

    PubMed

    Vatsa, Parul; Chiltz, Annick; Bourque, Stéphane; Wendehenne, David; Garcia-Brugger, Angela; Pugin, Alain

    2011-12-01

    Ionotropic glutamate receptors (iGluRs) are non-selective cation channels permeable to calcium, present in animals and plants. In mammals, glutamate is a well-known neurotransmitter and recently has been recognized as an immunomodulator. As animals and plants share common mechanisms that govern innate immunity with calcium playing a key role in plant defence activation, we have checked the involvement of putative iGluRs in plant defence signaling. Using tobacco cells, we first provide evidence supporting the activity of iGluRs as calcium channels and their involvement in NO production as reported in animals. Thereafter, iGluRs were shown to be activated in response to cryptogein, a well studied elicitor of defence response, and partly responsible for cryptogein-induced NO production. However, other cryptogein-induced calcium-dependent events including anion efflux, H(2)O(2) production, MAPK activation and hypersensitive response (HR) did not depend on iGluRs indicating that different calcium channels regulate different processes at the cell level. We have also demonstrated that cryptogein induces efflux of glutamate in the apoplast by exocytosis. Taken together, our results demonstrate for the first time, an involvement of a putative iGluR in plant defence signaling and NO production, by mechanisms that show homology with glutamate mode of action in mammals.

  1. Resveratrol regulates oxidative biomarkers and antioxidant enzymes in the brain of streptozotocin-induced diabetic rats.

    PubMed

    Sadi, Gökhan; Konat, Dilan

    2016-07-01

    Oxidative stress has been implicated in the progression of pathogenesis in diabetes mellitus and leads to a variety of deformations in the central nervous system. Recent studies have provided several insights on therapeutic uses of resveratrol in diabetic complications. The present study determines if resveratrol ameliorates oxidative stress and molecular changes in the brain frontal cortex of streptozotocin-induced diabetic rats. Rats were divided into four groups: control, diabetic, resveratrol-treated control, and resveratrol-treated diabetic. After diabetes induction, resveratrol (20 mg/kg) was given intraperitoneally once daily for 4 weeks. In addition to enzymatic activities, gene and protein expression of brain antioxidant enzymes were utilized by qRT-PCR and Western blot, respectively. The results indicated a significant elevation in total oxidant species (1.22-fold) and malonedialdehyde (1.38-fold) contents in diabetic rat brain cortex tissues. In addition, significant augmentation in the activities of catalase (1.38-fold) and superoxide dismutase (3-fold) was witnessed with the gene and protein expression levels reflecting a transcriptional regulation. Resveratrol treatment significantly normalized diabetic malonedialdehyde and oxidized glutathione levels and strengthens the action of all antioxidant enzymes. Recovery of the diabetes-associated changes reflects the reduction of oxidative conditions by resveratrol and reveals the decrease in the requirement for the activation of antioxidant defense systems in the brain tissues of diabetic rats. Potent antioxidant and neuroprotective properties of resveratrol against diabetes-induced oxidative damage were demonstrated and the results support the conduct of new studies searching for the molecular mechanism of diabetes-induced changes in brain tissues.

  2. Heme oxygenase-1: redox regulation and role in the hepatic response to oxidative stress.

    PubMed

    Bauer, Michael; Bauer, Inge

    2002-10-01

    Heme oxygenase (HO) catalyzes the oxidative cleavage of the alpha-mesocarbon of Fe-protoporphyrin-IX yielding equimolar amounts of biliverdin-IXalpha, free divalent iron, and carbon monoxide (CO). Among the three isoenzymes cloned to date, only HO-1 can be induced by a variety of seemingly disparate stimuli, most of which are linked by their ability to provoke oxidative stress. Although constitutive expression of HO-1 in the liver is restricted to Kupffer cells, the gene is inducible in nonparenchymal as well as in parenchymal liver cells. HO-1 induction potentially confers protection against oxidative stress in a variety of experimental models, such as liver ischemia/reperfusion secondary to transplantation or hemorrhage/resuscitation. Induction of HO-1 may protect the cell against oxidative injury by (a) controlling intracellular levels of "free" heme (a prooxidant), (b) producing biliverdin (an antioxidant), (c) improving nutritive perfusion via CO release, and (d) fostering the synthesis of the Fe-binding protein ferritin. Although protective effects of up-regulation of the HO pathway--presumably through production of bile pigments and CO--have been reported for a variety of cells and tissues, including the liver, evidence suggests that the protective action might be restricted to a rather narrow threshold of overexpression. High levels of HO-1 may even sensitize the cell to oxidative stress, e.g., through release of reactive iron. Transcriptional activation of the HO-1 gene is an integral part of the cellular response to oxidative stress, but its induction seems to be neither exclusively cytoprotective nor exclusively cytotoxic.

  3. Potato skin proteome is enriched with plant defence components.

    PubMed

    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, C(1) 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.

  4. 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

  5. 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.

  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. Histone Deacetylase HDA-2 Regulates Trichoderma atroviride Growth, Conidiation, Blue Light Perception, and Oxidative Stress Responses.

    PubMed

    Osorio-Concepción, Macario; Cristóbal-Mondragón, Gema Rosa; Gutiérrez-Medina, Braulio; Casas-Flores, Sergio

    2017-02-01

    Fungal blue-light photoreceptors have been proposed as integrators of light and oxidative stress. However, additional elements participating in the integrative pathway remain to be identified. In Trichoderma atroviride, the blue-light regulator (BLR) proteins BLR-1 and -2 are known to regulate gene transcription, mycelial growth, and asexual development upon illumination, and recent global transcriptional analysis revealed that the histone deacetylase-encoding gene hda-2 is induced by light. Here, by assessing responses to stimuli in wild-type and Δhda-2 backgrounds, we evaluate the role of HDA-2 in the regulation of genes responsive to light and oxidative stress. Δhda-2 strains present reduced growth, misregulation of the con-1 gene, and absence of conidia in response to light and mechanical injury. We found that the expression of hda-2 is BLR-1 dependent and HDA-2 in turn is essential for the transcription of early and late light-responsive genes that include blr-1, indicating a regulatory feedback loop. When subjected to reactive oxygen species (ROS), Δhda-2 mutants display high sensitivity whereas Δblr strains exhibit the opposite phenotype. Consistently, in the presence of ROS, ROS-related genes show high transcription levels in wild-type and Δblr strains but misregulation in Δhda-2 mutants. Finally, chromatin immunoprecipitations of histone H3 acetylated at Lys9/Lys14 on cat-3 and gst-1 promoters display low accumulation of H3K9K14ac in Δblr and Δhda-2 strains, suggesting indirect regulation of ROS-related genes by HDA-2. Our results point to a mutual dependence between HDA-2 and BLR proteins and reveal the role of these proteins in an intricate gene regulation landscape in response to blue light and ROS.

  8. 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

  9. Coupling of transcriptional response to oxidative stress and secondary metabolism regulation in filamentous fungi.

    PubMed

    Montibus, Mathilde; Pinson-Gadais, Laëtitia; Richard-Forget, Florence; Barreau, Christian; Ponts, Nadia

    2015-01-01

    To survive sudden and potentially lethal changes in their environment, filamentous fungi must sense and respond to a vast array of stresses, including oxidative stresses. The generation of reactive oxygen species, or ROS, is an inevitable aspect of existence under aerobic conditions. In addition, in the case of fungi with pathogenic lifestyles, ROS are produced by the infected hosts and serve as defense weapons via direct toxicity, as well as effectors in fungal cell death mechanisms. Filamentous fungi have thus developed complex and sophisticated responses to evade oxidative killing. Several steps are determinant in these responses, including the activation of transcriptional regulators involved in the control of the antioxidant machinery. Gathering and integrating the most recent advances in knowledge of oxidative stress responses in fungi are the main objectives of this review. Most of the knowledge coming from two models, the yeast Saccharomyces cerevisiae and fungi of the genus Aspergillus, is summarized. Nonetheless, recent information on various other fungi is delivered when available. Finally, special attention is given on the potential link between the functional interaction between oxidative stress and secondary metabolism that has been suggested in recent reports, including the production of mycotoxins.

  10. Neurotoxicity induced by arsenic in Gallus Gallus: Regulation of oxidative stress and heat shock protein response.

    PubMed

    Zhao, Panpan; Guo, Ying; Zhang, Wen; Chai, Hongliang; Xing, Houjuan; Xing, Mingwei

    2017-01-01

    Arsenic, a naturally occurring heavy metal pollutant, is one of the functioning risk factors for neurological toxicity in humans. However, little is known about the effects of arsenic on the nervous system of Gallus Gallus. To investigate whether arsenic induce neurotoxicity and influence the oxidative stress and heat shock proteins (Hsps) response in chickens, seventy-two 1-day-old male Hy-line chickens were treated with different doses of arsenic trioxide (As2O3). The histological changes, antioxidant enzyme activity, and the expressions of Hsps were detected. Results showed slightly histology changes were obvious in the brain tissues exposure to arsenic. The activities of Glutathione peroxidase (GSH-Px) and catalase (CAT) were decreased compared to the control, whereas the malondialdehyde (MDA) content was increased gradually along with increase in diet-arsenic. The mRNA levels of Hsps and protein expressions of Hsp60 and Hsp70 were up-regulated. These results suggested that sub-chronic exposure to arsenic induced neurotoxicity in chickens. Arsenic exposure disturbed the balance of oxidants and antioxidants. Increased heat shock response tried to protect chicken brain tissues from tissues damage caused by oxidative stress. The mechanisms of neurotoxicity induced by arsenic include oxidative stress and heat shock protein response in chicken brain tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Regulation of cytochrome C peroxidase activity by nitric oxide and laser irradiation.

    PubMed

    Osipov, A N; Stepanov, G O; Vladimirov, Yu A; Kozlov, A V; Kagan, V E

    2006-10-01

    Apoptosis can be induced by activation of so-called "death receptors" (extrinsic pathway) or multiple apoptotic factors (intrinsic pathway), which leads to release of cytochrome c from mitochondria. This event is considered to be a point of no return in apoptosis. One of the most important events in the development of apoptosis is the enhancement of cytochrome c peroxidase activity upon its interaction with cardiolipin, which modifies the active center of cytochrome c. In the present work, we have investigated the effects of nitric oxide on the cytochrome c peroxidase activity when cytochrome c is bound to cardiolipin or sodium dodecyl sulfate. We have observed that cytochrome c peroxidase activity, distinctly increased due to the presence of anionic lipids, is completely suppressed by nitric oxide. At the same time, nitrosyl complexes of cytochrome c, produced in the interaction with nitric oxide, demonstrated sensitivity to laser irradiation (441 nm) and were photolyzed during irradiation. This decomposition led to partial restoration of cytochrome c peroxidase activity. Finally, we conclude that nitric oxide and laser irradiation may serve as effective instruments for regulating the peroxidase activity of cytochrome c, and, probably, apoptosis.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. Metabolic pathways regulated by TAp73 in response to oxidative stress

    PubMed Central

    Agostini, Massimiliano; Annicchiarico-Petruzzelli, Margherita; Melino, Gerry; Rufini, Alessandro

    2016-01-01

    Reactive oxygen species are involved in both physiological and pathological processes including neurodegeneration and cancer. Therefore, cells have developed scavenging mechanisms to maintain redox homeostasis under control. Tumor suppressor genes play a critical role in the regulation of antioxidant genes. Here, we investigated whether the tumor suppressor gene TAp73 is involved in the regulation of metabolic adaptations triggered in response to oxidative stress. H2O2 treatment resulted in numerous biochemical changes in both control and TAp73 knockout (TAp73−/−) mouse embryonic fibroblasts, however the extent of these changes was more pronounced in TAp73−/− cells when compared to control cells. In particular, loss of TAp73 led to alterations in glucose, nucleotide and amino acid metabolism. In addition, H2O2 treatment resulted in increased pentose phosphate pathway (PPP) activity in null mouse embryonic fibroblasts. Overall, our results suggest that in the absence of TAp73, H2O2 treatment results in an enhanced oxidative environment, and at the same time in an increased pro-anabolic phenotype. In conclusion, the metabolic profile observed reinforces the role of TAp73 as tumor suppressor and indicates that TAp73 exerts this function, at least partially, by regulation of cellular metabolism. PMID:27119504

  17. 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.

  18. 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. © 2015 by The American Society of Hematology.

  19. Major vault protein regulates cell growth/survival signaling through oxidative modifications.

    PubMed

    Das, Dividutta; Wang, Yi-Hsuan; Hsieh, Cheng-Ying; Suzuki, Yuichiro J

    2016-01-01

    Major vault protein forms a hollow, barrel-like structure in the cell called the vault, whose functions and regulation are not well understood. The present study reports that major vault protein regulates growth/survival signaling in human airway smooth muscle cells through oxidative modifications. The promotion of protein S-glutathionylation by asthma mediators such as interleukin-22 and platelet-derived growth factor or by knocking down glutaredoxin-1 or thioredoxin activated cell growth signaling. Mass spectrometry identified that major vault protein is glutathionylated. Major vault protein knockdown enhanced cell death and inhibited STAT3 and Akt signaling. We identified a protein partner of major vault protein that is regulated by glutaredoxin-1, namely myosin-9, which was found to serve as a cell death factor. Knocking down myosin-9 or promoting protein S-glutathionylation by knocking down glutaredoxin-1 inhibited the death of airway smooth muscle cells by heating to simulate bronchial thermoplasty, a clinically successful procedure for the treatment of severe asthma. These results establish a novel signaling pathway in which ligand/receptor-mediated oxidation promotes the S-glutathionylation of major vault protein, which in turn binds to myosin-9 to suppress the heating-induced death of airway smooth muscle cells.

  20. 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

  1. Mitochondrial ROS regulate oxidative damage and mitophagy but not age-related muscle fiber atrophy

    PubMed Central

    Sakellariou, Giorgos K.; Pearson, Timothy; Lightfoot, Adam P.; Nye, Gareth A.; Wells, Nicola; Giakoumaki, Ifigeneia I.; Vasilaki, Aphrodite; Griffiths, Richard D.; Jackson, Malcolm J.; McArdle, Anne

    2016-01-01

    Age-related loss of skeletal muscle mass and function is a major contributor to morbidity and has a profound effect on the quality of life of older people. The potential role of age-dependent mitochondrial dysfunction and cumulative oxidative stress as the underlying cause of muscle aging remains a controversial topic. Here we show that the pharmacological attenuation of age-related mitochondrial redox changes in muscle with SS31 is associated with some improvements in oxidative damage and mitophagy in muscles of old mice. However, this treatment failed to rescue the age-related muscle fiber atrophy associated with muscle atrophy and weakness. Collectively, these data imply that the muscle mitochondrial redox environment is not a key regulator of muscle fiber atrophy during sarcopenia but may play a key role in the decline of mitochondrial organelle integrity that occurs with muscle aging. PMID:27681159

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

    PubMed Central

    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

  3. Jasmonate in plant defence: sentinel or double agent?

    PubMed

    Yan, Chun; Xie, Daoxin

    2015-12-01

    Plants and their biotic enemies, such as microbial pathogens and herbivorous insects, are engaged in a desperate battle which would determine their survival-death fate. Plants have evolved efficient and sophisticated systems to defend against such attackers. In recent years, significant progress has been made towards a comprehensive understanding of inducible defence system mediated by jasmonate (JA), a vital plant hormone essential for plant defence responses and developmental processes. This review presents an overview of JA action in plant defences and discusses how microbial pathogens evade plant defence system through hijacking the JA pathway.

  4. Regulation of oxidative-stress responsive genes by arecoline in human keratinocytes.

    PubMed

    Thangjam, G S; Kondaiah, P

    2009-10-01

    Arecoline, an arecanut alkaloid present in the saliva of betel quid chewers, has been implicated in the pathogenesis of a variety of inflammatory oral diseases, including oral submucous fibrosis and periodontitis. To understand the molecular basis of arecoline action in epithelial changes associated with these diseases, we investigated the effects of arecoline on human keratinocytes with respect to cell growth regulation and the expression of stress-responsive genes. Human keratinocyte cells (of the HaCaT cell line) were treated with arecoline, following which cell viability was assessed using the Trypan Blue dye-exclusion assay, cell growth and proliferation were analyzed using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and 5-bromo-2-deoxyuridine incorporation assays, cell cycle arrest and generation of reactive oxygen species were examined using flow cytometry, and gene expression changes were investigated using the reverse transcription-polymerase chain reaction technique. The role of oxidative stress, muscarinic acetylcholine receptor and mitogen-activated protein kinase (MAPK) pathways were studied using specific inhibitors. Western blot analysis was performed to study p38 MAPK activation. Arecoline induced the generation of reactive oxygen species and cell cycle arrest at the G1/G0 phase in HaCaT cells without affecting the expression of p21/Cip1. Arecoline-induced epithelial cell death at higher concentrations was caused by oxidative trauma without eliciting apoptosis. Sublethal concentrations of arecoline upregulated the expression of the following stress-responsive genes: heme oxygenase-1; ferritin light chain; glucose-6-phosphate dehydrogenase; glutamate-cysteine ligase catalytic subunit; and glutathione reductase. Additionally, there was a dose-dependent induction of interleukin-1alfa mRNA by arecoline via oxidative stress and p38 MAPK activation. Our data highlight the role of oxidative stress in arecoline-mediated cell death

  5. Skeletal muscle glucose uptake during contraction is regulated by nitric oxide and ROS independently of AMPK.

    PubMed

    Merry, Troy L; Steinberg, Gregory R; Lynch, Gordon S; McConell, Glenn K

    2010-03-01

    Reactive oxygen species (ROS) and nitric oxide (NO) have been implicated in the regulation of skeletal muscle glucose uptake during contraction, and there is evidence that they do so via interaction with AMP-activated protein kinase (AMPK). In this study, we tested the hypothesis that ROS and NO regulate skeletal muscle glucose uptake during contraction via an AMPK-independent mechanism. Isolated extensor digitorum longus (EDL) and soleus muscles from mice that expressed a muscle-specific kinase dead AMPKalpha2 isoform (AMPK-KD) and wild-type litter mates (WT) were stimulated to contract, and glucose uptake was measured in the presence or absence of the antioxidant N-acetyl-l-cysteine (NAC) or the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-l-arginine (l-NMMA). Contraction increased AMPKalpha2 activity in WT but not AMPK-KD EDL muscles. However, contraction increased glucose uptake in the EDL and soleus muscles of AMPK-KD and WT mice to a similar extent. In EDL muscles, NAC and l-NMMA prevented contraction-stimulated increases in oxidant levels (dichloroflourescein fluorescence) and NOS activity, respectively, and attenuated contraction-stimulated glucose uptake in both genotypes to a similar extent. In soleus muscles of AMPK-KD and WT mice, NAC prevented contraction-stimulated glucose uptake and l-NMMA had no effect. This is likely attributed to the relative lack of neuronal NOS in the soleus muscles compared with EDL muscles. Contraction increased AMPKalpha Thr(172) phosphorylation in EDL and soleus muscles of WT but not AMPK-KD mice, and this was not affected by NAC or l-NMMA treatment. In conclusion, ROS and NO are involved in regulating skeletal muscle glucose uptake during contraction via an AMPK-independent mechanism.

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

    PubMed Central

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

    2016-01-01

    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

  7. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Regulation of Protein Function by Reversible Methionine Oxidation and the Role of Selenoprotein MsrB1

    PubMed Central

    Kaya, Alaattin

    2015-01-01

    Abstract Significance: Protein structure and function can be regulated via post-translational modifications by numerous enzymatic and nonenzymatic mechanisms. Regulation involving oxidation of sulfur-containing residues emerged as a key mechanism of redox control. Unraveling the participants and principles of such regulation is necessary for understanding the biological significance of redox control of cellular processes. Recent Advances: Reversible oxidation of methionine residues by monooxygenases of the Mical family and subsequent reduction of methionine sulfoxides by a selenocysteine-containing methionine sulfoxide reductase B1 (MsrB1) was found to control the assembly and disassembly of actin in mammals, and the Mical/MsrB pair similarly regulates actin in fruit flies. This finding has opened up new avenues for understanding the use of stereospecific methionine oxidation in regulating cellular processes and the roles of MsrB1 and Micals in regulation of actin dynamics. Critical Issues: So far, Micals have been the only known partners of MsrB1, and actin is the only target. It is important to identify additional substrates of Micals and characterize other Mical-like enzymes. Future Directions: Oxidation of methionine, reviewed here, is an emerging but not well-established mechanism. Studies suggest that methionine oxidation is a form of oxidative damage of proteins, a modification that alters protein structure or function, a tool in redox signaling, and a mechanism that controls protein function. Understanding the functional impact of reversible oxidation of methionine will require identification of targets, substrates, and regulators of Micals and Msrs. Linking the biological processes, in which these proteins participate, might also lead to insights into disease conditions, which involve regulation of actin by Micals and Msrs. Antioxid. Redox Signal. 23, 814–822. PMID:26181576

  9. 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.

  10. 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.

  11. 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…

  12. EP300 contributes to high-altitude adaptation in Tibetans by regulating nitric oxide production.

    PubMed

    Zheng, Wang-Shan; He, Yao-Xi; Cui, Chao-Ying; Ouzhu, Luobu; Deji, Quzong; Peng, Yi; Bai, Cai-Juan; Duoji, Zhuoma; Gongga, Lanzi; Bian, Ba; Baima, Kangzhuo; Pan, Yong-Yue; Qu, la; Kang, Min; Ciren, Yangji; Baima, Yangji; Guo, Wei; Yang, la; Zhang, Hui; Zhang, Xiao-Ming; Guo, Yong-Bo; Xu, Shu-Hua; Chen, Hua; Zhao, Sheng-Guo; Cai, Yuan; Liu, Shi-Ming; Wu, Tian-Yi; Qi, Xue-Bin; Su, Bing

    2017-05-18

    The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300 (histone acetyltransferase p300), we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide (NO) concentration. Collectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.

  13. Redox Regulation of Human OGG1 Activity in Response to Cellular Oxidative Stress▿

    PubMed Central

    Bravard, Anne; Vacher, Monique; Gouget, Barbara; Coutant, Alexandre; de Boisferon, Florence Hillairet; Marsin, Stéphanie; Chevillard, Sylvie; Radicella, J. Pablo

    2006-01-01

    8-Oxoguanine (8-oxoG), a common and mutagenic form of oxidized guanine in DNA, is eliminated mainly through base excision repair. In human cells its repair is initiated by human OGG1 (hOGG1), an 8-oxoG DNA glycosylase. We investigated the effects of an acute cadmium exposure of human lymphoblastoid cells on the activity of hOGG1. We show that coinciding with alteration of the redox cellular status, the 8-oxoG DNA glycosylase activity of hOGG1 was nearly completely inhibited. However, the hOGG1 activity returned to normal levels once the redox cellular status was normalized. In vitro, the activity of purified hOGG1 was abolished by cadmium and could not be recovered by EDTA. In cells, however, the reversible inactivation of OGG1 activity by cadmium was strictly associated with reversible oxidation of the protein. Moreover, the 8-oxoG DNA glycosylase activity of purified OGG1 and that from crude extracts were modulated by cysteine-modifying agents. Oxidation of OGG1 by the thiol oxidant diamide led to inhibition of the activity and a protein migration pattern similar to that seen in cadmium-treated cells. These results suggest that cadmium inhibits hOGG1 activity mainly by indirect oxidation of critical cysteine residues and that excretion of the metal from the cells leads to normalization of the redox cell status and restoration of an active hOGG1. The results presented here unveil a novel redox-dependent mechanism for the regulation of OGG1 activity. PMID:16923968

  14. Regulation of brain glutamate metabolism by nitric oxide and S-nitrosylation.

    PubMed

    Raju, Karthik; Doulias, Paschalis-Thomas; Evans, Perry; Krizman, Elizabeth N; Jackson, Joshua G; Horyn, Oksana; Daikhin, Yevgeny; Nissim, Ilana; Yudkoff, Marc; Nissim, Itzhak; Sharp, Kim A; Robinson, Michael B; Ischiropoulos, Harry

    2015-07-07

    Nitric oxide (NO) is a signaling intermediate during glutamatergic neurotransmission in the central nervous system (CNS). NO signaling is in part accomplished through cysteine S-nitrosylation, a posttranslational modification by which NO regulates protein function and signaling. In our investigation of the protein targets and functional impact of S-nitrosylation in the CNS under physiological conditions, we identified 269 S-nitrosocysteine residues in 136 proteins in the wild-type mouse brain. The number of sites was significantly reduced in the brains of mice lacking endothelial nitric oxide synthase (eNOS(-/-)) or neuronal nitric oxide synthase (nNOS(-/-)). In particular, nNOS(-/-) animals showed decreased S-nitrosylation of proteins that participate in the glutamate/glutamine cycle, a metabolic process by which synaptic glutamate is recycled or oxidized to provide energy. (15)N-glutamine-based metabolomic profiling and enzymatic activity assays indicated that brain extracts from nNOS(-/-) mice converted less glutamate to glutamine and oxidized more glutamate than those from mice of the other genotypes. GLT1 [also known as EAAT2 (excitatory amino acid transporter 2)], a glutamate transporter in astrocytes, was S-nitrosylated at Cys(373) and Cys(561) in wild-type and eNOS(-/-) mice, but not in nNOS(-/-) mice. A form of rat GLT1 that could not be S-nitrosylated at the equivalent sites had increased glutamate uptake compared to wild-type GLT1 in cells exposed to an S-nitrosylating agent. Thus, NO modulates glutamatergic neurotransmission through the selective, nNOS-dependent S-nitrosylation of proteins that govern glutamate transport and metabolism. Copyright © 2015, American Association for the Advancement of Science.

  15. Regulation of brain glutamate metabolism by nitric oxide and S-nitrosylation

    PubMed Central

    Raju, Karthik; Doulias, Paschalis-Thomas; Evans, Perry; Krizman, Elizabeth N.; Jackson, Joshua G.; Horyn, Oksana; Daikhin, Yevgeny; Nissim, Ilana; Yudkoff, Marc; Nissim, Itzhak; Sharp, Kim A.; Robinson, Michael B.; Ischiropoulos, Harry

    2016-01-01

    Nitric oxide (NO) is a signaling intermediate during glutamatergic neurotransmission in the central nervous system (CNS). NO signaling is in part accomplished through cysteine S-nitrosylation, a posttranslational modification by which NO regulates protein function and signaling. In our investigation of the protein targets and functional impact of S-nitrosylation in the CNS under physiological conditions, we identified 269 S-nitrosocysteine residues in 136 proteins in the wild-type mouse brain. The number of sites was significantly reduced in the brains of mice lacking endothelial nitric oxide synthase (eNOS−/−) or neuronal nitric oxide synthase (nNOS−/−). In particular, nNOS−/− animals showed decreased S-nitrosylation of proteins that participate in the glutamate/glutamine cycle, a metabolic process by which synaptic glutamate is recycled or oxidized to provide energy. 15N-glutamine–based metabolomic profiling and enzymatic activity assays indicated that brain extracts from nNOS−/− mice converted less glutamate to glutamine and oxidized more glutamate than those from mice of the other genotypes. GLT1 [also known as EAAT2 (excitatory amino acid transporter 2)], a glutamate transporter in astrocytes, was S-nitrosylated at Cys373 and Cys561 in wild-type and eNOS−/− mice, but not in nNOS−/− mice. A form of rat GLT1 that could not be S-nitrosylated at the equivalent sites had increased glutamate uptake compared to wild-type GLT1 in cells exposed to an S-nitrosylating agent. Thus, NO modulates glutamatergic neurotransmission through the selective, nNOS-dependent S-nitrosylation of proteins that govern glutamate transport and metabolism. PMID:26152695

  16. Thioredoxin Binding Protein-2 Regulates Autophagy of Human Lens Epithelial Cells under Oxidative Stress via Inhibition of Akt Phosphorylation

    PubMed Central

    Yao, Ke; Zhang, Yidong; Chen, Guangdi; Lai, Kairan; Yin, Houfa

    2016-01-01

    Oxidative stress plays an essential role in the development of age-related cataract. Thioredoxin binding protein-2 (TBP-2) is a negative regulator of thioredoxin (Trx), which deteriorates cellular antioxidant system. Our study focused on the autophagy-regulating effect of TBP-2 under oxidative stress in human lens epithelial cells (LECs). Human lens epithelial cells were used for cell culture and treatment. Lentiviral-based transfection system was used for overexpression of TBP-2. Cytotoxicity assay, western blot analysis, GFP/mCherry-fused LC3 plasmid, immunofluorescence, and transmission electronic microscopy were performed. The results showed that autophagic response of LECs with increased LC3-II, p62, and GFP/mCherry-LC3 puncta (P < 0.01) was induced by oxidative stress. Overexpression of TBP-2 further strengthens this response and worsens the cell viability (P < 0.01). Knockdown of TBP-2 attenuates the autophagic response and cell viability loss induced by oxidative stress. TBP-2 mainly regulates autophagy in the initiation stage, which is mTOR-independent and probably caused by the dephosphorylation of Akt under oxidative stress. These findings suggest a novel role of TBP-2 in human LECs under oxidative stress. Oxidative stress can cause cell injury and autophagy in LECs, and TBP-2 regulates this response. Hence, this study provides evidence regarding the role of TBP-2 in lens and the possible mechanism of cataract development. PMID:27656263

  17. The histone methylase KMTox interacts with the redox-sensor peroxiredoxin-1 and targets genes involved in Toxoplasma gondii antioxidant defences.

    PubMed

    Sautel, Céline F; Ortet, Philippe; Saksouk, Nehmé; Kieffer, Sylvie; Garin, Jérôme; Bastien, Olivier; Hakimi, Mohamed-Ali

    2009-01-01

    The ability of living cells to alter their gene expression patterns in response to environmental changes is essential for viability. Oxidative stress represents a common threat for all aerobic life. In normally growing cells, in which hydrogen peroxide generation is transient or pulsed, the antioxidant systems efficiently control its concentration. Intracellular parasites must also protect themselves against the oxidative burst imposed by the host. In this work, we have investigated the role of KMTox, a new histone lysine methyltransferase, in the obligate intracellular parasite Toxoplasma gondii. KMTox is a nuclear protein that holds a High Mobility Group domain, which is thought to recognize bent DNA. The enzyme methylates both histones H4 and H2A in vitro with a great preference for the substrate in reduced conditions. Importantly, KMTox interacts specifically with the typical 2-cys peroxiredoxin-1 and the binding is to some extent enhanced upon oxidation. It appears that the cellular functions that are primarily regulated by the KMTox are antioxidant defences and maintenance of cellular homeostasis. KMTox may regulate gene expression in T. gondii by providing the rapid re-arrangement of chromatin domains and by interacting with the redox-sensor TgPrx1 contribute to establish the antioxidant 'firewall' in T. gondii.

  18. 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

  19. Actin as deathly switch? How auxin can suppress cell-death related defence.

    PubMed

    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.

  20. Dietary omega-3 but not omega-6 fatty acids down-regulate maternal dyslipidemia induced oxidative stress: A three generation study in rats.

    PubMed

    Ramaiyan, Breetha; Bettadahalli, Sadashivaiah; Talahalli, Ramaprasad Ravichandra

    2016-09-02

    Maternal nutrition modulates fetal metabolic programming and development later. Maternal dyslipidemia effects on oxidative stress (OS) in offsprings and its modulation by dietary fatty acids over generations remains to be elucidated. The objective of present study was to assess the long-term (three generations) effect of omega-3 fatty acids on OS under dyslipidemia. Weanling female Wistar rats were fed with control diet (7% lard), high fat diet (35% lard, HFL), high fat with fish oil (21% fish oil + 14% lard, HFF), high fat with canola oil (21% canola oil + 14% lard, HFC) and high fat with sunflower oil (21% sunflower oil + 14% lard, HFS). Following 60 days feeding, the female rats were mated with sexually matured males (fed normal chow diet) and continued with the above diet regimen during pregnancy and lactation. The pups after lactation were continued with their maternal diet for 60 days and subjected to mating and feeding trial as above for two generations. Serum lipid profiles, OS markers (lipid peroxidation, nitric oxide release and protein carbonyl) and antioxidant defence enzymes (catalase, SOD, glutathione peroxidase and glutathione transferase) were assessed in serum, liver and uterus of rats fed on experimental and control diets for three generations. Feeding HFL diet increased blood lipids, OS and lowered the antioxidant enzymes activity in serum, liver and uterus (p < 0.05). The reduction in the antioxidant enzymes in HFL group were higher in third followed by second generation compared to first generation (p < 0.05). Omega-3 fatty acids prevented the dyslipidemia induced loss of antioxidant enzyme activities in serum, liver and uterus. Our data show for the first time that offsprings born to dyslipidemic mothers' exhibit diminished enzymatic antioxidant defence and its progressive reduction in future generation, and dietary omega-3 fatty acids restore the enzymatic antioxidant defence in offsprings and suppress the markers of OS. Copyright

  1. Seasonal variations in the antioxidant defence systems and lipid peroxidation of the digestive gland of mussels.

    PubMed

    Viarengo, A; Canesi, L; Pertica, M; Livingstone, D R

    1991-01-01

    1. The seasonal variations in the level of antioxidant compounds (glutathione (GSH), vitamin E, carotenoids) and in the activity of antioxidant enzymes, superoxide dismutase (EC 1.15.1.1), catalase (EC 1.11.1.6), GSH-peroxidase (EC 1.11.1.9) in the digestive gland of mussels (Mytilus sp.) were evaluated. The lipid peroxidation process was also measured by determining the tissue concentration of malondialdehyde (MDA). 2. The physiological fluctuations of the antioxidant defence systems were inversely related to the accumulation of lipid peroxidation products (MDA) in the tissue. The observed seasonal variations are presumably related to the changing metabolic status of the animals, itself dependent on such factors as gonad ripening and food availability. 3. In particular, the obtained data indicate that a reduction of the antioxidant defence systems, occurring during winter, could be directly responsible for an enhanced susceptibility of mussels tissues to oxidative stress, as indicated by the high MDA concentration observed in this period.

  2. A mir-231-Regulated Protection Mechanism against the Toxicity of Graphene Oxide in Nematode Caenorhabditis elegans

    NASA Astrophysics Data System (ADS)

    Yang, Ruilong; Ren, Mingxia; Rui, Qi; Wang, Dayong

    2016-08-01

    Recently, several dysregulated microRNAs (miRNAs) have been identified in organisms exposed to graphene oxide (GO). However, their biological functions and mechanisms of the action are still largely unknown. Here, we investigated the molecular mechanism of mir-231 in the regulation of GO toxicity using in vivo assay system of Caenorhabditis elegans. We found that GO exposure inhibited the expression of mir-231::GFP in multiple tissues, in particular in the intestine. mir-231 acted in intestine to regulate the GO toxicity, and overexpression of mir-231 in intestine caused a susceptible property of nematodes to GO toxicity. smk-1 encoding a homologue to mammalian SMEK functioned as a targeted gene for mir-231, and was also involved in the intestinal regulation of GO toxicity. Mutation of smk-1 gene induced a susceptible property to GO toxicity, whereas the intestinal overexpression of smk-1 resulted in a resistant property to GO toxicity. Moreover, mutation of smk-1 gene suppressed the resistant property of mir-231 mutant to GO toxicity. In nematodes, SMK-1 further acted upstream of the transcriptional factor DAF-16/FOXO in insulin signaling pathway to regulate GO toxicity. Therefore, mir-231 may encode a GO-responsive protection mechanism against the GO toxicity by suppressing the function of the SMK-1 - DAF-16 signaling cascade in nematodes.

  3. Anionic Regulated NiFe (Oxy)Sulfide Electrocatalysts for Water Oxidation.

    PubMed

    Li, Bo-Quan; Zhang, Shu-Yuan; Tang, Cheng; Cui, Xiaoyang; Zhang, Qiang

    2017-07-01

    The construction of active sites with intrinsic oxygen evolution reaction (OER) is of great significance to overcome the limited efficiency of abundant sustainable energy devices such as fuel cells, rechargeable metal-air batteries, and in water splitting. Anionic regulation of electrocatalysts by modulating the electronic structure of active sites significantly promotes OER performance. To prove the concept, NiFeS electrocatalysts are fabricated with gradual variation of atomic ratio of S:O. With the rise of S content, the overpotential for water oxidation exhibits a volcano plot under anionic regulation. The optimized NiFeS-2 electrocatalyst under anionic regulation possesses the lowest OER overpotential of 286 mV at 10 mA cm(-2) and the fastest kinetics being 56.3 mV dec(-1) to date. The anionic regulation methodology not only serves as an effective strategy to construct superb OER electrocatalysts, but also enlightens a new point of view for the in-depth understanding of electrocatalysis at the electronic and atomic level. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. A Computational Screen for Regulators of Oxidative Phosphorylation Implicates SLIRP in Mitochondrial RNA Homeostasis

    PubMed Central

    Baughman, Joshua M.; Nilsson, Roland; Gohil, Vishal M.; Arlow, Daniel H.; Gauhar, Zareen; Mootha, Vamsi K.

    2009-01-01

    The human oxidative phosphorylation (OxPhos) system consists of approximately 90 proteins encoded by nuclear and mitochondrial genomes and serves as the primary cellular pathway for ATP biosynthesis. While the core protein machinery for OxPhos is well characterized, many of its assembly, maturation, and regulatory factors remain unknown. We exploited the tight transcriptional control of the genes encoding the core OxPhos machinery to identify novel regulators. We developed a computational procedure, which we call expression screening, which integrates information from thousands of microarray data sets in a principled manner to identify genes that are consistently co-expressed with a target pathway across biological contexts. We applied expression screening to predict dozens of novel regulators of OxPhos. For two candidate genes, CHCHD2 and SLIRP, we show that silencing with RNAi results in destabilization of OxPhos complexes and a marked loss of OxPhos enzymatic activity. Moreover, we show that SLIRP plays an essential role in maintaining mitochondrial-localized mRNA transcripts that encode OxPhos protein subunits. Our findings provide a catalogue of potential novel OxPhos regulators that advance our understanding of the coordination between nuclear and mitochondrial genomes for the regulation of cellular energy metabolism. PMID:19680543

  5. Structural insight into the oxidation-sensing mechanism of the antibiotic resistance of regulator MexR

    SciTech Connect

    Chen, Hao; Yi, Chengqi; Zhang, Jin; Zhang, Wenru; Ge, Zhiyun; Yang, Cai-Guang; He, Chuan

    2010-11-05

    MexR functions as the primary regulator of the mexAB-oprM multidrug efflux expression in Pseudomonas aeruginosa. It has been shown that MexR senses oxidative stress by interprotomer disulphide bond formation between redox-active cysteines. This oxidation induces MexR to dissociate from the promoter DNA, thus activating the transcriptional expression of efflux pump genes. In this study, we present the crystal structure of MexR in its oxidized form at a resolution of 2.1 {angstrom}. This crystal structure reveals the mechanism by which oxidative signal allosterically derepresses the MexR-controlled transcription activation.

  6. SYK regulates macrophage MHC-II expression via activation of autophagy in response to oxidized LDL

    PubMed Central

    Choi, Soo-Ho; Gonen, Ayelet; Diehl, Cody J; Kim, Jungsu; Almazan, Felicidad; Witztum, Joseph L; Miller, Yury I

    2015-01-01

    Adaptive immunity, which plays an important role in the development of atherosclerosis, is mediated by major histocompatibility complex (MHC)-dependent antigen presentation. In atherosclerotic lesions, macrophages constitute an important class of antigen-presenting cells that activate adaptive immune responses to oxidized low-density lipoprotein (OxLDL). It has been reported that autophagy regulates adaptive immune responses by enhancing antigen presentation to MHC class II (MHC-II). In a previous study, we have demonstrated that SYK (spleen tyrosine kinase) regulates generation of reactive oxygen species (ROS) and activation of MAPK8/JNK1 in macrophages. Because ROS and MAPK8 are known to regulate autophagy, in this study we investigated the role of SYK in autophagy, MHC-II expression and adaptive immune response to OxLDL. We demonstrate that OxLDL induces autophagosome formation, MHC-II expression, and phosphorylation of SYK in macrophages. Gene knockout and pharmacological inhibitors of NOX2 and MAPK8 reduced OxLDL-induced autophagy. Using bone marrow-derived macrophages isolated from wild-type and myeloid-specific SYK knockout mice, we demonstrate that SYK regulates OxLDL-induced ROS generation, MAPK8 activation, BECN1-BCL2 dissociation, autophagosome formation and presentation of OxLDL-derived antigens to CD4+ T cells. ldlr−/− syk−/− mice fed a high-fat diet produced lower levels of IgG to malondialdehyde (MDA)-LDL, malondialdehyde-acetaldehyde (MAA)-LDL, and OxLDL compared to ldlr−/− mice. These results provide new insights into the mechanisms by which SYK regulates MHC-II expression via autophagy in macrophages and may contribute to regulation of adaptive immune responses in atherosclerosis. PMID:25946330

  7. Regulation of the sympathetic nervous system by nitric oxide and oxidative stress in the rostral ventrolateral medulla: 2012 Academic Conference Award from the Japanese Society of Hypertension.

    PubMed

    Kishi, Takuya

    2013-10-01

    Sympathoexcitation has an important role in the pathogenesis of hypertension. Previous studies have demonstrated that nitric oxide (NO) and/or oxidative stress in the brain are important for the regulation of the sympathetic nervous system. We have investigated the role of NO derived from an overexpression of endothelial NO synthase (eNOS) or oxidative stress in the rostral ventrolateral medulla (RVLM), which is known as a vasomotor center in the brainstem, on the regulation of the sympathetic nervous system. Our results indicated that NO derived from an overexpression of eNOS in the RVLM caused sympathoinhibition via an increase in γ-amino butyric acid and that angiotensin II type 1 receptor (AT1R)-induced oxidative stress in the RVLM caused sympathoexcitation. We also demonstrated that oxidative stress in the RVLM caused sympathoexcitation via interactions with NO, effects on the signal transduction or apoptosis of the astrocytes. Furthermore, several orally administered AT1R blockers have been found to cause sympathoinhibition via a reduction in oxidative stress through the blockade of AT1R in the RVLM of hypertensive rats. In conclusion, our studies suggest that the increase in AT1R-induced oxidative stress and/or the decrease in NO in the RVLM mainly cause sympathoexcitation in hypertension.

  8. Narcissism, defence and the positive transference.

    PubMed

    Hanly, C

    1982-01-01

    Questions concerning the positive transference and its therapeutic use have been raised by the psychology of the self. By drawing upon Freud, Abraham and Sharpe, an attempt is made to test whether classical structural, dynamic and developmental theories still provide an adequate theoretical framework for understanding the vicissitudes of the positive transference in patients with significant narcissistic psychopathology. I propose the concept of a narcissistic mechanism of defence which, relying upon the convertibility of object libido into narcissistic libido (and the reverse), utilizes the substitution of activities and inanimate objects for persons in order to compensate for narcissistic injuries and to carry out unconscious aggression motivated by the same injuries. The case of Mrs M reveals that narcissistic transference phenomena, while requiring specific therapeutic interpretation, nevertheless are intrinsically related developmentally to object libidinal conflicts. The patient's narcissistic injuries were found to be intrinsically related to stage specific traumata at the oral, anal and phallic stages. Thus while the narcissistic aspects of these traumata had to be treated therapeutically in their own right, they could not have been successfully treated without the concurrent or sequential treatment of the object libidinal conflicts connected with them. Finally, it is argued that the hypothesis of a narcissistic defence mechanism supported by the hypothesis of pre-oedipal narcissistic projective and introjective identifications with narcissistically divinized or demonized parents within the framework of classical theory can account for the clinical phenomena of narcissistic neuroses.

  9. Insect-plant interactions: endocrine defences.

    PubMed

    Bowers, W S

    1984-01-01

    It is the inevitable consequence of evolution that competitive species living together in a restricted space must try to exclude each other. Plants and insects are prime examples of this eternal competition, and although neither of these is in danger of extinction, their mutual defensive strategies are of compelling interest to the human race. Plant defences based on the insecticidal activity of certain of their secondary chemicals are readily apparent. Only through research into the fundamentals of insect physiology and biochemistry are more subtle defensive mechanisms revealed, linked to the disruption of the insect endocrine system. A diverse number of chemical structures are found in plants, which interfere with hormone-mediated processes in insects. Examples include: mimics of the insect's juvenile hormones such as juvabione from the balsam fir and the juvocimenes from sweet basil, which lethally disrupt insect development, and the precocenes found in Ageratum species, which act as anti-juvenile hormonal agents. The latter appear to serve as 'suicide substrates', undergoing activation into cytotoxins when acted on by specialized enzymes resident in the insect endocrine gland (corpus allatum) that is responsible for juvenile hormone biosynthesis and secretion. Consideration of these plant defensive strategies, which have been reached through aeons of evolutionary experimentation, may assist the human race in its defences against its principal competitors for food, fibre and health.

  10. 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.

  11. Nitric oxide is an activity-dependent regulator of target neuron intrinsic excitability.

    PubMed

    Steinert, Joern R; Robinson, Susan W; Tong, Huaxia; Haustein, Martin D; Kopp-Scheinpflug, Cornelia; Forsythe, Ian D

    2011-07-28

    Activity-dependent changes in synaptic strength are well established as mediating long-term plasticity underlying learning and memory, but modulation of target neuron excitability could complement changes in synaptic strength and regulate network activity. It is thought that homeostatic mechanisms match intrinsic excitability to the incoming synaptic drive, but evidence for involvement of voltage-gated conductances is sparse. Here, we show that glutamatergic synaptic activity modulates target neuron excitability and switches the basis of action potential repolarization from Kv3 to Kv2 potassium channel dominance, thereby adjusting neuronal signaling between low and high activity states, respectively. This nitric oxide-mediated signaling dramatically increases Kv2 currents in both the auditory brain stem and hippocampus (>3-fold) transforming synaptic integration and information transmission but with only modest changes in action potential waveform. We conclude that nitric oxide is a homeostatic regulator, tuning neuronal excitability to the recent history of excitatory synaptic inputs over intervals of minutes to hours. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Redox regulation by thioredoxin superfamily; protection against oxidative stress and aging.

    PubMed

    Tanaka, T; Nakamura, H; Nishiyama, A; Hosoi, F; Masutani, H; Wada, H; Yodoi, J

    2000-12-01

    Thioredoxin (TRX) is a 12 kD protein with redox-active dithiol in the active site; -Cys-Gly-Pro-Cys-. We originally cloned human TRX as adult T cell leukemia derived factor (ADF) produced by HTLV-I transformed cells. TRX and related molecules maintain a cellular reducing enviroment, working in concert with the glutathione system. Physiologically, TRX has cytoprotective effects against oxidative stress. TRX promotes DNA binding of transcription factors such as NF-kB, AP-1, p53, and PEBP-2. The TRX superfamily, including thioredoxin-2 (mitochondrial thioredoxin) and glutaredoxin, are involved in biologically important phenomena via the redox-regulating system. Thioredoxin-binding protein-2, which we recently identified by a yeast two-hybrid system, is a type of endogenous modulator of TRX activity. TRX is secreted from the cells and exhibits cytokine-like and chemokine-like activities. Redox regulation by TRX plays a crucial role in biological responses against oxidative stress.

  13. Regulation of myometrial circulation and uterine vascular tone by constitutive nitric oxide.

    PubMed

    Toda, Noboru; Toda, Hiroshi; Okamura, Tomio

    2013-08-15

    Pregnancy is a physiological state that involves an increase in uterine blood flow, which is mediated in part by nitric oxide (NO) liberated from the endothelium and nitrergic neurons. The main focus of this review article is to provide information about how endogenous NO regulates uterine and placental blood flow and vascular tone in experimental animals and humans in vivo or in vitro in non-pregnant and pregnant states as well as pregnancy with pre-eclampsia. Uterine arteries from non-pregnant women respond to NO liberated from the endothelium and nitrergic nerves with relaxations, and the release of endothelial NO is influenced by the phase of the estrous cycle, with its enhanced release at the follicular phase when the estrogen level is high. NO bioavailability in the uteroplacental circulatory system is gradually increased during pregnancy. Pre-eclamptic pregnancies with or without intrauterine growth restriction show impaired uteroplacental blood flow accompanied by reduced NO synthesis due to down-regulation of eNOS as well as asymmetric dimethylarginine accumulation and by augmented NO degradation by oxidative stress. Further studies are expected to provide new mechanistic insights into the fascinating process of maternal uterine adaptation in humans and novel prophylactic and therapeutic measures against pre-eclampsia. © 2013 Elsevier B.V. All rights reserved.

  14. Oxidative stress-mediated down-regulation of bcl-2 promoter in hippocampal neurons.

    PubMed

    Pugazhenthi, Subbiah; Nesterova, Albina; Jambal, Purevsuren; Audesirk, Gerald; Kern, Marcey; Cabell, Leigh; Eves, Eva; Rosner, Marsha R; Boxer, Linda M; Reusch, Jane E-B

    2003-03-01

    Generation of oxidative stress/reactive oxygen species (ROS) is one of the causes of neuronal apoptosis. We have examined the effects of ROS at the transcriptional level in an immortalized hippocampal neuronal cell line (H19-7) and in rat primary hippocampal neurons. Treatment of H19-7 cells with hydrogen peroxide (150 micro m) resulted in a 40% decrease in Bcl-2 protein and a parallel decrease in bcl-2 mRNA levels. H19-7 cells overexpressing bcl-2 were found to be resistant to ROS-induced apoptosis. We had previously shown that bcl-2 promoter activity is positively regulated by the transcription factor cyclic AMP response element binding protein (CREB) in neurons. In the present study, we demonstrate that ROS decreases the activity of luciferase reporter gene driven by a cyclic AMP response element site containing bcl-2 promoter. Exposure of neurons to ROS for 6 h resulted in basal and fibroblast growth factor-2-stimulated phosphorylation/activation of CREB. Chronic 24 h treatment with ROS led to a significant (p < 0.01) decrease in CREB protein and CREB mRNA levels. Adenoviral overexpression of wild type CREB in H19-7 cells resulted in significant (p < 0.01) protection against ROS-induced apoptosis through up-regulation of Bcl-2 expression whereas dominant negative CREB exaggerated the injury. These findings demonstrate that loss of CREB function contributes to oxidative stress-induced neuronal dysfunction.

  15. Role of the Transforming Growth Factor-β in regulating hepatocellular carcinoma oxidative metabolism.

    PubMed

    Soukupova, Jitka; Malfettone, Andrea; Hyroššová, Petra; Hernández-Alvarez, María-Isabel; Peñuelas-Haro, Irene; Bertran, Esther; Junza, Alexandra; Capellades, Jordi; Giannelli, Gianluigi; Yanes, Oscar; Zorzano, Antonio; Perales, José Carlos; Fabregat, Isabel

    2017-10-02

    Transforming Growth Factor beta (TGF-β) induces tumor cell migration and invasion. However, its role in inducing metabolic reprogramming is poorly understood. Here we analyzed the metabolic profile of hepatocellular carcinoma (HCC) cells that show differences in TGF-β expression. Oxygen consumption rate (OCR), extracellular acidification rate (ECAR), metabolomics and transcriptomics were performed. Results indicated that the switch from an epithelial to a mesenchymal/migratory phenotype in HCC cells is characterized by reduced mitochondrial respiration, without significant differences in glycolytic activity. Concomitantly, enhanced glutamine anaplerosis and biosynthetic use of TCA metabolites were proved through analysis of metabolite levels, as well as metabolic fluxes from U-13C6-Glucose and U-13C5-Glutamine. This correlated with increase in glutaminase 1 (GLS1) expression, whose inhibition reduced cell migration. Experiments where TGF-β function was activated with extracellular TGF-β1 or inhibited through TGF-β receptor I silencing showed that TGF-β induces a switch from oxidative metabolism, coincident with a decrease in OCR and the upregulation of glutamine transporter Solute Carrier Family 7 Member 5 (SLC7A5) and GLS1. TGF-β also regulated the expression of key genes involved in the flux of glycolytic intermediates and fatty acid metabolism. Together, these results indicate that autocrine activation of the TGF-β pathway regulates oxidative metabolism in HCC cells.

  16. Mortalin and DJ-1 coordinately regulate hematopoietic stem cell function through the control of oxidative stress.

    PubMed

    Tai-Nagara, Ikue; Matsuoka, Sahoko; Ariga, Hiroyoshi; Suda, Toshio

    2014-01-02

    Hematopoietic stem cells (HSCs) maintain stemness through various mechanisms that protect against stressful conditions. Heat shock proteins (HSPs) preserve cell homeostasis during stress responses through protein quality control, suggesting that HSPs may safeguard HSCs against numerous traumas. Here, we show that mortalin, a mitochondrial HSP, plays an essential role in maintaining HSC properties by regulating oxidative stress. Mortalin is primarily localized in hematopoietic stem and progenitor cell (HSPC) compartments. In this study, the inhibition of mortalin function caused abnormal reactive oxygen species (ROS) elevation in HSCs and reduced HSC numbers. Knockdown (KD) of mortalin in HSPCs impaired their ability to repopulate and form colonies. Moreover, mortalin-KD HSCs could not maintain quiescence and showed severe downregulation of cyclin-dependent kinase inhibitor- and antioxidant-related genes. Conversely, HSCs that overexpressed mortalin maintained a high reconstitution capacity and low ROS levels. Furthermore, DJ-1, one of the genes responsible for Parkinson's disease, directly bound to mortalin and acted as a negative ROS regulator. Using DJ-1-deficient mice, we demonstrated that mortalin and DJ-1 coordinately maintain normal ROS levels and HSC numbers. Collectively, these results indicate that the mortalin/DJ-1 complex guards against mitochondrial oxidative stress and is indispensable for the maintenance of HSCs.

  17. Localized LoxL3-Dependent Fibronectin Oxidation Regulates Myofiber Stretch and Integrin-Mediated Adhesion.

    PubMed

    Kraft-Sheleg, Ortal; Zaffryar-Eilot, Shelly; Genin, Olga; Yaseen, Wesal; Soueid-Baumgarten, Sharon; Kessler, Ofra; Smolkin, Tatyana; Akiri, Gal; Neufeld, Gera; Cinnamon, Yuval; Hasson, Peleg

    2016-03-07

    For muscles to function, myofibers have to stretch and anchor at the myotendinous junction (MTJ), a region rich in extracellular matrix (ECM). Integrin signaling is required for MTJ formation, and mutations affecting the cascade lead to muscular dystrophies in mice and humans. Underlying mechanisms for integrin activation at the MTJ and ECM modifications regulating its signaling are unclear. We show that lysyl oxidase-like 3 (LoxL3) is a key regulator of integrin signaling that ensures localized control of the cascade. In LoxL3 mutants, myofibers anchor prematurely or overshoot to adjacent somites, and are loose and lack tension. We find that LoxL3 complexes with and directly oxidizes Fibronectin (FN), an ECM scaffold protein and integrin ligand enriched at the MTJ. We identify a mechanism whereby localized LoxL3 secretion from myofiber termini oxidizes FN, enabling enhanced integrin activation at the tips of myofibers and ensuring correct positioning and anchoring of myofibers along the MTJ. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Dioscin alleviates dimethylnitrosamine-induced acute liver injury through regulating apoptosis, oxidative stress and inflammation.

    PubMed

    Zhang, Weixin; Yin, Lianhong; Tao, Xufeng; Xu, Lina; Zheng, Lingli; Han, Xu; Xu, Youwei; Wang, Changyuan; Peng, Jinyong

    2016-07-01

    In our previous study, the effects of dioscin against alcohol-, carbon tetrachloride- and acetaminophen-induced liver damage have been found. However, the activity of it against dimethylnitrosamine (DMN)-induced acute liver injury remained unknown. In the present study, dioscin markedly decreased serum ALT and AST levels, significantly increased the levels of SOD, GSH-Px, GSH, and decreased the levels of MDA, iNOS and NO. Mechanism study showed that dioscin significantly decreased the expression levels of IL-1β, IL-6, TNF-α, IκBα, p50 and p65 through regulating TLR4/MyD88 pathway to rehabilitate inflammation. In addition, dioscin markedly up-regulated the expression levels of SIRT1, HO-1, NQO1, GST and GCLM through increasing nuclear translocation of Nrf2 against oxidative stress. Furthermore, dioscin significantly decreased the expression levels of FasL, Fas, p53, Bak, Caspase-3/9, and upregulated Bcl-2 level through decreasing IRF9 level against apoptosis. In conclusion, dioscin showed protective effect against DMN-induced acute liver injury via ameliorating apoptosis, oxidative stress and inflammation, which should be developed as a new candidate for the treatment of acute liver injury in the future.

  19. The radiosensitivity of satellite cells: cell cycle regulation, apoptosis and oxidative stress.

    PubMed

    Caiozzo, Vincent J; Giedzinski, Erich; Baker, Mike; Suarez, Tatiana; Izadi, Atefeh; Lan, Mary; Cho-Lim, Jennie; Tseng, Bertrand P; Limoli, Charles L

    2010-11-01

    Skeletal muscles are the organ of movement, and their growth, regeneration and maintenance are dependent in large part on a population of myogenic stem cells known as satellite cells. Skeletal muscles and these resident myogenic stem cells (i.e., satellite cells) are commonly exposed to significant doses of radiation during diagnostic procedures and/or during the radiotherapeutic management of cancer. The main objective of this study was to examine the effects of clinically relevant doses of γ radiation on satellite cell survival and proliferation, cell cycle regulation, apoptosis, DNA double-strand break repair, oxidative stress and NO production. Overall, our findings demonstrate that doses of γ radiation ≥5 Gy reduced satellite cell numbers by at least 70% due in part to elevated apoptosis and the inhibition of cell cycle progression. Radiation was also found to cause a significant and persistent increase in the level of reactive oxygen and nitrogen species. Interestingly, and within this backdrop of elevated oxidative stress, similar doses were found to produce substantial reductions in the levels of nitric oxide (NO). Proliferation of satellite cells has been shown to depend in part on the production of NO, and our findings give rise to the possibility that radiation-induced reductions in NO levels may provide a mechanism for the inhibition of satellite cell proliferation in vitro and possibly the regrowth of skeletal muscle exposed during clinical irradiation procedures.

  20. Concerted regulation of skeletal muscle contractility by oxygen tension and endogenous nitric oxide

    PubMed Central

    Eu, Jerry P.; Hare, Joshua M.; Hess, Douglas T.; Skaf, Michel; Sun, Junhui; Cardenas-Navina, Isabella; Sun, Qi-An; Dewhirst, Mark; Meissner, Gerhard; Stamler, Jonathan S.

    2003-01-01

    It is generally accepted that inhibition of nitric oxide synthase (NOS) facilitates, and thus nitric oxide (NO) inhibits, contractility of skeletal muscle. However, standard assessments of contractility are carried out at a nonphysiological oxygen tension [partial pressure of oxygen (pO2)] that can interfere with NO signaling (95% O2). We therefore examined, in normal and neuronal NOS (nNOS)-deficient mice, the influence of pO2 on whole-muscle contractility and on myocyte calcium flux and sarcomere shortening. Here, we demonstrate a significant enhancement of these measures of muscle performance at low physiological pO2 and an inhibitory influence at higher physiological pO2, which depend on endogenous nNOS. At 95% O2 (which produces oxidative stress; muscle core pO2 ≈400 mmHg), force production is enhanced but control of contractility by NO/nitrosylation is greatly attenuated. In addition, responsivity to pO2 is altered significantly in nNOS mutant muscle. These results reveal a fundamental role for the concerted action of NO and O2 in physiological regulation of skeletal muscle contractility, and suggest novel molecular aspects of myopathic disease. They suggest further that the role of NO in some cellular systems may require reexamination. PMID:14645704

  1. L-arginine regulates neuronal nitric oxide synthase production of superoxide and hydrogen peroxide.

    PubMed

    Tsai, Pei; Weaver, John; Cao, Guan Liang; Pou, Sovitj; Roman, Linda J; Starkov, Anatoly A; Rosen, Gerald M

    2005-03-15

    Tetrahydrobiopterin (H(4)B) in the absence of L-arginine has been shown to be an important factor in promoting the direct formation of hydrogen peroxide (H(2)O(2)) at the expense of superoxide (O(2)(*-)) by neuronal nitric oxide synthase (NOS1) [Rosen GM, Tsai P, Weaver J, Porasuphatana S, Roman LJ, Starkov AA, et al. Role of tetrahydrobiopterin in the regulation of neuronal nitric-oxide synthase-generated superoxide. J Biol Chem 2002;277:40275-80]. Based on these findings, it is hypothesized that L-arginine also shifts the equilibrium between O(2)(*-) and H(2)O(2). Experiments were designed to test this theory. As the concentration of L-arginine and N(omega)-hydroxyl-L-arginine increases, the rate of NADPH consumption for H(4)B-bound NOS1 decreased resulting in lower rates of both O(2)(*-) and H(2)O(2) generation, while increasing the rate of nitric oxide (*NO) production. At saturating concentrations of L-arginine or N(omega)-hydroxyl-L-arginine (50microM), NOS1 still produced O(2)(*-) and H(2)O(2). Both L-arginine and N(omega)-hydroxyl-L-arginine have greater impact on the rate of generation of O(2)(*-) than on H(2)O(2).

  2. Urm1: an essential regulator of JNK signaling and oxidative stress in Drosophila melanogaster.

    PubMed

    Khoshnood, B; Dacklin, I; Grabbe, C

    2016-05-01

    Ubiquitin-related modifier 1 (Urm1) is a ubiquitin-like molecule (UBL) with the dual capacity to act both as a sulphur carrier and posttranslational protein modifier. Here we characterize the Drosophila melanogaster homologues of Urm1 (CG33276) and its E1 activating enzyme Uba4 (CG13090), and show that they function together to induce protein urmylation in vivo. Urm1 conjugation to target proteins in general, and to the evolutionary conserved substrate Peroxiredoxin 5 (Prx5) specifically, is dependent on Uba4. A complete loss of Urm1 is lethal in flies, although a small number of adult zygotic Urm1 (n123) mutant escapers can be recovered. These escapers display a decreased general fitness and shortened lifespan, but in contrast to their S. cerevisiae counterparts, they are resistant to oxidative stress. Providing a molecular explanation, we demonstrate that cytoprotective JNK signaling is increased in Urm1 deficient animals. In agreement, molecular and genetic evidence suggest that elevated activity of the JNK downstream target genes Jafrac1 and gstD1 strongly contributes to the tolerance against oxidative stress displayed by Urm1 (n123) null mutants. In conclusion, Urm1 is a UBL that is involved in the regulation of JNK signaling and the response against oxidative stress in the fruit fly.

  3. Regulating infrared photoresponses in reduced graphene oxide phototransistors by defect and atomic structure control.

    PubMed

    Chang, Haixin; Sun, Zhenhua; Saito, Mitsuhiro; Yuan, Qinghong; Zhang, Han; Li, Jinhua; Wang, Zhongchang; Fujita, Takeshi; Ding, Feng; Zheng, Zijian; Yan, Feng; Wu, Hongkai; Chen, Mingwei; Ikuhara, Yuichi

    2013-07-23

    Defects play significant roles in properties of graphene and related device performances. Most studies of defects in graphene focus on their influences on electronic or luminescent optical properties, while controlling infrared optoelectronic performance of graphene by defect engineering remains a challenge. In the meantime, pristine graphene has very low infrared photoresponses of ~0.01 A/W due to fast photocarrier dynamics. Here we report regulating infrared photoresponses in reduced graphene oxide phototransistors by defect and atomic structure control for the first time. The infrared optoelectronic transport and photocurrent generation are significantly influenced and well controlled by oxygenous defects and structures in reduced graphene oxide. Moreover, remarkable infrared photoresponses are observed in photoconductor devices based on reduced graphene oxide with an external responsivity of ~0.7 A/W, at least over one order of magnitude higher than that from pristine graphene. External quantum efficiencies of infrared devices reach ultrahigh values of ~97%, which to our knowledge is one of the best efficiencies for infrared photoresponses from nonhybrid, pure graphene or graphene-based derivatives. The flexible infrared photoconductor devices demonstrate no photoresponse degradation even after 1000 bending tests. The results open up new routes to control optoelectronic behaviors of graphene for high-performance devices.

  4. REGULATION OF FMN SUBDOMAIN INTERACTIONS AND FUNCTION IN NEURONAL NITRIC OXIDE SYNTHASE‡

    PubMed Central

    Ilagan, Robielyn P.; Tejero, Jesús; Aulak, Kulwant S.; Sinha Ray, Sougata; Hemann, Craig; Wang, Zhi-Qiang; Gangoda, Mahinda; Zweier, Jay L.; Stuehr, Dennis J.

    2009-01-01

    Nitric oxide synthases (NOS) are modular, calmodulin (CaM)-dependent, flavo-heme enzymes that catalyze oxidation of L-arginine to generate nitric oxide (NO) and citrulline. During catalysis, the FMN subdomain cycles between interaction with an NADPH-FAD subdomain to receive electrons, and interaction with an oxygenase domain to deliver electrons to the NOS heme. This process can be described by a three-state, two equilibrium model for the conformation of the FMN subdomain, in which it exists in two distinct bound states (FMN-shielded), and one common unbound state (FMN-deshielded). We studied how each partner subdomain, the FMN redox state, and CaM binding may regulate the conformational equilibria of the FMN module in rat neuronal NOS (nNOS). We utilized four nNOS protein constructs of different subdomain composition, including the isolated FMN subdomain, and determined changes in the conformational state by measuring the degree of FMN shielding by fluorescence, electron paramagnetic resonance, or stopped-flow spectroscopic techniques. Our results suggest: (i) The NADPH-FAD subdomain has a far greater capacity to interact with the FMN subdomain than does the oxygenase domain. (ii) CaM binding has no direct effects on the FMN subdomain. (iii) CaM destabilizes interaction of the FMN subdomain with the NADPH-FAD subdomain but does not measurably increase its interaction with the oxygenase domain. Our results imply that a different set point and CaM regulation exists for either conformational equilibrium of the FMN subdomain. This helps to explain the unique electron transfer and catalytic behaviors of nNOS, relative to other dual-flavin enzymes. PMID:19290671

  5. Betaine affects muscle lipid metabolism via regulating the fatty acid uptake and oxidation in finishing pig.

    PubMed

    Li, Sisi; Wang, Haichao; Wang, Xinxia; Wang, Yizhen; Feng, Jie

    2017-01-01

    Betaine affects fat metabolism in animals, but the specific mechanism is still not clear. The purpose of this study was to investigate possible mechanisms of betaine in altering lipid metabolism in muscle tissue in finishing pigs. A total of 120 crossbred gilts (Landrace × Yorkshire × Duroc) with an average initial body weight of 70.1 kg were randomly allotted to three dietary treatments. The treatments included a corn-soybean meal basal diet supplemented with 0, 1250 or 2500 mg/kg betaine. The feeding experiment lasted 42 d. Betaine addition to the diet significantly increased the concentration of free fatty acids (FFA) in muscle (P < 0.05). Furthermore, the levels of serum cholesterol and high-density lipoprotein cholesterol were decreased (P < 0.05) and total cholesterol content was increased in muscle (P < 0.05) of betaine fed pigs. Experiments on genes involved in fatty acid transport showed that betaine increased expression of lipoprotein lipase(LPL), fatty acid translocase/cluster of differentiation (FAT/CD36), fatty acid binding protein (FABP3) and fatty acid transport protein (FATP1) (P < 0.05). The abundance of fatty acid transport protein and fatty acid binding protein were also increased by betaine (P < 0.05). As for the key factors involved in fatty acid oxidation, although betaine supplementation didn't affect the level of carnitine and malonyl-CoA, betaine increased mRNA and protein abundance of carnitine palmitransferase-1(CPT1) and phosphorylated-AMPK (P < 0.05). The results suggested that betaine may promoted muscle fatty acid uptake via up-regulating the genes related to fatty acid transporter including FAT/CD36, FATP1 and FABP3. On the other hand, betaine activated AMPK and up-regulated genes related to fatty acid oxidation including PPARα and CPT1. The underlying mechanism regulating fatty acid metabolism in pigs supplemented with betaine is associated with the up-regulation of genes involved in fatty acid transport and fatty

  6. Nitric oxide and the common cold.

    PubMed

    Proud, David

    2005-02-01

    The common cold is a clinical syndrome triggered by a variety of viral pathogens, but rhinoviruses are the most frequent cause. Complications of such infections include sinusitis, otitis media, and exacerbations of asthma and chronic obstructive lung disease. There is growing interest in host innate defence responses that may regulate the severity of viral responses. We will review recent evidence that nitric oxide is an important contributor to the host response during colds. Infection of human airway epithelial cells with human rhinovirus has been shown to lead to the increased expression of inducible nitric oxide synthase both in vitro and in vivo. This increase in epithelial inducible nitric oxide synthase correlates with increased levels of nitric oxide in exhaled air. Importantly, nitric oxide can inhibit human rhinovirus-induced epithelial expression of several pro-inflammatory cytokines and can inhibit viral replication in epithelial cells in vitro. Moreover, nitric oxide can modulate several signal transduction pathways that are associated with cytokine generation. Nitric oxide can also nitrosylate viral proteases and can interact with the immune system. Consistent with these observations, pilot studies have indicated that the increased generation of nitric oxide during rhinovirus infections is associated with fewer symptoms and more rapid viral clearance. Further studies are warranted to evaluate the role of nitric oxide in colds and to determine whether the administration of nitric oxide donor compounds could be a viable therapeutic approach for viral exacerbations of airway diseases.

  7. Resolving defence mechanisms: A perspective based on dissipative structure theory.

    PubMed

    Zhang, Wei; Guo, Ben-Yu

    2017-04-01

    Theories and classifications of defence mechanisms are not unified. This study addresses the psychological system as a dissipative structure which exchanges information with the external and internal world. When using defence mechanisms, the cognitive-affective schema of an individual could remain stable and ordered by excluding psychological entropy, obtaining psychological negentropy or by dissipating the energy of self-presentation. From this perspective, defences can be classified into three basic types: isolation, compensation and self-dissipation. However, not every kind of defence mechanisms can actually help the individual. Non-adaptive defences are just functioning as an effective strategy in the short run but can be a harmful approach in the long run, while adaptive defences could instead help the individual as a long-term mechanism. Thus, we would like to suggest that it is more useful for the individual to use more adaptive defence mechanisms and seek out social or interpersonal support when undergoing psychic difficulties. As this model of defences is theoretical at present, we therefore aim to support and enrich this viewpoint with empirical evidence. Copyright © 2017 Institute of Psychoanalysis.

  8. 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.

  9. 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

  10. Some Methods for Scenario Analysis in Defence Strategic Planning

    DTIC Science & Technology

    Scenarios are an important tool in the strategic planning process, and are increasingly used in both the Defence and business world. This paper...illustrated with small examples. We also demonstrate a single, flexible approach to combining these methods using a typical Defence strategic planning problem

  11. 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.

  12. Comparative analysis of passive defences in spiders (Araneae).

    PubMed

    Pekár, Stano

    2014-07-01

    Being frequent prey of many predators, including especially wasps and birds, spiders have evolved a variety of defence mechanisms. Here I studied patterns of passive defences, namely anachoresis, crypsis, masquerade, aposematism and Batesian mimicry, in spiders. Using published information pertaining more than 1000 spider species, the phylogenetic pattern of different passive defences (i.e. defences that decrease the risk of an encounter with the predator) was investigated. Furthermore, I studied the effect of foraging guild, geographical distribution and diel activity on the frequency of defences as these determine the predators diversity, presence and perception. I found that crypsis (background matching) combined with anachoresis (hiding) was the most frequent defence confined mainly to families/genera at the base of the tree. Aposematism (warning coloration) and Batesian mimicry (imitation of noxious/dangerous model) were found in taxa that branched later in the tree, and masquerade (imitation of inedible objects) was confined to families at intermediate positions of the tree. Aposematism and Batesian mimicry were restricted to a few lineages. Masquerade was used particularly by web-building species with nocturnal activity. Aposematism was rare but mainly used by web-building diurnal species. Batesian mimicry was frequently observed in cursorial species with diurnal activity. Cryptic species were more common in temperate zones, whereas aposematic and mimetic species were more common in the tropics. Here I show that the evolution of passive defences in spiders was influenced by the ecology of species. Then, I discuss the evolutionary significance of the particularly defences.

  13. Computed Tomography Technology: Development and Applications for Defence

    SciTech Connect

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

    2008-09-26

    Computed Tomography(CT) has revolutionized the field of Non-Destructive Testing and Evaluation (NDT and 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.

  14. 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

  15. [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.

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

    PubMed Central

    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

    2015-01-01

    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

  17. 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.

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

    PubMed

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

    2015-08-01

    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.

  19. Wound repair and anti-oxidative capacity is regulated by ITGB4 in airway epithelial cells.

    PubMed

    Liu, Chi; Liu, Hui-jun; Xiang, Yang; Tan, Yu-rong; Zhu, Xiao-lin; Qin, Xiao-qun

    2010-08-01

    Integrin beta 4 (ITGB4) is a structural adhesion molecule which engages in maintaining the integrity of airway epithelial cells. Its specific cytomembrane structural feature strongly indicates that ITGB4 may engage in many signaling pathways and physiologic processes. However, in addition to adhesion, the specific biologic significance of ITGB4 in airway epithelial cells is almost unknown. In this article, we investigated the expression and functional properties of ITGB4 in airway epithelial cells in vivo and in vitro. Human bronchial epithelial cell line (16HBE14O-cells) and primary rat tracheal epithelial cells (RTE cells) were used to determine ITGB4 expression under ozone tress or mechanical damage, respectively. An ovalbumin (OVA)-challenged asthma model was used to investigate ITGB4 expression after antigen exposure in vivo. In addition, an ITGB4 overexpression vector and ITGB4 silence virus vector were constructed and transfected into RTE cells. Then, wound repair ability and anti-oxidation capacity was evaluated. Our results demonstrated that, on the edge of mechanically wounded cell areas, ITGB4 expression was increased after mechanical injury. After ozone stress, upregulation expression of ITGB4 was also detected. In the OVA-challenged asthma model, ITGB4 expression was decreased on airway epithelial cells accompanying with structural disruption and damage of anti-oxidation capacity. Besides, our study revealed that upregulation of ITGB4 promotes wound repair ability and anti-oxidative ability, while such abilities were blocked when ITGB4 was silenced. Taken together, these results showed that ITGB4 was a new interesting molecule involved in the regulation of wound repair and anti-oxidation processes for airway epithelial cells.

  20. Houttuynia cordata Extract Improves Physical Endurance Performance by Regulating Endothelial Production of Nitric Oxide.

    PubMed

    Yang, Ui-Jeong; Maeng, Hyojin; Park, Tae-Sik; Shim, Soon-Mi

    2015-09-01

    Vascular function is mediated by various regulatory molecules, including endothelial nitric oxide (NO), which regulates the vasodilation of smooth muscle cells. We investigated whether standardized Houttuynia cordata extract (SHCE) could improve physical endurance performance by regulating the endothelial production of NO. For the standardization of Houttuynia cordata (HC) extract, its bioactive components were identified and quantified using ultraperformance liquid chromatography-mass spectrometry. Bioaccessibility and biological activity were measured by the in vitro digestion model system and free radical scavenging capacity, respectively. The vascular function in the endothelium was assessed by the phosphorylation of endothelial nitric oxide synthase (eNOS). A preliminary clinical trial was carried out to assess the physical endurance performance. HC extract was standardized to bioactive components, including chlorogenic acid, rutin, and quercitrin, with the concentration of 5.53, 6.09, and 16.15 mg from 1 g of dry weight, respectively. Bioaccessibility was 33.17%, 31.67%, and 11.18% for chlorogenic acid, rutin, and quercitrin, respectively. Antioxidant activities of SHCE were expressed as vitamin C equivalent antioxidant capacity in 55.81 and 17.23 mg/g of HC extract using ABTS and DPPH scavenging assay, respectively. In human aortic endothelial cells, insulin-mediated phosphorylation of eNOS was increased by SHCE in the presence of palmitate. However, the expression of blood pressure-regulating genes was not altered. The level of blood lactate concentration and the heart rate of subjects who drank SHCE were lower than those of subjects who drank plain water. Oxygen uptake from subjects drinking SHCE was slightly higher than that from those who drank plain water. This study demonstrated that SHCE decreased heart rate and blood lactate, increased oxygen uptake, and improved physical performance, presumably due to the increased NO production.

  1. Hydrogen peroxide modulates the dynamic microtubule cytoskeleton during the defence responses to Verticillium dahliae toxins in Arabidopsis.

    PubMed

    Yao, Lin-Lin; Zhou, Qun; Pei, Bao-Lei; Li, Ying-Zhang

    2011-09-01

    The molecular mechanisms of signal transduction of plants in response to infection by Verticillium dahliae (VD) are not well understood. We previously showed that NO may act as an upstream signalling molecule to trigger the depolymerization of cortical microtubules in Arabidopsis. In the present study, we used the wild-type, and atrbohD and atrbohF mutants of Arabidopsis to explore the mechanisms of action of H(2)O(2) signals and the dynamic microtubule cytoskeleton in defence responses. We demonstrated that H(2)O(2) may also act as an upstream signalling molecule to regulate cortical microtubule depolymerization. The depolymerization of the cortical microtubules played a functional role in the signalling pathway to mediate the expression of defence genes. The results indicate that H(2)O(2) modulates the dynamic microtubule cytoskeleton to trigger the expression of defence genes against V. dahliae toxins (VD-toxins) in Arabidopsis.

  2. Nitric Oxide Regulates The Lymphatic Reactivity Following Hemorrhagic Shock Through Atp-Sensitive Potassium Channel.

    PubMed

    Zhang, Li-Min; Qin, Li-Peng; Zhang, Yu-Ping; Zhao, Zi-Gang; Niu, Chun-Yu

    2016-06-01

    Lymphatic reactivity has been shown to exhibit a biphasic change following hemorrhagic shock, and nitric oxide (NO) is involved in this process. However, the precise mechanism responsible for NO regulation of the lymphatic reactivity along with the progression of hemorrhagic shock is unclear. Therefore, the present study was to investigate how NO participates in regulating the shock-induced biphasic changes in lymphatic reactivity and its underlying mechanisms. First, the expressions or contents of inducible NO synthase, nitrite plus nitrate, and elements of cAMP-PKA-KATP and cGMP-PKG-KATP pathway in thoracic ducts tissue were assessed. The results revealed that levels of nitrite plus nitrate, cAMP, cyclic guanosine monophosphate (cGMP), p-PKA, and p-PKG were increased gradually along with the process of shock. Second, the roles of cAMP-PKA-KATP and cGMP-PKG-KATP in NO regulating lymphatic response to gradient substance P were evaluated with an isolated lymphatic perfusion system. The results showed that the NOS substrate (L-Arg), PKA donor (8-Br-cAMP) decreased the reactivity of shock 0.5 h-lymphatics, and that the PKA inhibitor (H-89) and KATP inhibitor (glibenclamide) restrained the effects of L-Arg while glibenclamide abolished the effects of 8-Br-cAMP. Meanwhile, NOS antagonist (L-NAME), protein kinase G (PKG) inhibitor (KT-5823), and soluble guanylate cyclase inhibitor (ODQ) increased the reactivity of shock 2 h-lymphatics, whereas KATP opener (pinacidil) inhibited these elevated effects induced by either L-NAME, ODQ, or KT-5823. Taken together, these results indicate that NO regulation of lymphatic reactivity during shock involves both cAMP-PKA-KATP and cGMP-PKG-KATP pathways. These findings have potential significance for the treatment of hemorrhagic shock through regulating lymphatic reactivity.

  3. Dioscin Protects ANIT-Induced Intrahepatic Cholestasis Through Regulating Transporters, Apoptosis and Oxidative Stress

    PubMed Central

    Yao, Hong; Xu, Youwei; Yin, Lianhong; Tao, Xufeng; Xu, Lina; Qi, Yan; Han, Xu; Sun, Pengyuan; Liu, Kexin; Peng, Jinyong

    2017-01-01

    Intrahepatic cholestasis, a clinical syndrome, is caused by excessive accumulation of bile acids in body and liver. Proper regulation of bile acids in liver cells is critical for liver injury. We previously reported the effects of dioscin against α-naphthylisothio- cyanate (ANIT)-induced cholestasis in rats. However, the pharmacological and mechanism data are limited. In our work, the animals of rats and mice, and Sandwich-cultured hepatocytes (SCHs) were caused by ANIT, and dioscin was used for the treatment. The results showed that dioscin markedly altered relative liver weights, restored ALT, AST, ALP, TBIL, GSH, GSH-Px, MDA, SOD levels, and rehabilitated ROS level and cell apoptosis. In mechanism study, dioscin not only significantly regulated the protein levels of Ntcp, OAT1, OCT1, Bsep and Mrp2 to accelerate bile acids excretion, but also regulated the expression levels of Bak, Bcl-xl, Bcl-2, Bax, Caspase 3 and Caspase 9 in vivo and in vitro to improve apoptosis. In addition, dioscin markedly inhibited PI3K/Akt pathway and up-regulated the levels of Nrf2, GCLc, GCLm, NQO1 and HO-1 against oxidative stress (OS) caused by bile acids. These results were further validated by inhibition of PI3K and Akt using the inhibitors of wortmannin and perifosine in SCHs. Our data showed that dioscin had good action against ANIT-caused intrahepatic cholestasis through regulating transporters, apoptosis and OS. This natural product can be considered as one active compound to treat intrahepatic cholestasis in the future. PMID:28337145

  4. Ecological mechanisms for the coevolution of mating systems and defence.

    PubMed

    Campbell, Stuart A

    2015-02-01

    The diversity of flowering plants is evident in two seemingly unrelated aspects of life history: sexual reproduction, exemplified by the stunning variation in flower form and function, and defence, often in the form of an impressive arsenal of secondary chemistry. Researchers are beginning to appreciate that plant defence and reproduction do not evolve independently, but, instead, may have reciprocal and interactive (coevolutionary) effects on each other. Understanding the mechanisms for mating-defence interactions promises to broaden our understanding of how ecological processes can generate these two rich sources of angiosperm diversity. Here, I review current research on the role of herbivory as a driver of mating system evolution, and the role of mating systems in the evolution of defence strategies. I outline different ecological mechanisms and processes that could generate these coevolutionary patterns, and summarize theoretical and empirical support for each. I provide a conceptual framework for linking plant defence with mating system theory to better integrate these two research fields.

  5. 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.

  6. Asymmetric selection and the evolution of extraordinary defences.

    PubMed

    Urban, Mark C; Bürger, Reinhard; Bolnick, Daniel I

    2013-01-01

    Evolutionary biologists typically predict future evolutionary responses to natural selection by analysing evolution on an adaptive landscape. Much theory assumes symmetric fitness surfaces even though many stabilizing selection gradients deviate from symmetry. Here we revisit Lande's adaptive landscape and introduce novel analytical theory that includes asymmetric selection. Asymmetric selection and the resulting skewed trait distributions bias equilibrium mean phenotypes away from fitness peaks, usually toward the flatter shoulder of the individual fitness surface. We apply this theory to explain a longstanding paradox in biology and medicine: the evolution of excessive defences against enemies. These so-called extraordinary defences can evolve in response to asymmetrical selection when marginal risks of insufficient defence exceed marginal costs of excessive defence. Eco-evolutionary feedbacks between population abundances and asymmetric selection further exaggerate these defences. Recognizing the effect of asymmetrical selection on evolutionary trajectories will improve the accuracy of predictions and suggest novel explanations for apparent sub-optimality.

  7. Decreased structural defence of an invasive thistle under warming.

    PubMed

    Zhang, R; Leshak, A; Shea, K

    2012-01-01

    Plant structural defences play a key role in preventing fitness loss due to herbivory. However, how structural defences are affected by potential climate change is rarely examined. We examined how leaf morphological traits that relate to the structural defence of an invasive thistle, Carduus nutans, change in a warmer climate. We manipulated warming using open-top chambers (OTCs) and examined the morphology of leaves at three different positions (the 5th, 10th and 15th leaves, counted from the top of the plant) in two destructive summer censuses. We found that structural defence traits were different under ambient versus warmed conditions. Prickle densities (both the number of prickles per leaf area and the number of prickles per leaf mass) were significantly lower in plants grown in a warmer climate. Our results suggest that plant structural defences may be reduced under warming, and therefore should be considered when examining species' responses to climate change.

  8. The Iron-Dependent Regulation of the Candida albicans Oxidative Stress Response by the CCAAT-Binding Factor

    PubMed Central

    Chakravarti, Ananya; Camp, Kyle; McNabb, David S.

    2017-01-01

    Candida albicans is the most frequently encountered fungal pathogen in humans, capable of causing mucocutaneous and systemic infections in immunocompromised individuals. C. albicans virulence is influenced by multiple factors. Importantly, iron acquisition and avoidance of the immune oxidative burst are two critical barriers for survival in the host. Prior studies using whole genome microarray expression data indicated that the CCAAT-binding factor is involved in the regulation of iron uptake/utilization and the oxidative stress response. This study examines directly the role of the CCAAT-binding factor in regulating the expression of oxidative stress genes in response to iron availability. The CCAAT-binding factor is a heterooligomeric transcription factor previously shown to regulate genes involved in respiration and iron uptake/utilization in C. albicans. Since these pathways directly influence the level of free radicals, it seemed plausible the CCAAT-binding factor regulates genes necessary for the oxidative stress response. In this study, we show the CCAAT-binding factor is involved in regulating some oxidative stress genes in response to iron availability, including CAT1, SOD4, GRX5, and TRX1. We also show that CAT1 expression and catalase activity correlate with the survival of C. albicans to oxidative stress, providing a connection between iron obtainability and the oxidative stress response. We further explore the role of the various CCAAT-binding factor subunits in the formation of distinct protein complexes that modulate the transcription of CAT1 in response to iron. We find that Hap31 and Hap32 can compensate for each other in the formation of an active transcriptional complex; however, they play distinct roles in the oxidative stress response during iron limitation. Moreover, Hap43 was found to be solely responsible for the repression observed under iron deprivation. PMID:28122000

  9. Down-regulation of apurinic/apyrimidinic endonuclease 1 (APE1) in spinal motor neurones under oxidative stress.

    PubMed

    Chu, Tak-Ho; Guo, Anchen; Wu, Wutian

    2014-06-01

    Apurinic/apyrimidinic endonuclease 1 (APE1) is an intermediate enzyme in base excision repair which is important for removing damaged nucleotides under normal and pathological conditions. Accumulation of damaged bases causes genome instability and jeopardizes cell survival. Our study is to examine APE1 regulation under oxidative stress in spinal motor neurones which are vulnerable to oxidative insult. We challenged the motor neurone-like cell line NSC-34 with hydrogen peroxide and delineated APE1 function by applying various inhibitors. We also examined the expression of APE1 in spinal motor neurones after spinal root avulsion in adult rats. We showed that hydrogen peroxide induced APE1 down-regulation and cell death in a differentiated motor neurone-like cell line. Inhibiting the two functional domains of APE1, namely, DNA repair and redox domains potentiated hydrogen peroxide induced cell death. We further showed that p53 phosphorylation early after hydrogen peroxide treatment might contribute to the down-regulation of APE1. Our in vivo results similarly showed that APE1 was down-regulated after root avulsion injury in spinal motor neurones. Delay of motor neurone death suggested that APE1 might not cause immediate cell death but render motor neurones vulnerable to further oxidative insults. We conclude that spinal motor neurones down-regulate APE1 upon oxidative stress. This property renders motor neurones susceptible to continuous challenge of oxidative stress in pathological conditions. © 2013 British Neuropathological Society.

  10. Zinc regulates iNOS-derived nitric oxide formation in endothelial cells

    PubMed Central

    Cortese-Krott, Miriam M.; Kulakov, Larissa; Opländer, Christian; Kolb-Bachofen, Victoria; Kröncke, Klaus-D.; Suschek, Christoph V.

    2014-01-01

    Aberrant production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathogenesis of endothelial dysfunction and vascular disease. Mechanisms responsible for the fine-tuning of iNOS activity in inflammation are still not fully understood. Zinc is an important structural element of NOS enzymes and is known to inhibit its catalytical activity. In this study we aimed to investigate the effects of zinc on iNOS activity and expression in endothelial cells. We found that zinc down-regulated the expression of iNOS (mRNA+protein) and decreased cytokine-mediated activation of the iNOS promoter. Zinc-mediated regulation of iNOS expression was due to inhibition of NF-κB transactivation activity, as determined by a decrease in both NF-κB-driven luciferase reporter activity and expression of NF-κB target genes, including cyclooxygenase 2 and IL-1β. However, zinc did not affect NF-κB translocation into the nucleus, as assessed by Western blot analysis of nuclear and cytoplasmic fractions. Taken together our results demonstrate that zinc limits iNOS-derived high output NO production in endothelial cells by inhibiting NF-κB-dependent iNOS expression, pointing to a role of zinc as a regulator of iNOS activity in inflammation. PMID:25180171

  11. Regulation of β cell glucokinase by S-nitrosylation and association with nitric oxide synthase

    PubMed Central

    Rizzo, Mark A.; Piston, David W.

    2003-01-01

    Glucokinase (GK) activity plays a key role in glucose-stimulated insulin secretion from pancreatic β cells. Insulin regulates GK activity by modulating its association with secretory granules, although little is known about the mechanisms involved in regulating this association. Using quantitative imaging of multicolor fluorescent proteins fused to GK, we found that the dynamic association of GK with secretory granules is modulated through nitric oxide (NO). Our results in cultured β cells show that insulin stimulates NO production and leads to S-nitrosylation of GK. Furthermore, inhibition of NO synthase (NOS) activity blocks insulin-stimulated changes in both GK association with secretory granules and GK conformation. Mutation of cysteine 371 to serine blocks S-nitrosylation of GK and causes GK to remain tightly bound to secretory granules. GK was also found to interact stably with neuronal NOS as detected by coimmunoprecipitation and fluorescence resonance energy transfer. Finally, attachment of a nuclear localization signal sequence to NOS drives GK to the nucleus in addition to its normal cytoplasmic and granule targeting. Together, these data suggest that the regulation of GK localization and activity in pancreatic β cells is directly related to NO production and that the association of GK with secretory granules occurs through its interaction with NOS. PMID:12707306

  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. Chemical diversity and defence metabolism: how plants cope with pathogens and ozone pollution.

    PubMed

    Iriti, Marcello; Faoro, Franco

    2009-07-30

    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 (O(3)) 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.

  14. GSNOR-mediated de-nitrosylation in the plant defence response.

    PubMed

    Malik, Saad I; Hussain, Adil; Yun, Byung-Wook; Spoel, Steven H; Loake, Gary J

    2011-11-01

    A key feature of the plant defence response is the transient engagement of a nitrosative burst, resulting in the synthesis of reactive nitrogen intermediates (RNIs). Specific, highly reactive cysteine (Cys) residues of low pK(a) are a major site of action for these intermediates. The addition of an NO moiety to a Cys thiol to form an S-nitrosothiol (SNO), is termed S-nitrosylation. This redox-based post-translational modification is emerging as a key regulator of protein function in plant immunity. Here we highlight recent advances in our understanding of de-nitrosylation, the mechanism that depletes protein SNOs, with a focus on S-nitrosoglutathione reductase (GSNOR). This enzyme controls total cellular S-nitrosylation indirectly during the defence response by turning over S-nitrosoglutathione (GSNO), a major cache of NO bioactivity.

  15. Nickel-regulated heart rate variability: The roles of oxidative stress and inflammation

    SciTech Connect

    Chuang, Hsiao-Chi; Hsueh, Tzu-Wei; Chang, Chuen-Chau; Hwang, Jing-Shiang; Chuang, Kai-Jen; Yan, Yuan-Horng; Cheng, Tsun-Jen

    2013-01-15

    Heart rate variability (HRV) has been reported to be a putative marker of cardiac autonomic imbalance caused by exposure to ambient particulate matter (PM). Our objective in this study was to determine the effects on HRV from exposure to nickel, an important chemical component of ambient PM that results in oxidative stress and inflammation. HRV data were collected for 72 h before lung exposure (baseline) and 72 h after intratracheal exposure (response) to nickel sulphate (NiSO{sub 4}; 526 μg) in Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rats. The antioxidant N-acetyl-L-cysteine (NAC) and the anti-inflammatory celecoxib were intraperitoneally injected to examine post-exposure oxidative and inflammatory responses. Self-controlled experiments examined the effects of NiSO{sub 4} exposure on average normal-to-normal intervals (ANN), natural logarithm-transformed standard deviation of the normal-to-normal intervals (LnSDNN) and root mean square of successive differences of adjacent normal-to-normal intervals (LnRMSSD); the resulting data were sequentially analysed using the generalised estimating equation model. HRV effects on NiSO{sub 4}-exposed SH rats were greater than those on NiSO{sub 4}-exposed WKY rats. After adjusted the HRV responses in the WKY rats as control, ANN and LnRMSSD were found to be quadratically increased over 72 h after exposure to NiSO{sub 4}. Both NAC and celecoxib mitigated the NiSO{sub 4}-induced alterations in HRV during the exposure period. The results suggest that concurrent Ni-induced oxidative stress and inflammatory responses play important roles in regulating HRV. These findings help bridge the gap between epidemiological and clinical studies on the plausible mechanisms of the cardiovascular consequences induced by chemical components in ambient PM. -- Highlights: ► To determine the effects on HRV from exposure to nickel. ► ANN and LnRMSSD were found to be quadratically increased after exposure to Ni. ► NAC and

  16. 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.

  17. Plant-mediated effects on an insect-pathogen interaction vary with intraspecific genetic variation in plant defences.

    PubMed

    Shikano, Ikkei; Shumaker, Ketia L; Peiffer, Michelle; Felton, Gary W; Hoover, Kelli

    2017-04-01

    Baculoviruses are food-borne microbial pathogens that are ingested by insects on contaminated foliage. Oxidation of plant-derived phenolics, activated by insect feeding, can directly interfere with infections in the gut. Since phenolic oxidation is an important component of plant resistance against insects, baculoviruses are suggested to be incompatible with plant defences. However, plants among and within species invest differently in a myriad of chemical and physical defences. Therefore, we hypothesized that among eight soybean genotypes, some genotypes would be able to maintain both high resistance against an insect pest and high efficacy of a baculovirus. Soybean constitutive (non-induced) and jasmonic acid (JA)-induced (anti-herbivore response) resistance was measured against the fall armyworm Spodoptera frugiperda (weight gain, leaf consumption and utilization). Indicators of phenolic oxidation were measured as foliar phenolic content and peroxidase activity. Levels of armyworm mortality inflicted by baculovirus (SfMNPV) did not vary among soybean genotypes when the virus was ingested with non-induced foliage. Ingestion of the virus on JA-induced foliage reduced armyworm mortality, relative to non-induced foliage, on some soybean genotypes. Baculovirus efficacy was lower when ingested with foliage that contained higher phenolic content and defensive properties that reduced armyworm weight gain and leaf utilization. However, soybean genotypes that defended the plant by reducing consumption rate and strongly deterred feeding upon JA-induction did not reduce baculovirus efficacy, indicating that these defences may be more compatible with baculoviruses to maximize plant protection. Differential compatibility of defence traits with the third trophic level highlights an important cost/trade-off associated with plant defence strategies.

  18. Na⁺/H⁺ exchanger 1 participates in tobacco disease defence against Phytophthora parasitica var. nicotianae by affecting vacuolar pH and priming the antioxidative system.

    PubMed

    Chen, Xianyang; Bao, Hexigeduleng; Guo, Jie; Jia, Weitao; Tai, Fang; Nie, Lingling; Jiang, Ping; Feng, Juanjuan; Lv, Sulian; Li, Yinxin

    2014-11-01

    Despite the importance of NHX1 (Na(+)/H(+) exchanger 1) in plant salt tolerance, little is known about its other functions. In this study, intriguingly, it was found that NHX1 participated in plant disease defence against Phytophthora parasitica var. nicotianae (Ppn) in Nicotiana benthamiana. NbNHX1 was originally isolated from N. benthamiana, and characterized. The subcellular localization of NbNHX1 with its C-terminus fused with green fluorescent protein indicated that NbNHX1 localized primarily to the tonoplast. Tobacco rattle virus-induced NbNHX1 silencing led to reduced H(+) efflux from the vacuole to cytoplasts, and decreased Ppn resistance in N. benthamiana. After attack by Ppn, NbNHX1-silenced plants exhibited impaired ability to scavenge reactive oxidative species (ROS) induced by the pathogen. Pea early browning virus-mediated ectopic expression of SeNHX1 (from Salicornia europaea) or AtNHX1 (from Arabidopsis thaliana) both conferred enhanced Ppn resistance to N. benthamiana, with a lower H2O2 concentration after Ppn inoculation. Further investigation of the role of NHX1 demonstrated that transient overexpression of NbNHX1 improved the vacuolar pH and cellular ROS level in N. benthamiana, which was coupled with an enlarged NAD(P) (H) pool and higher expression of ROS-responsive genes. In contrast, NbNHX1 silencing led to a lower pH in the vacuole and a lower cellular ROS level in N. benthamiana, which was coupled with a decreased NAD(P) (H) pool and decreased expression of ROS-responsive genes. These results suggest that NHX1 is involved in plant disease defence; and regulation of vacuolar pH by NHX1, affecting the cellular oxidation state, primes the antioxidative system which is associated with Ppn resistance in tobacco.

  19. Kin recognition affects plant communication and defence

    PubMed Central

    Karban, Richard; Shiojiri, Kaori; Ishizaki, Satomi; Wetzel, William C.; Evans, Richard Y.

    2013-01-01

    The ability of many animals to recognize kin has allowed them to evolve diverse cooperative behaviours; such ability is less well studied for plants. Many plants, including Artemisia tridentata, have been found to respond to volatile cues emitted by experimentally wounded neighbours to increase levels of resistance to herbivory. We report that this communication was more effective among A. tridentata plants that were more closely related based on microsatellite markers. Plants in the field that received cues from experimentally clipped close relatives experienced less leaf herbivory over the growing season than those that received cues from clipped neighbours that were more distantly related. These results indicate that plants can respond differently to cues from kin, making it less likely that emitters will aid strangers and making it more likely that receivers will respond to cues from relatives. More effective defence adds to a growing list of favourable consequences of kin recognition for plants. PMID:23407838

  20. Kin recognition affects plant communication and defence.

    PubMed

    Karban, Richard; Shiojiri, Kaori; Ishizaki, Satomi; Wetzel, William C; Evans, Richard Y

    2013-04-07

    The ability of many animals to recognize kin has allowed them to evolve diverse cooperative behaviours; such ability is less well studied for plants. Many plants, including Artemisia tridentata, have been found to respond to volatile cues emitted by experimentally wounded neighbours to increase levels of resistance to herbivory. We report that this communication was more effective among A. tridentata plants that were more closely related based on microsatellite markers. Plants in the field that received cues from experimentally clipped close relatives experienced less leaf herbivory over the growing season than those that received cues from clipped neighbours that were more distantly related. These results indicate that plants can respond differently to cues from kin, making it less likely that emitters will aid strangers and making it more likely that receivers will respond to cues from relatives. More effective defence adds to a growing list of favourable consequences of kin recognition for plants.

  1. 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

  2. Plasticity in cell defence: access to and reactivity of critical protein residues and DNA response elements.

    PubMed

    Goldring, Chris; Kitteringham, Neil; Jenkins, Rosalind; Copple, Ian; Jeannin, Jean-Francois; Park, B Kevin

    2006-06-01

    Cellular and whole organ defence against pathogenic or chemical challenge is manifest as an adaptive response. Where appropriate, this may lead to induction of a cellular defence programme, thereby enhancing cell survival. When the challenge is overwhelming, the defence is breached and a switch is made to yield cell death, either by apoptosis or necrosis. Thus, a cell will defend itself where possible, but in extremis, it may recognise the futility of its resistance and allow itself to die. Transcription factor activation and access to the DNA regulatory elements that control a particular pattern of expression of defence genes is a major issue that may ultimately decide the fate of a cell in a changed environment. It is possible to visualise the access to the nucleus and to the genome, of paradigm gene loci or transcription factors, using a number of molecular techniques such as chromatin immunoprecipitation, in vivo footprinting and live/whole cell imaging. These methods are informative as to the array of transcription factors that may regulate a given gene, as well as the transitory nature of the transcriptional activation. The initial triggering of active transcription factor complexes typically occurs within the cytoplasm of the cell. Protein-protein interactions and signal transduction pathways, elucidated using a classical molecular genetics approach, have long been recognised as pivotal to the initial control of the levels and activity of transcription factors. We can now visualise modifications in critical residues of transcription factors and regulators during cellular response to chemical stress. These modifications may yield enhanced or repressed activity of transcription factors, they may be non-covalent or covalent, and they may occur in response to a variety of classes of chemicals. Such promiscuous signalling can provide plasticity in the cellular response to a wide array of chemical agents.

  3. Food level and sex shape predator-induced physiological stress: immune defence and antioxidant defence.

    PubMed

    Slos, Stefanie; De Meester, Luc; Stoks, Robby

    2009-09-01

    Despite the potential impact on prey fitness and predator-prey interactions, most studies of predation risk ignore physiological responses and their dependence upon food level and sex. Therefore, we reared male and female larvae of the damselfly Lestes viridis under predator stress (dragonfly larvae) at high and low food levels, and subsequently scored for important variables of insect immune defence (i.e. phenoloxidase) and antioxidant defence [i.e. superoxide dismutase, and catalase (CAT)]. Under predation risk, larvae did not decrease growth rate or immune defence, and only slightly reduced food intake in the high food treatment, probably because of time stress, i.e. little time available to complete the larval development. However, larvae facing predator stress did show an upregulation of antioxidant enzymes. This upregulation was dependent upon food level for CAT and both food level and sex for SOD, consistent with energetic constraints and sex differences in the link between longevity and adult fitness. Our results illustrate that predator stress can influence life history, behavioural and physiological responses differentially and in a context-dependent way. This implies that non-consumptive physiological effects of predators on their prey show independent yet similar complexities in behavioural and life history response variables. In general, our results advocate that mechanistic studies on predator-prey interactions may benefit from including physiological variables.

  4. Network Inference Algorithms Elucidate Nrf2 Regulation of Mouse Lung Oxidative Stress

    PubMed Central

    Singhal, Mudita; Malhotra, Deepti; Biswal, Shyam

    2008-01-01

    A variety of cardiovascular, neurological, and neoplastic conditions have been associated with oxidative stress, i.e., conditions under which levels of reactive oxygen species (ROS) are elevated over significant periods. Nuclear factor erythroid 2-related factor (Nrf2) regulates the transcription of several gene products involved in the protective response to oxidative stress. The transcriptional regulatory and signaling relationships linking gene products involved in the response to oxidative stress are, currently, only partially resolved. Microarray data constitute RNA abundance measures representing gene expression patterns. In some cases, these patterns can identify the molecular interactions of gene products. They can be, in effect, proxies for protein–protein and protein–DNA interactions. Traditional techniques used for clustering coregulated genes on high-throughput gene arrays are rarely capable of distinguishing between direct transcriptional regulatory interactions and indirect ones. In this study, newly developed information-theoretic algorithms that employ the concept of mutual information were used: the Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNE), and Context Likelihood of Relatedness (CLR). These algorithms captured dependencies in the gene expression profiles of the mouse lung, allowing the regulatory effect of Nrf2 in response to oxidative stress to be determined more precisely. In addition, a characterization of promoter sequences of Nrf2 regulatory targets was conducted using a Support Vector Machine classification algorithm to corroborate ARACNE and CLR predictions. Inferred networks were analyzed, compared, and integrated using the Collective Analysis of Biological Interaction Networks (CABIN) plug-in of Cytoscape. Using the two network inference algorithms and one machine learning algorithm, a number of both previously known and novel targets of Nrf2 transcriptional activation were identified. Genes predicted as

  5. Nitric oxide as a regulator of behavior: new ideas from Aplysia feeding.

    PubMed

    Susswein, Abraham J; Chiel, Hillel J

    2012-06-01

    Nitric oxide (NO) regulates Aplysia feeding by novel mechanisms, suggesting new roles for NO in controlling the behavior of higher animals. In Aplysia, (1) NO helps maintain arousal when produced by neurons responding to attempts to swallow food; (2) NO biases the motor system to reject and reposition food that resists swallowing; (3) if mechanically resistant food is not successfully swallowed, NO mediates the formation and expression of memories of food inedibility; (4) NO production at rest inhibits feeding, countering the effects of food stimuli exciting feeding. At a cellular level, NO-dependent channels contribute to the resting potential of neurons controlling food finding and food consumption. Increases in L-arginine after animals eat act as a post-feeding inhibitory signal, presumably by modulating NO production at rest. NO also signals non-feeding behaviors that are associated with feeding inhibition. Thus, depending on context, NO may enhance or inhibit feeding behavior. The different functions of NO may reflect the evolution of NO signaling from a response to tissue damage that was then elaborated and used for additional functions. These results suggest that in higher animals (1) elicited and background transmitter release may have similar effects; (2) NO may be produced by neurons without firing, influencing adjacent neurons; (3) background NO production may contribute to a neuron's resting potential; (4) circulating factors affecting background NO production may regulate spatially separated neurons; (5) L-arginine can be used to regulate neural activity; (6) L-arginine may be an effective post-ingestion metabolic s