Sample records for abstract reactive oxygen

  1. Reactive Oxygen Species in Cardiovascular Disease

    PubMed Central

    Sugamura, Koichi; Keaney, John F.

    2011-01-01

    Based on the ‘free-radical theory’ of disease, researchers have been trying to elucidate the role of oxidative stress from free radicals in cardiovascular disease. Considerable data indicate that ROS and oxidative stress are important features of cardiovascular diseases including atherosclerosis, hypertension, and congestive heart failure. However, blanket strategies with antioxidants to ameliorate cardiovascular disease have not generally yielded favorable results. However, our understanding or reactive oxygen species has evolved to the point that we now realize these species have important roles in physiology as well as pathophysiology. Thus, it is overly simplistic to assume a general antioxidant strategy will yield specific effects on cardiovascular disease. Indeed, there are several sources of reactive oxygen species that are known to be active in the cardiovascular system. This review will address our understanding of reactive oxygen species sources in cardiovascular disease and both animal and human data defining how reactive oxygen species contribute to physiology and pathology. PMID:21627987

  2. How does tunneling contribute to counterintuitive H-abstraction reactivity of nonheme Fe(IV)O oxidants with alkanes?

    PubMed

    Mandal, Debasish; Ramanan, Rajeev; Usharani, Dandamudi; Janardanan, Deepa; Wang, Binju; Shaik, Sason

    2015-01-21

    This article addresses the intriguing hydrogen-abstraction (H-abstraction) and oxygen-transfer (O-transfer) reactivity of a series of nonheme [Fe(IV)(O)(TMC)(Lax)](z+) complexes, with a tetramethyl cyclam ligand and a variable axial ligand (Lax), toward three substrates: 1,4-cyclohexadiene, 9,10-dihydroanthracene, and triphenyl phosphine. Experimentally, O-transfer-reactivity follows the relative electrophilicity of the complexes, whereas the corresponding H-abstraction-reactivity generally increases as the axial ligand becomes a better electron donor, hence exhibiting an antielectrophilic trend. Our theoretical results show that the antielectrophilic trend in H-abstraction is affected by tunneling contributions. Room-temperature tunneling increases with increase of the electron donation power of the axial-ligand, and this reverses the natural electrophilic trend, as revealed through calculations without tunneling, and leads to the observed antielectrophilic trend. By contrast, O-transfer-reactivity, not being subject to tunneling, retains an electrophilic-dependent reactivity trend, as revealed experimentally and computationally. Tunneling-corrected kinetic-isotope effect (KIE) calculations matched the experimental KIE values only if all of the H-abstraction reactions proceeded on the quintet state (S = 2) surface. As such, the present results corroborate the initially predicted two-state reactivity (TSR) scenario for these reactions. The increase of tunneling with the electron-releasing power of the axial ligand, and the reversal of the "natural" reactivity pattern, support the "tunneling control" hypothesis (Schreiner et al., ref 19). Should these predictions be corroborated, the entire field of C-H bond activation in bioinorganic chemistry would lay open to reinvestigation.

  3. Mitochondrial reactive oxygen species accelerate gastric cancer cell invasion

    PubMed Central

    Tamura, Masato; Matsui, Hirofumi; Tomita, Tsutomu; Sadakata, Hisato; Indo, Hiroko P.; Majima, Hideyuki J.; Kaneko, Tsuyoshi; Hyodo, Ichinosuke

    2014-01-01

    Tumor invasion is the most important factor to decide patient’s prognosis. The relation between reactive oxygen species and tumor invasion is mainly reported that nicotinamide adenine dinucleotide phosphate oxidase in the cell membrane is a reactive oxygen species producer for formulating an invadopodia. On the other hand, mitochondrion was known as one of the most important reactive oxygen species-producer in the cell via an energy transfer system. However, the relation between mitochondrial reactive oxygen species and the tumor invasion was not well clarified. In this study, we evaluated the relation between mitochondrial reactive oxygen species and tumor invasion using a normal gastric mucosal cell-line (RGM-1) and a cancerous mutant RGM-1 cell-line (RGK-1). Manganese superoxide dismutase-expressing RGK-1 cell-lines were used for a scavenging mitochondrial reactive oxygen species. The cells have been evaluated their movement ability as follows; cellular ruffling frequencies, wound healing assay to evaluate horizontal cellular migration, and invasion assay using matrigel to analyze vertical cellular migration. All cellular movement abilities were inhibited by scavenging mitochondrial reactive oxygen species with manganese superoxide dismutase. Therefore mitochondrial reactive oxygen species was one of factors enhancing the tumor invasion in gastric cancer. PMID:24426185

  4. Characterization and Reactivity of a Terminal Nickel(III)-Oxygen Adduct

    PubMed Central

    Pirovano, Paolo; Farquhar, Erik R.; Swart, Marcel; Fitzpatrick, Anthony J.; Morgan, Grace G.; McDonald, Aidan R.

    2015-01-01

    High-valent terminal metal-oxygen adducts are hypothesized to be the potent oxidising reactants in late transition metal oxidation catalysis. In particular, examples of high-valent terminal nickel-oxygen adducts are sparse, meaning there is a dearth in the understanding of such oxidants. In this study, a monoanionic NiII-bicarbonate complex was found to react in a 1:1 ratio with the one-electron oxidant tris(4-bromophenyl)ammoniumyl hexachloroantimonate, yielding a thermally unstable intermediate in high yield (~95%). Electronic absorption, electronic paramagnetic resonance and X-ray absorption spectroscopies and density functional theory calculations confirm its description as a low-spin (S = ½), square planar NiIII-oxygen adduct. This rare example of a high-valent terminal nickel-oxygen complex performs oxidations of organic substrates, including 2,6-ditertbutylphenol and triphenylphosphine, which are indicative of hydrogen atom abstraction and oxygen atom transfer reactivity, respectively. PMID:25612563

  5. Unusual Reactivity of the Martian Soil: Oxygen Release Upon Humidification

    NASA Technical Reports Server (NTRS)

    Yen, A. S.

    2002-01-01

    Recent lab results show that oxygen evolves from superoxide-coated mineral grains upon exposure to water vapor. This observation is additional support of the hypothesis that UV-generated O2 is responsible for the reactivity of the martian soil. Discussion of current NASA research opportunities, status of various programs within the Solar System Exploration Division, and employment opportunities within NASA Headquarters to support these programs. Additional information is contained in the original extended abstract.

  6. Characterization and reactivity of a terminal nickel(III)-oxygen adduct.

    PubMed

    Pirovano, Paolo; Farquhar, Erik R; Swart, Marcel; Fitzpatrick, Anthony J; Morgan, Grace G; McDonald, Aidan R

    2015-02-23

    High-valent terminal metal-oxygen adducts are hypothesized to be the potent oxidizing reactants in late transition metal oxidation catalysis. In particular, examples of high-valent terminal nickel-oxygen adducts are scarce, meaning there is a dearth in the understanding of such oxidants. A monoanionic Ni(II)-bicarbonate complex has been found to react in a 1:1 ratio with the one-electron oxidant tris(4-bromophenyl)ammoniumyl hexachloroantimonate, yielding a thermally unstable intermediate in high yield (ca. 95%). Electronic absorption, electronic paramagnetic resonance, and X-ray absorption spectroscopies and density functional theory calculations confirm its description as a low-spin (S = 1/2), square planar Ni(III)-oxygen adduct. This rare example of a high-valent terminal nickel-oxygen complex performs oxidations of organic substrates, including 2,6-di-tert-butylphenol and triphenylphosphine, which are indicative of hydrogen atom abstraction and oxygen atom transfer reactivity, respectively. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Characterization and Reactivity of a Terminal Nickel(III)-Oxygen Adduct

    DOE PAGES

    Pirovano, Paolo; Farquhar, Erik R.; Swart, Marcel; ...

    2015-01-22

    Here, high-valent terminal metal–oxygen adducts are hypothesized to be the potent oxidizing reactants in late transition metal oxidation catalysis. In particular, examples of high-valent terminal nickel–oxygen adducts are scarce, meaning there is a dearth in the understanding of such oxidants. A monoanionic Ni II-bicarbonate complex has been found to react in a 1:1 ratio with the one-electron oxidant tris(4-bromophenyl)ammoniumyl hexachloroantimonate, yielding a thermally unstable intermediate in high yield (ca. 95%). Electronic absorption, electronic paramagnetic resonance, and X-ray absorption spectroscopies and density functional theory calculations confirm its description as a low-spin (S=1/2), square planar Ni III–oxygen adduct. Moreover, this rare examplemore » of a high-valent terminal nickel–oxygen complex performs oxidations of organic substrates, including 2,6-di-tert-butylphenol and triphenylphosphine, which are indicative of hydrogen atom abstraction and oxygen atom transfer reactivity, respectively.« less

  8. Engineering of Pyranose Dehydrogenase for Increased Oxygen Reactivity

    PubMed Central

    Krondorfer, Iris; Lipp, Katharina; Brugger, Dagmar; Staudigl, Petra; Sygmund, Christoph; Haltrich, Dietmar; Peterbauer, Clemens K.

    2014-01-01

    Pyranose dehydrogenase (PDH), a member of the GMC family of flavoproteins, shows a very broad sugar substrate specificity but is limited to a narrow range of electron acceptors and reacts extremely slowly with dioxygen as acceptor. The use of substituted quinones or (organo)metals as electron acceptors is undesirable for many production processes, especially of food ingredients. To improve the oxygen reactivity, site-saturation mutagenesis libraries of twelve amino acids around the active site of Agaricus meleagris PDH were expressed in Saccharomyces cerevisiae. We established high-throughput screening assays for oxygen reactivity and standard dehydrogenase activity using an indirect Amplex Red/horseradish peroxidase and a DCIP/D-glucose based approach. The low number of active clones confirmed the catalytic role of H512 and H556. Only one position was found to display increased oxygen reactivity. Histidine 103, carrying the covalently linked FAD cofactor in the wild-type, was substituted by tyrosine, phenylalanine, tryptophan and methionine. Variant H103Y was produced in Pichia pastoris and characterized and revealed a five-fold increase of the oxygen reactivity. PMID:24614932

  9. Reactive oxygen species, oxidative stress, glaucoma and hyperbaric oxygen therapy.

    PubMed

    McMonnies, Charles

    This review examines the role of oxidative stress in damage to cells of the trabecular meshwork and associated impaired aqueous drainage as well as damage to retinal ganglion cells and associated visual field losses. Consideration is given to the interaction between vascular and mechanical explanations for pathological changes in glaucoma. For example, elevated intraocular pressure (IOP) forces may contribute to ischaemia but there is increasing evidence that altered blood flow in a wider sense is also involved. Both vascular and mechanical theories are involved through fluctuations in intraocular pressure and dysregulation of blood flow. Retinal function is very sensitive to changes in haemoglobin oxygen concentration and the associated variations in the production of reactive oxygen species. Reperfusion injury and production of reactive oxygen species occurs when IOP is elevated or blood pressure is low and beyond the capacity for blood flow autoregulation to maintain appropriate oxygen concentration. Activities such as those associated with postural changes, muscular effort, eye wiping and rubbing which cause IOP fluctuation, may have significant vascular, mechanical, reperfusion and oxidative stress consequences. Hyperbaric oxygen therapy exposes the eye to increased oxygen concentration and the risk of oxidative damage in susceptible individuals. However, oxygen concentration in aqueous humour, and the risk of damage to trabecular meshwork cells may be greater if hyperbaric oxygen is delivered by a hood which exposes the anterior ocular surface to higher than normal oxygen levels. Oronasal mask delivery of hyperbaric oxygen therapy appears to be indicated in these cases. Copyright © 2017 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

  10. Rosacea, reactive oxygen species, and azelaic Acid.

    PubMed

    Jones, David A

    2009-01-01

    Rosacea is a common skin condition thought to be primarily an inflammatory disorder. Neutrophils, in particular, have been implicated in the inflammation associated with rosacea and mediate many of their effects through the release of reactive oxygen species. Recently, the role of reactive oxygen species in the pathophysiology of rosacea has been recognized. Many effective agents for rosacea, including topical azelaic acid and topical metronidazole, have anti-inflammatory properties. in-vitro models have demonstrated the potent antioxidant effects of azelaic acid, providing a potential mechanistic explanation for its efficacy in the treatment of rosacea.

  11. REACTIVE OXYGEN SPECIES: IMPACT ON SKELETAL MUSCLE

    PubMed Central

    Powers, Scott K.; Ji, Li Li; Kavazis, Andreas N.; Jackson, Malcolm J.

    2014-01-01

    It is well established that contracting muscles produce both reactive oxygen and nitrogen species. Although the sources of oxidant production during exercise continue to be debated, growing evidence suggests that mitochondria are not the dominant source. Regardless of the sources of oxidants in contracting muscles, intense and prolonged exercise can result in oxidative damage to both proteins and lipids in the contracting myocytes. Further, oxidants regulate numerous cell signaling pathways and modulate the expression of many genes. This oxidant-mediated change in gene expression involves changes at transcriptional, mRNA stability, and signal transduction levels. Furthermore, numerous products associated with oxidant-modulated genes have been identified and include antioxidant enzymes, stress proteins, and mitochondrial electron transport proteins. Interestingly, low and physiological levels of reactive oxygen species are required for normal force production in skeletal muscle, but high levels of reactive oxygen species result in contractile dysfunction and fatigue. Ongoing research continues to explore the redox-sensitive targets in muscle that are responsible for both redox-regulation of muscle adaptation and oxidant-mediated muscle fatigue. PMID:23737208

  12. Measurement of Reactive Oxygen Species, Reactive Nitrogen Species, and Redox-Dependent Signaling in the Cardiovascular System

    PubMed Central

    Griendling, Kathy K.; Touyz, Rhian M.; Zweier, Jay L.; Dikalov, Sergey; Chilian, William; Chen, Yeong-Renn; Harrison, David G.; Bhatnagar, Aruni

    2017-01-01

    Reactive oxygen species and reactive nitrogen species are biological molecules that play important roles in cardiovascular physiology and contribute to disease initiation, progression, and severity. Because of their ephemeral nature and rapid reactivity, these species are difficult to measure directly with high accuracy and precision. In this statement, we review current methods for measuring these species and the secondary products they generate and suggest approaches for measuring redox status, oxidative stress, and the production of individual reactive oxygen and nitrogen species. We discuss the strengths and limitations of different methods and the relative specificity and suitability of these methods for measuring the concentrations of reactive oxygen and reactive nitrogen species in cells, tissues, and biological fluids. We provide specific guidelines, through expert opinion, for choosing reliable and reproducible assays for different experimental and clinical situations. These guidelines are intended to help investigators and clinical researchers avoid experimental error and ensure high-quality measurements of these important biological species. PMID:27418630

  13. Rosacea, Reactive Oxygen Species, and Azelaic Acid

    PubMed Central

    2009-01-01

    Rosacea is a common skin condition thought to be primarily an inflammatory disorder. Neutrophils, in particular, have been implicated in the inflammation associated with rosacea and mediate many of their effects through the release of reactive oxygen species. Recently, the role of reactive oxygen species in the pathophysiology of rosacea has been recognized. Many effective agents for rosacea, including topical azelaic acid and topical metronidazole, have anti-inflammatory properties. in-vitro models have demonstrated the potent antioxidant effects of azelaic acid, providing a potential mechanistic explanation for its efficacy in the treatment of rosacea. PMID:20967185

  14. Vacuum ultraviolet radiation/atomic oxygen synergism in materials reactivity

    NASA Technical Reports Server (NTRS)

    Koontz, Steven; Leger, Lubert; Albyn, Keith; Cross, Jon

    1990-01-01

    Experimental results are presented which indicate that low fluxes of vacuum UV (VUV) radiation exert a pronounced influence on the atomic oxygen reactivity of such fluorocarbon and fluorocarbon spacecraft materials as the FEP Teflon and PCTFE that are under consideration for the Space Station Freedom. With simultaneous exposure to VUV fluxes comparable to those experienced in LEO, the reactivity of these materials becomes comparable to that of Kapton; VUV radiation has also been shown to increase the reactivity of Kapton with thermal-energy oxygen atoms.

  15. Reactive Oxygen Species in Inflammation and Tissue Injury

    PubMed Central

    Mittal, Manish; Siddiqui, Mohammad Rizwan; Tran, Khiem; Reddy, Sekhar P.

    2014-01-01

    Abstract Reactive oxygen species (ROS) are key signaling molecules that play an important role in the progression of inflammatory disorders. An enhanced ROS generation by polymorphonuclear neutrophils (PMNs) at the site of inflammation causes endothelial dysfunction and tissue injury. The vascular endothelium plays an important role in passage of macromolecules and inflammatory cells from the blood to tissue. Under the inflammatory conditions, oxidative stress produced by PMNs leads to the opening of inter-endothelial junctions and promotes the migration of inflammatory cells across the endothelial barrier. The migrated inflammatory cells not only help in the clearance of pathogens and foreign particles but also lead to tissue injury. The current review compiles the past and current research in the area of inflammation with particular emphasis on oxidative stress-mediated signaling mechanisms that are involved in inflammation and tissue injury. Antioxid. Redox Signal. 20, 1126–1167. PMID:23991888

  16. Production and Consumption of Reactive Oxygen Species by Fullerenes

    EPA Science Inventory

    Reactive oxygen species (ROS) are one of the most important intermediates in chemical, photochemical, and biological processes. To understand the environmental exposure and toxicity of fullerenes better, the production and consumption of ROS (singlet oxygen, superoxide, hydrogen ...

  17. Redox and Reactive Oxygen Species Regulation of Mitochondrial Cytochrome c Oxidase Biogenesis

    PubMed Central

    Bourens, Myriam; Fontanesi, Flavia; Soto, Iliana C.; Liu, Jingjing

    2013-01-01

    Abstract Significance: Cytochrome c oxidase (COX), the last enzyme of the mitochondrial respiratory chain, is the major oxygen consumer enzyme in the cell. COX biogenesis involves several redox-regulated steps. The process is highly regulated to prevent the formation of pro-oxidant intermediates. Recent Advances: Regulation of COX assembly involves several reactive oxygen species and redox-regulated steps. These include: (i) Intricate redox-controlled machineries coordinate the expression of COX isoenzymes depending on the environmental oxygen concentration. (ii) COX is a heme A-copper metalloenzyme. COX copper metallation involves the copper chaperone Cox17 and several other recently described cysteine-rich proteins, which are oxidatively folded in the mitochondrial intermembrane space. Copper transfer to COX subunits 1 and 2 requires concomitant transfer of redox power. (iii) To avoid the accumulation of reactive assembly intermediates, COX is regulated at the translational level to minimize synthesis of the heme A-containing Cox1 subunit when assembly is impaired. Critical Issues: An increasing number of regulatory pathways converge to facilitate efficient COX assembly, thus preventing oxidative stress. Future Directions: Here we will review on the redox-regulated COX biogenesis steps and will discuss their physiological relevance. Forthcoming insights into the precise regulation of mitochondrial COX biogenesis in normal and stress conditions will likely open future perspectives for understanding mitochondrial redox regulation and prevention of oxidative stress. Antioxid. Redox Signal. 19, 1940–1952. PMID:22937827

  18. Mitochondria and Reactive Oxygen Species: Physiology and Pathophysiology

    PubMed Central

    Bolisetty, Subhashini; Jaimes, Edgar A.

    2013-01-01

    The air that we breathe contains nearly 21% oxygen, most of which is utilized by mitochondria during respiration. While we cannot live without it, it was perceived as a bane to aerobic organisms due to the generation of reactive oxygen and nitrogen metabolites by mitochondria and other cellular compartments. However, this dogma was challenged when these species were demonstrated to modulate cellular responses through altering signaling pathways. In fact, since this discovery of a dichotomous role of reactive species in immune function and signal transduction, research in this field grew at an exponential pace and the pursuit for mechanisms involved began. Due to a significant number of review articles present on the reactive species mediated cell death, we have focused on emerging novel pathways such as autophagy, signaling and maintenance of the mitochondrial network. Despite its role in several processes, increased reactive species generation has been associated with the origin and pathogenesis of a plethora of diseases. While it is tempting to speculate that anti-oxidant therapy would protect against these disorders, growing evidence suggests that this may not be true. This further supports our belief that these reactive species play a fundamental role in maintenance of cellular and tissue homeostasis. PMID:23528859

  19. Cytotoxic and Antitumor Activity of Sulforaphane: The Role of Reactive Oxygen Species

    PubMed Central

    Sestili, Piero

    2015-01-01

    According to recent estimates, cancer continues to remain the second leading cause of death and is becoming the leading one in old age. Failure and high systemic toxicity of conventional cancer therapies have accelerated the identification and development of innovative preventive as well as therapeutic strategies to contrast cancer-associated morbidity and mortality. In recent years, increasing body of in vitro and in vivo studies has underscored the cancer preventive and therapeutic efficacy of the isothiocyanate sulforaphane. In this review article, we highlight that sulforaphane cytotoxicity derives from complex, concurring, and multiple mechanisms, among which the generation of reactive oxygen species has been identified as playing a central role in promoting apoptosis and autophagy of target cells. We also discuss the site and the mechanism of reactive oxygen species' formation by sulforaphane, the toxicological relevance of sulforaphane-formed reactive oxygen species, and the death pathways triggered by sulforaphane-derived reactive oxygen species. PMID:26185755

  20. Microcarbon-based facial creams activate aerial oxygen under light to reactive oxygen species damaging cell

    NASA Astrophysics Data System (ADS)

    Maity, Sheli; Pakhira, Bholanath; Ghosh, Subrata; Saha, Royina; Sarkar, Ripon; Barui, Ananya; Sarkar, Sabyasachi

    2017-11-01

    Nanosized reduced graphene oxide (rGO) is found in active microcarbon used in popular face cream from the manufacturers like Ponds, Nevia, and Garnier which, under visible light exposure, gets activated by aerial oxygen to generate reactive oxygen species (ROS) harmful to skin.

  1. Reactive Pendant Mn═O in a Synthetic Structural Model of a Proposed S4 State in the Photosynthetic Oxygen Evolving Complex.

    PubMed

    Vaddypally, Shivaiah; Kondaveeti, Sandeep K; Karki, Santosh; Van Vliet, Megan M; Levis, Robert J; Zdilla, Michael J

    2017-04-05

    The molecular mechanism of the Oxygen Evolving Center of photosystem II has been under debate for decades. One frequently cited proposal is the nucleophilic attack by water hydroxide on a pendant Mn═O moiety, though no chemical example of this reactivity at a manganese cubane cluster has been reported. We describe here the preparation, characterization, and a reactivity study of a synthetic manganese cubane cluster with a pendant manganese-oxo moiety. Reaction of this cluster with alkenes results in oxygen and hydrogen atom transfer reactions to form alcohol- and ketone-based oxygen-containing products. Nitrene transfer from core imides is negligible. The inorganic product is a cluster identical to the precursor, but with the pendant Mn═O moiety replaced by a hydrogen abstracted from the organic substrate, and is isolated in quantitative yield. 18 O and 2 H isotopic labeling studies confirm the transfer of atoms between the cluster and the organic substrate. The results suggest that the core cubane structure of this model compound remains intact, and that the pendant Mn═O moiety is preferentially reactive.

  2. Comparison of two strategies for detection of reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Gao, Weidong; Zhou, Yuanshu; Gu, Yueqing

    2014-09-01

    Photodynamic therapy (PDT) is a clinically approved treatment that was applied to oncology , dermatology, and ophthalmology. Reactive oxygen species (ROS) play a important role in the efficacy of PDT. Online monitoring of reactive oxygen species is the key to understand effect of PDT treatment. We used Fluorescence probes DPBF and luminescent probe luminal to measure the ROS in cells. And we revaluate the relationship between the amount of light and cell survival. There is strongly correlated between the amount of light and cell kill.

  3. Influence of reactive oxygen species on the sterilization of microbes

    USDA-ARS?s Scientific Manuscript database

    The influence of reactive oxygen species on living cells, including various microbes, is discussed. A sterilization experiment with bacterial endospores reveals that an argoneoxygen plasma jet very effectively kills endospores of Bacillus atrophaeus (ATCC 9372), thereby indicating that oxygen radic...

  4. Active site densities, oxygen activation and adsorbed reactive oxygen in alcohol activation on npAu catalysts

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Lu-Cun; Friend, C. M.; Fushimi, Rebecca

    The activation of molecular O 2as well as the reactivity of adsorbed oxygen species is of central importance in aerobic selective oxidation chemistry on Au-based catalysts. Herein, we address the issue of O 2activation on unsupported nanoporous gold (npAu) catalysts by applying a transient pressure technique, a temporal analysis of products (TAP) reactor, to measure the saturation coverage of atomic oxygen, its collisional dissociation probability, the activation barrier for O 2dissociation, and the facility with which adsorbed O species activate methanol, the initial step in the catalytic cycle of esterification. The results from these experiments indicate that molecular O 2dissociationmore » is associated with surface silver, that the density of reactive sites is quite low, that adsorbed oxygen atoms do not spill over from the sites of activation onto the surrounding surface, and that methanol reacts quite facilely with the adsorbed oxygen atoms. In addition, the O species from O 2dissociation exhibits reactivity for the selective oxidation of methanol but not for CO. The TAP experiments also revealed that the surface of the npAu catalyst is saturated with adsorbed O under steady state reaction conditions, at least for the pulse reaction.« less

  5. Active site densities, oxygen activation and adsorbed reactive oxygen in alcohol activation on npAu catalysts

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Lu-Cun; Friend, C. M.; Fushimi, Rebecca

    2016-01-01

    The activation of molecular O 2as well as the reactivity of adsorbed oxygen species is of central importance in aerobic selective oxidation chemistry on Au-based catalysts. Herein, we address the issue of O 2activation on unsupported nanoporous gold (npAu) catalysts by applying a transient pressure technique, a temporal analysis of products (TAP) reactor, to measure the saturation coverage of atomic oxygen, its collisional dissociation probability, the activation barrier for O 2dissociation, and the facility with which adsorbed O species activate methanol, the initial step in the catalytic cycle of esterification. The results from these experiments indicate that molecular O 2dissociationmore » is associated with surface silver, that the density of reactive sites is quite low, that adsorbed oxygen atoms do not spill over from the sites of activation onto the surrounding surface, and that methanol reacts quite facilely with the adsorbed oxygen atoms. In addition, the O species from O 2dissociation exhibits reactivity for the selective oxidation of methanol but not for CO. The TAP experiments also revealed that the surface of the npAu catalyst is saturated with adsorbed O under steady state reaction conditions, at least for the pulse reaction.« less

  6. Formation and Detoxification of Reactive Oxygen Species

    ERIC Educational Resources Information Center

    Kuciel, Radoslawa; Mazurkiewicz, Aleksandra

    2004-01-01

    A model of reactive oxygen species metabolism is proposed as a laboratory exercise for students. The superoxide ion in this model is generated during the reaction of oxidation of xanthine, catalyzed by xanthine oxidase. The effect of catalase, superoxide dismutase, and allopurinol on superoxide ion generation and removal in this system is also…

  7. [Relationship among the Oxygen Concentration, Reactive Oxygen Species and the Biological Characteristics of Mouse Bone Marrow Hematopoietic Stem Cells].

    PubMed

    Ren, Si-Hua; He, Yu-Xin; Ma, Yi-Ran; Jin, Jing-Chun; Kang, Dan

    2016-02-01

    To investigate the effects of oxygen concentration and reactive oxygen species (ROS) on the biological characteristics of hematopoietic stem cells (HSC) and to analyzed the relationship among the oxygen concentration, ROS and the biological characteristics of mouse HSC through simulation of oxygen environment experienced by PB HSC during transplantation. The detection of reactive oxygen species (ROS), in vitro amplification, directional differentiation (BFU-E, CFU-GM, CFU-Mix), homing of adhesion molecules (CXCR4, CD44, VLA4, VLA5, P-selectin), migration rate, CFU-S of NOD/SCID mice irradiated with sublethal dose were performed to study the effect of oxgen concentration and reactive oxygen species on the biological characteristics of mouse BM-HSC and the relationship among them. The oxygen concentrations lower than normal oxygen concentration (especially hypoxic oxygen environment) could reduce ROS level and amplify more Lin(-) c-kit(+) Sca-1(+) BM HSC, which was more helpful to the growth of various colonies (BFU-E, CFU-GM, CFU-Mix) and to maintain the migratory ability of HSC, thus promoting CFU-S growth significantly after the transplantation of HSC in NOD/SCID mice irradiated by a sublethal dose. BM HSC exposed to oxygen environments of normal, inconstant oxygen level and strenuously thanging of oxygen concentration could result in higher level of ROS, at the same time, the above-mentioned features and functional indicators were relatively lower. The ROS levels of BM HSC in PB HSCT are closely related to the concentrations and stability of oxygen surrounding the cells. High oxygen concentration results in an high level of ROS, which is not helpful to maintain the biological characteristics of BM HSC. Before transplantation and in vitro amplification, the application of antioxidancs and constant oxygen level environments may be beneficial for transplantation of BMMSC.

  8. BIOMONITORING OF REACTIVE OXYGEN SPECIES IN BIOLOGICAL FLUIDS

    EPA Science Inventory

    Elevated levels of reactive oxygen species (ROS) are associated with several disease processes in humans, including cancer, asthma, diabetes, and cardiac disease. We have explored whether ROS can be measured directly in human fluids, and their value as a biomarker of exposure an...

  9. High-dose catecholamine treatment decreases polymorphonuclear leukocyte phagocytic capacity and reactive oxygen production.

    PubMed Central

    Wenisch, C; Parschalk, B; Weiss, A; Zedwitz-Liebenstein, K; Hahsler, B; Wenisch, H; Georgopoulos, A; Graninger, W

    1996-01-01

    Flow cytometry was used to study phagocytic function (uptake of fluorescein isothiocyanate-labeled bacteria) and release of reactive oxygen products (dihydrorhodamine 123 converted to rhodamine 123) following phagocytosis by neutrophil granulocytes of heparinized whole blood treated with adrenaline, noradrenaline, dopamine, dobutamine, or orciprenaline. Reduced neutrophil phagocytosis and reactive oxygen production were seen at 12 micrograms of adrenaline per liter (72% each compared with control values); at 120 micrograms of noradrenaline (72% each), dobutamine (83 and 80%, respectively), and orciprenaline (81 and 80%, respectively) per liter; and at 100 micrograms of dopamine per liter (66 and 70%) (P < 0.05 for all). At these dosages, neutrophil chemotaxis was reduced to < 50% of control values for all catecholamines. Treatment with catecholamines at lower dosages had no significant effect on phagocytosis or generation of reactive oxygen products or chemotaxis. The phagocytic capacity of granulocytes was related to the generation of reactive oxygen products (r = 0.789; P < 0.05). The results demonstrate that catecholamines have a suppressive effect on the response of phagocytic cells to bacterial pathogens at high therapeutic levels in blood. PMID:8807207

  10. Titanium-Oxygen Reactivity Study

    NASA Technical Reports Server (NTRS)

    Chafey, J. E.; Scheck, W. G.; Witzell, W. E.

    1962-01-01

    A program has been conducted at Astronautics to investigate the likelihood of occurrence of the catastrophic oxidation of titanium alloy sheet under conditions which simulate certain cases of accidental failure of the metal while it is in contact with liquid or gaseous oxygen. Three methods of fracturing the metal were used; they consisted of mechanical puncture, tensile fracture of welded joints, and perforation by very high velocity particles. The results of the tests which have been conducted provide further evidence of the reactivity of titanium with liquid and gaseous oxygen. The evidence indicates that the rapid fracturing of titanium sheet while it is in contact with oxygen initiates the catastrophic oxidation reaction. Initiation occurred when the speed of the fracture was some few feet per second, as in both the drop-weight puncture tests and the static tensile fracture tests of welded joints, as well as when the speed was several thousand feet per second, as in the simulated micrometeoroid penetration tests. The slow propagation of a crack, however, did not initiate the reaction. It may logically be concluded that the localized frictional heat of rapid fracture and/or spontaneous oxidation (exothermic) of minute particles emanating from the fracture cause initiation of the reaction. Under conditions of slow fracture, however, the small heat generated may be adequately dissipated and the reaction is not initiated. A portion of the study conducted consisted of investigating various means by which the reaction might be retarded or prevented. Providing a "barrier" at the titanium-oxygen interface consisting of either aluminum metal or a coating of a petroleum base corrosion inhibitor appeared to be only partially effective in retarding the reaction. The accidental puncturing or similar rupturing of thin-walled pressurized oxygen tanks on missiles and space vehicle will usually constitute loss of function, and may sometimes cause their catastrophic destruction

  11. Reactive Oxygen Species in the Regulation of Synaptic Plasticity and Memory

    PubMed Central

    Klann, Eric

    2011-01-01

    Abstract The brain is a metabolically active organ exhibiting high oxygen consumption and robust production of reactive oxygen species (ROS). The large amounts of ROS are kept in check by an elaborate network of antioxidants, which sometimes fail and lead to neuronal oxidative stress. Thus, ROS are typically categorized as neurotoxic molecules and typically exert their detrimental effects via oxidation of essential macromolecules such as enzymes and cytoskeletal proteins. Most importantly, excessive ROS are associated with decreased performance in cognitive function. However, at physiological concentrations, ROS are involved in functional changes necessary for synaptic plasticity and hence, for normal cognitive function. The fine line of role reversal of ROS from good molecules to bad molecules is far from being fully understood. This review focuses on identifying the multiple sources of ROS in the mammalian nervous system and on presenting evidence for the critical and essential role of ROS in synaptic plasticity and memory. The review also shows that the inability to restrain either age- or pathology-related increases in ROS levels leads to opposite, detrimental effects that are involved in impairments in synaptic plasticity and memory function. Antioxid. Redox Signal. 14, 2013–2054. PMID:20649473

  12. HIV-1, Reactive Oxygen Species and Vascular Complications

    PubMed Central

    Porter, Kristi M.; Sutliff, Roy L.

    2012-01-01

    Over 1 million people in the United States and 33 million individuals worldwide suffer from HIV/AIDS. Since its discovery, HIV/AIDS has been associated with an increased susceptibility to opportunistic infection due to immune dysfunction. Highly active antiretroviral therapies (HAART) restore immune function and, as a result, people infected with HIV-1 are living longer. This improved survival of HIV-1 patients has revealed a previously unrecognized risk of developing vascular complications, such as atherosclerosis and pulmonary hypertension. The mechanisms underlying these HIV-associated vascular disorders are poorly understood. However, HIV-induced elevations in reactive oxygen species, including superoxide and hydrogen peroxide, may contribute to vascular disease development and progression by altering cell function and redox-sensitive signaling pathways. In this review, we summarize the clinical and experimental evidence demonstrating HIV- and HIV antiretroviral therapy-induced alterations in reactive oxygen species (ROS) and how these effects likely contribute to vascular dysfunction and disease. PMID:22564529

  13. Imaging Reactive Oxygen Species-Induced Modifications in Living Systems

    PubMed Central

    Maulucci, Giuseppe; Bačić, Goran; Bridal, Lori; Schmidt, Harald H.H.W.; Tavitian, Bertrand; Viel, Thomas; Utsumi, Hideo; Yalçın, A. Süha

    2016-01-01

    Abstract Significance: Reactive Oxygen Species (ROS) may regulate signaling, ion channels, transcription factors, and biosynthetic processes. ROS-related diseases can be due to either a shortage or an excess of ROS. Recent Advances: Since the biological activity of ROS depends on not only concentration but also spatiotemporal distribution, real-time imaging of ROS, possibly in vivo, has become a need for scientists, with potential for clinical translation. New imaging techniques as well as new contrast agents in clinically established modalities were developed in the previous decade. Critical Issues: An ideal imaging technique should determine ROS changes with high spatio-temporal resolution, detect physiologically relevant variations in ROS concentration, and provide specificity toward different redox couples. Furthermore, for in vivo applications, bioavailability of sensors, tissue penetration, and a high signal-to-noise ratio are additional requirements to be satisfied. Future Directions: None of the presented techniques fulfill all requirements for clinical translation. The obvious way forward is to incorporate anatomical and functional imaging into a common hybrid-imaging platform. Antioxid. Redox Signal. 24, 939–958. PMID:27139586

  14. Reactive oxygen species generation and signaling in plants

    PubMed Central

    Tripathy, Baishnab Charan; Oelmüller, Ralf

    2012-01-01

    The introduction of molecular oxygen into the atmosphere was accompanied by the generation of reactive oxygen species (ROS) as side products of many biochemical reactions. ROS are permanently generated in plastids, peroxisomes, mitochiondria, the cytosol and the apoplast. Imbalance between ROS generation and safe detoxification generates oxidative stress and the accumulating ROS are harmful for the plants. On the other hand, specific ROS function as signaling molecules and activate signal transduction processes in response to various stresses. Here, we summarize the generation of ROS in the different cellular compartments and the signaling processes which are induced by ROS. PMID:23072988

  15. Measurement of Reactive Oxygen Species, Reactive Nitrogen Species, and Redox-Dependent Signaling in the Cardiovascular System: A Scientific Statement From the American Heart Association.

    PubMed

    Griendling, Kathy K; Touyz, Rhian M; Zweier, Jay L; Dikalov, Sergey; Chilian, William; Chen, Yeong-Renn; Harrison, David G; Bhatnagar, Aruni

    2016-08-19

    Reactive oxygen species and reactive nitrogen species are biological molecules that play important roles in cardiovascular physiology and contribute to disease initiation, progression, and severity. Because of their ephemeral nature and rapid reactivity, these species are difficult to measure directly with high accuracy and precision. In this statement, we review current methods for measuring these species and the secondary products they generate and suggest approaches for measuring redox status, oxidative stress, and the production of individual reactive oxygen and nitrogen species. We discuss the strengths and limitations of different methods and the relative specificity and suitability of these methods for measuring the concentrations of reactive oxygen and reactive nitrogen species in cells, tissues, and biological fluids. We provide specific guidelines, through expert opinion, for choosing reliable and reproducible assays for different experimental and clinical situations. These guidelines are intended to help investigators and clinical researchers avoid experimental error and ensure high-quality measurements of these important biological species. © 2016 American Heart Association, Inc.

  16. Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations

    PubMed Central

    Kalyanaraman, Balaraman; Darley-Usmar, Victor; Davies, Kelvin J.A.; Dennery, Phyllis A.; Forman, Henry Jay; Grisham, Matthew B.; Mann, Giovanni E.; Moore, Kevin; Roberts, L. Jackson; Ischiropoulos, Harry

    2013-01-01

    The purpose of this position paper is to present a critical analysis of the challenges and limitations of the most widely used fluorescent probes for detecting and measuring reactive oxygen and nitrogen species. Where feasible, we have made recommendations for the use of alternate probes and appropriate analytical techniques that measure the specific products formed from the reactions between fluorescent probes and reactive oxygen and nitrogen species. We have proposed guidelines that will help present and future researchers with regard to the optimal use of selected fluorescent probes and interpretation of results. PMID:22027063

  17. Inverse correlation between reactive oxygen species in unwashed semen and sperm motion parameters as measured by a computer-assisted semen analyzer.

    PubMed

    Takeshima, Teppei; Yumura, Yasushi; Yasuda, Kengo; Sanjo, Hiroyuki; Kuroda, Shinnosuke; Yamanaka, Hiroyuki; Iwasaki, Akira

    2017-01-01

    This study investigated the correlation between sperm motion parameters obtained by a computer-assisted semen analyzer and levels of reactive oxygen species in unwashed semen. In total, 847 patients, except for azoospermic patients were investigated. At the time of each patient's first consultation, semen parameters were measured using SMAS™ or CellSoft 3000™, and production of reactive oxygen species was measured using a computer-driven LKB Wallac Luminometer 1251 Analyzer. The patients were divided into two groups: reactive oxygen species - positive and negative. The semen parameters within each group were measured using one of the two computer-assisted semen analyzer systems and then compared. Correlations between reactive oxygen species levels and sperm motion parameters in semen from the reactive oxygen species - positive group were also investigated. Reactive oxygen species were detected in semen samples of 282 cases (33.3%). Sperm concentration (P < 0.01; P < 0.01), motility (P < 0.01; P < 0.05), and progressive motility (P < 0.01; P < 0.01) were markedly lower in the reactive oxygen species - positive group than in the reactive oxygen species - negative group. Among the sperm motion parameters in the reactive oxygen species - positive group, sperm concentration (P < 0.01; P < 0.01), motility (P < 0.05; P < 0.01), mALH (P < 0.05; P < 0.01), and progressive motility (P < 0.05; P < 0.01) also showed inverse correlations with the logarithmic transformed reactive oxygen species levels. Therefore, this study demonstrated that excessive reactive oxygen species in semen damage sperm concentration, motility, and other sperm motion parameters.

  18. Reactive Oxygen Species (ROS) generation by lunar simulants

    NASA Astrophysics Data System (ADS)

    Kaur, Jasmeet; Rickman, Douglas; Schoonen, Martin A.

    2016-05-01

    The current interest in human exploration of the Moon and past experiences of Apollo astronauts has rekindled interest into the possible harmful effects of lunar dust on human health. In comparison to the Apollo-era explorations, human explorers may be weeks on the Moon, which will raise the risk of inhalation exposure. The mineralogical composition of lunar dust is well documented, but its effects on human health are not fully understood. With the aim of understanding the reactivity of dusts that may be encountered on geologically different lunar terrains, we have studied Reactive Oxygen Species (ROS) generation by a suite of lunar simulants of different mineralogical-chemical composition dispersed in water and Simulated Lung Fluid (SLF). To further explore the reactivity of simulants under lunar environmental conditions, we compared the reactivity of simulants both in air and inert atmosphere. As the impact of micrometeorites with consequent shock-induced stresses is a major environmental factor on the Moon, we also studied the effect of mechanical stress on samples. Mechanical stress was induced by hand crushing the samples both in air and inert atmosphere. The reactivity of samples after crushing was analyzed for a period of up to nine days. Hydrogen peroxide (H2O2) in water and SLF was analyzed by an in situ electrochemical probe and hydroxyl radical (•OH) by Electron Spin Resonance (ESR) spectroscopy and Adenine probe. Out of all simulants, CSM-CL-S was found to be the most reactive simulant followed by OB-1 and then JSC-1A simulant. The overall reactivity of samples in the inert atmosphere was higher than in air. Fresh crushed samples showed a higher level of reactivity than uncrushed samples. Simulant samples treated to create agglutination, including the formation of zero-valent iron, showed less reactivity than untreated simulants. ROS generation in SLF is initially slower than in deionized water (DI), but the ROS formation is sustained for as long as 7

  19. Reactive Oxygen Species are Ubiquitous along Subsurface Redox Gradients

    NASA Astrophysics Data System (ADS)

    Nico, P. S.; Yuan, X.; Davis, J. A.; Dwivedi, D.; Williams, K. H.; Bhattacharyya, A.; Fox, P. M.

    2016-12-01

    Reactive oxygen species (hydroxyl radical, superoxide, hydrogen peroxide, etc.) are known to be important intermediates in many biological and earth system processes. They have been particularly well studied in the realms of atmospheric chemistry and aquatic photochemistry. However, recently there is increasing evidence that they are also present in impactful quantities in dark systems as a result of both biotic and abiotic reactions. Herein we will present a complementary suite of laboratory and field studies examining the presence and production of hydrogen peroxide under relevant subsurface conditions. The laboratory work examines the redox cycling between reduced organic matter, molecular oxygen, and Fe which results in not only the production of hydrogen peroxide and oxidation of organic functional groups but also the maintenance of steady-state concentration of Fe(II) under fully oxygenated aqueous conditions. The field studies involve three distinct locations, namely a shallow subsurface aquifer, a hyporheic zone redox gradient across a river meander, and a hillside shale seep. In all cases detectable quantities (tens of nanomolar) of hydrogen peroxide were measured. In general, concentrations peak under transitional redox conditions where there is the simultaneous presence of reduced Fe, organic matter, and at least trace dissolved oxygen. Many, but not all, of the observed dynamics in hydrogen peroxide production can be reproduced by a simple kinetic model representing the reactions between Fe, organic matter, and molecular oxygen, but many questions remain regarding the role of microorganisms and other redox active chemical species in determining the detected hydrogen peroxide concentrations. The consistent detection of hydrogen peroxide at these disparate locations supports the hypothesis that hydrogen peroxide, and by extension, the entire suite of reactive oxygen species are ubiquitous along subsurface redox gradients.

  20. Mechanisms of group A Streptococcus resistance to reactive oxygen species

    PubMed Central

    Henningham, Anna; Döhrmann, Simon; Nizet, Victor; Cole, Jason N.

    2015-01-01

    Streptococcus pyogenes, also known as group A Streptococcus (GAS), is an exclusively human Gram-positive bacterial pathogen ranked among the ‘top 10’ causes of infection-related deaths worldwide. GAS commonly causes benign and self-limiting epithelial infections (pharyngitis and impetigo), and less frequent severe invasive diseases (bacteremia, toxic shock syndrome and necrotizing fasciitis). Annually, GAS causes 700 million infections, including 1.8 million invasive infections with a mortality rate of 25%. In order to establish an infection, GAS must counteract the oxidative stress conditions generated by the release of reactive oxygen species (ROS) at the infection site by host immune cells such as neutrophils and monocytes. ROS are the highly reactive and toxic byproducts of oxygen metabolism, including hydrogen peroxide (H2O2), superoxide anion (O2•−), hydroxyl radicals (OH•) and singlet oxygen (O2*), which can damage bacterial nucleic acids, proteins and cell membranes. This review summarizes the enzymatic and regulatory mechanisms utilized by GAS to thwart ROS and survive under conditions of oxidative stress. PMID:25670736

  1. Mechanisms of group A Streptococcus resistance to reactive oxygen species.

    PubMed

    Henningham, Anna; Döhrmann, Simon; Nizet, Victor; Cole, Jason N

    2015-07-01

    Streptococcus pyogenes, also known as group A Streptococcus (GAS), is an exclusively human Gram-positive bacterial pathogen ranked among the 'top 10' causes of infection-related deaths worldwide. GAS commonly causes benign and self-limiting epithelial infections (pharyngitis and impetigo), and less frequent severe invasive diseases (bacteremia, toxic shock syndrome and necrotizing fasciitis). Annually, GAS causes 700 million infections, including 1.8 million invasive infections with a mortality rate of 25%. In order to establish an infection, GAS must counteract the oxidative stress conditions generated by the release of reactive oxygen species (ROS) at the infection site by host immune cells such as neutrophils and monocytes. ROS are the highly reactive and toxic byproducts of oxygen metabolism, including hydrogen peroxide (H2O2), superoxide anion (O2•(-)), hydroxyl radicals (OH•) and singlet oxygen (O2*), which can damage bacterial nucleic acids, proteins and cell membranes. This review summarizes the enzymatic and regulatory mechanisms utilized by GAS to thwart ROS and survive under conditions of oxidative stress. © FEMS 2015.

  2. Renal Carcinogenesis, Tumor Heterogeneity, and Reactive Oxygen Species: Tactics Evolved

    PubMed Central

    Shanmugasundaram, Karthigayan

    2016-01-01

    Abstract Significance: The number of kidney cancers is growing 3–5% each year due to unknown etiologies. Intra- and inter-tumor mediators increase oxidative stress and drive tumor heterogeneity. Recent Advances: Technology advancement in state-of-the-art instrumentation and methodologies allows researchers to detect and characterize global landscaping modifications in genes, proteins, and pathophysiology patterns at the single-cell level. Critical Issues: We postulate that the sources of reactive oxygen species (ROS) and their activation within subcellular compartments will change over a timeline of tumor evolvement and contribute to tumor heterogeneity. Therefore, the complexity of intracellular changes within a tumor and ROS-induced tumor heterogeneity coupled to the advancement of detecting these events globally are limited at the level of data collection, organization, and interpretation using software algorithms and bioinformatics. Future Directions: Integrative and collaborative research, combining the power of numbers with careful experimental design, protocol development, and data interpretation, will translate cancer biology and therapeutics to a heightened level or leave the abundant raw data as stagnant and underutilized. Antioxid. Redox Signal. 25, 685–701. PMID:27287984

  3. Oxygen delivery, consumption, and conversion to reactive oxygen species in experimental models of diabetic retinopathy

    PubMed Central

    Eshaq, Randa S.; Wright, William S.; Harris, Norman R.

    2014-01-01

    Retinal tissue receives its supply of oxygen from two sources – the retinal and choroidal circulations. Decreases in retinal blood flow occur in the early stages of diabetes, with the eventual development of hypoxia thought to contribute to pathological neovascularization. Oxygen consumption in the retina has been found to decrease in diabetes, possibly due to either a reduction in neuronal metabolism or to cell death. Diabetes also enhances the rate of conversion of oxygen to superoxide in the retina, with experimental evidence suggesting that mitochondrial superoxide not only drives the overall production of reactive oxygen species, but also initiates several pathways leading to retinopathy, including the increased activity of the polyol and hexosamine pathways, increased production of advanced glycation end products and expression of their receptors, and activation of protein kinase C. PMID:24936440

  4. Oxygen delivery, consumption, and conversion to reactive oxygen species in experimental models of diabetic retinopathy.

    PubMed

    Eshaq, Randa S; Wright, William S; Harris, Norman R

    2014-01-01

    Retinal tissue receives its supply of oxygen from two sources - the retinal and choroidal circulations. Decreases in retinal blood flow occur in the early stages of diabetes, with the eventual development of hypoxia thought to contribute to pathological neovascularization. Oxygen consumption in the retina has been found to decrease in diabetes, possibly due to either a reduction in neuronal metabolism or to cell death. Diabetes also enhances the rate of conversion of oxygen to superoxide in the retina, with experimental evidence suggesting that mitochondrial superoxide not only drives the overall production of reactive oxygen species, but also initiates several pathways leading to retinopathy, including the increased activity of the polyol and hexosamine pathways, increased production of advanced glycation end products and expression of their receptors, and activation of protein kinase C.

  5. Reactive Oxygen Species on the Early Earth and Survival of Bacteria

    NASA Technical Reports Server (NTRS)

    Balk, Melikea; Mason, Paul; Stams, Alfons J. M.; Smidt, Hauke; Freund, Friedemann; Rothschild, Lynn

    2011-01-01

    An oxygen-rich atmosphere appears to have been a prerequisite for complex, multicellular life to evolve on Earth and possibly elsewhere in the Universe. However it remains unclear how free oxygen first became available on the early Earth. A potentially important, and as yet poorly constrained pathway, is the production of oxygen through the weathering of rocks and release into the near-surface environment. Reactive Oxygen Species (ROS), as precursors to molecular oxygen, are a key step in this process, and may have had a decisive impact on the evolution of life, present and past. ROS are generated from minerals in igneous rocks during hydrolysis of peroxy defects, which consist of pairs of oxygen anions oxidized to the valence state -1 and during (bio) transformations of iron sulphide minerals. ROS are produced and consumed by intracellular and extracellular reactions of Fe, Mn, C, N, and S species. We propose that, despite an overall reducing or neutral oxidation state of the macroenvironment and the absence of free O2 in the atmosphere, organisms on the early Earth had to cope with ROS in their microenvironments. They were thus under evolutionary pressure to develop enzymatic and other defences against the potentially dangerous, even lethal effects of oxygen and its derived ROS. Conversely it appears that microorganisms learned to take advantage of the enormous reactive potential and energy gain provided by nascent oxygen. We investigate how oxygen might be released through weathering. We test microorganisms in contact with rock surfaces and iron sulphides. We model bacteria such as Deionococcus radiodurans and Desulfotomaculum, Moorella and Bacillus species for their ability to grow or survive in the presence of ROS. We examine how early Life might have adapted to oxygen.

  6. Investigation of the reactivity of organic materials in liquid oxygen

    NASA Technical Reports Server (NTRS)

    Chamberlain, D.; Irwin, K.; Kirshen, N.; Mill, T.; Stringham, R.

    1970-01-01

    Measurements of impact-ignition sensitivity and studies of the relative reactivity of t-butoxy and t-butyl peroxy radicals toward a variety of organic compounds reveal improved methods of selection of materials for safe use in a liquid oxygen environment.

  7. Effects of peptides on generation of reactive oxygen species in subcellular fractions of Drosophila melanogaster.

    PubMed

    Khavinson, V K; Myl'nikov, S V; Oparina, T I; Arutyunyan, A V

    2001-07-01

    We studied the effects of Epithalon (Ala-Glu-Asp-Gly) and Vilon (Lys-Glu) on free radical processes in highly inbred HA(+)line of Drosophila melanogaster. Vilon inhibited generation of reactive oxygen species in mitochondria, but stimulated this process in the cytosol. We found sex- and age-related differences in the generation of reactive oxygen species and cytosol antioxidant activity.

  8. Participation of reactive oxygen species in diabetes-induced endothelial dysfunction.

    PubMed

    Zúrová-Nedelcevová, Jana; Navarová, Jana; Drábiková, Katarína; Jancinová, Viera; Petríková, Margita; Bernátová, Iveta; Kristová, Viera; Snirc, Vladimír; Nosál'ová, Viera; Sotníková, Ruzena

    2006-12-01

    In the present study, the relationship between diabetes-induced hyperglycemia, reactive oxygen species production and endothelium-mediated arterial function was examined. The effect of antioxidant on the reactive oxygen species induced damage was tested. Diabetes was induced by streptozotocin (STZ), 3 x 30 mg/kg i.p., administered on three consecutive days. After 10 weeks of diabetes, the functional state of the endothelium of the aorta was tested, endothelemia evaluation was performed and systolic blood pressure was measured. Reactive oxygen species (ROS) formation in blood and the aorta was measured using luminol-enhanced chemiluminescence (CL). Levels of reduced glutathione (GSH) were determined in the aorta, kidney, and plasma. To study the involvement of hyperglycemia in functional impairment of the endothelium, aortal rings incubated in solution with high glucose concentration were tested in in vitro experiments. After 10 weeks of diabetes, endothelial injury was observed, exhibited by diminished endothelium-dependent relaxation of the aorta, increased endothelemia and by elevated systolic blood pressure. Using luminol-enhanced CL, a significant increase of ROS production was found in arterial tissue and blood. GSH levels were significantly increased in the kidney, while there were no GSH changes in plasma and the aorta. Incubation of aortic rings in solution with high glucose concentration led to impairment of endothelium-dependent relaxation. The synthetic antioxidant SMe1EC2 was able to restore reduced endothelium-mediated relaxation. Our results suggest an important role of hyperglycemia-induced ROS production in mediating endothelial dysfunction in experimental diabetes, confirmed by CL and the protective effect of the antioxidant SMe1EC2.

  9. Reactive oxygen species explicit dosimetry (ROSED) of a type 1 photosensitizer

    NASA Astrophysics Data System (ADS)

    Ong, Yi Hong; Kim, Michele M.; Huang, Zheng; Zhu, Timothy C.

    2018-02-01

    Type I photodynamic therapy (PDT) is based on the use of photochemical reactions mediated through an interaction between a tumor-selective photosensitizer, photoexcitation with a specific wavelength of light, and production of reactive oxygen species (ROS). The goal of this study is to develop a model to calculate reactive oxygen species concentration ([ROS]rx) after Tookad®-mediated vascular PDT. Mice with radiation-induced fibrosarcoma (RIF) tumors were treated with different light fluence and fluence rate conditions. Explicit measurements of photosensitizer drug concentration were made via diffuse reflective absorption spectrum using a contact probe before and after PDT. Blood flow and tissue oxygen concentration over time were measured during PDT as a mean to validate the photochemical parameters for the ROSED calculation. Cure index was computed from the rate of tumor regrowth after treatment and was compared against three calculated dose metrics: total light fluence, PDT dose, reacted [ROS]rx. The tumor growth study demonstrates that [ROS]rx serves as a better dosimetric quantity for predicting treatment outcome, as a clinically relevant tumor growth endpoint.

  10. Sensitivity of Ca2+ transport of mitochondria to reactive oxygen species.

    PubMed

    Yang, Z W; Yang, F Y

    1997-12-01

    The relationship between Ca2+ transport and energy transduction of myocardial mitochondria in the presence of reactive oxygen species was investigated. Following treatment with oxygen free radicals [superoxide(O2.-) or hydroxyl radical (.OH)], lipid free radicals in myocardial mitochondrial membrane could be detected by using the method of EPR spin trap. Simultaneously there were obvious alterations in the free Ca2+ ([Ca2+]m) in the mitochondrial matrix; the physical state of membrane lipid; the efficiency of oxidative phosphorylation (ADP/O); the value of the respiratory control ratio (RCR); and the membrane potential of the inner membrane of myocardial mitochondria. If the concentrations of reactive oxygen species were reduced by about 30%, the alterations in the physical state of the membrane lipid and energy transduction of myocardial mitochondria were not observed, but the changes in Ca2+ homeostasis remained. We conclude that Ca2+ transport by myocardial mitochondria is more sensitive to agents such as O2.- or OH, etc. than are oxidation phosphorylation and the respiratory chain.

  11. Reactive oxygen metabolites (ROMs) as an index of oxidative stress in obstructive sleep apnea patients.

    PubMed

    Christou, Kostas; Markoulis, Nikolaos; Moulas, Anargyros N; Pastaka, Chaido; Gourgoulianis, Kostantinos I

    2003-09-01

    Obstructive sleep apnea syndrome (OSA) is accompanied by oxygen desaturation and arousal from sleep. Free oxygen radicals are highly reactive molecules which could be produced by the OSA phenomenon of hypoxia/reoxygenation: cyclical alterations of arterial oxygen saturation with oxygen desaturation developing in response to apneas followed by resumption of oxygen saturation during hyperventilation. On the basis of these considerations, it was hypothesized that OSA may be linked to increased oxidative stress. Twenty-six participants gave an interview during which a physician asked them about their age, smoking habits, and symptoms such as excessive daytime sleepiness and snoring. Physical examination and polysomnography were performed during their hospitalization. Reactive oxygen metabolites (ROMs) were measured in blood samples by the diacron reactive oxygen metabolites (D-ROM) test. Twenty-one out of 26 subjects had an apnea/hypopnea index greater than 5 (OSA group). The measurement of free radicals was high in OSA patients. Furthermore, ROMs values in OSA patients were linearly correlated with the apnea/hypopnea index (R = 0.426; p = 0.042). The predictive value of a positive D-ROM test is 81%. ROMs were elevated in patients with OSA. When OSA was severe, similarly the value of ROMs in blood samples was enhanced, and the probable underlying mechanism for these events is the hypoxia/reoxygenation phenomenon.

  12. Role of Reactive Oxygen Species in Neonatal Pulmonary Vascular Disease

    PubMed Central

    Steinhorn, Robin H.

    2014-01-01

    Abstract Significance: Abnormal lung development in the perinatal period can result in severe neonatal complications, including persistent pulmonary hypertension (PH) of the newborn and bronchopulmonary dysplasia. Reactive oxygen species (ROS) play a substantive role in the development of PH associated with these diseases. ROS impair the normal pulmonary artery (PA) relaxation in response to vasodilators, and ROS are also implicated in pulmonary arterial remodeling, both of which can increase the severity of PH. Recent Advances: PA ROS levels are elevated when endogenous ROS-generating enzymes are activated and/or when endogenous ROS scavengers are inactivated. Animal models have provided valuable insights into ROS generators and scavengers that are dysregulated in different forms of neonatal PH, thus identifying potential therapeutic targets. Critical Issues: General antioxidant therapy has proved ineffective in reversing PH, suggesting that it is necessary to target specific signaling pathways for successful therapy. Future Directions: Development of novel selective pharmacologic inhibitors along with nonantioxidant therapies may improve the treatment outcomes of patients with PH, while further investigation of the underlying mechanisms may enable earlier detection of the disease. Antioxid. Redox Signal. 21, 1926–1942. PMID:24350610

  13. A ReaxFF-based molecular dynamics study of the mechanisms of interactions between reactive oxygen plasma species and the Candida albicans cell wall

    NASA Astrophysics Data System (ADS)

    Zhao, T.; Shi, L.; Zhang, Y. T.; Zou, L.; Zhang, L.

    2017-10-01

    Atmospheric pressure non-equilibrium plasmas have attracted significant attention and have been widely used to inactivate pathogens, yet the mechanisms underlying the interactions between plasma-generated species and bio-organisms have not been elucidated clearly. In this paper, reactive molecular dynamics simulations are employed to investigate the mechanisms of interactions between reactive oxygen plasma species (O, OH, and O2) and β-1,6-glucan (a model for the C. albicans cell wall) from a microscopic point of view. Our simulations show that O and OH species can break structurally important C-C and C-O bonds, while O2 molecules exhibit only weak, non-bonded interactions with β-1,6-glucan. Hydrogen abstraction from hydroxyl or CH groups occurs first in all bond cleavage mechanisms. This is followed by a cascade of bond cleavage and double bond formation events. These lead to the destruction of the fungal cell wall. O and OH have similar effects related to their bond cleavage mechanisms. Our simulation results provide fundamental insights into the mechanisms underlying the interactions between reactive oxygen plasma species and the fungal cell wall of C. albicans at the atomic level.

  14. Fluorinated methacrylamide chitosan sequesters reactive oxygen species to relieve oxidative stress while delivering oxygen.

    PubMed

    Patil, Pritam S; Leipzig, Nic D

    2017-08-01

    Antioxidants play an important role in regulating overabundant reactive oxygen species (ROS) in wound healing to reduce oxidative stress and inflammation. In this work, we demonstrate for the first time that functionalization of methacrylamide chitosan (MAC) with aliphatic pentadecafluoro chains, to synthesize pentadecafluoro-octanoyl methacrylamide chitosan (MACF), enhances the antioxidant capacity of the MAC base hydrogel material, while being able to deliver oxygen for future enhanced wound healing applications. As such, MACF was shown to sequester more nitric oxide (p < 0.01) and hydroxyl (p < 0.0001) radicals as compared to the negative control even when delivering additional oxygen. MACF's beneficial antioxidant capacity was further confirmed in in vitro cell culture experiments using human dermal fibroblasts stressed with 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH). © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2368-2374, 2017. © 2017 Wiley Periodicals, Inc.

  15. COMPARATIVE ANALYSIS OF REACTIVE OXYGEN SPECIES IN HUMAN PLASMA AND BLOOD

    EPA Science Inventory

    Reactive oxygen species (ROS) are commonly associated with diseased states (including asthma, cardiovascular disease, cancer) infections, and exposure to various toxicants in humans. It is of interest in epidemiology studies to characterize the association of oxidative stress in...

  16. Contribution of reactive oxygen species to the pathogenesis of pulmonary arterial hypertension

    PubMed Central

    Naik, Jay S.; Weise-Cross, Laura; Detweiler, Neil D.; Herbert, Lindsay M.; Yellowhair, Tracylyn R.; Resta, Thomas C.

    2017-01-01

    Pulmonary arterial hypertension is associated with a decreased antioxidant capacity. However, neither the contribution of reactive oxygen species to pulmonary vasoconstrictor sensitivity, nor the therapeutic efficacy of antioxidant strategies in this setting are known. We hypothesized that reactive oxygen species play a central role in mediating both vasoconstrictor and arterial remodeling components of severe pulmonary arterial hypertension. We examined the effect of the chemical antioxidant, TEMPOL, on right ventricular systolic pressure, vascular remodeling, and enhanced vasoconstrictor reactivity in both chronic hypoxia and hypoxia/SU5416 rat models of pulmonary hypertension. SU5416 is a vascular endothelial growth factor receptor antagonist and the combination of chronic hypoxia/SU5416 produces a model of severe pulmonary arterial hypertension with vascular plexiform lesions/fibrosis that is not present with chronic hypoxia alone. The major findings from this study are: 1) compared to hypoxia alone, hypoxia/SU5416 exposure caused more severe pulmonary hypertension, right ventricular hypertrophy, adventitial lesion formation, and greater vasoconstrictor sensitivity through a superoxide and Rho kinase-dependent Ca2+ sensitization mechanism. 2) Chronic hypoxia increased medial muscularization and superoxide levels, however there was no effect of SU5416 to augment these responses. 3) Treatment with TEMPOL decreased right ventricular systolic pressure in both hypoxia and hypoxia/SU5416 groups. 4) This effect of TEMPOL was associated with normalization of vasoconstrictor responses, but not arterial remodeling. Rather, medial hypertrophy and adventitial fibrotic lesion formation were more pronounced following chronic TEMPOL treatment in hypoxia/SU5416 rats. Our findings support a major role for reactive oxygen species in mediating enhanced vasoconstrictor reactivity and pulmonary hypertension in both chronic hypoxia and hypoxia/SU5416 rat models, despite a

  17. CO2 reactivity and brain oxygen pressure monitoring in severe head injury.

    PubMed

    Carmona Suazo, J A; Maas, A I; van den Brink, W A; van Santbrink, H; Steyerberg, E W; Avezaat, C J

    2000-09-01

    To investigate the effect of hyperventilation on cerebral oxygenation after severe head injury. A prospective, observational study. Neurointensive care unit at a university hospital. A total of 90 patients with severe head injury (Glasgow Coma Scale score < or =8), in whom continuous monitoring of brain tissue oxygen pressure (PbrO2) was performed as a measure of cerebral oxygenation. Arterial PCO2 was decreased each day over a 5-day period for 15 mins by increasing minute volume on the ventilator setting to 20% above baseline. Arterial blood gas analysis was performed before and after changing ventilator settings. Multimodality monitoring, including PbrO2, was performed in all patients. Absolute and relative PbrO2/PaCO2 reactivity was calculated. Outcome at 6 months was evaluated according to the Glasgow Outcome Scale. Effective hyperventilation, defined by a decrease of PaCO2 > or =2 torr (0.27 kPa), was obtained in 218 (84%) of 272 tests performed. Baseline PaCO2 averaged 32.3 +/- 4.5 torr (4.31 +/- 0.60 kPa). Average reduction in PaCO2 was 3.8 +/- 1.7 torr (0.51 +/- 0.23 kPa). PbrO2 decreased by 2.8 +/- 3.7 torr (0.37 +/- 0.49 kPa; p < .001) from a baseline value of 26.5 +/- 11.6 torr (3.53 +/- 1.55 kPa). PbrO2/PaCO2 reactivity was low on day 1 (0.8 +/- 2.3 torr [0.11 +/- 0.31 kPa]), increasing on subsequent days to 6.1 +/- 4.4 torr (0.81 +/- 0.59 kPa) on day 5. PbrO2/PaCO2 reactivity on days 1 and 2 was not related to outcome. In later phases in patients with unfavorable outcome, relative reactivity was increased more markedly, reaching statistical significance on day 5. Increased hyperventilation causes a significant reduction in PbrO2, providing further evidence for possible increased risk of secondary ischemic damage during hyperventilation. The low PbrO2/PaCO2 reactivity on day 1 indicates the decreased responsiveness of cerebral microvascular vessels to PaCO2 changes, caused by generalized vascular narrowing. The increasing PbrO2/PaCO2 reactivity from

  18. Reactive oxygen species modulator 1, a novel protein, combined with carcinoembryonic antigen in differentiating malignant from benign pleural effusion.

    PubMed

    Chen, Xianmeng; Zhang, Na; Dong, Jiahui; Sun, Gengyun

    2017-05-01

    The differential diagnosis of malignant pleural effusion and benign pleural effusion remains a clinical problem. Reactive oxygen species modulator 1 is a novel protein overexpressed in various human tumors. The objective of this study was to evaluate the diagnostic value of joint detection of reactive oxygen species modulator 1 and carcinoembryonic antigen in the differential diagnosis of malignant pleural effusion and benign pleural effusion. One hundred two consecutive patients with pleural effusion (including 52 malignant pleural effusion and 50 benign pleural effusion) were registered in this study. Levels of reactive oxygen species modulator 1 and carcinoembryonic antigen were measured by enzyme-linked immunosorbent assay and radioimmunoassay, respectively. Results showed that the concentrations of reactive oxygen species modulator 1 both in pleural fluid and serum of patients with malignant pleural effusion were significantly higher than those of benign pleural effusion (both p < 0.05). The diagnostic sensitivity and specificity of pleural fluid reactive oxygen species modulator 1 were 61.54% and 82.00%, respectively, with the optimized cutoff value of 589.70 pg/mL. However, the diagnostic sensitivity and specificity of serum reactive oxygen species modulator 1 were only 41.38% and 86.21%, respectively, with the cutoff value of 27.22 ng/mL, indicating that serum reactive oxygen species modulator 1 may not be a good option in the differential diagnosis of malignant pleural effusion and benign pleural effusion. The sensitivity and specificity of pleural fluid carcinoembryonic antigen were 69.23% and 88.00%, respectively, at the cutoff value of 3.05 ng/mL, while serum carcinoembryonic antigen were 80.77% and 72.00% at the cutoff value of 2.60 ng/mL. The sensitivity could be raised to 88.17% in parallel detection of plural fluid reactive oxygen species modulator 1 and carcinoembryonic antigen concentration, and the specificity could be improved to 97

  19. Abstractive dissociation of oxygen over Al(111): a nonadiabatic quantum model.

    PubMed

    Katz, Gil; Kosloff, Ronnie; Zeiri, Yehuda

    2004-02-22

    The dissociation of oxygen on a clean aluminum surface is studied theoretically. A nonadiabatic quantum dynamical model is used, based on four electronically distinct potential energy surfaces characterized by the extent of charge transfer from the metal to the adsorbate. A flat surface approximation is used to reduce the computation complexity. The conservation of the helicopter angular momentum allows Boltzmann averaging of the outcome of the propagation of a three degrees of freedom wave function. The dissociation event is simulated by solving the time-dependent Schrödinger equation for a period of 30 femtoseconds. As a function of incident kinetic energy, the dissociation yield follows the experimental trend. An attempt at simulation employing only the lowest adiabatic surface failed, qualitatively disagreeing with both experiment and nonadiabatic calculations. The final products, adsorptive dissociation and abstractive dissociation, are obtained by carrying out a semiclassical molecular dynamics simulation with surface hopping which describes the back charge transfer from an oxygen atom negative ion to the surface. The final adsorbed oxygen pair distribution compares well with experiment. By running the dynamical events backward in time, a correlation is established between the products and the initial conditions which lead to their production. Qualitative agreement is thus obtained with recent experiments that show suppression of abstraction by rotational excitation. (c) 2004 American Institute of Physics.

  20. Reactive Oxygen Species and NOX Enzymes Are Emerging as Key Players in Cutaneous Wound Repair

    PubMed Central

    Modarressi, Ali; Pittet-Cuénod, Brigitte

    2017-01-01

    Our understanding of the role of oxygen in cell physiology has evolved from its long-recognized importance as an essential factor in oxidative metabolism to its recognition as an important player in cell signaling. With regard to the latter, oxygen is needed for the generation of reactive oxygen species (ROS), which regulate a number of different cellular functions including differentiation, proliferation, apoptosis, migration, and contraction. Data specifically concerning the role of ROS-dependent signaling in cutaneous wound repair are very limited, especially regarding wound contraction. In this review we provide an overview of the current literature on the role of molecular and reactive oxygen in the physiology of wound repair as well as in the pathophysiology and therapy of chronic wounds, especially under ischemic and hyperglycemic conditions. PMID:29036938

  1. Effects of Pectic Polysaccharides Isolated from Leek on the Production of Reactive Oxygen and Nitrogen Species by Phagocytes

    PubMed Central

    Nikolova, Mariana; Ambrozova, Gabriela; Kratchanova, Maria; Denev, Petko; Kussovski, Veselin; Ciz, Milan

    2013-01-01

    Abstract The current survey investigates the effect of four polysaccharides isolated from fresh leek or alcohol insoluble substances (AIS) of leek on the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) from phagocytes. The ability of the polysaccharides to activate serum complement was also investigated. Despite the lack of antioxidant activity, the pectic polysaccharides significantly decreased the production of ROS by human neutrophils. Polysaccharides isolated from AIS markedly activated RAW 264.7 macrophages for RNS production in a concentration-dependent manner. The Western blot analysis revealed that this effect was due to the stimulation of the inducible nitric oxide synthase protein expression of macrophages. The polysaccharides extracted from AIS with water showed the ability to fix serum complement, especially through the alternative pathway. It was found that the polysaccharide that has the highest complement-fixing effect is characterized by the highest content of uronic acids and the highest molecular weight. PMID:23905651

  2. Staphyloxanthin photobleaching sensitizes methicillin-resistant Staphylococcus aureus to reactive oxygen species attack

    NASA Astrophysics Data System (ADS)

    Dong, Pu-Ting; Mohammad, Haroon; Hui, Jie; Wang, Xiaoyu; Li, Junjie; Liang, Lijia; Seleem, Mohamed N.; Cheng, Ji-Xin

    2018-02-01

    Given that the dearth of new antibiotic development loads an existential burden on successful infectious disease therapy, health organizations are calling for alternative approaches to combat methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we report a drug-free photonic approach to eliminate MRSA through photobleaching of staphyloxanthin, an indispensable membrane-bound antioxidant of S. aureus. The photobleaching process, uncovered through a transient absorption imaging study and quantitated by absorption spectroscopy and mass spectrometry, decomposes staphyloxanthin, and sensitizes MRSA to reactive oxygen species attack. Consequently, staphyloxanthin bleaching by low-level blue light eradicates MRSA synergistically with external or internal reactive oxygen species. The effectiveness of this synergistic therapy is validated in MRSA culture, MRSAinfected macrophage cells. Collectively, these findings highlight broad applications of staphyloxanthin photobleaching for treatment of MRSA infections.

  3. Blood modulates the kinetics of reactive oxygen release in pancreatic ischemia-reperfusion injury.

    PubMed

    Neeff, Hannes P; Sommer, Olaf; Meyer, Sebastian; Tinelli, Anja; Scholtes, Moritz; Hopt, Ulrich T; Drognitz, Oliver; von Dobschuetz, Ernst

    2012-10-01

    Reason for the unsuccessful use of antioxidants in transplantation might be the unknown kinetics of reactive oxygen species (ROS) release. In this study, we compared the kinetics of ROS release from rat pancreata in the presence and absence of blood. In vivo, ischemia-reperfusion injury (IRI) was induced in pancreata of male Wistar rats by occlusion of the arterial blood supply for 1 or 2 hours. In vitro, isolated pancreata were single-pass perfused with Krebs-Henseleit bicarbonate solution. Reactive oxygen species were quantified by electron spin resonance spectroscopy using CMH (1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine) as spin label. Thiols (glutathione), nicotinamide adenine dinucleotide phosphate-oxidase activity, myeloperoxidase activity, and adenosine triphosphate content were measured. During reperfusion, an increase in IRI-induced ROS in arterial blood was noted after 2 hours of warm ischemia. In sharp contrast, ROS release was immediate and short lived in blood-free perfused organs. The degree of tissue damage correlated with nicotinamide adenine dinucleotide phosphate-oxidase activity and adenosine triphosphate content. Antioxidative capacity of tissues was reduced. Electron spin resonance spectroscopy in conjunction with spin labels allows for the detection of ROS kinetics in pancreatic IRI. Reactive oxygen species kinetics are dependent on the length of the ischemic period and the presence or absence of blood.

  4. C-reactive protein and reactive oxygen metabolites in subjects with metabolic syndrome.

    PubMed

    Kotani, K; Sakane, N

    2012-01-01

    This cross-sectional study investigated the correlation between diacron reactive oxygen metabolites (d-ROMs) and high-sensitivity C-reactive protein (hs-CRP) in subjects with or without metabolic syndrome. Cardiometabolic risk factors, d-ROMs and hs-CRP were determined in 457 women: 123 with metabolic syndrome and 334 without metabolic syndrome. The correlation between d-ROMs and hs-CRP levels was compared between the two groups. The group with metabolic syndrome had significantly higher d-ROMs and hs-CRP levels than the group without metabolic syndrome. While the d-ROMs level was significantly and positively correlated with the hs-CRP level in both groups, the correlation level between the two groups was significantly different. Multiple linear regression analysis adjusted for other cardiometabolic risk factors also showed significant positive correlation between dROMs and hs-CRP levels in both groups. Subjects with metabolic syndrome may have a closer relationship between inflammation and oxidative stress than subjects without metabolic syndrome, possibly reflecting their increased predisposition to atherosclerosis. Further studies are necessary to confirm the observed relationship.

  5. Quantum mechanical calculations suggest that lytic polysaccharide monooxygenases use a copper-oxyl, oxygen-rebound mechanism

    PubMed Central

    Kim, Seonah; Ståhlberg, Jerry; Sandgren, Mats; Paton, Robert S.; Beckham, Gregg T.

    2014-01-01

    Lytic polysaccharide monooxygenases (LPMOs) exhibit a mononuclear copper-containing active site and use dioxygen and a reducing agent to oxidatively cleave glycosidic linkages in polysaccharides. LPMOs represent a unique paradigm in carbohydrate turnover and exhibit synergy with hydrolytic enzymes in biomass depolymerization. To date, several features of copper binding to LPMOs have been elucidated, but the identity of the reactive oxygen species and the key steps in the oxidative mechanism have not been elucidated. Here, density functional theory calculations are used with an enzyme active site model to identify the reactive oxygen species and compare two hypothesized reaction pathways in LPMOs for hydrogen abstraction and polysaccharide hydroxylation; namely, a mechanism that employs a η1-superoxo intermediate, which abstracts a substrate hydrogen and a hydroperoxo species is responsible for substrate hydroxylation, and a mechanism wherein a copper-oxyl radical abstracts a hydrogen and subsequently hydroxylates the substrate via an oxygen-rebound mechanism. The results predict that oxygen binds end-on (η1) to copper, and that a copper-oxyl–mediated, oxygen-rebound mechanism is energetically preferred. The N-terminal histidine methylation is also examined, which is thought to modify the structure and reactivity of the enzyme. Density functional theory calculations suggest that this posttranslational modification has only a minor effect on the LPMO active site structure or reactivity for the examined steps. Overall, this study suggests the steps in the LPMO mechanism for oxidative cleavage of glycosidic bonds. PMID:24344312

  6. First kinetic discrimination between carbon and oxygen reactivity of enols.

    PubMed

    García-Río, Luis; Mejuto, Juan C; Parajó, Mercedes; Pérez-Lorenzo, Moisés

    2008-11-07

    Nitrosation of enols shows a well-differentiated behavior depending on whether the reaction proceeds through the carbon (nucleophilic catalysis is observed) or the oxygen atom (general acid-base catalysis is observed). This is due to the different operating mechanisms for C- and O-nitrosation. Nitrosation of acetylacetone (AcAc) shows a simultaneous nucleophilic and acid-base catalysis. This simultaneous catalysis constitutes the first kinetic evidence of two independent reactions on the carbon and oxygen atom of an enol. The following kinetic study allows us to determine the rate constants for both reaction pathways. A similar reactivity of the nucleophilic centers with the nitrosonium ion is observed.

  7. Role of reactive oxygen and nitrogen species in the vascular responses to inflammation

    PubMed Central

    Kvietys, Peter R.; Granger, D. Neil

    2012-01-01

    Inflammation is a complex and potentially life-threatening condition that involves the participation of a variety of chemical mediators, signaling pathways, and cell types. The microcirculation, which is critical for the initiation and perpetuation of an inflammatory response, exhibits several characteristic functional and structural changes in response to inflammation. These include vasomotor dysfunction (impaired vessel dilation and constriction), the adhesion and transendothelial migration of leukocytes, endothelial barrier dysfunction (increased vascular permeability), blood vessel proliferation (angiogenesis), and enhanced thrombus formation. These diverse responses of the microvasculature largely reflect the endothelial cell dysfunction that accompanies inflammation and the central role of these cells in modulating processes as varied as blood flow regulation, angiogenesis, and thrombogenesis. The importance of endothelial cells in inflammation-induced vascular dysfunction is also predicated on the ability of these cells to produce and respond to reactive oxygen and nitrogen species. Inflammation seems to upset the balance between nitric oxide and superoxide within (and surrounding) endothelial cells, which is necessary for normal vessel function. This review is focused on defining the molecular targets in the vessel wall that interact with reactive oxygen species and nitric oxide to produce the characteristic functional and structural changes that occur in response to inflammation. This analysis of the literature is consistent with the view that reactive oxygen and nitrogen species contribute significantly to the diverse vascular responses in inflammation and supports efforts that are directed at targeting these highly reactive species to maintain normal vascular health in pathological conditions that are associated with acute or chronic inflammation. PMID:22154653

  8. Direct detection of free radicals and reactive oxygen species in thylakoids.

    PubMed

    Hideg, Eva; Kálai, Tamás; Hideg, Kálmán

    2011-01-01

    In plants, reactive oxygen species (ROS), also known as active oxygen species (AOS), are associated with normal, physiologic processes as well as with responses to adverse conditions. ROS are connected to stress in many ways: as primary elicitors, as products and propagators of oxidative damage, or as signal molecules initiating defense or adaptation. The photosynthetic electron transport is a major site of oxidative stress by visible or ultraviolet light, high or low temperature, pollutants or herbicides. ROS production can be presumed from detecting oxidatively damaged lipids, proteins, or pigments as well as from the alleviating effects of added antioxidants. On the contrary, measuring ROS by special sensor molecules provides more direct information. This chapter focuses on the application of spin trapping electron paramagnetic resonance (EPR) spectroscopy for detecting ROS: singlet oxygen and oxygen free radicals in thylakoid membrane preparations.

  9. Redox state, reactive oxygen species and adaptive growth in colonial hydroids.

    PubMed

    Blackstone, N W

    2001-06-01

    Colonial metazoans often encrust surfaces over which the food supply varies in time or space. In such an environment, adaptive colony development entails adjusting the timing and spacing of feeding structures and gastrovascular connections to correspond to this variable food supply. To investigate the possibility of such adaptive growth, within-colony differential feeding experiments were carried out using the hydroid Podocoryna carnea. Indeed, such colonies strongly exhibited adaptive growth, developing dense arrays of polyps (feeding structures) and gastrovascular connections in areas that were fed relative to areas that were starved, and this effect became more consistent over time. To investigate mechanisms of signaling between the food supply and colony development, measurements were taken of metabolic parameters that have been implicated in signal transduction in other systems, particularly redox state and levels of reactive oxygen species. Utilizing fluorescence microscopy of P. carnea cells in vivo, simultaneous measurements of redox state [using NAD(P)H] and hydrogen peroxide (using 2',7'-dichlorofluorescin diacetate) were taken. Both measures focused on polyp epitheliomuscular cells, since these exhibit the greatest metabolic activity. Colonies 3-5h after feeding were relatively oxidized, with low levels of peroxide, while colonies 24h after feeding were relatively reduced, with high levels of peroxide. The functional role of polyps in feeding and generating gastrovascular flow probably produced this dichotomy. Polyps 3-5h after feeding contract maximally, and this metabolic demand probably shifts the redox state in the direction of oxidation and diminishes levels of reactive oxygen species. In contrast, 24h after feeding, polyps are quiescent, and this lack of metabolic demand probably shifts the redox state in the direction of reduction and increases levels of reactive oxygen species. Within-colony differential feeding experiments were carried out on

  10. ARSENIC SPECIES CAUSE RELEASE OF IRON FROM FERRITIN GENERATING REACTIVE OXYGEN SPECIES

    EPA Science Inventory

    ARSENIC SPECIES CAUSE RELEASE OF IRON FROM FERRITIN GENERATING REACTIVE OXYGEN SPECIES

    Arsenic-associated cancer (lung, bladder, skin, liver, kidney) remains a significant world- wide public health problem (e.g., Taiwan, Chile, Bangladesh, India, China and Thailand). Rece...

  11. Antimicrobial strategies centered around reactive oxygen species - bactericidal antibiotics, photodynamic therapy and beyond

    PubMed Central

    Vatansever, Fatma; de Melo, Wanessa C.M.A.; Avci, Pinar; Vecchio, Daniela; Sadasivam, Magesh; Gupta, Asheesh; Chandran, Rakkiyappan; Karimi, Mahdi; Parizotto, Nivaldo A; Yin, Rui; Tegos, George P; Hamblin, Michael R

    2013-01-01

    Reactive oxygen species (ROS) can attack a diverse range of targets to exert antimicrobial activity, which accounts for their versatility in mediating host defense against a broad range of pathogens. Most ROS are formed by the partial reduction of molecular oxygen. Four major ROS are recognized comprising: superoxide (O2•−), hydrogen peroxide (H2O2), hydroxyl radical (•OH), and singlet oxygen (1O2), but they display very different kinetics and levels of activity. The effects of O2•− and H2O2 are less acute than those of •OH and 1O2, since the former are much less reactive and can be detoxified by endogenous antioxidants (both enzymatic and non-enzymatic) that are induced by oxidative stress. In contrast, no enzyme can detoxify •OH or 1O2, making them extremely toxic and acutely lethal. The present review will highlight the various methods of ROS formation and their mechanism of action. Antioxidant defenses against ROS in microbial cells and the use of ROS by antimicrobial host defense systems are covered. Antimicrobial approaches primarily utilizing ROS comprise both bactericidal antibiotics, and non-pharmacological methods such as photodynamic therapy, titanium dioxide photocatalysis, cold plasma and medicinal honey. A brief final section covers, reactive nitrogen species, and related therapeutics, such as acidified nitrite and nitric oxide releasing nanoparticles. PMID:23802986

  12. Regulation of signal transduction by reactive oxygen species in the cardiovascular system

    PubMed Central

    Brown, David I.; Griendling, Kathy K.

    2015-01-01

    Oxidative stress has long been implicated in cardiovascular disease, but more recently, the role of reactive oxygen species in normal physiological signaling has been elucidated. Signaling pathways modulated by reactive oxygen species (ROS) are complex and compartmentalized, and we are only beginning to identify the molecular modifications of specific targets. Here we review the current literature regarding ROS signaling in the cardiovascular system, focusing on the role of ROS in normal physiology and how dysregulation of signaling circuits contributes to cardiovascular diseases including atherosclerosis, ischemia-reperfusion injury, cardiomyopathy and heart failure. In particular, we consider how ROS modulate signaling pathways related to phenotypic modulation, migration and adhesion, contractility, proliferation and hypertrophy, angiogenesis, endoplasmic reticulum stress, apoptosis and senescence. Understanding the specific targets of ROS may guide the development of the next generation of ROS-modifying therapies to reduce morbidity and mortality associated with oxidative stress. PMID:25634975

  13. Plasma reactivity in high-power impulse magnetron sputtering through oxygen kinetics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vitelaru, Catalin; National Institute for Optoelectronics, Magurele-Bucharest, RO 077125; Lundin, Daniel

    2013-09-02

    The atomic oxygen metastable dynamics in a Reactive High-Power Impulse Magnetron Sputtering (R-HiPIMS) discharge has been characterized using time-resolved diode laser absorption in an Ar/O{sub 2} gas mixture with a Ti target. Two plasma regions are identified: the ionization region (IR) close to the target and further out the diffusion region (DR), separated by a transition region. The μs temporal resolution allows identifying the main atomic oxygen production and destruction routes, which are found to be very different during the pulse as compared to the afterglow as deduced from their evolution in space and time.

  14. Evidence for photochemical production of reactive oxygen species in desert soils.

    PubMed

    Georgiou, Christos D; Sun, Henry J; McKay, Christopher P; Grintzalis, Konstantinos; Papapostolou, Ioannis; Zisimopoulos, Dimitrios; Panagiotidis, Konstantinos; Zhang, Gaosen; Koutsopoulou, Eleni; Christidis, George E; Margiolaki, Irene

    2015-05-11

    The combination of intense solar radiation and soil desiccation creates a short circuit in the biogeochemical carbon cycle, where soils release significant amounts of CO2 and reactive nitrogen oxides by abiotic oxidation. Here we show that desert soils accumulate metal superoxides and peroxides at higher levels than non-desert soils. We also show the photogeneration of equimolar superoxide and hydroxyl radical in desiccated and aqueous soils, respectively, by a photo-induced electron transfer mechanism supported by their mineralogical composition. Reactivity of desert soils is further supported by the generation of hydroxyl radical via aqueous extracts in the dark. Our findings extend to desert soils the photogeneration of reactive oxygen species by certain mineral oxides and also explain previous studies on desert soil organic oxidant chemistry and microbiology. Similar processes driven by ultraviolet radiation may be operating in the surface soils on Mars.

  15. Methods for Detection of Mitochondrial and Cellular Reactive Oxygen Species

    PubMed Central

    Harrison, David G.

    2014-01-01

    Abstract Significance: Mitochondrial and cellular reactive oxygen species (ROS) play important roles in both physiological and pathological processes. Different ROS, such as superoxide (O2•−), hydrogen peroxide, and peroxynitrite (ONOO•−), stimulate distinct cell-signaling pathways and lead to diverse outcomes depending on their amount and subcellular localization. A variety of methods have been developed for ROS detection; however, many of these methods are not specific, do not allow subcellular localization, and can produce artifacts. In this review, we will critically analyze ROS detection and present advantages and the shortcomings of several available methods. Recent Advances: In the past decade, a number of new fluorescent probes, electron-spin resonance approaches, and immunoassays have been developed. These new state-of-the-art methods provide improved selectivity and subcellular resolution for ROS detection. Critical Issues: Although new methods for HPLC superoxide detection, application of fluorescent boronate-containing probes, use of cell-targeted hydroxylamine spin probes, and immunospin trapping have been available for several years, there has been lack of translation of these into biomedical research, limiting their widespread use. Future Directions: Additional studies to translate these new technologies from the test tube to physiological applications are needed and could lead to a wider application of these approaches to study mitochondrial and cellular ROS. Antioxid. Redox Signal. 20, 372–382. PMID:22978713

  16. Calcium and Reactive Oxygen Species in Acute Pancreatitis: Friend or Foe?

    PubMed Central

    Booth, David M.; Mukherjee, Rajarshi; Sutton, Robert

    2011-01-01

    Abstract Significance Acute pancreatitis (AP) is a debilitating and, at times, lethal inflammatory disease, the causes and progression of which are incompletely understood. Disruption of Ca2+ homeostasis in response to precipitants of AP leads to loss of mitochondrial integrity and cellular necrosis. Recent Advances While oxidative stress has been implicated as a major player in the pathogenesis of this disease, its precise roles remain to be defined. Recent developments are challenging the perception of reactive oxygen species (ROS) as nonspecific cytotoxic agents, suggesting that ROS promote apoptosis that may play a vital protective role in cellular stress since necrosis is avoided. Critical Issues Fresh clinical findings have indicated that antioxidant treatment does not ameliorate AP and may actually worsen the outcome. This review explores the complex links between cellular Ca2+ signaling and the intracellular redox environment, with particular relevance to AP. Future Directions Recent publications have underlined the importance of both Ca2+ and ROS within the pathogenesis of AP, particularly in the determination of cell fate. Future research should elucidate the subtle interplay between Ca2+ and redox mechanisms that operate to modulate mitochondrial function, with a view to devising strategies for the preservation of organellar function. Antioxid. Redox Signal. 15, 2683–2698. PMID:21861696

  17. Cysteine protects rabbit spermatozoa against reactive oxygen species-induced damages

    PubMed Central

    Fan, Xiaoteng; Pan, Yang; Lv, Shan; Pan, Chuanying; Lei, Anmin

    2017-01-01

    The process of cryopreservation results in over-production of reactive oxygen species, which is extremely detrimental to spermatozoa. The aim of this study was to investigate whether addition of cysteine to freezing extender would facilitate the cryosurvival of rabbit spermatozoa, and if so, how cysteine protects spermatozoa from cryodamages. Freshly ejaculated semen was diluted with Tris-citrate-glucose extender supplemented with different concentrations of cysteine. The motility, intact acrosomes, membrane integrity, mitochondrial potentials, 8-hydroxyguanosine level and sperm-zona pellucida binding capacity were examined. Furthermore, glutathione peroxidase (GPx) activity, glutathione content (GSH), and level of reactive oxygen species (ROS) and hydrogen peroxide of spermatozoa were analyzed. The values of motility, intact acrosomes, membrane integrity, mitochondrial potentials and sperm-zona pellucida binding capacity of the frozen-thawed spermatozoa in the treatment of cysteine were significantly higher than those of the control. Addition of cysteine to extenders improved the GPx activity and GSH content of spermatozoa, while lowered the ROS, DNA oxidative alterations and lipid peroxidation level, which makes spermatozoa avoid ROS to attack DNA, the plasma membrane and mitochondria. In conclusion, cysteine protects spermatozoa against ROS-induced damages during cryopreservation and post-thaw incubation. Addition of cysteine is recommended to facilitate the improvement of semen preservation for the rabbit breeding industry. PMID:28700739

  18. Herbivore derived fatty acid-amides elicit reactive oxygen species burst in plants

    USDA-ARS?s Scientific Manuscript database

    The formation of a reactive oxygen species (ROS) burst is a central response of plants to many forms of stress including pathogen attack, several abiotic stresses, damage and insect infestation. These ROS act as a direct defense as well as signaling and regulatory molecules. Perception of microbe or...

  19. Mutagenicity of arsenic in mammalian cells: role of reactive oxygen species

    NASA Technical Reports Server (NTRS)

    Hei, T. K.; Liu, S. X.; Waldren, C.

    1998-01-01

    Arsenite, the trivalent form of arsenic present in the environment, is a known human carcinogen that lacked mutagenic activity in bacterial and standard mammalian cell mutation assays. We show herein that when evaluated in an assay (AL cell assay), in which both intragenic and multilocus mutations are detectable, that arsenite is in fact a strong dose-dependent mutagen and that it induces mostly large deletion mutations. Cotreatment of cells with the oxygen radical scavenger dimethyl sulfoxide significantly reduces the mutagenicity of arsenite. Thus, the carcinogenicity of arsenite can be explained at least in part by it being a mutagen that depends on reactive oxygen species for its activity.

  20. Combined effect of protein and oxygen on reactive oxygen and nitrogen species in the plasma treatment of tissue

    NASA Astrophysics Data System (ADS)

    Gaur, Nishtha; Szili, Endre J.; Oh, Jun-Seok; Hong, Sung-Ha; Michelmore, Andrew; Graves, David B.; Hatta, Akimitsu; Short, Robert D.

    2015-09-01

    The influence of protein and molecular, ground state oxygen (O2) on the plasma generation, and transport of reactive oxygen and nitrogen species (RONS) in tissue are investigated. A tissue target, comprising a 1 mm thick gelatin film (a surrogate for real tissue), is placed on top of a 96-well plate; each well is filled with phosphate buffered saline (PBS, pH 7.4) containing one fluorescent or colorimetric reporter that is specific for one of three RONS (i.e., H2O2, NO2-, or OH•) or a broad spectrum reactive oxygen species reporter (2,7-dichlorodihydrofluorescein). A helium cold atmospheric plasma (CAP) jet contacts the top of the gelatin surface, and the concentrations of RONS generated in PBS are measured on a microplate reader. The data show that H2O2, NO2-, or OH• are generated in PBS underneath the target. Independently, measurements are made of the O2 concentration in the PBS with and without the gelatin target. Adding bovine serum albumin protein to the PBS or gelatin shows that protein either raises or inhibits RONS depending upon the O2 concentration. Our results are discussed in the context of plasma-soft tissue interactions that are important in the development of CAP technology for medicine, biology, and food manufacturing.

  1. Control of root growth and development by reactive oxygen species.

    PubMed

    Tsukagoshi, Hironaka

    2016-02-01

    Reactive oxygen species (ROS) are relatively simple molecules that exist within cells growing in aerobic conditions. ROS were originally associated with oxidative stress and seen as highly reactive molecules that are injurious to many cell components. More recently, however, the function of ROS as signal molecules in many plant cellular processes has become more evident. One of the most important functions of ROS is their role as a plant growth regulator. For example, ROS are key molecules in regulating plant root development, and as such, are comparable to plant hormones. In this review, the molecular mechanisms of ROS that are mainly associated with plant root growth are discussed. The molecular links between root growth regulation by ROS and other signals will also be briefly discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Diagnostics of reactive oxygen species produced by microplasmas

    NASA Astrophysics Data System (ADS)

    Sousa, J. S.; Puech, V.

    2013-11-01

    Atmospheric pressure generation of reactive oxygen species (ROS) by microplasmas was experimentally studied. The remarkable stability of the microcathode sustained discharge (MCSD) allowed the operation of dc glow discharges, free from the glow-to-arc transition, in He/O2/NO mixtures at atmospheric pressure. Absolute densities of the main ROS were measured by different optical diagnostics: singlet delta oxygen (O2(a 1Δg)) by infrared emission and vacuum ultraviolet absorption in the effluent, ozone (O3) by ultraviolet absorption in the effluent, and atomic oxygen inside the discharge by two-photon absorption laser induced fluorescence. The effect of different parameters, such as gas flow and mixture, and discharge current, on the production of these ROS was studied. High ROS densities up to 1016 cm-3 were achieved. It is shown that the density ratio of O2(a 1Δg) to O3 can be finely tuned in the range [10-3-10+4], through the values of discharge current and NO concentration, and that high O2(a 1Δg) and O3 densities can be transported over distances longer than 50 cm. The MCSD is, thus, a very suitable tool for the continuous production at atmospheric pressure of large fluxes of O2(a 1Δg) and O3, useful to a wide range of applications, notably in plasma medicine.

  3. Kinetic modeling of α-hydrogen abstractions from unsaturated and saturated oxygenate compounds by carbon-centered radicals.

    PubMed

    Paraskevas, Paschalis D; Sabbe, Maarten K; Reyniers, Marie-Françoise; Papayannakos, Nikos; Marin, Guy B

    2014-06-23

    Hydrogen abstractions are important elementary reactions in a variety of reacting media at high temperatures in which oxygenates and hydrocarbon radicals are present. Accurate kinetic data are obtained from CBS-QB3 ab initio (AI) calculations by using conventional transition-state theory within the high-pressure limit, including corrections for hindered rotation and tunneling. From the obtained results, a group-additive (GA) model is developed that allows the Arrhenius parameters and rate coefficients for abstraction of the α-hydrogen from a wide range of oxygenate compounds to be predicted at temperatures ranging from 300 to 1500 K. From a training set of 60 hydrogen abstractions from oxygenates by carbon-centered radicals, 15 GA values (ΔGAV°s) are obtained for both the forward and reverse reactions. Among them, four ΔGAV°s refer to primary contributions, and the remaining 11 ΔGAV°s refer to secondary ones. The accuracy of the model is further improved by introducing seven corrections for cross-resonance stabilization of the transition state from an additional set of 43 reactions. The determined ΔGAV°s are validated upon a test set of AI data for 17 reactions. The mean absolute deviation of the pre-exponential factors (log A) and activation energies (E(a)) for the forward reaction at 300 K are 0.238 log(m(3)  mol(-1)  s(-1)) and 1.5 kJ mol(-1), respectively, whereas the mean factor of deviation <ρ> between the GA-predicted and the AI-calculated rate coefficients is 1.6. In comparison with a compilation of 33 experimental rate coefficients, the <ρ> between the GA-predicted values and these experimental values is only 2.2. Hence, the constructed GA model can be reliably used in the prediction of the kinetics of α-hydrogen-abstraction reactions between a broad range of oxygenates and oxygenate radicals. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Correlation Between High-sensitivity C-reactive Protein and Reactive Oxygen Metabolites During A One-year Period Among Asymptomatic Subjects

    PubMed Central

    Kotani, Kazuhiko; Taniguchi, Nobuyuki

    2012-01-01

    Background Inflammation and oxidative stress are associated with human health and the disease status. The present study aimed to investigate the longitudinal correlation between the diacron reactive oxygen metabolites (d-ROMs) level, as an oxidative stress-related marker, and high-sensitivity C-reactive protein (hsCRP), as an inflammatory marker, during a one-year period among asymptomatic subjects. Methods The data, including anthropometric and biochemical markers, were collected at baseline and after the one-year period from 71 participants (male/female = 41/30, mean age 50 years). The correlation between the changes of the d-ROMs and hsCRP levels during the study period was examined. Results A simple correlation analysis showed a significant and positive correlation to exist between the changes of the d-ROMs and hsCRP levels (r = 0.40, P < 0.01). This significant correlation remained independent in a multiple linear regression analysis adjusted for confounding factors. Conclusions The present findings suggest that the relationship between the d-ROMs and hsCRP levels could be prospectively followed, and that monitoring both markers may help to better understand the cooperation of inflammation and oxidative stress in association with health and disease. Further studies are necessary to clarify the biological mechanism(s) responsible for the observed relationship. Keywords Oxidative stress; Oxygen reactive species; Inflammation; CRP PMID:22383928

  5. Reactive oxygen species enhance insulin sensitivity

    PubMed Central

    Loh, Kim; Deng, Haiyang; Fukushima, Atsushi; Cai, Xiaochu; Boivin, Benoit; Galic, Sandra; Bruce, Clinton; Shields, Benjamin J.; Skiba, Beata; Ooms, Lisa M.; Stepto, Nigel; Wu, Ben; Mitchell, Christina A.; Tonks, Nicholas K.; Watt, Matthew J.; Febbraio, Mark A.; Crack, Peter J.; Andrikopoulos, Sofianos; Tiganis, Tony

    2010-01-01

    SUMMARY Chronic reactive oxygen species (ROS) production by mitochondria may contribute to the development of insulin resistance, a primary feature of type 2 diabetes. In recent years it has become apparent that ROS generation in response to physiological stimuli such as insulin may also facilitate signaling by reversibly oxidizing and inhibiting protein tyrosine phosphatases (PTPs). Here we report that mice lacking one of the key enzymes involved in the elimination of physiological ROS, glutathione peroxidase 1 (Gpx1), were protected from high fat diet-induced insulin resistance. The increased insulin sensitivity in Gpx1−/− mice was attributed to insulin-induced phosphatidylinositol-3-kinase/Akt signaling and glucose uptake in muscle and could be reversed by the anti-oxidant N-acetylcysteine. Increased insulin signaling correlated with enhanced oxidation of the PTP family member PTEN, which terminates signals generated by phosphatidylinositol-3-kinase. These studies provide causal evidence for the enhancement of insulin signaling by ROS in vivo. PMID:19808019

  6. Effects of reactive oxygen species and interplay of antioxidants during physical exercise in skeletal muscles.

    PubMed

    Thirupathi, Anand; Pinho, Ricardo A

    2018-05-01

    A large number of researches have led to a substantial growth of knowledge about exercise and oxidative stress. Initial investigations reported that physical exercise generates free radical-mediated damages to cells; however, in recent years, studies have shown that regular exercise can upregulate endogenous antioxidants and reduce oxidative damage. Yet, strenuous exercise perturbs the antioxidant system by increasing the reactive oxygen species (ROS) content. These alterations in the cellular environment seem to occur in an exercise type-dependent manner. The source of ROS generation during exercise is debatable, but now it is well established that both contracting and relaxing skeletal muscles generate reactive oxygen species and reactive nitrogen species. In particular, exercises of higher intensity and longer duration can cause oxidative damage to lipids, proteins, and nucleotides in myocytes. In this review, we summarize the ROS effects and interplay of antioxidants in skeletal muscle during physical exercise. Additionally, we discuss how ROS-mediated signaling influences physical exercise in antioxidant system.

  7. Chaetocin reactivates the lytic replication of Epstein-Barr virus from latency via reactive oxygen species.

    PubMed

    Zhang, Shilun; Yin, Juan; Zhong, Jiang

    2017-01-01

    Oxidative stress, regarded as a negative effect of free radicals in vivo, takes place when organisms suffer from harmful stimuli. Some viruses can induce the release of reactive oxygen species (ROS) in infected cells, which may be closely related with their pathogenicity. In this report, chaetocin, a fungal metabolite reported to have antimicrobial and cytostatic activity, was studied for its effect on the activation of latent Epstein-Barr virus (EBV) in B95-8 cells. We found that chaetocin remarkably up-regulated EBV lytic transcription and DNA replication at a low concentration (50 nmol L -1 ). The activation of latent EBV was accompanied by an increased cellular ROS level. N-acetyl-L-cysteine (NAC), an ROS inhibitor, suppressed chaetocin-induced EBV activation. Chaetocin had little effect on histone H3K9 methylation, while NAC also significantly reduced H3K9 methylation. These results suggested that chaetocin reactivates latent EBV primarily via ROS pathways.

  8. Reactive oxygen species and lipid peroxidation product-scavenging ability of yogurt organisms.

    PubMed

    Lin, M Y; Yen, C L

    1999-08-01

    The antioxidative activity of the intracellular extracts of yogurt organisms was investigated. All 11 strains tested, including five strains of Streptococcus thermophilus and six strains of Lactobacillus delbrueckii ssp. bulgaricus, demonstrated an antioxidative effect on the inhibition of linoleic acid peroxidation. The antioxidative effect of intracellular extracts of 10(8) cells of yogurt organisms was equivalent to 25 to 96 ppm butylated hydroxytoluene, which indicated that all strains demonstrated excellent antioxidative activity. The scavenging of reactive oxygen species, hydroxyl radical, and hydrogen peroxide was studied for intracellular extracts of yogurt organisms. All strains showed reactive oxygen species-scavenging ability. Lactobacillus delbrueckii ssp. bulgaricus Lb demonstrated the highest hydroxyl radical-scavenging ability at 234 microM. Streptococcus thermophilus MC and 821 and L. delbrueckii ssp. bulgaricus 448 and 449 scavenged the most hydrogen peroxide at approximately 50 microM. The scavenging ability of lipid peroxidation products, t-butylhydroperoxide and malondialdehyde, was also evaluated. Results showed that the extracts were not able to scavenge the t-butylhydroperoxide. Nevertheless, malondialdehyde was scavenged well by most strains.

  9. Decorative black TiCxOy film fabricated by DC magnetron sputtering without importing oxygen reactive gas

    NASA Astrophysics Data System (ADS)

    Ono, Katsushi; Wakabayashi, Masao; Tsukakoshi, Yukio; Abe, Yoshiyuki

    2016-02-01

    Decorative black TiCxOy films were fabricated by dc (direct current) magnetron sputtering without importing the oxygen reactive gas into the sputtering chamber. Using a ceramic target of titanium oxycarbide (TiC1.59O0.31), the oxygen content in the films could be easily controlled by adjustment of total sputtering gas pressure without remarkable change of the carbon content. The films deposited at 2.0 and 4.0 Pa, those are higher pressure when compared with that in conventional magnetron sputtering, showed an attractive black color. In particular, the film at 4.0 Pa had the composition of TiC1.03O1.10, exhibited the L* of 41.5, a* of 0.2 and b* of 0.6 in CIELAB color space. These values were smaller than those in the TiC0.29O1.38 films (L* of 45.8, a* of 1.2 and b* of 1.2) fabricated by conventional reactive sputtering method from the same target under the conditions of gas pressure of 0.3 Pa and optimized oxygen reactive gas concentration of 2.5 vol.% in sputtering gas. Analysis of XRD and XPS revealed that the black film deposited at 4.0 Pa was the amorphous film composed of TiC, TiO and C. The adhesion property and the heat resisting property were enough for decorative uses. This sputtering process has an industrial advantage that the decorative black coating with color uniformity in large area can be easily obtained by plain operation because of unnecessary of the oxygen reactive gas importing which is difficult to be controlled uniformly in the sputtering chamber.

  10. Super-oxidation of silicon nanoclusters: magnetism and reactive oxygen species at the surface

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lepeshkin, Sergey; Baturin, Vladimir; Tikhonov, Evgeny

    2016-01-01

    Oxidation of silicon nanoclusters depending on the temperature and oxygen pressure is explored from first principles using the evolutionary algorithm, and structural and thermodynamic analysis. From our calculations of 90 SinOm clusters we found that under normal conditions oxidation does not stop at the stoichiometric SiO2 composition, as it does in bulk silicon, but goes further placing extra oxygen atoms on the cluster surface. These extra atoms are responsible for light emission, relevant to reactive oxygen species and many of them are magnetic. We argue that the super-oxidation effect is size-independent and discuss its relevance to nanotechnology and miscellaneous applications,more » including biomedical ones.« less

  11. Synthesis of {111} Facet-Exposed MgO with Surface Oxygen Vacancies for Reactive Oxygen Species Generation in the Dark.

    PubMed

    Hao, Ying-Juan; Liu, Bing; Tian, Li-Gang; Li, Fa-Tang; Ren, Jie; Liu, Shao-Jia; Liu, Ying; Zhao, Jun; Wang, Xiao-Jing

    2017-04-12

    Seeking a simple and moderate route to generate reactive oxygen species (ROS) for antibiosis is of great interest and challenge. This work demonstrates that molecule transition and electron rearrangement processes can directly occur only through chemisorption interaction between the adsorbed O 2 and high-energy {111} facet-exposed MgO with abundant surface oxygen vacancies (SOVs), hence producing singlet oxygen and superoxide anion radicals without light irradiation. These ROS were confirmed by electron paramagnetic resonance, in situ Raman, and scavenger experiments. Furthermore, heat plays a crucial role for the electron transfer process to accelerate the formation of ·O 2 - , which is verified by temperature kinetic experiments of nitro blue tetrazolium reduction in the dark. Therefore, the presence of oxygen vacancy can be considered as an intensification of the activation process. The designed MgO is acquired in one step via constructing a reduction atmosphere during the combustion reaction process, which has an ability similar to that of noble metal Pd to activate molecular oxygen and can be used as an effective bacteriocide in the dark.

  12. Detection of irradiation induced reactive oxygen species production in live cells

    NASA Astrophysics Data System (ADS)

    Gao, Bo; Zhu, Debin

    2006-09-01

    Reactive oxygen species (ROS) is thought to play an important role in cell signaling of apoptosis, necrosis, and proliferation. Light irradiation increases mitochondrial reactive oxygen species (ROS) production and mediates its intracellular signaling by adjusting the redox potential in tumor cells. Mitochondria are the main source of ROS in the living cell. Superoxide anions (0 II - are likely the first ROS generated in the mitochondria following radiation damage, and then convert to hydrogen peroxide (H II0 II), hydroxyl radical (•OH), and singlet oxygen (10 II), etc. Conventional methods for research ROS production in mitochondria mostly use isolated mitochondria rather than mitochondria in living cells. In this study, a highly selective probe to detect mitochondrial 0 II - in live cells, MitoSOX TM Red, was applied to quantify the mitochondrial ROS production in human lung adenocarcinoma cells (ASTC-a-1) with laser scanning microscope (LSM) after ultraviolet C (UVC) and He-Ne laser irradiation. Dichiorodihydrofluoresein diacetate (DCFHDA), a common used fluorescent probe for ROS detection without specificity, were used as a comparison to image the ROS production. The fluorescent image of MItoSOX TM Red counterstained with MitoTracker Deep Red 633, a mitochondria selective probe, shows that the mitochondrial ROS production increases distinctly after UVC and He-Ne laser irradiation. DCFH-DA diffuses labeling throughout the cell though its fluorescence increases markedly too. In conclusion, the fluorescent method with MitoSOX TM Red reagent is proved to be a promising technique to research the role of ROS in radiation induced apoptosis.

  13. ASRDI oxygen technology survey. Volume 3: Heat transfer and fluid dynamics. Abstracts of selected technical reports and publications

    NASA Technical Reports Server (NTRS)

    Schmidt, A. F. (Editor)

    1972-01-01

    Selected information is presented from an assemblage of reports and publications on heat transfer and fluid dynamics with direct applicability to oxygen systems. For each document cited, an abstract has been prepared together with key words and a listing of most important references found in the document. Additionally, an author index, a subject index, and a key word index have been provided to simplify the retrieval of specific information from this work. In each subject area - e.g., boiling heat transfer - the individual citations are listed alphabetically by first author, with review papers dually noted under the appropriate subject category and under review papers. Of the documents reviewed and evaluated for inclusion in this publication, coverage of existing information directly concerned with oxygen was given primary emphasis. However, work not specifically oxygen-designated but considered applicable to oxygen by the reviewer e.g., a two-phase friction factor correlation derived from nitrogen experiments is occasionally given where no actual oxygen data exist, as an aid to the reader. Approximately 130 abstracts are listed.

  14. [Changes of vascular reactivity and reactive oxygen species in conditions of varying duration of permanent stay in the alienation zone in mice].

    PubMed

    Tkachenko, M M; Kotsiuruba, A V; Baziliuk, O V; Horot', I V; Sahach, V F

    2010-01-01

    Peculiarities of changes in the vascular reactivity and in the content of reactive forms of oxygen and stable metabolites of nitric oxide (NO) were studied in the aorta preparations of C57BL/6 and BALB/c mice of the two age groups (6 and 18 mo.), which were born and permanently kept in the Chernobyl alienation zone. The results obtained showed a disturbance of acetylcholine-induced endothelium-dependent reactions of relaxation of smooth muscles of the thoracic aorta. A lower level of NO synthesis and lower level of oxidative arginase metabolism of arginine corresponded to a higher degree of damage of endothelium-dependent reactions of relaxation of the thoracic aorta smooth muscles. A decrease of NO synthesis in conditions of permanent effects of low doses of radiation was conditioned by an increase of generation of reactive forms of oxygen, namely, superoxide and hydroxyl radicals, which might be formed in mitochondria. In conditions of permanent effects of low doses of radiation a lesser level of protein nitrosothilation, same as lesser one of generation of OH-radical, corresponded to a higher level of damage of endothelium-dependent reactions.

  15. A single active site residue directs oxygenation stereospecificity in lipoxygenases: Stereocontrol is linked to the position of oxygenation

    PubMed Central

    Coffa, Gianguido; Brash, Alan R.

    2004-01-01

    Lipoxygenases are a class of dioxygenases that form hydroperoxy fatty acids with distinct positional and stereo configurations. Several amino acid residues influencing regiospecificity have been identified, whereas the basis of stereocontrol is not understood. We have now identified a single residue in the lipoxygenase catalytic domain that is important for stereocontrol; it is conserved as an Ala in S lipoxygenases and a Gly in R lipoxygenases. Our results with mutation of the conserved Ala to Gly in two S lipoxygenases (mouse 8S-LOX and human 15-LOX-2) and the corresponding Gly–Ala substitution in two R lipoxygenases (human 12R-LOX and coral 8R-LOX) reveal that the basis for R or S stereo-control also involves a switch in the position of oxygenation on the substrate. After the initial hydrogen abstraction, antarafacial oxygenation at one end or the other of the activated pair of double bonds (pentadiene) gives, for example, 8S or 12R product. The Ala residue promotes oxygenation on the reactive pentadiene at the end deep in the substrate binding pocket and S stereochemistry of the product hydroperoxide, and a Gly residue promotes oxygenation at the proximal end of the reactive pentadiene resulting in R stereochemistry. A model of lipoxygenase reaction specificity is proposed in which product regiochemistry and stereochemistry are determined by fixed relationships between substrate orientation, hydrogen abstraction, and the Gly or Ala residue we have identified. PMID:15496467

  16. The Synergistic Effect of Proteins and Reactive Oxygen Species on Electrochemical Behaviour of 316L Stainless Steel for Biomedical Applications

    NASA Astrophysics Data System (ADS)

    Simionescu, N.; Benea, L.; Dumitrascu, V. M.

    2018-06-01

    The stainless steels, especially 316L type is the most used metallic biomaterials for biomedical applications due to their good biocompatibility, low price, excellent corrosion resistance, availability, easy processing and high strength. Due to these favorable properties 316L stainless steel has become the most attractive biomaterial for dental implants, stents and orthopedic implants. However an implant material in the human body is exposed to an action effect of other molecules, including proteins (such as albumin) and reactive oxygen species (such as hydrogen peroxide - H2O2 ) produced by bacteria and immune cells. In the literature there are few studies to follow the effect of proteins and reactive oxygen species on 316L stainless steel used as implant material and are still unclear. The degree of corrosion resistance is the first criterion in the use of a metallic biomaterial in the oral or body environment. The aim of this research work is to investigate the influence of proteins (albumin) and reactive oxygen species (H2O2 ) in combination, taking into account the synergistic effect of these two factors on 316L stainless steel. Albumin is present in the body near implants and reactive oxygen species could appear in inflammatory processes as well. The study shows that the presence of albumin and reactive species influences the corrosion resistance of 316L stainless steel in biological solutions. In this research work the corrosion behavior of 316L stainless steel is analyzed by electrochemical methods such as: open circuit potential (OCP), Electrochemical Impedance Spectroscopy (EIS). It was found that, the electrochemical results are in a good agreement with micro photographs taken before and after corrosion assays. The albumin and reactive oxygen species have influence on 316L stainless steel behavior.

  17. Impact of plasma jet vacuum ultraviolet radiation on reactive oxygen species generation in bio-relevant liquids

    NASA Astrophysics Data System (ADS)

    Jablonowski, H.; Bussiahn, R.; Hammer, M. U.; Weltmann, K.-D.; von Woedtke, Th.; Reuter, S.

    2015-12-01

    Plasma medicine utilizes the combined interaction of plasma produced reactive components. These are reactive atoms, molecules, ions, metastable species, and radiation. Here, ultraviolet (UV, 100-400 nm) and, in particular, vacuum ultraviolet (VUV, 10-200 nm) radiation generated by an atmospheric pressure argon plasma jet were investigated regarding plasma emission, absorption in a humidified atmosphere and in solutions relevant for plasma medicine. The energy absorption was obtained for simple solutions like distilled water (dH2O) or ultrapure water and sodium chloride (NaCl) solution as well as for more complex ones, for example, Rosewell Park Memorial Institute (RPMI 1640) cell culture media. As moderate stable reactive oxygen species, hydrogen peroxide (H2O2) was studied. Highly reactive oxygen radicals, namely, superoxide anion (O2•-) and hydroxyl radicals (•OH), were investigated by the use of electron paramagnetic resonance spectroscopy. All species amounts were detected for three different treatment cases: Plasma jet generated VUV and UV radiation, plasma jet generated UV radiation without VUV part, and complete plasma jet including all reactive components additionally to VUV and UV radiation. It was found that a considerable amount of radicals are generated by the plasma generated photoemission. From the experiments, estimation on the low hazard potential of plasma generated VUV radiation is discussed.

  18. Sevoflurane protects rat mixed cerebrocortical neuronal-glial cell cultures against transient oxygen-glucose deprivation: involvement of glutamate uptake and reactive oxygen species.

    PubMed

    Canas, Paula T; Velly, Lionel J; Labrande, Christelle N; Guillet, Benjamin A; Sautou-Miranda, Valérie; Masmejean, Frédérique M; Nieoullon, André L; Gouin, François M; Bruder, Nicolas J; Pisano, Pascale S

    2006-11-01

    The purpose of this study was to clarify the role of glutamate and reactive oxygen species in sevoflurane-mediated neuroprotection on an in vitro model of ischemia-reoxygenation. Mature mixed cerebrocortical neuronal-glial cell cultures, treated or not with increasing concentrations of sevoflurane, were exposed to 90 min combined oxygen-glucose deprivation (OGD) in an anaerobic chamber followed by reoxygenation. Cell death was quantified by lactate dehydrogenase release into the media and cell viability by reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium by mitochondrial succinate dehydrogenase. Extracellular concentrations of glutamate and glutamate uptake were assessed at the end of the ischemic injury by high-performance liquid chromatography and incorporation of L-[H]glutamate into cells, respectively. Free radical generation in cells was assessed 6 h after OGD during the reoxygenation period using 2',7'-dichlorofluorescin diacetate, which reacts with intracellular radicals to be converted to its fluorescent product, 2',7'-dichlorofluorescin, in cell cytosol. Twenty-four hours after OGD, sevoflurane, in a concentration-dependent manner, significantly reduced lactate dehydrogenase release and increased cell viability. At the end of OGD, sevoflurane was able to reduce the OGD-induced decrease in glutamate uptake. This effect was impaired in the presence of threo-3-methyl glutamate, a specific inhibitor of the glial transporter GLT1. Sevoflurane counteracted the increase in extracellular level of glutamate during OGD and the generation of reactive oxygen species during reoxygenation. Sevoflurane had a neuroprotective effect in this in vitro model of ischemia-reoxygenation. This beneficial effect may be explained, at least in part, by sevoflurane-induced antiexcitotoxic properties during OGD, probably depending on GLT1, and by sevoflurane-induced decrease of reactive oxygen species generation during reoxygenation.

  19. Exposure to ultrafine particles, intracellular production of reactive oxygen species in leukocytes and altered levels of endothelial progenitor cells.

    PubMed

    Jantzen, Kim; Møller, Peter; Karottki, Dorina Gabriela; Olsen, Yulia; Bekö, Gabriel; Clausen, Geo; Hersoug, Lars-Georg; Loft, Steffen

    2016-06-01

    Exposure to particles in the fine and ultrafine size range has been linked to induction of low-grade systemic inflammation, oxidative stress and development of cardiovascular diseases. Declining levels of endothelial progenitor cells within systemic circulation have likewise been linked to progression of cardiovascular diseases. The objective was to determine if exposure to fine and ultrafine particles from indoor and outdoor sources, assessed by personal and residential indoor monitoring, is associated with altered levels of endothelial progenitor cells, and whether such effects are related to leukocyte-mediated oxidative stress. The study utilized a cross sectional design performed in 58 study participants from a larger cohort. Levels of circulating endothelial progenitor cells, defined as either late (CD34(+)KDR(+) cells) or early (CD34(+)CD133(+)KDR(+) cells) subsets were measured using polychromatic flow cytometry. We additionally measured production of reactive oxygen species in leukocyte subsets (lymphocytes, monocytes and granulocytes) by flow cytometry using intracellular 2',7'-dichlorofluoroscein. The measurements encompassed both basal levels of reactive oxygen species production and capacity for reactive oxygen species production for each leukocyte subset. We found that the late endothelial progenitor subset was negatively associated with levels of ultrafine particles measured within the participant residences and with reactive oxygen species production capacity in lymphocytes. Additionally, the early endothelial progenitor cell levels were positively associated with a personalised measure of ultrafine particle exposure and negatively associated with both basal and capacity for reactive oxygen species production in lymphocytes and granulocytes, respectively. Our results indicate that exposure to fine and ultrafine particles derived from indoor sources may have adverse effects on human vascular health. Copyright © 2016 The Authors. Published by Elsevier

  20. Reactive oxygen species-activated nanomaterials as theranostic agents.

    PubMed

    Kim, Kye S; Lee, Dongwon; Song, Chul Gyu; Kang, Peter M

    2015-01-01

    Reactive oxygen species (ROS) are generated from the endogenous oxidative metabolism or from exogenous pro-oxidant exposure. Oxidative stress occurs when there is excessive production of ROS, outweighing the antioxidant defense mechanisms which may lead to disease states. Hydrogen peroxide (H2O2) is one of the most abundant and stable forms of ROS, implicated in inflammation, cellular dysfunction and apoptosis, which ultimately lead to tissue and organ damage. This review is an overview of the role of ROS in different diseases. We will also examine ROS-activated nanomaterials with emphasis on hydrogen peroxide, and their potential medical implications. Further development of the biocompatible, stimuli-activated agent responding to disease causing oxidative stress, may lead to a promising clinical use.

  1. Protein lysine-Nζ alkylation and O-phosphorylation mediated by DTT-generated reactive oxygen species

    PubMed Central

    Kumar, Nigam; Ippel, Hans; Weber, Christian; Hackeng, Tilman; Mayo, Kevin H

    2013-01-01

    Reactive oxygen species (ROS) play crucial roles in physiology and pathology. In this report, we use NMR spectroscopy and mass spectrometry (MS) to demonstrate that proteins (galectin-1, ubiquitin, RNase, cytochrome c, myoglobin, and lysozyme) under reducing conditions with dithiothreitol (DTT) become alkylated at lysine-Nζ groups and O-phosphorylated at serine and threonine residues. These adduction reactions only occur in the presence of monophosphate, potassium, trace metals Fe/Cu, and oxygen, and are promoted by reactive oxygen species (ROS) generated via DTT oxidation. Superoxide mediates the chemistry, because superoxide dismutase inhibits the reaction, and hydroxyl and phosphoryl radicals are also likely involved. While lysine alkylation accounts for most of the adduction, low levels of phosphorylation are also observed at some serine and threonine residues, as determined by western blotting and MS fingerprinting. The adducted alkyl group is found to be a fragment of DTT that forms a Schiff base at lysine Nζ groups. Although its exact chemical structure remains unknown, the DTT fragment includes a SH group and a –CHOH–CH2– group. Chemical adduction appears to be promoted in the context of a well-folded protein, because some adducted sites in the proteins studied are considerably more reactive than others and the reaction occurs to a lesser extent with shorter, unfolded peptides and not at all with small organic molecules. A structural signature involving clusters of positively charged and other polar groups appears to facilitate the reaction. Overall, our findings demonstrate a novel reaction for DTT-mediated ROS chemistry with proteins. PMID:23315912

  2. Solar light-induced production of reactive oxygen species by single walled carbon nanotubes in water

    EPA Science Inventory

    Photosensitizing processes of engineered nanomaterials (ENMs) which include photo-induced production of reactive oxygen species (ROS) convert light energy into oxidizing chemical energy that mediates transformations of nanomaterials. The oxidative stress associated with ROS may p...

  3. Nanotechnology for Electroanalytical Biosensors of Reactive Oxygen and Nitrogen Species.

    PubMed

    Seenivasan, Rajesh; Kolodziej, Charles; Karunakaran, Chandran; Burda, Clemens

    2017-09-01

    Over the past several decades, nanotechnology has contributed to the progress of biomedicine, biomarker discovery, and the development of highly sensitive electroanalytical / electrochemical biosensors for in vitro and in vivo monitoring, and quantification of oxidative and nitrosative stress markers like reactive oxygen species (ROS) and reactive nitrogen species (RNS). A major source of ROS and RNS is oxidative stress in cells, which can cause many human diseases, including cancer. Therefore, the detection of local concentrations of ROS (e. g. superoxide anion radical; O 2 •- ) and RNS (e. g. nitric oxide radical; NO • and its metabolites) released from biological systems is increasingly important and needs a sophisticated detection strategy to monitor ROS and RNS in vitro and in vivo. In this review, we discuss the nanomaterials-based ROS and RNS biosensors utilizing electrochemical techniques with emphasis on their biomedical applications. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Candida albicans Biofilms Do Not Trigger Reactive Oxygen Species and Evade Neutrophil Killing

    PubMed Central

    Xie, Zhihong; Thompson, Angela; Sobue, Takanori; Kashleva, Helena; Xu, Hongbin; Vasilakos, John; Dongari-Bagtzoglou, Anna

    2012-01-01

    Neutrophils are found within Candida albicans biofilms in vivo and could play a crucial role in clearing the pathogen from biofilms forming on catheters and mucosal surfaces. Our goal was to compare the antimicrobial activity of neutrophils against developing and mature C. albicans biofilms and identify biofilm-specific properties mediating resistance to immune cells. Antibiofilm activity was measured with the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)2H-tetrazolium-5-carboxanilide assay and a molecular Candida viability assay. Reactive oxygen species generation was assessed by measuring fluorescence of 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate, acetyl ester in preloaded neutrophils. We found that mature biofilms were resistant to leukocytic killing and did not trigger reactive oxygen species, even though neutrophils retained their viability and functional activation potential. Beta-glucans found in the extracellular matrix negatively affected antibiofilm activities. We conclude that these polymers act as a decoy mechanism to prevent neutrophil activation and that this represents an important innate immune evasion mechanism of C. albicans biofilms. PMID:23033146

  5. Singlet oxygen detection in biological systems: Uses and limitations

    PubMed Central

    Koh, Eugene; Fluhr, Robert

    2016-01-01

    ABSTRACT The study of singlet oxygen in biological systems is challenging in many ways. Singlet oxygen is a relatively unstable ephemeral molecule, and its properties make it highly reactive with many biomolecules, making it difficult to quantify accurately. Several methods have been developed to study this elusive molecule, but most studies thus far have focused on those conditions that produce relatively large amounts of singlet oxygen. However, the need for more sensitive methods is required as one begins to explore the levels of singlet oxygen required in signaling and regulatory processes. Here we discuss the various methods used in the study of singlet oxygen, and outline their uses and limitations. PMID:27231787

  6. Impact of plasma jet vacuum ultraviolet radiation on reactive oxygen species generation in bio-relevant liquids

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jablonowski, H.; Hammer, M. U.; Reuter, S.

    Plasma medicine utilizes the combined interaction of plasma produced reactive components. These are reactive atoms, molecules, ions, metastable species, and radiation. Here, ultraviolet (UV, 100–400 nm) and, in particular, vacuum ultraviolet (VUV, 10–200 nm) radiation generated by an atmospheric pressure argon plasma jet were investigated regarding plasma emission, absorption in a humidified atmosphere and in solutions relevant for plasma medicine. The energy absorption was obtained for simple solutions like distilled water (dH{sub 2}O) or ultrapure water and sodium chloride (NaCl) solution as well as for more complex ones, for example, Rosewell Park Memorial Institute (RPMI 1640) cell culture media. As moderate stablemore » reactive oxygen species, hydrogen peroxide (H{sub 2}O{sub 2}) was studied. Highly reactive oxygen radicals, namely, superoxide anion (O{sub 2}{sup •−}) and hydroxyl radicals ({sup •}OH), were investigated by the use of electron paramagnetic resonance spectroscopy. All species amounts were detected for three different treatment cases: Plasma jet generated VUV and UV radiation, plasma jet generated UV radiation without VUV part, and complete plasma jet including all reactive components additionally to VUV and UV radiation. It was found that a considerable amount of radicals are generated by the plasma generated photoemission. From the experiments, estimation on the low hazard potential of plasma generated VUV radiation is discussed.« less

  7. Gastrodin: an ancient Chinese herbal medicine as a source for anti-osteoporosis agents via reducing reactive oxygen species.

    PubMed

    Huang, Qiang; Shi, Jun; Gao, Bo; Zhang, Hong-Yang; Fan, Jing; Li, Xiao-Jie; Fan, Jin-Zhu; Han, Yue-Hu; Zhang, Jin-Kang; Yang, Liu; Luo, Zhuo-Jing; Liu, Jian

    2015-04-01

    Increased levels of reactive oxygen species (ROS) are a crucial pathogenic factor of osteoporosis. Gastrodin, isolated from the traditional Chinese herbal agent Gastrodia elata, is a potent antioxidant. We hypothesized that gastrodin demonstrates protective effects against osteoporosis by partially reducing reactive oxygen species in human bone marrow mesenchymal stem cells (hBMMSCs) and a macrophage cell line (RAW264.7 cells). We investigated gastrodin on osteogenic and adipogenic differentiation under oxidative stress in hBMMSCs. We also tested gastrodin on osteoclastic differentiation in RAW264.7 cells. Hydrogen peroxide (H2O2) was used to establish an oxidative cell injury model. Our results showed that gastrodin significantly promoted the proliferation of hBMMSCs, improved some osteogenic markers, reduced lipid generation and inhibited the mRNA expression of several adipogenic genes in hBMMSCs. Moreover, gastrodin reduced the number of osteoclasts, TRAP activity and the expression of osteoclast-specific genes in RAW264.7 cells. Gastrodin suppressed the production of reactive oxygen species in both hBMMSCs and RAW264.7 cells. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Our data revealed that gastrodin treatment reduced the activity of serum bone degradation markers, such as CTX-1 and TRAP. Importantly, it ameliorated the micro-architecture of trabecular bones. Gastrodin decreased osteoclast numbers in vivo by TRAP staining. To conclude, these results indicated that gastrodin shows protective effects against osteoporosis linking to a reduction in reactive oxygen species, suggesting that gastrodin may be useful in the prevention and treatment of osteoporosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. The importance of conceptual models in the reactive transport simulation of oxygen ingress in sparsely fractured crystalline rock.

    PubMed

    Macquarrie, K T B; Mayer, K U; Jin, B; Spiessl, S M

    2010-03-01

    Redox evolution in sparsely fractured crystalline rocks is a key, and largely unresolved, issue when assessing the geochemical suitability of deep geological repositories for nuclear waste. Redox zonation created by the influx of oxygenated waters has previously been simulated using reactive transport models that have incorporated a variety of processes, resulting in predictions for the depth of oxygen penetration that may vary greatly. An assessment and direct comparison of the various underlying conceptual models are therefore needed. In this work a reactive transport model that considers multiple processes in an integrated manner is used to investigate the ingress of oxygen for both single fracture and fracture zone scenarios. It is shown that the depth of dissolved oxygen migration is greatly influenced by the a priori assumptions that are made in the conceptual models. For example, the ability of oxygen to access and react with minerals in the rock matrix may be of paramount importance for single fracture conceptual models. For fracture zone systems, the abundance and reactivity of minerals within the fractures and thin matrix slabs between the fractures appear to provide key controls on O(2) attenuation. The findings point to the need for improved understanding of the coupling between the key transport-reaction feedbacks to determine which conceptual models are most suitable and to provide guidance for which parameters should be targeted in field and laboratory investigations. Copyright 2009 Elsevier B.V. All rights reserved.

  9. Reactive oxygen species mediate pollen tube rupture to release sperm for fertilization in Arabidopsis

    NASA Astrophysics Data System (ADS)

    Duan, Qiaohong; Kita, Daniel; Johnson, Eric A.; Aggarwal, Mini; Gates, Laura; Wu, Hen-Ming; Cheung, Alice Y.

    2014-01-01

    In flowering plants, sperm are transported inside pollen tubes to the female gametophyte for fertilization. The female gametophyte induces rupture of the penetrating pollen tube, resulting in sperm release and rendering them available for fertilization. Here we utilize the Arabidopsis FERONIA (FER) receptor kinase mutants, whose female gametophytes fail to induce pollen tube rupture, to decipher the molecular mechanism of this critical male-female interactive step. We show that FER controls the production of high levels of reactive oxygen species at the entrance to the female gametophyte to induce pollen tube rupture and sperm release. Pollen tube growth assays in vitro and in the pistil demonstrate that hydroxyl free radicals are likely the most reactive oxygen molecules, and they induce pollen tube rupture in a Ca2+-dependent process involving Ca2+ channel activation. Our results provide evidence for a RHO GTPase-based signalling mechanism to mediate sperm release for fertilization in plants.

  10. Reactive oxygen species mediate pollen tube rupture to release sperm for fertilization in Arabidopsis.

    PubMed

    Duan, Qiaohong; Kita, Daniel; Johnson, Eric A; Aggarwal, Mini; Gates, Laura; Wu, Hen-Ming; Cheung, Alice Y

    2014-01-01

    In flowering plants, sperm are transported inside pollen tubes to the female gametophyte for fertilization. The female gametophyte induces rupture of the penetrating pollen tube, resulting in sperm release and rendering them available for fertilization. Here we utilize the Arabidopsis FERONIA (FER) receptor kinase mutants, whose female gametophytes fail to induce pollen tube rupture, to decipher the molecular mechanism of this critical male-female interactive step. We show that FER controls the production of high levels of reactive oxygen species at the entrance to the female gametophyte to induce pollen tube rupture and sperm release. Pollen tube growth assays in vitro and in the pistil demonstrate that hydroxyl free radicals are likely the most reactive oxygen molecules, and they induce pollen tube rupture in a Ca(2+)-dependent process involving Ca(2+) channel activation. Our results provide evidence for a RHO GTPase-based signalling mechanism to mediate sperm release for fertilization in plants.

  11. Singlet oxygen treatment of tumor cells triggers extracellular singlet oxygen generation, catalase inactivation and reactivation of intercellular apoptosis-inducing signaling☆

    PubMed Central

    Riethmüller, Michaela; Burger, Nils; Bauer, Georg

    2015-01-01

    Intracellular singlet oxygen generation in photofrin-loaded cells caused cell death without discrimination between nonmalignant and malignant cells. In contrast, extracellular singlet oxygen generation caused apoptosis induction selectively in tumor cells through singlet oxygen-mediated inactivation of tumor cell protective catalase and subsequent reactivation of intercellular ROS-mediated apoptosis signaling through the HOCl and the NO/peroxynitrite signaling pathway. Singlet oxygen generation by extracellular photofrin alone was, however, not sufficient for optimal direct inactivation of catalase, but needed to trigger the generation of cell-derived extracellular singlet oxygen through the interaction between H2O2 and peroxynitrite. Thereby, formation of peroxynitrous acid, generation of hydroxyl radicals and formation of perhydroxyl radicals (HO2.) through hydroxyl radical/H2O2 interaction seemed to be required as intermediate steps. This amplificatory mechanism led to the formation of singlet oxygen at a sufficiently high concentration for optimal inactivation of membrane-associated catalase. At low initial concentrations of singlet oxygen, an additional amplification step needed to be activated. It depended on singlet oxygen-dependent activation of the FAS receptor and caspase-8, followed by caspase-8-mediated enhancement of NOX activity. The biochemical mechanisms described here might be considered as promising principle for the development of novel approaches in tumor therapy that specifically direct membrane-associated catalase of tumor cells and thus utilize tumor cell-specific apoptosis-inducing ROS signaling. PMID:26225731

  12. Luteolin as reactive oxygen generator by X-ray and UV irradiation

    NASA Astrophysics Data System (ADS)

    Toyama, Michiru; Mori, Takashi; Takahashi, Junko; Iwahashi, Hitoshi

    2018-05-01

    Non-toxic X-ray-responsive substances can be used in the radiosensitization of cancer, like porphyrin mediated radiotherapy. However, most X-ray-responsive substances are toxic. To find novel non-toxic X-ray-responsive substances, we studied the X-ray and UV reactivity of 40 non-toxic compounds extracted from plants. Dihydroethidium was used as an indicator to detect reactive oxygen species (ROS) generated by the compounds under X-ray or UV irradiation. We found that 13 of the investigated compounds generated ROS under X-ray irradiation and 17 generated ROS under UV irradiation. Only 4 substances generated ROS under both X-ray and UV. In particular, luteolin exhibited the highest activity among the investigated compounds; therefore, the ROS generated by luteolin were thoroughly characterized. To identify the ROS, we employed a combination of ROS detection reagents and their quenchers. O2·- generation by luteolin was monitored using dihydroethidium and superoxide dismutase (as an O2·- quencher). OH· and 1O2 generation was determined using aminophenyl fluorescein with ethanol (OH· quencher) and Singlet Oxygen Sensor Green® with NaN3 (1O2 quencher), respectively. Generation of O2·- under X-ray and UV irradiation was observed; however, no OH· or 1O2 was detected. The production of ROS from luteolin is surprising, because luteolin is a well-known antioxidant.

  13. Up-regulation of A1M/α1-microglobulin in skin by heme and reactive oxygen species gives protection from oxidative damage.

    PubMed

    Olsson, Magnus G; Allhorn, Maria; Larsson, Jörgen; Cederlund, Martin; Lundqvist, Katarina; Schmidtchen, Artur; Sørensen, Ole E; Mörgelin, Matthias; Akerström, Bo

    2011-01-01

    During bleeding the skin is subjected to oxidative insults from free heme and radicals, generated from extracellular hemoglobin. The lipocalin α(1)-microglobulin (A1M) was recently shown to have reductase properties, reducing heme-proteins and other substrates, and to scavenge heme and radicals. We investigated the expression and localization of A1M in skin and the possible role of A1M in the protection of skin tissue from damage induced by heme and reactive oxygen species. Skin explants, keratinocyte cultures and purified collagen I were exposed to heme, reactive oxygen species, and/or A1M and investigated by biochemical methods and electron microscopy. The results demonstrate that A1M is localized ubiquitously in the dermal and epidermal layers, and that the A1M-gene is expressed in keratinocytes and up-regulated after exposure to heme and reactive oxygen species. A1M inhibited the heme- and reactive oxygen species-induced ultrastructural damage, up-regulation of antioxidation and cell cycle regulatory genes, and protein carbonyl formation in skin and keratinocytes. Finally, A1M bound to purified collagen I (K(d) = 0.96×10(-6) M) and could inhibit and repair the destruction of collagen fibrils by heme and reactive oxygen species. The results suggest that A1M may have a physiological role in protection of skin cells and matrix against oxidative damage following bleeding.

  14. Cytotoxicity of InP/ZnS quantum dots related to reactive oxygen species generation.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chibli, H.; Carlini, L.; Park, S.

    Indium phosphide (InP) quantum dots (QDs) have emerged as a presumably less hazardous alternative to cadmium-based particles, but their cytotoxicity has not been well examined. Although their constituent elements are of very low toxicity to cells in culture, they nonetheless exhibit phototoxicity related to generation of reactive oxygen species by excited electrons and/or holes interacting with water and molecular oxygen. Using spin-trap electron paramagnetic resonance (EPR) spectroscopy and reporter assays, we find a considerable amount of superoxide and a small amount of hydroxyl radical formed under visible illumination of biocompatible InP QDs with a single ZnS shell, comparable to whatmore » is seen with CdTe. A double thickness shell reduces the reactive oxygen species concentration approximately two-fold. Survival assays in five cell lines correspondingly indicate a distinct reduction in toxicity with the double-shell InP QDs. Toxicity varies significantly across cell lines according to the efficiency of uptake, being overall significantly less than what is seen with CdTe or CdSe/ZnS. This indicates that InP QDs are a useful alternative to cadmium-containing QDs, while remaining capable of electron-transfer processes that may be undesirable or which may be exploited for photosensitization applications.« less

  15. Cytotoxicity of InP/ZnS quantum dots related to reactive oxygen species generation.

    PubMed

    Chibli, Hicham; Carlini, Lina; Park, Soonhyang; Dimitrijevic, Nada M; Nadeau, Jay L

    2011-06-01

    Indium phosphide (InP) quantum dots (QDs) have emerged as a presumably less hazardous alternative to cadmium-based particles, but their cytotoxicity has not been well examined. Although their constituent elements are of very low toxicity to cells in culture, they nonetheless exhibit phototoxicity related to generation of reactive oxygen species by excited electrons and/or holes interacting with water and molecular oxygen. Using spin-trap electron paramagnetic resonance (EPR) spectroscopy and reporter assays, we find a considerable amount of superoxide and a small amount of hydroxyl radical formed under visible illumination of biocompatible InP QDs with a single ZnS shell, comparable to what is seen with CdTe. A double thickness shell reduces the reactive oxygen species concentration approximately two-fold. Survival assays in five cell lines correspondingly indicate a distinct reduction in toxicity with the double-shell InP QDs. Toxicity varies significantly across cell lines according to the efficiency of uptake, being overall significantly less than what is seen with CdTe or CdSe/ZnS. This indicates that InP QDs are a useful alternative to cadmium-containing QDs, while remaining capable of electron-transfer processes that may be undesirable or which may be exploited for photosensitization applications.

  16. Cytotoxicity of InP/ZnS quantum dots related to reactive oxygen species generation

    NASA Astrophysics Data System (ADS)

    Chibli, Hicham; Carlini, Lina; Park, Soonhyang; Dimitrijevic, Nada M.; Nadeau, Jay L.

    2011-06-01

    Indium phosphide (InP) quantum dots (QDs) have emerged as a presumably less hazardous alternative to cadmium-based particles, but their cytotoxicity has not been well examined. Although their constituent elements are of very low toxicity to cells in culture, they nonetheless exhibit phototoxicity related to generation of reactive oxygen species by excited electrons and/or holes interacting with water and molecular oxygen. Using spin-trap electron paramagnetic resonance (EPR) spectroscopy and reporter assays, we find a considerable amount of superoxide and a small amount of hydroxyl radical formed under visible illumination of biocompatible InP QDs with a single ZnS shell, comparable to what is seen with CdTe. A double thickness shell reduces the reactive oxygen species concentration approximately two-fold. Survival assays in five cell lines correspondingly indicate a distinct reduction in toxicity with the double-shell InP QDs. Toxicity varies significantly across cell lines according to the efficiency of uptake, being overall significantly less than what is seen with CdTe or CdSe/ZnS. This indicates that InP QDs are a useful alternative to cadmium-containing QDs, while remaining capable of electron-transfer processes that may be undesirable or which may be exploited for photosensitization applications.

  17. Fusogenic Reactive Oxygen Species Triggered Charge-Reversal Vector for Effective Gene Delivery.

    PubMed

    Liu, Xin; Xiang, Jiajia; Zhu, Dingcheng; Jiang, Liming; Zhou, Zhuxian; Tang, Jianbin; Liu, Xiangrui; Huang, Yongzhuo; Shen, Youqing

    2016-03-02

    A novel fusogenic lipidic polyplex (FLPP) vector is designed to fuse with cell membranes, mimicking viropexis, and eject the polyplex into the cytosol, where the cationic polymer is subsequently oxidized by intracellular reactive oxygen species and converts to being negatively charged, efficiently releasing the DNA. The vector delivering suicide gene achieves significantly better inhibition of tumor growth than doxorubicin. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Oxygen and Oxygen Toxicity: The Birth of Concepts

    PubMed Central

    Zhu, Hong; Traore, Kassim; Santo, Arben; Trush, Michael A.; Li, Y. Robert

    2018-01-01

    Molecular dioxygen (O2) is an essential element of aerobic life, yet incomplete reduction or excitation of O2 during aerobic metabolisms generates diverse oxygen-containing reactive species, commonly known as reactive oxygen species (ROS). On the one hand, ROS pose a serious threat to aerobic organisms via inducing oxidative damage to cellular constituents. On the other hand, these reactive species, when their generation is under homeostatic control, also play important physiological roles (e.g., constituting an important component of immunity and participating in redox signaling). This article defines oxygen and the key facts about oxygen, and discusses the relationship between oxygen and the emergence of early animals on Earth. The article then describes the discovery of oxygen by three historical figures and examines the birth of the concepts of oxygen toxicity and the underlying free radical mechanisms. The article ends with a brief introduction to the emerging field of ROS-mediated redox signaling and physiological responses. PMID:29707642

  19. The mystery of gold's chemical activity: local bonding, morphology and reactivity of atomic oxygen.

    PubMed

    Baker, Thomas A; Liu, Xiaoying; Friend, Cynthia M

    2011-01-07

    Recently, gold has been intensely studied as a catalyst for key synthetic reactions. Gold is an attractive catalyst because, surprisingly, it is highly active and very selective for partial oxidation processes suggesting promise for energy-efficient "green" chemistry. The underlying origin of the high activity of Au is a controversial subject since metallic gold is commonly thought to be inert. Herein, we establish that one origin of the high activity for gold catalysis is the extremely reactive nature of atomic oxygen bound in 3-fold coordination sites on metallic gold. This is the predominant form of O at low concentrations on the surface, which is a strong indication that it is most relevant to catalytic conditions. Atomic oxygen bound to metallic Au in 3-fold sites has high activity for CO oxidation, oxidation of olefins, and oxidative transformations of alcohols and amines. Among the factors identified as important in Au-O interaction are the morphology of the surface, the local binding site of oxygen, and the degree of order of the oxygen overlayer. In this Perspective, we present an overview of both theory and experiments that identify the reactive forms of O and their associated charge density distributions and bond strengths. We also analyze and model the release of Au atoms induced by O binding to the surface. This rough surface also has the potential for O(2) dissociation, which is a critical step if Au is to be activated catalytically. We further show the strong parallels between product distributions and reactivity for O-covered Au at low pressure (ultrahigh vacuum) and for nanoporous Au catalysts operating at atmospheric pressure as evidence that atomic O is the active species under working catalytic conditions when metallic Au is present. We briefly discuss the possible contributions of oxidants that may contain intact O-O bonds and of the Au-metal oxide support interface in Au catalysis. Finally, the challenges and future directions for fully

  20. The surface reactivity of acrylonitrile with oxygen atoms on an analogue of interstellar dust grains

    NASA Astrophysics Data System (ADS)

    Kimber, Helen J.; Toscano, Jutta; Price, Stephen D.

    2018-06-01

    Experiments designed to reveal the low-temperature reactivity on the surfaces of interstellar dust grains are used to probe the heterogeneous reaction between oxygen atoms and acrylonitrile (C2H3CN, H2C=CH-CN). The reaction is studied at a series of fixed surface temperatures between 14 and 100 K. After dosing the reactants on to the surface, temperature-programmed desorption, coupled with time-of-flight mass spectrometry, reveals the formation of a product with the molecular formula C3H3NO. This product results from the addition of a single oxygen atom to the acrylonitrile reactant. The oxygen atom attack appears to occur exclusively at the C=C double bond, rather than involving the cyano(-CN) group. The absence of reactivity at the cyano site hints that full saturation of organic molecules on dust grains may not always occur in the interstellar medium. Modelling the experimental data provides a reaction probability of 0.007 ± 0.003 for a Langmuir-Hinshelwood style (diffusive) reaction mechanism. Desorption energies for acrylonitrile, oxygen atoms, and molecular oxygen, from the multilayer mixed ice their deposition forms, are also extracted from the kinetic model and are 22.7 ± 1.0 kJ mol-1 (2730 ± 120 K), 14.2 ± 1.0 kJ mol-1 (1710 ± 120 K), and 8.5 ± 0.8 kJ mol-1 (1020 ± 100 K), respectively. The kinetic parameters we extract from our experiments indicate that the reaction between atomic oxygen and acrylonitrile could occur on interstellar dust grains on an astrophysical time-scale.

  1. Trojan Horse for Light-Triggered Bifurcated Production of Singlet Oxygen and Fenton-Reactive Iron within Cancer Cells.

    PubMed

    Cioloboc, Daniela; Kennedy, Christopher; Boice, Emily N; Clark, Emily R; Kurtz, Donald M

    2018-01-08

    Traditional photodynamic therapy for cancer relies on dye-photosensitized generation of singlet oxygen. However, therapeutically effective singlet oxygen generation requires well-oxygenated tissues, whereas many tumor environments tend to be hypoxic. We describe a platform for targeted enhancement of photodynamic therapy that produces singlet oxygen in oxygenated environments and hydroxyl radical, which is typically regarded as the most toxic reactive oxygen species, in hypoxic environments. The 24-subunit iron storage protein bacterioferritin (Bfr) has the unique property of binding 12 heme groups in its protein shell. We inserted the isostructural photosensitizer, zinc(II) protoporphyrin IX (ZnP), in place of the hemes and extended the surface-exposed N-terminal ends of the Bfr subunits with a peptide targeting a receptor that is hyperexpressed on the cell surface of many tumors and tumor vasculature. We then loaded the inner cavity with ∼2500 irons as a ferric oxyhydroxide polymer and finally conjugated 2 kDa polyethylene glycol to the outer surface. We showed that the inserted ZnP photosensitizes generation of both singlet oxygen and the hydroxyl radical, the latter via the reaction of photoreleased ferrous iron with hydrogen peroxide. This targeted iron-loaded ZnP-Bfr construct was endocytosed by C32 melanoma cells and localized to lysosomes. Irradiating the treated cells with light at wavelengths overlapping the ZnP Soret absorption band induced photosensitized intracellular Fe 2+ release and substantial lowering of cell viability. This targeted, light-triggered production of intracellular singlet oxygen and Fenton-reactive iron could potentially be developed into a phototherapeutic adjunct for many types of cancers.

  2. Reactivity and oxygen diffusion property of resistive barriers for Bi-2223/Ag tapes

    NASA Astrophysics Data System (ADS)

    Kováč, P.; Hušek, I.

    2002-12-01

    Reactivity of several oxide materials (OM) with BSCCO powder and oxygen diffusion through OM layer has been tested at temperature ≈840 °C in air. The OM (e.g.: BaZrO 3, SrCO 3, MgO and ZrO 2) showing the low or no reactivity with BSCCO have been mixed (10 wt.%) with precursor powder and used for single-core tapes. Bi-2223/Ag/OM/Ag single-core tapes with oxide barriers made of BaZrO 3, SrCO 3, ZrO 2 and Al 2O 3 have been also prepared by a standard powder-in-tube technique. The used OM in the direct contact with BSCCO influences the electrical properties of Bi-2223 phase differently. These is because the oxides react with BSCCO during the heat treatment and simultaneously affect the 2212→2223 phase transformation, the Bi-2223 grain growth and so also grain connectivity. SrCO 3 powder has been evaluated as the best material from the point of no destructive effect on 2223 phase transport current property. The oxide barrier controls the oxygen diffusion during the tape heat treatment and simultaneously the HTS phase formation kinetics, its purity and content within the superconducting core. For single-core Bi-2223/Ag/OM/Ag tapes, the highest current density was measured for Al 2O 3 due to only slightly reduced oxygen diffusion through the barrier.

  3. Singlet oxygen treatment of tumor cells triggers extracellular singlet oxygen generation, catalase inactivation and reactivation of intercellular apoptosis-inducing signaling.

    PubMed

    Riethmüller, Michaela; Burger, Nils; Bauer, Georg

    2015-12-01

    Intracellular singlet oxygen generation in photofrin-loaded cells caused cell death without discrimination between nonmalignant and malignant cells. In contrast, extracellular singlet oxygen generation caused apoptosis induction selectively in tumor cells through singlet oxygen-mediated inactivation of tumor cell protective catalase and subsequent reactivation of intercellular ROS-mediated apoptosis signaling through the HOCl and the NO/peroxynitrite signaling pathway. Singlet oxygen generation by extracellular photofrin alone was, however, not sufficient for optimal direct inactivation of catalase, but needed to trigger the generation of cell-derived extracellular singlet oxygen through the interaction between H2O2 and peroxynitrite. Thereby, formation of peroxynitrous acid, generation of hydroxyl radicals and formation of perhydroxyl radicals (HO2(.)) through hydroxyl radical/H2O2 interaction seemed to be required as intermediate steps. This amplificatory mechanism led to the formation of singlet oxygen at a sufficiently high concentration for optimal inactivation of membrane-associated catalase. At low initial concentrations of singlet oxygen, an additional amplification step needed to be activated. It depended on singlet oxygen-dependent activation of the FAS receptor and caspase-8, followed by caspase-8-mediated enhancement of NOX activity. The biochemical mechanisms described here might be considered as promising principle for the development of novel approaches in tumor therapy that specifically direct membrane-associated catalase of tumor cells and thus utilize tumor cell-specific apoptosis-inducing ROS signaling. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Involvement of reactive oxygen species in the electrochemical inhibition of barnacle (Amphibalanus amphitrite) settlement

    Treesearch

    Rodolfo E. Perez-Roa; Marc A. Anderson; Dan Rittschof; Christopher G. Hunt; Daniel R. Noguera

    2009-01-01

    The role of reactive oxygen species (ROS) in electrochemical biofouling inhibition was investigated using a series of abiotic tests and settlement experiments with larvae of the barnacle Amphibalanus amphitrite, a cosmopolitan fouler. Larval settlement, a measure of biofouling potential, was reduced from 43% ± 14% to 5% ± 6% upon the application of...

  5. Seed birth to death: dual functions of reactive oxygen species in seed physiology.

    PubMed

    Jeevan Kumar, S P; Rajendra Prasad, S; Banerjee, Rintu; Thammineni, Chakradhar

    2015-09-01

    Reactive oxygen species (ROS) are considered to be detrimental to seed viability. However, recent studies have demonstrated that ROS have key roles in seed germination particularly in the release of seed dormancy and embryogenesis, as well as in protection from pathogens. This review considers the functions of ROS in seed physiology. ROS are present in all cells and at all phases of the seed life cycle. ROS accumulation is important in breaking seed dormancy, and stimulating seed germination and protection from pathogens. However, excessive ROS accumulation can be detrimental. Therefore, knowledge of the mechanisms by which ROS influence seed physiology will provide insights that may not only allow the development of seed quality markers but also help us understand how dormancy can be broken in several recalcitrant species. Reactive oxygen species have a dual role in seed physiology. Understanding the relative importance of beneficial and detrimental effects of ROS provides great scope for the improvement and maintenance of seed vigour and quality, factors that may ultimately increase crop yields. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Cell signaling by reactive nitrogen and oxygen species in atherosclerosis

    NASA Technical Reports Server (NTRS)

    Patel, R. P.; Moellering, D.; Murphy-Ullrich, J.; Jo, H.; Beckman, J. S.; Darley-Usmar, V. M.

    2000-01-01

    The production of reactive oxygen and nitrogen species has been implicated in atherosclerosis principally as means of damaging low-density lipoprotein that in turn initiates the accumulation of cholesterol in macrophages. The diversity of novel oxidative modifications to lipids and proteins recently identified in atherosclerotic lesions has revealed surprising complexity in the mechanisms of oxidative damage and their potential role in atherosclerosis. Oxidative or nitrosative stress does not completely consume intracellular antioxidants leading to cell death as previously thought. Rather, oxidative and nitrosative stress have a more subtle impact on the atherogenic process by modulating intracellular signaling pathways in vascular tissues to affect inflammatory cell adhesion, migration, proliferation, and differentiation. Furthermore, cellular responses can affect the production of nitric oxide, which in turn can strongly influence the nature of oxidative modifications occurring in atherosclerosis. The dynamic interactions between endogenous low concentrations of oxidants or reactive nitrogen species with intracellular signaling pathways may have a general role in processes affecting wound healing to apoptosis, which can provide novel insights into the pathogenesis of atherosclerosis.

  7. Reactive oxygen species modulator 1 (Romo1) as a novel diagnostic marker for lung cancer-related malignant effusion

    PubMed Central

    Lee, Seung Hyeun; Park, Myung Jae; Choi, Sue In; Lee, Eun Joo; Lee, Sang Yeub; In, Kwang Ho

    2017-01-01

    Abstract Reactive oxygen species modulator 1 (Romo1) is a novel protein that plays an important role in intracellular reactive oxygen species generation. Recently, Romo1 has been suggested to have diagnostic and prognostic potential in lung cancer. However, there is no data on the diagnostic value of Romo1 level in malignant pleural effusion. We evaluated the clinical usefulness of Romo1 in pleural fluid for the diagnosis of malignant effusion in lung cancer patients. Pleural fluid Romo1 level was measured using enzyme-linked immunosorbent assay and compared between lung cancer-associated malignant effusion (n = 53; 29 adenocarcinomas and 24 squamous cell carcinomas) and benign pleural effusions (n = 91; 31 tuberculous pleurisy, 30 parapneumonic effusion, and 30 transudate). The discriminative power of Romo1 for lung cancer-associated malignant effusion was determined using receiver operating characteristic (ROC) curve analysis and compared with those of other tumor markers. Median Romo1 level in lung cancer-associated malignant effusion was 99.3 ng/mL, which was significantly higher than that in benign pleural effusions (P < 0.001). The optimal cutoff value of Romo1 to discriminate lung cancer-associated malignant effusion from benign effusions was 67.0 ng/mL with a sensitivity of 73.8% and a specificity of 84.1%. The area under the curve was 0.837 (95% confidence interval [CI]: 0.750–0.886), which was significantly better than that of cytokeratin 19 fragments (P < 0.001). Pleural fluid Romo1 could discriminate lung cancer from benign diseases with considerable sensitivity and specificity. Our findings suggest a diagnostic potential of Romo1 for lung cancer-associated malignant effusion. PMID:28121949

  8. Significant levels of extracellular reactive oxygen species produced by brown rot basidiomycetes on cellulose

    Treesearch

    Roni Cohen; Kenneth A. Jensen; Carl J. Houtman; Kenneth E. Hammel

    2002-01-01

    It is often proposed that brown rot basidiomycetes use extracellular reactive oxygen species (ROS) to accomplish the initial depolymerization of cellulose in wood, but little evidence has been presented to show that the fungi produce these oxidants in physiologically relevant quantities. We used [14C]phenethyl polyacrylate as a radical trap to estimate extracellular...

  9. MINIMAL ROLE FOR REACTIVE OXYGEN SPECIES IN DICHLOROACETIC ACID-INDUCED DYSMORPHOLOGY IN MOUSE WHOLE EMBRYO CULTURE.

    EPA Science Inventory

    Administration of dichloroacetate (DCA) to pregnant rats produces craniofacial, heart and other defects in their offspring. Exposure of zebrafish to DCA induces malformations and increases superoxide and nitric oxide production suggesting that reactive oxygen species (ROS) are as...

  10. Reactive oxygen species and plant resistance to fungal pathogens.

    PubMed

    Lehmann, Silke; Serrano, Mario; L'Haridon, Floriane; Tjamos, Sotirios E; Metraux, Jean-Pierre

    2015-04-01

    Reactive oxygen species (ROS) have been studied for their role in plant development as well as in plant immunity. ROS were consistently observed to accumulate in the plant after the perception of pathogens and microbes and over the years, ROS were postulated to be an integral part of the defence response of the plant. In this article we will focus on recent findings about ROS involved in the interaction of plants with pathogenic fungi. We will describe the ways to detect ROS, their modes of action and their importance in relation to resistance to fungal pathogens. In addition we include some results from works focussing on the fungal interactor and from studies investigating roots during pathogen attack. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Magnetic nanoparticles: reactive oxygen species generation and potential therapeutic applications

    NASA Astrophysics Data System (ADS)

    Mai, Trang; Hilt, J. Zach

    2017-07-01

    Magnetic nanoparticles have been demonstrated to produce reactive oxygen species (ROS), which play a major role in various cellular pathways, via Fenton and Haber-Weiss reaction. ROS act as a double-edged sword inside the body. At normal conditions, the generation of ROS is in balance with their elimination by scavenger systems, and they can promote cell proliferation as well as differentiation. However, at an increased level, they can cause damages to protein, lead to cellular apoptosis, and contribute to many diseases including cancer. Many recent studies proposed a variety of strategies to either suppress toxicity of ROS generation or exploit the elevated ROS levels for cancer therapy.

  12. Reactive oxygen species, antioxidants and fish mitochondria.

    PubMed

    Wilhelm Filho, Danilo

    2007-01-01

    In fishes, irrespective of their thermoregulatory capacity or metabolic rate, the main physiological source of reactive oxygen species (ROS) is mitochondria. During active swimming, ROS is by an large provided by red muscle mitochondria. Other tissues such as lens, liver, heart, swimbladder, roe and blood also afford important ROS production and antioxidant levels in resting fish. A close relationship between structure and function is evident in fish mitochondrion with a surface-to-volume optimization by the size of cristae to maximize electron transfer. The mechanism of fish mitochondrial superoxide anion (O2*-) and ROS production as well as the mechanism of mitochondrial coupling and proton leak seems similar to that of mammals. Contrary to mammalian red cells, fish erythrocytes possess nuclei and mitochondria. The presence of cardiolipin and the absence of cholesterol in fish mitochondrial membranes confer a high structural flexibility. The difference in phospholipid unsaturation may explain the greater proton leak in endotherms compared to thermoconformers. The present review summarizes our current understanding in respect to comparative aspects of fish mitochondrial function, with an emphasis on the adaptations to changes in temperature, O2 availability and O2 consumption, which are generally coupled to changes in antioxidant status and ROS production. Nevertheless, most work on this fascinating area has yet to be done. The literature on the effect of xenobiotics, aquatic contamination, and aquaculture issues are not reviewed. Data on the production of NO and reactive nitrogen species (RNS), on O2 sensing and on the role of ROS and RNS in cell signalling involving fish mitochondria are almost completely lacking in the literature.

  13. Release of elicitors from rice blast spores under the action of reactive oxygen species

    USDA-ARS?s Scientific Manuscript database

    The effects of reactive oxygen species (ROS) on secretion of hypothesized elicitors from spores of rice blast causal fungus Magnaporthe grisea were studied. For spore exposure to exogenous ROS, they were germinated for 5 h in 50 µM H2O2 followed by addition of catalase E.C. 1.11.1.6 (to decompose pe...

  14. Progress in understanding the molecular oxygen paradox - function of mitochondrial reactive oxygen species in cell signaling.

    PubMed

    Kuksal, Nidhi; Chalker, Julia; Mailloux, Ryan J

    2017-10-26

    The molecular oxygen (O2) paradox was coined to describe its essential nature and toxicity. The latter characteristic of O2 is associated with the formation of reactive oxygen species (ROS), which can damage structures vital for cellular function. Mammals are equipped with antioxidant systems to fend off the potentially damaging effects of ROS. However, under certain circumstances antioxidant systems can become overwhelmed leading to oxidative stress and damage. Over the past few decades, it has become evident that ROS, specifically H2O2, are integral signaling molecules complicating the previous logos that oxyradicals were unfortunate by-products of oxygen metabolism that indiscriminately damage cell structures. To avoid its potential toxicity whilst taking advantage of its signaling properties, it is vital for mitochondria to control ROS production and degradation. H2O2 elimination pathways are well characterized in mitochondria. However, less is known about how H2O2 production is controlled. The present review examines the importance of mitochondrial H2O2 in controlling various cellular programs and emerging evidence for how production is regulated. Recently published studies showing how mitochondrial H2O2 can be used as a secondary messenger will be discussed in detail. This will be followed with a description of how mitochondria use S-glutathionylation to control H2O2 production.

  15. Mitochondrion-Derived Reactive Oxygen Species Lead to Enhanced Amyloid Beta Formation

    PubMed Central

    Schütt, Tanja; Kurz, Christopher; Eckert, Schamim H.; Schiller, Carola; Occhipinti, Angelo; Mai, Sören; Jendrach, Marina; Eckert, Gunter P.; Kruse, Shane E.; Palmiter, Richard D.; Brandt, Ulrich; Dröse, Stephan; Wittig, Ilka; Willem, Michael; Haass, Christian; Reichert, Andreas S.; Müller, Walter E.

    2012-01-01

    Abstract Aims: Intracellular amyloid beta (Aβ) oligomers and extracellular Aβ plaques are key players in the progression of sporadic Alzheimer's disease (AD). Still, the molecular signals triggering Aβ production are largely unclear. We asked whether mitochondrion-derived reactive oxygen species (ROS) are sufficient to increase Aβ generation and thereby initiate a vicious cycle further impairing mitochondrial function. Results: Complex I and III dysfunction was induced in a cell model using the respiratory inhibitors rotenone and antimycin, resulting in mitochondrial dysfunction and enhanced ROS levels. Both treatments lead to elevated levels of Aβ. Presence of an antioxidant rescued mitochondrial function and reduced formation of Aβ, demonstrating that the observed effects depended on ROS. Conversely, cells overproducing Aβ showed impairment of mitochondrial function such as comprised mitochondrial respiration, strongly altered morphology, and reduced intracellular mobility of mitochondria. Again, the capability of these cells to generate Aβ was partly reduced by an antioxidant, indicating that Aβ formation was also ROS dependent. Moreover, mice with a genetic defect in complex I, or AD mice treated with a complex I inhibitor, showed enhanced Aβ levels in vivo. Innovation: We show for the first time that mitochondrion-derived ROS are sufficient to trigger Aβ production in vitro and in vivo. Conclusion: Several lines of evidence show that mitochondrion-derived ROS result in enhanced amyloidogenic amyloid precursor protein processing, and that Aβ itself leads to mitochondrial dysfunction and increased ROS levels. We propose that starting from mitochondrial dysfunction a vicious cycle is triggered that contributes to the pathogenesis of sporadic AD. Antioxid. Redox Signal. 16, 1421–1433. PMID:22229260

  16. Flaxseed oil increases aortic reactivity to phenylephrine through reactive oxygen species and the cyclooxygenase-2 pathway in rats

    PubMed Central

    2014-01-01

    Background Flaxseed oil has the highest concentration of omega-3 α-linolenic acid, which has been associated with cardiovascular benefit. However, the mechanism underlying the vascular effects induced through flaxseed oil is not well known. Thus, in the present study, we investigated the effects of flaxseed oil on vascular function in isolated rat aortic rings. Methods Wistar rats were treated daily with flaxseed oil or a control (mineral oil) intramuscular (i.m.) for fifteen days. Isolated aortic segments were used to evaluate cyclooxygenase-2 (COX-2) protein expression, superoxide anion levels and vascular reactivity experiments. Results Flaxseed oil treatment increased the vasoconstrictor response of aortic rings to phenylephrine. Endothelium removal increased the response to phenylephrine in aortic segments isolated from both groups, but the effect was smaller in the treated group. L-NAME incubation similarly increased the phenylephrine response in segments from both groups. The TXA2 synthase inhibitor furegrelate, the selective COX-2 inhibitor NS 398, the TP receptor antagonist SQ 29.548, the reactive oxygen species (ROS) scavenger apocynin, the superoxide anion scavengers tiron and the phospholipase A2 inhibitor dexamethasone partially reversed the flaxseed oil-induced increase in reactivity to phenylephrine. Conclusions These findings suggest that flaxseed oil treatment increased vascular reactivity to phenylephrine through an increase in ROS production and COX-2-derived TXA2 production. The results obtained in the present study provide new insight into the effects of flaxseed oil treatment (i.m.) on vascular function. PMID:24993607

  17. Interaction of plant growth regulators and reactive oxygen species to regulate petal senescence in wallflowers (Erysimum linifolium).

    PubMed

    Salleh, Faezah Mohd; Mariotti, Lorenzo; Spadafora, Natasha D; Price, Anna M; Picciarelli, Piero; Wagstaff, Carol; Lombardi, Lara; Rogers, Hilary

    2016-04-02

    In many species floral senescence is coordinated by ethylene. Endogenous levels rise, and exogenous application accelerates senescence. Furthermore, floral senescence is often associated with increased reactive oxygen species, and is delayed by exogenously applied cytokinin. However, how these processes are linked remains largely unresolved. Erysimum linifolium (wallflower) provides an excellent model for understanding these interactions due to its easily staged flowers and close taxonomic relationship to Arabidopsis. This has facilitated microarray analysis of gene expression during petal senescence and provided gene markers for following the effects of treatments on different regulatory pathways. In detached Erysimum linifolium (wallflower) flowers ethylene production peaks in open flowers. Furthermore senescence is delayed by treatments with the ethylene signalling inhibitor silver thiosulphate, and accelerated with ethylene released by 2-chloroethylphosphonic acid. Both treatments with exogenous cytokinin, or 6-methyl purine (which is an inhibitor of cytokinin oxidase), delay petal senescence. However, treatment with cytokinin also increases ethylene biosynthesis. Despite the similar effects on senescence, transcript abundance of gene markers is affected differentially by the treatments. A significant rise in transcript abundance of WLS73 (a putative aminocyclopropanecarboxylate oxidase) was abolished by cytokinin or 6-methyl purine treatments. In contrast, WFSAG12 transcript (a senescence marker) continued to accumulate significantly, albeit at a reduced rate. Silver thiosulphate suppressed the increase in transcript abundance both of WFSAG12 and WLS73. Activity of reactive oxygen species scavenging enzymes changed during senescence. Treatments that increased cytokinin levels, or inhibited ethylene action, reduced accumulation of hydrogen peroxide. Furthermore, although auxin levels rose with senescence, treatments that delayed early senescence did not affect

  18. Functional characterization of a reactive oxygen species modulator 1 gene in Litopenaeus vannamei.

    PubMed

    He, Hong-Hui; Chi, Yi-Miao; Yuan, Kai; Li, Xiao-Yun; Weng, Shao-Ping; He, Jian-Guo; Chen, Yi-Hong

    2017-11-01

    Reactive oxygen species (ROS) imparts a dual effect on multicellular organisms, wherein high levels are usually harmful, and low levels could facilitate in combating pathogenic microorganisms; therefore, the regulation of ROS production is critical. Previous studies have suggested that ROS contributes to resistance to the white spot syndrome virus (WSSV) or Vibrio alginolyticus in Litopenaeus vannamei. However, the regulation of ROS metabolism in L. vannamei remains elusive. In the present study, we proved that the overexpression of L. vannamei reactive oxygen species modulator 1 (LvROMO1) increases ROS production in Drosophila Schneider 2 (S2) cells. Real-time RT-PCR analysis indicated that LvROMO1 is induced by WSSV or V. alginolyticus infection and β-glucan or microcystin (MC-LR) injection. Further investigation showed that LvROMO1 responding to MC-LR, thereby inducing hemocytes to undergo apoptosis, and ultimately resulting in hepatopancreatic damage. And LvROMO1 downregulation induced an increase in the cumulative mortality of WSSV-infected shrimp by reducing ROS production and suppressing the expression of antimicrobial peptides genes. The findings of present study suggest that LvROMO1 plays an important role in ROS production in L. vannamei and is involved in innate immunity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Photoluminescent Gold Nanoclusters in Cancer Cells: Cellular Uptake, Toxicity, and Generation of Reactive Oxygen Species.

    PubMed

    Matulionyte, Marija; Dapkute, Dominyka; Budenaite, Laima; Jarockyte, Greta; Rotomskis, Ricardas

    2017-02-10

    In recent years, photoluminescent gold nanoclusters have attracted considerable interest in both fundamental biomedical research and practical applications. Due to their ultrasmall size, unique molecule-like optical properties, and facile synthesis gold nanoclusters have been considered very promising photoluminescent agents for biosensing, bioimaging, and targeted therapy. Yet, interaction of such ultra-small nanoclusters with cells and other biological objects remains poorly understood. Therefore, the assessment of the biocompatibility and potential toxicity of gold nanoclusters is of major importance before their clinical application. In this study, the cellular uptake, cytotoxicity, and intracellular generation of reactive oxygen species (ROS) of bovine serum albumin-encapsulated (BSA-Au NCs) and 2-(N-morpholino) ethanesulfonic acid (MES)capped photoluminescent gold nanoclusters (Au-MES NCs) were investigated. The results showed that BSA-Au NCs accumulate in cells in a similar manner as BSA alone, indicating an endocytotic uptake mechanism while ultrasmall Au-MES NCs were distributed homogeneously throughout the whole cell volume including cell nucleus. The cytotoxicity of BSA-Au NCs was negligible, demonstrating good biocompatibility of such BSA-protected Au NCs. In contrast, possibly due to ultrasmall size and thin coating layer, Au-MES NCs exhibited exposure time-dependent high cytotoxicity and higher reactivity which led to highly increased generation of reactive oxygen species. The results demonstrate the importance of the coating layer to biocompatibility and toxicity of ultrasmall photoluminescent gold nanoclusters.

  20. Photoluminescent Gold Nanoclusters in Cancer Cells: Cellular Uptake, Toxicity, and Generation of Reactive Oxygen Species

    PubMed Central

    Matulionyte, Marija; Dapkute, Dominyka; Budenaite, Laima; Jarockyte, Greta; Rotomskis, Ricardas

    2017-01-01

    In recent years, photoluminescent gold nanoclusters have attracted considerable interest in both fundamental biomedical research and practical applications. Due to their ultrasmall size, unique molecule-like optical properties, and facile synthesis gold nanoclusters have been considered very promising photoluminescent agents for biosensing, bioimaging, and targeted therapy. Yet, interaction of such ultra-small nanoclusters with cells and other biological objects remains poorly understood. Therefore, the assessment of the biocompatibility and potential toxicity of gold nanoclusters is of major importance before their clinical application. In this study, the cellular uptake, cytotoxicity, and intracellular generation of reactive oxygen species (ROS) of bovine serum albumin-encapsulated (BSA-Au NCs) and 2-(N-morpholino) ethanesulfonic acid (MES)-capped photoluminescent gold nanoclusters (Au-MES NCs) were investigated. The results showed that BSA-Au NCs accumulate in cells in a similar manner as BSA alone, indicating an endocytotic uptake mechanism while ultrasmall Au-MES NCs were distributed homogeneously throughout the whole cell volume including cell nucleus. The cytotoxicity of BSA-Au NCs was negligible, demonstrating good biocompatibility of such BSA-protected Au NCs. In contrast, possibly due to ultrasmall size and thin coating layer, Au-MES NCs exhibited exposure time-dependent high cytotoxicity and higher reactivity which led to highly increased generation of reactive oxygen species. The results demonstrate the importance of the coating layer to biocompatibility and toxicity of ultrasmall photoluminescent gold nanoclusters. PMID:28208642

  1. Cytoplasmic localization and ubiquitination of p21{sup Cip1} by reactive oxygen species

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hwang, Chae Young; Kim, Ick Young; Kwon, Ki-Sun

    2007-06-22

    Reactive oxygen species were previously shown to trigger p21{sup Cip1} protein degradation through a proteasome-dependent pathway, however the detailed mechanism of degradation remains to be elucidated. In this report, we showed that p21{sup Cip1} was degraded at an early phase after low dose H{sub 2}O{sub 2} treatment of a variety of cell types and that preincubation of cells with the antioxidant, N-acetylcysteine, prolonged p21{sup Cip1} half-life. A mutant p21{sup Cip1} in which all six lysines were changed to arginines was protected against H{sub 2}O{sub 2} treatment. Direct interaction between p21{sup Cip1} and Skp2 was elevated in the H{sub 2}O{sub 2}-treatedmore » cells. Disruption of the two nuclear export signal (NES) sequences in p21{sup Cip1}, or treatment with leptomycin B blocked H{sub 2}O{sub 2}-induced p21{sup Cip1} degradation. Altogether, these results demonstrate that reactive oxygen species induce p21{sup Cip1} degradation through an NES-, Skp2-, and ubiquitin-dependent pathway.« less

  2. Cell viability, reactive oxygen species, apoptosis, and necrosis in myoblast cultures exposed to low-level infrared laser.

    PubMed

    Alexsandra da Silva Neto Trajano, Larissa; da Silva, Camila Luna; de Carvalho, Simone Nunes; Cortez, Erika; Mencalha, André Luiz; de Souza da Fonseca, Adenilson; Stumbo, Ana Carolina

    2016-07-01

    Low-level infrared laser is considered safe and effective for treatment of muscle injuries. However, the mechanism involved on beneficial effects of laser therapy are not understood. The aim was to evaluate cell viability, reactive oxygen species, apoptosis, and necrosis in myoblast cultures exposed to low-level infrared laser at therapeutic fluences. C2C12 myoblast cultures at different (2 and 10 %) fetal bovine serum (FBS) concentrations were exposed to low-level infrared laser (808 nm, 100 mW) at different fluences (10, 35, and 70 J/cm(2)) and evaluated after 24, 48, and 72 h. Cell viability was evaluated by WST-1 assay; reactive oxygen species (ROS), apoptosis, and necrosis were evaluated by flow cytometry. Cell viability was decreased atthe lowest FBS concentration. Laser exposure increased the cell viability in myoblast cultures at 2 % FBS after 48 and 72 h, but no significant increase in ROS was observed. Apoptosis was decreased at the higher fluence and necrosis was increased at lower fluence in myoblast cultures after 24 h of laser exposure at 2 % FBS. No laser-induced alterations were obtained at 10 % FBS. Results show that level of reactive oxygen species is not altered, at least to those evaluated in this study, but low-level infrared laser exposure affects cell viability, apoptosis, and necrosis in myoblast cultures depending on laser fluence and physiologic conditions of cells.

  3. Impact of carbon, oxygen and sulfur content of microscale zerovalent iron particles on its reactivity towards chlorinated aliphatic hydrocarbons.

    PubMed

    Velimirovic, Milica; Larsson, Per-Olof; Simons, Queenie; Bastiaens, Leen

    2013-11-01

    Zerovalent iron (ZVI) abiotically degrades several chlorinated aliphatic hydrocarbons (CAHs) via reductive dechlorination, which offers perspectives for in situ groundwater remediation applications. The difference in reactivity between ZVI particles is often linked with their specific surface area. However, other parameters may influence the reactivity as well. Earlier, we reported for a set of microscale zerovalent iron (mZVI) particles the disappearance kinetic of different CAHs which were collected under consistent experimental conditions. In the present study, these kinetic data were correlated with the carbon, oxygen and sulfur content of mZVI particles. It was confirmed that not only the specific surface area affects the disappearance kinetic of CAHs, but also the chemical composition of the mZVI particles. The chemical composition, in addition, influences CAHs removal mechanism inducing sorption onto mZVI particles instead of dechlorination. Generally, high disappearance kinetic of CAHs was observed for particles containing less oxygen. A high carbon content, on the other hand, induced nonreactive sorption of the contaminants on the mZVI particles. To obtain efficient remediation of CAHs by mZVI particles, this study suggested that the carbon and oxygen content should not exceed 0.5% and 1% respectively. Finally, the efficiency of the mZVI particles may be improved to some extent by enriching them with sulfur. However, the impact of sulfur content on the reactivity of mZVI particles is less pronounced than that of the carbon and oxygen content. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. A mutation in the mitochondrial protein UQCRB promotes angiogenesis through the generation of mitochondrial reactive oxygen species

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chang, Junghwa; Jung, Hye Jin; Jeong, Seung Hun

    2014-12-12

    Highlights: • We constructed mitochondrial protein UQCRB mutant stable cell lines on the basis of a human case report. • These mutant cell lines exhibit pro-angiogenic activity with enhanced VEGF expression. • Proliferation of mutant cell lines was regulated by UQCRB inhibitors. • UQCRB may have a functional role in angiogenesis. - Abstract: Ubiquinol-cytochrome c reductase binding protein (UQCRB) is one of the subunits of mitochondrial complex III and is a target protein of the natural anti-angiogenic small molecule terpestacin. Previously, the biological role of UQCRB was thought to be limited to the maintenance of complex III. However, the identificationmore » and validation of UQCRB as a target protein of terpestacin enabled the role of UQCRB in oxygen sensing and angiogenesis to be elucidated. To explore the biological role of this protein further, UQCRB mutant stable cell lines were generated on the basis of a human case report. We demonstrated that these cell lines exhibited glycolytic and pro-angiogenic activities via mitochondrial reactive oxygen species (mROS)-mediated HIF1 signal transduction. Furthermore, a morphological abnormality in mitochondria was detected in UQCRB mutant stable cell lines. In addition, the proliferative effect of the UQCRB mutants was significantly regulated by the UQCRB inhibitors terpestacin and A1938. Collectively, these results provide a molecular basis for UQCRB-related biological processes and reveal potential key roles of UQCRB in angiogenesis and mitochondria-mediated metabolic disorders.« less

  5. Reactive oxygen species mediate growth and death in submerged plants

    PubMed Central

    Steffens, Bianka; Steffen-Heins, Anja; Sauter, Margret

    2013-01-01

    Aquatic and semi-aquatic plants are well adapted to survive partial or complete submergence which is commonly accompanied by oxygen deprivation. The gaseous hormone ethylene controls a number of adaptive responses to submergence including adventitious root growth and aerenchyma formation. Reactive oxygen species (ROS) act as signaling intermediates in ethylene-controlled submergence adaptation and possibly also independent of ethylene. ROS levels are controlled by synthesis, enzymatic metabolism, and non-enzymatic scavenging. While the actors are by and large known, we still have to learn about altered ROS at the subcellular level and how they are brought about, and the signaling cascades that trigger a specific response. This review briefly summarizes our knowledge on the contribution of ROS to submergence adaptation and describes spectrophotometrical, histochemical, and live cell imaging detection methods that have been used to study changes in ROS abundance. Electron paramagnetic resonance (EPR) spectroscopy is introduced as a method that allows identification and quantification of specific ROS in cell compartments. The use of advanced technologies such as EPR spectroscopy will be necessary to untangle the intricate and partially interwoven signaling networks of ethylene and ROS. PMID:23761805

  6. Oxygen anion (O- ) and hydroxide anion (HO- ) reactivity with a series of old and new refrigerants.

    PubMed

    Le Vot, Clotilde; Lemaire, Joël; Pernot, Pascal; Heninger, Michel; Mestdagh, Hélène; Louarn, Essyllt

    2018-04-01

    The reactivity of a series of commonly used halogenated compounds (trihalomethanes, chlorofluorocarbon, hydrochlorofluorocarbon, fluorocarbons, and hydrofluoroolefin) with hydroxide and oxygen anion is studied in a compact Fourier transform ion cyclotron resonance. O - is formed by dissociative electron attachment to N 2 O and HO - by a further ion-molecule reaction with ammonia. Kinetic experiments are performed by increasing duration of introduction of the studied molecule at a constant pressure. Hydroxide anion reactions mainly proceed by proton transfer for all the acidic compounds. However, nucleophilic substitution is observed for chlorinated and brominated compounds. For fluorinated compounds, a specific elimination of a neutral fluorinated alkene is observed in our results in parallel with the proton transfer reaction. Oxygen anion reacts rapidly and extensively with all compounds. Main reaction channels result from nucleophilic substitution, proton transfer, and formal H 2 + transfer. We highlight the importance of transfer processes (atom or ion) in the intermediate ion-neutral complex, explaining part of the observed reactivity and formed ions. In this paper, we present the first reactivity study of anions with HFO 1234yf. Finally, the potential of O - and HO - as chemical ionization reagents for trace analysis is discussed. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Eicosanoids up-regulate production of reactive oxygen species by NADPH-dependent oxidase in Spodoptera exigua phagocytic hemocytes

    USDA-ARS?s Scientific Manuscript database

    Eicosanoids mediate cellular immune responses in insects, including phagocytosis of invading microbes. Phagocytosis entails two major steps, the internalization of microbes and the subsequent killing of them via formation of reactive oxygen species (ROS). Here, we posed the hypothesis that eicosanoi...

  8. Redox-inactive metal ions modulate the reactivity and oxygen release of mononuclear non-haem iron(III)–peroxo complexes

    DOE PAGES

    Bang, Suhee; Lee, Yong -Min; Hong, Seungwoo; ...

    2014-09-14

    Redox-inactive metal ions that function as Lewis acids play pivotal roles in modulating the reactivity of oxygen-containing metal complexes and metalloenzymes, such as the oxygen-evolving complex in photosystem II and its small-molecule mimics. Here we report the synthesis and characterization of non-haem iron(III)–peroxo complexes that bind redox-inactive metal ions, (TMC)FeIII–(μ,η 2:η 2-O 2)–M n+ (M n+ = Sr 2+, Ca 2+, Zn 2+, Lu 3+, Y 3+ and Sc 3+; TMC, 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane). We demonstrate that the Ca 2+ and Sr 2+ complexes showed similar electrochemical properties and reactivities in one-electron oxidation or reduction reactions. However, the properties and reactivities ofmore » complexes formed with stronger Lewis acidities were found to be markedly different. In conclusion, complexes that contain Ca 2+ or Sr 2+ ions were oxidized by an electron acceptor to release O 2, whereas the release of O 2 did not occur for complexes that bind stronger Lewis acids. Furthermore, we discuss these results in the light of the functional role of the Ca 2+ ion in the oxidation of water to dioxygen by the oxygen-evolving complex.« less

  9. Redox-inactive metal ions modulate the reactivity and oxygen release of mononuclear non-haem iron(III)–peroxo complexes

    PubMed Central

    Bang, Suhee; Lee, Yong-Min; Hong, Seungwoo; Cho, Kyung-Bin; Nishida, Yusuke; Seo, Mi Sook; Sarangi, Ritimukta; Fukuzumi, Shunichi; Nam, Wonwoo

    2014-01-01

    Redox-inactive metal ions that function as Lewis acids play pivotal roles in modulating the reactivity of oxygen-containing metal complexes and metalloenzymes, such as the oxygen-evolving complex in photosystem II and its small-molecule mimics. Here we report the synthesis and characterization of non-haem iron(III)–peroxo complexes that bind redox-inactive metal ions, (TMC)FeIII–(μ,η2:η2-O2)–Mn+ (Mn+ = Sr2+, Ca2+, Zn2+, Lu3+, Y3+ and Sc3+; TMC, 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane). We demonstrate that the Ca2+ and Sr2+ complexes showed similar electrochemical properties and reactivities in one-electron oxidation or reduction reactions. However, the properties and reactivities of complexes formed with stronger Lewis acidities were found to be markedly different. Complexes that contain Ca2+ or Sr2+ ions were oxidized by an electron acceptor to release O2, whereas the release of O2 did not occur for complexes that bind stronger Lewis acids. We discuss these results in the light of the functional role of the Ca2+ ion in the oxidation of water to dioxygen by the oxygen-evolving complex. PMID:25242490

  10. Effects of Sildenafil and Tadalafil on Edema and Reactive Oxygen Species Production in an Experimental Model of Lung Ischemia-Reperfusion Injury.

    PubMed

    Guerra-Mora, J R; Perales-Caldera, E; Aguilar-León, D; Nava-Sanchez, C; Díaz-Cruz, A; Díaz-Martínez, N E; Santillán-Doherty, P; Torres-Villalobos, G; Bravo-Reyna, C C

    Lung ischemia-reperfusion injury is characterized by formation of reactive oxygen species and cellular swelling leading to pulmonary edema and primary graft dysfunction. Phosphodiesterase 5 inhibitors could ameliorate lung ischemia-reperfusion injury by interfering in many molecular pathways. The aim of this work was to evaluate and compare the effects of sildenafil and tadalafil on edema and reactive oxygen species formation in an ex vivo nonhuman animal model of lung ischemia-reperfusion injury. Thirty-two Wistar rats were distributed, treated, perfused and the cardiopulmonary blocks were managed as follows: control group: immediate excision and reperfusion without pretreatment; ischemia reperfusion group: treatment with dimethylsulfoxide 0.9% and excision 1 hour later; sildenafil group: treatment with sildenafil (0.7 mg/kg) and excision 1 hour later; and tadalafil group: treatment with tadalafil (0.15 mg/kg) and excision 2 hours later. All cardiopulmonary blocks except control group were preserved for 8 hours and then reperfused. Pulmonary arterial pressure, pulmonary venous pressure, and capillary filtration coefficient were measured. Reactive oxygen species were measured. Edema was similar between control and sildenafil groups, but significantly greater in the ischemia-reperfusion (P ≤ .04) and tadalafil (P ≤ .003) groups compared with the sildenafil group. The malondialdehyde levels were significantly lower in the sildenafil (P ≤ .001) and tadalafil (P ≤ .001) groups than the ischemia-reperfusion group. Administration of sildenafil, but not tadalafil, decreased edema in lung ischemia-reperfusion injury. Both drugs decreased reactive oxygen species formation in a lung ischemia-reperfusion injury model. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Reactive oxygen species: role in the development of cancer and various chronic conditions

    PubMed Central

    Waris, Gulam; Ahsan, Haseeb

    2006-01-01

    Oxygen derived species such as superoxide radical, hydrogen peroxide, singlet oxygen and hydroxyl radical are well known to be cytotoxic and have been implicated in the etiology of a wide array of human diseases, including cancer. Various carcinogens may also partly exert their effect by generating reactive oxygen species (ROS) during their metabolism. Oxidative damage to cellular DNA can lead to mutations and may, therefore, play an important role in the initiation and progression of multistage carcinogenesis. The changes in DNA such as base modification, rearrangement of DNA sequence, miscoding of DNA lesion, gene duplication and the activation of oncogenes may be involved in the initiation of various cancers. Elevated levels of ROS and down regulation of ROS scavengers and antioxidant enzymes are associated with various human diseases including various cancers. ROS are also implicated in diabtes and neurodegenerative diseases. ROS influences central cellular processes such as proliferation a, apoptosis, senescence which are implicated in the development of cancer. Understanding the role of ROS as key mediators in signaling cascades may provide various opportunities for pharmacological intervention. PMID:16689993

  12. Role of Auxin-Induced Reactive Oxygen Species in Root Gravitropism1

    PubMed Central

    Joo, Jung Hee; Bae, Yun Soo; Lee, June Seung

    2001-01-01

    We report our studies on root gravitropism indicating that reactive oxygen species (ROS) may function as a downstream component in auxin-mediated signal transduction. A transient increase in the intracellular concentration of ROS in the convex endodermis resulted from either gravistimulation or unilateral application of auxin to vertical roots. Root bending was also brought about by unilateral application of ROS to vertical roots pretreated with the auxin transport inhibitor N-1-naphthylphthalamic acid. Furthermore, the scavenging of ROS by antioxidants (N-acetylcysteine, ascorbic acid, and Trolox) inhibited root gravitropism. These results indicate that the generation of ROS plays a role in root gravitropism. PMID:11457956

  13. Function of reactive oxygen species during animal development: passive or active?

    PubMed

    Covarrubias, Luis; Hernández-García, David; Schnabel, Denhí; Salas-Vidal, Enrique; Castro-Obregón, Susana

    2008-08-01

    Oxidative stress is considered causal of aging and pathological cell death, however, very little is known about its function in the natural processes that support the formation of an organism. It is generally thought that cells must continuously protect themselves from the possible damage caused by reactive oxygen species (ROS) (passive ROS function). However, presently, ROS are recognized as physiologically relevant molecules that mediate cell responses to a variety of stimuli, and the activities of several molecules, some developmentally relevant, are directly or indirectly regulated by oxidative stress (active ROS function). Here we review recent data that are suggestive of specific ROS functions during development of animals, particularly mammals.

  14. Effect of CoQ homologues on reactive oxygen generation by mitochondria.

    PubMed

    Imada, Isuke; Sato, Eisuke F; Kira, Yukimi; Inoue, Masayasu

    2008-01-01

    Effect of CoQ compounds (Qs) on reactive oxygen (ROS) generation by mitochondrial complex I was studied using rat liver mitochondria and chemiluminescence probe L012. Kinetic analysis revealed that short chain Qs, such as Q2 and idebenone enhanced ROS generation by mitochondrial NADH oxidase system by a succinate-inhibitable mechanism. Lipid peroxidation in mitochondrial membranes induced by NADH and iron was inhibited by short chain Qs. The inhibitory activity was enhanced by co-oxidation of succinate as determined by chemiluminescence method and by electron spin resonance spectroscopy. These results suggested that the reduced form of short chain Qs inhibited mitochondrial ROS generation and lipid peroxidation.

  15. The Effect of Cerium Oxide Nanoparticle Valence State on Reactive Oxygen Species and Toxicity.

    PubMed

    Dunnick, Katherine M; Pillai, Rajalekshmi; Pisane, Kelly L; Stefaniak, Aleksandr B; Sabolsky, Edward M; Leonard, Stephen S

    2015-07-01

    Cerium oxide (CeO2) nanoparticles, which are used in a variety of products including solar cells, gas sensors, and catalysts, are expected to increase in industrial use. This will subsequently lead to additional occupational exposures, making toxicology screenings crucial. Previous toxicology studies have presented conflicting results as to the extent of CeO2 toxicity, which is hypothesized to be due to the ability of Ce to exist in both a +3 and +4 valence state. Thus, to study whether valence state and oxygen vacancy concentration are important in CeO2 toxicity, CeO2 nanoparticles were doped with gadolinium to adjust the cation (Ce, Gd) and anion (O) defect states. The hypothesis that doping would increase toxicity and decrease antioxidant abilities as a result of increased oxygen vacancies and inhibition of +3 to +4 transition was tested. Differences in toxicity and reactivity based on valence state were determined in RLE-6TN rat alveolar epithelial and NR8383 rat alveolar macrophage cells using enhanced dark field microscopy, electron paramagnetic resonance (EPR), and annexin V/propidium iodide cell viability stain. Results from EPR indicated that as doping increased, antioxidant potential decreased. Alternatively, doping had no effect on toxicity at 24 h. The present results imply that as doping increases, thus subsequently increasing the Ce(3+)/Ce(4+) ratio, antioxidant potential decreases, suggesting that differences in reactivity of CeO2 are due to the ability of Ce to transition between the two valence states and the presence of increased oxygen vacancies, rather than dependent on a specific valence state.

  16. Inducible Lung Epithelial Resistance Requires Multisource Reactive Oxygen Species Generation To Protect against Viral Infections

    PubMed Central

    2018-01-01

    ABSTRACT Viral pneumonias cause profound worldwide morbidity, necessitating novel strategies to prevent and treat these potentially lethal infections. Stimulation of intrinsic lung defenses via inhalation of synergistically acting Toll-like receptor (TLR) agonists protects mice broadly against pneumonia, including otherwise-lethal viral infections, providing a potential opportunity to mitigate infectious threats. As intact lung epithelial TLR signaling is required for the inducible resistance and as these cells are the principal targets of many respiratory viruses, the capacity of lung epithelial cells to be therapeutically manipulated to function as autonomous antiviral effectors was investigated. Our work revealed that mouse and human lung epithelial cells could be stimulated to generate robust antiviral responses that both reduce viral burden and enhance survival of isolated cells and intact animals. The antiviral protection required concurrent induction of epithelial reactive oxygen species (ROS) from both mitochondrial and dual oxidase sources, although neither type I interferon enrichment nor type I interferon signaling was required for the inducible protection. Taken together, these findings establish the sufficiency of lung epithelial cells to generate therapeutically inducible antiviral responses, reveal novel antiviral roles for ROS, provide mechanistic insights into inducible resistance, and may provide an opportunity to protect patients from viral pneumonia during periods of peak vulnerability. PMID:29764948

  17. Nutritional Countermeasures Targeting Reactive Oxygen Species in Cancer: From Mechanisms to Biomarkers and Clinical Evidence

    PubMed Central

    Samoylenko, Anatoly; Hossain, Jubayer Al; Mennerich, Daniela; Kellokumpu, Sakari; Hiltunen, Jukka Kalervo

    2013-01-01

    Abstract Reactive oxygen species (ROS) exert various biological effects and contribute to signaling events during physiological and pathological processes. Enhanced levels of ROS are highly associated with different tumors, a Western lifestyle, and a nutritional regime. The supplementation of food with traditional antioxidants was shown to be protective against cancer in a number of studies both in vitro and in vivo. However, recent large-scale human trials in well-nourished populations did not confirm the beneficial role of antioxidants in cancer, whereas there is a well-established connection between longevity of several human populations and increased amount of antioxidants in their diets. Although our knowledge about ROS generators, ROS scavengers, and ROS signaling has improved, the knowledge about the direct link between nutrition, ROS levels, and cancer is limited. These limitations are partly due to lack of standardized reliable ROS measurement methods, easily usable biomarkers, knowledge of ROS action in cellular compartments, and individual genetic predispositions. The current review summarizes ROS formation due to nutrition with respect to macronutrients and antioxidant micronutrients in the context of cancer and discusses signaling mechanisms, used biomarkers, and its limitations along with large-scale human trials. Antioxid. Redox Signal. 19, 2157–2196. PMID:23458328

  18. Baccharis trimera inhibits reactive oxygen species production through PKC and down-regulation p47 phox phosphorylation of NADPH oxidase in SK Hep-1 cells.

    PubMed

    de Araújo, Glaucy Rodrigues; Rabelo, Ana Carolina Silveira; Meira, Janaína Serenato; Rossoni-Júnior, Joamyr Victor; Castro-Borges, William de; Guerra-Sá, Renata; Batista, Maurício Azevedo; Silveira-Lemos, Denise da; Souza, Gustavo Henrique Bianco de; Brandão, Geraldo Célio; Chaves, Míriam Martins; Costa, Daniela Caldeira

    2017-02-01

    Baccharis trimera, popularly known as "carqueja", is a native South-American plant possessing a high concentration of polyphenolic compounds and therefore high antioxidant potential. Despite the antioxidant potential described for B. trimera, there are no reports concerning the signaling pathways involved in this process. So, the aim of the present study was to assess the influence of B. trimera on the modulation of PKC signaling pathway and to characterize the effect of the nicotinamide adenine dinucleotide phosphate oxidase enzyme (NOX) on the generation of reactive oxygen species in SK Hep-1 cells. SK-Hep 1 cells were treated with B. trimera, quercetin, or rutin and then stimulated or not with PMA/ionomycin and labeled with carboxy H 2 DCFDA for detection of reactive oxygen species by flow cytometer. The PKC expression by Western blot and enzyme activity was performed to evaluate the influence of B. trimera and quercetin on PKC signaling pathway. p47 phox and p47 phox phosphorylated expression was performed by Western blot to evaluate the influence of B. trimera on p47 phox phosphorylation. The results showed that cells stimulated with PMA/ionomycin (activators of PKC) showed significantly increased reactive oxygen species production, and this production returned to baseline levels after treatment with DPI (NOX inhibitor). Both B. trimera and quercetin modulated reactive oxygen species production through the inhibition of PKC protein expression and enzymatic activity, also with inhibition of p47 phox phosphorylation. Taken together, these results suggest that B. trimera has a potential mechanism for inhibiting reactive oxygen species production through the PKC signaling pathway and inhibition subunit p47 phox phosphorylation of nicotinamide adenine dinucleotide phosphate oxidase.

  19. Generation of reactive oxygen species and charge carriers in plasmonic photocatalytic Au@TiO2 nanostructures with enhanced activity.

    PubMed

    He, Weiwei; Cai, Junhui; Jiang, Xiumei; Yin, Jun-Jie; Meng, Qingbo

    2018-06-13

    The combination of semiconductor and plasmonic nanostructures, endowed with high efficiency light harvesting and surface plasmon confinement, has been a promising way for efficient utilization of solar energy. Although the surface plasmon resonance (SPR) assisted photocatalysis has been extensively studied, the photochemical mechanism, e.g. the effect of SPR on the generation of reactive oxygen species and charge carriers, is not well understood. In this study, we take Au@TiO2 nanostructures as a plasmonic photocatalyst to address this critical issue. The Au@TiO2 core/shell nanostructures with tunable SPR property were synthesized by the templating method with post annealing thermal treatment. It was found that Au@TiO2 nanostructures exhibit enhanced photocatalytic activity in either sunlight or visible light (λ > 420 nm). Electron spin resonance spectroscopy with spin trapping and spin labeling was used to investigate the enhancing effect of Au@TiO2 on the photo-induced reactive oxygen species and charge carriers. The formation of Au@TiO2 core/shell nanostructures resulted in a dramatic increase in light-induced generation of hydroxyl radicals, singlet oxygen, holes and electrons, as compared with TiO2 alone. This enhancement under visible light (λ > 420 nm) irradiation may be dominated by SPR induced local electrical field enhancement, while the enhancement under sunlight irradiation is dominated by the higher electron transfer from TiO2 to Au. These results unveiled that the superior photocatalytic activity of Au@TiO2 nanostructures correlates with enhanced generation of reactive oxygen species and charge carriers.

  20. Does Each Atom Count in the Reactivity of Vanadia Nanoclusters?

    PubMed

    Zhang, Mei-Qi; Zhao, Yan-Xia; Liu, Qing-Yu; Li, Xiao-Na; He, Sheng-Gui

    2017-01-11

    Vanadium oxide cluster anions (V 2 O 5 ) n V x O y - (n = 1-31; x = 0, 1; and x + y ≤ 5) with different oxygen deficiencies (Δ = 2y-1-5x = 0, ± 1, and ±2) have been prepared by laser ablation and reacted to abstract hydrogen atoms from alkane molecules (n-butane) in a fast flow reactor. When the cluster size n is less than 25, the Δ = 1 series [(V 2 O 5 ) n O - clusters] that can contain atomic oxygen radical anions (O •- ) generally have much higher reactivity than the other four cluster series (Δ = -2, -1, 0, and 2), indicating that each atom counts in the hydrogen-atom abstraction (HAA) reactivity. Unexpectedly, all of the five cluster series have similar HAA reactivity when the cluster size is greater than 25. The critical dimension of vanadia particles separating the cluster behavior (each atom counts) from the bulk behavior (each atom contributes a little part) is thus about 1.6 nm (∼V 50 O 125 ). The strong electron-phonon coupling of the vanadia particles has been proposed to create the O •- radicals (V 5+ = O 2- + heat → V 4+ -O •- ) for the n > 25 clusters with Δ = -2, -1, 0, and 2. Such a mechanism is supported by a comparative study with the scandium system [(Sc 2 O 3 ) n Sc x O y - (n = 1-29; x = 0, 1; and x + y ≤ 4)] for which the Δ = 1 series [(Sc 2 O 3 ) n O - clusters] always have much higher HAA reactivity than the other cluster series.

  1. Crosstalk of mitochondria with NADPH oxidase via reactive oxygen and nitrogen species signalling and its role for vascular function

    PubMed Central

    Di Lisa, Fabio; Oelze, Matthias; Kröller‐Schön, Swenja; Steven, Sebastian; Schulz, Eberhard; Münzel, Thomas

    2016-01-01

    Abstract Cardiovascular diseases are associated with and/or caused by oxidative stress. This concept has been proven by using the approach of genetic deletion of reactive species producing (pro‐oxidant) enzymes as well as by the overexpression of reactive species detoxifying (antioxidant) enzymes leading to a marked reduction of reactive oxygen and nitrogen species (RONS) and in parallel to an amelioration of the severity of diseases. Likewise, the development and progression of cardiovascular diseases is aggravated by overexpression of RONS producing enzymes as well as deletion of antioxidant RONS detoxifying enzymes. Thus, the consequences of the interaction (redox crosstalk) of superoxide/hydrogen peroxide produced by mitochondria with other ROS producing enzymes such as NADPH oxidases (Nox) are of outstanding importance and will be discussed including the consequences for endothelial nitric oxide synthase (eNOS) uncoupling as well as the redox regulation of the vascular function/tone in general (soluble guanylyl cyclase, endothelin‐1, prostanoid synthesis). Pathways and potential mechanisms leading to this crosstalk will be analysed in detail and highlighted by selected examples from the current literature including hypoxia, angiotensin II‐induced hypertension, nitrate tolerance, aging and others. The general concept of redox‐based activation of RONS sources via “kindling radicals” and enzyme‐specific “redox switches” will be discussed providing evidence that mitochondria represent key players and amplifiers of the burden of oxidative stress. Linked Articles This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc PMID:26660451

  2. Reactive Oxygen Species Function to Mediate the Fe Deficiency Response in an Fe-Efficient Apple Genotype: An Early Response Mechanism for Enhancing Reactive Oxygen Production

    PubMed Central

    Sun, Chaohua; Wu, Ting; Zhai, Longmei; Li, Duyue; Zhang, Xinzhong; Xu, Xuefeng; Ma, Huiqin; Wang, Yi; Han, Zhenhai

    2016-01-01

    Reactive oxygen species (ROS) are important signaling molecules in plants that contribute to stress acclimation. This study demonstrated that ROS play a critical role in Fe deficiency-induced signaling at an early stage in Malus xiaojinensis. Once ROS production has been initiated, prolonged Fe starvation leads to activation of ROS scavenging mechanisms. Further, we demonstrated that ROS scavengers are involved in maintaining the cellular redox homeostasis during prolonged Fe deficiency treatment. Taken together, our results describe a feedback repression loop for ROS to preserve redox homeostasis and maintain a continuous Fe deficiency response in the Fe-efficient woody plant M. xiaojinensis. More broadly, this study reveals a new mechanism in which ROS mediate both positive and negative regulation of plant responses to Fe deficiency stress. PMID:27899933

  3. Reactive Oxygen Species Function to Mediate the Fe Deficiency Response in an Fe-Efficient Apple Genotype: An Early Response Mechanism for Enhancing Reactive Oxygen Production.

    PubMed

    Sun, Chaohua; Wu, Ting; Zhai, Longmei; Li, Duyue; Zhang, Xinzhong; Xu, Xuefeng; Ma, Huiqin; Wang, Yi; Han, Zhenhai

    2016-01-01

    Reactive oxygen species (ROS) are important signaling molecules in plants that contribute to stress acclimation. This study demonstrated that ROS play a critical role in Fe deficiency-induced signaling at an early stage in Malus xiaojinensis . Once ROS production has been initiated, prolonged Fe starvation leads to activation of ROS scavenging mechanisms. Further, we demonstrated that ROS scavengers are involved in maintaining the cellular redox homeostasis during prolonged Fe deficiency treatment. Taken together, our results describe a feedback repression loop for ROS to preserve redox homeostasis and maintain a continuous Fe deficiency response in the Fe-efficient woody plant M. xiaojinensis . More broadly, this study reveals a new mechanism in which ROS mediate both positive and negative regulation of plant responses to Fe deficiency stress.

  4. The Fumarate Reductase of Bacteroides thetaiotaomicron, unlike That of Escherichia coli, Is Configured so that It Does Not Generate Reactive Oxygen Species

    PubMed Central

    Lu, Zheng

    2017-01-01

    ABSTRACT The impact of oxidative stress upon organismal fitness is most apparent in the phenomenon of obligate anaerobiosis. The root cause may be multifaceted, but the intracellular generation of reactive oxygen species (ROS) likely plays a key role. ROS are formed when redox enzymes accidentally transfer electrons to oxygen rather than to their physiological substrates. In this study, we confirm that the predominant intestinal anaerobe Bacteroides thetaiotaomicron generates intracellular ROS at a very high rate when it is aerated. Fumarate reductase (Frd) is a prominent enzyme in the anaerobic metabolism of many bacteria, including B. thetaiotaomicron, and prior studies of Escherichia coli Frd showed that the enzyme is unusually prone to ROS generation. Surprisingly, in this study biochemical analysis demonstrated that the B. thetaiotaomicron Frd does not react with oxygen at all: neither superoxide nor hydrogen peroxide is formed. Subunit-swapping experiments indicated that this difference does not derive from the flavoprotein subunit at which ROS normally arise. Experiments with the related enzyme succinate dehydrogenase discouraged the hypothesis that heme moieties are responsible. Thus, resistance to oxidation may reflect a shift of electron density away from the flavin moiety toward the iron-sulfur clusters. This study shows that the autoxidizability of a redox enzyme can be suppressed by subtle modifications that do not compromise its physiological function. One implication is that selective pressures might enhance the oxygen tolerance of an organism by manipulating the electronic properties of its redox enzymes so they do not generate ROS. PMID:28049145

  5. On the in vivo photochemical rate parameters for PDT reactive oxygen species modeling

    NASA Astrophysics Data System (ADS)

    Kim, Michele M.; Ghogare, Ashwini A.; Greer, Alexander; Zhu, Timothy C.

    2017-03-01

    Photosensitizer photochemical parameters are crucial data in accurate dosimetry for photodynamic therapy (PDT) based on photochemical modeling. Progress has been made in the last few decades in determining the photochemical properties of commonly used photosensitizers (PS), but mostly in solution or in vitro. Recent developments allow for the estimation of some of these photochemical parameters in vivo. This review will cover the currently available in vivo photochemical properties of photosensitizers as well as the techniques for measuring those parameters. Furthermore, photochemical parameters that are independent of environmental factors or are universal for different photosensitizers will be examined. Most photosensitizers discussed in this review are of the type II (singlet oxygen) photooxidation category, although type I photosensitizers that involve other reactive oxygen species (ROS) will be discussed as well. The compilation of these parameters will be essential for ROS modeling of PDT.

  6. On the in-vivo photochemical rate parameters for PDT reactive oxygen species modeling

    PubMed Central

    Kim, Michele M.; Ghogare, Ashwini A.; Greer, Alexander; Zhu, Timothy C.

    2017-01-01

    Photosensitizer photochemical parameters are crucial data in accurate dosimetry for photodynamic therapy (PDT) based on photochemical modeling. Progress has been made in the last few decades in determining the photochemical properties of commonly used photosensitizers (PS), but mostly in solution or in-vitro. Recent developments allow for the estimation of some of these photochemical parameters in-vivo. This review will cover the currently available in-vivo photochemical properties of photosensitizers as well as the techniques for measuring those parameters. Furthermore, photochemical parameters that are independent of environmental factors or are universal for different photosensitizers will be examined. Most photosensitizers discussed in this review are of the type II (singlet oxygen) photooxidation category, although type I photosensitizers that involve other reactive oxygen species (ROS) will be discussed as well. The compilation of these parameters will be essential for ROS modeling of PDT. PMID:28166056

  7. Reactive Oxygen Species in Normal and Tumor Stem Cells

    PubMed Central

    Zhou, Daohong; Shao, Lijian; Spitz, Douglas R.

    2014-01-01

    Reactive oxygen species (ROS) play an important role in determining the fate of normal stem cells. Low levels of ROS are required for stem cells to maintain quiescence and self-renewal. Increases in ROS production cause stem cell proliferation/differentiation, senescence, and apoptosis in a dose-dependent manner, leading to their exhaustion. Therefore, the production of ROS in stem cells is tightly regulated to ensure that they have the ability to maintain tissue homeostasis and repair damaged tissues for the life span of an organism. In this chapter, we discuss how the production of ROS in normal stem cells is regulated by various intrinsic and extrinsic factors and how the fate of these cells is altered by the dysregulation of ROS production under various pathological conditions. In addition, the implications of the aberrant production of ROS by tumor stem cells for tumor progression and treatment are also discussed. PMID:24974178

  8. Developing Master Keys to Brain Pathology, Cancer and Aging from the Structural Biology of Proteins Controlling Reactive Oxygen Species and DNA Repair

    PubMed Central

    Perry, J. Jefferson P.; Fan, Li; Tainer, John A.

    2007-01-01

    This review is focused on proteins with key roles in pathways controlling either reactive oxygen species or DNA damage responses, both of which are essential for preserving the nervous system. An imbalance of reactive oxygen species or inappropriate DNA damage response likely causes mutational or cytotoxic outcomes, which may lead to cancer and/or aging phenotypes. Moreover, individuals with hereditary disorders in proteins of these cellular pathways have significant neurological abnormalities. Mutations in a superoxide dismutase, which removes oxygen free radicals, may cause the neurodegenerative disease amyotrophic lateral sclerosis. Additionally, DNA repair disorders that affect the brain to varying extents include ataxia-telangiectasia-like disorder, Cockayne syndrome or Werner syndrome. Here, we highlight recent advances gained through structural biochemistry studies on enzymes linked to these disorders and other related enzymes acting within the same cellular pathways. We describe the current understanding of how these vital proteins coordinate chemical steps and integrate cellular signaling and response events. Significantly, these structural studies may provide a set of master keys to developing a unified understanding of the survival mechanisms utilized after insults by reactive oxygen species and genotoxic agents, and also provide a basis for developing an informed intervention in brain tumor and neurodegenerative disease progression. PMID:17174478

  9. Evaluation of reactive oxygen metabolites in patients with non-small cell lung cancer after chemotherapy.

    PubMed

    Wakabayashi, Toru; Kawashima, Tatsuo; Matsuzawa, Yasuo

    2014-01-01

    The aim of this study was to evaluate the level of reactive oxygen metabolites (ROMs) after chemotherapy in patients with non-small cell lung cancer (NSCLC) and its association with response to treatment. Fifty-eight untreated NSCLC patients and twenty-three healthy subjects were selected for the study. Patients received two courses of platinum-based chemotherapy and were evaluated for oxidative stress and treatment response. As a marker of reactive oxygen species, ROMs levels were measured using the d-ROMs test. ROMs level (mean ± standard deviation) before chemotherapy in NSCLC patients (416 ± 135 U.CARR) was significantly elevated (p = 0.016) compared to normal healthy subjects (320 ± 59 U.CARR). Patients who responded to chemotherapy showed significantly decreased (p = 0.014) ROMs levels after chemotherapy, whereas patients who had stable disease or progressive disease showed no change in ROMs level (p = 0.387). NSCLC patients had significantly elevated ROMs levels before chemotherapy compared with normal healthy subjects. Chemotherapy may suppress ROMs production in responders but not in non-responders. ROMs level may be a predictor of clinical outcome in patients receiving chemotherapy for NSCLC.

  10. A study of the oxygen dynamics in a reactive Ar/O2 high power impulse magnetron sputtering discharge using an ionization region model

    NASA Astrophysics Data System (ADS)

    Lundin, D.; Gudmundsson, J. T.; Brenning, N.; Raadu, M. A.; Minea, T. M.

    2017-05-01

    The oxygen dynamics in a reactive Ar/O2 high power impulse magnetron sputtering discharge has been studied using a new reactive ionization region model. The aim has been to identify the dominating physical and chemical reactions in the plasma and on the surfaces of the reactor affecting the oxygen plasma chemistry. We explore the temporal evolution of the density of the ground state oxygen molecule O 2 ( X 1 Σg - ) , the singlet metastable oxygen molecules O 2 ( a 1 Δ g ) and O 2 ( b 1 Σ g ) , the oxygen atom in the ground state O(3P), the metastable oxygen atom O(1D), the positive ions O2 + and O+, and the negative ion O-. We furthermore investigate the reaction rates for the gain and loss of these species. The density of atomic oxygen increases significantly as we move from the metal mode to the transition mode, and finally into the compound (poisoned) mode. The main gain rate responsible for the increase is sputtering of atomic oxygen from the oxidized target. Both in the poisoned mode and in the transition mode, sputtering makes up more than 80% of the total gain rate for atomic oxygen. We also investigate the possibility of depositing stoichiometric TiO2 in the transition mode.

  11. Comparative In Vivo Effects of Hemoglobin-Based Oxygen Carriers (HBOC) with Varying Prooxidant and Physiological Reactivity.

    PubMed

    Toma, Vlad Al; Farcaș, Anca D; Roman, Ioana; Sevastre, Bogdan; Hathazi, Denisa; Scurtu, Florina; Damian, Grigore; Silaghi-Dumitrescu, Radu

    2016-01-01

    A series of hemoglobin-based oxygen carrier candidates (HBOC), previously noted for their differences in prooxidative and physiological reactivity, were compared in terms of the negative effects displayed upon injection in Wistar rats. At the concentrations tested, antioxidant strategies based on albumin as well as based on rubrerythrin appear to offer observable physiological advantages.

  12. Cells with dysfunctional telomeres are susceptible to reactive oxygen species hydrogen peroxide via generation of multichromosomal fusions and chromosomal fragments bearing telomeres

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Woo, Seon Rang; Department of Biochemistry, College of Medicine, Korea University, Seoul 136-705; Park, Jeong-Eun

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Under conditions of telomere erosion, cells become extremely sensitive to H{sub 2}O{sub 2}. Black-Right-Pointing-Pointer Chromosomal regions adjacent to telomeres are cleaved by H{sub 2}O{sub 2} under such conditions. Black-Right-Pointing-Pointer H{sub 2}O{sub 2} thus causes multichromosomal fusions and generation of small chromosomal fragments. Black-Right-Pointing-Pointer N-acetylcysteine prevents H{sub 2}O{sub 2}-induced chromosomal aberrations. -- Abstract: During genotoxic stress, reactive oxygen species hydrogen peroxide (H{sub 2}O{sub 2}) is a prime mediator of the DNA damage response. Telomeres function both to assist in DNA damage repair and to inhibit chromosomal end-to-end fusion. Here, we show that telomere dysfunction renders cells susceptible to H{submore » 2}O{sub 2}, via generation of multichromosomal fusion and chromosomal fragments. H{sub 2}O{sub 2} caused formation of multichromosomal end-to-end fusions involving more than three chromosomes, preferentially when telomeres were erosive. Interestingly, extensive chromosomal fragmentation (yielding small-sized fragments) occurred only in cells exhibiting such multichromosomal fusions. Telomeres were absent from fusion points, being rather present in the small fragments, indicating that H{sub 2}O{sub 2} cleaves chromosomal regions adjacent to telomeres. Restoration of telomere function or addition of the antioxidant N-acetylcysteine prevented development of chromosomal aberrations and rescued the observed hypersensitivity to H{sub 2}O{sub 2}. Thus, chromosomal regions adjacent to telomeres become sensitive to reactive oxygen species hydrogen peroxide when telomeres are dysfunctional, and are cleaved to produce multichromosomal fusions and small chromosomal fragments bearing the telomeres.« less

  13. Cued Memory Reactivation During SWS Abolishes the Beneficial Effect of Sleep on Abstraction.

    PubMed

    Hennies, Nora; Lambon Ralph, Matthew A; Durrant, Simon J; Cousins, James N; Lewis, Penelope A

    2017-08-01

    Extracting regularities from stimuli in our environment and generalizing these to new situations are fundamental processes in human cognition. Sleep has been shown to enhance these processes, possibly by facilitating reactivation-triggered memory reorganization. Here, we assessed whether cued reactivation during slow wave sleep (SWS) promotes the beneficial effect of sleep on abstraction of statistical regularities. We used an auditory statistical learning task, in which the benefit of sleep has been firmly established. Participants were exposed to a probabilistically determined sequence of tones and subsequently tested for recognition of novel short sequences adhering to this same statistical pattern in both immediate and delayed recall sessions. In different groups, the exposure stream was replayed during SWS in the night between the recall sessions (SWS-replay group), in wake just before sleep (presleep replay group), or not at all (control group). Surprisingly, participants who received replay in sleep performed worse in the delayed recall session than the control and the presleep replay group. They also failed to show the association between SWS and task performance that has been observed in previous studies and was present in the controls. Importantly, sleep structure and sleep quality did not differ between groups, suggesting that replay during SWS did not impair sleep but rather disrupted or interfered with sleep-dependent mechanisms that underlie the extraction of the statistical pattern. These findings raise important questions about the scope of cued memory reactivation and the mechanisms that underlie sleep-related generalization. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  14. Reactive Oxygen Species-Producing Myeloid Cells Act as a Bone Marrow Niche for Sterile Inflammation-Induced Reactive Granulopoiesis.

    PubMed

    Zhu, Haiyan; Kwak, Hyun-Jeong; Liu, Peng; Bajrami, Besnik; Xu, Yuanfu; Park, Shin-Young; Nombela-Arrieta, Cesar; Mondal, Subhanjan; Kambara, Hiroto; Yu, Hongbo; Chai, Li; Silberstein, Leslie E; Cheng, Tao; Luo, Hongbo R

    2017-04-01

    Both microbial infection and sterile inflammation augment bone marrow (BM) neutrophil production, but whether the induced accelerated granulopoiesis is mediated by a common pathway and the nature of such a pathway are poorly defined. We recently established that BM myeloid cell-derived reactive oxygen species (ROS) externally regulate myeloid progenitor proliferation and differentiation in bacteria-elicited emergency granulopoiesis. In this article, we show that BM ROS levels are also elevated during sterile inflammation. Similar to in microbial infection, ROS were mainly generated by the phagocytic NADPH oxidase in Gr1 + myeloid cells. The myeloid cells and their ROS were uniformly distributed in the BM when visualized by multiphoton intravital microscopy, and ROS production was both required and sufficient for sterile inflammation-elicited reactive granulopoiesis. Elevated granulopoiesis was mediated by ROS-induced phosphatase and tensin homolog oxidation and deactivation, leading to upregulated PtdIns(3,4,5)P3 signaling and increased progenitor cell proliferation. Collectively, these results demonstrate that, although infection-induced emergency granulopoiesis and sterile inflammation-elicited reactive granulopoiesis are triggered by different stimuli and are mediated by distinct upstream signals, the pathways converge to NADPH oxidase-dependent ROS production by BM myeloid cells. Thus, BM Gr1 + myeloid cells represent a key hematopoietic niche that supports accelerated granulopoiesis in infective and sterile inflammation. This niche may be an excellent target in various immune-mediated pathologies or immune reconstitution after BM transplantation. Copyright © 2017 by The American Association of Immunologists, Inc.

  15. Reactive oxygen species-producing myeloid cells act as a bone marrow niche for sterile inflammation-induced reactive granulopoiesis

    PubMed Central

    Zhu, Haiyan; Kwak, Hyun-Jeong; Liu, Peng; Bajrami, Besnik; Xu, Yuanfu; Park, Shin-Young; Nombela-Arrieta, Cesar; Mondal, Subhanjan; Kambara, Hiroto; Yu, Hongbo; Chai, Li; Silberstein, Leslie E.; Cheng, Tao; Luo, Hongbo R.

    2017-01-01

    Summary Both microbial infection and sterile inflammation augment bone marrow (BM) neutrophil production, but whether the induced accelerated granulopoiesis is mediated by a common pathway and the nature of such a pathway are poorly defined. We recently established that BM myeloid cell-derived reactive oxygen species (ROS) externally regulate myeloid progenitor proliferation and differentiation in bacteria-elicited emergency granulopoiesis. Here we show that BM ROS levels are also elevated during sterile inflammation. Similar to in microbial infection, ROS were mainly generated by the phagocytic NADPH oxidase in Gr1+ myeloid cells. The myeloid cells and their ROS were uniformly distributed in the BM when visualized by multi-photon intravital microscopy, and ROS production was both required and sufficient for sterile inflammation-elicited reactive granulopoiesis. Elevated granulopoiesis was mediated by ROS-induced PTEN oxidation and deactivation leading to upregulated PtdIns(3,4,5)P3 signaling and increased progenitor cell proliferation. Collectively, these results demonstrate that although infection-induced emergency granulopoiesis and sterile inflammation-elicited reactive granulopoiesis are triggered by different stimuli and are mediated by distinct upstream signals, the pathways converge to NADPH oxidase-dependent ROS production by BM myeloid cells. Thus, BM Gr1+ myeloid cells represent a key hematopoietic niche that supports accelerated granulopoiesis in both infective and sterile inflammation. This niche may be an excellent target in various immune-mediated pathologies or immune reconstitution after BM transplantation. PMID:28235862

  16. Microplasma array patterning of reactive oxygen and nitrogen species onto polystyrene

    NASA Astrophysics Data System (ADS)

    Szili, Endre J.; Dedrick, James; Oh, Jun-Seok; Bradley, James W.; Boswell, Roderick W.; Charles, Christine; Short, Robert D.; Al-Bataineh, Sameer A.

    2017-02-01

    We investigate an approach for the patterning of reactive oxygen and nitrogen species (RONS) onto polystyrene using atmospheric-pressure microplasma arrays. The spectrally integrated and time-resolved optical emission from the array is characterised with respect to the applied voltage, applied-voltage frequency and pressure; and the array is used to achieve spatially resolved modification of polystyrene at three pressures: 500 Torr, 760 Torr and 1000 Torr. As determined by time-of-flight secondary ion mass spectrometry (ToF-SIMS), regions over which surface modification occurs are clearly restricted to areas that are exposed to individual microplasma cavities. Analysis of the negative-ion ToF-SIMS mass spectra from the centre of the modified microspots shows that the level of oxidation is dependent on the operating pressure, and closely correlated with the spatial distribution of the optical emission. The functional groups that are generated by the microplasma array on the polystyrene surface are shown to readily participate in an oxidative reaction in phosphate buffered saline solution (pH 7.4). Patterns of oxidised and chemically reactive functionalities could potentially be applied to the future development of biomaterial surfaces, where spatial control over biomolecule or cell function is needed.

  17. Reversing Conventional Reactivity of Mixed Oxo/Alkyl Rare-Earth Complexes: Non-Redox Oxygen Atom Transfer.

    PubMed

    Hong, Jianquan; Tian, Haiwen; Zhang, Lixin; Zhou, Xigeng; Del Rosal, Iker; Weng, Linhong; Maron, Laurent

    2018-01-22

    The preferential substitution of oxo ligands over alkyl ones of rare-earth complexes is commonly considered as "impossible" due to the high oxophilicity of metal centers. Now, it has been shown that simply assembling mixed methyl/oxo rare-earth complexes to a rigid trinuclear cluster framework cannot only enhance the activity of the Ln-oxo bond, but also protect the highly reactive Ln-alkyl bond, thus providing a previously unrecognized opportunity to selectively manipulate the oxo ligand in the presence of numerous reactive functionalities. Such trimetallic cluster has proved to be a suitable platform for developing the unprecedented non-redox rare-earth-mediated oxygen atom transfer from ketones to CS 2 and PhNCS. Controlled experiments and computational studies shed light on the driving force for these reactions, emphasizing the importance of the sterical accessibility and multimetallic effect of the cluster framework in promoting reversal of reactivity of rare-earth oxo complexes. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Aeroallergens Induce Reactive Oxygen Species Production and DNA Damage and Dampen Antioxidant Responses in Bronchial Epithelial Cells.

    PubMed

    Chan, Tze Khee; Tan, W S Daniel; Peh, Hong Yong; Wong, W S Fred

    2017-07-01

    Exposure to environmental allergens is a major risk factor for asthma development. Allergens possess proteolytic activity that is capable of disrupting the airway epithelium. Although there is increasing evidence pointing to asthma as an epithelial disease, the underlying mechanism that drives asthma has not been fully elucidated. In this study, we investigated the direct DNA damage potential of aeroallergens on human bronchial epithelial cells and elucidated the mechanisms mediating the damage. Human bronchial epithelial cells, BEAS-2B, directly exposed to house dust mites (HDM) resulted in enhanced DNA damage, as measured by the CometChip and the staining of DNA double-strand break marker, γH2AX. HDM stimulated cellular reactive oxygen species production, increased mitochondrial oxidative stress, and promoted nitrosative stress. Notably, expression of nuclear factor erythroid 2-related factor 2-dependent antioxidant genes was reduced immediately after HDM exposure, suggesting that HDM altered antioxidant responses. HDM exposure also reduced cell proliferation and induced cell death. Importantly, HDM-induced DNA damage can be prevented by the antioxidants glutathione and catalase, suggesting that HDM-induced reactive oxygen and nitrogen species can be neutralized by antioxidants. Mechanistic studies revealed that HDM-induced cellular injury is NADPH oxidase (NOX)-dependent, and apocynin, a NOX inhibitor, protected cells from double-strand breaks induced by HDM. Our results show that direct exposure of bronchial epithelial cells to HDM leads to the production of reactive oxygen and nitrogen species that damage DNA and induce cytotoxicity. Antioxidants and NOX inhibitors can prevent HDM-induced DNA damage, revealing a novel role for antioxidants and NOX inhibitors in mitigating allergic airway disease. Copyright © 2017 by The American Association of Immunologists, Inc.

  19. E-Cigarette Aerosol Exposure Induces Reactive Oxygen Species, DNA Damage, and Cell Death in Vascular Endothelial Cells.

    PubMed

    Anderson, Chastain; Majeste, Andrew; Hanus, Jakub; Wang, Shusheng

    2016-12-01

    Cigarette smoking remains one of the leading causes of preventable death worldwide. Vascular cell death and dysfunction is a central or exacerbating component in the majority of cigarette smoking related pathologies. The recent development of the electronic nicotine delivery systems known as e-cigarettes provides an alternative to conventional cigarette smoking; however, the potential vascular health risks of e-cigarette use remain unclear. This study evaluates the effects of e-cigarette aerosol extract (EAE) and conventional cigarette smoke extract (CSE) on human umbilical vein endothelial cells (HUVECs). A laboratory apparatus was designed to produce extracts from e-cigarettes and conventional cigarettes according to established protocols for cigarette smoking. EAE or conventional CSE was applied to human vascular endothelial cells for 4-72 h, dependent on the assay. Treated cells were assayed for reactive oxygen species, DNA damage, cell viability, and markers of programmed cell death pathways. Additionally, the anti-oxidants α-tocopherol and n-acetyl-l-cysteine were used to attempt to rescue e-cigarette induced cell death. Our results indicate that e-cigarette aerosol is capable of inducing reactive oxygen species, causing DNA damage, and significantly reducing cell viability in a concentration dependent fashion. Immunofluorescent and flow cytometry analysis indicate that both the apoptosis and programmed necrosis pathways are triggered by e-cigarette aerosol treatment. Additionally, anti-oxidant treatment provides a partial rescue of the induced cell death, indicating that reactive oxygen species play a causal role in e-cigarette induced cytotoxicity. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Regulation of reactive oxygen and nitrogen species by salicylic acid in rice plants under salinity stress conditions

    PubMed Central

    Mun, Bong-Gyu; Khan, Abdul Latif; Waqas, Muhammad; Kim, Hyun-Ho; Shahzad, Raheem; Imran, Muhammad

    2018-01-01

    This study investigated the regulatory role of exogenous salicylic acid (SA) in rice and its effects on toxic reactive oxygen and nitrogen species during short-term salinity stress. SA application (0.5 and 1.0 mM) during salinity-induced stress (100 mM NaCl) resulted in significantly longer shoot length and higher chlorophyll and biomass accumulation than with salinity stress alone. NaCl-induced reactive oxygen species production led to increased levels of lipid peroxidation in rice plants, which were significantly reduced following SA application. A similar finding was observed for superoxide dismutase; however, catalase (CAT) and ascorbate peroxidase (APX) were significantly reduced in rice plants treated with SA and NaCl alone and in combination. The relative mRNA expression of OsCATA and OsAPX1 was lower in rice plants during SA stress. Regarding nitrogenous species, S-nitrosothiol (SNO) was significantly reduced initially (one day after treatment [DAT]) but then increased in plants subjected to single or combined stress conditions. Genes related to SNO biosynthesis, S-nitrosoglutathione reductase (GSNOR1), NO synthase-like activity (NOA), and nitrite reductase (NIR) were also assessed. The mRNA expression of GSNOR1 was increased relative to that of the control, whereas OsNOA was expressed at higher levels in plants treated with SA and NaCl alone relative to the control. The mRNA expression of OsNR was decreased in plants subjected to single or combination treatment, except at 2 DAT, compared to the control. In conclusion, the current findings suggest that SA can regulate the generation of NaCl-induced oxygen and nitrogen reactive species in rice plants. PMID:29558477

  1. Fanconi Anemia Links Reactive Oxygen Species to Insulin Resistance and Obesity

    PubMed Central

    Li, Jie; Sipple, Jared; Maynard, Suzette; Mehta, Parinda A.; Rose, Susan R.; Davies, Stella M.

    2012-01-01

    Abstract Aims: Insulin resistance is a hallmark of obesity and type 2 diabetes. Reactive oxygen species (ROS) have been proposed to play a causal role in insulin resistance. However, evidence linking ROS to insulin resistance in disease settings has been scant. Since both oxidative stress and diabetes have been observed in patients with the Fanconi anemia (FA), we sought to investigate the link between ROS and insulin resistance in this unique disease model. Results: Mice deficient for the Fanconi anemia complementation group A (Fanca) or Fanconi anemia complementation group C (Fancc) gene seem to be diabetes-prone, as manifested by significant hyperglycemia and hyperinsulinemia, and rapid weight gain when fed with a high-fat diet. These phenotypic features of insulin resistance are characterized by two critical events in insulin signaling: a reduction in tyrosine phosphorylation of the insulin receptor (IR) and an increase in inhibitory serine phosphorylation of the IR substrate-1 in the liver, muscle, and fat tissues from the insulin-challenged FA mice. High levels of ROS, spontaneously accumulated or generated by tumor necrosis factor alpha in these insulin-sensitive tissues of FA mice, were shown to underlie the FA insulin resistance. Treatment of FA mice with the natural anti-oxidant Quercetin restores IR signaling and ameliorates the diabetes- and obesity-prone phenotypes. Finally, pairwise screen identifies protein-tyrosine phosphatase (PTP)-α and stress kinase double-stranded RNA-dependent protein kinase (PKR) that mediate the ROS effect on FA insulin resistance. Innovation: These findings establish a pathogenic and mechanistic link between ROS and insulin resistance in a unique human disease setting. Conclusion: ROS accumulation contributes to the insulin resistance in FA deficiency by targeting both PTP-α and PKR. Antioxid. Redox Signal. 00, 000–000. PMID:22482891

  2. The association between reactive oxygen metabolites and metabolic syndrome in asymptomatic Japanese men.

    PubMed

    Kotani, Kazuhiko; Taniguchi, Nobuyuki

    2011-10-01

    The association between the oxidative status and metabolic syndrome (MetS) should be studied in various populations with various oxidative stress-related markers. The aim of this cross-sectional study was to investigate the association between oxidative status, as assessed by the reactive oxygen metabolites (d-ROMs) test, and MetS in asymptomatic Japanese men, in relation to age. The serum d-ROMs levels were measured in cardiovascular disease-free, non-smoking, non-medicated males (n = 140), who were divided into groups as follows: Group 1, < 60 years (n = 75, mean age 46 ± 9 [SD] years), and Group 2, ≥ 60 years (n = 65, mean 68 ± 6 years). The MetS was determined by the NCEP-ATP recommendations with minor modifications for a Japanese population. There was no significant difference in the d-ROMs levels between the subjects with and without MetS in Group 2 (≥ 60 years), but the subjects with MetS (n = 38, 324 ± 59 U. Curr.) exhibited significantly higher d-ROMs levels than those without MetS (n = 37, 290 ± 49 U. Curr., P < 0.01) in Group 1 (< 60 years). These differences did not change even after adjustments for basic confounders. These results suggest that oxidative status, as assessed by the d-ROMs, can be enhanced among asymptomatic younger, but not older, Japanese males with MetS. Further studies are required to establish the observed associations. Oxidative stress; Reactive oxygen species; D-ROMs; Obesity; Metabolic syndrome.

  3. Reactive oxygen species in plant pathogenesis: the role of perylenequinone photosensitizers.

    PubMed

    Daub, Margaret E; Herrero, Sonia; Chung, Kuang-Ren

    2013-09-20

    Reactive oxygen species (ROS) play multiple roles in interactions between plants and microbes, both as host defense mechanisms and as mediators of pathogenic and symbiotic associations. One source of ROS in these interactions are photoactivated, ROS-generating perylenequinone pigments produced via polyketide metabolic pathways in plant-associated fungi. These natural products, including cercosporin, elsinochromes, hypocrellins, and calphostin C, are being utilized as medicinal agents, enzyme inhibitors, and in tumor therapy, but in nature, they play a role in the establishment of pathogenic associations between fungi and their plant hosts. Photoactivated perylenequinones are photosensitizers that use light energy to form singlet oxygen (¹O₂) and free radical oxygen species which damage cellular components based on localization of the perylenequinone molecule. Production of perylenequinones during infection commonly results in lipid peroxidation and membrane damage, leading to leakage of nutrients from cells into the intercellular spaces colonized by the pathogen. Perylenequinones show almost universal toxicity against organisms, including plants, mice, bacteria, and most fungi. The producing fungi are resistant, however, and serve as models for understanding resistance mechanisms. Studies of resistance mechanisms by perylenequinone-producing fungi such as Cercospora species are leading to an understanding of cellular resistance to ¹O₂ and oxidative stress. Recent studies show commonalities between resistance mechanisms in these fungi with extensive studies of ¹O₂ and oxidative stress responses in photosynthetic organisms. Such studies hold promise both for improved medical use and for engineering crop plants for disease resistance.

  4. Imaging Reactive Oxygen Species-Induced Modifications in Living Systems.

    PubMed

    Maulucci, Giuseppe; Bačić, Goran; Bridal, Lori; Schmidt, Harald Hhw; Tavitian, Bertrand; Viel, Thomas; Utsumi, Hideo; Yalçın, A Süha; De Spirito, Marco

    2016-06-01

    Reactive Oxygen Species (ROS) may regulate signaling, ion channels, transcription factors, and biosynthetic processes. ROS-related diseases can be due to either a shortage or an excess of ROS. Since the biological activity of ROS depends on not only concentration but also spatiotemporal distribution, real-time imaging of ROS, possibly in vivo, has become a need for scientists, with potential for clinical translation. New imaging techniques as well as new contrast agents in clinically established modalities were developed in the previous decade. An ideal imaging technique should determine ROS changes with high spatio-temporal resolution, detect physiologically relevant variations in ROS concentration, and provide specificity toward different redox couples. Furthermore, for in vivo applications, bioavailability of sensors, tissue penetration, and a high signal-to-noise ratio are additional requirements to be satisfied. None of the presented techniques fulfill all requirements for clinical translation. The obvious way forward is to incorporate anatomical and functional imaging into a common hybrid-imaging platform. Antioxid. Redox Signal. 24, 939-958.

  5. Reactive oxygen species, essential molecules, during plant-pathogen interactions.

    PubMed

    Camejo, Daymi; Guzmán-Cedeño, Ángel; Moreno, Alexander

    2016-06-01

    Reactive oxygen species (ROS) are continually generated as a consequence of the normal metabolism in aerobic organisms. Accumulation and release of ROS into cell take place in response to a wide variety of adverse environmental conditions including salt, temperature, cold stresses and pathogen attack, among others. In plants, peroxidases class III, NADPH oxidase (NOX) locates in cell wall and plasma membrane, respectively, may be mainly enzymatic systems involving ROS generation. It is well documented that ROS play a dual role into cells, acting as important signal transduction molecules and as toxic molecules with strong oxidant power, however some aspects related to its function during plant-pathogen interactions remain unclear. This review focuses on the principal enzymatic systems involving ROS generation addressing the role of ROS as signal molecules during plant-pathogen interactions. We described how the chloroplasts, mitochondria and peroxisomes perceive the external stimuli as pathogen invasion, and trigger resistance response using ROS as signal molecule. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. REACTIVE OXYGEN AND NITROGEN SPECIES IN PULMONARY HYPERTENSION

    PubMed Central

    Tabima, Diana M.; Frizzell, Sheila; Gladwin, Mark T.

    2013-01-01

    Pulmonary vascular disease can be defined as either a disease affecting the pulmonary capillaries and pulmonary arterioles, termed pulmonary arterial hypertension, or as a disease affecting the left ventricle, called pulmonary venous hypertension. Pulmonary arterial hypertension (PAH) is a disorder of the pulmonary circulation characterized by endothelial dysfunction, as well as intimal and smooth muscle proliferation. Progressive increases in pulmonary vascular resistance and pressure impair the performance of the right ventricle, resulting in declining cardiac output, reduced exercise capacity, right heart failure, and ultimately death. While the primary and heritable forms of the disease are thought to affect over 5,000 patients in the U.S., the disease can occur secondary to congenital heart disease, most advanced lung diseases, and many systemic diseases. Multiple studies implicate oxidative stress in the development of PAH. Further, this oxidative stress has been shown to be associated with alterations in reactive oxygen species (ROS), reactive nitrogen species (RNS) and nitric oxide (NO) signaling pathways, whereby bioavailable NO is decreased and ROS and RNS production are increased. Many canonical ROS and NO signaling pathways are simultaneously disrupted in PAH, with increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and xanthine oxidoreductase, uncoupling of endothelial NO synthase (eNOS), and reduction in mitochondrial number, as well as impaired mitochondrial function. Upstream dysregulation of ROS/NO redox homeostasis impairs vascular tone and contributes to the pathological activation of anti-apoptotic and mitogenic pathways, leading to cell proliferation and obliteration of the vasculature. This manuscript will review the available data regarding the role of oxidative and nitrosative stress and endothelial dysfunction in the pathophysiology of pulmonary hypertension, and provide a description of targeted therapies

  7. [Effect of low-energy 633 nm red light stimulation on proliferation and reactive oxygen species level of human epidermal cell line HaCaT].

    PubMed

    Chen, Z Y; Li, D L; Duan, X D; Peng, D Z

    2016-09-20

    To investigate the changes of proliferative activity and reactive oxygen species level of human epidermal cell line HaCaT after being irradiated with low-energy 633 nm red light. Irradiation distance was determined through preliminary experiment. HaCaT cells were conventionally sub-cultured with RPMI 1640 culture medium containing 10% fetal calf serum, 100 U/mL penicillin, and 100 μg/mL streptomycin. Cells of the third passage were used in the following experiments. (1) Cells were divided into blank control group and 0.082, 0.164, 0.245, 0.491, 1.472, 2.453, 4.910, and 9.810 J/cm(2) irradiation groups according to the random number table, with 3 wells in each group. Cells in blank control group were not irradiated, while cells in the latter 8 irradiation groups were irradiated with 633 nm red light for 10, 20, 30, 60, 180, 300, 600, and 1 200 s in turn. Cells were reirradiated once every 8 hours. After being irradiated for 48 hours (6 times) in irradiation groups, the proliferative activity of cells in 9 groups was determined with cell counting kit 8 and microplate reader (denoted as absorbance value). (2) Another batch of cells were grouped and irradiated as in experiment (1). After being irradiated for once in irradiation groups, cells in 9 groups were conventionally cultured for 60 min with detection reagent of reactive oxygen species. At post culture minute (PCM) 0 (immediately), 30, 60, and 120, reactive oxygen species level of cells was determined with microplate reader (denoted as absorbance value). (3) Another batch of cells were divided into blank control group, 0.082, 0.491, 2.453, and 9.810 J/cm(2) irradiation groups, and positive control group. Cells in blank control group and positive control group were not irradiated (positive control reagent of reactive oxygen species was added to cells in positive control group), and cells in irradiation groups were irradiated as in experiment (1) for once. The expression of reactive oxygen species in cells of each

  8. Serum derivative of reactive oxygen metabolites (d-ROMs) in pediatric hemato-oncological patients with neutropenic fever.

    PubMed

    Nishikawa, Takuro; Okamoto, Yasuhiro; Kodama, Yuichi; Tanabe, Takayuki; Shinkoda, Yuichi; Kawano, Yoshifumi

    2010-07-15

    Early markers for predicting the severity of neutropenic fever (NF) in patients with hemato-oncological patients have not yet been established. Reactive oxygen species are known to play an important role in the antimicrobial function of neutrophils. The aim of this study was to determine the serum levels of derivatives of reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP) levels in these patients, and to investigate the associations between these levels and the severity of NF. Twenty-seven pediatric hemato-oncological patients were enroled in this prospective study. Their median age was 10 years (range 1-19). Laboratory samples for C-reactive protein (CRP), d-ROMs, and BAP were collected at the onset of NF. The Free Radical Analytical System 4(R) was used to measure levels of d-ROMs and BAP. A total 36 NF episodes were evaluated. Levels of d-ROMs in NF patients with systemic inflammatory response syndrome (SIRS, n = 7) were significantly lower than those in subjects without SIRS (n = 29; 197.6 vs. 314.1 U.CARR, P = 0.017). There were no statistically significant differences in CRP, BAP, WBC count, or neutrophil count at the onset. The peak levels of CRP were significantly higher in patients with SIRS than in those without SIRS (23.9 vs. 6.1 mg/dl, P = 0.0003). Patients with low level of d-ROMs at the onset of NF should be observed stringently since they possibly have severe NF.

  9. NQO2 Is a Reactive Oxygen Species Generating Off-Target for Acetaminophen

    PubMed Central

    2014-01-01

    The analgesic and antipyretic compound acetaminophen (paracetamol) is one of the most used drugs worldwide. Acetaminophen overdose is also the most common cause for acute liver toxicity. Here we show that acetaminophen and many structurally related compounds bind quinone reductase 2 (NQO2) in vitro and in live cells, establishing NQO2 as a novel off-target. NQO2 modulates the levels of acetaminophen derived reactive oxygen species, more specifically superoxide anions, in cultured cells. In humans, NQO2 is highly expressed in liver and kidney, the main sites of acetaminophen toxicity. We suggest that NQO2 mediated superoxide production may function as a novel mechanism augmenting acetaminophen toxicity. PMID:25313982

  10. Modulation of Neutrophil Extracellular Trap and Reactive Oxygen Species Release by Periodontal Bacteria

    PubMed Central

    White, Phillipa C.; Milward, Michael R.; Cooper, Paul R.

    2017-01-01

    ABSTRACT Oral bacteria are the main trigger for the development of periodontitis, and some species are known to modulate neutrophil function. This study aimed to explore the release of neutrophil extracellular traps (NETs), associated antimicrobial proteins, and reactive oxygen species (ROS) in response to periodontal bacteria, as well as the underlying pathways. Isolated peripheral blood neutrophils were stimulated with 19 periodontal bacteria. NET and ROS release, as well as the expression of NET-bound antimicrobial proteins, elastase, myeloperoxidase, and cathepsin G, in response to these species was measured using fluorescence-based assays. NET and ROS release was monitored after the addition of NADP (NADPH) oxidase pathway modulators and inhibitors of Toll-like receptors (TLRs). Moreover, bacterial entrapment by NETs was visualized microscopically, and bacterial killing was assessed by bacterial culture. Certain microorganisms, e.g., Veillonella parvula and Streptococcus gordonii, stimulated higher levels of ROS and NET release than others. NETs were found to entrap, but not kill, all periodontal bacteria tested. NADPH oxidase pathway modulators decreased ROS production but not NET production in response to the bacteria. Interestingly, TLR inhibitors did not impact ROS and NET release. These data suggest that the variability in the neutrophil response toward different bacteria may contribute to the pathogenesis of periodontal diseases by mechanisms such as bacterial avoidance of host responses and activation of neutrophils. Moreover, our results indicate that bacterium-stimulated NET release may arise in part via NADPH oxidase-independent mechanisms. The role of TLR signaling in bacterium-induced ROS and NET release needs to be further elucidated. PMID:28947649

  11. Evaluation of reactive oxygen metabolites in patients with non-small cell lung cancer after chemotherapy

    PubMed Central

    2014-01-01

    Background The aim of this study was to evaluate the level of reactive oxygen metabolites (ROMs) after chemotherapy in patients with non-small cell lung cancer (NSCLC) and its association with response to treatment. Methods Fifty-eight untreated NSCLC patients and twenty-three healthy subjects were selected for the study. Patients received two courses of platinum-based chemotherapy and were evaluated for oxidative stress and treatment response. As a marker of reactive oxygen species, ROMs levels were measured using the d-ROMs test. Results ROMs level (mean ± standard deviation) before chemotherapy in NSCLC patients (416 ± 135 U.CARR) was significantly elevated (p = 0.016) compared to normal healthy subjects (320 ± 59 U.CARR). Patients who responded to chemotherapy showed significantly decreased (p = 0.014) ROMs levels after chemotherapy, whereas patients who had stable disease or progressive disease showed no change in ROMs level (p = 0.387). Conclusions NSCLC patients had significantly elevated ROMs levels before chemotherapy compared with normal healthy subjects. Chemotherapy may suppress ROMs production in responders but not in non-responders. ROMs level may be a predictor of clinical outcome in patients receiving chemotherapy for NSCLC. PMID:25180083

  12. Scavenging of reactive oxygen species and prevention of oxidative neuronal cell damage by a novel gallotannin, pistafolia A.

    PubMed

    Wei, Taotao; Sun, Handong; Zhao, Xingyu; Hou, Jingwu; Hou, Aijun; Zhao, Qinshi; Xin, Wenjuan

    2002-03-08

    Pistafolia A is a novel gallotannin isolated from the leaf extract of Pistacia weinmannifolia. In the present investigation, the ability of Pistafolia A to scavenge reactive oxygen species including hydroxyl radicals and superoxide anion was measured by ESR spin trapping technique. The inhibition effect on iron-induced lipid peroxidaiton in liposomes was studied. The protective effects of Pistafolia A against oxidative neuronal cell damage and apoptosis induced by peroxynitrite were also assessed. The results showed that Pistafolia A could scavenge both hydroxyl radicals and superoxide anion dose-dependently and inhibit lipid peroxidation effectively. In cerebellar granule cells pretreated with Pistafolia A, peroxynitrite-induced oxidative neuronal damage and apoptosis were prevented markedly. The antioxidant capacity of Pistafolia A was much more potent then that of the water-soluble analog of vitamin E, Trolox. The results suggested that Pistafolia A might be used as an effective natural antioxidant for the prevention and cure of neuronal diseases associated with the production of peroxynitrite and related reactive oxygen species.

  13. Induction of Tca8113 tumor cell apoptosis by icotinib is associated with reactive oxygen species mediated p38-MAPK activation.

    PubMed

    Yang, Cailing; Yan, Jianguo; Yuan, Guoyan; Zhang, Yinghua; Lu, Derong; Ren, Mingxin; Cui, Weigang

    2014-08-01

    Icotinib, a selective EGFR tyrosine kinase inhibitor (EGFR-TKI), has been shown to exhibit anti-tumor activity against several tumor cell lines. However, the exact molecular mechanism of icotinib's anti-tumor effect remains unknown. This study aims to examine the zytotoxic effect of icotinib on Tca8113 cells and its potential molecular mechanism. Icotinib significantly resulted in dose-dependent cell death as determined by MTT assay, accompanied by increased levels of Bax and DNA fragmentation. Icotinib could also induce Reactive Oxygen Species (ROS) generation. Further studies confirmed that scavenging of reactive oxygen species by N-acetyl-L-cysteine (NAC), and pharmacological inhibition of MAPK reversed icotinib-induced apoptosis in Tca8113 cells. Our data provide evidence that icotinib induces apoptosis, possibly via ROS-mediated MAPK pathway in Tca8113 cells.

  14. Cell Proliferation, Reactive Oxygen and Cellular Glutathione

    PubMed Central

    Day, Regina M.; Suzuki, Yuichiro J.

    2005-01-01

    A variety of cellular activities, including metabolism, growth, and death, are regulated and modulated by the redox status of the environment. A biphasic effect has been demonstrated on cellular proliferation with reactive oxygen species (ROS)—especially hydrogen peroxide and superoxide—in which low levels (usually submicromolar concentrations) induce growth but higher concentrations (usually >10–30 micromolar) induce apoptosis or necrosis. This phenomenon has been demonstrated for primary, immortalized and transformed cell types. However, the mechanism of the proliferative response to low levels of ROS is not well understood. Much of the work examining the signal transduction by ROS, including H2O2, has been performed using doses in the lethal range. Although use of higher ROS doses have allowed the identification of important signal transduction pathways, these pathways may be activated by cells only in association with ROS-induced apoptosis and necrosis, and may not utilize the same pathways activated by lower doses of ROS associated with increased cell growth. Recent data has shown that low levels of exogenous H2O2 up-regulate intracellular glutathione and activate the DNA binding activity toward antioxidant response element. The modulation of the cellular redox environment, through the regulation of cellular glutathione levels, may be a part of the hormetic effect shown by ROS on cell growth. PMID:18648617

  15. Contrasted Reactivity to Oxygen Tensions in Frankia sp. Strain CcI3 throughout Nitrogen Fixation and Assimilation

    PubMed Central

    Ghodhbane-Gtari, Faten; Hezbri, Karima; Ktari, Amir; Sbissi, Imed; Beauchemin, Nicholas; Gtari, Maher; Tisa, Louis S.

    2014-01-01

    Reconciling the irreconcilable is a primary struggle in aerobic nitrogen-fixing bacteria. Although nitrogenase is oxygen and reactive oxygen species-labile, oxygen tension is required to sustain respiration. In the nitrogen-fixing Frankia, various strategies have been developed through evolution to control the respiration and nitrogen-fixation balance. Here, we assessed the effect of different oxygen tensions on Frankia sp. strain CcI3 growth, vesicle production, and gene expression under different oxygen tensions. Both biomass and vesicle production were correlated with elevated oxygen levels under both nitrogen-replete and nitrogen-deficient conditions. The mRNA levels for the nitrogenase structural genes (nifHDK) were high under hypoxic and hyperoxic conditions compared to oxic conditions. The mRNA level for the hopanoid biosynthesis genes (sqhC and hpnC) was also elevated under hyperoxic conditions suggesting an increase in the vesicle envelope. Under nitrogen-deficient conditions, the hup2 mRNA levels increased with hyperoxic environment, while hup1 mRNA levels remained relatively constant. Taken together, these results indicate that Frankia protects nitrogenase by the use of multiple mechanisms including the vesicle-hopanoid barrier and increased respiratory protection. PMID:24987692

  16. Reactive Oxygen Species, Mitochondria, and Endothelial Cell Death during In Vitro Simulated Dives.

    PubMed

    Wang, Qiong; Guerrero, François; Mazur, Aleksandra; Lambrechts, Kate; Buzzacott, Peter; Belhomme, Marac; Theron, Michaël

    2015-07-01

    Excessive reactive oxygen species (ROS) is considered a consequence of hyperoxia and a major contributor to diving-derived vascular endothelial damage and decompression sickness. The aims of this work were: 1) to directly observe endothelial ROS production during simulated air dives as well as its relation with both mitochondrial activity and cell survival; and 2) to determine which ambient factor during air diving (hydrostatic pressure or oxygen and/or nitrogen partial pressure) is responsible for the observed modifications. In vitro diving simulation was performed with bovine arterial endothelial cells under real-time observation. The effects of air diving, hydrostatic, oxygen and nitrogen pressures, and N-acetylcysteine (NAC) treatment on mitochondrial ROS generation, mitochondrial membrane potential and cellular survival during simulation were investigated. Vascular endothelial cells performing air diving simulation suffered excessive mitochondrial ROS, mitochondrial depolarization, and cell death. These effects were prevented by NAC: after NAC treatment, the cells presented no difference in damage from nondiving cells. Oxygen diving showed a higher effect on ROS generation but lower impacts on mitochondrial depolarization and cell death than hydrostatic or nitrogen diving. Nitrogen diving had no effect on the inductions of ROS, mito-depolarization, or cell death. This study is the first direct observation of mitochondrial ROS production, mitochondrial membrane potential and cell survival during diving. Simulated air SCUBA diving induces excessive ROS production, which leads to mitochondrial depolarization and endothelial cell death. Oxygen partial pressure plays a crucial role in the production of ROS. Deleterious effects of hyperoxia-induced ROS are potentiated by hydrostatic pressure. These findings hold new implications for the pathogenesis of diving-derived endothelial dysfunction.

  17. Flavonoids in Microheterogeneous Media, Relationship between Their Relative Location and Their Reactivity towards Singlet Oxygen

    PubMed Central

    Günther, Germán; Berríos, Eduardo; Pizarro, Nancy; Valdés, Karina; Montero, Guillermo; Arriagada, Francisco; Morales, Javier

    2015-01-01

    In this work, the relationship between the molecular structure of three flavonoids (kaempferol, quercetin and morin), their relative location in microheterogeneous media (liposomes and erythrocyte membranes) and their reactivity against singlet oxygen was studied. The changes observed in membrane fluidity induced by the presence of these flavonoids and the influence of their lipophilicity/hydrophilicity on the antioxidant activity in lipid membranes were evaluated by means of fluorescent probes such as Laurdan and diphenylhexatriene (DPH). The small differences observed for the value of generalized polarization of Laurdan (GP) curves in function of the concentration of flavonoids, indicate that these three compounds promote similar alterations in liposomes and erythrocyte membranes. In addition, these compounds do not produce changes in fluorescence anisotropy of DPH, discarding their location in deeper regions of the lipid bilayer. The determined chemical reactivity sequence is similar in all the studied media (kaempferol < quercetin < morin). Morin is approximately 10 times more reactive than quercetin and 20 to 30 times greater than kaempferol, depending on the medium. PMID:26098745

  18. Effect of density gradient centrifugation on reactive oxygen species in human semen.

    PubMed

    Takeshima, Teppei; Yumura, Yasushi; Kuroda, Shinnosuke; Kawahara, Takashi; Uemura, Hiroji; Iwasaki, Akira

    2017-06-01

    Density gradient centrifugation can separate motile sperm from immotile sperm and other cells for assisted reproduction, but may also remove antioxidants from seminal plasma, resulting in oxidative stress. Therefore, we investigated reactive oxygen species (ROS) concentrations and distribution in semen before and after density gradient centrifugation. We assessed semen volume, sperm concentration, sperm motility, and ROS levels before and after density gradient centrifugation (300 x g for 20 minutes) in 143 semen samples from 118 patients. The ROS removal rate was evaluated in ROS-positive samples and ROS formation rate in ROS-negative samples. Thirty-eight of 143 untreated samples (26.6%) were ROS-positive; sperm motility was significantly lower in these samples than in ROS-negative samples (p < 0.05). After density gradient centrifugation, only seven of the 38 ROS-positive samples (18.42%) exhibited a ROS-positive lower layer (containing motile sperm) with a ROS removal rate of 81.58%, whereas the upper layer was ROS-positive in 24 samples (63.16%). In the ROS-negative group (n = 105), ROS was detected in 19 samples after centrifugation (18.10%, ROS generation rate), of which 18 were ROS-positive only in the upper layer or interface and the other was ROS-positive in both layers. Density gradient centrifugation can separate motile sperm from immotile sperm as well as remove ROS (including newly generated ROS). This data supports the view that density gradient centrifugation can select motile spermatozoa without enhancing oxidative stress. ROS: reactive oxygen species; SOD: superoxide dismutase; GPx: glutathione peroxidase; DNA: deoxyribonucleic acid; DGC: density gradient centrifugation; IUI: intrauterine insemination; IVF: in vitro fertilization; HEPES: 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; EDTA: ethylenediaminetetraacetic acid; HTF: HEPES-buffered human tubal fluid; IMSI: intracytoplasmic morphologically selected sperm injection; SMAS: sperm

  19. Reactive oxygen species-dependent wound responses in animals and plants.

    PubMed

    Suzuki, Nobuhiro; Mittler, Ron

    2012-12-15

    Animals and plants evolved sophisticated mechanisms that regulate their responses to mechanical injury. Wound response in animals mainly promotes wound healing processes, nerve cell regeneration, and immune system responses at the vicinity of the wound site. In contrast, wound response in plants is primarily directed at sealing the wound site via deposition of various compounds and generating systemic signals that activate multiple defense mechanisms in remote tissues. Despite these differences between animals and plants, recent studies have shown that reactive oxygen species (ROS) play very common signaling and coordination roles in the wound responses of both systems. This review provides an update on recent findings related to ROS-regulated coordination of intercellular communications and signal transduction during wound response in plants and animals. In particular, differences and similarities in H2O2-dependent long-distance signaling between zebrafish and Arabidopsis thaliana are discussed. Published by Elsevier Inc.

  20. Ethanol-induced erectile dysfunction and increased expression of pro-inflammatory proteins in the rat cavernosal smooth muscle are mediated by NADPH oxidase-derived reactive oxygen species.

    PubMed

    Leite, Letícia N; do Vale, Gabriel T; Simplicio, Janaina A; De Martinis, Bruno S; Carneiro, Fernando S; Tirapelli, Carlos R

    2017-06-05

    Ethanol consumption is associated with an increased risk of erectile dysfunction (ED), but the molecular mechanisms through which ethanol causes ED remain elusive. Reactive oxygen species are described as mediators of ethanol-induced cell toxicity/damage in distinctive tissues. The enzyme NADPH oxidase is the main source of reactive oxygen species in the endothelium and vascular smooth muscle cells and ethanol is described to increase NADPH oxidase activation and reactive oxygen species generation. This study evaluated the contribution of NADPH oxidase-derived reactive oxygen species to ethanol-induced ED, endothelial dysfunction and production of pro-inflammatory and redox-sensitive proteins in the rat cavernosal smooth muscle (CSM). Male Wistar rats were treated with ethanol (20% v/v) or ethanol plus apocynin (30mg/kg/day; p.o. gavage) for six weeks. Apocynin prevented both the decreased in acetylcholine-induced relaxation and intracavernosal pressure induced by ethanol. Ethanol increased superoxide anion (O 2 - ) generation and catalase activity in CSM, and treatment with apocynin prevented these responses. Similarly, apocynin prevented the ethanol-induced decreased of nitrate/nitrite (NOx), hydrogen peroxide (H 2 O 2 ) and SOD activity. Treatment with ethanol increased p47phox translocation to the membrane as well as the expression of Nox2, COX-1, catalase, iNOS, ICAM-1 and p65. Apocynin prevented the effects of ethanol on protein expression and p47phox translocation. Finally, treatment with ethanol increased both TNF-α production and neutrophil migration in CSM. The major new finding of this study is that NADPH oxidase-derived reactive oxygen species play a role on chronic ethanol consumption-induced ED and endothelial dysfunction in the rat CSM. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Is sperm freezability related to the post-thaw lipid peroxidation and the formation of reactive oxygen species in boars?

    PubMed

    Gómez-Fernández, J; Gómez-Izquierdo, E; Tomás, C; Mocé, E; de Mercado, E

    2013-04-01

    The aim of the present study was to determine whether the levels of reactive oxygen species (ROS) substances production and the levels of lipid peroxidation of the sperm membrane were related to the quality that the ejaculates exhibited after cryopreservation in boars. Ejaculates from 42 healthy boars were used in this study and they were cryopreserved with the lactose-egg yolk extender (LEY). Several sperm quality parameters were assessed by flow cytometry in samples incubated for 30 and 150 min at 37 °C after thawing: the percentage of sperm with intact plasma membrane (SIPM), intracellular reactive oxygen substances production through mean of DCF fluorescence intensity of total sperm (mean-DCF) and the percentage of viable and non-viable sperm containing oxidized BODIPY (VSOB and NVSOB). In addition, the percentages of total motile (TMS) and progressively motile sperm (PMS) were assessed at the same incubation times with a computer-assisted sperm analysis system. The classification of the ejaculates into good or bad freezers was performed through hierarchical cluster analysis from SIPM and TMS at 150 min post-thawing. The ejaculates of those males classified as good freezers exhibited higher (p < 0.05) SPIM, TMS and PMS than the bad freezers, although both groups presented similar (p > 0.05) VSOB, NVSOB and mean-DCF. Therefore, these results show that lipid peroxidation and the amount of reactive oxygen substances in the sperm after cryopreservation are similar between boars classified as good or bad freezers. © 2012 Blackwell Verlag GmbH.

  2. Changes in Cerebral Partial Oxygen Pressure and Cerebrovascular Reactivity During Intracranial Pressure Plateau Waves.

    PubMed

    Lang, Erhard W; Kasprowicz, Magdalena; Smielewski, Peter; Pickard, John; Czosnyka, Marek

    2015-08-01

    Plateau waves in intracranial pressure (ICP) are frequently recorded in neuro intensive care and are not yet fully understood. To further investigate this phenomenon, we analyzed partial pressure of cerebral oxygen (pbtO2) and a moving correlation coefficient between ICP and mean arterial blood pressure (ABP), called PRx, along with the cerebral oxygen reactivity index (ORx), which is a moving correlation coefficient between cerebral perfusion pressure (CPP) and pbtO2 in an observational study. We analyzed 55 plateau waves in 20 patients after severe traumatic brain injury. We calculated ABP, ABP pulse amplitude (ampABP), ICP, CPP, pbtO2, heart rate (HR), ICP pulse amplitude (ampICP), PRx, and ORx, before, during, and after each plateau wave. The analysis of variance with Bonferroni post hoc test was used to compare the differences in the variables before, during, and after the plateau wave. We considered all plateau waves, even in the same patient, independent because they are separated by long intervals. We found increases for ICP and ampICP according to our operational definitions for plateau waves. PRx increased significantly (p = 0.00026), CPP (p < 0.00001) and pbtO2 (p = 0.00007) decreased significantly during the plateau waves. ABP, ampABP, and HR remained unchanged. PRx during the plateau was higher than before the onset of wave in 40 cases (73 %) with no differences in baseline parameters for those with negative and positive ΔPRx (difference during and after). ORx showed an increase during and a decrease after the plateau waves, however, not statistically significant. PbtO2 overshoot after the wave occurred in 35 times (64 %), the mean difference was 4.9 ± 4.6 Hg (mean ± SD), and we found no difference in baseline parameters between those who overshoot and those who did not overshoot. Arterial blood pressure remains stable in ICP plateau waves, while cerebral autoregulatory indices show distinct changes, which indicate cerebrovascular

  3. Reactive oxygen species on bone mineral density and mechanics in Cu,Zn superoxide dismutase (Sod1) knockout mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Smietana, Michael J.; Arruda, Ellen M.; Mechanical Engineering, University of Michigan, 2250 GG Brown, 2350 Hayward, Ann Arbor, MI 48109

    Research highlights: {yields} Reactive oxygen species (ROS) are considered to be a factor in the onset of a number of age-associated conditions, including loss of BMD. {yields} Cu,Zn-superoxide dismutase (Sod1) deficient mice have increased ROS, reduced bone mineral density, decreased bending stiffness, and decreased strength compared to WT controls. {yields} Increased ROS caused by the deficiency of Sod1, may be responsible for the changes in BMD and bone mechanics and therefore represent an appropriate model for studying mechanisms of age-associated bone loss. -- Abstract: Reactive oxygen species (ROS) play a role in a number of degenerative conditions including osteoporosis. Micemore » deficient in Cu,Zn-superoxide dismutase (Sod1) (Sod1{sup -/-} mice) have elevated oxidative stress and decreased muscle mass and strength compared to wild-type mice (WT) and appear to have an accelerated muscular aging phenotype. Thus, Sod1{sup -/-} mice may be a good model for evaluating the effects of free radical generation on diseases associated with aging. In this experiment, we tested the hypothesis that the structural integrity of bone as measured by bending stiffness (EI; N/mm{sup 2}) and strength (MPa) is diminished in Sod1{sup -/-} compared to WT mice. Femurs were obtained from male and female WT and Sod1{sup -/-} mice at 8 months of age and three-point bending tests were used to determine bending stiffness and strength. Bones were also analyzed for bone mineral density (BMD; mg/cc) using micro-computed tomography. Femurs were approximately equal in length across all groups, and there were no significant differences in BMD or EI with respect to gender in either genotype. Although male and female mice demonstrated similar properties within each genotype, Sod1{sup -/-} mice exhibited lower BMD and EI of femurs from both males and females compared with gender matched WT mice. Strength of femurs was also lower in Sod1{sup -/-} mice compared to WT as well as between genders

  4. Constitutive NF-κB activation and tumor-growth promotion by Romo1-mediated reactive oxygen species production

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chung, Jin Sil; Lee, Sora; Yoo, Young Do, E-mail: ydy1130@korea.ac.kr

    2014-08-08

    Highlights: • Romo1 expression is required for constitutive nuclear DNA-binding activity of NF-κB. • Romo1 depletion suppresses tumor growth in vivo. • Romo1 presents a potential therapeutic target for diseases. - Abstract: Deregulation of nuclear factor-κB (NF-κB) and related pathways contribute to tumor cell proliferation and invasion. Mechanisms for constitutive NF-κB activation are not fully explained; however, the underlying defects appear to generate and maintain pro-oxidative conditions. In hepatocellular carcinoma (HCC) tissues, up-regulation of reactive oxygen species modulator 1 (Romo1) correlates positively with tumor size. In the present study, we showed that Romo1 expression is required to maintain constitutive nuclearmore » DNA-binding activity of NF-κB and transcriptional activity through constitutive IκBα phosphorylation. Overexpression of Romo1 promoted p65 nuclear translocation and DNA-binding activity. We also show that Romo1 depletion suppressed anchorage-independent colony formation by HCC cells and suppressed tumor growth in vivo. Based on these findings, Romo1 may be a principal regulatory factor in the maintenance of constitutive NF-κB activation in tumor cells. In the interest of anti-proliferative treatments for cancer, Romo1 may also present a productive target for drug development.« less

  5. Role of NADPH oxidases and reactive oxygen species in regulation of bone turnover and the skeletal toxicity of alcohol

    USDA-ARS?s Scientific Manuscript database

    Recent studies with genetically modified mice and dietary antioxidants have suggested an important role for superoxide derived from NADPH oxidase (NOX) enzymes and other reactive oxygen species (ROS) such as hydrogen peroxide in regulation of normal bone turnover during development and also in the r...

  6. Correlation between Mitochondrial Reactive Oxygen and Severity of Atherosclerosis.

    PubMed

    Dorighello, Gabriel G; Paim, Bruno A; Kiihl, Samara F; Ferreira, Mônica S; Catharino, Rodrigo R; Vercesi, Anibal E; Oliveira, Helena C F

    2016-01-01

    Atherosclerosis has been associated with mitochondria dysfunction and damage. Our group demonstrated previously that hypercholesterolemic mice present increased mitochondrial reactive oxygen (mtROS) generation in several tissues and low NADPH/NADP+ ratio. Here, we investigated whether spontaneous atherosclerosis in these mice could be modulated by treatments that replenish or spare mitochondrial NADPH, named citrate supplementation, cholesterol synthesis inhibition, or both treatments simultaneously. Robust statistical analyses in pooled group data were performed in order to explain the variation of atherosclerosis lesion areas as related to the classic atherosclerosis risk factors such as plasma lipids, obesity, and oxidative stress, including liver mtROS. Using three distinct statistical tools (univariate correlation, adjusted correlation, and multiple regression) with increasing levels of stringency, we identified a novel significant association and a model that reliably predicts the extent of atherosclerosis due to variations in mtROS. Thus, results show that atherosclerosis lesion area is positively and independently correlated with liver mtROS production rates. Based on these findings, we propose that modulation of mitochondrial redox state influences the atherosclerosis extent.

  7. Blue-Light Inhibition of Listeria monocytogenes Growth Is Mediated by Reactive Oxygen Species and Is Influenced by σB and the Blue-Light Sensor Lmo0799

    PubMed Central

    O'Donoghue, Beth; NicAogáin, Kerrie; Bennett, Claire; Conneely, Alan; Tiensuu, Teresa; Johansson, Jörgen

    2016-01-01

    ABSTRACT Listeria monocytogenes senses blue light via the flavin mononucleotide-containing sensory protein Lmo0799, leading to activation of the general stress response sigma factor SigB (σB). In this study, we investigated the physiological response of this foodborne pathogen to blue light. We show that blue light (460 to 470 nm) doses of 1.5 to 2 mW cm−2 cause inhibition of growth on agar-based and liquid culture media. The inhibitory effects are dependent on cell density, with reduced effects evident when high cell numbers are present. The addition of 20 mM dimethylthiourea, a scavenger of reactive oxygen species, or catalase to the medium reverses the inhibitory effects of blue light, suggesting that growth inhibition is mediated by the formation of reactive oxygen species. A mutant strain lacking σB (ΔsigB) was found to be less inhibited by blue light than the wild type, likely indicating the energetic cost of deploying the general stress response. When a lethal dose of light (8 mW cm−2) was applied to cells, the ΔsigB mutant displayed a marked increase in sensitivity to light compared to the wild type. To investigate the role of the blue-light sensor Lmo0799, mutants were constructed that either had a deletion of the gene (Δlmo0799) or alteration in a conserved cysteine residue at position 56, which is predicted to play a pivotal role in the photocycle of the protein (lmo0799 C56A). Both mutants displayed phenotypes similar to the ΔsigB mutant in the presence of blue light, providing genetic evidence that residue 56 is critical for light sensing in L. monocytogenes. Taken together, these results demonstrate that L. monocytogenes is inhibited by blue light in a manner that depends on reactive oxygen species, and they demonstrate clear light-dependent phenotypes associated with σB and the blue-light sensor Lmo0799. IMPORTANCE Listeria monocytogenes is a bacterial foodborne pathogen that can cause life-threatening infections in humans. It is known to

  8. Nebivolol prevents ethanol-induced reactive oxygen species generation and lipoperoxidation in the rat kidney by regulating NADPH oxidase activation and expression.

    PubMed

    do Vale, Gabriel T; Gonzaga, Natália A; Simplicio, Janaina A; Tirapelli, Carlos R

    2017-03-15

    We studied whether the β 1 -adrenergic antagonist nebivolol would prevent ethanol-induced reactive oxygen species generation and lipoperoxidation in the rat renal cortex. Male Wistar rats were treated with ethanol (20% v/v) for 2 weeks. Nebivolol (10mg/kg/day; p.o. gavage) prevented both the increase in superoxide anion (O 2 - ) generation and thiobarbituric acid reactive substances (TBARS) concentration induced by ethanol in the renal cortex. Ethanol decreased nitrate/nitrite (NOx) concentration in the renal cortex, and nebivolol prevented this response. Nebivolol did not affect the reduction of hydrogen peroxide (H 2 O 2 ) concentration induced by ethanol. Nebivolol prevented the ethanol-induced increase of catalase (CAT) activity. Both SOD activity and the levels of reduced glutathione (GSH) were not affected by treatment with nebivolol or ethanol. Neither ethanol nor nebivolol affected the expression of Nox1, Nox4, eNOS, nNOS, CAT, Nox organizer 1 (Noxo1), c-Src, p47 phox or superoxide dismutase (SOD) isoforms in the renal cortex. On the other hand, treatment with ethanol increased Nox2 expression, and nebivolol prevented this response. Finally, nebivolol reduced the expression of protein kinase (PK) Cδ and Rac1. The major finding of our study is that nebivolol prevented ethanol-induced reactive oxygen species generation and lipoperoxidation in the kidney by a mechanism that involves reduction on the expression of Nox2, a catalytic subunit of NADPH oxidase. Additionally, we demonstrated that nebivolol reduces NADPH oxidase-derived reactive oxygen species by decreasing the expression of PKCδ and Rac1, which are important activators of NADPH oxidase. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Using Paraquat to Generate Anion Free Radicals and Hydrogen Peroxide in "In Vitro": Antioxidant Effect of Vitamin E--A Procedure to Teach Theoretical and Experimental Principles of Reactive Oxygen Species Biochemistry

    ERIC Educational Resources Information Center

    Jimenez-Del-Rio, Marlene; Suarez-Cedeno, Gerson; Velez-Pardo, Carlos

    2010-01-01

    The theoretical basis of reactive oxygen species and their impact on health issues are relatively easy to understand by biomedical students. The detection of reactive oxygen species requires expensive equipment, the procedures are time consuming and costly, and the results are hard to interpret. Moreover, cause-and-effect relationships in the…

  10. Functional links between stability and reactivity of strontium ruthenate single crystals during oxygen evolution

    NASA Astrophysics Data System (ADS)

    Chang, Seo Hyoung; Danilovic, Nemanja; Chang, Kee-Chul; Subbaraman, Ram; Paulikas, Arvydas P.; Fong, Dillon D.; Highland, Matthew J.; Baldo, Peter M.; Stamenkovic, Vojislav R.; Freeland, John W.; Eastman, Jeffrey A.; Markovic, Nenad M.

    2014-06-01

    In developing cost-effective complex oxide materials for the oxygen evolution reaction, it is critical to establish the missing links between structure and function at the atomic level. The fundamental and practical implications of the relationship on any oxide surface are prerequisite to the design of new stable and active materials. Here we report an intimate relationship between the stability and reactivity of oxide catalysts in exploring the reaction on strontium ruthenate single-crystal thin films in alkaline environments. We determine that for strontium ruthenate films with the same conductance, the degree of stability, decreasing in the order (001)>(110)>(111), is inversely proportional to the activity. Both stability and reactivity are governed by the potential-induced transformation of stable Ru4+ to unstable Run>4+. This ordered(Ru4+)-to-disordered(Run>4+) transition and the development of active sites for the reaction are determined by a synergy between electronic and morphological effects.

  11. Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

    PubMed Central

    Montezano, Augusto C.

    2014-01-01

    Abstract Significance: Reactive oxygen species (ROS) are signaling molecules that are important in physiological processes, including host defense, aging, and cellular homeostasis. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in the onset and/or progression of chronic diseases, including hypertension. Recent Advances: Although oxidative stress may not be the only cause of hypertension, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors, such as salt loading, activation of the renin-angiotensin-aldosterone system, and sympathetic hyperactivity, at least in experimental models. A major source for ROS in the cardiovascular-renal system is a family of nicotinamide adenine dinucleotide phosphate oxidases (Noxs), including the prototypic Nox2-based Nox, and Nox family members: Nox1, Nox4, and Nox5. Critical Issues: Although extensive experimental data support a role for increased ROS levels and altered redox signaling in the pathogenesis of hypertension, the role in clinical hypertension is unclear, as a direct causative role of ROS in blood pressure elevation has yet to be demonstrated in humans. Nevertheless, what is becoming increasingly evident is that abnormal ROS regulation and aberrant signaling through redox-sensitive pathways are important in the pathophysiological processes which is associated with vascular injury and target-organ damage in hypertension. Future Directions: There is a paucity of clinical information related to the mechanisms of oxidative stress and blood pressure elevation, and a few assays accurately measure ROS directly in patients. Such further ROS research is needed in humans and in the development of adequately validated analytical methods to accurately assess oxidative stress in the clinic. Antioxid. Redox Signal. 20, 164–182. PMID:23600794

  12. Reactive Oxygen Species Inactivation of Surfactant Involves Structural and Functional Alterations to Surfactant Proteins SP-B and SP-C

    PubMed Central

    Rodríguez-Capote, Karina; Manzanares, Dahis; Haines, Thomas; Possmayer, Fred

    2006-01-01

    Exposing bovine lipid extract surfactant (BLES), a clinical surfactant, to reactive oxygen species arising from hypochlorous acid or the Fenton reaction resulted in an increase in lipid (conjugated dienes, lipid aldehydes) and protein (carbonyls) oxidation products and a reduction in surface activity. Experiments where oxidized phospholipids (PL) were mixed with BLES demonstrated that this addition hampered BLES biophysical activity. However the effects were only moderately greater than with control PL. These results imply a critical role for protein oxidation. BLES oxidation by either method resulted in alterations in surfactant proteins SP-B and SP-C, as evidenced by altered Coomassie blue and silver staining. Western blot analyses showed depressed reactivity with specific antibodies. Oxidized SP-C showed decreased palmitoylation. Reconstitution experiments employing PL, SP-B, and SP-C isolated from control or oxidized BLES demonstrated that protein oxidation was more deleterious than lipid oxidation. Furthermore, addition of control SP-B can improve samples containing oxidized SP-C, but not vice versa. We conclude that surfactant oxidation arising from reactive oxygen species generated by air pollution or leukocytes interferes with surfactant function through oxidation of surfactant PL and proteins, but that protein oxidation, in particular SP-B modification, produces the major deleterious effects. PMID:16443649

  13. Reactive Oxygen Species in Metabolic and Inflammatory Signaling.

    PubMed

    Forrester, Steven J; Kikuchi, Daniel S; Hernandes, Marina S; Xu, Qian; Griendling, Kathy K

    2018-03-16

    Reactive oxygen species (ROS) are well known for their role in mediating both physiological and pathophysiological signal transduction. Enzymes and subcellular compartments that typically produce ROS are associated with metabolic regulation, and diseases associated with metabolic dysfunction may be influenced by changes in redox balance. In this review, we summarize the current literature surrounding ROS and their role in metabolic and inflammatory regulation, focusing on ROS signal transduction and its relationship to disease progression. In particular, we examine ROS production in compartments such as the cytoplasm, mitochondria, peroxisome, and endoplasmic reticulum and discuss how ROS influence metabolic processes such as proteasome function, autophagy, and general inflammatory signaling. We also summarize and highlight the role of ROS in the regulation metabolic/inflammatory diseases including atherosclerosis, diabetes mellitus, and stroke. In order to develop therapies that target oxidative signaling, it is vital to understand the balance ROS signaling plays in both physiology and pathophysiology, and how manipulation of this balance and the identity of the ROS may influence cellular and tissue homeostasis. An increased understanding of specific sources of ROS production and an appreciation for how ROS influence cellular metabolism may help guide us in the effort to treat cardiovascular diseases. © 2018 American Heart Association, Inc.

  14. Piperine impairs cell cycle progression and causes reactive oxygen species-dependent apoptosis in rectal cancer cells.

    PubMed

    Yaffe, Paul B; Doucette, Carolyn D; Walsh, Mark; Hoskin, David W

    2013-02-01

    Piperine, an alkaloid phytochemical found in the fruit of black and long pepper plants, is reported to inhibit the growth of cancer cells; however, the mechanism of action in human cancer cells is not clear. In this study we investigated the effect of piperine on the growth of HRT-18 human rectal adenocarcinoma cells. MTT assays showed that piperine inhibited the metabolic activity of HRT-18 cells in a dose- and time-dependent fashion, suggesting a cytostatic and/or cytotoxic effect. Flow cytometric analysis of Oregon Green 488-stained and propidium iodide-stained HRT-18 cells showed that piperine inhibited cell cycle progression. Piperine also caused HRT-18 cells to die by apoptosis, as determined by Annexin-V-FLUOS staining and characteristic changes in cell morphology. Flow cytometric analysis of dihydroethidium- and 2',7'-dichlorofluorescein diacetate-stained HRT-18 cells showed increased production of reactive oxygen species in piperine-treated cells. Furthermore, the antioxidant N-acetylcysteine reduced apoptosis in cultures of piperine-treated HRT-18 cells, indicating that piperine-induced cytotoxicity was mediated at least in part by reactive oxygen species. The cytostatic and cytotoxic effects of piperine on rectal cancer cells suggest that this dietary phytochemical may be useful in cancer treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Reactive Oxygen Species (ROS): Beneficial Companions of Plants’ Developmental Processes

    PubMed Central

    Singh, Rachana; Singh, Samiksha; Parihar, Parul; Mishra, Rohit K.; Tripathi, Durgesh K.; Singh, Vijay P.; Chauhan, Devendra K.; Prasad, Sheo M.

    2016-01-01

    Reactive oxygen species (ROS) are generated inevitably in the redox reactions of plants, including respiration and photosynthesis. In earlier studies, ROS were considered as toxic by-products of aerobic pathways of the metabolism. But in recent years, concept about ROS has changed because they also participate in developmental processes of plants by acting as signaling molecules. In plants, ROS regulate many developmental processes such as cell proliferation and differentiation, programmed cell death, seed germination, gravitropism, root hair growth and pollen tube development, senescence, etc. Despite much progress, a comprehensive update of advances in the understanding of the mechanisms evoked by ROS that mediate in cell proliferation and development are fragmentry and the matter of ROS perception and the signaling cascade remains open. Therefore, keeping in view the above facts, an attempt has been made in this article to summarize the recent findings regarding updates made in the regulatory action of ROS at various plant developmental stages, which are still not well-known. PMID:27729914

  16. REACTIVE OXYGEN SPECIES IN WHOLE BLOOD, BLOOD PLASMA AND BREAST MILK: VALIDATION OF A POTENTIAL MARKER OF EXPOSURE AND EFFECT

    EPA Science Inventory

    Reactive oxygen species (ROS) are recognized to contribute to the pathobiology of many diseases. We have applied a simple chemiluminescent (CL) probe to detect ROS in various biological fluids (plasma, whole blood, urine and breast milk) in an environmental arsenic drinking wate...

  17. Enhanced reactive oxygen species through direct copper sulfide nanoparticle-doxorubicin complexation

    NASA Astrophysics Data System (ADS)

    Li, Yajuan; Cupo, Michela; Guo, Liangran; Scott, Julie; Chen, Yi-Tzai; Yan, Bingfang; Lu, Wei

    2017-12-01

    CuS-based nanostructures loading the chemotherapeutic agent doxorubicin (DOX) exerted excellent cancer photothermal chemotherapy under multi-external stimuli. The DOX loading was generally designed through electrostatic interaction or chemical linkers. However, the interaction between DOX molecules and CuS nanoparticles has not been investigated. In this work, we use PEGylated hollow copper sulfide nanoparticles (HCuSNPs) to directly load DOX through the DOX/Cu2+ chelation process. Distinctively, the synthesized PEG-HCuSNPs-DOX release the DOX/Cu2+ complexes into surrounding environment, which generate significant reactive oxygen species (ROS) in a controlled manner by near-infrared laser. The CuS nanoparticle-mediated photothermal ablation facilitates the ROS-induced cancer cell killing effect. Our current work reveals a DOX/Cu2+-mediated ROS-enhanced cell-killing effect in addition to conventional photothermal chemotherapy through the direct CuS nanoparticle-DOX complexation.

  18. Nitrating reactive nitric oxygen species transform acetaminophen to 3-nitroacetaminophen.

    PubMed

    Lakshmi, V M; Hsu, F F; Davis, B B; Zenser, T V

    2000-09-01

    Nitrating reactive nitric oxygen species (RNOS) elicit many of the deleterious effects of the inflammatory response. Their high reactivity and short half-life make RNOS analysis difficult. Reaction of acetaminophen (APAP) with RNOS generated by various conditions was evaluated by HPLC. When [(14)C]APAP was incubated at pH 7.4, the same new product (3NAP) was produced by at least three separate pathways represented by the following conditions: myeloperoxidase oxidation of NO(2)(-), NO(2)Cl, and ONOO(-) or Sin-1. Diethylamine NONO and spermine NONO did not convert APAP to 3NAP. 3NAP was stable at pH 5, 7.4, or 9, and at pH 7.4 with ONOO(-), spermine NONO, Sin-1, or H(2)O(2). HOCl transformed 3NAP, which was prevented by APAP, ascorbic acid, taurine, or NO(2)(-). ONOO(-)-derived 3NAP was identified by (1)H NMR as 3-nitroacetaminophen or 3-nitro-N-acetyl-p-aminophenol, and the product mass was verified by EI/ESI mass spectrometry. Human polymorphonuclear neutrophils incubated with [(14)C]APAP and stimulated with beta-phorbol 12-myristate 13-acetate produced 3NAP in the presence of NO(2)(-). Neutrophil 3NAP formation was verified by mass spectrometry and was consistent with myeloperoxidase oxidation of NO(2)(-). Spermine NONO supported 3NAP formation by stimulated cells in the absence of NO(2)(-). Results demonstrate that 3NAP is a product of nitrating RNOS generated by at least three separate pathways and may be a biomarker for nitrating mediators of inflammation.

  19. Kinetic modeling of α-hydrogen abstractions from unsaturated and saturated oxygenate compounds by hydrogen atoms.

    PubMed

    Paraskevas, Paschalis D; Sabbe, Maarten K; Reyniers, Marie-Françoise; Papayannakos, Nikos G; Marin, Guy B

    2014-10-09

    Hydrogen-abstraction reactions play a significant role in thermal biomass conversion processes, as well as regular gasification, pyrolysis, or combustion. In this work, a group additivity model is constructed that allows prediction of reaction rates and Arrhenius parameters of hydrogen abstractions by hydrogen atoms from alcohols, ethers, esters, peroxides, ketones, aldehydes, acids, and diketones in a broad temperature range (300-2000 K). A training set of 60 reactions was developed with rate coefficients and Arrhenius parameters calculated by the CBS-QB3 method in the high-pressure limit with tunneling corrections using Eckart tunneling coefficients. From this set of reactions, 15 group additive values were derived for the forward and the reverse reaction, 4 referring to primary and 11 to secondary contributions. The accuracy of the model is validated upon an ab initio and an experimental validation set of 19 and 21 reaction rates, respectively, showing that reaction rates can be predicted with a mean factor of deviation of 2 for the ab initio and 3 for the experimental values. Hence, this work illustrates that the developed group additive model can be reliably applied for the accurate prediction of kinetics of α-hydrogen abstractions by hydrogen atoms from a broad range of oxygenates.

  20. Reactive oxygen species production, induced by atmospheric modification, alter conidial quality of Beauveria bassiana.

    PubMed

    Pérez-Guzmán, D; Montesinos-Matías, R; Arce-Cervantes, O; Gómez-Quiroz, L E; Loera, O; Garza-López, P M

    2016-08-01

    The aim of this study was to determine the relationship between reactive oxygen species (ROS) production and conidial infectivity in Beauveria bassiana. Beauveria bassiana Bb 882.5 was cultured in solid-state culture (SSC) using rice under three oxygen conditions (21%, or pulses at 16 and 26%). Hydrophobicity was determined using exclusion phase assay. Bioassays with larvae or adults of Tenebrio molitor allowed the measurements of infectivity parameters. A fluorometric method was used for ROS quantification (superoxide and total peroxides). NADPH oxidase (NOX) activity was determined by specific inhibition. Conidial hydrophobicity decreased by O2 pulses. Mortality of larvae was only achieved with conidia harvested from cultures under 21% O2 ; whereas for adult insects, the infectivity parameters deteriorated in conidia obtained after pulses at 16 and 26% O2 . At day 7, ROS production increased after 16 and 26% O2 treatments. NOX activity induced ROS production at early stages of the culture. Modification of atmospheric oxygen increases ROS production, reducing conidial quality and infectivity. This is the first study in which conidial infectivity and ROS production in B. bassiana has been related, enhancing the knowledge of the effect of O2 pulses in B. bassiana. © 2016 The Society for Applied Microbiology.

  1. Surface-Selective Preferential Production of Reactive Oxygen Species on Piezoelectric Ceramics for Bacterial Killing.

    PubMed

    Tan, Guoxin; Wang, Shuangying; Zhu, Ye; Zhou, Lei; Yu, Peng; Wang, Xiaolan; He, Tianrui; Chen, Junqi; Mao, Chuanbin; Ning, Chengyun

    2016-09-21

    Reactive oxygen species (ROS) can be used to kill bacterial cells, and thus the selective generation of ROS from material surfaces is an emerging direction in antibacterial material discovery. We found the polarization of piezoelectric ceramic causes the two sides of the disk to become positively and negatively charged, which translate into cathode and anode surfaces in an aqueous solution. Because of the microelectrolysis of water, ROS are preferentially formed on the cathode surface. Consequently, the bacteria are selectively killed on the cathode surface. However, the cell experiment suggested that the level of ROS is safe for normal mammalian cells.

  2. Reperfusion injury and reactive oxygen species: The evolution of a concept☆

    PubMed Central

    Granger, D. Neil; Kvietys, Peter R.

    2015-01-01

    Reperfusion injury, the paradoxical tissue response that is manifested by blood flow-deprived and oxygen-starved organs following the restoration of blood flow and tissue oxygenation, has been a focus of basic and clinical research for over 4-decades. While a variety of molecular mechanisms have been proposed to explain this phenomenon, excess production of reactive oxygen species (ROS) continues to receive much attention as a critical factor in the genesis of reperfusion injury. As a consequence, considerable effort has been devoted to identifying the dominant cellular and enzymatic sources of excess ROS production following ischemia-reperfusion (I/R). Of the potential ROS sources described to date, xanthine oxidase, NADPH oxidase (Nox), mitochondria, and uncoupled nitric oxide synthase have gained a status as the most likely contributors to reperfusion-induced oxidative stress and represent priority targets for therapeutic intervention against reperfusion-induced organ dysfunction and tissue damage. Although all four enzymatic sources are present in most tissues and are likely to play some role in reperfusion injury, priority and emphasis has been given to specific ROS sources that are enriched in certain tissues, such as xanthine oxidase in the gastrointestinal tract and mitochondria in the metabolically active heart and brain. The possibility that multiple ROS sources contribute to reperfusion injury in most tissues is supported by evidence demonstrating that redox-signaling enables ROS produced by one enzymatic source (e.g., Nox) to activate and enhance ROS production by a second source (e.g., mitochondria). This review provides a synopsis of the evidence implicating ROS in reperfusion injury, the clinical implications of this phenomenon, and summarizes current understanding of the four most frequently invoked enzymatic sources of ROS production in post-ischemic tissue. PMID:26484802

  3. Effect of ectomycorrhizal colonization and drought on reactive oxygen species metabolism of Nothofagus dombeyi roots.

    PubMed

    Alvarez, Maricel; Huygens, Dries; Fernandez, Carlos; Gacitúa, Yessy; Olivares, Erick; Saavedra, Isabel; Alberdi, Miren; Valenzuela, Eduardo

    2009-08-01

    Infection with ectomycorrhizal fungi can increase the ability of plants to resist drought stress through morphophysiological and biochemical mechanisms. However, the metabolism of antioxidative enzyme activities in the ectomycorrhizal symbiosis remains poorly understood. This study investigated biomass production, reactive oxygen metabolism (hydrogen peroxide and malondialdehyde concentration) and antioxidant enzyme activity (superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase) in pure cultures of the ectomycorrhizal fungi Descolea antartica Sing. and Pisolithus tinctorius (Pers.) Coker & Couch, and non-mycorrhizal and mycorrhizal roots of Nothofagus dombeyi (Mirb.) roots under well-watered conditions and drought conditions (DC). The studied ectomycorrhizal fungi regulated their antioxidative enzyme metabolism differentially in response to drought, resulting in cellular damage in D. antartica but not in P. tinctorius. Ectomycorrhizal inoculation and water treatment had a significant effect on all parameters studied, including relative water content of the plant. As such, N. dombeyi plants in symbiosis experienced a lower oxidative stress effect than non-mycorrhizal plants under DC. Additionally, ectomycorrhizal N. dombeyi roots showed a greater antioxidant enzyme activity relative to non-mycorrhizal roots, an effect which was further expressed under DC. The association between the non-specific P. tinctorius and N. dombeyi had a more effective reactive oxygen species (ROS) metabolism than the specific D. antartica-N. dombeyi symbiosis. We conclude that the combination of effective ROS prevention and ROS detoxification by ectomycorrhizal plants resulted in reduced cellular damage and increased plant growth relative to non-mycorrhizal plants under drought.

  4. Differential effects of temperature on reactive oxygen/nitrogen species production in rat pachytene spermatocytes and round spermatids.

    PubMed

    Pino, José A; Osses, Nelson; Oyarzún, Daniela; Farías, Jorge G; Moreno, Ricardo D; Reyes, Juan G

    2013-02-01

    Reactive oxygen species (ROS) and reactive nitrogen species (RNS) like superoxide and nitric oxide are produced by testis and spermatogenic cells in response to heat stress. However, the magnitude and mechanisms of this production in spermatogenic cells have not been described. In this work, we evaluated ROS/RNS production, its pharmacology, mitochondrial oxidative metabolism, membrane potential and antioxidant capacity at different temperatures in isolated rat pachytene spermatocytes and round spermatids. Our results showed an increment in ROS/RNS production by pachytene spermatocytes when increasing the temperature to 40 °C. Instead, ROS/RNS production by round spermatids did not change at temperatures higher than 33 °C. ROS/RNS production was sensitive to NADPH oxidase inhibitor diphenylene iodonium or the mitochondrial complex I inhibitor rotenone. No additive effects were observed for these two compounds. Our results suggest an important mitochondrial ROS/RNS production in spermatogenic cells. Oligomycin-insensitive oxygen consumption (uncoupled oxygen consumption) increased with temperature and was significantly larger in round spermatids than pachytene spermatocytes, indicating a likely round spermatid mitochondrial uncoupling at high temperatures. A similar conclusion can be reached by measuring the mitochondrial membrane potential using rhodamine 123 fluorescence in permeabilized cells or JC-1 fluorescence in intact cells. The antioxidant capacity was higher in round spermatids than pachytene spermatocytes at 40 °C. Our results strongly suggest that at high temperatures (40 °C) pachytene spermatocytes are more susceptible to oxidative stress, but round spermatids are more protected because of a temperature-induced mitochondrial uncoupling together with a larger antioxidant capacity.

  5. Induction of molecular endpoints by reactive oxygen species in human lung cells predicted by physical chemical properties of engineered nanoparticles

    EPA Science Inventory

    A series of six titanium dioxide and two cerium oxide engineered nanomaterials were assessed for their ability to induce cytotoxicity, reactive oxygen species (ROS), and various types of DNA and protein damage in human respiratory BEAS-2B cells exposed in vitro for 72 hours at se...

  6. The role of reactive oxygen species in the degradation of lignin derived dissolved organic matter

    NASA Astrophysics Data System (ADS)

    Waggoner, Derek C.; Wozniak, Andrew S.; Cory, Rose M.; Hatcher, Patrick G.

    2017-07-01

    Evidence suggests that reactive oxygen species (ROS) are important in transforming the chemical composition of the large pool of terrestrially-derived dissolved organic matter (DOM) exported from land to water annually. However, due to the challenges inherent in isolating the effects of individual ROS on DOM composition, the role of ROS in the photochemical alteration of DOM remains poorly characterized. In this work, terrestrial DOM was independently exposed to singlet oxygen (1O2), and superoxide (O2-rad under controlled laboratory conditions). Using ultra-high resolution mass spectrometry to track molecular level alterations of DOM by ROS, these findings suggest exposure to 1O2 (generated using Rose Bengal and visible light) removed formulas with an O/C > 0.3, and primarily resulted in DOM comprised of formulas with higher oxygen content, while O2-rad exposure (from KO2 in DMSO) removed formulas with O/C < 0.3 and produced aliphatic formulas (H/C > 1.5). Comparison of DOM altered by ROS in this study to riverine and coastal DOM showed that (20-80%) overlap in formulas, providing evidence for the role of ROS in shaping the composition of DOM exported from rivers to oceans.

  7. WETTING AND REACTIVE AIR BRAZING OF BSCF FOR OXYGEN SEPARATION DEVICES

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    LaDouceur, Richard M.; Meier, Alan; Joshi, Vineet V.

    Reactive air brazes Ag-CuO and Ag-V2O5 were evaluated for brazing Ba0.5Sr0.5Co0.8Fe0.2O(3-δ) (BSCF). BSCF has been determined in previous work to have the highest potential mixed ionic/electronic conducting (MIEC) ceramic material based on the design and oxygen flux requirements of an oxy-fuel plant such as an integrated gasification combined cycle (IGCC) used to facilitate high-efficiency carbon capture. Apparent contact angles were observed for Ag-CuO and Ag-V2O5 mixtures at 1000 °C for isothermal hold times of 0, 10, 30, and 60 minutes. Wetting apparent contact angles (θ<90°) were obtained for 1%, 2%, and 5% Ag-CuO and Ag-V2O5 mixtures, with the apparent contactmore » angles between 74° and 78° for all compositions and furnace dwell times. Preliminary microstructural analysis indicates that two different interfacial reactions are occurring: Ag-CuO interfacial microstructures revealed the same dissolution of copper oxide into the BSCF matrix to form copper-cobalt-oxygen rich dissolution products along the BSCF grain boundaries and Ag-V2O5 interfacial microstructures revealed the infiltration and replacement of cobalt and iron with vanadium and silver filling pores in the BSCF microstructure. The Ag-V2O5 interfacial reaction product layer was measured to be significantly thinner than the Ag-CuO reaction product layer. Using a fully articulated four point flexural bend test fixture, the flexural fracture strength for BSCF was determined to be 95 ± 33 MPa. The fracture strength will be used to ascertain the success of the reactive air braze alloys. Based on these results, brazes were fabricated and mechanically tested to begin to optimize the brazing parameters for this system. Ag-2.5% CuO braze alloy with a 2.5 minute thermal cycle achieved a hermetic seal with a joint flexural strength of 34 ± 15 MPa and Ag-1% V2O5 with a 30 minute thermal cycle had a joint flexural strength of 20 ± 15 MPa.« less

  8. Extra-Cellular But Extra-Ordinarily Important for Cells: Apoplastic Reactive Oxygen Species Metabolism

    PubMed Central

    Podgórska, Anna; Burian, Maria; Szal, Bożena

    2017-01-01

    Reactive oxygen species (ROS), by their very nature, are highly reactive, and it is no surprise that they can cause damage to organic molecules. In cells, ROS are produced as byproducts of many metabolic reactions, but plants are prepared for this ROS output. Even though extracellular ROS generation constitutes only a minor part of a cell’s total ROS level, this fraction is of extraordinary importance. In an active apoplastic ROS burst, it is mainly the respiratory burst oxidases and peroxidases that are engaged, and defects of these enzymes can affect plant development and stress responses. It must be highlighted that there are also other less well-known enzymatic or non-enzymatic ROS sources. There is a need for ROS detoxification in the apoplast, and almost all cellular antioxidants are present in this space, but the activity of antioxidant enzymes and the concentration of low-mass antioxidants is very low. The low antioxidant efficiency in the apoplast allows ROS to accumulate easily, which is a condition for ROS signaling. Therefore, the apoplastic ROS/antioxidant homeostasis is actively engaged in the reception and reaction to many biotic and abiotic stresses. PMID:28878783

  9. Influence of reactive oxygen species during deposition of iron oxide films by high power impulse magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Stranak, V.; Hubicka, Z.; Cada, M.; Bogdanowicz, R.; Wulff, H.; Helm, C. A.; Hippler, R.

    2018-03-01

    Iron oxide films were deposited using high power impulse magnetron sputtering (HiPIMS) of an iron cathode in an argon/oxygen gas mixture at different gas pressures (0.5 Pa, 1.5 Pa, and 5.0 Pa). The HiPIMS system was operated at a repetition frequency f  =  100 Hz with a duty cycle of 1%. A main goal is a comparison of film growth during conventional and electron cyclotron wave resonance-assisted HiPIMS. The deposition plasma was investigated by means of optical emission spectroscopy and energy-resolved mass spectrometry. Active oxygen species were detected and their kinetic energy was found to depend on the gas pressure. Deposited films were characterized by means of spectroscopic ellipsometry and grazing incidence x-ray diffraction. Optical properties and crystallinity of as-deposited films were found to depend on the deposition conditions. Deposition of hematite iron oxide films with the HiPIMS-ECWR discharge is attributed to the enhanced production of reactive oxygen species.

  10. Interfacial microstructure and shear strength of reactive air brazed oxygen transport membrane ceramic-metal alloy joints

    NASA Astrophysics Data System (ADS)

    FR, Wahid Muhamad; Yoon, Dang-Hyok; Raju, Kati; Kim, Seyoung; Song, Kwang-sup; Yu, Ji Haeng

    2018-01-01

    To fabricate a multi-layered structure for maximizing oxygen production, oxygen transport membrane (OTM) ceramics need to be joined or sealed hermetically metal supports for interfacing with the peripheral components of the system. Therefore, in this study, Ag-10 wt% CuO was evaluated as an effective filler material for the reactive air brazing of dense Ce0.9Gd0.1O2-δ-La0.7Sr0.3MnO3±δ (GDC-LSM) OTM ceramics. Thermal decomposition in air and wetting behavior of the braze filler was performed. Reactive air brazing was performed at 1050 °C for 30 min in air to join GDC-LSM with four different commercially available high temperature-resistant metal alloys, such as Crofer 22 APU, Inconel 600, Fecralloy, and AISI 310S. The microstructure and elemental distribution of the ceramic-ceramic and ceramic-metal interfaces were examined from polished cross-sections. The mechanical shear strength at room temperature for the as-brazed and isothermally aged (800 °C for 24 h) joints of all the samples was compared. The results showed that the strength of the ceramic-ceramic joints was decreased marginally by aging; however, in the case of metal-ceramic joints, different decreases in strengths were observed according to the metal alloy used, which was explained based on the formation of different oxide layers at the interfaces.

  11. Mitochondrial Reactive Oxygen Species Trigger Hypoxia-Induced Transcription

    NASA Astrophysics Data System (ADS)

    Chandel, N. S.; Maltepe, E.; Goldwasser, E.; Mathieu, C. E.; Simon, M. C.; Schumacker, P. T.

    1998-09-01

    Transcriptional activation of erythropoietin, glycolytic enzymes, and vascular endothelial growth factor occurs during hypoxia or in response to cobalt chloride (CoCl2) in Hep3B cells. However, neither the mechanism of cellular O2 sensing nor that of cobalt is fully understood. We tested whether mitochondria act as O2 sensors during hypoxia and whether hypoxia and cobalt activate transcription by increasing generation of reactive oxygen species (ROS). Results show (i) wild-type Hep3B cells increase ROS generation during hypoxia (1.5% O2) or CoCl2 incubation, (ii) Hep3B cells depleted of mitochondrial DNA (ρ 0 cells) fail to respire, fail to activate mRNA for erythropoietin, glycolytic enzymes, or vascular endothelial growth factor during hypoxia, and fail to increase ROS generation during hypoxia; (iii) ρ 0 cells increase ROS generation in response to CoCl2 and retain the ability to induce expression of these genes; and (iv) the antioxidants pyrrolidine dithiocarbamate and ebselen abolish transcriptional activation of these genes during hypoxia or CoCl2 in wild-type cells, and abolish the response to CoCl2 in ρ 0 cells. Thus, hypoxia activates transcription via a mitochondria-dependent signaling process involving increased ROS, whereas CoCl2 activates transcription by stimulating ROS generation via a mitochondria-independent mechanism.

  12. Copper-Exchanged Zeolite L Traps Oxygen

    NASA Technical Reports Server (NTRS)

    Sharma, Pramod K.; Seshan, Panchalam K.

    1991-01-01

    Brief series of simple chemical treatments found to enhance ability of zeolite to remove oxygen from mixture of gases. Thermally stable up to 700 degrees C and has high specific surface area which provides high capacity for adsorption of gases. To increase ability to adsorb oxygen selectively, copper added by ion exchange, and copper-exchanged zeolite reduced with hydrogen. As result, copper dispersed atomically on inner surfaces of zeolite, making it highly reactive to oxygen, even at room temperature. Reactivity to oxygen even greater at higher temperatures.

  13. Real-Time In Vivo Monitoring of Reactive Oxygen Species in Guard Cells.

    PubMed

    Park, Ky Young; Roubelakis-Angelakis, Kalliopi A

    2018-01-01

    The intra-/intercellular homeostasis of reactive oxygen species (ROS), and especially of superoxides (O 2 .- ) and hydrogen peroxide (O 2 .- ) participate in signalling cascades which dictate developmental processes and reactions to biotic/abiotic stresses. Polyamine oxidases terminally oxidize/back convert polyamines generating H 2 O 2 . Recently, an NADPH-oxidase/Polyamine oxidase feedback loop was identified to control oxidative burst under salinity. Thus, the real-time localization/monitoring of ROS in specific cells, such as the guard cells, can be of great interest. Here we present a detailed description of the real-time in vivo monitoring of ROS in the guard cells using H 2 O 2 - and O 2 .- specific fluorescing probes, which can be used for studying ROS accumulation generated from any source, including the amine oxidases-dependent pathway, during development and stress.

  14. IGF-I enhances cellular senescence via the reactive oxygen species-p53 pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Cellular senescence plays an important role in tumorigenesis and aging process. Black-Right-Pointing-Pointer We demonstrated IGF-I enhanced cellular senescence in primary confluent cells. Black-Right-Pointing-Pointer IGF-I enhanced cellular senescence in the ROS and p53-dependent manner. Black-Right-Pointing-Pointer These results may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. -- Abstract: Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated {beta}-galactosidase (SA-{beta}-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the presentmore » study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, {gamma}H2AX, the increased levels of p53 and p21 proteins, and activated SA-{beta}-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-{beta}-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.« less

  15. Heme Amplifies the Innate Immune Response to Microbial Molecules through Spleen Tyrosine Kinase (Syk)-dependent Reactive Oxygen Species Generation*

    PubMed Central

    Fernandez, Patricia L.; Dutra, Fabianno F.; Alves, Letícia; Figueiredo, Rodrigo T.; Mourão-Sa, Diego; Fortes, Guilherme B.; Bergstrand, Sophie; Lönn, David; Cevallos, Ricardo R.; Pereira, Renata M. S.; Lopes, Ulisses G.; Travassos, Leonardo H.; Paiva, Claudia N.; Bozza, Marcelo T.

    2010-01-01

    Infectious diseases that cause hemolysis are among the most threatening human diseases, because of severity and/or global distribution. In these conditions, hemeproteins and heme are released, but whether heme affects the inflammatory response to microorganism molecules remains to be characterized. Here, we show that heme increased the lethality and cytokine secretion induced by LPS in vivo and enhanced the secretion of cytokines by macrophages stimulated with various agonists of innate immune receptors. Activation of nuclear factor κB (NF-κB) and MAPKs and the generation of reactive oxygen species were essential to the increase in cytokine production induced by heme plus LPS. This synergistic effect of heme and LPS was blocked by a selective inhibitor of spleen tyrosine kinase (Syk) and was abrogated in dendritic cells deficient in Syk. Moreover, inhibition of Syk and the downstream molecules PKC and PI3K reduced the reactive oxygen species generation by heme. Our results highlight a mechanism by which heme amplifies the secretion of cytokines triggered by microbial molecule activation and indicates possible pathways for therapeutic intervention during hemolytic infectious diseases. PMID:20729208

  16. Novel interactions of mitochondria and reactive oxygen/nitrogen species in alcohol mediated liver disease

    PubMed Central

    Mantena, Sudheer K; King, Adrienne L; Andringa, Kelly K; Landar, Aimee; Darley-Usmar, Victor; Bailey, Shannon M

    2007-01-01

    Mitochondrial dysfunction is known to be a contributing factor to a number of diseases including chronic alcohol induced liver injury. While there is a detailed understanding of the metabolic pathways and proteins of the liver mitochondrion, little is known regarding how changes in the mitochondrial proteome may contribute to the development of hepatic pathologies. Emerging evidence indicates that reactive oxygen and nitrogen species disrupt mitochondrial function through post-translational modifications to the mitochondrial proteome. Indeed, various new affinity labeling reagents are available to test the hypothesis that post-translational modification of proteins by reactive species contributes to mitochondrial dysfunction and alcoholic fatty liver disease. Specialized proteomic techniques are also now available, which allow for identification of defects in the assembly of multi-protein complexes in mitochondria and the resolution of the highly hydrophobic proteins of the inner membrane. In this review knowledge gained from the study of changes to the mitochondrial proteome in alcoholic hepatotoxicity will be described and placed into a mechanistic framework to increase understanding of the role of mitochondrial dysfunction in liver disease. PMID:17854139

  17. Laccase and its role in production of extracellular reactive oxygen species during wood decay by the brown rot basidiomycete Postia placenta

    Treesearch

    Dongsheng Wei; Carl J. Houtman; Alexander N. Kapich; Christopher G. Hunt; Daniel Cullen; Kenneth E. Hammel

    2010-01-01

    Brown rot basidiomycetes initiate wood decay by producing extracellular reactive oxygen species that depolymerize the structural polysaccharides of lignocellulose. Secreted fungal hydroquinones are considered one contributor because they have been shown to reduce Fe3+, thus generating perhydroxyl radicals and Fe2+, which...

  18. Reactive Oxygen Species/Nitric Oxide Mediated Inter-Organ Communication in Skeletal Muscle Wasting Diseases

    PubMed Central

    Leitner, Lucia M.; Wilson, Rebecca J.; Yan, Zhen

    2017-01-01

    Abstract Significance: Cachexia is defined as a complex metabolic syndrome that is associated with underlying illness and a loss of muscle with or without loss of fat mass. This disease is associated with a high incidence with chronic diseases such as heart failure, cancer, chronic obstructive pulmonary disease (COPD), and acquired immunodeficiency syndrome (AIDS), among others. Since there is currently no effective treatment available, cachectic patients have a poor prognosis. Elucidation of the underlying mechanisms is, therefore, an important medical task. Recent Advances: There is accumulating evidence that the diseased organs such as heart, lung, kidney, or cancer tissue secrete soluble factors, including Angiotensin II, myostatin (growth differentiation factor 8 [GDF8]), GDF11, tumor growth factor beta (TGFβ), which act on skeletal muscle. There, they induce a set of genes called atrogenes, which, among others, induce the ubiquitin-proteasome system, leading to protein degradation. Moreover, elevated reactive oxygen species (ROS) levels due to modulation of NADPH oxidases (Nox) and mitochondrial function contribute to disease progression, which is characterized by loss of muscle mass, exercise resistance, and frailty. Critical issues: Although substantial progress was achieved to elucidate the pathophysiology of cachexia, effectice therapeutic strategies are urgently needed. Future Directions: With the identification of key components of the aberrant inter-organ communication leading to cachexia, studies in mice and men to inhibit ROS formation, induction of anti-oxidative superoxide dismutases, and upregulation of muscular nitric oxide (NO) formation either by pharmacological tools or by exercise are promising approaches to reduce the extent of skeletal muscle wasting. Antioxid. Redox Signal. 26, 700–717. PMID:27835923

  19. BCI induces apoptosis via generation of reactive oxygen species and activation of intrinsic mitochondrial pathway in H1299 lung cancer cells.

    PubMed

    Shin, Jong-Woon; Kwon, Sae-Bom; Bak, Yesol; Lee, Sang-Ku; Yoon, Do-Young

    2018-03-28

    The compound (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI) is known as an inhibitor of dual specific phosphatase 1/6 and mitogen-activated protein kinase. However, its precise anti-lung cancer mechanism remains unknown. In this study, the effects of BCI on the viability of non-small cell lung cancer cell lines NCI-H1299, A549, and NCI-H460 were evaluated. We confirmed that BCI significantly inhibited the viability of p53(-) NCI-H1299 cells as compared to NCI-H460 and A549 cells, which express wild-type p53. Furthermore, BCI treatment increased the level of cellular reactive oxygen species and pre-treatment of cells with N-acetylcysteine markedly attenuated BCI-mediated apoptosis of NCI-H1299 cells. BCI induced cellular morphological changes, inhibited viability, and produced reactive oxygen species in NCI-H1299 cells in a dose-dependent manner. BCI induced processing of caspase-9, caspase-3, and poly ADP-ribose polymerase as well as the release of cytochrome c from the mitochondria into the cytosol. In addition, BCI downregulated Bcl-2 expression and enhanced Bax expression in a dose-dependent manner in NCI-H1299 cells. However, BCI failed to modulate the expression of the death receptor and extrinsic factor caspase-8 and Bid, a linker between the intrinsic and extrinsic apoptotic pathways in NCI-H1299 cells. Thus, BCI induces apoptosis via generation of reactive oxygen species and activation of the intrinsic pathway in NCI-H1299 cells.

  20. Hypothalamic Apelin/Reactive Oxygen Species Signaling Controls Hepatic Glucose Metabolism in the Onset of Diabetes

    PubMed Central

    Drougard, Anne; Duparc, Thibaut; Brenachot, Xavier; Carneiro, Lionel; Gouazé, Alexandra; Fournel, Audren; Geurts, Lucie; Cadoudal, Thomas; Prats, Anne-Catherine; Pénicaud, Luc; Vieau, Didier; Lesage, Jean; Leloup, Corinne; Benani, Alexandre; Cani, Patrice D.; Valet, Philippe

    2014-01-01

    Abstract Aims: We have previously demonstrated that central apelin is implicated in the control of peripheral glycemia, and its action depends on nutritional (fast versus fed) and physiological (normal versus diabetic) states. An intracerebroventricular (icv) injection of a high dose of apelin, similar to that observed in obese/diabetic mice, increase fasted glycemia, suggesting (i) that apelin contributes to the establishment of a diabetic state, and (ii) the existence of a hypothalamic to liver axis. Using pharmacological, genetic, and nutritional approaches, we aim at unraveling this system of regulation by identifying the hypothalamic molecular actors that trigger the apelin effect on liver glucose metabolism and glycemia. Results: We show that icv apelin injection stimulates liver glycogenolysis and gluconeogenesis via an over-activation of the sympathetic nervous system (SNS), leading to fasted hyperglycemia. The effect of central apelin on liver function is dependent of an increased production of hypothalamic reactive oxygen species (ROS). These data are strengthened by experiments using lentiviral vector-mediated over-expression of apelin in hypothalamus of mice that present over-activation of SNS associated to an increase in hepatic glucose production. Finally, we report that mice fed a high-fat diet present major alterations of hypothalamic apelin/ROS signaling, leading to activation of glycogenolysis. Innovation/Conclusion: These data bring compelling evidence that hypothalamic apelin is one master switch that participates in the onset of diabetes by directly acting on liver function. Our data support the idea that hypothalamic apelin is a new potential therapeutic target to treat diabetes. Antioxid. Redox Signal. 20, 557–573. PMID:23879244

  1. The Determination and Analysis of Site-Specific Rates of Mitochondrial Reactive Oxygen Species Production

    PubMed Central

    Quinlan, Casey L.; Perevoschikova, Irina V.; Goncalves, Renata L.S.; Hey-Mogensen, Martin; Brand, Martin D.

    2014-01-01

    Mitochondrial reactive oxygen species (ROS) are widely implicated in physiological and pathological pathways. We propose that it is critical to understand the specific sites of mitochondrial ROS production and their mechanisms of action. Mitochondria possess at least eight distinct sites of ROS production in the electron transport chain and matrix compartment. In this chapter, we describe the nature of the mitochondrial ROS-producing machinery and the relative capacities of each site. We provide detailed methods for the measurement of H2O2 release and the conditions under which maximal rates from each site can be achieved in intact skeletal muscle mitochondria. PMID:23791102

  2. Reactive oxygen species generation in aqueous solutions containing GdVO4:Eu3+ nanoparticles and their complexes with methylene blue

    NASA Astrophysics Data System (ADS)

    Hubenko, Kateryna; Yefimova, Svetlana; Tkacheva, Tatyana; Maksimchuk, Pavel; Borovoy, Igor; Klochkov, Vladimir; Kavok, Nataliya; Opolonin, Oleksander; Malyukin, Yuri

    2018-04-01

    It this letter, we report the study of free radicals and reactive oxygen species (ROS) generation in water solutions containing gadolinium orthovanadate GdVO4:Eu3+ nanoparticles (VNPs) and their complexes with methylene blue (MB) photosensitizer. The catalytic activity was studied under UV-Vis and X-ray irradiation by three methods (conjugated dienes test, OH· radical, and singlet oxygen detection). It has been shown that the VNPs-MB complexes reveal high efficiency of ROS generation under UV-Vis irradiation associated with both high efficiency of OH· radicals generation by VNPs and singlet oxygen generation by MB due to nonradiative excitation energy transfer from VNPs to MB molecules. Contrary to that under X-ray irradiation, the strong OH . radicals scavenging by VNPs has been observed.

  3. Reactive oxygen species generation in aqueous solutions containing GdVO4:Eu3+ nanoparticles and their complexes with methylene blue.

    PubMed

    Hubenko, Kateryna; Yefimova, Svetlana; Tkacheva, Tatyana; Maksimchuk, Pavel; Borovoy, Igor; Klochkov, Vladimir; Kavok, Nataliya; Opolonin, Oleksander; Malyukin, Yuri

    2018-04-13

    It this letter, we report the study of free radicals and reactive oxygen species (ROS) generation in water solutions containing gadolinium orthovanadate GdVO 4 :Eu 3+ nanoparticles (VNPs) and their complexes with methylene blue (MB) photosensitizer. The catalytic activity was studied under UV-Vis and X-ray irradiation by three methods (conjugated dienes test, OH· radical, and singlet oxygen detection). It has been shown that the VNPs-MB complexes reveal high efficiency of ROS generation under UV-Vis irradiation associated with both high efficiency of OH· radicals generation by VNPs and singlet oxygen generation by MB due to nonradiative excitation energy transfer from VNPs to MB molecules. Contrary to that under X-ray irradiation, the strong OH . radicals scavenging by VNPs has been observed.

  4. The challenges of using fluorescent probes to detect and quantify specific reactive oxygen species in living cells.

    PubMed

    Winterbourn, Christine C

    2014-02-01

    Small molecule fluorescent probes are vital tools for monitoring reactive oxygen species in cells. The types of probe available, the extent to which they are specific or quantitative and complications in interpreting results are discussed. Most commonly used probes (e.g. dihydrodichlorofluorescein, dihydrorhodamine) have some value in providing information on changes to the redox environment of the cell, but they are not specific for any one oxidant and the response is affected by numerous chemical interactions and not just increased oxidant generation. These probes generate the fluorescent end product by a free radical mechanism, and to react with hydrogen peroxide they require a metal catalyst. Probe radicals can react with oxygen, superoxide, and various antioxidant molecules, all of which influence the signal. Newer generation probes such as boronates act by a different mechanism in which nucleophilic attack by the oxidant on a blocking group releases masked fluorescence. Boronates react with hydrogen peroxide, peroxynitrite, hypochlorous acid and in some cases superoxide, so are selective but not specific. They react with hydrogen peroxide very slowly, and kinetic considerations raise questions about how the reaction could occur in cells. Data from oxidant-sensitive fluorescent probes can provide some information on cellular redox activity but is widely misinterpreted. Recently developed non-redox probes show promise but are not generally available and more information on specificity and cellular reactions is needed. We do not yet have probes that can quantify cellular production of specific oxidants. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Generation of reactive oxygen species by a novel berberine–bile acid analog mediates apoptosis in hepatocarcinoma SMMC-7721 cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Qingyong, E-mail: li_qingyong@126.com; Zhang, Li; Zu, Yuangang

    2013-04-19

    Graphical abstract: - Highlights: • Anticancer effects of B4, a novel berberine–bile acid analog, were tested. • B4 inhibited cell proliferation in hepatocellular carcinoma cells. • It also stimulated mitochondrial ROS production and membrane depolarization. • Effects of B4 were inhibited by a non-specific ROS scavenger. • Regulation of ROS generation may be a strategy for treating hepatic carcinoma. - Abstract: 2,3-Methenedioxy-9-O-(3′α,7′α-dihydroxy-5′β-cholan-24′-propy-lester) berberine (B4) is a novel berberine–bile acid analog synthesized in our laboratory. Previously, we showed that B4 exerted greater cytotoxicity than berberine in several human cancer cell lines. Therefore, we further evaluated the mechanism governing its anticancer actionsmore » in hepatocellular carcinoma SMMC-7721 cells. B4 inhibited the proliferation of SMMC-7721 cells, and stimulated reactive oxygen species (ROS) production and mitochondrial membrane depolarization; anti-oxidant capacity was reduced. B4 also induced the release of cytochrome c from the mitochondria to the cytosol and an increase in poly ADP-ribose polymerase (PARP) cleavage products, reflective of caspase-3 activation. Moreover, B4 induced the nuclear translocation of apoptosis-inducing factor (AIF) and a rise in DNA fragmentation. Pretreatment with the anti-oxidant N-acetylcysteine (NAC) inhibited B4-mediated effects, including cytotoxicity, ROS production, mitochondrial membrane depolarization increase in intracellular Ca{sup 2+}, cytochrome c release, PARP cleavage, and AIF translocation. Our data suggest that B4 induces ROS-triggered caspase-dependent and caspase-independent apoptosis pathways in SMMC-7721 cells and that ROS production may be a specific potential strategy for treating hepatic carcinoma.« less

  6. Non-thermal dielectric barrier discharge plasma induces angiogenesis through reactive oxygen species.

    PubMed

    Arjunan, Krishna P; Clyne, Alisa Morss

    2011-01-01

    Vascularization plays a key role in processes such as wound healing and tissue engineering. Non-thermal plasma, which primarily produces reactive oxygen species (ROS), recently emerged as an efficient tool in medical applications. Liquids and endothelial cells were treated with a non-thermal dielectric barrier discharge plasma. Plasma treatment of phosphate buffered saline (PBS) and serum-free medium increased ROS concentration in a dose-dependent manner, with a higher concentration in serum-free medium. ROS concentration in cells peaked 1 hour after treatment. 4.2 J/cm(2) increased cell proliferation, 2D and 3D migration, as well as tube formation. A fibroblast growth factor-2 (FGF-2) neutralizing antibody and ROS scavengers for hydrogen peroxide and hydroxyl radicals abrogated these angiogenic effects. Non-thermal plasma may be a potential tool for applying ROS in precise doses to enhance vascularization.

  7. Reactive Oxygen Species-Inducible ECF σ Factors of Bradyrhizobium japonicum

    PubMed Central

    Masloboeva, Nadezda; Reutimann, Luzia; Stiefel, Philipp; Follador, Rainer; Leimer, Nadja; Hennecke, Hauke; Mesa, Socorro; Fischer, Hans-Martin

    2012-01-01

    Extracytoplasmic function (ECF) σ factors control the transcription of genes involved in different cellular functions, such as stress responses, metal homeostasis, virulence-related traits, and cell envelope structure. The genome of Bradyrhizobium japonicum, the nitrogen-fixing soybean endosymbiont, encodes 17 putative ECF σ factors belonging to nine different ECF σ factor families. The genes for two of them, ecfQ (bll1028) and ecfF (blr3038), are highly induced in response to the reactive oxygen species hydrogen peroxide (H2O2) and singlet oxygen (1O2). The ecfF gene is followed by the predicted anti-σ factor gene osrA (blr3039). Mutants lacking EcfQ, EcfF plus OsrA, OsrA alone, or both σ factors plus OsrA were phenotypically characterized. While the symbiotic properties of all mutants were indistinguishable from the wild type, they showed increased sensitivity to singlet oxygen under free-living conditions. Possible target genes of EcfQ and EcfF were determined by microarray analyses, and candidate genes were compared with the H2O2-responsive regulon. These experiments disclosed that the two σ factors control rather small and, for the most part, distinct sets of genes, with about half of the genes representing 13% of the members of H2O2-responsive regulon. To get more insight into transcriptional regulation of both σ factors, the 5′ ends of ecfQ and ecfF mRNA were determined. The presence of conserved sequence motifs in the promoter region of ecfQ and genes encoding EcfQ-like σ factors in related α-proteobacteria suggests regulation via a yet unknown transcription factor. By contrast, we have evidence that ecfF is autoregulated by transcription from an EcfF-dependent consensus promoter, and its product is negatively regulated via protein-protein interaction with OsrA. Conserved cysteine residues 129 and 179 of OsrA are required for normal function of OsrA. Cysteine 179 is essential for release of EcfF from an EcfF-OsrA complex upon H2O2 stress while

  8. Xanthohumol induces generation of reactive oxygen species and triggers apoptosis through inhibition of mitochondrial electron transfer chain complex I.

    PubMed

    Zhang, Bo; Chu, Wei; Wei, Peng; Liu, Ying; Wei, Taotao

    2015-12-01

    Xanthohumol is a prenylflavonoid extracted from hops (Humulus lupulus). It possesses anti-cancer and anti-inflammatory activities in vitro and in vivo, and offers therapeutic benefits for treatment of metabolic syndromes. However, the precise mechanisms underlying its pharmacological effects remain to be elucidated, together with its cellular target. Here, we provide evidence that xanthohumol directly interacts with the mitochondrial electron transfer chain complex I (NADH dehydrogenase), inhibits the oxidative phosphorylation, triggers the production of reactive oxygen species, and induces apoptosis. In addition, we show that as a result of the inhibition of the mitochondrial oxidative phosphorylation, xanthohumol exposure causes a rapid decrease of mitochondrial transmembrane potential. Furthermore, we showed that xanthohumol up-regulates the glycolytic capacity in cells, and thus compensates cellular ATP generation. Dissection of the multiple steps of aerobic respiration by extracellular flux assays revealed that xanthohumol specifically inhibits the activity of mitochondrial complex I, but had little effect on that of complex II, III and IV. Inhibition of complex I by xanthohumol caused the overproduction of reactive oxygen species, which are responsible for the induction of apoptosis in cancer cells. We also found that isoxanthohumol, the structural isomer of xanthohumol, is inactive to cells, suggesting that the reactive 2-hydroxyl group of xanthohumol is crucial for its targeting to the mitochondrial complex I. Together, the remodeling of cell metabolism revealed here has therapeutic potential for the use of xanthohumol. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Reactivity of chemisorbed oxygen atoms and their catalytic consequences during CH4-O2 catalysis on supported Pt clusters.

    PubMed

    Chin, Ya-Huei Cathy; Buda, Corneliu; Neurock, Matthew; Iglesia, Enrique

    2011-10-12

    Kinetic and isotopic data and density functional theory treatments provide evidence for the elementary steps and the active site requirements involved in the four distinct kinetic regimes observed during CH(4) oxidation reactions using O(2), H(2)O, or CO(2) as oxidants on Pt clusters. These four regimes exhibit distinct rate equations because of the involvement of different kinetically relevant steps, predominant adsorbed species, and rate and equilibrium constants for different elementary steps. Transitions among regimes occur as chemisorbed oxygen (O*) coverages change on Pt clusters. O* coverages are given, in turn, by a virtual O(2) pressure, which represents the pressure that would give the prevalent steady-state O* coverages if their adsorption-desorption equilibrium was maintained. The virtual O(2) pressure acts as a surrogate for oxygen chemical potentials at catalytic surfaces and reflects the kinetic coupling between C-H and O═O activation steps. O* coverages and virtual pressures depend on O(2) pressure when O(2) activation is equilibrated and on O(2)/CH(4) ratios when this step becomes irreversible as a result of fast scavenging of O* by CH(4)-derived intermediates. In three of these kinetic regimes, C-H bond activation is the sole kinetically relevant step, but occurs on different active sites, which evolve from oxygen-oxygen (O*-O*), to oxygen-oxygen vacancy (O*-*), and to vacancy-vacancy (*-*) site pairs as O* coverages decrease. On O*-saturated cluster surfaces, O*-O* site pairs activate C-H bonds in CH(4) via homolytic hydrogen abstraction steps that form CH(3) groups with significant radical character and weak interactions with the surface at the transition state. In this regime, rates depend linearly on CH(4) pressure but are independent of O(2) pressure. The observed normal CH(4)/CD(4) kinetic isotope effects are consistent with the kinetic-relevance of C-H bond activation; identical (16)O(2)-(18)O(2) isotopic exchange rates in the presence or

  10. Extracellular Production of Reactive Oxygen Species by Marine Microbiota

    NASA Astrophysics Data System (ADS)

    Schneider, R. J.; Roe, K. L.; Voelker, B. M.; Hansel, C. M.

    2016-02-01

    The reactive oxygen species (ROS) superoxide (O2-) and hydrogen peroxide (H2O2) are important to the cycling of trace metals and carbon in marine systems. Previous studies have shown that biological ROS production in the ocean may be significant. We examined the ability of five common species of diatoms to produce and break down ROS in the presence and absence of light by suspending cells on filters and measuring downstream ROS concentrations using chemiluminescence probes. Results show a wide range of rates (undetectable to 7.3 x 10-16 mol cell-1 hr-1) and suggest that extracellular ROS production occurs through a variety of pathways. H2O2 decay appears to be mediated primarily by active cell processes, while O2- appears to occur through a combination of active and passive cell processes. Extracellular H2O2 production and decay were also determined for twelve species of heterotrophic bacteria using two different methodologies. Measured decay rates were consistent despite methodological differences. By contrast, large variability of production rates was observed could vary significantly even among between replicates of the same species measured using the same methodology. Although production rates cannot be stated with certainty, it is likely that extracellular H2O2 production occurs in most bacterial species.

  11. White Blood Cells, Neutrophils, and Reactive Oxygen Metabolites among Asymptomatic Subjects.

    PubMed

    Kotani, Kazuhiko; Sakane, Naoki

    2012-06-01

    Chronic inflammation and oxidative stress are associated with health and the disease status. The objective of the present study was to investigate the association among white blood cell (WBC) counts, neutrophil counts as a WBC subpopulation, and diacron reactive oxygen metabolites (d-ROMs) levels in an asymptomatic population. The clinical data, including general cardiovascular risk variables and high-sensitivity C-reactive protein (hs-CRP), were collected from 100 female subjects (mean age, 62 years) in outpatient clinics. The correlation of the d-ROMs with hs-CRP, WBC, and neutrophil counts was examined. The mean/median levels were WBC counts 5.9 × 10(9)/L, neutrophil counts 3.6 × 10(9)/L, hs-CRP 0.06 mg/dL, and d-ROMs 359 CURR U. A simple correlation analysis showed a significant positive correlation of the d-ROMs with the WBC counts, neutrophil counts, or hs-CRP levels. The correlation between d-ROMs and neutrophil counts (β = 0.22, P < 0.05), as well as that between d-ROMs and hs-CRP (β = 0.28, P < 0.01), remained significant and independent in a multiple linear regression analysis adjusted for other variables. A multiple linear regression analysis showed that WBC counts had only a positive correlation tendency to the d-ROMs. Neutrophils may be slightly but more involved in the oxidative stress status, as assessed by d-ROMs, in comparison to the overall WBC. Further studies are needed to clarify the biologic mechanism(s) of the observed relationship.

  12. Generator-specific targets of mitochondrial reactive oxygen species.

    PubMed

    Bleier, Lea; Wittig, Ilka; Heide, Heinrich; Steger, Mirco; Brandt, Ulrich; Dröse, Stefan

    2015-01-01

    To understand the role of reactive oxygen species (ROS) in oxidative stress and redox signaling it is necessary to link their site of generation to the oxidative modification of specific targets. Here we have studied the selective modification of protein thiols by mitochondrial ROS that have been implicated as deleterious agents in a number of degenerative diseases and in the process of biological aging, but also as important players in cellular signal transduction. We hypothesized that this bipartite role might be based on different generator sites for "signaling" and "damaging" ROS and a directed release into different mitochondrial compartments. Because two main mitochondrial ROS generators, complex I (NADH:ubiquinone oxidoreductase) and complex III (ubiquinol:cytochrome c oxidoreductase; cytochrome bc1 complex), are known to predominantly release superoxide and the derived hydrogen peroxide (H2O2) into the mitochondrial matrix and the intermembrane space, respectively, we investigated whether these ROS generators selectively oxidize specific protein thiols. We used redox fluorescence difference gel electrophoresis analysis to identify redox-sensitive targets in the mitochondrial proteome of intact rat heart mitochondria. We observed that the modified target proteins were distinctly different when complex I or complex III was employed as the source of ROS. These proteins are potential targets involved in mitochondrial redox signaling and may serve as biomarkers to study the generator-dependent dual role of mitochondrial ROS in redox signaling and oxidative stress. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Calcium Signaling and Reactive Oxygen Species in Mitochondria.

    PubMed

    Bertero, Edoardo; Maack, Christoph

    2018-05-11

    In heart failure, alterations of Na + and Ca 2+ handling, energetic deficit, and oxidative stress in cardiac myocytes are important pathophysiological hallmarks. Mitochondria are central to these processes because they are the main source for ATP, but also reactive oxygen species (ROS), and their function is critically controlled by Ca 2+ During physiological variations of workload, mitochondrial Ca 2+ uptake is required to match energy supply to demand but also to keep the antioxidative capacity in a reduced state to prevent excessive emission of ROS. Mitochondria take up Ca 2+ via the mitochondrial Ca 2+ uniporter, which exists in a multiprotein complex whose molecular components were identified only recently. In heart failure, deterioration of cytosolic Ca 2+ and Na + handling hampers mitochondrial Ca 2+ uptake and the ensuing Krebs cycle-induced regeneration of the reduced forms of NADH (nicotinamide adenine dinucleotide) and NADPH (nicotinamide adenine dinucleotide phosphate), giving rise to energetic deficit and oxidative stress. ROS emission from mitochondria can trigger further ROS release from neighboring mitochondria termed ROS-induced ROS release, and cross talk between different ROS sources provides a spatially confined cellular network of redox signaling. Although low levels of ROS may serve physiological roles, higher levels interfere with excitation-contraction coupling, induce maladaptive cardiac remodeling through redox-sensitive kinases, and cell death through mitochondrial permeability transition. Targeting the dysregulated interplay between excitation-contraction coupling and mitochondrial energetics may ameliorate the progression of heart failure. © 2018 American Heart Association, Inc.

  14. Generation of Reactive Oxygen Species from Silicon Nanowires

    PubMed Central

    Leonard, Stephen S; Cohen, Guy M; Kenyon, Allison J; Schwegler-Berry, Diane; Fix, Natalie R; Bangsaruntip, Sarunya; Roberts, Jenny R

    2014-01-01

    Processing and synthesis of purified nanomaterials of diverse composition, size, and properties is an evolving process. Studies have demonstrated that some nanomaterials have potential toxic effects and have led to toxicity research focusing on nanotoxicology. About two million workers will be employed in the field of nanotechnology over the next 10 years. The unknown effects of nanomaterials create a need for research and development of techniques to identify possible toxicity. Through a cooperative effort between National Institute for Occupational Safety and Health and IBM to address possible occupational exposures, silicon-based nanowires (SiNWs) were obtained for our study. These SiNWs are anisotropic filamentary crystals of silicon, synthesized by the vapor–liquid–solid method and used in bio-sensors, gas sensors, and field effect transistors. Reactive oxygen species (ROS) can be generated when organisms are exposed to a material causing cellular responses, such as lipid peroxidation, H2O2 production, and DNA damage. SiNWs were assessed using three different in vitro environments (H2O2, RAW 264.7 cells, and rat alveolar macrophages) for ROS generation and possible toxicity identification. We used electron spin resonance, analysis of lipid peroxidation, measurement of H2O2 production, and the comet assay to assess generation of ROS from SiNW and define possible mechanisms. Our results demonstrate that SiNWs do not appear to be significant generators of free radicals. PMID:25452695

  15. Generation of reactive oxygen species from silicon nanowires.

    PubMed

    Leonard, Stephen S; Cohen, Guy M; Kenyon, Allison J; Schwegler-Berry, Diane; Fix, Natalie R; Bangsaruntip, Sarunya; Roberts, Jenny R

    2014-01-01

    Processing and synthesis of purified nanomaterials of diverse composition, size, and properties is an evolving process. Studies have demonstrated that some nanomaterials have potential toxic effects and have led to toxicity research focusing on nanotoxicology. About two million workers will be employed in the field of nanotechnology over the next 10 years. The unknown effects of nanomaterials create a need for research and development of techniques to identify possible toxicity. Through a cooperative effort between National Institute for Occupational Safety and Health and IBM to address possible occupational exposures, silicon-based nanowires (SiNWs) were obtained for our study. These SiNWs are anisotropic filamentary crystals of silicon, synthesized by the vapor-liquid-solid method and used in bio-sensors, gas sensors, and field effect transistors. Reactive oxygen species (ROS) can be generated when organisms are exposed to a material causing cellular responses, such as lipid peroxidation, H2O2 production, and DNA damage. SiNWs were assessed using three different in vitro environments (H2O2, RAW 264.7 cells, and rat alveolar macrophages) for ROS generation and possible toxicity identification. We used electron spin resonance, analysis of lipid peroxidation, measurement of H2O2 production, and the comet assay to assess generation of ROS from SiNW and define possible mechanisms. Our results demonstrate that SiNWs do not appear to be significant generators of free radicals.

  16. Biological Activities of Reactive Oxygen and Nitrogen Species: Oxidative Stress versus Signal Transduction

    PubMed Central

    Weidinger, Adelheid; Kozlov, Andrey V.

    2015-01-01

    In the past, reactive oxygen and nitrogen species (RONS) were shown to cause oxidative damage to biomolecules, contributing to the development of a variety of diseases. However, recent evidence has suggested that intracellular RONS are an important component of intracellular signaling cascades. The aim of this review was to consolidate old and new ideas on the chemical, physiological and pathological role of RONS for a better understanding of their properties and specific activities. Critical consideration of the literature reveals that deleterious effects do not appear if only one primary species (superoxide radical, nitric oxide) is present in a biological system, even at high concentrations. The prerequisite of deleterious effects is the formation of highly reactive secondary species (hydroxyl radical, peroxynitrite), emerging exclusively upon reaction with another primary species or a transition metal. The secondary species are toxic, not well controlled, causing irreversible damage to all classes of biomolecules. In contrast, primary RONS are well controlled (superoxide dismutase, catalase), and their reactions with biomolecules are reversible, making them ideal for physiological/pathophysiological intracellular signaling. We assume that whether RONS have a signal transducing or damaging effect is primarily defined by their quality, being primary or secondary RONS, and only secondly by their quantity. PMID:25884116

  17. Multiphase composition changes and reactive oxygen species formation during limonene oxidation in the new Cambridge Atmospheric Simulation Chamber (CASC)

    NASA Astrophysics Data System (ADS)

    Gallimore, Peter J.; Mahon, Brendan M.; Wragg, Francis P. H.; Fuller, Stephen J.; Giorio, Chiara; Kourtchev, Ivan; Kalberer, Markus

    2017-08-01

    The chemical composition of organic aerosols influences their impacts on human health and the climate system. Aerosol formation from gas-to-particle conversion and in-particle reaction was studied for the oxidation of limonene in a new facility, the Cambridge Atmospheric Simulation Chamber (CASC). Health-relevant oxidising organic species produced during secondary organic aerosol (SOA) formation were quantified in real time using an Online Particle-bound Reactive Oxygen Species Instrument (OPROSI). Two categories of reactive oxygen species (ROS) were identified based on time series analysis: a short-lived component produced during precursor ozonolysis with a lifetime of the order of minutes, and a stable component that was long-lived on the experiment timescale (˜ 4 h). Individual organic species were monitored continuously over this time using Extractive Electrospray Ionisation (EESI) Mass Spectrometry (MS) for the particle phase and Proton Transfer Reaction (PTR) MS for the gas phase. Many first-generation oxidation products are unsaturated, and we observed multiphase aging via further ozonolysis reactions. Volatile products such as C9H14O (limonaketone) and C10H16O2 (limonaldehyde) were observed in the gas phase early in the experiment, before reacting again with ozone. Loss of C10H16O4 (7-hydroxy limononic acid) from the particle phase was surprisingly slow. A combination of reduced C = C reactivity and viscous particle formation (relative to other SOA systems) may explain this, and both scenarios were tested in the Pretty Good Aerosol Model (PG-AM). A range of characterisation measurements were also carried out to benchmark the chamber against existing facilities. This work demonstrates the utility of CASC, particularly for understanding the reactivity and health-relevant properties of organic aerosols using novel, highly time-resolved techniques.

  18. Effects of the oxygenation level on formation of different reactive oxygen species during photodynamic therapy.

    PubMed

    Price, Michael; Heilbrun, Lance; Kessel, David

    2013-01-01

    We examined the effect of the oxygenation level on efficacy of two photosensitizing agents, both of which target lysosomes for photodamage, but via different photochemical pathways. Upon irradiation, the chlorin termed NPe6 forms singlet oxygen in high yield while the bacteriopheophorbide WST11 forms only oxygen radicals (in an aqueous environment). Photokilling efficacy by WST11 in cell culture was impaired when the atmospheric oxygen concentration was reduced from 20% to 1%, while photokilling by NPe6 was unaffected. Studies in a cell-free system revealed that the rates of photobleaching of these agents, as a function of the oxygenation level, were correlated with results described above. Moreover, the rate of formation of oxygen radicals by either agent was more sensitive to the level of oxygenation than was singlet oxygen formation by NPe6. These data indicate that the photochemical process that leads to oxygen radical formation is more dependent on the oxygenation level than is the pathway leading to formation of singlet oxygen. © 2013 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2013 The American Society of Photobiology.

  19. Internal stress and opto-electronic properties of ZnO thin films deposited by reactive sputtering in various oxygen partial pressures

    NASA Astrophysics Data System (ADS)

    Tuyaerts, Romain; Poncelet, Olivier; Raskin, Jean-Pierre; Proost, Joris

    2017-10-01

    In this article, we propose ZnO thin films as a suitable material for piezoresistors in transparent and flexible electronics. ZnO thin films have been deposited by DC reactive magnetron sputtering at room temperature at various oxygen partial pressures. All the films have a wurtzite structure with a strong (0002) texture measured by XRD and are almost stoichiometric as measured by inductively coupled plasma optical emission spectroscopy. The effect of oxygen concentration on grain growth has been studied by in-situ multi-beam optical stress sensor, showing internal stress going from 350 MPa to -1.1 GPa. The transition between tensile and compressive stress corresponds to the transition between metallic and oxidized mode of reactive sputtering. This transition also induces a large variation in optical properties—from absorbent to transparent, and in the resistivity—from 4 × 10 - 2 Ω .cm to insulating. Finally, the piezoresistance of the thin film has been studied and showed a gauge factor (ΔR/R)/ɛ comprised between -5.8 and -8.5.

  20. Photosensitization of CdSe/ZnS QDs and reliability of assays for reactive oxygen species production.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cooper, D. R.; Dimitrijevic, N. M.; Nadeau, J. L.

    CdSe/ZnS quantum dots (QDs) conjugated to biomolecules that can act as electron donors are said to be 'photosensitized': that is, they are able to oxidize or reduce molecules whose redox potential lies inside their band edges, in particular molecular oxygen and water. This leads to the formation of reactive oxygen species (ROS) and phototoxicity. In this work, we quantify the generation of different forms of ROS from as-synthesized QDs in toluene; water-solubilized, unconjugated QDs; QDs conjugated to the neurotransmitter dopamine; and dopamine alone. Results of indirect fluorescent ROS assays, both in solution and inside cells, are compared with those ofmore » spin-trap electron paramagentic resonance spectroscopy (EPR). The effect of these particles on the metabolism of mammalian cells is shown to be dependent upon light exposure and proportional to the amount of ROS generated.« less

  1. Inorganic Polyphosphates Regulate Hexokinase Activity and Reactive Oxygen Species Generation in Mitochondria of Rhipicephalus (Boophilus) microplus Embryo

    PubMed Central

    Fraga, Amanda; Moraes, Jorge; da Silva, José Roberto; Costa, Evenilton P.; Menezes, Jackson; da Silva Vaz Jr, Itabajara; Logullo, Carlos; da Fonseca, Rodrigo Nunes; Campos, Eldo

    2013-01-01

    The physiological roles of polyphosphates (poly P) recently found in arthropod mitochondria remain obscure. Here, the possible involvement of poly P with reactive oxygen species generation in mitochondria of Rhipicephalus microplus embryos was investigated. Mitochondrial hexokinase and scavenger antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione reductase were assayed during embryogenesis of R. microplus. The influence of poly P3 and poly P15 were analyzed during the period of higher enzymatic activity during embryogenesis. Both poly Ps inhibited hexokinase activity by up to 90% and, interestingly, the mitochondrial membrane exopolyphosphatase activity was stimulated by the hexokinase reaction product, glucose-6-phosphate. Poly P increased hydrogen peroxide generation in mitochondria in a situation where mitochondrial hexokinase is also active. The superoxide dismutase, catalase and glutathione reductase activities were higher during embryo cellularization, at the end of embryogenesis and during embryo segmentation, respectively. All of the enzymes were stimulated by poly P3. However, superoxide dismutase was not affected by poly P15, catalase activity was stimulated only at high concentrations and glutathione reductase was the only enzyme that was stimulated in the same way by both poly Ps. Altogether, our results indicate that inorganic polyphosphate and mitochondrial membrane exopolyphosphatase regulation can be correlated with the generation of reactive oxygen species in the mitochondria of R. microplus embryos. PMID:23983617

  2. Serum concentrations of the derivatives of reactive oxygen metabolites (d-ROMs) in dogs with leishmaniosis.

    PubMed

    Paltrinieri, Saverio; Ravicini, Sara; Rossi, Gabriele; Roura, Xavier

    2010-12-01

    Leishmania infantum interferes with the oxidative metabolism of phagocytes. In order to assess whether derivatives of reactive oxygen metabolites (d-ROMs) decrease due to infection or increase due to inflammation, d-ROMs were measured in serum collected from control dogs (Group 1; n = 12), from dogs seropositive for Leishmania either symptomatic (Group 2; n = 27) or not (Group 3; n = 14), and from dogs with other diseases (Group 4; n = 16). The concentrations of d-ROMs in the four groups, expressed in Carratelli Units (U CARR) were, respectively, 75.4 ± 39.5 (median, 81.6), 108.2 ± 96.3 (73.4), 73.5 ± 62.2 (62.0), 127.7 ± 97.3 (94.3). There were no significant differences between groups, but dogs with values higher than the reference interval were found, mostly in Groups 2 and 4 (which had serum C-reactive protein levels consistent with inflammation), whilst low values were occasionally found in Groups 2 and 3. Inflammation may mask decreases in d-ROMs induced by Leishmania infection. Copyright © 2009 Elsevier Ltd. All rights reserved.

  3. Targeted modulation of reactive oxygen species in the vascular endothelium.

    PubMed

    Shuvaev, Vladimir V; Muzykantov, Vladimir R

    2011-07-15

    'Endothelial cells lining vascular luminal surface represent an important site of signaling and injurious effects of reactive oxygen species (ROS) produced by other cells and endothelium itself in ischemia, inflammation and other pathological conditions. Targeted delivery of ROS modulating enzymes conjugated with antibodies to endothelial surface molecules (vascular immunotargeting) provides site-specific interventions in the endothelial ROS, unattainable by other formulations including PEG-modified enzymes. Targeting of ROS generating enzymes (e.g., glucose oxidase) provides ROS- and site-specific models of endothelial oxidative stress, whereas targeting of antioxidant enzymes SOD and catalase offers site-specific quenching of superoxide anion and H(2)O(2). These targeted antioxidant interventions help to clarify specific role of endothelial ROS in vascular and pulmonary pathologies and provide basis for design of targeted therapeutics for treatment of these pathologies. In particular, antibody/catalase conjugates alleviate acute lung ischemia/reperfusion injury, whereas antibody/SOD conjugates inhibit ROS-mediated vasoconstriction and inflammatory endothelial signaling. Encapsulation in protease-resistant, ROS-permeable carriers targeted to endothelium prolongs protective effects of antioxidant enzymes, further diversifying the means for targeted modulation of endothelial ROS. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Reactive oxygen species (ROS) and cancer: Role of antioxidative nutraceuticals.

    PubMed

    Prasad, Sahdeo; Gupta, Subash C; Tyagi, Amit K

    2017-02-28

    Extensive research over the past half a century indicates that reactive oxygen species (ROS) play an important role in cancer. Although low levels of ROS can be beneficial, excessive accumulation can promote cancer. One characteristic of cancer cells that distinguishes them from normal cells is their ability to produce increased numbers of ROS and their increased dependence on an antioxidant defense system. ROS are produced as a byproduct intracellularly by mitochondria and other cellular elements and exogenously by pollutants, tobacco, smoke, drugs, xenobiotics, and radiation. ROS modulate various cell signaling pathways, which are primarily mediated through the transcription factors NF-κB and STAT3, hypoxia-inducible factor-1α, kinases, growth factors, cytokines and other proteins, and enzymes; these pathways have been linked to cellular transformation, inflammation, tumor survival, proliferation, invasion, angiogenesis, and metastasis of cancer. ROS are also associated with epigenetic changes in genes, which is helpful in diagnosing diseases. This review considers the role of ROS in the various stages of cancer development. Finally, we provide evidence that nutraceuticals derived from Mother Nature are highly effective in eliminating cancer cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Pleiotropic Effects of Biguanides on Mitochondrial Reactive Oxygen Species Production.

    PubMed

    Pecinova, Alena; Drahota, Zdenek; Kovalcikova, Jana; Kovarova, Nikola; Pecina, Petr; Alan, Lukas; Zima, Michal; Houstek, Josef; Mracek, Tomas

    2017-01-01

    Metformin is widely prescribed as a first-choice antihyperglycemic drug for treatment of type 2 diabetes mellitus, and recent epidemiological studies showed its utility also in cancer therapy. Although it is in use since the 1970s, its molecular target, either for antihyperglycemic or antineoplastic action, remains elusive. However, the body of the research on metformin effect oscillates around mitochondrial metabolism, including the function of oxidative phosphorylation (OXPHOS) apparatus. In this study, we focused on direct inhibitory mechanism of biguanides (metformin and phenformin) on OXPHOS complexes and its functional impact, using the model of isolated brown adipose tissue mitochondria. We demonstrate that biguanides nonspecifically target the activities of all respiratory chain dehydrogenases (mitochondrial NADH, succinate, and glycerophosphate dehydrogenases), but only at very high concentrations (10 -2 -10 -1  M) that highly exceed cellular concentrations observed during the treatment. In addition, these concentrations of biguanides also trigger burst of reactive oxygen species production which, in combination with pleiotropic OXPHOS inhibition, can be toxic for the organism. We conclude that the beneficial effect of biguanides should probably be associated with subtler mechanism, different from the generalized inhibition of the respiratory chain.

  6. Reactive oxygen species in response of plants to gravity stress

    NASA Astrophysics Data System (ADS)

    Jadko, Sergiy

    2016-07-01

    Reactive oxygen species (ROS) as second messengers can induce stress response of plants. Thioredoxins (Trx) and peroxiredoxins (Prx) can function as sensors and transmitters of the ROS in stress signaling and antioxidant response. 12-14 days old tissue culture of Arabidopsis thaliana have been investigated. Hypergravity stress was induced by centrifugation at 10 and 20 g during 30 and 90 min and than intensity of spontaneous chemiluminescence (SChL/ROS content), Trx and Prx activities were determined. All experiments were repeated from 3 to 5 times and the obtained data were statistically treated. In the tissue culture under development of the stress there were an increase in intensity of SChL and Trx and Prx activities. Thus, under hypergravity stress in the plant occurred early increase in the ROS level and the ROS induced the increase in the Trx and Prx activities. Prx and Trx can also participate in the formation of stress respons as acceptors and transducers of the redox signals. Increase in the activity of these enzymes primarily aimed at increasing of the total antioxidant activity in the cells to prevent of the plant to development of oxidative degradation by ROS.

  7. Regulation of signal transduction by reactive oxygen species in the cardiovascular system.

    PubMed

    Brown, David I; Griendling, Kathy K

    2015-01-30

    Oxidative stress has long been implicated in cardiovascular disease, but more recently, the role of reactive oxygen species (ROS) in normal physiological signaling has been elucidated. Signaling pathways modulated by ROS are complex and compartmentalized, and we are only beginning to identify the molecular modifications of specific targets. Here, we review the current literature on ROS signaling in the cardiovascular system, focusing on the role of ROS in normal physiology and how dysregulation of signaling circuits contributes to cardiovascular diseases, including atherosclerosis, ischemia-reperfusion injury, cardiomyopathy, and heart failure. In particular, we consider how ROS modulate signaling pathways related to phenotypic modulation, migration and adhesion, contractility, proliferation and hypertrophy, angiogenesis, endoplasmic reticulum stress, apoptosis, and senescence. Understanding the specific targets of ROS may guide the development of the next generation of ROS-modifying therapies to reduce morbidity and mortality associated with oxidative stress. © 2015 American Heart Association, Inc.

  8. Ionized gas (plasma) delivery of reactive oxygen species (ROS) into artificial cells

    NASA Astrophysics Data System (ADS)

    Hong, Sung-Ha; Szili, Endre J.; Jenkins, A. Toby A.; Short, Robert D.

    2014-09-01

    This study was designed to enhance our understanding of how reactive oxygen species (ROS), generated ex situ by ionized gas (plasma), can affect the regulation of signalling processes within cells. A model system, comprising of a suspension of phospholipid vesicles (cell mimics) encapsulating a ROS reporter, was developed to study the plasma delivery of ROS into cells. For the first time it was shown that plasma unequivocally delivers ROS into cells over a sustained period and without compromising cell membrane integrity. An important consideration in cell and biological assays is the presence of serum, which significantly reduced the transfer efficiency of ROS into the vesicles. These results are key to understanding how plasma treatments can be tailored for specific medical or biotechnology applications. Further, the phospholipid vesicle ROS reporter system may find use in other studies involving the application of free radicals in biology and medicine.

  9. Biosensors for spatiotemporal detection of reactive oxygen species in cells and tissues.

    PubMed

    Erard, Marie; Dupré-Crochet, Sophie; Nüße, Oliver

    2018-05-01

    Redox biology has become a major issue in numerous areas of physiology. Reactive oxygen species (ROS) have a broad range of roles from signal transduction to growth control and cell death. To understand the nature of these roles, accurate measurement of the reactive compounds is required. An increasing number of tools for ROS detection is available; however, the specificity and sensitivity of these tools are often insufficient. Furthermore, their specificity has been rarely evaluated in complex physiological conditions. Many ROS probes are sensitive to environmental conditions in particular pH, which may interfere with ROS detection and cause misleading results. Accurate detection of ROS in physiology and pathophysiology faces additional challenges concerning the precise localization of the ROS and the timing of their production and disappearance. Certain ROS are membrane permeable, and certain ROS probes move across cells and organelles. Targetable ROS probes such as fluorescent protein-based biosensors are required for accurate localization. Here we analyze these challenges in more detail, provide indications on the strength and weakness of current tools for ROS detection, and point out developments that will provide improved ROS detection methods in the future. There is no universal method that fits all situations in physiology and cell biology. A detailed knowledge of the ROS probes is required to choose the appropriate method for a given biological problem. The knowledge of the shortcomings of these probes should also guide the development of new sensors.

  10. Hexavalent chromium induces reactive oxygen species and impairs the antioxidant power of human erythrocytes and lymphocytes: Decreased metal reducing and free radical quenching ability of the cells.

    PubMed

    Husain, Nazim; Mahmood, Riaz

    2017-08-01

    The toxicity of hexavalent chromium [Cr(VI)] in biological systems is thought to be closely associated with the generation of free radicals and reactive oxygen species. These species are produced when Cr(VI) is reduced to its trivalent form in the cell. This process results in oxidative stress due to an imbalance between the detoxifying ability of the cell and the production of free radicals. We have studied the effect of potassium dichromate (K 2 Cr 2 O 7 ), a [Cr(VI)] compound, on the antioxidant power of human erythrocytes and lymphocytes under in vitro conditions. Incubation of erythrocytes and lymphocytes with different concentrations of K 2 Cr 2 O 7 resulted in a marked dose-dependent decrease in reduced glutathione and an increase in oxidized glutathione and reactive oxygen species levels. The antioxidant power of the cells was decreased, as determined by metal reducing and free radical quenching assays. These results show that [Cr(VI)] upregulates the generation of reactive oxygen species and, as a consequence, the cellular antioxidant defences are compromised. The resulting oxidative stress may contribute to Cr(VI)-induced cellular damage.

  11. Molecular mechanisms for the reaction between (˙)OH radicals and proline: insights on the role as reactive oxygen species scavenger in plant stress.

    PubMed

    Signorelli, Santiago; Coitiño, E Laura; Borsani, Omar; Monza, Jorge

    2014-01-09

    The accumulation of proline (Pro) and overproduction of reactive oxygen species (ROS) by plants exposed to stress is well-documented. In vitro assays show that enzyme inactivation by hydroxyl radicals ((•)OH) can be avoided in the presence of Pro, suggesting this amino acid might act as a (•)OH scavenger. Although production of hydroxyproline (Hyp) has been hypothesized in connection with such antioxidant activity, no evidence on the detailed mechanism of scavenging has been reported. To elucidate whether and how Hyp might be produced, we used density functional theory calculations coupled to a polarizable continuum model to explore 27 reaction channels including H-abstraction by (•)OH and (•)OH/H2O addition. The structure and energetics of stable species and transition states for each reaction channel were characterized at the PCM-(U)M06/6-31G(d,p) level in aqueous solution. Evidence is found for a main pathway in which Pro scavenges (•)OH by successive H-abstractions (ΔG(‡,298) = 4.1 and 7.5 kcal mol(-1)) to yield 3,4-Δ-Pro. A companion pathway with low barriers yielding Δ(1)-pyrroline-5-carboxylate (P5C) is also supported, linking with 5-Hyp through hydration. However, this connection remains unlikely in stressed plants because P5C would be efficiently recycled to Pro (contributing to its accumulation) by P5C reductase, hypothesis coined here as the "Pro-Pro cycle".

  12. Measuring vascular reactivity with resting-state blood oxygenation level-dependent (BOLD) signal fluctuations: A potential alternative to the breath-holding challenge?

    PubMed

    Jahanian, Hesamoddin; Christen, Thomas; Moseley, Michael E; Pajewski, Nicholas M; Wright, Clinton B; Tamura, Manjula K; Zaharchuk, Greg

    2017-07-01

    Measurement of the ability of blood vessels to dilate and constrict, known as vascular reactivity, is often performed with breath-holding tasks that transiently raise arterial blood carbon dioxide (P a CO 2 ) levels. However, following the proper commands for a breath-holding experiment may be difficult or impossible for many patients. In this study, we evaluated two approaches for obtaining vascular reactivity information using blood oxygenation level-dependent signal fluctuations obtained from resting-state functional magnetic resonance imaging data: physiological fluctuation regression and coefficient of variation of the resting-state functional magnetic resonance imaging signal. We studied a cohort of 28 older adults (69 ± 7 years) and found that six of them (21%) could not perform the breath-holding protocol, based on an objective comparison with an idealized respiratory waveform. In the subjects that could comply, we found a strong linear correlation between data extracted from spontaneous resting-state functional magnetic resonance imaging signal fluctuations and the blood oxygenation level-dependent percentage signal change during breath-holding challenge ( R 2  = 0.57 and 0.61 for resting-state physiological fluctuation regression and resting-state coefficient of variation methods, respectively). This technique may eliminate the need for subject cooperation, thus allowing the evaluation of vascular reactivity in a wider range of clinical and research conditions in which it may otherwise be impractical.

  13. Insights on the antitumor effects of kahweol on human breast cancer: Decreased survival and increased production of reactive oxygen species and cytotoxicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cárdenas, Casimiro; IBIMA; Research Support Central Services

    Highlights: • Kahweol inhibits growth and attachment-independent proliferation of tumor cells. • Kahweol induces apoptosis in MDA-MB231 human breast cancer cells. • Kahweol-induced apoptosis involves caspase activation and cytochrome c release. • Kahweol does not protect against hydrogen peroxide cytotoxicity. • Kahweol increases hydrogen peroxide production by human breast cancer cells. - Abstract: The present study aims to identify the modulatory effects of kahweol, an antioxidant diterpene present in coffee beans, on a panel of human tumor cell lines. Kahweol inhibits tumor cell proliferation and clonogenicity and induces apoptosis in several kinds of human tumor cells. In the estrogen receptor-negativemore » MDA-MB231 human breast cancer, the mentioned effects are accompanied by caspases 3/7 and 9 activation and cytochrome c release. On the other hand, kahweol increases the production of reactive oxygen species and their cytotoxicity in human breast cancer cells but not in normal cells. Taken together, our data suggest that kahweol is an antitumor compound with inhibitory effects on tumor cell growth and survival, especially against MDA-MB231 breast cancer cells.« less

  14. Effects of reactive oxygen species on sperm function.

    PubMed

    Guthrie, H D; Welch, G R

    2012-11-01

    Reactive oxygen species (ROS) formation and membrane lipid peroxidation have been recognized as problems for sperm survival and fertility. The precise roles and detection of superoxide (SO), hydrogen peroxide (HP), and membrane lipid peroxidation have been problematic, because of the low specificity and sensitivity of the established chemiluminescence assay technologies. We developed flow cytometric assays to measure SO, HP, membrane lipid peroxidation, and inner mitochondrial transmembrane potential in boar sperm. These methods were sufficiently sensitive to permit detection of early changes in ROS formation in sperm cells that were still viable. Basal ROS formation and membrane lipid peroxidation in the absence of ROS generators were low in viable sperm of both fresh and frozen-thawed boar semen, affecting less than 4% of the sperm cells on average. However, this is not the case in other species, as human, bovine, and poultry sperm have large increases in sperm ROS formation, lipid peroxidation, loss of motility, and death in vitro. Closer study of the effects of ROS formation on the relationship between sperm motility and ATP content in boar sperm was conducted using menadione (mitochondrial SO generator) and HP treatment. Menadione or HP caused an immediate disruption of motility with delayed or no decrease in sperm ATP content, respectively. Overall, the inhibitory effects of ROS on motility point to a mitochondrial-independent mechanism. The reduction in motility may have been due to a ROS-induced lesion in ATP utilization or in the contractile apparatus of the flagellum. Published by Elsevier Inc.

  15. Variation in levels of reactive oxygen species is explained by maternal identity, sex and body-size-corrected clutch size in a lizard

    NASA Astrophysics Data System (ADS)

    Olsson, Mats; Wilson, Mark; Uller, Tobias; Mott, Beth; Isaksson, Caroline

    2009-01-01

    Many organisms show differences between males and females in growth rate and crucial life history parameters, such as longevity. Considering this, we may expect levels of toxic metabolic by-products of the respiratory chain, such as reactive oxygen species (ROS), to vary with age and sex. Here, we analyse ROS levels in female Australian painted dragon lizards ( Ctenophorus pictus) and their offspring using fluorescent probes and flow cytometry. Basal level of four ROS species (singlet oxygen, peroxynitrite, superoxide and H2O2) measured with a combined marker, and superoxide measured specifically, varied significantly among families but not between the sexes. When blood cells from offspring were chemically encouraged to accelerate the electron transport chain by mitochondrial uncoupling, net superoxide levels were three times higher in daughters than sons (resulting in levels outside of the normal ROS range) and varied among mothers depending on offspring sex (significant interaction between maternal identity and offspring sex). In offspring, there were depressive effects on ROS of size-controlled relative clutch size, which relies directly on circulating levels of vitellogenin, a confirmed antioxidant in some species. Thus, levels of reactive oxygen species varies among females, offspring and in relation to reproductive investment in a manner that makes its regulatory processes likely targets of selection.

  16. Global Profiling of Reactive Oxygen and Nitrogen Species in Biological Systems

    PubMed Central

    Zielonka, Jacek; Zielonka, Monika; Sikora, Adam; Adamus, Jan; Joseph, Joy; Hardy, Micael; Ouari, Olivier; Dranka, Brian P.; Kalyanaraman, Balaraman

    2012-01-01

    Herein we describe a high-throughput fluorescence and HPLC-based methodology for global profiling of reactive oxygen and nitrogen species (ROS/RNS) in biological systems. The combined use of HPLC and fluorescence detection is key to successful implementation and validation of this methodology. Included here are methods to specifically detect and quantitate the products formed from interaction between the ROS/RNS species and the fluorogenic probes, as follows: superoxide using hydroethidine, peroxynitrite using boronate-based probes, nitric oxide-derived nitrosating species with 4,5-diaminofluorescein, and hydrogen peroxide and other oxidants using 10-acetyl-3,7-dihydroxyphenoxazine (Amplex® Red) with and without horseradish peroxidase, respectively. In this study, we demonstrate real-time monitoring of ROS/RNS in activated macrophages using high-throughput fluorescence and HPLC methods. This global profiling approach, simultaneous detection of multiple ROS/RNS products of fluorescent probes, developed in this study will be useful in unraveling the complex role of ROS/RNS in redox regulation, cell signaling, and cellular oxidative processes and in high-throughput screening of anti-inflammatory antioxidants. PMID:22139901

  17. The Effect of Reactive Oxygen Species on Embryo Quality in IVF.

    PubMed

    Siristatidis, Charalampos; Vogiatzi, Paraskevi; Varounis, Christos; Askoxylaki, Marily; Chrelias, Charalampos; Papantoniou, Nikolaos

    2016-01-01

    BACKROUND/AIM: Reactive oxygen species (ROS) are involved in critical biological processes in human reproduction. The aim of this study was to evaluate the association of embryo quality following in vitro fertilization (IVF), with ROS levels in the serum and follicular fluid (FF). Eighty-five participants underwent ovarian stimulation and IVF; ROS levels were measured in blood samples on the day of oocyte retrieval and in the FF from follicular aspirates using enzyme-linked immunosorbent assay. These values were associated with the quality of embryos generated. Univariable zero-inflated Poisson model revealed that ROS levels at both oocyte retrieval and in FF were not associated with the number of grade I, II, III and IV embryos (p>0.05). Age, body mass index, stimulation protocol and smoking status were not associated with the number of embryos of any grade (p>0.05). Neither ROS levels in serum nor in FF are associated with the quality of embryos produced following IVF. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Singlet oxygen generation as a major cause for parasitic reactions during cycling of aprotic lithium-oxygen batteries

    NASA Astrophysics Data System (ADS)

    Mahne, Nika; Schafzahl, Bettina; Leypold, Christian; Leypold, Mario; Grumm, Sandra; Leitgeb, Anita; Strohmeier, Gernot A.; Wilkening, Martin; Fontaine, Olivier; Kramer, Denis; Slugovc, Christian; Borisov, Sergey M.; Freunberger, Stefan A.

    2017-03-01

    Non-aqueous metal-oxygen batteries depend critically on the reversible formation/decomposition of metal oxides on cycling. Irreversible parasitic reactions cause poor rechargeability, efficiency, and cycle life, and have predominantly been ascribed to the reactivity of reduced oxygen species with cell components. These species, however, cannot fully explain the side reactions. Here we show that singlet oxygen forms at the cathode of a lithium-oxygen cell during discharge and from the onset of charge, and accounts for the majority of parasitic reaction products. The amount increases during discharge, early stages of charge, and charging at higher voltages, and is enhanced by the presence of trace water. Superoxide and peroxide appear to be involved in singlet oxygen generation. Singlet oxygen traps and quenchers can reduce parasitic reactions effectively. Awareness of the highly reactive singlet oxygen in non-aqueous metal-oxygen batteries gives a rationale for future research towards achieving highly reversible cell operation.

  19. Reactive oxygen metabolites (ROMs) are associated with cardiovascular disease in chronic hemodialysis patients.

    PubMed

    Bossola, Maurizio; Vulpio, Carlo; Colacicco, Luigi; Scribano, Donata; Zuppi, Cecilia; Tazza, Luigi

    2012-02-11

    The aim of our study was to measure reactive oxygen metabolites (ROMs) in chronic hemodialysis (HD) patients and evaluate the possible association with cardiovascular disease (CVD) and mortality. We measured ROMs in 76 HD patients and correlated with CVD, cardiovascular (CV) events in the follow-up and all-cause and CVD-related mortality. The levels of ROMs presented a median value of 270 (238.2-303.2) CARR U (interquartile range). We created a ROC curve (ROMs levels vs. CVD) and we identified a cut-off point of 273 CARR U. Patients with ROMs levels ≥273 CARR U were significantly older, had higher C-reactive protein levels and lower creatinine concentrations. The prevalence of CVD was higher in patients with ROMs levels ≥273 (87.1%) than in those with ROMs levels <273 CARR U (17.7%; p<0.0001). ROMs levels were significantly higher in patients with CVD (317±63.8) than in those without (242.7±49.1; p<0.0001). At multiple regression analysis, age, creatinine and C-reactive protein were independent factors associated with ROMs. At multiple logistic regression analysis the association between ROMs and CVD was independent (OR: 1.02, 95% CI: 1.00-1.05; p=0.03). Twenty six patients developed cardiovascular (CV) events during the follow-up. Of these, seven were in the group with ROMs levels <273 CARR U and 19 in the group with ROMs levels ≥273 CARR U. The logistic regression analysis showed that both age (OR: 1.06, 95% CI: 1.01-1.12; p=0.013) and ROMs levels (OR: 1.10, 95% CI: 1.00-1.02; p=0.045) were independently associated with CV events in the follow-up. ROMs are independently associated with CVD and predict CV events in chronic HD patients.

  20. Reactive oxygen species are involved in lipopolysaccharide-induced intrauterine growth restriction and skeletal development retardation in mice.

    PubMed

    Xu, De-Xiang; Chen, Yuan-Hua; Zhao, Lei; Wang, Hua; Wei, Wei

    2006-12-01

    Maternal infection is a cause of adverse developmental outcomes including embryonic resorption, intrauterine fetal death, and preterm labor. Lipopolysaccharide-induced developmental toxicity at early gestational stages has been well characterized. The purpose of the present study was to investigate the effects of maternal lipopolysaccharide exposure at late gestational stages on intrauterine fetal growth and skeletal development and to assess the potential role of reactive oxygen species in lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation. The timed pregnant CD-1 mice were intraperitoneally injected with lipopolysaccharide (25 to 75 microg/kg per day) on gestational day 15 to 17. To investigate the role of reactive oxygen species on lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation, the pregnant mice were injected with alpha-phenyl-N-t-butylnitrone (100 mg/kg, intraperitoneally) at 30 minutes before lipopolysaccharide (75 microg/kg per day, intraperitoneally), followed by an additional dose of alpha-phenyl-N-t-butylnitrone (50 mg/kg, intraperitoneally) at 3 hours after lipopolysaccharide. The number of live fetuses, dead fetuses, and resorption sites was counted on gestational day 18. Live fetuses in each litter were weighed. Crown-rump and tail lengths were examined and skeletal development was evaluated. Maternal lipopolysaccharide exposure significantly increased fetal mortality, reduced fetal weight and crown-rump and tail lengths of live fetuses, and retarded skeletal ossification in caudal vertebrae, anterior and posterior phalanges, and supraoccipital bone in a dose-dependent manner. Alpha-phenyl-N-t-butylnitrone, a free radical spin-trapping agent, almost completely blocked lipopolysaccharide-induced fetal death (63.2% in lipopolysaccharide group versus 6.5% in alpha-phenyl-N-t-butylnitrone + lipopolysaccharide group, P < .01). In addition, alpha

  1. Lysophosphatidic acid induces reactive oxygen species generation by activating protein kinase C in PC-3 human prostate cancer cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lin, Chu-Cheng; Lin, Chuan-En; Lin, Yueh-Chien

    2013-11-01

    Highlights: •LPA induces ROS generation through LPA{sub 1} and LPA{sub 3}. •LPA induces ROS generation by activating PLC. •PKCζ mediates LPA-induced ROS generation. -- Abstract: Prostate cancer is one of the most frequently diagnosed cancers in males, and PC-3 is a cell model popularly used for investigating the behavior of late stage prostate cancer. Lysophosphatidic acid (LPA) is a lysophospholipid that mediates multiple behaviors in cancer cells, such as proliferation, migration and adhesion. We have previously demonstrated that LPA enhances vascular endothelial growth factor (VEGF)-C expression in PC-3 cells by activating the generation of reactive oxygen species (ROS), which ismore » known to be an important mediator in cancer progression. Using flow cytometry, we showed that LPA triggers ROS generation within 10 min and that the generated ROS can be suppressed by pretreatment with the NADPH oxidase (Nox) inhibitor diphenylene iodonium. In addition, transfection with LPA{sub 1} and LPA{sub 3} siRNA efficiently blocked LPA-induced ROS production, suggesting that both receptors are involved in this pathway. Using specific inhibitors and siRNA, phospholipase C (PLC) and protein kinase C (PKC) were also suggested to participate in LPA-induced ROS generation. Overall, we demonstrated that LPA induces ROS generation in PC-3 prostate cancer cells and this is mediated through the PLC/PKC/Nox pathway.« less

  2. Teaching the basics of reactive oxygen species and their relevance to cancer biology: Mitochondrial reactive oxygen species detection, redox signaling, and targeted therapies.

    PubMed

    Kalyanaraman, Balaraman; Cheng, Gang; Hardy, Micael; Ouari, Olivier; Bennett, Brian; Zielonka, Jacek

    2018-05-01

    Reactive oxygen species (ROS) have been implicated in tumorigenesis (tumor initiation, tumor progression, and metastasis). Of the many cellular sources of ROS generation, the mitochondria and the NADPH oxidase family of enzymes are possibly the most prevalent intracellular sources. In this article, we discuss the methodologies to detect mitochondria-derived superoxide and hydrogen peroxide using conventional probes as well as newly developed assays and probes, and the necessity of characterizing the diagnostic marker products with HPLC and LC-MS in order to rigorously identify the oxidizing species. The redox signaling roles of mitochondrial ROS, mitochondrial thiol peroxidases, and transcription factors in response to mitochondria-targeted drugs are highlighted. ROS generation and ROS detoxification in drug-resistant cancer cells and the relationship to metabolic reprogramming are discussed. Understanding the subtle role of ROS in redox signaling and in tumor proliferation, progression, and metastasis as well as the molecular and cellular mechanisms (e.g., autophagy) could help in the development of combination therapies. The paradoxical aspects of antioxidants in cancer treatment are highlighted in relation to the ROS mechanisms in normal and cancer cells. Finally, the potential uses of newly synthesized exomarker probes for in vivo superoxide and hydrogen peroxide detection and the low-temperature electron paramagnetic resonance technique for monitoring oxidant production in tumor tissues are discussed. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Antiplatelet Aggregation Activity of Walnut Hull Extract via Suppression of Reactive Oxygen Species Generation and Caspase Activation.

    PubMed

    Meshkini, Azadeh; Tahmasbi, Masoumeh

    2017-06-01

    Walnut hull (wal hull) is an agricultural by-product that is widely used in traditional medicine for alleviating pain and treating skin diseases, however, recently it has gained much attention in modern pharmacology due to its antioxidant properties. The current study was aimed to determine the total phenolic, flavonoid, and tannin content of Persian wal hull extract and evaluate its biological effects on platelet function. Experimental data showed that acetone extract of wal hulls has a high content of polyphenolic compounds and antioxidant properties. The analytical study of crude extract by gas chromatography-mass spectrometry demonstrated different types of high- and low-molecular-weight compounds that are basically and biologically important. Moreover, an in vitro study revealed that wal hull extract at a concentration of 50 μg/mL inhibited thrombin-induced platelet aggregation and protein secretion by 50%, without any cytotoxic effects on platelets. The examined extract suppressed reactive oxygen species generation and also caspase activation in thrombin-stimulated platelets. Identically, N-acetylcysteine inhibited the increase of reactive oxygen species level induced by thrombin in platelets, and supported a link between cellular redox status and caspase activation in activated platelets. Presumably, the antiplatelet activity of wal hull extract is related to its polyphenolic compounds and their antioxidant properties. Therefore, wal hulls can be considered as a candidate for thrombotic disorders. Copyright © 2017. Published by Elsevier B.V.

  4. Mucosal reactive oxygen species decrease virulence by disrupting Campylobacter jejuni phosphotyrosine signaling

    PubMed Central

    Corcionivoschi, Nicolae; Alvarez, Luis A.; Sharp, Thomas H.; Strengert, Monika; Alemka, Abofu; Mantell, Judith; Verkade, Paul; Knaus, Ulla G.; Bourke, Billy

    2013-01-01

    Summary Reactive oxygen species (ROS) play key roles in mucosal defense, yet how they are induced and the consequences for pathogens are unclear. We report that ROS generated by epithelial NADPH oxidases (Nox1/Duox2) during Campylobacter jejuni infection impair bacterial capsule formation and virulence by altering bacterial signal transduction. Upon C. jejuni invasion, ROS released from the intestinal mucosa inhibit the bacterial phosphotyrosine network that is regulated by the outer membrane tyrosine kinase Cjtk (Cj1170/OMP50). ROS-mediated Cjtk inactivation results in an overall decrease in the phosphorylation of C. jejuni outer membrane / periplasmic proteins including UDP-GlcNAc/Glc 4-epimerase (Gne), an enzyme required for N-glycosylation and capsule formation. Cjtk positively regulates Gne by phosphorylating an active site tyrosine, while loss of Cjtk or ROS treatment inhibits Gne activity, causing altered polysaccharide synthesis. Thus, epithelial NADPH oxidases are an early antibacterial defense system in the intestinal mucosa that modifies virulence by disrupting bacterial signaling. PMID:22817987

  5. Recent developments in the role of reactive oxygen species in allergic asthma

    PubMed Central

    Qu, Jingjing; Li, Yuanyuan; Zhong, Wen

    2017-01-01

    Allergic asthma has a global prevalence, morbidity, and mortality. Many environmental factors, such as pollutants and allergens, are highly relevant to allergic asthma. The most important pathological symptom of allergic asthma is airway inflammation. Accordingly, the unique role of reactive oxygen species (ROS) had been identified as a main reason for this respiratory inflammation. Many studies have shown that inhalation of different allergens can promote ROS generation. Recent studies have demonstrated that several pro-inflammatory mediators are responsible for the development of allergic asthma. Among these mediators, endogenous or exogenous ROS are responsible for the airway inflammation of allergic asthma. Furthermore, several inflammatory cells induce ROS and allergic asthma development. Airway inflammation, airway hyper-responsiveness, tissue injury, and remodeling can be induced by excessive ROS production in animal models. Based on investigations of allergic asthma and ROS formation mechanisms, we have identified several novel anti-inflammatory therapeutic treatments. This review describes the recent data linking ROS to the pathogenesis of allergic asthma. PMID:28203435

  6. Atrial fibrillation in the elderly: the potential contribution of reactive oxygen species

    PubMed Central

    Schillinger, Kurt J.; Patel, Vickas V.

    2012-01-01

    Atrial fibrillation (AF) is the most commonly encountered cardiac arrhythmia, and is a significant source of healthcare expenditures throughout the world. It is an arrhythmia with a very clearly defined predisposition for individuals of advanced age, and this fact has led to intense study of the mechanistic links between aging and AF. By promoting oxidative damage to multiple subcellular and cellular structures, reactive oxygen species (ROS) have been shown to induce the intra- and extra-cellular changes necessary to promote the pathogenesis of AF. In addition, the generation and accumulation of ROS have been intimately linked to the cellular processes which underlie aging. This review begins with an overview of AF pathophysiology, and introduces the critical structures which, when damaged, predispose an otherwise healthy atrium to AF. The available evidence that ROS can lead to damage of these critical structures is then reviewed. Finally, the evidence linking the process of aging to the pathogenesis of AF is discussed. PMID:23341843

  7. Exopolysaccharides from Burkholderia cenocepacia inhibit neutrophil chemotaxis and scavenge reactive oxygen species.

    PubMed

    Bylund, Johan; Burgess, Lee-Anna; Cescutti, Paola; Ernst, Robert K; Speert, David P

    2006-02-03

    Bacteria belonging to the Burkholderia cepacia complex are important opportunistic pathogens in compromised hosts, particularly patients with cystic fibrosis or chronic granulomatous disease. Isolates of B. cepacia complex may produce large amounts of exopolysaccharides (EPS) that endow the bacteria with a mucoid phenotype and appear to facilitate bacterial persistence during infection. We showed that EPS from a clinical B. cenocepacia isolate interfered with the function of human neutrophils in vitro; it inhibited chemotaxis and production of reactive oxygen species (ROS), both essential components of innate neutrophil-mediated host defenses. These inhibitory effects were not due to cytotoxicity or interference with intracellular calcium signaling. EPS also inhibited enzymatic generation of ROS in cell-free systems, indicating that it scavenges these bactericidal products. B. cenocepacia EPS is structurally distinct from Pseudomonas aeruginosa alginate, yet they share the capacity to scavenge ROS and inhibit chemotaxis. These properties could explain why the two bacterial species resist clearance from the infected cystic fibrosis lung.

  8. Reactive oxygen species-related activities of nano-iron metal and nano-iron oxides.

    PubMed

    Wu, Haohao; Yin, Jun-Jie; Wamer, Wayne G; Zeng, Mingyong; Lo, Y Martin

    2014-03-01

    Nano-iron metal and nano-iron oxides are among the most widely used engineered and naturally occurring nanostructures, and the increasing incidence of biological exposure to these nanostructures has raised concerns about their biotoxicity. Reactive oxygen species (ROS)-induced oxidative stress is one of the most accepted toxic mechanisms and, in the past decades, considerable efforts have been made to investigate the ROS-related activities of iron nanostructures. In this review, we summarize activities of nano-iron metal and nano-iron oxides in ROS-related redox processes, addressing in detail the known homogeneous and heterogeneous redox mechanisms involved in these processes, intrinsic ROS-related properties of iron nanostructures (chemical composition, particle size, and crystalline phase), and ROS-related bio-microenvironmental factors, including physiological pH and buffers, biogenic reducing agents, and other organic substances. Copyright © 2014. Published by Elsevier B.V.

  9. Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases.

    PubMed

    Callaway, Danielle A; Jiang, Jean X

    2015-07-01

    Osteoclasts are cells derived from bone marrow macrophages and are important in regulating bone resorption during bone homeostasis. Understanding what drives osteoclast differentiation and activity is important when studying diseases characterized by heightened bone resorption relative to formation, such as osteoporosis. In the last decade, studies have indicated that reactive oxygen species (ROS), including superoxide and hydrogen peroxide, are crucial components that regulate the differentiation process of osteoclasts. However, there are still many unanswered questions that remain. This review will examine the mechanisms by which ROS can be produced in osteoclasts as well as how it may affect osteoclast differentiation and activity through its actions on osteoclastogenesis signaling pathways. In addition, the contribution of ROS to the aging-associated disease of osteoporosis will be addressed and how targeting ROS may lead to the development of novel therapeutic treatment options.

  10. Effect of Single Layer Centrifugation on reactive oxygen species and sperm mitochondrial membrane potential in cooled stallion semen.

    PubMed

    Morrell, J M; Lagerqvist, A; Humblot, P; Johannisson, A

    2016-04-06

    Additional means are needed for evaluating the quality of stallion spermatozoa in semen doses for AI. Mitochondrial membrane potential (ΔΨm) has been linked to fertility in some species, but is rarely used in the evaluation of cooled stallion semen; metabolic activity may be associated with reactive oxygen species production (ROS). In the present study, ΔΨm and ROS production were measured in doses of cooled stallion semen. The effect of colloid centrifugation on these parameters was also investigated. In this case, colloid centrifugation involves centrifuging a sperm sample through a silane-coated silica colloid formulation to retrieve the most robust spermatozoa. High and low ΔΨm in cooled stallion semen varied between stallions and between ejaculates, but was not affected by single-layer centrifugation (SLC). The SLC-selected spermatozoa produced significantly less hydrogen peroxide than controls (P < 0.001), which could explain the increased longevity and retention of fertilising capacity seen in previous studies. For SLC samples, ΔΨm was positively associated with viable spermatozoa that were not producing reactive oxygen species (r = 0.49; P < 0.001) and negatively associated with ROS production (for superoxide: r = -0.4, P < 0.01; for hydrogen peroxide: r = -0.39, P < 0.05). There was no clear association between ΔΨm and ROS production in control samples.

  11. Reactive oxygen species potentiate the negative inotropic effect of cardiac M2-muscarinic receptor stimulation.

    PubMed

    Peters, S L; Sand, C; Batinik, H D; Pfaffendorf, M; van Zwieten, P A

    2001-08-01

    The aim of the present study was to investigate the influence of reactive oxygen species (ROS) on the contractile responses of rat isolated left atria to muscarinic receptor stimulation. ROS were generated by means of electrolysis (30 mA, 75 s) of the organ bath fluid. Twenty minutes after the electrolysis period, the electrically paced atria (3 Hz) were stimulated with the adenylyl cyclase activator forskolin (1 microM). Subsequently, cumulative acetylcholine concentration-response curves were constructed (0.01 nM-10 microM). In addition, phosphoinositide turnover and adenylyl cyclase activity under basal and stimulated conditions were measured. For these biochemical experiments we used the stable acetylcholine analogue carbachol. The atria exposed to reactive oxygen species were influenced more potently (pD2 control: 6.2 vs. 7.1 for electrolysis-treated atria, P<0.05) and more effectively (Emax control: 40% vs. 90% reduction of the initial amplitude, P<0.05) by acetylcholine. In contrast, ROS exposure did not alter the responses to adenosine, whose receptor is also coupled via a Gi-protein to adenylyl cyclase. The basal (40% vs. control, P<0.05) as well as the carbachol-stimulated (-85% vs. control, P<0.05) inositol-phosphate formation was reduced in atria exposed to ROS. The forskolin-stimulated adenylyl cyclase activity was identical in both groups but carbachol stimulation induced a more pronounced reduction in adenylyl cyclase activity in the electrolysis-treated atria. Accordingly we may conclude that ROS enhance the negative inotropic response of isolated rat atria to acetylcholine by both a reduction of the positive (inositide turnover) and increase of the negative (adenylyl cyclase inhibition) inotropic components of cardiac muscarinic receptor stimulation. This phenomenon is most likely M2-receptor specific, since the negative inotropic response to adenosine is unaltered by ROS exposure.

  12. Protective effects of myricitrin against osteoporosis via reducing reactive oxygen species and bone-resorbing cytokines

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Huang, Qiang; Gao, Bo; Wang, Long

    Oxidative stress is a crucial pathogenic factor in the development of osteoporosis. Myricitrin, isolated from Myrica cerifera, is a potent antioxidant. We hypothesized that myricitrin possessed protective effects against osteoporosis by partially reducing reactive oxygen species (ROS) and bone-resorbing cytokines in osteoblastic MC3T3-E1 cells and human bone marrow stromal cells (hBMSCs). We investigated myricitrin on osteogenic differentiation under oxidative stress. Hydrogen peroxide (H{sub 2}O{sub 2}) was used to establish an oxidative cell injury model. Our results revealed that myricitrin significantly improved some osteogenic markers in these cells. Myricitrin decreased lipid production and reduced peroxisome proliferator-activated receptor gamma-2 (PPARγ2) expression inmore » hBMSCs. Moreover, myricitrin reduced the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and IL-6 and partially suppressed ROS production. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Our results demonstrated that myricitrin supplementation reduced serum malondialdehyde (MDA) activity and increased reduced glutathione (GSH) activity. Importantly, it ameliorated the micro-architecture of trabecular bones in the 4th lumbar vertebrae (L4) and distal femur. Taken together, these results indicated that the protective effects of myricitrin against osteoporosis are linked to a reduction in ROS and bone-resorbing cytokines, suggesting that myricitrin may be useful in bone metabolism diseases, particularly osteoporosis. - Highlights: • Myricitrin protects MC3T3-E1 cells and hBMSCs from oxidative stress. • It is accompanied by a decrease in oxidative stress and bone-resorbing cytokines. • Myricitrin decreases serum reactive oxygen species to some degree. • Myricitrin partly reverses ovariectomy effects in vivo. • Myricitrin may represent a beneficial anti-osteoporosis treatment method.« less

  13. Spreading the news: subcellular and organellar reactive oxygen species production and signalling.

    PubMed

    Mignolet-Spruyt, Lorin; Xu, Enjun; Idänheimo, Niina; Hoeberichts, Frank A; Mühlenbock, Per; Brosché, Mikael; Van Breusegem, Frank; Kangasjärvi, Jaakko

    2016-06-01

    As plants are sessile organisms that have to attune their physiology and morphology continuously to varying environmental challenges in order to survive and reproduce, they have evolved complex and integrated environment-cell, cell-cell, and cell-organelle signalling circuits that regulate and trigger the required adjustments (such as alteration of gene expression). Although reactive oxygen species (ROS) are essential components of this network, their pathways are not yet completely unravelled. In addition to the intrinsic chemical properties that define the array of interaction partners, mobility, and stability, ROS signalling specificity is obtained via the spatiotemporal control of production and scavenging at different organellar and subcellular locations (e.g. chloroplasts, mitochondria, peroxisomes, and apoplast). Furthermore, these cellular compartments may crosstalk to relay and further fine-tune the ROS message. Hence, plant cells might locally and systemically react upon environmental or developmental challenges by generating spatiotemporally controlled dosages of certain ROS types, each with specific chemical properties and interaction targets, that are influenced by interorganellar communication and by the subcellular location and distribution of the involved organelles, to trigger the suitable acclimation responses in association with other well-established cellular signalling components (e.g. reactive nitrogen species, phytohormones, and calcium ions). Further characterization of this comprehensive ROS signalling matrix may result in the identification of new targets and key regulators of ROS signalling, which might be excellent candidates for engineering or breeding stress-tolerant plants. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  14. Physiological and pathophysiological reactive oxygen species as probed by EPR spectroscopy: the underutilized research window on muscle ageing

    PubMed Central

    A. Abdel‐Rahman, Engy; Mahmoud, Ali M.; Khalifa, Abdulrahman M.

    2016-01-01

    Abstract Reactive oxygen and nitrogen species (ROS and RNS) play crucial roles in triggering, mediating and regulating physiological and pathophysiological signal transduction pathways within the cell. Within the cell, ROS efflux is firmly controlled both spatially and temporally, making the study of ROS dynamics a challenging task. Different approaches have been developed for ROS assessment; however, many of these assays are not capable of direct identification or determination of subcellular localization of different ROS. Here we highlight electron paramagnetic resonance (EPR) spectroscopy as a powerful technique that is uniquely capable of addressing questions on ROS dynamics in different biological specimens and cellular compartments. Due to their critical importance in muscle functions and dysfunction, we discuss in some detail spin trapping of various ROS and focus on EPR detection of nitric oxide before highlighting how EPR can be utilized to probe biophysical characteristics of the environment surrounding a given stable radical. Despite the demonstrated ability of EPR spectroscopy to provide unique information on the identity, quantity, dynamics and environment of radical species, its applications in the field of muscle physiology, fatiguing and ageing are disproportionately infrequent. While reviewing the limited examples of successful EPR applications in muscle biology we conclude that the field would greatly benefit from more studies exploring ROS sources and kinetics by spin trapping, protein dynamics by site‐directed spin labelling, and membrane dynamics and global redox changes by spin probing EPR approaches. PMID:26801204

  15. Endoplasmic Reticulum Stress and Nox-Mediated Reactive Oxygen Species Signaling in the Peripheral Vasculature: Potential Role in Hypertension

    PubMed Central

    Nabeebaccus, Adam A.; Shah, Ajay M.; Camargo, Livia L.; Filho, Sidney V.; Lopes, Lucia R.

    2014-01-01

    Abstract Significance: Reactive oxygen species (ROS) are produced during normal endoplasmic reticulum (ER) metabolism. There is accumulating evidence showing that under stress conditions such as ER stress, ROS production is increased via enzymes of the NADPH oxidase (Nox) family, especially via the Nox2 and Nox4 isoforms, which are involved in the regulation of blood pressure. Hypertension is a major contributor to cardiovascular and renal disease, and it has a complex pathophysiology involving the heart, kidney, brain, vessels, and immune system. ER stress activates the unfolded protein response (UPR) signaling pathway that has prosurvival and proapoptotic components. Recent Advances: Here, we summarize the evidence regarding the association of Nox enzymes and ER stress, and its potential contribution in the setting of hypertension, including the role of other conditions that can lead to hypertension (e.g., insulin resistance and diabetes). Critical Issues: A better understanding of this association is currently of great interest, as it will provide further insights into the cellular mechanisms that can drive the ER stress-induced adaptive versus maladaptive pathways linked to hypertension and other cardiovascular conditions. More needs to be learnt about the precise signaling regulation of Nox(es) and ER stress in the cardiovascular system. Future Directions: The development of specific approaches that target individual Nox isoforms and the UPR signaling pathway may be important for the achievement of therapeutic efficacy in hypertension. Antioxid. Redox Signal. 20, 121–134. PMID:23472786

  16. Phototransformation of estrogens mediated by Mn(III), not by reactive oxygen species, in the presence of humic acids.

    PubMed

    Wang, Xinghao; Yao, Jiayi; Wang, Siyuan; Pan, Xiaoxue; Xiao, Ruiyang; Huang, Qingguo; Wang, Zunyao; Qu, Ruijuan

    2018-06-01

    Photodegradation of pollutants is classically explained by reaction with reactive oxygen species. However Mn(III) may also remove pollutants, but direct evidence is actually lacking. Here we investigated the role of soluble Mn(III) on phototransformation of four typical estrogens, namely estrone (E1), 17β-estradiol (E2), estriol (E3), and 17α-ethynylestradiol (EE2), in the presence of Mn(II) and humic acid. Conversion rates of 60.2%, 89.0%, 87.6%, and 80.2% were achieved for E1, E2, E3, and EE2, respectively, after 72 h visible light irradiation. A detailed quenching experiments revealed that soluble Mn(III), and not reactive oxygen species, was the oxidant responsible for estrogen removal. The determination of Mn(III) concentration provided direct proof of the role of Mn(III)-based oxidizers in the conversion of estrogens. Soluble Mn(III) can form complexes with humic acid, and about 6.51 μM of Mn(III)-humic acid was formed from 20 μM of Mn(II) in the presence of 5 mg/L of humic acid. Furthermore, product identification and theoretical computation demonstrated that estrogens are mainly converted into oligomers (dimers, trimers, tetramers, etc.) via a single-electron process. According to these results, the oxidation of Mn(II) to Mn(III) is initiated by superoxide ion (O 2 •- ) generated from dissolved oxygen in the presence of humic acid under visible light irradiation. The formed soluble Mn(III) strips the estrogens of a single electron to generate phenoxyl radicals, which undergo oligomerization, while leads to regeneration of Mn(II). Hence, the photochemical Mn(II)-Mn(III) redox cycling may significantly influence the fate and transformation of estrogens in waters. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Atomic Oxygen Effects

    NASA Technical Reports Server (NTRS)

    Miller, Sharon K. R.

    2014-01-01

    Atomic oxygen, which is the most predominant species in low Earth orbit, is highly reactive and can break chemical bonds on the surface of a wide variety of materials leading to volatilization or surface oxidation which can result in failure of spacecraft materials and components. This presentation will give an overview of how atomic oxygen reacts with spacecraft materials, results of space exposure testing of a variety of materials, and examples of failures caused by atomic oxygen.

  18. Challenges and advances in quantum dot fluorescent probes to detect reactive oxygen and nitrogen species: a review.

    PubMed

    Adegoke, Oluwasesan; Forbes, Patricia B C

    2015-03-03

    The pathological and physiological effects of reactive oxygen and nitrogen species (ROS/RNS) have instigated increasing awareness in the scientific field with respect to the development of suitable probes for their detection. Among the various probes developed to date, semiconductor quantum dots (QDs) fluorescent probes have attracted significant attention. The unfavourable properties of ROS/RNS with respect to their detection, such as their short lifetimes and the competitive presence of various endogenous reactive species, capable of interfering with the probe in biological matrices, have hindered the effective performance of most probes as well as complicating the design of suitable probes. The development of novel QD fluorescent probes capable of circumventing these problems is thus, of scientific interest. In this review, we highlight the challenges faced, pros and cons and published developments to date, with respect to QD fluorescent probes for ROS/RNS such as H2O2, O2(·-), ·OH, HOCl, NO and ONOO(-). Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Plasmonic photocatalyst-like fluorescent proteins for generating reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Leem, Jung Woo; Kim, Seong-Ryul; Choi, Kwang-Ho; Kim, Young L.

    2018-03-01

    The recent advances in photocatalysis have opened a variety of new possibilities for energy and biomedical applications. In particular, plasmonic photocatalysis using hybridization of semiconductor materials and metal nanoparticles has recently facilitated the rapid progress in enhancing photocatalytic efficiency under visible or solar light. One critical underlying aspect of photocatalysis is that it generates and releases reactive oxygen species (ROS) as intermediate or final products upon light excitation or activation. Although plasmonic photocatalysis overcomes the limitation of UV irradiation, synthesized metal/semiconductor nanomaterial photocatalysts often bring up biohazardous and environmental issues. In this respect, this review article is centered in identifying natural photosensitizing organic materials that can generate similar types of ROS as those of plasmonic photocatalysis. In particular, we propose the idea of plasmonic photocatalyst-like fluorescent proteins for ROS generation under visible light irradiation. We recapitulate fluorescent proteins that have Type I and Type II photosensitization properties in a comparable manner to plasmonic photocatalysis. Plasmonic photocatalysis and protein photosensitization have not yet been compared systemically in terms of ROS photogeneration under visible light, although the phototoxicity and cytotoxicity of some fluorescent proteins are well recognized. A comprehensive understanding of plasmonic photocatalyst-like fluorescent proteins and their potential advantages will lead us to explore new environmental, biomedical, and defense applications.

  20. Mitochondrial membrane permeabilization and cell death during myocardial infarction: roles of calcium and reactive oxygen species

    PubMed Central

    Webster, Keith A

    2013-01-01

    Excess generation of reactive oxygen species (ROS) and cytosolic calcium accumulation play major roles in the initiation of programmed cell death during acute myocardial infarction. Cell death may include necrosis, apoptosis and autophagy, and combinations thereof. During ischemia, calcium handling between the sarcoplasmic reticulum and myofilament is disrupted and calcium is diverted to the mitochondria causing swelling. Reperfusion, while essential for survival, reactivates energy transduction and contractility and causes the release of ROS and additional ionic imbalance. During acute ischemia–reperfusion, the principal death pathways are programmed necrosis and apoptosis through the intrinsic pathway, initiated by the opening of the mitochondrial permeability transition pore and outer mitochondrial membrane permeabilization, respectively. Despite intense investigation, the mechanisms of action and modes of regulation of mitochondrial membrane permeabilization are incompletely understood. Extrinsic apoptosis, necroptosis and autophagy may also contribute to ischemia–reperfusion injury. In this review, the roles of dysregulated calcium and ROS and the contributions of Bcl-2 proteins, as well as mitochondrial morphology in promoting mitochondrial membrane permeability change and the ensuing cell death during myocardial infarction are discussed. PMID:23176689

  1. Reactive Oxygen Species and Inhibitors of Inflammatory Enzymes, NADPH Oxidase, and iNOS in Experimental Models of Parkinson's Disease

    PubMed Central

    Koppula, Sushruta; Kumar, Hemant; Kim, In Su; Choi, Dong-Kug

    2012-01-01

    Reactive oxygen species (ROSs) are emerging as important players in the etiology of neurodegenerative disorders including Parkinson's disease (PD). Out of several ROS-generating systems, the inflammatory enzymes nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and inducible nitric oxide synthase (iNOS) were believed to play major roles. Mounting evidence suggests that activation of NADPH oxidase and the expression of iNOS are directly linked to the generation of highly reactive ROS which affects various cellular components and preferentially damage midbrain dopaminergic neurons in PD. Therefore, appropriate management or inhibition of ROS generated by these enzymes may represent a therapeutic target to reduce neuronal degeneration seen in PD. Here, we have summarized recently developed agents and patents claimed as inhibitors of NADPH oxidase and iNOS enzymes in experimental models of PD. PMID:22577256

  2. Reactive oxygen species may play an essential role in driving biological evolution: The Cambrian Explosion as an example.

    PubMed

    Yang, Dong; Guo, Xuejun; Xie, Tian; Luo, Xiaoyan

    2018-01-01

    The Cambrian Explosion is one of the most significant events in the history of life; essentially all easily fossilizable animal body plans first evolved during this event. Although many theories have been proposed to explain this event, its cause remains unresolved. Here, we propose that the elevated level of oxygen, in combination with the increased mobility and food intake of metazoans, led to increased cellular levels of reactive oxygen species (ROS), which drove evolution by enhancing mutation rates and providing new regulatory mechanisms. Our hypothesis may provide a unified explanation for the Cambrian Explosion as it incorporates both environmental and developmental factors and is also consistent with ecological explanations for animal radiation. Future studies should focus on testing this hypothesis, and may lead to important insights into evolution. Copyright © 2017. Published by Elsevier B.V.

  3. Vascular Cell Adhesion Molecule-1 Expression and Signaling During Disease: Regulation by Reactive Oxygen Species and Antioxidants

    PubMed Central

    Marchese, Michelle E.; Abdala-Valencia, Hiam

    2011-01-01

    Abstract The endothelium is immunoregulatory in that inhibiting the function of vascular adhesion molecules blocks leukocyte recruitment and thus tissue inflammation. The function of endothelial cells during leukocyte recruitment is regulated by reactive oxygen species (ROS) and antioxidants. In inflammatory sites and lymph nodes, the endothelium is stimulated to express adhesion molecules that mediate leukocyte binding. Upon leukocyte binding, these adhesion molecules activate endothelial cell signal transduction that then alters endothelial cell shape for the opening of passageways through which leukocytes can migrate. If the stimulation of this opening is blocked, inflammation is blocked. In this review, we focus on the endothelial cell adhesion molecule, vascular cell adhesion molecule-1 (VCAM-1). Expression of VCAM-1 is induced on endothelial cells during inflammatory diseases by several mediators, including ROS. Then, VCAM-1 on the endothelium functions as both a scaffold for leukocyte migration and a trigger of endothelial signaling through NADPH oxidase-generated ROS. These ROS induce signals for the opening of intercellular passageways through which leukocytes migrate. In several inflammatory diseases, inflammation is blocked by inhibition of leukocyte binding to VCAM-1 or by inhibition of VCAM-1 signal transduction. VCAM-1 signal transduction and VCAM-1-dependent inflammation are blocked by antioxidants. Thus, VCAM-1 signaling is a target for intervention by pharmacological agents and by antioxidants during inflammatory diseases. This review discusses ROS and antioxidant functions during activation of VCAM-1 expression and VCAM-1 signaling in inflammatory diseases. Antioxid. Redox Signal. 15, 1607–1638. PMID:21050132

  4. Epac2-Rap1 Signaling Regulates Reactive Oxygen Species Production and Susceptibility to Cardiac Arrhythmias

    PubMed Central

    Yang, Zhaokang; Kirton, Hannah M.; Al-Owais, Moza; Thireau, Jérôme; Richard, Sylvain; Peers, Chris

    2017-01-01

    Abstract Aims: In the heart, β1-adrenergic signaling involves cyclic adenosine monophosphate (cAMP) acting via both protein kinase-A (PKA) and exchange protein directly activated by cAMP (Epac): a guanine nucleotide exchange factor for the small GTPase Rap1. Inhibition of Epac-Rap1 signaling has been proposed as a therapeutic strategy for both cancer and cardiovascular disease. However, previous work suggests that impaired Rap1 signaling may have detrimental effects on cardiac function. The aim of the present study was to investigate the influence of Epac2-Rap1 signaling on the heart using both in vivo and in vitro approaches. Results: Inhibition of Epac2 signaling induced early afterdepolarization arrhythmias in ventricular myocytes. The underlying mechanism involved an increase in mitochondrial reactive oxygen species (ROS) and activation of the late sodium current (INalate). Arrhythmias were blocked by inhibition of INalate or the mitochondria-targeted antioxidant, mitoTEMPO. In vivo, inhibition of Epac2 caused ventricular tachycardia, torsades de pointes, and sudden death. The in vitro and in vivo effects of Epac2 inhibition were mimicked by inhibition of geranylgeranyltransferase-1, which blocks interaction of Rap1 with downstream targets. Innovation: Our findings show for the first time that Rap1 acts as a negative regulator of mitochondrial ROS production in the heart and that impaired Epac2-Rap1 signaling causes arrhythmias due to ROS-dependent activation of INalate. This has implications for the use of chemotherapeutics that target Epac2-Rap1 signaling. However, selective inhibition of INalate provides a promising strategy to prevent arrhythmias caused by impaired Epac2-Rap1 signaling. Conclusion: Epac2-Rap1 signaling attenuates mitochondrial ROS production and reduces myocardial arrhythmia susceptibility. Antioxid. Redox Signal. 27, 117–132. PMID:27649969

  5. [Effects of elevated ozone concentrations on reactive oxygen metabolism and related gene expression in Ginkgo biloba leaves].

    PubMed

    Ruan, Ya Nan; Xu, Sheng; Guo, Long; Zhu, Ming Zhu; Wang, Cong; Li, Shu Yuan; Wang, Hong Yan

    2017-11-01

    By using the open top chambers (OTCs) fumigation method, this paper investigated the changes of foliar injury, level of reactive oxygen species (ROS), activities and gene expression of antioxidant enzymes in Ginkgo biloba leaves under different ozone (ambient ozone≈40, 80, 160, 200 nmol·mol -1 ) concentrations, in order to study the effects of elevated ozone (O 3 ) concentrations on reactive metabolism. The results showed that the obvious foliar injuries were observed in 160 and 200 nmol·mol -1 O 3 treatments, while no visible injury was observed in 80 nmol·mol -1 O 3 and ambient O 3 treatments. After 20 d, a significant increase in O 2 -· generation rate was observed in G. biloba leaves exposed to 160, 200 nmol·mol -1 O 3 , compared with ambient ozone and 80 nmol·mol -1 O 3 , and there were no significant differences between ambient O 3 and 80 nmol·mol -1 treatments. After 40 d, H 2 O 2 content of G. biloba leaves in 160 and 200 nmol·mol -1 O 3 was significantly higher than that in 80 nmol·mol -1 and ambient ozone, respectively. The activities of catalase (CAT) in 160 and 200 nmol·mol -1 treatments were also significantly higher than that in 80 nmol·mol -1 and ambient O 3 treatments. The ascorbate peroxidase (APX) activity of leaves for each elevated O 3 treatment was lower than that of ambient ozone. The level of CAT and APX expression increased progressively after 40 d O 3 treatment. The expression intensity of GbD was conspicuously strengthened along with the increase of ozone concentration and fumigation time. Le-vel of reactive oxygen increased, activities of antioxidant enzyme decreased, level of gene expression down-regulated, and foliar visible injury was observed in leaves of G. biloba in elevated ozone stress.

  6. Peroxide Activation for Electrophilic Reactivity by the Binuclear Non-heme Iron Enzyme AurF

    DOE PAGES

    Park, Kiyoung; Li, Ning; Kwak, Yeonju; ...

    2017-05-01

    Binuclear non-heme iron enzymes activate O 2 for diverse chemistries that include oxygenation of organic substrates and hydrogen atom abstraction. This process often involves the formation of peroxo-bridged biferric intermediates, only some of which can perform electrophilic reactions. To elucidate the geometric and electronic structural requirements to activate peroxo reactivity, the active peroxo intermediate in 4-aminobenzoate N-oxygenase (AurF) has been characterized spectroscopically and computationally. A magnetic circular dichroism study of reduced AurF shows that its electronic and geometric structures are poised to react rapidly with O 2. Nuclear resonance vibrational spectroscopic definition of the peroxo intermediate formed in this reactionmore » shows that the active intermediate has a protonated peroxo bridge. Density functional theory computations on the structure established here show that the protonation activates peroxide for electrophilic/single-electron-transfer reactivity. As a result, this activation of peroxide by protonation is likely also relevant to the reactive peroxo intermediates in other binuclear non-heme iron enzymes.« less

  7. Peroxide Activation for Electrophilic Reactivity by the Binuclear Non-heme Iron Enzyme AurF

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Park, Kiyoung; Li, Ning; Kwak, Yeonju

    Binuclear non-heme iron enzymes activate O 2 for diverse chemistries that include oxygenation of organic substrates and hydrogen atom abstraction. This process often involves the formation of peroxo-bridged biferric intermediates, only some of which can perform electrophilic reactions. To elucidate the geometric and electronic structural requirements to activate peroxo reactivity, the active peroxo intermediate in 4-aminobenzoate N-oxygenase (AurF) has been characterized spectroscopically and computationally. A magnetic circular dichroism study of reduced AurF shows that its electronic and geometric structures are poised to react rapidly with O 2. Nuclear resonance vibrational spectroscopic definition of the peroxo intermediate formed in this reactionmore » shows that the active intermediate has a protonated peroxo bridge. Density functional theory computations on the structure established here show that the protonation activates peroxide for electrophilic/single-electron-transfer reactivity. As a result, this activation of peroxide by protonation is likely also relevant to the reactive peroxo intermediates in other binuclear non-heme iron enzymes.« less

  8. Dynamics of localized charges in dopamine-modified TiO{sub 2} and their effect on the formation of reactive oxygen species.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dimitrijevic, N.; Rozhkova, E.; Rajh, T.

    Modification of TiO{sub 2} nanoparticles with dopamine enables harvesting of visible light and promotes spatial separation of charges. The formation of reactive oxygen species (OH, {sup 1}O{sub 2}, O{sub 2}{sup -}, HO{sub 2}, H{sub 2}O{sub 2}) upon illumination of TiO{sub 2}/dopamine was studied using complementary spin-trap EPR and radical-induced fluorescence techniques. The localization of holes on dopamine suppresses oxidation of adsorbed water molecules at the surface of nanoparticles, and thus formation of OH radicals. At the same time, dopamine does not affect electronic properties of photogenerated electrons and their reaction with dissolved oxygen to produce superoxide anions. Superoxide anions aremore » proposed to generate singlet oxygen through dismutation reaction, resulting in a low yield of {sup 1}O{sub 2} detected.« less

  9. Reactive oxygen species and nitric oxide are involved in polyamine-induced growth inhibition in wheat plants.

    PubMed

    Recalde, Laura; Vázquez, Analía; Groppa, María D; Benavides, María Patricia

    2018-03-06

    Polyamines (PAs) produce H 2 O 2 and nitric oxide (NO) during their normal catabolism and modulate plant growth and development. To explore the biochemical basis of PAs-induced growth inhibition in Triticum aestivum L seedlings, we examined the role of O 2 ·- , H 2 O 2 or NO in shoot and root development. Although all PA treatments resulted in a variable reduction of root and shoot elongation, spermine (Spm) caused the greater inhibition in a similar way to that observed with the NO donor, sodium nitroprusside (SNP). In both cases, O 2 ·- production was completely blocked whereas H 2 O 2 formation was high in the root apex under SNP or Spm treatments. Catalase recovered root and shoot growth in SNP but not in Spm-treated plants, revealing the involvement of H 2 O 2 in SNP-root length reduction. The addition of the NO scavenger, cPTIO, restored root length in SNP- or Spm-treated plants, respectively, and partially recovered O 2 ·- levels, compared to the plants exposed to PAs or SNP without cPTIO. A strong correlation was observed between root growth restoration and O 2 ·- accumulation after treating roots with SNP + aminoguanidine, a diamine oxidase inhibitor, and with SNP + 1,8-diaminoctane, a polyamine oxidase inhibitor, confirming the essential role of O 2 ·- formation for root growth and the importance of the origin and level of H 2 O 2 . The differential modulation of wheat growth by PAs through reactive oxygen species or NO is discussed. Graphical abstract Polyamines, nitric oxide and ROS interaction in plants during plant growth.

  10. Nanoparticle Inhalation Impairs Coronary Microvascular Reactivity via a Local Reactive Oxygen Species-Dependent Mechanism

    PubMed Central

    LeBlanc, A. J.; Moseley, A. M.; Chen, B. T.; Frazer, D.; Castranova, V.

    2010-01-01

    We have shown that nanoparticle inhalation impairs endothelium-dependent vasodilation in coronary arterioles. It is unknown whether local reactive oxygen species (ROS) contribute to this effect. Rats were exposed to TiO2 nanoparticles via inhalation to produce a pulmonary deposition of 10 µg. Coronary arterioles were isolated from the left anterior descending artery distribution, and responses to acetylcholine, arachidonic acid, and U46619 were assessed. Contributions of nitric oxide synthase and prostaglandin were assessed via competitive inhibition with NG-Monomethyl-L-Arginine (L-NMMA) and indomethacin. Microvascular wall ROS were quantified via dihydroethidium (DHE) fluorescence. Coronary arterioles from rats exposed to nano-TiO2 exhibited an attenuated vasodilator response to ACh, and this coincided with a 45% increase in DHE fluorescence. Coincubation with 2,2,6,6-tetramethylpiperidine-N-oxyl and catalase ameliorated impairments in ACh-induced vasodilation from nanoparticle exposed rats. Incubation with either L-NMMA or indomethacin significantly attenuated Ach-induced vasodilation in sham-control rats, but had no effect in rats exposed to nano-TiO2. Arachidonic acid induced vasoconstriction in coronary arterioles from rats exposed to nano-TiO2, but dilated arterioles from sham-control rats. These results suggest that nanoparticle exposure significantly impairs endothelium-dependent vasoreactivity in coronary arterioles, and this may be due in large part to increases in microvascular ROS. Furthermore, altered prostanoid formation may also contribute to this dysfunction. Such disturbances in coronary microvascular function may contribute to the cardiac events associated with exposure to particles in this size range. PMID:20033351

  11. Novel roles of folic acid as redox regulator: Modulation of reactive oxygen species sinker protein expression and maintenance of mitochondrial redox homeostasis on hepatocellular carcinoma.

    PubMed

    Lai, Kun-Goung; Chen, Chi-Fen; Ho, Chun-Te; Liu, Jun-Jen; Liu, Tsan-Zon; Chern, Chi-Liang

    2017-06-01

    We provide herein several lines of evidence to substantiate that folic acid (or folate) is a micronutrient capable of functioning as a novel redox regulator on hepatocellular carcinoma. First, we uncovered that folate deficiency could profoundly downregulate two prominent anti-apoptotic effectors including survivin and glucose-regulated protein-78. Silencing of either survivin or glucose-regulated protein-78 via small interfering RNA interfering technique established that both effectors could serve as reactive oxygen species sinker proteins. Second, folate deficiency-triggered oxidative-nitrosative stress could strongly induce endoplasmic reticulum stress that in turn could provoke cellular glutathione depletion through the modulation of the following two crucial events: (1) folate deficiency could strongly inhibit Bcl-2 expression leading to severe suppression of the mitochondrial glutathione pool and (2) folate deficiency could also profoundly inhibit two key enzymes that governing cellular glutathione redox regulation including γ-glutamylcysteinyl synthetase heavy chain, a catalytic enzyme for glutathione biosynthesis, and mitochondrial isocitrate dehydrogenase 2, an enzyme responsible for providing nicotinamide adenine dinucleotide phosphate necessary for regenerating oxidized glutathione disulfide back to glutathione via mitochondrial glutathione reductase. Collectively, we add to the literature new data to strengthen the notion that folate is an essential micronutrient that confers a novel role to combat reactive oxygen species insults and thus serves as a redox regulator via upregulating reactive oxygen species sinker proteins and averting mitochondrial glutathione depletion through proper maintenance of redox homeostasis via positively regulating glutathione biosynthesis, glutathione transporting system, and mitochondrial glutathione recycling process.

  12. Radiation-Driven Formation of Reactive Oxygen Species in Oxychlorine-Containing Mars Surface Analogues.

    PubMed

    Georgiou, Christos D; Zisimopoulos, Dimitrios; Kalaitzopoulou, Electra; Quinn, Richard C

    2017-04-01

    The present study demonstrates that γ-radiolyzed perchlorate-containing Mars soil salt analogues (in a CO 2 atmosphere) generate upon H 2 O wetting the reactive oxygen species (ROS) superoxide radical (O 2 •- ), hydrogen peroxide (H 2 O 2 ), and hydroxyl radicals ( • OH). This study also validates that analogue radiolysis forms oxychlorine species that, in turn, can UV-photolyze to • OH upon UV photolysis. This investigation was made possible by the development of a new assay for inorganic-origin O 2 •- and H 2 O 2 determination and by the modification of a previous assay for soil • OH. Results show that radiolyzed Mg(ClO 4 ) 2 generates H 2 O 2 and • OH; and when included as part of a mixture analogous to the salt composition of samples analyzed at the Mars Phoenix site, the analogue generated O 2 •- , H 2 O 2 , and • OH, with • OH levels 150-fold higher than in the radiolyzed Mg(ClO 4 ) 2 samples. Radiolyzed Mars Phoenix site salt analogue that did not contain Mg(ClO 4 ) 2 generated only • OH also at 150-fold higher concentration than Mg(ClO 4 ) 2 alone. Additionally, UV photolysis of the perchlorate γ radiolysis product chlorite (ClO 2 - ) generated the oxychlorine products trihalide (Cl 3 - ), chlorine dioxide (ClO 2 • ), and hypochlorite (ClO - ), with the formation of • OH by UV photolysis of ClO - . While the generation of ROS may have contributed in part to 14 CO 2 production in the Viking Labeled Release (LR) experiment and O 2 (g) release in the Viking Gas Exchange (GEx) experiment, our results indicate that they are not likely to be the major contributor to the LR and GEx results. However, due to their highly reactive nature, they are expected to play a significant role in the alteration of organics on Mars. Additionally, experiments with hypochlorite show that the thermal stability of NaClO is in the range of the thermal stability observed for thermally liable oxidant responsible for the Viking LR results. Key Words: Mars-Oxygen

  13. Salicylic acid signaling inhibits apoplastic reactive oxygen species signaling.

    PubMed

    Xu, Enjun; Brosché, Mikael

    2014-06-04

    Reactive oxygen species (ROS) are used by plants as signaling molecules during stress and development. Given the amount of possible challenges a plant face from their environment, plants need to activate and prioritize between potentially conflicting defense signaling pathways. Until recently, most studies on signal interactions have focused on phytohormone interaction, such as the antagonistic relationship between salicylic acid (SA)-jasmonic acid and cytokinin-auxin. In this study, we report an antagonistic interaction between SA signaling and apoplastic ROS signaling. Treatment with ozone (O3) leads to a ROS burst in the apoplast and induces extensive changes in gene expression and elevation of defense hormones. However, Arabidopsis thaliana dnd1 (defense no death1) exhibited an attenuated response to O3. In addition, the dnd1 mutant displayed constitutive expression of defense genes and spontaneous cell death. To determine the exact process which blocks the apoplastic ROS signaling, double and triple mutants involved in various signaling pathway were generated in dnd1 background. Simultaneous elimination of SA-dependent and SA-independent signaling components from dnd1 restored its responsiveness to O3. Conversely, pre-treatment of plants with SA or using mutants that constitutively activate SA signaling led to an attenuation of changes in gene expression elicited by O3. Based upon these findings, we conclude that plants are able to prioritize the response between ROS and SA via an antagonistic action of SA and SA signaling on apoplastic ROS signaling.

  14. Salicylic acid signaling inhibits apoplastic reactive oxygen species signaling

    PubMed Central

    2014-01-01

    Background Reactive oxygen species (ROS) are used by plants as signaling molecules during stress and development. Given the amount of possible challenges a plant face from their environment, plants need to activate and prioritize between potentially conflicting defense signaling pathways. Until recently, most studies on signal interactions have focused on phytohormone interaction, such as the antagonistic relationship between salicylic acid (SA)-jasmonic acid and cytokinin-auxin. Results In this study, we report an antagonistic interaction between SA signaling and apoplastic ROS signaling. Treatment with ozone (O3) leads to a ROS burst in the apoplast and induces extensive changes in gene expression and elevation of defense hormones. However, Arabidopsis thaliana dnd1 (defense no death1) exhibited an attenuated response to O3. In addition, the dnd1 mutant displayed constitutive expression of defense genes and spontaneous cell death. To determine the exact process which blocks the apoplastic ROS signaling, double and triple mutants involved in various signaling pathway were generated in dnd1 background. Simultaneous elimination of SA-dependent and SA-independent signaling components from dnd1 restored its responsiveness to O3. Conversely, pre-treatment of plants with SA or using mutants that constitutively activate SA signaling led to an attenuation of changes in gene expression elicited by O3. Conclusions Based upon these findings, we conclude that plants are able to prioritize the response between ROS and SA via an antagonistic action of SA and SA signaling on apoplastic ROS signaling. PMID:24898702

  15. Fundamental roles of reactive oxygen species and protective mechanisms in the female reproductive system.

    PubMed

    Fujii, Junichi; Iuchi, Yoshihito; Okada, Futoshi

    2005-09-02

    Controlled oxidation, such as disulfide bond formation in sperm nuclei and during ovulation, plays a fundamental role in mammalian reproduction. Excess oxidation, however, causes oxidative stress, resulting in the dysfunction of the reproductive process. Antioxidation reactions that reduce the levels of reactive oxygen species are of prime importance in reproductive systems in maintaining the quality of gametes and support reproduction. While anti-oxidative enzymes, such as superoxide dismutase and peroxidase, play a central role in eliminating oxidative stress, reduction-oxidation (redox) systems, comprised of mainly glutathione and thioredoxin, function to reduce the levels of oxidized molecules. Aldo-keto reductase, using NADPH as an electron donor, detoxifies carbonyl compounds resulting from the oxidation of lipids and proteins. Thus, many antioxidative and redox enzyme genes are expressed and aggressively protect gametes and embryos in reproductive systems.

  16. Sunlight-Triggered Nanoparticle Synergy: Teamwork of Reactive Oxygen Species and Nitric Oxide Released from Mesoporous Organosilica with Advanced Antibacterial Activity.

    PubMed

    Gehring, Julia; Trepka, Bastian; Klinkenberg, Nele; Bronner, Hannah; Schleheck, David; Polarz, Sebastian

    2016-03-09

    Colonization of surfaces by microorganisms is an urging problem. In combination with the increasing antibiotic resistance of pathogenic bacteria, severe infections are reported more frequently in medical settings. Therefore, there is a large demand to explore innovative surface coatings that provide intrinsic and highly effective antibacterial activity. Materials containing silver nanoparticles have been developed in the past for this purpose, but this solution has come into criticism due to various disadvantages like notable toxicity against higher organisms, the high price, and low abundance of silver. Here, we introduce a new, sunlight-mediated organosilica nanoparticle (NP) system based on silver-free antibacterial activity. The simultaneous release of nitric oxide (NO) in combination with singlet oxygen and superoxide radicals (O2(•-)) as reactive oxygen species (ROS) leads to the emergence of highly reactive peroxynitrite molecules with significantly enhanced biocidal activity. This special cooperative effect can only be realized, if the ROS-producing moieties and the functional entities releasing NO are spatially separated from each other. In one type of particle, Rose Bengal as an efficient singlet oxygen ((1)O2) producer was covalently bound to SH functionalities applying thiol-ene click chemistry. "Charging" the second type of particles with NO was realized by quantitatively transferring the thiol groups into S-nitrosothiol functionalities. We probed the oxidation power of ROS-NP alone and in combination with NO-NP using sunlight as a trigger. The high antibacterial efficiency of dual-action nanoparticles was demonstrated using disinfection assays with the pathogenic bacterium Pseudomonas aeruginosa.

  17. Nanosecond-Pulsed DBD Plasma-Generated Reactive Oxygen Species Trigger Immunogenic Cell Death in A549 Lung Carcinoma Cells through Intracellular Oxidative Stress

    PubMed Central

    Lin, Abraham; Truong, Billy; Patel, Sohil; Kaushik, Nagendra; Choi, Eun Ha; Fridman, Gregory; Fridman, Alexander; Miller, Vandana

    2017-01-01

    A novel application for non-thermal plasma is the induction of immunogenic cancer cell death for cancer immunotherapy. Cells undergoing immunogenic death emit danger signals which facilitate anti-tumor immune responses. Although pathways leading to immunogenic cell death are not fully understood; oxidative stress is considered to be part of the underlying mechanism. Here; we studied the interaction between dielectric barrier discharge plasma and cancer cells for oxidative stress-mediated immunogenic cell death. We assessed changes to the intracellular oxidative environment after plasma treatment and correlated it to emission of two danger signals: surface-exposed calreticulin and secreted adenosine triphosphate. Plasma-generated reactive oxygen and charged species were recognized as the major effectors of immunogenic cell death. Chemical attenuators of intracellular reactive oxygen species successfully abrogated oxidative stress following plasma treatment and modulated the emission of surface-exposed calreticulin. Secreted danger signals from cells undergoing immunogenic death enhanced the anti-tumor activity of macrophages. This study demonstrated that plasma triggers immunogenic cell death through oxidative stress pathways and highlights its potential development for cancer immunotherapy. PMID:28467380

  18. Plateau Waves of Intracranial Pressure and Partial Pressure of Cerebral Oxygen.

    PubMed

    Lang, Erhard W; Kasprowicz, Magdalena; Smielewski, Peter; Pickard, John; Czosnyka, Marek

    2016-01-01

    This study investigates 55 intracranial pressure (ICP) plateau waves recorded in 20 patients after severe traumatic brain injury (TBI) with a focus on a moving correlation coefficient between mean arterial pressure (ABP) and ICP, called PRx, which serves as a marker of cerebrovascular reactivity, and a moving correlation coefficient between ABP and cerebral partial pressure of oxygen (pbtO2), called ORx, which serves as a marker for cerebral oxygen reactivity. ICP and ICPamplitude increased significantly during the plateau waves, whereas CPP and pbtO2 decreased significantly. ABP, ABP amplitude, and heart rate remained unchanged. In 73 % of plateau waves PRx increased during the wave. ORx showed an increase during and a decrease after the plateau waves, which was not statistically significant. Our data show profound cerebral vasoparalysis on top of the wave and, to a lesser extent, impairment of cerebral oxygen reactivity. The different behavior of the indices may be due to the different latencies of the cerebral blood flow and oxygen level control mechanisms. While cerebrovascular reactivity is a rapidly reacting mechanism, cerebral oxygen reactivity is slower.

  19. Direct observation of the oxygenated species during oxygen reduction on a platinum fuel cell cathode

    NASA Astrophysics Data System (ADS)

    Casalongue, Hernan Sanchez; Kaya, Sarp; Viswanathan, Venkatasubramanian; Miller, Daniel J.; Friebel, Daniel; Hansen, Heine A.; Nørskov, Jens K.; Nilsson, Anders; Ogasawara, Hirohito

    2013-12-01

    The performance of polymer electrolyte membrane fuel cells is limited by the reduction at the cathode of various oxygenated intermediates in the four-electron pathway of the oxygen reduction reaction. Here we use ambient pressure X-ray photoelectron spectroscopy, and directly probe the correlation between the adsorbed species on the surface and the electrochemical potential. We demonstrate that, during the oxygen reduction reaction, hydroxyl intermediates on the cathode surface occur in several configurations with significantly different structures and reactivities. In particular, we find that near the open-circuit potential, non-hydrated hydroxyl is the dominant surface species. On the basis of density functional theory calculations, we show that the removal of hydration enhances the reactivity of oxygen species. Tuning the hydration of hydroxyl near the triple phase boundary will be crucial for designing more active fuel cell cathodes.

  20. Lignin Contribution to the Global Carbon Pool: Investigating the Abiotic Modification of Lignin by Reactive Oxygen Species

    NASA Astrophysics Data System (ADS)

    Waggoner, Derek Charles

    Evidence suggests that reactive oxygen species (ROS), largely generated through photochemical processes, are important in transforming the chemical composition of the large pool of terrestrially-derived dissolved organic matter (DOM) exported from land to water annually. However, due to the challenges inherent in isolating the effects of individual ROS on DOM composition, the role of ROS in the photochemical alteration of DOM remains poorly characterized. The main focus of the studies within this dissertation aim to more thoroughly characterize the alterations to lignin, used as an analog for terrestrial DOM, resulting from reactions with ROS. To investigate the possibility that the alteration of lignin, through reactions involving ROS, could lead to the production of compounds not recognized as having terrestrial origin, lignin-derived DOM was prepared from a sample of Atlantic white cedar (Chamaecyparis thyoides) and used for a number of studies. Lignin-derived DOM was independently exposed to hydroxyl radical (•OH) generated by Fenton reaction, singlet oxygen (1O2) produced using the photosensitizer Rose Bengal, and superoxide (O2-•) via stable potassium superoxide solution, under controlled laboratory conditions to accentuate how each ROS is responsible for the alteration of lignin. Advanced analytical techniques including high performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR), and Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS), were employed to characterize alteration to lignin taking place following various ROS treatments. Results of these studies have shown distinct differences in the types of new compounds observed from exposure to each ROS as well as ROS reactivity. The alteration of lignin to compounds not typically associated with terrestrial DOM has been demonstrated upon exposure to ROS. It is also suggested that ROS could selectively react with different fractions of lignin like compounds based

  1. Microcystin-LR Induced Reactive Oxygen Species Mediate Cytoskeletal Disruption and Apoptosis of Hepatocytes in Cyprinus carpio L.

    PubMed Central

    Jiang, Jinlin; Shan, Zhengjun; Xu, Weili; Wang, Xiaorong; Zhou, Junying; Kong, Deyang; Xu, Jing

    2013-01-01

    Microcystins (MCs) are a group of cyclic hepatotoxic peptides produced by cyanobacteria. Microcystin-LR (MC-LR) contains Leucine (L) and Arginine (R) in the variable positions, and is one of the most common and potently toxic peptides. MC-LR can inhibit protein phosphatase type 1 and type 2A (PP1 and PP2A) activities and induce excessive production of reactive oxygen species (ROS). The underlying mechanism of the inhibition of PP1 and PP2A has been extensively studied. The over-production of ROS is considered to be another main mechanism behind MC-LR toxicity; however, the detailed toxicological mechanism involved in over-production of ROS in carp (Cyprinus carpio L.) remains largely unclear. In our present study, the hydroxyl radical (•OH) was significantly induced in the liver of carp after a relatively short-term exposure to MC-LR. The elevated reactive oxygen species (ROS) production may play an important role in the disruption of microtubule structure. Pre-injection of the antioxidant N-acetyl-cysteine (NAC) provided significant protection to the cytoskeleton, however buthionine sulfoximine (BSO) exacerbated cytoskeletal destruction. In addition, the elevated ROS formation induced the expression of apoptosis-related genes, including p38, JNKa, and bcl-2. A significant increase in apoptotic cells was observed at 12 - 48 hours. Our study further supports evidence that ROS are involved in MC-LR induced damage to liver cells in carp, and indicates the need for further study of the molecular mechanisms behind MC-LR toxicity. PMID:24376844

  2. Design and UV-curable behaviour of boron based reactive diluent for epoxy acrylate oligomer used for flame retardant wood coating

    PubMed Central

    Chambhare, Sachin U.; Lokhande, Gunawant P.; Jagtap, Ramanand N.

    2017-01-01

    Abstract Difunctional boron-containing reactive flame retardant for UV-curable epoxy acrylate oligomer was synthesized from phenyl boronic acid and glycidyl methacrylate. The synthesized reactive diluent was utilized to formulate ultraviolet (UV)-curable wood coatings. The weight fractions of reactive diluent in coatings formulation was varied from 5 to 25 wt % with constant photoinitiator concentration. The molecular structure of reactive flame retardant was confirmed by Fourier-transform infrared, Nuclear magnetic resonance (NMR) and 11B NMR spectral analysis. Further, the efficacy of flame retardant behaviour of coatings was evaluated using limiting oxygen index and UL-94 vertical burning test. Thermal stability of cured coatings films were estimated from thermogravimetric and differential scanning calorimetry analysis. The effects of varying concentration of reactive diluent on the viscosity of coatings formulation along with optical, mechanical and chemical resistance properties of coatings were also evaluated. The coatings gel content, water absorption behaviour, contact angle analysis and stain resistance were also studied. PMID:29491786

  3. Menadione induces the formation of reactive oxygen species and depletion of GSH-mediated apoptosis and inhibits the FAK-mediated cell invasion.

    PubMed

    Kim, Yun Jeong; Shin, Yong Kyoo; Sohn, Dong Suep; Lee, Chung Soo

    2014-09-01

    Menadione induces apoptosis in tumor cells. However, the mechanism of apoptosis in ovarian cancer cells exposed to menadione is not clear. In addition, it is unclear whether menadione-induced apoptosis is mediated by the depletion of glutathione (GSH) contents that is associated with the formation of reactive oxygen species. Furthermore, the effect of menadione on the invasion and migration of human epithelial ovarian cancer cells has not been studied. Therefore, we investigated the effects of menadione exposure on apoptosis, cell adhesion, and cell migration using the human epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3. The results suggest that menadione may induce apoptotic cell death in ovarian carcinoma cell lines by activating the mitochondrial pathway and the caspase-8- and Bid-dependent pathways. The apoptotic effect of menadione appears to be mediated by the formation of reactive oxygen species and the depletion of GSH. Menadione inhibited fetal-bovine-serum-induced cell adhesion and migration of OVCAR-3 cells, possibly through the suppression the focal adhesion kinase (FAK)-dependent activation of cytoskeletal-associated components. Therefore, menadione might be beneficial in the treatment of epithelial ovarian adenocarcinoma and combination therapy.

  4. Proline dehydrogenase promotes senescence through the generation of reactive oxygen species.

    PubMed

    Nagano, Taiki; Nakashima, Akio; Onishi, Kengo; Kawai, Kosuke; Awai, Yuto; Kinugasa, Mizuki; Iwasaki, Tetsushi; Kikkawa, Ushio; Kamada, Shinji

    2017-04-15

    Cellular senescence is a complex stress response characterized by permanent loss of proliferative capacity and is implicated in age-related disorders. Although the transcriptional activity of p53 (encoded by TP53 ) is known to be vital for senescence induction, the downstream effector genes critical for senescence remain unsolved. Recently, we have identified the proline dehydrogenase gene ( PRODH ) to be upregulated specifically in senescent cells in a p53-dependent manner, and the functional relevance of this to senescence is yet to be defined. Here, we conducted functional analyses to explore the relationship between PRODH and the senescence program. We found that genetic and pharmacological inhibition of PRODH suppressed senescent phenotypes induced by DNA damage. Furthermore, ectopic expression of wild-type PRODH, but not enzymatically inactive forms, induced senescence associated with the increase in reactive oxygen species (ROS) and the accumulation of DNA damage. Treatment with N-acetyl-L-cysteine, a ROS scavenger, prevented senescence induced by PRODH overexpression. These results indicate that PRODH plays a causative role in DNA damage-induced senescence through the enzymatic generation of ROS. © 2017. Published by The Company of Biologists Ltd.

  5. Targeting reactive oxygen species in development and progression of pancreatic cancer

    PubMed Central

    Durand, Nisha; Storz, Peter

    2017-01-01

    Introduction Pancreatic ductal adenocarcinoma (PDA) is characterized by expression of oncogenic KRas which drives all aspects of tumorigenesis. Oncogenic KRas induces the formation of reactive oxygen species (ROS) which have been implicated in initiation and progression of PDA. To facilitate tumor promoting levels and to avoid oncogene-induced senescence or cytotoxicity, ROS homeostasis in PDA cells is balanced by additional up-regulation of antioxidant systems. Areas Covered We examine the sources of ROS in PDA, the mechanisms by which ROS homeostasis is maintained, and the biological consequences of ROS in PDA. Additionally, we discuss the potential mechanisms for targeting ROS homoeostasis as a point of therapeutic intervention. An extensive review of the relevant literature as it relates to the topic was conducted using PubMed. Expert Commentary Even though oncogenic mutations in the KRAS gene have been detected in over 95% of human pancreatic adenocarcinoma, targeting its gene product, KRas, has been difficult. The dependency of PDA cells on balancing ROS homeostasis could be an angle for new prevention or treatment strategies. These include use of antioxidants to prevent formation or progression of precancerous lesions, or methods to increase ROS in tumor cells to toxic levels. PMID:27841037

  6. Lycopene cyclase paralog CruP protects against reactive oxygen species in oxygenic photosynthetic organisms.

    PubMed

    Bradbury, Louis M T; Shumskaya, Maria; Tzfadia, Oren; Wu, Shi-Biao; Kennelly, Edward J; Wurtzel, Eleanore T

    2012-07-03

    In photosynthetic organisms, carotenoids serve essential roles in photosynthesis and photoprotection. A previous report designated CruP as a secondary lycopene cyclase involved in carotenoid biosynthesis [Maresca J, et al. (2007) Proc Natl Acad Sci USA 104:11784-11789]. However, we found that cruP KO or cruP overexpression plants do not exhibit correspondingly reduced or increased production of cyclized carotenoids, which would be expected if CruP was a lycopene cyclase. Instead, we show that CruP aids in preventing accumulation of reactive oxygen species (ROS), thereby reducing accumulation of β-carotene-5,6-epoxide, a ROS-catalyzed autoxidation product, and inhibiting accumulation of anthocyanins, which are known chemical indicators of ROS. Plants with a nonfunctional cruP accumulate substantially higher levels of ROS and β-carotene-5,6-epoxide in green tissues. Plants overexpressing cruP show reduced levels of ROS, β-carotene-5,6-epoxide, and anthocyanins. The observed up-regulation of cruP transcripts under photoinhibitory and lipid peroxidation-inducing conditions, such as high light stress, cold stress, anoxia, and low levels of CO(2), fits with a role for CruP in mitigating the effects of ROS. Phylogenetic distribution of CruP in prokaryotes showed that the gene is only present in cyanobacteria that live in habitats characterized by large variation in temperature and inorganic carbon availability. Therefore, CruP represents a unique target for developing resilient plants and algae needed to supply food and biofuels in the face of global climate change.

  7. Reactive oxygen species and nitric oxide in plant mitochondria: origin and redundant regulatory systems.

    PubMed

    Blokhina, Olga; Fagerstedt, Kurt V

    2010-04-01

    Plant mitochondria differ from their mammalian counterparts in many respects, which are due to the unique and variable surroundings of plant mitochondria. In green leaves, plant mitochondria are surrounded by ample respiratory substrates and abundant molecular oxygen, both resulting from active photosynthesis, while in roots and bulky rhizomes and fruit carbohydrates may be plenty, whereas oxygen levels are falling. Several enzymatic complexes in mitochondrial electron transport chain (ETC) are capable of reactive oxygen species (ROS) formation under physiological and pathological conditions. Inherently connected parameters such as the redox state of electron carriers in the ETC, ATP synthase activity and inner mitochondrial membrane potential, when affected by external stimuli, can give rise to ROS formation via complexes I and III, and by reverse electron transport (RET) from complex II. Superoxide radicals produced are quickly scavenged by superoxide dismutase (MnSOD), and the resulting H(2)O(2) is detoxified by peroxiredoxin-thioredoxin system or by the enzymes of ascorbate-glutathione cycle, found in the mitochondrial matrix. Arginine-dependent nitric oxide (NO)-releasing activity of enzymatic origin has been detected in plant mitochondria. The molecular identity of the enzyme is not clear but the involvement of mitochondria-localized enzymes responsible for arginine catabolism, arginase and ornithine aminotransferase has been shown in the regulation of NO efflux. Besides direct control by antioxidants, mitochondrial ROS production is tightly controlled by multiple redundant systems affecting inner membrane potential: NAD(P)H-dependent dehydrogenases, alternative oxidase (AOX), uncoupling proteins, ATP-sensitive K(+) channel and a number of matrix and intermembrane enzymes capable of direct electron donation to ETC. NO removal, on the other hand, takes place either by reactions with molecular oxygen or superoxide resulting in peroxynitrite, nitrite or nitrate

  8. Resveratrol induced inhibition of Escherichia coli proceeds via membrane oxidation and independent of diffusible reactive oxygen species generation.

    PubMed

    Subramanian, Mahesh; Goswami, Manish; Chakraborty, Saikat; Jawali, Narendra

    2014-01-01

    Resveratrol (5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol), a redox active phytoalexin with a large number of beneficial activities is also known for antibacterial property. However the mechanism of action of resveratrol against bacteria remains unknown. Due to its extensive redox property it was envisaged if reactive oxygen species (ROS) generation by resveratrol could be a reason behind its antibacterial activity. Employing Escherichia coli as a model organism we have evaluated the role of diffusible reactive oxygen species in the events leading to inhibition of this organism by resveratrol. Evidence for the role of ROS in E. coli treated with resveratrol was investigated by direct quantification of ROS by flow cytometry, supplementation with ROS scavengers, depletion of intracellular glutathione, employing mutants devoid of enzymatic antioxidant defences, induction of adaptive response prior to resveratrol challenge and monitoring oxidative stress response elements oxyR, soxS and soxR upon resveratrol treatment. Resveratrol treatment did not result in scavengable ROS generation in E. coli cells. However, evidence towards membrane damage was obtained by potassium leakage (atomic absorption spectrometry) and propidium iodide uptake (flow cytometry and microscopy) as an early event. Based on the comprehensive evidences this study concludes for the first time the antibacterial property of resveratrol against E. coli does not progress via the diffusible ROS but is mediated by site-specific oxidative damage to the cell membrane as the primary event.

  9. Exposure of Bacterial Biofilms to Electrical Current Leads to Cell Death Mediated in Part by Reactive Oxygen Species

    PubMed Central

    Brinkman, Cassandra L.; Schmidt-Malan, Suzannah M.; Karau, Melissa J.; Greenwood-Quaintance, Kerryl; Hassett, Daniel J.; Mandrekar, Jayawant N.

    2016-01-01

    Bacterial biofilms may form on indwelling medical devices such as prosthetic joints, heart valves and catheters, causing challenging-to-treat infections. We have previously described the ‘electricidal effect’, in which bacterial biofilms are decreased following exposure to direct electrical current. Herein, we sought to determine if the decreased bacterial quantities are due to detachment of biofilms or cell death and to investigate the role that reactive oxygen species (ROS) play in the observed effect. Using confocal and electron microscopy and flow cytometry, we found that direct current (DC) leads to cell death and changes in the architecture of biofilms formed by Gram-positive and Gram-negative bacteria. Reactive oxygen species (ROS) appear to play a role in DC-associated cell death, as there was an increase in ROS-production by Staphylococcus aureus and Staphylococcus epidermidis biofilms following exposure to DC. An increase in the production of ROS response enzymes catalase and superoxide dismutase (SOD) was observed for S. aureus, S. epidermidis and Pseudomonas aeruginosa biofilms following exposure to DC. Additionally, biofilms were protected from cell death when supplemented with antioxidants and oxidant scavengers, including catalase, mannitol and Tempol. Knocking out SOD (sodAB) in P. aeruginosa led to an enhanced DC effect. Microarray analysis of P. aeruginosa PAO1 showed transcriptional changes in genes related to the stress response and cell death. In conclusion, the electricidal effect results in death of bacteria in biofilms, mediated, at least in part, by production of ROS. PMID:27992529

  10. Resveratrol induced inhibition of Escherichia coli proceeds via membrane oxidation and independent of diffusible reactive oxygen species generation

    PubMed Central

    Subramanian, Mahesh; Goswami, Manish; Chakraborty, Saikat; Jawali, Narendra

    2014-01-01

    Resveratrol (5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol), a redox active phytoalexin with a large number of beneficial activities is also known for antibacterial property. However the mechanism of action of resveratrol against bacteria remains unknown. Due to its extensive redox property it was envisaged if reactive oxygen species (ROS) generation by resveratrol could be a reason behind its antibacterial activity. Employing Escherichia coli as a model organism we have evaluated the role of diffusible reactive oxygen species in the events leading to inhibition of this organism by resveratrol. Evidence for the role of ROS in E. coli treated with resveratrol was investigated by direct quantification of ROS by flow cytometry, supplementation with ROS scavengers, depletion of intracellular glutathione, employing mutants devoid of enzymatic antioxidant defences, induction of adaptive response prior to resveratrol challenge and monitoring oxidative stress response elements oxyR, soxS and soxR upon resveratrol treatment. Resveratrol treatment did not result in scavengable ROS generation in E. coli cells. However, evidence towards membrane damage was obtained by potassium leakage (atomic absorption spectrometry) and propidium iodide uptake (flow cytometry and microscopy) as an early event. Based on the comprehensive evidences this study concludes for the first time the antibacterial property of resveratrol against E. coli does not progress via the diffusible ROS but is mediated by site-specific oxidative damage to the cell membrane as the primary event. PMID:25009788

  11. Exposure of Bacterial Biofilms to Electrical Current Leads to Cell Death Mediated in Part by Reactive Oxygen Species.

    PubMed

    Brinkman, Cassandra L; Schmidt-Malan, Suzannah M; Karau, Melissa J; Greenwood-Quaintance, Kerryl; Hassett, Daniel J; Mandrekar, Jayawant N; Patel, Robin

    2016-01-01

    Bacterial biofilms may form on indwelling medical devices such as prosthetic joints, heart valves and catheters, causing challenging-to-treat infections. We have previously described the 'electricidal effect', in which bacterial biofilms are decreased following exposure to direct electrical current. Herein, we sought to determine if the decreased bacterial quantities are due to detachment of biofilms or cell death and to investigate the role that reactive oxygen species (ROS) play in the observed effect. Using confocal and electron microscopy and flow cytometry, we found that direct current (DC) leads to cell death and changes in the architecture of biofilms formed by Gram-positive and Gram-negative bacteria. Reactive oxygen species (ROS) appear to play a role in DC-associated cell death, as there was an increase in ROS-production by Staphylococcus aureus and Staphylococcus epidermidis biofilms following exposure to DC. An increase in the production of ROS response enzymes catalase and superoxide dismutase (SOD) was observed for S. aureus, S. epidermidis and Pseudomonas aeruginosa biofilms following exposure to DC. Additionally, biofilms were protected from cell death when supplemented with antioxidants and oxidant scavengers, including catalase, mannitol and Tempol. Knocking out SOD (sodAB) in P. aeruginosa led to an enhanced DC effect. Microarray analysis of P. aeruginosa PAO1 showed transcriptional changes in genes related to the stress response and cell death. In conclusion, the electricidal effect results in death of bacteria in biofilms, mediated, at least in part, by production of ROS.

  12. A Conformational Change in C-Reactive Protein Enhances Leukocyte Recruitment and Reactive Oxygen Species Generation in Ischemia/Reperfusion Injury.

    PubMed

    Thiele, Jan R; Zeller, Johannes; Kiefer, Jurij; Braig, David; Kreuzaler, Sheena; Lenz, Yvonne; Potempa, Lawrence A; Grahammer, Florian; Huber, Tobias B; Huber-Lang, M; Bannasch, Holger; Stark, G Björn; Peter, Karlheinz; Eisenhardt, Steffen U

    2018-01-01

    C-reactive protein circulates as a pentameric protein (pCRP). pCRP is a well-established diagnostic marker as plasma levels rise in response to tissue injury and inflammation. We recently described pro-inflammatory properties of CRP, which are mediated by conformational changes from pCRP to bioactive isoforms expressing pro-inflammatory neo-epitopes [pCRP* and monomeric C-reactive protein (mCRP)]. Here, we investigate the role of CRP isoforms in renal ischemia/reperfusion injury (IRI). Rat kidneys in animals with and without intraperitoneally injected pCRP were subjected to IRI by the time of pCRP exposure and were subsequently analyzed for monocyte infiltration, caspase-3 expression, and tubular damage. Blood urea nitrogen (BUN) was analyzed pre-ischemia and post-reperfusion. CRP effects on leukocyte recruitment were investigated via intravital imaging of rat-striated muscle IRI. Localized conformational CRP changes were analyzed by immunohistochemistry using conformation specific antibodies. 1,6-bis(phosphocholine)-hexane (1,6-bisPC), which stabilizes CRP in its native pentameric form was used to validate CRP effects. Leukocyte activation was assessed by quantification of reactive oxygen species (ROS) induction by CRP isoforms ex vivo and in vitro through electron spin resonance spectroscopy. Signaling pathways were analyzed by disrupting lipid rafts with nystatin and subsequent ROS detection. In order to confirm the translational relevance of our findings, biopsies of microsurgical human free tissue transfers before and after IRI were examined by immunofluorescence for CRP deposition and co-localization of CD68 + leukocytes. The application of pCRP aggravates tissue damage in renal IRI. 1,6-bisPC reverses these effects via inhibition of the conformational change that leads to exposure of pro-inflammatory epitopes in CRP (pCRP* and mCRP). Structurally altered CRP induces leukocyte-endothelial interaction and induces ROS formation in leukocytes, the latter can be

  13. Cardiomyocyte hypertrophy induced by Endonuclease G deficiency requires reactive oxygen radicals accumulation and is inhibitable by the micropeptide humanin.

    PubMed

    Blasco, Natividad; Cámara, Yolanda; Núñez, Estefanía; Beà, Aida; Barés, Gisel; Forné, Carles; Ruíz-Meana, Marisol; Girón, Cristina; Barba, Ignasi; García-Arumí, Elena; García-Dorado, David; Vázquez, Jesús; Martí, Ramon; Llovera, Marta; Sanchis, Daniel

    2018-06-01

    The endonuclease G gene (Endog), which codes for a mitochondrial nuclease, was identified as a determinant of cardiac hypertrophy. How ENDOG controls cardiomyocyte growth is still unknown. Thus, we aimed at finding the link between ENDOG activity and cardiomyocyte growth. Endog deficiency induced reactive oxygen species (ROS) accumulation and abnormal growth in neonatal rodent cardiomyocytes, altering the AKT-GSK3β and Class-II histone deacethylases (HDAC) signal transduction pathways. These effects were blocked by ROS scavengers. Lack of ENDOG reduced mitochondrial DNA (mtDNA) replication independently of ROS accumulation. Because mtDNA encodes several subunits of the mitochondrial electron transport chain, whose activity is an important source of cellular ROS, we investigated whether Endog deficiency compromised the expression and activity of the respiratory chain complexes but found no changes in these parameters nor in ATP content. MtDNA also codes for humanin, a micropeptide with possible metabolic functions. Nanomolar concentrations of synthetic humanin restored normal ROS levels and cell size in Endog-deficient cardiomyocytes. These results support the involvement of redox signaling in the control of cardiomyocyte growth by ENDOG and suggest a pathway relating mtDNA content to the regulation of cell growth probably involving humanin, which prevents reactive oxygen radicals accumulation and hypertrophy induced by Endog deficiency. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Hybrid TiO2 -Ruthenium Nano-photosensitizer Synergistically Produces Reactive Oxygen Species in both Hypoxic and Normoxic Conditions.

    PubMed

    Gilson, Rebecca C; Black, Kvar C L; Lane, Daniel D; Achilefu, Samuel

    2017-08-28

    Photodynamic therapy (PDT) is widely used to treat diverse diseases, but its dependence on oxygen to produce cytotoxic reactive oxygen species (ROS) diminishes the therapeutic effect in a hypoxic environment, such as solid tumors. Herein, we developed a ROS-producing hybrid nanoparticle-based photosensitizer capable of maintaining high levels of ROS under both normoxic and hypoxic conditions. Conjugation of a ruthenium complex (N3) to a TiO 2 nanoparticle afforded TiO 2 -N3. Upon exposure of TiO 2 -N3 to light, the N3 injected electrons into TiO 2 to produce three- and four-fold more hydroxyl radicals and hydrogen peroxide, respectively, than TiO 2 at 160 mmHg. TiO 2 -N3 maintained three-fold higher hydroxyl radicals than TiO 2 under hypoxic conditions via N3-facilitated electron-hole reduction of adsorbed water molecules. The incorporation of N3 transformed TiO 2 from a dual type I and II PDT agent to a predominantly type I photosensitizer, irrespective of the oxygen content. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Balancing the generation and elimination of reactive oxygen species

    USGS Publications Warehouse

    Rodriguez, Rusty; Redman, Regina

    2005-01-01

    Fossil records suggest that bacteria developed the ability to photosynthesize ≈3,500 million years ago (mya), initiating a very slow accumulation of atmospheric oxygen (1). Recent geochemical models suggest that atmospheric oxygen did not accumulate to levels conducive for aerobic life until 500–1,000 mya (2, 3). The oxygenation of Earth's atmosphere resulted in the emergence of aerobic organisms followed by a great diversification of biological species and the eventual evolution of humans.

  16. Reactive Oxygen Species Alter Autocrine and Paracrine Signaling

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zangar, Richard C.; Bollinger, Nikki; Weber, Thomas J.

    2011-12-01

    Cytochrome P450 (P450) 3A4 (CYP3A4) is the most abundant P450 protein in human liver and intestine and is highly inducible by a variety of drugs and other compounds. The P450 catalytic cycle is known to uncouple and release reactive oxygen species (ROS), but the effects of ROS from P450 and other enzymes in the endo-plasmic reticulum have been poorly studied from the perspective of effects on cell biology. In this study, we expressed low levels of CYP3A4 in HepG2 cells, a human hepatocarcinoma cell line, and examined effects on intracellular levels of ROS and on the secretion of a varietymore » of growth factors that are important in extracellular communication. Using the redox-sensitive dye RedoxSensor red, we demonstrate that CYP3A4 expression increases levels of ROS in viable cells. A customELISA microarray platform was employed to demonstrate that expression of CYP3A4 increased secretion of amphiregulin, intracellular adhesion molecule 1, matrix metalloprotease 2, platelet-derived growth factor (PDGF), and vascular endothelial growth factor, but suppressed secretion of CD14. The antioxidant N-acetylcysteine suppressed all P450-dependent changes in protein secretion except for CD14. Quantitative RT-PCR demonstrated that changes in protein secretion were consistently associated with corresponding changes in gene expression. Inhibition of the NF-{kappa}B pathway blocked P450 effects on PDGF secretion. CYP3A4 expression also altered protein secretion in human mammary epithelial cells and C10 mouse lung cells. Overall, these results suggest that increased ROS production in the endoplasmic reticulum alters the secretion of proteins that have key roles in paracrine and autocrine signaling.« less

  17. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system and proinflammatory cytokines in hypertension

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Su, Qing; Qin, Da-Nian, E-mail: dnqin@stu.edu.cn; Wang, Fu-Xin

    Aims: To explore whether reactive oxygen species (ROS) scavenger (tempol) in the hypothalamic paraventricular nucleus (PVN) attenuates renin–angiotensin system (RAS) and proinflammatory cytokines (PICs), and decreases the blood pressure and sympathetic activity in angiotensin II (ANG II)-induced hypertension. Methods and results: Male Sprague–Dawley rats were infused intravenously with ANG II (10 ng/kg per min) or normal saline (NS) for 4 weeks. These rats were treated with bilateral PVN infusion of oxygen free radical scavenger tempol (TEMP, 20 μg/h) or vehicle (artificial cerebrospinal fluid, aCSF) for 4 weeks. ANG II infusion resulted in increased mean arterial pressure (MAP) and renal sympatheticmore » nerve activity (RSNA). These ANG II-infused rats also had higher levels of gp91{sup phox} (a subunit of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), and interleukin-1beta (IL-1β) in the PVN than the control animals. Treatment with PVN infusion of TEMP attenuated the overexpression of gp91{sup phox}, ACE and IL-1β within the PVN, and decreased sympathetic activity and MAP in ANG II-infused rats. Conclusion: These findings suggest that ANG II infusion induces elevated PICs and oxidative stress in the PVN, which contribute to the sympathoexcitation in hypertension. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system, proinflammatory cytokines and oxidative stress in ANG II-induced hypertension. - Highlights: • The effect of chronic inhibiting PVN superoxide on hypertension was investigated. • ANG II infusion induced increased proinflammatory cytokines and superoxide in PVN. • ANG II infusion resulted in oxidative stress, sympathoexcitation and hypertension. • Chronic inhibiting PVN superoxide attenuates RAS and cytokines in hypertension.« less

  18. The Fumarate Reductase of Bacteroides thetaiotaomicron, unlike That of Escherichia coli, Is Configured so that It Does Not Generate Reactive Oxygen Species.

    PubMed

    Lu, Zheng; Imlay, James A

    2017-01-03

    The impact of oxidative stress upon organismal fitness is most apparent in the phenomenon of obligate anaerobiosis. The root cause may be multifaceted, but the intracellular generation of reactive oxygen species (ROS) likely plays a key role. ROS are formed when redox enzymes accidentally transfer electrons to oxygen rather than to their physiological substrates. In this study, we confirm that the predominant intestinal anaerobe Bacteroides thetaiotaomicron generates intracellular ROS at a very high rate when it is aerated. Fumarate reductase (Frd) is a prominent enzyme in the anaerobic metabolism of many bacteria, including B. thetaiotaomicron, and prior studies of Escherichia coli Frd showed that the enzyme is unusually prone to ROS generation. Surprisingly, in this study biochemical analysis demonstrated that the B. thetaiotaomicron Frd does not react with oxygen at all: neither superoxide nor hydrogen peroxide is formed. Subunit-swapping experiments indicated that this difference does not derive from the flavoprotein subunit at which ROS normally arise. Experiments with the related enzyme succinate dehydrogenase discouraged the hypothesis that heme moieties are responsible. Thus, resistance to oxidation may reflect a shift of electron density away from the flavin moiety toward the iron-sulfur clusters. This study shows that the autoxidizability of a redox enzyme can be suppressed by subtle modifications that do not compromise its physiological function. One implication is that selective pressures might enhance the oxygen tolerance of an organism by manipulating the electronic properties of its redox enzymes so they do not generate ROS. Whether in sediments or pathogenic biofilms, the structures of microbial communities are configured around the sensitivities of their members to oxygen. Oxygen triggers the intracellular formation of reactive oxygen species (ROS), and the sensitivity of a microbe to oxygen likely depends upon the rates at which ROS are formed

  19. Reactive oxygen species: players in the cardiovascular effects of testosterone

    PubMed Central

    Carneiro, Fernando S.; Carvalho, Maria Helena C.; Reckelhoff, Jane F.

    2015-01-01

    Androgens are essential for the development and maintenance of male reproductive tissues and sexual function and for overall health and well being. Testosterone, the predominant and most important androgen, not only affects the male reproductive system, but also influences the activity of many other organs. In the cardiovascular system, the actions of testosterone are still controversial, its effects ranging from protective to deleterious. While early studies showed that testosterone replacement therapy exerted beneficial effects on cardiovascular disease, some recent safety studies point to a positive association between endogenous and supraphysiological levels of androgens/testosterone and cardiovascular disease risk. Among the possible mechanisms involved in the actions of testosterone on the cardiovascular system, indirect actions (changes in the lipid profile, insulin sensitivity, and hemostatic mechanisms, modulation of the sympathetic nervous system and renin-angiotensin-aldosterone system), as well as direct actions (modulatory effects on proinflammatory enzymes, on the generation of reactive oxygen species, nitric oxide bioavailability, and on vasoconstrictor signaling pathways) have been reported. This mini-review focuses on evidence indicating that testosterone has prooxidative actions that may contribute to its deleterious actions in the cardiovascular system. The controversial effects of testosterone on ROS generation and oxidant status, both prooxidant and antioxidant, in the cardiovascular system and in cells and tissues of other systems are reviewed. PMID:26538238

  20. Ethanol stimulates epithelial sodium channels by elevating reactive oxygen species

    PubMed Central

    Bao, Hui-Fang; Song, John Z.; Duke, Billie J.; Ma, He-Ping; Denson, Donald D.

    2012-01-01

    Alcohol affects total body sodium balance, but the molecular mechanism of its effect remains unclear. We used single-channel methods to examine how ethanol affects epithelial sodium channels (ENaC) in A6 distal nephron cells. The data showed that ethanol significantly increased both ENaC open probability (Po) and the number of active ENaC in patches (N). 1-Propanol and 1-butanol also increased ENaC activity, but iso-alcohols did not. The effects of ethanol were mimicked by acetaldehyde, the first metabolic product of ethanol, but not by acetone, the metabolic product of 2-propanol. Besides increasing open probability and apparent density of active channels, confocal microscopy and surface biotinylation showed that ethanol significantly increased α-ENaC protein in the apical membrane. The effects of ethanol on ENaC Po and N were abolished by a superoxide scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL) and blocked by the phosphatidylinositol 3-kinase inhibitor LY294002. Consistent with an effect of ethanol-induced reactive oxygen species (ROS) on ENaC, primary alcohols and acetaldehyde elevated intracellular ROS, but secondary alcohols did not. Taken together with our previous finding that ROS stimulate ENaC, the current results suggest that ethanol stimulates ENaC by elevating intracellular ROS probably via its metabolic product acetaldehyde. PMID:22895258

  1. Controllable generation of reactive oxygen species by femtosecond-laser irradiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yan, Wei; He, Hao, E-mail: haohe@tju.edu.cn; Wang, Yintao

    Femtosecond lasers have been advancing Biophotonics research in the past two decades with multiphoton microscopy, microsurgery, and photodynamic therapy. Nevertheless, laser irradiation is identified to bring photodamage to cells via reactive oxygen species (ROS) generation with unclear mechanism. Meanwhile, currently in biological researches, there is no effective method to provide controllable ROS production precisely, which originally is leaked from mitochondria during respiration and plays a key role in a lot of important cellular processes and cellular signaling pathways. In this study, we show the process of how the tightly focused femtosecond-laser induces ROS generation solely in mitochondria at the verymore » beginning and then release to cytosol if the stimulus is intense enough. At certain weak power levels, the laser pulses induce merely moderate Ca{sup 2+} release but this is necessary for the laser to generate ROS in mitochondria. Cellular original ROS are also involved with a small contribution. When the power is above a threshold, ROS are then released to cytosol, indicating photodamage overwhelming cellular repair ability. The mechanisms in those two cases are quite different. Those results clarify parts of the mechanism in laser-induced ROS generation. Hence, it is possible to further this optical scheme to provide controllable ROS generation for ROS-related biological researches including mitochondrial diseases and aging.« less

  2. Hemoglobin fructation promotes heme degradation through the generation of endogenous reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Goodarzi, M.; Moosavi-Movahedi, A. A.; Habibi-Rezaei, M.; Shourian, M.; Ghourchian, H.; Ahmad, F.; Farhadi, M.; Saboury, A. A.; Sheibani, N.

    2014-09-01

    Protein glycation is a cascade of nonenzymatic reactions between reducing sugars and amino groups of proteins. It is referred to as fructation when the reducing monosaccharide is fructose. Some potential mechanisms have been suggested for the generation of reactive oxygen species (ROS) by protein glycation reactions in the presence of glucose. In this state, glucose autoxidation, ketoamine, and oxidative advance glycation end products (AGEs) formation are considered as major sources of ROS and perhaps heme degradation during hemoglobin glycation. However, whether fructose mediated glycation produces ROS and heme degradation is unknown. Here we report that ROS (H2O2) production occurred during hemoglobin fructation in vitro using chemiluminescence methods. The enhanced heme exposure and degradation were determined using UV-Vis and fluorescence spectrophotometry. Following accumulation of ROS, heme degradation products were accumulated reaching a plateau along with the detected ROS. Thus, fructose may make a significant contribution to the production of ROS, glycation of proteins, and heme degradation during diabetes.

  3. Restraining reactive oxygen species in Listeria monocytogenes promotes the apoptosis of glial cells.

    PubMed

    Li, Sen; Li, Yixuan; Chen, Guowei; Zhang, Jingchen; Xu, Fei; Wu, Man

    2017-07-01

    Listeria monocytogenes is a facultative anaerobic foodborne pathogen that can traverse the blood-brain barrier and cause brain infection. L. monocytogenes infection induces host cell apoptosis in several cell types. In this study, we investigated the apoptosis of human glioma cell line U251 invaded by L. monocytogenes and evaluated the function of bacterial reactive oxygen species (ROS) during infection. Bacterial ROS level was reduced by carrying out treatment with N-acetyl cysteine (NAC) and diphenyleneiodonium chloride (DPI). After infection, the apoptosis of U251 cells was examined by flow cytometry assay and propidium iodide staining. DPI and NAC efficiently decreased ROS level in L. monocytogenes without affecting bacterial growth. Moreover, the apoptosis of glial cells was enhanced upon invasion of DPI- and NAC-pretreated L. monocytogenes. Results indicate that the apoptosis of glial cells can be induced by L. monocytogenes, and that the inhibition of bacterial ROS increases the apoptosis of host cells.

  4. Fluorescent in vivo imaging of reactive oxygen species and redox potential in plants.

    PubMed

    Ortega-Villasante, Cristina; Burén, Stefan; Blázquez-Castro, Alfonso; Barón-Sola, Ángel; Hernández, Luis E

    2018-04-05

    Reactive oxygen species (ROS) are by-products of aerobic metabolism, and excessive production can result in oxidative stress and cell damage. In addition, ROS function as cellular messengers, working as redox regulators in a multitude of biological processes. Understanding ROS signalling and stress responses requires methods for precise imaging and quantification to monitor local, subcellular and global ROS dynamics with high selectivity, sensitivity and spatiotemporal resolution. In this review, we summarize the present knowledge for in vivo plant ROS imaging and detection, using both chemical probes and fluorescent protein-based biosensors. Certain characteristics of plant tissues, for example high background autofluorescence in photosynthetic organs and the multitude of endogenous antioxidants, can interfere with ROS and redox potential detection, making imaging extra challenging. Novel methods and techniques to measure in vivo plant ROS and redox changes with better selectivity, accuracy, and spatiotemporal resolution are therefore desirable to fully acknowledge the remarkably complex plant ROS signalling networks. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Autophagy, programmed cell death and reactive oxygen species in sexual reproduction in plants.

    PubMed

    Kurusu, Takamitsu; Kuchitsu, Kazuyuki

    2017-05-01

    Autophagy is one of the major cellular processes of recycling of proteins, metabolites and intracellular organelles, and plays crucial roles in the regulation of innate immunity, stress responses and programmed cell death (PCD) in many eukaryotes. It is also essential in development and sexual reproduction in many animals. In plants, although autophagy-deficient mutants of Arabidopsis thaliana show phenotypes in abiotic and biotic stress responses, their life cycle seems normal and thus little had been known until recently about the roles of autophagy in development and reproduction. Rice mutants defective in autophagy show sporophytic male sterility and immature pollens, indicating crucial roles of autophagy during pollen maturation. Enzymatic production of reactive oxygen species (ROS) by respiratory burst oxidase homologues (Rbohs) play multiple roles in regulating anther development, pollen tube elongation and fertilization. Significance of autophagy and ROS in the regulation of PCD of transient cells during plant sexual reproduction is discussed in comparison with animals.

  6. Baicalin Scavenged Reactive Oxygen Species and Protected Human Keratinocytes Against UVB-induced Cytotoxicity.

    PubMed

    Chang, Wen-Shin; Lin, En-Yuan; Hsu, Shih-Wei; Hu, Pei-Shin; Chuang, Chin-Liang; Liao, Cheng-Hsi; Fu, Chun-Kai; Su, Chung-Hao; Gong, Chi-Li; Hsiao, Chieh-Lun; Bau, DA-Tian; Tsai, Chia-Wen

    Ultraviolet B (UVB), with a wavelength of 280-320 nm, represents one of the most important environmental factors for skin disorders, including sunburn, hyperpigmentation, solar keratosis, solar elastosis and skin cancer. Therefore, protection against excessive UVA-induced damage is useful for prevention of sunburn and other human diseases. Baicalin, a major component of traditional Chinese medicine Scutellaria baicalensis, has been reported to possess antioxidant and cytostatic capacities. In this study, we examined whether baicalin is also capable of protecting human keratinocytes from UVB irradiation. The results showed that baicalin effectively scavenged reactive oxygen species (ROS) elevated within 4 h after UVB radiation and reversed the UVB-suppressed cell viability and UVB-induced apoptosis after 24 h. Our results demonstrated the utility of baicalin to complement the contributions of traditional Chinese medicine in UVB-induced damage to skin and suggested their potential application as pharmaceutical agents in long-term sun-shining injury prevention. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. Generation of reactive oxygen species from porous silicon microparticles in cell culture medium.

    PubMed

    Low, Suet Peng; Williams, Keryn A; Canham, Leigh T; Voelcker, Nicolas H

    2010-06-01

    Nanostructured (porous) silicon is a promising biodegradable biomaterial, which is being intensively researched as a tissue engineering scaffold and drug-delivery vehicle. Here, we tested the biocompatibility of non-treated and thermally-oxidized porous silicon particles using an indirect cell viability assay. Initial direct cell culture on porous silicon determined that human lens epithelial cells only poorly adhered to non-treated porous silicon. Using an indirect cell culture assay, we found that non-treated microparticles caused complete cell death, indicating that these particles generated a toxic product in cell culture medium. In contrast, thermally-oxidized microparticles did not reduce cell viability significantly. We found evidence for the generation of reactive oxygen species (ROS) by means of the fluorescent probe 2',7'-dichlorofluorescin. Our results suggest that non-treated porous silicon microparticles produced ROS, which interacted with the components of the cell culture medium, leading to the formation of cytotoxic species. Oxidation of porous silicon microparticles not only mitigated, but also abolished the toxic effects.

  8. ent-Jungermannenone C Triggers Reactive Oxygen Species-Dependent Cell Differentiation in Leukemia Cells.

    PubMed

    Yue, Zongwei; Xiao, Xinhua; Wu, Jinbao; Zhou, Xiaozhou; Liu, Weilong; Liu, Yaxi; Li, Houhua; Chen, Guoqiang; Wu, Yingli; Lei, Xiaoguang

    2018-02-23

    Acute myeloid leukemia (AML) is a hematologic malignancy that is characterized by clonal proliferation of myeloid blasts. Despite the progress that has been made in the treatment of various malignant hematopoietic diseases, the effective treatment of AML remains very challenging. Differentiation therapy has emerged as a promising approach for leukemia treatment, and new and effective chemical agents to trigger the differentiation of AML cells, especially drug-resistant cells, are urgently required. Herein, the natural product jungermannenone C, a tetracyclic diterpenoid isolated from liverworts, is reported to induce cell differentiation in AML cells. Interestingly, the unnatural enantiomer of jungermannenone C (1) was found to be more potent than jungermannenone C in inducing cell differentiation. Furthermore, compound 1 targets peroxiredoxins I and II by selectively binding to the conserved cysteine residues and leads to cellular reactive oxygen species accumulation. Accordingly, ent-jungermannenone C (1) shows potential for further investigation as an effective differentiation therapy against AML.

  9. Chemical reactivity of hydrogen, nitrogen, and oxygen atoms at temperatures below 100 k

    NASA Technical Reports Server (NTRS)

    Mcgee, H. A., Jr.

    1973-01-01

    The synthesis of unusual compounds by techniques employing cryogenic cooling to retard their very extreme reactivity was investigated. Examples of such species that were studied are diimide (N2H2), cyclobutadiene (C4H4), cyclopropanone (C3H4O), oxirene (C2H2O), and many others. Special purpose cryogenically cooled inlet arrangements were designed such that the analyses incurred no warm-up of the cold, and frequently explosively unstable, compounds. Controlled energy electron impact techniques were used to measure critical potentials and to develop the molecular energetics and thermodynamics of these molecules and to gain some insight into their kinetic characteristics as well. Three and four carbon strained ring molecules were studied. Several reactions of oxygen and hydrogen atoms with simple molecules of H, N, C, and O in hard quench configurations were studied. And the quench stabilization of BH3 was explored as a model system in cryochemistry.

  10. Protective mechanisms of helminths against reactive oxygen species are highly promising drug targets.

    PubMed

    Perbandt, Markus; Ndjonka, Dieudonne; Liebau, Eva

    2014-01-01

    Helminths that are the causative agents of numerous neglected tropical diseases continue to be a major problem for human global health. In the absence of vaccines, control relies solely on pharmacoprophylaxis and pharmacotherapy to reduce transmission and to relieve symptoms. There are only a few drugs available and resistance in helminths of lifestock has been observed to the same drugs that are also used to treat humans. Clearly there is an urgent need to find novel antiparasitic compounds. Not only are helminths confronted with their own metabolically derived toxic and redox-active byproducts but also with the production of reactive oxygen species (ROS) by the host immune system, adding to the overall oxidative burden of the parasite. Antioxidant enzymes of helminths have been identified as essential proteins, some of them biochemically distinct to their host counterpart and thus appealing drug targets. In this review we have selected a few enzymatic antioxidants of helminths that are thought to be druggable.

  11. Mitochondrial reactive oxygen species regulate the strength of inhibitory GABA-mediated synaptic transmission

    NASA Astrophysics Data System (ADS)

    Accardi, Michael V.; Daniels, Bryan A.; Brown, Patricia M. G. E.; Fritschy, Jean-Marc; Tyagarajan, Shiva K.; Bowie, Derek

    2014-01-01

    Neuronal communication imposes a heavy metabolic burden in maintaining ionic gradients essential for action potential firing and synaptic signalling. Although cellular metabolism is known to regulate excitatory neurotransmission, it is still unclear whether the brain’s energy supply affects inhibitory signalling. Here we show that mitochondrial-derived reactive oxygen species (mROS) regulate the strength of postsynaptic GABAA receptors at inhibitory synapses of cerebellar stellate cells. Inhibition is strengthened through a mechanism that selectively recruits α3-containing GABAA receptors into synapses with no discernible effect on resident α1-containing receptors. Since mROS promotes the emergence of postsynaptic events with unique kinetic properties, we conclude that newly recruited α3-containing GABAA receptors are activated by neurotransmitter released onto discrete postsynaptic sites. Although traditionally associated with oxidative stress in neurodegenerative disease, our data identify mROS as a putative homeostatic signalling molecule coupling cellular metabolism to the strength of inhibitory transmission.

  12. Photo-excitation of carotenoids causes cytotoxicity via singlet oxygen production

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yoshii, Hiroshi, E-mail: yoshii@nirs.go.jp; Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui 910-1193; Yoshii, Yukie, E-mail: yukiey@nirs.go.jp

    Highlights: Black-Right-Pointing-Pointer Some photo-excited carotenoids have photosensitizing ability. Black-Right-Pointing-Pointer They are able to produce ROS. Black-Right-Pointing-Pointer Photo-excited fucoxanthin can produce singlet oxygen through energy transfer. -- Abstract: Carotenoids, natural pigments widely distributed in algae and plants, have a conjugated double bond system. Their excitation energies are correlated with conjugation length. We hypothesized that carotenoids whose energy states are above the singlet excited state of oxygen (singlet oxygen) would possess photosensitizing properties. Here, we demonstrated that human skin melanoma (A375) cells are damaged through the photo-excitation of several carotenoids (neoxanthin, fucoxanthin and siphonaxanthin). In contrast, photo-excitation of carotenoids that possess energymore » states below that of singlet oxygen, such as {beta}-carotene, lutein, loroxanthin and violaxanthin, did not enhance cell death. Production of reactive oxygen species (ROS) by photo-excited fucoxanthin or neoxanthin was confirmed using a reporter assay for ROS production with HeLa Hyper cells, which express a fluorescent indicator protein for intracellular ROS. Fucoxanthin and neoxanthin also showed high cellular penetration and retention. Electron spin resonance spectra using 2,2,6,6-tetramethil-4-piperidone as a singlet oxygen trapping agent demonstrated that singlet oxygen was produced via energy transfer from photo-excited fucoxanthin to oxygen molecules. These results suggest that carotenoids such as fucoxanthin, which are capable of singlet oxygen production through photo-excitation and show good penetration and retention in target cells, are useful as photosensitizers in photodynamic therapy for skin disease.« less

  13. Fullerene (C60) nanoparticles exert photocytotoxicity through modulation of reactive oxygen species and p38 mitogen-activated protein kinase activation in the MCF-7 cancer cell line

    NASA Astrophysics Data System (ADS)

    Li, Zhi; Zhang, Fei-long; Wang, Zhiyuan; Pan, Li-li; Shen, Ying-ying; Zhang, Zhen-zhong

    2013-12-01

    The photocytotoxicity of water-dispersed 100-300 nm fullerene amino acid derivatives nanoparticles was studied. The nanoparticle solution of fullerene derivatives, l-phenylalanine (C60-phe) and glycine (C60-gly), suppressed the in vitro growth of MCF-7 cells lines, induced cancer cells apoptosis, and caused a perturbation of the cell cycle. These nanoparticle solutions increased intracellular reactive oxygen species after irradiation. C60-phe or C60-gly upregulated the expression of phosphorylated (p)p38 mitogen-activated protein kinase (MAPK). N-Acetyl- l-cysteine significantly depressed the composite-induced activation of p38MAPK, and the kinase inhibitor SB203580 significantly prevented C60 derivative-induced cell apoptosis. This study revealed that p38MAPK is activated by C60 nanoparticles through triggering reactive oxygen species generation, leading to cancer cell injuries.

  14. Production of reactive oxygen species in mitochondria of HeLa cells under oxidative stress.

    PubMed

    Chernyak, Boris V; Izyumov, Denis S; Lyamzaev, Konstantin G; Pashkovskaya, Alina A; Pletjushkina, Olga Y; Antonenko, Yuri N; Sakharov, Dmitrii V; Wirtz, Karel W A; Skulachev, Vladimir P

    2006-01-01

    Mitochondria can be a source of reactive oxygen species (ROS) and a target of oxidative damage during oxidative stress. In this connection, the effect of photodynamic treatment (PDT) with Mitotracker Red (MR) as a mitochondria-targeted photosensitizer has been studied in HeLa cells. It is shown that MR produces both singlet oxygen and superoxide anion upon photoactivation and causes photoinactivation of gramicidin channels in a model system (planar lipid bilayer). Mitochondria-targeted antioxidant (MitoQ) inhibits this effect. In living cells, MR-mediated PDT initiates a delayed ("dark") accumulation of ROS, which is accelerated by inhibitors of the respiratory chain (piericidin, rotenone and myxothiazol) and inhibited by MitoQ and diphenyleneiodonium (an inhibitor of flavin enzymes), indicating that flavin of Complex I is involved in the ROS production. PDT causes necrosis that is prevented by MitoQ. Treatment of the cell with hydrogen peroxide causes accumulation of ROS, and the effects of inhibitors and MitoQ are similar to that described for the PDT model. Apoptosis caused by H2O2 is augmented by the inhibitors of respiration and suppressed by MitoQ. It is concluded that the initial segments of the respiratory chain can be an important source of ROS, which are targeted to mitochondria, determining the fate of the cell subjected to oxidative stress.

  15. Reactive Oxygen Species Tune Root Tropic Responses1[OPEN

    PubMed Central

    Krieger, Gat

    2016-01-01

    The default growth pattern of primary roots of land plants is directed by gravity. However, roots possess the ability to sense and respond directionally to other chemical and physical stimuli, separately and in combination. Therefore, these root tropic responses must be antagonistic to gravitropism. The role of reactive oxygen species (ROS) in gravitropism of maize and Arabidopsis (Arabidopsis thaliana) roots has been previously described. However, which cellular signals underlie the integration of the different environmental stimuli, which lead to an appropriate root tropic response, is currently unknown. In gravity-responding roots, we observed, by applying the ROS-sensitive fluorescent dye dihydrorhodamine-123 and confocal microscopy, a transient asymmetric ROS distribution, higher at the concave side of the root. The asymmetry, detected at the distal elongation zone, was built in the first 2 h of the gravitropic response and dissipated after another 2 h. In contrast, hydrotropically responding roots show no transient asymmetric distribution of ROS. Decreasing ROS levels by applying the antioxidant ascorbate, or the ROS-generation inhibitor diphenylene iodonium attenuated gravitropism while enhancing hydrotropism. Arabidopsis mutants deficient in Ascorbate Peroxidase 1 showed attenuated hydrotropic root bending. Mutants of the root-expressed NADPH oxidase RBOH C, but not rbohD, showed enhanced hydrotropism and less ROS in their roots apices (tested in tissue extracts with Amplex Red). Finally, hydrostimulation prior to gravistimulation attenuated the gravistimulated asymmetric ROS and auxin signals that are required for gravity-directed curvature. We suggest that ROS, presumably H2O2, function in tuning root tropic responses by promoting gravitropism and negatively regulating hydrotropism. PMID:27535793

  16. Production of ozone and reactive oxygen species after welding.

    PubMed

    Liu, H H; Wu, Y C; Chen, H L

    2007-11-01

    Many toxic substances including heavy metals, ozone, carbon monoxide, carbon dioxide, and nitrogen oxides are generated during welding. Ozone (O(3)) is a strong oxidant that generates reactive oxygen species (ROS) in tissue, and ambient ROS exposure associated with particles has been determined to cause DNA damage. Ozone is produced within 30 seconds during welding. However, the length of time that O(3) remains in the air after welding is completed (post-welding) is unknown. The current study aimed to assess the distributions of ambient ROS and O(3) before the start of welding (pre-welding), during welding, and after welding. The highest O(3) levels, equal to 195 parts per billion (ppb), appeared during welding. Ozone levels gradually decreased to 60 ppb 10 minutes after the welding was completed. The highest ROS level was found in samples taken during welding, followed by samples taken after the welding was completed. The lowest ROS level was found in samples taken before the welding had started. Ozone and ROS levels were poorly correlated, but a similar trend was found for O(3) and ROS levels in particles (microM/mg). Although particles were not generated after welding, ROS and O(3) still persisted for more than 10 minutes. Meanwhile, because O(3) continues after welding, how long the occupational protective system should be used depends on the welding materials and the methods used. In addition, the relationship between metal fumes and ROS generation during the welding process should be further investigated.

  17. Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Hyoung Jun; Han, Jeongsu; Jang, Yunseon

    Highlights: • DHA prevents PQ-induced dopaminergic neuronal loss via decreasing of excessive ROS. • DHA increases GR and GCLm derivate GSH pool by enhancement of Nrf2 expression. • Protective mechanism is removal of PQ-induced ROS via DHA-dependent GSH pool. • DHA may be a good preventive strategy for Parkinson’s disease (PD) therapy. - Abstract: Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson’s disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson’s disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuronmore » loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis.« less

  18. Oxoferryl-porphyrin radical catalytic intermediate in cytochrome bd oxidases protects cells from formation of reactive oxygen species.

    PubMed

    Paulus, Angela; Rossius, Sebastiaan Gijsbertus Hendrik; Dijk, Madelon; de Vries, Simon

    2012-03-16

    The quinol-linked cytochrome bd oxidases are terminal oxidases in respiration. These oxidases harbor a low spin heme b(558) that donates electrons to a binuclear heme b(595)/heme d center. The reaction with O(2) and subsequent catalytic steps of the Escherichia coli cytochrome bd-I oxidase were investigated by means of ultra-fast freeze-quench trapping followed by EPR and UV-visible spectroscopy. After the initial binding of O(2), the O-O bond is heterolytically cleaved to yield a kinetically competent heme d oxoferryl porphyrin π-cation radical intermediate (compound I) magnetically interacting with heme b(595). Compound I accumulates to 0.75-0.85 per enzyme in agreement with its much higher rate of formation (~20,000 s(-1)) compared with its rate of decay (~1,900 s(-1)). Compound I is next converted to a short lived heme d oxoferryl intermediate (compound II) in a phase kinetically matched to the oxidation of heme b(558) before completion of the reaction. The results indicate that cytochrome bd oxidases like the heme-copper oxidases break the O-O bond in a single four-electron transfer without a peroxide intermediate. However, in cytochrome bd oxidases, the fourth electron is donated by the porphyrin moiety rather than by a nearby amino acid. The production of reactive oxygen species by the cytochrome bd oxidase was below the detection level of 1 per 1000 turnovers. We propose that the two classes of terminal oxidases have mechanistically converged to enzymes in which the O-O bond is broken in a single four-electron transfer reaction to safeguard the cell from the formation of reactive oxygen species.

  19. Inhibitory activities of soluble and bound millet seed phenolics on free radicals and reactive oxygen species.

    PubMed

    Chandrasekara, Anoma; Shahidi, Fereidoon

    2011-01-12

    Oxidative stress, caused by reactive oxygen species (ROS), is responsible for modulating several pathological conditions and aging. Soluble and bound phenolic extracts of commonly consumed millets, namely, kodo, finger (Ravi), finger (local), foxtail, proso, little, and pearl, were investigated for their phenolic content and inhibition of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and ROS, namely, hydroxyl radical, peroxyl radical, hydrogen peroxide (H(2)O(2)), hypochlorous acid (HOCl), and singlet oxygen ((1)O(2)). Inhibition of DPPH and hydroxyl radicals was detrmined using electron paramagnetic resonance (EPR) spectroscopy. The peroxyl radical inhibitory activity was measured using the oxygen radical absorbance capacity (ORAC) assay. The scavenging of H(2)O(2), HOCl, and (1)O(2) was evaluated using colorimetric methods. The results were expressed as micromoles of ferulic acid equivalents (FAE) per gram of grain on a dry weight basis. In addition, major hydroxycinnamic acids were identified and quantified using high-performance liquid chromatography (HPLC) and HPLC-mass spectrometry (MS). All millet varieties displayed effective radical and ROS inhibition activities, which generally positively correlated with phenolic contents, except for hydroxyl radical. HPLC analysis revealed the presence of ferulic and p-coumaric acids as major hydroxycinnamic acids in phenolic extract and responsible for the observed effects. Bound extracts of millet contributed 38-99% to ROS scavenging, depending on the variety and the test system employed. Hence, bound phenolics must be included in the evaluation of the antioxidant activity of millets and other cereals.

  20. Oxygen Activation and Radical Transformations in Heme Proteins and Metalloporphyrins

    PubMed Central

    2017-01-01

    As a result of the adaptation of life to an aerobic environment, nature has evolved a panoply of metalloproteins for oxidative metabolism and protection against reactive oxygen species. Despite the diverse structures and functions of these proteins, they share common mechanistic grounds. An open-shell transition metal like iron or copper is employed to interact with O2 and its derived intermediates such as hydrogen peroxide to afford a variety of metal–oxygen intermediates. These reactive intermediates, including metal-superoxo, -(hydro)peroxo, and high-valent metal–oxo species, are the basis for the various biological functions of O2-utilizing metalloproteins. Collectively, these processes are called oxygen activation. Much of our understanding of the reactivity of these reactive intermediates has come from the study of heme-containing proteins and related metalloporphyrin compounds. These studies not only have deepened our understanding of various functions of heme proteins, such as O2 storage and transport, degradation of reactive oxygen species, redox signaling, and biological oxygenation, etc., but also have driven the development of bioinorganic chemistry and biomimetic catalysis. In this review, we survey the range of O2 activation processes mediated by heme proteins and model compounds with a focus on recent progress in the characterization and reactivity of important iron–oxygen intermediates. Representative reactions initiated by these reactive intermediates as well as some context from prior decades will also be presented. We will discuss the fundamental mechanistic features of these transformations and delineate the underlying structural and electronic factors that contribute to the spectrum of reactivities that has been observed in nature as well as those that have been invented using these paradigms. Given the recent developments in biocatalysis for non-natural chemistries and the renaissance of radical chemistry in organic synthesis, we

  1. Numerical simulation of physicochemical interactions between oxygen atom and phosphatidylcholine due to direct irradiation of atmospheric pressure nonequilibrium plasma to biological membrane with quantum mechanical molecular dynamics

    NASA Astrophysics Data System (ADS)

    Uchida, Satoshi; Yoshida, Taketo; Tochikubo, Fumiyoshi

    2017-10-01

    Plasma medicine is one of the most attractive applications using atmospheric pressure nonequilibrium plasma. With respect to direct contact of the discharge plasma with a biological membrane, reactive oxygen species play an important role in induction of medical effects. However, complicated interactions between the plasma radicals and membrane have not been understood well. In the present work, we simulated elemental processes at the first stage of physicochemical interactions between oxygen atom and phosphatidylcholine using the quantum mechanical molecular dynamics code in a general software AMBER. The change in the above processes was classified according to the incident energy of oxygen atom. At an energy of 1 eV, the abstraction of a hydrogen atom and recombination to phosphatidylcholine were simultaneously occurred in chemical attachment of incident oxygen atom. The exothermal energy of the reaction was about 80% of estimated one based on the bond energies of ethane. An oxygen atom over 10 eV separated phosphatidylcholine partially. The behaviour became increasingly similar to physical sputtering. The reaction probability of oxygen atom was remarkably high in comparison with that of hydrogen peroxide. These results suggest that we can uniformly estimate various physicochemical dynamics of reactive oxygen species against membrane lipids.

  2. Induction of Mitochondrial Reactive Oxygen Species Production by Itraconazole, Terbinafine, and Amphotericin B as a Mode of Action against Aspergillus fumigatus

    PubMed Central

    Shekhova, Elena

    2017-01-01

    ABSTRACT Drug resistance in fungal pathogens is of incredible importance to global health, yet the mechanisms of drug action remain only loosely defined. Antifungal compounds have been shown to trigger the intracellular accumulation of reactive oxygen species (ROS) in human-pathogenic yeasts, but the source of those ROS remained unknown. In the present study, we examined the role of endogenous ROS for the antifungal activity of the three different antifungal substances itraconazole, terbinafine, and amphotericin B, which all target the fungal cell membrane. All three antifungals had an impact on fungal redox homeostasis by causing increased intracellular ROS production. Interestingly, the elevated ROS levels induced by antifungals were abolished by inhibition of the mitochondrial respiratory complex I with rotenone. Further, evaluation of lipid peroxidation using the thiobarbituric acid assay revealed that rotenone pretreatment decreased ROS-induced lipid peroxidation during incubation of Aspergillus fumigatus with itraconazole and terbinafine. By applying the mitochondrion-specific lipid peroxidation probe MitoPerOx, we also confirmed that ROS are induced in mitochondria and subsequently cause significant oxidation of mitochondrial membrane in the presence of terbinafine and amphotericin B. To summarize, our study suggests that the induction of ROS production contributes to the ability of antifungal compounds to inhibit fungal growth. Moreover, mitochondrial complex I is the main source of deleterious ROS production in A. fumigatus challenged with antifungal compounds. PMID:28848005

  3. New Insight into the Role of Reactive Oxygen Species (ROS) in Cellular Signal-Transduction Processes.

    PubMed

    Russell, Eileen G; Cotter, Thomas G

    2015-01-01

    Reactive oxygen species (ROS) were once considered to be deleterious agents, contributing to a vast range of pathologies. But, now their protective effects are being appreciated. Both their damaging and beneficial effects are initiated when they target distinct molecules and consequently begin functioning as part of complex signal-transduction pathways. The recognition of ROS as signaling mediators has driven a wealth of research into their roles in both normal and pathophysiological states. The present review assesses the relevant recent literature to outline the current perspectives on redox-signaling mechanisms, physiological implications, and therapeutic strategies. This study highlights that a more fundamental knowledge about many aspects of redox signaling will allow better targeting of ROS, which would in turn improve prophylactic and pharmacotherapy for redox-associated diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Oxygen Concentration Inside a Functioning Photosynthetic Cell

    PubMed Central

    Kihara, Shigeharu; Hartzler, Daniel A.; Savikhin, Sergei

    2014-01-01

    The excess oxygen concentration in the photosynthetic membranes of functioning oxygenic photosynthetic cells was estimated using classical diffusion theory combined with experimental data on oxygen production rates of cyanobacterial cells. The excess oxygen concentration within the plesiomorphic cyanobacterium Gloeobactor violaceus is only 0.025 μM, or four orders of magnitude lower than the oxygen concentration in air-saturated water. Such a low concentration suggests that the first oxygenic photosynthetic bacteria in solitary form could have evolved ∼2.8 billion years ago without special mechanisms to protect them against reactive oxygen species. These mechanisms instead could have been developed during the following ∼500 million years while the oxygen level in the Earth’s atmosphere was slowly rising. Excess oxygen concentrations within individual cells of the apomorphic cyanobacteria Synechocystis and Synechococcus are 0.064 and 0.25 μM, respectively. These numbers suggest that intramembrane and intracellular proteins in isolated oxygenic photosynthetic cells are not subjected to excessively high oxygen levels. The situation is different for closely packed colonies of photosynthetic cells. Calculations show that the excess concentration within colonies that are ∼40 μm or larger in diameter can be comparable to the oxygen concentration in air-saturated water, suggesting that species forming colonies require protection against reactive oxygen species even in the absence of oxygen in the surrounding atmosphere. PMID:24806920

  5. TCDD decreases ATP levels and increases reactive oxygen production through changes in mitochondrial F F{sub 1}-ATP synthase and ubiquinone

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shertzer, Howard G.; Genter, Mary Beth; Shen, Dongxiao

    2006-12-15

    Mitochondria generate ATP and participate in signal transduction and cellular pathology and/or cell death. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) decreases hepatic ATP levels and generates mitochondrial oxidative DNA damage, which is exacerbated by increasing mitochondrial glutathione redox state and by inner membrane hyperpolarization. This study identifies mitochondrial targets of TCDD that initiate and sustain reactive oxygen production and decreased ATP levels. One week after treating mice with TCDD, liver ubiquinone (Q) levels were significantly decreased, while rates of succinoxidase and Q-cytochrome c oxidoreductase activities were increased. However, the expected increase in Q reduction state following TCDD treatment did not occur; instead, Q wasmore » more oxidized. These results could be explained by an ATP synthase defect, a premise supported by the unusual finding that TCDD lowers ATP/O ratios without concomitant changes in respiratory control ratios. Such results suggest either a futile cycle in ATP synthesis, or hydrolysis of newly synthesized ATP prior to release. The TCDD-mediated decrease in Q, concomitant with an increase in respiration, increases complex 3 redox cycling. This acts in concert with glutathione to increase membrane potential and reactive oxygen production. The proposed defect in ATP synthase explains both the greater respiratory rates and the lower tissue ATP levels.« less

  6. Reactive oxygen species levels control NF-κB activation by low dose deferasirox in erythroid progenitors of low risk myelodysplastic syndromes.

    PubMed

    Meunier, Mathieu; Ancelet, Sarah; Lefebvre, Christine; Arnaud, Josiane; Garrel, Catherine; Pezet, Mylène; Wang, Yan; Faure, Patrice; Szymanski, Gautier; Duployez, Nicolas; Preudhomme, Claude; Biard, Denis; Polack, Benoit; Cahn, Jean-Yves; Moulis, Jean Marc; Park, Sophie

    2017-12-01

    Anemia is a frequent cytopenia in myelodysplastic syndromes (MDS) and most patients require red blood cell transfusion resulting in iron overload (IO). Deferasirox (DFX) has become the standard treatment of IO in MDS and it displays positive effects on erythropoiesis. In low risk MDS samples, mechanisms improving erythropoiesis after DFX treatment remain unclear. Herein, we addressed this question by using liquid cultures with iron overload of erythroid precursors treated with low dose of DFX (3μM), which corresponds to DFX 5 mg/kg/day, an unusual dose used for iron chelation. We highlight a decreased apoptosis rate and an increased proportion of cycling cells, both leading to higher proliferation rates. The iron chelation properties of low dose DFX failed to activate the Iron Regulatory Proteins and to support iron depletion, but low dose DFX dampers intracellular reactive oxygen species. Furthermore low concentrations of DFX activate the NF-κB pathway in erythroid precursors triggering anti-apoptotic and anti-inflammatory signals. Establishing stable gene silencing of the Thioredoxin (TRX) 1 genes, a NF-κB modulator, showed that fine-tuning of reactive oxygen species (ROS) levels regulates NF-κB. These results justify a clinical trial proposing low dose DFX in MDS patients refractory to erythropoiesis stimulating agents.

  7. Reactive oxygen species levels control NF-κB activation by low dose deferasirox in erythroid progenitors of low risk myelodysplastic syndromes

    PubMed Central

    Meunier, Mathieu; Ancelet, Sarah; Lefebvre, Christine; Arnaud, Josiane; Garrel, Catherine; Pezet, Mylène; Wang, Yan; Faure, Patrice; Szymanski, Gautier; Duployez, Nicolas; Preudhomme, Claude; Biard, Denis; Polack, Benoit; Cahn, Jean-Yves; Moulis, Jean Marc; Park, Sophie

    2017-01-01

    Anemia is a frequent cytopenia in myelodysplastic syndromes (MDS) and most patients require red blood cell transfusion resulting in iron overload (IO). Deferasirox (DFX) has become the standard treatment of IO in MDS and it displays positive effects on erythropoiesis. In low risk MDS samples, mechanisms improving erythropoiesis after DFX treatment remain unclear. Herein, we addressed this question by using liquid cultures with iron overload of erythroid precursors treated with low dose of DFX (3μM), which corresponds to DFX 5 mg/kg/day, an unusual dose used for iron chelation. We highlight a decreased apoptosis rate and an increased proportion of cycling cells, both leading to higher proliferation rates. The iron chelation properties of low dose DFX failed to activate the Iron Regulatory Proteins and to support iron depletion, but low dose DFX dampers intracellular reactive oxygen species. Furthermore low concentrations of DFX activate the NF-κB pathway in erythroid precursors triggering anti-apoptotic and anti-inflammatory signals. Establishing stable gene silencing of the Thioredoxin (TRX) 1 genes, a NF-κB modulator, showed that fine-tuning of reactive oxygen species (ROS) levels regulates NF-κB. These results justify a clinical trial proposing low dose DFX in MDS patients refractory to erythropoiesis stimulating agents. PMID:29285268

  8. Detection of oxygen species generated by WO{sub 3} modification fullerene/TiO{sub 2} in the degradation of 1,5-diphenyl carbazide

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Meng, Ze-Da; Department of Advanced Materials Science and Engineering, Hanseo University, Seosan-si, Chungnam-do 356-706; Zhu, Lei

    2014-08-15

    Highlights: • Reactive oxygen species were detected through oxidation reaction from DPCI to DPCO. • Generated reactive oxygen species and hydroxyl radicals can be analysed by DPCI degradation. • C{sub 60} have good effect in photo/ultrasonic degradation process. • Enhanced adsorption capacity can increase the degradation effect. • Photocatalytic activity attributed to photo-absorption effect by C{sub 60} and cooperative effect of WO{sub 3} and TiO{sub 2}. - Abstract: In the present work, powders with different relative mole ratios of WO{sub 3}-fullerene/TiO{sub 2} were irradiated by visible light and ultrasonic. The composite obtained was characterized by BET surface area measurements, X-raymore » diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), fourier transform infrared (FT-IR), transmission electron microscopy (TEM) and UV–vis analysis. A methylene blue (MB) solution under visible light and ultrasonic irradiation was used to determine the catalytic activity. The generation of reactive oxygen species were detected through the oxidation reaction from 1,5-diphenyl carbazide (DPCI) to 1,5-diphenyl carbazone (DPCO). Finally, we performed experiments to find the optimum relative mole ratio of fullerene for the degradation of MB.« less

  9. Formation of reactive oxygen by N2O decomposition over binuclear cationic sites of Fe-ferrierite zeolite: Periodic DFT + U study

    NASA Astrophysics Data System (ADS)

    Avdeev, Vasilii I.; Bedilo, Alexander F.

    2018-03-01

    The electronic nature of sites over Fe-ferrierite zeolite stabilizing active α-oxygen is analyzed by the periodic DFT + U approach. It is shown that two antiferromagnetically coupled Fe2+ cations with bridging OH-bonds form a stable bi-nuclear site of the [Fe2+<2OH>Fe2+] doped FER complex. Frontier orbitals of this complex populated by two electrons with minority spins are localized in the bandgap. As a result, [Fe2+<2OH>Fe2+] unit acquires the properties of a binuclear Lewis acid dipolarophile for 1,3-dipole N2O. First reaction step of N2O decomposition follows the Huisgen‧s concept of the 1,3-dipolar cycloaddition concept followed by the formation of reactive oxygen species Fesbnd O.

  10. Real-time in vivo detection of biomaterial-induced reactive oxygen species.

    PubMed

    Liu, Wendy F; Ma, Minglin; Bratlie, Kaitlin M; Dang, Tram T; Langer, Robert; Anderson, Daniel G

    2011-03-01

    The non-specific host response to implanted biomaterials is often a key challenge of medical device design. To evaluate biocompatibility, measuring the release of reactive oxygen species (ROS) produced by inflammatory cells in response to biomaterial surfaces is a well-established method. However, the detection of ROS in response to materials implanted in vivo has not yet been demonstrated. Here, we develop a bioluminescence whole animal imaging approach to observe ROS released in response to subcutaneously-implanted materials in live animals. We compared the real-time generation of ROS in response to two representative materials, polystyrene and alginate, over the course of 28 days. High levels of ROS were observed near polystyrene, but not alginate implants, and persisted throughout the course of 28 days. Histological analysis revealed that high levels of ROS correlated not only with the presence of phagocytic cells at early timepoints, but also fibrosis at later timepoints, suggesting that ROS may be involved in both the acute and chronic phase of the foreign body response. These data are the first in vivo demonstration of ROS generation in response to implanted materials, and describe a novel technique to evaluate the host response. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Reactive oxygen species in plasma against E. coli cells survival rate

    NASA Astrophysics Data System (ADS)

    Zhou, Ren-Wu; Zhang, Xian-Hui; Zong, Zi-Chao; Li, Jun-Xiong; Yang, Zhou-Bin; Liu, Dong-Ping; Yang, Si-Ze

    2015-08-01

    In this paper, we report on the contrastive analysis of inactivation efficiency of E. coli cells in solution with different disinfection methods. Compared with the hydrogen peroxide solution and the ozone gas, the atmospheric-pressure He plasma can completely kill the E. coli cells in the shortest time. The inactivation efficiency of E. coli cells in solution can be well described by using the chemical reaction rate model. X-ray photoelectron spectroscopy (XPS) analysis shows that the C-O or C=O content of the inactivated E. coli cell surface by plasma is predominantly increased, indicating the quantity of oxygen-containing species in plasma is more than those of two other methods, and then the C-C or C-H bonds can be broken, leading to the etching of organic compounds. Analysis also indicates that plasma-generated species can play a crucial role in the inactivation process by their direct reactions or the decompositions of reactive species, such as ozone into OH radicals in water, then reacting with E. coli cells. Project supported by the Natural Science Foundation of Fujian Province, China (Grant No. 2014J01025), the National Natural Science Foundation of China (Grant No. 11275261), and the Funds from the Fujian Provincial Key Laboratory for Plasma and Magnetic Resonance, China.

  12. Uncoupling proteins and the control of mitochondrial reactive oxygen species production.

    PubMed

    Mailloux, Ryan J; Harper, Mary-Ellen

    2011-09-15

    Reactive oxygen species (ROS), natural by-products of aerobic respiration, are important cell signaling molecules, which left unchecked can severely impair cellular functions and induce cell death. Hence, cells have developed a series of systems to keep ROS in the nontoxic range. Uncoupling proteins (UCPs) 1-3 are mitochondrial anion carrier proteins that are purported to play important roles in minimizing ROS emission from the electron transport chain. The function of UCP1 in this regard is highly contentious. However, UCPs 2 and 3 are generally thought to be activated by ROS or ROS by-products to induce proton leak, thus providing a negative feedback loop for mitochondrial ROS production. In our laboratory, we have not only confirmed that ROS activate UCP2 and UCP3, but also demonstrated that UCP2 and UCP3 are controlled by covalent modification by glutathione. Furthermore, the reversible glutathionylation is required to activate/inhibit UCP2 and UCP3, but not UCP1. Hence, our findings are consistent with the notion that UCPs 2 and 3 are acutely activated by ROS, which then directly modulate the glutathionylation status of the UCP to decrease ROS emission and participate in cell signaling mechanisms. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Uncoupling protein-3 lowers reactive oxygen species production in isolated mitochondria

    PubMed Central

    Toime, Laurence J.; Brand, Martin D.

    2010-01-01

    Mitochondria are the major cellular producers of reactive oxygen species (ROS), and mitochondrial ROS production increases steeply with increased protonmotive force. The uncoupling proteins (UCP1, UCP2 and UCP3) and adenine nucleotide translocase induce proton leak in response to exogenously added fatty acids, superoxide or lipid peroxidation products. “Mild uncoupling” by these proteins may provide a negative feedback loop to decrease protonmotive force and attenuate ROS production. Using wild type and Ucp3−/− mice, we found that native UCP3 actively lowers the rate of ROS production in isolated energized skeletal muscle mitochondria, in the absence of exogenous activators. The estimated specific activity of UCP3 in lowering ROS production was 90 to 500 times higher than that of the adenine nucleotide translocase. The mild uncoupling hypothesis was tested by measuring whether the effect of UCP3 on ROS production could be mimicked by chemical uncoupling. A chemical uncoupler mimicked the effect of UCP3 at early time points after mitochondrial energization, in support of the mild uncoupling hypothesis. However, at later time points the uncoupler did not mimic UCP3, suggesting that UCP3 can also affect on ROS production through a membrane potential-independent mechanism. PMID:20493945

  14. Paraoxonase-1 gene Q192R polymorphism and reactive oxygen metabolites.

    PubMed

    Kotani, K; Tsuzaki, K; Sakane, N

    2012-01-01

    Paraoxonase-1 (PON1) is a high-density lipoprotein-associated antioxidant enzyme. The Q192R polymorphism of the PON1 gene can protect against oxidative conditions, but the relationship between Q192R polymorphism and oxidative stress-related markers remains controversial. In this study, the diacron reactive oxygen metabolites (d-ROMs) test was used to investigate the relationship between Q192R polymorphism and oxidative stress-related markers in Japanese subjects. Patients without a history of overt cardiovascular disease who were not receiving antioxidant medication were enrolled in a cross-sectional clinic-based study. An allele-specific polymerase chain reaction method was used to assess the PON1 Q192R polymorphism and compare the level of d-ROMs between genotypes. A total of 103 subjects were analysed. The RR genotype was associated with a significantly lower level of d-ROMs than the RQ and QQ genotypes. After multivariate analysis the relationship between the genotypes and level of d-ROMs remained independently significant. The RR genotype may be protective against oxidative stress in cardiovascular diseasefree Japanese subjects. In addition, the d-ROMs test can be useful for examining the role of the PON1 Q192R polymorphism under oxidative conditions.

  15. Role of dissolved oxygen on the degradation mechanism of Reactive Green 19 and electricity generation in photocatalytic fuel cell.

    PubMed

    Lee, Sin-Li; Ho, Li-Ngee; Ong, Soon-An; Wong, Yee-Shian; Voon, Chun-Hong; Khalik, Wan Fadhilah; Yusoff, Nik Athirah; Nordin, Noradiba

    2018-03-01

    In this study, a membraneless photocatalytic fuel cell with zinc oxide loaded carbon photoanode and platinum loaded carbon cathode was constructed to investigate the impact of dissolved oxygen on the mechanism of dye degradation and electricity generation of photocatalytic fuel cell. The photocatalytic fuel cell with high and low aeration rate, no aeration and nitrogen purged were investigated, respectively. The degradation rate of diazo dye Reactive Green 19 and the electricity generation was enhanced in photocatalytic fuel cell with higher dissolved oxygen concentration. However, the photocatalytic fuel cell was still able to perform 37% of decolorization in a slow rate (k = 0.033 h -1 ) under extremely low dissolved oxygen concentration (approximately 0.2 mg L -1 ) when nitrogen gas was introduced into the fuel cell throughout the 8 h. However, the change of the UV-Vis spectrum indicates that the intermediates of the dye could not be mineralized under insufficient dissolved oxygen level. In the aspect of electricity generation, the maximum short circuit current (0.0041 mA cm -2 ) and power density (0.00028 mW cm -2 ) of the air purged photocatalytic fuel cell was obviously higher than that with nitrogen purging (0.0015 mA cm -2 and 0.00008 mW cm -2 ). Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Reciprocal regulation of TGF-β and reactive oxygen species: A perverse cycle for fibrosis

    PubMed Central

    Liu, Rui-Ming; Desai, Leena P.

    2015-01-01

    Transforming growth factor beta (TGF-β) is the most potent pro-fibrogenic cytokine and its expression is increased in almost all of fibrotic diseases. Although signaling through Smad pathway is believed to play a central role in TGF-β's fibrogenesis, emerging evidence indicates that reactive oxygen species (ROS) modulate TGF-β's signaling through different pathways including Smad pathway. TGF-β1 increases ROS production and suppresses antioxidant enzymes, leading to a redox imbalance. ROS, in turn, induce/activate TGF-β1 and mediate many of TGF-β's fibrogenic effects, forming a vicious cycle (see graphic flow chart on the right). Here, we review the current knowledge on the feed-forward mechanisms between TGF-β1 and ROS in the development of fibrosis. Therapeutics targeting TGF-β-induced and ROS-dependent cellular signaling represents a novel approach in the treatment of fibrotic disorders. PMID:26496488

  17. Hydrogen abstraction from deoxyribose by a neighboring 3'-uracil peroxyl radical.

    PubMed

    Schyman, Patric; Eriksson, Leif A; Laaksonen, Aatto

    2009-05-07

    Theoretical examination of the reactivity of the uracil-5-peroxyl radical when abstracting a hydrogen atom from a neighboring 5'-deoxyribose in 5'-ApU-5-peroxyl-3' has been performed using density functional theory with the MPWB1K functional. Halogenated uracils are often used as radiosensitizers in DNA since the reactive uracil-5-yl radical is formed upon radiation and is known to create strand break and alkali-labile sites. Under aerobic conditions, such as in the cell, it has been proposed that the uracil-5-peroxyl radical is formed and would be the damaging agent. Our results show low reactivity for the uracil-5-peroxyl radical, determined by calculating the activation and reaction energies for the plausible hydrogen abstraction sites C1', C2', and C3' of the neighboring 5'-deoxyribose. These findings support the hypothesis that hydrogen abstraction primarily occurs by the uracil-5-yl radical, also under aerobic conditions, prior to formation of the peroxyl radical.

  18. THE EFFECT OF TUNGSTATE NANOPARTICLES ON REACTIVE OXYGEN SPECIES AND CYTOTOXICITY IN RAW 264.7 MOUSE MONOCYTE MACROPHAGE CELLS

    PubMed Central

    Dunnick, Katherine M.; Badding, Melissa A.; Schwegler-Berry, Diane; Patete, Jonathan M.; Koenigsmann, Christopher; Wong, Stanislaus S.; Leonard, Stephen S.

    2015-01-01

    Due to their unique size, surface area, and chemical characteristics, nanoparticles’ use in consumer products has increased. However, the toxicity of nanoparticle (NP) exposure during the manufacturing process has not been fully assessed. Tungstate NP are used in numerous products, including but not limited to scintillator detectors and fluorescent lighting. As with many NP, no apparent toxicity studies have been completed with tungstate NP. The hypothesis that tungstate NP in vitro exposure results in reactive oxygen species (ROS) formation and cytotoxicity was examined. Differences in toxicity based on tungstate NP size, shape (sphere vs. wire), and chemical characteristics were determined. RAW 264.7 mouse monocyte macrophages were exposed to tungstate NP, and ROS formation was assessed via electron spin resonance (ESR), and several assays including hydrogen peroxide, intracellular ROS, and Comet. Results showed ROS production induced by tungstate nanowire exposure, but this exposure did not result in oxidative DNA damage. Nanospheres showed neither ROS nor DNA damage following cellular exposure. Cells were exposed over 72 h to assess cytotoxicity using an MTT (tetrazolium compound) assay. Results showed that differences in cell death between wires and spheres occurred at 24 h but were minimal at both 48 and 72 h. The present results indicate that tungstate nanowires are more reactive and produce cell death within 24 h of exposure, whereas nanospheres are less reactive and did not produce cell death. Results suggest that differences in shape may affect reactivity. However, regardless of the differences in reactivity, in general both shapes produced mild ROS and resulted in minimal cell death at 48 and 72 h in RAW 264.7 cells. PMID:25208664

  19. Light irradiation helps magnetotactic bacteria eliminate intracellular reactive oxygen species.

    PubMed

    Li, Kefeng; Wang, Pingping; Chen, Chuanfang; Chen, Changyou; Li, Lulu; Song, Tao

    2017-09-01

    Magnetotactic bacteria (MTB) demonstrate photoresponse. However, little is known about the biological significance of this behaviour. Magnetosomes exhibit peroxidase-like activity and can scavenge reactive oxygen species (ROS). Magnetosomes extracted from the Magnetospirillum magneticum strain AMB-1 show enhanced peroxidase-like activity under illumination. The present study investigated the effects of light irradiation on nonmagnetic (without magnetosomes) and magnetic (with magnetosomes) AMB-1 cells. Results showed that light irradiation did not affect the growth of nonmagnetic and magnetic cells but significantly increased magnetosome synthesis and reduced intracellular ROS level in magnetic cells. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to analyse the expression level of magnetosome formation-associated genes (mamA, mms6, mms13 and mmsF) and stress-related genes (recA, oxyR, SOD, amb0664 and amb2684). Results showed that light irradiation upregulated the expression of mms6, mms13 and mmsF. Furthermore, light irradiation upregulated the expression of stress-related genes in nonmagnetic cells but downregulated them in magnetic cells. Additionally, magnetic cells exhibited stronger phototactic behaviour than nonmagnetic ones. These results suggested that light irradiation could heighten the ability of MTB to eliminate intracellular ROS and help them adapt to lighted environments. This phenomenon may be related to the enhanced peroxidase-like activity of magnetosomes under light irradiation. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  20. LDL Particle Size and Reactive Oxygen Metabolites in Dyslipidemic Patients

    PubMed Central

    Kotani, Kazuhiko; Tsuzaki, Kokoro; Taniguchi, Nobuyuki; Sakane, Naoki

    2012-01-01

    Objectives: Small dense low-density lipoprotein (sdLDL) which has a small LDL particle size with greater susceptibility to oxidation is regarded as a risk marker for cardiovascular disease. The diacron reactive oxygen metabolites (d-ROMs) test has recently been introduced as an oxidative stress-related marker in the clinic. The aim of the present study was to investigate the correlation between the mean LDL particle size and the oxidative stress status as evaluated by the d-ROMs in dyslipidemic patients. Methods: The study included 278 dyslipidemic patients (121 male and 157 female, mean age, 60 years). Clinical data including the conventional atherosclerotic risk factors in addition to the mean LDL particle size measured with the gel electrophoresis and the d-ROMs were collected. Results: Male patients had a significantly smaller mean LDL particle size than females (262.2 ± 7.5 [SD] vs. 264.3 ± 6.7 Å, P<0.05), while female patients had a significantly higher d-ROMs level than males (318 ± 68 vs. 350 ± 72 U. Carr., P<0.01). A multiple regression analysis revealed that there was an independent, significant, and inverse correlation between the mean LDL particle size and the d-ROMs (β=−0.19, P<0.05). Conclusions: These findings of the co-existence of both markers suggest that sdLDL and oxidative stress can be cooperative in atherogenesis, possibly leading to the incidence of CVD, in dyslipidemic patients. PMID:22448308

  1. LDL Particle Size and Reactive Oxygen Metabolites in Dyslipidemic Patients.

    PubMed

    Kotani, Kazuhiko; Tsuzaki, Kokoro; Taniguchi, Nobuyuki; Sakane, Naoki

    2012-03-01

    Small dense low-density lipoprotein (sdLDL) which has a small LDL particle size with greater susceptibility to oxidation is regarded as a risk marker for cardiovascular disease. The diacron reactive oxygen metabolites (d-ROMs) test has recently been introduced as an oxidative stress-related marker in the clinic. The aim of the present study was to investigate the correlation between the mean LDL particle size and the oxidative stress status as evaluated by the d-ROMs in dyslipidemic patients. The study included 278 dyslipidemic patients (121 male and 157 female, mean age, 60 years). Clinical data including the conventional atherosclerotic risk factors in addition to the mean LDL particle size measured with the gel electrophoresis and the d-ROMs were collected. Male patients had a significantly smaller mean LDL particle size than females (262.2 ± 7.5 [SD] vs. 264.3 ± 6.7 Å, P<0.05), while female patients had a significantly higher d-ROMs level than males (318 ± 68 vs. 350 ± 72 U. Carr., P<0.01). A multiple regression analysis revealed that there was an independent, significant, and inverse correlation between the mean LDL particle size and the d-ROMs (β=-0.19, P<0.05). These findings of the co-existence of both markers suggest that sdLDL and oxidative stress can be cooperative in atherogenesis, possibly leading to the incidence of CVD, in dyslipidemic patients.

  2. Axial ligand tuning of a nonheme iron(IV)–oxo unit for hydrogen atom abstraction

    PubMed Central

    Sastri, Chivukula V.; Lee, Jimin; Oh, Kyungeun; Lee, Yoon Jin; Lee, Junghyun; Jackson, Timothy A.; Ray, Kallol; Hirao, Hajime; Shin, Woonsup; Halfen, Jason A.; Kim, Jinheung; Que, Lawrence; Shaik, Sason; Nam, Wonwoo

    2007-01-01

    The reactivities of mononuclear nonheme iron(IV)–oxo complexes bearing different axial ligands, [FeIV(O)(TMC)(X)]n+ [where TMC is 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane and X is NCCH3 (1-NCCH3), CF3COO− (1-OOCCF3), or N3− (1-N3)], and [FeIV(O)(TMCS)]+ (1′-SR) (where TMCS is 1-mercaptoethyl-4,8,11-trimethyl-1,4,8,11-tetraazacyclotetradecane), have been investigated with respect to oxo-transfer to PPh3 and hydrogen atom abstraction from phenol OH and alkylaromatic CH bonds. These reactivities were significantly affected by the identity of the axial ligands, but the reactivity trends differed markedly. In the oxidation of PPh3, the reactivity order of 1-NCCH3 > 1-OOCCF3 > 1-N3 > 1′-SR was observed, reflecting a decrease in the electrophilicity of iron(IV)–oxo unit upon replacement of CH3CN with an anionic axial ligand. Surprisingly, the reactivity order was inverted in the oxidation of alkylaromatic CH and phenol OH bonds, i.e., 1′-SR > 1-N3 > 1-OOCCF3 > 1-NCCH3. Furthermore, a good correlation was observed between the reactivities of iron(IV)–oxo species in H atom abstraction reactions and their reduction potentials, Ep,c, with the most reactive 1′-SR complex exhibiting the lowest potential. In other words, the more electron-donating the axial ligand is, the more reactive the iron(IV)–oxo species becomes in H atom abstraction. Quantum mechanical calculations show that a two-state reactivity model applies to this series of complexes, in which a triplet ground state and a nearby quintet excited-state both contribute to the reactivity of the complexes. The inverted reactivity order in H atom abstraction can be rationalized by a decreased triplet-quintet gap with the more electron-donating axial ligand, which increases the contribution of the much more reactive quintet state and enhances the overall reactivity. PMID:18048327

  3. Blood oxygen-level dependent functional assessment of cerebrovascular reactivity: Feasibility for intraoperative 3 Tesla MRI.

    PubMed

    Fierstra, Jorn; Burkhardt, Jan-Karl; van Niftrik, Christiaan Hendrik Bas; Piccirelli, Marco; Pangalu, Athina; Kocian, Roman; Neidert, Marian Christoph; Valavanis, Antonios; Regli, Luca; Bozinov, Oliver

    2017-02-01

    To assess the feasibility of functional blood oxygen-level dependent (BOLD) MRI to evaluate intraoperative cerebrovascular reactivity (CVR) at 3 Tesla field strength. Ten consecutive neurosurgical subjects scheduled for a clinical intraoperative MRI examination were enrolled in this study. In addition to the clinical protocol a BOLD sequence was implemented with three cycles of 44 s apnea to calculate CVR values on a voxel-by-voxel basis throughout the brain. The CVR range was then color-coded and superimposed on an anatomical volume to create high spatial resolution CVR maps. Ten subjects (mean age 34.8 ± 13.4; 2 females) uneventfully underwent the intraoperative BOLD protocol, with no complications occurring. Whole-brain CVR for all subjects was (mean ± SD) 0.69 ± 0.42, whereas CVR was markedly higher for tumor subjects as compared to vascular subjects, 0.81 ± 0.44 versus 0.33 ± 0.10, respectively. Furthermore, color-coded functional maps could be robustly interpreted for a whole-brain assessment of CVR. We demonstrate that intraoperative BOLD MRI is feasible in creating functional maps to assess cerebrovascular reactivity throughout the brain in subjects undergoing a neurosurgical procedure. Magn Reson Med 77:806-813, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  4. Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Meeran, Syed M.; Katiyar, Suchitra; Katiyar, Santosh K.

    2008-05-15

    Phytochemicals show promise as potential chemopreventive or chemotherapeutic agents against various cancers. Here we report the chemotherapeutic effects of berberine, a phytochemical, on human prostate cancer cells. The treatment of human prostate cancer cells (PC-3) with berberine induced dose-dependent apoptosis but this effect of berberine was not seen in non-neoplastic human prostate epithelial cells (PWR-1E). Berberine-induced apoptosis was associated with the disruption of the mitochondrial membrane potential, release of apoptogenic molecules (cytochrome c and Smac/DIABLO) from mitochondria and cleavage of caspase-9,-3 and PARP proteins. This effect of berberine on prostate cancer cells was initiated by the generation of reactive oxygenmore » species (ROS) irrespective of their androgen responsiveness, and the generation of ROS was through the increased induction of xanthine oxidase. Treatment of cells with allopurinol, an inhibitor of xanthine oxidase, inhibited berberine-induced oxidative stress in cancer cells. Berberine-induced apoptosis was blocked in the presence of antioxidant, N-acetylcysteine, through the prevention of disruption of mitochondrial membrane potential and subsequently release of cytochrome c and Smac/DIABLO. In conclusion, the present study reveals that the berberine-mediated cell death of human prostate cancer cells is regulated by reactive oxygen species, and therefore suggests that berberine may be considered for further studies as a promising therapeutic candidate for prostate cancer.« less

  5. Negative Regulation of Autophagy by Sulfide Is Independent of Reactive Oxygen Species.

    PubMed

    Laureano-Marín, Ana M; Moreno, Inmaculada; Romero, Luis C; Gotor, Cecilia

    2016-06-01

    Accumulating experimental evidence in mammalian, and recently plant, systems has led to a change in our understanding of the role played by hydrogen sulfide in life processes. In plants, hydrogen sulfide mitigates stress and regulates important plant processes such as photosynthesis, stomatal movement, and autophagy, although the underlying mechanism is not well known. In this study, we provide new experimental evidence that, together with our previous findings, demonstrates the role of hydrogen sulfide in regulating autophagy. We used green fluorescent protein fluorescence associated with autophagic bodies and immunoblot analysis of the ATG8 protein to show that sulfide (and no other molecules such as sulfur-containing molecules or ammonium) was able to inhibit the autophagy induced in Arabidopsis (Arabidopsis thaliana) roots under nitrogen deprivation. Our results showed that sulfide was unable to scavenge reactive oxygen species generated by nitrogen limitation, in contrast to well-established reducers. In addition, reducers were unable to inhibit the accumulation of autophagic bodies and ATG8 protein forms to the same extent as sulfide. Therefore, we conclude that sulfide represses autophagy via a mechanism that is independent of redox conditions. © 2016 American Society of Plant Biologists. All Rights Reserved.

  6. Chlorogenic acid ameliorates alcohol-induced liver injuries through scavenging reactive oxygen species.

    PubMed

    Kim, Hyunjin; Pan, Jeong Hoon; Kim, Sung Hwan; Lee, Jin Hyup; Park, Jeen-Woo

    2018-05-19

    The key role of oxidative stress in alcoholic liver disease (ALD) has been established by the large body of evidence from previous studies. Excessive consumption of ethanol induces the production of a variety of reactive oxygen species (ROS) in the liver, such as superoxide, H 2 O 2 , and hydroxyl radical. These products activate oxidant-sensitive signaling cascades and modulators of apoptosis. Because ROS accumulation is closely related to ALD, a number of studies have investigated the benefits of antioxidants. Recent studies demonstrated that polyphenol chlorogenic acid (CGA) has antioxidant properties and health benefits, such as reduction of relative risk of cardiovascular diseases and hepatoprotective effects against acetaminophen toxicity. However, the protective effects of CGA against ALD have not been studied in detail. We hypothesize that CGA plays a role in preventing ALD through its antioxidant properties. In this study, we investigated the protective effects of CGA against liver injuries in vivo. Reduced alcohol-induced-steatosis, apoptotic cell death, and fibrosis due to reduced levels of oxidative stress were observed. These findings suggest that CGA treatment can be an effective approach to attenuate ALD through the suppression of oxidative stress. Copyright © 2018. Published by Elsevier B.V.

  7. [Hyperoxia induces reactive oxygen species production and promotes SIRT1 nucleocytoplasmic shuttling of peripheral blood mononuclear cells in premature infants in vitro].

    PubMed

    Yang, Xi; Dong, Wenbin; Li, Qingping; Kang, Lan; Lei, Xiaoping; Zhang, Lianyu; Lu, Youying; Zhai, Xuesong

    2015-12-01

    To explore the relationship between deacetylase sirtuin 1 (SIRT1) and reactive oxygen species (ROS) after oxygen therapy in the peripheral blood mononuclear cells (PBMCs) of the premature infants. According to the fraction of inspired O2 (FiO2), premature infants diagnosed with respiratory distress syndrome (RDS) (gestational age <32 weeks), were divided into three groups: low dosage oxygen group (FiO2 <300 mL/L), moderate dosage oxygen group (FiO2; 300 mL/L-400 mL/L), high dosage oxygen group (FiO2 >400 mL/L). After 48 hours of oxygen treatment, PBMCs and serum were collected from the peripheral blood. Then the intracellular ROS level was detected by MitoSOX(TM) Red labeling combined with confocal laser scanning microscopy; the malondialdehyde (MDA) content in the serum was determined by the whole spectrum spectrophotometer; the SIRT1 localization was observed by immunofluorescence staining; and the SIRT1 levels in PBMCs were examined by Western blotting. With the increase of FiO2, the ROS, MDA content and the rate of SIRT1 nucleocytoplasmic shuttling of PBMCs gradually increased and SIRT1 protein expression was significantly lowered. Hyperoxia induces ROS production in premature infants, promotes SIRT1 to cross from nucleus to cytoplasm, inhibits the resistant ability of SIRT1 to oxidative stress.

  8. 12-Chloracetyl-PPD, a novel dammarane derivative, shows anti-cancer activity via delay the progression of cell cycle G2/M phase and reactive oxygen species-mediate cell apoptosis.

    PubMed

    Wang, Xu De; Sun, Yuan Yuan; Zhao, Chen; Qu, Fan Zhi; Zhao, Yu Qing

    2017-03-05

    (20R)-Dammarane-3β, 12β, 20, 25-tetrol (25-OH-PPD) is a ginsenoside isolated from Panax ginseng (C. A. Meyer). This compound exhibits anti-cancer activities on many human cancer cell lines. In this study, we investigated anti-cancer mechanisms of 12β-O-( L -Chloracetyl)-dammar-20(22)-ene-3β,25-diol(12-Chloracetyl-PPD), a modified 25-OH-PPD. We found that compound 12-Chloracetyl-PPD resulted in a concentration-dependent inhibition of viability in prostate, breast, and gastric cancer cells, without affecting the viability of normal cell (human gastric epithelial cell line-GES-1, hair follicle dermal papilla cell line-HHDPC and rat myocardial cell line-H9C2). In MDA-MB-435 and C4-2B cancer cells, 12-Chloracetyl-PPD induced G2/M cell cycle arrest, down-regulated mouse double minute 2 (MDM2) expression, up-regulated p53 expression, triggered apoptosis, and stimulated reactive oxygen species production. Apoptosis can be attenuated by the reactive oxygen species scavenger N-acetylcysteine. Our results suggested that compound 12-Chloracetyl-PPD showed obvious anti-cancer activity based on delaying cell cycle arrest and inducing cell apoptosis by reactive oxygen species production, which supported development of 12-Chloracetyl-PPD as a potential agent for cancer chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Hampering Effect of Cholesterol on the Permeation of Reactive Oxygen Species through Phospholipids Bilayer: Possible Explanation for Plasma Cancer Selectivity

    NASA Astrophysics Data System (ADS)

    van der Paal, Jonas; Verheyen, Claudia; Neyts, Erik C.; Bogaerts, Annemie

    2017-01-01

    In recent years, the ability of cold atmospheric pressure plasmas (CAPS) to selectively induce cell death in cancer cells has been widely established. This selectivity has been assigned to the reactive oxygen and nitrogen species (RONS) created in CAPs. To provide new insights in the search for an explanation for the observed selectivity, we calculate the transfer free energy of multiple ROS across membranes containing a varying amount of cholesterol. The cholesterol fraction is investigated as a selectivity parameter because membranes of cancer cells are known to contain lower fractions of cholesterol compared to healthy cells. We find that cholesterol has a significant effect on the permeation of reactive species across a membrane. Indeed, depending on the specific reactive species, an increasing cholesterol fraction can lead to (i) an increase of the transfer free energy barrier height and width, (ii) the formation of a local free energy minimum in the center of the membrane and (iii) the creation of extra free energy barriers due to the bulky sterol rings. In the context of plasma oncology, these observations suggest that the increased ingress of RONS in cancer cells can be explained by the decreased cholesterol fraction of their cell membrane.

  10. Oxoferryl-Porphyrin Radical Catalytic Intermediate in Cytochrome bd Oxidases Protects Cells from Formation of Reactive Oxygen Species*

    PubMed Central

    Paulus, Angela; Rossius, Sebastiaan Gijsbertus Hendrik; Dijk, Madelon; de Vries, Simon

    2012-01-01

    The quinol-linked cytochrome bd oxidases are terminal oxidases in respiration. These oxidases harbor a low spin heme b558 that donates electrons to a binuclear heme b595/heme d center. The reaction with O2 and subsequent catalytic steps of the Escherichia coli cytochrome bd-I oxidase were investigated by means of ultra-fast freeze-quench trapping followed by EPR and UV-visible spectroscopy. After the initial binding of O2, the O–O bond is heterolytically cleaved to yield a kinetically competent heme d oxoferryl porphyrin π-cation radical intermediate (compound I) magnetically interacting with heme b595. Compound I accumulates to 0.75–0.85 per enzyme in agreement with its much higher rate of formation (∼20,000 s−1) compared with its rate of decay (∼1,900 s−1). Compound I is next converted to a short lived heme d oxoferryl intermediate (compound II) in a phase kinetically matched to the oxidation of heme b558 before completion of the reaction. The results indicate that cytochrome bd oxidases like the heme-copper oxidases break the O–O bond in a single four-electron transfer without a peroxide intermediate. However, in cytochrome bd oxidases, the fourth electron is donated by the porphyrin moiety rather than by a nearby amino acid. The production of reactive oxygen species by the cytochrome bd oxidase was below the detection level of 1 per 1000 turnovers. We propose that the two classes of terminal oxidases have mechanistically converged to enzymes in which the O–O bond is broken in a single four-electron transfer reaction to safeguard the cell from the formation of reactive oxygen species. PMID:22287551

  11. Oxygen concentration inside a functioning photosynthetic cell.

    PubMed

    Kihara, Shigeharu; Hartzler, Daniel A; Savikhin, Sergei

    2014-05-06

    The excess oxygen concentration in the photosynthetic membranes of functioning oxygenic photosynthetic cells was estimated using classical diffusion theory combined with experimental data on oxygen production rates of cyanobacterial cells. The excess oxygen concentration within the plesiomorphic cyanobacterium Gloeobactor violaceus is only 0.025 μM, or four orders of magnitude lower than the oxygen concentration in air-saturated water. Such a low concentration suggests that the first oxygenic photosynthetic bacteria in solitary form could have evolved ∼2.8 billion years ago without special mechanisms to protect them against reactive oxygen species. These mechanisms instead could have been developed during the following ∼500 million years while the oxygen level in the Earth's atmosphere was slowly rising. Excess oxygen concentrations within individual cells of the apomorphic cyanobacteria Synechocystis and Synechococcus are 0.064 and 0.25 μM, respectively. These numbers suggest that intramembrane and intracellular proteins in isolated oxygenic photosynthetic cells are not subjected to excessively high oxygen levels. The situation is different for closely packed colonies of photosynthetic cells. Calculations show that the excess concentration within colonies that are ∼40 μm or larger in diameter can be comparable to the oxygen concentration in air-saturated water, suggesting that species forming colonies require protection against reactive oxygen species even in the absence of oxygen in the surrounding atmosphere. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  12. The bacterial pigment pyocyanin inhibits the NLRP3 inflammasome through intracellular reactive oxygen and nitrogen species

    PubMed Central

    Virreira Winter, Sebastian; Zychlinsky, Arturo

    2018-01-01

    Inflammasomes are cytosolic complexes that mature and secrete the inflammatory cytokines interleukin 1β (IL-1β) and IL-18 and induce pyroptosis. The NLRP3 (NACHT, LRR, and PYD domains–containing protein 3) inflammasome detects many pathogen- and danger-associated molecular patterns, and reactive oxygen species (ROS)/reactive nitrogen species (RNS) have been implicated in its activation. The phenazine pyocyanin (PCN) is a virulence factor of Pseudomonas aeruginosa and generates superoxide in cells. Here we report that PCN inhibits IL-1β and IL-18 release and pyroptosis upon NLRP3 inflammasome activation in macrophages by preventing speck formation and Caspase-1 maturation. Of note, PCN did not regulate the AIM2 (absent in melanoma 2) or NLRC4 inflammasomes or tumor necrosis factor (TNF) secretion. Imaging of the fluorescent glutathione redox potential sensor Grx1-roGFP2 indicated that PCN provokes cytosolic and nuclear but not mitochondrial redox changes. PCN-induced intracellular ROS/RNS inhibited the NLRP3 inflammasome posttranslationally, and hydrogen peroxide or peroxynitrite alone were sufficient to block its activation. We propose that cytosolic ROS/RNS inhibit the NLRP3 inflammasome and that PCN's anti-inflammatory activity may help P. aeruginosa evade immune recognition. PMID:29414783

  13. Increased Interleukin-23 in Hashimoto's Thyroiditis Disease Induces Autophagy Suppression and Reactive Oxygen Species Accumulation.

    PubMed

    Zheng, Tingting; Xu, Chengcheng; Mao, Chaoming; Mou, Xiao; Wu, Fei; Wang, Xuefeng; Bu, Ling; Zhou, Yuepeng; Luo, Xuan; Lu, Qingyan; Liu, Hongli; Yuan, Guoyue; Wang, Shengjun; Chen, Deyu; Xiao, Yichuan

    2018-01-01

    Hashimoto's thyroiditis (HT) represents the most common organ-specific autoimmune disease. Inflammatory factors and reactive oxygen species (ROS) play detrimental roles during the pathogenesis of HT. In this study, we found that thyroid follicular cells (TFCs) from HT patients expressed an elevated level of interleukin-23 (IL-23), which contributed to autophagy suppression and ROS accumulation. Additionally, IL-23-induced autophagy suppression and ROS accumulation in human TFCs was attributed to AKT/mTOR/NF-κB signaling pathway activation. Inhibition of either IL-23 by a specific neutralization antibody, or mTOR by rapamycin, or NF-κB by IKK-16, significantly reversed the autophagy suppression and ROS accumulation. These results demonstrate a key role for IL-23 in HT pathogenesis and provide a potential therapeutic strategy against IL-23 or its signaling pathway in HT.

  14. Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)

    PubMed Central

    Ristow, Michael; Schmeisser, Kathrin

    2014-01-01

    Increasing evidence indicates that reactive oxygen species (ROS), consisting of superoxide, hydrogen peroxide, and multiple others, do not only cause oxidative stress, but rather may function as signaling molecules that promote health by preventing or delaying a number of chronic diseases, and ultimately extend lifespan. While high levels of ROS are generally accepted to cause cellular damage and to promote aging, low levels of these may rather improve systemic defense mechanisms by inducing an adaptive response. This concept has been named mitochondrial hormesis or mitohormesis. We here evaluate and summarize more than 500 publications from current literature regarding such ROS-mediated low-dose signaling events, including calorie restriction, hypoxia, temperature stress, and physical activity, as well as signaling events downstream of insulin/IGF-1 receptors, AMP-dependent kinase (AMPK), target-of-rapamycin (TOR), and lastly sirtuins to culminate in control of proteostasis, unfolded protein response (UPR), stem cell maintenance and stress resistance. Additionally, consequences of interfering with such ROS signals by pharmacological or natural compounds are being discussed, concluding that particularly antioxidants are useless or even harmful. PMID:24910588

  15. Cytotoxicity and reactive oxygen species generation from aggregated carbon and carbonaceous nanoparticulate materials

    PubMed Central

    Garza, Kristine M; Soto, Karla F; Murr, Lawrence E

    2008-01-01

    We have investigated the cytotoxicity and reactive oxygen species (ROS) generation for indoor and outdoor soots: candle, wood, diesel, tire, and natural gas burner soots – along with surrogate black carbon, various multiwall carbon nanotube aggregate materials, TiO2 (anatase) and chrysotile asbestos as reference materials. All soots were observed utilizing TEM and FESEM to be composed of aggregated, primary spherules (20–80 nm diameter) forming complex, branched fractal structures. These spherules were composed of intercalated, turbostratic arrangements of curved graphene fragments with varying concentrations of polycyclic aromatic hydrocarbon (PAH) isomers. In vitro cultures with an immortalized human lung epithelial carcinoma cell line (A549) treated with these materials showed decreased cell viability and variations in ROS production, with no correlations to PAH content. The data demonstrate that soots are cytotoxic and that cytotoxicity is not related to PAH content but is related to ROS generation, suggesting that soot induces cellular oxidative stress and that cell viability assays can be indicators of ROS production. PMID:18488419

  16. Experiencing Art: The Influence of Expertise and Painting Abstraction Level

    PubMed Central

    Pihko, Elina; Virtanen, Anne; Saarinen, Veli-Matti; Pannasch, Sebastian; Hirvenkari, Lotta; Tossavainen, Timo; Haapala, Arto; Hari, Riitta

    2011-01-01

    How does expertise influence the perception of representational and abstract paintings? We asked 20 experts on art history and 20 laypersons to explore and evaluate a series of paintings ranging in style from representational to abstract in five categories. We compared subjective esthetic judgments and emotional evaluations, gaze patterns, and electrodermal reactivity between the two groups of participants. The level of abstraction affected esthetic judgments and emotional valence ratings of the laypersons but had no effect on the opinions of the experts: the laypersons’ esthetic and emotional ratings were highest for representational paintings and lowest for abstract paintings, whereas the opinions of the experts were independent of the abstraction level. The gaze patterns of both groups changed as the level of abstraction increased: the number of fixations and the length of the scanpaths increased while the duration of the fixations decreased. The viewing strategies – reflected in the target, location, and path of the fixations – however indicated that experts and laypersons paid attention to different aspects of the paintings. The electrodermal reactivity did not vary according to the level of abstraction in either group but expertise was reflected in weaker responses, compared with laypersons, to information received about the paintings. PMID:21941475

  17. Ionizing radiation accelerates Drp1-dependent mitochondrial fission, which involves delayed mitochondrial reactive oxygen species production in normal human fibroblast-like cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kobashigawa, Shinko, E-mail: kobashin@nagasaki-u.ac.jp; Suzuki, Keiji; Yamashita, Shunichi

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer We report first time that ionizing radiation induces mitochondrial dynamic changes. Black-Right-Pointing-Pointer Radiation-induced mitochondrial fission was caused by Drp1 localization. Black-Right-Pointing-Pointer We found that radiation causes delayed ROS from mitochondria. Black-Right-Pointing-Pointer Down regulation of Drp1 rescued mitochondrial dysfunction after radiation exposure. -- Abstract: Ionizing radiation is known to increase intracellular level of reactive oxygen species (ROS) through mitochondrial dysfunction. Although it has been as a basis of radiation-induced genetic instability, the mechanism involving mitochondrial dysfunction remains unclear. Here we studied the dynamics of mitochondrial structure in normal human fibroblast like cells exposed to ionizing radiation. Delayed mitochondrial O{submore » 2}{sup {center_dot}-} production was peaked 3 days after irradiation, which was coupled with accelerated mitochondrial fission. We found that radiation exposure accumulated dynamin-related protein 1 (Drp1) to mitochondria. Knocking down of Drp1 expression prevented radiation induced acceleration of mitochondrial fission. Furthermore, knockdown of Drp1 significantly suppressed delayed production of mitochondrial O{sub 2}{sup {center_dot}-}. Since the loss of mitochondrial membrane potential, which was induced by radiation was prevented in cells knocking down of Drp1 expression, indicating that the excessive mitochondrial fission was involved in delayed mitochondrial dysfunction after irradiation.« less

  18. Selective Sensitization of Zinc Finger Protein Oxidation by Reactive Oxygen Species through Arsenic Binding*

    PubMed Central

    Zhou, Xixi; Cooper, Karen L.; Sun, Xi; Liu, Ke J.; Hudson, Laurie G.

    2015-01-01

    Cysteine oxidation induced by reactive oxygen species (ROS) on redox-sensitive targets such as zinc finger proteins plays a critical role in redox signaling and subsequent biological outcomes. We found that arsenic exposure led to oxidation of certain zinc finger proteins based on arsenic interaction with zinc finger motifs. Analysis of zinc finger proteins isolated from arsenic-exposed cells and zinc finger peptides by mass spectrometry demonstrated preferential oxidation of C3H1 and C4 zinc finger configurations. C2H2 zinc finger proteins that do not bind arsenic were not oxidized by arsenic-generated ROS in the cellular environment. The findings suggest that selectivity in arsenic binding to zinc fingers with three or more cysteines defines the target proteins for oxidation by ROS. This represents a novel mechanism of selective protein oxidation and demonstrates how an environmental factor may sensitize certain target proteins for oxidation, thus altering the oxidation profile and redox regulation. PMID:26063799

  19. Control of vascular smooth muscle function by Src-family kinases and reactive oxygen species in health and disease

    PubMed Central

    MacKay, Charles E; Knock, Greg A

    2015-01-01

    Abstract Reactive oxygen species (ROS) are now recognised as second messenger molecules that regulate cellular function by reversibly oxidising specific amino acid residues of key target proteins. Amongst these are the Src-family kinases (SrcFKs), a multi-functional group of non-receptor tyrosine kinases highly expressed in vascular smooth muscle (VSM). In this review we examine the evidence supporting a role for ROS-induced SrcFK activity in normal VSM contractile function and in vascular remodelling in cardiovascular disease. VSM contractile responses to G-protein-coupled receptor stimulation, as well as hypoxia in pulmonary artery, are shown to be dependent on both ROS and SrcFK activity. Specific phosphorylation targets are identified amongst those that alter intracellular Ca2+ concentration, including transient receptor potential channels, voltage-gated Ca2+ channels and various types of K+ channels, as well as amongst those that regulate actin cytoskeleton dynamics and myosin phosphatase activity, including focal adhesion kinase, protein tyrosine kinase-2, Janus kinase, other focal adhesion-associated proteins, and Rho guanine nucleotide exchange factors. We also examine a growing weight of evidence in favour of a key role for SrcFKs in multiple pro-proliferative and anti-apoptotic signalling pathways relating to oxidative stress and vascular remodelling, with a particular focus on pulmonary hypertension, including growth-factor receptor transactivation and downstream signalling, hypoxia-inducible factors, positive feedback between SrcFK and STAT3 signalling and positive feedback between SrcFK and NADPH oxidase dependent ROS production. We also discuss evidence for and against the potential therapeutic targeting of SrcFKs in the treatment of pulmonary hypertension. PMID:25384773

  20. Ultrastable BSA-capped gold nanoclusters with a polymer-like shielding layer against reactive oxygen species in living cells

    NASA Astrophysics Data System (ADS)

    Zhou, Wenjuan; Cao, Yuqing; Sui, Dandan; Guan, Weijiang; Lu, Chao; Xie, Jianping

    2016-05-01

    The prevalence of reactive oxygen species (ROS) production and the enzyme-containing intracellular environment could lead to the fluorescence quenching of bovine serum albumin (BSA)-capped gold nanoclusters (AuNCs). Here we report an efficient strategy to address this issue, where a polymer-like shielding layer is designed to wrap around the Au core to significantly improve the stability of AuNCs against ROS and protease degradation. The key of our design is to covalently incorporate a thiolated AuNC into the BSA-AuNC via carbodiimide-activated coupling, leading to the formation of a AuNC pair inside the cross-linked BSA molecule. The as-designed paired AuNCs in BSA (or BSA-p-AuNCs for short) show improved performances in living cells.The prevalence of reactive oxygen species (ROS) production and the enzyme-containing intracellular environment could lead to the fluorescence quenching of bovine serum albumin (BSA)-capped gold nanoclusters (AuNCs). Here we report an efficient strategy to address this issue, where a polymer-like shielding layer is designed to wrap around the Au core to significantly improve the stability of AuNCs against ROS and protease degradation. The key of our design is to covalently incorporate a thiolated AuNC into the BSA-AuNC via carbodiimide-activated coupling, leading to the formation of a AuNC pair inside the cross-linked BSA molecule. The as-designed paired AuNCs in BSA (or BSA-p-AuNCs for short) show improved performances in living cells. Electronic supplementary information (ESI) available: Detailed experimental materials, apparatus, experimental procedures and characterization data. See DOI: 10.1039/c6nr02178f

  1. Lipophilic Compound-Mediated Gene Expression and Implication for Intervention in Reactive Oxygen Species (ROS)-Related Diseases: Mini-review

    PubMed Central

    Nakamura, Yukiko K.; Omaye, Stanley T.

    2010-01-01

    In addition to exhibiting antioxidant properties, conjugated linoleic acid (CLA) and vitamin E may modulate gene expression of endogenous antioxidant enzymes. Depending on cellular microenvironments, such modulation reflects either antioxidant or prooxidant outcomes. Although epidemiological/experimental studies have indicated that CLA and vitamin E have health promoting properties, recent findings from clinical trials have been inconclusive. Discrepancies between the results found from prospective studies and recent clinical trials might be attributed to concentration-dependent cellular microenvironment alterations. We give a perspective of possible molecular mechanisms of actions of these lipophilic compounds and their implications for interventions of reactive oxygen species (ROS)-related diseases. PMID:22254050

  2. Excess Iodide Induces an Acute Inhibition of the Sodium/Iodide Symporter in Thyroid Male Rat Cells by Increasing Reactive Oxygen Species

    PubMed Central

    Arriagada, Alejandro A.; Albornoz, Eduardo; Opazo, Ma. Cecilia; Becerra, Alvaro; Vidal, Gonzalo; Fardella, Carlos; Michea, Luis; Carrasco, Nancy; Simon, Felipe; Elorza, Alvaro A.; Bueno, Susan M.; Kalergis, Alexis M.

    2015-01-01

    Na+/I− symporter (NIS) mediates iodide (I−) uptake in the thyroid gland, the first and rate-limiting step in the biosynthesis of the thyroid hormones. The expression and function of NIS in thyroid cells is mainly regulated by TSH and by the intracellular concentration of I−. High doses of I− for 1 or 2 days inhibit the synthesis of thyroid hormones, a process known as the Wolff-Chaikoff effect. The cellular mechanisms responsible for this physiological response are mediated in part by the inhibition of I− uptake through a reduction of NIS expression. Here we show that inhibition of I− uptake occurs as early as 2 hours or 5 hours after exposure to excess I− in FRTL-5 cells and the rat thyroid gland, respectively. Inhibition of I− uptake was not due to reduced NIS expression or altered localization in thyroid cells. We observed that incubation of FRTL-5 cells with excess I− for 2 hours increased H2O2 generation. Furthermore, the inhibitory effect of excess I− on NIS-mediated I− transport could be recapitulated by H2O2 and reverted by reactive derived oxygen species scavengers. The data shown here support the notion that excess I− inhibits NIS at the cell surface at early times by means of a posttranslational mechanism that involves reactive derived oxygen species. PMID:25594695

  3. Mobile Phone Radiation Induces Reactive Oxygen Species Production and DNA Damage in Human Spermatozoa In Vitro

    PubMed Central

    De Iuliis, Geoffry N.; Newey, Rhiannon J.; King, Bruce V.; Aitken, R. John

    2009-01-01

    Background In recent times there has been some controversy over the impact of electromagnetic radiation on human health. The significance of mobile phone radiation on male reproduction is a key element of this debate since several studies have suggested a relationship between mobile phone use and semen quality. The potential mechanisms involved have not been established, however, human spermatozoa are known to be particularly vulnerable to oxidative stress by virtue of the abundant availability of substrates for free radical attack and the lack of cytoplasmic space to accommodate antioxidant enzymes. Moreover, the induction of oxidative stress in these cells not only perturbs their capacity for fertilization but also contributes to sperm DNA damage. The latter has, in turn, been linked with poor fertility, an increased incidence of miscarriage and morbidity in the offspring, including childhood cancer. In light of these associations, we have analyzed the influence of RF-EMR on the cell biology of human spermatozoa in vitro. Principal Findings Purified human spermatozoa were exposed to radio-frequency electromagnetic radiation (RF-EMR) tuned to 1.8 GHz and covering a range of specific absorption rates (SAR) from 0.4 W/kg to 27.5 W/kg. In step with increasing SAR, motility and vitality were significantly reduced after RF-EMR exposure, while the mitochondrial generation of reactive oxygen species and DNA fragmentation were significantly elevated (P<0.001). Furthermore, we also observed highly significant relationships between SAR, the oxidative DNA damage bio-marker, 8-OH-dG, and DNA fragmentation after RF-EMR exposure. Conclusions RF-EMR in both the power density and frequency range of mobile phones enhances mitochondrial reactive oxygen species generation by human spermatozoa, decreasing the motility and vitality of these cells while stimulating DNA base adduct formation and, ultimately DNA fragmentation. These findings have clear implications for the safety of

  4. Benzene's metabolites alter c-MYB activity via reactive oxygen species in HD3 cells.

    PubMed

    Wan, Joanne; Winn, Louise M

    2007-07-15

    Benzene is a known leukemogen that is metabolized to form reactive intermediates and reactive oxygen species (ROS). The c-Myb oncoprotein is a transcription factor that has a critical role in hematopoiesis. c-Myb transcript and protein have been overexpressed in a number of leukemias and cancers. Given c-Myb's role in hematopoiesis and leukemias, it is hypothesized that benzene interferes with the c-Myb signaling pathway and that this involves ROS. To investigate our hypothesis, we evaluated whether benzene, 1,4-benzoquinone, hydroquinone, phenol, and catechol generated ROS in chicken erythroblast HD3 cells, as measured by 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (DCFDA) and dihydrorhodamine-123 (DHR-123), and whether the addition of 100 U/ml of the antioxidating enzyme superoxide dismutase (SOD) could prevent ROS generation. Reduced to oxidized glutathione ratios (GSH:GSSG) were also assessed as well as hydroquinone and benzoquinone's effects on c-Myb protein levels and activation of a transiently transfected reporter construct. Finally we attempted to abrogate benzene metabolite mediated increases in c-Myb activity with the use of SOD. We found that benzoquinone, hydroquinone, and catechol increased DCFDA fluorescence, increased DHR-123 fluorescence, decreased GSH:GSSG ratios, and increased reporter construct expression after 24 h of exposure. SOD was able to prevent DCFDA fluorescence and c-Myb activity caused by benzoquinone and hydroquinone only. These results are consistent with other studies, which suggest metabolite differences in benzene-mediated toxicity. More importantly, this study supports the hypothesis that benzene may mediate its toxicity through ROS-mediated alterations in the c-Myb signaling pathway.

  5. The Role of Reactive-Oxygen-Species in Microbial Persistence and Inflammation

    PubMed Central

    Spooner, Ralee; Yilmaz, Özlem

    2011-01-01

    The mechanisms of chronic infections caused by opportunistic pathogens are of keen interest to both researchers and health professionals globally. Typically, chronic infectious disease can be characterized by an elevation in immune response, a process that can often lead to further destruction. Reactive-Oxygen-Species (ROS) have been strongly implicated in the aforementioned detrimental response by host that results in self-damage. Unlike excessive ROS production resulting in robust cellular death typically induced by acute infection or inflammation, lower levels of ROS produced by host cells are increasingly recognized to play a critical physiological role for regulating a variety of homeostatic cellular functions including growth, apoptosis, immune response, and microbial colonization. Sources of cellular ROS stimulation can include “danger-signal-molecules” such as extracellular ATP (eATP) released by stressed, infected, or dying cells. Particularly, eATP-P2X7 receptor mediated ROS production has been lately found to be a key modulator for controlling chronic infection and inflammation. There is growing evidence that persistent microbes can alter host cell ROS production and modulate eATP-induced ROS for maintaining long-term carriage. Though these processes have yet to be fully understood, exploring potential positive traits of these “injurious” molecules could illuminate how opportunistic pathogens maintain persistence through physiological regulation of ROS signaling. PMID:21339989

  6. Mequindox induced cellular DNA damage via generation of reactive oxygen species.

    PubMed

    Liu, Jing; Ouyang, Man; Jiang, Jun; Mu, Peiqiang; Wu, Jun; Yang, Qi; Zhang, Caihui; Xu, Weiying; Wang, Lijuan; Huen, Michael S Y; Deng, Yiqun

    2012-01-24

    Mequindox, a quinoxaline-N-dioxide derivative that possesses antibacterial properties, has been widely used as a feed additive in the stockbreeding industry in China. While recent pharmacological studies have uncovered potential hazardous effects of mequindox, exactly how mequindox induces pathological changes and the cellular responses associated with its consumption remain largely unexplored. In this study, we investigated the cellular responses associated with mequindox treatment. We report here that mequindox inhibits cell proliferation by arresting cells at the G2/M phase of the cell cycle. Interestingly, this mequindox-associated deleterious effect on cell proliferation was observed in human, pig as well as chicken cells, suggesting that mequindox acts on evolutionarily conserved target(s). To further understand the mequindox-host interaction and the mechanism underlying mequindox-induced cell cycle arrest, we measured the cellular content of DNA damage, which is known to perturb cell proliferation and compromise cell survival. Accordingly, using γ-H2AX as a surrogate marker for DNA damage, we found that mequindox treatment induced cellular DNA damage, which paralleled the chemical-induced elevation of reactive oxygen species (ROS) levels. Importantly, expression of the antioxidant enzyme catalase partially alleviated these mequindox-associated effects. Taken together, our results suggest that mequindox cytotoxicity is attributable, in part, to its role as a potent inducer of DNA damage via ROS. © 2011 Elsevier B.V. All rights reserved.

  7. Mechanism of artemisinin phytotoxicity action: induction of reactive oxygen species and cell death in lettuce seedlings.

    PubMed

    Yan, Zhi-Qiang; Wang, Dan-Dan; Ding, Lan; Cui, Hai-Yan; Jin, Hui; Yang, Xiao-Yan; Yang, Jian-She; Qin, Bo

    2015-03-01

    Artemisinin has been recognized as an allelochemical that inhibits growth of several plant species. However, its mode of action is not well clarified. In this study, the mechanism of artemisinin phytotoxicity on lettuce seedlings was investigated. Root and shoot elongation of lettuce seedlings were inhibited by artemisinin in a concentration-dependent manner. The compound effectively arrested cell division and caused loss of cell viability in root tips of lettuce. Overproduction of reactive oxygen species (ROS) was induced by artemisinin. Lipid peroxidation, proline overproduction and reduction of chlorophyll content in lettuce seedlings were found after treatments. These results suggested that artemisinin could induce ROS overproduction, which caused membrane lipids peroxidation and cell death, and impacted mitosis and physiological processes, resulting in growth inhibition of receptor plants. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  8. Detection and Characterization of Reactive Oxygen and Nitrogen Species in Biological Systems by Monitoring Species-Specific Products.

    PubMed

    Hardy, Micael; Zielonka, Jacek; Karoui, Hakim; Sikora, Adam; Michalski, Radosław; Podsiadły, Radosław; Lopez, Marcos; Vasquez-Vivar, Jeannette; Kalyanaraman, Balaraman; Ouari, Olivier

    2018-05-20

    Since the discovery of the superoxide dismutase enzyme, the generation and fate of short-lived oxidizing, nitrosating, nitrating, and halogenating species in biological systems has been of great interest. Despite the significance of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in numerous diseases and intracellular signaling, the rigorous detection of ROS and RNS has remained a challenge. Recent Advances: Chemical characterization of the reactions of selected ROS and RNS with electron paramagnetic resonance (EPR) spin traps and fluorescent probes led to the establishment of species-specific products, which can be used for specific detection of several forms of ROS and RNS in cell-free systems and in cultured cells in vitro and in animals in vivo. Profiling oxidation products from the ROS and RNS probes provides a rigorous method for detection of those species in biological systems. Formation and detection of species-specific products from the probes enables accurate characterization of the oxidative environment in cells. Measurement of the total signal (fluorescence, chemiluminescence, etc.) intensity does not allow for identification of the ROS/RNS formed. It is critical to identify the products formed by using chromatographic or other rigorous techniques. Product analyses should be accompanied by monitoring of the intracellular probe level, another factor controlling the yield of the product(s) formed. More work is required to characterize the chemical reactivity of the ROS/RNS probes, and to develop new probes/detection approaches enabling real-time, selective monitoring of the specific products formed from the probes. Antioxid. Redox Signal. 28, 1416-1432.

  9. Free radicals, reactive oxygen species, oxidative stress and its classification.

    PubMed

    Lushchak, Volodymyr I

    2014-12-05

    Reactive oxygen species (ROS) initially considered as only damaging agents in living organisms further were found to play positive roles also. This paper describes ROS homeostasis, principles of their investigation and technical approaches to investigate ROS-related processes. Especial attention is paid to complications related to experimental documentation of these processes, their diversity, spatiotemporal distribution, relationships with physiological state of the organisms. Imbalance between ROS generation and elimination in favor of the first with certain consequences for cell physiology has been called "oxidative stress". Although almost 30years passed since the first definition of oxidative stress was introduced by Helmut Sies, to date we have no accepted classification of oxidative stress. In order to fill up this gape here classification of oxidative stress based on its intensity is proposed. Due to that oxidative stress may be classified as basal oxidative stress (BOS), low intensity oxidative stress (LOS), intermediate intensity oxidative stress (IOS), and high intensity oxidative stress (HOS). Another classification of potential interest may differentiate three categories such as mild oxidative stress (MOS), temperate oxidative stress (TOS), and finally severe (strong) oxidative stress (SOS). Perspective directions of investigations in the field include development of sophisticated classification of oxidative stresses, accurate identification of cellular ROS targets and their arranged responses to ROS influence, real in situ functions and operation of so-called "antioxidants", intracellular spatiotemporal distribution and effects of ROS, deciphering of molecular mechanisms responsible for cellular response to ROS attacks, and ROS involvement in realization of normal cellular functions in cellular homeostasis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Elementary surface processes during reactive magnetron sputtering of chromium

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Monje, Sascha; Corbella, Carles, E-mail: carles.corbella@rub.de; Keudell, Achim von

    2015-10-07

    The elementary surface processes occurring on chromium targets exposed to reactive plasmas have been mimicked in beam experiments by using quantified fluxes of Ar ions (400–800 eV) and oxygen atoms and molecules. For this, quartz crystal microbalances were previously coated with Cr thin films by means of high-power pulsed magnetron sputtering. The measured growth and etching rates were fitted by flux balance equations, which provided sputter yields of around 0.05 for the compound phase and a sticking coefficient of O{sub 2} of 0.38 on the bare Cr surface. Further fitted parameters were the oxygen implantation efficiency and the density of oxidationmore » sites at the surface. The increase in site density with a factor 4 at early phases of reactive sputtering is identified as a relevant mechanism of Cr oxidation. This ion-enhanced oxygen uptake can be attributed to Cr surface roughening and knock-on implantation of oxygen atoms deeper into the target. This work, besides providing fundamental data to control oxidation state of Cr targets, shows that the extended Berg's model constitutes a robust set of rate equations suitable to describe reactive magnetron sputtering of metals.« less

  11. Cold atmospheric-pressure air plasma treatment of C6 glioma cells: effects of reactive oxygen species in the medium produced by the plasma on cell death

    NASA Astrophysics Data System (ADS)

    Wang, Yuyang; Cheng, Cheng; Gao, Peng; Li, Shaopeng; Shen, Jie; Lan, Yan; Yu, Yongqiang; Chu, Paul K.

    2017-02-01

    An atmospheric-pressure air plasma is employed to treat C6 glioma cells in vitro. To elucidate on the mechanism causing cell death and role of reactive species (RS) in the medium produced by the plasma, the concentration of the long-lived RS such as hydrogen peroxide, nitrate, and ozone in the plasma-treated liquid (phosphate-buffered saline solution) is measured. When vitamin C is added to the medium as a ROS quencher, the viability of C6 glioma cells after the plasma treatment is different from that without vitamin C. The results demonstrate that reactive oxygen species (ROS) such as H2O2, and O3 constitute the main factors for inactivation of C6 glioma cells and the reactive nitrogen species (RNS) may only play an auxiliary role in cell death.

  12. Generation and Role of Reactive Oxygen and Nitrogen Species Induced by Plasma, Lasers, Chemical Agents, and Other Systems in Dentistry

    PubMed Central

    Jha, Nayansi; Ryu, Jae Jun

    2017-01-01

    The generation of reactive oxygen and nitrogen species (RONS) has been found to occur during inflammatory procedures, during cell ischemia, and in various crucial developmental processes such as cell differentiation and along cell signaling pathways. The most common sources of intracellular RONS are the mitochondrial electron transport system, NADH oxidase, and cytochrome P450. In this review, we analyzed the extracellular and intracellular sources of reactive species, their cell signaling pathways, the mechanisms of action, and their positive and negative effects in the dental field. In dentistry, ROS can be found—in lasers, photosensitizers, bleaching agents, cold plasma, and even resin cements, all of which contribute to the generation and prevalence of ROS. Nonthermal plasma has been used as a source of ROS for biomedical applications and has the potential for use with dental stem cells as well. There are different types of dental stem cells, but their therapeutic use remains largely untapped, with the focus currently on only periodontal ligament stem cells. More research is necessary in this area, including studies about ROS mechanisms with dental cells, along with the utilization of reactive species in redox medicine. Such studies will help to provide successful treatment modalities for various diseases. PMID:29204250

  13. Bioconvertible vitamin antioxidants improve sunscreen photoprotection against UV-induced reactive oxygen species.

    PubMed

    Hanson, Kerry M; Clegg, Robert M

    2003-01-01

    The ability of sunscreens and antioxidants to deactivate highly destructive reactive oxygen species in human skin has remained inconclusive. Two-photon fluorescence imaging microscopy was used to determine the effect of sunscreen/antioxidant combinations upon UV-induced ROS generation in ex vivo human skin. A sunscreen combination containing octylmethoxycinnamate (Parsol MCX) and avobenzone (Parsol 1789) at SPF 8 and SPF 15 was tested for its ability to prevent UV radiation from generating ROS in the viable epidermal strata of ex vivo human skin. A UV dose equivalent to two hours of North American solar UV was used to irradiate the skin. Each sunscreen reduced the amount of ROS induced in the viable strata by a value consistent with the SPF level. UV photons that were not absorbed/scattered by the sunscreen formulations generated ROS within the viable epidermal layers. The addition of the bioconvertible antioxidants vitamin E acetate and sodium ascorbyl phosphate (STAY-C 50) improves photoprotection by converting to vitamins E and C, respectively, within the skin. The bioconversion forms an antioxidant reservoir that deactivates the ROS generated (within the strata granulosum, spinosum, and basale) by the UV photons that the sunscreens do not block in the stratum corneum.

  14. Electronic Structure of the Ferryl Intermediate in the α-Ketoglutarate Dependent Non-Heme Iron Halogenase SyrB2: Contributions to H Atom Abstraction Reactivity.

    PubMed

    Srnec, Martin; Wong, Shaun D; Matthews, Megan L; Krebs, Carsten; Bollinger, J Martin; Solomon, Edward I

    2016-04-20

    Low temperature magnetic circular dichroism (LT MCD) spectroscopy in combination with quantum-chemical calculations are used to define the electronic structure associated with the geometric structure of the Fe(IV)═O intermediate in SyrB2 that was previously determined by nuclear resonance vibrational spectroscopy. These studies elucidate key frontier molecular orbitals (FMOs) and their contribution to H atom abstraction reactivity. The VT MCD spectra of the enzymatic S = 2 Fe(IV)═O intermediate with Br(-) ligation contain information-rich features that largely parallel the corresponding spectra of the S = 2 model complex (TMG3tren)Fe(IV)═O (Srnec, M.; Wong, S. D.; England, J; Que, L; Solomon, E. I. Proc. Natl. Acad. Sci. USA 2012, 109, 14326-14331). However, quantitative differences are observed that correlate with π-anisotropy and oxo donor strength that perturb FMOs and affect reactivity. Due to π-anisotropy, the Fe(IV)═O active site exhibits enhanced reactivity in the direction of the substrate cavity that proceeds through a π-channel that is controlled by perpendicular orientation of the substrate C-H bond relative to the halide-Fe(IV)═O plane. Also, the increased intrinsic reactivity of the SyrB2 intermediate relative to the ferryl model complex is correlated to a higher oxyl character of the Fe(IV)═O at the transition states resulting from the weaker ligand field of the halogenase.

  15. Methane Activation Mediated by a Series of Cerium-Vanadium Bimetallic Oxide Cluster Cations: Tuning Reactivity by Doping.

    PubMed

    Ma, Jia-Bi; Meng, Jing-Heng; He, Sheng-Gui

    2016-04-18

    The reactions of cerium-vanadium cluster cations Cex Vy Oz (+) with CH4 are investigated by time-of-flight mass spectrometry and density functional theory calculations. (CeO2 )m (V2 O5 )n (+) clusters (m=1,2, n=1-5; m=3, n=1-4) with dimensions up to nanosize can abstract one hydrogen atom from CH4 . The theoretical study indicates that there are two types of active species in (CeO2 )m (V2 O5 )n (+) , V[(Ot )2 ](.) and [(Ob )2 CeOt ](.) (Ot and Ob represent terminal and bridging oxygen atoms, respectively); the former is less reactive than the latter. The experimentally observed size-dependent reactivities can be rationalized by considering the different active species and mechanisms. Interestingly, the reactivity of the (CeO2 )m (V2 O5 )n (+) clusters falls between those of (CeO2 )2-4 (+) and (V2 O5 )1-5 (+) in terms of C-H bond activation, thus the nature of the active species and the cluster reactivity can be effectively tuned by doping. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. The role of metals in production and scavenging of reactive oxygen species in photosystem II.

    PubMed

    Pospíšil, Pavel

    2014-07-01

    Metal ions play a crucial role in enzymatic reactions in all photosynthetic organisms such as cyanobacteria, algae and plants. It well known that metal ions maintain the binding of substrate in the active site of the metalloenzymes and control the redox activity of the metalloenzyme in the enzymatic reaction. A large pigment-protein complex, PSII, known to serve as a water-plastoquinone oxidoreductase, contains three metal centers comprising non-heme iron, heme iron of Cyt b559 and the water-splitting manganese complex. Metal ions bound to PSII proteins maintain the electron transport from water to plastoquinone and regulate the pro-oxidant and antioxidant activity in PSII. In this review, attention is focused on the role of PSII metal centers in (i) the formation of superoxide anion and hydroxyl radicals by sequential one-electron reduction of molecular oxygen and the formation of hydrogen peroxide by incomplete two-electron oxidation of water; and (ii) the elimination of superoxide anion radical by one-electron oxidation and reduction (superoxide dismutase activity) and of hydrogen peroxide by two-electron oxidation and reduction (catalase activity). The balance between the formation and elimination of reactive oxygen species by PSII metal centers is discussed as an important aspect in the prevention of photo-oxidative damage of PSII proteins and lipids. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  17. Arsenite induces cell transformation by reactive oxygen species, AKT, ERK1/2, and p70S6K1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Carpenter, Richard L.; Jiang, Yue; Jing, Yi

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer Chronic exposure to arsenite induces cell proliferation and transformation. Black-Right-Pointing-Pointer Arsenite-induced transformation increases ROS production and downstream signalings. Black-Right-Pointing-Pointer Inhibition of ROS levels via catalase reduces arsenite-induced cell transformation. Black-Right-Pointing-Pointer Interruption of AKT, ERK, or p70S6K1 inhibits arsenite-induced cell transformation. -- Abstract: Arsenic is naturally occurring element that exists in both organic and inorganic formulations. The inorganic form arsenite has a positive association with development of multiple cancer types. There are significant populations throughout the world with high exposure to arsenite via drinking water. Thus, human exposure to arsenic has become a significant public health problem. Recent evidencemore » suggests that reactive oxygen species (ROS) mediate multiple changes to cell behavior after acute arsenic exposure, including activation of proliferative signaling and angiogenesis. However, the role of ROS in mediating cell transformation by chronic arsenic exposure is unknown. We found that cells chronically exposed to sodium arsenite increased proliferation and gained anchorage-independent growth. This cell transformation phenotype required constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. We also observed these cells constitutively produce ROS, which was required for the constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. Suppression of ROS levels by forced expression of catalase also reduced cell proliferation and anchorage-independent growth. These results indicate cell transformation induced by chronic arsenic exposure is mediated by increased cellular levels of ROS, which mediates activation of AKT, ERK1/2, and p70S6K1.« less

  18. Roles of reactive oxygen species in UVA-induced oxidation of 5,6-dihydroxyindole-2-carboxylic acid-melanin as studied by differential spectrophotometric method.

    PubMed

    Ito, Shosuke; Kikuta, Marina; Koike, Shota; Szewczyk, Grzegorz; Sarna, Michal; Zadlo, Andrzej; Sarna, Tadeusz; Wakamatsu, Kazumasa

    2016-05-01

    Eumelanin photoprotects pigmented tissues from ultraviolet (UV) damage. However, UVA-induced tanning seems to result from the photooxidation of preexisting melanin and does not contribute to photoprotection. We investigated the mechanism of UVA-induced degradation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA)-melanin taking advantage of its solubility in a neutral buffer and using a differential spectrophotometric method to detect subtle changes in its structure. Our methodology is suitable for examining the effects of various agents that interact with reactive oxygen species (ROS) to determine how ROS is involved in the UVA-induced oxidative modifications. The results show that UVA radiation induces the oxidation of DHICA to indole-5,6-quinone-2-carboxylic acid in eumelanin, which is then cleaved to form a photodegraded, pyrrolic moiety and finally to form free pyrrole-2,3,5-tricarboxylic acid. The possible involvement of superoxide radical and singlet oxygen in the oxidation was suggested. The generation and quenching of singlet oxygen by DHICA-melanin was confirmed by direct measurements of singlet oxygen phosphorescence. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Temperature controls oxidative phosphorylation and reactive oxygen species production through uncoupling in rat skeletal muscle mitochondria.

    PubMed

    Jarmuszkiewicz, Wieslawa; Woyda-Ploszczyca, Andrzej; Koziel, Agnieszka; Majerczak, Joanna; Zoladz, Jerzy A

    2015-06-01

    Mitochondrial respiratory and phosphorylation activities, mitochondrial uncoupling, and hydrogen peroxide formation were studied in isolated rat skeletal muscle mitochondria during experimentally induced hypothermia (25 °C) and hyperthermia (42 °C) compared to the physiological temperature of resting muscle (35 °C). For nonphosphorylating mitochondria, increasing the temperature from 25 to 42 °C led to a decrease in membrane potential, hydrogen peroxide production, and quinone reduction levels. For phosphorylating mitochondria, no temperature-dependent changes in these mitochondrial functions were observed. However, the efficiency of oxidative phosphorylation decreased, whereas the oxidation and phosphorylation rates and oxidative capacities of the mitochondria increased, with increasing assay temperature. An increase in proton leak, including uncoupling protein-mediated proton leak, was observed with increasing assay temperature, which could explain the reduced oxidative phosphorylation efficiency and reactive oxygen species production. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Increased Interleukin-23 in Hashimoto’s Thyroiditis Disease Induces Autophagy Suppression and Reactive Oxygen Species Accumulation

    PubMed Central

    Zheng, Tingting; Xu, Chengcheng; Mao, Chaoming; Mou, Xiao; Wu, Fei; Wang, Xuefeng; Bu, Ling; Zhou, Yuepeng; Luo, Xuan; Lu, Qingyan; Liu, Hongli; Yuan, Guoyue; Wang, Shengjun; Chen, Deyu; Xiao, Yichuan

    2018-01-01

    Hashimoto’s thyroiditis (HT) represents the most common organ-specific autoimmune disease. Inflammatory factors and reactive oxygen species (ROS) play detrimental roles during the pathogenesis of HT. In this study, we found that thyroid follicular cells (TFCs) from HT patients expressed an elevated level of interleukin-23 (IL-23), which contributed to autophagy suppression and ROS accumulation. Additionally, IL-23-induced autophagy suppression and ROS accumulation in human TFCs was attributed to AKT/mTOR/NF-κB signaling pathway activation. Inhibition of either IL-23 by a specific neutralization antibody, or mTOR by rapamycin, or NF-κB by IKK-16, significantly reversed the autophagy suppression and ROS accumulation. These results demonstrate a key role for IL-23 in HT pathogenesis and provide a potential therapeutic strategy against IL-23 or its signaling pathway in HT. PMID:29434604

  1. Investigations of blue light-induced reactive oxygen species from flavin mononucleotide on inactivation of E. coli.

    PubMed

    Liang, Ji-Yuan; Cheng, Chien-Wei; Yu, Chin-Hao; Chen, Liang-Yü

    2015-02-01

    The micronutrients in many cellular processes, riboflavin, flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD) are photo-sensitive to UV and visible light for generating reactive oxygen species (ROS). Produced from phosphorylation of riboflavin, FMN is more water-soluble and rapidly transformed into free riboflavin after ingestion. This study investigated the application of visible blue light with FMN to development of an effective antimicrobial treatment. The photosensitization of bacterial viability with FMN was investigated by light quality, intensity, time, and irradiation dosage. The blue light-induced photochemical reaction with FMN could inactivate Escherichiacoli by the generated ROS in damaging nucleic acids, which was validated. This novel photodynamic technique could be a safe practice for photo-induced inactivation of environmental microorganism to achieve hygienic requirements in food processing. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Horseradish Peroxidase-Encapsulated Hollow Silica Nanospheres for Intracellular Sensing of Reactive Oxygen Species

    NASA Astrophysics Data System (ADS)

    Chen, Hsin-Yi; Wu, Si-Han; Chen, Chien-Tsu; Chen, Yi-Ping; Chang, Feng-Peng; Chien, Fan-Ching; Mou, Chung-Yuan

    2018-04-01

    Reactive oxygen species (ROS) have crucial roles in cell signaling and homeostasis. Overproduction of ROS can induce oxidative damage to various biomolecules and cellular structures. Therefore, developing an approach capable of monitoring and quantifying ROS in living cells is significant for physiology and clinical diagnoses. Some cell-permeable fluorogenic probes developed are useful for the detection of ROS while in conjunction with horseradish peroxidase (HRP). Their intracellular scenario is however hindered by the membrane-impermeable property of enzymes. Herein, a new approach for intracellular sensing of ROS by using horseradish peroxidase-encapsulated hollow silica nanospheres (designated HRP@HSNs), with satisfactory catalytic activity, cell membrane permeability, and biocompatibility, was prepared via a microemulsion method. These HRP@HSNs, combined with selective probes or targeting ligands, could be foreseen as ROS-detecting tools in specific organelles or cell types. As such, dihydrorhodamine 123-coupled HRP@HSNs were used for the qualitative and semi-quantitative analysis of physiological H2O2 levels in activated RAW 264.7 macrophages. We envision that this HSNs encapsulating active enzymes can be conjugated with selective probes and targeting ligands to detect ROS in specific organelles or cell types of interest.

  3. Screening reactive oxygen species scavenging properties of platinum nanoparticles on a microfluidic chip.

    PubMed

    Zheng, Wenfu; Jiang, Bo; Hao, Yi; Zhao, Yuyun; Zhang, Wei; Jiang, Xingyu

    2014-09-12

    Hyperglycemia, hyperlipidemia and inflammation are key risk factors for atherosclerosis and can lead to overproduction of reactive oxygen species (ROS), which plays a critical role in vascular endothelial dysfunction and subsequent progress of atherosclerosis. However, there is currently a lack of effective drugs that deal with ROS. Platinum nanoparticles (Pt-NPs) have proven to be promising antioxidant drugs in vitro and in vivo. To optimize the efficacy of Pt-NP based drugs, we synthesized and characterized the ROS scavenging properties of three kinds of small molecules that capped Pt-NPs (Pt-AMP-NPs, Pt-ATT-NPs, Pt-MI-NPs) on a blood vessel-mimicking microfluidic chip. The Pt-NPs showed superior superoxide dismutase (SOD)-like functions and can scavenge ROS and recover compromised cell-cell junctions under hyperglycemic, hyperlipidemic and proinflammatory conditions. Amongst these NPs, Pt-AMP-NPs showed the most superior antioxidant properties, suggesting its potency to serve as a novel drug to treat vascular diseases such as atherosclerosis. Our microfluidic chip, providing physiological hemodynamic conditions for the experiments, is potentially a promising tool for a wide range of biological research on the vascular system.

  4. Negative Regulation of Autophagy by Sulfide Is Independent of Reactive Oxygen Species1

    PubMed Central

    Laureano-Marín, Ana M.; Moreno, Inmaculada

    2016-01-01

    Accumulating experimental evidence in mammalian, and recently plant, systems has led to a change in our understanding of the role played by hydrogen sulfide in life processes. In plants, hydrogen sulfide mitigates stress and regulates important plant processes such as photosynthesis, stomatal movement, and autophagy, although the underlying mechanism is not well known. In this study, we provide new experimental evidence that, together with our previous findings, demonstrates the role of hydrogen sulfide in regulating autophagy. We used green fluorescent protein fluorescence associated with autophagic bodies and immunoblot analysis of the ATG8 protein to show that sulfide (and no other molecules such as sulfur-containing molecules or ammonium) was able to inhibit the autophagy induced in Arabidopsis (Arabidopsis thaliana) roots under nitrogen deprivation. Our results showed that sulfide was unable to scavenge reactive oxygen species generated by nitrogen limitation, in contrast to well-established reducers. In addition, reducers were unable to inhibit the accumulation of autophagic bodies and ATG8 protein forms to the same extent as sulfide. Therefore, we conclude that sulfide represses autophagy via a mechanism that is independent of redox conditions. PMID:27208225

  5. CCL11 enhances excitotoxic neuronal death by producing reactive oxygen species in microglia.

    PubMed

    Parajuli, Bijay; Horiuchi, Hiroshi; Mizuno, Tetsuya; Takeuchi, Hideyuki; Suzumura, Akio

    2015-12-01

    The chemokine CCL11 (also known as eotaxin-1) is a potent eosinophil chemoattractant that mediates allergic diseases such as asthma, atopic dermatitis, and inflammatory bowel diseases. Previous studies demonstrated that concentrations of CCL11 are elevated in the sera and cerebrospinal fluids (CSF) of patients with neuroinflammatory disorders, including multiple sclerosis. Moreover, the levels of CCL11 in plasma and CSF increase with age, and CCL11 suppresses adult neurogenesis in the central nervous system (CNS), resulting in memory impairment. However, the precise source and function of CCL11 in the CNS are not fully understood. In this study, we found that activated astrocytes release CCL11, whereas microglia predominantly express the CCL11 receptor. CCL11 significantly promoted the migration of microglia, and induced microglial production of reactive oxygen species by upregulating nicotinamide adenine dinucleotide phosphate-oxidase 1 (NOX1), thereby promoting excitotoxic neuronal death. These effects were reversed by inhibition of NOX1. Our findings suggest that CCL11 released from activated astrocytes triggers oxidative stress via microglial NOX1 activation and potentiates glutamate-mediated neurotoxicity, which may be involved in the pathogenesis of various neurological disorders. © 2015 Wiley Periodicals, Inc.

  6. Ciclopirox induces autophagy through reactive oxygen species-mediated activation of JNK signaling pathway

    PubMed Central

    Zhou, Hongyu; Shen, Tao; Shang, Chaowei; Luo, Yan; Liu, Lei; Yan, Juming; Li, Yan; Huang, Shile

    2014-01-01

    Ciclopirox olamine (CPX), a fungicide, has been demonstrated as a potential anticancer agent. However, the underlying anticancer mechanism is not well understood. Here, we found that CPX induced autophagy in human rhabdomyosarcoma (Rh30 and RD) cells. It appeared that CPX-induced autophagy was attributed to induction of reactive oxygen species (ROS), as N-acetyl-L-cysteine (NAC), a ROS scavenger and antioxidant, prevented this process. Furthermore, we observed that CPX induced activation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 MAPK, which was also blocked by NAC. However, only inhibition of JNK (with SP600125) or expression of dominant negative c-Jun partially prevented CPX-induced autophagy, indicating that ROS-mediated activation of JNK signaling pathway contributed to CPX-induced autophagy. Of interest, inhibition of autophagy by chloroquine (CQ) enhanced CPX-induced cell death, indicating that CPX-induced autophagy plays a pro-survival role in human rhabdomyosarcoma cells. Our finding suggests that the combination with autophagy inhibitors may be a novel strategy in potentiating the anticancer activity of CPX for treatment of rhabdomyosarcoma. PMID:25294812

  7. Mitochondrial Reactive Oxygen Species and Kidney Hypoxia in the Development of Diabetic Nephropathy

    PubMed Central

    Schiffer, Tomas A.; Friederich-Persson, Malou

    2017-01-01

    The underlying mechanisms in the development of diabetic nephropathy are currently unclear and likely consist of a series of dynamic events from the early to late stages of the disease. Diabetic nephropathy is currently without curative treatments and it is acknowledged that even the earliest clinical manifestation of nephropathy is preceded by an established morphological renal injury that is in turn preceded by functional and metabolic alterations. An early manifestation of the diabetic kidney is the development of kidney hypoxia that has been acknowledged as a common pathway to nephropathy. There have been reports of altered mitochondrial function in the diabetic kidney such as altered mitophagy, mitochondrial dynamics, uncoupling, and cellular signaling through hypoxia inducible factors and AMP-kinase. These factors are also likely to be intertwined in a complex manner. In this review, we discuss how these pathways are connected to mitochondrial production of reactive oxygen species (ROS) and how they may relate to the development of kidney hypoxia in diabetic nephropathy. From available literature, it is evident that early correction and/or prevention of mitochondrial dysfunction may be pivotal in the prevention and treatment of diabetic nephropathy. PMID:28443030

  8. Mitochondrial Reactive Oxygen Species and Kidney Hypoxia in the Development of Diabetic Nephropathy.

    PubMed

    Schiffer, Tomas A; Friederich-Persson, Malou

    2017-01-01

    The underlying mechanisms in the development of diabetic nephropathy are currently unclear and likely consist of a series of dynamic events from the early to late stages of the disease. Diabetic nephropathy is currently without curative treatments and it is acknowledged that even the earliest clinical manifestation of nephropathy is preceded by an established morphological renal injury that is in turn preceded by functional and metabolic alterations. An early manifestation of the diabetic kidney is the development of kidney hypoxia that has been acknowledged as a common pathway to nephropathy. There have been reports of altered mitochondrial function in the diabetic kidney such as altered mitophagy, mitochondrial dynamics, uncoupling, and cellular signaling through hypoxia inducible factors and AMP-kinase. These factors are also likely to be intertwined in a complex manner. In this review, we discuss how these pathways are connected to mitochondrial production of reactive oxygen species (ROS) and how they may relate to the development of kidney hypoxia in diabetic nephropathy. From available literature, it is evident that early correction and/or prevention of mitochondrial dysfunction may be pivotal in the prevention and treatment of diabetic nephropathy.

  9. Feedback between p21 and reactive oxygen production is necessary for cell senescence

    PubMed Central

    Passos, João F; Nelson, Glyn; Wang, Chunfang; Richter, Torsten; Simillion, Cedric; Proctor, Carole J; Miwa, Satomi; Olijslagers, Sharon; Hallinan, Jennifer; Wipat, Anil; Saretzki, Gabriele; Rudolph, Karl Lenhard; Kirkwood, Tom B L; von Zglinicki, Thomas

    2010-01-01

    Cellular senescence—the permanent arrest of cycling in normally proliferating cells such as fibroblasts—contributes both to age-related loss of mammalian tissue homeostasis and acts as a tumour suppressor mechanism. The pathways leading to establishment of senescence are proving to be more complex than was previously envisaged. Combining in-silico interactome analysis and functional target gene inhibition, stochastic modelling and live cell microscopy, we show here that there exists a dynamic feedback loop that is triggered by a DNA damage response (DDR) and, which after a delay of several days, locks the cell into an actively maintained state of ‘deep' cellular senescence. The essential feature of the loop is that long-term activation of the checkpoint gene CDKN1A (p21) induces mitochondrial dysfunction and production of reactive oxygen species (ROS) through serial signalling through GADD45-MAPK14(p38MAPK)-GRB2-TGFBR2-TGFβ. These ROS in turn replenish short-lived DNA damage foci and maintain an ongoing DDR. We show that this loop is both necessary and sufficient for the stability of growth arrest during the establishment of the senescent phenotype. PMID:20160708

  10. TMEM16A Contributes to Endothelial Dysfunction by Facilitating Nox2 NADPH Oxidase-Derived Reactive Oxygen Species Generation in Hypertension.

    PubMed

    Ma, Ming-Ming; Gao, Min; Guo, Kai-Min; Wang, Mi; Li, Xiang-Yu; Zeng, Xue-Lin; Sun, Lu; Lv, Xiao-Fei; Du, Yan-Hua; Wang, Guan-Lei; Zhou, Jia-Guo; Guan, Yong-Yuan

    2017-05-01

    Ca 2+ -activated Cl - channels play a crucial role in various physiological processes. However, the role of TMEM16A in vascular endothelial dysfunction during hypertension is unclear. In this study, we investigated the specific involvement of TMEM16A in regulating endothelial function and blood pressure and the underlying mechanism. Reverse transcription-polymerase chain reaction, Western blotting, coimmunoprecipitation, confocal imaging, patch-clamp recordings, and TMEM16A endothelial-specific transgenic and knockout mice were used. We found that TMEM16A was expressed abundantly and functioned as a Ca 2+ -activated Cl - channel in endothelial cells. Angiotensin II induced endothelial dysfunction with an increase in TMEM16A expression. The knockout of endothelial-specific TMEM16A significantly lowered the blood pressure and ameliorated endothelial dysfunction in angiotensin II-induced hypertension, whereas the overexpression of endothelial-specific TMEM16A resulted in the opposite effects. These results were related to the increased reactive oxygen species production, Nox2-containing NADPH oxidase activation, and Nox2 and p22phox protein expression that were facilitated by TMEM16A on angiotensin II-induced hypertensive challenge. Moreover, TMEM16A directly bound with Nox2 and reduced the degradation of Nox2 through the proteasome-dependent degradation pathway. Therefore, TMEM16A is a positive regulator of endothelial reactive oxygen species generation via Nox2-containing NADPH oxidase, which induces endothelial dysfunction and hypertension. Modification of TMEM16A may be a novel therapeutic strategy for endothelial dysfunction-associated diseases. © 2017 American Heart Association, Inc.

  11. Reactive Oxygen Species-Induced TXNIP Drives Fructose-Mediated Hepatic Inflammation and Lipid Accumulation Through NLRP3 Inflammasome Activation

    PubMed Central

    Zhang, Xian; Zhang, Jian-Hua; Chen, Xu-Yang; Hu, Qing-Hua; Wang, Ming-Xing; Jin, Rui; Zhang, Qing-Yu; Wang, Wei; Wang, Rong; Kang, Lin-Lin; Li, Jin-Sheng; Li, Meng

    2015-01-01

    Abstract Aims: Increased fructose consumption predisposes the liver to nonalcoholic fatty liver disease (NAFLD), but the mechanisms are elusive. Thioredoxin-interacting protein (TXNIP) links oxidative stress to NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and this signaling axis may be involved in fructose-induced NAFLD. Here, we explore the role of reactive oxygen species (ROS)-induced TXNIP overexpression in fructose-mediated hepatic NLRP3 inflammasome activation, inflammation, and lipid accumulation. Results: Rats were fed a 10% fructose diet for 8 weeks and treated with allopurinol and quercetin during the last 4 weeks. Five millimolars of fructose-exposed hepatocytes (primary rat hepatocytes, rat hepatic parenchymal cells [RHPCs], HLO2, HepG2) were co-incubated with antioxidants or caspase-1 inhibitor or subjected to TXNIP or NLRP3 siRNA interference. Fructose induced NLRP3 inflammasome activation and pro-inflammatory cytokine secretion, janus-activated kinase 2/signal transducers and activators of transcription 3-mediated inflammatory signaling, and expression alteration of lipid metabolism-related genes in cultured hepatocytes and rat livers. NLRP3 silencing and caspase-1 suppression blocked these effects in primary rat hepatocytes and RHPCs, confirming that inflammasome activation alters hepatocyte lipid metabolism. Hepatocellular ROS and TXNIP were increased in animal and cell models. TXNIP silencing blocked NLRP3 inflammasome activation, inflammation, and lipid metabolism perturbations but not ROS induction in fructose-exposed hepatocytes, whereas antioxidants addition abrogated TXNIP induction and diminished the detrimental effects in fructose-exposed hepatocytes and rat livers. Innovation and Conclusions: This study provides a novel mechanism for fructose-induced NAFLD pathogenesis by which the ROS-TXNIP pathway mediates hepatocellular NLRP3 inflammasome activation, inflammation and lipid accumulation. Antioxidant

  12. Mitochondrial stress controls the radiosensitivity of the oxygen effect: Implications for radiotherapy.

    PubMed

    Richardson, Richard B; Harper, Mary-Ellen

    2016-04-19

    It has been more than 60 years since the discovery of the oxygen effect that empirically demonstrates the direct association between cell radiosensitivity and oxygen tension, important parameters in radiotherapy. Yet the mechanisms underlying this principal tenet of radiobiology are poorly understood. Better understanding of the oxygen effect may explain difficulty in eliminating hypoxic tumor cells, a major cause of regrowth after therapy. Our analysis utilizes the Howard-Flanders and Alper formula, which describes the relationship of radiosensitivity with oxygen tension. Here, we assign and qualitatively assess the relative contributions of two important mechanisms. The first mechanism involves the emission of reactive oxygen species from the mitochondrial electron transport chain, which increases with oxygen tension. The second mechanism is related to an energy and repair deficit, which increases with hypoxia. Following a radiation exposure, the uncoupling of the oxidative phosphorylation system (proton leak) in mitochondria lowers the emission of reactive oxygen species which has implications for fractionated radiotherapy, particularly of hypoxic tumors. Our analysis shows that, in oxygenated tumor and normal cells, mitochondria, rather than the nucleus, are the primary loci of radiotherapy effects, especially for low linear energy transfer radiation. Therefore, the oxygen effect can be explained by radiation-induced effects in mitochondria that generate reactive oxygen species, which in turn indirectly target nuclear DNA.

  13. Reactive oxygen species as a signal in glucose-stimulated insulin secretion.

    PubMed

    Pi, Jingbo; Bai, Yushi; Zhang, Qiang; Wong, Victoria; Floering, Lisa M; Daniel, Kiefer; Reece, Jeffrey M; Deeney, Jude T; Andersen, Melvin E; Corkey, Barbara E; Collins, Sheila

    2007-07-01

    One of the unique features of beta-cells is their relatively low expression of many antioxidant enzymes. This could render beta-cells susceptible to oxidative damage but may also provide a system that is sensitive to reactive oxygen species as signals. In isolated mouse islets and INS-1(832/13) cells, glucose increases intracellular accumulation of H2O2. In both models, insulin secretion could be stimulated by provision of either exogenous H2O2 or diethyl maleate, which raises intracellular H2O2 levels. Provision of exogenous H2O2 scavengers, including cell permeable catalase and N-acetyl-L-cysteine, inhibited glucose-stimulated H2O2 accumulation and insulin secretion (GSIS). In contrast, cell permeable superoxide dismutase, which metabolizes superoxide into H2O2, had no effect on GSIS. Because oxidative stress is an important risk factor for beta-cell dysfunction in diabetes, the relationship between glucose-induced H2O2 generation and GSIS was investigated under various oxidative stress conditions. Acute exposure of isolated mouse islets or INS-1(832/13) cells to oxidative stressors, including arsenite, 4-hydroxynonenal, and methylglyoxal, led to decreased GSIS. This impaired GSIS was associated with increases in a battery of endogenous antioxidant enzymes. Taken together, these findings suggest that H2O2 derived from glucose metabolism is one of the metabolic signals for insulin secretion, whereas oxidative stress may disturb its signaling function.

  14. Core-shell AgSiO2-protoporphyrin IX nanoparticle: Effect of the Ag core on reactive oxygen species generation

    NASA Astrophysics Data System (ADS)

    Lismont, M.; Pá; ez-Martinez, C.; Dreesen, L.

    2015-03-01

    Photodynamic therapy (PDT) for cancer is based on the use of a light sensitive molecule to produce, under specific irradiation, toxic reactive oxygen species (ROS). A way to improve the therapy efficiency is to increase the amount of produced ROS near cancer cells. This aim can be achieved by using a metal enhanced process arising when an optically active molecule is located near a metallic nanoparticle (NP). Here, the coupling effect between silver (Ag) NPs and protoporphyrin IX (PpIX) molecules, a clinically approved photosensitizer, is studied compared first, to PpIX fluorescence yield and second, to ROS production efficiency. By applying a modified Stöber process, PpIX was encapsulated into a silica (SiO2) shell, surrounding a 60 nm sized Ag core. We showed that, compared to SiO2-PpIX NPs, Ag coated SiO2-PpIX NPs dramatically decreased PpIX fluorescence together with singlet oxygen production efficiency. However, after incubation time in the dark, the amount of superoxide anions generated by the Ag doped sample was higher than the control sample one.

  15. Fructose as a novel photosensitizer: Characterization of reactive oxygen species and an application in degradation of diuron and chlorpyrifos.

    PubMed

    Nayak, Shaila; Muniz, Juan; Sales, Christopher M; Tikekar, Rohan V

    2016-02-01

    The objective of this study was to identify reactive oxygen species (ROS) generated from the exposure of fructose solution to the 254 nm ultraviolet (UV) light and evaluate whether fructose can be used as a photosensitizer for accelerated photo-degradation of diuron and chlorpyrifos. We demonstrated that hydrogen peroxide, singlet oxygen ((1)O2) and acidic photolysis products were generated upon UV exposure of fructose. Consistent with these findings, UV induced degradation of chlorpyrifos and diuron was accelerated by the presence of 500 mM fructose. The average first order photo-degradation rate constants in the absence and presence of 500 mM fructose were 0.92 and 2.07 min(-1) respectively for diuron and 0.04 and 0.07 min(-1) for chlorpyrifos. The quantum yields (ɸ) for direct photo-degradation of diuron and chlorpyrifos were 0.003 and 0.001 respectively. In the presence of 500 mM fructose, these values increased to 0.006 and 0.002 respectively. Thus, fructose may be an effective photosensitizer. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Contribution of reactive oxygen species to the anticancer activity of aminoalkanol derivatives of xanthone.

    PubMed

    Sypniewski, Daniel; Szkaradek, Natalia; Loch, Tomasz; Waszkielewicz, Anna M; Gunia-Krzyżak, Agnieszka; Matczyńska, Daria; Sołtysik, Dagna; Marona, Henryk; Bednarek, Ilona

    2018-06-01

    Reactive oxygen species (ROS) are critically involved in the action of anticancer agents. In this study, we investigated the role of ROS in the anticancer mechanism of new aminoalkanol derivatives of xanthone. Most xanthones used in the study displayed significant pro-oxidant effects similar to those of gambogic acid, one of the most active anticancer xanthones. The pro-oxidant activity of our xanthones was shown both directly (by determination of ROS induction, effects on the levels of intracellular antioxidants, and expression of antioxidant enzymes) and indirectly by demonstrating that the overexpression of manganese superoxide dismutase decreases ROS-mediated cell senescence. We also observed that mitochondrial dysfunction and cellular apoptosis enhancement correlated with xanthone-induced oxidative stress. Finally, we showed that the use of the antioxidant N-acetyl-L-cysteine partly reversed these effects of aminoalkanol xanthones. Our results demonstrated that novel aminoalkanol xanthones mediated their anticancer activity primarily through ROS elevation and enhanced oxidative stress, which led to mitochondrial cell death stimulation; this mechanism was similar to the activity of gambogic acid.

  17. The Role of Reactive Oxygen Species (ROS) in the Biological Activities of Metallic Nanoparticles

    PubMed Central

    Abdal Dayem, Ahmed; Hossain, Mohammed Kawser; Lee, Soo Bin; Kim, Kyeongseok; Saha, Subbroto Kumar; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2017-01-01

    Nanoparticles (NPs) possess unique physical and chemical properties that make them appropriate for various applications. The structural alteration of metallic NPs leads to different biological functions, specifically resulting in different potentials for the generation of reactive oxygen species (ROS). The amount of ROS produced by metallic NPs correlates with particle size, shape, surface area, and chemistry. ROS possess multiple functions in cellular biology, with ROS generation a key factor in metallic NP-induced toxicity, as well as modulation of cellular signaling involved in cell death, proliferation, and differentiation. In this review, we briefly explained NP classes and their biomedical applications and describe the sources and roles of ROS in NP-related biological functions in vitro and in vivo. Furthermore, we also described the roles of metal NP-induced ROS generation in stem cell biology. Although the roles of ROS in metallic NP-related biological functions requires further investigation, modulation and characterization of metallic NP-induced ROS production are promising in the application of metallic NPs in the areas of regenerative medicine and medical devices. PMID:28075405

  18. Role of reactive oxygen species in the anticancer activity of botanicals: Comparing sensitivity profiles

    PubMed Central

    Cohen, Zoya; Maimon, Yair; Samuels, Noah; Berger, Raanan

    2017-01-01

    Numerous botanicals have been shown to exhibit in vitro and in vivo anticancer activity, some of which is the result of the induction of reactive oxygen species (ROS) in cancer cells with a high ROS content. The present study compared sensitivities to a series of botanicals among cancer cell lines, using an XTT viability test, in order to create a specific cancer-herb profile. Of the 27 botanicals screened, 10 exhibited a cytotoxic effect, 7 of which were ROS-mediated. The sensitivity profiles of the ROS-inducing botanicals in 10 cancer cell lines were similar, unlike 3 cytotoxic ROS-independent botanicals that displayed divergent botanical-specific profiles. The correlation between sensitivity profiles of ROS-inducing botanicals suggests a common mechanism of action, in contrast to the varied mechanism of ROS-independent botanicals. This implies that the investigation of the anticancer activity of botanicals should start with the examination of ROS-mediated activity. Further investigation of ROS sensitivity among various tumor types is required in order to guide research into developing evidence-based guidelines in the use of botanicals for cancer treatment. PMID:28454445

  19. Extracellular ultrathin fibers sensitive to intracellular reactive oxygen species: Formation of intercellular membrane bridges

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jung, Se-Hui; Park, Jin-Young; Joo, Jung-Hoon

    2011-07-15

    Membrane bridges are key cellular structures involved in intercellular communication; however, dynamics for their formation are not well understood. We demonstrated the formation and regulation of novel extracellular ultrathin fibers in NIH3T3 cells using confocal and atomic force microscopy. At adjacent regions of neighboring cells, phorbol 12-myristate 13-acetate (PMA) and glucose oxidase induced ultrathin fiber formation, which was prevented by Trolox, a reactive oxygen species (ROS) scavenger. The height of ROS-sensitive ultrathin fibers ranged from 2 to 4 nm. PMA-induced formation of ultrathin fibers was inhibited by cytochalasin D, but not by Taxol or colchicine, indicating that ultrathin fibers mainlymore » comprise microfilaments. PMA-induced ultrathin fibers underwent dynamic structural changes, resulting in formation of intercellular membrane bridges. Thus, these fibers are formed by a mechanism(s) involving ROS and involved in formation of intercellular membrane bridges. Furthermore, ultrastructural imaging of ultrathin fibers may contribute to understanding the diverse mechanisms of cell-to-cell communication and the intercellular transfer of biomolecules, including proteins and cell organelles.« less

  20. The angiotensin II-AT1 receptor stimulates reactive oxygen species within the cell nucleus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pendergrass, Karl D.; Gwathmey, TanYa M.; Michalek, Ryan D.

    2009-06-26

    We and others have reported significant expression of the Ang II Type 1 receptor (AT1R) on renal nuclei; thus, the present study assessed the functional pathways and distribution of the intracellular AT1R on isolated nuclei. Ang II (1 nM) stimulated DCF fluorescence, an intranuclear indicator of reactive oxygen species (ROS), while the AT1R antagonist losartan or the NADPH oxidase (NOX) inhibitor DPI abolished the increase in ROS. Dual labeling of nuclei with antibodies against nucleoporin 62 (Nup62) and AT1R or the NADPH oxidase isoform NOX4 revealed complete overlap of the Nup62 and AT1R (99%) by flow cytometry, while NOX4 wasmore » present on 65% of nuclei. Treatment of nuclei with a PKC agonist increased ROS while the PKC inhibitor GF109203X or PI3 kinase inhibitor LY294002 abolished Ang II stimulation of ROS. We conclude that the Ang II-AT1R-PKC axis may directly influence nuclear function within the kidney through a redox sensitive pathway.« less

  1. Reactive Oxygen Species as Additional Determinants for Cytotoxicity of Clostridium difficile Toxins A and B

    PubMed Central

    Frädrich, Claudia; Beer, Lara-Antonia; Gerhard, Ralf

    2016-01-01

    Clostridium difficile infections can induce mild to severe diarrhoea and the often associated characteristic pseudomembranous colitis. Two protein toxins, the large glucosyltransferases TcdA and TcdB, are the main pathogenicity factors that can induce all clinical symptoms in animal models. The classical molecular mode of action of these homologous toxins is the inhibition of Rho GTPases by mono-glucosylation. Rho-inhibition leads to breakdown of the actin cytoskeleton, induces stress-activated and pro-inflammatory signaling and eventually results in apoptosis of the affected cells. An increasing number of reports, however, have documented further qualities of TcdA and TcdB, including the production of reactive oxygen species (ROS) by target cells. This review summarizes observations dealing with the production of ROS induced by TcdA and TcdB, dissects pathways that contribute to this phenomenon and speculates about ROS in mediating pathogenesis. In conclusion, ROS have to be considered as a discrete, glucosyltransferase-independent quality of at least TcdB, triggered by different mechanisms. PMID:26797634

  2. Reactive oxygen species acts as executor in radiation enhancement and autophagy inducing by AgNPs.

    PubMed

    Wu, Hao; Lin, Jun; Liu, Peidang; Huang, Zhihai; Zhao, Peng; Jin, Haizhen; Ma, Jun; Wen, Longping; Gu, Ning

    2016-09-01

    Malignant glioma is one of the most common intracranial tumor with a dismal prognosis. The radiosensitizing effect of silver nanoparticles (AgNPs) on glioma both in vitro and in vivo were demonstrated in the previous studies of our group. However, the underlying mechanism is still unclear. In this present study, the use of antioxidants is employed for the regulating of reactive oxygen species (ROS) in U251 cells treated with various agents, and the results shows that ROS played an essential role in the autophagy inducing and radiosensitization effect of AgNPs. Moreover, the inhibition of protective autophagy with 3-MA is another way to increase ROS, resulting in the increasing of cell death and apoptosis. Taken together, understanding the relationship between the elevated ROS and autophagy and the effect of ROS should be useful to the clinical applications of AgNPs. These findings could potentially be exploited for new therapeutic strategies in glioma radiotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. The Role of Heme and Reactive Oxygen Species in Proliferation and Survival of Trypanosoma cruzi

    PubMed Central

    Paes, Marcia Cristina; Cosentino-Gomes, Daniela; de Souza, Cíntia Fernandes; Nogueira, Natália Pereira de Almeida; Meyer-Fernandes, José Roberto

    2011-01-01

    Trypanosoma cruzi, the protozoan responsible for Chagas disease, has a complex life cycle comprehending two distinct hosts and a series of morphological and functional transformations. Hemoglobin degradation inside the insect vector releases high amounts of heme, and this molecule is known to exert a number of physiological functions. Moreover, the absence of its complete biosynthetic pathway in T. cruzi indicates heme as an essential molecule for this trypanosomatid survival. Within the hosts, T. cruzi has to cope with sudden environmental changes especially in the redox status and heme is able to increase the basal production of reactive oxygen species (ROS) which can be also produced as byproducts of the parasite aerobic metabolism. In this regard, ROS sensing is likely to be an important mechanism for the adaptation and interaction of these organisms with their hosts. In this paper we discuss the main features of heme and ROS susceptibility in T. cruzi biology. PMID:22007287

  4. Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release

    PubMed Central

    Zorov, Dmitry B.; Juhaszova, Magdalena; Sollott, Steven J.

    2014-01-01

    Byproducts of normal mitochondrial metabolism and homeostasis include the buildup of potentially damaging levels of reactive oxygen species (ROS), Ca2+, etc., which must be normalized. Evidence suggests that brief mitochondrial permeability transition pore (mPTP) openings play an important physiological role maintaining healthy mitochondria homeostasis. Adaptive and maladaptive responses to redox stress may involve mitochondrial channels such as mPTP and inner membrane anion channel (IMAC). Their activation causes intra- and intermitochondrial redox-environment changes leading to ROS release. This regenerative cycle of mitochondrial ROS formation and release was named ROS-induced ROS release (RIRR). Brief, reversible mPTP opening-associated ROS release apparently constitutes an adaptive housekeeping function by the timely release from mitochondria of accumulated potentially toxic levels of ROS (and Ca2+). At higher ROS levels, longer mPTP openings may release a ROS burst leading to destruction of mitochondria, and if propagated from mitochondrion to mitochondrion, of the cell itself. The destructive function of RIRR may serve a physiological role by removal of unwanted cells or damaged mitochondria, or cause the pathological elimination of vital and essential mitochondria and cells. The adaptive release of sufficient ROS into the vicinity of mitochondria may also activate local pools of redox-sensitive enzymes involved in protective signaling pathways that limit ischemic damage to mitochondria and cells in that area. Maladaptive mPTP- or IMAC-related RIRR may also be playing a role in aging. Because the mechanism of mitochondrial RIRR highlights the central role of mitochondria-formed ROS, we discuss all of the known ROS-producing sites (shown in vitro) and their relevance to the mitochondrial ROS production in vivo. PMID:24987008

  5. Reactive oxygen species mediate human hepatocyte injury during hypoxia/reoxygenation.

    PubMed

    Bhogal, Ricky Harminder; Curbishley, Stuart M; Weston, Christopher J; Adams, David H; Afford, Simon C

    2010-11-01

    Increasing evidence shows that reactive oxygen species (ROS) may be critical mediators of liver damage during the relative hypoxia of ischemia/reperfusion injury (IRI) associated with transplant surgery or of the tissue microenvironment created as a result of chronic hepatic inflammation or infection. Much work has been focused on Kupffer cells or liver resident macrophages with respect to the generation of ROS during IRI. However, little is known about the contribution of endogenous hepatocyte ROS production or its potential impact on the parenchymal cell death associated with IRI and chronic hepatic inflammation. For the first time, we show that human hepatocytes isolated from nondiseased liver tissue and human hepatocytes isolated from diseased liver tissue exhibit marked differences in ROS production in response to hypoxia/reoxygenation (H-R). Furthermore, several different antioxidants are able to abrogate hepatocyte ROS-induced cell death during hypoxia and H-R. These data provide clear evidence that endogenous ROS production by mitochondria and nicotinamide adenine dinucleotide phosphate oxidase drives human hepatocyte apoptosis and necrosis during hypoxia and H-R and may therefore play an important role in any hepatic diseases characterized by a relatively hypoxic liver microenvironment. In conclusion, these data strongly suggest that hepatocytes and hepatocyte-derived ROS are active participants driving hepatic inflammation. These novel findings highlight important functional/metabolic differences between hepatocytes isolated from normal donor livers, hepatocytes isolated from normal resected tissue obtained during surgery for malignant neoplasms, and hepatocytes isolated from livers with end-stage disease. Furthermore, the targeting of hepatocyte ROS generation with antioxidants may offer therapeutic potential for the adjunctive treatment of IRI and chronic inflammatory liver diseases. © 2010 AASLD.

  6. Oxidation-extraction spectrometry of reactive oxygen species (ROS) generated by chlorophyllin magnesium (Chl-Mg) under ultrasonic irradiation

    NASA Astrophysics Data System (ADS)

    Guo, Yuwei; Cheng, Chunping; Wang, Jun; Jin, Xudong; Liu, Bin; Wang, Zhiqiu; Gao, Jingqun; Kang, Pingli

    2011-09-01

    In order to examine the mechanism and process of sonodynamic reaction, the chlorophyllin magnesium (Chl-Mg) acting as a sonosensitizer was irradiated by ultrasound, and the generation of reactive oxygen species (ROS) were detected by the method of oxidation-extraction spectrometry (OES). That is, under ultrasonic irradiation in the presence of Chl-Mg, the 1,5-diphenyl carbazide (DPCI) is oxidized by generated ROS into 1,5-diphenyl carbazone (DPCO), which can be extracted by mixed organic solvent and display a obvious visible absorption at 563 nm wavelength. Besides, the generation conditions of ROS were also reviewed. The results demonstrated that the quantities of generated ROS increased with the increase of ultrasonic irradiation time, Chl-Mg concentration and DPCI concentration. Finally, several radical scavengers (l-Histidine (His), 2,6-Di-tert-butyl-methylphenol (BHT) and Vitamin C (VC)) were used to determine the kind of the generated ROS. It was found that at least the hydroxyl radical (OH) and singlet oxygen ( 1O 2) were generated in the presence of Chl-Mg under ultrasonic irradiation. It is wish that this paper might offer some valuable references for the study on the mechanism of SDT and the application of Chl-Mg in tumor treatment.

  7. NADPH Oxidase Plays a Role on Ethanol-Induced Hypertension and Reactive Oxygen Species Generation in the Vasculature.

    PubMed

    Marchi, Katia Colombo; Ceron, Carla Speroni; Muniz, Jaqueline J; De Martinis, Bruno S; Tanus-Santos, José E; Tirapelli, Carlos Renato

    2016-09-01

    Investigate the role of NADPH oxidase on ethanol-induced hypertension and vascular oxidative stress. Male Wistar rats were treated with ethanol (20% v/v). Apocynin (10 mg/kg/day, i.p.) prevented ethanol-induced hypertension. The increased contractility of endothelium-intact and endothelium-denuded aortic rings from ethanol-treated rats to phenylephrine was prevented by apocynin. Ethanol consumption increased superoxide anion (O2 (-)) generation and lipid peroxidation and apocynin prevented these responses. The decrease on plasma and vascular nitrate/nitrite (NOx) levels induced by ethanol was not prevented by apocynin. Treatment with ethanol did not affect aortic levels of hydrogen peroxide (H2O2) or reduced glutathione (GSH). Ethanol did not alter the activities of xanthine oxidase (XO), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Ethanol increased the expression of Nox1, PKCδ, nNOS, SAPK/JNK and SOD2 in the rat aorta and apocynin prevented these responses. No difference on aortic expression of Nox2, Nox4, p47phox, Nox organizer 1 (Noxo1), eNOS and iNOS was detected after treatment with ethanol. Ethanol treatment did not alter the phosphorylation of SAPK/JNK, p38MAPK, c-Src, Rac1 or PKCδ. The major new finding of our study is that the increased vascular generation of reactive oxygen species (ROS) induced by ethanol is related to increased vascular Nox1/NADPH oxidase expression. This mechanism is involved in vascular dysfunction and hypertension induced by ethanol. Additionally, we conclude that ethanol consumption induces the expression of different proteins that regulate vascular contraction and growth and that NADPH oxidase-derived ROS play a role in such response. The key findings of our study are that ethanol-induced hypertension is mediated by NADPH oxidase. Moreover, increased vascular Nox1 expression is related to the generation of reactive oxygen species (ROS) by ethanol. Finally, ROS induced by ethanol increase the

  8. The Comparative Study of the Effects of Extremely Low Frequency Electromagnetic Fields and Infrasound on Water Molecule Dissociation and Generation of Reactive Oxygen Species

    DTIC Science & Technology

    2008-11-01

    ISTC Project No. #1592P The Comparative Study of The Effects of Extremely Low Frequency Electromagnetic Fields and Infrasound on Water Molecule...performed under the agreement with the International Science and Technology Center ( ISTC ), Moscow. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704...dissociation and generation of reactive oxygen spaces. 5a. CONTRACT NUMBER ISTC Registration No: A-1592p 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

  9. Oxygen radicals as key mediators in neurological disease: fact or fiction?

    PubMed

    Halliwell, B

    1992-01-01

    A free radical is any species capable of independent existence that contains one or more unpaired electrons. Free radicals and other reactive oxygen species are frequently proposed to be involved in the pathology of several neurological disorders. Criteria for establishing such involvement are presented. Development of new methods for measuring oxidative damage should enable elucidation of the precise role of reactive oxygen species in neurological disorders.

  10. Uric acid and transforming growth factor in fructose-induced production of reactive oxygen species in skeletal muscle

    PubMed Central

    Maarman, Gerald J.; Ojuka, Edward

    2016-01-01

    The consumption of fructose, a major constituent of the modern diet, has raised increasing concern about the effects of fructose on health. Research suggests that excessive intake of fructose (>50 g/d) causes hyperuricemia, insulin resistance, mitochondrial dysfunction, de novo lipogenesis by the liver, and increased production of reactive oxygen species (ROS) in muscle. In a number of tissues, uric acid has been shown to stimulate the production of ROS via activation of transforming growth factor β1 and NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 4. The role of uric acid in fructose-induced production of ROS in skeletal muscle, however, has not been investigated. This review examines the evidence for fructose-induced production of ROS in skeletal muscle, highlights proposed mechanisms, and identifies gaps in current knowledge. PMID:26946251

  11. Chemical Kinetics of Hydrogen Atom Abstraction from Allylic Sites by 3O2; Implications for Combustion Modeling and Simulation.

    PubMed

    Zhou, Chong-Wen; Simmie, John M; Somers, Kieran P; Goldsmith, C Franklin; Curran, Henry J

    2017-03-09

    Hydrogen atom abstraction from allylic C-H bonds by molecular oxygen plays a very important role in determining the reactivity of fuel molecules having allylic hydrogen atoms. Rate constants for hydrogen atom abstraction by molecular oxygen from molecules with allylic sites have been calculated. A series of molecules with primary, secondary, tertiary, and super secondary allylic hydrogen atoms of alkene, furan, and alkylbenzene families are taken into consideration. Those molecules include propene, 2-butene, isobutene, 2-methylfuran, and toluene containing the primary allylic hydrogen atom; 1-butene, 1-pentene, 2-ethylfuran, ethylbenzene, and n-propylbenzene containing the secondary allylic hydrogen atom; 3-methyl-1-butene, 2-isopropylfuran, and isopropylbenzene containing tertiary allylic hydrogen atom; and 1-4-pentadiene containing super allylic secondary hydrogen atoms. The M06-2X/6-311++G(d,p) level of theory was used to optimize the geometries of all of the reactants, transition states, products and also the hinder rotation treatments for lower frequency modes. The G4 level of theory was used to calculate the electronic single point energies for those species to determine the 0 K barriers to reaction. Conventional transition state theory with Eckart tunnelling corrections was used to calculate the rate constants. The comparison between our calculated rate constants with the available experimental results from the literature shows good agreement for the reactions of propene and isobutene with molecular oxygen. The rate constant for toluene with O 2 is about an order magnitude slower than that experimentally derived from a comprehensive model proposed by Oehlschlaeger and coauthors. The results clearly indicate the need for a more detailed investigation of the combustion kinetics of toluene oxidation and its key pyrolysis and oxidation intermediates. Despite this, our computed barriers and rate constants retain an important internal consistency. Rate constants

  12. Quantitative reactive modeling and verification.

    PubMed

    Henzinger, Thomas A

    Formal verification aims to improve the quality of software by detecting errors before they do harm. At the basis of formal verification is the logical notion of correctness , which purports to capture whether or not a program behaves as desired. We suggest that the boolean partition of software into correct and incorrect programs falls short of the practical need to assess the behavior of software in a more nuanced fashion against multiple criteria. We therefore propose to introduce quantitative fitness measures for programs, specifically for measuring the function, performance, and robustness of reactive programs such as concurrent processes. This article describes the goals of the ERC Advanced Investigator Project QUAREM. The project aims to build and evaluate a theory of quantitative fitness measures for reactive models. Such a theory must strive to obtain quantitative generalizations of the paradigms that have been success stories in qualitative reactive modeling, such as compositionality, property-preserving abstraction and abstraction refinement, model checking, and synthesis. The theory will be evaluated not only in the context of software and hardware engineering, but also in the context of systems biology. In particular, we will use the quantitative reactive models and fitness measures developed in this project for testing hypotheses about the mechanisms behind data from biological experiments.

  13. Programmable flow system for automation of oxygen radical absorbance capacity assay using pyrogallol red for estimation of antioxidant reactivity.

    PubMed

    Ramos, Inês I; Gregório, Bruno J R; Barreiros, Luísa; Magalhães, Luís M; Tóth, Ildikó V; Reis, Salette; Lima, José L F C; Segundo, Marcela A

    2016-04-01

    An automated oxygen radical absorbance capacity (ORAC) method based on programmable flow injection analysis was developed for the assessment of antioxidant reactivity. The method relies on real time spectrophotometric monitoring (540 nm) of pyrogallol red (PGR) bleaching mediated by peroxyl radicals in the presence of antioxidant compounds within the first minute of reaction, providing information about their initial reactivity against this type of radicals. The ORAC-PGR assay under programmable flow format affords a strict control of reaction conditions namely reagent mixing, temperature and reaction timing, which are critical parameters for in situ generation of peroxyl radical from 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). The influence of reagent concentrations and programmable flow conditions on reaction development was studied, with application of 37.5 µM of PGR and 125 mM of AAPH in the flow cell, guaranteeing first order kinetics towards peroxyl radicals and pseudo-zero order towards PGR. Peroxyl-scavenging reactivity of antioxidants, bioactive compounds and phenolic-rich beverages was estimated employing the proposed methodology. Recovery assays using synthetic saliva provided values of 90 ± 5% for reduced glutathione. Detection limit calculated using the standard antioxidant compound Trolox was 8 μM. RSD values were <3.4 and <4.9%, for intra and inter-assay precision, respectively. Compared to previous batch automated ORAC assays, the developed system also accounted for high sampling frequency (29 h(-1)), low operating costs and low generation of waste. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Oxidation of tertiary amines by cytochrome p450-kinetic isotope effect as a spin-state reactivity probe.

    PubMed

    Li, Chunsen; Wu, Wei; Cho, Kyung-Bin; Shaik, Sason

    2009-08-24

    Two types of tertiary amine oxidation processes, namely, N-dealkylation and N-oxygenation, by compound I (Cpd I) of cytochrome P450 are studied theoretically using hybrid DFT calculations. All the calculations show that both N-dealkylation and N-oxygenation of trimethylamine (TMA) proceed preferentially from the low-spin (LS) state of Cpd I. Indeed, the computed kinetic isotope effects (KIEs) for the rate-controlling hydrogen abstraction step of dealkylation show that only the KIE(LS) fits the experimental datum, whereas the corresponding value for the high-spin (HS) process is much higher. These results second those published before for N,N-dimethylaniline (DMA), and as such, they further confirm the conclusion drawn then that KIEs can be a sensitive probe of spin state reactivity. The ferric-carbinolamine of TMA decomposes most likely in a non-enzymatic reaction since the Fe-O bond dissociation energy (BDE) is negative. The computational results reveal that in the reverse reaction of N-oxygenation, the N-oxide of aromatic amine can serve as a better oxygen donor than that of aliphatic amine to generate Cpd I. This capability of the N-oxo derivatives of aromatic amines to transfer oxygen to the heme, and thereby generate Cpd I, is in good accord with experimental data previously reported.

  15. Accelerated Oxygen Atom Transfer and C-H Bond Oxygenation by Remote Redox Changes in Fe 3Mn-Iodosobenzene Adducts

    DOE PAGES

    de Ruiter, Graham; Carsch, Kurtis M.; Gul, Sheraz; ...

    2017-03-24

    In this paper, we report the synthesis, characterization, and reactivity of [LFe 3(PhPz) 3OMn( sPhIO)][OTf] x (3: x=2; 4: x=3), where 4 is one of very few examples of iodosobenzene–metal adducts characterized by X-ray crystallography. Access to these rare heterometallic clusters enabled differentiation of the metal centers involved in oxygen atom transfer (Mn) or redox modulation (Fe). Specifically, 57Fe Mössbauer and X-ray absorption spectroscopy provided unique insights into how changes in oxidation state (Fe III 2Fe IIMn II vs. Fe III 3Mn II) influence oxygen atom transfer in tetranuclear Fe 3Mn clusters. Finally, in particular, a one-electron redox change atmore » a distal metal site leads to a change in oxygen atom transfer reactivity by ca. two orders of magnitude.« less

  16. Reactive oxygen species level in follicular fluid--embryo quality marker in IVF?

    PubMed

    Das, S; Chattopadhyay, R; Ghosh, S; Ghosh, S; Goswami, S K; Chakravarty, B N; Chaudhury, K

    2006-09-01

    The impact of oxidative stress in female reproduction is not clear. Contradictory reports on the effect of various oxidative stress markers on follicular fluid, oocytes and embryo quality and fertilization potential exist. The objectives of this study were to examine reactive oxygen species (ROS) levels in follicular fluid of women undergoing IVF and to relate these levels to embryo formation and quality. A total of 208 follicular fluid samples were obtained from 78 women undergoing controlled ovarian stimulation and analysed for ROS and lipid peroxidation (LPO). These samples were divided into groups I and II which represented follicular fluid containing grade III and grade II oocytes, respectively. These groups were further subdivided into groups IA, IB, IIA and IIB according to embryo quality. Subgroups IA and IIA consisted of follicular fluid samples corresponding to grade I/II embryo formation. Subgroups IB and IIB represented fertilization failure/pro-nucleolus (PN) arrest/grade III embryos. No significant correlation was observed in ROS levels on comparing groups I and II (P > 0.05). However, ROS levels were observed to be significantly different on comparing groups IA and IB (P < or = 0.01) and groups IIA and IIB (P < or = 0.05). LPO levels further supported our results. ROS levels in follicular fluid appear to play a significant role in embryo formation and quality.

  17. Mitochondria-derived reactive oxygen species drive GANT61-induced mesothelioma cell apoptosis.

    PubMed

    Lim, Chuan Bian; Prêle, Cecilia M; Baltic, Svetlana; Arthur, Peter G; Creaney, Jenette; Watkins, D Neil; Thompson, Philip J; Mutsaers, Steven E

    2015-01-30

    Gli transcription factors of the Hedgehog (Hh) pathway have been reported to be drivers of malignant mesothelioma (MMe) cell survival. The Gli inhibitor GANT61 induces apoptosis in various cancer cell models, and has been associated directly with Gli inhibition. However various chemotherapeutics can induce cell death through generation of reactive oxygen species (ROS) but whether ROS mediates GANT61-induced apoptosis is unknown. In this study human MMe cells were treated with GANT61 and the mechanisms regulating cell death investigated. Exposure of MMe cells to GANT61 led to G1 phase arrest and apoptosis, which involved ROS but not its purported targets, GLI1 or GLI2. GANT61 triggered ROS generation and quenching of ROS protected MMe cells from GANT61-induced apoptosis. Furthermore, we demonstrated that mitochondria are important in mediating GANT61 effects: (1) ROS production and apoptosis were blocked by mitochondrial inhibitor rotenone; (2) GANT61 promoted superoxide formation in mitochondria; and (3) mitochondrial DNA-deficient LO68 cells failed to induce superoxide, and were more resistant to apoptosis induced by GANT61 than wild-type cells. Our data demonstrate for the first time that GANT61 induces apoptosis by promoting mitochondrial superoxide generation independent of Gli inhibition, and highlights the therapeutic potential of mitochondrial ROS-mediated anticancer drugs in MMe.

  18. Fabrication of Super-Hydrophobic Microchannels via Strain-Recovery Deformations of Polystyrene and Oxygen Reactive Ion Etch.

    PubMed

    Chakraborty, Anirban; Xiang, Mingming; Luo, Cheng

    2013-08-19

    In this article, we report a simple approach to generate micropillars (whose top portions are covered by sub-micron wrinkles) on the inner surfaces of polystyrene (PS) microchannels, as well as on the top surface of the PS substrate, based on strain-recovery deformations of the PS and oxygen reactive ion etch (ORIE). Using this approach, two types of micropillar-covered microchannels are fabricated. Their widths range from 118 μm to 132 μm, depths vary from 40 μm to 44 μm, and the inclined angles of their sidewalls are from 53° to 64°. The micropillars enable these microchannels to have super-hydrophobic properties. The contact angles observed on the channel-structured surfaces are above 162°, and the tilt angles to make water drops roll off from these channel-structured substrates can be as small as 1°.

  19. Mitochondrial reactive oxygen species and complex II levels are associated with the outcome of hepatocellular carcinoma

    PubMed Central

    WU, JIANHUA; ZHAO, FEI; ZHAO, YUFEI; GUO, ZHANJUN

    2015-01-01

    In the present study, two oxidative stress parameters, reactive oxygen species (ROS) and mitochondrial respiratory complex II, were evaluated in the mitochondria of hepatocellular carcinoma (HCC) cells to determine the association between these parameters and the carcinogenesis and clinical outcome of HCC. High levels of ROS and low levels of complex II were found to be associated with reduced post-operative survival in HCC patients using the log-rank test. Furthermore, multivariate analysis confirmed that the levels of ROS [relative risk (RR)=2.867; 95% confidence interval (CI), 1.062–7.737; P=0.038] and complex II (RR=5.422; 95% CI, 1.273–23.088; P=0.022) were independent predictors for the survival of patients with HCC. Therefore, the analysis of ROS and complex II levels may provide a useful research and therapeutic tool for the prediction of HCC prognosis and treatment. PMID:26622849

  20. Metabolic and Homeostatic Changes in Seizures and Acquired Epilepsy—Mitochondria, Calcium Dynamics and Reactive Oxygen Species

    PubMed Central

    Kovac, Stjepana; Dinkova Kostova, Albena T.; Melzer, Nico; Meuth, Sven G.; Gorji, Ali

    2017-01-01

    Acquired epilepsies can arise as a consequence of brain injury and result in unprovoked seizures that emerge after a latent period of epileptogenesis. These epilepsies pose a major challenge to clinicians as they are present in the majority of patients seen in a common outpatient epilepsy clinic and are prone to pharmacoresistance, highlighting an unmet need for new treatment strategies. Metabolic and homeostatic changes are closely linked to seizures and epilepsy, although, surprisingly, no potential treatment targets to date have been translated into clinical practice. We summarize here the current knowledge about metabolic and homeostatic changes in seizures and acquired epilepsy, maintaining a particular focus on mitochondria, calcium dynamics, reactive oxygen species and key regulators of cellular metabolism such as the Nrf2 pathway. Finally, we highlight research gaps that will need to be addressed in the future which may help to translate these findings into clinical practice. PMID:28885567

  1. Damage-induced reactive oxygen species regulate vimentin and dynamic collagen-based projections to mediate wound repair

    PubMed Central

    Freisinger, Chrissy; Rindy, Julie; Golenberg, Netta; Frecentese, Grace; Gibson, Angela; Eliceiri, Kevin W

    2018-01-01

    Tissue injury leads to early wound-associated reactive oxygen species (ROS) production that mediate tissue regeneration. To identify mechanisms that function downstream of redox signals that modulate regeneration, a vimentin reporter of mesenchymal cells was generated by driving GFP from the vimentin promoter in zebrafish. Early redox signaling mediated vimentin reporter activity at the wound margin. Moreover, both ROS and vimentin were necessary for collagen production and reorganization into projections at the leading edge of the wound. Second harmonic generation time-lapse imaging revealed that the collagen projections were associated with dynamic epithelial extensions at the wound edge during wound repair. Perturbing collagen organization by burn wound disrupted epithelial projections and subsequent wound healing. Taken together our findings suggest that ROS and vimentin integrate early wound signals to orchestrate the formation of collagen-based projections that guide regenerative growth during efficient wound repair. PMID:29336778

  2. Gulf War illnesses are autoimmune illnesses caused by reactive oxygen species which were caused by nerve agent prophylaxis.

    PubMed

    Moss, J I

    2012-08-01

    Gulf War illnesses (GWI share many of the features of chronic fatigue syndrome (CFS) and both CFS and GWI may be the result of chronic immune system processes. The main suspected cause for GWI, the drug pyridostigmine bromide (PB), has been shown to cause neuronal damage from reactive oxygen species (ROS). ROS have been associated with IgM mediated autoimmune responses against ROS induced neoepitopes in depressed patients and this may also apply to CFS. It therefore follows that the drug used in the Gulf War caused ROS, the ROS modified native molecules, and that this trigged the autoimmune condition we refer to as Gulf War illnesses. Similar mechanisms may apply to other autoimmune illnesses. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Friend or foe? Reactive oxygen species production, scavenging and signaling in plant response to environmental stresses.

    PubMed

    Czarnocka, Weronika; Karpiński, Stanisław

    2018-01-10

    In the natural environment, plants are exposed to a variety of biotic and abiotic stress conditions that trigger rapid changes in the production and scavenging of reactive oxygen species (ROS). The production and scavenging of ROS is compartmentalized, which means that, depending on stimuli type, they can be generated and eliminated in different cellular compartments such as the apoplast, plasma membrane, chloroplasts, mitochondria, peroxisomes, and endoplasmic reticulum. Although the accumulation of ROS is generally harmful to cells, ROS play an important role in signaling pathways that regulate acclimatory and defense responses in plants, such as systemic acquired acclimation (SAA) and systemic acquired resistance (SAR). However, high accumulations of ROS can also trigger redox homeostasis disturbance which can lead to cell death, and in consequence, to a limitation in biomass and yield production. Different ROS have various half-lifetimes and degrees of reactivity toward molecular components such as lipids, proteins, and nucleic acids. Thus, they play different roles in intra- and extra-cellular signaling. Despite their possible damaging effect, ROS should mainly be considered as signaling molecules that regulate local and systemic acclimatory and defense responses. Over the past two decades it has been proven that ROS together with non-photochemical quenching (NPQ), hormones, Ca 2+ waves, and electrical signals are the main players in SAA and SAR, two physiological processes essential for plant survival and productivity in unfavorable conditions. Copyright © 2018. Published by Elsevier Inc.

  4. Singlet Oxygen Formation during the Charging Process of an Aprotic Lithium-Oxygen Battery.

    PubMed

    Wandt, Johannes; Jakes, Peter; Granwehr, Josef; Gasteiger, Hubert A; Eichel, Rüdiger-A

    2016-06-06

    Aprotic lithium-oxygen (Li-O2 ) batteries have attracted considerable attention in recent years owing to their outstanding theoretical energy density. A major challenge is their poor reversibility caused by degradation reactions, which mainly occur during battery charge and are still poorly understood. Herein, we show that singlet oxygen ((1) Δg ) is formed upon Li2 O2 oxidation at potentials above 3.5 V. Singlet oxygen was detected through a reaction with a spin trap to form a stable radical that was observed by time- and voltage-resolved in operando EPR spectroscopy in a purpose-built spectroelectrochemical cell. According to our estimate, a lower limit of approximately 0.5 % of the evolved oxygen is singlet oxygen. The occurrence of highly reactive singlet oxygen might be the long-overlooked missing link in the understanding of the electrolyte degradation and carbon corrosion reactions that occur during the charging of Li-O2 cells. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Cellular death, reactive oxygen species (ROS) and diabetic complications.

    PubMed

    Volpe, Caroline Maria Oliveira; Villar-Delfino, Pedro Henrique; Dos Anjos, Paula Martins Ferreira; Nogueira-Machado, José Augusto

    2018-01-25

    Chronic or intermittent hyperglycemia is associated with the development of diabetic complications. Several signaling pathways can be altered by having hyperglycemia in different tissues, producing oxidative stress, the formation of advanced glycation end products (AGEs), as well as the secretion of the pro-inflammatory cytokines and cellular death (pathological autophagy and/or apoptosis). However, the signaling pathways that are directly triggered by hyperglycemia appear to have a pivotal role in diabetic complications due to the production of reactive oxygen species (ROS), oxidative stress, and cellular death. The present review will discuss the role of cellular death in diabetic complications, and it will suggest the cause and the consequences between the hyperglycemia-induced signaling pathways and cell death. The signaling pathways discussed in this review are to be described step-by-step, together with their respective inhibitors. They involve diacylglycerol, the activation of protein kinase C (PKC) and NADPH-oxidase system, and the consequent production of ROS. This was initially entitled the "dangerous metabolic route in diabetes". The historical usages and the recent advancement of new drugs in controlling possible therapeutical targets have been highlighted, in order to evaluate the evolution of knowledge in this sensitive area. It has recently been shown that the metabolic responses to stimuli (i.e., hyperglycemia) involve an integrated network of signaling pathways, in order to define the exact responses. Certain new drugs have been experimentally tested-or suggested and proposed-for their ability to modulate the possible biochemical therapeutical targets for the downregulation of retinopathy, nephropathy, neuropathy, heart disease, angiogenesis, oxidative stress, and cellular death. The aim of this study was to critically and didactically evaluate the exact steps of these signaling pathways and hence mark the indicated sites for the actions of such

  6. Cryogenic foam insulation: Abstracted publications

    NASA Technical Reports Server (NTRS)

    Williamson, F. R.

    1977-01-01

    A group of documents were chosen and abstracted which contain information on the properties of foam materials and on the use of foams as thermal insulation at cryogenic temperatures. The properties include thermal properties, mechanical properties, and compatibility properties with oxygen and other cryogenic fluids. Uses of foams include applications as thermal insulation for spacecraft propellant tanks, and for liquefied natural gas storage tanks and pipelines.

  7. Generation of reactive oxygen species (ROS) is a key factor for stimulation of macrophage proliferation by ceramide 1-phosphate

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Arana, Lide; Gangoiti, Patricia; Ouro, Alberto

    2012-02-15

    We previously demonstrated that ceramide 1-phosphate (C1P) is mitogenic for fibroblasts and macrophages. However, the mechanisms involved in this action were only partially described. Here, we demonstrate that C1P stimulates reactive oxygen species (ROS) formation in primary bone marrow-derived macrophages, and that ROS are required for the mitogenic effect of C1P. ROS production was dependent upon prior activation of NADPH oxidase by C1P, which was determined by measuring phosphorylation of the p40phox subunit and translocation of p47phox from the cytosol to the plasma membrane. In addition, C1P activated cytosolic calcium-dependent phospholipase A{sub 2} and protein kinase C-{alpha}, and NADPH oxidasemore » activation was blocked by selective inhibitors of these enzymes. These inhibitors, and inhibitors of ROS production, blocked the mitogenic effect of C1P. By using BHNB-C1P (a photolabile caged-C1P analog), we demonstrate that all of these C1P actions are caused by intracellular C1P. It can be concluded that the enzyme responsible for C1P-stimulated ROS generation in bone marrow-derived macrophages is NADPH oxidase, and that this enzyme is downstream of PKC-{alpha} and cPLA{sub 2}-{alpha} in this pathway. -- Highlights: Black-Right-Pointing-Pointer Ceramide 1-phosphate (C1P) stimulates reactive oxygen species (ROS) formation. Black-Right-Pointing-Pointer The enzyme responsible for ROS generation by C1P in macrophages is NADPH oxidase. Black-Right-Pointing-Pointer NADPH oxidase lies downstream of cPLA{sub 2}-{alpha} and PKC-{alpha} in this pathway. Black-Right-Pointing-Pointer ROS generation is essential for the stimulation of macrophage proliferation by C1P.« less

  8. Combined experimental and theoretical approach to understand the reactivity of a mononuclear Cu(II)-hydroperoxo complex in oxygenation reactions.

    PubMed

    Kamachi, Takashi; Lee, Yong-Min; Nishimi, Tomonori; Cho, Jaeheung; Yoshizawa, Kazunari; Nam, Wonwoo

    2008-12-18

    A copper(II) complex bearing a pentadentate ligand, [Cu(II)(N4Py)(CF(3)SO(3))(2)] (1) (N4Py = N,N-bis(2-pyridylmethyl)bis(2-pyridyl)methylamine), was synthesized and characterized with various spectroscopic techniques and X-ray crystallography. A mononuclear Cu(II)-hydroperoxo complex, [Cu(II)(N4Py)(OOH)](+) (2), was then generated in the reaction of 1 and H(2)O(2) in the presence of base, and the reactivity of the intermediate was investigated in the oxidation of various substrates at -40 degrees C. In the reactivity studies, 2 showed a low oxidizing power such that 2 reacted only with triethylphosphine but not with other substrates such as thioanisole, benzyl alcohol, 1,4-cyclohexadiene, cyclohexene, and cyclohexane. In theoretical work, we have conducted density functional theory (DFT) calculations on the epoxidation of ethylene by 2 and a [Cu(III)(N4Py)(O)](+) intermediate (3) at the B3LYP level. The activation barrier is calculated to be 39.7 and 26.3 kcal/mol for distal and proximal oxygen attacks by 2, respectively. This result indicates that the direct ethylene epoxidation by 2 is not a plausible pathway, as we have observed in the experimental work. In contrast, the ethylene epoxidation by 3 is a downhill and low-barrier process. We also found that 2 cannot be a precursor to 3, since the homolytic cleavage of the O-O bond of 2 is very endothermic (i.e., 42 kcal/mol). On the basis of the experimental and theoretical results, we conclude that a mononuclear Cu(II)-hydroperoxo species bearing a pentadentate N5 ligand is a sluggish oxidant in oxygenation reactions.

  9. Mouse lung fibroblasts are highly susceptible to necroptosis in a reactive oxygen species-dependent manner.

    PubMed

    Hussain, Muadh; Zimmermann, Vanessa; van Wijk, Sjoerd J L; Fulda, Simone

    2018-07-01

    Mouse embryonic fibroblasts (MEFs) have extensively been used to study necroptosis, a recently identified form of programmed cell death. However, very little is yet known about the role of necroptosis and its regulation by reactive oxygen species (ROS) in cell types naturally exposed to high oxygen levels such as mouse lung fibroblasts (MLFs). Here, we discover that MLFs are highly susceptible to undergo necroptosis in a ROS-dependent manner upon exposure to a prototypic death receptor-mediated necroptotic stimulus, i.e. cotreatment with tumor necrosis factor (TNF)α, Smac mimetic and the caspase inhibitor zVAD.fmk (TSZ). Kinetic analysis revealed that TSZ rapidly induces cell death in MLFs. Pharmacological inhibition of receptor-interacting protein kinase (RIPK)1 by necrostatin-1 (Nec-1) or RIPK3 by GSK'872 significantly rescues TSZ-stimulated cell death. Also, genetic silencing of RIPK3 or mixed lineage kinase domain-like pseudokinase (MLKL) significantly protects MLFs from TSZ-mediated cell death. Prior to cell death, TSZ significantly increases production of ROS. Importantly, addition of radical scavengers such as butylated hydroxyanisole (BHA) or α-Tocopherol (α-Toc) significantly suppresses TSZ-induced cell death in parallel with a significant reduction of ROS generation. Consistently, BHA prevented TSZ-triggered phosphorylation of MLKL similar to the addition of GSK'872. Thus, our study demonstrates for the first time that MLFs are prone to undergo necroptosis in response to a prototypic necroptotic stimulus and identifies ROS as important mediators of TSZ-triggered necroptosis. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Reactive Oxygen Species Production by Forward and Reverse Electron Fluxes in the Mitochondrial Respiratory Chain

    PubMed Central

    Selivanov, Vitaly A.; Votyakova, Tatyana V.; Pivtoraiko, Violetta N.; Zeak, Jennifer; Sukhomlin, Tatiana; Trucco, Massimo; Roca, Josep; Cascante, Marta

    2011-01-01

    Reactive oxygen species (ROS) produced in the mitochondrial respiratory chain (RC) are primary signals that modulate cellular adaptation to environment, and are also destructive factors that damage cells under the conditions of hypoxia/reoxygenation relevant for various systemic diseases or transplantation. The important role of ROS in cell survival requires detailed investigation of mechanism and determinants of ROS production. To perform such an investigation we extended our rule-based model of complex III in order to account for electron transport in the whole RC coupled to proton translocation, transmembrane electrochemical potential generation, TCA cycle reactions, and substrate transport to mitochondria. It fits respiratory electron fluxes measured in rat brain mitochondria fueled by succinate or pyruvate and malate, and the dynamics of NAD+ reduction by reverse electron transport from succinate through complex I. The fitting of measured characteristics gave an insight into the mechanism of underlying processes governing the formation of free radicals that can transfer an unpaired electron to oxygen-producing superoxide and thus can initiate the generation of ROS. Our analysis revealed an association of ROS production with levels of specific radicals of individual electron transporters and their combinations in species of complexes I and III. It was found that the phenomenon of bistability, revealed previously as a property of complex III, remains valid for the whole RC. The conditions for switching to a state with a high content of free radicals in complex III were predicted based on theoretical analysis and were confirmed experimentally. These findings provide a new insight into the mechanisms of ROS production in RC. PMID:21483483

  11. Ceramic oxygen transport membrane array reactor and reforming method

    DOEpatents

    Kelly, Sean M.; Christie, Gervase Maxwell; Rosen, Lee J.; Robinson, Charles; Wilson, Jamie R.; Gonzalez, Javier E.; Doraswami, Uttam R.

    2016-09-27

    A commercially viable modular ceramic oxygen transport membrane reforming reactor for producing a synthesis gas that improves the thermal coupling of reactively-driven oxygen transport membrane tubes and catalyst reforming tubes required to efficiently and effectively produce synthesis gas.

  12. Effects of irradiation distance on supply of reactive oxygen species to the bottom of a Petri dish filled with liquid by an atmospheric O{sub 2}/He plasma jet

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kawasaki, Toshiyuki, E-mail: kawasaki@nbu.ac.jp; Kusumegi, Shota; Kudo, Akihiro

    The impact of irradiation distances on plasma jet-induced specific effects on the supply of reactive oxygen species (ROS) to the bottom of a Petri dish filled with liquid was investigated using a KI-starch gel reagent that can be employed as a ROS indicator even in water. O{sub 3} exposure experiments without plasma irradiation were also performed to elucidate the specific effects of the plasma jet. Relative concentrations of ROS transported to the bottom were evaluated using absorbance measurements. The results indicated that ROS supply to the bottom is markedly enhanced by the plasma jet irradiation at shorter irradiation distances, whereasmore » similar results could not be obtained for the O{sub 3} exposure. In these cases, the liquid mixing in the depth direction was also enhanced by the plasma jet irradiation only, and the supply of reactive atomic oxygen to the liquid surface was markedly increased as well.« less

  13. Arteriolar oxygen reactivity: where is the sensor and what is the mechanism of action?

    PubMed Central

    2016-01-01

    Abstract Arterioles in the peripheral microcirculation are exquisitely sensitive to changes in PO2 in their environment: increases in PO2 cause vasoconstriction while decreases in PO2 result in vasodilatation. However, the cell type that senses O2 (the O2 sensor) and the signalling pathway that couples changes in PO2 to changes in arteriolar tone (the mechanism of action) remain unclear. Many (but not all) ex vivo studies of isolated cannulated resistance arteries and large, first‐order arterioles support the hypothesis that these vessels are intrinsically sensitive to PO2 with the smooth muscle, endothelial cells, or red blood cells serving as the O2 sensor. However, in situ studies testing these hypotheses in downstream arterioles have failed to find evidence of intrinsic O2 sensitivity, and instead have supported the idea that extravascular cells sense O2. Similarly, ex vivo studies of isolated, cannulated resistance arteries and large first‐order arterioles support the hypotheses that O2‐dependent inhibition of production of vasodilator cyclooxygenase products or O2‐dependent destruction of nitric oxide mediates O2 reactivity of these upstream vessels. In contrast, most in vivo studies of downstream arterioles have disproved these hypotheses and instead have provided evidence supporting the idea that O2‐dependent production of vasoconstrictors mediates arteriolar O2 reactivity, with significant regional heterogeneity in the specific vasoconstrictor involved. Oxygen‐induced vasoconstriction may serve as a protective mechanism to reduce the oxidative burden to which a tissue is exposed, a process that is superimposed on top of the local mechanisms which regulate tissue blood flow to meet a tissue's metabolic demand. PMID:27324312

  14. [Hemoglobin oxygen transport capacity in surgical endotoxicosis ].

    PubMed

    Poryadin, G V; Vlasov, A P; Trofimov, V A; Vlasova, T I; Kamkina, O V; Grigoryev, A G; Vlasov, P A

    2016-01-01

    In surgical endointoxication hemoglobin oxygen transport capacity of red blood cells (hemoglobin affinity ligands: the ability to bind and release ligands) is reduced and is associated with the severity of endogenous intoxication. Violation of oxygen transport function of hemoglobin at endogenous intoxication is associated with conformational changes of a biomolecule, and its possible influence on reactive oxygen species, which confirmed in experiments in vitro: under the influence of oxygen-iron ascorbate ability of hemoglobin deteriorates. Largely similar structural and functional changes in hemoglobin occur in patients with surgical endotoxicosis.

  15. The food-borne pathogen Campylobacter jejuni responds to the bile salt deoxycholate with countermeasures to reactive oxygen species

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Negretti, Nicholas M.; Gourley, Christopher R.; Clair, Geremy

    In this study, bile plays an important role in digestion, absorption of fats, and the excretion of waste products, while concurrently providing a critical barrier against colonization by harmful bacteria. Previous studies have demonstrated that gut pathogens react to bile by adapting their protein synthesis. The ability of pathogens to respond to bile is remarkably complex and still incompletely understood. Here we show that Campylobacter jejuni, a leading bacterial cause of human diarrheal illness worldwide, responds to deoxycholate, a component of bile, by altering global gene transcription in a manner consistent with a strategy to mitigate exposure to reactive oxygenmore » stress. More specifically, continuous growth of C. jejuni in deoxycholate was found to: induce the production of reactive oxygen species (ROS); decrease succinate dehydrogenase activity (complex II of the electron transport chain); increase catalase activity that is involved in H 2O 2 breakdown; and result in DNA strand breaks. Congruently, by adding 4-hydroxy-TEMPO (TEMPOL), a superoxide dismutase mimic, that reacts with superoxide to cultures under deoxycholate-mediated ROS stress, C. jejuni growth in the presence of deoxycholate was rescued. We postulate that continuous exposure of a number of enteric pathogens to deoxycholate stimulates a conserved survival response to this stressor.« less

  16. The food-borne pathogen Campylobacter jejuni responds to the bile salt deoxycholate with countermeasures to reactive oxygen species

    DOE PAGES

    Negretti, Nicholas M.; Gourley, Christopher R.; Clair, Geremy; ...

    2017-11-13

    In this study, bile plays an important role in digestion, absorption of fats, and the excretion of waste products, while concurrently providing a critical barrier against colonization by harmful bacteria. Previous studies have demonstrated that gut pathogens react to bile by adapting their protein synthesis. The ability of pathogens to respond to bile is remarkably complex and still incompletely understood. Here we show that Campylobacter jejuni, a leading bacterial cause of human diarrheal illness worldwide, responds to deoxycholate, a component of bile, by altering global gene transcription in a manner consistent with a strategy to mitigate exposure to reactive oxygenmore » stress. More specifically, continuous growth of C. jejuni in deoxycholate was found to: induce the production of reactive oxygen species (ROS); decrease succinate dehydrogenase activity (complex II of the electron transport chain); increase catalase activity that is involved in H 2O 2 breakdown; and result in DNA strand breaks. Congruently, by adding 4-hydroxy-TEMPO (TEMPOL), a superoxide dismutase mimic, that reacts with superoxide to cultures under deoxycholate-mediated ROS stress, C. jejuni growth in the presence of deoxycholate was rescued. We postulate that continuous exposure of a number of enteric pathogens to deoxycholate stimulates a conserved survival response to this stressor.« less

  17. Sex as a response to oxidative stress: a twofold increase in cellular reactive oxygen species activates sex genes.

    PubMed

    Nedelcu, Aurora M; Marcu, Oana; Michod, Richard E

    2004-08-07

    Organisms are constantly subjected to factors that can alter the cellular redox balance and result in the formation of a series of highly reactive molecules known as reactive oxygen species (ROS). As ROS can be damaging to biological structures, cells evolved a series of mechanisms (e.g. cell-cycle arrest, programmed cell death) to respond to high levels of ROS (i.e. oxidative stress). Recently, we presented evidence that in a facultatively sexual lineage--the multicellular green alga Volvox carteri--sex is an additional response to increased levels of stress, and probably ROS and DNA damage. Here we show that, in V. carteri, (i) sex is triggered by an approximately twofold increase in the level of cellular ROS (induced either by the natural sex-inducing stress, namely heat, or by blocking the mitochondrial electron transport chain with antimycin A), and (ii) ROS are responsible for the activation of sex genes. As most types of stress result in the overproduction of ROS, we believe that our findings will prove to extend to other facultatively sexual lineages, which could be indicative of the ancestral role of sex as an adaptive response to stress and ROS-induced DNA damage. Copyright 2004 The Royal Society

  18. Impact reactivity of materials at very high oxygen pressure

    NASA Technical Reports Server (NTRS)

    Connor, H. W.; Minchey, J. G.; Crowder, R.; Davidson, R.

    1983-01-01

    The requirements for impact testing of materials in an oxygen atmosphere at pressures from 82.7 MPa (12,000 psi) to 172 MPa (25,000 psi) were evaluated. The impact tester system was evaluated for potential pressure increases from 69 MPa (10,000 psi) to 82.7 MPa (12,000 psi). The low pressure oxygen and nitrogen systems, the impact tower, the impact test cell, and the high pressure oxygen system were evaluated individually. Although the structural integrity of the impact test cell and the compressor were sufficient for operation at 82.7 MPa (12,000 psi), studies revealed possible material incompatibility at that pressure and above. It was recommended that if a component should be replaced for 82.7 MPa (12,000 psi) operation the replacement should meet the final objectives of 172 MPa (25,000 psi). Recommended changes in the system include; use of Monel 400 for pressures above 82.7 MPa (12,000 psi), use of bellows to replace the seal in the impact tester, use of a sapphire window attached to a fiber optic for event sensing, and use of a three diaphragm compressor.

  19. Lipopolysaccharide treatment reduces rat platelet aggregation independent of intracellular reactive-oxygen species generation.

    PubMed

    Lopes-Pires, M Elisa; Casarin, André L; Pereira-Cunha, Fernanda G; Lorand-Metze, Irene; Antunes, Edson; Marcondes, Sisi

    2012-01-01

    High production of reactive-oxygen species (ROS) by blood cells is involved in damage of the vascular endothelium and multiple organ dysfunction in sepsis. However, little is known about the intraplatelet ROS production in sepsis and its consequences on platelet reactivity. In this study, we evaluated whether the treatment of rats with lipopolysaccharide (LPS) affects platelet aggregation through intraplatelet ROS generation. Rats were injected with LPS (1 mg/kg, i.p.), and at 2 to 72 h thereafter, adenosine diphosphate (ADP) (3-10 µM) induced platelet aggregation was evaluated. Production of ROS in platelets was measured by flow cytometry using 2',7'-dichlorofluorescein diacetate (DCFH-DA). Treatment of rats with LPS time-dependently inhibited ADP-induced platelet aggregation within 72 h. The inhibitory effect of LPS on platelet aggregation was further increased when the platelets were incubated with polyethylene glycol-superoxide dismutase (PEG-SOD; 30 U/mL), polyethylene glycol-catalase (PEG-CAT; 1000 U/mL) or the NADPH oxidase inhibitor diphenyleneiodonium (DPI; 10 µM). The ROS production in non-stimulated platelets did not differ between control and LPS-treated rats. However, in ADP-activated platelets, generation of ROS was increased by 3.0- and 7.0-fold, as evaluated at 8 and 48 h after LPS injection, respectively. This increased ROS production was significantly reduced when platelets were incubated in vitro with DPI, PEG-SOD or PEG-CAT. In contrast, treatment of rats with N-acetylcysteine (150 mg/kg, i.p.) significantly reduced the inhibitory effect of LPS on platelet aggregation, and prevented the increased ROS production by in vivo LPS. Our results indicate that the increased intraplatelet ROS production does not contribute to the inhibitory effect of LPS on platelet aggregation; however, the maintenance of redox balance in LPS-treated rats is fundamental to restore the normal platelet response in these animals.

  20. Hyperglycemia-induced mouse trophoblast spreading is mediated by reactive oxygen species.

    PubMed

    Sánchez-Santos, Alejandra; Martínez-Hernández, María G; Contreras-Ramos, Alejandra; Ortega-Camarillo, Clara; Baiza-Gutman, Luis A

    2018-04-01

    During embryo implantation, the outer layer of the blastocyst interacts with the endometrium giving rise to the development of the trophoblast cell lineage. The cells in this lineage participate in the penetration of endometrium due to their motility and invasive properties. The mechanisms that regulate the differentiation and invasive ability of these cells are essential for the establishment and maintenance of an efficient exchange between maternal and fetal tissues during pregnancy. In this context, hyperglycemia can induce oxidative stress causing alterations in the placenta. This study evaluated the role of reactive oxygen species (ROS) in the actions of high glucose concentration (HG) on trophoblast spreading and the expression of extracellular proteases in cultured mouse conceptuses. Blastocysts from gestational day 4 (GD4) were cultured until GD7 in HAM-F10 medium and further treated for 48 hr with HG (25 mM glucose) from GD7 to GD9. This treatment induced larger trophoblast outgrowths and increased ROS concentration, which was associated with increased expression levels of urokinase-type plasminogen activator (PLAU), plasminogen activator inhibitor 1 (PAI-1), and matrix metalloproteinase 9 (MMP-9). These effects were prevented by treatment with the non-specific antioxidant N-acetylcysteine (NAC) or apocynin, an inhibitor of NADPH oxidase. Our data suggest that the HG-induced trophoblast spreading and the expression of PLAU, PAI-1, and MMP-9 were mediated by the production of ROS via NADPH oxidase activity. Our results shed light on placental alterations in gestational diabetes mellitus. © 2018 Wiley Periodicals, Inc.

  1. Detection of reactive oxygen species in mainstream cigarette smoke by a fluorescent probe

    NASA Astrophysics Data System (ADS)

    Liu, Li; Xu, Shi-jie; Li, Song-zhan

    2009-07-01

    A mass of reactive oxygen species(ROS) are produced in the process of smoking. Superfluous ROS can induce the oxidative stress in organism, which will cause irreversible damage to cells. Fluorescent probe is taken as a marker of oxidative stress in biology and has been applied to ROS detection in the field of biology and chemistry for high sensitivity, high simplicity of data collection and high resolution. As one type of fluorescent probe, dihydrorhodamine 6G (dR6G) will be oxidized to the fluorescent rhodamine 6G, which could be used to detect ROS in mainstream cigarette smoke. We investigated the action mechanism of ROS on dR6G, built up the standard curve of R6G fluorescence intensity with its content, achieved the variation pattern of R6G fluorescence intensity with ROS content in mainstream cigarette smoke and detected the contents of ROS from the 4 types of cigarettes purchased in market. The result shows that the amount of ROS has close relationship with the types of tobacco and cigarette production technology. Compared with other detecting methods such as electronic spin resonance(ESR), chromatography and mass spectrometry, this detection method by the fluorescent probe has higher efficiency and sensitivity and will have wide applications in the ROS detection field.

  2. Spin Biochemistry Modulates Reactive Oxygen Species (ROS) Production by Radio Frequency Magnetic Fields

    PubMed Central

    Usselman, Robert J.; Hill, Iain; Singel, David J.; Martino, Carlos F.

    2014-01-01

    The effects of weak magnetic fields on the biological production of reactive oxygen species (ROS) from intracellular superoxide (O2 •−) and extracellular hydrogen peroxide (H2O2) were investigated in vitro with rat pulmonary arterial smooth muscle cells (rPASMC). A decrease in O2 •− and an increase in H2O2 concentrations were observed in the presence of a 7 MHz radio frequency (RF) at 10 μTRMS and static 45 μT magnetic fields. We propose that O2 •− and H2O2 production in some metabolic processes occur through singlet-triplet modulation of semiquinone flavin (FADH•) enzymes and O2 •− spin-correlated radical pairs. Spin-radical pair products are modulated by the 7 MHz RF magnetic fields that presumably decouple flavin hyperfine interactions during spin coherence. RF flavin hyperfine decoupling results in an increase of H2O2 singlet state products, which creates cellular oxidative stress and acts as a secondary messenger that affects cellular proliferation. This study demonstrates the interplay between O2 •− and H2O2 production when influenced by RF magnetic fields and underscores the subtle effects of low-frequency magnetic fields on oxidative metabolism, ROS signaling, and cellular growth. PMID:24681944

  3. Alteration of Neutrophil Reactive Oxygen Species Production by Extracts of Devil's Claw (Harpagophytum).

    PubMed

    Muzila, Mbaki; Rumpunen, Kimmo; Wright, Helen; Roberts, Helen; Grant, Melissa; Nybom, Hilde; Sehic, Jasna; Ekholm, Anders; Widén, Cecilia

    2016-01-01

    Harpagophytum, Devil's Claw, is a genus of tuberiferous xerophytic plants native to southern Africa. Some of the taxa are appreciated for their medicinal effects and have been traditionally used to relieve symptoms of inflammation. The objectives of this pilot study were to investigate the antioxidant capacity and the content of total phenols, verbascoside, isoverbascoside, and selected iridoids, as well as to investigate the capacity of various Harpagophytum taxa in suppressing respiratory burst in terms of reactive oxygen species produced by human neutrophils challenged with phorbol myristate acetate (PMA), opsonised Staphylococcus aureus, and Fusobacterium nucleatum. Harpagophytum plants were classified into different taxa according to morphology, and DNA analysis was used to confirm the classification. A putative new variety of H. procumbens showed the highest degree of antioxidative capacity. Using PMA, three Harpagophytum taxa showed anti-inflammatory effects with regard to the PBS control. A putative hybrid between H. procumbens and H. zeyheri in contrast showed proinflammatory effect on the response of neutrophils to F. nucleatum in comparison with treatment with vehicle control. Harpagophytum taxa were biochemically very variable and the response in suppressing respiratory burst differed. Further studies with larger number of subjects are needed to corroborate anti-inflammatory effects of different taxa of Harpagophytum.

  4. Alteration of Neutrophil Reactive Oxygen Species Production by Extracts of Devil's Claw (Harpagophytum)

    PubMed Central

    Muzila, Mbaki; Wright, Helen; Roberts, Helen; Grant, Melissa; Nybom, Hilde; Sehic, Jasna; Ekholm, Anders

    2016-01-01

    Harpagophytum, Devil's Claw, is a genus of tuberiferous xerophytic plants native to southern Africa. Some of the taxa are appreciated for their medicinal effects and have been traditionally used to relieve symptoms of inflammation. The objectives of this pilot study were to investigate the antioxidant capacity and the content of total phenols, verbascoside, isoverbascoside, and selected iridoids, as well as to investigate the capacity of various Harpagophytum taxa in suppressing respiratory burst in terms of reactive oxygen species produced by human neutrophils challenged with phorbol myristate acetate (PMA), opsonised Staphylococcus aureus, and Fusobacterium nucleatum. Harpagophytum plants were classified into different taxa according to morphology, and DNA analysis was used to confirm the classification. A putative new variety of H. procumbens showed the highest degree of antioxidative capacity. Using PMA, three Harpagophytum taxa showed anti-inflammatory effects with regard to the PBS control. A putative hybrid between H. procumbens and H. zeyheri in contrast showed proinflammatory effect on the response of neutrophils to F. nucleatum in comparison with treatment with vehicle control. Harpagophytum taxa were biochemically very variable and the response in suppressing respiratory burst differed. Further studies with larger number of subjects are needed to corroborate anti-inflammatory effects of different taxa of Harpagophytum. PMID:27429708

  5. Mitochondrial Reactive Oxygen Species Trigger Hypoxia-Inducible Factor-Dependent Extension of the Replicative Life Span during Hypoxia▿

    PubMed Central

    Bell, Eric L.; Klimova, Tatyana A.; Eisenbart, James; Schumacker, Paul T.; Chandel, Navdeep S.

    2007-01-01

    Physiological hypoxia extends the replicative life span of human cells in culture. Here, we report that hypoxic extension of replicative life span is associated with an increase in mitochondrial reactive oxygen species (ROS) in primary human lung fibroblasts. The generation of mitochondrial ROS is necessary for hypoxic activation of the transcription factor hypoxia-inducible factor (HIF). The hypoxic extension of replicative life span is ablated by a dominant negative HIF. HIF is sufficient to induce telomerase reverse transcriptase mRNA and telomerase activity and to extend replicative life span. Furthermore, the down-regulation of the von Hippel-Lindau tumor suppressor protein by RNA interference increases HIF activity and extends replicative life span under normoxia. These findings provide genetic evidence that hypoxia utilizes mitochondrial ROS as signaling molecules to activate HIF-dependent extension of replicative life span. PMID:17562866

  6. Cytosolic Irradiation of Femtosecond Laser Induces Mitochondria-dependent Apoptosis-like Cell Death via Intrinsic Reactive Oxygen Cascades

    PubMed Central

    Yoon, Jonghee; Ryu, Seung-wook; Lee, Seunghee; Choi, Chulhee

    2015-01-01

    High-intensity femtosecond lasers have recently been used to irreversibly disrupt nanoscale structures, such as intracellular organelles, and to modify biological functions in a reversible manner: so-called nanosurgery and biophotomodulation. Femtosecond laser pulses above the threshold intensity sufficient for reversible biophotomodulation can cause irreversible changes in the irradiated cell, eventually leading to cell death. Here, we demonstrated that cytosolic irradiation with a femtosecond laser produced intrinsic cascades of reactive oxygen species (ROS), which led to rapid apoptosis-like cell death via a caspase and poly (ADP-ribose) polymerase 1 (PARP-1) signaling pathway. We further showed that cells with enhanced mitochondrial fusion activity are more resilient to laser-induced stress compared to those with enforced mitochondrial fission. Taken together, these findings provide fundamental insight into how optical stimulation intervenes in intrinsic cellular signaling pathways and functions. PMID:25648455

  7. Cytosolic irradiation of femtosecond laser induces mitochondria-dependent apoptosis-like cell death via intrinsic reactive oxygen cascades.

    PubMed

    Yoon, Jonghee; Ryu, Seung-Wook; Lee, Seunghee; Choi, Chulhee

    2015-02-04

    High-intensity femtosecond lasers have recently been used to irreversibly disrupt nanoscale structures, such as intracellular organelles, and to modify biological functions in a reversible manner: so-called nanosurgery and biophotomodulation. Femtosecond laser pulses above the threshold intensity sufficient for reversible biophotomodulation can cause irreversible changes in the irradiated cell, eventually leading to cell death. Here, we demonstrated that cytosolic irradiation with a femtosecond laser produced intrinsic cascades of reactive oxygen species (ROS), which led to rapid apoptosis-like cell death via a caspase and poly (ADP-ribose) polymerase 1 (PARP-1) signaling pathway. We further showed that cells with enhanced mitochondrial fusion activity are more resilient to laser-induced stress compared to those with enforced mitochondrial fission. Taken together, these findings provide fundamental insight into how optical stimulation intervenes in intrinsic cellular signaling pathways and functions.

  8. Accelerated Oxygen Atom Transfer and C-H Bond Oxygenation by Remote Redox Changes in Fe3 Mn-Iodosobenzene Adducts.

    PubMed

    de Ruiter, Graham; Carsch, Kurtis M; Gul, Sheraz; Chatterjee, Ruchira; Thompson, Niklas B; Takase, Michael K; Yano, Junko; Agapie, Theodor

    2017-04-18

    We report the synthesis, characterization, and reactivity of [LFe 3 (PhPz) 3 OMn( s PhIO)][OTf] x (3: x=2; 4: x=3), where 4 is one of very few examples of iodosobenzene-metal adducts characterized by X-ray crystallography. Access to these rare heterometallic clusters enabled differentiation of the metal centers involved in oxygen atom transfer (Mn) or redox modulation (Fe). Specifically, 57 Fe Mössbauer and X-ray absorption spectroscopy provided unique insights into how changes in oxidation state (Fe III 2 Fe II Mn II vs. Fe III 3 Mn II ) influence oxygen atom transfer in tetranuclear Fe 3 Mn clusters. In particular, a one-electron redox change at a distal metal site leads to a change in oxygen atom transfer reactivity by ca. two orders of magnitude. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Surface reactivity of mercury on the oxygen-terminated hematite(0001) surface: a first-principle study

    NASA Astrophysics Data System (ADS)

    Jung, J. E.; Wilcox, J.

    2016-12-01

    Hematite (α-Fe2O3) is a common mineral found in Earth's near-surface environment. Due to its nontoxicity, corrosion-resistance, and high thermal stability, α-Fe2O3 has attracted attentions as materials for various applications such as photocatalysts, gas sensors, as well as for the removal of heavy metals. In this study, α-Fe2O3 is chosen for potential mercury (Hg) sorbent in order to remove Hg from coal-fired power plants. Specifically, theoretical approaches using density functional theory (DFT) is used to understand surface reactivity of Hg on oxygen (O) terminated α-Fe2O3(0001) surface. The most probable adsorption sites of Hg, chlorine (Cl), and mercury chloride (HgCl) on the α-Fe2O3 surface are found based on adsorption energy calculations, and the oxidation states of the adsorbates are determined by Bader charge analysis. Additionally, projected density of states (PDOS) analysis characterizes the surface-adsorbate bonding mechanism. The results of adsorption energy calculation proposes that Hg physisorbs to the α-Fe2O3(0001) surface with adsorption energy of -0.278 eV, and the subsequent Bader charge analysis confirms that Hg is slightly oxidized. In addition, Cl introduced to the Hg-adsorbed surface strengthens Hg stability on the α-Fe2O3(0001) surface as evidenced by a shortened Hg-surface equilibrium distance. The PDOS analysis also suggests that Cl enhances the chemical bonding between the surface and the adsorbate, thereby increasing adsorption strength. In summary, α-Fe2O3 has ability to adsorb and oxidize Hg, and this reactivity is enhanced in the presence of Cl.

  10. Analysis of reactive oxygen metabolites (ROMs) after cardiovascular surgery as a marker of oxidative stress.

    PubMed

    Kanaoka, Yuji; Inagaki, Ei-ichirou; Hamanaka, Souhei; Masaki, Hisao; Tanemoto, Kazuo

    2010-10-01

    The transient systemic low perfusion that occurs during cardiovascular surgery leads to oxidative stress and the production of free radicals. A systemic increase of various markers of oxidative stress has been shown to occur during cardiopulmonary bypass (CPB). However, these markers have not been adequately evaluated because they seem to be reactive and short-lived. Here, oxidative stress was measured using the free radical analytical system (FRAS 4) assessing the derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP). Blood samples were taken from 21 patients undergoing elective cardiovascular surgery. CPB was used in 15 patients, and abdominal aortic aneurysm (AAA) surgery without CPB was performed in 6. Measurements of d-ROMs and BAP were taken before surgery, 1 day, 1 week, and 2 weeks after surgery, and oxidative stress was evaluated. The d-ROM level increased gradually after cardiovascular surgery up to 2 weeks. Over time, the d-ROM level after surgery involving CPB became higher than that after AAA surgery. This difference reached statistical significance at 1 week and lasted to 2 weeks. The prolongation of CPB was prone to elevate the d-ROM level whereas the duration of the aortic clamp in AAA surgery had no relation to the d-ROM level. The BAP was also elevated after surgery, and was positively correlated with the level of d-ROMs. In this study, patients who underwent cardiovascular surgery involving CPB had significant oxidative damage. The production of ROMs was shown to depend on the duration of CPB. Damage can be reduced if CPB is avoided. When CPB must be used, shortening the CPB time may be effective in reducing oxidative stress.

  11. Measurement of Reactive Oxygen Species in the Culture Media Using Acridan Lumigen PS-3 Assay

    PubMed Central

    Uy, Benedict; McGlashan, Susan R.; Shaikh, Shamim B.

    2011-01-01

    Reactive oxygen species (ROS) are generated continuously during aerobic metabolism. ROS are highly reactive molecules and in excessive amounts, can lead to protein and DNA oxidation, protein cross-linking, and cell death. Cell-culture models provide a valuable tool in understanding the mechanisms that lead to cell death. Accumulation of ROS within cells and/or their release into the culture media are highly cell type-specific. The ability to estimate ROS levels in the culture media is an important step in understanding the mechanisms contributing to disease processes. In this paper, we describe the optimization of a simple method to estimate ROS levels in the culture media using the Acridan Lumigen PS-3 reagent provided in the Amersham ECL Plus kit (GE Healthcare, UK). We have shown that the Acridan Lumigen PS-3 assay generates ROS-specific chemiluminescence in fresh as well as media stored at −20°C, in as little as 10–20 μl of samples. The method was able to detect the dose (of stimulants)- and time (acute and chronic)-dependent changes in ROS levels in media collected from various cell types. Our results suggest that the kit reagents, PBS buffer, and various media did not contribute significantly to the overall chemiluminescence generated in the assay; however, we suggest that the unused medium specific for each cell type should be used as blanks and final readings of test samples normalized against these readings. As this method uses commonly available laboratory equipment and commercially available reagents, we believe this assay is convenient, economical, and specific in estimating ROS released extracellularly into the culture media. PMID:21966257

  12. Measurement of reactive oxygen species in the culture media using Acridan Lumigen PS-3 assay.

    PubMed

    Uy, Benedict; McGlashan, Susan R; Shaikh, Shamim B

    2011-09-01

    Reactive oxygen species (ROS) are generated continuously during aerobic metabolism. ROS are highly reactive molecules and in excessive amounts, can lead to protein and DNA oxidation, protein cross-linking, and cell death. Cell-culture models provide a valuable tool in understanding the mechanisms that lead to cell death. Accumulation of ROS within cells and/or their release into the culture media are highly cell type-specific. The ability to estimate ROS levels in the culture media is an important step in understanding the mechanisms contributing to disease processes. In this paper, we describe the optimization of a simple method to estimate ROS levels in the culture media using the Acridan Lumigen PS-3 reagent provided in the Amersham ECL Plus kit (GE Healthcare, UK). We have shown that the Acridan Lumigen PS-3 assay generates ROS-specific chemiluminescence in fresh as well as media stored at -20°C, in as little as 10-20 μl of samples. The method was able to detect the dose (of stimulants)- and time (acute and chronic)-dependent changes in ROS levels in media collected from various cell types. Our results suggest that the kit reagents, PBS buffer, and various media did not contribute significantly to the overall chemiluminescence generated in the assay; however, we suggest that the unused medium specific for each cell type should be used as blanks and final readings of test samples normalized against these readings. As this method uses commonly available laboratory equipment and commercially available reagents, we believe this assay is convenient, economical, and specific in estimating ROS released extracellularly into the culture media.

  13. The role of iron and reactive oxygen species in the production of CO2 in arctic soil waters

    NASA Astrophysics Data System (ADS)

    Trusiak, Adrianna; Treibergs, Lija A.; Kling, George W.; Cory, Rose M.

    2018-03-01

    Hydroxyl radical (radOH) is a highly reactive oxidant of dissolved organic carbon (DOC) in the environment. radOH production in the dark was observed through iron and DOC mediated Fenton reactions in natural environments. Specifically, when dissolved oxygen (O2) was added to low oxygen and anoxic soil waters in arctic Alaska, radOH was produced in proportion to the concentrations of reduced iron (Fe(II)) and DOC. Here we demonstrate that Fe(II) was the main electron donor to O2 to produce radOH. In addition to quantifying radOH production, hydrogen peroxide (H2O2) was detected in soil waters as a likely intermediate in radOH production from oxidation of Fe(II). For the first time in natural systems we detected carbon dioxide (CO2) production from radOH oxidation of DOC. More than half of the arctic soil waters tested showed production of CO2 under conditions conducive for production of radOH. Findings from this study strongly suggest that DOC is the main sink for radOH, and that radOH can oxidize DOC to yield CO2. Thus, this iron-mediated, dark chemical oxidation of DOC may be an important component of the arctic carbon cycle.

  14. Intermittent hypoxia activates peptidylglycine α-amidating monooxygenase in rat brain stem via reactive oxygen species-mediated proteolytic processing

    PubMed Central

    Sharma, Suresh D.; Raghuraman, Gayatri; Lee, Myeong-Seon; Prabhakar, Nanduri R.; Kumar, Ganesh K.

    2009-01-01

    Intermittent hypoxia (IH) associated with sleep apneas leads to cardiorespiratory abnormalities that may involve altered neuropeptide signaling. The effects of IH on neuropeptide synthesis have not been investigated. Peptidylglycine α-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the α-amidation of neuropeptides, which confers biological activity to a large number of neuropeptides. PAM consists of O2-sensitive peptidylglycine α-hydroxylating monooxygenase (PHM) and peptidyl-α-hydroxyglycine α-amidating lyase (PAL) activities. Here, we examined whether IH alters neuropeptide synthesis by affecting PAM activity and, if so, by what mechanisms. Experiments were performed on the brain stem of adult male rats exposed to IH (5% O2 for 15 s followed by 21% O2 for 5 min; 8 h/day for up to 10 days) or continuous hypoxia (0.4 atm for 10 days). Analysis of brain stem extracts showed that IH, but not continuous hypoxia, increased PHM, but not PAL, activity of PAM and that the increase of PHM activity was associated with a concomitant elevation in the levels of α-amidated forms of substance P and neuropeptide Y. IH increased the relative abundance of 42- and 35-kDa forms of PHM (∼1.6- and 2.7-fold, respectively), suggesting enhanced proteolytic processing of PHM, which appears to be mediated by an IH-induced increase of endoprotease activity. Kinetic analysis showed that IH increases Vmax but has no effect on Km. IH increased generation of reactive oxygen species in the brain stem, and systemic administration of antioxidant prevented IH-evoked increases of PHM activity, proteolytic processing of PHM, endoprotease activity, and elevations in substance P and neuropeptide Y amide levels. Taken together, these results demonstrate that IH activates PHM in rat brain stem via reactive oxygen species-dependent posttranslational proteolytic processing and further suggest that PAM activation may contribute to IH-mediated peptidergic neurotransmission in rat brain stem

  15. Intermittent hypoxia activates peptidylglycine alpha-amidating monooxygenase in rat brain stem via reactive oxygen species-mediated proteolytic processing.

    PubMed

    Sharma, Suresh D; Raghuraman, Gayatri; Lee, Myeong-Seon; Prabhakar, Nanduri R; Kumar, Ganesh K

    2009-01-01

    Intermittent hypoxia (IH) associated with sleep apneas leads to cardiorespiratory abnormalities that may involve altered neuropeptide signaling. The effects of IH on neuropeptide synthesis have not been investigated. Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the alpha-amidation of neuropeptides, which confers biological activity to a large number of neuropeptides. PAM consists of O(2)-sensitive peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL) activities. Here, we examined whether IH alters neuropeptide synthesis by affecting PAM activity and, if so, by what mechanisms. Experiments were performed on the brain stem of adult male rats exposed to IH (5% O(2) for 15 s followed by 21% O(2) for 5 min; 8 h/day for up to 10 days) or continuous hypoxia (0.4 atm for 10 days). Analysis of brain stem extracts showed that IH, but not continuous hypoxia, increased PHM, but not PAL, activity of PAM and that the increase of PHM activity was associated with a concomitant elevation in the levels of alpha-amidated forms of substance P and neuropeptide Y. IH increased the relative abundance of 42- and 35-kDa forms of PHM ( approximately 1.6- and 2.7-fold, respectively), suggesting enhanced proteolytic processing of PHM, which appears to be mediated by an IH-induced increase of endoprotease activity. Kinetic analysis showed that IH increases V(max) but has no effect on K(m). IH increased generation of reactive oxygen species in the brain stem, and systemic administration of antioxidant prevented IH-evoked increases of PHM activity, proteolytic processing of PHM, endoprotease activity, and elevations in substance P and neuropeptide Y amide levels. Taken together, these results demonstrate that IH activates PHM in rat brain stem via reactive oxygen species-dependent posttranslational proteolytic processing and further suggest that PAM activation may contribute to IH-mediated peptidergic

  16. The essential oil of bergamot stimulates reactive oxygen species production in human polymorphonuclear leukocytes.

    PubMed

    Cosentino, Marco; Luini, Alessandra; Bombelli, Raffaella; Corasaniti, Maria T; Bagetta, Giacinto; Marino, Franca

    2014-08-01

    Bergamot (Citrus aurantium L. subsp. bergamia) essential oil (BEO) is used in folk medicine as an antiseptic and anthelminthic and to facilitate wound healing. Evidence indicates that BEO has substantial antimicrobial activity; however its effects on immunity have never been examined. We studied the effects of BEO on reactive oxygen species (ROS) production in human polymorphonuclear leukocytes (PMN) and the role of Ca(2+) in the functional responses evoked by BEO in these cells. Results show that BEO increased intracellular ROS production in human PMN, an effect that required the contribution of extracellular (and, to a lesser extent, of intracellular) Ca(2+) . Bergamot essential oil also significantly increased ROS production induced by the chemotactic peptide N-formyl-Met-Leu-Phe and reduced the response to the protein kinase C activator phorbol myristate acetate. In conclusion, this is the first report showing the ability of BEO to increase ROS production in human PMN. This effect could both contribute to the activity of BEO in infections and in tissue healing as well as underlie an intrinsic proinflammatory potential. The relevance of these findings for the clinical uses of BEO needs careful consideration. Copyright © 2014 John Wiley & Sons, Ltd.

  17. Small molecule CP-31398 induces reactive oxygen species-dependent apoptosis in human multiple myeloma.

    PubMed

    Arihara, Yohei; Takada, Kohichi; Kamihara, Yusuke; Hayasaka, Naotaka; Nakamura, Hajime; Murase, Kazuyuki; Ikeda, Hiroshi; Iyama, Satoshi; Sato, Tsutomu; Miyanishi, Koji; Kobune, Masayoshi; Kato, Junji

    2017-09-12

    Reactive oxygen species (ROS) are normal byproducts of a wide variety of cellular processes. ROS have dual functional roles in cancer cell pathophysiology. At low to moderate levels, ROS act as signaling transducers to activate cell proliferation, migration, invasion, and angiogenesis. In contrast, high levels of ROS induce cell death. In multiple myeloma (MM), ROS overproduction is the trigger for apoptosis induced by several anticancer compounds, including proteasome inhibitors. However, no drugs for which oxidative stress is the main mechanism of action are currently used for treatment of MM in clinical situations. In this study, we demonstrate that the p53-activating small molecule CP-31398 (CP) effectively inhibits the growth of MM cell lines and primary MM isolates from patients. CP also suppresses the growth of MM xenografts in mice. Mechanistically, CP was found to induce intrinsic apoptosis in MM cells via increasing ROS production. Interestingly, CP-induced apoptosis occurs regardless of the p53 status, suggesting that CP has additional mechanisms of action. Our findings thus indicate that CP could be an attractive candidate for treatment of MM patients harboring p53 abnormalities; this satisfies an unmet clinical need, as such individuals currently have a poor prognosis.

  18. Sustained contraction and endothelial dysfunction induced by reactive oxygen species in porcine coronary artery.

    PubMed

    Ishihara, Yasuhiro; Sekine, Masaya; Hatano, Ai; Shimamoto, Norio

    2008-09-01

    A combination of purine and xanthine oxidase (XOD) dose-dependently elicited sustained contraction of porcine coronary arterial rings and resulted in increased concentrations of superoxide anions and hydrogen peroxide. These contractile responses appeared, with a delay, after the application of purine and XOD, used as a reactive oxygen species (ROS)-generating system. Coronary arteries precontracted with prostaglandin F(2alpha) failed to relax in response to substance P after exposing the arterial preparation to this ROS-generating system. The contractile response of the coronary artery to the ROS-generating system was almost completely inhibited by catalase (130 U/ml), and was partially inhibited by superoxide dismutase (60 U/ml), or mannitol (30 mM). A voltage-dependent L-type Ca(2+) channel antagonist, nicardipine, had no effect on contraction. Dysfunction of endothelial cells was completely prevented by catalase, but not by superoxide dismutase or mannitol. These results suggest that superoxide anions, hydrogen peroxide and hydroxyl radicals might be involved in eliciting sustained, delayed-onset coronary artery contraction, which is not related to L-type Ca(2+) channels. They also suggest that hydrogen peroxide might play a major role in endothelial dysfunction of the porcine coronary artery.

  19. Oxidative stress-induced necrotic cell death via mitochondira-dependent burst of reactive oxygen species.

    PubMed

    Choi, Kyungsun; Kim, Jinho; Kim, Gyung W; Choi, Chulhee

    2009-11-01

    Oxidative stress is deeply involved in various brain diseases, including neurodegenerative diseases, stroke, and ischemia/reperfusion injury. Mitochondria are thought to be the target and source of oxidative stress. We investigated the role of mitochondria in oxidative stress-induced necrotic neuronal cell death in a neuroblastoma cell line and a mouse model of middle cerebral artery occlusion. The exogenous administration of hydrogen peroxide was used to study the role of oxidative stress on neuronal cell survival and mitochondrial function in vitro. Hydrogen peroxide induced non-apoptotic neuronal cell death in a c-Jun N-terminal kinase- and poly(ADP-ribosyl) polymerase-dependent manner. Unexpectedly, hydrogen peroxide treatment induced transient hyperpolarization of the mitochondrial membrane potential and a subsequent delayed burst of endogenous reactive oxygen species (ROS). The inhibition of mitochondrial hyperpolarization by diphenylene iodonium or rotenone, potent inhibitors of mitochondrial respiratory chain complex I, resulted in reduced ROS production and subsequent neuronal cell death in vitro and in vivo. The inhibition of mitochondrial hyperpolarization can protect neuronal cells from oxidative stress-induced necrotic cell death, suggesting a novel method of therapeutic intervention in oxidative stress-induced neurological disease.

  20. C-phycocyanin protects against low fertility by inhibiting reactive oxygen species in aging mice

    PubMed Central

    Li, Yan-Jiao; Han, Zhe; Ge, Lei; Zhou, Cheng-Jie; Zhao, Yue-Fang; Wang, Dong-Hui; Ren, Jing; Niu, Xin-Xin; Liang, Cheng-Guang

    2016-01-01

    Women over 35 have higher rates of infertility, largely due to deterioration of oocyte quality characterized by fragmentation, abnormal meiotic spindle-chromosome complexes, and oxidative stress. C-phycocyanin (PC) is a biliprotein enriched in Spirulina platensis that is known to possess antioxidant, anti-inflammatory, and radical-scavenging properties. D-galactose-induced aging acceleration in mice has been extensively used to study aging mechanisms and for pharmaceutical screening. In this study, adult female B6D2F/1 mice injected with D-galactose were used as a model to test the age-reversing effects of PC on degenerated reproductive ability. Our results show that PC can prevent oocyte fragmentation and aneuploidy by maintaining cytoskeletal integrity. Moreover, PC can reverse the expression of antioxidant genes, increase superoxide dismutase (SOD) activity and decrease methane dicarboxylic aldehyde (MDA) content, and normalize mitochondria distribution. PC exerts its benefit by inhibiting reactive oxygen species (ROS) production, which decreases apoptosis. Finally, we observe a significant increase in litter size after PC administration to D-galactose-induced aging mice. Our study demonstrates for the first time that D-galactose-induced impaired female reproductive capability can be partially rescued by the antioxidant effects of PC. PMID:27008700