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.

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.

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

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.

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

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

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.

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.

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.

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.

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.

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

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.

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.

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.

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

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

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 ...

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.

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

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

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.

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

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

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.

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

Silibinin activates AMP-activated protein kinase to protect neuronal cells from oxygen and glucose deprivation-re-oxygenation.

PubMed

Xie, Zhi; Ding, Sheng-quan; Shen, Ya-fang

2014-11-14

In this study, we explored the cytoprotective potential of silibinin against oxygen-glucose deprivation (OGD)-induced neuronal cell damages, and studied underling mechanisms. In vitro model of ischemic stroke was created by keeping neuronal cells (SH-SY5Y cells and primary mouse cortical neurons) in an OGD condition followed by re-oxygenation. Pre-treatment of silibinin significantly inhibited OGD/re-oxygenation-induced necrosis and apoptosis of neuronal cells. OGD/re-oxygenation-induced reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) reduction were also inhibited by silibinin. At the molecular level, silibinin treatment in SH-SY5Y cells and primary cortical neurons led to significant AMP-activated protein kinase (AMPK) signaling activation, detected by phosphorylations of AMPKα1, its upstream kinase liver kinase B1 (LKB1) and the downstream target acetyl-CoA Carboxylase (ACC). Pharmacological inhibition or genetic depletion of AMPK alleviated the neuroprotective ability of silibinin against OGD/re-oxygenation. Further, ROS scavenging ability by silibinin was abolished with AMPK inhibition or silencing. While A-769662, the AMPK activator, mimicked silibinin actions and suppressed ROS production and neuronal cell death following OGD/re-oxygenation. Together, these results show that silibinin-mediated neuroprotection requires activation of AMPK signaling. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

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

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

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.

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.

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.

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...

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

Activation of NOX2 by the stimulation of ionotropic and metabotropic glutamate receptors contributes to glutamate neurotoxicity in vivo through the production of reactive oxygen species and calpain activation.

PubMed

Guemez-Gamboa, Alicia; Estrada-Sánchez, Ana María; Montiel, Teresa; Páramo, Blanca; Massieu, Lourdes; Morán, Julio

2011-11-01

Prolonged activation of glutamate receptors leads to excitotoxicity. Several processes such as reactive oxygen species (ROS) production and activation of the calcium-dependent protease, calpain, contribute to glutamate-induced damage. It has been suggested that the ROS-producing enzyme, NADPH oxidase (NOX), plays a role in excitotoxicity. Studies have reported NOX activation after NMDA receptor stimulation during excitotoxic damage, but the role of non-NMDA and metabotropic receptors is unknown. We evaluated the roles of different glutamate receptor subtypes on NOX activation and neuronal death induced by the intrastriatal administration of glutamate in mice. In wild-type mice, NOX2 immunoreactivity in neurons and microglia was stimulated by glutamate administration, and it progressively increased as microglia became activated; calpain activity was also induced. By contrast, mice lacking NOX2 were less vulnerable to excitotoxicity, and there was reduced ROS production and protein nitrosylation, microglial reactivity, and calpain activation. These results suggest that NOX2 is stimulated by glutamate in neurons and reactive microglia through the activation of ionotropic and metabotropic receptors. Neuronal damage involves ROS production by NOX2, which, in turn, contributes to calpain activation.

Activation of sperm EGFR by light irradiation is mediated by reactive oxygen species.

PubMed

Shahar, Shiran; Hillman, Pnina; Lubart, Rachel; Ickowicz, Debby; Breitbart, Haim

2014-01-01

To acquire fertilization competence, spermatozoa must undergo several biochemical and motility changes in the female reproductive tract, collectively called capacitation. Actin polymerization and the development of hyperactivated motility (HAM) are part of the capacitation process. In a recent study, we showed that irradiation of human sperm with visible light stimulates HAM through a mechanism involving reactive-oxygen-species (ROS), Ca(2+) influx, protein kinases A (PKA), and sarcoma protein kinase (Src). Here, we showed that this effect of light on HAM is mediated by ROS-dependent activation of the epidermal growth factor receptor (EGFR). Interestingly, ROS-mediated HAM even when the EGFR was activated by EGF, the physiological ligand of EGFR. Light irradiation stimulated ROS-dependent actin polymerization, and this effect was abrogated by PBP10, a peptide which activates the actin-severing protein, gelsolin, and causes actin-depolymerization in human sperm. Light-stimulated tyrosine phosphorylation of Src-dependent gelsolin, resulting in enhanced HAM. Thus, light irradiation stimulates HAM through a mechanism involving Src-mediated actin polymerization. Light-stimulated HAM and in vitro-fertilization (IVF) rate in mouse sperm, and these effects were mediated by ROS and EGFR. In conclusion, we show here that irradiation of sperm with visible light, enhances their fertilization capacity via a mechanism requiring ROS, EGFR and HAM. © 2014 The American Society of Photobiology.

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…

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.

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

Reactive oxygen radicals and gaseous transmitters in carotid body activation by intermittent hypoxia.

PubMed

Prabhakar, Nanduri R; Peng, Ying-Jie; Yuan, Guoxiang; Nanduri, Jayasri

2018-05-01

Sleep apnea is a prevalent respiratory disease characterized by periodic cessation of breathing during sleep causing intermittent hypoxia (IH). Sleep apnea patients and rodents exposed to IH exhibit elevated sympathetic nerve activity and hypertension. A heightened carotid body (CB) chemoreflex has been implicated in causing autonomic abnormalities in IH-treated rodents and in sleep apnea patients. The purpose of this article is to review the emerging evidence showing that interactions between reactive oxygen species (ROS) and gaseous transmitters as a mechanism cause hyperactive CB by IH. Rodents treated with IH exhibit markedly elevated ROS in the CB, which is due to transcriptional upregulation of pro-oxidant enzymes by hypoxia-inducible factor (HIF)-1 and insufficient transcriptional regulation of anti-oxidant enzymes by HIF-2. ROS, in turn, increases cystathionine γ-lyase (CSE)-dependent H 2 S production in the CB. Blockade of H 2 S synthesis prevents IH-evoked CB activation. However, the effects of ROS on H 2 S production are not due to direct effects on CSE enzyme activity but rather due to inactivation of heme oxygenase-2 (HO-2), a carbon monoxide (CO) producing enzyme. CO inhibits H 2 S production through inactivation of CSE by PKG-dependent phosphorylation. During IH, reduced CO production resulting from inactivation of HO-2 by ROS releases the inhibition of CO on CSE thereby increasing H 2 S. Inhibiting H 2 S synthesis prevented IH-evoked sympathetic activation and hypertension.

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.

[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.

Substance P influenced gelatinolytic activity via reactive oxygen species in human pulp cells.

PubMed

Wang, F-M; Hu, T; Cheng, R; Tan, H; Zhou, X-D

2008-10-01

To investigate the effects of substance P (SP) on gelatinolytic activity of matrix metalloproteinases (MMPs) in human pulp cells. Human dental pulp cells were isolated and cultured. Subconfluent cells, between the third and sixth passages, were maintained under serum deprivation for 18 h followed by the treatment of varying doses of SP (1 pmol L(-1), 100 pmol L(-1), 10 nmol L(-1), 1 micromol L(-1) and 100 micromol L(-1)). Conditioned media were then subjected to gelatin zymography using 8% sodium dodecyl sulphate polyacrylamide gel electrophoresis minigels containing 1.5 g L(-1) gelatin. The effect of SP on intracellular reactive oxygen species (ROS) was also examined by confocal microscopy. ROS scavenger N-Acetyl-L-cysteine (NAC, 5 mmol L(-1)) was utilized to evaluate the roles of ROS pathway in mediating the impact of SP on cellular gelatinolytic activity. Data were analysed using analysis of variance with Bonferroni correction for multiple comparisons or an unpaired Student's t-test. Substance P, at levels above 1 micromol L(-1), remarkably enhanced MMP-2 activity reflected by the band migrating at 66 kDa (P < 0.05). A gelatinolytic band at approximately 44 kDa appeared to be intensified in a SP dose-dependent manner. In addition, it was demonstrated that SP could induce ROS production in pulp cells and ROS scavenger NAC was further found to significantly reduce MMP-2 activity (P < 0.05), as well as other bands of gelatinolytic proteinases. Substance P can influence gelatinolytic activity in human pulp cells via ROS pathway.

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...

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

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

Activation of planarian TRPA1 by reactive oxygen species reveals a conserved mechanism for nociception

PubMed Central

Arenas, Oscar M.; Zaharieva, Emanuela E.; Para, Alessia; Vásquez-Doorman, Constanza; Petersen, Christian P.; Gallio, Marco

2017-01-01

All animals must detect noxious stimuli to initiate protective behavior, but the evolutionary origin of nociceptive systems is not well understood. Here, we show that noxious heat and irritant chemicals elicit robust escape behaviors in the planarian Schmidtea mediterranea, and that the conserved ion channel TRPA1 is required for these responses. TRPA1 mutant flies (Drosophila) are also defective in noxious heat responses. Unexpectedly, we find that either planarian or human TRPA1 can restore noxious heat avoidance to TRPA1 mutant Drosophila, even though neither is directly activated by heat. Instead, our data suggest that TRPA1 activation is mediated by H2O2/Reactive Oxygen Species, early markers of tissue damage rapidly produced as a result of heat exposure. Together, our data reveal a core function for TRPA1 in noxious heat transduction, demonstrate its conservation from planarians to humans, and imply that animal nociceptive systems may share a common ancestry, tracing back to a progenitor that lived more than 500 million years ago. PMID:29184198

Synthesis of SiC/Ag/Cellulose Nanocomposite and Its Antibacterial Activity by Reactive Oxygen Species Generation

PubMed Central

Borkowski, Andrzej; Cłapa, Tomasz; Szala, Mateusz; Gąsiński, Arkadiusz; Selwet, Marek

2016-01-01

We describe the synthesis of nanocomposites, based on nanofibers of silicon carbide, silver nanoparticles, and cellulose. Silver nanoparticle synthesis was achieved with chemical reduction using hydrazine by adding two different surfactants to obtain a nanocomposite with silver nanoparticles of different diameters. Determination of antibacterial activity was based on respiration tests. Enzymatic analysis indicates oxidative stress, and viability testing was conducted using an epifluorescence microscope. Strong bactericidal activity of nanocomposites was found against bacteria Escherichia coli and Bacillus cereus, which were used in the study as typical Gram-negative and Gram-positive bacteria, respectively. It is assumed that reactive oxygen species generation was responsible for the observed antibacterial effect of the investigated materials. Due to the properties of silicon carbide nanofiber, the obtained nanocomposite may have potential use in technology related to water and air purification. Cellulose addition prevented silver nanoparticle release and probably enhanced bacterial adsorption onto aggregates of the nanocomposite material. PMID:28335299

Leinamycin E1 acting as an anticancer prodrug activated by reactive oxygen species.

PubMed

Huang, Sheng-Xiong; Yun, Bong-Sik; Ma, Ming; Basu, Hirak S; Church, Dawn R; Ingenhorst, Gudrun; Huang, Yong; Yang, Dong; Lohman, Jeremy R; Tang, Gong-Li; Ju, Jianhua; Liu, Tao; Wilding, George; Shen, Ben

2015-07-07

Leinamycin (LNM) is a potent antitumor antibiotic produced by Streptomyces atroolivaceus S-140, featuring an unusual 1,3-dioxo-1,2-dithiolane moiety that is spiro-fused to a thiazole-containing 18-membered lactam ring. Upon reductive activation in the presence of cellular thiols, LNM exerts its antitumor activity by an episulfonium ion-mediated DNA alkylation. Previously, we have cloned the lnm gene cluster from S. atroolivaceus S-140 and characterized the biosynthetic machinery responsible for the 18-membered lactam backbone and the alkyl branch at C3 of LNM. We now report the isolation and characterization of leinamycin E1 (LNM E1) from S. atroolivacues SB3033, a ΔlnmE mutant strain of S. atroolivaceus S-140. Complementary to the reductive activation of LNM by cellular thiols, LNM E1 can be oxidatively activated by cellular reactive oxygen species (ROS) to generate a similar episulfonium ion intermediate, thereby alkylating DNA and leading to eventual cell death. The feasibility of exploiting LNM E1 as an anticancer prodrug activated by ROS was demonstrated in two prostate cancer cell lines, LNCaP and DU-145. Because many cancer cells are under higher cellular oxidative stress with increased levels of ROS than normal cells, these findings support the idea of exploiting ROS as a means to target cancer cells and highlight LNM E1 as a novel lead for the development of anticancer prodrugs activated by ROS. The structure of LNM E1 also reveals critical new insights into LNM biosynthesis, setting the stage to investigate sulfur incorporation, as well as the tailoring steps that convert the nascent hybrid peptide-polyketide biosynthetic intermediate into LNM.

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.

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

Reactive oxygen species are required for driving efficient and sustained aerobic glycolysis during CD4+ T cell activation.

PubMed

Previte, Dana M; O'Connor, Erin C; Novak, Elizabeth A; Martins, Christina P; Mollen, Kevin P; Piganelli, Jon D

2017-01-01

The immune system is necessary for protecting against various pathogens. However, under certain circumstances, self-reactive immune cells can drive autoimmunity, like that exhibited in type 1 diabetes (T1D). CD4+ T cells are major contributors to the immunopathology in T1D, and in order to drive optimal T cell activation, third signal reactive oxygen species (ROS) must be present. However, the role ROS play in mediating this process remains to be further understood. Recently, cellular metabolic programs have been shown to dictate the function and fate of immune cells, including CD4+ T cells. During activation, CD4+ T cells must transition metabolically from oxidative phosphorylation to aerobic glycolysis to support proliferation and effector function. As ROS are capable of modulating cellular metabolism in other models, we sought to understand if blocking ROS also regulates CD4+ T cell activation and effector function by modulating T cell metabolism. To do so, we utilized an ROS scavenging and potent antioxidant manganese metalloporphyrin (MnP). Our results demonstrate that redox modulation during activation regulates the mTOR/AMPK axis by maintaining AMPK activation, resulting in diminished mTOR activation and reduced transition to aerobic glycolysis in diabetogenic splenocytes. These results correlated with decreased Myc and Glut1 upregulation, reduced glucose uptake, and diminished lactate production. In an adoptive transfer model of T1D, animals treated with MnP demonstrated delayed diabetes progression, concurrent with reduced CD4+ T cell activation. Our results demonstrate that ROS are required for driving and sustaining T cell activation-induced metabolic reprogramming, and further support ROS as a target to minimize aberrant immune responses in autoimmunity.

Dynamic activation of Src induced by low-power laser irradiation in living cells mediated by reactive oxygen species

NASA Astrophysics Data System (ADS)

Zhang, Juntao; Gao, Xuejuan; Xing, Da; Liu, Lei

2007-11-01

Low-power laser irradiation (LPLI) leads to photochemical reaction and then activates intracellular several signaling pathway. Reactive oxygen species (ROS) are considered to be the primary messengers produced by LPLI. Here, we studied the signaling pathway mediated by ROS upon the stimulation of LPLI. Src tyrosine kinases are well-known targets of ROS and can be activated by oxidative events. Using a Src reporter based on fluorescence resonance energy transfer (FRET) technique, we visualized the dynamic Src activation in Hela cells immediately after LPLI. Moreover, Src activity was enhanced by increasing the duration of LPLI. In addition, our results suggested that ROS were key mediators of Src activation, as ROS scavenger, vitamin C decreased and exogenous H IIO II increased the activity of Src. Meanwhile, Gö6983 loading did not block the effect of LPLI. CCK-8 experiments proved that cell vitality was prominently improved by LPLI with all the doses we applied in our experiments ranging from 3 to 25J/cm2. The results indicated that LPLI/ROS/Src pathway may be involved in the LPLI biostimulation effects.

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.

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

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

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.

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.

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.

Asian Dust Particles Induce Macrophage Inflammatory Responses via Mitogen-Activated Protein Kinase Activation and Reactive Oxygen Species Production

PubMed Central

Higashisaka, Kazuma; Fujimura, Maho; Taira, Mayu; Yoshida, Tokuyuki; Tsunoda, Shin-ichi; Baba, Takashi; Yamaguchi, Nobuyasu; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Nasu, Masao; Tsutsumi, Yasuo

2014-01-01

Asian dust is a springtime meteorological phenomenon that originates in the deserts of China and Mongolia. The dust is carried by prevailing winds across East Asia where it causes serious health problems. Most of the information available on the impact of Asian dust on human health is based on epidemiological investigations, so from a biological standpoint little is known of its effects. To clarify the effects of Asian dust on human health, it is essential to assess inflammatory responses to the dust and to evaluate the involvement of these responses in the pathogenesis or aggravation of disease. Here, we investigated the induction of inflammatory responses by Asian dust particles in macrophages. Treatment with Asian dust particles induced greater production of inflammatory cytokines interleukin-6 and tumor necrosis factor-α (TNF-α) compared with treatment with soil dust. Furthermore, a soil dust sample containing only particles ≤10 μm in diameter provoked a greater inflammatory response than soil dust samples containing particles >10 μm. In addition, Asian dust particles-induced TNF-α production was dependent on endocytosis, the production of reactive oxygen species, and the activation of nuclear factor-κB and mitogen-activated protein kinases. Together, these results suggest that Asian dust particles induce inflammatory disease through the activation of macrophages. PMID:24987712

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.

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

Unraveling the enhanced photocatalytic activity and phototoxicity of ZnO/metal hybrid nanostructures from generation of reactive oxygen species and charge carriers.

PubMed

He, Weiwei; Wu, Haohao; Wamer, Wayne G; Kim, Hyun-Kyung; Zheng, Jiwen; Jia, Huimin; Zheng, Zhi; Yin, Jun-Jie

2014-09-10

An effective way for promoting photocatalytic activity of a semiconductor is deposition of noble metal nanoparticles (NPs) onto it. In this paper, we deposited Ag and Pd onto ZnO NPs to form ZnO/Ag and ZnO/Pd hybrid nanostructures. It was found that both Ag and Pd nanocomponents can greatly enhance the photocatalytic activity and phototoxicity of ZnO toward human skin cells. Using electron spin resonance spectroscopy with spin trapping and spin labeling techniques, we observed that either deposition of Ag or Pd resulted in a significant increase in photogenerated electrons and holes and production of reactive oxygen species including hydroxyl radicals, superoxide, and singlet oxygen. We compared the enhancing effects of Ag and Pd and found that Pd is more effective than Ag in promoting the generation of hydroxyl radicals and holes and the photocatalytic activity of ZnO. Conversely, Ag is more effective than Pd in enhancing electron transfer and the generation of superoxide and singlet oxygen. The mechanism underlying the differences in the effects of Ag and Pd may be related to differences in Fermi levels for Ag and Pd and band bending accompanied by effects on Schottky barriers. The results of these studies provide information valuable for designing hybrid nanomaterials having photocatalytic and photobiological activities useful for applications such as water purification and formulation of antibacterial products.

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.

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

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.

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

Assessment of the Antioxidant and Reactive Oxygen Species Scavenging Activity of Methanolic Extract of Caesalpinia crista Leaf

PubMed Central

Mandal, Sourav; Hazra, Bibhabasu; Sarkar, Rhitajit; Biswas, Santanu; Mandal, Nripendranath

2011-01-01

“Oxidative stress” is initiated by reactive oxygen species (ROS), which are responsible for majority of the diseases. However, antioxidants with ROS scavenging ability may have great relevance in the prevention of oxidative stress. The present study was undertaken, using a 70% methanolic extract of Caesalpinia crista leaves, to examine different in vitro tests in diversified fields including total antioxidant activity, scavenging activities for various ROS, iron chelating activity and phenolic and flavonoid contents. Total antioxidant activity was evaluated as trolox equivalent antioxidant capacity value of 0.546 ± 0.014. The extract was investigated for different ROS scavenging activities and IC50 values were found to be 0.44 ± 0.1 mg/ml, 24.9 ± 0.98 μg/ml, 33.72 ± 0.85 μg/ml, 61.13 ± 3.24 μg/mL and 170.51 ± 4.68 μg/mL for hydroxyl, superoxide, nitric oxide, singlet oxygen and hypochlorous acid, respectively; however, no significant results were obtained in scavenging of hydrogen peroxide and peroxynitrite anion. The extract was found to be a potent iron chelator with IC50 = 279.85 ± 4.72 μg/mL. The plant extract (100 mg) yielded 50.23 ± 0.003 mg/mL gallic acid equivalent phenolic content and 106.83 ± 0.0003 mg/mL quercetin equivalent flavonoid content. In the in vivo experiments, the extract treatment showed significant increase in the level of superoxide dismutase, catalase, glutathione-S-transferase and reduced glutathione. In a word, it may be concluded that 70% methanol extract of C. crista leaves acts as an antioxidant and ROS scavenger; which may be due to the presence of phenolic and flavonoid compounds. PMID:19596746

Reactive oxygen species and associated reactivity of peroxymonosulfate activated by soluble iron species

NASA Astrophysics Data System (ADS)

Watts, Richard J.; Yu, Miao; Teel, Amy L.

2017-10-01

The activation of peroxymonosulfate by iron (II), iron (III), and iron (III)-EDTA for in situ chemical oxidation (ISCO) was compared using nitrobenzene as a hydroxyl radical probe, anisole as a hydroxyl radical + sulfate radical probe, and hexachloroethane as a reductant + nucleophile probe. In addition, activated peroxymonosulfate was investigated for the treatment of the model groundwater contaminants perchloroethylene (PCE) and trichloroethylene (TCE). The relative activities of hydroxyl radical and sulfate radical in the degradation of the probe compounds and PCE and TCE were isolated using the radical scavengers tert-butanol and isopropanol. Iron (II), iron (III), and iron (III)-EDTA effectively activated peroxymonosulfate to generate hydroxyl radical and sulfate radical, but only a minimal flux of reductants or nucleophiles. Iron (III)-EDTA was a more effective activator than iron (II) and iron (III), and also provided a non-hydroxyl radical, non-sulfate radical degradation pathway. The contribution of sulfate radical relative to hydroxyl radical followed the order of anisole > > TCE > PCE > > nitrobenzene; i.e., sulfate radical was less dominant in the oxidation of more oxidized target compounds. Sulfate radical is often assumed to be the primary oxidant in activated peroxymonosulfate and persulfate systems, but the results of this research demonstrate that the reactivity of sulfate radical with the target compound must be considered before drawing such a conclusion.

Reactive oxygen species and associated reactivity of peroxymonosulfate activated by soluble iron species.

PubMed

Watts, Richard J; Yu, Miao; Teel, Amy L

2017-10-01

The activation of peroxymonosulfate by iron (II), iron (III), and iron (III)-EDTA for in situ chemical oxidation (ISCO) was compared using nitrobenzene as a hydroxyl radical probe, anisole as a hydroxyl radical+sulfate radical probe, and hexachloroethane as a reductant+nucleophile probe. In addition, activated peroxymonosulfate was investigated for the treatment of the model groundwater contaminants perchloroethylene (PCE) and trichloroethylene (TCE). The relative activities of hydroxyl radical and sulfate radical in the degradation of the probe compounds and PCE and TCE were isolated using the radical scavengers tert-butanol and isopropanol. Iron (II), iron (III), and iron (III)-EDTA effectively activated peroxymonosulfate to generate hydroxyl radical and sulfate radical, but only a minimal flux of reductants or nucleophiles. Iron (III)-EDTA was a more effective activator than iron (II) and iron (III), and also provided a non-hydroxyl radical, non-sulfate radical degradation pathway. The contribution of sulfate radical relative to hydroxyl radical followed the order of anisole>TCE>PCE >nitrobenzene; i.e., sulfate radical was less dominant in the oxidation of more oxidized target compounds. Sulfate radical is often assumed to be the primary oxidant in activated peroxymonosulfate and persulfate systems, but the results of this research demonstrate that the reactivity of sulfate radical with the target compound must be considered before drawing such a conclusion. Published by Elsevier B.V.

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.

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.

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.

Trimethyltin-activated cyclooxygenase stimulates tumor necrosis factor-alpha release from glial cells through reactive oxygen species.

PubMed

Viviani, B; Corsini, E; Pesenti, M; Galli, C L; Marinovich, M

2001-04-15

Exposure of a primary culture of glial cells to the classical neurotoxicant trimethyltin (TMT) results in the release of prostaglandin (PG)E(2) and tumor necrosis factor (TNF)-alpha. Prior treatment of glial cells with either the nonspecific inhibitor of cyclooxygenase and lypoxygenase eicosatetraynoic acid (ETYA) or the cyclooxygenase inhibitor indomethacin completely prevented TMT-induced PGE(2) production and TNF-alpha release, suggesting a role for cyclooxygenase metabolites in TMT-induced TNF-alpha release. Exposure of glial cells to increasing concentrations of PGE(2) or other prostanoids did not increase TNF-alpha synthesis, while the presence of exogenous PGE(2) during treatment of glial cells with TMT actually suppressed TNF-alpha release. The activation of arachidonic acid metabolism produces reactive oxygen species (ROS). Scavenging of ROS by means of the antioxidant trolox prevented the TMT-induced release of TNF-alpha from glial cells, while indomethacin was found to suppress ROS formation induced by 1 microM TMT in glial cells. These results suggest that activation of arachidonic acid metabolism causes TNF-alpha release through the production of ROS rather than PGE(2). Indeed, PGE(2) may exert negative feedback on the release of TNF-alpha. Copyright 2001 Academic Press.

Reactive oxygen species are involved in regulating alpha1-adrenoceptor-activated vascular smooth muscle contraction.

PubMed

Tsai, Ming-Ho; Jiang, Meei Jyh

2010-08-23

Reactive oxygen species (ROS) were shown to mediate aberrant contractility in hypertension, yet the physiological roles of ROS in vascular smooth muscle contraction have remained elusive. This study aimed to examine whether ROS regulate alpha1-adrenoceptor-activated contraction by altering myosin phosphatase activities. Using endothelium-denuded rat tail artery (RTA) strips, effects of anti-oxidants on isometric force, ROS production, phosphorylation of the 20-kDa myosin light chain (MLC20), and myosin phosphatase stimulated by alpha1-adrenoceptor agonist phenylephrine were examined. An antioxidant, N-acetyl-L-cysteine (NAC), and two NADPH oxidase inhibitors, apocynin and VAS2870, dose-dependently inhibited contraction activated by phenylephrine. Phenylephrine stimulated superoxide anion production that was diminished by the pretreatment of apocynin, VAS2870, superoxide scavenger tiron or mitochondria inhibitor rotenone, but not by xanthine oxidase inhibitor allopurinol or cyclooxygenase inhibitor indomethacin. Concurrently, NADPH oxidase activity in RTA homogenates increased within 1 min upon phenylephrine stimulation, sustained for 10 min, and was abolished by the co-treatment with apocynin, but not allopurinol or rotenone. Phenylephrine-induced MLC20 phosphorylation was dose-dependently decreased by apocynin. Furthermore, apocynin inhibited phenylephrine-stimulated RhoA translocation to plasma membrane and phosphorylation of both myosin phosphatase regulatory subunit MYPT1Thr855 and myosin phosphatase inhibitor CPI-17Thr38. ROS, probably derived from NADPH oxidase and mitochondria, partially regulate alpha1-adrenoceptor-activated smooth muscle contraction by altering myosin phosphatase-mediated MLC20 phosphorylation through both RhoA/Rho kinase- and CPI-17-dependent pathways.

Mitochondrial reactive oxygen species enhance AMP-activated protein kinase activation in the endothelium of patients with coronary artery disease and diabetes.

PubMed

Mackenzie, Ruth M; Salt, Ian P; Miller, William H; Logan, Angela; Ibrahim, Hagar A; Degasperi, Andrea; Dymott, Jane A; Hamilton, Carlene A; Murphy, Michael P; Delles, Christian; Dominiczak, Anna F

2013-03-01

The aim of the present study was to determine whether the endothelial dysfunction associated with CAD (coronary artery disease) and T2D (Type 2 diabetes mellitus) is concomitant with elevated mtROS (mitochondrial reactive oxygen species) production in the endothelium and establish if this, in turn, regulates the activity of endothelial AMPK (AMP-activated protein kinase). We investigated endothelial function, mtROS production and AMPK activation in saphenous veins from patients with advanced CAD. Endothelium-dependent vasodilation was impaired in patients with CAD and T2D relative to those with CAD alone. Levels of mitochondrial H(2)O(2) and activity of AMPK were significantly elevated in primary HSVECs (human saphenous vein endothelial cells) from patients with CAD and T2D compared with those from patients with CAD alone. Incubation with the mitochondria-targeted antioxidant, MitoQ(10) significantly reduced AMPK activity in HSVECs from patients with CAD and T2D but not in cells from patients with CAD alone. Elevated mtROS production in the endothelium of patients with CAD and T2D increases AMPK activation, supporting a role for the kinase in defence against oxidative stress. Further investigation is required to determine whether pharmacological activators of AMPK will prove beneficial in the attenuation of endothelial dysfunction in patients with CAD and T2D.

Electrochemically reduced water exerts superior reactive oxygen species scavenging activity in HT1080 cells than the equivalent level of hydrogen-dissolved water

PubMed Central

Hamasaki, Takeki; Harada, Gakuro; Nakamichi, Noboru; Kabayama, Shigeru; Teruya, Kiichiro; Fugetsu, Bunshi; Gong, Wei; Sakata, Ichiro; Shirahata, Sanetaka

2017-01-01

Electrochemically reduced water (ERW) is produced near a cathode during electrolysis and exhibits an alkaline pH, contains richly dissolved hydrogen, and contains a small amount of platinum nanoparticles. ERW has reactive oxygen species (ROS)-scavenging activity and recent studies demonstrated that hydrogen-dissolved water exhibits ROS-scavenging activity. Thus, the antioxidative capacity of ERW is postulated to be dependent on the presence of hydrogen levels; however, there is no report verifying the role of dissolved hydrogen in ERW. In this report, we clarify whether the responsive factor for antioxidative activity in ERW is dissolved hydrogen. The intracellular ROS scavenging activity of ERW and hydrogen-dissolved water was tested by both fluorescent stain method and immuno spin trapping assay. We confirm that ERW possessed electrolysis intensity-dependent intracellular ROS-scavenging activity, and ERW exerts significantly superior ROS-scavenging activity in HT1080 cells than the equivalent level of hydrogen-dissolved water. ERW retained its ROS-scavenging activity after removal of dissolved hydrogen, but lost its activity when autoclaved. An oxygen radical absorbance capacity assay, the 2,2-diphenyl-1-picrylhydrazyl assay and chemiluminescence assay could not detect radical-scavenging activity in both ERW and hydrogen-dissolved water. These results indicate that ERW contains electrolysis-dependent hydrogen and an additional antioxidative factor predicted to be platinum nanoparticles. PMID:28182635

Electrochemically reduced water exerts superior reactive oxygen species scavenging activity in HT1080 cells than the equivalent level of hydrogen-dissolved water.

PubMed

Hamasaki, Takeki; Harada, Gakuro; Nakamichi, Noboru; Kabayama, Shigeru; Teruya, Kiichiro; Fugetsu, Bunshi; Gong, Wei; Sakata, Ichiro; Shirahata, Sanetaka

2017-01-01

Electrochemically reduced water (ERW) is produced near a cathode during electrolysis and exhibits an alkaline pH, contains richly dissolved hydrogen, and contains a small amount of platinum nanoparticles. ERW has reactive oxygen species (ROS)-scavenging activity and recent studies demonstrated that hydrogen-dissolved water exhibits ROS-scavenging activity. Thus, the antioxidative capacity of ERW is postulated to be dependent on the presence of hydrogen levels; however, there is no report verifying the role of dissolved hydrogen in ERW. In this report, we clarify whether the responsive factor for antioxidative activity in ERW is dissolved hydrogen. The intracellular ROS scavenging activity of ERW and hydrogen-dissolved water was tested by both fluorescent stain method and immuno spin trapping assay. We confirm that ERW possessed electrolysis intensity-dependent intracellular ROS-scavenging activity, and ERW exerts significantly superior ROS-scavenging activity in HT1080 cells than the equivalent level of hydrogen-dissolved water. ERW retained its ROS-scavenging activity after removal of dissolved hydrogen, but lost its activity when autoclaved. An oxygen radical absorbance capacity assay, the 2,2-diphenyl-1-picrylhydrazyl assay and chemiluminescence assay could not detect radical-scavenging activity in both ERW and hydrogen-dissolved water. These results indicate that ERW contains electrolysis-dependent hydrogen and an additional antioxidative factor predicted to be platinum nanoparticles.

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.

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.

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.

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

Neuroprotective Effects of Reactive Oxygen Species Mediated by BDNF-Independent Activation of TrkB

PubMed Central

Huang, Yang Zhong; McNamara, James O.

2012-01-01

Reactive oxygen species (ROS) have diverse biological consequences in the mammalian CNS, but the molecular targets mediating these pleiotropic effects are incompletely understood. Like ROS, the neurotrophin receptor, TrkB receptor tyrosine kinase, has diverse effects in the developing and mature mammalian brain. Our discovery that zinc can transactivate TrkB, together with the finding that ROS can trigger zinc release from cytosolic zinc binding proteins, led us to hypothesize that ROS can transactivate TrkB in CNS neurons by a zinc-dependent mechanism. We found that both exogenous H2O2 and endogenous ROS activate TrkB signaling by a Src family kinase-dependent but brain-derived neurotrophic factor-independent mechanism in cultured rat cortical neurons. Exogenous H2O2 enhances cytosolic zinc content in a metallothionein-3 (MT-3)-requiring manner. Both exogenous H2O2 and endogenous ROS mediated transactivation of TrkB requires intracellular zinc and MT-3. The ROS-triggered transactivation of TrkB exerts neuroprotective effects, because inhibition of TrkB kinase activity or uncoupling Shc signaling from TrkB exacerbates neuronal cell death induced by H2O2. Thus, we propose a molecular signaling event whereby ROS induce release of zinc from cytosolic MT-3, the increased cytosolic zinc transactivates TrkB, and the enhanced Shc signaling downstream from TrkB promotes prosurvival effects. We suggest that such neuroprotective effects mediated by ROS are operative in diverse acute and chronic neurological disorders. PMID:23115189

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.

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.

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.

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.

Oxygen Activation at the Active Site of a Fungal Lytic Polysaccharide Monooxygenase

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

O'Dell, William B.; Agarwal, Pratul K.; Meilleur, Flora

Lytic polysaccharide monooxygenases have attracted vast attention owing to their abilities to disrupt glycosidic bonds via oxidation instead of hydrolysis and to enhance enzymatic digestion of recalcitrant substrates including chitin and cellulose. Here, we determined the high-resolution X-ray crystal structures of an enzyme from Neurospora crassa in the resting state and of a copper(II) dioxo intermediate complex formed in the absence of substrate. X-ray crystal structures also revealed “pre-bound” molecular oxygen adjacent to the active site. An examination of protonation states enabled by neutron crystallography and density functional theory calculations identified a role for a conserved histidine in promoting oxygenmore » activation. Our results provide a new structural description of oxygen activation by substrate free lytic polysaccharide monooxygenases and provide insights that can be extended to reactivity in the enzyme–substrate complex.« less

Oxygen Activation at the Active Site of a Fungal Lytic Polysaccharide Monooxygenase

DOE PAGES

O'Dell, William B.; Agarwal, Pratul K.; Meilleur, Flora

2016-12-22

Lytic polysaccharide monooxygenases have attracted vast attention owing to their abilities to disrupt glycosidic bonds via oxidation instead of hydrolysis and to enhance enzymatic digestion of recalcitrant substrates including chitin and cellulose. Here, we determined the high-resolution X-ray crystal structures of an enzyme from Neurospora crassa in the resting state and of a copper(II) dioxo intermediate complex formed in the absence of substrate. X-ray crystal structures also revealed “pre-bound” molecular oxygen adjacent to the active site. An examination of protonation states enabled by neutron crystallography and density functional theory calculations identified a role for a conserved histidine in promoting oxygenmore » activation. Our results provide a new structural description of oxygen activation by substrate free lytic polysaccharide monooxygenases and provide insights that can be extended to reactivity in the enzyme–substrate complex.« less

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

Reactive Oxygene Species and Thioredoxin Activity in Plants at Development of Hypergravity and Oxidative Stresses

NASA Astrophysics Data System (ADS)

Jadko, Sergiy

Early increasing of reactive oxygen species (ROS) content, including H2O2, occurs in plant cells under various impacts and than these ROS can function as signaling molecules in starting of cell stress responses. At the same time thioredoxins (TR) are significant ROS and H2O2 sensors and transmitters to activation of various redox sensitive proteins, transcription factors and MAP kinases. This study was aimed to investigate early increasing of ROS and H2O2 contents and TR activity in the pea roots and in tissue culture under hypergravity and oxidative stresses. Pea roots of 3-5 days old seedlings and 12-14 days old tissue culture of Arabidopsis thaliana were studied. The pea seedlings were grown on wet filter paper and the tissue culture was grown on MS medium in dark conditions under 24oC. Hypergravity stress was induced by centrifugation at 10 and 15 g. Chemiluminescence (ChL) intensity for ROS concentration, H2O2 content and TR activity were determined. All experiments were repeated by 3-5 times. Early and reliable increasing of ChL intensity and H2O2 contents in the pea roots and in the tissue culture took place under hypergravity and oxidative stresses to 30, 60 and 90 min. At the same time TR activity increased on 11 and 19 percents only to 60 and 90 min. Thus under hypergravity and oxidative stresses in both investigated plants take place early increasing of ROS and H2O2 contents which as second messengers lead to increasing of TR activity with creating of ROS-TR stress signaling pathway.

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.

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

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.

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...

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

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

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.

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

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.

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

Impact of trans-resveratrol-sulfates and -glucuronides on endothelial nitric oxide synthase activity, nitric oxide release and intracellular reactive oxygen species.

PubMed

Ladurner, Angela; Schachner, Daniel; Schueller, Katharina; Pignitter, Marc; Heiss, Elke H; Somoza, Veronika; Dirsch, Verena M

2014-10-17

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenolic natural product mainly present in grape skin, berries and peanuts. In the vasculature resveratrol is thought to boost endothelial function by increasing endothelial nitric oxide synthase (eNOS) expression, by enhancing eNOS activity, and by reduction of reactive oxygen species (ROS) levels. Recent studies show that dietary resveratrol is metabolized in the liver and intestine into resveratrol-sulfate and -glucuronide derivatives questioning the relevance of multiple reported mechanistic in vitro data on resveratrol. In this study, we compare side by side different physiologically relevant resveratrol metabolites (resveratrol sulfates- and -glucuronides) and their parent compound in their influence on eNOS enzyme activity, endothelial NO release, and intracellular ROS levels. In contrast to resveratrol, none of the tested resveratrol metabolites elevated eNOS enzyme activity and endothelial NO release or affected intracellular ROS levels, leaving the possibility that not tested metabolites are active and able to explain in vivo findings.

Impact of Trans-Resveratrol-Sulfates and -Glucuronides on Endothelial Nitric Oxide Synthase Activity, Nitric Oxide Release and Intracellular Reactive Oxygen Species

PubMed Central

Ladurner, Angela; Schachner, Daniel; Schueller, Katharina; Pignitter, Marc; Heiss, Elke H.; Somoza, Veronika; Dirsch, Verena M.

2015-01-01

Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a polyphenolic natural product mainly present in grape skin, berries and peanuts. In the vasculature resveratrol is thought to boost endothelial function by increasing endothelial nitric oxide synthase (eNOS) expression, by enhancing eNOS activity, and by reduction of reactive oxygen species (ROS) levels. Recent studies show that dietary resveratrol is metabolized in the liver and intestine into resveratrol-sulfate and -glucuronide derivatives questioning the relevance of multiple reported mechanistic in vitro data on resveratrol. In this study, we compare side by side different physiologically relevant resveratrol metabolites (resveratrol sulfates- and -glucuronides) and their parent compound in their influence on eNOS enzyme activity, endothelial NO release, and intracellular ROS levels. In contrast to resveratrol, none of the tested resveratrol metabolites elevated eNOS enzyme activity and endothelial NO release or affected intracellular ROS levels, leaving the possibility that not tested metabolites are active and able to explain in vivo findings. PMID:25329867

Moringa oleifera fruit induce apoptosis via reactive oxygen species-dependent activation of mitogen-activated protein kinases in human melanoma A2058 cells

PubMed Central

Guon, Tae Eun; Chung, Ha Sook

2017-01-01

The present study was performed to determine the effect of Moringa oleifera fruit extract on the apoptosis of human melanoma A2058 cells. A2058 cells were treated for 72 h with Moringa oleifera fruit extract at 50–100 µg/ml, and cell viability with apoptotic changes was examined. The involvement of reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) was examined. It was revealed that Moringa oleifera fruit extract significantly inhibited the cell viability and promoted apoptosis of A2058 cells in a concentration-dependent manner. Moringa oleifera fruit extract-treated A2058 cells exhibited increased activities of cleaved caspase-9 and caspase-3. It also caused an enhancement of MAPK phosphorylation and ROS production. The pro-apoptotic activity of Moringa oleifera fruit extract was significantly reversed by pretreatment with the c-Jun N-terminal kinase (JNK) inhibitor SP600125, extracellular-signal-regulated kinase (ERK) inhibitor PD98058 or ROS inhibitor N-acetyl-L-cysteine. Taken together, Moringa oleifera fruit extract is effective in inducing mitochondrial apoptosis of A2058 cells, which is mediated through induction of ROS formation, and JNK and ERK activation. Moringa oleifera fruit extract may thus have therapeutic benefits for human melanoma A2058 cells. PMID:28789398

Moringa oleifera fruit induce apoptosis via reactive oxygen species-dependent activation of mitogen-activated protein kinases in human melanoma A2058 cells.

PubMed

Guon, Tae Eun; Chung, Ha Sook

2017-08-01

The present study was performed to determine the effect of Moringa oleifera fruit extract on the apoptosis of human melanoma A2058 cells. A2058 cells were treated for 72 h with Moringa oleifera fruit extract at 50-100 µg/ml, and cell viability with apoptotic changes was examined. The involvement of reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) was examined. It was revealed that Moringa oleifera fruit extract significantly inhibited the cell viability and promoted apoptosis of A2058 cells in a concentration-dependent manner. Moringa oleifera fruit extract-treated A2058 cells exhibited increased activities of cleaved caspase-9 and caspase-3. It also caused an enhancement of MAPK phosphorylation and ROS production. The pro-apoptotic activity of Moringa oleifera fruit extract was significantly reversed by pretreatment with the c-Jun N-terminal kinase (JNK) inhibitor SP600125, extracellular-signal-regulated kinase (ERK) inhibitor PD98058 or ROS inhibitor N-acetyl-L-cysteine. Taken together, Moringa oleifera fruit extract is effective in inducing mitochondrial apoptosis of A2058 cells, which is mediated through induction of ROS formation, and JNK and ERK activation. Moringa oleifera fruit extract may thus have therapeutic benefits for human melanoma A2058 cells.

Steap4 Plays a Critical Role in Osteoclastogenesis in Vitro by Regulating Cellular Iron/Reactive Oxygen Species (ROS) Levels and cAMP Response Element-binding Protein (CREB) Activation*

PubMed Central

Zhou, Jian; Ye, Shiqiao; Fujiwara, Toshifumi; Manolagas, Stavros C.; Zhao, Haibo

2013-01-01

Iron is essential for osteoclast differentiation, and iron overload in a variety of hematologic diseases is associated with excessive bone resorption. Iron uptake by osteoclast precursors via the transferrin cycle increases mitochondrial biogenesis, reactive oxygen species production, and activation of cAMP response element-binding protein, a critical transcription factor downstream of receptor activator of NF-κB-ligand-induced calcium signaling. These changes are required for the differentiation of osteoclast precursors to mature bone-resorbing osteoclasts. However, the molecular mechanisms regulating cellular iron metabolism in osteoclasts remain largely unknown. In this report, we provide evidence that Steap4, a member of the six-transmembrane epithelial antigen of prostate (Steap) family proteins, is an endosomal ferrireductase with a critical role in cellular iron utilization in osteoclasts. Specifically, we show that Steap4 is the only Steap family protein that is up-regulated during osteoclast differentiation. Knocking down Steap4 expression in vitro by lentivirus-mediated short hairpin RNAs inhibits osteoclast formation and decreases cellular ferrous iron, reactive oxygen species, and the activation of cAMP response element-binding protein. These results demonstrate that Steap4 is a critical enzyme for cellular iron uptake and utilization in osteoclasts and, thus, indispensable for osteoclast development and function. PMID:23990467

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

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.

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

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.

Transparent electrical conducting films by activated reactive evaporation

DOEpatents

Bunshah, Rointan; Nath, Prem

1982-01-01

Process and apparatus for producing transparent electrical conducting thin films by activated reactive evaporation. Thin films of low melting point metals and alloys, such as indium oxide and indium oxide doped with tin, are produced by physical vapor deposition. The metal or alloy is vaporized by electrical resistance heating in a vacuum chamber, oxygen and an inert gas such as argon are introduced into the chamber, and vapor and gas are ionized by a beam of low energy electrons in a reaction zone between the resistance heater and the substrate. There is a reaction between the ionized oxygen and the metal vapor resulting in the metal oxide which deposits on the substrate as a thin film which is ready for use without requiring post deposition heat treatment.

Antioxidative defence mechanisms against reactive oxygen species in bovine retained and not-retained placenta: activity of glutathione peroxidase, glutathione transferase, catalase and superoxide dismutase.

PubMed

Kankofer, M

2001-05-01

Glutathione peroxidase (GSH-Px), glutathione transferase (GSH-Tr), catalase (CAT) and superoxide dismutase (SOD)-the members of enzymatic antioxidative defence mechanisms against reactive oxygen species-may play an important role in proper or improper release of bovine fetal membranes. The aim of the following study was the determination of GSH-Px, GSH-Tr, CAT and SOD activity in order to define antioxidative status of bovine placenta during retention of fetal membranes (RFM) in cows. Placental samples were collected immediately after spontaneous parturition or during caesarean section before term and at term and divided into six groups as follows: A: caesarean section before term without RFM; B: caesarean section before term with RFM; C: caesarean section at term without RFM; D: caesarean section at term with RFM; E: spontaneous delivery at term without RFM; F: spontaneous delivery at term with RFM. The enzyme activities in placental homogenates were measured spectrophotometrically. GSH-Px activity was statistically significantly higher in fetal than in maternal placenta in all examined groups, increased towards parturition and was higher in caesarean section groups than spontaneous delivery groups. Statistically significantly higher activities were noticed in retained than not-retained placentae. GSH-Tr activity was significantly lower in fetal than in maternal placenta. In preterm groups, the activity was statistically significantly higher in retained than not retained placenta. In term groups, the opposite relationship was observed, higher values in caesarean section groups than spontaneous delivery were noticed. CAT activity was statistically significantly higher in fetal than in maternal part of placenta in all groups examined. The highest values in C and D groups and the differences between retained and not-retained placenta were observed. SOD exhibited the highest values in preterm placenta and alterations between retained and not-retained fetal membranes

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

Mitochondrial reactive oxygen species activate the slow force response to stretch in feline myocardium

PubMed Central

Caldiz, Claudia I; Garciarena, Carolina D; Dulce, Raúl A; Novaretto, Leonardo P; Yeves, Alejandra M; Ennis, Irene L; Cingolani, Horacio E; Chiappe de Cingolani, Gladys; Pérez, Néstor G

2007-01-01

When the length of the myocardium is increased, a biphasic response to stretch occurs involving an initial rapid increase in force followed by a delayed slow increase called the slow force response (SFR). Confirming previous findings involving angiotensin II in the SFR, it was blunted by AT1 receptor blockade (losartan). The SFR was accompanied by an increase in reactive oxygen species (ROS) of ∼30% and in intracellular Na+ concentration ([Na+]i) of ∼2.5 mmol l−1 over basal detected by H2DCFDA and SBFI fluorescence, respectively. Abolition of ROS by 2-mercapto-propionyl-glycine (MPG) and EUK8 suppressed the increase in [Na+]i and the SFR, which were also blunted by Na+/H+ exchanger (NHE-1) inhibition (HOE642). NADPH oxidase inhibition (apocynin or DPI) or blockade of the ATP-sensitive mitochondrial potassium channels (5HD or glybenclamide) suppressed both the SFR and the increase in [Na+]i after stretch, suggesting that endogenous angiotensin II activated NADPH oxidase leading to ROS release by the ATP-sensitive mitochondrial potassium channels, which promoted NHE-1 activation. Supporting the notion of ROS-mediated NHE-1 activation, stretch increased the ERK1/2 and p90rsk kinases phosphorylation, effect that was cancelled by losartan. In agreement, the SFR was cancelled by inhibiting the ERK1/2 signalling pathway with PD98059. Angiotensin II at a dose that mimics the SFR (1 nmol l−1) induced an increase in ·O2− production of ∼30–40% detected by lucigenin in cardiac slices, an effect that was blunted by losartan, MPG, apocynin, 5HD and glybenclamide. Taken together the data suggest a pivotal role of mitochondrial ROS in the genesis of the SFR to stretch. PMID:17823205

[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

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.

Ebselen exerts antifungal activity by regulating glutathione (GSH) and reactive oxygen species (ROS) production in fungal cells.

PubMed

Thangamani, Shankar; Eldesouky, Hassan E; Mohammad, Haroon; Pascuzzi, Pete E; Avramova, Larisa; Hazbun, Tony R; Seleem, Mohamed N

2017-01-01

Ebselen, an organoselenium compound and a clinically safe molecule has been reported to possess potent antifungal activity, but its antifungal mechanism of action and in vivo antifungal activity remain unclear. The antifungal effect of ebselen was tested against Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, Cryptococcus neoformans, and C. gattii clinical isolates. Chemogenomic profiling and biochemical assays were employed to identify the antifungal target of ebselen. Ebselen's antifungal activity in vivo was investigated in a Caenorhabditis elegans animal model. Ebselen exhibits potent antifungal activity against both Candida spp. and Cryptococcus spp., at concentrations ranging from 0.5 to 2μg/ml. Ebselen rapidly eradicates a high fungal inoculum within 2h of treatment. Investigation of the drug's antifungal mechanism of action indicates that ebselen depletes intracellular glutathione (GSH) levels, leading to increased production of reactive oxygen species (ROS), and thereby disturbs the redox homeostasis in fungal cells. Examination of ebselen's in vivo antifungal activity in two Caenorhabditis elegans models of infection demonstrate that ebselen is superior to conventional antifungal drugs (fluconazole, flucytosine and amphotericin) in reducing Candida and Cryptococcus fungal load. Ebselen possesses potent antifungal activity against clinically relevant isolates of both Candida and Cryptococcus by regulating GSH and ROS production. The potent in vivo antifungal activity of ebselen supports further investigation for repurposing it for use as an antifungal agent. The present study shows that ebselen targets glutathione and also support that glutathione as a potential target for antifungal drug development. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

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.

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

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

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.

Ferrocenes as potential chemotherapeutic drugs: Synthesis, cytotoxic activity, reactive oxygen species production and micronucleus assay

PubMed Central

Pérez, Wanda I.; Soto, Yarelys; Ortíz, Carmen; Matta, Jaime; Meléndez, Enrique

2014-01-01

Three new ferrocene complexes were synthesized with 4-(1H-pyrrol-1-yl)phenol group appended to one of the Cp ring. These are: 1,1′-4-(1H-pyrrol-1-yl)phenyl ferrocenedicarboxylate, (“Fc-(CO2-Ph-4-Py)2”), 1,4-(1H-pyrrol-1-yl)phenyl, 1′-carboxyl ferrocenecarboxylate (“Fc-(CO2-Ph-4-Py)CO2H”) and 4-(1H-pyrrol-1-yl)phenyl ferroceneacetylate (“Fc-CH2CO2-Ph-4-Py”). The new species were characterized by standard analytical methods. Cyclic voltammetry experiments showed that Fc-CH2CO2-Ph-4-Py has redox potential very similar to the Fc/Fc+ redox couple whereas Fc-(CO2-Ph-4-Py)2 and Fc-(CO2-Ph-4-Py)CO2H have redox potentials of over 400 mV higher than Fc/Fc+ redox couple. The in vitro studies on Fc-(CO2-Ph-4-Py)2 and Fc-(CO2-Ph-4-Py)CO2H revealed that these two compounds have moderate anti-proliferative activity on MCF-7 breast cancer cell line. In contrast Fc-CH2CO2-Ph-4-Py which displayed low anti-proliferative activity. In the HT-29 colon cancer cell line, the new species showed low anti-proliferaive activity. Cytokinesis-block micronucleus assay (CBMN) was performed on these ferrocenes and it was determined they induce micronucleus formation on binucleated cells and moderate genotoxic effects on the MCF-7 breast cancer cell line. There is a correlation between the IC50 values of the ferrocenes and the amount of micronucleus formation activity on binucleated cells and the reactive oxygen species (ROS) production on MCF-7 cell line. PMID:25555734

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.

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

Transparent electrical conducting films by activated reactive evaporation

DOEpatents

Bunshah, R.; Nath, P.

1982-06-22

Process and apparatus for producing transparent electrical conducting thin films by activated reactive evaporation is disclosed. Thin films of low melting point metals and alloys, such as indium oxide and indium oxide doped with tin, are produced by physical vapor deposition. The metal or alloy is vaporized by electrical resistance heating in a vacuum chamber, oxygen and an inert gas such as argon are introduced into the chamber, and vapor and gas are ionized by a beam of low energy electrons in a reaction zone between the resistance heater and the substrate. There is a reaction between the ionized oxygen and the metal vapor resulting in the metal oxide which deposits on the substrate as a thin film which is ready for use without requiring post deposition heat treatment. 1 fig.

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.

Hydroxychavicol, a Piper betle leaf component, induces apoptosis of CML cells through mitochondrial reactive oxygen species-dependent JNK and endothelial nitric oxide synthase activation and overrides imatinib resistance.

PubMed

Chakraborty, Jayashree B; Mahato, Sanjit K; Joshi, Kalpana; Shinde, Vaibhav; Rakshit, Srabanti; Biswas, Nabendu; Choudhury Mukherjee, Indrani; Mandal, Labanya; Ganguly, Dipyaman; Chowdhury, Avik A; Chaudhuri, Jaydeep; Paul, Kausik; Pal, Bikas C; Vinayagam, Jayaraman; Pal, Churala; Manna, Anirban; Jaisankar, Parasuraman; Chaudhuri, Utpal; Konar, Aditya; Roy, Siddhartha; Bandyopadhyay, Santu

2012-01-01

Alcoholic extract of Piper betle (Piper betle L.) leaves was recently found to induce apoptosis of CML cells expressing wild type and mutated Bcr-Abl with imatinib resistance phenotype. Hydroxy-chavicol (HCH), a constituent of the alcoholic extract of Piper betle leaves, was evaluated for anti-CML activity. Here, we report that HCH and its analogues induce killing of primary cells in CML patients and leukemic cell lines expressing wild type and mutated Bcr-Abl, including the T315I mutation, with minimal toxicity to normal human peripheral blood mononuclear cells. HCH causes early but transient increase of mitochondria-derived reactive oxygen species. Reactive oxygen species-dependent persistent activation of JNK leads to an increase in endothelial nitric oxide synthase-mediated nitric oxide generation. This causes loss of mitochondrial membrane potential, release of cytochrome c from mitochondria, cleavage of caspase 9, 3 and poly-adenosine diphosphate-ribose polymerase leading to apoptosis. One HCH analogue was also effective in vivo in SCID mice against grafts expressing the T315I mutation, although to a lesser extent than grafts expressing wild type Bcr-Abl, without showing significant bodyweight loss. Our data describe the role of JNK-dependent endothelial nitric oxide synthase-mediated nitric oxide for anti-CML activity of HCH and this molecule merits further testing in pre-clinical and clinical settings. © 2011 Japanese Cancer Association.

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...

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

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.

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

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

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

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

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.

Reactive oxygen species activate differentiation gene transcription of acute myeloid leukemia cells via the JNK/c-JUN signaling pathway.

PubMed

Lam, Chung Fan; Yeung, Hoi Ting; Lam, Yuk Man; Ng, Ray Kit

2018-05-01

Reactive oxygen species (ROS) and altered cellular redox status are associated with many malignancies. Acute myeloid leukemia (AML) cells are maintained at immature state by differentiation blockade, which involves deregulation of transcription factors in myeloid differentiation. AML cells can be induced to differentiate by phorbol-12-myristate-13-acetate (PMA), which possesses pro-oxidative activity. However, the signaling events mediated by ROS in the activation of transcriptional program during AML differentiation has not been fully elucidated. Here, we investigated AML cell differentiation by treatment with PMA and ROS scavenger N-acetyl-l-cysteine (NAC). We observed elevation of intracellular ROS level in the PMA-treated AML cells, which correlated with differentiated cell morphology and increased CD11b + mature cell population. The effect of PMA can be abolished by NAC co-treatment, supporting the involvement of ROS in the process. Moreover, we demonstrated that short ROS elevation mediated cell cycle arrest, but failed to activate myeloid gene transcription; whereas prolonged ROS elevation activated JNK/c-JUN signaling pathway. Inhibition of JNK suppressed the expression of key myeloid transcriptional regulators c-JUN, SPI-1 and MAFB, and prevented AML cells from undergoing terminal differentiation. These findings provide new insights into the crucial role of JNK/c-Jun signaling pathway in the activation of transcriptional program during ROS-mediated AML differentiation. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Pentagalloyl glucose increases elastin deposition, decreases reactive oxygen species and matrix metalloproteinase activity in pulmonary fibroblasts under inflammatory conditions.

PubMed

Parasaram, Vaideesh; Nosoudi, Nasim; Chowdhury, Aniqa; Vyavahare, Naren

2018-04-30

Emphysema is characterized by degradation of lung alveoli that leads to poor airflow in lungs. Irreversible elastic fiber degradation by matrix metalloproteinases (MMPs) and reactive oxygen species (ROS) activity leads to loss of elasticity and drives the progression of this disease. We investigated if a polyphenol, pentagalloyl glucose (PGG) can increase elastin production in pulmonary fibroblasts. We also studied the effect of PGG treatment in reducing MMP activity and ROS levels in cells. We exposed rat pulmonary fibroblasts to two different types of inflammatory environments i.e., tumor necrosis factor-α (TNF-α) and cigarette smoke extract (CSE) to mimic the disease. Parameters like lysyl oxidase (LOX) and elastin gene expression, MMP-9 activity in the medium, lysyl oxidase (LOX) activity and ROS levels were studied to assess the effect of PGG on pulmonary fibroblasts. CSE inhibited lysyl oxidase (LOX) enzyme activity that resulted in a decreased elastin formation. Similarly, TNF-α treated cells showed less elastin in the cell layers. Both these agents caused increase in MMP activity and ROS levels in cells. However, when supplemented with PGG treatment along with these two inflammatory agents, we saw a significant increase in elastin deposition, reduction in both MMP activity and ROS levels. Thus PGG, which has anti-inflammatory, anti-oxidant properties coupled with its ability to aid in elastic fiber formation, can be a multifunctional drug to potentially arrest the progression of emphysema. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Pancreatic two P domain K+ channels TALK-1 and TALK-2 are activated by nitric oxide and reactive oxygen species

PubMed Central

Duprat, F; Girard, C; Jarretou, G; Lazdunski, M

2005-01-01

This study firstly shows with in situ hybridization on human pancreas that TALK-1 and TALK-2, two members of the 2P domain potassium channel (K2P) family, are highly and specifically expressed in the exocrine pancreas and absent in Langherans islets. On the contrary, expression of TASK-2 in mouse pancreas is found both in the exocrine pancreas and in the Langherans islets. This study also shows that TALK-1 and TALK-2 channels, expressed in Xenopus oocytes, are strongly and specifically activated by nitric oxide (obtained with a mixture of sodium nitroprussate (SNP) and dithiothreitol (DTT)), superoxide anion (obtained with xanthine and xanthine oxidase) and singlet oxygen (obtained upon photoactivation of rose bengal, and with chloramine T). Other nitric oxide and reactive oxygen species (NOS and ROS) donors, as well as reducing conditions were found to be ineffective on TALK-1, TALK-2 and TASK-2 (sin-1, angeli's salt, SNP alone, tBHP, H2O2, and DTT). These results suggest that, in the exocrine pancreas, specific members of the NOS and ROS families could act as endogenous modulators of TALK channels with a role in normal secretion as well as in disease states such as acute pancreatitis and apoptosis. PMID:15513946

Chemical properties and reactive oxygen and nitrogen species quenching activities of dry sugar-amino acid maillard reaction mixtures exposed to baking temperatures.

PubMed

Chen, Xiu-Min; Liang, Ningjian; Kitts, David D

2015-10-01

Maillard reaction products (MRPs) derived from 10 different, dry sugar-amino acid reaction model systems were examined for changes in color index (E), sugar loss, and formation of α-dicarbonyl compounds; the changes were correlated with relative activities to quench both reactive oxygen (ROS) and reactive nitrogen (RNS) species. Reducing sugars, xylose, ribose, fructose, glucose, and non-reducing sucrose were reacted with glycine (Xyl-Gly, Rib-Gly, Fru-Gly, Glc-Gly, and Suc-Gly), or lysine (Xyl-Lys, Rib-Lys, Fru-Lys, Glc-Lys, and Suc-Lys), respectively, at temperatures of 150°C and 180°C for time periods ranging from 5 to 60min. ROS quenching capacity was negatively correlated with color index (E) (r=-0.604, P<0.001), and positively correlated with sugar loss (r=0.567, P<0.001). MRPs also exhibited activity to quench RNS as assessed by nitric oxide (NO) inhibition in differentiated Caco-2 cells that were induced with interferon-γ (IFN-γ) and phorbol ester (PMA) cocktail. We also showed a correlation between RNS and color index, sugar loss, and ROS quenching activities for MR mixtures that were heated for a short time (e.g. 10min) at 150°C. MRP quenching of ROS was largely influenced by sugar type, whereas, RNS quenching was dependent more so on the interaction between reactants and reaction conditions used to generate MRPs. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effect of mineral trioxide aggregate on phagocytic activity and production of reactive oxygen, nitrogen species and arginase activity by M1 and M2 macrophages.

PubMed

Rezende, T M B; Vieira, L Q; Cardoso, F P; Oliveira, R R; de Oliveira Mendes, S T; Jorge, M L R; Ribeiro Sobrinho, A P

2007-08-01

To assess the influence of co-culture with mineral trioxide aggregate (MTA) on phagocytosis and the production of reactive oxygen intermediates (ROI) and nitrogen (NO) species and the arginase activity by M1 and M2 peritoneal macrophages. Cellular viability, adherence and phagocytosis of Saccharomyces boulardii were assayed in the presence of MTA. Macrophages were stimulated with zymosan for ROI assays and with Fusobacterium nucleatum and Peptostreptococcus anaerobius and IFN-gamma for NO production and arginase activity, when in contact with capillaries containing MTA. Data were analysed by T, anova, Kruskall-Wallis and Mann-Whitney tests. M2 macrophages displayed greater cellular viability in polypropylene tubes, greater ability to ingest yeast and smaller production of ROI and higher arginase activity when compared with M1 macrophages. Both macrophages, M1 and M2, presented similar cell adherence and NO production. The addition of bacterial preparations to macrophages interfered with NO and arginase productions. MTA did not interfere with any of the parameters measured. Phagocytosis and the ability of the two macrophage subtypes to eliminate microbes were not affected by MTA.

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

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...

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

NADPH oxidase activity and reactive oxygen species production in brain and kidney of adult male hypertensive Ren-2 transgenic rats.

PubMed

Vokurková, M; Rauchová, H; Řezáčová, L; Vaněčková, I; Zicha, J

2015-01-01

Hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play an important role in brain control of blood pressure (BP). One of the important mechanisms involved in the pathogenesis of hypertension is the elevation of reactive oxygen species (ROS) production by nicotine adenine dinucleotide phosphate (NADPH) oxidase. The aim of our present study was to investigate NADPH oxidase-mediated superoxide (O(2)(-)) production and to search for the signs of lipid peroxidation in hypothalamus and medulla oblongata as well as in renal medulla and cortex of hypertensive male rats transgenic for the murine Ren-2 renin gene (Ren-2 TGR) and their age-matched normotensive controls - Hannover Sprague Dawley rats (HanSD). We found no difference in the activity of NADPH oxidase measured as a lucigenin-mediated O(2)(-) production in the hypothalamus and medulla oblongata. However, we observed significantly elevated NADPH oxidase in both renal cortex and medulla of Ren-2 TGR compared with HanSD. Losartan (LOS) treatment (10 mg/kg body weight/day) for 2 months (Ren-2 TGR+LOS) did not change NADPH oxidase-dependent O(2)(-) production in the kidney. We detected significantly elevated indirect markers of lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS) in Ren-2 TGR, while they were significantly decreased in Ren-2 TGR+LOS. In conclusion, the present study shows increased NADPH oxidase activities in renal cortex and medulla with significantly increased TBARS in renal cortex. No significant changes of NADPH oxidase and markers of lipid peroxidation were detected in the studied brain regions.

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.

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

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.

Pigment epithelium-derived factor stimulates skeletal muscle glycolytic activity through NADPH oxidase-dependent reactive oxygen species production.

PubMed

Carnagarin, Revathy; Carlessi, Rodrigo; Newsholme, Philip; Dharmarajan, Arun M; Dass, Crispin R

2016-09-01

Pigment epithelium-derived factor is a multifunctional serpin implicated in insulin resistance in metabolic disorders. Recent evidence suggests that exposure of peripheral tissues such as skeletal muscle to PEDF has profound metabolic consequences with predisposition towards chronic conditions such as obesity, type 2 diabetes, metabolic syndrome and polycystic ovarian syndrome. Chronic inflammation shifts muscle metabolism towards increased glycolysis and decreased oxidative metabolism. In the present study, we demonstrate a novel effect of PEDF on cellular metabolism in mouse cell line (C2C12) and human primary skeletal muscle cells. PEDF addition to skeletal muscle cells induced enhanced phospholipase A2 activity. This was accompanied with increased production of reactive oxygen species in a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent manner that triggered a shift towards a more glycolytic phenotype. Extracellular flux analysis and glucose consumption assays demonstrated that PEDF treatment resulted in enhanced glycolysis but did not change mitochondrial respiration. Our results demonstrate that skeletal muscle cells express a PEDF-inducible oxidant generating system that enhances glycolysis but is sensitive to antioxidants and NADPH oxidase inhibition. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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.

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

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.

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

Clear microstructure-performance relationships in Mn-containing perovskite and hexaaluminate compounds prepared by activated reactive synthesis.

PubMed

Laassiri, Said; Bion, Nicolas; Duprez, Daniel; Royer, Sébastien; Alamdari, Houshang

2014-03-07

Microstructural properties of mixed oxides play essential roles in their oxygen mobility and consequently in their catalytic performances. Two families of mixed oxides (perovskite and hexaaluminate) with different microstructural features, such as crystal size and specific surface area, were prepared using the activated reactive synthesis (ARS) method. It was shown that ARS is a flexible route to synthesize both mixed oxides with nano-scale crystal size and high specific surface area. Redox properties and oxygen mobility were found to be strongly affected by the material microstructure. Catalytic activities of hexaaluminate and perovskite materials for methane oxidation were discussed in the light of structural, redox and oxygen mobility properties.

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.

Study on the effect of reactive oxygen species-mediated oxidative stress on the activation of mitochondrial apoptosis and the tenderness of yak meat.

PubMed

Wang, Lin-Lin; Yu, Qun-Li; Han, Ling; Ma, Xiu-Li; Song, Ren-De; Zhao, Suo-Nan; Zhang, Wen-Hua

2018-04-01

This study investigated the effect of reactive oxygen species-mediated oxidative stress on activation of mitochondrial apoptosis and tenderness of yak meat during postmortem ageing. Oxidative stress degree, Ca 2+ levels, membrane permeability transition pore opening, mitochondrial membrane potential, apoptotic factors and the shear force were examined. Results showed that the ROS generated by H 2 O 2 significantly increased mitochondrial oxidative stress by decreasing the activities of superoxide dismutase, catalase and glutathione peroxidase, and increasing lipid peroxidation. Furthermore, oxidative stress enhanced Ca 2+ production and cytochrome c release, changed the levels of Bcl-2 family proteins and activated caspase-9 and -3 activities. Ultimately, oxidative stress increased the apoptosis rate and tenderness of yak meat. These observations confirmed that ROS-mediated oxidative stress participates in the activation of the apoptotic cascade reaction involving Ca 2+ and Bcl-2 family proteins. The results further suggested that ROS-mediated oxidative stress plays a significant role in meat tenderization through the mitochondrial apoptotic pathway. Copyright © 2017. Published by Elsevier Ltd.

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.

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.

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

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.

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

Contribution of transition metals in the reactive oxygen species activity of PM emissions from retrofitted heavy-duty vehicles

NASA Astrophysics Data System (ADS)

Verma, Vishal; Shafer, Martin M.; Schauer, James J.; Sioutas, Constantinos

2010-12-01

We assessed the contribution of water-soluble transition metals to the reactive oxygen species (ROS) activity of diesel exhaust particles (DEPs) from four heavy-duty vehicles in five retrofitted configurations (V-SCRT, Z-SCRT, DPX, hybrid, and school bus). A heavy-duty truck without any control device served as the baseline vehicle. Particles were collected from all vehicle-configurations on a chassis dynamometer under three driving conditions: cruise (80 km h -1), transient UDDS, and idle. A sensitive macrophage-based in vitro assay was used to determine the ROS activity of collected particles. The contribution of water-soluble transition metals in the measured activity was quantified by their removal using a Chelex ® complexation method. The study demonstrates that despite an increase in the intrinsic ROS activity (per mass basis) of exhaust PM with use of most control technologies, the overall ROS activity (expressed per km or per h) was substantially reduced for retrofitted configurations compared to the baseline vehicle. Chelex treatment of DEPs water extracts removed a substantial (≥70%) and fairly consistent fraction of the ROS activity, which ascertains the dominant role of water-soluble metals in PM-induced cellular oxidative stress. However, relatively lower removal of the activity in few vehicle-configurations (V-SCRT, DPX and school bus idle), despite a large aggregate metals removal, indicated that not all species were associated with the measured activity. A univariate regression analysis identified several transition metals (Fe, Cr, Co and Mn) as significantly correlated ( R > 0.60; p < 0.05) with the ROS activity. Multivariate linear regression model incorporating Fe, Cr and Co explained 90% of variability in ROS levels, with Fe accounting for the highest (84%) fraction of the variance.

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

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

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

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

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.

Tangeretin reduces ultraviolet B (UVB)-induced cyclooxygenase-2 expression in mouse epidermal cells by blocking mitogen-activated protein kinase (MAPK) activation and reactive oxygen species (ROS) generation.

PubMed

Yoon, Ji Hye; Lim, Tae-Gyu; Lee, Kyung Mi; Jeon, Ae Ji; Kim, Su Yeon; Lee, Ki Won

2011-01-12

The present study examined the effects of tangeretin, a polymethoxylated flavonone present in citrus fruits, on ultraviolet B (UVB)-induced cyclooxygenase-2 (COX-2) expression in JB6 P+ mouse skin epidermal cells. Tangeretin suppressed UVB-induced COX-2 expression and transactivation of nuclear factor-κB and activator protein-1 in JB6 P+ cells. Moreover, tangeretin blocked UVB-induced phosphorylation of Akt and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated protein kinase, c-Jun N-terminal kinase, and p38, and attenuated the phosphorylation of MAPK kinases 1/2, 3/6, and 4. Tangeretin also limited the endogenous generation of reactive oxygen species (ROS), thereby protecting the cells against oxidative stress. However, tangeretin did not scavenge the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and influence the nicotinamide adenine dinucleotide phosphate oxidase activity. These results suggest that the anti-inflammatory effects of tangeretin stem from its modulation of cell signaling and suppression of intracellular ROS generation. Tangeretin may have a potent chemopreventive effect in skin cancer.

Active-oxygen scavenging activity of plant extracts.

PubMed

Masaki, H; Sakaki, S; Atsumi, T; Sakurai, H

1995-01-01

To find antioxidative compounds present in plants, 65 types of plant extract were tested using the neotetrazolium method for evidence of superoxide anion-scavenging effects and 7 plant extracts were selected for further investigation. The activity of active-oxygen scavengers such as superoxide anion radicals, hydroxyl radicals, singlet oxygens and lipid peroxides in the 7 plant extracts (Aeseclus hippocastanum L., Hamamelis virginiana L. Polygonum cuspidatum Sieb., Quercus robur L., Rosemarinous officinalis L., Salvia officinalis L. and Sanguisorba officinalis L.) was examined in detail by both ESR spin-trapping and malondialdehyde generation. Furthermore, the active-oxygen scavenging activity of these plant extracts was evaluated using a murine dermal fibroblast culture system. Both Aeseclus hippocastanum L. and Hamamelis virginia L. were found to have strong active-oxygen scavenging activity of and protective activity against cell damage induced by active oxygen. Both Aeseclus hippocastanum L. and Hamamelis virginiana L. are proposed as potent plant extracts with potential application as anti-aging or anti-wrinkle material for the skin.

[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.

A novel nematode effector suppresses plant immunity by activating host reactive oxygen species-scavenging system.

PubMed

Lin, Borong; Zhuo, Kan; Chen, Shiyan; Hu, Lili; Sun, Longhua; Wang, Xiaohong; Zhang, Lian-Hui; Liao, Jinling

2016-02-01

Evidence is emerging that plant-parasitic nematodes can secrete effectors to interfere with the host immune response, but it remains unknown how these effectors can conquer host immune responses. Here, we depict a novel effector, MjTTL5, that could suppress plant immune response. Immunolocalization and transcriptional analyses showed that MjTTL5 is expressed specifically within the subventral gland of Meloidogyne javanica and up-regulated in the early parasitic stage of the nematode. Transgenic Arabidopsis lines expressing MjTTL5 were significantly more susceptible to M. javanica infection than wild-type plants, and vice versa, in planta silencing of MjTTL5 substantially increased plant resistance to M. javanica. Yeast two-hybrid, coimmunoprecipitation and bimolecular fluorescent complementation assays showed that MjTTL5 interacts specifically with Arabidopsis ferredoxin : thioredoxin reductase catalytic subunit (AtFTRc), a key component of host antioxidant system. The expression of AtFTRc is induced by the infection of M. javanica. Interaction between AtFTRc and MjTTL could drastically increase host reactive oxygen species-scavenging activity, and result in suppression of plant basal defenses and attenuation of host resistance to the nematode infection. Our results demonstrate that the host ferredoxin : thioredoxin system can be exploited cunningly by M. javanica, revealing a novel mechanism utilized by plant-parasitic nematodes to subjugate plant innate immunity and thereby promoting parasitism. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

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

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.

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.

AMPK activation by Tanshinone IIA protects neuronal cells from oxygen-glucose deprivation

PubMed Central

Weng, Yingfeng; Lin, Jixian; Liu, Hui; Wu, Hui; Yan, Zhimin; Zhao, Jing

2018-01-01

The current study tested the potential neuroprotective function of Tanshinone IIA (ThIIA) in neuronal cells with oxygen-glucose deprivation (ODG) and re-oxygenation (OGDR). In SH-SY5Y neuronal cells and primary murine cortical neurons, ThIIA pre-treatment attenuated OGDR-induced viability reduction and apoptosis. Further, OGDR-induced mitochondrial depolarization, reactive oxygen species production, lipid peroxidation and DNA damages in neuronal cells were significantly attenuated by ThIIA. ThIIA activated AMP-activated protein kinase (AMPK) signaling, which was essential for neuroprotection against OGDR. AMPKα1 knockdown or complete knockout in SH-SY5Y cells abolished ThIIA-induced AMPK activation and neuroprotection against OGDR. Further studies found that ThIIA up-regulated microRNA-135b to downregulate the AMPK phosphatase Ppm1e. Notably, knockdown of Ppm1e by targeted shRNA or forced microRNA-135b expression also activated AMPK and protected SH-SY5Y cells from OGDR. Together, AMPK activation by ThIIA protects neuronal cells from OGDR. microRNA-135b-mediated silence of Ppm1e could be the key mechanism of AMPK activation by ThIIA. PMID:29435120

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.

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.

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

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.

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.

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.

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.

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.

Granzyme B of cytotoxic T cells induces extramitochondrial reactive oxygen species production via caspase-dependent NADPH oxidase activation.

PubMed

Aguiló, Juan I; Anel, Alberto; Catalán, Elena; Sebastián, Alvaro; Acín-Pérez, Rebeca; Naval, Javier; Wallich, Reinhard; Simon, Markus M; Pardo, Julián

2010-07-01

Induction of reactive oxygen species (ROS) is a hallmark of granzyme B (gzmB)-mediated pro-apoptotic processes and target cell death. However, it is unclear to what extent the generated ROS derive from mitochondrial and/or extra-mitochondrial sources. To clarify this point, we have produced a mutant EL4 cell line, termed EL4-rho(0), which lacks mitochondrial DNA, associated with a decreased mitochondrial membrane potential and a defective ROS production through the electron transport chain of oxidative phosphorylation. When incubated with either recombinant gzmB plus streptolysin or ex vivo gzmB(+) cytotoxic T cells, EL4-rho(0) cells showed phosphatydylserine translocation, caspase 3 activation, Bak conformational change, cytochrome c release and apoptotic morphology comparable to EL4 cells. Moreover, EL4-rho(0) cells produced ROS at levels similar to EL4 under these conditions. GzmB-mediated ROS production was almost totally abolished in both cell lines by the pan-caspase inhibitor, Z-VAD-fmk. However, addition of apocynin, a specific inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, led to a significant reduction of ROS production and cell death only in EL4-rho(0) but not EL4 cells. These data suggest that gzmB-induced cell death is accompanied by a caspase-dependent pathway of extra-mitochondrial ROS production, most probably through activation of NADPH oxidase.

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.

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

[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.

Liver X receptor agonist alleviated high glucose-induced endothelial progenitor cell dysfunction via inhibition of reactive oxygen species and activation of AMP-activated protein kinase.

PubMed

Li, Xiaoxia; Song, Yimeng; Han, Yingying; Wang, Dawei; Zhu, Yi

2012-08-01

Liver X receptors (LXRs) are key regulators of cholesterol homeostasis. Synthetic LXR agonists are anti-atherogenic and anti-inflammatory. However, the effect of LXR agonists on endothelial progenitor cell (EPC) function is largely unknown. Here, we explored the effect of the LXR agonist TO901317 (TO) on EPC biology and the underlying mechanisms. Endothelial progenitor cells were cultured in mannitol or 30 mm glucose (high glucose) for 24 hours. For TO treatments, cells were pretreated with TO (10 μm) for 12 hours, then mannitol or high glucose was added for an additional 24 hours. EPCs function, reactive oxygen species (ROS) release, and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) were analyzed. TO could restore the high glucose-impaired adhesion and migration capacity of EPCs. High glucose impaired EPC-mediated angiogenesis, and TO reversed the impairment. TO also alleviated ROS release induced by high glucose. Western blot analysis revealed that high glucose downregulated the phosphorylation of AMPK and endothelial nitric oxide synthase, which could be reversed with TO treatment. Furthermore, inhibiting AMPK activation by compound C could abolish the protective effects of TO on EPCs. TO had a protective effect on EPCs under high glucose by inhibiting ROS release and activating AMPK. © 2012 John Wiley & Sons Ltd.

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.

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.

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

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

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

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.

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

Reactive oxygen species (ROS) activity of ambient fine particles (PM2.5) measured in Seoul, Korea.

PubMed

Park, Jieun; Park, Eun Ha; Schauer, James J; Yi, Seung-Muk; Heo, Jongbae

2018-05-16

Substantial increase in level of particulate matter has raised concerns in South Korea recently. Ambient particulate matter is classified as Group I carcinogen (IARC, 2013) and multiple epidemiological studies has demonstrated adverse health effects due to exposure of particulate matter. Fine particulate matter (PM 2.5 ) which has a diameter <2.5 μm is likely to penetrate deeply into lung and is known to be eliciting adverse health effects. A number of epidemiological studies have been conducted on adverse health effects of PM-related diseases and mortality rate, yet particulate matter (PM)-induced reactive oxygen species (ROS) activity at the cellular level has not been actively studied in Korea. This study assessed PM-induced oxidative potential by exposure of collected ambient PM 2.5 samples to the rat alveolar macrophage cell line. The characteristics of PM 2.5 in Korea were further characterized by linking chemical constituents and contributing sources to ROS. PM 2.5 mass concentration during the cold season was relatively higher than mass concentration during the warm season and chemical constituents except for Secondary Organic Carbon (SOC) and SO 4 2- which both showed similar trends in both the cold and cold seasons. The concentration of crustal elements was especially high during the cold season which can be an indication of long range transport of Asian dust. Water soluble organic carbon and water soluble transition metals (Cr and Zn) were also shown to be correlated to oxidative potential and metals such as As and V were shown to have a high contribution to ROS activity according to stepwise multiple linear regression. Principal Component Analysis (PCA) results identified six factors that can be interpreted as soil, mobile, industry, secondary inorganic aerosol, secondary organic aerosol and oil combustion. Moreover, through Principal Component Regression (PCR), industry, soil, mobile and SIA were shown to be statistically significant sources in a

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

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

Reversible amorphization and the catalytically active state of crystalline Co3O4 during oxygen evolution

PubMed Central

Bergmann, Arno; Martinez-Moreno, Elias; Teschner, Detre; Chernev, Petko; Gliech, Manuel; de Araújo, Jorge Ferreira; Reier, Tobias; Dau, Holger; Strasser, Peter

2015-01-01

Water splitting catalysed by earth-abundant materials is pivotal for global-scale production of non-fossil fuels, yet our understanding of the active catalyst structure and reactivity is still insufficient. Here we report on the structurally reversible evolution of crystalline Co3O4 electrocatalysts during oxygen evolution reaction identified using advanced in situ X-ray techniques. At electrode potentials facilitating oxygen evolution, a sub-nanometre shell of the Co3O4 is transformed into an X-ray amorphous CoOx(OH)y which comprises di-μ-oxo-bridged Co3+/4+ ions. Unlike irreversible amorphizations, here, the formation of the catalytically-active layer is reversed by re-crystallization upon return to non-catalytic electrode conditions. The Co3O4 material thus combines the stability advantages of a controlled, stable crystalline material with high catalytic activity, thanks to the structural flexibility of its active amorphous oxides. We propose that crystalline oxides may be tailored for generating reactive amorphous surface layers at catalytic potentials, just to return to their stable crystalline state under rest conditions. PMID:26456525

Reversible amorphization and the catalytically active state of crystalline Co3O4 during oxygen evolution.

PubMed

Bergmann, Arno; Martinez-Moreno, Elias; Teschner, Detre; Chernev, Petko; Gliech, Manuel; de Araújo, Jorge Ferreira; Reier, Tobias; Dau, Holger; Strasser, Peter

2015-10-12

Water splitting catalysed by earth-abundant materials is pivotal for global-scale production of non-fossil fuels, yet our understanding of the active catalyst structure and reactivity is still insufficient. Here we report on the structurally reversible evolution of crystalline Co3O4 electrocatalysts during oxygen evolution reaction identified using advanced in situ X-ray techniques. At electrode potentials facilitating oxygen evolution, a sub-nanometre shell of the Co3O4 is transformed into an X-ray amorphous CoOx(OH)y which comprises di-μ-oxo-bridged Co(3+/4+) ions. Unlike irreversible amorphizations, here, the formation of the catalytically-active layer is reversed by re-crystallization upon return to non-catalytic electrode conditions. The Co3O4 material thus combines the stability advantages of a controlled, stable crystalline material with high catalytic activity, thanks to the structural flexibility of its active amorphous oxides. We propose that crystalline oxides may be tailored for generating reactive amorphous surface layers at catalytic potentials, just to return to their stable crystalline state under rest conditions.

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

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

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.

Hesperetin Induces the Apoptosis of Gastric Cancer Cells via Activating Mitochondrial Pathway by Increasing Reactive Oxygen Species.

PubMed

Zhang, Jixiang; Wu, Dandan; Vikash; Song, Jia; Wang, Jing; Yi, Jiasheng; Dong, Weiguo

2015-10-01

Hesperetin, has been shown to exert biological activities on various types of human cancers. However, few related studies on gastric cancer are available. In this study, we sought to investigate the effect of hesperetin on gastric cancer and clarify its specific mechanism. Cell Counting Kit-8, 2',7'-dichlorofluorescin diacetate, JC-1, Hoechst 33258 staining, and western bolt were used to detect cell viability, levels of intracellular reactive oxygen species (ROS), changes in mitochondrial membrane potential (△ψ m), cell apoptosis, and expressions of mitochondrial pathway proteins, respectively. Meanwhile, xenograft tumor models in nude mice were made to evaluate the effect of hesperetin on gastric cancer in vivo. Compared with the control group, the proliferation of gastric cancer cells in hesperetin groups was significantly inhibited (P < 0.05), and dose- and time-dependent effects were observed. Pretreatment with H2O2 (1 mM) or N-acetyl-L-cysteine (5 mM) enhanced or attenuated the hesperetin-induced inhibition of cell viability (P < 0.05). Percentages of apoptotic cells, levels of intracellular ROS, and △ψ m varied with the dose and treatment time of hesperetin (P < 0.05), and hesperetin caused an increase in the levels of AIF, Apaf-1, Cyt C, caspase-3, caspase-9, and Bax and a decrease in Bcl-2 levels (P < 0.05). Meanwhile, hesperetin significantly inhibited the growth of xenograft tumors (P < 0.05). Our study suggests that hesperetin could inhibit the proliferation and induce the apoptosis of gastric cancer cells via activating the mitochondrial pathway by increasing the ROS.

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...

ABNORMAL INFLORESCENCE MERISTEM1 Functions in Salicylic Acid Biosynthesis to Maintain Proper Reactive Oxygen Species Levels for Root Meristem Activity in Rice

PubMed Central

Zhao, Hongyu; Ruan, Wenyuan; Deng, Minjuan; Wang, Fang; Peng, Jinrong; Luo, Jie; Chen, Zhixiang

2017-01-01

Root meristem activity determines root growth and root architecture and consequently affects water and nutrient uptake in plants. However, our knowledge about the regulation of root meristem activity in crop plants is very limited. Here, we report the isolation and characterization of a short root mutant in rice (Oryza sativa) with reduced root meristem activity. This root growth defect is caused by a mutation in ABNORMAL INFLORESCENCE MERISTEM1 (AIM1), which encodes a 3-hydroxyacyl-CoA dehydrogenase, an enzyme involved in β-oxidation. The reduced root meristem activity of aim1 results from reduced salicylic acid (SA) levels and can be rescued by SA application. Furthermore, reduced SA levels are associated with reduced levels of reactive oxygen species (ROS) in aim1, likely due to increased expression of redox and ROS-scavenging-related genes, whose increased expression is (at least in part) caused by reduced expression of the SA-inducible transcriptional repressors WRKY62 and WRKY76. Like SA, ROS application substantially increased root length and root meristem activity in aim1. These results suggest that AIM1 is required for root growth in rice due to its critical role in SA biosynthesis: SA maintains root meristem activity through promoting ROS accumulation by inducing the activity of WRKY transcriptional repressors, which repress the expression of redox and ROS-scavenging genes. PMID:28298519

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

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

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.

Associations between Viral Infection History Symptoms, Granulocyte Reactive Oxygen Species Activity, and Active Rheumatoid Arthritis Disease in Untreated Women at Onset: Results from a Longitudinal Cohort Study of Tatarstan Women

PubMed Central

Arleevskaya, Marina I.; Shafigullina, Albina Z.; Filina, Yulia V.; Lemerle, Julie; Renaudineau, Yves

2017-01-01

To evaluate the effects of infectious episodes at early stages of rheumatoid arthritis (eRA) development, 59 untreated eRA patients, 77 first-degree relatives, from a longitudinal Tatarstan women cohort, were included, and compared to 67 healthy women without rheumatoid arthritis (RA) in their family history. At inclusion, informations were collected regarding both the type and incidence of infectious symptom episodes in the preceding year, and granulocyte reactive oxygen species (ROS) were studied at the basal level and after stimulation with serum-treated zymosan (STZ). In the eRA group, clinical [disease activity score (DAS28), health assessment questionnaire] and biological parameters associated with inflammation (erythrocyte sedimentation rate, C-reactive protein) or with RA [rheumatoid factor, anticyclic citrullinated peptide (anti-CCP2) antibodies] were evaluated. An elevated incidence of infection events in the previous year characterized the eRA and relative groups. In addition, a history of herpes simplex virus (HSV) episodes was associated with disease activity, while an elevated incidence of anti-CCP2 autoantibody characterized eRA patients with a history of viral upper respiratory tract infection symptoms (V-URI). Granulocyte ROS activity in eRA patients was quantitatively [STZ peak and its area under the curve (AUC)] and qualitatively (STZ time of peak) altered, positively correlated with disease activity, and parameters were associated with viral symptoms including HSV exacerbation/recurrence, and V-URI. In conclusion, our study provides arguments to consider a history of increased viral infection symptoms in RA at the early stage and such involvement needs to be studied further. PMID:29259607

Associations between Viral Infection History Symptoms, Granulocyte Reactive Oxygen Species Activity, and Active Rheumatoid Arthritis Disease in Untreated Women at Onset: Results from a Longitudinal Cohort Study of Tatarstan Women.

PubMed

Arleevskaya, Marina I; Shafigullina, Albina Z; Filina, Yulia V; Lemerle, Julie; Renaudineau, Yves

2017-01-01

To evaluate the effects of infectious episodes at early stages of rheumatoid arthritis (eRA) development, 59 untreated eRA patients, 77 first-degree relatives, from a longitudinal Tatarstan women cohort, were included, and compared to 67 healthy women without rheumatoid arthritis (RA) in their family history. At inclusion, informations were collected regarding both the type and incidence of infectious symptom episodes in the preceding year, and granulocyte reactive oxygen species (ROS) were studied at the basal level and after stimulation with serum-treated zymosan (STZ). In the eRA group, clinical [disease activity score (DAS28), health assessment questionnaire] and biological parameters associated with inflammation (erythrocyte sedimentation rate, C-reactive protein) or with RA [rheumatoid factor, anticyclic citrullinated peptide (anti-CCP2) antibodies] were evaluated. An elevated incidence of infection events in the previous year characterized the eRA and relative groups. In addition, a history of herpes simplex virus (HSV) episodes was associated with disease activity, while an elevated incidence of anti-CCP2 autoantibody characterized eRA patients with a history of viral upper respiratory tract infection symptoms (V-URI). Granulocyte ROS activity in eRA patients was quantitatively [STZ peak and its area under the curve (AUC)] and qualitatively (STZ time of peak) altered, positively correlated with disease activity, and parameters were associated with viral symptoms including HSV exacerbation/recurrence, and V-URI. In conclusion, our study provides arguments to consider a history of increased viral infection symptoms in RA at the early stage and such involvement needs to be studied further.

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

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.

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.

Negative Regulation of Leptin-induced Reactive Oxygen Species (ROS) Formation by Cannabinoid CB1 Receptor Activation in Hypothalamic Neurons.

PubMed

Palomba, Letizia; Silvestri, Cristoforo; Imperatore, Roberta; Morello, Giovanna; Piscitelli, Fabiana; Martella, Andrea; Cristino, Luigia; Di Marzo, Vincenzo

2015-05-29

The adipocyte-derived, anorectic hormone leptin was recently shown to owe part of its regulatory effects on appetite-regulating hypothalamic neuropeptides to the elevation of reactive oxygen species (ROS) levels in arcuate nucleus (ARC) neurons. Leptin is also known to exert a negative regulation on hypothalamic endocannabinoid levels and hence on cannabinoid CB1 receptor activity. Here we investigated the possibility of a negative regulation by CB1 receptors of leptin-mediated ROS formation in the ARC. Through pharmacological and molecular biology experiments we report data showing that leptin-induced ROS accumulation is 1) blunted by arachidonyl-2'-chloroethylamide (ACEA) in a CB1-dependent manner in both the mouse hypothalamic cell line mHypoE-N41 and ARC neuron primary cultures, 2) likewise blocked by a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, troglitazone, in a manner inhibited by T0070907, a PPAR-γ antagonist that also inhibited the ACEA effect on leptin, 3) blunted under conditions of increased endocannabinoid tone due to either pharmacological or genetic inhibition of endocannabinoid degradation in mHypoE-N41 and primary ARC neuronal cultures from MAGL(-/-) mice, respectively, and 4) associated with reduction of both PPAR-γ and catalase activity, which are reversed by both ACEA and troglitazone. We conclude that CB1 activation reverses leptin-induced ROS formation and hence possibly some of the ROS-mediated effects of the hormone by preventing PPAR-γ inhibition by leptin, with subsequent increase of catalase activity. This mechanism might underlie in part CB1 orexigenic actions under physiopathological conditions accompanied by elevated hypothalamic endocannabinoid levels. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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.

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

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.

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

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.

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

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.

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.

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.

Manganese-Oxygen Intermediates in O-O Bond Activation and Hydrogen-Atom Transfer Reactions.

PubMed

Rice, Derek B; Massie, Allyssa A; Jackson, Timothy A

2017-11-21

Biological systems capitalize on the redox versatility of manganese to perform reactions involving dioxygen and its derivatives superoxide, hydrogen peroxide, and water. The reactions of manganese enzymes influence both human health and the global energy cycle. Important examples include the detoxification of reactive oxygen species by manganese superoxide dismutase, biosynthesis by manganese ribonucleotide reductase and manganese lipoxygenase, and water splitting by the oxygen-evolving complex of photosystem II. Although these enzymes perform very different reactions and employ structurally distinct active sites, manganese intermediates with peroxo, hydroxo, and oxo ligation are commonly proposed in catalytic mechanisms. These intermediates are also postulated in mechanisms of synthetic manganese oxidation catalysts, which are of interest due to the earth abundance of manganese. In this Account, we describe our recent efforts toward understanding O-O bond activation pathways of Mn III -peroxo adducts and hydrogen-atom transfer reactivity of Mn IV -oxo and Mn III -hydroxo complexes. In biological and synthetic catalysts, peroxomanganese intermediates are commonly proposed to decay by either Mn-O or O-O cleavage pathways, although it is often unclear how the local coordination environment influences the decay mechanism. To address this matter, we generated a variety of Mn III -peroxo adducts with varied ligand environments. Using parallel-mode EPR and Mn K-edge X-ray absorption techniques, the decay pathway of one Mn III -peroxo complex bearing a bulky macrocylic ligand was investigated. Unlike many Mn III -peroxo model complexes that decay to oxo-bridged-Mn III Mn IV dimers, decay of this Mn III -peroxo adduct yielded mononuclear Mn III -hydroxo and Mn IV -oxo products, potentially resulting from O-O bond activation of the Mn III -peroxo unit. These results highlight the role of ligand sterics in promoting the formation of mononuclear products and mark an important

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

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.

The Correlation Between Small Dense LDL and Reactive Oxygen Metabolites in a Physical Activity Intervention in Hyperlipidemic Subjects.

PubMed

Kotani, Kazuhiko; Tsuzaki, Kokoro; Sakane, Naoki; Taniguchi, Nobuyuki

2012-06-01

Small dense low-density lipoprotein (sdLDL), which has a small LDL particle size with a greater susceptibility to oxidation, is considered a risk marker for cardiovascular disease (CVD). The diacron reactive oxygen metabolites (d-ROMs) have recently been introduced as a clinically useful oxidative stress-related marker. Physical activity can reduce the CVD risk. The present study investigated the correlation between the changes of the mean LDL particle size and the oxidative stress status, as assessed by the d-ROMs, in a physical activity intervention in hyperlipidemic subjects. We performed a 6-month intervention study of 30 hyperlipidemic subjects (12 male/18 female, mean age 64 years), focusing on a moderate physical activity increase. The clinical data, including the atherosclerotic risk factors besides the mean LDL particle size measured with the gel electrophoresis and the d-ROMs, were evaluated pre- and post-intervention. The mean LDL particle size was significantly larger in the post-intervention than in the pre-intervention evaluation (26.9 ± 0.3 (SD) vs. 27.1 ± 0.4 nm, P < 0.01), while the d-ROMs levels were significantly reduced in the post-intervention period compared to those at pre-intervention (319 ± 77 vs. 290 ± 73 U. Carr., P < 0.05). A stepwise multiple regression analysis revealed that there was an independent, significant and inverse correlation between the pre- and post-intervention changes of the d-ROMs and the mean LDL particle size (β = -0.55, P < 0.01). The intervention study suggests that sdLDL and oxidative stress can concomitantly affect the risk of developing CVD and that both factors can improve by even a moderate increase in physical activity among hyperlipidemic subjects.

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.

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

ABNORMAL INFLORESCENCE MERISTEM1 Functions in Salicylic Acid Biosynthesis to Maintain Proper Reactive Oxygen Species Levels for Root Meristem Activity in Rice.

PubMed

Xu, Lei; Zhao, Hongyu; Ruan, Wenyuan; Deng, Minjuan; Wang, Fang; Peng, Jinrong; Luo, Jie; Chen, Zhixiang; Yi, Keke

2017-03-01

Root meristem activity determines root growth and root architecture and consequently affects water and nutrient uptake in plants. However, our knowledge about the regulation of root meristem activity in crop plants is very limited. Here, we report the isolation and characterization of a short root mutant in rice ( Oryza sativa ) with reduced root meristem activity. This root growth defect is caused by a mutation in ABNORMAL INFLORESCENCE MERISTEM1 ( AIM1 ), which encodes a 3-hydroxyacyl-CoA dehydrogenase, an enzyme involved in β-oxidation. The reduced root meristem activity of aim1 results from reduced salicylic acid (SA) levels and can be rescued by SA application. Furthermore, reduced SA levels are associated with reduced levels of reactive oxygen species (ROS) in aim1 , likely due to increased expression of redox and ROS-scavenging-related genes, whose increased expression is (at least in part) caused by reduced expression of the SA-inducible transcriptional repressors WRKY62 and WRKY76. Like SA, ROS application substantially increased root length and root meristem activity in aim1 These results suggest that AIM1 is required for root growth in rice due to its critical role in SA biosynthesis: SA maintains root meristem activity through promoting ROS accumulation by inducing the activity of WRKY transcriptional repressors, which repress the expression of redox and ROS-scavenging genes. © 2017 American Society of Plant Biologists. All rights reserved.

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.

Chemical manipulation of oxygen vacancy and antibacterial activity in ZnO.

PubMed

V, Lakshmi Prasanna; Vijayaraghavan, Rajagopalan

2017-08-01

Pure and doped ZnO (cation and anion doping) compositions have been designed in order to manipulate oxygen vacancy and antibacterial activity of ZnO. In this connection, we have synthesized and characterized micron sized ZnO, N doped micron sized ZnO, nano ZnO, nano Na and La doped ZnO. The intrinsic vacancies in pure ZnO and the vacancies created by N and Na doping in ZnO have been confirmed by X-ray Photoelectron Spectroscopy(XPS) and Photoluminiscence Spectroscopy(PL). Reactive oxygen species (ROS) such as hydroxyl radicals, superoxide radicals and H 2 O 2 responsible for antibacterial activity have been estimated by PL, UV-Vis spectroscopy and KMnO 4 titrations respectively. It was found that nano Na doped ZnO releases highest amount of ROS followed by nano ZnO, micron N doped ZnO while micron ZnO releases the least amount of ROS. The concentration of vacancies follows the same sequence. This illustrates directly the correlation between ROS and oxygen vacancy in well designed pure and doped ZnO. For the first time, material design in terms of cation doping and anion doping to tune oxygen vacancies has been carried out. Interaction energy (E g ), between the bacteria and nanoparticles has been calculated based on Extended Derjaguin-Landau-Verwey-Overbeek (EDLVO) theory and is correlated with antibacterial activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of oxygen availability on the activities of ammonia-oxidizing archaea.

PubMed

Qin, Wei; Meinhardt, Kelley A; Moffett, James W; Devol, Allan H; Virginia Armbrust, E; Ingalls, Anitra E; Stahl, David A

2017-06-01

Recent studies point to the importance of oxygen (O 2 ) in controlling the distribution and activity of marine ammonia-oxidizing archaea (AOA), one of the most abundant prokaryotes in the ocean. The AOA are associated with regions of low O 2 tension in oceanic oxygen minimum zones (OMZs), and O 2 availability is suggested to influence their production of the ozone-depleting greenhouse gas nitrous oxide (N 2 O). We show that marine AOA available in pure culture sustain high ammonia oxidation activity at low μM O 2 concentrations, characteristic of suboxic regions of OMZs (<10 µM O 2 ), and that atmospheric concentrations of O 2 may inhibit the growth of some environmental populations. We quantify the increasing N 2 O production by marine AOA with decreasing O 2 tensions, consistent with the plausibility of an AOA contribution to the accumulation of N 2 O at the oxic-anoxic redox boundaries of OMZs. Variable sensitivity to peroxide also suggests that endogenous or exogenous reactive oxygen species are of importance in determining the environmental distribution of some populations. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

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...

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

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.

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

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.

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

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.

Hexavalent chromium targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent caspase-3 activation in L-02 hepatocytes.

PubMed

Xiao, Fang; Li, Yanhong; Dai, Lu; Deng, Yuanyuan; Zou, Yue; Li, Peng; Yang, Yuan; Zhong, Caigao

2012-09-01

Hexavalent chromium [Cr(VI)], which is used for various industrial applications, such as leather tanning and chroming, can cause a number of human diseases including inflammation and cancer. Cr(VI) exposure leads to severe damage to the liver, but the mechanisms involved in Cr(VI)-mediated toxicity in the liver are unclear. The present study provides evidence that Cr(VI) enhances reactive oxygen species (ROS) accumulation by inhibiting the mitochondrial respiratory chain complex (MRCC) I. Cr(VI) did not affect the expression levels of antioxidative proteins such as superoxide dismutase (SOD), catalase and thioredoxin (Trx), indicating that the antioxidative system was not involved in Cr(VI)-induced ROS accumulation. We found that ROS mediated caspase-3 activation partially depends on the downregulation of the heat shock protein (HSP) 70 and 90. In order to confirm our hypothesis that ROS plays a key role in Cr(VI)-mediated cytotoxicity, we used N-acetylcysteine (NAC) to inhibit the accumulation of ROS. NAC successfully blocked the inhibition of HSP70 and HSP90 as well as the activation of caspase-3, suggesting that ROS is essential in Cr(VI)-induced caspase-3 activation. By applying different MRCC substrates as electron donors, we also confirmed that Cr(VI) could accept the electrons leaked from MRCC I and the reduction occurs at MRCC I. In conclusion, the present study demonstrates that Cr(VI) induces ROS-dependent caspase-3 activation by inhibiting MRCC I activity, and MRCC I has been identified as a new target and a new mechanism for the apoptosis-inducing activity displayed by Cr(VI).

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.

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.

Direct evidence for tumor necrosis factor-induced mitochondrial reactive oxygen intermediates and their involvement in cytotoxicity.

PubMed Central

Goossens, V; Grooten, J; De Vos, K; Fiers, W

1995-01-01

Tumor necrosis factor (TNF) is selectively cytotoxic to some types of tumor cells in vitro and exerts antitumor activity in vivo. Reactive oxygen intermediates (ROIs) have been implicated in the direct cytotoxic activity of TNF. By using confocal microscopy, flow cytometry, and the ROI-specific probe dihydrorhodamine 123, we directly demonstrate that intracellular ROIs are formed after TNF stimulation. These ROIs are observed exclusively under conditions where cells are sensitive to the cytotoxic activity of TNF, suggesting a direct link between both phenomena. ROI scavengers, such as butylated hydroxyanisole, effectively blocked the formation of free radicals and arrested the cytotoxic response, confirming that the observed ROIs are cytocidal. The mitochondrial glutathione system scavenges the major part of the produced ROIs, an activity that could be blocked by diethyl maleate; under these conditions, TNF-induced ROIs detectable by dihydrorhodamine 123 oxidation were 5- to 20-fold higher. Images Fig. 1 Fig. 4 PMID:7667254

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.

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...

Identification of carbon-encapsulated iron nanoparticles as active species in non-precious metal oxygen reduction catalysts

PubMed Central

Varnell, Jason A.; Tse, Edmund C. M.; Schulz, Charles E.; Fister, Tim T.; Haasch, Richard T.; Timoshenko, Janis; Frenkel, Anatoly I.; Gewirth, Andrew A.

2016-01-01

The widespread use of fuel cells is currently limited by the lack of efficient and cost-effective catalysts for the oxygen reduction reaction. Iron-based non-precious metal catalysts exhibit promising activity and stability, as an alternative to state-of-the-art platinum catalysts. However, the identity of the active species in non-precious metal catalysts remains elusive, impeding the development of new catalysts. Here we demonstrate the reversible deactivation and reactivation of an iron-based non-precious metal oxygen reduction catalyst achieved using high-temperature gas-phase chlorine and hydrogen treatments. In addition, we observe a decrease in catalyst heterogeneity following treatment with chlorine and hydrogen, using Mössbauer and X-ray absorption spectroscopy. Our study reveals that protected sites adjacent to iron nanoparticles are responsible for the observed activity and stability of the catalyst. These findings may allow for the design and synthesis of enhanced non-precious metal oxygen reduction catalysts with a higher density of active sites. PMID:27538720

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...

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.

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.

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.

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.

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...

Structural elucidation and antioxidant activity of lignin isolated from rice straw and alkali‑oxygen black liquor.

PubMed

Jiang, Bo; Zhang, Yu; Gu, Lihui; Wu, Wenjuan; Zhao, Huifang; Jin, Yongcan

2018-05-17

Alkali‑oxygen cooking of lignocellulose offers lignin many structural properties and bioactivities for biorefinery. In this work, milled wood lignin (MWL) and alkali‑oxygen lignin (AOL) were isolated from rice straw and alkali‑oxygen black liquor, respectively. The lignin structure was characterized by spectroscopy and wet chemistry. Antioxidant activity of lignins was assessed by DPPH·and ABTS scavenging ability assay. Results showed the oxidization and condensation of lignin occurred during alkali‑oxygen cooking. The p-hydroxyphenyl was more easily removed from rice straw than guaiacyl and syringyl units. The ester or ether linkages derived from hydroxycynnamic acids, and the main interunit linkages, i.e. β-O-4' bonds, were mostly cleaved. Lignin-xylan complex had high reactivity under alkali‑oxygen condition. Tricin, incorporated into lignin, was detected in MWL but was absent in AOL. Nitrobenzene oxidation showed MWL can well represent the protolignin of rice straw, and the products yield decreased dramatically after alkali‑oxygen cooking. AOL had higher radical scavenging ability than MWL indicating alkali‑oxygen cooking was an effective pathway for the enhancement of antioxidant activity of lignin. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Reactive Oxygen Species-Mediated Loss of Synaptic Akt1 Signaling Leads to Deficient Activity-Dependent Protein Translation Early in Alzheimer's Disease.

PubMed

Ahmad, Faraz; Singh, Kunal; Das, Debajyoti; Gowaikar, Ruturaj; Shaw, Eisha; Ramachandran, Arathy; Rupanagudi, Khader Valli; Kommaddi, Reddy Peera; Bennett, David A; Ravindranath, Vijayalakshmi

2017-12-01

Synaptic deficits are known to underlie the cognitive dysfunction seen in Alzheimer's disease (AD). Generation of reactive oxygen species (ROS) by β-amyloid has also been implicated in AD pathogenesis. However, it is unclear whether ROS contributes to synaptic dysfunction seen in AD pathogenesis and, therefore, we examined whether altered redox signaling could contribute to synaptic deficits in AD. Activity dependent but not basal translation was impaired in synaptoneurosomes from 1-month old presymptomatic APP Swe /PS1ΔE9 (APP/PS1) mice, and this deficit was sustained till middle age (MA, 9-10 months). ROS generation leads to oxidative modification of Akt1 in the synapse and consequent reduction in Akt1-mechanistic target of rapamycin (mTOR) signaling, leading to deficiency in activity-dependent protein translation. Moreover, we found a similar loss of activity-dependent protein translation in synaptoneurosomes from postmortem AD brains. Loss of activity-dependent protein translation occurs presymptomatically early in the pathogenesis of AD. This is caused by ROS-mediated loss of pAkt1, leading to reduced synaptic Akt1-mTOR signaling and is rescued by overexpression of Akt1. ROS-mediated damage is restricted to the synaptosomes, indicating selectivity. We demonstrate that ROS-mediated oxidative modification of Akt1 contributes to synaptic dysfunction in AD, seen as loss of activity-dependent protein translation that is essential for synaptic plasticity and maintenance. Therapeutic strategies promoting Akt1-mTOR signaling at synapses may provide novel target(s) for disease-modifying therapy in AD. Antioxid. Redox Signal. 27, 1269-1280.

5-Hydroxytryptamine1A receptor/Gibetagamma stimulates mitogen-activated protein kinase via NAD(P)H oxidase and reactive oxygen species upstream of src in chinese hamster ovary fibroblasts.

PubMed Central

Mukhin, Y V; Garnovskaya, M N; Collinsworth, G; Grewal, J S; Pendergrass, D; Nagai, T; Pinckney, S; Greene, E L; Raymond, J R

2000-01-01

The hypothesis of this work is that the 'serotonin' or 5-hydroxytryptamine (5-HT)(1A) receptor, which activates the extracellular signal-regulated kinase (ERK) through a G(i)betagamma-mediated pathway, does so through the intermediate actions of reactive oxygen species (ROS). Five criteria were shown to support a key role for ROS in the activation of ERK by the 5-HT(1A) receptor. (1) Antioxidants inhibit activation of ERK by 5-HT. (2) Application of cysteine-reactive oxidant molecules activates ERK. (3) The 5-HT(1A) receptor alters cellular redox properties, and generates both superoxide and hydrogen peroxide. (4) A specific ROS-producing enzyme [NAD(P)H oxidase] is involved in the activation of ERK. (5) There is specificity both in the effects of various chemical oxidizers, and in the putative location of the ROS in the ERK activation pathway. We propose that NAD(P)H oxidase is located in the ERK activation pathway stimulated by the transfected 5-HT(1A) receptor in Chinese hamster ovary (CHO) cells downstream of G(i)betagamma subunits and upstream of or at the level of the non-receptor tyrosine kinase, Src. Moreover, these experiments provide confirmation that the transfected human 5-HT(1A) receptor induces the production of ROS (superoxide and hydrogen peroxide) in CHO cells, and support the possibility that an NAD(P)H oxidase-like enzyme might be involved in the 5-HT-mediated generation of both superoxide and hydrogen peroxide. PMID:10727402

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

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

Humic acid effect on catalase activity and the generation of reactive oxygen species in corn (Zea mays).

PubMed

Cordeiro, Flávio Couto; Santa-Catarina, Claudete; Silveira, Vanildo; de Souza, Sonia Regina

2011-01-01

Humic acids (HAs) have positive effects on plant physiology, but the molecular mechanisms underlying these events are only partially understood. The induction of root growth and emission of lateral roots (LRs) promoted by exogenous auxin is a natural phenomenon. Exogenous auxins are also associated with HA. Gas nitric oxide (NO) is a secondary messenger produced endogenously in plants. It is associated with metabolic events dependent on auxin. With the application of auxin, NO production is significantly increased, resulting in positive effects on plant physiology. Thus it is possible to evaluate the beneficial effects of the application of HA as an effect of auxin. To investigate the effects of HA the parameters of root growth, Zea mays was studied by evaluating the application of 3 mM C L⁻¹ of HA extracted from Oxisol and 100 µM SNP (sodium nitroprusside) and the NO donor, subject to two N-NO₃⁻, high dose (5.0 mM N-NO₃⁻) and low dose (5.0 mM N-NO₃⁻). Treatments with HA and NO were positively increased, regardless of the N-NO₃⁻ taken, as assessed by fresh weight and dry root, issue of LRs. The effects were more pronounced in the treatment with a lower dose of N-NO₃⁻. Detection of reactive oxygen species (ROS) in vivo and catalase activity were evaluated; these tests were associated with root growth. Under application of the bioactive substances tested, detection of ROS and catalase activity increased, especially in treatments with lower doses of N-NO₃⁻. The results of this experiment indicate that the effects of HA are dependent on ROS generation, which act as a messenger that induces root growth and the emission of LRs.

Activation of apurinic/apyrimidinic endonuclease in human cells by reactive oxygen species and its correlation with their adaptive response to genotoxicity of free radicals

PubMed Central

Ramana, Chilakamarti V.; Boldogh, Istvan; Izumi, Tadahide; Mitra, Sankar

1998-01-01

Apurinic/apyrimidinic (AP) endonuclease (APE; EC 4.2.99.18) plays a central role in repair of DNA damage due to reactive oxygen species (ROS) because its DNA 3′-phosphoesterase activity removes 3′ blocking groups in DNA that are generated by DNA glycosylase/AP-lyases during removal of oxidized bases and by direct ROS reaction with DNA. The major human APE (APE-1) gene is activated selectively by sublethal levels of a variety of ROS and ROS generators, including ionizing radiation, but not by other genotoxicants—e.g., UV light and alkylating agents. Increased expression of APE mRNA and protein was observed both in the HeLa S3 tumor line and in WI 38 primary fibroblasts, and it was accompanied by translocation of the endonuclease to the nucleus. ROS-treated cells showed a significant increase in resistance to the cytotoxicity of such ROS generators as H2O2 and bleomycin, but not to UV light. This “adaptive response” appears to result from enhanced repair of cytotoxic DNA lesions due to an increased activity of APE-1, which may be limiting in the base excision repair process for ROS-induced toxic lesions. PMID:9560228

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

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.

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.

Cold induces reactive oxygen species production and activation of the NF-kappa B response in endothelial cells and inflammation in vivo.

PubMed

Awad, E M; Khan, S Y; Sokolikova, B; Brunner, P M; Olcaydu, D; Wojta, J; Breuss, J M; Uhrin, P

2013-09-01

Organs intended for transplantation are generally stored in the cold for better preservation of their function. However, following transplantation and reperfusion, the microvasculature of transplanted organs often proves to be activated. Extensive leukocyte adhesion and microthrombus formation contribute to failure of the transplanted organ. In this study we analyzed cold-induced changes to the activation status of cultured endothelial cells, possibly contributing to organ failure. We exposed human umbilical vein endothelial cells (HUVECs) to temperatures below 37 °C (mostly to 8 °C) for 30 min and upon rewarming to 37 °C kept incubating them for up to 24 h. We also in vivo locally exposed mice to cold. The exposure to low temperatures induced, in HUVECs, expression of the prothrombotic factors plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF) and of the inflammatory adhesion molecules, E-selectin, intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Furthermore, upon rewarming for 30 min, we detected activation of the inflammatory NF-κB pathway, as measured by transient NF-κB translocation to the nucleus and IκBα degradation. Using butylated hydroxytoluene (BHT), a scavenger of reactive oxygen species (ROS), we further demonstrated that cold-induced NF-κB activation depends on ROS production. Local exposure to cold also, in vivo, induced ROS production and ICAM-1 expression and resulted in leukocyte infiltration. Our results point to a causative link between ROS production and NF-κB activation, suppression of which had been shown to be beneficial during hypothermic storage and subsequent rewarming of organs for transplantation. © 2013 International Society on Thrombosis and Haemostasis.

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.

Reactive oxygen species play a role in muscle wasting during thyrotoxicosis.

PubMed

Bernardes, Sara Santos; Guarnier, Flávia Alessandra; Marinello, Poliana Camila; Armani, André; Simão, Andréa Name Colado; Cecchini, Rubens; Cecchini, Alessandra Lourenço

2014-09-01

The role of reactive oxygen species (ROS) in muscle protein hydrolysis and protein oxidation in thyrotoxicosis has not been explored. This study indicates that ROS play a role in skeletal muscle wasting pathways in thyrotoxicosis. Two experimental groups (rats) were treated for 5 days with either 3,3',5-triiodothyronine (HT) or HT with α-tocopherol (HT + αT). Two controls were used, vehicle (Control) and control treated with αT (Control + αT). Serum T3, peritoneal fat, serum glycerol, muscle and body weight, temperature, mitochondrial metabolism (cytochrome c oxidase activity), oxidative stress parameters and proteolytic activities were examined. High body temperature induced by HT returned to normal when animals were treated with αT, although total body and muscle weight did not. An increase in lipolysis was observed in the HT + αT group, as peritoneal fat decreased significantly together with an increase in serum glycerol. GSH, GSSG and total radical-trapping antioxidant parameter (TRAP) decreased and catalase activity increased in the HT group. The glutathione redox ratio was higher in HT + αT than in both HT and Control + αT groups. Carbonyl proteins, AOPP, mitochondrial and chymotrypsin-like proteolytic activities were higher in the HT group than in the Control. HT treatment with αT restored mitochondrial metabolism, TRAP, carbonyl protein, chymotrypsin-like activity and AOPP to the level as that of the Control + αT. Calpain activity was lower in the HT + αT group than in HT and Control + αT and superoxide dismutase (SOD) activity was higher in the HT + αT group than in the Control + αT. Although αT did not reverse muscle loss, ROS was involved in proteolysis to some degree.

Activation of CD40 with platelet derived CD154 promotes reactive oxygen species dependent death of human hepatocytes during hypoxia and reoxygenation.

PubMed

Bhogal, Ricky H; Weston, Christopher J; Curbishley, Stuart M; Adams, David H; Afford, Simon C

2012-01-01

Hypoxia and hypoxia-reoxygenation (H-R) are pathogenic factors in many liver diseases that lead to hepatocyte death as a result of reactive oxygen species (ROS) accumulation. The tumor necrosis factor super-family member CD154 can also induce hepatocyte apoptosis via activation of its receptor CD40 and induction of autocrine/paracrine Fas Ligand/CD178 but the relationship between CD40 activation, ROS generation and apoptosis is poorly understood. We hypothesised that CD40 activation and ROS accumulation act synergistically to drive human hepatocyte apoptosis. Human hepatocytes were isolated from liver tissue and exposed to an in vitro model of hypoxia and H-R in the presence or absence of CD154 and/or various inhibitors. Hepatocyte ROS production, apoptosis and necrosis were determined by labelling cells with 2',7'-dichlorofluorescin, Annexin-V and 7-AAD respectively in a three-colour reporter flow cytometry assay. Exposure of human hepatocytes to recombinant CD154 or platelet-derived soluble CD154 augments ROS accumulation during H-R resulting in NADPH oxidase-dependent apoptosis and necrosis. The inhibition of c-Jun N-terminal Kinase and p38 attenuated CD154-mediated apoptosis but not necrosis. CD154-mediated apoptosis of hepatocytes involves ROS generation that is amplified during hypoxia-reoxygenation. This finding provides a molecular mechanism to explain the role of platelets in hepatocyte death during ischemia-reperfusion injury.

Activation of a Ca2+-dependent cation conductance with properties of TRPM2 by reactive oxygen species in lens epithelial cells.

PubMed

Keckeis, Susanne; Wernecke, Laura; Salchow, Daniel J; Reichhart, Nadine; Strauß, Olaf

2017-08-01

Ion channels are crucial for maintenance of ion homeostasis and transparency of the lens. The lens epithelium is the metabolically and electrophysiologically active cell type providing nutrients, ions and water to the lens fiber cells. Ca 2+ -dependent non-selective ion channels seem to play an important role for ion homeostasis. The aim of the study was to identify and characterize Ca 2+ - and reactive oxygen species (ROS)-dependent non-selective cation channels in human lens epithelial cells. RT-PCR revealed gene expression of the Ca 2+ -activated non-selective cation channels TRPC3, TRPM2, TRPM4 and Ano6 in both primary lens epithelial cells and the cell line HLE-B3, whereas TRPM5 mRNA was only found in HLE-B3 cells. Using whole-cell patch-clamp technique, ionomycin evoked non-selective cation currents with linear current-voltage relationship in both cell types. The current was decreased by flufenamic acid (FFA), 2-APB, 9-phenanthrol and miconazole, but insensitive to DIDS, ruthenium red, and intracellularly applied spermine. H 2 O 2 evoked a comparable current, abolished by FFA. TRPM2 protein expression in HLE-B3 cells was confirmed by means of immunocytochemistry and western blot. In summary, we conclude that lens epithelial cells functionally express Ca 2+ - and H 2 O 2 -activated non-selective cation channels with properties of TRPM2. Copyright © 2017. Published by Elsevier Ltd.

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.

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.

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.

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

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

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.

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.

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.

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.

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.

Reactive oxygen species stabilize hypoxia-inducible factor-1 alpha protein and stimulate transcriptional activity via AMP-activated protein kinase in DU145 human prostate cancer cells.

PubMed

Jung, Seung-Nam; Yang, Woo Kyeom; Kim, Joungmok; Kim, Hak Su; Kim, Eun Ju; Yun, Hee; Park, Hyunsung; Kim, Sung Soo; Choe, Wonchae; Kang, Insug; Ha, Joohun

2008-04-01

Hypoxia-inducible factor (HIF-1) plays a central role in the cellular adaptive response to hypoxic conditions, which are closely related to pathophysiological conditions, such as cancer. Although reactive oxygen species (ROS) have been implicated in the regulation of hypoxic and non-hypoxic induction of HIF-1 under various conditions, the role of ROS is quite controversial, and the mechanism underlying the HIF-1 regulation by ROS is not completely understood yet. Here, we investigated the biochemical mechanism for the ROS-induced HIF-1 by revealing a novel role of adenosine monophosphate-activated protein kinase (AMPK) and the upstream signal components. AMPK plays an essential role as energy-sensor under adenosine triphosphate-deprived conditions. Here we report that ROS induced by a direct application of H(2)O(2) and menadione to DU145 human prostate carcinoma resulted in accumulation of HIF-1alpha protein by attenuation of its degradation and activation of its transcriptional activity in an AMPK-dependent manner. By way of contrast, AMPK was required only for the transcriptional activity of HIF-1 under hypoxic condition, revealing a differential role of AMPK in these two stimuli. Furthermore, our data show that inhibition of AMPK enhances HIF-1alpha ubiquitination under ROS condition. Finally, we show that the regulation of HIF-1 by AMPK in response to ROS is under the control of c-Jun N-terminal kinase and Janus kinase 2 pathways. Collectively, our findings identify AMPK as a key determinant of HIF-1 functions in response to ROS and its possible role in the sophisticated HIF-1 regulatory mechanisms.

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.

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

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.

Reactive Oxygen Species-Mediated Loss of Synaptic Akt1 Signaling Leads to Deficient Activity-Dependent Protein Translation Early in Alzheimer's Disease

PubMed Central

Ahmad, Faraz; Singh, Kunal; Das, Debajyoti; Gowaikar, Ruturaj; Shaw, Eisha; Ramachandran, Arathy; Rupanagudi, Khader Valli; Kommaddi, Reddy Peera; Bennett, David A.

2017-01-01

Abstract Aims: Synaptic deficits are known to underlie the cognitive dysfunction seen in Alzheimer's disease (AD). Generation of reactive oxygen species (ROS) by β-amyloid has also been implicated in AD pathogenesis. However, it is unclear whether ROS contributes to synaptic dysfunction seen in AD pathogenesis and, therefore, we examined whether altered redox signaling could contribute to synaptic deficits in AD. Results: Activity dependent but not basal translation was impaired in synaptoneurosomes from 1-month old presymptomatic APPSwe/PS1ΔE9 (APP/PS1) mice, and this deficit was sustained till middle age (MA, 9–10 months). ROS generation leads to oxidative modification of Akt1 in the synapse and consequent reduction in Akt1-mechanistic target of rapamycin (mTOR) signaling, leading to deficiency in activity-dependent protein translation. Moreover, we found a similar loss of activity-dependent protein translation in synaptoneurosomes from postmortem AD brains. Innovation: Loss of activity-dependent protein translation occurs presymptomatically early in the pathogenesis of AD. This is caused by ROS-mediated loss of pAkt1, leading to reduced synaptic Akt1-mTOR signaling and is rescued by overexpression of Akt1. ROS-mediated damage is restricted to the synaptosomes, indicating selectivity. Conclusions: We demonstrate that ROS-mediated oxidative modification of Akt1 contributes to synaptic dysfunction in AD, seen as loss of activity-dependent protein translation that is essential for synaptic plasticity and maintenance. Therapeutic strategies promoting Akt1-mTOR signaling at synapses may provide novel target(s) for disease-modifying therapy in AD. Antioxid. Redox Signal. 27, 1269–1280. PMID:28264587

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

Synergistic anticandidal activity of pure polyphenol curcumin I in combination with azoles and polyenes generates reactive oxygen species leading to apoptosis.

PubMed

Sharma, Monika; Manoharlal, Raman; Negi, Arvind Singh; Prasad, Rajendra

2010-08-01

We have shown previously that pure polyphenol curcumin I (CUR-I) shows antifungal activity against Candida species. By employing the chequerboard method, filter disc and time-kill assays, in the present study we demonstrate that CUR-I at non-antifungal concentration interacts synergistically with azoles and polyenes. For this, pure polyphenol CUR-I was tested for synergy with five azole and two polyene drugs - fluconazole (FLC), miconazole, ketoconazole (KTC), itraconazole (ITR), voriconazole (VRC), nystatin (NYS) and amphotericin B (AMB) - against 21 clinical isolates of Candida albicans with reduced antifungal sensitivity, as well as a drug-sensitive laboratory strain. Notably, there was a 10-35-fold drop in the MIC(80) values of the drugs when CUR-I was used in combination with azoles and polyenes, with fractional inhibitory concentration index (FICI) values ranging between 0.09 and 0.5. Interestingly, the synergistic effect of CUR-I with FLC and AMB was associated with the accumulation of reactive oxygen species, which could be reversed by the addition of an antioxidant such as ascorbic acid. Furthermore, the combination of CUR-I and FLC/AMB triggered apoptosis that could also be reversed by ascorbic acid. We provide the first evidence that pure CUR-I in combination with azoles and polyenes represents a novel therapeutic strategy to improve the activity of common antifungals.

Evaluation of the Catalytic Activity and Cytotoxicity of Palladium Nanocubes. The Role of Oxygen

PubMed Central

Dahal, Eshan; Curtiss, Jessica; Subedi, Deepak; Chen, Gen; Houston, Jessica P.; Smirnov, Sergei

2015-01-01

Recently it has been reported that palladium nanocubes (PdNC) are capable of generating singlet oxygen without photo-excitation simply via chemisorption of molecular oxygen on its surface. Such a trait would make PdNC a highly versatile catalyst suitable in organic synthesis and a Reactive Oxygen Species (ROS) inducing cancer treatment reagent. Here we thoroughly investigated the catalytic activity of PdNC with respect to their ability to produce singlet oxygen and to oxidize 3,5,3′,5′-tetramethyl-benzidine (TMB), as well as, analyzed the cytotoxic properties of PdNC on HeLa cells. Our findings showed no evidence of singlet oxygen production by PdNC. The nanocubes’ activity is not necessarily linked to activation of oxygen. The oxidation of substrate on PdNC can be a first step followed by PdNC regeneration with oxygen or other oxidant. The catalytic activity of PdNC towards oxidation of TMB is very high and shows direct two-electrons oxidation when the surface of PdNC is clean and the ratio of TMB/PdNC is not very high. Sequential one electron oxidation is observed when the pristine quality of PdNC surface is compromised by serum or uncontrolled impurities and/or the ratio of TMB/PdNC is high. Clean PdNC in serum-free media efficiently induce apoptosis of HeLa cells. It is the primary route of cell death and is associated with hyperpolarization of mitochondria, contrary to a common mitochondrial depolarization initiated by ROS. Again, the effects are very sensitive to how well the pristine surface of PdNC is preserved, suggesting that PdNC can be used as an apoptosis inducing agent but only with appropriate drug delivery system. PMID:25886644

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...

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

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

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

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.

Calcium Signaling Is Involved in Cadmium-Induced Neuronal Apoptosis via Induction of Reactive Oxygen Species and Activation of MAPK/mTOR Network

PubMed Central

Luo, Yan; Chen, Zi; Liu, Lei; Zhou, Hongyu; Chen, Wenxing; Shen, Tao; Han, Xiuzhen; Chen, Long; Huang, Shile

2011-01-01

Cadmium (Cd), a toxic environmental contaminant, induces oxidative stress, leading to neurodegenerative disorders. Recently we have demonstrated that Cd induces neuronal apoptosis in part by activation of the mitogen-activated protein kineses (MAPK) and mammalian target of rapamycin (mTOR) pathways. However, the underlying mechanism remains elusive. Here we show that Cd elevated intracellular calcium ion ([Ca2+]i) level in PC12, SH-SY5Y cells and primary murine neurons. BAPTA/AM, an intracellular Ca2+ chelator, abolished Cd-induced [Ca2+]i elevation, and blocked Cd activation of MAKPs including extracellular signal-regulated kinase 1/2 (Erk1/2), c-Jun N-terminal kinase (JNK) and p38, and mTOR-mediated signaling pathways, as well as cell death. Pretreatment with the extracellular Ca2+ chelator EGTA also prevented Cd-induced [Ca2+]i elevation, MAPK/mTOR activation, as well as cell death, suggesting that Cd-induced extracellular Ca2+ influx plays a critical role in contributing to neuronal apoptosis. In addition, calmodulin (CaM) antagonist trifluoperazine (TFP) or silencing CaM attenuated the effects of Cd on MAPK/mTOR activation and cell death. Furthermore, Cd-induced [Ca2+]i elevation or CaM activation resulted in induction of reactive oxygen species (ROS). Pretreatment with BAPTA/AM, EGTA or TFP attenuated Cd-induced ROS and cleavage of caspase-3 in the neuronal cells. Our findings indicate that Cd elevates [Ca2+]i, which induces ROS and activates MAPK and mTOR pathways, leading to neuronal apoptosis. The results suggest that regulation of Cd-disrupted [Ca2+]i homeostasis may be a new strategy for prevention of Cd-induced neurodegenerative diseases. PMID:21544200

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.

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

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.

Activation of p47phox as a Mechanism of Bupivacaine-Induced Burst Production of Reactive Oxygen Species and Neural Toxicity.

PubMed

Li, Yu-Jie; Zhao, Wei; Yu, Xu-Jiao; Li, Feng-Xian; Liu, Zi-Ting; Li, Le; Xu, Shi-Yuan

2017-01-01

Bupivacaine has been shown to induce neurotoxicity through inducing excessive reactive oxygen species (ROS), but the underlying mechanism remains unclear. NOX2 is one of the most important sources of ROS in the nervous system, and its activation requires the membrane translocation of subunit p47phox. However, the role of p47phox in bupivacaine-induced neurotoxicity has not been explored. In our in vitro study, cultured human SH-SY5Y neuroblastoma cells were treated with 1.5 mM bupivacaine to induce neurotoxicity. Membrane translocation of p47phox was assessed by measuring the cytosol/membrane ratio of p47phox. The effects of the NOX inhibitor VAS2870 and p47phox-siRNA on bupivacaine-induced neurotoxicity were investigated. Furthermore, the effect of VAS2870 on bupivacaine-induced neurotoxicity was assessed in vivo in rats. All these changes were reversed by pretreatment with VAS2870 or transfection with p47phox-siRNA in SH-SY5Y cells. Similarly, pretreatment with VAS2870 attenuated bupivacaine-induced neuronal toxicity in rats. It is concluded that enhancing p47phox membrane translocation is a major mechanism whereby bupivacaine induced neurotoxicity and that pretreatment with VAS2870 or local p47phox gene knockdown attenuated bupivacaine-induced neuronal cell injury.

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

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.

Benzo(a)pyrene quinones increase cell proliferation, generate reactive oxygen species, and transactivate the epidermal growth factor receptor in breast epithelial cells.

PubMed

Burdick, Andrew D; Davis, John W; Liu, Ke Jian; Hudson, Laurie G; Shi, Honglian; Monske, Michael L; Burchiel, Scott W

2003-11-15

Polycyclic aromatic hydrocarbons, such as benzo(a)pyrene (BaP), are known mammary carcinogens in rodents and may be involved in human breast cancer. We have reported previously that BaP can mimic growth factor signaling and increase cell proliferation in primary human mammary epithelial cells and the human mammary epithelial cell line MCF-10A. BaP-quinones (BPQs) are important metabolites of BaP that have been associated with the production of reactive oxygen species. Using a model of epidermal growth factor (EGF) withdrawal in MCF-10A, we hypothesized that production of reactive oxygen species by BPQs could lead to the activation of the EGF receptor (EGFR). Here, we demonstrate through electron paramagnetic resonance spectroscopy and flow cytometry that 1,6-BPQ and 3,6-BPQ produce superoxide anion and hydrogen peroxide in MCF-10A cells. Furthermore, we show that BPQs increase EGFR, Akt, and extracellular signal-regulated kinase activity, leading to increased cell number in the absence of EGF. The BPQ-induced EGFR activity and associated cell proliferation were attenuated by the EGFR inhibitor AG1478, as well as by the antioxidant N-acetyl cysteine. Overexpression of catalase, but not Cu/Zn superoxide dismutase, reduced the extent of BPQ-dependent increased cell number and EGFR pathway activation. Moreover, the direct treatment of MCF-10A cells with hydrogen peroxide enhanced EGFR, Akt, and extracellular-regulated kinase phosphorylation that could be similarly inhibited by AG1478, N-acetyl cysteine, and catalase. Taken together, these data indicate that BPQs, through the generation of hydrogen peroxide, activate the EGFR in MCF-10A cells, leading to increased cell number under EGF-deficient conditions.

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

Oxygen-Promoted Methane Activation on Copper

DOE PAGES

Niu, Tianchao; Jiang, Zhao; Zhu, Yaguang; ...

2017-11-01

The role of oxygen in the activation of C–H bonds in methane on clean and oxygen-precovered Cu(111) and Cu 2O(111) surfaces was studied with combined in situ near-ambient-pressure scanning tunneling microscopy and X-ray photoelectron spectroscopy. Activation of methane at 300 K and “moderate pressures” was only observed on oxygen-precovered Cu(111) surfaces. Density functional theory calculations reveal that the lowest activation energy barrier of C–H on Cu(111) in the presence of chemisorbed oxygen is related to a two-active-site, four-centered mechanism, which stabilizes the required transition-state intermediate by dipole–dipole attraction of O–H and Cu–CH 3 species. Furthermore, the C–H bond activation barriersmore » on Cu 2O(111) surfaces are large due to the weak stabilization of H and CH 3 fragments.« less

Oxygen-Promoted Methane Activation on Copper

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

Niu, Tianchao; Jiang, Zhao; Zhu, Yaguang

The role of oxygen in the activation of C–H bonds in methane on clean and oxygen-precovered Cu(111) and Cu 2O(111) surfaces was studied with combined in situ near-ambient-pressure scanning tunneling microscopy and X-ray photoelectron spectroscopy. Activation of methane at 300 K and “moderate pressures” was only observed on oxygen-precovered Cu(111) surfaces. Density functional theory calculations reveal that the lowest activation energy barrier of C–H on Cu(111) in the presence of chemisorbed oxygen is related to a two-active-site, four-centered mechanism, which stabilizes the required transition-state intermediate by dipole–dipole attraction of O–H and Cu–CH 3 species. Furthermore, the C–H bond activation barriersmore » on Cu 2O(111) surfaces are large due to the weak stabilization of H and CH 3 fragments.« less

Green tea catechin intervention of reactive oxygen species-mediated ERK pathway activation and chronically induced breast cell carcinogenesis

PubMed Central

Rathore, Kusum; Choudhary, Shambhunath; Odoi, Agricola; Wang, Hwa-Chain R.

2012-01-01

Long-term exposure to low doses of environmental carcinogens contributes to sporadic human breast cancers. Epidemiologic and experimental studies indicate that green tea catechins (GTCs) may intervene with breast cancer development. We have been developing a chronically induced breast cell carcinogenesis model wherein we repeatedly expose non-cancerous, human breast epithelial MCF10A cells to bioachievable picomolar concentrations of environmental carcinogens, such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P), to progressively induce cellular acquisition of cancer-associated properties, as measurable end points. The model is then used as a target to identify non-cytotoxic preventive agents effective in suppression of cellular carcinogenesis. Here, we demonstrate, for the first time, a two-step strategy that initially used end points that were transiently induced by short-term exposure to NNK and B[a]P as targets to detect GTCs capable of blocking the acquisition of cancer-associated properties and subsequently used end points constantly induced by long-term exposure to carcinogens as targets to verify GTCs capable of suppressing carcinogenesis. We detected that short-term exposure to NNK and B[a]P resulted in elevation of reactive oxygen species (ROS), leading to Raf-independent extracellular signal-regulated kinase (ERK) pathway activation and subsequent induction of cell proliferation and DNA damage. These GTCs, at non-cytotoxic levels, were able to suppress chronically induced cellular carcinogenesis by blocking carcinogen-induced ROS elevation, ERK activation, cell proliferation and DNA damage in each exposure cycle. Our model may help accelerate the identification of preventive agents to intervene in carcinogenesis induced by long-term exposure to environmental carcinogens, thereby safely and effectively reducing the health risk of sporadic breast cancer. PMID:22045026

BMI-1 Mediates Estrogen-Deficiency-Induced Bone Loss by Inhibiting Reactive Oxygen Species Accumulation and T Cell Activation.

PubMed

Li, Jinbo; Wang, Qian; Yang, Renlei; Zhang, Jiaqi; Li, Xing; Zhou, Xichao; Miao, Dengshun

2017-05-01

Previous studies have shown that estrogen regulates bone homeostasis through regulatory effects on oxidative stress. However, it is unclear how estrogen deficiency triggers reactive oxygen species (ROS) accumulation. Recent studies provide evidence that the B lymphoma Mo-MLV insertion region 1 (BMI-1) plays a critical role in protection against oxidative stress and that this gene is directly regulated by estrogen via estrogen receptor (ER) at the transcriptional level. In this study, ovariectomized mice were given drinking water with/without antioxidant N-acetyl-cysteine (NAC, 1 mg/mL) supplementation, and compared with each other and with sham mice. Results showed that ovariectomy resulted in bone loss with increased osteoclast surface, increased ROS levels, T cell activation, and increased TNF and RANKL levels in serum and in CD4 T cells; NAC supplementation largely prevented these alterations. BMI-1 expression levels were dramatically downregulated in CD4 T cells from ovariectomized mice. We supplemented drinking water to BMI-1-deficient mice with/without NAC and compared them with each other and with wild-type (WT) mice. We found that BMI-1 deficiency mimicked alterations observed in ovariectomy whereas NAC supplementation reversed all alterations induced by BMI-1 deficiency. Because T cells are critical in mediating ovariectomy-induced bone loss, we further assessed whether BMI-1 overexpression in lymphocytes can protect against estrogen deficiency-induced osteoclastogenesis and bone loss by inhibiting oxidative stress, T cell activation, and RANKL production. When WT and Eμ-BMI-1 transgenic mice with BMI-1 specifically overexpressed in lymphocytes were ovariectomized and compared with each other and with WT sham mice, we found that BMI-1 overexpression in lymphocytes clearly reversed all alterations induced by ovariectomy. Results from this study indicate that estrogen deficiency downregulates BMI-1 and subsequently increases ROS, T cell activation, and

Kinetic Modeling of the Mitochondrial Energy Metabolism of Neuronal Cells: The Impact of Reduced α-Ketoglutarate Dehydrogenase Activities on ATP Production and Generation of Reactive Oxygen Species

PubMed Central

Berndt, Nikolaus; Bulik, Sascha; Holzhütter, Hermann-Georg

2012-01-01

Reduced activity of brain α-ketoglutarate dehydrogenase complex (KGDHC) occurs in a number of neurodegenerative diseases like Parkinson's disease and Alzheimer's disease. In order to quantify the relation between diminished KGDHC activity and the mitochondrial ATP generation, redox state, transmembrane potential, and generation of reactive oxygen species (ROS) by the respiratory chain (RC), we developed a detailed kinetic model. Model simulations revealed a threshold-like decline of the ATP production rate at about 60% inhibition of KGDHC accompanied by a significant increase of the mitochondrial membrane potential. By contrast, progressive inhibition of the enzyme aconitase had only little impact on these mitochondrial parameters. As KGDHC is susceptible to ROS-dependent inactivation, we also investigated the reduction state of those sites of the RC proposed to be involved in ROS production. The reduction state of all sites except one decreased with increasing degree of KGDHC inhibition suggesting an ROS-reducing effect of KGDHC inhibition. Our model underpins the important role of reduced KGDHC activity in the energetic breakdown of neuronal cells during development of neurodegenerative diseases. PMID:22719765

Antiproliferative activity of Alisol B in MDA-MB-231 cells is mediated by apoptosis, dysregulation of mitochondrial functions, cell cycle arrest and generation of reactive oxygen species.

PubMed

Zhang, Aifeng; Sheng, Yuqing; Zou, Mingchang

2017-03-01

Previous studies have demonstrated that Alisol B has inhibitory activity in cancer cells. However, the exact mechanism through which inhibition is achieved is still poorly understood. In the present study, the authors examined the effects of Alisol B in human breast cancer cells. Alisol B showed significant anticancer activity in MDA-MB-231 cells. The results demonstrated that the cytotoxicity induced by Alisol B was mediated by induction of apoptosis, decrease in mitochondrial membrane potential, cell cycle arrest, activation of caspases and accumulation of ROS (reactive oxygen species) level. Interestingly, pretreatment of cells with the general caspase inhibitor z-VAD-FMK significantly prevented Alisol B-induced apoptosis. Furthermore, western blot analysis revealed the upregulation of p-p38 and downregulation of p-AKT, p-p65 and p-mTOR. Taken together, the above results suggest that Alisol B suppresses the growth of MDA-MB-231 cells mainly through induction of apoptosis; this outcome may represent the major mechanism of Alisol B-mediated apoptosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Escherichia coli avoids high dissolved oxygen stress by activation of SoxRS and manganese-superoxide dismutase.

PubMed

Baez, Antonino; Shiloach, Joseph

2013-03-12

High concentrations of reactive oxygen species (ROS) were reported to cause oxidative stress to E. coli cells associated with reduced or inhibited growth. The high ROS concentrations described in these reports were generated by exposing the bacteria to H2O2 and superoxide-generating chemicals which are non-physiological growth conditions. However, the effect of molecular oxygen on oxidative stress response has not been evaluated. Since the use of oxygen-enriched air is a common strategy to support high density growth of E. coli, it was important to investigate the effect of high dissolved oxygen concentrations on the physiology and growth of E. coli and the way it responds to oxidative stress. To determine the effect of elevated oxygen concentrations on the growth characteristics, specific gene expression and enzyme activity in E. coli, the parental and SOD-deficient strain were evaluated when the dissolved oxygen (dO2) level was increased from 30% to 300%. No significant differences in the growth parameters were observed in the parental strain except for a temporary decrease of the respiration and acetate accumulation profile. By performing transcriptional analysis, it was determined that the parental strain responded to the oxidative stress by activating the SoxRS regulon. However, following the dO2 switch, the SOD-deficient strain activated both the SoxRS and OxyR regulons but it was unable to resume its initial growth rate. The transcriptional analysis and enzyme activity results indicated that when E. coli is exposed to dO2 shift, the superoxide stress regulator SoxRS is activated and causes the stimulation of the superoxide dismutase system. This enables the E. coli to protect itself from the poisoning effects of oxygen. The OxyR protecting system was not activated, indicating that H2O2 did not increase to stressing levels.

Escherichia coli avoids high dissolved oxygen stress by activation of SoxRS and manganese-superoxide dismutase

PubMed Central

2013-01-01

Background High concentrations of reactive oxygen species (ROS) were reported to cause oxidative stress to E. coli cells associated with reduced or inhibited growth. The high ROS concentrations described in these reports were generated by exposing the bacteria to H2O2 and superoxide-generating chemicals which are non-physiological growth conditions. However, the effect of molecular oxygen on oxidative stress response has not been evaluated. Since the use of oxygen-enriched air is a common strategy to support high density growth of E. coli, it was important to investigate the effect of high dissolved oxygen concentrations on the physiology and growth of E. coli and the way it responds to oxidative stress. Results To determine the effect of elevated oxygen concentrations on the growth characteristics, specific gene expression and enzyme activity in E. coli, the parental and SOD-deficient strain were evaluated when the dissolved oxygen (dO2) level was increased from 30% to 300%. No significant differences in the growth parameters were observed in the parental strain except for a temporary decrease of the respiration and acetate accumulation profile. By performing transcriptional analysis, it was determined that the parental strain responded to the oxidative stress by activating the SoxRS regulon. However, following the dO2 switch, the SOD-deficient strain activated both the SoxRS and OxyR regulons but it was unable to resume its initial growth rate. Conclusion The transcriptional analysis and enzyme activity results indicated that when E. coli is exposed to dO2 shift, the superoxide stress regulator SoxRS is activated and causes the stimulation of the superoxide dismutase system. This enables the E. coli to protect itself from the poisoning effects of oxygen. The OxyR protecting system was not activated, indicating that H2O2 did not increase to stressing levels. PMID:23497217

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.

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

Activation of CD40 with Platelet Derived CD154 Promotes Reactive Oxygen Species Dependent Death of Human Hepatocytes during Hypoxia and Reoxygenation

PubMed Central

Bhogal, Ricky H.; Weston, Christopher J.; Curbishley, Stuart M.; Adams, David H.; Afford, Simon C.

2012-01-01

Background Hypoxia and hypoxia-reoxygenation (H-R) are pathogenic factors in many liver diseases that lead to hepatocyte death as a result of reactive oxygen species (ROS) accumulation. The tumor necrosis factor super-family member CD154 can also induce hepatocyte apoptosis via activation of its receptor CD40 and induction of autocrine/paracrine Fas Ligand/CD178 but the relationship between CD40 activation, ROS generation and apoptosis is poorly understood. We hypothesised that CD40 activation and ROS accumulation act synergistically to drive human hepatocyte apoptosis. Methods Human hepatocytes were isolated from liver tissue and exposed to an in vitro model of hypoxia and H-R in the presence or absence of CD154 and/or various inhibitors. Hepatocyte ROS production, apoptosis and necrosis were determined by labelling cells with 2′,7′-dichlorofluorescin, Annexin-V and 7-AAD respectively in a three-colour reporter flow cytometry assay. Results Exposure of human hepatocytes to recombinant CD154 or platelet-derived soluble CD154 augments ROS accumulation during H-R resulting in NADPH oxidase-dependent apoptosis and necrosis. The inhibition of c-Jun N-terminal Kinase and p38 attenuated CD154-mediated apoptosis but not necrosis. Conclusions CD154-mediated apoptosis of hepatocytes involves ROS generation that is amplified during hypoxia-reoxygenation. This finding provides a molecular mechanism to explain the role of platelets in hepatocyte death during ischemia-reperfusion injury. PMID:22295117

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.

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

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

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

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

Reactive oxygen species trigger motoneuron death in non-cell-autonomous models of ALS through activation of c-Abl signaling.

PubMed

Rojas, Fabiola; Gonzalez, David; Cortes, Nicole; Ampuero, Estibaliz; Hernández, Diego E; Fritz, Elsa; Abarzua, Sebastián; Martinez, Alexis; Elorza, Alvaro A; Alvarez, Alejandra; Court, Felipe; van Zundert, Brigitte

2015-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which pathogenesis and death of motor neurons are triggered by non-cell-autonomous mechanisms. We showed earlier that exposing primary rat spinal cord cultures to conditioned media derived from primary mouse astrocyte conditioned media (ACM) that express human SOD1(G93A) (ACM-hSOD1(G93A)) quickly enhances Nav channel-mediated excitability and calcium influx, generates intracellular reactive oxygen species (ROS), and leads to death of motoneurons within days. Here we examined the role of mitochondrial structure and physiology and of the activation of c-Abl, a tyrosine kinase that induces apoptosis. We show that ACM-hSOD1(G93A), but not ACM-hSOD1(WT), increases c-Abl activity in motoneurons, interneurons and glial cells, starting at 60 min; the c-Abl inhibitor STI571 (imatinib) prevents this ACM-hSOD1(G93A)-mediated motoneuron death. Interestingly, similar results were obtained with ACM derived from astrocytes expressing SOD1(G86R) or TDP43(A315T). We further find that co-application of ACM-SOD1(G93A) with blockers of Nav channels (spermidine, mexiletine, or riluzole) or anti-oxidants (Trolox, esculetin, or tiron) effectively prevent c-Abl activation and motoneuron death. In addition, ACM-SOD1(G93A) induces alterations in the morphology of neuronal mitochondria that are related with their membrane depolarization. Finally, we find that blocking the opening of the mitochondrial permeability transition pore with cyclosporine A, or inhibiting mitochondrial calcium uptake with Ru360, reduces ROS production and c-Abl activation. Together, our data point to a sequence of events in which a toxic factor(s) released by ALS-expressing astrocytes rapidly induces hyper-excitability, which in turn increases calcium influx and affects mitochondrial structure and physiology. ROS production, mediated at least in part through mitochondrial alterations, trigger c-Abl signaling and lead to motoneuron death.

Reactive oxygen species trigger motoneuron death in non-cell-autonomous models of ALS through activation of c-Abl signaling

PubMed Central

Rojas, Fabiola; Gonzalez, David; Cortes, Nicole; Ampuero, Estibaliz; Hernández, Diego E.; Fritz, Elsa; Abarzua, Sebastián; Martinez, Alexis; Elorza, Alvaro A.; Alvarez, Alejandra; Court, Felipe; van Zundert, Brigitte

2015-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which pathogenesis and death of motor neurons are triggered by non-cell-autonomous mechanisms. We showed earlier that exposing primary rat spinal cord cultures to conditioned media derived from primary mouse astrocyte conditioned media (ACM) that express human SOD1G93A (ACM-hSOD1G93A) quickly enhances Nav channel-mediated excitability and calcium influx, generates intracellular reactive oxygen species (ROS), and leads to death of motoneurons within days. Here we examined the role of mitochondrial structure and physiology and of the activation of c-Abl, a tyrosine kinase that induces apoptosis. We show that ACM-hSOD1G93A, but not ACM-hSOD1WT, increases c-Abl activity in motoneurons, interneurons and glial cells, starting at 60 min; the c-Abl inhibitor STI571 (imatinib) prevents this ACM-hSOD1G93A-mediated motoneuron death. Interestingly, similar results were obtained with ACM derived from astrocytes expressing SOD1G86R or TDP43A315T. We further find that co-application of ACM-SOD1G93A with blockers of Nav channels (spermidine, mexiletine, or riluzole) or anti-oxidants (Trolox, esculetin, or tiron) effectively prevent c-Abl activation and motoneuron death. In addition, ACM-SOD1G93A induces alterations in the morphology of neuronal mitochondria that are related with their membrane depolarization. Finally, we find that blocking the opening of the mitochondrial permeability transition pore with cyclosporine A, or inhibiting mitochondrial calcium uptake with Ru360, reduces ROS production and c-Abl activation. Together, our data point to a sequence of events in which a toxic factor(s) released by ALS-expressing astrocytes rapidly induces hyper-excitability, which in turn increases calcium influx and affects mitochondrial structure and physiology. ROS production, mediated at least in part through mitochondrial alterations, trigger c-Abl signaling and lead to motoneuron death. PMID:26106294

Event-Associated Oxygen Consumption Rate Increases ca. Five-Fold When Interictal Activity Transforms into Seizure-Like Events In Vitro.

PubMed

Schoknecht, Karl; Berndt, Nikolaus; Rösner, Jörg; Heinemann, Uwe; Dreier, Jens P; Kovács, Richard; Friedman, Alon; Liotta, Agustin

2017-09-07

Neuronal injury due to seizures may result from a mismatch of energy demand and adenosine triphosphate (ATP) synthesis. However, ATP demand and oxygen consumption rates have not been accurately determined, yet, for different patterns of epileptic activity, such as interictal and ictal events. We studied interictal-like and seizure-like epileptiform activity induced by the GABA A antagonist bicuculline alone, and with co-application of the M-current blocker XE-991, in rat hippocampal slices. Metabolic changes were investigated based on recording partial oxygen pressure, extracellular potassium concentration, and intracellular flavine adenine dinucleotide (FAD) redox potential. Recorded data were used to calculate oxygen consumption and relative ATP consumption rates, cellular ATP depletion, and changes in FAD/FADH₂ ratio by applying a reactive-diffusion and a two compartment metabolic model. Oxygen-consumption rates were ca. five times higher during seizure activity than interictal activity. Additionally, ATP consumption was higher during seizure activity (~94% above control) than interictal activity (~15% above control). Modeling of FAD transients based on partial pressure of oxygen recordings confirmed increased energy demand during both seizure and interictal activity and predicted actual FAD autofluorescence recordings, thereby validating the model. Quantifying metabolic alterations during epileptiform activity has translational relevance as it may help to understand the contribution of energy supply and demand mismatches to seizure-induced injury.

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.

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.

Antioxidant Activity of Oxygen Evolving Enhancer Protein 1 Purified from Capsosiphon fulvescens.

PubMed

Kim, Eun-Young; Choi, Youn Hee; Lee, Jung Im; Kim, In-Hye; Nam, Taek-Jeong

2015-06-01

This study was conducted to determine the antioxidant activity of a protein purified from Capsosiphon fulvescens. The purification steps included sodium acetate (pH 6) extraction and diethylaminoethyl-cellulose, reversed phase Shodex C4P-50 column chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis indicated that the molecular weight of the purified protein was 33 kDa. The N-terminus and partial peptide amino acid sequence of this protein was identical to the sequence of oxygen evolving enhancer (OEE) 1 protein. The antioxidant activity of the OEE 1 was determined in vitro using a scavenging test with 4 types of reactive oxygen species (ROS), including the 2,2-diphenyl-1-picrylhydrazyl radical, hydroxyl radical, superoxide anion, and hydrogen peroxide (H2 O2 ). OEE 1 had higher H2 O2 scavenging activity, which proved to be the result of enzymatic antioxidants rather than nonenzymatic antioxidants. In addition, OEE 1 showed less H2 O2 -mediated ROS formation in HepG2 cells. In conclusion, this study demonstrates that OEE 1 purified from C. fulvescens is an excellent antioxidant. © 2015 Institute of Food Technologists®

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.

Quercetin improves the in vitro development of porcine oocytes by decreasing reactive oxygen species levels

PubMed Central

Kang, Jung-Taek; Kwon, Dae-Kee; Park, Sol-Ji; Kim, Su-Jin; Moon, Joon-Ho; Koo, Ok-Jae; Jang, Goo

2013-01-01

Quercetin is a plant-derived flavonoid found in fruits or vegetables that has antioxidant properties and acts as a free radical scavenger. We investigated the effects of quercetin on porcine oocyte nuclear maturation and embryonic development after parthenogenetic activation. We then evaluated the antioxidant activities of quercetin by measuring reactive oxygen species (ROS) levels in matured oocytes. Immature oocytes were untreated or treated with 1, 10, and 50 µg/mL quercetin during in vitro maturation (IVM). Quercetin treatment did not improve oocyte nuclear maturation, but significantly higher blastocyst rates (p < 0.05) of parthenogenetically activated oocytes were achieved when the IVM medium was supplemented with an adequate concentration of quercetin (1 µg/mL). However, cleavage rates and blastocyst cell numbers were not affected. Oocytes treated with 1 or 10 µg/mL quercetin had significantly lower (p < 0.05) levels of ROS than the control and group treated with the highest concentration of quercetin (50 µg/mL). Moreover, this highest concentration was detrimental to oocyte nuclear maturation and blastocyst formation. Based on our findings, we concluded that exogenous quercetin reduces ROS levels during oocyte maturation and is beneficial for subsequent embryo development. PMID:23388446

Induction of apoptosis by [8]-shogaol via reactive oxygen species generation, glutathione depletion, and caspase activation in human leukemia cells.

PubMed

Shieh, Po-Chuen; Chen, Yi-Own; Kuo, Daih-Huang; Chen, Fu-An; Tsai, Mei-Ling; Chang, Ing-Shing; Wu, Hou; Sang, Shengmin; Ho, Chi-Tang; Pan, Min-Hsiung

2010-03-24

Ginger, the rhizome of Zingiber officinale , is a traditional medicine with a carminative effect and antinausea, anti-inflammatory, and anticarcinogenic properties. This study examined the growth inhibitory effects of [8]-shogaol, one of the pungent phenolic compounds in ginger, on human leukemia HL-60 cells. It demonstrated that [8]-shogaol was able to induce apoptosis in a time- and concentration-dependent manner. Treatment with [8]-shogaol caused a rapid loss of mitochondrial transmembrane potential, stimulation of reactive oxygen species (ROS) production, release of mitochondrial cytochrome c into cytosol, and subsequent induction of procaspase-9 and procaspase-3 processing. Taken together, these results suggest for the first time that ROS production and depletion of glutathione that contributed to [8]-shogaol-induced apoptosis in HL-60 cells.

Induction of Apoptosis by [8]-shogaol via Reactive Oxygen Species Generation, Glutathione Depletion and Caspase Activation in Human Leukemia Cells

PubMed Central

Shieh, Po-Chuen; Chen, Yi-Own; Kuo, Daih-Huang; Chen, Fu-An; Tsai, Mei-Ling; Chang, Ing-Shing; Wu, Hou; Sang, Shengmin; Ho, Chi-Tang; Pan, Min-Hsiung

2010-01-01

Ginger, the rhizome of Zingiber officinale, is a traditional medicine with carminative effect, anti-nausea, anti-inflammatory, and anti-carcinogenic properties. This study examined the growth inhibitory effects of [8]-shogaol, one of pungent phenolic compounds in ginger, on human leukemia HL-60 cells. It demonstrated that [8]-shogaol was able to induce apoptosis in a time- and concentration-dependent manner. Treatment with [8]-shogaol caused a rapid loss of mitochondrial transmembrane potential, stimulation of reactive oxygen species (ROS) production, release of mitochondrial cytochrome c into cytosol, and subsequent induction of procaspase-9 and procaspase-3 processing. Taken together, these results suggest for the first time that ROS production and depletion of the glutathione that committed to [8]-shogaol-induced apoptosis in HL-60 cells. PMID:20163181

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.

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

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

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.

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

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

Fetal programming alters reactive oxygen species production in sheep cardiac mitochondria.

PubMed

von Bergen, Nicholas H; Koppenhafer, Stacia L; Spitz, Douglas R; Volk, Kenneth A; Patel, Sonali S; Roghair, Robert D; Lamb, Fred S; Segar, Jeffrey L; Scholz, Thomas D

2009-04-01

Exposure to an adverse intrauterine environment is recognized as an important risk factor for the development of cardiovascular disease later in life. Although oxidative stress has been proposed as a mechanism for the fetal programming phenotype, the role of mitochondrial O(2)(*-) (superoxide radical) production has not been explored. To determine whether mitochondrial ROS (reactive oxygen species) production is altered by in utero programming, pregnant ewes were given a 48-h dexamethasone (dexamethasone-exposed, 0.28 mg.kg(-1) of body weight.day(-1)) or saline (control) infusion at 27-28 days gestation (term=145 days). Intact left ventricular mitochondria and freeze-thaw mitochondrial membranes were studied from offspring at 4-months of age. AmplexRed was used to measure H(2)O(2) production. Activities of the antioxidant enzymes Mn-SOD (manganese superoxide dismutase), GPx (glutathione peroxidase) and catalase were measured. Compared with controls, a significant increase in Complex I H(2)O(2) production was found in intact mitochondria from dexamethasone-exposed animals. The treatment differences in Complex I-driven H(2)O(2) production were not seen in mitochondrial membranes. Consistent changes in H(2)O(2) production from Complex III in programmed animals were not found. Despite the increase in H(2)O(2) production in intact mitochondria from programmed animals, dexamethasone exposure significantly increased mitochondrial catalase activity, whereas Mn-SOD and GPx activities were unchanged. The results of the present study point to an increase in the rate of release of H(2)O(2) from programmed mitochondria despite an increase in catalase activity. Greater mitochondrial H(2)O(2) release into the cell may play a role in the development of adult disease following exposure to an adverse intrauterine environment.

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.

Cardiovascular reactivity, stress, and physical activity

PubMed Central

Huang, Chun-Jung; Webb, Heather E.; Zourdos, Michael C.; Acevedo, Edmund O.

2013-01-01

Psychological stress has been proposed as a major contributor to the progression of cardiovascular disease (CVD). Acute mental stress can activate the sympathetic-adrenal-medullary (SAM) axis, eliciting the release of catecholamines (NE and EPI) resulting in the elevation of heart rate (HR) and blood pressure (BP). Combined stress (psychological and physical) can exacerbate these cardiovascular responses, which may partially contribute to the elevated risk of CVD and increased proportionate mortality risks experienced by some occupations (e.g., firefighting and law enforcement). Studies have supported the benefits of physical activity on physiological and psychological health, including the cardiovascular response to acute stress. Aerobically trained individuals exhibit lower sympathetic nervous system (e.g., HR) reactivity and enhanced cardiovascular efficiency (e.g., lower vascular reactivity and decreased recovery time) in response to physical and/or psychological stress. In addition, resistance training has been demonstrated to attenuate cardiovascular responses and improve mental health. This review will examine stress-induced cardiovascular reactivity and plausible explanations for how exercise training and physical fitness (aerobic and resistance exercise) can attenuate cardiovascular responses to stress. This enhanced functionality may facilitate a reduction in the incidence of stroke and myocardial infarction. Finally, this review will also address the interaction of obesity and physical activity on cardiovascular reactivity and CVD. PMID:24223557

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.

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

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

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.

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.

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.

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.

Low Oxygen Tension Enhances Expression of Myogenic Genes When Human Myoblasts Are Activated from G0 Arrest

PubMed Central

Sellathurai, Jeeva; Nielsen, Joachim; Hejbøl, Eva Kildall; Jørgensen, Louise Helskov; Dhawan, Jyotsna; Nielsen, Michael Friberg Bruun; Schrøder, Henrik Daa

2016-01-01

Objectives Most cell culture studies have been performed at atmospheric oxygen tension of 21%, however the physiological oxygen tension is much lower and is a factor that may affect skeletal muscle myoblasts. In this study we have compared activation of G0 arrested myoblasts in 21% O2 and in 1% O2 in order to see how oxygen tension affects activation and proliferation of human myoblasts. Materials and Methods Human myoblasts were isolated from skeletal muscle tissue and G0 arrested in vitro followed by reactivation at 21% O2 and 1% O2. The effect was assesses by Real-time RT-PCR, immunocytochemistry and western blot. Results and Conclusions We found an increase in proliferation rate of myoblasts when activated at a low oxygen tension (1% O2) compared to 21% O2. In addition, the gene expression studies showed up regulation of the myogenesis related genes PAX3, PAX7, MYOD, MYOG (myogenin), MET, NCAM, DES (desmin), MEF2A, MEF2C and CDH15 (M-cadherin), however, the fraction of DES and MYOD positive cells was not increased by low oxygen tension, indicating that 1% O2 may not have a functional effect on the myogenic response. Furthermore, the expression of genes involved in the TGFβ, Notch and Wnt signaling pathways were also up regulated in low oxygen tension. The differences in gene expression were most pronounced at day one after activation from G0-arrest, thus the initial activation of myoblasts seemed most sensitive to changes in oxygen tension. Protein expression of HES1 and β-catenin indicated that notch signaling may be induced in 21% O2, while the canonical Wnt signaling may be induced in 1% O2 during activation and proliferation of myoblasts. PMID:27442119

Activation of p47phox as a Mechanism of Bupivacaine-Induced Burst Production of Reactive Oxygen Species and Neural Toxicity

PubMed Central

Zhao, Wei; Yu, Xu-jiao; Li, Feng-xian; Liu, Zi-ting

2017-01-01

Bupivacaine has been shown to induce neurotoxicity through inducing excessive reactive oxygen species (ROS), but the underlying mechanism remains unclear. NOX2 is one of the most important sources of ROS in the nervous system, and its activation requires the membrane translocation of subunit p47phox. However, the role of p47phox in bupivacaine-induced neurotoxicity has not been explored. In our in vitro study, cultured human SH-SY5Y neuroblastoma cells were treated with 1.5 mM bupivacaine to induce neurotoxicity. Membrane translocation of p47phox was assessed by measuring the cytosol/membrane ratio of p47phox. The effects of the NOX inhibitor VAS2870 and p47phox-siRNA on bupivacaine-induced neurotoxicity were investigated. Furthermore, the effect of VAS2870 on bupivacaine-induced neurotoxicity was assessed in vivo in rats. All these changes were reversed by pretreatment with VAS2870 or transfection with p47phox-siRNA in SH-SY5Y cells. Similarly, pretreatment with VAS2870 attenuated bupivacaine-induced neuronal toxicity in rats. It is concluded that enhancing p47phox membrane translocation is a major mechanism whereby bupivacaine induced neurotoxicity and that pretreatment with VAS2870 or local p47phox gene knockdown attenuated bupivacaine-induced neuronal cell injury. PMID:28751934

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.

Induction of reactive oxygen species in marine phytoplankton under crude oil exposure.

PubMed

Ozhan, Koray; Zahraeifard, Sara; Smith, Aaron P; Bargu, Sibel

2015-12-01

Exposure of phytoplankton to the water-accommodated fraction of crude oil can elicit a number of stress responses, but the mechanisms that drive these responses are unclear. South Louisiana crude oil was selected to investigate its effects on population growth, chlorophyll a (Chl a) content, antioxidative defense, and lipid peroxidation, for the marine diatom, Ditylum brightwellii, and the dinoflagellate, Heterocapsa triquetra, in laboratory-based microcosm experiments. The transcript levels of several possible stress-responsive genes in D. brightwellii were also measured. The microalgae were exposed to crude oil for up to 96 h, and Chl a content, superoxide dismutase (SOD), the glutathione pool (GSH and GSSG), and lipid peroxidation content were analyzed. The cell growth of both phytoplankton species was inhibited with increasing crude oil concentrations. Crude oil exposure did not affect Chl a content significantly in cells. SOD activities showed similar responses in both species, being enhanced at 4- and 8-mg/L crude oil exposure. Only H. triquetra demonstrated enhanced activity in GSSG pool and lipid peroxidation at 8-mg/L crude oil exposure, suggesting that phytoplankton species have distinct physiological responses and tolerance levels to crude oil exposure. This study indicated the activation of reactive oxygen species (ROS) in phytoplankton under crude oil exposure; however, the progressive damage in cells is still unknown. Thus, ROS-related damage in nucleic acid, lipids, proteins, and DNA, due to crude oil exposure could be a worthwhile subject of study to better understand crude oil toxicity at the base of the food web.

Airborne particulate matter PM2.5 from Mexico City affects the generation of reactive oxygen species by blood neutrophils from asthmatics: an in vitro approach.

PubMed

Sierra-Vargas, Martha Patricia; Guzman-Grenfell, Alberto Martin; Blanco-Jimenez, Salvador; Sepulveda-Sanchez, Jose David; Bernabe-Cabanillas, Rosa Maria; Cardenas-Gonzalez, Beatriz; Ceballos, Guillermo; Hicks, Juan Jose

2009-06-29

The Mexico City Metropolitan Area is densely populated, and toxic air pollutants are generated and concentrated at a higher rate because of its geographic characteristics. It is well known that exposure to particulate matter, especially to fine and ultra-fine particles, enhances the risk of cardio-respiratory diseases, especially in populations susceptible to oxidative stress. The aim of this study was to evaluate the effect of fine particles on the respiratory burst of circulating neutrophils from asthmatic patients living in Mexico City. In total, 6 subjects diagnosed with mild asthma and 11 healthy volunteers were asked to participate. Neutrophils were isolated from peripheral venous blood and incubated with fine particles, and the generation of reactive oxygen species was recorded by chemiluminescence. We also measured plasma lipoperoxidation susceptibility and plasma myeloperoxidase and paraoxonase activities by spectrophotometry. Asthmatic patients showed significantly lower plasma paraoxonase activity, higher susceptibility to plasma lipoperoxidation and an increase in myeloperoxidase activity that differed significantly from the control group. In the presence of fine particles, neutrophils from asthmatic patients showed an increased tendency to generate reactive oxygen species after stimulation with fine particles (PM2.5). These findings suggest that asthmatic patients have higher oxidation of plasmatic lipids due to reduced antioxidant defense. Furthermore, fine particles tended to increase the respiratory burst of blood human neutrophils from the asthmatic group.On the whole, increased myeloperoxidase activity and susceptibility to lipoperoxidation with a concomitant decrease in paraoxonase activity in asthmatic patients could favor lung infection and hence disrupt the control of asthmatic crises.

Airborne particulate matter PM2.5 from Mexico City affects the generation of reactive oxygen species by blood neutrophils from asthmatics: an in vitro approach

PubMed Central

Sierra-Vargas, Martha Patricia; Guzman-Grenfell, Alberto Martin; Blanco-Jimenez, Salvador; Sepulveda-Sanchez, Jose David; Bernabe-Cabanillas, Rosa Maria; Cardenas-Gonzalez, Beatriz; Ceballos, Guillermo; Hicks, Juan Jose

2009-01-01

Background The Mexico City Metropolitan Area is densely populated, and toxic air pollutants are generated and concentrated at a higher rate because of its geographic characteristics. It is well known that exposure to particulate matter, especially to fine and ultra-fine particles, enhances the risk of cardio-respiratory diseases, especially in populations susceptible to oxidative stress. The aim of this study was to evaluate the effect of fine particles on the respiratory burst of circulating neutrophils from asthmatic patients living in Mexico City. Methods In total, 6 subjects diagnosed with mild asthma and 11 healthy volunteers were asked to participate. Neutrophils were isolated from peripheral venous blood and incubated with fine particles, and the generation of reactive oxygen species was recorded by chemiluminescence. We also measured plasma lipoperoxidation susceptibility and plasma myeloperoxidase and paraoxonase activities by spectrophotometry. Results Asthmatic patients showed significantly lower plasma paraoxonase activity, higher susceptibility to plasma lipoperoxidation and an increase in myeloperoxidase activity that differed significantly from the control group. In the presence of fine particles, neutrophils from asthmatic patients showed an increased tendency to generate reactive oxygen species after stimulation with fine particles (PM2.5). Conclusion These findings suggest that asthmatic patients have higher oxidation of plasmatic lipids due to reduced antioxidant defense. Furthermore, fine particles tended to increase the respiratory burst of blood human neutrophils from the asthmatic group. On the whole, increased myeloperoxidase activity and susceptibility to lipoperoxidation with a concomitant decrease in paraoxonase activity in asthmatic patients could favor lung infection and hence disrupt the control of asthmatic crises. PMID:19563660

Inactivation of biologically active dna by gamma ray induced superoxide radicals and their dismutation products singlet molecular oxygen and hydrogen peroxide

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

Vanhemmen, J.J.; Meuling, W.J.A.

1975-01-01

The reactivity of gamma ray induced superoxide radicals and dismutation products (singlet molecular oxygen and hydrogen peroxide) with DNA were studied. Superoxide dismutase, which removes superoxide radicals and inhibits the formation of singlet oxygen, protects biologically active DNA (OX174 RF) against inactivation by ionizing radiation. Catalase, which removes hydrogen peroxide, also protects the DNA. Attempts with various chemical sources of singlet oxygen to determine whether this species inactivates DNA did not yield an unequivocal answer. It was concluded that a combination of the protonated form of the superoxide radical and hydrogen peroxide inactivates DNA. (Author) (GRA)

Preparation of reactive oxygen scavenging peptides from tilapia (Oreochromis niloticus) skin gelatin: optimization using response surface methodology.

PubMed

Zhuang, Yongliang; Sun, Liping

2011-04-01

Gelatin extracted from tilapia skin was hydrolyzed with Properase E. Response surface methodology (RSM) was applied to optimize the hydrolysis condition (temperature [T], enzyme-to-substrate ratio [E/S], pH and reaction time [t]), to obtain the hydrolysate with the highest hydroxyl radical (•OH) scavenging activity. The optimum conditions obtained were T of 44.2 °C, E/S of 2.2%, pH of 9.2, and t of 3.4 h. The predicted •OH scavenging activity of the hydrolysate under the optimum conditions was 60.7%, and the actually experimental scavenging activity was 60.8%. The hydrolysate was fractionated by ultrafiltration, and 4 fractions were collected. The fraction TSGH4 (MW<2000 Da) showed the strongest •OH scavenging activity with the highest yield. Furthermore, reactive oxygen species (ROS) scavenging activities of TSGH4 with different concentrations were investigated in 5 model systems, including superoxide anion radical (•O2), •OH, hydrogen peroxide (H2O2), peroxynitrite (ONOO-), and nitric oxide (NO•), compared with reduced glutathione (GSH). The results showed that TSGH4 significantly scavenged these ROS, and could be used as a functional ingredient in medicine and food industries.

Influence of lightweight ambulatory oxygen on oxygen use and activity patterns of COPD patients receiving long-term oxygen therapy.

PubMed

Casaburi, Richard; Porszasz, Janos; Hecht, Ariel; Tiep, Brian; Albert, Richard K; Anthonisen, Nicholas R; Bailey, William C; Connett, John E; Cooper, J Allen; Criner, Gerard J; Curtis, Jeffrey; Dransfield, Mark; Lazarus, Stephen C; Make, Barry; Martinez, Fernando J; McEvoy, Charlene; Niewoehner, Dennis E; Reilly, John J; Scanlon, Paul; Scharf, Steven M; Sciurba, Frank C; Woodruff, Prescott

2012-02-01

Lightweight ambulatory oxygen devices are provided on the assumptions that they enhance compliance and increase activity, but data to support these assumptions are lacking. We studied 22 patients with severe chronic obstructive pulmonary disease receiving long-term oxygen therapy (14 men, average age = 66.9 y, FEV(1) = 33.6%pred, PaO(2) at rest = 51.7 torr) who were using E-cylinders as their portable oxygen. Subjects were recruited at 5 sites and studied over a 2-week baseline period and for 6 months after randomizing them to either continuing to use 22-lb E-cylinders towed on a cart or to carrying 3.6-lb aluminum cylinders. Utilizing novel electronic devices, ambulatory and stationary oxygen use was monitored continuously over the 2 weeks prior to and the 6 months following randomization. Subjects wore tri-axial accelerometers to monitor physical activity during waking hours for 2-3 weeks prior to, and at 3 and 6 months after, randomization. Seventeen subjects completed the study. At baseline, subjects used 17.2 hours of stationary and 2.5 hours of ambulatory oxygen daily. At 6 months, ambulatory oxygen use was 1.4 ± 1.0 hrs in those randomized to E-cylinders and 1.9 ± 2.4 hrs in those using lightweight oxygen (P = NS). Activity monitoring revealed low activity levels prior to randomization and no significant increase over time in either group. In this group of severe chronic obstructive pulmonary disease patients, providing lightweight ambulatory oxygen did not increase either oxygen use or activity. Future efforts might focus on strategies to encourage oxygen use and enhance activity in this patient group. This trial is registered at ClinicalTrials.gov (NCT003257540).

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.

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

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

Differential sympathetic neural control of oxygenation in resting and exercising human skeletal muscle.

PubMed Central

Hansen, J; Thomas, G D; Harris, S A; Parsons, W J; Victor, R G

1996-01-01

Metabolic products of skeletal muscle contraction activate metaboreceptor muscle afferents that reflexively increase sympathetic nerve activity (SNA) targeted to both resting and exercising skeletal muscle. To determine effects of the increased sympathetic vasoconstrictor drive on muscle oxygenation, we measured changes in tissue oxygen stores and mitochondrial cytochrome a,a3 redox state in rhythmically contracting human forearm muscles with near infrared spectroscopy while simultaneously measuring muscle SNA with microelectrodes. The major new finding is that the ability of reflex-sympathetic activation to decrease muscle oxygenation is abolished when the muscle is exercised at an intensity > 10% of maximal voluntary contraction (MVC). During high intensity handgrip, (45% MVC), contraction-induced decreases in muscle oxygenation remained stable despite progressive metaboreceptor-mediated reflex increases in SNA. During mild to moderate handgrips (20-33% MVC) that do not evoke reflex-sympathetic activation, experimentally induced increases in muscle SNA had no effect on oxygenation in exercising muscles but produced robust decreases in oxygenation in resting muscles. The latter decreases were evident even during maximal metabolic vasodilation accompanying reactive hyperemia. We conclude that in humans sympathetic neural control of skeletal muscle oxygenation is sensitive to modulation by metabolic events in the contracting muscles. These events are different from those involved in either metaboreceptor muscle afferent activation or reactive hyperemia. PMID:8755671

[Active forms of oxygen and nitrogen in blood cells of patients with rheumatoid arthritis: effect of laser therapy].

PubMed

Ostrakhovich, E A; Ilich-Stoianovich, O; Afanas'ev, I B

2001-01-01

Infrared pulse laser therapy was studied for its impact on the production of active forms of oxygen and nitrogen by neutrophils from patients with rheumatoid arthritis (RA). The authors determined the non-activated and PMA-activated production of superoxide anion-radical, peroxynitrite, peripheral neurophilic NAD.PH-oxidase and superoxide dismutase activities, and the red blood cell concentrations of reduced glutathione. Before therapy, non-activation RA neurophilic production of superoxide was much higher than in donors. Laser therapy made this parameter normal. Similarly, neutrophilic peroxynitrite production (defined by dihydrorhodamine oxidation) in RA patients was 1.7 times higher than the normal values. IF-laser therapy decreased peroxynitrite production to the values observed in donors. It is important that the therapy caused increased SOD activity (that was lower in RA patients prior to therapy) up to apparently control values. Thus, IF-laser therapy has a certain antioxidative effect by increasing SOD activity in RA patients' blood cells and reducing the production of highly reactive oxygen and nitrogen forms.

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

Comparative study of the antioxidant and reactive oxygen species scavenging properties in the extracts of the fruits of Terminalia chebula, Terminalia belerica and Emblica officinalis

PubMed Central

2010-01-01

Background Cellular damage caused by reactive oxygen species (ROS) has been implicated in several diseases, and hence natural antioxidants have significant importance in human health. The present study was carried out to evaluate the in vitro antioxidant and reactive oxygen species scavenging activities of Terminalia chebula, Terminalia belerica and Emblica officinalis fruit extracts. Methods The 70% methanol extracts were studied for in vitro total antioxidant activity along with phenolic and flavonoid contents and reducing power. Scavenging ability of the extracts for radicals like DPPH, hydroxyl, superoxide, nitric oxide, hydrogen peroxide, peroxynitrite, singlet oxygen, hypochlorous acid were also performed to determine the potential of the extracts. Results The ability of the extracts of the fruits in exhibiting their antioxative properties follow the order T. chebula >E. officinalis >T. belerica. The same order is followed in their flavonoid content, whereas in case of phenolic content it becomes E. officinalis >T. belerica >T. chebula. In the studies of free radicals' scavenging, where the activities of the plant extracts were inversely proportional to their IC50 values, T. chebula and E. officinalis were found to be taking leading role with the orders of T. chebula >E. officinalis >T. belerica for superoxide and nitric oxide, and E. officinalis >T. belerica >T. chebula for DPPH and peroxynitrite radicals. Miscellaneous results were observed in the scavenging of other radicals by the plant extracts, viz., T. chebula >T. belerica >E. officinalis for hydroxyl, T. belerica >T. chebula >E. officinalis for singlet oxygen and T. belerica >E. officinalis >T. chebula for hypochlorous acid. In a whole, the studied fruit extracts showed quite good efficacy in their antioxidant and radical scavenging abilities, compared to the standards. Conclusions The evidences as can be concluded from the study of the 70% methanol extract of the fruits of Terminalia chebula

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

Co-occurring increases of calcium and organellar reactive oxygen species determine differential activation of antioxidant and defense enzymes in Ulva compressa (Chlorophyta) exposed to copper excess.

PubMed

Gonzalez, Alberto; Vera, Jeannette; Castro, Jorge; Dennett, Geraldine; Mellado, Macarena; Morales, Bernardo; Correa, Juan A; Moenne, Alejandra

2010-10-01

In order to analyse copper-induced calcium release and (reactive oxygen species) ROS accumulation and their role in antioxidant and defense enzymes activation, the marine alga Ulva compressa was exposed to 10 µM copper for 7 d. The level of calcium, extracellular hydrogen peroxide (eHP), intracellular hydrogen peroxide (iHP) and superoxide anions (SA) as well as the activities of ascorbate peroxidase (AP), glutathione reductase (GR), glutathione-S-transferase (GST), phenylalanine ammonia lyase (PAL) and lipoxygenase (LOX) were determined. Calcium release showed a triphasic pattern with peaks at 2, 3 and 12 h. The second peak was coincident with increases in eHP and iHP and the third peak with the second increase of iHP. A delayed wave of SA occurred after day 3 and was not accompanied by calcium release. The accumulation of iHP and SA was mainly inhibited by organellar electron transport chains inhibitors (OETCI), whereas calcium release was inhibited by ryanodine. AP activation ceased almost completely after the use of OETCI. On the other hand, GR and GST activities were partially inhibited, whereas defense enzymes were not inhibited. In contrast, PAL and LOX were inhibited by ryanodine, whereas AP was not inhibited. Thus, copper stress induces calcium release and organellar ROS accumulation that determine the differential activation of antioxidant and defense enzymes. © 2010 Blackwell Publishing Ltd.

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.

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

Ampelopsin-induced reactive oxygen species enhance the apoptosis of colon cancer cells by activating endoplasmic reticulum stress-mediated AMPK/MAPK/XAF1 signaling

PubMed Central

Park, Ga Bin; Jeong, Jee-Yeong; Kim, Daejin

2017-01-01

Ampelopsin (Amp) is bioactive natural product and exerts anti-cancer effects against several cancer types. The present study investigated the anti-colon cancer activity of Amp and explored its mechanism of action. The treatment of colon cancer cells with Amp resulted in the dose- and time-dependent induction of apoptosis via the activation of endoplasmic reticulum (ER) stress, 5′ adenosine monophosphate-activated protein kinase (AMPK), and c-Jun N-terminal protein kinase (JNK)/p38 mitogen-activated protein kinases (MAPKs). Salubrinal, an ER stress inhibitor, prevented the upregulation of ER stress-associated proteins, including phosphorylated protein kinase RNA-like ER kinase, phosphorylated eukaryotic translation initiation factor 2α, glucose-regulated protein 78, and CCAAT/enhancer-binding protein homologous protein, as well as suppressing AMPK activation and the MAPK signaling pathway. Knockdown of AMPK by RNA interference failed to block ER stress. Additionally, SP600125 (a JNK inhibitor) and SB203580 (a p38-MAPK inhibitor) effectively inhibited apoptosis and attenuated the expression of X-linked IAP-associated factor 1 (XAF1) and apoptotic Bcl-2 family proteins (BCL2 antagonist/killer 1 and BCL2-associated X protein) in Amp-treated colon cancer cells. Furthermore, reactive oxygen species (ROS)-mediated ER stress/AMPK apoptotic signaling pathway in Amp-treated colon cancer cells were markedly inhibited by treatment with N-acetyl-L-cysteine, a ROS scavenger. These results demonstrate that treatment with Amp induces the apoptotic death of colon cancer cells through ER stress-initiated AMPK/MAPK/XAF1 signaling. These results also provide experimental information for developing Amp as therapeutic drug against colon cancer. PMID:29250183

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

Cytosolic NADP(+)-dependent isocitrate dehydrogenase protects macrophages from LPS-induced nitric oxide and reactive oxygen species.

PubMed

Maeng, Oky; Kim, Yong Chan; Shin, Han-Jae; Lee, Jie-Oh; Huh, Tae-Lin; Kang, Kwang-il; Kim, Young Sang; Paik, Sang-Gi; Lee, Hayyoung

2004-04-30

Macrophages activated by microbial lipopolysaccharides (LPS) produce bursts of nitric oxide and reactive oxygen species (ROS). Redox protection systems are essential for the survival of the macrophages since the nitric oxide and ROS can be toxic to them as well as to pathogens. Using suppression subtractive hybridization (SSH) we found that cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) is strongly upregulated by nitric oxide in macrophages. The levels of IDPc mRNA and of the corresponding enzymatic activity were markedly increased by treatment of RAW264.7 cells or peritoneal macrophages with LPS or SNAP (a nitric oxide donor). Over-expression of IDPc reduced intracellular peroxide levels and enhanced the survival of H2O2- and SNAP-treated RAW264.7 macrophages. IDPc is known to generate NADPH, a cellular reducing agent, via oxidative decarboxylation of isocitrate. The expression of enzymes implicated in redox protection, superoxide dismutase (SOD) and catalase, was relatively unaffected by LPS and SNAP. We propose that the induction of IDPc is one of the main self-protection mechanisms of macrophages against LPS-induced oxidative stress.

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

Single-cell analysis of dihydroartemisinin-induced apoptosis through reactive oxygen species-mediated caspase-8 activation and mitochondrial pathway in ASTC-a-1 cells using fluorescence imaging techniques

NASA Astrophysics Data System (ADS)

Lu, Ying-Ying; Chen, Tong-Sheng; Wang, Xiao-Ping; Li, Li

2010-07-01

Dihydroartemisinin (DHA), a front-line antimalarial herbal compound, has been shown to possess promising anticancer activity with low toxicity. We have previously reported that DHA induced caspase-3-dependent apoptosis in human lung adenocarcinoma cells. However, the cellular target and molecular mechanism of DHA-induced apoptosis is still poorly defined. We use confocal fluorescence microscopy imaging, fluorescence resonance energy transfer, and fluorescence recovery after photobleaching techniques to explore the roles of DHA-elicited reactive oxygen species (ROS) in the DHA-induced Bcl-2 family proteins activation, mitochondrial dysfunction, caspase cascade, and cell death. Cell Counting Kit-8 assay and flow cytometry analysis showed that DHA induced ROS-mediated apoptosis. Confocal imaging analysis in a single living cell and Western blot assay showed that DHA triggered ROS-dependent Bax translocation, mitochondrial membrane depolarization, alteration of mitochondrial morphology, cytochrome c release, caspase-9, caspase-8, and caspase-3 activation, indicating the coexistence of ROS-mediated mitochondrial and death receptor pathway. Collectively, our findings demonstrate for the first time that DHA induces cell apoptosis by triggering ROS-mediated caspase-8/Bid activation and the mitochondrial pathway, which provides some novel insights into the application of DHA as a potential anticancer drug and a new therapeutic strategy by targeting ROS signaling in lung adenocarcinoma therapy in the future.

Eckol protects V79-4 lung fibroblast cells against gamma-ray radiation-induced apoptosis via the scavenging of reactive oxygen species and inhibiting of the c-Jun NH(2)-terminal kinase pathway.

PubMed

Zhang, Rui; Kang, Kyoung Ah; Piao, Mei Jing; Ko, Dong Ok; Wang, Zhi Hong; Lee, In Kyung; Kim, Bum Joon; Jeong, Il Yun; Shin, Taekyun; Park, Jae Woo; Lee, Nam Ho; Hyun, Jin Won

2008-09-04

The radioprotective effect of eckol against gamma-ray radiation-induced oxidative stress and its possible protective mechanisms were investigated. Eckol was found to reduce the intracellular reactive oxygen species generated by gamma-ray radiation. Moreover, eckol also protected against radiation-induced cellular DNA damage and membrane lipid peroxidation, which are the main targets of radiation-induced damage. In addition, eckol recovered the cell viability damaged by radiation via the inhibition of apoptosis. Irradiated cells with eckol treatment reduced the expression of bax, the activation of caspase 9 and caspase 3, which were induced by radiation. However, irradiated cells with eckol recovered the expression of bcl-2 and mitochondrial cytochrome c which were decreased by radiation. The anti-apoptotic effect of eckol exerted via the inhibition of mitogen-activated protein kinase kinase-4 (MKK4/SEK1)-c-Jun NH(2)-terminal kinase (JNK)-activator protein 1 (AP-1) cascades induced by radiation. In summary, the results suggest that eckol protects cells against the oxidative stress induced by radiation via the reduction of reactive oxygen species and the attenuation of activation in SEK1-JNK-AP-1 pathway.

The [NiFe]-Hydrogenase of Pyrococcus furiosus Exhibits a New Type of Oxygen Tolerance.

PubMed

Kwan, Patrick; McIntosh, Chelsea L; Jennings, David P; Hopkins, R Chris; Chandrayan, Sanjeev K; Wu, Chang-Hao; Adams, Michael W W; Jones, Anne K

2015-10-28

We report the first direct electrochemical characterization of the impact of oxygen on the hydrogen oxidation activity of an oxygen-tolerant, group 3, soluble [NiFe]-hydrogenase: hydrogenase I from Pyrococcus furiosus (PfSHI), which grows optimally near 100 °C. Chronoamperometric experiments were used to probe the sensitivity of PfSHI hydrogen oxidation activity to both brief and prolonged exposure to oxygen. For experiments between 15 and 80 °C, following short (<200 s) exposure to 14 μM O2 under oxidizing conditions, PfSHI always maintains some fraction of its initial hydrogen oxidation activity; i.e., it is oxygen-tolerant. Reactivation experiments show that two inactive states are formed by interaction with oxygen and both can be quickly (<150 s) reactivated. Analogous experiments, in which the interval of oxygen exposure is extended to 900 s, reveal that the response is highly temperature-dependent. At 25 °C, under sustained 1% O2/ 99% H2 exposure, the H2oxidation activity drops nearly to zero. However, at 80 °C, up to 32% of the enzyme's oxidation activity is retained. Reactivation of PfSHI following sustained exposure to oxygen occurs on a much longer time scale (tens of minutes), suggesting that a third inactive species predominates under these conditions. These results stand in contrast to the properties of oxygen-tolerant, group 1 [NiFe]-hydrogenases, which form a single state upon reaction with oxygen, and we propose that this new type of hydrogenase should be referred to as oxygen-resilient. Furthermore, PfSHI, like other group 3 [NiFe]-hydrogenases, does not possess the proximal [4Fe3S] cluster associated with the oxygen tolerance of some group 1 enzymes. Thus, a new mechanism is necessary to explain the observed oxygen tolerance in soluble, group 3 [NiFe]-hydrogenases, and we present a model integrating both electrochemical and spectroscopic results to define the relationships of these inactive states.

Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma

PubMed Central

Singer, E; Judkins, J; Salomonis, N; Matlaf, L; Soteropoulos, P; McAllister, S; Soroceanu, L

2015-01-01

Glioblastoma (GBM) resistance to therapy is the most common cause of tumor recurrence, which is ultimately fatal in 90% of the patients 5 years after initial diagnosis. A sub-population of tumor cells with stem-like properties, glioma stem cells (GSCs), is specifically endowed to resist or adapt to the standard therapies, leading to therapeutic resistance. Several anticancer agents, collectively termed redox therapeutics, act by increasing intracellular levels of reactive oxygen species (ROS). In this study, we investigated mechanisms underlying GSC response and resistance to cannabidiol (CBD), a non-toxic, non-psychoactive cannabinoid and redox modulator. Using primary GSCs, we showed that CBD induced a robust increase in ROS, which led to the inhibition of cell survival, phosphorylated (p)-AKT, self-renewal and a significant increase in the survival of GSC-bearing mice. Inhibition of self-renewal was mediated by the activation of the p-p38 pathway and downregulation of key stem cell regulators Sox2, Id1 and p-STAT3. Following CBD treatment, a subset of GSC successfully adapted, leading to tumor regrowth. Microarray, Taqman and functional assays revealed that therapeutic resistance was mediated by enhanced expression of the antioxidant response system Xc catalytic subunit xCT (SLC7A11 (solute carrier family 7 (anionic amino-acid transporter light chain), member 11)) and ROS-dependent upregulation of mesenchymal (MES) markers with concomitant downregulation of proneural (PN) markers, also known as PN–MES transition. This ‘reprogramming' of GSCs occurred in culture and in vivo and was partially due to activation of the NFE2L2 (NRF2 (nuclear factor, erythroid 2-like)) transcriptional network. Using genetic knockdown and pharmacological inhibitors of SLC7A11, we demonstrated that combining CBD treatment with the inhibition of system Xc resulted in synergistic ROS increase leading to robust antitumor effects, that is, decreased GSC survival, self-renewal, and

Changes in the Antioxidant Systems as Part of the Signaling Pathway Responsible for the Programmed Cell Death Activated by Nitric Oxide and Reactive Oxygen Species in Tobacco Bright-Yellow 2 Cells1

PubMed Central

de Pinto, Maria Concetta; Tommasi, Franca; De Gara, Laura

2002-01-01

Nitric oxide (NO) has been postulated to be required, together with reactive oxygen species (ROS), for the activation of the hypersensitive reaction, a defense response induced in the noncompatible plant-pathogen interaction. However, its involvement in activating programmed cell death (PCD) in plant cells has been questioned. In this paper, the involvement of the cellular antioxidant metabolism in the signal transduction triggered by these bioactive molecules has been investigated. NO and ROS levels were singularly or simultaneously increased in tobacco (Nicotiana tabacum cv Bright-Yellow 2) cells by the addition to the culture medium of NO and/or ROS generators. The individual increase in NO or ROS had different effects on the studied parameters than the simultaneous increase in the two reactive species. NO generation did not cause an increase in phenylalanine ammonia-lyase (PAL) activity or induction of cellular death. It only induced minor changes in ascorbate (ASC) and glutathione (GSH) metabolisms. An increase in ROS induced oxidative stress in the cells, causing an oxidation of the ASC and GSH redox pairs; however, it had no effect on PAL activity and did not induce cell death when it was generated at low concentrations. In contrast, the simultaneous increase of NO and ROS activated a process of death with the typical cytological and biochemical features of hypersensitive PCD and a remarkable rise in PAL activity. Under the simultaneous generation of NO and ROS, the cellular antioxidant capabilities were also suppressed. The involvement of ASC and GSH as part of the transduction pathway leading to PCD is discussed. PMID:12376637

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

Targeting Cancer Cells with Reactive Oxygen and Nitrogen Species Generated by Atmospheric-Pressure Air Plasma

PubMed Central

Hoan, Nguyen Ngoc; Kim, Churl Ho; Moon, Eunpyo; Choi, Kyeong Sook; Yang, Sang Sik; Lee, Jong-Soo

2014-01-01

The plasma jet has been proposed as a novel therapeutic method for cancer. Anticancer activity of plasma has been reported to involve mitochondrial dysfunction. However, what constituents generated by plasma is linked to this anticancer process and its mechanism of action remain unclear. Here, we report that the therapeutic effects of air plasma result from generation of reactive oxygen/nitrogen species (ROS/RNS) including H2O2, Ox, OH−, •O2, NOx, leading to depolarization of mitochondrial membrane potential and mitochondrial ROS accumulation. Simultaneously, ROS/RNS activate c-Jun NH2-terminal kinase (JNK) and p38 kinase. As a consequence, treatment with air plasma jets induces apoptotic death in human cervical cancer HeLa cells. Pretreatment of the cells with antioxidants, JNK and p38 inhibitors, or JNK and p38 siRNA abrogates the depolarization of mitochondrial membrane potential and impairs the air plasma-induced apoptotic cell death, suggesting that the ROS/RNS generated by plasma trigger signaling pathways involving JNK and p38 and promote mitochondrial perturbation, leading to apoptosis. Therefore, administration of air plasma may be a feasible strategy to eliminate cancer cells. PMID:24465942

Soyasaponins Can Blunt Inflammation by Inhibiting the Reactive Oxygen Species-Mediated Activation of PI3K/Akt/NF-kB Pathway

PubMed Central

Zha, Longying; Chen, Jiading; Sun, Suxia; Mao, Limei; Chu, Xinwei; Deng, Hong; Cai, Junwei; Li, Xuefeng; Liu, Zhenqi; Cao, Wenhong

2014-01-01

We and others have recently shown that soyasaponins abundant in soybeans can decrease inflammation by suppressing the nuclear factor kappa B (NF-kB)-mediated inflammation. However, the exact molecular mechanisms by which soyasaponins inhibit the NF-kB pathway have not been established. In this study in macrophages, soyasaponins (A1, A2 and I) inhibited the lipopolysaccharide (LPS)-induced release of inflammatory marker prostaglandin E2 (PGE2) to a similar extent as the NF-kB inhibitor (BAY117082). Soyasaponins (A1, A2 and I) also suppressed the LPS-induced expression of cyclooxygenase 2 (COX-2), another inflammatory marker, in a dose-dependent manner by inhibiting NF-kB activation. In defining the associated mechanisms, we found that soyasaponins (A1, A2 and I) blunted the LPS-induced IKKα/β phosphorylation, IkB phosphorylation and degradation, and NF-kB p65 phosphorylation and nuclear translocation. In studying the upstream targets of soyasaponins on the NF-kB pathway, we found that soyasaponins (A1, A2 and I) suppressed the LPS-induced activation of PI3K/Akt similarly as the PI3K inhibitor LY294002, which alone blocked the LPS-induced activation of NF-kB. Additionally, soyasaponins (A1, A2 and I) reduced the LPS-induced production of reactive oxygen species (ROS) to the same extent as the anti-oxidant N-acetyl-L-cysteine, which alone inhibited the LPS-induced phosphorylation of Akt, IKKα/β, IkBα, and p65, transactivity of NF-kB, PGE2 production, and malondialdehyde production. Finally, our results show that soyasaponins (A1, A2 and I) elevated SOD activity and the GSH/GSSG ratio. Together, these results show that soyasaponins (A1, A2 and I) can blunt inflammation by inhibiting the ROS-mediated activation of the PI3K/Akt/NF-kB pathway. PMID:25233217

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.

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

Reactive oxygen species are key mediators of the nitric oxide apoptotic pathway in anterior pituitary cells.

PubMed

Machiavelli, Leticia I; Poliandri, Ariel H; Quinteros, Fernanda A; Cabilla, Jimena P; Duvilanski, Beatriz H

2007-03-01

We previously showed that long-term exposure of anterior pituitary cells to nitric oxide (NO) induces apoptosis. The intracellular signals underlying this effect remained unclear. In this study, we searched for possible mechanisms involved in the early stages of the NO apoptotic cascade. Caspase 3 was activated by NO with no apparent disruption of mitochondrial membrane potential. NO caused a rapid increase of reactive oxygen species (ROS), and this increase seems to be dependent of mitochondrial electron transport chain. The antioxidant N-acetyl-cysteine avoided ROS increase, prevented the NO-induced caspase 3 activation, and reduced the NO apoptotic effect. Catalase was inactivated by NO, while glutathione peroxidase (GPx) activity and reduced glutathione (GSH) were not modified at first, but increased at later times of NO exposure. The increase of GSH level is important for the scavenging of the NO-induced ROS overproduction. Our results indicate that ROS have an essential role as a trigger of the NO apoptotic cascade in anterior pituitary cells. The permanent inhibition of catalase may strengthen the oxidative damage induced by NO. GPx activity and GSH level augment in response to the oxidative damage, though this increase seems not to be enough to rescue the cells from the NO effect.

Small molecule CP-31398 induces reactive oxygen species-dependent apoptosis in human multiple myeloma

PubMed Central

Arihara, Yohei; Takada, Kohichi; Kamihara, Yusuke; Hayasaka, Naotaka; Nakamura, Hajime; Murase, Kazuyuki; Ikeda, Hiroshi; Iyama, Satoshi; Sato, Tsutomu; Miyanishi, Koji; Kobune, Masayoshi; Kato, Junji

2017-01-01

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. PMID:29029480

Hydrolase stabilization via entanglement in poly(propylene sulfide) nanoparticles: stability towards reactive oxygen species.

PubMed

Allen, Brett L; Johnson, Jermaine D; Walker, Jeremy P

2012-07-27

In the advancement of green syntheses and sustainable reactions, enzymatic biocatalysis offers extremely high reaction rates and selectivity that goes far beyond the reach of chemical catalysts; however, these enzymes suffer from typical environmental constraints, e.g. operational temperature, pH and tolerance to oxidative environments. A common hydrolase enzyme, diisopropylfluorophosphatase (DFPase, EC 3.1.8.2), has demonstrated a pronounced efficacy for the hydrolysis of a variety of substrates for potential toxin remediation, but suffers from the aforementioned limitations. As a means to enhance DFPase's stability in oxidative environments, enzymatic covalent immobilization within the polymeric matrix of poly(propylene sulfide) (PPS) nanoparticles was performed. By modifying the enzyme's exposed lysine residues via thiolation, DFPase is utilized as a comonomer/crosslinker in a mild emulsion polymerization. The resultant polymeric polysulfide shell acts as a 'sacrificial barrier' by first oxidizing to polysulfoxides and polysulfones, rendering DFPase in an active state. DFPase-PPS nanoparticles thus retain activity upon exposure to as high as 50 parts per million (ppm) of hypochlorous acid (HOCl), while native DFPase is observed as inactive at 500 parts per billion (ppb). This trend is also confirmed by enzyme-generated (chloroperoxidase (CPO), EC 1.11.1.10) reactive oxygen species (ROS) including both HOCl (3 ppm) and ClO(2) (100 ppm).

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.

Preventive treatment of astaxanthin provides neuroprotection through suppression of reactive oxygen species and activation of antioxidant defense pathway after stroke in rats.

PubMed

Pan, Lei; Zhou, Ying; Li, Xiu-Fang; Wan, Qing-Jia; Yu, Le-Hua

2017-04-01

Astaxanthin, a natural antioxidant carotenoid, has been shown to reduce cerebral ischemic injury in rodents. However, there have not been any studies specifically addressing whether preventive administration of astaxanthin can protect against cerebral ischemia. The purpose of this study was to examine whether pretreatment of astaxanthin can protect against ischemic injuries in the adult rats. The rats were pre-administered intragastrically with astaxanthin for seven days (once a day), and middle cerebral artery occlusion was performed at 1h after the final administration. It was found that astaxanthin prevented neurological deficits and reduced cerebral infarction volume. To evaluate the mechanisms underlying this protection, brain tissues were assayed for free radical damage, antioxidant gene expression, cell apoptosis and regeneration. The results showed that the mechanisms involved suppression of reactive oxygen species, activation of antioxidant defense pathway, and inhibition of apoptosis as well as promotion of neural regeneration. Astaxanthin did not alter body weights and the protective effect was found to be dose-dependent. Collectively, our data suggest that pretreatment of astaxanthin can protect against ischemia-related damages in brain tissue through multiple mechanisms, hinting that astaxanthin may have significant protective effects for patients vulnerable or prone to ischemic events. Copyright © 2017 Elsevier Inc. All rights reserved.

MIF-driven activation of macrophages induces killing of intracellular Trypanosoma cruzi dependent on endogenous production of tumor necrosis factor, nitric oxide and reactive oxygen species.

PubMed

Cutrullis, Romina A; Petray, Patricia B; Corral, Ricardo S

2017-02-01

The proinflammatory cytokine macrophage migration inhibitory factor (MIF) is a key player in innate immunity. MIF has been considered critical for controlling acute infection by the protozoan Trypanosoma cruzi, but the underlying mechanisms are poorly understood. Our study aimed to analyze whether MIF could favor microbicidal activity of the macrophage, a site where T. cruzi grows and the initial effector cell against this parasite. Using murine macrophages infected in vitro, we examined the effect of MIF on their parasiticidal ability and attempted to identify inflammatory agents involved in MIF-induced protection. Our findings show that MIF is readily secreted from peritoneal macrophages upon T. cruzi infection. MIF activates both primary and J774 phagocytes boosting the endogenous production of tumor necrosis factor-alpha via mitogen-activated protein kinase p38 signaling, as well as the release of nitric oxide and reactive oxygen species, leading to enhanced pathogen elimination. MIF can also potentiate the effect of interferon-gamma on T. cruzi killing by J774 and mouse peritoneal macrophages, rendering these cells more competent in reducing intracellular parasite burden. The present results unveil a novel innate immune pathway that contributes to host defense and broaden our understanding of the regulation of inflammatory mediators implicated in early parasite containment that is decisive for resistance to T. cruzi infection. Copyright © 2016 Elsevier GmbH. All rights reserved.

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...