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Sample records for acid reactive species

  1. 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

  2. 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

  3. Reactivity of pyruvic acid and its derivatives towards reactive oxygen species.

    PubMed

    Kładna, Aleksandra; Marchlewicz, Mariola; Piechowska, Teresa; Kruk, Irena; Aboul-Enein, Hassan Y

    2015-11-01

    Pyruvic acid and its derivatives occurring in most biological systems are known to exhibit several pharmacological properties, such as anti-inflammatory, neuroprotective or anticancer, many of which are suggested to originate from their antioxidant and free radical scavenger activity. The therapeutic potential of these compounds is a matter of particular interest, due to their mechanisms of action, particularly their possible antioxidant behaviour. Here, we report the results of a study of the effect of pyruvic acid (PA), ethyl pyruvate (EP) and sodium pyruvate (SP) on reactions generating reactive oxygen species (ROS), such as superoxide anion radicals, hydroxyl radicals and singlet oxygen, and their total antioxidant capacity. Chemiluminescence (CL) and spectrophotometry techniques were employed. The pyruvate analogues studied were found to inhibit the CL signal arising from superoxide anion radicals in a dose-dependent manner with IC50 = 0.0197 ± 0.002 mM for EP and IC50 = 69.2 ± 5.2 mM for PA. These compounds exhibited a dose-dependent decrease in the CL signal of the luminol + H2O2 system over the range 0.5-10 mM with IC50 values of 1.71 ± 0.12 mM for PA, 3.85 ± 0.21 mM for EP and 22.91 ± 1.21 mM for SP. Furthermore, these compounds also inhibited hydroxyl radical-dependent deoxyribose degradation in a dose-dependent manner over the range 0.5-200 mM, with IC50 values of 33.2 ± 0.3 mM for SP, 116.1 ± 6.2 mM for EP and 168.2 ± 6.2 mM for PA. All the examined compounds also showed antioxidant capacity when estimated using the ferric-ferrozine assay. The results suggest that the antioxidant activities of pyruvate derivatives may reflect a direct effect on scavenging ROS and, in part, be responsible for their pharmacological actions. PMID:25754627

  4. Reactive oxygen species abrogate the anticarcinogenic effect of eicosapentaenoic acid in Atm-deficient mice.

    PubMed

    Schubert, Ralf; Reichenbach, Janine; Koch, Claudia; Kloess, Stephan; Koehl, Ulrike; Mueller, Klaus; Baer, Patrick; Beermann, Christopher; Boehles, Hansjosef; Zielen, Stefan

    2010-01-01

    Recent studies have demonstrated that n-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) are able to suppress cell proliferation and inhibit tumor growth. The objective of our study was to investigate the influence of a high dose EPA on the development of the tumor phenotype in ataxia-telangiectasia mutated (Atm)-deficient mice, a genetic cancer model that is associated with increased levels of oxidative stress. We analyzed toxicity, proliferation, cell-cycle progression, and apoptosis of EPA in vitro and latency to tumorigenesis in vivo. Because of the impact of reactive oxygen species (ROS) on the tumor incidence in ataxia telangiectasia (AT), we further analyzed the effect of EPA on the generation of ROS and oxidative DNA damage (ODD). EPA effectively inhibited proliferation, altered cell-cycle progression, and induced apoptosis of tumor cells (AT-4). EPA showed no effect on the latency to tumorigenesis in Atm-deficient mice. EPA treatment was accompanied by a significant increase of ROS and ODD. Our results demonstrate the antiproliferative effect of EPA on tumor cells by alteration of cell-cycle progression and induction of apoptosis in vitro. On the other hand, EPA treatment of Atm-deficient mice led to the formation of ROS and accumulation of ODD that might have abrogated the anticarcinogenic effect caused by EPA. PMID:20574919

  5. Reactive oxygen species, abscisic acid and ethylene interact to regulate sunflower seed germination.

    PubMed

    El-Maarouf-Bouteau, Hayat; Sajjad, Yasar; Bazin, Jérémie; Langlade, Nicolas; Cristescu, Simona M; Balzergue, Sandrine; Baudouin, Emmanuel; Bailly, Christophe

    2015-02-01

    Sunflower (Helianthus annuus L.) seed dormancy is regulated by reactive oxygen species (ROS) and can be alleviated by incubating dormant embryos in the presence of methylviologen (MV), a ROS-generating compound. Ethylene alleviates sunflower seed dormancy whereas abscisic acid (ABA) represses germination. The purposes of this study were to identify the molecular basis of ROS effect on seed germination and to investigate their possible relationship with hormone signalling pathways. Ethylene treatment provoked ROS generation in embryonic axis whereas ABA had no effect on their production. The beneficial effect of ethylene on germination was lowered in the presence of antioxidant compounds, and MV suppressed the inhibitory effect of ABA. MV treatment did not alter significantly ethylene nor ABA production during seed imbibition. Microarray analysis showed that MV treatment triggered differential expression of 120 probe sets (59 more abundant and 61 less abundant genes), and most of the identified transcripts were related to cell signalling components. Many transcripts less represented in MV-treated seeds were involved in ABA signalling, thus suggesting an interaction between ROS and ABA signalling pathways at the transcriptional level. Altogether, these results shed new light on the crosstalk between ROS and plant hormones in seed germination. PMID:24811898

  6. Mechanistic and kinetic study on the reactions of coumaric acids with reactive oxygen species: a DFT approach.

    PubMed

    Garzón, Andrés; Bravo, Iván; Barbero, Antonio J; Albaladejo, José

    2014-10-01

    The mechanism and kinetics of reactions between coumaric acids and a series of reactive oxygen species ((•)OX) was studied through the density functional theory (DFT). H atom abstraction from -OH and -COOH groups and addition to the nonaromatic double bond were the most representative reaction pathways chosen for which free energy barriers and rate constants were calculated within the transition state theory (TST) framework. From these calculations, it was estimated that (•)OH > (•)OCH3 > (•)OOH > (•)OOCH3 is the order of reactivity of (•)OX with any coumaric acid. The highest rate constant was estimated for p-coumaric acid + (•)OH reaction, whereas the rest of the (•)OX species are more reactive with o-coumaric acid. On the basis of the calculated rate constants, H abstraction from a -OH group should be the main mechanism for the reactions involving (•)OCH3, (•)OOH, and (•)OOCH3 radicals. Nevertheless, the addition mechanism, which sometimes is not considered in theoretical studies on reactions of phenolic compounds with electrophilic species, could play a relevant role in the global mechanism of coumaric acid + (•)OH reactions. PMID:25166496

  7. Reactive oxygen species are involved in gibberellin/abscisic acid signaling in barley aleurone cells.

    PubMed

    Ishibashi, Yushi; Tawaratsumida, Tomoya; Kondo, Koji; Kasa, Shinsuke; Sakamoto, Masatsugu; Aoki, Nozomi; Zheng, Shao-Hui; Yuasa, Takashi; Iwaya-Inoue, Mari

    2012-04-01

    Reactive oxygen species (ROS) act as signal molecules for a variety of processes in plants. However, many questions about the roles of ROS in plants remain to be clarified. Here, we report the role of ROS in gibberellin (GA) and abscisic acid (ABA) signaling in barley (Hordeum vulgare) aleurone cells. The production of hydrogen peroxide (H2O2), a type of ROS, was induced by GA in aleurone cells but suppressed by ABA. Furthermore, exogenous H2O2 appeared to promote the induction of α-amylases by GA. In contrast, antioxidants suppressed the induction of α-amylases. Therefore, H2O2 seems to function in GA and ABA signaling, and in regulation of α-amylase production, in aleurone cells. To identify the target of H2O2 in GA and ABA signaling, we analyzed the interrelationships between H2O2 and DELLA proteins Slender1 (SLN1), GA-regulated Myb transcription factor (GAmyb), and ABA-responsive protein kinase (PKABA) and their roles in GA and ABA signaling in aleurone cells. In the presence of GA, exogenous H2O2 had little effect on the degradation of SLN1, the primary transcriptional repressor mediating GA signaling, but it promoted the production of the mRNA encoding GAMyb, which acts downstream of SLN1 and involves induction of α-amylase mRNA. Additionally, H2O2 suppressed the production of PKABA mRNA, which is induced by ABA:PKABA represses the production of GAMyb mRNA. From these observations, we concluded that H2O2 released the repression of GAMyb mRNA by PKABA and consequently promoted the production of α-amylase mRNA, thus suggesting that the H2O2 generated by GA in aleurone cells is a signal molecule that antagonizes ABA signaling. PMID:22291200

  8. Carnosic Acid Induces Apoptosis Through Reactive Oxygen Species-mediated Endoplasmic Reticulum Stress Induction in Human Renal Carcinoma Caki Cells

    PubMed Central

    Min, Kyoung-jin; Jung, Kyong-Jin; Kwon, Taeg Kyu

    2014-01-01

    Background: Carnosic acid, which is one of extract components of rosemary, has anti-inflammatory, anti-oxidant, and anti-cancer effects. However, the anti-cancer effect of carnosic acid in human renal carcinoma cells is unknown. Methods: Flow cytometry analysis was used to examine the effects of carnosic acid on apoptosis, and Asp-Glu-Val-Asp-ase activity assay kit was used to investigate the involvement of caspase activation. To determine protein expression of apoptotic and endoplasmic reticulum (ER) stress-related proteins, we used Western blotting. Intracellular accumulation of reactive oxygen species (ROS) was determined using the fluorescent probes 2’, 7’-dichlorodihydrofluorescein diacetate (H2DCFDA). Results: Carnosic acid induced sub-diploid DNA content, sub-G1, population and poly (ADP-ribose) polymerase (PARP) cleavage and activated caspase-3. A pan-caspase inhibitor, a benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone, markedly reduced apoptosis in carnosic acid-treated cells. Carnosic acid promoted intracellular ROS production, and pretreatment with the ROS scavengers (N-acetyl-L-cysteine and glutathione ethyl ester) inhibited carnosic acid-induced apoptosis. Furthermore, carnosic acid also induced expression of ER stress marker proteins, including activating transcription factor 4 (ATF4) and CCAAT/enhancer-binding protein-homologous protein (CHOP), in a dose- and time-dependent manner. Down-regulation of ATF4 and CHOP by small interfering RNA (siRNA) markedly reduced carnosic acid-induced sub-G1 population and PARP cleavage. In addition, carnosic acid induced apoptosis in human breast carcinoma MDA-MB-361 and human hepatocellular carcinoma SK-HEP1 cells, but not in normal human skin fibroblast cells and normal mouse kidney epithelial TMCK-1 cells. Conclusion: Carnosic acid induced apoptosis through production of ROS and induction of ER stress in human renal carcinoma Caki cells. PMID:25337586

  9. Graphene oxide induces plasma membrane damage, reactive oxygen species accumulation and fatty acid profiles change in Pichia pastoris.

    PubMed

    Zhang, Meng; Yu, Qilin; Liang, Chen; Liu, Zhe; Zhang, Biao; Li, Mingchun

    2016-10-01

    During the past couple of years, graphene nanomaterials were extremely popular among the scientists due to the promising properties in many aspects. Before the materials being well applied, we should first focus on their biosafety and toxicity. In this study, we investigated the toxicity of synthesized graphene oxide (GO) against the model industrial organism Pichia pastoris. We found that the synthesized GO showed dose-dependent toxicity to P. pastoris, through cell membrane damage and intracellular reactive oxygen species (ROS) accumulation. In response to these cell stresses, cells had normal unsaturated fatty acid (UFA) levels but increased contents of polyunsaturated fatty acid (PUFA) with up-regulation of UFA synthesis-related genes on the transcriptional level, which made it overcome the stress under GO attack. Two UFA defective strains (spt23Δ and fad12Δ) were used to demonstrate the results above. Hence, this study suggested a close connection between PUFAs and cell survival against GO. PMID:27376352

  10. Uric acid and transforming growth factor in fructose-induced production of reactive oxygen species in skeletal muscle.

    PubMed

    Madlala, Hlengiwe P; Maarman, Gerald J; Ojuka, Edward

    2016-04-01

    The consumption of fructose, a major constituent of the modern diet, has raised increasing concern about the effects of fructose on health. Research suggests that excessive intake of fructose (>50 g/d) causes hyperuricemia, insulin resistance, mitochondrial dysfunction, de novo lipogenesis by the liver, and increased production of reactive oxygen species (ROS) in muscle. In a number of tissues, uric acid has been shown to stimulate the production of ROS via activation of transforming growth factor β1 and NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 4. The role of uric acid in fructose-induced production of ROS in skeletal muscle, however, has not been investigated. This review examines the evidence for fructose-induced production of ROS in skeletal muscle, highlights proposed mechanisms, and identifies gaps in current knowledge. PMID:26946251

  11. Effect of phenolic acids of microbial origin on production of reactive oxygen species in mitochondria and neutrophils

    PubMed Central

    2012-01-01

    Background Several low-molecular-weight phenolic acids are present in the blood of septic patients at high levels. The microbial origin of the most of phenolic acids in the human body was shown previously, but pathophysiological role of the phenolic acids is not clear. Sepsis is associated with the excessive production of reactive oxygen species (ROS) in both the circulation and the affected organs. In this work the influence of phenolic acids on ROS production in mitochondria and neutrophils was investigated. Methods ROS production in mitochondria and neutrophils was determined by MCLA- and luminol-dependent chemiluminescence. The rate of oxygen consumption by mitochondria was determined polarographically. The difference of electric potentials on the inner mitochondrial membrane was registered using a TPP+-selective electrode. The formation of phenolic metabolites in monocultures by the members of the main groups of the anaerobic human microflora and aerobic pathogenic bacteria was investigated by the method of gas chromatography–mass spectrometry. Results All phenolic acids had impact on mitochondria and neutrophils, the main producers of ROS in tissues and circulation. Phenolic acids (benzoic and cinnamic acids) producing the pro-oxidant effect on mitochondria inhibited ROS formation in neutrophils. Their effect on mitochondria was abolished by dithiothreitol (DTT). Phenyllactate and p-hydroxyphenyllactate decreased ROS production in both mitochondria and neutrophils. Bifidobacteria and lactobacilli produced in vitro considerable amounts of phenyllactic and p-hydroxyphenyllactic acids, Clostridia s. produced great quantities of phenylpropionic and p-hydroxyphenylpropionic acids, p-hydroxyphenylacetic acid was produced by Pseudomonas aeruginosa and Acinetobacter baumanii; and benzoic acid, by Serratia marcescens. Conclusions The most potent activators of ROS production in mitochondria are phenolic acids whose effect is mediated via the interaction with thiol

  12. Determination of carnosine, anserine, homocarnosine, pentosidine and thiobarbituric acid reactive substances contents in meat from different animal species.

    PubMed

    Peiretti, Pier Giorgio; Medana, Claudio; Visentin, Sonja; Giancotti, Valeria; Zunino, Valentina; Meineri, Giorgia

    2011-06-15

    The aim of this research was to determine the content of the histidinic antioxidants, advanced glycation end products (pentosidine) and thiobarbituric acid reactive substance (TBARS) in the meat from different animal species. Carnosine, anserine, homocarnosine and pentosidine were quantified by HPLC/MS, while TBARS was determined by photometric measurements. The total CRCs (carnosine+anserine+homocarnosine) content was in the increasing order: beef

  13. Candida albicans erythroascorbate peroxidase regulates intracellular methylglyoxal and reactive oxygen species independently of D-erythroascorbic acid.

    PubMed

    Kwak, Min-Kyu; Song, Sung-Hyun; Ku, MyungHee; Kang, Sa-Ouk

    2015-07-01

    Candida albicans D-erythroascorbate peroxidase (EAPX1), which can catalyze the oxidation of D-erythroascorbic acid (EASC) to water, was observed to be inducible in EAPX1-deficient and EAPX1-overexpressing cells via activity staining. EAPX1-deficient cells have remarkably increased intracellular reactive oxygen species and methylglyoxal independent of the intracellular EASC content. The increased methylglyoxal caused EAPX1-deficient cells to activate catalase-peroxidase and cytochrome c peroxidase, which led to defects in cell growth, viability, mitochondrial respiration, filamentation and virulence. These findings indicate that EAPX1 mediates cell differentiation and virulence by regulating intracellular methylglyoxal along with oxidative stresses, regardless of endogenous EASC biosynthesis or alternative oxidase expression. PMID:25957768

  14. Ursolic acid isolated from guava leaves inhibits inflammatory mediators and reactive oxygen species in LPS-stimulated macrophages.

    PubMed

    Kim, Min-Hye; Kim, Jin Nam; Han, Sung Nim; Kim, Hye-Kyeong

    2015-06-01

    Psidium guajava (guava) leaves have been frequently used for the treatment of rheumatism, fever, arthritis and other inflammatory conditions. The purpose of this study was to identify major anti-inflammatory compounds from guava leaf extract. The methanol extract and its hexane-, dichloromethane-, ethylacetate-, n-butanol- and water-soluble phases derived from guava leaves were evaluated to determine their inhibitory activity on nitric oxide (NO) production by RAW 264.7 cells stimulated with lipopolysaccharide (LPS). The methanol extract decreased NO production in a dose-dependent manner without cytotoxicity at a concentration range of 0-100 μg/mL. The n-butanol soluble phase was the most potent among the five soluble phases. Four compounds were isolated by reversed-phase HPLC from the n-butanol soluble phase and identified to be avicularin, guaijaverin, leucocyanidin and ursolic acid by their NMR spectra. Among these compounds, ursolic acid inhibited LPS-induced NO production in a dose-dependent manner without cytotoxity at a concentration range of 1-10 µM, but the other three compounds had no effect. Ursolic acid also inhibited LPS-induced prostaglandin E2 production. A western blot analysis showed that ursolic acid decreased the LPS-stimulated inducible nitric oxide synthase and cyclooxygenase protein levels. In addition, ursolic acid suppressed the production of intracellular reactive oxygen species in LPS-stimulated RAW 264.7 cells, as measured by flow cytometry. Taken together, these results identified ursolic acid as a major anti-inflammatory compound in guava leaves. PMID:25753845

  15. Transient Influx of Nickel in Root Mitochondria Modulates Organic Acid and Reactive Oxygen Species Production in Nickel Hyperaccumulator Alyssum murale*

    PubMed Central

    Agrawal, Bhavana; Czymmek, Kirk J.; Sparks, Donald L.; Bais, Harsh P.

    2013-01-01

    Mitochondria are important targets of metal toxicity and are also vital for maintaining metal homeostasis. Here, we examined the potential role of mitochondria in homeostasis of nickel in the roots of nickel hyperaccumulator plant Alyssum murale. We evaluated the biochemical basis of nickel tolerance by comparing the role of mitochondria in closely related nickel hyperaccumulator A. murale and non-accumulator Alyssum montanum. Evidence is presented for the rapid and transient influx of nickel in root mitochondria of nickel hyperaccumulator A. murale. In an early response to nickel treatment, substantial nickel influx was observed in mitochondria prior to sequestration in vacuoles in the roots of hyperaccumulator A. murale compared with non-accumulator A. montanum. In addition, the mitochondrial Krebs cycle was modulated to increase synthesis of malic acid and citric acid involvement in nickel hyperaccumulation. Furthermore, malic acid, which is reported to form a complex with nickel in hyperaccumulators, was also found to reduce the reactive oxygen species generation induced by nickel. We propose that the interaction of nickel with mitochondria is imperative in the early steps of nickel uptake in nickel hyperaccumulator plants. Initial uptake of nickel in roots results in biochemical responses in the root mitochondria indicating its vital role in homeostasis of nickel ions in hyperaccumulation. PMID:23322782

  16. Effects of nitrogen dioxide and its acid mist on reactive oxygen species production and antioxidant enzyme activity in Arabidopsis plants.

    PubMed

    Liu, Xiaofang; Hou, Fen; Li, Guangke; Sang, Nan

    2015-08-01

    Nitrogen dioxide (NO2) is one of the most common and harmful air pollutants. To analyze the response of plants to NO2 stress, we investigated the morphological change, reactive oxygen species (ROS) production and antioxidant enzyme activity in Arabidopsis thaliana (Col-0) exposed to 1.7, 4, 8.5, and 18.8 mg/m(3) NO2. The results indicate that NO2 exposure affected plant growth and chlorophyll (Chl) content, and increased oxygen free radical (O2(-)) production rate in Arabidopsis shoots. Furthermore, NO2 elevated the levels of lipid peroxidation and protein oxidation, accompanied by the induction of antioxidant enzyme activities and change of ascorbate (AsA) and glutathione (GSH) contents. Following this, we mimicked nitric acid mist under experimental conditions, and confirmed the antioxidant mechanism of the plant to the stress. Our results imply that NO2 and its acid mist caused pollution risk to plant systems. During the process, increased ROS acted as a signal to induce a defense response, and antioxidant status played an important role in plant protection against NO2/nitric acid mist-caused oxidative damage. PMID:26257351

  17. Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis.

    PubMed

    Lee, Hyoung Jun; Han, Jeongsu; Jang, Yunseon; Kim, Soo Jeong; Park, Ji Hoon; Seo, Kang Sik; Jeong, Soyeon; Shin, Soyeon; Lim, Kyu; Heo, Jun Young; Kweon, Gi Ryang

    2015-01-30

    Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson's disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson's disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis. PMID:25545062

  18. The reactions of hypochlorous acid, the reactive oxygen species produced by myeloperoxidase, with lipids.

    PubMed

    Spickett, C M; Jerlich, A; Panasenko, O M; Arnhold, J; Pitt, A R; Stelmaszyńska, T; Schaur, R J

    2000-01-01

    Myeloperoxidase (MPO), an abundant enzyme in phagocytes, has been implicated in the pathogenesis of various inflammatory diseases including atherosclerosis. The major oxidant produced by MPO, hypochlorous acid (HOCl), is able to modify a great variety of biomolecules by chlorination and/or oxidation. In this paper the reactions of lipids (preferentially unsaturated fatty acids and cholesterol) with either reagent HOCl or HOCl generated by the MPO-hydrogen peroxide-chloride system are reviewed. One of the major issues has been whether the reaction of HOCl with lipids of low density lipoprotein (LDL) yields predominantly chlorohydrins or lipid hydroperoxides. Electrospray mass spectrometry provided direct evidence that chlorohydrins rather than peroxides are the major products of HOCl- or MPO-treated LDL phosphatidylcholines. Nevertheless lipid peroxidation is a possible alternative reaction of HOCl with polyunsaturated fatty acids if an additional radical source such as pre-formed lipid hydroperoxides is available. In phospholipids carrying a primary amino group such as phosphatidylethanolamine chloramines are the preferred products compared to chlorohydrins. Cholesterol can be converted by HOCl to great variety of oxysterols besides three isomers of chlorohydrins. For the situation in vivo it appears that the type of reaction occurring between HOCl and lipids would very much depend on the circumstances, e.g. the pH and the presence of radical initiators. The biological effects of lipid chlorohydrins are not yet well understood. It has been shown that chlorohydrins of both unsaturated fatty acids as well as of cholesterol may cause lysis of target cells, possibly by disruption of membrane structures. PMID:11996112

  19. Protective effects of α-tocopherol and ascorbic acid against cardol-induced cell death and reactive oxygen species generation in Staphylococcus aureus.

    PubMed

    Murata, Wakae; Tanaka, Toshio; Kubo, Isao; Fujita, Ken-ichi

    2013-06-01

    Cardol (C₁₅:₃), isolated from cashew (Anacardium occidentale L.) nut shell liquid, has been shown to exhibit bactericidal activity against various strains of Staphylococcus aureus, including methicillin-resistant strains. The maximum level of reactive oxygen species generation was detected at around the minimum bactericidal concentration of cardol, while reactive oxygen species production drastically decreased at doses above the minimum bactericidal concentration. The primary response for bactericidal activity around the bactericidal concentration was noted to primarily originate from oxidative stress such as intracellular reactive oxygen species generation. High doses of cardol (C₁₅:₃) were shown to induce leakage of K⁺ from S. aureus cells, which may be related to the decrease in reactive oxygen species. Antioxidants such as α-tocopherol and ascorbic acid restricted reactive oxygen species generation and restored cellular damage induced by the lipid. Cardol (C₁₅:₃) overdose probably disrupts the native membrane-associated function as it acts as a surfactant. The maximum antibacterial activity of cardols against S. aureus depends on their log P values (partition coefficient in octanol/water) and is related to their similarity to those of anacardic acids isolated from the same source. PMID:23670625

  20. Long-chain bases, phosphatidic acid, MAPKs, and reactive oxygen species as nodal signal transducers in stress responses in Arabidopsis

    PubMed Central

    Saucedo-García, Mariana; Gavilanes-Ruíz, Marina; Arce-Cervantes, Oscar

    2015-01-01

    Due to their sessile condition, plants have developed sensitive, fast, and effective ways to contend with environmental changes. These mechanisms operate as informational wires conforming extensive and intricate networks that are connected in several points. The responses are designed as pathways orchestrated by molecules that are transducers of protein and non-protein nature. Their chemical nature imposes selective features such as specificity, formation rate, and generation site to the informational routes. Enzymes such as mitogen-activated protein kinases and non-protein, smaller molecules, such as long-chain bases, phosphatidic acid, and reactive oxygen species are recurrent transducers in the pleiotropic responses to biotic and abiotic stresses in plants. In this review, we considered these four components as nodal points of converging signaling pathways that start from very diverse stimuli and evoke very different responses. These pleiotropic effects may be explained by the potentiality that every one of these four mediators can be expressed from different sources, cellular location, temporality, or magnitude. Here, we review recent advances in our understanding of the interplay of these four specific signaling components in Arabidopsis cells, with an emphasis on drought, cold and pathogen stresses. PMID:25763001

  1. Salicylic acid determines differential senescence produced by two Turnip mosaic virus strains involving reactive oxygen species and early transcriptomic changes.

    PubMed

    Manacorda, Carlos Augusto; Mansilla, Carmen; Debat, Humberto Julio; Zavallo, Diego; Sánchez, Flora; Ponz, Fernando; Asurmendi, Sebastián

    2013-12-01

    Losses produced by virus diseases depend mostly on symptom severity. Turnip mosaic virus (TuMV) is one of the most damaging and widespread potyvirus infecting members of the family Brassicaceae, including Arabidopsis thaliana. We used JPN1 and UK1 TuMV strains to characterize viral infections regarding symptom development, senescence progression, antioxidant response, reactive oxygen species (ROS) accumulation, and transcriptional profiling. Both isolates, despite accumulating similar viral titers, induced different symptomatology and strong differences in oxidative status. Early differences in several senescence-associated genes linked to the ORE1 and ORS1 regulatory networks as well as persistent divergence in key ROS production and scavenging systems of the plant were detected. However, at a later stage, both strains induced nutrient competition, indicating that senescence rates are influenced by different mechanisms upon viral infections. Analyses of ORE1 and ORS1 levels in infected Brassica juncea plants showed a similar pattern, suggesting a conserved differential response to both strains in Brassicaceae spp. Transcriptional analysis of the ORE1 and ORS1 regulons showed similarities between salicylic acid (SA) response and the early induction triggered by UK1, the most severe strain. By means of SA-defective NahG transgenic plants, we found that differential senescence progression and ROS accumulation between strains rely on an intact SA pathway. PMID:23945002

  2. Potato chip intake increases ascorbic acid levels and decreases reactive oxygen species in SMP30/GNL knockout mouse tissues.

    PubMed

    Kondo, Yoshitaka; Sakuma, Rui; Ichisawa, Megumi; Ishihara, Katsuyuki; Kubo, Misako; Handa, Setsuko; Mugita, Hiroyuki; Maruyama, Naoki; Koga, Hidenori; Ishigami, Akihito

    2014-09-24

    Potato chips (PC) contain abundant amounts of the free radical scavenger ascorbic acid (AA) due to the rapid dehydration of potato tubers (Solanum tuberosum) that occurs during frying. To evaluate the antioxidant activity of PC, this study examined reactive oxygen species (ROS) levels in tissues from SMP30/GNL knockout (KO) mice that cannot synthesize AA and determined AA and ROS levels after the animals were fed 20 and 10% PC diets for 7 weeks. Compared with AA-sufficient mice, AA-depleted SMP30/GNL KO mice showed high ROS levels in tissues. SMP30/GNL KO mice fed a PC diet showed high AA and low ROS levels in the brain, heart, lung, testis, soleus muscle, plantaris muscle, stomach, small intestine, large intestine, eyeball, and epididymal fat compared with AA-depleted mice. The data suggest that PC intake increases AA levels and enhances ROS scavenging activity in tissues of SMP30/GNL KO mice, which are a promising model for evaluating the antioxidant activity of foods. PMID:25180784

  3. Epoxyeicosatrienoic acids attenuate reactive oxygen species level, mitochondrial dysfunction, caspase activation, and apoptosis in carcinoma cells treated with arsenic trioxide.

    PubMed

    Liu, Liu; Chen, Chen; Gong, Wei; Li, Yuanjing; Edin, Matthew L; Zeldin, Darryl C; Wang, Dao Wen

    2011-11-01

    Epoxyeicosatrienoic acids (EETs) and the cytochrome P450 epoxygenase CYP2J2 promote tumorogenesis in vivo and in vitro via direct stimulation of tumor cell growth and inhibition of tumor cell apoptosis. Herein, we describe a novel mechanism of inhibition of tumor cell apoptosis by EETs. In Tca-8113 cancer cells, the antileukemia drug arsenic trioxide (ATO) led to the generation of reactive oxygen species (ROS), impaired mitochondrial function, and induced apoptosis. 11,12-EET pretreatment increased expression of the antioxidant enzymes superoxide dismutase and catalase and inhibited ATO-induced apoptosis. 11,12-EET also prevented the ATO-induced activation of p38 mitogen-activated protein kinase, c-Jun NH(2)-terminal kinase, caspase-3, and caspase-9. Therefore, 11,12-EET-pretreatment attenuated the ROS generation, loss of mitochondrial function, and caspase activation observed after ATO treatment. Moreover, the CYP2J2-specific inhibitor compound 26 enhanced arsenic cytotoxicity to a clinically relevant concentration of ATO (1-2 μM). Both the thiol-containing antioxidant, N-acetyl-cysteine, and 11,12-EET reversed the synergistic effect of the two agents. Taken together, these data indicate that 11,12-EET inhibits apoptosis induced by ATO through a mechanism that involves induction of antioxidant proteins and attenuation of ROS-mediated mitochondrial dysfunction. PMID:21846841

  4. Temporal-Spatial Interaction between Reactive Oxygen Species and Abscisic Acid Regulates Rapid Systemic Acclimation in Plants[W][OPEN

    PubMed Central

    Suzuki, Nobuhiro; Miller, Gad; Salazar, Carolina; Mondal, Hossain A.; Shulaev, Elena; Cortes, Diego F.; Shuman, Joel L.; Luo, Xiaozhong; Shah, Jyoti; Schlauch, Karen; Shulaev, Vladimir; Mittler, Ron

    2013-01-01

    Being sessile organisms, plants evolved sophisticated acclimation mechanisms to cope with abiotic challenges in their environment. These are activated at the initial site of exposure to stress, as well as in systemic tissues that have not been subjected to stress (termed systemic acquired acclimation [SAA]). Although SAA is thought to play a key role in plant survival during stress, little is known about the signaling mechanisms underlying it. Here, we report that SAA in plants requires at least two different signals: an autopropagating wave of reactive oxygen species (ROS) that rapidly spreads from the initial site of exposure to the entire plant and a stress-specific signal that conveys abiotic stress specificity. We further demonstrate that SAA is stress specific and that a temporal–spatial interaction between ROS and abscisic acid regulates rapid SAA to heat stress in plants. In addition, we demonstrate that the rapid ROS signal is associated with the propagation of electric signals in Arabidopsis thaliana. Our findings unravel some of the basic signaling mechanisms underlying SAA in plants and reveal that signaling events and transcriptome and metabolome reprogramming of systemic tissues in response to abiotic stress occur at a much faster rate than previously envisioned. PMID:24038652

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

    SciTech Connect

    Lin, Chu-Cheng; Lin, Chuan-En; Lin, Yueh-Chien; Ju, Tsai-Kai; Huang, Yuan-Li; Lee, Ming-Shyue; Chen, Jiun-Hong; Lee, Hsinyu

    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 is 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.

  6. beta-aminobutyric acid primes an NADPH oxidase-dependent reactive oxygen species production during grapevine-triggered immunity.

    PubMed

    Dubreuil-Maurizi, Carole; Trouvelot, Sophie; Frettinger, Patrick; Pugin, Alain; Wendehenne, David; Poinssot, Benoît

    2010-08-01

    The molecular mechanisms underlying the process of priming are poorly understood. In the present study, we investigated the early signaling events triggered by beta-aminobutyric acid (BABA), a well-known priming-mediated plant resistance inducer. Our results indicate that, in contrast to oligogalacturonides (OG), BABA does not elicit typical defense-related early signaling events nor defense-gene expression in grapevine. However, in OG-elicited cells pretreated with BABA, production of reactive oxygen species (ROS) and expression of the respiratory-burst oxidase homolog RbohD gene were primed. In response to the causal agent of downy mildew Plasmopara viticola, a stronger ROS production was specifically observed in BABA-treated leaves. This process was correlated with an increased resistance. The NADPH oxidase inhibitor diphenylene iodonium (DPI) abolished this primed ROS production and reduced the BABA-induced resistance (BABA-IR). These results suggest that priming of an NADPH oxidase-dependent ROS production contributes to BABA-IR in the Vitis-Plasmopara pathosystem. PMID:20615112

  7. Serotonin modulates Arabidopsis root growth via changes in reactive oxygen species and jasmonic acid-ethylene signaling.

    PubMed

    Pelagio-Flores, Ramón; Ruiz-Herrera, León Francisco; López-Bucio, José

    2016-09-01

    Serotonin (5-hydroxytryptamine) is a bioactive indoleamine with neurotransmitter function in vertebrates, which represents an emerging signaling molecule in plants, playing key roles in the development and defense. In this study, the role of reactive oxygen species (ROS) and jasmonic acid (JA)-ethylene (Et) signaling in root developmental alterations induced by serotonin was investigated. An Arabidopsis thaliana mutant defective at the RADICAL-INDUCED CELL DEATH1 (RCD1) locus was resistant to paraquat-induced ROS accumulation in primary roots and showed decreased inhibition or root growth in response to serotonin. A suite of JA- and Et-related mutants including coronatine insensitive1, jasmonic acid resistant1 (jar1), etr1, ein2 and ein3 showed tolerance to serotonin in the inhibition of primary root growth and ROS redistribution within the root tip when compared with wild-type (WT) seedlings. Competence assays between serotonin and AgNO3 , a well-known blocker of Et action, showed that primary root growth in medium supplemented with serotonin was normalized by AgNO3 , whereas roots of eto3, an Et overproducer mutant, were oversensitive to serotonin. Comparison of ROS levels in WT, etr1, jar1 and rcd1 primary root tips using the ROS-specific probe 2',7'-dichlorofluorescein diacetate and confocal imaging showed that serotonin inhibition of primary root growth likely occurs independently of its conversion into melatonin. Our results provide compelling evidence that serotonin affects ROS distribution in roots, involving RCD1 and components of the JA-Et signaling pathways. PMID:26864878

  8. Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis

    SciTech Connect

    Lee, Hyoung Jun; Han, Jeongsu; Jang, Yunseon; Kim, Soo Jeong; Park, Ji Hoon; Seo, Kang Sik; Jeong, Soyeon; Shin, Soyeon; Lim, Kyu; Heo, Jun Young; Kweon, Gi Ryang

    2015-01-30

    Highlights: • DHA prevents PQ-induced dopaminergic neuronal loss via decreasing of excessive ROS. • DHA increases GR and GCLm derivate GSH pool by enhancement of Nrf2 expression. • Protective mechanism is removal of PQ-induced ROS via DHA-dependent GSH pool. • DHA may be a good preventive strategy for Parkinson’s disease (PD) therapy. - Abstract: Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson’s disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson’s disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis.

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

    SciTech Connect

    Li, Qingyong; Zhang, Li; Zu, Yuangang; Liu, Tianyu; Zhang, Baoyou; He, Wuna

    2013-04-19

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

  10. Islet glutamic acid decarboxylase modified by reactive oxygen species is recognized by antibodies from patients with type 1 diabetes mellitus

    PubMed Central

    Trigwell, S M; Radford, P M; Page, S R; Loweth, A C; James, R F L; Morgan, N G; Todd, I

    2001-01-01

    The generation of an autoimmune response against islet beta-cells is central to the pathogenesis of type 1 diabetes mellitus, and this response is driven by the stimulation of autoreactive lymphocytes by components of the beta-cells themselves. Reactive oxygen species (ROS) have been implicated in the beta-cell destruction which leads to type 1 diabetes and may modify beta-cell components so as to enhance their immunogenicity. We investigated the effects of oxidation reactions catalysed by copper or iron on the major beta-cell autoantigen glutamic acid decarboxylase (GAD). Lysates of purified rat islets were exposed to copper or iron sulphate with or without hydrogen peroxide or ascorbic acid. Immunostaining showed that these treatments generated high molecular weight covalently linked aggregates containing GAD. These are not formed by intermolecular disulphide bonds between cysteine residues since they cannot be resolved into monomeric form when electrophoresed under extreme reducing conditions. There was no modification of insulin or pro-insulin by ROS. The same oxidative changes to GAD could be induced in viable islet cells treated with copper sulphate and hydrogen peroxide, and thus the modifications are not an artefact of the catalysed oxidation of cell-free lysates. Sera from patients with type 1 diabetes and stiffman syndrome containing GAD antibodies reacted predominantly with the highest molecular weight modified protein band of GAD: normal human sera did not precipitate GAD. Thus, oxidatively modified aggregates of GAD react with serum antibodies of type 1 diabetes patients and some SMS patients: this is consistent with oxidative modifications of autoantigens being relevant to the pathogenesis of type 1 diabetes. PMID:11703367

  11. Islet glutamic acid decarboxylase modified by reactive oxygen species is recognized by antibodies from patients with type 1 diabetes mellitus.

    PubMed

    Trigwell, S M; Radford, P M; Page, S R; Loweth, A C; James, R F; Morgan, N G; Todd, I

    2001-11-01

    The generation of an autoimmune response against islet beta-cells is central to the pathogenesis of type 1 diabetes mellitus, and this response is driven by the stimulation of autoreactive lymphocytes by components of the beta-cells themselves. Reactive oxygen species (ROS) have been implicated in the beta-cell destruction which leads to type 1 diabetes and may modify beta-cell components so as to enhance their immunogenicity. We investigated the effects of oxidation reactions catalysed by copper or iron on the major beta-cell autoantigen glutamic acid decarboxylase (GAD). Lysates of purified rat islets were exposed to copper or iron sulphate with or without hydrogen peroxide or ascorbic acid. Immunostaining showed that these treatments generated high molecular weight covalently linked aggregates containing GAD. These are not formed by intermolecular disulphide bonds between cysteine residues since they cannot be resolved into monomeric form when electrophoresed under extreme reducing conditions. There was no modification of insulin or pro-insulin by ROS. The same oxidative changes to GAD could be induced in viable islet cells treated with copper sulphate and hydrogen peroxide, and thus the modifications are not an artefact of the catalysed oxidation of cell-free lysates. Sera from patients with type 1 diabetes and stiffman syndrome containing GAD antibodies reacted predominantly with the highest molecular weight modified protein band of GAD: normal human sera did not precipitate GAD. Thus, oxidatively modified aggregates of GAD react with serum antibodies of type 1 diabetes patients and some SMS patients: this is consistent with oxidative modifications of autoantigens being relevant to the pathogenesis of type 1 diabetes. PMID:11703367

  12. Is alpha-lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity.

    PubMed

    Petersen Shay, Kate; Moreau, Régis F; Smith, Eric J; Hagen, Tory M

    2008-06-01

    The chemical reduction and oxidation (redox) properties of alpha-lipoic acid (LA) suggest that it may have potent antioxidant potential. A significant number of studies now show that LA and its reduced form, dihydrolipoic acid (DHLA), directly scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) species and protect cells against a host of insults where oxidative stress is part of the underlying etiology. However, owing to its limited and transient accumulation in tissues following oral intake, the efficacy of nonprotein-bound LA to function as a physiological antioxidant has been questioned. Herein, we review the evidence that the micronutrient functions of LA may be more as an effector of important cellular stress response pathways that ultimately influence endogenous cellular antioxidant levels and reduce proinflammatory mechanisms. This would promote a sustained improvement in cellular resistance to pathologies where oxidative stress is involved, which would not be forthcoming if LA solely acted as a transient ROS scavenger. PMID:18409172

  13. Scavenging of reactive oxygen and nitrogen species by the prodrug sulfasalazine and its metabolites 5-aminosalicylic acid and sulfapyridine.

    PubMed

    Couto, Diana; Ribeiro, Daniela; Freitas, Marisa; Gomes, Ana; Lima, José L F C; Fernandes, Eduarda

    2010-01-01

    Sulfasalazine is a prodrug composed by a molecule of 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), linked by an azo bond, which has been shown to be effective in the therapy of inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease, as well as of rheumatic diseases, such as rheumatoid arthritis and ankylosing spondylitis. The precise mechanism of action of sulfasalazine and/or its metabolites has not been completely elucidated, though its antioxidant effects are well established and are probably due to its scavenging effects against reactive oxygen and nitrogen species (ROS and RNS), as well as metal chelating properties, in association to its inhibitory effects over neutrophil oxidative burst. The present work was focused on screening and comparing the potential scavenging activity for an array of ROS (O(2)(•-), H(2)O(2), (1)O(2), ROO(•) and HOCl) and RNS ((•)NO and ONOO(-)), mediated by sulfasalazine and its metabolites 5-ASA and SP, using validated in vitro screening systems. The results showed that both 5-ASA and sulfasalazine were able to scavenge all the tested ROS while SP was practically ineffective in all the assays. For HOCl, (1)O(2), and ROO(•), 5-ASA showed the best scavenging effects. A new and important finding of the present study was the strong scavenging effect of 5-ASA against (1)O(2). 5-ASA was shown to be a strong scavenger of (•)NO and ONOO(-). Sulfasalazine was also able to scavenge these RNS, although with a much lower potency than 5-ASA. SP was unable to scavenge (•)NO in the tested concentrations but was shown to scavenge ONOO(-), with a higher strength when the assay was performed in the presence of 25 mM bicarbonate, suggesting further scavenging of oxidizing carbonate radical. In conclusion, the ROS- and RNS-scavenging effects of sulfasalazine and its metabolites shown in this study may contribute to the anti-inflammatory effects mediated by sulfasalazine through the prevention of the

  14. Organochlorine insecticides induce NADPH oxidase-dependent reactive oxygen species in human monocytic cells via phospholipase A2/arachidonic acid.

    PubMed

    Mangum, Lee C; Borazjani, Abdolsamad; Stokes, John V; Matthews, Anberitha T; Lee, Jung Hwa; Chambers, Janice E; Ross, Matthew K

    2015-04-20

    Bioaccumulative organohalogen chemicals, such as organochlorine (OC) insecticides, have been increasingly associated with disease etiology; however, the mechanistic link between chemical exposure and diseases, such as atherosclerosis, cancer, and diabetes, is complex and poorly defined. Systemic oxidative stress stemming from OC exposure might play a vital role in the development of these pathologies. Monocytes are important surveillance cells of the innate immune system that respond to extracellular signals possessing danger-associated molecular patterns by synthesizing oxyradicals, such as superoxide, for the purpose of combating infectious pathogens. We hypothesized that OC chemicals can be toxic to monocytes because of an inappropriate elevation in superoxide-derived reactive oxygen species (ROS) capable of causing cellular oxidative damage. Reactive oxyradicals are generated in monocytes in large part by NADPH oxidase (Nox). The present study was conducted to examine the ability of two chlorinated cyclodiene compounds, trans-nonachlor and dieldrin, as well as p,p'-DDE, a chlorinated alicyclic metabolite of DDT, to stimulate Nox activity in a human monocytic cell line and to elucidate the mechanisms for this activation. Human THP-1 monocytes treated with either trans-nonachlor or dieldrin (0.1-10 μM in the culture medium) exhibited elevated levels of intracellular ROS, as evidenced by complementary methods, including flow cytometry analysis using the probe DCFH-DA and hydroethidine-based fluorometric and UPLC-MS assays. In addition, the induced reactive oxygen flux caused by trans-nonachlor was also observed in two other cell lines, murine J774 macrophages and human HL-60 cells. The central role of Nox in OC-mediated oxidative stress was demonstrated by the attenuated superoxide production in OC-exposed monocytes treated with the Nox inhibitors diphenyleneiodonium and VAS-2870. Moreover, monocytes challenged with OCs exhibited increased phospho-p47(phox

  15. Evaluation of fatty acid oxidation by reactive oxygen species induced in liquids using atmospheric-pressure nonthermal plasma jets

    NASA Astrophysics Data System (ADS)

    Tani, Atsushi; Fukui, Satoshi; Ikawa, Satoshi; Kitano, Katsuhisa

    2015-10-01

    We investigated fatty acid oxidation by atmospheric-pressure nonthermal helium plasma using linoleic acid, an unsaturated fatty acid, together with evaluating active species induced in liquids. If the ambient gas contains oxygen, direct plasma such as plasma jets coming into contact with the liquid surface supplies various active species, such as singlet oxygen, ozone, and superoxide anion radicals, to the liquid. The direct plasma easily oxidizes linoleic acid, indicating that fatty acid oxidation will occur in the direct plasma. In contrast, afterglow flow, where the plasma is terminated in a glass tube and does not touch the surface of the liquid sample, supplies mainly superoxide anion radicals. The fact that there was no clear observation of linoleic acid oxidation using the afterglow reveals that it may not affect lipids, even in an atmosphere containing oxygen. The afterglow flow can potentially be used for the sterilization of aqueous solutions using the reduced pH method, in medical and dental applications, because it provides bactericidal activity in the aqueous solution despite containing a smaller amount of active species.

  16. Bacterial responses to reactive chlorine species.

    PubMed

    Gray, Michael J; Wholey, Wei-Yun; Jakob, Ursula

    2013-01-01

    Hypochlorous acid (HOCl), the active ingredient of household bleach, is the most common disinfectant in medical, industrial, and domestic use and plays an important role in microbial killing in the innate immune system. Given the critical importance of the antimicrobial properties of chlorine to public health, it is surprising how little is known about the ways in which bacteria sense and respond to reactive chlorine species (RCS). Although the literature on bacterial responses to reactive oxygen species (ROS) is enormous, work addressing bacterial responses to RCS has begun only recently. Transcriptomic and proteomic studies now provide new insights into how bacteria mount defenses against this important class of antimicrobial compounds. In this review, we summarize the current knowledge, emphasizing the overlaps between RCS stress responses and other more well-characterized bacterial defense systems, and identify outstanding questions that represent productive avenues for future research. PMID:23768204

  17. UV Light-Induced Generation of Reactive Oxygen Species and Antimicrobial Properties of Cellulose Fabric Modified by 3,3',4,4'-Benzophenone Tetracarboxylic Acid.

    PubMed

    Hou, Aiqin; Feng, Guanchen; Zhuo, Jingyuan; Sun, Gang

    2015-12-23

    3,3',4,4'-Benzophenone tetracarboxylic acid (BPTCA) could directly react with hydroxyl groups on cellulose to form ester bonds. The modified cotton fabrics not only provided good wrinkle-free and ultraviolet (UV) protective functions, but also exhibited important photochemical properties such as producing reactive oxygen species (ROS) including hydroxyl radicals (HO(•)) and hydrogen peroxide (H2O2) under UV light exposure. The amounts of the produced hydroxyl radical and hydrogen peroxide were measured, and photochemical reactive mechanism of the BPTCA treated cellulose was discussed. The results reveal that the fabrics possess good washing durability in generation of hydroxyl radicals and hydrogen peroxide. The cotton fabrics modified with different concentrations of BPTCA and cured at an elevated temperature demonstrated excellent antimicrobial activities, which provided 99.99% antibacterial activities against both E. coli and S. aureus. The advanced materials have potential applications in medical textiles and biological material fields. PMID:26636826

  18. Arachidonic acid stimulates TNFα production in Kupffer cells via a reactive oxygen species-pERK1/2-Egr1-dependent mechanism.

    PubMed

    Cubero, Francisco Javier; Nieto, Natalia

    2012-07-15

    Kupffer cells are a key source of mediators of alcohol-induced liver damage such as reactive oxygen species, chemokines, growth factors, and eicosanoids. Since diets rich in polyunsaturated fatty acids are a requirement for the development of alcoholic liver disease, we hypothesized that polyunsaturated fatty acids could synergize with ethanol to promote Kupffer cell activation and TNFα production, hence, contributing to liver injury. Primary Kupffer cells from control and from ethanol-fed rats incubated with arachidonic acid showed similar proliferation rates than nontreated cells; however, arachidonic acid induced phenotypic changes, lipid peroxidation, hydroperoxides, and superoxide radical generation. Similar effects occurred in human Kupffer cells. These events were greater in Kupffer cells from ethanol-fed rats, and antioxidants and inhibitors of arachidonic acid metabolism prevented them. Arachidonic acid treatment increased NADPH oxidase activity. Inhibitors of NADPH oxidase and of arachidonic acid metabolism partially prevented the increase in oxidant stress. Upon arachidonic acid stimulation, there was a rapid and sustained increase in TNFα, which was greater in Kupffer cells from ethanol-fed rats than in Kupffer cells from control rats. Arachidonic acid induced ERK1/2 phosphorylation and nuclear translocation of early growth response-1 (Egr1), and ethanol synergized with arachidonic acid to promote this effect. PD98059, a mitogen extracellular kinase 1/2 inhibitor, and curcumin, an Egr1 inhibitor, blocked the arachidonic acid-mediated upregulation of TNFα in Kupffer cells. This study unveils the mechanism whereby arachidonic acid and ethanol increase TNFα production in Kupffer cells, thus contributing to alcoholic liver disease. PMID:22538404

  19. Generation of reactive oxygen species from 5-aminolevulinic acid and Glutamate in cooperation with excited CdSe/ZnS QDs

    NASA Astrophysics Data System (ADS)

    Duong, Hong Dinh; Lee, Jee Won; Rhee, Jong Il

    2014-08-01

    CdSe/ZnS quantum dots (QDs) can be joined in the reductive pathway involving the electron transfer to an acceptor or in the oxidative pathway involving the hole transfer to a donor. They were exploited in the oxidation reactions of 5-aminolevulinic acid (ALA) and glutamate (GLU) for the generation of reactive oxygen species (ROS) such as hydroxyl radical (HO●) and superoxide anion (O2 ● -). Fast and highly efficient oxidation reactions of ALA to produce HO● and of GLU to produce O2 ●- were observed in the cooperation of mercaptopropionic acid (MPA)-capped CdSe/ZnS QDs under LED irradiation. Fluorescence spectroscopy and electron spin resonance (ESR) spectroscopy were used to evaluate the generation of different forms of ROS. Confocal fluorescent microscopic images of the size and morphology of HeLa cells confirmed the ROS generation from ALA or GLU in cooperation with CdSe/ZnS QDs under LED irradiation.

  20. Effects of reactive oxygen and nitrogen species induced by ammonium dinitramide decomposition in aqueous solutions of deoxyribose nucleic acid.

    PubMed

    Steel-Goodwin, L; Kuhlman, K J; Miller, C; Pace, M D; Carmichael, A J

    1997-01-01

    Ammonium dinitramide (ADN), a potential rocket fuel, decomposes in water forming NO2. The chemistry of this ADN-released NO2 in oxygenated biological systems is complex both in the number of potential chemical species and in the number of parallel and consecutive reactions that can theoretically occur. High-pressure liquid chromatography (HPLC) studies revealed ADN fragmented deoxyribose nucleic acid (DNA). Damage to DNA standard solutions was caused by at least two major pathways, one arising from reactions of NO2 with oxygen and one arising from a reaction with superoxide (O2-.). The radical species generated when ADN is incubated with standard solutions of DNA, pH 7.5, in the presence of the spin trap agent n-tert-butyl-alpha-nitrone (PBN) was compared with the PBN-radical adducts generated in the presence of ADN and O2-. or of ADN and hydrogen peroxide (H2O2). The ADN-induced PBN radical adducts increased linearly over the 90-minute study period. The values of peak intensity in the presence of O2-. and in the presence of H2O2, were 828% and 7.08%, respectively, of the ADN-induced radicals alone. The synergistic effect of ADN with O2- may provide an understanding of the sensitivity of the rat blastocyst to aDN at the preimplantation stage of development and the lack of toxicity in in vivo studies in tissues high in catalase. PMID:9142377

  1. Halogen-induced organic aerosol (XOA) formation and decarboxylation of carboxylic acids by reactive halogen species - a time-resolved aerosol flow-reactor study

    NASA Astrophysics Data System (ADS)

    Ofner, Johannes; Zetzsch, Cornelius

    2013-04-01

    Reactive halogen species (RHS) are released to the atmosphere from various sources like photo-activated sea-salt aerosol and salt lakes. Recent studies (Cai et al., 2006 and 2008, Ofner et al., 2012) indicate that RHS are able to interact with SOA precursors similarly to common atmospheric oxidizing gases like OH radicals and ozone. The reaction of RHS with SOA precursors like terpenes forms so-called halogen-induced organic aerosol (XOA). On the other hand, RHS are also able to change the composition of functional groups, e.g. to initiate the decarboxylation of carboxylic acids (Ofner et al., 2012). The present study uses a 50 cm aerosol flow-reactor, equipped with a solar simulator to investigate the time-resolved evolution and transformation of vibrational features in the mid-infrared region. The aerosol flow-reactor is coupled to a home-made multi-reflection cell (Ofner et al., 2010), integrated into a Bruker IFS 113v FTIR spectrometer. The reactor is operated with an inlet feed (organic compound) and a surrounding feed (reactive halogen species). The moveable inlet of the flow reactor allows us to vary reaction times between a few seconds and up to about 3 minutes. Saturated vapours of different SOA precursors and carboxylic acids were fed into the flow reactor using the moveable inlet. The surrounding feed inside the flow reactor was a mixture of zero air with molecular chlorine as the precursor for the formation of reactive halogen species. Using this setup, the formation of halogen-induced organic aerosol could be monitored with a high time resolution using FTIR spectroscopy. XOA formation is characterized by hydrogen-atom abstraction, carbon-chlorine bond formation and later, even formation of carboxylic acids. Several changes of the entire structure of the organic precursor, caused by the reaction of RHS, are visible. While XOA formation is a very fast process, the decarboxylation of carboxylic acids, induced by RHS is rather slow. However, XOA formation

  2. Targeting Reactive Carbonyl Species with Natural Sequestering Agents.

    PubMed

    Hwang, Sung Won; Lee, Yoon-Mi; Aldini, Giancarlo; Yeum, Kyung-Jin

    2016-01-01

    Reactive carbonyl species generated by the oxidation of polyunsaturated fatty acids and sugars are highly reactive due to their electrophilic nature, and are able to easily react with the nucleophilic sites of proteins as well as DNA causing cellular dysfunction. Levels of reactive carbonyl species and their reaction products have been reported to be elevated in various chronic diseases, including metabolic disorders and neurodegenerative diseases. In an effort to identify sequestering agents for reactive carbonyl species, various analytical techniques such as spectrophotometry, high performance liquid chromatography, western blot, and mass spectrometry have been utilized. In particular, recent advances using a novel high resolution mass spectrometry approach allows screening of complex mixtures such as natural products for their sequestering ability of reactive carbonyl species. To overcome the limited bioavailability and bioefficacy of natural products, new techniques using nanoparticles and nanocarriers may offer a new attractive strategy for increased in vivo utilization and targeted delivery of bioactives. PMID:26927058

  3. Reactive Sulfur Species-Mediated Activation of the Keap1-Nrf2 Pathway by 1,2-Naphthoquinone through Sulfenic Acids Formation under Oxidative Stress.

    PubMed

    Shinkai, Yasuhiro; Abiko, Yumi; Ida, Tomoaki; Miura, Takashi; Kakehashi, Hidenao; Ishii, Isao; Nishida, Motohiro; Sawa, Tomohiro; Akaike, Takaaki; Kumagai, Yoshito

    2015-05-18

    Sulfhydration by a hydrogen sulfide anion and electrophile thiolation by reactive sulfur species (RSS) such as persulfides/polysulfides (e.g., R-S-SH/R-S-Sn-H(R)) are unique reactions in electrophilic signaling. Using 1,2-dihydroxynaphthalene-4-thioacetate (1,2-NQH2-SAc) as a precursor to 1,2-dihydroxynaphthalene-4-thiol (1,2-NQH2-SH) and a generator of reactive oxygen species (ROS), we demonstrate that protein thiols can be modified by a reactive sulfenic acid to form disulfide adducts that undergo rapid cleavage in the presence of glutathione (GSH). As expected, 1,2-NQH2-SAc is rapidly hydrolyzed and partially oxidized to yield 1,2-NQ-SH, resulting in a redox cycling reaction that produces ROS through a chemical disproportionation reaction. The sulfenic acid forms of 1,2-NQ-SH and 1,2-NQH2-SH were detected by derivatization experiments with dimedone. 1,2-NQH2-SOH modified Keap1 at Cys171 to produce a Keap1-S-S-1,2-NQH2 adduct. Subsequent exposure of A431 cells to 1,2-NQ or 1,2-NQH2-SAc caused an extensive chemical modification of cellular proteins in both cases. Protein adduction by 1,2-NQ through a thio ether (C-S-C) bond slowly declined through a GSH-dependent S-transarylation reaction, whereas that originating from 1,2-NQH2-SAc through a disulfide (C-S-S-C) bond was rapidly restored to the free protein thiol in the cells. Under these conditions, 1,2-NQH2-SAc activated Nrf2 and upregulated its target genes, which were enhanced by pretreatment with buthionine sulfoximine (BSO), to deplete cellular GSH. Pretreatment of catalase conjugated with poly(ethylene glycol) suppressed Nrf2 activation by 1,2-NQH2-SAc. These results suggest that RSS-mediated reversible electrophilic signaling takes place through sulfenic acids formation under oxidative stress. PMID:25807370

  4. Roles of reactive oxygen species in UVA-induced oxidation of 5,6-dihydroxyindole-2-carboxylic acid-melanin as studied by differential spectrophotometric method.

    PubMed

    Ito, Shosuke; Kikuta, Marina; Koike, Shota; Szewczyk, Grzegorz; Sarna, Michal; Zadlo, Andrzej; Sarna, Tadeusz; Wakamatsu, Kazumasa

    2016-05-01

    Eumelanin photoprotects pigmented tissues from ultraviolet (UV) damage. However, UVA-induced tanning seems to result from the photooxidation of preexisting melanin and does not contribute to photoprotection. We investigated the mechanism of UVA-induced degradation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA)-melanin taking advantage of its solubility in a neutral buffer and using a differential spectrophotometric method to detect subtle changes in its structure. Our methodology is suitable for examining the effects of various agents that interact with reactive oxygen species (ROS) to determine how ROS is involved in the UVA-induced oxidative modifications. The results show that UVA radiation induces the oxidation of DHICA to indole-5,6-quinone-2-carboxylic acid in eumelanin, which is then cleaved to form a photodegraded, pyrrolic moiety and finally to form free pyrrole-2,3,5-tricarboxylic acid. The possible involvement of superoxide radical and singlet oxygen in the oxidation was suggested. The generation and quenching of singlet oxygen by DHICA-melanin was confirmed by direct measurements of singlet oxygen phosphorescence. PMID:26920809

  5. Reactive oxygen species and anti-proteinases.

    PubMed

    Siddiqui, Tooba; Zia, Mohammad Khalid; Ali, Syed Saqib; Rehman, Ahmed Abdur; Ahsan, Haseeb; Khan, Fahim Halim

    2016-01-01

    Reactive oxygen species (ROS) cause damage to macromolecules such as proteins, lipids and DNA and alters their structure and function. When generated outside the cell, ROS can induce damage to anti-proteinases. Anti-proteinases are proteins that are involved in the control and regulation of proteolytic enzymes. The damage caused to anti-proteinase barrier disturbs the proteinase-anti-proteinases balance and uncontrolled proteolysis at the site of injury promotes tissue damage. Studies have shown that ROS damages anti-proteinase shield of the body by inactivating key members such as alpha-2-macroglobulin, alpha-1-antitrypsin. Hypochlorous acid inactivates α-1-antitrypsin by oxidizing a critical reactive methionine residue. Superoxide and hypochlorous acid are physiological inactivators of alpha-2-macroglobulin. The damage to anti-proteinase barrier induced by ROS is a hallmark of diseases such as atherosclerosis, emphysema and rheumatoid arthritis. Thus, understanding the behaviour of ROS-induced damage to anti-proteinases may helps us in development of strategies that could control these inflammatory reactions and diseases. PMID:26699123

  6. ASCORBATE PEROXIDASE6 protects Arabidopsis desiccating and germinating seeds from stress and mediates cross talk between reactive oxygen species, abscisic acid, and auxin.

    PubMed

    Chen, Changming; Letnik, Ilya; Hacham, Yael; Dobrev, Petre; Ben-Daniel, Bat-Hen; Vanková, Radomíra; Amir, Rachel; Miller, Gad

    2014-09-01

    A seed's ability to properly germinate largely depends on its oxidative poise. The level of reactive oxygen species (ROS) in Arabidopsis (Arabidopsis thaliana) is controlled by a large gene network, which includes the gene coding for the hydrogen peroxide-scavenging enzyme, cytosolic ASCORBATE PEROXIDASE6 (APX6), yet its specific function has remained unknown. In this study, we show that seeds lacking APX6 accumulate higher levels of ROS, exhibit increased oxidative damage, and display reduced germination on soil under control conditions and that these effects are further exacerbated under osmotic, salt, or heat stress. In addition, ripening APX6-deficient seeds exposed to heat stress displayed reduced germination vigor. This, together with the increased abundance of APX6 during late stages of maturation, indicates that APX6 activity is critical for the maturation-drying phase. Metabolic profiling revealed an altered activity of the tricarboxylic acid cycle, changes in amino acid levels, and elevated metabolism of abscisic acid (ABA) and auxin in drying apx6 mutant seeds. Further germination assays showed an impaired response of the apx6 mutants to ABA and to indole-3-acetic acid. Relative suppression of abscisic acid insensitive3 (ABI3) and ABI5 expression, two of the major ABA signaling downstream components controlling dormancy, suggested that an alternative signaling route inhibiting germination was activated. Thus, our study uncovered a new role for APX6, in protecting mature desiccating and germinating seeds from excessive oxidative damage, and suggested that APX6 modulate the ROS signal cross talk with hormone signals to properly execute the germination program in Arabidopsis. PMID:25049361

  7. ASCORBATE PEROXIDASE6 Protects Arabidopsis Desiccating and Germinating Seeds from Stress and Mediates Cross Talk between Reactive Oxygen Species, Abscisic Acid, and Auxin1[C][W][OPEN

    PubMed Central

    Chen, Changming; Letnik, Ilya; Hacham, Yael; Dobrev, Petre; Ben-Daniel, Bat-Hen; Vanková, Radomíra; Amir, Rachel; Miller, Gad

    2014-01-01

    A seed’s ability to properly germinate largely depends on its oxidative poise. The level of reactive oxygen species (ROS) in Arabidopsis (Arabidopsis thaliana) is controlled by a large gene network, which includes the gene coding for the hydrogen peroxide-scavenging enzyme, cytosolic ASCORBATE PEROXIDASE6 (APX6), yet its specific function has remained unknown. In this study, we show that seeds lacking APX6 accumulate higher levels of ROS, exhibit increased oxidative damage, and display reduced germination on soil under control conditions and that these effects are further exacerbated under osmotic, salt, or heat stress. In addition, ripening APX6-deficient seeds exposed to heat stress displayed reduced germination vigor. This, together with the increased abundance of APX6 during late stages of maturation, indicates that APX6 activity is critical for the maturation-drying phase. Metabolic profiling revealed an altered activity of the tricarboxylic acid cycle, changes in amino acid levels, and elevated metabolism of abscisic acid (ABA) and auxin in drying apx6 mutant seeds. Further germination assays showed an impaired response of the apx6 mutants to ABA and to indole-3-acetic acid. Relative suppression of abscisic acid insensitive3 (ABI3) and ABI5 expression, two of the major ABA signaling downstream components controlling dormancy, suggested that an alternative signaling route inhibiting germination was activated. Thus, our study uncovered a new role for APX6, in protecting mature desiccating and germinating seeds from excessive oxidative damage, and suggested that APX6 modulate the ROS signal cross talk with hormone signals to properly execute the germination program in Arabidopsis. PMID:25049361

  8. Activation of peroxisome proliferator-activated receptor α ameliorates perfluorododecanoic acid-induced production of reactive oxygen species in rat liver.

    PubMed

    Liu, Hui; Zhang, Hongxia; Cui, Ruina; Guo, Xuejiang; Wang, Dazhi; Dai, Jiayin

    2016-06-01

    Perfluorododecanoic acid (PFDoA) is a ubiquitous environmental pollutant known to cause hepatocellular hypertrophy; however, the mechanisms of hepatotoxicity remain poorly understood. In this study, male rats were exposed to 0, 0.05, 0.2 and 0.5 mg/kg/day of PFDoA for 110 days. After two-dimensional differential gel electrophoresis and MALDI-TOF/TOF analysis, 73 differentially expressed proteins involved in lipid metabolism, inflammation, stress response and other functions were successfully identified. Among them, six significantly changed proteins (CTE1, MTE1, HADHA, ECH1, ALDH2 and CPS1) were found to be regulated by peroxisome proliferator-activated receptor alpha (PPARα). The anti-oxidant enzyme activity assays of superoxide dismutase and glutathione peroxidase and the content of thiobarbituric acid-reactive substances in the liver implied that PFDoA caused oxidative stress. The mRNA levels of PPARα in rat primary hepatocytes were knocked down by lentivirus-mediated RNAi. Furthermore, targeted protein levels of CTE1 and MTE1 were down-regulated, while those of HADHA, ALDH2 and CPS1 were up-regulated. After PFDoA exposure, however, the targeted protein levels of CTE1 and ALDH2 increased compared with those of the knockdown untreated group. The reactive oxygen species (ROS) content in rat hepatocytes assayed by flow cytometry significantly increased in the PPARα knockdown groups, consistent with the PPARα antagonist GW6471- and agonist WY14643-treated groups. These results strongly suggested that PPARα played an important role in suppressing ROS content in hepatocytes following PFDoA exposure. PMID:26168851

  9. Role of reactive oxygen and nitrogen species in acute respiratory distress syndrome.

    PubMed

    Fink, Mitchell P

    2002-02-01

    Reactive oxygen species are reactive, partially reduced derivatives of molecular oxygen (O 2 ). Important reactive oxygen species in biologic systems include superoxide radical anion, hydrogen peroxide, and hydroxyl radical. Closely related species include the hypohalous acids, particularly hypochlorous acid; chloramine and substituted chloramines; and singlet oxygen. Reactive nitrogen species are derived from the simple diatomic gas, nitric oxide. Peroxynitrite and its protonated form, peroxynitrous acid, are the most significant reactive nitrogen species in biologic systems. A variety of enzymatic and nonenzymatic processes can generate reactive oxygen species and reactive nitrogen species in mammalian cells. An extensive body of experimental evidence from studies using animal models supports the view that reactive oxygen species and reactive nitrogen species are important in the pathogenesis of acute respiratory distress syndrome. This view is further supported by data from clinical studies that correlate biochemical evidence of reactive oxygen species-mediated or reactive nitrogen species-mediated stress with the development of acute respiratory distress syndrome. Despite these data, pharmacologic strategies directed at minimizing reactive oxygen species-mediated or reactive nitrogen species-mediated damage have yet to be successfully introduced into clinical practice. The most extensively studied compound in this regard is N -acetylcysteine; unfortunately, clinical trials with this compound in patients with acute respiratory distress syndrome have yielded disappointing results. PMID:12205400

  10. Laboratory studies of the reactive uptake of biogenic species: Evidence for the direct polymerization of isoprene, terpenes and sesquiterpenes on acidic aerosols

    NASA Astrophysics Data System (ADS)

    Li, S.; Liggio, J.; Mihele, C.; Brook, J.

    2006-12-01

    Numerous studies on heterogeneous reactions have shown that polymerization of semi-volatile and volatile organic compounds occurs in aerosols. To date, most evidence suggests that gaseous hydrocarbon oxidation products containing carbonyl functionality are the prime candidates for these processes. Such processes involve primarily hydration, acetal formation, polymerization and aldol-condensation reactions, resulting in oligomer products of potential significance with respect to secondary organic aerosol formation (SOA). However, little information on the heterogeneous reactions of unsaturated hydrocarbons (olefins) is known. Given that biogenic species, many of them unsaturated, make up a considerable portion of hydrocarbons emitted globally, direct reactive uptake of these compounds on aerosols would also potentially be a major source of SOA. In the present study, individual biogenic hydrocarbons were exposed to pre-existing acidic sulfate aerosols within a 2 m3 Teflon reaction chamber under varying relative humidity conditions. An Aerosol Mass Spectrometer was used to quantify any subsequent increase in organic mass as a function of time, and to obtain information regarding the structure of products via aerosol mass spectra. A Proton Transfer Reaction Mass Spectrometer was used to measure the gas-phase concentrations of isoprene, terpenes (?-pinene, ?-pinene, limonene, and carene) and sesquiterpenes (?-caryophylene and humulene) in the reaction chamber. Results from these experiments show that a significant amount of these compounds are taken up by the acidic aerosols rapidly, in a polymerization process which was highly dependent on the particle acidity. This polymerization mechanism likely involves the oxygenation of the resulting polymers via acid catalyzed hydration. The uptake of the unsaturated hydrocarbons suggests that gas-phase oxidation of biogenics to condensable products is not the only route to SOA. Details of the polymerization and hydration

  11. Synergistic activities of a silver(I) glutamic acid complex and reactive oxygen species (ROS): a novel antimicrobial and chemotherapeutic agent.

    PubMed

    Batarseh, K I; Smith, M A

    2012-01-01

    The antimicrobial and chemotherapeutic activities of a silver(I) glutamic acid complex with the synergistic concomitant generation of reactive oxygen species (ROS) were investigated here. The ROS generation system employed was via Fenton chemistry. The antimicrobial and chemotherapeutic activities were investigated on Staphylococcus aureus ATCC 43300 and Escherichia coli bacteria, and Vero and MCF-7 tumor cell lines, respectively. Antimicrobial activities were conducted by determining minimum inhibitory concentration (MIC), while chemotherapeutic efficacies were done by serial dilution using standard techniques to determine the half maximal inhibitory concentration (IC50). The antimicrobial and chemotherapeutic results obtained were compared with positive control drugs gentamicin, oxacillin, penicillin, streptomycin and cisplatin, a ubiquitously used platinum-based antitumor drug, and with the silver(I) glutamic acid complex and hydrogen peroxide separately. Based on MIC and IC50 values, it was determined that this synergistic approach was very effective at extremely low concentrations, especially when compared with the other drugs evaluated here. This finding might be of great significance regarding metronomic dosing when this synergistic approach is clinically implemented. Since silver at low concentrations exhibits no toxic, mutagenic and carcinogenic activities, this might offer an alternative approach for the development of safer silver-based antimicrobial and chemotherapeutic drugs, thereby reducing or even eliminating the toxicity associated with current drugs. Accordingly, the present approach might be integrated into the systemic clinical treatment of infectious diseases and cancer. PMID:22680634

  12. Virus-induced gene silencing reveals control of reactive oxygen species accumulation and salt tolerance in tomato by γ-aminobutyric acid metabolic pathway.

    PubMed

    Bao, Hexigeduleng; Chen, Xianyang; Lv, Sulian; Jiang, Ping; Feng, Juanjuan; Fan, Pengxiang; Nie, Lingling; Li, Yinxin

    2015-03-01

    γ-Aminobutyric acid (GABA) accumulates in many plant species in response to environmental stress. However, the physiological function of GABA or its metabolic pathway (GABA shunt) in plants remains largely unclear. Here, the genes, including glutamate decarboxylases (SlGADs), GABA transaminases (SlGABA-Ts) and succinic semialdehyde dehydrogenase (SlSSADH), controlling three steps of the metabolic pathway of GABA, were studied through virus-induced gene silencing approach in tomato. Silencing of SlGADs (GABA biosynthetic genes) and SlGABA-Ts (GABA catabolic genes) led to increased accumulation of reactive oxygen species (ROS) as well as salt sensitivity under 200 mm NaCl treatment. Targeted quantitative analysis of metabolites revealed that GABA decreased and increased in the SlGADs- and SlGABA-Ts-silenced plants, respectively, whereas succinate (the final product of GABA metabolism) decreased in both silenced plants. Contrarily, SlSSADH-silenced plants, also defective in GABA degradation process, showed dwarf phenotype, curled leaves and enhanced accumulation of ROS in normal conditions, suggesting the involvement of a bypath for succinic semialdehyde catabolism to γ-hydroxybutyrate as reported previously in Arabidopsis, were less sensitive to salt stress. These results suggest that GABA shunt is involved in salt tolerance of tomato, probably by affecting the homeostasis of metabolites such as succinate and γ-hydroxybutyrate and subsequent ROS accumulation under salt stress. PMID:25074245

  13. [Nanocerium restores the erythrocytes stability to acid hemolysis by inhibition of oxygen and nitrogen reactive species in old rats].

    PubMed

    Kotsuruba, A V; Kopjak, B S; Sagach, V F; Spivak, N Ja

    2015-01-01

    In experiments in vivo the effect of nanocerium (cerium oxide nanoparticles) on the stability of red blood cells to acid hemolysis, levels of both ROS and RNS generation and H2S pools in plasma and erythrocytes of old rats were investigated. In red blood cells of old rats the proton penetration into the matrix of erythrocytes showed a significant raising and the fate of labile "aging" erythrocytes in old animals compared with adult were up- regulated. These phenomena paralleled with significant up-regulation of ROS and RNS generation. Introduction for 14 days per os to old rats 0.1 mg/kg of nanocerium fully restored resistance of erythrocytes to acid hemolysis by ROS and RNS in both plasma and erythrocytes reduction. Nanocerium decreased the erythrocytes and, conversely, significantly increased the plasma's pools of H2S. PMID:26040029

  14. Regulation of reactive oxygen species-mediated abscisic acid signaling in guard cells and drought tolerance by glutathione

    PubMed Central

    Munemasa, Shintaro; Muroyama, Daichi; Nagahashi, Hiroki; Nakamura, Yoshimasa; Mori, Izumi C.; Murata, Yoshiyuki

    2013-01-01

    The phytohormone abscisic acid (ABA) induces stomatal closure in response to drought stress, leading to reduction of transpirational water loss. A thiol tripeptide glutathione (GSH) is an important regulator of cellular redox homeostasis in plants. Although it has been shown that cellular redox state of guard cells controls ABA-mediated stomatal closure, roles of GSH in guard cell ABA signaling were largely unknown. Recently we demonstrated that GSH functions as a negative regulator of ABA signaling in guard cells. In this study we performed more detailed analyses to reveal how GSH regulates guard cell ABA signaling using the GSH-deficient Arabidopsis mutant cad2-1. The cad2-1 mutant exhibited reduced water loss from rosette leaves. Whole-cell current recording using patch clamp technique revealed that the cad2-1 mutation did not affect ABA regulation of S-type anion channels. We found enhanced activation of Ca2+ permeable channels by hydrogen peroxide (H2O2) in cad2-1 guard cells. The cad2-1 mutant showed enhanced H2O2-induced stomatal closure and significant increase of ROS accumulation in whole leaves in response to ABA. Our findings provide a new understanding of guard cell ABA signaling and a new strategy to improve plant drought tolerance. PMID:24312112

  15. Mitochondrial-derived reactive oxygen species play a vital role in the salicylic acid signaling pathway in Arabidopsis thaliana.

    PubMed

    Nie, Shengjun; Yue, Haiyun; Zhou, Jun; Xing, Da

    2015-01-01

    Plant mitochondria constitute a major source of ROS and are proposed to act as signaling organelles in the orchestration of defense response. At present, the signals generated and then integrated by mitochondria are still limited. Here, fluorescence techniques were used to monitor the events of mitochondria in vivo, as well as the induction of mitochondrial signaling by a natural defensive signal chemical salicylic acid (SA). An inhibition of respiration was observed in isolated mitochondria subjected to SA. The cytochrome reductase activity analysis in isolated mitochondria demonstrated that SA might act directly on the complex III in the respiration chain by inhibiting the activity. With this alteration, a quick burst of mitochondrial ROS (mtROS) was stimulated. SA-induced mtROS caused mitochondrial morphology transition in leaf tissue or protoplasts expressing mitochondria-GFP (43C5) and depolarization of membrane potential. However, the application of AsA, an H2O2 scavenger, significantly prevented both events, indicating that both of them are attributable to ROS accumulation. In parallel, SA-induced mtROS up-regulated AOX1a transcript abundance and this induction was correlated with the disease resistance, whereas AsA-pretreatment interdicted this effect. It is concluded that mitochondria play an essential role in the signaling pathway of SA-induced ROS generation, which possibly provided new insight into the SA-mediated biological processes, including plant defense response. PMID:25811367

  16. Mitochondrial-Derived Reactive Oxygen Species Play a Vital Role in the Salicylic Acid Signaling Pathway in Arabidopsis thaliana

    PubMed Central

    Nie, Shengjun; Yue, Haiyun; Zhou, Jun; Xing, Da

    2015-01-01

    Plant mitochondria constitute a major source of ROS and are proposed to act as signaling organelles in the orchestration of defense response. At present, the signals generated and then integrated by mitochondria are still limited. Here, fluorescence techniques were used to monitor the events of mitochondria in vivo, as well as the induction of mitochondrial signaling by a natural defensive signal chemical salicylic acid (SA). An inhibition of respiration was observed in isolated mitochondria subjected to SA. The cytochrome reductase activity analysis in isolated mitochondria demonstrated that SA might act directly on the complex III in the respiration chain by inhibiting the activity. With this alteration, a quick burst of mitochondrial ROS (mtROS) was stimulated. SA-induced mtROS caused mitochondrial morphology transition in leaf tissue or protoplasts expressing mitochondria-GFP (43C5) and depolarization of membrane potential. However, the application of AsA, an H2O2 scavenger, significantly prevented both events, indicating that both of them are attributable to ROS accumulation. In parallel, SA-induced mtROS up-regulated AOX1a transcript abundance and this induction was correlated with the disease resistance, whereas AsA-pretreatment interdicted this effect. It is concluded that mitochondria play an essential role in the signaling pathway of SA-induced ROS generation, which possibly provided new insight into the SA-mediated biological processes, including plant defense response. PMID:25811367

  17. SURVEY AND SUMMARY: Mutagenic potentials of damaged nucleic acids produced by reactive oxygen/nitrogen species: approaches using synthetic oligonucleotides and nucleotides

    PubMed Central

    Kamiya, Hiroyuki

    2003-01-01

    DNA and DNA precursors (deoxyribonucleotides) suffer damage by reactive oxygen/nitrogen species. They are important mutagens for organisms, due to their endogenous formation. Damaged DNA and nucleotides cause alterations of the genetic information by the mispairing properties of the damaged bases, such as 8-hydroxyguanine (7,8-dihydro- 8-oxoguanine) and 2-hydroxyadenine. Here, the author reviews the mutagenic potentials of damaged bases in DNA and of damaged DNA precursors formed by reactive oxygen/nitrogen species, focusing on the results obtained with synthetic oligonucleotides and 2′-deoxyribonucleoside 5′-triphosphates. PMID:12527759

  18. Zooming into sub-organellar localization of reactive oxygen species in guard cell chloroplasts during abscisic acid and methyl jasmonate treatments

    PubMed Central

    Leshem, Yehoram; Levine, Alex

    2013-01-01

    Regulation of stomata movements is crucial for plants ability to cope with their changing environment. Guard cell’s (GC) water potential directs water flux inside/outside this cell, which eventually is causing the stoma to open or close, respectively. Some of the osmolytes which accumulates in the GC cytoplasm and are known to play a role in stomata opening are sugars, arising from chloroplast starch degradation. During stomata closure, the accumulated osmolytes are removed from the GC cytoplasm. Surprisingly little is known about prevention of starch degradation and forming additional sugars which may interfere with osmotic changes that are necessary for correct closure of stomata.   One of the early events leading to stomata closure is production of reactive oxygen species (ROS) in various sub-cellular sites and organelles of the stoma. Here we report that ROS production during abscisic acid (ABA) and methyl jasmonate (MJ) stimuli in Arabidopsis GC chloroplasts were more than tripled. Moreover, ROS were detected on the sub-organelle level in compartments that are typically occupied by starch grains. This observation leads us to suspect that ROS function in that particular location is necessary for stomata closure. We therefore hypothesize that these ROS are involved in redox control that lead to the inactivation of starch degradation that takes place in these compartments, thus contributing to the stoma closure in an additional way. PMID:23887496

  19. Arabidopsis OST1 protein kinase mediates the regulation of stomatal aperture by abscisic acid and acts upstream of reactive oxygen species production.

    PubMed

    Mustilli, Anna-Chiara; Merlot, Sylvain; Vavasseur, Alain; Fenzi, Francesca; Giraudat, Jérôme

    2002-12-01

    During drought, the plant hormone abscisic acid (ABA) triggers stomatal closure, thus reducing water loss. Using infrared thermography, we isolated two allelic Arabidopsis mutants (ost1-1 and ost1-2) impaired in the ability to limit their transpiration upon drought. These recessive ost1 mutations disrupted ABA induction of stomatal closure as well as ABA inhibition of light-induced stomatal opening. By contrast, the ost1 mutations did not affect stomatal regulation by light or CO(2), suggesting that OST1 is involved specifically in ABA signaling. The OST1 gene was isolated by positional cloning and was found to be expressed in stomatal guard cells and vascular tissue. In-gel assays indicated that OST1 is an ABA-activated protein kinase related to the Vicia faba ABA-activated protein kinase (AAPK). Reactive oxygen species (ROS) were shown recently to be an essential intermediate in guard cell ABA signaling. ABA-induced ROS production was disrupted in ost1 guard cells, whereas applied H(2)O(2) or calcium elicited the same degree of stomatal closure in ost1 as in the wild type. These results suggest that OST1 acts in the interval between ABA perception and ROS production. The relative positions of ost1 and the other ABA-insensitive mutations in the ABA signaling network (abi1-1, abi2-1, and gca2) are discussed. PMID:12468729

  20. Abscisic Acid and LATERAL ROOT ORGAN DEFECTIVE/NUMEROUS INFECTIONS AND POLYPHENOLICS Modulate Root Elongation via Reactive Oxygen Species in Medicago truncatula1[W][OPEN

    PubMed Central

    Zhang, Chang; Bousquet, Amanda; Harris, Jeanne M.

    2014-01-01

    Abscisic acid (ABA) modulates root growth in plants grown under normal and stress conditions and can rescue the root growth defects of the Medicago truncatula lateral root-organ defective (latd) mutant. Here, we demonstrate that reactive oxygen species (ROS) function downstream of ABA in the regulation of root growth by controlling cell elongation. We also show that the MtLATD/NUMEROUS INFECTIONS AND POLYPHENOLICS (NIP) nitrate transporter is required for ROS homeostasis and cell elongation in roots and that this balance is perturbed in latd mutants, leading to an excess of superoxide and hydrogen peroxide and a corresponding decrease in cell elongation. We found that expression of the superoxide-generating NADPH oxidase genes, MtRbohA and MtRbohC (for respiratory burst oxidase homologs), is increased in latd roots and that inhibition of NADPH oxidase activity pharmacologically can both reduce latd root ROS levels and increase cell length, implicating NADPH oxidase function in latd root growth defects. Finally, we demonstrate that ABA treatment alleviates ectopic ROS accumulation in latd roots, restores MtRbohC expression to wild-type levels, and promotes an increase in cell length. Reducing the expression of MtRbohC using RNA interference leads to increased root elongation in both wild-type and latd roots. These results reveal a mechanism by which the MtLATD/NIP nitrate transporter and ABA modulate root elongation via superoxide generation by the MtRbohC NADPH oxidase. PMID:25192698

  1. Zooming into sub-organellar localization of reactive oxygen species in guard cell chloroplasts during abscisic acid and methyl jasmonate treatments.

    PubMed

    Leshem, Yehoram; Levine, Alex

    2013-10-01

    Regulation of stomata movements is crucial for plants ability to cope with their changing environment. Guard cells' (GC) water potential directs water flux inside/outside this cell, which eventually is causing the stoma to open or close, respectively. Some of the osmolytes which accumulates in the GC cytoplasm and are known to play a role in stomata opening are sugars, arising from chloroplast starch degradation. During stomata closure, the accumulated osmolytes are removed from the GC cytoplasm. Surprisingly little is known about prevention of starch degradation and forming additional sugars which may interfere with osmotic changes that are necessary for correct closure of stomata. One of the early events leading to stomata closure is production of reactive oxygen species (ROS) in various subcellular sites and organelles of the stoma. Here we report that ROS production during abscisic acid (ABA) and methyl jasmonate (MJ) stimuli in Arabidopsis GC chloroplasts were more than tripled. Moreover, ROS were detected on the suborganelle level in compartments that are typically occupied by starch grains. This observation leads us to suspect that ROS function in that particular location is necessary for stomata closure. We therefore hypothesize that these ROS are involved in redox control that lead to the inactivation of starch degradation that takes place in these compartments, thus contributing to the stoma closure in an additional way. PMID:23887496

  2. Limited effect of reactive oxygen species on the composition of susceptible essential amino acids in the midguts of Lymantria dispar caterpillars.

    PubMed

    Barbehenn, Raymond V; Niewiadomski, Julie; Kochmanski, Joseph; Constabel, C Peter

    2012-11-01

    The essential amino acids (EAAs) arginine, histidine, lysine, and methionine, as well as cysteine (semiessential), are believed to be susceptible to reactions with reactive oxygen species (ROS) in biological systems. The decreased availability of these EAAs could harm insect nutrition, since several of them can also be limiting for protein synthesis. However, no in vivo studies have quantified the effect of ROS in the midguts of insect herbivores on EAA composition. This study examined the association between elevated levels of ROS in the midgut fluid of Lymantria dispar caterpillars and the compositions of EAAs (protein-bound + protein-free) in their midgut fluid and frass. Contrary to expectation, the compositions of EAAs were not significantly decreased by ROS in midgut fluid ex vivo when incubated with phenolic compounds. Two in vivo comparisons of low- and high-ROS-producing leaves also showed similar results: there were no significant decreases in the compositions of EAAs in the midgut fluids and/or frass of larvae with elevated levels of ROS in their midguts. In addition, waste nitrogen excretion was not significantly increased from larvae on high-ROS treatments, as would be expected if ROS produced unbalanced EAA compositions. These results suggest that L. dispar larvae are able to tolerate elevated levels of ROS in their midguts without nutritionally significant changes in the compositions of susceptible EAAs in their food. PMID:22961657

  3. Reactive Oxygen Species and Neutrophil Function.

    PubMed

    Winterbourn, Christine C; Kettle, Anthony J; Hampton, Mark B

    2016-06-01

    Neutrophils are essential for killing bacteria and other microorganisms, and they also have a significant role in regulating the inflammatory response. Stimulated neutrophils activate their NADPH oxidase (NOX2) to generate large amounts of superoxide, which acts as a precursor of hydrogen peroxide and other reactive oxygen species that are generated by their heme enzyme myeloperoxidase. When neutrophils engulf bacteria they enclose them in small vesicles (phagosomes) into which superoxide is released by activated NOX2 on the internalized neutrophil membrane. The superoxide dismutates to hydrogen peroxide, which is used by myeloperoxidase to generate other oxidants, including the highly microbicidal species hypochlorous acid. NOX activation occurs at other sites in the cell, where it is considered to have a regulatory function. Neutrophils also release oxidants, which can modify extracellular targets and affect the function of neighboring cells. We discuss the identity and chemical properties of the specific oxidants produced by neutrophils in different situations, and what is known about oxidative mechanisms of microbial killing, inflammatory tissue damage, and signaling. PMID:27050287

  4. Measurement of reactive species for plasma medicine

    NASA Astrophysics Data System (ADS)

    Ono, Ryo

    2015-09-01

    Plasma medicine has been intensively studied over the last decade. Reactive oxygen and nitrogen species are responsible for the therapeutic effects in plasma medicine. To examine the therapeutic effects of reactive species, the densities of OH, O, and NO were measured using laser-induced fluorescence (LIF). A helium atmospheric-pressure plasma jet (10 kV, 10 kHz of 40 μs pulses) and a nanosecond streamer discharge (24 kV, 8 ns, 30 Hz) were utilized to treat mouse melanoma cells in a culture medium. Correlation between the dose of reactive species and deactivation rate of melanoma cells was measured with the aid of LIF. The results showed that the rate of cell death correlates with OH density, but not with O and NO densities. Next, a method to supply a specific reactive species to living organisms was developed. It utilizes photolysis of helium-buffered H2O and O2 by vacuum ultraviolet (VUV) light to produce reactive species. The VUV method was utilized to sterilize Bacillus atrophaeus on agar plate. With the VUV method, it was succeeded to show sterilization only by OH radicals. A 30 s treatment with approximately 0.1 ppm OH radicals caused visible sterilization.

  5. Reactive Oxygen Species and Cellular Oxygen Sensing

    PubMed Central

    Cash, Timothy P; Pan, Yi; Simon, M. Celeste

    2008-01-01

    Many organisms activate adaptive transcriptional programs to help them cope with decreased oxygen levels, or hypoxia, in their environment. These responses are triggered by various oxygen sensing systems in bacteria, yeast and metazoans. In metazoans, the hypoxia inducible factors (HIFs) mediate the adaptive transcriptional response to hypoxia by upregulating genes involved in maintaining bioenergetic homeostasis. The HIFs in turn are regulated by HIF-specific prolyl hydroxlase activity, which is sensitive to cellular oxygen levels and other factors such as tricarboxylic acid cycle metabolites and reactive oxygen species (ROS). Establishing a role for ROS in cellular oxygen sensing has been challenging since ROS are intrinsically unstable and difficult to measure. However, recent advances in fluorescence energy transfer resonance (FRET)-based methods for measuring ROS are alleviating some of the previous difficulties associated with dyes and luminescent chemicals. In addition, new genetic models have demonstrated that functional mitochondrial electron transport and associated ROS production during hypoxia are required for HIF stabilization in mammalian cells. Current efforts are directed at how ROS mediate prolyl hydroxylase activity and hypoxic HIF stabilization. Progress in understanding this process has been enhanced by the development of the FRET-based ROS probe, an vivo prolyl hydroxylase reporter and various genetic models harboring mutations in components of the mitochondrial electron transport chain. PMID:17893032

  6. Reactive oxygen species as glomerular autacoids.

    PubMed

    Baud, L; Fouqueray, B; Philippe, C; Ardaillou, R

    1992-04-01

    There is considerable evidence suggesting that reactive oxygen species (ROS; superoxide anion, hydrogen peroxide, hydroxyl radical, hypochlorous acid) are implicated in the pathogenesis of toxic, ischemic, and immunologically mediated glomerular injury. The capacity of glomerular cells, especially mesangial cells, to generate ROS in response to several stimuli suggests that these autacoids may play a role in models of glomerular injury that are independent of infiltrating polymorphonuclear leukocytes and monocytes. The mechanisms whereby ROS formation results in morphologic lesions and in modifications of glomerular permeability, blood flow, and filtration rate have been inferred from in vitro studies. They involve direct and indirect injury to resident cells (mesangiolysis) and glomerular basement membrane (in concert with metalloproteases) and alteration of both the release and binding of vasoactive substances, such as bioactive lipids (e.g., prostaglandin E2, prostacyclin, thromboxane), cytokines (e.g., tumor necrosis factor alpha), and possibly endothelium-derived relaxing factor. The importance of such processes appears to be modulated by the intrinsic antioxidant defenses of the glomeruli. Further studies are needed to address the role of ROS in human glomerular diseases. PMID:1600128

  7. Combination of Tolfenamic acid and curcumin induces colon cancer cell growth inhibition through modulating specific transcription factors and reactive oxygen species

    PubMed Central

    Sankpal, Umesh T.; Nagaraju, Ganji Purnachandra; Gottipolu, Sriharika R.; Hurtado, Myrna; Jordan, Christopher G.; Simecka, Jerry W.; Shoji, Mamoru; El-Rayes, Bassel; Basha, Riyaz

    2016-01-01

    Curcumin (Cur) has been extensively studied in several types of malignancies including colorectal cancer (CRC); however its clinical application is greatly affected by low bioavailability. Several strategies to improve the therapeutic response of Cur are being pursued, including its combination with small molecules and drugs. We investigated the therapeutic efficacy of Cur in combination with the small molecule tolfenamic acid (TA) in CRC cell lines. TA has been shown to inhibit the growth of human cancer cells in vitro and in vivo, via targeting the transcription factor specificity protein1 (Sp1) and suppressing survivin expression. CRC cell lines HCT116 and HT29 were treated with TA and/or Cur and cell viability was measured 24–72 hours post-treatment. While both agents caused a steady reduction in cell viability, following a clear dose/time-dependent response, the combination of TA+Cur showed higher growth inhibition when compared to either single agent. Effects on apoptosis were determined using flow cytometry (JC-1 staining to measure mitochondrial membrane potential), Western blot analysis (c-PARP expression) and caspase 3/7 activity. Reactive oxygen species (ROS) levels were measured by flow cytometry and the translocation of NF-kB into the nucleus was determined using immunofluorescence. Results showed that apoptotic markers and ROS activity were significantly upregulated following combination treatment, when compared to the individual agents. This was accompanied by decreased expression of Sp1, survivin and NF-kB translocation. The combination of TA+Cur was more effective in HCT116 cells than HT29 cells. These results demonstrate that TA may enhance the anti-proliferative efficacy of Cur in CRC cells. PMID:26672603

  8. Arachidonic acid- and prostaglandin E2-induced cerebral vasodilation is mediated by carbon monoxide, independent of reactive oxygen species in piglets

    PubMed Central

    Leffler, Charles W.

    2011-01-01

    Arachidonic acid (AA) and prostaglandin (PG) E2 stimulate carbon monoxide (CO) production, and AA metabolism is known to be associated with the generation of reactive oxygen species (ROS). This study was conducted to address the hypothesis that CO and/or ROS mediate cerebrovascular dilation in newborn pigs. Experiments were performed on anesthetized newborn pigs with closed cranial windows. Different concentrations of AA (10−8-10−6 M), PGE2 (10−8-10−6 M), iloprost (10−8-10−6 M), and their vehicle (artificial cerebrospinal fluid) were given. Piglets with PGE2 and iloprost received indomethacin (5 mg/kg iv) to inhibit cyclooxygenase. AA, PGE2, and iloprost caused concentration-dependent increases in pial arteriolar diameter. The effects of both AA and PGE2 in producing cerebral vascular dilation and associated CO production were blocked by the heme oxygenase inhibitor chromium mesoporphyrin (2 × 10−5 M), but not by the prostacyclin analog, iloprost. ROS inhibitor tempol (SOD mimetic) (1 × 10−5 M) and the H2O2 scavenger catalase (1,000 U/ml) also do not block these vasodilator effects of AA and PGE2. Heme-l-lysinate-induced cerebrovascular dilation and CO production was blocked by chromium mesoporphyrin. Hypoxanthine plus xanthine oxidase, a combination that is known to generate ROS, caused pial arteriolar dilation and CO production that was inhibited by tempol and catalase. These data suggest that AA- and PGE2-induced cerebral vascular dilation is mediated by CO, independent of ROS. PMID:21984542

  9. Blood radicals: reactive nitrogen species, reactive oxygen species, transition metal ions, and the vascular system.

    PubMed

    Darley-Usmar, V; Halliwell, B

    1996-05-01

    Free radicals, such as superoxide, hydroxyl and nitric oxide, and other "reactive species", such as hydrogen peroxide, hypochlorous acid and peroxynitrite, are formed in vivo. Some of these molecules, e.g. superoxide and nitric oxide, can be physiologically useful, but they can also cause damage under certain circumstances. Excess production of reactive oxygen or nitrogen species (ROS, RNS), their production in inappropriate relative amounts (especially superoxide and NO) or deficiencies in antioxidant defences may result in pathological stress to cells and tissues. This oxidative stress can have multiple effects. It can induce defence systems, and render tissues more resistant to subsequent insult. If oxidative stress is excessive or if defence and repair responses are inadequate, cell injury can be caused by such mechanisms as oxidative damage to essential proteins, lipid peroxidation, DNA strand breakage and base modification, and rises in the concentration of intracellular "free" Ca(2+). Considerable evidence supports the view that oxidative damage involving both ROS and RNS is an important contributor to the development of atherosclerosis. Peroxynitrite (derived by reaction of superoxide with nitric oxide) and transition metal ions (perhaps released by injury to the vessel wall) may contribute to lipid peroxidation in atherosclerotic lesions. PMID:8860419

  10. 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…

  11. Reactive Nitrogen Species Reactivities with Nitrones: Theoretical and Experimental Studies

    PubMed Central

    Nash, Kevin M.; Rockenbauer, Antal; Villamena, Frederick A.

    2012-01-01

    Reactive nitrogen species (RNS) such as nitrogen dioxide (•NO2), peroxynitrite (ONOO–), and nitrosoperoxycarbonate (ONOOCO2–) are among the most damaging species present in biological systems due to their ability to cause modification of key biomolecular systems through oxidation, nitrosylation and nitration. Nitrone spin traps are known to react with free radicals and non-radicals via electrophilic and nucleophilic addition reactions, and have been employed as reagents to detect radicals using electron paramagnetic resonance (EPR) spectroscopy, and as pharmacological agents against oxidative stress-mediated injury. This study examines the reactivity of cyclic nitrones such as 5,5-dimethylpyrroline N-oxide (DMPO) with, •NO2, ONOO–, ONOOCO2–, SNAP and SIN-1 using EPR. The thermochemistries of nitrone reactivity with RNS, and isotropic hfsc's of the addition products were also calculated at the PCM(water)/B3LYP/6-31+G**//B3LYP/6-31G* level of theory with and without explicit water molecules in order to rationalize the nature of the observed EPR spectra. Spin trapping of other RNS such as azide (•N3), nitrogen trioxide (•NO3), amino (•NH2) radicals, and nitroxyl (HNO) were also theoretically and experimentally investigated by EPR spin trapping and mass spectrometry. This study also shows other spin traps such as AMPO, EMPO and DEPMPO can react with radical and non-radical RNS, thus, making spin traps suitable probes as well as antioxidants against RNS mediated oxidative damage. PMID:22775566

  12. 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

  13. [The two faces of reactive oxygen species].

    PubMed

    Zabłocka, Agnieszka; Janusz, Maria

    2008-01-01

    Oxidative stress has been implicated in playing a crucial role in aging and in the pathogeneses of a number of diseases, including neurodegenerative disorders such as Alzheimer's disease. Oxidative stress occurs due to an imbalance in prooxidant and antioxidant levels. Reactive oxygen species (ROS) are highly reactive and may modify and inactivate proteins, lipids, DNA, and RNA and induce cellular dysfunctions. To prevent free radical-induced cellular damage, the organism has developed a defense mechanism, the antioxidative system. This system includes antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx), and glutathione reductase (GSSGR) and low-molecular antioxidants such as glutathion and plasma proteins. Glutathion plays a key role in maintaining the physiological balance between prooxidants and antioxidants. Plasma proteins can inhibit ROS generation and lipid peroxidation by chelating free transition metals. The major exogenous antioxidants are vitamins E, C, and A. PMID:18388851

  14. Reactivity of the cadmium ion in concentrated phosphoric acid solutions.

    PubMed

    De Gyves, J; Gonzales, J; Louis, C; Bessiere, J

    1989-07-01

    The solvation transfer coefficients which characterize the changes of ion reactivity with phosphoric acid concentration have been calculated for cadmium from the constants of the successive chloride complexes, and for silver and diethyldithiophosphate from potentiometric measurements. They evidence the strong desolvation of the cadmium species in concentrated phosphoric acid media, causing a remarkable increase of its reactivity. They allow the results of liquid-liquid extraction, precipitation and flotation reactions to be correctly interpreted and their changes to be foreseen when the reagents are modified. PMID:18964794

  15. Reactive nitrogen species in the respiratory tract.

    PubMed

    Ricciardolo, Fabio L M; Di Stefano, Antonino; Sabatini, Federica; Folkerts, Gert

    2006-03-01

    Endogenous Nitric Oxide (NO) plays a key role in the physiological regulation of airway functions. In response to various stimuli activated inflammatory cells (e.g., eosinophils and neutrophils) generate oxidants ("oxidative stress") which in conjunction with exaggerated enzymatic release of NO and augmented NO metabolites produce the formation of strong oxidizing reactive nitrogen species, such as peroxynitrite, in various airway diseases including asthma, chronic obstructive pulmonary diseases (COPD), cystic fibrosis and acute respiratory distress syndrome (ARDS). Reactive nitrogen species provoke amplification of inflammatory processes in the airways and lung parenchyma causing DNA damage, inhibition of mitochondrial respiration, protein dysfunction and cell damage ("nitrosative stress"). These effects alter respiratory homeostasis (such as bronchomotor tone and pulmonary surfactant activity) and the long-term persistence of "nitrosative stress" may contribute to the progressive deterioration of pulmonary functions leading to respiratory failure. Recent studies showing that protein nitration can be dynamic and reversible ("denitration mechanisms") open new horizons in the treatment of chronic respiratory diseases affected by the deleterious actions of "nitrosative stress". PMID:16464450

  16. Reactive oxygen species at phospholipid bilayers: distribution, mobility and permeation.

    PubMed

    Cordeiro, Rodrigo M

    2014-01-01

    Reactive oxygen species (ROS) are involved in biochemical processes such as redox signaling, aging, carcinogenesis and neurodegeneration. Although biomembranes are targets for reactive oxygen species attack, little is known about the role of their specific interactions. Here, molecular dynamics simulations were employed to determine the distribution, mobility and residence times of various reactive oxygen species at the membrane-water interface. Simulations showed that molecular oxygen (O2) accumulated at the membrane interior. The applicability of this result to singlet oxygen ((1)O2) was discussed. Conversely, superoxide (O2(-)) radicals and hydrogen peroxide (H2O2) remained at the aqueous phase. Both hydroxyl (HO) and hydroperoxyl (HO2) radicals were able to penetrate deep into the lipid headgroups region. Due to membrane fluidity and disorder, these radicals had access to potential peroxidation sites along the lipid hydrocarbon chains, without having to overcome the permeation free energy barrier. Strikingly, HO2 radicals were an order of magnitude more concentrated in the headgroups region than in water, implying a large shift in the acid-base equilibrium between HO2 and O2(-). In comparison with O2, both HO and HO2 radicals had lower lateral mobility at the membrane. Simulations revealed that there were intermittent interruptions in the H-bond network around the HO radicals at the headgroups region. This effect is expected to be unfavorable for the H-transfer mechanism involved in HO diffusion. The implications for lipid peroxidation and for the effectiveness of membrane antioxidants were evaluated. PMID:24095673

  17. REACTIVE OXYGEN SPECIES AND COLORECTAL CANCER

    PubMed Central

    Sreevalsan, Sandeep; Safe, Stephen

    2013-01-01

    Several agents used for treatment of colon and other cancers induce reactive oxygen species (ROS) and this plays an important role in their anticancer activities. In addition to the well-known proapoptotic effects of ROS inducers, these compounds also decrease expression of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 and several pro-oncogenic Spregulated genes important for cancer cell proliferation, survival and metastasis. The mechanism of these responses involve ROS-dependent downregulation of microRNA-27a (miR-27a) or miR-20a (and paralogs) and induction of two Sp-repressors, ZBTB10 and ZBTB4 respectively. This pathway significantly contributes to the anticancer activity of ROS inducers and should be considered in development of drug combinations for cancer chemotherapy. PMID:25584043

  18. Downregulation of Reactive Oxygen Species in Apoptosis

    PubMed Central

    Jeong, Chul-Ho; Joo, Sang Hoon

    2016-01-01

    Generation of reactive oxygen species (ROS) by diverse anti-cancer drugs or phytochemicals has been closely related with the induction of apoptosis in cancers. Also, the downregulation of ROS by these chemicals has been found to block initiation of carcinogenesis. Therefore, modulation of ROS by phytochemicals emerges as a crucial mechanism to regulate apoptosis in cancer prevention or therapy. This review summarizes the current understanding of the selected chemical compounds and related cellular components that modulate ROS during apoptotic process. Metformin, quercetin, curcumin, vitamin C, and other compounds have been shown to downregulate ROS in the cellular apoptotic process, and some of them even induce apoptosis in cancer cells. The cellular components mediating the downregulation of ROS include nuclear factor erythroid 2-related factor 2 antioxidant signaling pathway, thioredoxin, catalase, glutathione, heme oxygenase-1, and uncoupling proteins. The present review provides information on the relationship between these compounds and the cellular components in modulating ROS in apoptotic cancer cells. PMID:27051644

  19. Reactive oxygen species in abiotic stress signaling.

    PubMed

    Jaspers, Pinja; Kangasjärvi, Jaakko

    2010-04-01

    Reactive oxygen species (ROS) are known to accumulate during abiotic stresses, and different cellular compartments respond to them by distinctive profiles of ROS formation. In contrast to earlier views, it is becoming increasingly evident that even during stress, ROS production is not necessarily a symptom of cellular dysfunction but might represent a necessary signal in adjusting the cellular machinery to the altered conditions. ROS can modulate many signal transduction pathways, such as mitogen-activated protein kinase cascades, and ultimately influence the activity of transcription factors. However, the picture of ROS-mediated signaling is still fragmentary and the issues of ROS perception as well as the signaling specificity remain open. Here, we review some of the recent advances in plant abiotic stress signaling with emphasis on processes known to be affected heavily by ROS. PMID:20028478

  20. REACTIVE OXYGEN SPECIES IN PULMONARY VASCULAR REMODELING

    PubMed Central

    Aggarwal, Saurabh; Gross, Christine M.; Sharma, Shruti; Fineman, Jeffrey R.; Black, Stephen M.

    2014-01-01

    The pathogenesis of pulmonary hypertension is a complex multifactorial process that involves the remodeling of pulmonary arteries. This remodeling process encompasses concentric medial thickening of small arterioles, neomuscularization of previously nonmuscular capillary-like vessels, and structural wall changes in larger pulmonary arteries. The pulmonary arterial muscularization is characterized by vascular smooth muscle cell (SMC) hyperplasia and hypertrophy. In addition, in uncontrolled pulmonary hypertension, the clonal expansion of apoptosis-resistant endothelial cells leads to the formation of plexiform lesions. Based upon a large number of studies in animal models, the three major stimuli that drive the vascular remodeling process are inflammation, shear stress and hypoxia. Although, the precise mechanisms by which these stimuli impair pulmonary vascular function and structure are unknown, reactive oxygen species (ROS)-mediated oxidative damage appears to play an important role. ROS are highly reactive due to their unpaired valence shell electron. Oxidative damage occurs when the production of ROS exceeds the quenching capacity of the anti-oxidant mechanisms of the cell. ROS can be produced from complexes in the cell membrane (nicotinamide adenine dinucleotide phosphate-oxidase), cellular organelles (peroxisomes and mitochondria), and in the cytoplasm (xanthine oxidase). Furthermore, low levels of tetrahydrobiopterin (BH4) and L-arginine the rate limiting co-factor and substrate for endothelial nitric oxide synthase (eNOS), can cause the uncoupling of eNOS, resulting in decreased NO production and increased ROS production. This review will focus on the ROS generation systems, scavenger antioxidants, and oxidative stress associated alterations in vascular remodeling in pulmonary hypertension. PMID:23897679

  1. Reactive Carbonyl Species In Vivo: Generation and Dual Biological Effects

    PubMed Central

    Semchyshyn, Halyna M.

    2014-01-01

    Reactive carbonyls are widespread species in living organisms and mainly known for their damaging effects. The most abundant reactive carbonyl species (RCS) are derived from oxidation of carbohydrates, lipids, and amino acids. Chemical modification of proteins, nucleic acids, and aminophospholipids by RCS results in cytotoxicity and mutagenicity. In addition to their direct toxicity, modification of biomolecules by RCS gives rise to a multitude of adducts and cross links that are increasingly implicated in aging and pathology of a wide range of human diseases. Understanding of the relationship between metabolism of RCS and the development of pathological disorders and diseases may help to develop effective approaches to prevent a number of disorders and diseases. On the other hand, constant persistence of RCS in cells suggests that they perform some useful role in living organisms. The most beneficial effects of RCS are their establishment as regulators of cell signal transduction and gene expression. Since RCS can modulate different biological processes, new tools are required to decipher the precise mechanisms underlying dual effects of RCS. PMID:24634611

  2. Physical exercise, reactive oxygen species and neuroprotection.

    PubMed

    Radak, Zsolt; Suzuki, Katsuhiko; Higuchi, Mitsuru; Balogh, Laszlo; Boldogh, Istvan; Koltai, Erika

    2016-09-01

    Regular exercise has systemic beneficial effects, including the promotion of brain function. The adaptive response to regular exercise involves the up-regulation of the enzymatic antioxidant system and modulation of oxidative damage. Reactive oxygen species (ROS) are important regulators of cell signaling. Exercise, via intensity-dependent modulation of metabolism and/or directly activated ROS generating enzymes, regulates the cellular redox state of the brain. ROS are also involved in the self-renewal and differentiation of neuronal stem cells and the exercise-mediated neurogenesis could be partly associated with ROS production. Exercise has strong effects on the immune system and readily alters the production of cytokines. Certain cytokines, especially IL-6, IL-1, TNF-α, IL-18 and IFN gamma, are actively involved in the modulation of synaptic plasticity and neurogenesis. Cytokines can also contribute to ROS production. ROS-mediated alteration of lipids, protein, and DNA could directly affect brain function, while exercise modulates the accumulation of oxidative damage. Oxidative alteration of macromolecules can activate signaling processes, membrane remodeling, and gene transcription. The well known neuroprotective effects of exercise are partly due to redox-associated adaptation. PMID:26828019

  3. Reactive Oxygen Species in Cancer Stem Cells

    PubMed Central

    Shi, Xiaoke; Zhang, Yan; Zheng, Junheng

    2012-01-01

    Abstract Significance: Reactive oxygen species (ROS), byproducts of aerobic metabolism, are increased in many types of cancer cells. Increased endogenous ROS lead to adaptive changes and may play pivotal roles in tumorigenesis, metastasis, and resistance to radiation and chemotherapy. In contrast, the ROS generated by xenobiotics disturb the redox balance and may selectively kill cancer cells but spare normal cells. Recent Advances: Cancer stem cells (CSCs) are integral parts of pathophysiological mechanisms of tumor progression, metastasis, and chemo/radio resistance. Currently, intracellular ROS in CSCs is an active field of research. Critical Issues: Normal stem cells such as hematopoietic stem cells reside in niches characterized by hypoxia and low ROS, both of which are critical for maintaining the potential for self-renewal and stemness. However, the roles of ROS in CSCs remain poorly understood. Future Directions: Based on the regulation of ROS levels in normal stem cells and CSCs, future research may evaluate the potential therapeutic application of ROS elevation by exogenous xenobiotics to eliminate CSCs. Antioxid. Redox Signal. 16, 1215–1228. PMID:22316005

  4. Senescence, Stress, and Reactive Oxygen Species

    PubMed Central

    Jajic, Ivan; Sarna, Tadeusz; Strzalka, Kazimierz

    2015-01-01

    Generation of reactive oxygen species (ROS) is one of the earliest responses of plant cells to various biotic and abiotic stresses. ROS are capable of inducing cellular damage by oxidation of proteins, inactivation of enzymes, alterations in the gene expression, and decomposition of biomembranes. On the other hand, they also have a signaling role and changes in production of ROS can act as signals that change the transcription of genes that favor the acclimation of plants to abiotic stresses. Among the ROS, it is believed that H2O2 causes the largest changes in the levels of gene expression in plants. A wide range of plant responses has been found to be triggered by H2O2 such as acclimation to drought, photooxidative stress, and induction of senescence. Our knowledge on signaling roles of singlet oxygen (1O2) has been limited by its short lifetime, but recent experiments with a flu mutant demonstrated that singlet oxygen does not act primarily as a toxin but rather as a signal that activates several stress-response pathways. In this review we summarize the latest progress on the signaling roles of ROS during senescence and abiotic stresses and we give a short overview of the methods that can be used for their assessment. PMID:27135335

  5. Reactive oxygen species in leaf abscission signaling

    PubMed Central

    Sakamoto, Masaru; Munemura, Ikuko; Tomita, Reiko

    2008-01-01

    Reactive oxygen species (ROS) are produced in response to many environmental stresses, such as UV, chilling, salt and pathogen attack. These stresses also accompany leaf abscission in some plants, however, the relationship between these stresses and abscission is poorly understood. In our recent report, we developed an in vitro abscission system that reproduces stress-induced pepper leaf abscission in planta. Using this system, we demonstrated that continuous production of hydrogen peroxide (H2O2) is involved in leaf abscission signaling. Continuous H2O2 production is required to induce expression of the cell wall-degrading enzyme, cellulase and functions downstream of ethylene in abscission signaling. Furthermore, enhanced production of H2O2 occurs at the execution phase of abscission, suggesting that H2O2 also plays a role in the cell-wall degradation process. These data suggest that H2O2 has several roles in leaf abscission signaling. Here, we propose a model for these roles. PMID:19704438

  6. Ovarian toxicity from reactive oxygen species.

    PubMed

    Luderer, Ulrike

    2014-01-01

    Oxidative stress occurs when cellular mechanisms to regulate levels of reactive oxygen species (ROS) are overwhelmed due to overproduction of ROS and/or deficiency of antioxidants. This chapter describes accumulating evidence that oxidative stress is involved in ovarian toxicity caused by diverse stimuli, including environmental toxicants. There is strong evidence that ROS are involved in initiation of apoptosis in antral follicles caused by several chemical and physical agents. Although less attention has been focused on the roles of ROS in primordial and primary follicle death, several studies have shown protective effects of antioxidants and/or evidence of oxidative damage, suggesting that ROS may play a role in these smaller follicles as well. Oxidative damage to lipids in the oocyte has been implicated as a cause of persistently poor oocyte quality after early life exposure to several toxicants. Developing germ cells in the fetal ovary have also been shown to be sensitive to toxicants and ionizing radiation, which induce oxidative stress. Recent studies have begun to elucidate the mechanisms by which ROS mediate ovarian toxicity. PMID:24388188

  7. Reactive Oxygen Species in Combustion Aerosols

    NASA Astrophysics Data System (ADS)

    Balasubramanian, R.; See, S.

    2007-12-01

    Research on airborne particulate matter (PM) has received increased concern in recent years after it was identified as a major component of the air pollution mix that is strongly associated with premature mortality and morbidity. Particular attention has been paid to understanding the potential health impacts of fine particles (PM2.5), which primarily originate from combustion sources. One group of particulate-bound chemical components of health concern is reactive oxygen species (ROS), which include molecules such as hydrogen peroxide (H2O2), ions such as hypochlorite ion (OCl-), free radicals such as hydroxyl radical (·OH) and superoxide anion (·O2-) which is both an ion and a radical. However, the formation of ROS in PM is not clearly understood yet. Furthermore, the concentration of ROS in combustion particles of different origin has not been quantified. The primary objective of this work is to study the effect of transition metals on the production of ROS in PM2.5 by determining the concentrations of ROS and metals. Both soluble and total metals were measured to evaluate their respective associations with ROS. PM2.5 samples were collected from several outdoor and indoor combustion sources, including those emitted from on-road vehicles, food cooking, incense sticks, and cigarette smoke. PM2.5 samples were also collected from the background air in both the ambient outdoor and indoor environments to assess the levels of particulate-bound transition metals and ROS with no combustion activities in the vicinity of sampling locations. Results obtained from this comprehensive study on particulate-bound ROS will be presented and discussed.

  8. Reactive oxygen species and boar sperm function.

    PubMed

    Awda, Basim J; Mackenzie-Bell, Meghan; Buhr, Mary M

    2009-09-01

    Boar spermatozoa are very susceptible to reactive oxygen species (ROS), but ROS involvement in damage and/or capacitation is unclear. The impact of exposing fresh boar spermatozoa to an ROS-generating system (xanthine/xanthine oxidase; XA/XO) on sperm ROS content, membrane lipid peroxidation, phospholipase (PL) A activity, and motility, viability, and capacitation was contrasted to ROS content and sperm function after cryopreservation. Exposing boar sperm (n = 4-5 ejaculates) to the ROS-generating system for 30 min rapidly increased hydrogen peroxide (H2O2) and lipid peroxidation in all sperm, increased PLA in dead sperm, and did not affect intracellular O2- (flow cytometry of sperm labeled with 2',7'-dichlorodihydrofluorscein diacetate, BODIPY 581/591 C11, bis-BODIPY-FL C11, hydroethidine, respectively; counterstained for viability). Sperm viability remained high, but sperm became immotile. Cryopreservation decreased sperm motility, viability, and intracellular O2- significantly, but did not affect H2O2. As expected, more sperm incubated in capacitating media than Beltsville thawing solution buffer underwent acrosome reactions and protein tyrosine phosphorylation (four proteins, 58-174 kDa); which proteins were tyrosine phosphorylated was pH dependent. Pre-exposing sperm to the ROS-generating system increased the percentage of sperm that underwent acrosome reactions after incubation in capacitating conditions (P < 0.025), and decreased capacitation-dependent increases in two tyrosine-phosphorylated proteins (P < or = 0.035). In summary, H2O2 is the major free radical mediating direct ROS effects, but not cryopreservation changes, on boar sperm. Boar sperm motility, acrosome integrity, and lipid peroxidation are more sensitive indicators of oxidative stress than viability and PLA activity. ROS may stimulate the acrosome reaction in boar sperm through membrane lipid peroxidation and PLA activation. PMID:19357363

  9. Skin, Reactive Oxygen Species, and Circadian Clocks

    PubMed Central

    Ndiaye, Mary A.; Nihal, Minakshi; Wood, Gary S.

    2014-01-01

    Abstract Significance: Skin, a complex organ and the body's first line of defense against environmental insults, plays a critical role in maintaining homeostasis in an organism. This balance is maintained through a complex network of cellular machinery and signaling events, including those regulating oxidative stress and circadian rhythms. These regulatory mechanisms have developed integral systems to protect skin cells and to signal to the rest of the body in the event of internal and environmental stresses. Recent Advances: Interestingly, several signaling pathways and many bioactive molecules have been found to be involved and even important in the regulation of oxidative stress and circadian rhythms, especially in the skin. It is becoming increasingly evident that these two regulatory systems may, in fact, be interconnected in the regulation of homeostasis. Important examples of molecules that connect the two systems include serotonin, melatonin, vitamin D, and vitamin A. Critical Issues: Excessive reactive oxygen species and/or dysregulation of antioxidant system and circadian rhythms can cause critical errors in maintaining proper barrier function and skin health, as well as overall homeostasis. Unfortunately, the modern lifestyle seems to contribute to increasing alterations in redox balance and circadian rhythms, thereby posing a critical problem for normal functioning of the living system. Future Directions: Since the oxidative stress and circadian rhythm systems seem to have areas of overlap, future research needs to be focused on defining the interactions between these two important systems. This may be especially important in the skin where both systems play critical roles in protecting the whole body. Antioxid. Redox Signal. 20, 2982–2996. PMID:24111846

  10. Gallic Acid Induces a Reactive Oxygen Species-Provoked c-Jun NH2-Terminal Kinase-Dependent Apoptosis in Lung Fibroblasts

    PubMed Central

    Chen, Chiu-Yuan; Chen, Kun-Chieh; Yang, Tsung-Ying; Liu, Hsiang-Chun; Hsu, Shih-Lan

    2013-01-01

    Idiopathic pulmonary fibrosis is a chronic lung disorder characterized by fibroblasts proliferation and extracellular matrix accumulation. Induction of fibroblast apoptosis therefore plays a crucial role in the resolution of this disease. Gallic acid (3,4,5-trihydroxybenzoic acid), a common botanic phenolic compound, has been reported to induce apoptosis in tumor cell lines and renal fibroblasts. The present study was undertaken to examine the role of mitogen-activated protein kinases (MAPKs) in lung fibroblasts apoptosis induced by gallic acid. We found that treatment with gallic acid resulted in activation of c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and protein kinase B (PKB, Akt), but not p38MAPK, in mouse lung fibroblasts. Inhibition of JNK using pharmacologic inhibitor (SP600125) and genetic knockdown (JNK specific siRNA) significantly inhibited p53 accumulation, reduced PUMA and Fas expression, and abolished apoptosis induced by gallic acid. Moreover, treatment with antioxidants (vitamin C, N-acetyl cysteine, and catalase) effectively diminished gallic acid-induced hydrogen peroxide production, JNK and p53 activation, and cell death. These observations imply that gallic acid-mediated hydrogen peroxide formation acts as an initiator of JNK signaling pathways, leading to p53 activation and apoptosis in mouse lung fibroblasts. PMID:23533505

  11. Reactive Oxygen Species: Physiological and Physiopathological Effects on Synaptic Plasticity

    PubMed Central

    Beckhauser, Thiago Fernando; Francis-Oliveira, José; De Pasquale, Roberto

    2016-01-01

    In the mammalian central nervous system, reactive oxygen species (ROS) generation is counterbalanced by antioxidant defenses. When large amounts of ROS accumulate, antioxidant mechanisms become overwhelmed and oxidative cellular stress may occur. Therefore, ROS are typically characterized as toxic molecules, oxidizing membrane lipids, changing the conformation of proteins, damaging nucleic acids, and causing deficits in synaptic plasticity. High ROS concentrations are associated with a decline in cognitive functions, as observed in some neurodegenerative disorders and age-dependent decay of neuroplasticity. Nevertheless, controlled ROS production provides the optimal redox state for the activation of transductional pathways involved in synaptic changes. Since ROS may regulate neuronal activity and elicit negative effects at the same time, the distinction between beneficial and deleterious consequences is unclear. In this regard, this review assesses current research and describes the main sources of ROS in neurons, specifying their involvement in synaptic plasticity and distinguishing between physiological and pathological processes implicated. PMID:27625575

  12. [Reactive oxygen species and fibrosis in tissues and organs - review].

    PubMed

    Meng, Juan-Xia; Zhao, Ming-Feng

    2012-10-01

    Reactive oxygen species (ROS) is a kind of molecules derived by oxygen in the metabolic process of aerobic cells, which mainly includes superoxide, hydroxyl radicals, alkoxyl, hydrogen peroxide, hypochlorous acid, ozone, etc. They can destroy the structure and function of cells through the damage of biological macromolecules such as DNA, proteins and the lipid peroxidation. ROS also can regulate the proliferation, differentiation and apoptosis of cells through several signaling pathways and participate in fibrogenesis of many organs including hepatic and pulmonary fibrosis. Recent study shows that ROS might have an important effect on the forming of myelofibrosis. Consequently, ROS plays a significant role in the fibrogenesis of tissues and organs. In this review, the relevance between ROS and common tissues and organs fibrosis is summarized. PMID:23114165

  13. Reactive Oxygen Species: Physiological and Physiopathological Effects on Synaptic Plasticity.

    PubMed

    Beckhauser, Thiago Fernando; Francis-Oliveira, José; De Pasquale, Roberto

    2016-01-01

    In the mammalian central nervous system, reactive oxygen species (ROS) generation is counterbalanced by antioxidant defenses. When large amounts of ROS accumulate, antioxidant mechanisms become overwhelmed and oxidative cellular stress may occur. Therefore, ROS are typically characterized as toxic molecules, oxidizing membrane lipids, changing the conformation of proteins, damaging nucleic acids, and causing deficits in synaptic plasticity. High ROS concentrations are associated with a decline in cognitive functions, as observed in some neurodegenerative disorders and age-dependent decay of neuroplasticity. Nevertheless, controlled ROS production provides the optimal redox state for the activation of transductional pathways involved in synaptic changes. Since ROS may regulate neuronal activity and elicit negative effects at the same time, the distinction between beneficial and deleterious consequences is unclear. In this regard, this review assesses current research and describes the main sources of ROS in neurons, specifying their involvement in synaptic plasticity and distinguishing between physiological and pathological processes implicated. PMID:27625575

  14. Reactive solute transport in acidic streams

    USGS Publications Warehouse

    Broshears, R.E.

    1996-01-01

    Spatial and temporal profiles of Ph and concentrations of toxic metals in streams affected by acid mine drainage are the result of the interplay of physical and biogeochemical processes. This paper describes a reactive solute transport model that provides a physically and thermodynamically quantitative interpretation of these profiles. The model combines a transport module that includes advection-dispersion and transient storage with a geochemical speciation module based on MINTEQA2. Input to the model includes stream hydrologic properties derived from tracer-dilution experiments, headwater and lateral inflow concentrations analyzed in field samples, and a thermodynamic database. Simulations reproduced the general features of steady-state patterns of observed pH and concentrations of aluminum and sulfate in St. Kevin Gulch, an acid mine drainage stream near Leadville, Colorado. These patterns were altered temporarily by injection of sodium carbonate into the stream. A transient simulation reproduced the observed effects of the base injection.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  16. Production and Consumption of Reactive Oxygen Species by Fullerenes

    EPA Science Inventory

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

  17. A case of mistaken identity: are reactive oxygen species actually reactive sulfide species?

    PubMed

    DeLeon, Eric R; Gao, Yan; Huang, Evelyn; Arif, Maaz; Arora, Nitin; Divietro, Alexander; Patel, Shivali; Olson, Kenneth R

    2016-04-01

    Stepwise one-electron reduction of oxygen to water produces reactive oxygen species (ROS) that are chemically and biochemically similar to reactive sulfide species (RSS) derived from one-electron oxidations of hydrogen sulfide to elemental sulfur. Both ROS and RSS are endogenously generated and signal via protein thiols. Given the similarities between ROS and RSS, we wondered whether extant methods for measuring the former would also detect the latter. Here, we compared ROS to RSS sensitivity of five common ROS methods: redox-sensitive green fluorescent protein (roGFP), 2', 7'-dihydrodichlorofluorescein, MitoSox Red, Amplex Red, and amperometric electrodes. All methods detected RSS and were as, or more, sensitive to RSS than to ROS. roGFP, arguably the "gold standard" for ROS measurement, was more than 200-fold more sensitive to the mixed polysulfide H2Sn(n = 1-8) than to H2O2 These findings suggest that RSS may be far more prevalent in intracellular signaling than previously appreciated and that the contribution of ROS may be overestimated. This conclusion is further supported by the observation that estimated daily sulfur metabolism and ROS production are approximately equal and the fact that both RSS and antioxidant mechanisms have been present since the origin of life, nearly 4 billion years ago, long before the rise in environmental oxygen 600 million years ago. Although ROS are assumed to be the most biologically relevant oxidants, our results question this paradigm. We also anticipate our findings will direct attention toward development of novel and clinically relevant anti-(RSS)-oxidants. PMID:26764057

  18. Guanidino compounds generate reactive oxygen species.

    PubMed

    Mori, A; Kohno, M; Masumizu, T; Noda, Y; Packer, L

    1996-09-01

    Methylguanidine, guanidinoacetic acid and guanidinosuccinic acid are endogenous substances in body tissues. Extremely high levels of these substances are known to be related to the pathogenesis of epilepsy and renal failure such as uremia. In this study it was demonstrated that methylguanidine, guanidinoacetic acid and guanidinosuccinic acid, and arginine generate hydroxyl radicals in aqueous solution. These findings suggest that a high level of guanidino compounds accumulating near or within cells such as neurons (in an epileptogenic focus) or nephrons (in uremic patients) may cause free radical damage leading to these clinical disorders. Arginine may have a similar role in the pathogenesis of hyperarginemia. PMID:8886279

  19. 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. PMID:25670736

  20. Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence.

    PubMed

    Reiter, R J; Tan, D X; Manchester, L C; Qi, W

    2001-01-01

    Melatonin (N-acetyl-5-methoxytryptamine), an endogenously produced indole found throughout the animal kingdom, was recently reported, using a variety of techniques, to be a scavenger of a number of reactive oxygen and reactive nitrogen species both in vitro and in vivo. Initially, melatonin was discovered to directly scavenge the high toxic hydroxyl radical (*OH). The methods used to prove the interaction of melatonin with the *OH included the generation of the radical using Fenton reagents or the ultraviolet photolysis of hydrogen peroxide (H202) with the use of spin-trapping agents, followed by electron spin resonance (ESR) spectroscopy, pulse radiolysis followed by ESR, and several spectrofluorometric and chemical (salicylate trapping in vivo) methodologies. One product of the reaction of melatonin with the *OH was identified as cyclic 3-hydroxymelatonin (3-OHM) using high-performance liquid chromatography with electrochemical (HPLC-EC) detection, electron ionization mass spectrometry (EIMS), proton nuclear magnetic resonance (1H NMR) and COSY 1H NMR. Cyclic 3-OHM appears in the urine of humans and other mammals and in rat urine its concentration increases when melatonin is given exogenously or after an imposed oxidative stress (exposure to ionizing radiation). Urinary cyclic 3-OHM levels are believed to be a biomarker (footprint molecule) of in vivo *OH production and its scavenging by melatonin. Although the data are less complete, besides the *OH, melatonin in cell-free systems has been shown to directly scavenge H2O2, singlet oxygen (1O2) and nitric oxide (NO*), with little or no ability to scavenge the superoxide anion radical (O2*-) In vitro, melatonin also directly detoxifies the peroxynitrite anion (ONOO-) and/or peroxynitrous acid (ONOOH), or the activated form of this molecule, ONOOH*; the product of the latter interaction is proposed to be 6-OHM. How these in vitro findings relate to the in vivo antioxidant actions of melatonin remains to be

  1. Xanthine Oxidoreductase-Derived Reactive Species: Physiological and Pathological Effects

    PubMed Central

    Bortolotti, Massimo

    2016-01-01

    Xanthine oxidoreductase (XOR) is the enzyme that catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid and is widely distributed among species. In addition to this housekeeping function, mammalian XOR is a physiological source of superoxide ion, hydrogen peroxide, and nitric oxide, which can function as second messengers in the activation of various pathways. This review intends to address the physiological and pathological roles of XOR-derived oxidant molecules. The cytocidal action of XOR products has been claimed in relation to tissue damage, in particular damage induced by hypoxia and ischemia. Attempts to exploit this activity to eliminate unwanted cells via the construction of conjugates have also been reported. Moreover, different aspects of XOR activity related to phlogosis, endothelial activation, leukocyte activation, and vascular tone regulation, have been taken into consideration. Finally, the positive and negative outcomes concerning cancer pathology have been analyzed because XOR products may induce mutagenesis, cell proliferation, and tumor progression, but they are also associated with apoptosis and cell differentiation. In conclusion, XOR activity generates free radicals and other oxidant reactive species that may result in either harmful or beneficial outcomes. PMID:26823950

  2. Xanthine Oxidoreductase-Derived Reactive Species: Physiological and Pathological Effects.

    PubMed

    Battelli, Maria Giulia; Polito, Letizia; Bortolotti, Massimo; Bolognesi, Andrea

    2016-01-01

    Xanthine oxidoreductase (XOR) is the enzyme that catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid and is widely distributed among species. In addition to this housekeeping function, mammalian XOR is a physiological source of superoxide ion, hydrogen peroxide, and nitric oxide, which can function as second messengers in the activation of various pathways. This review intends to address the physiological and pathological roles of XOR-derived oxidant molecules. The cytocidal action of XOR products has been claimed in relation to tissue damage, in particular damage induced by hypoxia and ischemia. Attempts to exploit this activity to eliminate unwanted cells via the construction of conjugates have also been reported. Moreover, different aspects of XOR activity related to phlogosis, endothelial activation, leukocyte activation, and vascular tone regulation, have been taken into consideration. Finally, the positive and negative outcomes concerning cancer pathology have been analyzed because XOR products may induce mutagenesis, cell proliferation, and tumor progression, but they are also associated with apoptosis and cell differentiation. In conclusion, XOR activity generates free radicals and other oxidant reactive species that may result in either harmful or beneficial outcomes. PMID:26823950

  3. Scavenging of reactive oxygen species by silibinin dihemisuccinate.

    PubMed

    Mira, L; Silva, M; Manso, C F

    1994-08-17

    Silibinin dihemisuccinate (SDH) is a flavonoid of plant origin with hepatoprotective effects which have been partially attributed to its ability to scavenge oxygen free radicals. In the present paper the antioxidant properties of SDH were evaluated by studying the ability of this drug to react with relevant biological oxidants such as superoxide anion radical (O2-), hydrogen peroxide (H2O2), hydroxyl radical (HO.) and hypochlorous acid (HOCl). In addition, its effect on lipid peroxidation was investigated. SDH is not a good scavenger of O2- and no reaction with H2O2 was detected within the sensitivity limit of our assay. However, it reacts rapidly with HO. radicals in free solution at approximately diffusion-controlled rate (K = (1.0-1.2) x 10(10)/M/sec) and appears to be a weak iron ion chelator. SDH at concentrations in the micromolar range protected alpha 1-antiproteinase against inactivation by HOCl, showing that it is a potent scavenger of this oxidizing species. Luminol-dependent chemiluminescence induced by HOCl was also inhibited by SDH. The reaction of SDH with HOCl was monitored by the modification of the UV-visible spectrum of SDH. The studies on rat liver microsome lipid peroxidation induced by Fe(III)/ascorbate showed that SDH has an inhibitory effect, which is dependent on its concentration and the magnitude of lipid peroxidation. This work supports the reactive oxygen species scavenger action ascribed to SDH. PMID:8080448

  4. Theoretical study on the reactivity of sulfate species with hydrocarbons

    USGS Publications Warehouse

    Ma, Q.; Ellis, G.S.; Amrani, A.; Zhang, T.; Tang, Y.

    2008-01-01

    The abiotic, thermochemically controlled reduction of sulfate to hydrogen sulfide coupled with the oxidation of hydrocarbons, is termed thermochemical sulfate reduction (TSR), and is an important alteration process that affects petroleum accumulations in nature. Although TSR is commonly observed in high-temperature carbonate reservoirs, it has proven difficult to simulate in the laboratory under conditions resembling nature. The present study was designed to evaluate the relative reactivities of various sulfate species in order to provide greater insight into the mechanism of TSR and potentially to fill the gap between laboratory experimental data and geological observations. Accordingly, quantum mechanics density functional theory (DFT) was used to determine the activation energy required to reach a potential transition state for various aqueous systems involving simple hydrocarbons and different sulfate species. The entire reaction process that results in the reduction of sulfate to sulfide is far too complex to be modeled entirely; therefore, we examined what is believed to be the rate limiting step, namely, the reduction of sulfate S(VI) to sulfite S(IV). The results of the study show that water-solvated sulfate anions SO42 - are very stable due to their symmetrical molecular structure and spherical electronic distributions. Consequently, in the absence of catalysis, the reactivity of SO42 - is expected to be extremely low. However, both the protonation of sulfate to form bisulfate anions (HSO4-) and the formation of metal-sulfate contact ion-pairs could effectively destabilize the sulfate molecular structure, thereby making it more reactive. Previous reports of experimental simulations of TSR generally have involved the use of acidic solutions that contain elevated concentrations of HSO4- relative to SO42 -. However, in formation waters typically encountered in petroleum reservoirs, the concentration of HSO4- is likely to be significantly lower than the levels

  5. Redox signaling regulated by electrophiles and reactive sulfur species.

    PubMed

    Nishida, Motohiro; Kumagai, Yoshito; Ihara, Hideshi; Fujii, Shigemoto; Motohashi, Hozumi; Akaike, Takaaki

    2016-03-01

    Redox signaling is a key modulator of oxidative stress induced by nonspecific insults of biological molecules generated by reactive oxygen species. Current redox biology is revisiting the traditional concept of oxidative stress, such that toxic effects of reactive oxygen species are protected by diverse antioxidant systems upregulated by oxidative stress responses that are physiologically mediated by redox-dependent cell signaling pathways. Redox signaling is thus precisely regulated by endogenous electrophilic substances that are generated from reactive oxygen species and nitric oxide and its derivative reactive species during stress responses. Among electrophiles formed endogenously, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) has unique cell signaling functions, and pathways for its biosynthesis, signaling mechanism, and metabolism in cells have been clarified. Reactive sulfur species such as cysteine hydropersulfides that are abundant in cells are likely involved in 8-nitro-cGMP metabolism. These new aspects of redox biology may stimulate innovative and multidisciplinary research in cell and stem cell biology; infectious diseases, cancer, metabolic syndrome, ageing, and neurodegenerative diseases; and other oxidative stress-related disorders. This review focuses on the most recent progress in the biosynthesis, cell signaling, and metabolism of 8-nitro-cGMP, which is a likely target for drug development and lead to discovery of novel therapeutics for many diseases. PMID:27013774

  6. Redox signaling regulated by electrophiles and reactive sulfur species

    PubMed Central

    Nishida, Motohiro; Kumagai, Yoshito; Ihara, Hideshi; Fujii, Shigemoto; Motohashi, Hozumi; Akaike, Takaaki

    2016-01-01

    Redox signaling is a key modulator of oxidative stress induced by nonspecific insults of biological molecules generated by reactive oxygen species. Current redox biology is revisiting the traditional concept of oxidative stress, such that toxic effects of reactive oxygen species are protected by diverse antioxidant systems upregulated by oxidative stress responses that are physiologically mediated by redox-dependent cell signaling pathways. Redox signaling is thus precisely regulated by endogenous electrophilic substances that are generated from reactive oxygen species and nitric oxide and its derivative reactive species during stress responses. Among electrophiles formed endogenously, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) has unique cell signaling functions, and pathways for its biosynthesis, signaling mechanism, and metabolism in cells have been clarified. Reactive sulfur species such as cysteine hydropersulfides that are abundant in cells are likely involved in 8-nitro-cGMP metabolism. These new aspects of redox biology may stimulate innovative and multidisciplinary research in cell and stem cell biology; infectious diseases, cancer, metabolic syndrome, ageing, and neurodegenerative diseases; and other oxidative stress-related disorders. This review focuses on the most recent progress in the biosynthesis, cell signaling, and metabolism of 8-nitro-cGMP, which is a likely target for drug development and lead to discovery of novel therapeutics for many diseases. PMID:27013774

  7. Laser spectroscopy of chemically reactive species

    SciTech Connect

    Wu, Ming; Sears, T.J.

    1993-02-01

    We report the observation of stimulated emission pumping spectra in the NCO radical formed in a supersonic free jet expansion by the reaction between photolytically generated CN radicals and O{sub 2}. The spectra give rotationally resolved information on high lying vibrational levels that are difficult or impossible to detect by conventional single photon spectroscopic techniques. These new data provide detailed insight into the Renner-Teller, spin-orbit and Fermi-resonance coupling in the molecule. They also provide a solid basis for future state-selected chemical and dynamical studies involving this important radical species.

  8. 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.

  9. Reactive oxygen species production by catechol stabilized copper nanoparticles

    NASA Astrophysics Data System (ADS)

    Chen, Cheng; Ahmed, Ishtiaq; Fruk, Ljiljana

    2013-11-01

    Stable Cu nanoparticles (NPs) prepared using catechol containing dopamine-based linkers could generate reactive oxygen species (ROS) that can activate peroxidase enzymes and catalyze the degradation of fluorescent dye pollutants.Stable Cu nanoparticles (NPs) prepared using catechol containing dopamine-based linkers could generate reactive oxygen species (ROS) that can activate peroxidase enzymes and catalyze the degradation of fluorescent dye pollutants. Electronic supplementary information (ESI) available: Details of the synthesis of dopamine linkers and Cu NPs, peroxidase activity tests, H2O2 calibration and degradation tests for resorufin, RB and MB. See DOI: 10.1039/c3nr03563h

  10. Role of reactive oxygen species in myocardial remodeling.

    PubMed

    Zhang, Min; Shah, Ajay M

    2007-03-01

    Adverse cardiac remodeling is a fundamental process in the progression to chronic heart failure. Although the mechanisms underlying cardiac remodeling are multi-factorial, a significant body of evidence points to the crucial roles of increased reactive oxygen species. This article reviews recent advances in delineating the different sources of production for reactive oxygen species (namely mitochondria, xanthine oxidase, uncoupled nitric oxide synthases, and NADPH oxidases) that may be involved in cardiac remodeling and the aspects of the remodeling process that they affect. These data could suggest new ways of targeting redox pathways for the prevention and treatment of adverse cardiac remodeling. PMID:17386182

  11. Biological reactivity and biomarkers of the neutrophil oxidant, hypochlorous acid.

    PubMed

    Winterbourn, Christine C

    2002-12-27

    Free radicals or reactive oxygen species are thought to contribute to the pathology of many diseases. These include inflammatory conditions, where neutrophils accumulate in large numbers and are stimulated to produce superoxide and other reactive oxidants. Hypochlorous acid (HOCl), produced by myeloperoxidase-catalysed oxidation of chloride by hydrogen peroxide, is the major strong oxidant generated by these cells. Neutrophil-mediated injury may also be important in toxicology when an initial insult is followed by an inflammatory response. It is important to characterize the inflammatory component of such injury and the extent to which it involves reactive oxidants. On the one hand, this requires an understanding of how neutrophil oxidants react with cells and tissue constituents. On the other, specific biomarkers are needed so that oxidative damage can be quantified in clinical material and related to disease severity. This presentation considers biologically relevant reactions of HOCl and the biomarker assays that can be applied to probing the pathological role of myeloperoxidase and its products. PMID:12505315

  12. Reactive Species Processes in Plasma-, Gas-, and Liquid-Phase

    NASA Astrophysics Data System (ADS)

    Reuter, Stephan; Winter, Joern; Hammer, Malte; Schmidt-Bleker, Ansgar; Iseni, Sylvain; Tresp, Helena; Dünnbier, Mario; Masur, Kai; Wende, Kristian; Weltmann, Klaus-Dieter

    2013-09-01

    Especially for the field of plasma medicine, plasmas interacting with liquids are of great interest for environmental, chemical, and biomedical applications. In this work we present optical diagnostics on atmospheric pressure plasma jets interacting with liquids. Combining the diagnostic results with numerical simulations yields an understanding of fundamental processes such as air species diffusion into the jet effluents or the influence on humidity. Especially for plasma treatment of physiological liquids in ambient air, atmospheric species play a key role. To achieve a desired reactive component output, the generation processes from these ambient air species are controlled. Plasma jets are characterized by planar laser induced fluorescence spectroscopy, by absorption and emission spectroscopy, and by flow simulations. With the gained knowledge we are able to tailor the reactive component composition and to influence plasma jet-liquid interaction. We show that reactive species generation within plasma treated liquid can be tuned and apply the findings to biological cells to investigate the effect of reactive oxygen and nitrogen species (RONS). The plasma treated liquids are investigated regarding their pH value, OH radicals, nitrate and nitrite, and H2O2 content. From the tailored plasma treatment a significant insight into the relevant transport processes in plasma treatment of liquids has been gained. Support by the German BMBF 03Z2DN11&12 is acknowledged.

  13. Reactive Oxygen Species (Ros-Induced) Ros Release

    PubMed Central

    Zorov, Dmitry B.; Filburn, Charles R.; Klotz, Lars-Oliver; Zweier, Jay L.; Sollott, Steven J.

    2000-01-01

    We sought to understand the relationship between reactive oxygen species (ROS) and the mitochondrial permeability transition (MPT) in cardiac myocytes based on the observation of increased ROS production at sites of spontaneously deenergized mitochondria. We devised a new model enabling incremental ROS accumulation in individual mitochondria in isolated cardiac myocytes via photoactivation of tetramethylrhodamine derivatives, which also served to report the mitochondrial transmembrane potential, ΔΨ. This ROS accumulation reproducibly triggered abrupt (and sometimes reversible) mitochondrial depolarization. This phenomenon was ascribed to MPT induction because (a) bongkrekic acid prevented it and (b) mitochondria became permeable for calcein (∼620 daltons) concurrently with depolarization. These photodynamically produced “triggering” ROS caused the MPT induction, as the ROS scavenger Trolox prevented it. The time required for triggering ROS to induce the MPT was dependent on intrinsic cellular ROS-scavenging redox mechanisms, particularly glutathione. MPT induction caused by triggering ROS coincided with a burst of mitochondrial ROS generation, as measured by dichlorofluorescein fluorescence, which we have termed mitochondrial “ROS-induced ROS release” (RIRR). This MPT induction/RIRR phenomenon in cardiac myocytes often occurred synchronously and reversibly among long chains of adjacent mitochondria demonstrating apparent cooperativity. The observed link between MPT and RIRR could be a fundamental phenomenon in mitochondrial and cell biology. PMID:11015441

  14. PYR/PYL/RCAR Abscisic Acid Receptors Regulate K+ and Cl− Channels through Reactive Oxygen Species-Mediated Activation of Ca2+ Channels at the Plasma Membrane of Intact Arabidopsis Guard Cells1[W][OPEN

    PubMed Central

    Wang, Yizhou; Chen, Zhong-Hua; Zhang, Ben; Hills, Adrian; Blatt, Michael R.

    2013-01-01

    The discovery of the START family of abscisic acid (ABA) receptors places these proteins at the front of a protein kinase/phosphatase signal cascade that promotes stomatal closure. The connection of these receptors to Ca2+ signals evoked by ABA has proven more difficult to resolve, although it has been implicated by studies of the pyrbactin-insensitive pyr1/pyl1/pyl2/pyl4 quadruple mutant. One difficulty is that flux through plasma membrane Ca2+ channels and Ca2+ release from endomembrane stores coordinately elevate cytosolic free Ca2+ concentration ([Ca2+]i) in guard cells, and both processes are facilitated by ABA. Here, we describe a method for recording Ca2+ channels at the plasma membrane of intact guard cells of Arabidopsis (Arabidopsis thaliana). We have used this method to resolve the loss of ABA-evoked Ca2+ channel activity at the plasma membrane in the pyr1/pyl1/pyl2/pyl4 mutant and show the consequent suppression of [Ca2+]i increases in vivo. The basal activity of Ca2+ channels was not affected in the mutant; raising the concentration of Ca2+ outside was sufficient to promote Ca2+ entry, to inactivate current carried by inward-rectifying K+ channels and to activate current carried by the anion channels, both of which are sensitive to [Ca2+]i elevations. However, the ABA-dependent increase in reactive oxygen species (ROS) was impaired. Adding the ROS hydrogen peroxide was sufficient to activate the Ca2+ channels and trigger stomatal closure in the mutant. These results offer direct evidence of PYR/PYL/RCAR receptor coupling to the activation by ABA of plasma membrane Ca2+ channels through ROS, thus affecting [Ca2+]i and its regulation of stomatal closure. PMID:23899646

  15. Reactive nitrogen species mediate oxidative stress and astrogliosis provoked by in vivo administration of phytanic acid in cerebellum of adolescent rats: A potential contributing pathomechanism of cerebellar injury in peroxisomal disorders.

    PubMed

    Borges, C G; Canani, C R; Fernandes, C G; Zanatta, Â; Seminotti, B; Ribeiro, C A J; Leipnitz, G; Vargas, C R; Wajner, M

    2015-09-24

    Phytanic acid (Phyt) accumulates in various peroxisomal diseases including Refsum disease (RD) and Zellweger syndrome (ZS). Since the pathogenesis of the neurological symptoms and especially the cerebellar abnormalities in these disorders are poorly known, we investigated the effects of in vivo intracerebral administration of Phyt on a large spectrum of redox homeostasis parameters in the cerebellum of young rats. Malondialdehyde (MDA) levels, sulfhydryl oxidation, carbonyl content, nitrite and nitrate concentrations, 2',7'-dichlorofluorescein (DCFH) oxidation, total (tGS) and reduced glutathione (GSH) levels and the activities of important antioxidant enzymes were determined at different periods after Phyt administration. Immunohistochemical analysis was also carried out in the cerebellum. Phyt significantly increased MDA and nitric oxide (NO) production and decreased GSH levels, without altering tGS, DCFH oxidation, sulfhydryl oxidation, carbonyl content and the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD). Furthermore, immunohistochemical analysis revealed that Phyt caused astrogliosis and protein nitrosative damage in the cerebellum. It was also observed that the NO synthase inhibitor Nω-Nitro-L-arginine methyl ester (L-NAME) prevented the increase of MDA and NO production as well as the decrease of GSH and the immunohistochemical alterations caused by Phyt, strongly suggesting that reactive nitrogen species (RNS) were involved in these effects. The present data provide in vivo solid evidence that Phyt disrupts redox homeostasis and causes astrogliosis in rat cerebellum probably mediated by RNS production. It is therefore presumed that disequilibrium of redox status may contribute at least in part to the cerebellum alterations characteristic of patients affected by RD and other disorders with Phyt accumulation. PMID:26188285

  16. A STRESS-RESPONSIVE NAC1-Regulated Protein Phosphatase Gene Rice Protein Phosphatase18 Modulates Drought and Oxidative Stress Tolerance through Abscisic Acid-Independent Reactive Oxygen Species Scavenging in Rice1[W][OPEN

    PubMed Central

    You, Jun; Zong, Wei; Hu, Honghong; Li, Xianghua; Xiao, Jinghua; Xiong, Lizhong

    2014-01-01

    Plants respond to abiotic stresses through a complexity of signaling pathways, and the dephosphorylation mediated by protein phosphatase (PP) is an important event in this process. We identified a rice (Oryza sativa) PP2C gene, OsPP18, as a STRESS-RESPONSIVE NAC1 (SNAC1)-regulated downstream gene. The ospp18 mutant was more sensitive than wild-type plants to drought stress at both the seedling and panicle development stages. Rice plants with OsPP18 suppressed through artificial microRNA were also hypersensitive to drought stress. Microarray analysis of the mutant revealed that genes encoding reactive oxygen species (ROS) scavenging enzymes were down-regulated in the ospp18 mutant, and the mutant exhibited reduced activities of ROS scavenging enzymes and increased sensitivity to oxidative stresses. Overexpression of OsPP18 in rice led to enhanced osmotic and oxidative stress tolerance. The expression of OsPP18 was induced by drought stress but not induced by abscisic acid (ABA). Although OsPP18 is a typical PP2C with enzymatic activity, it did not interact with SNF1-RELATED PROTEIN KINASE2 protein kinases, which function in ABA signaling. Meanwhile, the expression of ABA-responsive genes was not affected in the ospp18 mutant, and the ABA sensitivities of the ospp18 mutant and OsPP18-overexpressing plants were also not altered. Together, these findings suggest that OsPP18 is a unique PP2C gene that is regulated by SNAC1 and confers drought and oxidative stress tolerance by regulating ROS homeostasis through ABA-independent pathways. PMID:25318938

  17. Optical emission studies of reactive species in plasma deposition

    SciTech Connect

    Kampas, F.J.; Griffith, R.W.

    1981-01-01

    Optical emission studies of the glow-discharge deposition of a-Si:H alloys reveal the presence of reactive species derived from process gases and impurities. Studies of the dependences of emission intensities upon deposition parameters elucidate the mechanisms of formation of these species. Effects of impurities detected by emission spectroscopy upon a-Si:H film electronic properties are discussed. A model of the chemical reactions involved in film growth is presented.

  18. Oxidation of LDL by myeloperoxidase and reactive nitrogen species: reaction pathways and antioxidant protection.

    PubMed

    Carr, A C; McCall, M R; Frei, B

    2000-07-01

    Oxidative modification of low density lipoprotein (LDL) appears to play an important role in atherogenesis. Although the precise mechanisms of LDL oxidation in vivo are unknown, several lines of evidence implicate myeloperoxidase and reactive nitrogen species, in addition to ceruloplasmin and 15-lipoxygenase. Myeloperoxidase generates a number of reactive species, including hypochlorous acid, chloramines, tyrosyl radicals, and nitrogen dioxide. These reactive species oxidize the protein, lipid, and antioxidant components of LDL. Modification of apolipoprotein B results in enhanced uptake of LDL by macrophages with subsequent formation of lipid-laden foam cells. Nitric oxide synthases produce nitric oxide and, under certain conditions, superoxide radicals. Numerous other sources of superoxide radicals have been identified in the arterial wall, including NAD(P)H oxidases and xanthine oxidase. Nitric oxide and superoxide readily combine to form peroxynitrite, a reactive nitrogen species capable of modifying LDL. In this review, we examine the reaction pathways involved in LDL oxidation by myeloperoxidase and reactive nitrogen species and the potential protective effects of the antioxidant vitamins C and E. PMID:10894808

  19. Pyrroloquinoline-quinone: a reactive oxygen species scavenger in bacteria.

    PubMed

    Misra, Hari S; Khairnar, Nivedita P; Barik, Atanu; Indira Priyadarsini, K; Mohan, Hari; Apte, Shree K

    2004-12-01

    Transgenic Escherichia coli expressing pyrroloquinoline-quinone (PQQ) synthase gene from Deinococcus radiodurans showed superior survival during Rose Bengal induced oxidative stress. Such cells showed significantly low levels of protein carbonylation as compared to non-transgenic control. In vitro, PQQ reacted with reactive oxygen species with rate constants comparable to other well known antioxidants, producing non-reactive molecular products. PQQ also protected plasmid DNA and proteins from the oxidative damage caused by gamma-irradiation in solution. The data suggest that radioprotective/oxidative stress protective ability of PQQ in bacteria may be consequent to scavenging of reactive oxygen species per se and induction of other free radical scavenging mechanism. PMID:15581610

  20. 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...

  1. Reactive oxygen species in cancer: a dance with the devil.

    PubMed

    Schumacker, Paul T

    2015-02-01

    Reactive oxygen species (ROS) can initiate cancer, but oxidant generation in tumors leaves them vulnerable to further stresses. In this issue of Cancer Cell, Harris and colleagues show that augmenting oxidant stress in normal cells limits tumor initiation and progression. Hence, strategic targeting of antioxidant systems may undermine survival of new tumor cells. PMID:25670075

  2. DNA damage by reactive species: Mechanisms, mutation and repair.

    PubMed

    Jena, N R

    2012-07-01

    DNA is continuously attacked by reactive species that can affect its structure and function severely. Structural modifications to DNA mainly arise from modifications in its bases that primarily occur due to their exposure to different reactive species. Apart from this, DNA strand break, inter- and intra-strand crosslinks and DNA-protein crosslinks can also affect the structure of DNA significantly. These structural modifications are involved in mutation, cancer and many other diseases. As it has the least oxidation potential among all the DNA bases, guanine is frequently attacked by reactive species, producing a plethora of lethal lesions. Fortunately, living cells are evolved with intelligent enzymes that continuously protect DNA from such damages. This review provides an overview of different guanine lesions formed due to reactions of guanine with different reactive species. Involvement of these lesions in inter- and intra-strand crosslinks, DNA-protein crosslinks and mutagenesis are discussed. How certain enzymes recognize and repair different guanine lesions in DNA are also presented. PMID:22750987

  3. A role for reactive oxygen species in postharvest biocontrol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reactive oxygen species (ROS) play an important role in plant defense responses against pathogens. There is evidence that microbial biocontrol agents also induce a transient production of ROS in a host plant which triggers local and systemic defense responses. In this study, we explored the abilit...

  4. Adipose dysfunction, interaction of reactive oxygen species, and inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This American Society for Nutrition sponsored symposium summary contains information about the symposium focus and the general content of speaker presentation. The focus of the symposium was to delineate the significance of obesity-associated reactive oxygen species (ROS), inflammation, and adipose ...

  5. Reactivity of Fe(II) species associated with clay minerals.

    PubMed

    Hofstetter, Thomas B; Schwarzenbach, René P; Haderlein, Stefan B

    2003-02-01

    Mineral-bound Fe(II) species represent important natural reductants of pollutants in the anaerobic subsurface. At clay minerals, three types of Fe(II) species in fundamentally different chemical environments may be present simultaneously, i.e., structural Fe(II), Fe(II) complexed by surface hydroxyl groups, and Fe(II) bound by ion exchange. We investigated the accessibility and reactivity of these three types of Fe(II) species in suspensions of two different clay minerals containing either ferrous iron-bearing nontronite or iron-free hectorite. Nitroaromatic compounds (NACs) exhibiting different sorption behavior on clays were used to probe the reactivity of the various types of reduced iron species. The clay treatment allowed for a preparation of nontronite and hectorite surfaces with Fe(II) adsorbed by surface hydroxyl groups at the edge surfaces. Furthermore, hectorite suspensions with additional Fe(II) bound to the ion exchange sites at the basal siloxane surfaces were set up. We found that both structural Fe(II) and Fe(II) complexed by surface hydroxyl groups of nontronite reduced the NACs to anilines. An electron balance revealed that more than 10% of the total iron in nontronite was reactive Fe(II). Fe(II) bound by ion exchange did not contribute to the observed reduction of NACs. Reversible adsorption of the NACs at the basal siloxane surface of the clays strongly retarded NAC reduction, even in the presence of high concentrations of Fe(II) bound by ion exchange to the basal siloxane surfaces. Our work shows that in natural systems a fraction of the total Fe(II) present on clays may contribute to the pool of highly reactive Fe(II) species in the subsurface. Furthermore, this work may help to distinguish between Fe(II) species of different reactivity regarding pollutant reduction. Although structural iron in clays represents only a small fraction of the total iron pool in soils and aquifers, reactive Fe(II) species originating from the reduction of

  6. Enzymatic Production of Extracellular Reactive Oxygen Species by Marine Microorganisms

    NASA Astrophysics Data System (ADS)

    Diaz, J. M.; Andeer, P. F.; Hansel, C. M.

    2014-12-01

    Reactive oxygen species (ROS) serve as intermediates in a myriad of biogeochemically important processes, including cell signaling pathways, cellular oxidative stress responses, and the transformation of both nutrient and toxic metals such as iron and mercury. Abiotic reactions involving the photo-oxidation of organic matter were once considered the only important sources of ROS in the environment. However, the recent discovery of substantial biological ROS production in marine systems has fundamentally shifted this paradigm. Within the last few decades, marine phytoplankton, including diatoms of the genus Thalassiosira, were discovered to produce ample extracellular quantities of the ROS superoxide. Even more recently, we discovered widespread production of extracellular superoxide by phylogenetically and ecologically diverse heterotrophic bacteria at environmentally significant levels (up to 20 amol cell-1 hr-1), which has introduced the revolutionary potential for substantial "dark" cycling of ROS. Despite the profound biogeochemical importance of extracellular biogenic ROS, the cellular mechanisms underlying the production of this ROS have remained elusive. Through the development of a gel-based assay to identify extracellular ROS-producing proteins, we have recently found that enzymes typically involved in antioxidant activity also produce superoxide when molecular oxygen is the only available electron acceptor. For example, large (~3600 amino acids) heme peroxidases are involved in extracellular superoxide production by a bacterium within the widespread Roseobacter clade. In Thalassiosira spp., extracellular superoxide is produced by flavoproteins such as glutathione reductase and ferredoxin NADP+ reductase. Thus, extracellular ROS production may occur via secreted and/or cell surface enzymes that modulate between producing and degrading ROS depending on prevailing geochemical and/or ecological conditions.

  7. Long-lived reactive species formed on proteins induce changes in protein and lipid turnover.

    PubMed

    Davies, Michael

    2014-10-01

    Proteins are major targets for oxidative damage in vivo due to their high abundance and rapid rates of reaction with both one-electron (radical) and two-electron oxidants (e.g. singlet oxygen, hypochlorous acid, peroxynitrous acid, reactive aldehydes). The turnover of both native and modified proteins is critical for maintenance of cell homeostasis, with this occurring via multiple pathways including proteasomes (for cytosolic species), the Lon protease (in mitochondria), and the endo-lysosomal systems (both extra- and intra-cellular species). Evidence has been presented for both enhanced and diminished rates of catabolism of modified proteins, as well as altered turnover of native (unmodified) proteins as a result of damage to these systems, potentially as a result of the accumulation of damaged proteins. In recent studies we have shown that long-lived reactive species forms on proteins (hydroperoxides, chloramines and aldehydes) can modify the activity of proteasomal and lysosomal enzymes. Some of the above species are efficient inhibitors of the tryptic and chymotryptic activities of the 26S proteasome, as well as lysosomal cathepsin and acid lipase activities. These are key species in the turnover of both proteins and lipoproteins. The loss of enzyme activity is accompanied in many cases, by oxidation of critical thiol residues via molecular reactions. For reactive aldehydes (either free or protein-bound) direct enzyme inhibition can occur as well as modulation of protein levels and, in the case of lysosomes, changes in lysosomal numbers. Overall, these data indicate that the formation of reactive species on proteins can modulate cell function by multiple pathways including interference with the turnover of native proteins (including critical cell signalling molecules) and alterations in the rate of clearance of modified proteins. Both pathways may contribute to the development of a number of human pathologies associated with oxidative damage. PMID:26461411

  8. Fluctuating hydrodynamics of multi-species reactive mixtures

    SciTech Connect

    Bhattacharjee, Amit Kumar; Donev, Aleksandar; Balakrishnan, Kaushik; Garcia, Alejandro L.; Bell, John B.

    2015-06-14

    We formulate and study computationally the fluctuating compressible Navier-Stokes equations for reactive multi-species fluid mixtures. We contrast two different expressions for the covariance of the stochastic chemical production rate in the Langevin formulation of stochastic chemistry, and compare both of them to predictions of the chemical master equation for homogeneous well-mixed systems close to and far from thermodynamic equilibrium. We develop a numerical scheme for inhomogeneous reactive flows, based on our previous methods for non-reactive mixtures [Balakrishnan , Phys. Rev. E 89, 013017 (2014)]. We study the suppression of non-equilibrium long-ranged correlations of concentration fluctuations by chemical reactions, as well as the enhancement of pattern formation by spontaneous fluctuations. Good agreement with available theory demonstrates that the formulation is robust and a useful tool in the study of fluctuations in reactive multi-species fluids. At the same time, several problems with Langevin formulations of stochastic chemistry are identified, suggesting that future work should examine combining Langevin and master equation descriptions of hydrodynamic and chemical fluctuations.

  9. Fluctuating hydrodynamics of multi-species reactive mixtures

    NASA Astrophysics Data System (ADS)

    Bhattacharjee, Amit Kumar; Balakrishnan, Kaushik; Garcia, Alejandro L.; Bell, John B.; Donev, Aleksandar

    2015-06-01

    We formulate and study computationally the fluctuating compressible Navier-Stokes equations for reactive multi-species fluid mixtures. We contrast two different expressions for the covariance of the stochastic chemical production rate in the Langevin formulation of stochastic chemistry, and compare both of them to predictions of the chemical master equation for homogeneous well-mixed systems close to and far from thermodynamic equilibrium. We develop a numerical scheme for inhomogeneous reactive flows, based on our previous methods for non-reactive mixtures [Balakrishnan , Phys. Rev. E 89, 013017 (2014)]. We study the suppression of non-equilibrium long-ranged correlations of concentration fluctuations by chemical reactions, as well as the enhancement of pattern formation by spontaneous fluctuations. Good agreement with available theory demonstrates that the formulation is robust and a useful tool in the study of fluctuations in reactive multi-species fluids. At the same time, several problems with Langevin formulations of stochastic chemistry are identified, suggesting that future work should examine combining Langevin and master equation descriptions of hydrodynamic and chemical fluctuations.

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

    EPA Science Inventory

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

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

  11. Unnatural reactive amino acid genetic code additions

    SciTech Connect

    Deiters, Alexander; Cropp, T. Ashton; Chin, Jason W.; Anderson, J. Christopher; Schultz, Peter G.

    2011-08-09

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNAsyn-thetases, pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  12. Unnatural reactive amino acid genetic code additions

    SciTech Connect

    Deiters, Alexander; Cropp, Ashton T; Chin, Jason W; Anderson, Christopher J; Schultz, Peter G

    2013-05-21

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  13. Unnatural reactive amino acid genetic code additions

    SciTech Connect

    Deiters, Alexander; Cropp, T. Ashton; Chin, Jason W.; Anderson, J. Christopher; Schultz, Peter G.

    2014-08-26

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  14. Unnatural reactive amino acid genetic code additions

    SciTech Connect

    Deiters, Alexander; Cropp, T. Ashton; Chin, Jason W.; Anderson, J. Christopher; Schultz, Peter G.

    2011-02-15

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  15. Role of reactive oxygen species in low level light therapy

    NASA Astrophysics Data System (ADS)

    Chen, Aaron Chi-Hao; Huang, Ying-Ying; Arany, Praveen R.; Hamblin, Michael R.

    2009-02-01

    This review will focus on the role of reactive oxygen species in the cellular and tissue effects of low level light therapy (LLLT). Coincidentally with the increase in electron transport and in ATP, there has also been observed by intracellular fluorescent probes and electron spin resonance an increase in intracellular reactive oxygen species (ROS) such as superoxide, hydrogen peroxide, singlet oxygen and hydroxyl radical. ROS scavengers, antioxidants and ROS quenchers block many LLLT processes. It has been proposed that light between 400-500- nm may produce ROS by a photosensitization process involving flavins, while longer wavelengths may directly produce ROS from the mitochondria. Several redox-sensitive transcription factors are known such as NF-kB and AP1, that are able to initiate transcription of genes involved in protective responses to oxidative stress. It may be the case that LLLT can be pro-oxidant in the short-term, but anti-oxidant in the long-term.

  16. Role of reactive nitrogen species in male infertility

    PubMed Central

    2012-01-01

    Reactive nitrogen species (RNS) is a subset of free oxygen radicals called reactive oxygen species (ROS). Physiological levels of ROS are necessary to maintain the reproductive functions such as cell signaling, tight junction regulation, production of hormones, capacitation, acrosomal reaction, sperm motility, and zona pellucida binding. However, an excess of RNS can adversely affect reproductive potential by causing testicular dysfunction, decreased gonadotropin secretion, and abnormal semen parameters. Because such levels of RNS have been demonstrated in males with fertility problems and routine semen analysis has not been able to accurately predict IVF outcomes, it is imperative that novel strategies be developed in order to both assess and treat oxidative stress. This article describes both physiological and pathological roles of this unique subset of ROS. PMID:23241221

  17. Role of reactive oxygen and nitrogen species in etiopathogenesis of rheumatoid arthritis.

    PubMed

    Bauerová, K; Bezek, A

    1999-10-01

    Rheumatoid arthritis (RA) is a chronic disease affecting up to 3% of the population in most countries. The causes of RA have not been completely elucidated. This paper aims to review the role of reactive oxygen and nitrogen species in the etiopathogenesis of RA. Reactive oxygen species (ROS), such as superoxide radical, hydrogen peroxide, hydroxyl radical and hypochlorous acid, as well as reactive nitrogen species (RNS), such as nitric oxide and peroxynitrite, contribute significantly to tissue injury in RA. Several mechanisms are involved in the generation and action of ROS and RNS. Superoxide radical, hydrogen peroxide and nitric oxide do not directly damage the majority of biological molecules. They are however converted into the highly reactive hydroxyl radical, which reacts with almost all molecules in living cells. The resulting chronic inflammation process can be reduced with antioxidant therapy. To date, scavenging, preventive, and enzyme antioxidants are available. The most important mode is scavenging of the hydroxyl radical and of hypochlorous acid. Another important way is to inhibit production of RNS and ROS by neutrophils, monocytes, and macrophages. The control of inflammation in arthritic patients by natural as well as synthetic antioxidants could become a relevant component of antirheumatic prevention and therapy. PMID:10703714

  18. Multiple species reactive chemical transport in groundwater: A verification exercise

    SciTech Connect

    Narasimhan, T.N.; Apps, J.A.; Zhu, Ming.

    1991-04-01

    Two multiple-species reactive chemical transport models (FASTCHEM and DYNAMIX) were tested against each other to check for consistency of solutions. For the particular problem studied, FASTCHEM and DYNAMIX led to differences in aqueous concentrations and mineral assemblages primarily because FASTCHEM ignores redox reactions in the transport phase of the calculations. Also, the spatial concentration profiles generated by FASTCHEM tend to be sharper than those generated by DYNAMIX because FASTCHEM is particularly designed to handle advection-dominated transport systems.

  19. Reactive oxygen species and antioxidant vitamins: mechanisms of action.

    PubMed

    Frei, B

    1994-09-26

    This article is a brief overview of the mechanisms of production of reactive oxygen species in biologic systems, and the various antioxidant defense systems that provide protection against oxidative damage to biologic macromolecules. The mechanisms of lipid peroxidation and antioxidant protection are explained using a specific example, viz., oxidative modification of human low density lipoprotein and its prevention by vitamin C, vitamin E, and beta-carotene. PMID:8085584

  20. Reactive oxygen species: The good, the bad, and the enigma

    PubMed Central

    Ogrunc, Müge

    2014-01-01

    Work carried out primarily in the laboratory of Fabrizio d’Adda di Fagagna unveils the mitogenic properties of Ras-induced reactive oxygen species (ROS) and their relationship with the DNA damage response. Combined data from studies of cultured cells, zebrafish models, and clinical material consistently support a role of the RAS-RAC1-NOX4 axis in ROS induction, hyperproliferation, and senescence. PMID:27308352

  1. The origin of Reactive Halogen Species in the Polar Troposphere

    NASA Astrophysics Data System (ADS)

    Platt, U.

    2011-12-01

    Reactive halogen species (RHS) play an important role in various parts of the troposphere e.g. in coastal regions, over salt pans, in volcanic plumes and in polar regions. Despite much progress in recent years the origin and some of the chemical interactions of reactive halogen species (RHS) in the polar troposphere are still not quantitatively understood. Among the many unanswered questions are: Why is there an Antarctic - Arctic asymmetry of reactive iodine species? What drives the autocatalytic bromine release from sea salt (the bromine explosion)? Why does the bromine explosion almost exclusively occur during springtime? What is the effect of coupling cycles involving different halogens? What is the vertical extent of the layer containing RHS? The presentation gives an overview of new ground-based field observations illustrating the above questions and providing answers to some of them. Also, recent advances in satellite observations of tropospheric BrO are discussed. In particular new insight is being gained from the synergistic use of satellite observations and ground based measurements of BrO. Also the question of a NOx - driven (rather than HOx - driven) bromine explosion is discussed.

  2. 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

  3. 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

  4. AMELIORATION OF ACID MINE DRAINAGE USING REACTIVE MIXTURES IN PERMEABLE REACTIVE BARRIERS

    EPA Science Inventory

    The generation and release of acidic drainage from mine wastes is an environmental problem of international scale. The use of zero-valent iron and/or iron mixtures in subsurface Permeable Reactive Barriers (PRB) presents a possible passive alternative for remediating acidic grou...

  5. The roles of reactive species in micropollutant degradation in the UV/free chlorine system.

    PubMed

    Fang, Jingyun; Fu, Yun; Shang, Chii

    2014-01-01

    The UV/free chlorine process forms reactive species such as hydroxyl radicals (HO(•)), chlorine atoms (Cl(•)), Cl2(•-), and O(•-). The specific roles of these reactive species in aqueous micropollutant degradation in the UV/chlorine process under different conditions were investigated using a steady-state kinetic model. Benzoic acid (BA) was chosen as the model micropollutant. The steady-state kinetic model developed fitted the experimental data well. The results showed that HO(•) and Cl(•) contributed substantially to BA degradation, while the roles of the other reactive species such as Cl2(•-) and O(•-) were negligible. The overall degradation rate of BA decreased as the pH increased from 6 to 9. In particular, the relative contributions of HO(•) and Cl(•) to the degradation changed from 34.7% and 65.3% respectively at pH 6 to 37.9% and 62% respectively at pH 9 under the conditions evaluated. Their relative contributions also changed slightly with variations in chlorine dosage, BA concentration and chloride concentration. The scavenging effect of natural organic matter (NOM) on Cl(•) was relatively small compared to that on HO(•), while bicarbonate preferentially reduced the contribution of Cl(•). This study is the first to demonstrate the contributions of different reactive species to the micropollutant degradation in the UV/chlorine system under environmentally relevant conditions. PMID:24400681

  6. Reactive Distillation for Esterification of Bio-based Organic Acids

    SciTech Connect

    Fields, Nathan; Miller, Dennis J.; Asthana, Navinchandra S.; Kolah, Aspi K.; Vu, Dung; Lira, Carl T.

    2008-09-23

    The following is the final report of the three year research program to convert organic acids to their ethyl esters using reactive distillation. This report details the complete technical activities of research completed at Michigan State University for the period of October 1, 2003 to September 30, 2006, covering both reactive distillation research and development and the underlying thermodynamic and kinetic data required for successful and rigorous design of reactive distillation esterification processes. Specifically, this project has led to the development of economical, technically viable processes for ethyl lactate, triethyl citrate and diethyl succinate production, and on a larger scale has added to the overall body of knowledge on applying fermentation based organic acids as platform chemicals in the emerging biorefinery. Organic acid esters constitute an attractive class of biorenewable chemicals that are made from corn or other renewable biomass carbohydrate feedstocks and replace analogous petroleum-based compounds, thus lessening U.S. dependence on foreign petroleum and enhancing overall biorefinery viability through production of value-added chemicals in parallel with biofuels production. Further, many of these ester products are candidates for fuel (particularly biodiesel) components, and thus will serve dual roles as both industrial chemicals and fuel enhancers in the emerging bioeconomy. The technical report from MSU is organized around the ethyl esters of four important biorenewables-based acids: lactic acid, citric acid, succinic acid, and propionic acid. Literature background on esterification and reactive distillation has been provided in Section One. Work on lactic acid is covered in Sections Two through Five, citric acid esterification in Sections Six and Seven, succinic acid in Section Eight, and propionic acid in Section Nine. Section Ten covers modeling of ester and organic acid vapor pressure properties using the SPEAD (Step Potential

  7. Amine Reactivity with Nanoclusters of Sulfuric Acid and Ammonia

    NASA Astrophysics Data System (ADS)

    Johnston, M. V.; Bzdek, B. R.; DePalma, J.

    2011-12-01

    Alkyl amines have emerged as key species in new particle formation and growth. This interest is reinforced by ambient measurements of amines (e.g. Smith et al., 2010) and enhanced levels of nitrogen (e.g. Bzdek et al., 2011) during growth of newly formed particles. An important mechanism of amine uptake is aminium salt formation, either by substituting for ammonium ions that already exist in the particle or by opening new channels for salt formation that are not favorable with ammonia. This presentation will focus on recent experimental and computational work in our group to study amine uptake into charged nanoclusters of sulfuric acid and ammonia. In the experimental work, clusters are produced by electrospray of an ammonium sulfate solution and then drawn into a Fourier transform ion cyclotron resonance mass spectrometer where a specific cluster is isolated and exposed to amine vapor. We find that amine reactivity is dependent on the size, composition and charge of the isolated cluster. For small clusters of either polarity, all ammonium ions reside on the surface and amine substitution occurs with near unit reaction probability. As the cluster size increases, an ammonium ion can be encapsulated in the center of the cluster, which provides a steric hindrance to amine substitution. Negatively charged clusters are more likely to be acidic than positively charged clusters. For acidic clusters, incoming amine molecules first substitute for preexisting ammonium ions and then add to the cluster until a "neutralized" aminium bisulfate composition is reached. Computational studies of these clusters provide fundamental insight into the thermodynamics and kinetics of amine uptake.

  8. Reactive oxygen species generation and signaling in plants

    PubMed Central

    Tripathy, Baishnab Charan; Oelmüller, Ralf

    2012-01-01

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

  9. Implications for reactive oxygen species in schizophrenia pathogenesis.

    PubMed

    Koga, Minori; Serritella, Anthony V; Sawa, Akira; Sedlak, Thomas W

    2016-09-01

    Oxidative stress is a well-recognized participant in the pathophysiology of multiple brain disorders, particularly neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. While not a dementia, a wide body of evidence has also been accumulating for aberrant reactive oxygen species and inflammation in schizophrenia. Here we highlight roles for oxidative stress as a common mechanism by which varied genetic and epidemiologic risk factors impact upon neurodevelopmental processes that underlie the schizophrenia syndrome. While there is longstanding evidence that schizophrenia may not have a single causative lesion, a common pathway involving oxidative stress opens the possibility for intervention at susceptible phases. PMID:26589391

  10. Post-translational modifications mediated by reactive nitrogen species

    PubMed Central

    del Río, Luis A; Barroso, Juan B

    2008-01-01

    In animal cells, nitric oxide and NO-derived molecules have been shown to mediate post-translational modifications such as S-nitrosylation and protein tyrosine nitration which are associated with cell signalling and pathological processes, respectively. In plant cells, knowledge of the function of these post-translational modifications under physiological and stress conditions is still very rudimentary. In this addendum, we briefly examine how reactive nitrogen species (RNS) can exert important effects on proteins that could mediate signalling processes in plants. PMID:19841652

  11. Redox Processes in Neurodegenerative Disease Involving Reactive Oxygen Species

    PubMed Central

    Kovacic, Peter; Somanathan, Ratnasamy

    2012-01-01

    Much attention has been devoted to neurodegenerative diseases involving redox processes. This review comprises an update involving redox processes reported in the considerable literature in recent years. The mechanism involves reactive oxygen species and oxidative stress, usually in the brain. There are many examples including Parkinson’s, Huntington’s, Alzheimer’s, prions, Down’s syndrome, ataxia, multiple sclerosis, Creutzfeldt-Jacob disease, amyotrophic lateral sclerosis, schizophrenia, and Tardive Dyskinesia. Evidence indicates a protective role for antioxidants, which may have clinical implications. A multifaceted approach to mode of action appears reasonable. PMID:23730253

  12. Cellular reactive oxygen species inhibit MPYS induction of IFNβ.

    PubMed

    Jin, Lei; Lenz, Laurel L; Cambier, John C

    2010-01-01

    Many inflammatory diseases, as well as infections, are accompanied by elevation in cellular levels of Reactive Oxygen Species (ROS). Here we report that MPYS, a.k.a. STING, which was recently shown to mediate activation of IFNβ expression during infection, is a ROS sensor. ROS induce intermolecular disulfide bonds formation in MPYS homodimer and inhibit MPYS IFNβ stimulatory activity. Cys-64, -148, -292, -309 and the potential C₈₈xxC₉₁ redox motif in MPYS are indispensable for IFNβ stimulation and IRF3 activation. Thus, our results identify a novel mechanism for ROS regulation of IFNβ stimulation. PMID:21170271

  13. Modulation of macrophage-mediated cytotoxicity by kerosene soot: Possible role of reactive oxygen species

    SciTech Connect

    Arif, J.M.; Khan, S.G.; Ashquin, M.; Rahman, Q. )

    1993-05-01

    The involvement of reactive oxygen species (ROS) in the cytotoxicity of soot on rat alveolar macrophages has been postulated. A single intratracheal injection of soot (5 mg) in corn oil significantly induced the macrophage population, hydrogen peroxide (H[sub 2]O[sub 2]) generation, thiobarbituric acid (TBA)-reactive substanced of lipid peroxidation, and the activities of extracellular acid phosphatase (AP) and lactate dehydrogenase (LDH) at 1, 4, 8, and 16 days of postinoculation. The activities of glutathione peroxidase (GPX) and catalase (CAT) were significantly inhibited at all the stages, while glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) showed a different pattern. These results show that soot is cytotoxic to alveolar macrophages and suggest that ROS may play a primary role in the cytotoxic process. 28 refs., 4 figs., 1 tab.

  14. Prooxidant action of knipholone anthrone: copper dependent reactive oxygen species generation and DNA damage.

    PubMed

    Habtemariam, S; Dagne, E

    2009-07-01

    Knipholone (KP) and knipholone anthrone (KA) are natural 4-phenylanthraquinone structural analogues with established differential biological activities including in vitro antioxidant and cytotoxic properties. By using DNA damage as an experimental model, the comparative Cu(II)-dependent prooxidant action of these two compounds were studied. In the presence of Cu(II) ions, the antioxidant KA (3.1-200 microM) but not KP (6-384 microM) caused a concentration-dependent pBR322 plasmid DNA strand scission. The DNA damage induced by KA could be abolished by reactive oxygen species scavengers, glutathione and catalase as well as EDTA and a specific Cu(I) chelator bathocuproine disulfonic acid. In addition to Cu(II) chelating activity, KA readily reduces Cu(II) to Cu(I). Copper-dependent generation of reactive oxygen species and the subsequent macromolecular damage may be involved in the antimicrobial and cytotoxic activity of KA. PMID:19345716

  15. Reactive oxygen species formed in organic lithium-oxygen batteries.

    PubMed

    Schwager, Patrick; Dongmo, Saustin; Fenske, Daniela; Wittstock, Gunther

    2016-04-20

    Li-oxygen batteries with organic electrolytes are of general interest because of their theoretically high gravimetric energy density. Among the great challenges for this storage technology is the generation of reactive oxygen species such as superoxides and peroxides that may react with the organic solvent molecules and other cell components. The generation of such species has been assumed to occur during the charging reaction. Here we show that superoxide is formed also during the discharge reaction in lithium ion-containing dimethyl sulfoxide electrolytes and is released into the solution. This is shown independently by fluorescence microscopy after reaction with the selective reagent 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole and by local detection using a microelectrode of a scanning electrochemcial microscope positioned in a defined distance of 10 to 90 μm above the gas diffusion electrode. PMID:26911793

  16. Scavenging activity of "beta catechin" on reactive oxygen species generated by photosensitization of riboflavin.

    PubMed

    Kumari, M V; Yoneda, T; Hiramatsu, M

    1996-05-01

    "beta CATECHIN", a preparation containing green tea extract, ascorbic acid, sunflower seed extract, dunaliella carotene and natural vitamin E, has been designed as a model "universal antioxidant" that offers protection via its scavenging action on a wide range of free radicals, both water-soluble and fat-soluble. Reactive oxygen species like singlet oxygen, hydroxyl and superoxide radicals, are often generated in biological systems during photosensitized oxidation reactions. We report on the simultaneous effect of "beta CATECHIN" on active oxygen species generated during the photosensitized oxidation of riboflavin using 2,2,6,6-tetramethyl-4-piperidone (TMPD) as a "spin-trapping" agent. The intensities of the resulting stable nitroxide radical adduct, 2,2,6,6-tetramethyl-4-piperidone-1-oxyl (TEMPONE), were detected by electron spin resonance (ESR) spectroscopy. Results show simultaneous, nonspecific and complete scavenging action of reactive oxygen species generated in our in vitro model system by "beta CATECHIN". It is therefore suggested that "beta CATECHIN" could offer protection against free radical insult and in preventing cancer and other diseases that are mediated by reactive oxygen species. PMID:8739038

  17. 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.

  18. Stimulation of reactive oxygen, but not reactive nitrogen species, in vascular endothelial cells exposed to low levels of arsenite.

    PubMed

    Barchowsky, A; Klei, L R; Dudek, E J; Swartz, H M; James, P E

    1999-12-01

    Elevated levels of arsenite, the trivalent form of arsenic, in drinking water correlates with increased vascular disease and vessel remodeling. Previous studies from this laboratory demonstrated that environmentally relevant concentrations of arsenite caused oxidant-dependent increases in nuclear transcription factor levels in cultured porcine vascular endothelial cells. The current studies characterized the reactive species generated in these cells exposed to levels of arsenite that initiate cell signaling. These exposures did not deplete 5'-triphosphate, nor did they affect basal or bradykinin-stimulated intracellular free Ca2+ levels, indicating that they were not lethal. Electron paramagnetic resonance (EPR) spectroscopy, including spin trapping with carboxy-PTIO (cPTIO), demonstrated that 5 microM or less of arsenite did not increase *NO levels over a 30-min period relative to *NO release stimulated by bradykinin. However, these same levels of arsenite rapidly increased both oxygen consumption and superoxide formation, as measured by EPR oximetry and spin trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), respectively. Pretreatment of the cells with DPI, apocynin, or superoxide dismutase abolished arsenite-stimulated DMPO-OH adduct formation. Finally arsenite increased extracellular accumulation of H2O2, measured as oxidation of homovanillic acid, with the same time and dose dependence, as seen for superoxide formation. These data suggest that superoxide and H2O2 are the predominant reactive species produced by endothelial cells after arsenite exposures that stimulate cell signaling and activate transcription factors. PMID:10641735

  19. Properties of reactive oxygen species by quantum Monte Carlo

    SciTech Connect

    Zen, Andrea; Trout, Bernhardt L.; Guidoni, Leonardo

    2014-07-07

    The electronic properties of the oxygen molecule, in its singlet and triplet states, and of many small oxygen-containing radicals and anions have important roles in different fields of chemistry, biology, and atmospheric science. Nevertheless, the electronic structure of such species is a challenge for ab initio computational approaches because of the difficulties to correctly describe the statical and dynamical correlation effects in presence of one or more unpaired electrons. Only the highest-level quantum chemical approaches can yield reliable characterizations of their molecular properties, such as binding energies, equilibrium structures, molecular vibrations, charge distribution, and polarizabilities. In this work we use the variational Monte Carlo (VMC) and the lattice regularized Monte Carlo (LRDMC) methods to investigate the equilibrium geometries and molecular properties of oxygen and oxygen reactive species. Quantum Monte Carlo methods are used in combination with the Jastrow Antisymmetrized Geminal Power (JAGP) wave function ansatz, which has been recently shown to effectively describe the statical and dynamical correlation of different molecular systems. In particular, we have studied the oxygen molecule, the superoxide anion, the nitric oxide radical and anion, the hydroxyl and hydroperoxyl radicals and their corresponding anions, and the hydrotrioxyl radical. Overall, the methodology was able to correctly describe the geometrical and electronic properties of these systems, through compact but fully-optimised basis sets and with a computational cost which scales as N{sup 3} − N{sup 4}, where N is the number of electrons. This work is therefore opening the way to the accurate study of the energetics and of the reactivity of large and complex oxygen species by first principles.

  20. Properties of reactive oxygen species by quantum Monte Carlo.

    PubMed

    Zen, Andrea; Trout, Bernhardt L; Guidoni, Leonardo

    2014-07-01

    The electronic properties of the oxygen molecule, in its singlet and triplet states, and of many small oxygen-containing radicals and anions have important roles in different fields of chemistry, biology, and atmospheric science. Nevertheless, the electronic structure of such species is a challenge for ab initio computational approaches because of the difficulties to correctly describe the statical and dynamical correlation effects in presence of one or more unpaired electrons. Only the highest-level quantum chemical approaches can yield reliable characterizations of their molecular properties, such as binding energies, equilibrium structures, molecular vibrations, charge distribution, and polarizabilities. In this work we use the variational Monte Carlo (VMC) and the lattice regularized Monte Carlo (LRDMC) methods to investigate the equilibrium geometries and molecular properties of oxygen and oxygen reactive species. Quantum Monte Carlo methods are used in combination with the Jastrow Antisymmetrized Geminal Power (JAGP) wave function ansatz, which has been recently shown to effectively describe the statical and dynamical correlation of different molecular systems. In particular, we have studied the oxygen molecule, the superoxide anion, the nitric oxide radical and anion, the hydroxyl and hydroperoxyl radicals and their corresponding anions, and the hydrotrioxyl radical. Overall, the methodology was able to correctly describe the geometrical and electronic properties of these systems, through compact but fully-optimised basis sets and with a computational cost which scales as N(3) - N(4), where N is the number of electrons. This work is therefore opening the way to the accurate study of the energetics and of the reactivity of large and complex oxygen species by first principles. PMID:25005287

  1. Properties of reactive oxygen species by quantum Monte Carlo

    NASA Astrophysics Data System (ADS)

    Zen, Andrea; Trout, Bernhardt L.; Guidoni, Leonardo

    2014-07-01

    The electronic properties of the oxygen molecule, in its singlet and triplet states, and of many small oxygen-containing radicals and anions have important roles in different fields of chemistry, biology, and atmospheric science. Nevertheless, the electronic structure of such species is a challenge for ab initio computational approaches because of the difficulties to correctly describe the statical and dynamical correlation effects in presence of one or more unpaired electrons. Only the highest-level quantum chemical approaches can yield reliable characterizations of their molecular properties, such as binding energies, equilibrium structures, molecular vibrations, charge distribution, and polarizabilities. In this work we use the variational Monte Carlo (VMC) and the lattice regularized Monte Carlo (LRDMC) methods to investigate the equilibrium geometries and molecular properties of oxygen and oxygen reactive species. Quantum Monte Carlo methods are used in combination with the Jastrow Antisymmetrized Geminal Power (JAGP) wave function ansatz, which has been recently shown to effectively describe the statical and dynamical correlation of different molecular systems. In particular, we have studied the oxygen molecule, the superoxide anion, the nitric oxide radical and anion, the hydroxyl and hydroperoxyl radicals and their corresponding anions, and the hydrotrioxyl radical. Overall, the methodology was able to correctly describe the geometrical and electronic properties of these systems, through compact but fully-optimised basis sets and with a computational cost which scales as N3 - N4, where N is the number of electrons. This work is therefore opening the way to the accurate study of the energetics and of the reactivity of large and complex oxygen species by first principles.

  2. Markers of protein oxidation by hydroxyl radical and reactive nitrogen species in tissues of aging rats.

    PubMed

    Leeuwenburgh, C; Hansen, P; Shaish, A; Holloszy, J O; Heinecke, J W

    1998-02-01

    Many lines of evidence implicate oxidative damage in aging. Possible pathways include reactions that modify aromatic amino acid residues on proteins. o-Tyrosine is a stable marker for oxidation of protein-bound phenylalanine by hydroxyl radical, whereas 3-nitrotyrosine is a marker for oxidation of protein-bound tyrosine by reactive nitrogen species. To test the hypothesis that proteins damaged by hydroxyl radical and reactive nitrogen accumulate with aging, we used isotope dilution gas chromatography-mass spectrometry to measure levels of o-tyrosine and 3-nitrotyrosine in heart, skeletal muscle, and liver from young adult (9 mo) and old (24 mo) female Long-Evans/Wistar hybrid rats. We also measured these markers in young adult and old rats that received antioxidant supplements (alpha-tocopherol, beta-carotene, butylated hydroxytoluene, and ascorbic acid) from the age of 5 mo. We found that aging did not significantly increase levels of protein-bound o-tyrosine or 3-nitrotyrosine in any of the tissues. Antioxidant supplementation had no effect on the levels of protein-bound o-tyrosine and 3-nitrotyrosine in either young or old animals. These observations indicate that the o-tyrosine and 3-nitrotyrosine do not increase significantly in heart, skeletal muscle, and liver in old rats, suggesting that proteins damaged by hydroxyl radical and reactive nitrogen species do not accumulate in these tissues with advancing age. PMID:9486304

  3. Effect of reactive oxygen species (ROS) generating system for control of airborne microorganisms in meat processing environment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effectiveness of reactive oxygen species (ROS) generating AirOcare equipment on the reduction of airborne bacteria in a meat processing environment was determined. Serratia marcescens and lactic acid bacteria (Lactococcus lactis subsp. lactis and Lactobacillus plantarum) were used to artificiall...

  4. Tissue injury by reactive oxygen species and the protective effects of flavonoids.

    PubMed

    de Groot, H; Rauen, U

    1998-01-01

    Reactive oxygen species contribute decisively to a great variety of diseases. Flavonoids are benzo-gamma-pyrone derivatives of plant origin found in various fruits and vegetables but also in tea and in red wine. Some of the flavonoids, such as quercetin and silibinin, can effectively protect cells and tissues against the deleterious effects of reactive oxygen species. Their antioxidant activity results from scavenging of free radicals and other oxidizing intermediates, from the chelation of iron or copper ions and from inhibition of oxidases. For their free radical scavenging properties, scavenging of lipid- and protein-derived radicals is presumably of special importance. A non-radical reactive oxygen species effectively trapped by flavonoids is hypochlorous acid. In general, the antioxidative properties of flavonoids are favoured by a high degree of OH substitution. On the other hand, inhibition of enzymatic functions other than oxidases, e.g., inhibition of lipoxygenase and thus prevention of the formation of leukotrienes, may also participate in the cell and tissue protective properties of flavonoids. PMID:9646056

  5. 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

  6. Reactive oxygen species in eradicating acute myeloid leukemic stem cells

    PubMed Central

    Zhang, Hui; Fang, Hai

    2014-01-01

    Leukemic stem cells (LSCs) have been proven to drive leukemia initiation, progression and relapse, and are increasingly being used as a critical target for therapeutic intervention. As an essential feature in LSCs, reactive oxygen species (ROS) homeostasis has been extensively exploited in the past decade for targeting LSCs in acute myeloid leukemia (AML). Most, if not all, agents that show therapeutic benefits are able to alter redox status by inducing ROS, which confers selectivity in eradicating AML stem cells but sparing normal counterparts. In this review, we provide the comprehensive update of ROS-generating agents in the context of their impacts on our understanding of the pathogenesis of AML and its therapy. We anticipate that further characterizing these ROS agents will help us combat against AML in the coming era of LSC-targeting strategy.

  7. Reactive oxygen species, ageing and the hormesis police.

    PubMed

    Ludovico, Paula; Burhans, William C

    2014-02-01

    For more than 50 years, the free radical theory served as the paradigm guiding most investigations of ageing. However, recent studies in a variety of organisms have identified conceptual and practical limitations to this theory. Some of these limitations are related to the recent discovery that caloric restriction and other experimental manipulations promote longevity by inducing hormesis effects in association with increased reactive oxygen species (ROS). The beneficial role of ROS in lifespan extension is consistent with the essential role of these molecules in cell signalling. However, the identity of specific forms of ROS that promote longevity remains unclear. In this article, we argue that in several model systems, hydrogen peroxide plays a crucial role in the induction of hormesis. PMID:23965186

  8. Reactive oxygen species and hydrogen peroxide generation in cell migration

    PubMed Central

    Rudzka, Dominika A; Cameron, Jenifer M; Olson, Michael F

    2015-01-01

    Directional cell migration is a complex process that requires spatially and temporally co-ordinated regulation of actin cytoskeleton dynamics. In response to external cues, signals are transduced to elicit cytoskeletal responses. It has emerged that reactive oxygen species, including hydrogen peroxide, are important second messengers in pathways that influence the actin cytoskeleton, although the identities of key proteins regulated by hydrogen peroxide are largely unknown. We recently showed that oxidation of cofilin1 is elevated in migrating cells relative to stationary cells, and that the effect of this post-translational modification is to reduce cofilin1-actin binding and to inhibit filamentous-actin severing by cofilin1. These studies revealed that cofilin1 regulation by hydrogen peroxide contributes to directional cell migration, and established a template for discovering additional proteins that are regulated in an analogous manner. PMID:27066166

  9. Reactive Oxygen Species Driven Angiogenesis by Inorganic Nanorods

    PubMed Central

    Patra, Chitta Ranjan; Kim, Jong Ho; Pramanik, Kallal; d’Uscio, Livius V.; Patra, Sujata; Pal, Krishnendu; Ramchandran, Ramani; Strano, Michael S; Mukhopadhyay, Debabrata

    2011-01-01

    The exact mechanism of angiogenesis by europium hydroxide nanorods was unclear. In this study we have showed that formation of reactive oxygen species (H2O2 and O2•−) are involved in redox signaling pathways during angiogenesis, important for cardiovascular and ischemic diseases. Here we used single-walled carbon nanotube (SWNT) sensor array to measure the single-molecule efflux of H2O2 and a HPLC method for the determination of O2•− from endothelial cells in response to pro-angiogenic factors. Additionally, ROS-mediated angiogenesis using inorganic nanorods was observed in transgenic (fli1a:EGFP) zebrafish embryos. PMID:21967244

  10. 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. PMID:26950921

  11. Reactive oxygen species production and discontinuous gas exchange in insects

    PubMed Central

    Boardman, Leigh; Terblanche, John S.; Hetz, Stefan K.; Marais, Elrike; Chown, Steven L.

    2012-01-01

    While biochemical mechanisms are typically used by animals to reduce oxidative damage, insects are suspected to employ a higher organizational level, discontinuous gas exchange mechanism to do so. Using a combination of real-time, flow-through respirometry and live-cell fluorescence microscopy, we show that spiracular control associated with the discontinuous gas exchange cycle (DGC) in Samia cynthia pupae is related to reactive oxygen species (ROS). Hyperoxia fails to increase mean ROS production, although minima are elevated above normoxic levels. Furthermore, a negative relationship between mean and mean ROS production indicates that higher ROS production is generally associated with lower . Our results, therefore, suggest a possible signalling role for ROS in DGC, rather than supporting the idea that DGC acts to reduce oxidative damage by regulating ROS production. PMID:21865257

  12. Reactive oxygen species in organ-specific autoimmunity.

    PubMed

    Di Dalmazi, Giulia; Hirshberg, Jason; Lyle, Daniel; Freij, Joudeh B; Caturegli, Patrizio

    2016-12-01

    Reactive oxygen species (ROS) have been extensively studied in the induction of inflammation and tissue damage, especially as it relates to aging. In more recent years, ROS have been implicated in the pathogenesis of autoimmune diseases. Here, ROS accumulation leads to apoptosis and autoantigen structural changes that result in novel specificities. ROS have been implicated not only in the initiation of the autoimmune response but also in its amplification and spreading to novel epitopes, through the unmasking of cryptic determinants. This review will examine the contribution of ROS to the pathogenesis of four organ specific autoimmune diseases (Hashimoto thyroiditis, inflammatory bowel disease, multiple sclerosis, and vitiligo), and compare it to that of a better characterized systemic autoimmune disease (rheumatoid arthritis). It will also discuss tobacco smoking as an environmental factor endowed with both pro-oxidant and anti-oxidant properties, thus capable of differentially modulating the autoimmune response. PMID:27491295

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

    PubMed

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

    2015-01-01

    Reactive oxygen species (ROS) are generated from the endogenous oxidative metabolism or from exogenous pro-oxidant exposure. Oxidative stress occurs when there is excessive production of ROS, outweighing the antioxidant defense mechanisms which may lead to disease states. Hydrogen peroxide (H2O2) is one of the most abundant and stable forms of ROS, implicated in inflammation, cellular dysfunction and apoptosis, which ultimately lead to tissue and organ damage. This review is an overview of the role of ROS in different diseases. We will also examine ROS-activated nanomaterials with emphasis on hydrogen peroxide, and their potential medical implications. Further development of the biocompatible, stimuli-activated agent responding to disease causing oxidative stress, may lead to a promising clinical use. PMID:26328770

  14. Reactive Oxygen Species, Apoptosis, and Mitochondrial Dysfunction in Hearing Loss

    PubMed Central

    Fujimoto, Chisato

    2015-01-01

    Reactive oxygen species (ROS) production is involved in several apoptotic and necrotic cell death pathways in auditory tissues. These pathways are the major causes of most types of sensorineural hearing loss, including age-related hearing loss, hereditary hearing loss, ototoxic drug-induced hearing loss, and noise-induced hearing loss. ROS production can be triggered by dysfunctional mitochondrial oxidative phosphorylation and increases or decreases in ROS-related enzymes. Although apoptotic cell death pathways are mostly activated by ROS production, there are other pathways involved in hearing loss that do not depend on ROS production. Further studies of other pathways, such as endoplasmic reticulum stress and necrotic cell death, are required. PMID:25874222

  15. Reactive oxygen species in development and infection processes.

    PubMed

    Marschall, Robert; Tudzynski, Paul

    2016-09-01

    Reactive oxygen species (ROS) are important signaling molecules that affect vegetative and pathogenic processes in pathogenic fungi. There is growing evidence that ROS are not only secreted during the interaction of host and pathogen but also involved in tightly controlled intracellular processes. The major ROS producing enzymes are NADPH oxidases (Nox). Recent investigations in fungi revealed that Nox-activity is responsible for the formation of infection structures, cytoskeleton architecture as well as interhyphal communication. However, information about the localization and site of action of the Nox complexes in fungi is limited and signaling pathways and intracellular processes affected by ROS have not been fully elucidated. This review focuses on the role of ROS as signaling molecules in fungal "model" organisms: it examines the role of ROS in vegetative and pathogenic processes and gives special attention to Nox complexes and their function as important signaling hubs. PMID:27039026

  16. The Role of Reactive Oxygen Species in Microvascular Remodeling

    PubMed Central

    Staiculescu, Marius C.; Foote, Christopher; Meininger, Gerald A.; Martinez-Lemus, Luis A.

    2014-01-01

    The microcirculation is a portion of the vascular circulatory system that consists of resistance arteries, arterioles, capillaries and venules. It is the place where gases and nutrients are exchanged between blood and tissues. In addition the microcirculation is the major contributor to blood flow resistance and consequently to regulation of blood pressure. Therefore, structural remodeling of this section of the vascular tree has profound implications on cardiovascular pathophysiology. This review is focused on the role that reactive oxygen species (ROS) play on changing the structural characteristics of vessels within the microcirculation. Particular attention is given to the resistance arteries and the functional pathways that are affected by ROS in these vessels and subsequently induce vascular remodeling. The primary sources of ROS in the microcirculation are identified and the effects of ROS on other microcirculatory remodeling phenomena such as rarefaction and collateralization are briefly reviewed. PMID:25535075

  17. Reactive oxygen species-targeted therapeutic interventions for atrial fibrillation

    PubMed Central

    Sovari, Ali A.; Dudley, Samuel C.

    2012-01-01

    Atrial fibrillation (AF) is the most common arrhythmia that requires medical attention, and its incidence is increasing. Current ion channel blockade therapies and catheter ablation have significant limitations in treatment of AF, mainly because they do not address the underlying pathophysiology of the disease. Oxidative stress has been implicated as a major underlying pathology that promotes AF; however, conventional antioxidants have not shown impressive therapeutic effects. A more careful design of antioxidant therapies and better selection of patients likely are required to treat effectively AF with antioxidant agents. Current evidence suggest inhibition of prominent cardiac sources of reactive oxygen species (ROS) such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and targeting subcellular compartments with the highest levels of ROS may prove to be effective therapies for AF. Increased serum markers of oxidative stress may be an important guide in selecting the AF patients who will most likely respond to antioxidant therapy. PMID:22934062

  18. Reactive oxygen species-activated nanomaterials as theranostic agents

    PubMed Central

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

    2015-01-01

    Reactive oxygen species (ROS) are generated from the endogenous oxidative metabolism or from exogenous pro-oxidant exposure. Oxidative stress occurs when there is excessive production of ROS, outweighing the antioxidant defense mechanisms which may lead to disease states. Hydrogen peroxide (H2O2) is one of the most abundant and stable forms of ROS, implicated in inflammation, cellular dysfunction and apoptosis, which ultimately lead to tissue and organ damage. This review is an overview of the role of ROS in different diseases. We will also examine ROS-activated nanomaterials with emphasis on hydrogen peroxide, and their potential medical implications. Further development of the biocompatible, stimuli-activated agent responding to disease causing oxidative stress, may lead to a promising clinical use. PMID:26328770

  19. 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

  20. Mitochondrial Reactive Oxygen Species Modulate Mosquito Susceptibility to Plasmodium Infection

    PubMed Central

    Oliveira, Giselle A.; Andersen, John F.; Oliveira, Marcus F.; Oliveira, Pedro L.; Barillas-Mury, Carolina

    2012-01-01

    Background Mitochondria perform multiple roles in cell biology, acting as the site of aerobic energy-transducing pathways and as an important source of reactive oxygen species (ROS) that modulate redox metabolism. Methodology/Principal Findings We demonstrate that a novel member of the mitochondrial transporter protein family, Anopheles gambiae mitochondrial carrier 1 (AgMC1), is required to maintain mitochondrial membrane potential in mosquito midgut cells and modulates epithelial responses to Plasmodium infection. AgMC1 silencing reduces mitochondrial membrane potential, resulting in increased proton-leak and uncoupling of oxidative phosphorylation. These metabolic changes reduce midgut ROS generation and increase A. gambiae susceptibility to Plasmodium infection. Conclusion We provide direct experimental evidence indicating that ROS derived from mitochondria can modulate mosquito epithelial responses to Plasmodium infection. PMID:22815925

  1. Reactive oxygen species and energy machinery: an integrated dynamic model.

    PubMed

    Korla, Kalyani

    2016-08-01

    The role of several important reactive oxygen species (ROS) on the Krebs cycle, the electron transport chain (ETC) and the two important shuttles has been modelled. Major part of the ROS is produced during oxygen reduction in the ETC, which has been kinetically simulated, and the changes in the final concentrations of several important metabolites were found. The simulation is based on chemical kinetics equation, and the associated set of differential equations was solved by the ordinary differential equation package in Octave. The validity of the model is checked by comparing the experimental results available in the literature with the simulations when a part of the ETC is blocked (80%) in the script. The present approach is versatile and flexible and has potential applications in various simulations. It is easy to study the change in concentrations of various metabolites when a particular enzyme or pathway is blocked (say by a drug). The Octave script is presented in the text. PMID:26309069

  2. Bioreductively Activated Reactive Oxygen Species (ROS) Generators as MRSA Inhibitors.

    PubMed

    Khodade, Vinayak S; Sharath Chandra, Mallojjala; Banerjee, Ankita; Lahiri, Surobhi; Pulipeta, Mallikarjuna; Rangarajan, Radha; Chakrapani, Harinath

    2014-07-10

    The number of cases of drug resistant Staphylococcus aureus infections is on the rise globally and new strategies to identify drug candidates with novel mechanisms of action are in urgent need. Here, we report the synthesis and evaluation of a series of benzo[b]phenanthridine-5,7,12(6H)-triones, which were designed based on redox-active natural products. We find that the in vitro inhibitory activity of 6-(prop-2-ynyl)benzo[b]phenanthridine-5,7,12(6H)-trione (1f) against methicillin-resistant Staphylococcus aureus (MRSA), including a panel of patient-derived strains, is comparable or better than vancomycin. We show that the lead compound generates reactive oxygen species (ROS) in the cell, contributing to its antibacterial activity. PMID:25050164

  3. Reactive oxygen species production and discontinuous gas exchange in insects.

    PubMed

    Boardman, Leigh; Terblanche, John S; Hetz, Stefan K; Marais, Elrike; Chown, Steven L

    2012-03-01

    While biochemical mechanisms are typically used by animals to reduce oxidative damage, insects are suspected to employ a higher organizational level, discontinuous gas exchange mechanism to do so. Using a combination of real-time, flow-through respirometry and live-cell fluorescence microscopy, we show that spiracular control associated with the discontinuous gas exchange cycle (DGC) in Samia cynthia pupae is related to reactive oxygen species (ROS). Hyperoxia fails to increase mean ROS production, although minima are elevated above normoxic levels. Furthermore, a negative relationship between mean and mean ROS production indicates that higher ROS production is generally associated with lower . Our results, therefore, suggest a possible signalling role for ROS in DGC, rather than supporting the idea that DGC acts to reduce oxidative damage by regulating ROS production. PMID:21865257

  4. NADPH oxidase-derived reactive oxygen species in cardiac pathophysiology

    PubMed Central

    Cave, Alison; Grieve, David; Johar, Sofian; Zhang, Min; Shah, Ajay M

    2005-01-01

    Chronic heart failure, secondary to left ventricular hypertrophy or myocardial infarction, is a condition with increasing morbidity and mortality. Although the mechanisms underlying the development and progression of this condition remain a subject of intense interest, there is now growing evidence that redox-sensitive pathways play an important role. This article focuses on the involvement of reactive oxygen species derived from a family of superoxide-generating enzymes, termed NADPH oxidases (NOXs), in the pathophysiology of ventricular hypertrophy, the accompanying interstitial fibrosis and subsequent heart failure. In particular, the apparent ability of the different NADPH oxidase isoforms to define the response of a cell to a range of physiological and pathophysiological stimuli is reviewed. If confirmed, these data would suggest that independently targeting different members of the NOX family may hold the potential for therapeutic intervention in the treatment of cardiac disease. PMID:16321803

  5. Reactive oxygen species: their relation to pneumoconiosis and carcinogenesis.

    PubMed

    Vallyathan, V; Shi, X; Castranova, V

    1998-10-01

    Occupational exposures to mineral particles cause pneumoconiosis and other diseases, including cancer. Recent studies have suggested that reactive oxygen species (ROS) may play a key role in the mechanisms of disease initiation and progression following exposure to these particles. ROS-induced primary stimuli result in the increased secretion of proinflammatory cytokines and other mediators, promoting events that appear to be important in the progression of cell injury and pulmonary disease. We have provided evidence supporting the hypothesis that inhalation of insoluble particles such as asbestos, agricultural dusts, coal, crystalline silica, and inorganic dust can be involved in facilitating multiple pathways for persistent generation of ROS, which may lead to a continuum of inflammation leading to progression of disease. This article briefly summarizes some of the recent findings from our laboratories with emphasis on the molecular events by which ROS are involved in promoting pneumoconiosis and carcinogenesis. PMID:9788890

  6. REACTIVE OXYGEN AND NITROGEN SPECIES IN PULMONARY HYPERTENSION

    PubMed Central

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

    2013-01-01

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

  7. Plasma-generated reactive oxygen species for biomedical applications

    NASA Astrophysics Data System (ADS)

    Sousa, J. S.; Hammer, M. U.; Winter, J.; Tresp, H.; Duennbier, M.; Iseni, S.; Martin, V.; Puech, V.; Weltmann, K. D.; Reuter, S.

    2012-10-01

    To get a better insight into the effects of reactive oxygen species (ROS) on cellular components, fundamental studies are essential to determine the nature and concentration of plasma-generated ROS, and the chemistry induced in biological liquids by those ROS. In this context, we have measured the absolute density of the main ROS created in three different atmospheric pressure plasma sources: two geometrically distinct RF-driven microplasma jets (μ-APPJ [1] and kinpen [2]), and an array of microcathode sustained discharges [3]. Optical diagnostics of the plasma volumes and effluent regions have been performed: UV absorption for O3 and IR emission for O2(a^1δ) [4]. High concentrations of both ROS have been obtained (10^14--10^17cm-3). The effect of different parameters, such as gas flows and mixtures and power coupled to the plasmas, has been studied. For plasma biomedicine, the determination of the reactive species present in plasma-treated liquids is of great importance. In this work, we focused on the measurement of the concentration of H2O2 and NOX radicals, generated in physiological solutions like NaCl and PBS.[4pt] [1] N. Knake et al., J. Phys. D: App. Phys. 41, 194006 (2008)[0pt] [2] K.D. Weltmann et al., Pure Appl. Chem. 82, 1223 (2010)[0pt] [3] J.S. Sousa et al., Appl. Phys. Lett. 97, 141502 (2010)[0pt] [4] J.S. Sousa et al., Appl. Phys. Lett. 93, 011502 (2008)

  8. Nitric oxide and reactive oxygen species are required for systemic acquired resistance in plants

    PubMed Central

    El-Shetehy, Mohamed; Wang, Caixia; Shine, M B; Yu, Keshun; Kachroo, Aardra; Kachroo, Pradeep

    2015-01-01

    Systemic acquired resistance (SAR) is a form of broad-spectrum disease resistance that is induced in response to primary infection and that protects uninfected portions of the plant against secondary infections by related or unrelated pathogens. SAR is associated with an increase in chemical signals that operate in a collective manner to confer protection against secondary infections. These include, the phytohormone salicylic acid (SA), glycerol-3-phosphate (G3P), azelaic acid (AzA) and more recently identified signals nitric oxide (NO) and reactive oxygen species (ROS). NO, ROS, AzA and G3P function in the same branch of the SAR pathway, and in parallel to the SA-regulated branch. NO and ROS function upstream of AzA/G3P and different reactive oxygen species functions in an additive manner to mediate chemical cleavage of the C9 double bond on C18 unsaturated fatty acids to generate AzA. The parallel and additive functioning of various chemical signals provides important new insights in the overlapping pathways leading to SAR. PMID:26375184

  9. Effects of reactive oxygen species on sperm function.

    PubMed

    Guthrie, H D; Welch, G R

    2012-11-01

    Reactive oxygen species (ROS) formation and membrane lipid peroxidation have been recognized as problems for sperm survival and fertility. The precise roles and detection of superoxide (SO), hydrogen peroxide (HP), and membrane lipid peroxidation have been problematic, because of the low specificity and sensitivity of the established chemiluminescence assay technologies. We developed flow cytometric assays to measure SO, HP, membrane lipid peroxidation, and inner mitochondrial transmembrane potential in boar sperm. These methods were sufficiently sensitive to permit detection of early changes in ROS formation in sperm cells that were still viable. Basal ROS formation and membrane lipid peroxidation in the absence of ROS generators were low in viable sperm of both fresh and frozen-thawed boar semen, affecting less than 4% of the sperm cells on average. However, this is not the case in other species, as human, bovine, and poultry sperm have large increases in sperm ROS formation, lipid peroxidation, loss of motility, and death in vitro. Closer study of the effects of ROS formation on the relationship between sperm motility and ATP content in boar sperm was conducted using menadione (mitochondrial SO generator) and HP treatment. Menadione or HP caused an immediate disruption of motility with delayed or no decrease in sperm ATP content, respectively. Overall, the inhibitory effects of ROS on motility point to a mitochondrial-independent mechanism. The reduction in motility may have been due to a ROS-induced lesion in ATP utilization or in the contractile apparatus of the flagellum. PMID:22704396

  10. Reactive oxygen species in bovine embryo in vitro production.

    PubMed

    Dalvit, G C; Cetica, P D; Pintos, L N; Beconi, M T

    2005-08-01

    Oxidative modifications of cell components due to the action of reactive oxygen species (ROS) is one of the most potentially damaging processes for proper cell function. However, in the last few years it has been observed that ROS participate in physiological processes. The aim of this work was to determine ROS generation during in vitro production of bovine embryos. Cumulus-oocyte complexes were recovered by aspiration of antral follicles from ovaries obtained from slaughtered cows and cultured in medium 199 for 22 h at 39 degrees C in 5% CO2: 95% humidified air. In vitro fertilization was carried out in IVF-mSOF with frozen-thawed semen in the same culture conditions and embryo in vitro culture in IVC-mSOF at 90% N2: 5% CO2: 5% O2. ROS was determined in denuded oocytes and embryos at successive stages of development by the 2',7'-dichlorodihydrofluorescein diacetate fluorescent assay. ROS production was not modified during oocyte maturation. However, a gradual increase in ROS production was observed up to the late morula stage during embryo in vitro culture (P < 0.05). In expanded blastocysts, ROS level decreased to reach values similar to the corresponding in oocytes. In the bovine species, the variation in ROS level during the complete process of embryo in vitro production was determined for the first time. PMID:16187501

  11. Antioxidants protect against reactive oxygen species associated with adriamycin-treated cardiomyocytes.

    PubMed

    DeAtley, S M; Aksenov, M Y; Aksenova, M V; Harris, B; Hadley, R; Cole Harper, P; Carney, J M; Butterfield, D A

    1999-02-01

    Adriamycin (ADM) is a broad-spectrum antineoplastic antibiotic used to treat cancer patients. However, the usefulness of this drug is presently limited by the development of a dose-dependent cardiotoxicity. A current hypothesis for the ADM-induced cardiotoxicity is the production of reactive oxygen radicals by the drug. We utilized the fluorescent indicator 2',7'-dichlorodihydrofluorescein diacetate (DCFH/DA), in which fluorescence appears if reactive oxygen species (ROS) are present, to investigate the ability of ADM to generate reactive oxygen species and the potential protective effect of antioxidants in a cultured cardiomyocyte model. All three of the antioxidants (alpha-phenyl-tert-butyl nitrone (PBN), trolox, and 5-aminosalicylic acid (5-ASA)) tested in our ADM-treated myocytes provided protection against the oxidative stress induced by the drug. These findings suggest that antioxidants modulate ADM-induced oxidative stress, and they are discussed in terms of a possible therapeutic strategy in the prevention of cardiotoxicity resulting from ADM administration. PMID:10211937

  12. Production of fusaric acid by Fusarium species.

    PubMed Central

    Bacon, C W; Porter, J K; Norred, W P; Leslie, J F

    1996-01-01

    Fusaric acid is a mycotoxin with low to moderate toxicity, which is of concern since it might be synergistic with other cooccurring mycotoxins. Fusaric acid is widespread on corn and corn-based food and feeds and is frequently found in grain, where Fusarium spp. are also isolated. We surveyed 78 strains of Fusarium moniliforme, F. crookwellense, F. subglutinans, F. sambucinum, F. napiforme, F. heterosporum, F. oxysporum, F. solani, and F. proliferatum for their ability to produce fusaric acid. Strains in Fusarium section Liseola also were assigned to mating population of the Gibberella fujikuroi species complex. The fungi could be divided into three classes, low (< 100 micrograms/g), moderate (100 to 500 micrograms/g), and high (> 500 micrograms/g), based on the amounts of this mycotoxin produced in culture on autoclaved corn. Strains of mating populations C from rice consistently produced moderate to high concentrations of fusaric acid. Two isolates, one each from mating populations C and D, produced fusaric acid in excess of 1,000 micrograms/g of corn. No isolates of any of the Fusarium species examined were negative for the production of fusaric acid on autoclaved corn. PMID:8899996

  13. Male infertility testing: reactive oxygen species and antioxidant capacity.

    PubMed

    Ko, Edmund Y; Sabanegh, Edmund S; Agarwal, Ashok

    2014-12-01

    Reactive oxygen species (ROS) are an integral component of sperm developmental physiology, capacitation, and function. Elevated ROS levels, from processes such as infection or inflammation, can be associated with aberrations of sperm development, function, and fertilizing capacity. We review the impact of ROS on sperm physiology, its place in infertility evaluation, the implications for reproductive outcomes, and antioxidant therapy. Our systematic review of PubMed literature from the last 3 decades focuses on the physiology and etiology of ROS and oxidative stress (OS), evaluation of ROS, and antioxidants. ROS is normally produced physiologically and is used to maintain cellular processes such as sperm maturation, capacitation, and sperm-oocyte interaction. When ROS production exceeds the buffering capacity of antioxidants, OS occurs and can have a negative impact on sperm and fertility. ROS and antioxidant capacity testing can potentially add additional prognostic information to standard laboratory testing for the infertile male, although its role as standard part of an evaluation has yet to be determined. Elevated ROS levels have been implicated with abnormal semen parameters and male infertility, but the impact of ROS on fertilization rates and pregnancy is controversial. This is partly because of the lack of consensus on what type of patients may be suitable for ROS testing and assay standardization. Routine ROS testing for the infertile male is not currently recommended. PMID:25458618

  14. Reactive oxygen species: players in the cardiovascular effects of testosterone.

    PubMed

    Tostes, Rita C; Carneiro, Fernando S; Carvalho, Maria Helena C; Reckelhoff, Jane F

    2016-01-01

    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

  15. Redox Roles of Reactive Oxygen Species in Cardiovascular Diseases

    PubMed Central

    He, Feng; Zuo, Li

    2015-01-01

    Cardiovascular disease (CVD), a major cause of mortality in the world, has been extensively studied over the past decade. However, the exact mechanism underlying its pathogenesis has not been fully elucidated. Reactive oxygen species (ROS) play a pivotal role in the progression of CVD. Particularly, ROS are commonly engaged in developing typical characteristics of atherosclerosis, one of the dominant CVDs. This review will discuss the involvement of ROS in atherosclerosis, specifically their effect on inflammation, disturbed blood flow and arterial wall remodeling. Pharmacological interventions target ROS in order to alleviate oxidative stress and CVD symptoms, yet results are varied due to the paradoxical role of ROS in CVD. Lack of effectiveness in clinical trials suggests that understanding the exact role of ROS in the pathophysiology of CVD and developing novel treatments, such as antioxidant gene therapy and nanotechnology-related antioxidant delivery, could provide a therapeutic advance in treating CVDs. While genetic therapies focusing on specific antioxidant expression seem promising in CVD treatments, multiple technological challenges exist precluding its immediate clinical applications. PMID:26610475

  16. Reactive Oxygen Species and Targeted Therapy for Pancreatic Cancer

    PubMed Central

    2016-01-01

    Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Reactive oxygen species (ROS) are generally increased in pancreatic cancer cells compared with normal cells. ROS plays a vital role in various cellular biological activities including proliferation, growth, apoptosis, and invasion. Besides, ROS participates in tumor microenvironment orchestration. The role of ROS is a doubled-edged sword in pancreatic cancer. The dual roles of ROS depend on the concentration. ROS facilitates carcinogenesis and cancer progression with mild-to-moderate elevated levels, while excessive ROS damages cancer cells dramatically and leads to cell death. Based on the recent knowledge, either promoting ROS generation to increase the concentration of ROS with extremely high levels or enhancing ROS scavenging ability to decrease ROS levels may benefit the treatment of pancreatic cancer. However, when faced with oxidative stress, the antioxidant programs of cancer cells have been activated to help cancer cells to survive in the adverse condition. Furthermore, ROS signaling and antioxidant programs play the vital roles in the progression of pancreatic cancer and in the response to cancer treatment. Eventually, it may be the novel target for various strategies and drugs to modulate ROS levels in pancreatic cancer therapy. PMID:26881012

  17. NSAIDs and Cardiovascular Diseases: Role of Reactive Oxygen Species

    PubMed Central

    Ghosh, Rajeshwary; Alajbegovic, Azra; Gomes, Aldrin V.

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs worldwide. NSAIDs are used for a variety of conditions including pain, rheumatoid arthritis, and musculoskeletal disorders. The beneficial effects of NSAIDs in reducing or relieving pain are well established, and other benefits such as reducing inflammation and anticancer effects are also documented. The undesirable side effects of NSAIDs include ulcers, internal bleeding, kidney failure, and increased risk of heart attack and stroke. Some of these side effects may be due to the oxidative stress induced by NSAIDs in different tissues. NSAIDs have been shown to induce reactive oxygen species (ROS) in different cell types including cardiac and cardiovascular related cells. Increases in ROS result in increased levels of oxidized proteins which alters key intracellular signaling pathways. One of these key pathways is apoptosis which causes cell death when significantly activated. This review discusses the relationship between NSAIDs and cardiovascular diseases (CVD) and the role of NSAID-induced ROS in CVD. PMID:26457127

  18. UV-induced reactive oxygen species in photocarcinogenesis and photoaging.

    PubMed

    Scharffetter-Kochanek, K; Wlaschek, M; Brenneisen, P; Schauen, M; Blaudschun, R; Wenk, J

    1997-11-01

    The increase in UV irradiation on earth due to the stratospheric ozone depletion represents a major environmental threat to the skin increasing its risk of photooxidative damage by UV-induced reactive oxygen species (ROS). Increased ROS load has been implicated in several pathological states including photoaging and photocarcinogenesis of the skin. Large efforts have been made to better define the involvement of distinct ROS in photocarcinogenesis and photoaging. Both pathological processes share common features; however, they reveal unique molecular characteristics which finally determine the fate of the cell and its host. As well as causing permanent genetic changes involving protooncogenes and tumor suppressor genes, ROS activate cytoplasmic signal transduction pathways that are related to growth differentiation, senescence, transformation and tissue degradation. This review focuses on the role of UV-induced ROS in the photodamage of the skin resulting in biochemical and clinical characteristics of photocarcinogenesis and photoaging. A decrease in the ROS load by efficient sunscreens and/or otherwise protective agents may represent a promising strategy to prevent or at least minimize ROS induced cutaneous pathological states. PMID:9426184

  19. Reactive oxygen species promote raft formation in T lymphocytes.

    PubMed

    Lu, Shu-Ping; Lin Feng, Ming-Hsien; Huang, Huey-Lan; Huang, Ya-Ching; Tsou, Wen-I; Lai, Ming-Zong

    2007-04-01

    Lipid rafts are involved in many cell biology events, yet the molecular mechanisms on how rafts are formed are poorly understood. In this study we probed the possible requirement of reactive oxygen species (ROS) for T-cell receptor (TCR)-induced lipid raft formation. Microscopy and biochemical analyses illustrated that blockage of ROS production, by superoxide dismutase-mimic MnTBAP, significantly reduced partitioning of LAT, phospho-LAT, and PLC-gamma in lipid rafts. Another antioxidant N-acetylcysteine (NAC) displayed a similar suppressive effect on the entry of phospho-LAT into raft microdomains. The involvement of ROS in TCR-mediated raft assembly was observed in T-cell hybridomas, T leukemia cells, and normal T cells. Removal of ROS was accompanied by an attenuated activation of LAT and PKCtheta, with reduced production of IL-2. Consistently, treating T cells with the ROS-producer tert-butyl hydrogen peroxide (TBHP) greatly enhanced membrane raft formation, distribution of phospho-LAT into lipid rafts, and increased IL-2 production. Our results indicate for the first time that ROS contribute to TCR-induced membrane raft formation. PMID:17349922

  20. 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.

  1. Reactive oxygen species (ROS): involvement in bovine follicular cysts etiopathogenesis.

    PubMed

    Rizzo, Annalisa; Minoia, Giuseppe; Trisolini, Carmelinda; Mutinati, Maddalena; Spedicato, Massimo; Jirillo, Felicita; Sciorsci, Raffaele Luigi

    2009-01-01

    Ovulation is compared to an acute inflammatory process during which vasoactive agents, prostanoids, leukotrienes and Reactive Oxygen Species (ROS) develop. The aim of this study was to evaluate the levels of ROS in cystic and follicular fluid, in order to establish their involvement in the etiopathogenesis of Cystic Ovarian Follicle (COF) in dairy cows. The study was conducted in 30 healthy cows (group C) and 30 cows affected by COF (group COF). The fluid of follicular cysts and of preovulatory follicles was drawn by means of ultrasound guided aspiration from the cows of both groups. The fluid obtained was analyzed by a photometric analytical system to detect ROS level. ROS concentration was statistically lower in the cystic fluid than in the follicular one (62.4 +/- 13.36 U.Carr vs. 84.89 +/- 26.99 U.Carr) (p<0.05), thus suggesting that an alteration of the cascade responsible for ROS production may be implicated in the complex etipathogenesis of COF. PMID:19874233

  2. 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.

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

    PubMed Central

    Harrison, David G.

    2014-01-01

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

  4. Photosensitizing Nanoparticles and The Modulation of Reactive Oxygen Species generation

    NASA Astrophysics Data System (ADS)

    Tada, Dayane; Baptista, Mauricio

    2015-05-01

    The association of PhotoSensitizer (PS) molecules with nanoparticles (NPs) forming photosensitizing NPs, has emerged as a therapeutic strategy to improve PS tumor targeting, to protect PS from deactivation reactions and to enhance both PS solubility and circulation time. Since association with NPs usually alters PS photophysical and photochemical properties, photosensitizing NPs are an important tool to modulate reactive oxygen species (ROS) generation. Depending on the design of the photosensitizing NP, i.e., type of PS, the NP material and the method applied for the construction of the photosensitizing NP, the deactivation routes of the excited state can be controlled, allowing the generation of either singlet oxygen or other ROS. Controlling the type of generated ROS is desirable not only in biomedical applications, as in Photodynamic Therapy where the type of ROS affects therapeutic efficiency, but also in other technological relevant fields like energy conversion, where the electron and energy transfer processes are necessary to increase the efficiency of photoconversion cells. The current review highlights some of the recent developments in the design of Photosensitizing NPs aimed at modulating the primary photochemical events after light absorption.

  5. Reactive oxygen species in diabetic nephropathy: friend or foe?

    PubMed

    Bondeva, Tzvetanka; Wolf, Gunter

    2014-11-01

    Based on the numerous cellular and animal studies over the last decades, it has been postulated that reactive oxygen species (ROS) are important secondary messengers for signalling pathways associated with apoptosis, proliferation, damage and inflammation. Their adverse effects were considered to play a leading role in the onset and progression of type 1 and type 2 diabetes mellitus as well as in the complication of diabetic disease leading to vascular-, cardiac-, neuro-degeneration, diabetic retinopathy and diabetic nephropathy. All these complications were mostly linked to the generation of the superoxide anion, due to a prolonged hyperglycaemia in diabetes, and this anion was almost 'blamed for everything', despite the fact that its measurement and detection in life systems is extremely complicated due to the short lifespan of the superoxide anion. Therefore, a tremendous amount of research has been focused on finding ways to suppress ROS production. However, a recent report from Dugan et al. shed new insights into the life detection of superoxide generation in diabetes and raised the question of whether we treat the diabetes-related complications correctly or the target is somewhat different as thought. This review will focus on some aspects of this novel concept for the role of ROS in diabetic nephropathy. PMID:24589719

  6. Generation of Reactive Oxygen Species from Silicon Nanowires

    PubMed Central

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

    2014-01-01

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

  7. 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

  8. 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

  9. NSAIDs and Cardiovascular Diseases: Role of Reactive Oxygen Species.

    PubMed

    Ghosh, Rajeshwary; Alajbegovic, Azra; Gomes, Aldrin V

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs worldwide. NSAIDs are used for a variety of conditions including pain, rheumatoid arthritis, and musculoskeletal disorders. The beneficial effects of NSAIDs in reducing or relieving pain are well established, and other benefits such as reducing inflammation and anticancer effects are also documented. The undesirable side effects of NSAIDs include ulcers, internal bleeding, kidney failure, and increased risk of heart attack and stroke. Some of these side effects may be due to the oxidative stress induced by NSAIDs in different tissues. NSAIDs have been shown to induce reactive oxygen species (ROS) in different cell types including cardiac and cardiovascular related cells. Increases in ROS result in increased levels of oxidized proteins which alters key intracellular signaling pathways. One of these key pathways is apoptosis which causes cell death when significantly activated. This review discusses the relationship between NSAIDs and cardiovascular diseases (CVD) and the role of NSAID-induced ROS in CVD. PMID:26457127

  10. Matairesinol inhibits angiogenesis via suppression of mitochondrial reactive oxygen species

    SciTech Connect

    Lee, Boram; Kim, Ki Hyun; Jung, Hye Jin; Kwon, Ho Jeong

    2012-04-27

    Highlights: Black-Right-Pointing-Pointer Matairesinol suppresses mitochondrial ROS generation during hypoxia. Black-Right-Pointing-Pointer Matairesinol exhibits potent anti-angiogenic activity both in vitro and in vivo. Black-Right-Pointing-Pointer Matairesinol could be a basis for the development of novel anti-angiogenic agents. -- Abstract: Mitochondrial reactive oxygen species (mROS) are involved in cancer initiation and progression and function as signaling molecules in many aspects of hypoxia and growth factor-mediated signaling. Here we report that matairesinol, a natural small molecule identified from the cell-based screening of 200 natural plants, suppresses mROS generation resulting in anti-angiogenic activity. A non-toxic concentration of matairesinol inhibited the proliferation of human umbilical vein endothelial cells. The compound also suppressed in vitro angiogenesis of tube formation and chemoinvasion, as well as in vivo angiogenesis of the chorioallantoic membrane at non-toxic doses. Furthermore, matairesinol decreased hypoxia-inducible factor-1{alpha} in hypoxic HeLa cells. These results demonstrate that matairesinol could function as a novel angiogenesis inhibitor by suppressing mROS signaling.

  11. Reactive Oxygen Species, Apoptosis, Antimicrobial Peptides and Human Inflammatory Diseases

    PubMed Central

    Oyinloye, Babatunji Emmanuel; Adenowo, Abiola Fatimah; Kappo, Abidemi Paul

    2015-01-01

    Excessive free radical generation, especially reactive oxygen species (ROS) leading to oxidative stress in the biological system, has been implicated in the pathogenesis and pathological conditions associated with diverse human inflammatory diseases (HIDs). Although inflammation which is considered advantageous is a defensive mechanism in response to xenobiotics and foreign pathogen; as a result of cellular damage arising from oxidative stress, if uncontrolled, it may degenerate to chronic inflammation when the ROS levels exceed the antioxidant capacity. Therefore, in the normal resolution of inflammatory reactions, apoptosis is acknowledged to play a crucial role, while on the other hand, dysregulation in the induction of apoptosis by enhanced ROS production could also result in excessive apoptosis identified in the pathogenesis of HIDs. Apparently, a careful balance must be maintained in this complex environment. Antimicrobial peptides (AMPs) have been proposed in this review as an excellent candidate capable of playing prominent roles in maintaining this balance. Consequently, in novel drug design for the treatment and management of HIDs, AMPs are promising candidates owing to their size and multidimensional properties as well as their wide spectrum of activities and indications of reduced rate of resistance. PMID:25850012

  12. Reactive oxygen species a double-edged sword for mesothelioma

    PubMed Central

    Catalani, Simona; Galati, Rossella

    2015-01-01

    It is well known that oxidative stress can lead to chronic inflammation which, in turn, could mediate most chronic diseases including cancer. Oxidants have been implicated in the activity of crocidolite and amosite, the most powerful types of asbestos associated to the occurrence of mesothelioma. Currently rates of mesothelioma are rising and estimates indicate that the incidence of mesothelioma will peak within the next 10–15 years in the western world, while in Japan the peak is predicted not to occur until 40 years from now. Although the use of asbestos has been banned in many countries around the world, production of and the potentially hazardous exposure to asbestos is still present with locally high incidences of mesothelioma. Today a new man-made material, carbon nanotubes, has arisen as a concern; carbon nanotubes may display ‘asbestos-like’ pathogenicity with mesothelioma induction potential. Carbon nanotubes resulted in the greatest reactive oxygen species generation. How oxidative stress activates inflammatory pathways leading to the transformation of a normal cell to a tumor cell, to tumor cell survival, proliferation, invasion, angiogenesis, chemoresistance, and radioresistance, is the aim of this review. PMID:26078352

  13. 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

  14. Reactive oxygen species: their relation to pneumoconiosis and carcinogenesis.

    PubMed Central

    Vallyathan, V; Shi, X; Castranova, V

    1998-01-01

    Occupational exposures to mineral particles cause pneumoconiosis and other diseases, including cancer. Recent studies have suggested that reactive oxygen species (ROS) may play a key role in the mechanisms of disease initiation and progression following exposure to these particles. ROS-induced primary stimuli result in the increased secretion of proinflammatory cytokines and other mediators, promoting events that appear to be important in the progression of cell injury and pulmonary disease. We have provided evidence supporting the hypothesis that inhalation of insoluble particles such as asbestos, agricultural dusts, coal, crystalline silica, and inorganic dust can be involved in facilitating multiple pathways for persistent generation of ROS, which may lead to a continuum of inflammation leading to progression of disease. This article briefly summarizes some of the recent findings from our laboratories with emphasis on the molecular events by which ROS are involved in promoting pneumoconiosis and carcinogenesis. Images Figure 1 Figure 2 Figure 3 Figure 5 Figure 6 Figure 7 Figure 8 PMID:9788890

  15. Reactive oxygen species at the crossroads of inflammasome and inflammation

    PubMed Central

    Harijith, Anantha; Ebenezer, David L.; Natarajan, Viswanathan

    2014-01-01

    Inflammasomes form a crucial part of the innate immune system. These are multi-protein oligomer platforms that are composed of intracellular sensors which are coupled with caspase and interleukin activating systems. Nod-like receptor protein (NLRP) 3, and 6 and NLRC4 and AIM2 are the prominent members of the inflammasome family. Inflammasome activation leads to pyroptosis, a process of programmed cell death distinct from apoptosis through activation of Caspase and further downstream targets such as IL-1β and IL-18 leading to activation of inflammatory cascade. Reactive oxygen species (ROS) serves as important inflammasome activating signals. ROS activates inflammasome through mitogen-activated protein kinases (MAPK) and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2). Dysregulation of inflammasome plays a significant role in various pathological processes. Viral infections such as Dengue and Respiratory syncytial virus activate inflammasomes. Crystal compounds in silicosis and gout also activate ROS. In diabetes, inhibition of autophagy with resultant accumulation of dysfunctional mitochondria leads to enhanced ROS production activating inflammasomes. Activation of inflammasomes can be dampened by antioxidants such as SIRT-1. Inflammasome and related cascade could serve as future therapeutic targets for various pathological conditions. PMID:25324778

  16. Are reactive oxygen species still the basis for diabetic complications?

    PubMed

    Di Marco, Elyse; Jha, Jay C; Sharma, Arpeeta; Wilkinson-Berka, Jennifer L; Jandeleit-Dahm, Karin A; de Haan, Judy B

    2015-07-01

    Despite the wealth of pre-clinical support for a role for reactive oxygen and nitrogen species (ROS/RNS) in the aetiology of diabetic complications, enthusiasm for antioxidant therapeutic approaches has been dampened by less favourable outcomes in large clinical trials. This has necessitated a re-evaluation of pre-clinical evidence and a more rational approach to antioxidant therapy. The present review considers current evidence, from both pre-clinical and clinical studies, to address the benefits of antioxidant therapy. The main focus of the present review is on the effects of direct targeting of ROS-producing enzymes, the bolstering of antioxidant defences and mechanisms to improve nitric oxide availability. Current evidence suggests that a more nuanced approach to antioxidant therapy is more likely to yield positive reductions in end-organ injury, with considerations required for the types of ROS/RNS involved, the timing and dosage of antioxidant therapy, and the selective targeting of cell populations. This is likely to influence future strategies to lessen the burden of diabetic complications such as diabetes-associated atherosclerosis, diabetic nephropathy and diabetic retinopathy. PMID:25927680

  17. Reactive oxygen species and mitochondria: A nexus of cellular homeostasis

    PubMed Central

    Dan Dunn, Joe; Alvarez, Luis AJ; Zhang, Xuezhi; Soldati, Thierry

    2015-01-01

    Reactive oxygen species (ROS) are integral components of multiple cellular pathways even though excessive or inappropriately localized ROS damage cells. ROS function as anti-microbial effector molecules and as signaling molecules that regulate such processes as NF-kB transcriptional activity, the production of DNA-based neutrophil extracellular traps (NETs), and autophagy. The main sources of cellular ROS are mitochondria and NADPH oxidases (NOXs). In contrast to NOX-generated ROS, ROS produced in the mitochondria (mtROS) were initially considered to be unwanted by-products of oxidative metabolism. Increasing evidence indicates that mtROS have been incorporated into signaling pathways including those regulating immune responses and autophagy. As metabolic hubs, mitochondria facilitate crosstalk between the metabolic state of the cell with these pathways. Mitochondria and ROS are thus a nexus of multiple pathways that determine the response of cells to disruptions in cellular homeostasis such as infection, sterile damage, and metabolic imbalance. In this review, we discuss the roles of mitochondria in the generation of ROS-derived anti-microbial effectors, the interplay of mitochondria and ROS with autophagy and the formation of DNA extracellular traps, and activation of the NLRP3 inflammasome by ROS and mitochondria. PMID:26432659

  18. Reactive oxygen species and mitochondria: A nexus of cellular homeostasis.

    PubMed

    Dan Dunn, Joe; Alvarez, Luis Aj; Zhang, Xuezhi; Soldati, Thierry

    2015-12-01

    Reactive oxygen species (ROS) are integral components of multiple cellular pathways even though excessive or inappropriately localized ROS damage cells. ROS function as anti-microbial effector molecules and as signaling molecules that regulate such processes as NF-kB transcriptional activity, the production of DNA-based neutrophil extracellular traps (NETs), and autophagy. The main sources of cellular ROS are mitochondria and NADPH oxidases (NOXs). In contrast to NOX-generated ROS, ROS produced in the mitochondria (mtROS) were initially considered to be unwanted by-products of oxidative metabolism. Increasing evidence indicates that mtROS have been incorporated into signaling pathways including those regulating immune responses and autophagy. As metabolic hubs, mitochondria facilitate crosstalk between the metabolic state of the cell with these pathways. Mitochondria and ROS are thus a nexus of multiple pathways that determine the response of cells to disruptions in cellular homeostasis such as infection, sterile damage, and metabolic imbalance. In this review, we discuss the roles of mitochondria in the generation of ROS-derived anti-microbial effectors, the interplay of mitochondria and ROS with autophagy and the formation of DNA extracellular traps, and activation of the NLRP3 inflammasome by ROS and mitochondria. PMID:26432659

  19. Reactive oxygen species, nutrition, hypoxia and diseases: Problems solved?

    PubMed Central

    Görlach, Agnes; Dimova, Elitsa Y.; Petry, Andreas; Martínez-Ruiz, Antonio; Hernansanz-Agustín, Pablo; Rolo, Anabela P.; Palmeira, Carlos M.; Kietzmann, Thomas

    2015-01-01

    Within the last twenty years the view on reactive oxygen species (ROS) has changed; they are no longer only considered to be harmful but also necessary for cellular communication and homeostasis in different organisms ranging from bacteria to mammals. In the latter, ROS were shown to modulate diverse physiological processes including the regulation of growth factor signaling, the hypoxic response, inflammation and the immune response. During the last 60–100 years the life style, at least in the Western world, has changed enormously. This became obvious with an increase in caloric intake, decreased energy expenditure as well as the appearance of alcoholism and smoking; These changes were shown to contribute to generation of ROS which are, at least in part, associated with the occurrence of several chronic diseases like adiposity, atherosclerosis, type II diabetes, and cancer. In this review we discuss aspects and problems on the role of intracellular ROS formation and nutrition with the link to diseases and their problematic therapeutical issues. PMID:26339717

  20. Are Reactive Oxygen Species Always Detrimental to Pathogens?

    PubMed Central

    Bozza, Marcelo T.

    2014-01-01

    Abstract Reactive oxygen species (ROS) are deadly weapons used by phagocytes and other cell types, such as lung epithelial cells, against pathogens. ROS can kill pathogens directly by causing oxidative damage to biocompounds or indirectly by stimulating pathogen elimination by various nonoxidative mechanisms, including pattern recognition receptors signaling, autophagy, neutrophil extracellular trap formation, and T-lymphocyte responses. Thus, one should expect that the inhibition of ROS production promote infection. Increasing evidences support that in certain particular infections, antioxidants decrease and prooxidants increase pathogen burden. In this study, we review the classic infections that are controlled by ROS and the cases in which ROS appear as promoters of infection, challenging the paradigm. We discuss the possible mechanisms by which ROS could promote particular infections. These mechanisms are still not completely clear but include the metabolic effects of ROS on pathogen physiology, ROS-induced damage to the immune system, and ROS-induced activation of immune defense mechanisms that are subsequently hijacked by particular pathogens to act against more effective microbicidal mechanisms of the immune system. The effective use of antioxidants as therapeutic agents against certain infections is a realistic possibility that is beginning to be applied against viruses. Antioxid. Redox Signal. 20, 1000–1037. PMID:23992156

  1. Reactive oxygen species delay control of lymphocytic choriomeningitis virus

    PubMed Central

    Lang, P A; Xu, H C; Grusdat, M; McIlwain, D R; Pandyra, A A; Harris, I S; Shaabani, N; Honke, N; Kumar Maney, S; Lang, E; Pozdeev, V I; Recher, M; Odermatt, B; Brenner, D; Häussinger, D; Ohashi, P S; Hengartner, H; Zinkernagel, R M; Mak, T W; Lang, K S

    2013-01-01

    Cluster of differentiation (CD)8+ T cells are like a double edged sword during chronic viral infections because they not only promote virus elimination but also induce virus-mediated immunopathology. Elevated levels of reactive oxygen species (ROS) have been reported during virus infections. However, the role of ROS in T-cell-mediated immunopathology remains unclear. Here we used the murine lymphocytic choriomeningitis virus to explore the role of ROS during the processes of virus elimination and induction of immunopathology. We found that virus infection led to elevated levels of ROS producing granulocytes and macrophages in virus-infected liver and spleen tissues that were triggered by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Lack of the regulatory subunit p47phox of the NADPH oxidase diminished ROS production in these cells. While CD8+ T cells exhibited ROS production that was independent of NADPH oxidase expression, survival and T-cell function was elevated in p47phox-deficient (Ncf1−/−) mice. In the absence of p47phox, enhanced T-cell immunity promoted virus elimination and blunted corresponding immunopathology. In conclusion, we find that NADPH-mediated production of ROS critically impairs the immune response, impacting elimination of virus and outcome of liver cell damage. PMID:23328631

  2. Reactive Oxygen Species and Respiratory Plasticity Following Intermittent Hypoxia

    PubMed Central

    MacFarlane, P.M.; Wilkerson, J.E.R.; Lovett-Barr, M.R.; Mitchell, G.S.

    2008-01-01

    The neural network controlling breathing exhibits plasticity in response to environmental or physiological challenges. For example, while hypoxia initiates rapid and robust increases in respiratory motor output to defend against hypoxemia, it also triggers persistent changes, or plasticity, in chemosensory neurons and integrative pathways that transmit brainstem respiratory activity to respiratory motor neurons. Frequently studied models of hypoxia-induced respiratory plasticity include: 1) carotid chemosensory plasticity and metaplasticity induced by chronic intermittent hypoxia (CIH), and 2) acute intermittent hypoxia (AIH) induced phrenic long-term facilitation (pLTF) in naïve and CIH preconditioned rats. These forms of plasticity share some mechanistic elements, although they differ in anatomical location and the requirement for CIH preconditioning. Both forms of plasticity require serotonin receptor activation and formation of reactive oxygen species (ROS). While the cellular sources and targets of ROS are not well known, recent evidence suggests that ROS modify the balance of protein phosphatase and kinase activities, shifting the balance towards net phosphorylation and favoring cellular reactions that induce and/or maintain plasticity. Here, we review possible sources of ROS, and the impact of ROS on phosphorylation events relevant to respiratory plasticity. PMID:18692605

  3. Pharmacological modulation of reactive oxygen species in cancer treatment.

    PubMed

    Ribas, Judit; Mattiolo, Paolo; Boix, Jacint

    2015-01-01

    Aerobic metabolism of mammalian cells leads to the generation of reactive oxygen species (ROS). To cope with this toxicity, evolution provided cells with effective antioxidant systems like glutathione. Current anticancer therapies focus on the cancer dependence on oncogenes and non-oncogenes. Tumors trigger mechanisms to circumvent the oncogenic stress and to escape cell death. In this context we have studied 2-phenylethinesulfoxamine (PES), which disables the cell protective mechanisms to confront the proteotoxicity of damaged and unfolded proteins. Proteotoxic stress is increased in tumor cells, thus providing an explanation for the anticancer selectivity of PES. In addition, we have found that PES induces a severe oxidative stress and the activation of p53. The reduction of the cell content in glutathione by means of L-buthionine-sulfoximine (BSO) synergizes with PES. In conclusion, we have found that ROS constitutes a central element in a series of positive feed-back loops in the cell. ROS, p53, proteotoxicity, autophagy and mitochondrial dynamics are interconnected with the mechanisms leading to cell death, either apoptotic or necrotic. This network of interactions provides multiple targets for drug discovery and development in cancer. PMID:25395102

  4. Redox Roles of Reactive Oxygen Species in Cardiovascular Diseases.

    PubMed

    He, Feng; Zuo, Li

    2015-01-01

    Cardiovascular disease (CVD), a major cause of mortality in the world, has been extensively studied over the past decade. However, the exact mechanism underlying its pathogenesis has not been fully elucidated. Reactive oxygen species (ROS) play a pivotal role in the progression of CVD. Particularly, ROS are commonly engaged in developing typical characteristics of atherosclerosis, one of the dominant CVDs. This review will discuss the involvement of ROS in atherosclerosis, specifically their effect on inflammation, disturbed blood flow and arterial wall remodeling. Pharmacological interventions target ROS in order to alleviate oxidative stress and CVD symptoms, yet results are varied due to the paradoxical role of ROS in CVD. Lack of effectiveness in clinical trials suggests that understanding the exact role of ROS in the pathophysiology of CVD and developing novel treatments, such as antioxidant gene therapy and nanotechnology-related antioxidant delivery, could provide a therapeutic advance in treating CVDs. While genetic therapies focusing on specific antioxidant expression seem promising in CVD treatments, multiple technological challenges exist precluding its immediate clinical applications. PMID:26610475

  5. Reactive Oxygen Species and the Brain in Sleep Apnea

    PubMed Central

    Wang, Yang; Zhang, Shelley XL; Gozal, David

    2010-01-01

    Rodents exposed to intermittent hypoxia (IH), a model of obstructive sleep apnea (OSA), manifest impaired learning and memory and somnolence. Increased levels of reactive oxygen species (ROS), oxidative tissue damage, and apoptotic neuronal cell death are associated with the presence of IH-induced CNS dysfunction. Furthermore, treatment with antioxidants or overexpression of antioxidant enzymes is neuroprotective during IH. These findings mimic clinical cases of OSA and suggest that ROS may play a key causal role in OSA-induced neuropathology. Controlled production of ROS occurs in multiple subcellular compartments of normal cells and de-regulation of such processes may result in excessive ROS production. The mitochondrial electron transport chain, especially complexes I and III, and the NADPH oxidase in the cellular membrane are the two main sources of ROS in brain cells, although other systems, including xanthine oxidase, phospholipase A2, lipoxygenase, cyclooxygenase, and cytochrome P450, may all play a role. The initial evidence for NADPH oxidase and mitochondrial involvement in IH-induced ROS production and neuronal injury unquestionably warrants future research efforts. PMID:20833273

  6. Tamoxifen reduces fat mass by boosting reactive oxygen species

    PubMed Central

    Liu, L; Zou, P; Zheng, L; Linarelli, L E; Amarell, S; Passaro, A; Liu, D; Cheng, Z

    2015-01-01

    As the pandemic of obesity is growing, a variety of animal models have been generated to study the mechanisms underlying the increased adiposity and development of metabolic disorders. Tamoxifen (Tam) is widely used to activate Cre recombinase that spatiotemporally controls target gene expression and regulates adiposity in laboratory animals. However, a critical question remains as to whether Tam itself affects adiposity and possibly confounds the functional study of target genes in adipose tissue. Here we administered Tam to Cre-absent forkhead box O1 (FoxO1) floxed mice (f-FoxO1) and insulin receptor substrate Irs1/Irs2 double floxed mice (df-Irs) and found that Tam induced approximately 30% reduction (P<0.05) in fat mass with insignificant change in body weight. Mechanistically, Tam promoted reactive oxygen species (ROS) production, apoptosis and autophagy, which was associated with downregulation of adipogenic regulator peroxisome proliferator-activated receptor gamma and dedifferentiation of mature adipocytes. However, normalization of ROS potently suppressed Tam-induced apoptosis, autophagy and adipocyte dedifferentiation, suggesting that ROS may account, at least in part, for the changes. Importantly, Tam-induced ROS production and fat mass reduction lasted for 4–5 weeks in the f-FoxO1 and df-Irs mice. Our data suggest that Tam reduces fat mass via boosting ROS, thus making a recovery period crucial for posttreatment study. PMID:25569103

  7. [Comparative antioxidant action on the level of reactive oxygen species in normal and transformed fibroblasts].

    PubMed

    Liublinskaia, O G; Kirpichnikova, K M; Gamaleĭ, I A

    2013-01-01

    We studied the changes in the level of reactive oxygen species (ROS) in normal (3T3) and transformed (3T3-SV40) murine fibroblasts under the antioxidant action for 15 min using fluorescent probe carbo- xy-H2DCFDA. We have shown that N-acetylcysteine (NAC) decreased ROS level in both cellular types. Another antioxidant, alpha-lipoic acid (ALA), and its reduced form, dihydrolipoic acid (DHLA), caused the prooxidant effects. Both ALA and DHLA in the concentration range of 0.1-1.25 mM increased ROS level in dose dependent manner in both cellular types. The ability of ALA and DHLA to activate hydrogen peroxide production is discussed. PMID:25509127

  8. Amino acid decarboxylations produced by lipid-derived reactive carbonyls in amino acid mixtures.

    PubMed

    Hidalgo, Francisco J; León, M Mercedes; Zamora, Rosario

    2016-10-15

    The formation of 2-phenylethylamine and phenylacetaldehyde in mixtures of phenylalanine, a lipid oxidation product, and a second amino acid was studied to determine the role of the second amino acid in the degradation of phenylalanine produced by lipid-derived reactive carbonyls. The presence of the second amino acid usually increased the formation of the amine and reduced the formation of the Strecker aldehyde. The reasons for this behaviour seem to be related to the α-amino group and the other functional groups (mainly amino or similar groups) present in the side-chain of the amino acid. These groups are suggested to modify the lipid-derived reactive carbonyl but not the reaction mechanism because the Ea of formation of both 2-phenylethylamine and phenylacetaldehyde remained unchanged in all studied systems. All these results suggest that the amine/aldehyde ratio obtained by amino acid degradation can be modified by adding free amino acids during food formulation. PMID:27173560

  9. Metabolism of reactive oxygen species and reactive nitrogen species in pepper (Capsicum annuum L.) plants under low temperature stress.

    PubMed

    Airaki, Morad; Leterrier, Marina; Mateos, Rosa M; Valderrama, Raquel; Chaki, Mounira; Barroso, Juan B; Del Río, Luis A; Palma, José M; Corpas, Francisco J

    2012-02-01

    Low temperature is an environmental stress that affects crop production and quality and regulates the expression of many genes, and the level of a number of proteins and metabolites. Using leaves from pepper (Capsicum annum L.) plants exposed to low temperature (8 °C) for different time periods (1 to 3 d), several key components of the metabolism of reactive nitrogen and oxygen species (RNS and ROS, respectively) were analysed. After 24 h of exposure at 8 °C, pepper plants exhibited visible symptoms characterized by flaccidity of stems and leaves. This was accompanied by significant changes in the metabolism of RNS and ROS with an increase of both protein tyrosine nitration (NO(2) -Tyr) and lipid peroxidation, indicating that low temperature induces nitrosative and oxidative stress. During the second and third days at low temperature, pepper plants underwent cold acclimation by adjusting their antioxidant metabolism and reverting the observed nitrosative and oxidative stress. In this process, the levels of the soluble non-enzymatic antioxidants ascorbate and glutathione, and the activity of the main NADPH-generating dehydrogenases were significantly induced. This suggests that ascorbate, glutathione and the NADPH-generating dehydrogenases have a role in the process of cold acclimation through their effect on the redox state of the cell. PMID:21414013

  10. Fish oil increases mitochondrial phospholipid unsaturation, upregulating reactive oxygen species and apoptosis in rat colonocytes.

    PubMed

    Hong, Mee Young; Chapkin, Robert S; Barhoumi, Rola; Burghardt, Robert C; Turner, Nancy D; Henderson, Cara E; Sanders, Lisa M; Fan, Yang-Yi; Davidson, Laurie A; Murphy, Mary E; Spinka, Christine M; Carroll, Raymond J; Lupton, Joanne R

    2002-11-01

    We have shown that a combination of fish oil (high in n-3 fatty acids) with the butyrate-producing fiber pectin, upregulates apoptosis in colon cells exposed to the carcinogen azoxymethane, protecting against colon tumor development. We now hypothesize that n-3 fatty acids prime the colonocytes such that butyrate can initiate apoptosis. To test this, 30 Sprague-Dawley rats were provided with diets differing in the fatty acid composition (corn oil, fish oil or a purified fatty acid ethyl ester diet). Intact colon crypts were exposed ex vivo to butyrate, and analyzed for reactive oxygen species (ROS), mitochondrial membrane potential (MMP), translocation of cytochrome C to the cytosol, and caspase-3 activity (early events in apoptosis). The fatty acid composition of the three major mitochondrial phospholipids was also determined, and an unsaturation index calculated. The unsaturation index in cardiolipin was correlated with ROS levels (R = 0.99; P = 0.02). When colon crypts from fish oil and FAEE-fed rats were exposed to butyrate, MMP decreased (P = 0.041); and translocation of cytochrome C to the cytosol (P = 0.037) and caspase-3 activation increased (P = 0.032). The data suggest that fish oil may prime the colonocytes for butyrate-induced apoptosis by enhancing the unsaturation of mitochondrial phospholipids, especially cardiolipin, resulting in an increase in ROS and initiating apoptotic cascade. PMID:12419841

  11. Fish oil increases mitochondrial phospholipid unsaturation, upregulating reactive oxygen species and apoptosis in rat colonocytes

    NASA Technical Reports Server (NTRS)

    Hong, Mee Young; Chapkin, Robert S.; Barhoumi, Rola; Burghardt, Robert C.; Turner, Nancy D.; Henderson, Cara E.; Sanders, Lisa M.; Fan, Yang-Yi; Davidson, Laurie A.; Murphy, Mary E.; Spinka, Christine M.; Carroll, Raymond J.; Lupton, Joanne R.

    2002-01-01

    We have shown that a combination of fish oil (high in n-3 fatty acids) with the butyrate-producing fiber pectin, upregulates apoptosis in colon cells exposed to the carcinogen azoxymethane, protecting against colon tumor development. We now hypothesize that n-3 fatty acids prime the colonocytes such that butyrate can initiate apoptosis. To test this, 30 Sprague-Dawley rats were provided with diets differing in the fatty acid composition (corn oil, fish oil or a purified fatty acid ethyl ester diet). Intact colon crypts were exposed ex vivo to butyrate, and analyzed for reactive oxygen species (ROS), mitochondrial membrane potential (MMP), translocation of cytochrome C to the cytosol, and caspase-3 activity (early events in apoptosis). The fatty acid composition of the three major mitochondrial phospholipids was also determined, and an unsaturation index calculated. The unsaturation index in cardiolipin was correlated with ROS levels (R = 0.99; P = 0.02). When colon crypts from fish oil and FAEE-fed rats were exposed to butyrate, MMP decreased (P = 0.041); and translocation of cytochrome C to the cytosol (P = 0.037) and caspase-3 activation increased (P = 0.032). The data suggest that fish oil may prime the colonocytes for butyrate-induced apoptosis by enhancing the unsaturation of mitochondrial phospholipids, especially cardiolipin, resulting in an increase in ROS and initiating apoptotic cascade.

  12. 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. PMID:21133411

  13. Reactive Oxygen Species Alter Autocrine and Paracrine Signaling

    SciTech Connect

    Zangar, Richard C.; Bollinger, Nikki; Weber, Thomas J.; Tan, Ruimin; Markillie, Lye Meng; Karin, Norman J.

    2011-12-01

    Cytochrome P450 (P450) 3A4 (CYP3A4) is the most abundant P450 protein in human liver and intestine and is highly inducible by a variety of drugs and other compounds. The P450 catalytic cycle is known to uncouple and release reactive oxygen species (ROS), but the effects of ROS from P450 and other enzymes in the endo-plasmic reticulum have been poorly studied from the perspective of effects on cell biology. In this study, we expressed low levels of CYP3A4 in HepG2 cells, a human hepatocarcinoma cell line, and examined effects on intracellular levels of ROS and on the secretion of a variety of growth factors that are important in extracellular communication. Using the redox-sensitive dye RedoxSensor red, we demonstrate that CYP3A4 expression increases levels of ROS in viable cells. A customELISA microarray platform was employed to demonstrate that expression of CYP3A4 increased secretion of amphiregulin, intracellular adhesion molecule 1, matrix metalloprotease 2, platelet-derived growth factor (PDGF), and vascular endothelial growth factor, but suppressed secretion of CD14. The antioxidant N-acetylcysteine suppressed all P450-dependent changes in protein secretion except for CD14. Quantitative RT-PCR demonstrated that changes in protein secretion were consistently associated with corresponding changes in gene expression. Inhibition of the NF-{kappa}B pathway blocked P450 effects on PDGF secretion. CYP3A4 expression also altered protein secretion in human mammary epithelial cells and C10 mouse lung cells. Overall, these results suggest that increased ROS production in the endoplasmic reticulum alters the secretion of proteins that have key roles in paracrine and autocrine signaling.

  14. Are mitochondrial reactive oxygen species required for autophagy?

    SciTech Connect

    Jiang, Jianfei; Maeda, Akihiro; Ji, Jing; Baty, Catherine J.; Watkins, Simon C.; Greenberger, Joel S.; Kagan, Valerian E.

    2011-08-19

    Highlights: {yields} Autophageal and apoptotic pathways were dissected in cytochrome c deficient cells. {yields} Staurosporine (STS)-induced autophagy was not accompanied by ROS generation. {yields} Autophagy was detectable in mitochondrial DNA deficient {rho}{sup 0} cells. {yields} Mitochondrial ROS are not required for the STS-induced autophagy in HeLa cells. -- Abstract: Reactive oxygen species (ROS) are said to participate in the autophagy signaling. Supporting evidence is obscured by interference of autophagy and apoptosis, whereby the latter heavily relies on ROS signaling. To dissect autophagy from apoptosis we knocked down expression of cytochrome c, the key component of mitochondria-dependent apoptosis, in HeLa cells using shRNA. In cytochrome c deficient HeLa1.2 cells, electron transport was compromised due to the lack of electron shuttle between mitochondrial respiratory complexes III and IV. A rapid and robust LC3-I/II conversion and mitochondria degradation were observed in HeLa1.2 cells treated with staurosporine (STS). Neither generation of superoxide nor accumulation of H{sub 2}O{sub 2} was detected in STS-treated HeLa1.2 cells. A membrane permeable antioxidant, PEG-SOD, plus catalase exerted no effect on STS-induced LC3-I/II conversion and mitochondria degradation. Further, STS caused autophagy in mitochondria DNA-deficient {rho}{sup o} HeLa1.2 cells in which both electron transport and ROS generation were completely disrupted. Counter to the widespread view, we conclude that mitochondrial ROS are not required for the induction of autophagy.

  15. Vitiligo, reactive oxygen species and T-cells.

    PubMed

    Glassman, Steven J

    2011-02-01

    The acquired depigmenting disorder of vitiligo affects an estimated 1% of the world population and constitutes one of the commonest dermatoses. Although essentially asymptomatic, the psychosocial impact of vitiligo can be severe. The cause of vitiligo remains enigmatic, hampering efforts at successful therapy. The underlying pathogenesis of the pigment loss has, however, been clarified to some extent in recent years, offering the prospect of effective treatment, accurate prognosis and rational preventative strategies. Vitiligo occurs when functioning melanocytes disappear from the epidermis. A single dominant pathway is unlikely to account for all cases of melanocyte loss in vitiligo; rather, it is the result of complex interactions of biochemical, environmental and immunological events, in a permissive genetic milieu. ROS (reactive oxygen species) and H2O2 in excess can damage biological processes, and this situation has been documented in active vitiligo skin. Tyrosinase activity is impaired by excess H2O2 through oxidation of methionine residues in this key melanogenic enzyme. Mechanisms for repairing this oxidant damage are also damaged by H2O2, compounding the effect. Numerous proteins and peptides, in addition to tyrosinase, are similarly affected. It is possible that oxidant stress is the principal cause of vitiligo. However, there is also ample evidence of immunological phenomena in vitiligo, particularly in established chronic and progressive disease. Both innate and adaptive arms of the immune system are involved, with a dominant role for T-cells. Sensitized CD8+ T-cells are targeted to melanocyte differentiation antigens and destroy melanocytes either as the primary event in vitiligo or as a secondary promotive consequence. There is speculation on the interplay, if any, between ROS and the immune system in the pathogenesis of vitiligo. The present review focuses on the scientific evidence linking alterations in ROS and/or T-cells to vitiligo. PMID

  16. Development of fluorometric reactive oxygen species assay for photosafety evaluation.

    PubMed

    Seto, Yoshiki; Ohtake, Hiroto; Kato, Masashi; Onoue, Satomi

    2016-08-01

    The present investigation involved an attempt to develop a new reactive oxygen species (ROS) assay system for the photosafety assessment of chemicals using 1,3-diphenylisobenzofuran (DPBF), a fluorescent probe for monitoring ROS generation. The assay conditions of the fluorometric ROS (fROS) assay were optimized focusing on the solvent system, concentration of DPBF, fluorescent determination, screening run time and reproducibility. The photoreactivity of 21 phototoxic and 11 non-phototoxic compounds was assessed by fROS assay, and the obtained ROS data were compared with the results from a micellar ROS (mROS) assay and in vitro/in vivo phototoxicity information to confirm the predictive capacity of the fROS assay. In the optimized fROS assay, intra-day and inter-day precision levels (coefficient of variation) were found to be below 5%, and the Z'-factor for DPBF fluorescence quenching showed a large separation between positive and negative controls. Of all tested compounds, 3 false positive and 7 false negative predictions were observed in the fROS assay, and the negative predictivity for the fROS assay was found to be lower than that for the mROS assay. Although the fROS assay has some limitations, the procedures for it were highly simplified with a marked reduction in screening run time and one analytical sample for monitoring ROS generation from compounds. The fROS assay has the potential to become a new tool for photosafety assessment at an early stage of product development. PMID:27058001

  17. Reactivity of anti-human C-reactive protein (CRP) and serum amyloid P component (SAP) monoclonal antibodies with limulin and pentraxins of other species.

    PubMed Central

    Ying, S C; Marchalonis, J J; Gewurz, A T; Siegel, J N; Jiang, H; Gewurz, B E; Gewurz, H

    1992-01-01

    Limulus polyphemus C-reactive protein (CRP) (limulin) has approximately 30% amino acid sequence homology and shares at least one idiotypic determinant associated with ligand-binding activity with human CRP (hCRP); limulin also shares amino acid sequence homology and lectin activity with human serum amyloid P component (hSAP). In the present study panels of 14 anti-hCRP monoclonal antibodies (mAb) directed to distinct hCRP epitopes and 11 anti-hSAP mAb directed to distinct epitopes of hSAP were tested for reactivity with limulin and pentraxins of other species including rabbit CRP (raCRP), rat CRP and hamster female protein (FP) by ELISA and Western blot analyses. None of the anti-human pentraxin mAb showed strong cross-reactivity with limulin; only five mAb reacted with limulin at all, and cross-reactivities of these mAb with the other pentraxins, when present, also were weak. Cross-reactivity of limulin with hCRP and hSAP was similar, and in light of comparable amino acid sequence homology, suggests this molecule can be considered the limulus SAP as well as the limulus CRP. Several anti-hCRP mAb cross-reacted strongly with rabbit CRP and rat CRP; a few anti-hSAP cross-reacted strongly with FP; and weak cross-reactions were observed between hCRP and hSAP, but cross-reactivities between the pentraxins generally were limited and weak. A rabbit polyclonal antibody raised to highly conserved limulin peptide 141-156 and strongly reactive with limulin reacted weakly with hCRP and raCRP but failed to react with rat CRP, hSAP or FP. These studies emphasize a limited but distinct antigenic similarity between limulin, hCRP and other pentraxins, and identify mAb reactive with potential regions of shared structure and/or function between pentraxins of different species. Images Figure 1 Figure 2 PMID:1378818

  18. Borrelia burgdorferi membranes are the primary targets of reactive oxygen species

    PubMed Central

    Boylan, Julie A; Lawrence, Kevin A; Downey, Jennifer S; Gherardini, Frank C

    2008-01-01

    Spirochetes living in an oxygen-rich environment or when challenged by host immune cells are exposed to reactive oxygen species (ROS). These species can harm/destroy cysteinyl residues, iron-sulphur clusters, DNA and polyunsaturated lipids, leading to inhibition of growth or cell death. Because Borrelia burgdorferi contains no intracellular iron, DNA is most likely not a major target for ROS via Fenton reaction. In support of this, growth of B. burgdorferi in the presence of 5 mM H2O2 had no effect on the DNA mutation rate (spontaneous coumermycin A1 resistance), and cells treated with 10 mM t-butyl hydroperoxide or 10 mM H2O2 show no increase in DNA damage. Unlike most bacteria, B. burgdorferi incorporates ROS-susceptible polyunsaturated fatty acids from the environment into their membranes. Analysis of lipoxidase-treated B. burgdorferi cells by Electron Microscopy showed significant irregularities indicative of membrane damage. Fatty acid analysis of cells treated with lipoxidase indicated that host-derived linoleic acid had been dramatically reduced (50-fold) in these cells, with a corresponding increase in the levels of malondialdehyde by-product (fourfold). These data suggest that B. burgdorferi membrane lipids are targets for attack by ROS encountered in the various stages of the infective cycle. PMID:18373524

  19. Protein reactivity with singlet oxygen: Influence of the solvent exposure of the reactive amino acid residues.

    PubMed

    Sjöberg, Béatrice; Foley, Sarah; Staicu, Angela; Pascu, Alexandru; Pascu, Mihail; Enescu, Mironel

    2016-06-01

    The singlet oxygen quenching rate constants were measured for three model proteins, bovine serum albumin, β-lactoglobulin and lysozyme. The results were analyzed by comparing them with the corresponding singlet oxygen quenching rate constants for a series of tripeptides with the basic formula GlyAAGly where the central amino acid (AA) was the oxidizable amino acid, tryptophan, tyrosine, methionine and histidine. It was found that the reaction rate constant in proteins can be satisfactorily modelled by the sum of the individual contributions of the oxidizable AA residues corrected for the solvent accessible surface area (SASA) effects. The best results were obtained when the SASA of the AA residues were determined by averaging over molecular dynamics simulated trajectories of the proteins. The limits of this geometrical correction of the AA residue reactivity are also discussed. PMID:27045278

  20. Singlet Oxygen Is the Major Reactive Oxygen Species Involved in Photooxidative Damage to Plants1[W

    PubMed Central

    Triantaphylidès, Christian; Krischke, Markus; Hoeberichts, Frank Alfons; Ksas, Brigitte; Gresser, Gabriele; Havaux, Michel; Van Breusegem, Frank; Mueller, Martin Johannes

    2008-01-01

    Reactive oxygen species act as signaling molecules but can also directly provoke cellular damage by rapidly oxidizing cellular components, including lipids. We developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry-based quantitative method that allowed us to discriminate between free radical (type I)- and singlet oxygen (1O2; type II)-mediated lipid peroxidation (LPO) signatures by using hydroxy fatty acids as specific reporters. Using this method, we observed that in nonphotosynthesizing Arabidopsis (Arabidopsis thaliana) tissues, nonenzymatic LPO was almost exclusively catalyzed by free radicals both under normal and oxidative stress conditions. However, in leaf tissues under optimal growth conditions, 1O2 was responsible for more than 80% of the nonenzymatic LPO. In Arabidopsis mutants favoring 1O2 production, photooxidative stress led to a dramatic increase of 1O2 (type II) LPO that preceded cell death. Furthermore, under all conditions and in mutants that favor the production of superoxide and hydrogen peroxide (two sources for type I LPO reactions), plant cell death was nevertheless always preceded by an increase in 1O2-dependent (type II) LPO. Thus, besides triggering a genetic cell death program, as demonstrated previously with the Arabidopsis fluorescent mutant, 1O2 plays a major destructive role during the execution of reactive oxygen species-induced cell death in leaf tissues. PMID:18676660

  1. Reactivity of Resorcinol Formaldehyde Resin with Nitric Acid

    SciTech Connect

    King, William D.; Fondeur, Fernando F.; Wilmarth, William R.; Pettis, Myra E.

    2005-10-25

    Solid-state infrared spectroscopy, differential scanning calorimetry, and elemental analysis have been used to evaluate the reactivity of resorcinol formaldehyde resin with nitric acid and characterize the solid product. Two distinct reactions were identified within the temperature range 25-55 C. The first reaction is primarily associated with resin nitration, while the second involves bulk oxidation and degradation of the polymer network leading to dissolution and off-gassing. The threshold conditions promoting reaction have been identified. Reaction was confirmed with nitric acid concentrations as low as 3 M at 25 C applied temperature and 0.625 M at 66 C. Although a nitrated resin product can be isolated under appropriate experimental conditions, calorimetry testing indicates no significant hazard associated with handling the dry material.

  2. REACTIVITY OF RESORCINOL FORMALDEHYDE RESIN WITH NITRIC ACID

    SciTech Connect

    King, W; Fernando Fondeur, F; Bill Wilmarth, B; Myra Pettis, M; Shirley Mccollum, S

    2006-06-14

    Solid-state infrared spectroscopy, differential scanning calorimetry, and elemental analysis have been used to evaluate the reactivity of resorcinol formaldehyde resin with nitric acid and characterize the solid product. Two distinct reactions were identified within the temperature range 25-55 C. The first reaction is primarily associated with resin nitration, while the second involves bulk oxidation and degradation of the polymer network leading to dissolution and off-gassing. Reaction was confirmed with nitric acid concentrations as low as 3 M at 25 C applied temperature and 0.625 M at 66 C. Although a nitrated resin product can be isolated under appropriate experimental conditions, calorimetry testing indicates no significant hazard associated with handling the dry material.

  3. Upsides and Downsides of Reactive Oxygen Species for Cancer: The Roles of Reactive Oxygen Species in Tumorigenesis, Prevention, and Therapy

    PubMed Central

    Gupta, Subash C.; Hevia, David; Patchva, Sridevi; Park, Byoungduck; Koh, Wonil

    2012-01-01

    Abstract Significance: Extensive research during the last quarter century has revealed that reactive oxygen species (ROS) produced in the body, primarily by the mitochondria, play a major role in various cell-signaling pathways. Most risk factors associated with chronic diseases (e.g., cancer), such as stress, tobacco, environmental pollutants, radiation, viral infection, diet, and bacterial infection, interact with cells through the generation of ROS. Recent Advances: ROS, in turn, activate various transcription factors (e.g., nuclear factor kappa-light-chain-enhancer of activated B cells [NF-κB], activator protein-1, hypoxia-inducible factor-1α, and signal transducer and activator of transcription 3), resulting in the expression of proteins that control inflammation, cellular transformation, tumor cell survival, tumor cell proliferation and invasion, angiogenesis, and metastasis. Paradoxically, ROS also control the expression of various tumor suppressor genes (p53, Rb, and PTEN). Similarly, γ-radiation and various chemotherapeutic agents used to treat cancer mediate their effects through the production of ROS. Interestingly, ROS have also been implicated in the chemopreventive and anti-tumor action of nutraceuticals derived from fruits, vegetables, spices, and other natural products used in traditional medicine. Critical Issues: These statements suggest both “upside” (cancer-suppressing) and “downside” (cancer-promoting) actions of the ROS. Thus, similar to tumor necrosis factor-α, inflammation, and NF-κB, ROS act as a double-edged sword. This paradox provides a great challenge for researchers whose aim is to exploit ROS stress for the development of cancer therapies. Future Directions: The various mechanisms by which ROS mediate paradoxical effects are discussed in this article. The outstanding questions and future directions raised by our current understanding are discussed. Antioxid. Redox Signal. 16, 1295–1322. PMID:22117137

  4. Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis.

    PubMed

    Khan, Saeed R

    2014-09-01

    Calcium oxalate (CaOx) kidney stones are formed attached to Randall's plaques (RPs) or Randall's plugs. Mechanisms involved in the formation and growth are poorly understood. It is our hypothesis that stone formation is a form of pathological biomineralization or ectopic calcification. Pathological calcification and plaque formation in the body is triggered by reactive oxygen species (ROS) and the development of oxidative stress (OS). This review explores clinical and experimental data in support of ROS involvement in the formation of CaOx kidney stones. Under normal conditions the production of ROS is tightly controlled, increasing when and where needed. Results of clinical and experimental studies show that renal epithelial exposure to high oxalate and crystals of CaOx/calcium phosphate (CaP) generates excess ROS, causing injury and inflammation. Major markers of OS and inflammation are detectable in urine of stone patients as well as rats with experimentally induced CaOx nephrolithiasis. Antioxidant treatments reduce crystal and oxalate induced injury in tissue culture and animal models. Significantly lower serum levels of antioxidants, alpha-carotene, beta-carotene and beta-cryptoxanthine have been found in individuals with a history of kidney stones. A diet rich in antioxidants has been shown to reduce stone episodes. ROS regulate crystal formation, growth and retention through the timely production of crystallization modulators. In the presence of abnormal calcium, citrate, oxalate, and/or phosphate, however, there is an overproduction of ROS and a decrease in the antioxidant capacity resulting in OS, renal injury and inflammation. Cellular degradation products in the urine promote crystallization in the tubular lumen at a faster rate thus blocking the tubule and plugging the tubular openings at the papillary tips forming Randall's plugs. Renal epithelial cells lining the loops of Henle/collecting ducts may become osteogenic, producing membrane vesicles at

  5. KRIT1 Regulates the Homeostasis of Intracellular Reactive Oxygen Species

    PubMed Central

    Goitre, Luca; Balzac, Fiorella; Degani, Simona; Degan, Paolo; Marchi, Saverio; Pinton, Paolo; Retta, Saverio Francesco

    2010-01-01

    KRIT1 is a gene responsible for Cerebral Cavernous Malformations (CCM), a major cerebrovascular disease characterized by abnormally enlarged and leaky capillaries that predispose to seizures, focal neurological deficits, and fatal intracerebral hemorrhage. Comprehensive analysis of the KRIT1 gene in CCM patients has suggested that KRIT1 functions need to be severely impaired for pathogenesis. However, the molecular and cellular functions of KRIT1 as well as CCM pathogenesis mechanisms are still research challenges. We found that KRIT1 plays an important role in molecular mechanisms involved in the maintenance of the intracellular Reactive Oxygen Species (ROS) homeostasis to prevent oxidative cellular damage. In particular, we demonstrate that KRIT1 loss/down-regulation is associated with a significant increase in intracellular ROS levels. Conversely, ROS levels in KRIT1−/− cells are significantly and dose-dependently reduced after restoration of KRIT1 expression. Moreover, we show that the modulation of intracellular ROS levels by KRIT1 loss/restoration is strictly correlated with the modulation of the expression of the antioxidant protein SOD2 as well as of the transcriptional factor FoxO1, a master regulator of cell responses to oxidative stress and a modulator of SOD2 levels. Furthermore, we show that the KRIT1-dependent maintenance of low ROS levels facilitates the downregulation of cyclin D1 expression required for cell transition from proliferative growth to quiescence. Finally, we demonstrate that the enhanced ROS levels in KRIT1−/− cells are associated with an increased cell susceptibility to oxidative DNA damage and a marked induction of the DNA damage sensor and repair gene Gadd45α, as well as with a decline of mitochondrial energy metabolism. Taken together, our results point to a new model where KRIT1 limits the accumulation of intracellular oxidants and prevents oxidative stress-mediated cellular dysfunction and DNA damage by enhancing the

  6. Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis

    PubMed Central

    2014-01-01

    Calcium oxalate (CaOx) kidney stones are formed attached to Randall’s plaques (RPs) or Randall’s plugs. Mechanisms involved in the formation and growth are poorly understood. It is our hypothesis that stone formation is a form of pathological biomineralization or ectopic calcification. Pathological calcification and plaque formation in the body is triggered by reactive oxygen species (ROS) and the development of oxidative stress (OS). This review explores clinical and experimental data in support of ROS involvement in the formation of CaOx kidney stones. Under normal conditions the production of ROS is tightly controlled, increasing when and where needed. Results of clinical and experimental studies show that renal epithelial exposure to high oxalate and crystals of CaOx/calcium phosphate (CaP) generates excess ROS, causing injury and inflammation. Major markers of OS and inflammation are detectable in urine of stone patients as well as rats with experimentally induced CaOx nephrolithiasis. Antioxidant treatments reduce crystal and oxalate induced injury in tissue culture and animal models. Significantly lower serum levels of antioxidants, alpha-carotene, beta-carotene and beta-cryptoxanthine have been found in individuals with a history of kidney stones. A diet rich in antioxidants has been shown to reduce stone episodes. ROS regulate crystal formation, growth and retention through the timely production of crystallization modulators. In the presence of abnormal calcium, citrate, oxalate, and/or phosphate, however, there is an overproduction of ROS and a decrease in the antioxidant capacity resulting in OS, renal injury and inflammation. Cellular degradation products in the urine promote crystallization in the tubular lumen at a faster rate thus blocking the tubule and plugging the tubular openings at the papillary tips forming Randall’s plugs. Renal epithelial cells lining the loops of Henle/collecting ducts may become osteogenic, producing membrane vesicles

  7. Inactivation of pyruvate dehydrogenase kinase 2 by mitochondrial reactive oxygen species.

    PubMed

    Hurd, Thomas R; Collins, Yvonne; Abakumova, Irina; Chouchani, Edward T; Baranowski, Bartlomiej; Fearnley, Ian M; Prime, Tracy A; Murphy, Michael P; James, Andrew M

    2012-10-12

    Reactive oxygen species are byproducts of mitochondrial respiration and thus potential regulators of mitochondrial function. Pyruvate dehydrogenase kinase 2 (PDHK2) inhibits the pyruvate dehydrogenase complex, thereby regulating entry of carbohydrates into the tricarboxylic acid (TCA) cycle. Here we show that PDHK2 activity is inhibited by low levels of hydrogen peroxide (H(2)O(2)) generated by the respiratory chain. This occurs via reversible oxidation of cysteine residues 45 and 392 on PDHK2 and results in increased pyruvate dehydrogenase complex activity. H(2)O(2) derives from superoxide (O(2)(.)), and we show that conditions that inhibit PDHK2 also inactivate the TCA cycle enzyme, aconitase. These findings suggest that under conditions of high mitochondrial O(2)(.) production, such as may occur under nutrient excess and low ATP demand, the increase in O(2)() and H(2)O(2) may provide feedback signals to modulate mitochondrial metabolism. PMID:22910903

  8. Inactivation of Pyruvate Dehydrogenase Kinase 2 by Mitochondrial Reactive Oxygen Species*

    PubMed Central

    Hurd, Thomas R.; Collins, Yvonne; Abakumova, Irina; Chouchani, Edward T.; Baranowski, Bartlomiej; Fearnley, Ian M.; Prime, Tracy A.; Murphy, Michael P.; James, Andrew M.

    2012-01-01

    Reactive oxygen species are byproducts of mitochondrial respiration and thus potential regulators of mitochondrial function. Pyruvate dehydrogenase kinase 2 (PDHK2) inhibits the pyruvate dehydrogenase complex, thereby regulating entry of carbohydrates into the tricarboxylic acid (TCA) cycle. Here we show that PDHK2 activity is inhibited by low levels of hydrogen peroxide (H2O2) generated by the respiratory chain. This occurs via reversible oxidation of cysteine residues 45 and 392 on PDHK2 and results in increased pyruvate dehydrogenase complex activity. H2O2 derives from superoxide (O2˙̄), and we show that conditions that inhibit PDHK2 also inactivate the TCA cycle enzyme, aconitase. These findings suggest that under conditions of high mitochondrial O2˙̄ production, such as may occur under nutrient excess and low ATP demand, the increase in O2˙̄ and H2O2 may provide feedback signals to modulate mitochondrial metabolism. PMID:22910903

  9. The Injury and Therapy of Reactive Oxygen Species in Intracerebral Hemorrhage Looking at Mitochondria

    PubMed Central

    Qu, Jie; Chen, Weixiang; Hu, Rong; Feng, Hua

    2016-01-01

    Intracerebral hemorrhage is an emerging major health problem often resulting in death or disability. Reactive oxygen species (ROS) have been identified as one of the major damaging factors in ischemic stroke. However, there is less discussion about ROS in hemorrhage stroke. Metabolic products of hemoglobin, excitatory amino acids, and inflammatory cells are all sources of ROS, and ROS harm the central nervous system through cell death and structural damage, especially disruption of the blood-brain barrier. We have considered the antioxidant system of the CNS itself and the drugs aiming to decrease ROS after ICH, and we find that mitochondria are key players in all of these aspects. Moreover, when the mitochondrial permeability transition pore opens, ROS-induced ROS release, which leads to extensive liberation of ROS and mitochondrial failure, occurs. Therefore, the mitochondrion may be a significant target for elucidating the problem of ROS in ICH; however, additional experimental support is required. PMID:27293511

  10. Role of reactive oxygen species produced by NADPH oxidase in gibberellin biosynthesis during barley seed germination.

    PubMed

    Kai, Kyohei; Kasa, Shinsuke; Sakamoto, Masatsugu; Aoki, Nozomi; Watabe, Gaku; Yuasa, Takashi; Iwaya-Inoue, Mari; Ishibashi, Yushi

    2016-05-01

    NADPH oxidase catalyzes the production of the superoxide anion (O2(-)), a reactive oxygen species (ROS), and regulates the germination of barley (Hordeum vulgare L.). Diphenyleneiodonium (DPI) chloride, an NADPH oxidase inhibitor, delayed barley germination, and exogenous H2O2 (an ROS) partially rescued it. Six enzymes, ent-copalyl diphosphate synthase (CPS), ent-kaurene synthase (KS), ent-kaurene oxidase (KO), ent-kaurenoic acid oxidase (KAO), GA20-oxidase (GA20ox) and GA3-oxidase (GA3ox), catalyze the transformation of trans-geranylgeranyl diphosphate to active gibberellin, which promotes germination. Exogenous H2O2 promoted the expressions of HvKAO1 and HvGA3ox1 in barley embryos. These results suggest that ROS produced by NADPH oxidase are involved in gibberellin biosynthesis through the regulation of HvKAO1 and HvGA3ox1. PMID:27110861

  11. Protection of neuronal cells against reactive oxygen species by carnosine and related compounds.

    PubMed

    Boldyrev, Alexander; Bulygina, Elena; Leinsoo, Toomas; Petrushanko, Irina; Tsubone, Shiori; Abe, Hiroki

    2004-01-01

    Carnosine and related compounds were compared in terms of their abilities to decrease the levels of reactive oxygen species (ROS) in suspensions of isolated neurons activated by N-methyl-D-aspartic acid (NMDA) using both stationary fluorescence measurements and flow cytometry. Carnosine was found to suppress the fluorescent signal induced by ROS production and decreased the proportion of highly fluorescent neurons, while histidine showed opposite effects. N-Acetylated derivatives of both carnosine and histidine demonstrated weak (statistically indistinguishable) suppressive effects on the ROS signal. N-Methylated derivatives of carnosine suppressed intracellular ROS generation to the same extent as carnosine. This rank of effectiveness is distinct from that previously obtained for the anti-radical ability of CRCs (anserine>carnosine>ophidine). These differences suggest that the similar ability of carnosine and its N-methylated derivatives to protect neuronal cells against the excitotoxic effect of NMDA is not solely related to the antioxidant properties of these compounds. PMID:14698913

  12. The Roles of Mitochondrial Reactive Oxygen Species in Cellular Signaling and Stress Response in Plants.

    PubMed

    Huang, Shaobai; Van Aken, Olivier; Schwarzländer, Markus; Belt, Katharina; Millar, A Harvey

    2016-07-01

    Mitochondria produce ATP via respiratory oxidation of organic acids and transfer of electrons to O2 via the mitochondrial electron transport chain. This process produces reactive oxygen species (ROS) at various rates that can impact respiratory and cellular function, affecting a variety of signaling processes in the cell. Roles in redox signaling, retrograde signaling, plant hormone action, programmed cell death, and defense against pathogens have been attributed to ROS generated in plant mitochondria (mtROS). The shortcomings of the black box-idea of mtROS are discussed in the context of mechanistic considerations and the measurement of mtROS The overall aim of this update is to better define our current understanding of mtROS and appraise their potential influence on cellular function in plants. Furthermore, directions for future research are provided, along with suggestions to increase reliability of mtROS measurements. PMID:27021189

  13. Quantitative assessment of reactive oxygen species generation by cavitation incepted efficiently using nonlinear propagation effect

    NASA Astrophysics Data System (ADS)

    Yasuda, Jun; Yoshizawa, Shin; Umemura, Shin-ichiro

    2015-10-01

    Sonodynamic treatment is a treatment method that uses chemical bio-effect of cavitation bubbles. Reactive oxygen species that can kill cancerous tissue is induced by such chemical effect of cavitation bubbles and it is important to generate them efficiently for effective sonodynamic treatment. Cavitation cloud can be formed by an effect of nonlinear propagation and focus and in this study, it was experimentally investigated if cavitation cloud was useful for efficient generation of reactive oxygen species. As a result, it was demonstrated that cavitation cloud would be useful for efficient generation of reactive oxygen species.

  14. Drug-induced reactive oxygen species (ROS) rely on cell membrane properties to exert anticancer effects

    PubMed Central

    Molavian, Hamid R.; Goldman, Aaron; Phipps, Colin J.; Kohandel, Mohammad; Wouters, Bradly G.; Sengupta, Shiladitya; Sivaloganathan, Sivabal

    2016-01-01

    Pharmacological concentrations of small molecule natural products, such as ascorbic acid, have exhibited distinct cell killing outcomes between cancer and normal cells whereby cancer cells undergo apoptosis or necrosis while normal cells are not adversely affected. Here, we develop a mathematical model for ascorbic acid that can be utilized as a tool to understand the dynamics of reactive oxygen species (ROS) induced cell death. We determine that not only do endogenous antioxidants such as catalase contribute to ROS-induced cell death, but also cell membrane properties play a critical role in the efficacy of ROS as a cytotoxic mechanism against cancer cells vs. normal cells. Using in vitro assays with breast cancer cells, we have confirmed that cell membrane properties are essential for ROS, in the form of hydrogen peroxide (H2O2), to induce cell death. Interestingly, we did not observe any correlation between intracellular H2O2 and cell survival, suggesting that cell death by H2O2 is triggered by interaction with the cell membrane and not necessarily due to intracellular levels of H2O2. These findings provide a putative mechanistic explanation for the efficacy and selectivity of therapies such as ascorbic acid that rely on ROS-induced cell death for their anti-tumor properties. PMID:27278439

  15. Redox cycling and generation of reactive oxygen species in commercial infant formulas.

    PubMed

    Boatright, William L; Crum, Andrea D

    2016-04-01

    Three nationally prominent commercial powdered infant formulas generated hydrogen peroxide, ranging from 10.46 to 11.62 μM, when prepared according to the manufacturer's instructions. Treating infant formulas with the chelating agent diethylene triamine pentaacetic acid (DTPA) significantly reduced H2O2 generation. In contrast, the addition of disodium ethylenediaminetetraacetic acid (EDTA) elevated the level of H2O2 generated in the same infant formulas by approximately 3- to 4-fold above the untreated infant formulas. The infant formulas contained ascorbate radicals ranging from about 138 nM to 40 nM. Treatment with catalase reduced the ascorbate radical contents by as much as 67%. Treatment with DTPA further reduced ascorbate radical signals to below quantifiable levels in most samples, further implicating the involvement of transition metal redox cycling in reactive oxygen species (ROS) formation. Supportive evidence of the generation of ROS is provided using luminol-enhanced luminescence (LEL) in both model mixtures of ascorbic acid and in commercial infant formulas. PMID:26593482

  16. Drug-induced reactive oxygen species (ROS) rely on cell membrane properties to exert anticancer effects.

    PubMed

    Molavian, Hamid R; Goldman, Aaron; Phipps, Colin J; Kohandel, Mohammad; Wouters, Bradly G; Sengupta, Shiladitya; Sivaloganathan, Sivabal

    2016-01-01

    Pharmacological concentrations of small molecule natural products, such as ascorbic acid, have exhibited distinct cell killing outcomes between cancer and normal cells whereby cancer cells undergo apoptosis or necrosis while normal cells are not adversely affected. Here, we develop a mathematical model for ascorbic acid that can be utilized as a tool to understand the dynamics of reactive oxygen species (ROS) induced cell death. We determine that not only do endogenous antioxidants such as catalase contribute to ROS-induced cell death, but also cell membrane properties play a critical role in the efficacy of ROS as a cytotoxic mechanism against cancer cells vs. normal cells. Using in vitro assays with breast cancer cells, we have confirmed that cell membrane properties are essential for ROS, in the form of hydrogen peroxide (H2O2), to induce cell death. Interestingly, we did not observe any correlation between intracellular H2O2 and cell survival, suggesting that cell death by H2O2 is triggered by interaction with the cell membrane and not necessarily due to intracellular levels of H2O2. These findings provide a putative mechanistic explanation for the efficacy and selectivity of therapies such as ascorbic acid that rely on ROS-induced cell death for their anti-tumor properties. PMID:27278439

  17. 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...

  18. 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...

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

    PubMed Central

    Sestili, Piero; Fimognari, Carmela

    2015-01-01

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

  20. Reactivation of a commercial diesel oxidation catalyst by acid washing.

    PubMed

    Galisteo, Francisco Cabello; Mariscal, Rafael; Granados, Manuel López; Fierro, José Luis García; Brettes, Pilar; Salas, Oscar

    2005-05-15

    The catalytic activity of samples taken from an oxidation catalyst mounted on diesel-driven automobiles and aged under road conditions was recovered to a significant extent by washing with a dilute solution of citric acid. The characterization of samples arising from a fresh, a vehicle-aged, and a regenerated catalyst was carried out by scanning electron microscopy (SEM-EDS), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Relatively high levels of S and P, in the form of aluminum sulfate and phosphate, respectively, together with contaminant Si were detected in the used catalyst. Washing of the vehicle-aged catalytic oxidation converter revealed high efficiency in the extraction of the main contaminants detected (S and P) by this nondestructive methodology. The results of the experiments reported here should encourage the development of a technology based on this reactivation procedure for the rejuvenation of the catalytic device mounted on diesel exhaust pipes. PMID:15952394

  1. Involvement of Cytochrome P450 in Reactive Oxygen Species Formation and Cancer.

    PubMed

    Hrycay, Eugene G; Bandiera, Stelvio M

    2015-01-01

    This review examines the involvement of cytochrome P450 (CYP) enzymes in the formation of reactive oxygen species in biological systems and discusses the possible involvement of reactive oxygen species and CYP enzymes in cancer. Reactive oxygen species are formed in biological systems as byproducts of the reduction of molecular oxygen and include the superoxide radical anion (∙O2-), hydrogen peroxide (H2O2), hydroxyl radical (∙OH), hydroperoxyl radical (HOO∙), singlet oxygen ((1)O2), and peroxyl radical (ROO∙). Two endogenous sources of reactive oxygen species are the mammalian CYP-dependent microsomal electron transport system and the mitochondrial electron transport chain. CYP enzymes catalyze the oxygenation of an organic substrate and the simultaneous reduction of molecular oxygen. If the transfer of oxygen to a substrate is not tightly controlled, uncoupling occurs and leads to the formation of reactive oxygen species. Reactive oxygen species are capable of causing oxidative damage to cellular membranes and macromolecules that can lead to the development of human diseases such as cancer. In normal cells, intracellular levels of reactive oxygen species are maintained in balance with intracellular biochemical antioxidants to prevent cellular damage. Oxidative stress occurs when this critical balance is disrupted. Topics covered in this review include the role of reactive oxygen species in intracellular cell signaling and the relationship between CYP enzymes and cancer. Outlines of CYP expression in neoplastic tissues, CYP enzyme polymorphism and cancer risk, CYP enzymes in cancer therapy and the metabolic activation of chemical procarcinogens by CYP enzymes are also provided. PMID:26233903

  2. Contribution of reactive oxygen and nitrogen species to particulate-induced lung injury.

    PubMed Central

    Zhu, S; Manuel, M; Tanaka, S; Choe, N; Kagan, E; Matalon, S

    1998-01-01

    Recently, a second pathway for the generation of potential oxidants with the reactivity of the hydroxyl radical without the need for metal catalysis has been described. In response to various inflammatory stimuli, lung endothelial, alveolar, and airway epithelial cells, as well as activated alveolar macrophages, produce both nitric oxide (.NO) and superoxide anion radicals (O2.-). .NO regulates pulmonary vascular and airway tone and plays an important role in lung host defense against various bacteria. However, .NO may be cytotoxic by inhibiting critical enzymes such as mitochondrial aconitase and ribonucleotide reductase, by S-nitrosolation of thiol groups, or by binding to their iron-sulfur centers. In addition, .NO reacts with O2.- at a near diffusion-limited rate to form the strong oxidant peroxynitrite (ONOO-), which can nitrate and oxidize key amino acids in various lung proteins such as surfactant protein A, and inhibit their functions. The presence of ONOO- in the lungs of patients with acute respiratory distress syndrome has been demonstrated by measuring levels of nitrotyrosine, the stable product of tyrosine nitration. Various studies have shown that inhalation or intratracheal instillation of various respirable mineral dusts or asbestos fibers increased levels of inducible nitric oxide synthase mRNA. In this presentation, we review the evidence for the upregulation of .NO in the lungs of animals exposed to mineral particulates and assess the contribution of reactive nitrogen species in the pathogenesis of the resultant lung injury. PMID:9788891

  3. 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

  4. Ionic Liquids and Ionizing Radiation: Reactivity of Highly Energetic Species

    SciTech Connect

    Wishart, J.F.

    2010-11-04

    Due to their unique properties, ionic liquids present many opportunities for basic research on the interactions of radiation with materials under conditions not previously available. At the same time, there are practical applied reasons for characterizing, understanding, and being able to predict how ionic-liquid-based devices and industrial-scale systems will perform under conditions of extreme reactivity, including radiation. This perspective discusses current issues in ionic liquid physical chemistry, provides a brief introduction to radiation chemistry, draws attention to some key findings in ionic liquid radiation chemistry, and identifies some current hot topics and new opportunities.

  5. The reactive nitrogen species peroxynitrite is a potent inhibitor of renal Na-K-ATPase activity

    PubMed Central

    Reifenberger, Matthew S.; Arnett, Krista L.; Gatto, Craig; Milanick, Mark A.

    2008-01-01

    Peroxynitrite is a reactive nitrogen species produced when nitric oxide and superoxide react. In vivo studies suggest that reactive oxygen species and, perhaps, peroxynitrite can influence Na-K-ATPase function. However, the direct effects of peroxynitrite on Na-K-ATPase function remain unknown. We show that a single bolus addition of peroxynitrite inhibited purified renal Na-K-ATPase activity, with IC50 of 107 ± 9 μM. To mimic cellular/physiological production of peroxynitrite, a syringe pump was used to slowly release (∼0.85 μM/s) peroxynitrite. The inhibition of Na-K-ATPase activity induced by this treatment was similar to that induced by a single bolus addition of equal cumulative concentration. Peroxynitrite produced 3-nitrotyrosine residues on the α, β, and FXYD subunits of the Na pump. Interestingly, the flavonoid epicatechin, which prevented tyrosine nitration, was unable to blunt peroxynitrite-induced ATPase inhibition, suggesting that tyrosine nitration is not required for inhibition. Peroxynitrite led to a decrease in iodoacetamidofluorescein labeling, implying that cysteine modifications were induced. Glutathione was unable to reverse ATPase inhibition. The presence of Na+ and low MgATP during peroxynitrite treatment increased the IC50 to 145 ± 10 μM, while the presence of K+ and low MgATP increased the IC50 to 255 ± 13 μM. This result suggests that the EPNa conformation of the pump is slightly more sensitive to peroxynitrite than the E(K) conformation. Taken together, these results show that peroxynitrite is a potent inhibitor of Na-K-ATPase activity and that peroxynitrite can induce amino acid modifications to the pump. PMID:18701626

  6. Myosin-cross-reactive antigens from four different lactic acid bacteria are fatty acid hydratases.

    PubMed

    Yang, Bo; Chen, Haiqin; Song, Yuanda; Chen, Yong Q; Zhang, Hao; Chen, Wei

    2013-01-01

    The 67 kDa myosin-cross-reactive antigen (MCRA) is a member of the MCRA family of proteins present in a wide range of bacteria and was predicted to have fatty acid isomerase function. We have now characterised the catalytic activity of MCRAs from four LAB stains, including Lactobacillus rhamnosus LGG, L. plantarum ST-III, L. acidophilus NCFM and Bifidobacterium animalis subsp. lactis BB-12. MCRA genes from these strains were cloned and expressed in Escherichia coli, and the recombinant protein function was analysed with lipid profiles by GC-MS. The four MCRAs catalysed the conversion of linoleic acid and oleic acid to their respective 10-hydroxy derivatives, which suggests that MCRA proteins catalyse the first step in conjugated linoleic acid production. This is the first report of MCRA from L. rhamnosus with such catalytic function. PMID:22955678

  7. Reactions and reactivity of myeloperoxidase-derived oxidants: differential biological effects of hypochlorous and hypothiocyanous acids.

    PubMed

    Pattison, David I; Davies, Michael J; Hawkins, Clare L

    2012-08-01

    Myeloperoxidase (MPO) is recognised to play important roles both in the immune system and during the development of numerous human pathologies. MPO is released by activated neutrophils, monocytes and some tissue macrophages, where it catalyses the conversion of hydrogen peroxide to hypohalous acids (HOX; X = Cl, Br, SCN) in the presence of halide and pseudo-halide ions. The major reactive species produced by MPO under physiological conditions are hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN), with the ratio of these oxidants critically dependent on the concentration of thiocyanate ions (SCN⁻). The reactivity and selectivity of HOCl and HOSCN for biological targets are markedly different, indicating that SCN⁻ ions have the potential to modulate both the extent and nature of oxidative damage in vivo. This article reviews recent developments in our understanding of the role of SCN⁻ in modulating the formation of MPO-derived oxidants, particularly in respect to the differences in reaction kinetics and targets of HOCl compared to HOSCN and the ability of these two oxidants to induce damage in biological systems. PMID:22348603

  8. Development of polylactic acid-based materials through reactive modification

    NASA Astrophysics Data System (ADS)

    Fowlks, Alison Camille

    2009-12-01

    Polylactic acid (PLA)-based systems have shown to be of great potential for the development of materials requiring biobased content, biodegradation, and sufficient properties. The efforts in this study are directed toward addressing the current research need to overcome some of the inherent drawbacks of PLA. To meet this need, reactive extrusion was employed to develop new materials based on PLA by grafting, compounding, and polymer blending. In the first part of this work, maleic anhydride (MA) was grafted onto PLA by reactive extrusion. Two structurally different peroxides were used to initiate grafting and results were reported on the basis of grafting, molecular weight, and thermal behavior. An inverse relationship between degree of grafting and molecular weight was established. It was also found that, regardless of peroxide type, there is an optimum peroxid-to-MA ratio of 0.5:2 that promotes maximum grafting, beyond which degradation reactions become predominant. Overall, it was found that the maleated copolymer (MAPLA) could be used as an interfacial modifier in PLA-based composites. Therefore, MAPLA was incorporated into PLA-talc composites in varying concentrations. The influence of the MAPLA addition on the mechanical and thermal behavior was investigated. When added in an optimum concentration, MAPLA improved the tensile strength and crystallization of the composite. Furthermore, microscopic observation confirmed the compatibilization effect of MAPLA in PLA-talc composites. Vinyltrimethoxysilane was free-radically grafted onto the backbone of PLA and subsequently moisture crosslinked. The effects of monomer, initiator, and catalyst concentration on the degree of crosslinking and the mechanical and thermal properties were investigated. The presence of a small amount of catalyst showed to be a major contributor to the crosslinking formation in the time frame investigated, shown by an increase in gel content and decrease in crystallinity. Furthermore

  9. Species-level variability in extracellular production rates of reactive oxygen species by diatoms

    NASA Astrophysics Data System (ADS)

    Schneider, Robin; Roe, Kelly; Hansel, Colleen; Voelker, Bettina

    2016-03-01

    Biological production and decay of the reactive oxygen species (ROS) hydrogen peroxide (H2O2) and superoxide (O2-) likely have significant effects on the cycling of trace metals and carbon in marine systems. In this study, extracellular production rates of H2O2 and O2- were determined for five species of marine diatoms in the presence and absence of light. Production of both ROS was measured in parallel by suspending cells on filters and measuring the ROS downstream using chemiluminescence probes. In addition, the ability of these organisms to break down O2- and H2O2 was examined by measuring recovery of O2- and H2O2 added to the influent medium. O2- production rates ranged from undetectable to 7.3 x 10-16 mol cell-1 hr-1, while H2O2 production rates ranged from undetectable to 3.4 x 10-16 mol cell-1 hr-1. Results suggest that extracellular ROS production occurs through a variety of pathways even amongst organisms of the same genus. Thalassiosira spp. produced more O2- in light than dark, even when the organisms were killed, indicating that O2- is produced via a passive photochemical process on the cell surface. The ratio of H2O¬2 to O2- production rates was consistent with production of H2O2 solely through dismutation of O2- for T. oceanica, while T. pseudonana made much more H2O2 than O2 . T. weissflogii only produced H2O2 when stressed or killed. P. tricornutum cells did not make cell-associated ROS, but did secrete H2O2-producing substances into the growth medium. In all organisms, recovery rates for killed cultures (94-100% H2O2; 10-80% O2-) were consistently higher than those for live cultures (65-95% H2O2; 10-50% O2-). While recovery rates for killed cultures in H2O2 indicate that nearly all H2O2 was degraded by active cell processes, O2- decay appeared to occur via a combination of active and passive processes. Overall, this study shows that the rates and pathways for ROS production and decay vary greatly among diatom species, even between those that are

  10. Species-Level Variability in Extracellular Production Rates of Reactive Oxygen Species by Diatoms

    PubMed Central

    Schneider, Robin J.; Roe, Kelly L.; Hansel, Colleen M.; Voelker, Bettina M.

    2016-01-01

    Biological production and decay of the reactive oxygen species (ROS) hydrogen peroxide (H2O2) and superoxide (O2-) likely have significant effects on the cycling of trace metals and carbon in marine systems. In this study, extracellular production rates of H2O2 and O2- were determined for five species of marine diatoms in the presence and absence of light. Production of both ROS was measured in parallel by suspending cells on filters and measuring the ROS downstream using chemiluminescence probes. In addition, the ability of these organisms to break down O2- and H2O2 was examined by measuring recovery of O2- and H2O2 added to the influent medium. O2- production rates ranged from undetectable to 7.3 × 10−16 mol cell−1 h−1, while H2O2 production rates ranged from undetectable to 3.4 × 10−16 mol cell−1 h−1. Results suggest that extracellular ROS production occurs through a variety of pathways even amongst organisms of the same genus. Thalassiosira spp. produced more O2- in light than dark, even when the organisms were killed, indicating that O2- is produced via a passive photochemical process on the cell surface. The ratio of H2O2 to O2- production rates was consistent with production of H2O2 solely through dismutation of O2- for T. oceanica, while T. pseudonana made much more H2O2 than O2-. T. weissflogii only produced H2O2 when stressed or killed. P. tricornutum cells did not make cell-associated ROS, but did secrete H2O2-producing substances into the growth medium. In all organisms, recovery rates for killed cultures (94–100% H2O2; 10–80% O2-) were consistently higher than those for live cultures (65–95% H2O2; 10–50% O2-). While recovery rates for killed cultures in H2O2 indicate that nearly all H2O2 was degraded by active cell processes, O2- decay appeared to occur via a combination of active and passive processes. Overall, this study shows that the rates and pathways for ROS production and decay vary greatly among diatom species, even

  11. Species-Level Variability in Extracellular Production Rates of Reactive Oxygen Species by Diatoms.

    PubMed

    Schneider, Robin J; Roe, Kelly L; Hansel, Colleen M; Voelker, Bettina M

    2016-01-01

    Biological production and decay of the reactive oxygen species (ROS) hydrogen peroxide (H2O2) and superoxide (O[Formula: see text]) likely have significant effects on the cycling of trace metals and carbon in marine systems. In this study, extracellular production rates of H2O2 and O[Formula: see text] were determined for five species of marine diatoms in the presence and absence of light. Production of both ROS was measured in parallel by suspending cells on filters and measuring the ROS downstream using chemiluminescence probes. In addition, the ability of these organisms to break down O[Formula: see text] and H2O2 was examined by measuring recovery of O[Formula: see text] and H2O2 added to the influent medium. O[Formula: see text] production rates ranged from undetectable to 7.3 × 10(-16) mol cell(-1) h(-1), while H2O2 production rates ranged from undetectable to 3.4 × 10(-16) mol cell(-1) h(-1). Results suggest that extracellular ROS production occurs through a variety of pathways even amongst organisms of the same genus. Thalassiosira spp. produced more O[Formula: see text] in light than dark, even when the organisms were killed, indicating that O[Formula: see text] is produced via a passive photochemical process on the cell surface. The ratio of H2O2 to O[Formula: see text] production rates was consistent with production of H2O2 solely through dismutation of O[Formula: see text] for T. oceanica, while T. pseudonana made much more H2O2 than O[Formula: see text]. T. weissflogii only produced H2O2 when stressed or killed. P. tricornutum cells did not make cell-associated ROS, but did secrete H2O2-producing substances into the growth medium. In all organisms, recovery rates for killed cultures (94-100% H2O2; 10-80% O[Formula: see text]) were consistently higher than those for live cultures (65-95% H2O2; 10-50% O[Formula: see text]). While recovery rates for killed cultures in H2O2 indicate that nearly all H2O2 was degraded by active cell processes, O

  12. Humic acid in drinking well water induces inflammation through reactive oxygen species generation and activation of nuclear factor-κB/activator protein-1 signaling pathways: A possible role in atherosclerosis

    SciTech Connect

    Hseu, You-Cheng; Senthil Kumar, K.J.; Chen, Chih-Sheng; Cho, Hsin-Ju; Lin, Shu-Wei; Shen, Pei-Chun; Lin, Cheng-Wen; Lu, Fung-Jou; Yang, Hsin-Ling

    2014-01-15

    Humic acid (HA) has been implicated as one of the etiological factors in the peripheral vasculopathy of blackfoot disease (BFD) in Taiwan. However, the underlying pathophysiological mechanisms of BFD are not well defined. In this study, we used an in vitro and in vivo model, in which HA (25–200 μg/mL) activated macrophages to produce pro-inflammatory molecules by activating their transcriptional factors. HA exposure induced NO and PGE{sub 2} production followed by induction of iNOS and COX-2 through NF-κB/AP-1 transactivation in macrophages. In addition, the production of TNF-α and IL-1β was significantly increased by HA. Moreover, HA-induced iNOS and COX-2 expression were down-regulated by the NF-κB and AP-1 inhibitors pyrrolidine dithiocarbamate (PDTC) and Tanshinone, respectively. Furthermore, generations of ROS and nitrotyrosine, as well as activation of the AKT and MAPKs signaling cascades were observed after HA exposure. Specifically, HA-induced NF-κB activation was mediated by ROS and AKT, and that HA-induced AP-1 activation was mediated by JNK and ERK. Notably, HA-mediated AKT, JNK, and ERK activation was ROS-independent. The inflammatory potential of HA was correlated with increased expression of HO-1 and Nrf2. Furthermore, an in vivo study confirms that mice exposed to HA, the serum levels of TNF-α and IL-1β was significantly increased in a dose-dependent manner. This report marks the first confirmation that environmental exposure of HA induces inflammation in macrophages, which may be one of the main causes of early atherogenesis in blackfoot disease. - Highlights: • Humic acid (HA) induce pro-inflammatory cytokines and mediators in macrophages. • HA-induced inflammation is mediated by ROS and NF-κB/AP-1 signaling pathways. • The inflammatory potential of HA correlated with activation of Nrf2/HO-1 genes. • HA exposure to mice increased pro-inflammatory cytokines production in vivo. • HA may be one of the main causes of early

  13. Development of nitroxide radicals-containing polymer for scavenging reactive oxygen species from cigarette smoke

    NASA Astrophysics Data System (ADS)

    Yoshitomi, Toru; Kuramochi, Kazuhiro; Binh Vong, Long; Nagasaki, Yukio

    2014-06-01

    We developed a nitroxide radicals-containing polymer (NRP), which is composed of poly(4-methylstyrene) possessing nitroxide radicals as a side chain via amine linkage, to scavenge reactive oxygen species (ROS) from cigarette smoke. In this study, the NRP was coated onto cigarette filters and its ROS-scavenging activity from streaming cigarette smoke was evaluated. The intensity of electron spin resonance signals of the NRP in the filter decreased after exposure to cigarette smoke, indicating consumption of nitroxide radicals. To evaluate the ROS-scavenging activity of the NRP-coated filter, the amount of peroxy radicals in an extract of cigarette smoke was measured using UV-visible spectrophotometry and 1,1-diphenyl-2-picrylhydrazyl (DPPH). The absorbance of DPPH at 517 nm decreased with exposure to cigarette smoke. When NRP-coated filters were used, the decrease in the absorbance of DPPH was prevented. In contrast, both poly[4-(cyclohexylamino)methylstyrene]- and poly(acrylic acid)-coated filters, which have no nitroxide radical, did not show any effect, indicating that the nitroxide radicals in the NRP scavenge the ROS in cigarette smoke. As a result, the extract of cigarette smoke passed through the NRP-coated filter has a lower cellular toxicity than smoke passed through poly[4-(cyclohexylamino)methylstyrene]- and poly(acrylic acid)-coated filters. Accordingly, NRP is a promising material for ROS scavenging from cigarette smoke.

  14. Energy conversion, redox catalysis and generation of reactive oxygen species by respiratory complex I.

    PubMed

    Hirst, Judy; Roessler, Maxie M

    2016-07-01

    Complex I (NADH:ubiquinone oxidoreductase) is critical for respiration in mammalian mitochondria. It oxidizes NADH produced by the Krebs' tricarboxylic acid cycle and β-oxidation of fatty acids, reduces ubiquinone, and transports protons to contribute to the proton-motive force across the inner membrane. Complex I is also a significant contributor to cellular oxidative stress. In complex I, NADH oxidation by a flavin mononucleotide, followed by intramolecular electron transfer along a chain of iron-sulfur clusters, delivers electrons and energy to bound ubiquinone. Either at cluster N2 (the terminal cluster in the chain) or upon the binding/reduction/dissociation of ubiquinone/ubiquinol, energy from the redox process is captured to initiate long-range energy transfer through the complex and drive proton translocation. This review focuses on current knowledge of how the redox reaction and proton transfer are coupled, with particular emphasis on the formation and role of semiquinone intermediates in both energy transduction and reactive oxygen species production. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt. PMID:26721206

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

    PubMed

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

    2013-09-01

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

  16. Reactive oxygen species in signalling the transcriptional activation of WIPK expression in tobacco.

    PubMed

    Xu, Juan; Yang, Kwang-Yeol; Yoo, Seung Jin; Liu, Yidong; Ren, Dongtao; Zhang, Shuqun

    2014-07-01

    Plant mitogen-activated protein kinases represented by tobacco WIPK (wounding-induced protein kinase) and its orthologs in other species are unique in their regulation at transcriptional level in response to stress and pathogen infection. We previously demonstrated that transcriptional activation of WIPK is essential for induced WIPK activity, and activation of salicylic acid-induced protein kinase (SIPK) by the constitutively active NtMEK2(DD) is sufficient to induce WIPK gene expression. Here, we report that the effect of SIPK on WIPK gene expression is mediated by reactive oxygen species (ROS). Using a combination of pharmacological and gain-of-function transgenic approaches, we studied the relationship among SIPK activation, WIPK gene activation in response to fungal cryptogein, light-dependent ROS generation in chloroplasts, and ROS generated via NADPH oxidase. In the conditional gain-of-function GVG-NtMEK2(DD) transgenic tobacco, induction of WIPK expression is dependent on the ROS generation in chloroplasts. Consistently, methyl viologen, an inducer of ROS generation in chloroplasts, highly activated WIPK expression. In addition to chloroplast-originated ROS, H(2)O(2) generated from the cell-surface NADPH oxidase could also activate WIPK gene expression, and inhibition of cryptogein-induced ROS generation also abolished WIPK gene activation. Our data demonstrate that WIPK gene activation is mediated by ROS, which provides a mechanism by which ROS influence cellular signalling processes in plant stress/defence response. PMID:24392654

  17. Humic acid in drinking well water induces inflammation through reactive oxygen species generation and activation of nuclear factor-κB/activator protein-1 signaling pathways: a possible role in atherosclerosis.

    PubMed

    Hseu, You-Cheng; Senthil Kumar, K J; Chen, Chih-Sheng; Cho, Hsin-Ju; Lin, Shu-Wei; Shen, Pei-Chun; Lin, Cheng-Wen; Lu, Fung-Jou; Yang, Hsin-Ling

    2014-01-15

    Humic acid (HA) has been implicated as one of the etiological factors in the peripheral vasculopathy of blackfoot disease (BFD) in Taiwan. However, the underlying pathophysiological mechanisms of BFD are not well defined. In this study, we used an in vitro and in vivo model, in which HA (25-200μg/mL) activated macrophages to produce pro-inflammatory molecules by activating their transcriptional factors. HA exposure induced NO and PGE2 production followed by induction of iNOS and COX-2 through NF-κB/AP-1 transactivation in macrophages. In addition, the production of TNF-α and IL-1β was significantly increased by HA. Moreover, HA-induced iNOS and COX-2 expression were down-regulated by the NF-κB and AP-1 inhibitors pyrrolidine dithiocarbamate (PDTC) and Tanshinone, respectively. Furthermore, generations of ROS and nitrotyrosine, as well as activation of the AKT and MAPKs signaling cascades were observed after HA exposure. Specifically, HA-induced NF-κB activation was mediated by ROS and AKT, and that HA-induced AP-1 activation was mediated by JNK and ERK. Notably, HA-mediated AKT, JNK, and ERK activation was ROS-independent. The inflammatory potential of HA was correlated with increased expression of HO-1 and Nrf2. Furthermore, an in vivo study confirms that mice exposed to HA, the serum levels of TNF-α and IL-1β was significantly increased in a dose-dependent manner. This report marks the first confirmation that environmental exposure of HA induces inflammation in macrophages, which may be one of the main causes of early atherogenesis in blackfoot disease. PMID:24239652

  18. Species differences in the reactivation of organophosphate-inhibited plasma esterases by diacetylmonoxime.

    PubMed

    Ecobichon, D J

    1976-04-01

    A study was conducted to assess whether the protection afforded to organophosphatepoisoned animals by diacetylmonoxime (DAM) was correlated with the reactivation of non-essential aliesterases (AliE). In vitro, the DAM-catalyzed reactivation of plasma AliE and cholinesterases (psi ChE) of rat, rabbit and guinea pig inhibited by 10-5 M diisopropylphosphorofluoridate (DFP) and O,O-dimethyl-2,2-dichlorovinyl phosphate (DDVP) was investigated. Marked reactivation of the rat plasma enzymes was achieved with 10mM DAM. Higher concentrations (30 mM) were necessary for the slow reactivation of rabbit and guinea pig plasma AliE. Reactivation of the psiChE of these species was comparatively slow. Reactivation of DDVP-inhibited esterases proceeded in all species at a more rapid rate than those inhibited by DFP. The dependence of psiChE reactivation upon concomitant more rapid reactivation of AliE by DAM was demonstrated using Sephadex fractionated AliE and psiChE but only a marked effect was observed with the rat, suggesting that the plasma AliE of this species is functionally different. The in vitro observations were confirmed by in vivo studies in rats and rabbits. DAM (50 or 150 mg/kg), administered to atropinized rats 15 min before a lethal dose of DFP, protected the animals. Few severe toxic signs were observed and reactivation of both plasma AliE and psiChE occurred. In contrast, DAM protected the rabbit against a lethal dose of DFP but only reactivation of the erythrocyte acetylcholinesterase was observed. PMID:1276991

  19. SYNTHESIS, REACTIVITY, AND CATALYTIC BEHAVIOR OF IRON/ZINC-CONTAINING SPECIES INVOLVED IN OXIDATION OF HYDROCARBONS UNDER GIF-TYPE CONDITIONS. (R823377)

    EPA Science Inventory

    The present study explores the nature and reactivity of iron- and zinc-containing species
    generated in hydrocarbon-oxidizing Gif(IV)-type solutions Fe catalyst/Zn/O-2 in pyridine/acetic acid
    (10:1 v/v). The ultimate goal of this investigation is to unravel the role of metal...

  20. Balancing the generation and elimination of reactive oxygen species

    USGS Publications Warehouse

    Rodriguez, Rusty; Redman, Regina

    2005-01-01

    Fossil records suggest that bacteria developed the ability to photosynthesize ≈3,500 million years ago (mya), initiating a very slow accumulation of atmospheric oxygen (1). Recent geochemical models suggest that atmospheric oxygen did not accumulate to levels conducive for aerobic life until 500–1,000 mya (2, 3). The oxygenation of Earth's atmosphere resulted in the emergence of aerobic organisms followed by a great diversification of biological species and the eventual evolution of humans.

  1. Principles for integrating reactive species into in vivo biological processes: Examples from exercise physiology.

    PubMed

    Margaritelis, Nikos V; Cobley, James N; Paschalis, Vassilis; Veskoukis, Aristidis S; Theodorou, Anastasios A; Kyparos, Antonios; Nikolaidis, Michalis G

    2016-04-01

    The equivocal role of reactive species and redox signaling in exercise responses and adaptations is an example clearly showing the inadequacy of current redox biology research to shed light on fundamental biological processes in vivo. Part of the answer probably relies on the extreme complexity of the in vivo redox biology and the limitations of the currently applied methodological and experimental tools. We propose six fundamental principles that should be considered in future studies to mechanistically link reactive species production to exercise responses or adaptations: 1) identify and quantify the reactive species, 2) determine the potential signaling properties of the reactive species, 3) detect the sources of reactive species, 4) locate the domain modified and verify the (ir)reversibility of post-translational modifications, 5) establish causality between redox and physiological measurements, 6) use selective and targeted antioxidants. Fulfilling these principles requires an idealized human experimental setting, which is certainly a utopia. Thus, researchers should choose to satisfy those principles, which, based on scientific evidence, are most critical for their specific research question. PMID:26721187

  2. Scavenging capacity of marine carotenoids against reactive oxygen and nitrogen species in a membrane-mimicking system.

    PubMed

    Rodrigues, Eliseu; Mariutti, Lilian R B; Mercadante, Adriana Z

    2012-08-01

    Carotenoid intake has been associated with the decrease of the incidence of some chronic diseases by minimizing the in vivo oxidative damages induced by reactive oxygen (ROS) and nitrogen species (RNS). The carotenoids are well-known singlet oxygen quenchers; however, their capacity to scavenge other reactive species, such as peroxyl radical (ROO•, hydroxyl radical (HO•), hypochlorous acid (HOCl) and anion peroxynitrite (ONOO⁻), still needs to be more extensively studied, especially using membrane-mimicking systems, such as liposomes. Moreover, the identification of carotenoids possessing high antioxidant capacity can lead to new alternatives of drugs or nutritional supplements for prophylaxis or therapy of pathological conditions related to oxidative damages, such as cardiovascular diseases. The capacity to scavenge ROO•, HO•, HOCl and ONOO⁻ of seven carotenoids found in marine organisms was determined in liposomes based on the fluorescence loss of a fluorescent lipid (C₁₁-BODIPY⁵⁸¹/⁵⁹¹) due to its oxidation by these reactive species. The carotenoid-bearing hydroxyl groups were generally more potent ROS scavengers than the carotenes, whilst β-carotene was the most efficient ONOO⁻ scavenger. The role of astaxanthin as an antioxidant should be highlighted, since it was a more potent scavenger of ROO•, HOCl and ONOO⁻ than α-tocopherol. PMID:23015774

  3. Roles of Reactive Oxygen and Nitrogen Species in Pain

    PubMed Central

    Salvemini, Daniela; Little, Joshua W.; Doyle, Timothy; Neumann, William L.

    2011-01-01

    Peroxynitrite (PN, ONOO−) and its reactive oxygen precursor superoxide (SO, O2·−), are critically important in the development of pain of several etiologies including in the development of pain associated with chronic use of opiates such as morphine (also known as opiate-induced hyperalgesia and antinociceptive tolerance). This is now an emerging field in which considerable progress has been made in terms of understanding the relative contribution of SO, PN, and nitroxidative stress in pain signaling at the molecular and biochemical levels. Aggressive research in this area is poised to provide the pharmacological basis for development of novel non-narcotic analgesics that are based upon the unique ability to selectively eliminate SO and/or PN. As we have a better understanding of the role of SO and PN in pathophysiological settings, targeting PN may be a better therapeutic strategy than targeting SO. This is due to the fact that unlike PN, which has no currently known beneficial role, SO may play a significant role in learning and memory [1]. Thus, the best approach may be to spare SO while directly targeting its downstream product, PN. Over the last 15 years, our team has spearheaded research concerning the roles of SO/PN in pain and these results are currently leading to the development of solid therapeutic strategies in this important area. PMID:21277369

  4. Laser spectroscopy of chemically reactive species. [NCO radical

    SciTech Connect

    Wu, Ming; Sears, T.J.

    1993-01-01

    We report the observation of stimulated emission pumping spectra in the NCO radical formed in a supersonic free jet expansion by the reaction between photolytically generated CN radicals and O[sub 2]. The spectra give rotationally resolved information on high lying vibrational levels that are difficult or impossible to detect by conventional single photon spectroscopic techniques. These new data provide detailed insight into the Renner-Teller, spin-orbit and Fermi-resonance coupling in the molecule. They also provide a solid basis for future state-selected chemical and dynamical studies involving this important radical species.

  5. Role of reactive oxygen species and TRP channels in the cough reflex.

    PubMed

    Taylor-Clark, Thomas E

    2016-09-01

    The cough reflex is evoked by noxious stimuli in the airways. Although this reflex is essential for health, it can be triggered chronically in inflammatory and infectious airway disease. Neuronal transient receptor potential (TRP) channels such as ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) are polymodal receptors expressed on airway nociceptive afferent nerves. Reactive oxygen species (ROS) and other reactive compounds are associated with inflammation, from either NADPH oxidase or mitochondria. These reactive compounds cause activation and hyperexcitability of nociceptive afferents innervating the airways, and evidence suggests key contributions of TRPA1 and TRPV1. PMID:27016063

  6. NADPH Oxidase 1 and Its Derived Reactive Oxygen Species Mediated Tissue Injury and Repair

    PubMed Central

    Fu, Xiu-Jun; Peng, Ying-Bo; Hu, Yi-Ping; Shi, You-Zhen; Yao, Min; Zhang, Xiong

    2014-01-01

    Reactive oxygen species are mostly viewed to cause oxidative damage to various cells and induce organ dysfunction after ischemia-reperfusion injury. However, they are also considered as crucial molecules for cellular signal transduction in biology. NADPH oxidase, whose only function is reactive oxygen species production, has been extensively investigated in many cell types especially phagocytes. The deficiency of NADPH oxidase extends the process of inflammation and delays tissue repair, which causes chronic granulomatous disease in patients. NADPH oxidase 1, one member of the NADPH oxidase family, is not only constitutively expressed in a variety of tissues, but also induced to increase expression in both mRNA and protein levels under many circumstances. NADPH oxidase 1 and its derived reactive oxygen species are suggested to be able to regulate inflammation reaction, cell proliferation and migration, and extracellular matrix synthesis, which contribute to the processes of tissue injury and repair. PMID:24669283

  7. Measurements of Reactive Iodine Species on the Isles of Shoals, Gulf of Maine

    NASA Astrophysics Data System (ADS)

    Pikelnaya, O.; Hurlock, S. C.; Trick, S.; Stutz, J.

    2005-12-01

    The chemistry of reactive iodine species has received considerable attention in the past five years. The presence of iodine oxides in the marine boundary layer (MBL) can influence ozone levels, either through well-known catalytic destruction cycles, or through its influence on NO/NO2 and OH/HO2 ratios. In addition, iodine oxides have been linked to aerosol nucleation events in the MBL. Currently, the observational database on reactive iodine species is limited to a very few geographical locations, and the levels of reactive iodine compounds along the North American coast are currently unknown. This lack of information severely restricts our ability to assess the significance of iodine chemistry on a global scale. Here we present the first observations of IO, OIO, and I2 on the Isles of Shoals, Gulf of Maine, during ICARTT 2004, using simultaneous measurements by long-path (LP) and a multi-axis (MAX) differential optical absorption spectroscopy (DOAS) systems.. Both instruments clearly identified reactive iodine species. IO mixing ratios reached 7ppt on several days. OIO was observed during the day, while I2 was elevated at night. Our observations will be discussed with respect to the current knowledge of iodine chemistry, possible iodine sources, and the influence of iodine chemistry on ozone concentrations and aerosol nucleation. Prospects for deriving spatial distributions of reactive iodine species will also be discussed.

  8. Reactive Transport Modeling of Acid Gas Generation and Condensation

    SciTech Connect

    G. Zhahg; N. Spycher; E. Sonnenthal; C. Steefel

    2005-01-25

    Pulvirenti et al. (2004) recently conducted a laboratory evaporation/condensation experiment on a synthetic solution of primarily calcium chloride. This solution represents one potential type of evaporated pore water at Yucca Mountain, Nevada, a site proposed for geologic storage of high-level nuclear waste. These authors reported that boiling this solution to near dryness (a concentration factor >75,000 relative to actual pore waters) leads to the generation of acid condensate (pH 4.5) presumably due to volatilization of HCl (and minor HF and/or HNO{sub 3}). To investigate the various processes taking place, including boiling, gas transport, and condensation, their experiment was simulated by modifying an existing multicomponent and multiphase reactive transport code (TOUGHREACT). This code was extended with a Pitzer ion-interaction model to deal with high ionic strength. The model of the experiment was set-up to capture the observed increase in boiling temperature (143 C at {approx}1 bar) resulting from high concentrations of dissolved salts (up to 8 m CaCl{sub 2}). The computed HCI fugacity ({approx} 10{sup -4} bars) generated by boiling under these conditions is not sufficient to lower the pH of the condensate (cooled to 80 and 25 C) down to observed values unless the H{sub 2}O mass fraction in gas is reduced below {approx}10%. This is because the condensate becomes progressively diluted by H{sub 2}O gas condensation. However, when the system is modeled to remove water vapor, the computed pH of instantaneous condensates decreases to {approx}1.7, consistent with the experiment (Figure 1). The results also show that the HCl fugacity increases, and calcite, gypsum, sylvite, halite, MgCl{sub 2}4H{sub 2}O and CaCl{sub 2} precipitate sequentially with increasing concentration factors.

  9. The role of reactive oxygen species and autophagy in safingol-induced cell death

    PubMed Central

    Ling, L-U; Tan, K-B; Lin, H; Chiu, G N C

    2011-01-01

    Safingol is a sphingolipid with promising anticancer potential, which is currently in phase I clinical trial. Yet, the underlying mechanisms of its action remain largely unknown. We reported here that safingol-induced primarily accidental necrotic cell death in MDA-MB-231 and HT-29 cells, as shown by the increase in the percentage of cells stained positive for 7-aminoactinomycin , collapse of mitochondria membrane potential and depletion of intracellular ATP. Importantly, safingol treatment produced time- and concentration-dependent reactive oxygen species (ROS) generation. Autophagy was triggered following safingol treatment, as reflected by the formation of autophagosomes, acidic vacuoles, increased light chain 3-II and Atg biomarkers expression. Interestingly, scavenging ROS with N-acetyl--cysteine could prevent the autophagic features and reverse safingol-induced necrosis. Our data also suggested that autophagy was a cell repair mechanism, as suppression of autophagy by 3-methyladenine or bafilomycin A1 significantly augmented cell death on 2-5 μ safingol treatment. In addition, Bcl-xL and Bax might be involved in the regulation of safingol-induced autophagy. Finally, glucose uptake was shown to be inhibited by safingol treatment, which was associated with an increase in p-AMPK expression. Taken together, our data suggested that ROS was the mediator of safingol-induced cancer cell death, and autophagy is likely to be a mechanism triggered to repair damages from ROS generation on safingol treatment. PMID:21390063

  10. Autophagy induction upon reactive oxygen species in Cd-stressed Arabidopsis thaliana

    NASA Astrophysics Data System (ADS)

    Zhang, WeiNa; Chen, WenLi

    2010-02-01

    Autophagy is a protein degradation process in which cells recycle cytoplasmic contents when subjected to environmental stress conditions or during certain stages of development. Upon the induction of autophagy, a double membrane autophagosome forms around cytoplasmic components and delivers them to the vacuole for degradation. In plants, autophagy has been shown previously to be induced during abiotic stresses including oxidative stress. Cd, as a toxicity heavy metal, resulted in the production of reactive oxygen species (ROS). In this paper, we demonstrated that ROS contributed to the induction of autophagy in Cd-stressed Arabidopsis thaliana. However, pre-incubation with ascorbic acid (AsA, antioxidant molecule) and catalase (CAT, a H2O2-specific scavenger) decreased the ROS production and the number of autolysosomal-like structures. Together our results indicated that the oxidative condition was essential for autophagy, as treatment with AsA and CAT abolished the formation of autophagosomes, and ROS may function as signal molecules to induce autophagy in abiotic stress.

  11. Oxidases and Peroxidases in Cardiovascular and Lung Disease: New Concepts in Reactive Oxygen Species Signaling

    PubMed Central

    Ghouleh, Imad Al; Khoo, Nicholas K.H.; Knaus, Ulla G.; Griendling, Kathy K.; Touyz, Rhian M.; Thannickal, Victor J.; Barchowsky, Aaron; Nauseef, William M.; Kelley, Eric E.; Bauer, Phillip M.; Darley-Usmar, Victor; Shiva, Sruti; Cifuentes-Pagano, Eugenia; Freeman, Bruce A.; Gladwin, Mark T.; Pagano, Patrick J.

    2011-01-01

    Reactive oxygen species (ROS) are involved in numerous physiological and pathophysiological responses. Increasing evidence implicates ROS as signaling molecules involved in the propagation of cellular pathways. The NADPH oxidase (Nox) family of enzymes is a major source of ROS in the cell and has been related to the progression of many diseases and even in environmental toxicity. The complexity of this family’s effects on cellular processes stems from the fact that there are 7 members, each with unique tissue distribution, cellular localization and expression. Nox proteins also differ in activation mechanisms and the major ROS detected as their product. To add to this complexity, mounting evidence suggests that other cellular oxidases or their products may be involved in Nox regulation. The overall redox and metabolic status of the cell, specifically the mitochondria, also has implications on ROS signaling. Signaling of such molecules as electrophillic fatty acids has impact on many redox sensitive pathologies, and thus, as anti-inflammatory molecules, contributes to the complexity of ROS regulation. The following review is based on the proceedings of a recent international Oxidase Signaling Symposium at the University of Pittsburgh’s Vascular Medicine Institute and Department of Pharmacology and Chemical Biology, and encompasses further interaction and discussion among the presenters. PMID:21722728

  12. Effect of reactive oxygen species on the biosynthesis and structure of newly synthesized proteoglycans.

    PubMed

    Panasyuk, A; Frati, E; Ribault, D; Mitrovic, D

    1994-02-01

    The effect of reactive oxygen species (ROS) generated by a xanthine oxidase hypoxanthine system (mainly H2O2) on proteoglycan (PG) metabolism and structure was investigated in vitro, using cell monolayers of cultured rabbit articular chondrocytes and purified resident and newly synthesized proteoglycans. It was shown that ROS generated in this system frequently stimulate (at low concentrations), and consistently inhibit (at higher concentrations), the incorporation of 35SO4 and 3H-glucosamine into PG molecules synthesized by cultured chondrocytes. The inhibition of isotopes' incorporation at higher enzyme concentrations was suppressed completely by heating xanthine oxidase and allopurinol with superoxide dismutase (SOD) and catalase. ROS at high concentration also inhibited 3H-uridine incorporation but had no effect on 35SO4 and 3H-uridine uptake by the cells. They also alter hyaluronan (HA) and PG monomers by fragmenting the core protein moiety and destroying the hyaluronic acid binding region. Altered PG monomers do not interact with HA to form complexes, but fragmented HA still retain a significant PG monomer-binding capacity. PG-HA complexes are easily and irreversibly destroyed by ROS. These results suggest that ROS may at low fluxes stimulate PG-synthesis under physiological conditions and alter cartilage metabolism and structure in conditions where they are overproduced, such as in rheumatoid arthritis, and in hemochromatosis and other iron storage diseases. PMID:8005511

  13. Reactive Oxygen Species Regulate T Cell Immune Response in the Tumor Microenvironment.

    PubMed

    Chen, Xinfeng; Song, Mengjia; Zhang, Bin; Zhang, Yi

    2016-01-01

    Reactive oxygen species (ROS) produced by cellular metabolism play an important role as signaling messengers in immune system. ROS elevated in the tumor microenvironment are associated with tumor-induced immunosuppression. T cell-based therapy has been recently approved to be effective for cancer treatment. However, T cells often become dysfunctional after reaching the tumor site. It has been reported that ROS participate extensively in T cells activation, apoptosis, and hyporesponsiveness. The sensitivity of T cells to ROS varies among different subsets. ROS can be regulated by cytokines, amino acid metabolism, and enzymatic activity. Immunosuppressive cells accumulate in the tumor microenvironment and induce apoptosis and functional suppression of T cells by producing ROS. Thus, modulating the level of ROS may be important to prolong survival of T cells and enhance their antitumor function. Combining T cell-based therapy with antioxidant treatment such as administration of ROS scavenger should be considered as a promising strategy in cancer treatment, aiming to improve antitumor T cells immunity. PMID:27547291

  14. Reactive Oxygen Species Regulate T Cell Immune Response in the Tumor Microenvironment

    PubMed Central

    Chen, Xinfeng; Song, Mengjia

    2016-01-01

    Reactive oxygen species (ROS) produced by cellular metabolism play an important role as signaling messengers in immune system. ROS elevated in the tumor microenvironment are associated with tumor-induced immunosuppression. T cell-based therapy has been recently approved to be effective for cancer treatment. However, T cells often become dysfunctional after reaching the tumor site. It has been reported that ROS participate extensively in T cells activation, apoptosis, and hyporesponsiveness. The sensitivity of T cells to ROS varies among different subsets. ROS can be regulated by cytokines, amino acid metabolism, and enzymatic activity. Immunosuppressive cells accumulate in the tumor microenvironment and induce apoptosis and functional suppression of T cells by producing ROS. Thus, modulating the level of ROS may be important to prolong survival of T cells and enhance their antitumor function. Combining T cell-based therapy with antioxidant treatment such as administration of ROS scavenger should be considered as a promising strategy in cancer treatment, aiming to improve antitumor T cells immunity. PMID:27547291

  15. 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). PMID:22743846

  16. Mercuric ions inhibit mitogen-activated protein kinase dephosphorylation by inducing reactive oxygen species.

    PubMed

    Haase, Hajo; Engelhardt, Gabriela; Hebel, Silke; Rink, Lothar

    2011-01-01

    Mercury intoxication profoundly affects the immune system, in particular, signal transduction of immune cells. However, the mechanism of the interaction of mercury with cellular signaling pathways, such as mitogen activated protein kinases (MAPK), remains elusive. Therefore, the objective of this study is to investigate three potential ways in which Hg(2+) ions could inhibit MAPK dephosphorylation in the human T-cell line Jurkat: (1) by direct binding to phosphatases; (2) by releasing cellular zinc (Zn(2+)); and (3) by inducing reactive oxygen species (ROS). Hg(2+) causes production of ROS, measured by dihydrorhodamine 123, and triggers ROS-mediated Zn(2+) release, detected with FluoZin-3. Yet, phosphatase-inhibition is not mediated by binding of Zn(2+) or Hg(2+). Rather, phosphatases are inactivated by at least two forms of thiol oxidation; initial inhibition is reversible with reducing agents such as Tris(2-carboxyethyl)phosphine. Prolonged inhibition leads to non-reversible phosphatase oxidation, presumably oxidizing the cysteine thiol to sulfinic- or sulfonic acid. Notably, phosphatases are a particularly sensitive target for Hg(2+)-induced oxidation, because phosphatase activity is inhibited at concentrations of Hg(2+) that have only minor impact on over all thiol oxidation. This phosphatase inhibition results in augmented, ROS-dependent MAPK phosphorylation. MAPK are important regulators of T-cell function, and MAPK-activation by inhibition of phosphatases seems to be one of the molecular mechanisms by which mercury affects the immune system. PMID:20951154

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

    NASA Astrophysics Data System (ADS)

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

    2012-07-01

    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 ClO2 (100 ppm).

  18. Reactive oxygen species: physiological roles in the regulation of vascular cells.

    PubMed

    Vara, D; Pula, G

    2014-01-01

    Reactive oxygen species (ROS) are now appreciated to play several important roles in a number of biological processes and regulate cell physiology and function. ROS are a heterogeneous chemical class that includes radicals, such as superoxide ion (O2(•-)), hydroxyl radical (OH(•)) and nitric oxide (NO(•)), and non-radicals, such as hydrogen peroxide (H2O2), singlet oxygen ((1)O2), hypochlorous acid (HOCl), and peroxynitrite (NO3 (-)). In the cardiovascular system, besides playing a critical role in the development and progression of vasculopathies and other important pathologies such as congestive heart failure, atherosclerosis and thrombosis, ROS also regulate physiological processes. Evidence from a wealth of cardiovascular research studies suggests that ROS act as second messengers and play an essential role in vascular homeostasis by influencing discrete signal transduction pathways in various systems and cell types. They are produced throughout the vascular system, regulate differentiation and contractility of vascular smooth muscle cells, control vascular endothelial cell proliferation and migration, mediate platelet activation and haemostasis, and significantly contribute to the immune response. Our understanding of ROS chemistry and cell biology has evolved to the point of realizing that different ROS have distinct and important roles in cardiovascular physiology. This review will outline sources, functions and molecular mechanisms of action of different ROS in the cardiovascular system and will describe their emerging role in healthy cardiovascular physiology and homeostasis. PMID:24894168

  19. [Role of neutrophil-derived reactive oxygen species in host defense and inflammation].

    PubMed

    Aratani, Yasuaki; Miura, Noriko; Ohno, Naohito; Suzuki, Kazuo

    2012-01-01

    Neutrophil accumulation is a critical event in the pathogenesis of inflammation. The generation of hypochlorous acid by myeloperoxidase (MPO) in neutrophils is crucial to the host defense response. MPO-deficient (MPO-KO) mice showed severely reduced cytotoxicity to Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans and other microorganisms, demonstrating that an MPO-dependent oxidative system is important for in vivo host defense against fungi. On the other hand, impaired reactive oxygen species (ROS) production by neutrophils has previously been shown to cause an abnormal inflammatory response. In the present study, we have found that MPO-KO mice exhibit more severe pulmonary inflammation than wild-type mice when challenged with an intranasal administration of zymosan. In addition to measuring the kinetics of neutrophil accumulation, we also measured the production of macrophage inflammatory protein-2 (MIP-2) in the lung, and we correlate the degree of neutrophil accumulation with the production of this mediator. Our results demonstrate that MPO regulates the production of MIP-2, which may modulate neutrophil accumulation during lung inflammation. PMID:22728595

  20. Colloidal gold nanorings for improved photodynamic therapy through field-enhanced generation of reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Hu, Yue; Yang, Yamin; Wang, Hongjun; Du, Henry

    2013-02-01

    Au nanostructures that exhibit strong localized surface plasmon resonance (SPR) have excellent potential for photo-medicine, among a host of other applications. Here, we report the synthesis and use of colloidal gold nanorings (GNRs) with potential for enhanced photodynamic therapy of cancer. The GNRs were fabricated via galvanic replacement reaction of sacrificial Co nanoparticles in gold salt solution with low molecular weight (Mw = 2,500) poly(vinylpyrrolidone) (PVP) as a stabilizing agent. The size and the opening of the GNRs were controlled by the size of the starting Co particles and the concentration of the gold salt. UV-Vis absorption measurements indicated the tunability of the SPR of the GNRs from 560 nm to 780 nm. MTT assay showed that GNRs were non-toxic and biocompatible when incubated with breast cancer cells as well as the healthy counterpart cells. GNRs conjugated with 5-aminolevulinic acid (5-ALA) photosensitizer precursor led to elevated formation of reactive oxygen species and improved efficacy of photodynamic therapy of breast cancer cells under light irradiation compared to 5-ALA alone. These results can be attributed to significantly enhance localized electromagnetic field of the GNRs.

  1. Reactive oxygen species differentially affect T cell receptor-signaling pathways.

    PubMed

    Cemerski, Saso; Cantagrel, Alain; Van Meerwijk, Joost P M; Romagnoli, Paola

    2002-05-31

    Oxidative stress plays an important role in the induction of T lymphocyte hyporesponsiveness observed in several human pathologies including cancer, rheumatoid arthritis, leprosy, and AIDS. To investigate the molecular basis of oxidative stress-induced T cell hyporesponsiveness, we have developed an in vitro system in which T lymphocytes are rendered hyporesponsive by co-culture with oxygen radical-producing activated neutrophils. We have observed a direct correlation between the level of T cell hyporesponsiveness induced and the concentration of reactive oxygen species produced. Moreover, induction of T cell hyporesponsiveness is blocked by addition of N-acetyl cysteine, Mn(III)tetrakis(4-benzoic acid)porphyrin chloride, and catalase, confirming the critical role of oxidative stress in this system. The pattern of tyrosine-phosphorylated proteins was profoundly altered in hyporesponsive as compared with normal T cells. In hyporesponsive T cells, T cell receptor (TCR) ligation no longer induced phospholipase C-gamma1 activation and caused reduced Ca(2+) flux. In contrast, despite increased levels of ERK1/2 phosphorylation, TCR-dependent activation of mitogen-activated protein kinase ERK1/2 was unaltered in hyporesponsive T lymphocytes. A late TCR-signaling event such as caspase 3 activation was as well unaffected in hyporesponsive T lymphocytes. Our data indicate that TCR-signaling pathways are differentially affected by physiological levels of oxidative stress and would suggest that although "hyporesponsive" T cells have lost certain effector functions, they may have maintained or gained others. PMID:11916964

  2. Endogenous reactive oxygen species content and modulation of tyrosine phosphorylation during sperm capacitation.

    PubMed

    Donà, G; Fiore, C; Tibaldi, E; Frezzato, F; Andrisani, A; Ambrosini, G; Fiorentin, D; Armanini, D; Bordin, L; Clari, G

    2011-10-01

    Generation of controlled amounts of reactive oxygen species (ROS) and phosphorylation of protein tyrosine (Tyr) residues are two main cellular changes involved in sperm capacitation. This study examined the relationship between tyrosine-phosphorylation (Tyr-P) and endogenous ROS production during sperm capacitation, and correlated them with both sperm motility and functionality expressed as acrosome-reacted cells. Immediate ROS generation was observed to peak after a 45-min incubation, followed by a rapid decrease in ROS content and successive regeneration of the ROS peak in 3 h and later. These two peaks were directly correlated with both the Tyr-P process involving sperm heads and tails, and the acrosome reaction (69 ± 8% and 65 ± 4%, respectively). The period of low-ROS content resulted in low Tyr-P patterns, located exclusively in the cell midpiece, and drastic reduction in acrosome-reacted cells. Ascorbic acid addition inhibited both Tyr-P patterns and acrosome reactions, whereas NADPH induced high ROS generation, with Tyr-P patterns located only on sperm tails, and prevented the acrosome reaction. Sperm hyperactivation was insensitive to ROS content. This is an important parameter for evaluation of sperm capacitation, which is achieved only when both ROS generation reaches a peak and Tyr-P involves the sperm head. PMID:20738429

  3. Roles of Reactive Oxygen Species on Insulin Resistance in Adipose Tissue

    PubMed Central

    2016-01-01

    Obesity resulting from the delivery of an excess amount of energy to adipose tissue from glucose or free fatty acids is associated with insulin resistance and adipose tissue inflammation. Reactive oxygen species (ROS) have been implicated as contributors to both the onset and the progression of insulin resistance. ROS can be generated by overloading the mitochondrial oxidative phosphorylation system, and also by nicotinamide adenine dinucleotide phosphate oxidases (NOX) produced by either adipocytes, which only produce NOX4, or by macrophages, which produce mainly NOX2. The source of the ROS might differ in the early, intermediate and late stages of obesity, switching from NOX4-dependence in the early phases to NOX2-dependence, in the intermediate phase, and transiting to mitochondria-dependence later in the time course of obesity. Thus, depending on the stage of obesity, ROS can be generated by three distinct mechanisms: i.e., NOX4, NOX2, and mitochondria. In this review, we will discuss whether NOX4-, NOX2-, and/or mitochondria-derived ROS is/are causal in the onset of adipocyte insulin resistance as obesity progresses. Moreover, we will review the pathophysiological roles of NOX4, NOX2, and mitochondria-derived ROS on adipose tissue inflammation. PMID:27352152

  4. Increase of reactive oxygen species by desferrioxamine during experimental Chagas' disease

    PubMed Central

    Francisco, Amanda Fortes; de Abreu Vieira, Paula Melo; Arantes, Jerusa Marilda; Silva, Maisa; Pedrosa, Maria Lúcia; Elói-Santos, Silvana Maria; Martins-Filho, Olindo Assis; Teixeira-Carvalho, Andréa; Araújo, Márcio Sobreira Silva; Tafuri, Washington Luiz; Carneiro, Cláudia Martins

    2010-01-01

    Oxidative stress is common in inflammatory processes associated with many diseases including Chagas' disease. The aim of the present study was to evaluate, in a murine model, biomarkers of oxidative stress together with components of the antioxidant system in order to provide an overview of the mechanism of action of the iron chelator desferrioxamine (DFO). The study population comprised 48 male Swiss mice, half of which were treated daily by intraperitoneal injection of DFO over a 35-day period, while half were administered sterile water in a similar manner. On the 14th day of the experiment, 12 DFO-treated mice and an equal number of untreated mice were experimentally infected with Trypanosoma cruzi. Serum concentrations of nitric oxide and superoxide dismutase and hepatic levels of total glutathione, thiobarbituric acid reactive species and protein carbonyl, were determined on days 0, 7, 14 and 21 post-infection. The results obtained revealed that DFO enhances antioxidant activity in the host but also increases oxidative stress, indicating that the mode of action of the drug involves a positive contribution to the host together with an effect that is not beneficial to the parasite. PMID:20663295

  5. Nucleic acid relationships among Acholeplasma species.

    PubMed Central

    Aulakh, G S; Stephens, E B; Rose, D L; Tully, J G; Barile, M F

    1983-01-01

    3H-labeled Acholeplasma DNA probes were generated in vitro by the nick-translation method and used to determine the nucleotide sequence homology among the type strains of the eight currently recognized species of Acholeplasma. Very little nucleotide sequence homology (less than or equal to 18%) was found among the eight species, with heteroduplexes showing at least 12% or more mismatching as determined by thermal elution midpoints. The small amount of nucleotide sequence homology among the eight species indicates that these species are quite distinct and are not closely related to each other genomically. PMID:6826524

  6. The reactivity of lattice carbon and nitrogen species in molybdenum (oxy)carbonitrides prepared by single-source routes

    SciTech Connect

    AlShalwi, M.; Hargreaves, J.S.J.; Liggat, J.J.; Todd, D.

    2012-05-15

    Highlights: Black-Right-Pointing-Pointer Molybdenum (oxy)carbonitrides have been prepared from single source routes. Black-Right-Pointing-Pointer Nitrogen species are more reactive than carbon species within the carbonitrides. Black-Right-Pointing-Pointer The reactivity of nitrogen species is a function of carbonitride composition. -- Abstract: Molybdenum (oxy)carbonitrides of different compositions have been prepared from hexamethylenetetramine molybdate and ethylenediamine molybdate precursors and the reactivity of the lattice carbon and nitrogen species within them has been determined by temperature programmed reduction and thermal volatilisation studies. Nitrogen is found to be much more reactive than carbon and the nature of its reactivity is influenced by composition with the presence of carbon enhancing the reactivity of nitrogen. The difference in reactivity observed indicates that molybdenum carbonitrides are not suitable candidates as reagents for which the simultaneous loss of nitrogen and carbon from the lattice would be desirable.

  7. Modeling the diurnal cycle of conserved and reactive species in the convective boundary layer using SOMCRUS

    NASA Astrophysics Data System (ADS)

    Lenschow, Donald H.; Gurarie, David; Patton, Edward G.

    2016-03-01

    We have developed a one-dimensional second-order closure numerical model to study the vertical turbulent transport of trace reactive species in the convective (daytime) planetary boundary layer (CBL), which we call the Second-Order Model for Conserved and Reactive Unsteady Scalars (SOMCRUS). The temporal variation of the CBL depth is calculated using a simple mixed-layer model with a constant entrainment coefficient and zero-order discontinuity at the CBL top. We then calculate time-varying continuous profiles of mean concentrations and vertical turbulent fluxes, variances, and covariances of both conserved and chemically reactive scalars in a diurnally varying CBL. The set of reactive species is the O3-NO-NO2 triad. The results for both conserved and reactive species are compared with large-eddy simulations (LES) for the same free-convection case using the same boundary and initial conditions. For the conserved species, we compare three cases with different combinations of surface fluxes, and CBL and free-troposphere concentrations. We find good agreement of SOMCRUS with LES for the mean concentrations and fluxes of both conserved and reactive species except near the CBL top, where SOMCRUS predicts a somewhat shallower depth, and has sharp transitions in both the mean and turbulence variables, in contrast to more smeared-out variations in the LES due to horizontal averaging. Furthermore, SOMCRUS generally underestimates the variances and species-species covariances. SOMCRUS predicts temperature-species covariances similar to LES near the surface, but much smaller magnitude peak values near the CBL top, and a change in sign of the covariances very near the CBL top, while the LES predicts a change in sign of the covariances in the lower half of the CBL. SOMCRUS is also able to estimate the intensity of segregation (the ratio of the species-species covariance to the product of their means), which can alter the rates of second-order chemical reactions; however, for

  8. Influence of dissolved organic matter on photogenerated reactive oxygen species and metal-oxide nanoparticle toxicity.

    PubMed

    Li, Yang; Niu, Junfeng; Shang, Enxiang; Crittenden, John Charles

    2016-07-01

    The effect of humic acid (HA) or fulvic acid (FA) on reactive oxygen species (ROS) generation by six metal-oxide nanoparticles (NPs) and their toxicities toward Escherichia coli was investigated under UV irradiation. Dissolved organic matter (DOM) decreased OH generation by TiO2, ZnO, and Fe2O3, with FA inhibiting OH generation more than HA. The generated OH in NPs/DOM mixtures was higher than the measured concentrations because DOM consumes OH faster than its molecular probe. None of NPs/FA mixtures produced O2(-). The generated O2(-) concentrations in NPs/HA mixtures (except Fe2O3/HA) were higher than the sum of O2(-) concentrations that produced as NPs and HA were presented by themselves. Synergistic O2(-) generation in NPs/HA mixtures resulted from O2 reduction by electron transferred from photoionized HA to NPs. DOM increased (1)O2 generation by TiO2, CuO, CeO2, and SiO2, and FA promoted (1)O2 generation more than HA. Enhanced (1)O2 generation resulted from DOM sensitization of NPs. HA did not increase (1)O2 generation by ZnO and Fe2O3 primarily because released ions quenched (1)O2 precursor ((3)HA*). Linear correlation was developed between total ROS concentrations generated by NPs/DOM mixtures and bacterial survival rates (R(2) ≥ 0.80). The results implied the necessity of considering DOM when investigating the photoreactivity of NPs. PMID:27064207

  9. Effect of reactive oxygen species on lysosomal membrane integrity. A study on a lysosomal fraction.

    PubMed

    Zdolsek, J M; Svensson, I

    1993-01-01

    Using a lysosome-enriched "light mitochondrial" fraction of a rat liver homogenate, the effects of the reactive oxygen species hydrogen peroxide, superoxide- and hydroxyl radicals were determined. Alterations in the intralysosomal pH and the release of a lysosomal marker enzyme, N-acetyl-glucosaminidase, were used as indicators of changes in the lysosomal membrane integrity. Lipid peroxidation of the fraction was assayed by TBARS measurement. Neither superoxide radicals, generated by hypoxanthine/xanthine oxidase, nor a bolus dose of hydrogen peroxide (0.5-1.5 mM) induced any lysosomal damage. If, however, Fe(III)ADP was included in the superoxide radical-generating system, lysosomal membrane damage was detected, both as an increase in lysosomal pH and as a release of N-acetyl-glucosaminidase, but only after a lag phase of about 7 min. Lipid peroxidation, on the other hand, proceeded gradually. Lysosomes treated with hydrogen peroxide displayed similar dose-dependent alterations, albeit only if both Fe(III)ADP and the reducing amino acid cysteine were added. In the latter system, however, alterations of the lysosomal membrane stability occurred more rapidly, showing a lag phase of only 2 min. Lipid peroxidation, which proceeded faster and displayed no lag phase, levelled out within 10 min. The results indicate that neither superoxide radicals nor hydrogen peroxide are by themselves damaging to lysosomes. Available catalytically active iron in Fe(II) form, however, allows reactions yielding powerful oxidative species--probably hydroxyl radicals formed via Fenton reactions--to take place inducing peroxidation of the lysosomal membranes resulting in dissipation of the proton-gradient and leakage of their enzyme contents. PMID:8148962

  10. Stabilization of thylakoid membranes in isoprene-emitting plants reduces formation of reactive oxygen species.

    PubMed

    Velikova, Violeta; Sharkey, Thomas D; Loreto, Francesco

    2012-01-01

    Isoprene is emitted by a significant fraction of the world's vegetation. Isoprene makes leaves more thermotolerant, yet we do not fully understand how. We have recently shown that isoprene stabilizes thylakoid membranes under heat stress. Here we show that heat-stressed, isoprene-emitting transgenic Arabidopsis plants also produce a lower pool of reactive oxygen and reactive nitrogen species, and that this was especially due to a lower accumulation of H2O2 in isoprene emitting plants. It remains difficult to disentangle whether in heat stressed plants isoprene also directly reacts with and quenches reactive oxygen species (ROS), or reduces ROS formation by stabilizing thylakoids. We present considerations that make the latter a more likely mechanism, under our experimental circumstances. PMID:22301981

  11. NADPH Oxidase- and Mitochondria-derived Reactive Oxygen Species in Proinflammatory Microglial Activation: A Bipartisan Affair?

    PubMed Central

    Bordt, Evan A.; Polster, Brian M.

    2014-01-01

    Microglia are the resident immune cells of the brain and play major roles in central nervous system development, maintenance, and disease. Brain insults cause microglia to proliferate, migrate, and transform into one or more activated states. Classical M1 activation triggers the production of proinflammatory factors such as tumor necrosis factor- α (TNF-α), interleukin-1β (IL-1β), nitric oxide (NO), and reactive oxygen species which, in excess, can exacerbate brain injury. The mechanisms underlying microglial activation are not fully understood, yet reactive oxygen species are increasingly implicated as mediators of microglial activation. In this review, we highlight studies linking reactive oxygen species, in particular hydrogen peroxide derived from NADPH oxidase-generated superoxide, to the classical activation of microglia. In addition, we critically evaluate controversial evidence suggesting a specific role for mitochondrial reactive oxygen species in the activation of the NLRP3 inflammasome, a multiprotein complex that mediates the production of IL-1β and IL-18. Finally, the limitations of common techniques used to implicate mitochondrial ROS in microglial and inflammasome activation, such as the use of the mitochondrially-targeted ROS indicator MitoSOX and the mitochondrially-targeted antioxidant MitoTEMPO, are also discussed. PMID:25091898

  12. Mitochondrial function and reactive oxygen species action in relation to boar motility

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flow cytometric assays were developed for reactive oxygen species (ROS) formation (ROS-induced oxidization of hydroethidine to ethidium), membrane lipid peroxidation (C11-BODIPY-581/591 oxidation), and mitochondrial transmembrane potential (MMP) (MMP-induced JC-1 aggregation, red fluorescence) in vi...

  13. Water-soluble fullerene materials for bioapplications: photoinduced reactive oxygen species generation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The photoinduced reactive oxygen species (ROS) generation from several water-soluble fullerenes was examined. Macromolecular or small molecular water-soluble fullerene complexes/derivatives were prepared and their 1O2 and O2•- generation abilities were evaluated by EPR spin-trapping methods. As a r...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  15. Detection of reactive oxygen species in primary cultures of cerebellar granule cells.

    PubMed

    Atlante, A; Passarella, S

    1999-12-01

    The aim of this work was to develop a novel procedure useful to detect the formation of two reactive oxygen species, i.e. superoxide and singlet oxygen, in neuron monolayer primary cultures, thus, making possible the investigation of the effect of certain compounds on reactive oxygen species formation. Thus, use was made of two reactive oxygen species detecting systems consisting of ferricytochrome c (Fe-cyt c) and imidazole-RNO (N, N-dimethyl-4-nitrosoaniline) which allow for the photometric detection of superoxide anion and singlet oxygen, respectively. Both of them were used to assess the formation of reactive oxygen species in cerebellar granule cells exposed to glutamate: both superoxide anion and singlet oxygen proved to be generated in glutamate neurotoxicity in a way sensitive to glutamate NMDA-receptor inhibitor, MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a, d)cyclohepten-5,10-imine hydrogen maleate), to Ca(2+) complexing agent, EGTA, and to certain antioxidants. In principle, the reported protocol can be applied to any cell type in culture. PMID:10592334

  16. Effects of reactive oxygen species action on sperm function in spermatozoa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reactive oxygen species (ROS) formation and lipid peroxidation have been recognized as problems for sperm survival and fertility. The precise roles and detection of superoxide (SO), hydrogen peroxide (HP), and membrane lipid peroxidation have been problematic because of the low specificity and sens...

  17. Mitochondrial function and reactive oxygen species action in relation to boar motility.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flow cytometric assays of viable boar sperm were developed to measure reactive oxygen species (ROS) formation (oxidization of hydroethidine to ethidium), membrane lipid peroxidation (oxidation of lipophilic probe C11-BODIPY581/591), and mitochondrial inner transmembrane potential (aggregation of mit...

  18. Reactive Oxygen Species Are Involved in Plant Defense against a Gall Midge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reactive oxygen species (ROS) play a major role in plant defense against pathogens, but evidence for their role in defense against insects is still preliminary and inconsistent. In this study, we examined the potential role of ROS in defense of wheat and rice against Hessian fly (Mayetiola destruct...

  19. Interconnection of reactive oxygen species chemistry across the interfaces of atmospheric, environmental, and biological processes.

    PubMed

    Anglada, Josep M; Martins-Costa, Marilia; Francisco, Joseph S; Ruiz-López, Manuel F

    2015-03-17

    Oxidation reactions are ubiquitous and play key roles in the chemistry of the atmosphere, in water treatment processes, and in aerobic organisms. Ozone (O3), hydrogen peroxide (H2O2), hydrogen polyoxides (H2Ox, x > 2), associated hydroxyl and hydroperoxyl radicals (HOx = OH and HO2), and superoxide and ozonide anions (O2(-) and O3(-), respectively) are the primary oxidants in these systems. They are commonly classified as reactive oxygen species (ROS). Atmospheric chemistry is driven by a complex system of chain reactions of species, including nitrogen oxides, hydroxyl and hydroperoxide radicals, alkoxy and peroxy radicals, and ozone. HOx radicals contribute to keeping air clean, but in polluted areas, the ozone concentration increases and creates a negative impact on plants and animals. Indeed, ozone concentration is used to assess air quality worldwide. Clouds have a direct effect on the chemical composition of the atmosphere. On one hand, cloud droplets absorb many trace atmospheric gases, which can be scavenged by rain and fog. On the other hand, ionic species can form in this medium, which makes the chemistry of the atmosphere richer and more complex. Furthermore, recent studies have suggested that air-cloud interfaces might have a significant impact on the overall chemistry of the troposphere. Despite the large differences in molecular composition, concentration, and thermodynamic conditions among atmospheric, environmental, and biological systems, the underlying chemistry involving ROS has many similarities. In this Account, we examine ROS and discuss the chemical characteristics common to all of these systems. In water treatment, ROS are key components of an important subset of advanced oxidation processes. Ozonation, peroxone chemistry, and Fenton reactions play important roles in generating sufficient amounts of hydroxyl radicals to purify wastewater. Biochemical processes within living organisms also involve ROS. These species can come from pollutants in

  20. Correlation between the acid-base properties of the La2O3 catalyst and its methane reactivity.

    PubMed

    Chu, Changqing; Zhao, Yonghui; Li, Shenggang; Sun, Yuhan

    2016-06-28

    Density functional theory and coupled cluster theory calculations were carried out to study the effects of the acid-base properties of the La2O3 catalyst on its catalytic activity in the oxidative coupling of methane (OCM) reaction. The La(3+)-O(2-) pair site for CH4 activation is considered as a Lewis acid-Brönsted base pair. Using the Lewis acidity and the Brönsted basicity in the fluoride affinity and proton affinity scales as quantitative measures of the acid-base properties, the energy barrier for CH4 activation at the pair site can be linearly correlated with these acid-base properties. The pair site consisting of a strong Lewis acid La(3+) site and a strong Brönsted base O(2-) site is the most reactive for CH4 activation. In addition, the basicity of the La2O3 catalyst was traditionally measured by temperature-programmed desorption of CO2, but the CO2 chemisorption energy is better regarded as a combined measure of the acid-base properties of the pair site. A linear relationship of superior quality was found between the energy barrier for CH4 activation and the CO2 chemisorption energy, and the pair site favorable for CO2 chemisorption is also more reactive for CH4 activation, leading to the conflicting role of the "basicity" of the La2O3 catalyst in the OCM reaction. The necessity for very high reaction temperatures in the OCM reaction is rationalized by the requirement for the recovery of the most reactive acid-base pair site, which unfortunately also reacts most readily with the byproduct CO2 to form the very stable CO3(2-) species. PMID:27265027

  1. Phase I Metabolic Stability and Electrophilic Reactivity of 2-Phenylaminophenylacetic Acid Derived Compounds.

    PubMed

    Pang, Yi Yun; Tan, Yee Min; Chan, Eric Chun Yong; Ho, Han Kiat

    2016-07-18

    Diclofenac and lumiracoxib are two highly analogous 2-phenylaminophenylacetic acid anti-inflammatory drugs exhibiting occasional dose-limiting hepatotoxicities. Prior data indicate that bioactivation and reactive metabolite formation play roles in the observed toxicity, but the exact chemical influence of the substituents remains elusive. In order to elucidate the role of chemical influence on metabolism related toxicity, metabolic stability and electrophilic reactivity were investigated for a series of structurally related analogues and their resulting metabolites. The resulting analogues embody progressive physiochemical changes through varying halogeno- and aliphatic substituents at two positions and were subjected to in vitro human liver microsomal metabolic stability and cell-based GSH depletion assays (to measure electrophilic reactivity). LC-MS/MS analysis of the GSH trapped reactive intermediates derived from the analogues was then used to identify the putative structures of reactive metabolites. We found that chemical modifications of the structural backbone led to noticeable perturbations of metabolic stability, electrophilic reactivity, and structures and composition of reactive metabolites. With the acquired data, the relationships between stability, reactivity, and toxicity were investigated in an attempt to correlate between Phase I metabolism and in vitro toxicity. A positive correlation was identified between reactivity and in vitro toxicity, indicating that electrophilic reactivity can be an indicator for in vitro toxicity. All in all, the effect of substituents on the structures and reactivity of the metabolites, however subtle the changes, should be taken into consideration during future drug design involving similar chemical features. PMID:27245204

  2. Reactivity of chlorine radical with submicron palmitic acid particles: kinetic measurements and product identification

    NASA Astrophysics Data System (ADS)

    Mendez, M.; Ciuraru, R.; Gosselin, S.; Batut, S.; Visez, N.; Petitprez, D.

    2013-12-01

    The heterogeneous reaction of Cl• radicals with submicron palmitic acid (PA) particles was studied in an aerosol flow tube in the presence or in the absence of O2. Fine particles were generated by homogeneous condensation of PA vapours and introduced into the reactor, where chlorine atoms were produced by photolysis of Cl2 using UV lamps surrounding the reactor. The effective reactive uptake coefficient (γ) has been determined from the rate loss of PA measured by gas chromatography-mass spectrometer (GC/MS) analysis of reacted particles as a function of the chlorine exposure. In the absence of O2, γ = 14 ± 5 indicates efficient secondary chemistry involving Cl2. GC/MS analysis has shown the formation of monochlorinated and polychlorinated compounds in the oxidized particles. Although the PA particles are solid, the complete mass can be consumed. In the presence of oxygen, the reaction is still dominated by secondary chemistry but the propagation chain length is smaller than in the absence of O2, which leads to an uptake coefficient γ = 3 ± 1. In the particulate phase, oxocarboxylic acids and dicarboxylic acids were identified by GC/MS. The formation of alcohols and monocarboxylic acids is also suspected. A reaction pathway for the main products and more functionalized species is proposed. All these results show that solid organic particles could be efficiently oxidized by gas-phase radicals not only on their surface but also in bulk by mechanisms which are still unclear. They help to understand the aging of primary tropospheric aerosol containing fatty acids.

  3. A carnosine intervention study in overweight human volunteers: bioavailability and reactive carbonyl species sequestering effect

    NASA Astrophysics Data System (ADS)

    Regazzoni, Luca; de Courten, Barbora; Garzon, Davide; Altomare, Alessandra; Marinello, Cristina; Jakubova, Michaela; Vallova, Silvia; Krumpolec, Patrik; Carini, Marina; Ukropec, Jozef; Ukropcova, Barbara; Aldini, Giancarlo

    2016-06-01

    Carnosine is a natural dipeptide able to react with reactive carbonyl species, which have been recently associated with the onset and progression of several human diseases. Herein, we report an intervention study in overweight individuals. Carnosine (2 g/day) was orally administered for twelve weeks in order to evaluate its bioavailability and metabolic fate. Two carnosine adducts were detected in the urine samples of all subjects. Such adducts are generated from a reaction with acrolein, which is one of the most toxic and reactive compounds among reactive carbonyl species. However, neither carnosine nor adducts have been detected in plasma. Urinary excretion of adducts and carnosine showed a positive correlation although a high variability of individual response to carnosine supplementation was observed. Interestingly, treated subjects showed a significant decrease in the percentage of excreted adducts in reduced form, accompanied by a significant increase of the urinary excretion of both carnosine and carnosine-acrolein adducts. Altogether, data suggest that acrolein is entrapped in vivo by carnosine although the response to its supplementation is possibly influenced by individual diversities in terms of carnosine dietary intake, metabolism and basal production of reactive carbonyl species.

  4. A carnosine intervention study in overweight human volunteers: bioavailability and reactive carbonyl species sequestering effect.

    PubMed

    Regazzoni, Luca; de Courten, Barbora; Garzon, Davide; Altomare, Alessandra; Marinello, Cristina; Jakubova, Michaela; Vallova, Silvia; Krumpolec, Patrik; Carini, Marina; Ukropec, Jozef; Ukropcova, Barbara; Aldini, Giancarlo

    2016-01-01

    Carnosine is a natural dipeptide able to react with reactive carbonyl species, which have been recently associated with the onset and progression of several human diseases. Herein, we report an intervention study in overweight individuals. Carnosine (2 g/day) was orally administered for twelve weeks in order to evaluate its bioavailability and metabolic fate. Two carnosine adducts were detected in the urine samples of all subjects. Such adducts are generated from a reaction with acrolein, which is one of the most toxic and reactive compounds among reactive carbonyl species. However, neither carnosine nor adducts have been detected in plasma. Urinary excretion of adducts and carnosine showed a positive correlation although a high variability of individual response to carnosine supplementation was observed. Interestingly, treated subjects showed a significant decrease in the percentage of excreted adducts in reduced form, accompanied by a significant increase of the urinary excretion of both carnosine and carnosine-acrolein adducts. Altogether, data suggest that acrolein is entrapped in vivo by carnosine although the response to its supplementation is possibly influenced by individual diversities in terms of carnosine dietary intake, metabolism and basal production of reactive carbonyl species. PMID:27265207

  5. A carnosine intervention study in overweight human volunteers: bioavailability and reactive carbonyl species sequestering effect

    PubMed Central

    Regazzoni, Luca; de Courten, Barbora; Garzon, Davide; Altomare, Alessandra; Marinello, Cristina; Jakubova, Michaela; Vallova, Silvia; Krumpolec, Patrik; Carini, Marina; Ukropec, Jozef; Ukropcova, Barbara; Aldini, Giancarlo

    2016-01-01

    Carnosine is a natural dipeptide able to react with reactive carbonyl species, which have been recently associated with the onset and progression of several human diseases. Herein, we report an intervention study in overweight individuals. Carnosine (2 g/day) was orally administered for twelve weeks in order to evaluate its bioavailability and metabolic fate. Two carnosine adducts were detected in the urine samples of all subjects. Such adducts are generated from a reaction with acrolein, which is one of the most toxic and reactive compounds among reactive carbonyl species. However, neither carnosine nor adducts have been detected in plasma. Urinary excretion of adducts and carnosine showed a positive correlation although a high variability of individual response to carnosine supplementation was observed. Interestingly, treated subjects showed a significant decrease in the percentage of excreted adducts in reduced form, accompanied by a significant increase of the urinary excretion of both carnosine and carnosine-acrolein adducts. Altogether, data suggest that acrolein is entrapped in vivo by carnosine although the response to its supplementation is possibly influenced by individual diversities in terms of carnosine dietary intake, metabolism and basal production of reactive carbonyl species. PMID:27265207

  6. Nanopore reactive adsorbents for the high-efficiency removal of waste species

    DOEpatents

    Yang, Arthur Jing-Min; Zhang, Yuehua

    2005-01-04

    A nanoporous reactive adsorbent incorporates a relatively small number of relatively larger reactant, e.g., metal, enzyme, etc., particles (10) forming a discontinuous or continuous phase interspersed among and surrounded by a continuous phase of smaller adsorbent particles (12) and connected interstitial pores (14) therebetween. The reactive adsorbent can effectively remove inorganic or organic impurities in a liquid by causing the liquid to flow through the adsorbent. For example, silver ions may be adsorbed by the adsorbent particles (12) and reduced to metallic silver by reducing metal, such as ions, as the reactant particles (10). The column can be regenerated by backwashing with the liquid effluent containing, for example, acetic acid.

  7. OH reactivity measurements from Boreal tree species in a plant chamber

    NASA Astrophysics Data System (ADS)

    Nölscher, Anke; Custer, Thomas; Sinha, Vinayak; Kiendler-Scharr, Astrid; Kleist, Einhard; Tillmann, Ralf; Wildt, Jürgen; Williams, Jonathan

    2010-05-01

    Boreal forest covers a large area (ca. 15 million km2) comparable in size to the Tropical rain forest (ca. 17 million km2). The vegetation in Boreal regions is typically conifer forest which is known to emit significant amounts of biogenic volatile organic compounds (BVOCS), such as monoterpenes, sesquiterpenes, methanol and acetone. Many of these organic chemicals react rapidly with hydroxyl (OH) radicals to produce aerosols or secondary pollutants such as ozone. The total effect of the emitted species on the OH radical can be determined by measuring the total OH reactivity directly. Therefore a new measurement method was recently devised (Sinha et al., 2008). The Jülich plant atmosphere chamber (JPAC) at the Forschungszentrum-Jülich was used to investigate the overall reactivity of emissions from several Boreal tree species under controlled conditions in October 2009. Vegetation, temperature and light intensities typical of the Hyytiälä measurement station in Finland were used in these experiments and the levels of CO2, humidity and NOx were controlled. In addition to the reactivity measurement, a gas chromatograph (GC), a proton transfer reaction mass spectrometer (PTRMS) and a time-of-flight PTRMS (TOF-PTRMS) were used to quantify individual organic chemicals emitted by the plants for comparison with the overall reactivity. Experiments were performed under three different conditions. 1) Lower temperatures (T=20° C) resulted in low plant emissions with no diurnal variation. The total measured OH reactivity ranged from below detection limit (3 sec-1) to 7 sec-1 during the day and overnight rose to 8-13 sec-1. 2) Higher temperatures (T=35° C) produced higher emissions of volatile organic compounds and a clear diurnal trend. Reactivity data matched well with these results rising to 30-50 sec-1 by day and during the night sinking again to 8-13 sec-1. 3) Finally a control experiment was performed without trees in the plant chamber. In this experiment

  8. Reactivity of Hontomín carbonate rocks to acidic solution injection: reactive "push-pull" tracer tests results

    NASA Astrophysics Data System (ADS)

    De Gaspari, Francesca; Cabeza, Yoar; Luquot, Linda; Rötting, Tobias; Saaltink, Maarten W.; Carrera, Jesus

    2014-05-01

    Several field tests will be carried out in order to characterize the reservoir for CO2 injection in Hontomín (Burgos, Spain) as part of the Compostilla project of "Fundación Ciudad de la Energía" (CIUDEN). Once injected, the dissolution of the CO2 in the resident brine will increase the acidity of the water and lead to the dissolution of the rocks, constituted mainly by carbonates. This mechanism will cause changes in the aquifer properties such as porosity and permeability. To reproduce the effect of the CO2 injection, a reactive solution with 2% of acetic acid is going to be injected in the reservoir and extracted from the same well (reactive "push-pull" tracer tests) to identify and quantify the geochemical reactions occurring into the aquifer. The reactivity of the rock will allow us also to evaluate the changes of its properties. Previously, theoretical calculations of Damkhöler numbers were done to determine the acid concentrations and injection flow rates needed to generate ramified-wormholes patterns, during theses "push-pull" experiments. The aim of this work is to present the results and a preliminary interpretation of the field tests.

  9. Nanofiltration, bipolar electrodialysis and reactive extraction hybrid system for separation of fumaric acid from fermentation broth.

    PubMed

    Prochaska, Krystyna; Staszak, Katarzyna; Woźniak-Budych, Marta Joanna; Regel-Rosocka, Magdalena; Adamczak, Michalina; Wiśniewski, Maciej; Staniewski, Jacek

    2014-09-01

    A novel approach based on a hybrid system allowing nanofiltration, bipolar electrodialysis and reactive extraction, was proposed to remove fumaric acid from fermentation broth left after bioconversion of glycerol. The fumaric salts can be concentrated in the nanofiltration process to a high yield (80-95% depending on pressure), fumaric acid can be selectively separated from other fermentation components, as well as sodium fumarate can be conversed into the acid form in bipolar electrodialysis process (stack consists of bipolar and anion-exchange membranes). Reactive extraction with quaternary ammonium chloride (Aliquat 336) or alkylphosphine oxides (Cyanex 923) solutions (yield between 60% and 98%) was applied as the final step for fumaric acid recovery from aqueous streams after the membrane techniques. The hybrid system permitting nanofiltration, bipolar electrodialysis and reactive extraction was found effective for recovery of fumaric acid from the fermentation broth. PMID:24983693

  10. Reactive species in non-equilibrium atmospheric-pressure plasmas: Generation, transport, and biological effects

    NASA Astrophysics Data System (ADS)

    Lu, X.; Naidis, G. V.; Laroussi, M.; Reuter, S.; Graves, D. B.; Ostrikov, K.

    2016-05-01

    Non-equilibrium atmospheric-pressure plasmas have recently become a topical area of research owing to their diverse applications in health care and medicine, environmental remediation and pollution control, materials processing, electrochemistry, nanotechnology and other fields. This review focuses on the reactive electrons and ionic, atomic, molecular, and radical species that are produced in these plasmas and then transported from the point of generation to the point of interaction with the material, medium, living cells or tissues being processed. The most important mechanisms of generation and transport of the key species in the plasmas of atmospheric-pressure plasma jets and other non-equilibrium atmospheric-pressure plasmas are introduced and examined from the viewpoint of their applications in plasma hygiene and medicine and other relevant fields. Sophisticated high-precision, time-resolved plasma diagnostics approaches and techniques are presented and their applications to monitor the reactive species and plasma dynamics in the plasma jets and other discharges, both in the gas phase and during the plasma interaction with liquid media, are critically reviewed. The large amount of experimental data is supported by the theoretical models of reactive species generation and transport in the plasmas, surrounding gaseous environments, and plasma interaction with liquid media. These models are presented and their limitations are discussed. Special attention is paid to biological effects of the plasma-generated reactive oxygen and nitrogen (and some other) species in basic biological processes such as cell metabolism, proliferation, survival, etc. as well as plasma applications in bacterial inactivation, wound healing, cancer treatment and some others. Challenges and opportunities for theoretical and experimental research are discussed and the authors' vision for the emerging convergence trends across several disciplines and application domains is presented to

  11. Ethanol and Reactive Species Increase Basal Sequence Heterogeneity of Hepatitis C Virus and Produce Variants with Reduced Susceptibility to Antivirals

    PubMed Central

    Seronello, Scott; Montanez, Jessica; Presleigh, Kristen; Barlow, Miriam; Park, Seung Bum; Choi, Jinah

    2011-01-01

    Hepatitis C virus (HCV) exhibits a high level of genetic variability, and variants with reduced susceptibility to antivirals can occur even before treatment begins. In addition, alcohol decreases efficacy of antiviral therapy and increases sequence heterogeneity of HCV RNA but how ethanol affects HCV sequence is unknown. Ethanol metabolism and HCV infection increase the level of reactive species that can alter cell metabolism, modify signaling, and potentially act as mutagen to the viral RNA. Therefore, we investigated whether ethanol and reactive species affected the basal sequence variability of HCV RNA in hepatocytes. Human hepatoma cells supporting a continuous replication of genotype 1b HCV RNA (Con1, AJ242652) were exposed to ethanol, acetaldehyde, hydrogen peroxide, or L-buthionine-S,R-sulfoximine (BSO) that decreases intracellular glutathione as seen in patients. Then, NS5A region was sequenced and compared with genotype 1b HCV sequences in the database. Ethanol and BSO elevated nucleotide and amino acid substitution rates of HCV RNA by 4–18 folds within 48 hrs which were accompanied by oxidative RNA damage. Iron chelator and glutathione ester decreased both RNA damage and mutation rates. Furthermore, infectious HCV and HCV core gene were sufficient to induce oxidative RNA damage even in the absence of ethanol or BSO. Interestingly, the dn/ds ratio and percentage of sites undergoing positive selection increased with ethanol and BSO, resulting in an increased detection of NS5A variants with reduced susceptibility to interferon alpha, cyclosporine, and ribavirin and others implicated in immune tolerance and modulation of viral replication. Therefore, alcohol is likely to synergize with virus-induced oxidative/nitrosative stress to modulate the basal mutation rate of HCV. Positive selection induced by alcohol and reactive species may contribute to antiviral resistance. PMID:22087316

  12. 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

    2015-01-01

    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. PMID:25960012

  13. A Porous Tissue Engineering Scaffold Selectively Degraded by Cell-Generated Reactive Oxygen Species

    PubMed Central

    Martin, John R.; Gupta, Mukesh K.; Page, Jonathan M.; Yu, Fang; Davidson, Jeffrey M.; Guelcher, Scott A.

    2014-01-01

    Biodegradable tissue engineering scaffolds are commonly fabricated from poly(lactide-co-glycolide) (PLGA) or similar polyesters that degrade by hydrolysis. PLGA hydrolysis generates acidic breakdown products that trigger an accelerated, autocatalytic degradation mechanism that can create mismatched rates of biomaterial breakdown and tissue formation. Reactive oxygen species (ROS) are key mediators of cell function in both health and disease, especially at sites of inflammation and tissue healing, and induction of inflammation and ROS are natural components of the in vivo response to biomaterial implantation. Thus, polymeric biomaterials that are selectively degraded by cell-generated ROS may have potential for creating tissue engineering scaffolds with better matched rates of tissue in-growth and cell-mediated scaffold biodegradation. To explore this approach, a series of poly(thioketal) (PTK) urethane (PTK-UR) biomaterial scaffolds were synthesized that degrade specifically by an ROS-dependent mechanism. PTK-UR scaffolds had significantly higher compressive moduli than analogous poly(ester urethane) (PEUR) scaffolds formed from hydrolytically-degradable ester-based diols (p < 0.05). Unlike PEUR scaffolds, the PTK-UR scaffolds were stable under aqueous conditions out to 25 weeks but were selectively degraded by ROS, indicating that their biodegradation would be exclusively cell-mediated. The in vitro oxidative degradation rates of the PTK-URs followed first-order degradation kinetics, were significantly dependent on PTK composition (p < 0.05), and correlated to ROS concentration. In subcutaneous rat wounds, PTK-UR scaffolds supported cellular infiltration and granulation tissue formation, followed first-order degradation kinetics over 7 weeks, and produced significantly greater stenting of subcutaneous wounds compared to PEUR scaffolds. These combined results indicate that ROS-degradable PTK-UR tissue engineering scaffolds have significant advantages over analogous

  14. Ethylene-induced flavonol accumulation in guard cells suppresses reactive oxygen species and moderates stomatal aperture.

    PubMed

    Watkins, Justin M; Hechler, Paul J; Muday, Gloria K

    2014-04-01

    Guard cell swelling controls the aperture of stomata, pores that facilitate gas exchange and water loss from leaves. The hormone abscisic acid (ABA) has a central role in regulation of stomatal closure through synthesis of second messengers, which include reactive oxygen species (ROS). ROS accumulation must be minimized by antioxidants to keep concentrations from reaching damaging levels within the cell. Flavonols are plant metabolites that have been implicated as antioxidants; however, their antioxidant activity in planta has been debated. Flavonols accumulate in guard cells of Arabidopsis thaliana, but not surrounding pavement cells, as visualized with a flavonol-specific dye. The expression of a reporter driven by the promoter of CHALCONE SYNTHASE, a gene encoding a flavonol biosynthetic enzyme, in guard cells, but not pavement cells, suggests guard cell-specific flavonoid synthesis. Increased levels of ROS were detected using a fluorescent ROS sensor in guard cells of transparent testa4-2, which has a null mutation in CHALCONE SYNTHASE and therefore synthesizes no flavonol antioxidants. Guard cells of transparent testa4-2 show more rapid ABA-induced closure than the wild type, suggesting that flavonols may dampen the ABA-dependent ROS burst that drives stomatal closing. The levels of flavonols are positively regulated in guard cells by ethylene treatment in the wild type, but not in the ethylene-insensitive2-5 mutant. In addition, in both ethylene-overproducing1 and ethylene-treated wild-type plants, elevated flavonols lead to decreasing ROS and slower ABA-mediated stomatal closure. These results are consistent with flavonols suppressing ROS accumulation and decreasing the rate of ABA-dependent stomatal closure, with ethylene-induced increases in guard cell flavonols modulating these responses. PMID:24596331

  15. Longevity of animals under reactive oxygen species stress and disease susceptibility due to global warming.

    PubMed

    Paital, Biswaranjan; Panda, Sumana Kumari; Hati, Akshaya Kumar; Mohanty, Bobllina; Mohapatra, Manoj Kumar; Kanungo, Shyama; Chainy, Gagan Bihari Nityananda

    2016-02-26

    The world is projected to experience an approximate doubling of atmospheric CO2 concentration in the next decades. Rise in atmospheric CO2 level as one of the most important reasons is expected to contribute to raise the mean global temperature 1.4 °C-5.8 °C by that time. A survey from 128 countries speculates that global warming is primarily due to increase in atmospheric CO2 level that is produced mainly by anthropogenic activities. Exposure of animals to high environmental temperatures is mostly accompanied by unwanted acceleration of certain biochemical pathways in their cells. One of such examples is augmentation in generation of reactive oxygen species (ROS) and subsequent increase in oxidation of lipids, proteins and nucleic acids by ROS. Increase in oxidation of biomolecules leads to a state called as oxidative stress (OS). Finally, the increase in OS condition induces abnormality in physiology of animals under elevated temperature. Exposure of animals to rise in habitat temperature is found to boost the metabolism of animals and a very strong and positive correlation exists between metabolism and levels of ROS and OS. Continuous induction of OS is negatively correlated with survivability and longevity and positively correlated with ageing in animals. Thus, it can be predicted that continuous exposure of animals to acute or gradual rise in habitat temperature due to global warming may induce OS, reduced survivability and longevity in animals in general and poikilotherms in particular. A positive correlation between metabolism and temperature in general and altered O2 consumption at elevated temperature in particular could also increase the risk of experiencing OS in homeotherms. Effects of global warming on longevity of animals through increased risk of protein misfolding and disease susceptibility due to OS as the cause or effects or both also cannot be ignored. Therefore, understanding the physiological impacts of global warming in relation to

  16. Longevity of animals under reactive oxygen species stress and disease susceptibility due to global warming

    PubMed Central

    Paital, Biswaranjan; Panda, Sumana Kumari; Hati, Akshaya Kumar; Mohanty, Bobllina; Mohapatra, Manoj Kumar; Kanungo, Shyama; Chainy, Gagan Bihari Nityananda

    2016-01-01

    The world is projected to experience an approximate doubling of atmospheric CO2 concentration in the next decades. Rise in atmospheric CO2 level as one of the most important reasons is expected to contribute to raise the mean global temperature 1.4 °C-5.8 °C by that time. A survey from 128 countries speculates that global warming is primarily due to increase in atmospheric CO2 level that is produced mainly by anthropogenic activities. Exposure of animals to high environmental temperatures is mostly accompanied by unwanted acceleration of certain biochemical pathways in their cells. One of such examples is augmentation in generation of reactive oxygen species (ROS) and subsequent increase in oxidation of lipids, proteins and nucleic acids by ROS. Increase in oxidation of biomolecules leads to a state called as oxidative stress (OS). Finally, the increase in OS condition induces abnormality in physiology of animals under elevated temperature. Exposure of animals to rise in habitat temperature is found to boost the metabolism of animals and a very strong and positive correlation exists between metabolism and levels of ROS and OS. Continuous induction of OS is negatively correlated with survivability and longevity and positively correlated with ageing in animals. Thus, it can be predicted that continuous exposure of animals to acute or gradual rise in habitat temperature due to global warming may induce OS, reduced survivability and longevity in animals in general and poikilotherms in particular. A positive correlation between metabolism and temperature in general and altered O2 consumption at elevated temperature in particular could also increase the risk of experiencing OS in homeotherms. Effects of global warming on longevity of animals through increased risk of protein misfolding and disease susceptibility due to OS as the cause or effects or both also cannot be ignored. Therefore, understanding the physiological impacts of global warming in relation to

  17. Methylmercury-induced reactive oxygen species formation in neonatal cerebral astrocytic cultures is attenuated by antioxidants.

    PubMed

    Shanker, Gouri; Aschner, Michael

    2003-01-31

    Excessive generation of reactive oxygen species (ROS) has been suggested as a causal factor in various neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease [Brain Res. 830 (1999) 10-15; Biochem. J. 310 (1995) 83-90; Free Radic. Biol. Med. 27 (1999) 612-616]. The present work examined the role of ROS in the neurotoxicity of methylmercury (MeHg). ROS formation in primary astrocytic cultures of neonatal rat cerebral cortex was monitored by 2',7'-dichlorodihydrofluorescein diacetate (H(2)DCF-DA) fluorescence. MeHg, at 10 and 20 microM caused a significant increase in ROS formation (10 microM, P<0.01; 20 microM, P<0.001). Additional studies established the effectiveness of antioxidants/free radical scavengers in attenuating the MeHg-stimulated ROS formation in the following rank-order: (1) Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a non-thiol containing antioxidant, (2) n-propyl gallate (PG), a free radical scavenger, (3) superoxide dismutase (SOD), an antioxidant enzyme that dismutates superoxide anion radical, (4) alpha-phenyl-tert-butyl nitrone (PBN), a lipophilic hydroxyl radical spin trapping agent. A significant inhibition of MeHg-induced ROS generation was also noted in astrocytes preincubated (3 h) with arachidonyl trifluoromethyl ketone (AACOCF(3,) 20 microM, P<0.05), a specific inhibitor of cytosolic phospholipase A(2) (cPLA(2)). Conversely, pretreatment (24 h) with 100 microM buthionine-L-sulfoxamine [BSO, a glutathione (GSH) synthesis inhibitor], significantly increased (P<0.05) ROS formation in MeHg treated astrocytes compared to controls. Combined, these studies invoke ROS as potent mediators of MeHg cytotoxicity and support the hypothesis that excessive ROS generation, at least in part, plays an important role in MeHg-induced neurotoxicity. PMID:12573536

  18. Propylthiouracil prevents cutaneous and pulmonary fibrosis in the reactive oxygen species murine model of systemic sclerosis

    PubMed Central

    2013-01-01

    Introduction Recent advances suggest that the cellular redox state may play a significant role in the progression of fibrosis in systemic sclerosis (SSc). Another, and as yet poorly accounted for, feature of SSc is its overlap with thyroid abnormalities. Previous reports demonstrate that hypothyroidism reduces oxidant stress. The aim of this study was therefore to evaluate the effect of propylthiouracil (PTU), and of the hypothyroidism induced by it, on the development of cutaneous and pulmonary fibrosis in the oxidant stress murine model of SSc. Methods Chronic oxidant stress SSc was induced in BALB/c mice by daily subcutaneous injections of hypochlorous acid (HOCl) for 6 weeks. Mice (n = 25) were randomized into three arms: HOCl (n = 10), HOCl plus PTU (n = 10) or vehicle alone (n = 5). PTU administration was initiated 30 minutes after HOCl subcutaneous injection and continued daily for 6 weeks. Skin and lung fibrosis were evaluated by histologic methods. Immunohistochemical staining for alpha-smooth muscle actin (α-SMA) in cutaneous and pulmonary tissues was performed to evaluate myofibroblast differentiation. Lung and skin concentrations of vascular endothelial growth factor (VEGF), extracellular signal-related kinase (ERK), rat sarcoma protein (Ras), Ras homolog gene family (Rho), and transforming growth factor (TGF) β were analyzed by Western blot. Results Injections of HOCl induced cutaneous and lung fibrosis in BALB/c mice. PTU treatment prevented both dermal and pulmonary fibrosis. Myofibroblast differentiation was also inhibited by PTU in the skin and lung. The increase in cutaneous and pulmonary expression of VEGF, ERK, Ras, and Rho in mice treated with HOCl was significantly prevented in mice co-administered ////with PTU. Conclusions PTU, probably through its direct effect on reactive oxygen species or indirectly through thyroid function inhibition, prevents the development of cutaneous and pulmonary fibrosis by blocking the activation of the Ras

  19. Mercuric ions inhibit mitogen-activated protein kinase dephosphorylation by inducing reactive oxygen species

    SciTech Connect

    Haase, Hajo; Engelhardt, Gabriela; Hebel, Silke; Rink, Lothar

    2011-01-01

    Mercury intoxication profoundly affects the immune system, in particular, signal transduction of immune cells. However, the mechanism of the interaction of mercury with cellular signaling pathways, such as mitogen activated protein kinases (MAPK), remains elusive. Therefore, the objective of this study is to investigate three potential ways in which Hg{sup 2+} ions could inhibit MAPK dephosphorylation in the human T-cell line Jurkat: (1) by direct binding to phosphatases; (2) by releasing cellular zinc (Zn{sup 2+}); and (3) by inducing reactive oxygen species (ROS). Hg{sup 2+} causes production of ROS, measured by dihydrorhodamine 123, and triggers ROS-mediated Zn{sup 2+} release, detected with FluoZin-3. Yet, phosphatase-inhibition is not mediated by binding of Zn{sup 2+} or Hg{sup 2+}. Rather, phosphatases are inactivated by at least two forms of thiol oxidation; initial inhibition is reversible with reducing agents such as Tris(2-carboxyethyl)phosphine. Prolonged inhibition leads to non-reversible phosphatase oxidation, presumably oxidizing the cysteine thiol to sulfinic- or sulfonic acid. Notably, phosphatases are a particularly sensitive target for Hg{sup 2+}-induced oxidation, because phosphatase activity is inhibited at concentrations of Hg{sup 2+} that have only minor impact on over all thiol oxidation. This phosphatase inhibition results in augmented, ROS-dependent MAPK phosphorylation. MAPK are important regulators of T-cell function, and MAPK-activation by inhibition of phosphatases seems to be one of the molecular mechanisms by which mercury affects the immune system.

  20. Nucleotide receptor signaling in murine macrophages is linked to reactive oxygen species generation.

    PubMed

    Pfeiffer, Zachary A; Guerra, Alma N; Hill, Lindsay M; Gavala, Monica L; Prabhu, Usha; Aga, Mini; Hall, David J; Bertics, Paul J

    2007-05-15

    Macrophage activation is critical in the innate immune response and can be regulated by the nucleotide receptor P2X7. In this regard, P2X7 signaling is not well understood but has been implicated in controlling reactive oxygen species (ROS) generation by various leukocytes. Although ROS can contribute to microbial killing, the role of ROS in nucleotide-mediated cell signaling is unclear. In this study, we report that the P2X7 agonists ATP and 3'-O-(4-benzoyl) benzoic ATP (BzATP) stimulate ROS production by RAW 264.7 murine macrophages. These effects are potentiated in lipopolysaccharide-primed cells, demonstrating an important interaction between extracellular nucleotides and microbial products in ROS generation. In terms of nucleotide receptor specificity, RAW 264.7 macrophages that are deficient in P2X7 are greatly reduced in their capacity to generate ROS in response to BzATP treatment (both with and without LPS priming), thus supporting a role for P2X7 in this process. Because MAP kinase activation is key for nucleotide regulation of macrophage function, we also tested the hypothesis that P2X7-mediated MAP kinase activation is dependent on ROS production. We observed that BzATP stimulates MAP kinase (ERK1/ERK2, p38, and JNK1/JNK2) phosphorylation and that the antioxidants N-acetylcysteine and ascorbic acid strongly attenuate BzATP-mediated JNK1/JNK2 and p38 phosphorylation but only slightly reduce BzATP-induced ERK1/ERK2 phosphorylation. These studies reveal that P2X7 can contribute to macrophage ROS production, that this effect is potentiated upon lipopolysaccharide exposure, and that ROS are important participants in the extracellular nucleotide-mediated activation of several MAP kinase systems. PMID:17448897

  1. The Defensive Role of Cumulus Cells Against Reactive Oxygen Species Insult in Metaphase II Mouse Oocytes.

    PubMed

    Shaeib, Faten; Khan, Sana N; Ali, Iyad; Thakur, Mili; Saed, Mohammed G; Dai, Jing; Awonuga, Awoniyi O; Banerjee, Jashoman; Abu-Soud, Husam M

    2016-04-01

    We investigated the ability of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), hydroxyl radical ((·)OH), and hypochlorous acid (HOCl), to overcome the defensive capacity of cumulus cells and elucidate the mechanism through which ROS differentially deteriorate oocyte quality. Metaphase II mouse oocytes with (n = 1634) and without cumulus cells (n = 1633) were treated with increasing concentration of ROS, and the deterioration in oocyte quality was assessed by the changes in the microtubule morphology and chromosomal alignment. Oocyte and cumulus cell viability and cumulus cell number were assessed by indirect immunofluorescence, staining of gap junction protein, and trypan blue staining. The treated oocytes showed decreased quality as a function of increasing concentrations of ROS when compared to controls. Cumulus cells show protection against H2O2 and (·)OH insult at lower concentrations, but this protection was lost at higher concentrations (>50 μmol/L). At higher H2O2 concentrations, treatment dramatically influenced the cumulus cell number and viability with resulting reduction in the antioxidant capacity making the oocyte more susceptible to oxidative damage. However, cumulus cells offered no significant protection against HOCl at any concentration used. In all circumstances in which cumulus cells did not offer protection to the oocyte, both cumulus cell number and viability were decreased. Therefore, the deterioration in oocyte quality may be caused by one or more of the following: a decrease in the antioxidant machinery by the loss of cumulus cells, the lack of scavengers for specific ROS, and/or the ability of the ROS to overcome these defenses. PMID:26468254

  2. Reactive Oxygen Species are involved in BMP-Induced Dendritic Growth in Cultured Rat Sympathetic Neurons

    PubMed Central

    Chandrasekaran, Vidya; Lea, Charlotte; Sosa, Jose Carlo; Higgins, Dennis; Lein, Pamela J.

    2015-01-01

    Previous studies have shown that bone morphogenetic proteins (BMPs) promote dendritic growth in sympathetic neurons; however, the downstream signaling molecules that mediate the dendrite promoting activity of BMPs are not well characterized. Here we test the hypothesis that reactive oxygen species (ROS)-mediated signaling links BMP receptor activation to dendritic growth. In cultured rat sympathetic neurons, exposure to any of three mechanistically distinct antioxidants, diphenylene iodinium (DPI), nordihydroguiaretic acid (NGA) or desferroxamine (DFO), blocked de novo BMP-induced dendritic growth. Addition of DPI to cultures previously induced with BMP to extend dendrites caused dendritic retraction while DFO and NGA prevented further growth of dendrites. The inhibition of the dendrite promoting activity of BMPs by antioxidants was concentration-dependent and occurred without altering axonal growth or neuronal cell survival. Antioxidant treatment did not block BMP activation of SMAD 1,5 as determined by nuclear localization of these SMADs. While BMP treatment did not cause a detectable increase in intracellular ROS in cultured sympathetic neurons as assessed using fluorescent indicator dyes, BMP treatment increased the oxygen consumption rate in cultured sympathetic neurons as determined using the Seahorse XF24 Analyzer, suggesting increased mitochondrial activity. In addition, BMPs upregulated expression of NADPH oxidase 2 (NOX2) and either pharmacological inhibition or siRNA knockdown of NOX2 significantly decreased BMP-7 induced dendritic growth. Collectively, these data support the hypothesis that ROS are involved in the downstream signaling events that mediate BMP7-induced dendritic growth in sympathetic neurons, and suggest that ROS-mediated signaling positively modulates dendritic complexity in peripheral neurons. PMID:26079955

  3. Potential molecular mechanisms underlying muscle fatigue mediated by reactive oxygen and nitrogen species

    PubMed Central

    Debold, Edward P.

    2015-01-01

    Intense contractile activity causes a dramatic decline in the force and velocity generating capacity of skeletal muscle within a few minutes, a phenomenon that characterizes fatigue. Much of the research effort has focused on how elevated levels of the metabolites of ATP hydrolysis might inhibit the function of the contractile proteins. However, there is now growing evidence that elevated levels of reactive oxygen and nitrogen species (ROS/RNS), which also accumulate in the myoplasm during fatigue, also play a causative role in this type of fatigue. The most compelling evidence comes from observations demonstrating that pre-treatment of intact muscle with a ROS scavenger can significantly attenuate the development of fatigue. A clear advantage of this line of inquiry is that the molecular targets and protein modifications of some of the ROS scavengers are well-characterized enabling researchers to begin to identify potential regions and even specific amino acid residues modified during fatigue. Combining this knowledge with assessments of contractile properties from the whole muscle level down to the dynamic motions within specific contractile proteins enable the linking of the structural modifications to the functional impacts, using advanced chemical and biophysical techniques. Based on this approach at least two areas are beginning emerge as potentially important sites, the regulatory protein troponin and the actin binding region of myosin. This review highlights some of these recent efforts which have the potential to offer uniquely precise information on the underlying molecular basis of fatigue. This work may also have implications beyond muscle fatigue as ROS/RNS mediated protein modifications are also thought to play a role in the loss of muscle function with aging and in some acute pathologies like cardiac arrest and ischemia. PMID:26388779

  4. Reactive oxygen species modulate Anopheles gambiae immunity against bacteria and Plasmodium.

    PubMed

    Molina-Cruz, Alvaro; DeJong, Randall J; Charles, Bradley; Gupta, Lalita; Kumar, Sanjeev; Jaramillo-Gutierrez, Giovanna; Barillas-Mury, Carolina

    2008-02-01

    The involvement of reactive oxygen species (ROS) in mosquito immunity against bacteria and Plasmodium was investigated in the malaria vector Anopheles gambiae. Strains of An. gambiae with higher systemic levels of ROS survive a bacterial challenge better, whereas reduction of ROS by dietary administration of antioxidants significantly decreases survival, indicating that ROS are required to mount effective antibacterial responses. Expression of several ROS detoxification enzymes increases in the midgut and fat body after a blood meal. Furthermore, expression of several of these enzymes increases to even higher levels when mosquitoes are fed a Plasmodium berghei-infected meal, indicating that the oxidative stress after a blood meal is exacerbated by Plasmodium infection. Paradoxically, a complete lack of induction of catalase mRNA and lower catalase activity were observed in P. berghei-infected midguts. This suppression of midgut catalase expression is a specific response to ookinete midgut invasion and is expected to lead to higher local levels of hydrogen peroxide. Further reduction of catalase expression by double-stranded RNA-mediated gene silencing promoted parasite clearance by a lytic mechanism and reduced infection significantly. High mosquito mortality is often observed after P. berghei infection. Death appears to result in part from excess production of ROS, as mortality can be decreased by oral administration of uric acid, a strong antioxidant. We conclude that ROS modulate An. gambiae immunity and that the mosquito response to P. berghei involves a local reduction of detoxification of hydrogen peroxide in the midgut that contributes to limit Plasmodium infection through a lytic mechanism. PMID:18065421

  5. Titanium dioxide nanoparticles increase plasma glucose via reactive oxygen species-induced insulin resistance in mice.

    PubMed

    Hu, Hailong; Guo, Qian; Wang, Changlin; Ma, Xiao; He, Hongjuan; Oh, Yuri; Feng, Yujie; Wu, Qiong; Gu, Ning

    2015-10-01

    There have been few reports about the possible toxic effects of titanium dioxide (TiO2 ) nanoparticles on the endocrine system. We explored the endocrine effects of oral administration to mice of anatase TiO2 nanoparticles (0, 64 and 320 mg kg(-1) body weight per day to control, low-dose and high-dose groups, respectively, 7 days per week for 14 weeks). TiO2 nanoparticles were characterized by scanning and transmission electron microscopy (TEM) and dynamic light scattering (DLS), and their physiological distribution was investigated by inductively coupled plasma. Biochemical analyzes included plasma glucose, insulin, heart blood triglycerides (TG), free fatty acid (FFA), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 and reactive oxygen species (ROS)-related markers (total SOD, GSH and MDA). Phosphorylation of IRS1, Akt, JNK1, and p38 MAPK were analyzed by western blotting. Increased titanium levels were found in the liver, spleen, small intestine, kidney and pancreas. Biochemical analyzes showed that plasma glucose significantly increased whereas there was no difference in plasma insulin secretion. Increased ROS levels were found in serum and the liver, as evidenced by reduced total SOD activity and GSH level and increased MDA content. Western blotting showed that oral administration of TiO2 nanoparticles induced insulin resistance (IR) in mouse liver, shown by increased phosphorylation of IRS1 (Ser307) and reduced phosphorylation of Akt (Ser473). The pathway by which TiO2 nanoparticles increase ROS-induced IR were included in the inflammatory response and phosphokinase, as shown by increased serum levels of TNF-α and IL-6 and increased phosphorylation of JNK1 and p38 MAPK in liver. These results show that oral administration of TiO2 nanoparticles increases ROS, resulting in IR and increasing plasma glucose in mice. PMID:25826740

  6. Scoparone attenuates RANKL-induced osteoclastic differentiation through controlling reactive oxygen species production and scavenging

    SciTech Connect

    Lee, Sang-Hyun; Jang, Hae-Dong

    2015-02-15

    Scoparone, one of the bioactive components of Artemisia capillaris Thunb, has various biological properties including immunosuppressive, hepatoprotective, anti-allergic, anti-inflammatory, and antioxidant effects. This study aims at evaluating the anti-osteoporotic effect of scoparone and its underlying mechanism in vitro. Scoparone demonstrated potent cellular antioxidant capacity. It was also found that scoparone inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and suppressed cathepsin K and tartrate-resistant acid phosphatase (TRAP) expression via c-jun N-terminal kinase (JNK)/extracellular signal-regulated kinase (ERK)/p38-mediated c-Fos–nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) signaling pathway. During osteoclast differentiation, the production of general reactive oxygen species (ROS) and superoxide anions was dose-dependently attenuated by scoparone. In addition, scoparone diminished NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 1 (Nox1) expression and activation via the tumor necrosis factor receptor-associated factor 6 (TRAF6)–cSrc–phosphatidylinositol 3-kinase (PI3k) signaling pathway and prevented the disruption of mitochondrial electron transport chain system. Furthermore, scoparone augmented the expression of superoxide dismutase 1 (SOD1) and catalase (CAT). The overall results indicate that the inhibitory effect of scoparone on RANKL-induced osteoclast differentiation is attributed to the suppressive effect on ROS and superoxide anion production by inhibiting Nox1 expression and activation and protecting the mitochondrial electron transport chain system and the scavenging effect of ROS resulting from elevated SOD1 and CAT expression. - Highlights: • Scoparone dose-dependently inhibited RANKL-induced osteoclast differentiation. • Scoparone diminished general ROS and superoxide anions in a dose-dependent manner. • Scoparone inhibited Nox1 expression and

  7. Evaluation of the Reactivity of Reillex HPQ in 64 Percent Nitric Acid

    SciTech Connect

    Crooks, W.J. III

    2001-02-20

    The purpose of this work was to evaluate the reactivity of Reillex HPQ in 64 percent nitric acid and to address an accident scenario in which 64 percent nitric acid solution is inadvertently added to an HB-Line ion exchange column containing Reillex HPQ anion exchange resin.

  8. 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

  9. Biochemical changes in rat testis induced in vitro by reactive oxygen species.

    PubMed

    Nechifor, Marina Tamara; Constantin, Carolina; Manda, Gina; Neagu, Monica; Dinu, Diana

    2006-01-01

    We report the effects of reactive oxygen species generated by ultraviolet-A radiation on some biochemical parameters specific for oxidative stress, in rat testis homogenates. Results show an increase in lipid peroxidation products under ultraviolet-A exposure, and suggest that the involved mechanism is typical for a radical-mediated chain reaction. The amount of SH groups also increases during irradiation, probably as a consequence of conformational changes in proteins. Electrophoresis results revealed protein pattern changes mainly in the low molecular weight domain. The catalytic activities of alkaline phosphatase and gamma-glutamil transpeptidase are modified under the oxidative conditions generated by reactive oxygen species. The changes of the enzymatic activities are UVA exposure time-dependent, suggesting that conformational modifications are responsible for enzymatic activities enhancement. PMID:18389730

  10. The role of reactive oxygen species on Plasmodium melanotic encapsulation in Anopheles gambiae

    PubMed Central

    Kumar, Sanjeev; Christophides, George K.; Cantera, Rafael; Charles, Bradley; Han, Yeon Soo; Meister, Stephan; Dimopoulos, George; Kafatos, Fotis C.; Barillas-Mury, Carolina

    2003-01-01

    Malaria transmission depends on the competence of some Anopheles mosquitoes to sustain Plasmodium development (susceptibility). A genetically selected refractory strain of Anopheles gambiae blocks Plasmodium development, melanizing, and encapsulating the parasite in a reaction that begins with tyrosine oxidation, and involves three quantitative trait loci. Morphological and microarray mRNA expression analysis suggest that the refractory and susceptible strains have broad physiological differences, which are related to the production and detoxification of reactive oxygen species. Physiological studies corroborate that the refractory strain is in a chronic state of oxidative stress, which is exacerbated by blood feeding, resulting in increased steady-state levels of reactive oxygen species, which favor melanization of parasites as well as Sephadex beads. PMID:14623973

  11. The role of reactive oxygen species on Plasmodium melanotic encapsulation in Anopheles gambiae.

    PubMed

    Kumar, Sanjeev; Christophides, George K; Cantera, Rafael; Charles, Bradley; Han, Yeon Soo; Meister, Stephan; Dimopoulos, George; Kafatos, Fotis C; Barillas-Mury, Carolina

    2003-11-25

    Malaria transmission depends on the competence of some Anopheles mosquitoes to sustain Plasmodium development (susceptibility). A genetically selected refractory strain of Anopheles gambiae blocks Plasmodium development, melanizing, and encapsulating the parasite in a reaction that begins with tyrosine oxidation, and involves three quantitative trait loci. Morphological and microarray mRNA expression analysis suggest that the refractory and susceptible strains have broad physiological differences, which are related to the production and detoxification of reactive oxygen species. Physiological studies corroborate that the refractory strain is in a chronic state of oxidative stress, which is exacerbated by blood feeding, resulting in increased steady-state levels of reactive oxygen species, which favor melanization of parasites as well as Sephadex beads. PMID:14623973

  12. Deoxyamphimedine, a pyridoacridine alkaloid, damages DNA via the production of reactive oxygen species.

    PubMed

    Marshall, Kathryn M; Andjelic, Cynthia D; Tasdemir, Deniz; Concepción, Gisela P; Ireland, Chris M; Barrows, Louis R

    2009-01-01

    Marine pyridoacridines are a class of aromatic chemicals that share an 11H-pyrido[4,3,2-mn]acridine skeleton. Pyridoacridine alkaloids display diverse biological activities including cytotoxicity, fungicidal and bactericidal properties, production of reactive oxygen species (ROS) and topoisomerase inhibition. These activities are often dependent on slight modifications to the pyridoacridine skeleton. Here we demonstrate that while structurally similar to neoamphimedine and amphimedine, the biological activity of deoxyamphimedine differs greatly. Deoxyamphimedine damages DNA in vitro independent of topoisomerase enzymes through the generation of reactive oxygen species. Its activity was decreased in low oxygen, with the removal of a reducing agent and in the presence of anti-oxidants. Deoxyamphimedine also showed enhanced toxicity in cells sensitive to single or double strand DNA breaks, consistent with the in vitro activity. PMID:19597581

  13. Chemically reactive species in liquids generated by atmospheric-pressure plasmas and their roles in plasma medicine

    SciTech Connect

    Hamaguchi, Satoshi

    2013-07-11

    Plasmas whose gas temperatures are close to room temperature may be generated in ambient air or a gas at atmospheric pressure with the use of low-frequency high voltage or low-power radio-frequency (RF) or microwave power applied to electrodes. Such plasmas can serve as a powerful source of free radicals and/or chemically reactive species that arise from atoms and molecules of the ambient gas. Recently use of such plasmas for medical purposes has attracted much attention as they can be implemented in possible medical devices that can cause blood coagulation, heal wounds, facilitate angiogenesis, sterilize surgical devices as well as living tissues without harming healthy cells, and selectively inactivate cancer cells. Especially of interest among reactive species generated by atmospheric-pressure plasmas (APP) are reactive oxygen species (ROS) and reactive nitrogen species (RNS) that are generated in liquid phase. Since most living tissues and cells are immersed in liquids (such as blood or culture media), reactive species generated by APPs in the gas phase are transported to the liquid phase and possibly converted to different types of reactive species therein before causing some influence on the tissues or cells. In this study, the rate equations are solved to evaluate concentrations of various reactive species in pure water that are originated by plasma reactions in atmosphere and possible effects of such species (including ROS/RNS) on living tissues and cells are discussed.

  14. Chemically reactive species in liquids generated by atmospheric-pressure plasmas and their roles in plasma medicine

    NASA Astrophysics Data System (ADS)

    Hamaguchi, Satoshi

    2013-07-01

    Plasmas whose gas temperatures are close to room temperature may be generated in ambient air or a gas at atmospheric pressure with the use of low-frequency high voltage or low-power radio-frequency (RF) or microwave power applied to electrodes. Such plasmas can serve as a powerful source of free radicals and/or chemically reactive species that arise from atoms and molecules of the ambient gas. Recently use of such plasmas for medical purposes has attracted much attention as they can be implemented in possible medical devices that can cause blood coagulation, heal wounds, facilitate angiogenesis, sterilize surgical devices as well as living tissues without harming healthy cells, and selectively inactivate cancer cells. Especially of interest among reactive species generated by atmospheric-pressure plasmas (APP) are reactive oxygen species (ROS) and reactive nitrogen species (RNS) that are generated in liquid phase. Since most living tissues and cells are immersed in liquids (such as blood or culture media), reactive species generated by APPs in the gas phase are transported to the liquid phase and possibly converted to different types of reactive species therein before causing some influence on the tissues or cells. In this study, the rate equations are solved to evaluate concentrations of various reactive species in pure water that are originated by plasma reactions in atmosphere and possible effects of such species (including ROS/RNS) on living tissues and cells are discussed.

  15. 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

  16. Mitochondrial Reactive Oxygen Species at the Heart of the Matter: New Therapeutic Approaches for Cardiovascular Diseases

    PubMed Central

    Kornfeld, Opher S.; Hwang, Sunhee; Disatnik, Marie-Hélène; Chen, Che-Hong; Qvit, Nir; Mochly-Rosen, Daria

    2015-01-01

    Reactive oxygen species (ROS) have been implicated in a variety of age-related diseases including multiple cardiovascular disorders. However, translation of ROS scavengers (anti-oxidants) into the clinic has not been successful. These anti-oxidants grossly reduce total levels of cellular ROS including ROS that participate in physiological signaling. In this review, we challenge the traditional anti-oxidant therapeutic approach that targets ROS directly with novel approaches that improve mitochondrial functions to more effectively treat cardiovascular diseases. PMID:25999419

  17. Using fluorescence-activated flow cytometry to determine reactive oxygen species formation and membrane lipid peroxidation in viable boar spermatozoa.

    PubMed

    Guthrie, H David; Welch, Glenn R

    2010-01-01

    Fluorescence-activated flow cytometry analyses were developed for determination of reactive oxygen species (ROS) formation and membrane lipid peroxidation in live spermatozoa loaded with, respectively, hydroethidine (HE) or the lipophilic probe 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-undecanoic acid, C(11)BODIPY(581/591) (BODIPY). ROS was detected by red fluorescence emission from oxidization of HE and membrane lipid peroxidation was detected by green fluorescence emission from oxidation of BODIPY in individual live sperm. Of the reactive oxygen species generators tested, BODIPY oxidation was specific for FeSo4/ascorbate (FeAc), because menadione and H(2)O(2) had little or no effect. The oxidization of hydroethidine to ethidium was specific for menadione and H(2)O(2); FeAc had no effect. The incidence of basal or spontaneous ROS formation and membrane lipid peroxidation were low in boar sperm (<1% of live sperm) in fresh semen or after low temperature storage; however the sperm were quite susceptible to treatment-induced ROS formation and membrane lipid peroxidation. PMID:20072917

  18. Detection and quantification of reactive oxygen species (ROS) in indoor air.

    PubMed

    Montesinos, V Nahuel; Sleiman, Mohamad; Cohn, Sebastian; Litter, Marta I; Destaillats, Hugo

    2015-06-01

    Reactive oxygen species (ROS), such as free radicals and peroxides, are environmental trace pollutants potentially associated with asthma and airways inflammation. These compounds are often not detected in indoor air due to sampling and analytical limitations. This study developed and validated an experimental method to sample, identify and quantify ROS in indoor air using fluorescent probes. Tests were carried out simultaneously using three different probes: 2',7'-dichlorofluorescin (DCFH) to detect a broad range of ROS, Amplex ultra Red® (AuR) to detect peroxides, and terephthalic acid (TPA) to detect hydroxyl radicals (HO(•)). For each test, air samples were collected using two impingers in series kept in an ice bath, containing each 10 mL of 50 mM phosphate buffer at pH 7.2. In tests with TPA, that probe was also added to the buffer prior to sampling; in the other two tests, probes and additional reactants were added immediately after sampling. The concentration of fluorescent byproducts was determined fluorometrically. Calibration curves were developed by reacting DCFH and AuR with known amounts of H2O2, and using known amounts of 2-hydroxyterephthalic acid (HTPA) for TPA. Low detection limits (9-13 nM) and quantification limits (18-22 nM) were determined for all three probes, which presented a linear response in the range 10-500 nM for AuR and TPA, and 100-2000 nM for DCFH. High collection efficiency (CE) and recovery efficiency (RE) were observed for DCFH (CE=RE=100%) and AuR (CE=100%; RE=73%) by sampling from a laboratory-developed gas phase H2O2 generator. Interference of co-occurring ozone was evaluated and quantified for the three probes by sampling from the outlet of an ozone generator. The method was demonstrated by sampling air emitted by two portable air cleaners: a strong ozone generator (AC1) and a plasma generator (AC2). High ozone levels emitted by AC1 did not allow for simultaneous determination of ROS levels due to high background levels

  19. Diverting Hydrogenations with Wilkinson's Catalyst towards Highly Reactive Rhodium(I) Species.

    PubMed

    Perea-Buceta, Jesus E; Fernández, Israel; Heikkinen, Sami; Axenov, Kirill; King, Alistair W T; Niemi, Teemu; Nieger, Martin; Leskelä, Markku; Repo, Timo

    2015-11-23

    The addition of Barton's base has a dramatic effect on the classic rhodium(III)-mediated hydrogenations promoted by Wilkinson's catalyst. Following the initial oxidative addition, a barrierless reductive elimination of HCl from the traditional rhodium(III) intermediates instantly produces a rhodium(I) monohydride species, which is remarkably reactive in the hydrogenation of several internal alkynes and functionalized trisubstituted alkenes. The direct formation of this species is unprecedented upon addition of molecular hydrogen and its catalytic potential has been hitherto barely explored. PMID:26437764

  20. Optical diagnostics of reactive species in atmospheric-pressure nonthermal plasma

    NASA Astrophysics Data System (ADS)

    Ono, Ryo

    2016-03-01

    This paper reviews optical measurements of reactive species in atmospheric-pressure nonthermal plasmas: streamer discharge, dielectric barrier discharge (DBD), plasma jet, and plasma-assisted ignition and combustion. Measurements of OH, O, N, {{\\text{O}}3} , NO, {{\\text{N}}2} (A, B, C), {{\\text{O}}2} (a, b), {{\\text{N}}2}(v) , {{\\text{O}}2}(v) , He*, Ar*, \\text{N}2+ , CH, and CH2O by laser-induced fluorescence, absorption, optical emission spectroscopy, and coherent anti-Stokes Raman scattering methods are included. Reactive species measurement in low-frequency (\\cong 1 Hz) pulsed streamer discharge is introduced, and reactive species production and reaction processes indicated by these measurements are described in detail. Measurements in high-frequency DBD, atmospheric-pressure diffuse discharge, and dc corona discharge are described. Measurements in plasma jets are also reviewed: rf plasma jets, kHz plasma jets, and additional plasma jets. Finally, measurements in plasma-assisted ignition and combustion are described and reviewed in addition to measurements in conventional spark ignition. A comprehensive list of the reviewed measurements is provided.

  1. Reactive oxygen species in chick hair cells after gentamicin exposure in vitro.

    PubMed

    Hirose, K; Hockenbery, D M; Rubel, E W

    1997-02-01

    Reactive oxygen species have been invoked as a causative agent of cell death in many different developmental and pathological states. The presence of free radicals and their importance of hair cell death due to aminoglycosides is suggested by a number of studies that have demonstrated a protective effect of antioxidants. By using dichlorofluorescin (DCFH) a fluorescent compound that is a reporter of reactive oxygen species, we have shown that free radicals are rapidly produced by avian hair cells in vitro after exposure to gentamicin. In addition, free radical scavengers, catalase and glutathione, were tested with DCFH fluorescent imaging for their ability to quench the production of reactive oxygen species in hair cells after drug exposure. Both free radical scavengers were very effective in suppressing drug-induced production of free radicals. Next, we investigated the ability of these antioxidants to preserve the structural integrity of hair cells after exposure to gentamicin. We were not able to detect any attenuation of the hair cell loss using antioxidants in conjunction with gentamicin. This result must be qualified by the fact that the antioxidants used were not effective over long-term gentamicin exposure. Therefore, methodological constraints prevented adequately testing possible protective effects of the free radical scavengers in this model system. PMID:9119753

  2. Generation of reactive oxygen species and radiation response in lymphocytes and tumor cells.

    PubMed

    Shankar, Bhavani; Kumar, S Santosh; Sainis, K B

    2003-10-01

    Several types of lymphoid and myeloid tumor cells are known to be relatively resistant to radiation-induced apoptosis compared to normal lymphocytes. The intracellular generation of reactive oxygen species was measured in irradiated spleen cells from C57BL/6 and BALB/c mice and murine tumor cells (EL-4 and P388) by flow cytometry using dichlorodihydrofluoresceindiacetate and dihydrorhodamine 123 as fluorescent probes. The amount of reactive oxygen species generated per cell was low in the tumor cells compared to spleen cells exposed to 1 to 10 Gy of gamma radiation. This could be due to the higher total antioxidant levels in tumor cells compared to normal cells. Further, the changes in mitochondrial membrane potential and cytoplasmic Ca2+ content were appreciable in lymphocytes even at a dose of 1 Gy. In EL-4 cells, no such changes were observed at any of the doses used. About 65% of spleen cells underwent apoptosis 24 h after 1 Gy irradiation. However, under the same conditions, EL-4 and P388 cells failed to undergo apoptosis, but they accumulated in G2/M phase. Thus the intrinsic radioresistance of tumor cells may be due to a decreased generation of reactive oxygen species after irradiation and down-regulation of the subsequent events leading to apoptosis. PMID:12968927

  3. Reactive oxygen species (ROS) mediates non-freezing cold injury of rat sciatic nerve

    PubMed Central

    Geng, Zhiwei; Tong, Xiaoyan; Jia, Hongjuan

    2015-01-01

    Non-freezing cold injury is an injury characterized by neuropathy, developing when patients expose to cold environments. Reactive oxygen species (ROS) has been shown as a contributing factor for the non-freezing cold nerve injury. However, the detailed connections between non-freezing cold nerve injury and ROS have not been described. In order to investigate the relationship between non-freezing cold nerve injury and reactive oxygen species, we study the effects of two cooling methods-the continuous cooling and the intermittent cooling with warming intervals-on rat sciatic nerves. Specifically, we assess the morphological changes and ROS production of the sciatic nerves underwent different cooling treatments. Our data shows both types of cooling methods cause nerve injury and ROS production. However, despite of identical cooling degree and duration, the sciatic nerves processed by intermittent cooling with warming intervals present more ROS production, severer reperfusion injury and pathological destructions than the sciatic nerves processed by continuous cooling. This result indicates reactive oxygen species, as a product of reperfusion, facilitates non-freezing cold nerve injury. PMID:26629065

  4. Selective decreased de novo synthesis of glomerular proteoglycans under the influence of reactive oxygen species.

    PubMed Central

    Kashihara, N; Watanabe, Y; Makino, H; Wallner, E I; Kanwar, Y S

    1992-01-01

    The effect of reactive oxygen species on de novo synthesis of heparan sulfate proteoglycans (HSPGs) of the renal glomerulus was investigated in an organ perfusion system. Isolated kidneys were perfused for 7 hr with a medium containing [35S]sulfate to label sulfated proteoglycans or [35S]methionine to label total glomerular glycoproteins. For the generation of reactive oxygen species, xanthine and xanthine oxidase were included in the perfusion medium, and catalase and superoxide dismutase were used as scavenging agents. Proteoglycans were characterized by Sepharose CL-6B and DEAE-Sephacel chromatographies and SDS/PAGE analysis. The labeled glycoproteins were immunoprecipitated with anti-HSPG, anti-type IV collagen, and anti-laminin, and their specific radioactivities were determined. With exposure to reactive oxygen species, a drastic dose-dependent decrease in de novo synthesis of proteoglycans was seen, and that effect was reversible by catalase treatment. No alterations in the biochemical characteristics of proteoglycans were noted. Immunoprecipitation studies revealed a 16-fold decrease in the synthesis of nascent core peptide of HSPGs, while at comparable concentrations of xanthine and xanthine oxidase, synthesis of type IV collagen and laminin slightly decreased (approximately 15%). Morphologic studies revealed a 14-fold decrease in [35S]sulfate-associated autoradiographic grains overlying the glomerular basement membrane, a critical component of the ultrafiltration apparatus. Relevance of the selective decreased de novo synthesis of HSPGs of the glomerular basement membrane is discussed in terms of increased glomerular permeability to plasma proteins. Images PMID:1631123

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

    PubMed

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

    2016-04-15

    It is well established that taurine shows potent protection against glutamate-induced injury to neurons in stroke. The neuroprotection may result from multiple mechanisms. Increasing evidences suggest that NADPH oxidases (Nox), the primary source of superoxide induced by N-methyl-d-aspartate (NMDA) receptor activation, are involved in the process of oxidative stress. We found that 100μM NMDA induced oxidative stress by increasing the reactive oxygen species level, which contributed to the cell death, in vitro. Neuron cultures pretreated with 25mM taurine showed lower percentage of death cells and declined reactive oxygen species level. Moreover, taurine attenuated Nox2/Nox4 protein expression and enzyme activity and declined intracellular calcium intensity during NMDA-induced neuron injury. Additionally, taurine also showed neuroprotection against H2O2-induced injury, accompanying with Nox inhibition. So, we suppose that protection of taurine against reactive oxygen species during NMDA-induced neuron injury is associated with Nox inhibition, probably in a calcium-dependent manner. PMID:26945820

  6. Reactive Halogen Species in the Polar Troposphere - Will there be an influence of Sea Ice Change?

    NASA Astrophysics Data System (ADS)

    Platt, U.; Friess, U.; Pöhler, D.; Sihler, H.; Wagner, T.

    2012-12-01

    Reactive halogen species (RHS, e.g. BrO, IO, HOBr) play an important role in polar regions (and also in other parts of the troposphere e.g. in coastal regions, over salt pans, in and volcanic plumes). Despite much progress in recent years the origin and some of the chemical interactions of reactive halogen species (RHS) in the polar troposphere are still not quantitatively understood. Among the many unanswered questions are: Why is there an Antarctic - Arctic asymmetry of reactive iodine species? What drives the autocatalytic bromine release from sea salt (the bromine explosion)? Why does the bromine explosion almost exclusively occur during springtime? What is the effect of coupling cycles involving different halogens? What is the vertical extent of the layer containing RHS? What is the influence of Sea Ice change? In particular the shrinking sea ice volume will shift the balance from multi-year sea ice to one year sea ice and also lead to reduced ice thickness, thus it appears plausible that halogen activation may be enhanced (at least in the Arctic). The presentation gives an overview of ground-based and aircraft observations and recent advances in satellite observations illustrating the above questions and providing answers to some of them. In particular new insight is being gained from the synergistic use of satellite observations and ground based measurements of BrO. Also the question of a NOx - driven (rather than HOx - driven) bromine explosion is discussed.

  7. Aqueous reactive species induced by a surface air discharge: Heterogeneous mass transfer and liquid chemistry pathways

    NASA Astrophysics Data System (ADS)

    Liu, D. X.; Liu, Z. C.; Chen, C.; Yang, A. J.; Li, D.; Rong, M. Z.; Chen, H. L.; Kong, M. G.

    2016-04-01

    Plasma-liquid interaction is a critical area of plasma science and a knowledge bottleneck for many promising applications. In this paper, the interaction between a surface air discharge and its downstream sample of deionized water is studied with a system-level computational model, which has previously reached good agreement with experimental results. Our computational results reveal that the plasma-induced aqueous species are mainly H+, nitrate, nitrite, H2O2 and O3. In addition, various short-lived aqueous species are also induced, regardless whether they are generated in the gas phase first. The production/loss pathways for aqueous species are quantified for an air gap width ranging from 0.1 to 2 cm, of which heterogeneous mass transfer and liquid chemistry are found to play a dominant role. The short-lived reactive oxygen species (ROS) and reactive nitrogen species (RNS) are strongly coupled in liquid-phase reactions: NO3 is an important precursor for short-lived ROS, and in turn OH, O2‑ and HO2 play a crucial role for the production of short-lived RNS. Also, heterogeneous mass transfer depends strongly on the air gap width, resulting in two distinct scenarios separated by a critical air gap of 0.5 cm. The liquid chemistry is significantly different in these two scenarios.

  8. Aqueous reactive species induced by a surface air discharge: Heterogeneous mass transfer and liquid chemistry pathways.

    PubMed

    Liu, D X; Liu, Z C; Chen, C; Yang, A J; Li, D; Rong, M Z; Chen, H L; Kong, M G

    2016-01-01

    Plasma-liquid interaction is a critical area of plasma science and a knowledge bottleneck for many promising applications. In this paper, the interaction between a surface air discharge and its downstream sample of deionized water is studied with a system-level computational model, which has previously reached good agreement with experimental results. Our computational results reveal that the plasma-induced aqueous species are mainly H(+), nitrate, nitrite, H2O2 and O3. In addition, various short-lived aqueous species are also induced, regardless whether they are generated in the gas phase first. The production/loss pathways for aqueous species are quantified for an air gap width ranging from 0.1 to 2 cm, of which heterogeneous mass transfer and liquid chemistry are found to play a dominant role. The short-lived reactive oxygen species (ROS) and reactive nitrogen species (RNS) are strongly coupled in liquid-phase reactions: NO3 is an important precursor for short-lived ROS, and in turn OH, O2(-) and HO2 play a crucial role for the production of short-lived RNS. Also, heterogeneous mass transfer depends strongly on the air gap width, resulting in two distinct scenarios separated by a critical air gap of 0.5 cm. The liquid chemistry is significantly different in these two scenarios. PMID:27033381

  9. Aqueous reactive species induced by a surface air discharge: Heterogeneous mass transfer and liquid chemistry pathways

    PubMed Central

    Liu, D. X.; Liu, Z. C.; Chen, C.; Yang, A. J.; Li, D.; Rong, M. Z.; Chen, H. L.; Kong, M. G.

    2016-01-01

    Plasma-liquid interaction is a critical area of plasma science and a knowledge bottleneck for many promising applications. In this paper, the interaction between a surface air discharge and its downstream sample of deionized water is studied with a system-level computational model, which has previously reached good agreement with experimental results. Our computational results reveal that the plasma-induced aqueous species are mainly H+, nitrate, nitrite, H2O2 and O3. In addition, various short-lived aqueous species are also induced, regardless whether they are generated in the gas phase first. The production/loss pathways for aqueous species are quantified for an air gap width ranging from 0.1 to 2 cm, of which heterogeneous mass transfer and liquid chemistry are found to play a dominant role. The short-lived reactive oxygen species (ROS) and reactive nitrogen species (RNS) are strongly coupled in liquid-phase reactions: NO3 is an important precursor for short-lived ROS, and in turn OH, O2− and HO2 play a crucial role for the production of short-lived RNS. Also, heterogeneous mass transfer depends strongly on the air gap width, resulting in two distinct scenarios separated by a critical air gap of 0.5 cm. The liquid chemistry is significantly different in these two scenarios. PMID:27033381

  10. Structure-specific reactivity of alumina supported monomeric vanadium oxide species.

    SciTech Connect

    Kim, H.; Ferguson, G. A.; Chang, L.; Zygmunt, S. A.; Stair, P. C.; Curtiss, L. A.

    2012-01-01

    Oxidative dehydrogenation (ODH) catalysts based on vanadium oxide are active for the production of alkenes, chemicals of great commercial importance. The current industrial practice for alkene production is based on energy-intensive, dehydrogenation reactions. UV resonance and visible Raman measurements, combined with density functional studies, are used to study for the first time the structure-reactivity relationships for alumina-supported monomeric vanadium oxide species. The relationship between the structure of three vanadium oxide monomeric surface species on a {theta}-alumina surface, and their reducibility by H{sub 2} was determined by following changes in the vanadia's UV Raman and resonance Raman spectra after reaction with H{sub 2} at temperatures from 450 to 650 C. The H{sub 2} reducibility sequence for the three monomeric species is bidentate > 'molecular' > tridentate. The reaction pathways for H{sub 2} reduction on the three vanadium oxide monomeric structures on a {theta}-alumina surface were investigated using density functional theory. Reduction by H{sub 2} begins with reaction at the V=O bond in all three species. However, the activation energy, Gibbs free energy change under reaction conditions, and the final V oxidation state are species-dependent. The calculated ordering of reactivity is consistent with the observed experimental ordering and provides an explanation for the ordering. The results suggest that synthesis strategies can be devised to obtain vanadium oxide structures with greatly enhanced activity for ODH resulting in more efficient catalysts.

  11. 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

  12. Preorganized Hydrogen Bond Donor Catalysts: Acidities and Reactivities.

    PubMed

    Samet, Masoud; Kass, Steven R

    2015-08-01

    Measured DMSO pKa values for a series of rigid tricyclic adamantane-like triols containing 0-3 trifluoromethyl groups (i.e., 3(0)-3(3)) are reported. The three compounds with CF3 substituents are similar or more acidic than acetic acid (pKa = 13.5 (3(1)), 9.5 (3(2)), 7.3 (3(3)) vs 12.6 (HOAc)), and the resulting hydrogen bond network enables a remote γ-trifluoromethyl group to enhance the acidity as well as one located at the α-position. Catalytic abilities of 3(0)-3(3) were also examined. In a nonpolar environment a rate enhancement of up to 100-fold over flexible acyclic analogs was observed presumably due to an entropic advantage of the locked-in structure. Gas-phase acidities are found to correlate with the catalytic activity better than DMSO pKa values and appear to be a better measure of acidities in low dielectric constant media. These trends are reduced or reversed in polar solvents highlighting the importance of the reaction environment. PMID:26140305

  13. Experimental study of the hydrothermal reactivity of organic acids and acid anions: II. Acetic acid, acetate, and valeric acid

    NASA Astrophysics Data System (ADS)

    McCollom, Thomas M.; Seewald, Jeffrey S.

    2003-10-01

    Organic acids and acid anions occur in substantial concentrations in many aqueous geologic fluids and are thought to take part in a variety of geochemical processes ranging from the transport of metals in ore-forming fluids to the formation of natural gas to serving as a metabolic energy source for microbes in subsurface habitats. The widespread occurrence of organic acids and their potential role in diverse geologic processes has led to numerous experimental studies of their thermal stability, yet there remain substantial gaps in our knowledge of the factors that control the rates and reaction pathways for the decomposition of these compounds under geologic conditions. In order to address some of these uncertainties, a series of laboratory experiments were conducted to examine the behavior of organic acids and acid anions under hydrothermal conditions in the presence of minerals. Reported here are results of experiments where aqueous solutions of acetic acid, sodium acetate, or valeric acid ( n-pentanoic acid) were heated at 325°C, 350 bars in the presence of the mineral assemblages hematite + magnetite + pyrite, pyrite + pyrrhotite + magnetite, and hematite + magnetite. The results indicate that aqueous acetic acid and acetate decompose by a combination of two reaction pathways: decarboxylation and oxidation. Both reactions are promoted by minerals, with hematite catalyzing the oxidation reaction while magnetite catalyzes decarboxylation. The oxidation reaction is much faster, so that oxidation dominates the decomposition of acetic acid and acetate when hematite is present. In contrast to previous reports that acetate decomposed more slowly than acetic acid, we found that acetate decomposed at slightly faster rates than the acid in the presence of minerals. Although longer-chain monocarboxylic acids are generally thought to decompose by decarboxylation, valeric acid appeared to decompose primarily by "deformylation" to 1-butene plus formic acid. Subsequent

  14. The Roles of Mitochondrial Reactive Oxygen Species in Cellular Signaling and Stress Response in Plants1[OPEN

    PubMed Central

    Millar, A. Harvey

    2016-01-01

    Mitochondria produce ATP via respiratory oxidation of organic acids and transfer of electrons to O2 via the mitochondrial electron transport chain. This process produces reactive oxygen species (ROS) at various rates that can impact respiratory and cellular function, affecting a variety of signaling processes in the cell. Roles in redox signaling, retrograde signaling, plant hormone action, programmed cell death, and defense against pathogens have been attributed to ROS generated in plant mitochondria (mtROS). The shortcomings of the black box-idea of mtROS are discussed in the context of mechanistic considerations and the measurement of mtROS. The overall aim of this update is to better define our current understanding of mtROS and appraise their potential influence on cellular function in plants. Furthermore, directions for future research are provided, along with suggestions to increase reliability of mtROS measurements. PMID:27021189

  15. Investigations of blue light-induced reactive oxygen species from flavin mononucleotide on inactivation of E. coli.

    PubMed

    Liang, Ji-Yuan; Cheng, Chien-Wei; Yu, Chin-Hao; Chen, Liang-Yü

    2015-02-01

    The micronutrients in many cellular processes, riboflavin, flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD) are photo-sensitive to UV and visible light for generating reactive oxygen species (ROS). Produced from phosphorylation of riboflavin, FMN is more water-soluble and rapidly transformed into free riboflavin after ingestion. This study investigated the application of visible blue light with FMN to development of an effective antimicrobial treatment. The photosensitization of bacterial viability with FMN was investigated by light quality, intensity, time, and irradiation dosage. The blue light-induced photochemical reaction with FMN could inactivate Escherichiacoli by the generated ROS in damaging nucleic acids, which was validated. This novel photodynamic technique could be a safe practice for photo-induced inactivation of environmental microorganism to achieve hygienic requirements in food processing. PMID:25617617

  16. Upconversion nanoprobes for efficiently in vitro imaging reactive oxygen species and in vivo diagnosing rheumatoid arthritis.

    PubMed

    Chen, Zhaowei; Liu, Zhen; Li, Zhenhua; Ju, Enguo; Gao, Nan; Zhou, Li; Ren, Jinsong; Qu, Xiaogang

    2015-01-01

    Over-generation of reactive oxygen species (ROS) is closely associated with the biological processes of rheumatoid arthritis (RA). Thus, efficient monitoring ROS in inflammatory joints would be essential for better understanding the pathogenesis and optimizing therapeutic interventions. Herein, we designed a ratiometric nanoprobe utilizing upconversion nanoparticles (UCNPs) conjugated with chromophore labeled hyaluronic acid (HA) for high sensitively sensing ROS in the aqueous solution, bioimaging ROS in inflammatory mimic cells and diagnosing RA in vivo. In this approach, the conjugation of HA conferred UCNPs not only water solubility but also biocompatibility and ROS recognizing properties. Particularly, the HA backbone cleavage and detachment of chromophore labeled HA fragments from UCNPs induced by ROS inhibited the luminescent energy transfer (LRET) and allowed rational metric upconversion luminescence (UCL) emission as the detection signal. Importantly, the upconversion nanoprobe showed high effectiveness for early assessing the treatment response of arthritic animals to an antiarthritic drug-methotrexate (MTX). PMID:25477167

  17. Inhibition of Cancer Cell Proliferation by PPARγ is Mediated by a Metabolic Switch that Increases Reactive Oxygen Species Levels

    PubMed Central

    Srivastava, Nishi; Kollipara, Rahul K.; Singh, Dinesh K.; Sudderth, Jessica; Hu, Zeping; Nguyen, Hien; Wang, Shan; Humphries, Caroline G.; Carstens, Ryan; Huffman, Kenneth E.; DeBerardinis, Ralph J.; Kittler, Ralf

    2014-01-01

    SUMMARY The nuclear receptor peroxisome-proliferation activated receptor gamma (PPARγ), a transcriptional master regulator of glucose and lipid metabolism, inhibits the growth of several common cancers including lung cancer. In this study, we show that the mechanism by which activation of PPARγ inhibits proliferation of lung cancer cells is based on metabolic changes. We found that treatment with the PPARγ agonist pioglitazone triggers a metabolic switch that inhibits pyruvate oxidation and reduces glutathione levels. These PPARγ-induced metabolic changes result in a marked increase of reactive oxygen species (ROS) levels that lead to rapid hypophosphorylation of retinoblastoma protein (RB) and cell cycle arrest. The antiproliferative effect of PPARγ activation can be prevented by suppressing pyruvate dehydrogenase kinase 4 (PDK4) or β-oxidation of fatty acids in vitro and in vivo. Our proposed mechanism also suggests that metabolic changes can rapidly and directly inhibit cell cycle progression of cancer cells by altering ROS levels. PMID:25264247

  18. Inhibition of cancer cell proliferation by PPARγ is mediated by a metabolic switch that increases reactive oxygen species levels.

    PubMed

    Srivastava, Nishi; Kollipara, Rahul K; Singh, Dinesh K; Sudderth, Jessica; Hu, Zeping; Nguyen, Hien; Wang, Shan; Humphries, Caroline G; Carstens, Ryan; Huffman, Kenneth E; DeBerardinis, Ralph J; Kittler, Ralf

    2014-10-01

    The nuclear receptor peroxisome-proliferation-activated receptor gamma (PPARγ), a transcriptional master regulator of glucose and lipid metabolism, inhibits the growth of several common cancers, including lung cancer. In this study, we show that the mechanism by which activation of PPARγ inhibits proliferation of lung cancer cells is based on metabolic changes. We found that treatment with the PPARγ agonist pioglitazone triggers a metabolic switch that inhibits pyruvate oxidation and reduces glutathione levels. These PPARγ-induced metabolic changes result in a marked increase of reactive oxygen species (ROS) levels that lead to rapid hypophosphorylation of retinoblastoma protein (RB) and cell-cycle arrest. The antiproliferative effect of PPARγ activation can be prevented by suppressing pyruvate dehydrogenase kinase 4 (PDK4) or β-oxidation of fatty acids in vitro and in vivo. Our proposed mechanism also suggests that metabolic changes can rapidly and directly inhibit cell-cycle progression of cancer cells by altering ROS levels. PMID:25264247

  19. Isolating Toxic Insulin Amyloid Reactive Species that Lack β-Sheets and Have Wide pH Stability

    PubMed Central

    Heldt, Caryn L.; Kurouski, Dmitry; Sorci, Mirco; Grafeld, Elizabeth; Lednev, Igor K.; Belfort, Georges

    2011-01-01

    Amyloid diseases, including Alzheimer's disease, are characterized by aggregation of normally functioning proteins or peptides into ordered, β-sheet rich fibrils. Most of the theories on amyloid toxicity focus on the nuclei or oligomers in the fibril formation process. The nuclei and oligomers are transient species, making their full characterization difficult. We have isolated toxic protein species that act like an oligomer and may provide the first evidence of a stable reactive species created by disaggregation of amyloid fibrils. This reactive species was isolated by dissolving amyloid fibrils at high pH and it has a mass >100 kDa and a diameter of 48 ± 15 nm. It seeds the formation of fibrils in a dose dependent manner, but using circular dichroism and deep ultraviolet resonance Raman spectroscopy, the reactive species was found to not have a β-sheet rich structure. We hypothesize that the reactive species does not decompose at high pH and maintains its structure in solution. The remaining disaggregated insulin, excluding the toxic reactive species that elongated the fibrils, returned to native structured insulin. This is the first time, to our knowledge, that a stable reactive species of an amyloid reaction has been separated and characterized by disaggregation of amyloid fibrils. PMID:21641325

  20. Production characteristics of reactive oxygen/nitrogen species in water using atmospheric pressure discharge plasmas

    NASA Astrophysics Data System (ADS)

    Takahashi, Kazuhiro; Satoh, Kohki; Itoh, Hidenori; Kawaguchi, Hideki; Timoshkin, Igor; Given, Martin; MacGregor, Scott

    2016-07-01

    A pulsed discharge, a DC corona discharge, and a plasma jet are separately generated above a water surface, and reactive oxygen species and reactive nitrogen species (ROS/RNS) in the water are investigated. ROS/RNS in water after the sparging of the off-gas of a packed-bed dielectric barrier discharge (PB-DBD) are also investigated. H2O2, NO2 ‑, and NO3 ‑ are detected after plasma exposure and only NO3 ‑ after off-gas sparging. Short-lifetime species in plasma are found to play an important role in H2O2 and NO2 ‑ production and long-lifetime species in NO3 ‑ production. NO x may inhibit H2O2 production through OH consumption to produce HNO2 and HNO3. O3 does not contribute to ROS/RNS production. The pulsed plasma exposure is found to be effective for the production of H2O2 and NO2 ‑, and the off-gas sparging of the PB-DBD for the production of NO3 ‑.

  1. Atmospheric and ocean measurements of reactive organic species from the Tropical Atlantic ocean.

    NASA Astrophysics Data System (ADS)

    Williams, J.; Holzinger, R.; Gros, V.; Hofmann, R.; Xu, X.; Wallace, D.

    2003-04-01

    Reactive organic species play an important role in the chemistry of the atmosphere. Large uncertainties exist in how the ocean influences the global budgets of reactive organic species. The first German SOLAS cruise M55 carried instrumentation to measure a range of organic species in the atmosphere and ocean surface layer. Between 12th October and 15th November the research vessel Meteor steamed from Curacao to Cameroon approximately along 10^o N. Approximately mid-Atlantic the ship performed two transects (N-S and S-N) reaching the equator and crossing the ITCZ twice. An assessment will be given of the organics over the Tropical Atlantic including data from 2 PTR-MS systems (air and water), canister air collection followed by GC-MS analysis, cartridge collection followed by 2D-GC-FID analysis, as well as ozone and CO instruments. The prevailing wind was easterly at all times so that air with decreasing extents of ocean contact time was encountered during the crossing. Longitudinal and interhemispheric gradients of organic species will be presented.

  2. Optimizing Pulse Waveforms in Plasma Jets for Reactive Oxygen Species (ROS) Production

    NASA Astrophysics Data System (ADS)

    Norberg, Seth; Babaeva, Natalia Yu.; Kushner, Mark J.

    2012-10-01

    Reactive oxygen species (ROS) are desired in numerous applications from the destruction of harmful proteins and bacteria for sterilization in the medical field to taking advantage of the metastable characteristics of O2(^1δ) to transfer energy to other species. Advances in atmospheric pressure plasma jets in recent years show the possibility of using this application as a source of reactive oxygen species. In this paper, we report on results from a computational investigation of atmospheric pressure plasma jets in a dielectric barrier discharge (DBD) configuration. The computer model used in this study, nonPDPSIM, solves transport equations for charged and neutral species, Poisson's equation for the electric potential, the electron energy conservation equation for the electron temperature, and Navier-Stokes equations for the neutral gas flow. A Monte Carlo simulation is used to track sheath accelerated secondary electrons emitted from surfaces and the energy of ions incident onto surfaces. Rate coefficients and transport coefficients for the bulk plasma are obtained from local solutions of Boltzmann's equation for the electron energy distribution. Radiation transport is addressed using a Green's function approach. Various waveforms for the voltage source were examined in analogy to spiker-sustainer systems used at lower gas pressures.

  3. Reactive Oxygen Species Mediate Epstein-Barr Virus Reactivation by N-Methyl-N’-Nitro-N-Nitrosoguanidine

    PubMed Central

    Huang, Sheng-Yen; Fang, Chih-Yeu; Wu, Chung-Chun; Tsai, Ching-Hwa; Lin, Su-Fang; Chen, Jen-Yang

    2013-01-01

    N-nitroso compounds (NOCs) and Epstein-Barr virus (EBV) reactivation have been suggested to play a role in the development of nasopharyngeal carcinoma (NPC). Although chemicals have been shown to be a risk factor contributing to the carcinogenesis of NPC, the underlying mechanism is not fully understood. We demonstrated recently that N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) enhances the genomic instability and tumorigenicity of NPC cells via induction of EBV reactivation. However, the mechanisms that trigger EBV reactivation from latency remain unclear. Here, we address the role of ROS in induction of EBV reactivation under MNNG treatment. EBV reactivation was induced in over 70% of EBV-positive NA cells and the promoter of Rta (Rp) was activated after MNNG treatment. Inhibitor experiments revealed ATM, p38 MAPK and JNK were activated by ROS and involved in MNNG-induced EBV reactivation. Significantly, ROS scavengers N-acetyl-L-cysteine (NAC), catalase and reduced glutathione inhibited EBV reactivation under MNNG and H2O2 treatment, suggesting ROS mediate EBV reactivation. The p53 was essential for EBV reactivation and the Rp activation by MNNG. Moreover, the p53 was phosphorylated, translocated into nucleus, and bound to Rp following ROS stimulation. The results suggest ROS play an important role in initiation of EBV reactivation by MNNG through a p53-dependent mechanism. Our findings demonstrate novel signaling mechanisms used by NOCs to induce EBV reactivation and provide a novel insight into NOCs link the EBV reactivation in the contribution to the development of NPC. Notably, this study indicates that antioxidants might be effective for inhibiting N-nitroso compound-induced EBV reactivation and therefore could be promising preventive and therapeutic agents for EBV reactivation-associated malignancies. PMID:24376853

  4. Fatty acid and sterol composition of three phytomonas species.

    PubMed

    Nakamura, C V; Waldow, L; Pelegrinello, S R; Ueda-Nakamura, T; Filho, B A; Filho, B P

    1999-01-01

    Fatty acid and sterol analysis were performed on Phytomonas serpens and Phytomonas sp. grown in chemically defined and complex medium, and P. françai cultivated in complex medium. The three species of the genus Phytomonas had qualitatively identical fatty acid patterns. Oleic, linoleic, and linolenic were the major unsaturated fatty acids. Miristic and stearic were the major saturated fatty acids. Ergosterol was the only sterol isolated from Phytmonas sp. and P. serpens grown in a sterol-free medium, indicating that it was synthesized de novo. When P. françai that does not grow in defined medium was cultivated in a complex medium, cholesterol was the only sterol detected. The fatty acids and sterol isolated from Phytomonas sp. and P. serpens grown in a chemically defined lipid-free medium indicated that they were able to biosynthesize fatty acids and ergosterol from acetate or from acetate precursors such as glucose or threonine. PMID:10446013

  5. Reactivity of monoclonal antibodies to species-specific antigens of Entamoeba histolytica.

    PubMed

    Tachibana, H; Kobayashi, S; Nagakura, K; Kaneda, Y; Takeuchi, T

    1991-01-01

    Twenty monoclonal antibodies were produced against trophozoites of Entamoeba histolytica strains HK-9 and HM-1: IMSS. When reactivity to various enteric protozoa was examined by an indirect fluorescence antibody test, 15 of the monoclonal antibodies were strongly reactive with E. histolytica trophozoites. Species-specific antigens recognized by these monoclonal antibodies were located on the plasma membrane, nucleus, cytoplasm, and cytoskeletal structures of the trophozoites. Two of the remaining five monoclonals reacted strongly with trophozoites of the E. histolytica-like Laredo strain. The determinant antigen was located in the cytoplasm. The three remaining monoclonal antibodies were found to recognize cross-reactive antigens between E. histolytica and E. histolytica-like Laredo, E. hartmanni, E. coli, Dientamoeba fragilis, Giardia lamblia, and Trichomonas hominis. These three antibodies were also reactive with T. vaginalis and mammalian cells such as HeLa cells. Thus, the combined use of monoclonal antibodies seems capable of distinguishing E. histolytica and/or E. histolytica-like Laredo from other enteric protozoa. PMID:1724012

  6. The Bacterial Fermentation Product Butyrate Influences Epithelial Signaling via Reactive Oxygen Species-Mediated Changes in Cullin-1 Neddylation1

    PubMed Central

    Kumar, Amrita; Wu, Huixia; Collier-Hyams, Lauren S.; Kwon, Young-Man; Hanson, Jason M.; Neish, Andrew S.

    2010-01-01

    The human enteric flora plays a significant role in intestinal health and disease. Populations of enteric bacteria can inhibit the NF-κB pathway by blockade of IκB-α ubiquitination, a process catalyzed by the E3-SCFβ-TrCP ubiquitin ligase. The activity of this ubiquitin ligase is regulated via covalent modification of the Cullin-1 subunit by the ubiquitin-like protein NEDD8. We previously reported that interaction of viable commensal bacteria with mammalian intestinal epithelial cells resulted in a rapid and reversible generation of reactive oxygen species (ROS) that modulated neddylation of Cullin-1 and resulted in suppressive effects on the NF-κB pathway. Herein, we demonstrate that butyrate and other short chain fatty acids supplemented to model human intestinal epithelia in vitro and human tissue ex vivo results in loss of neddylated Cul-1 and show that physiological concentrations of butyrate modulate the ubiquitination and degradation of a target of the E3-SCFβ-TrCP ubiquitin ligase, the NF-κB inhibitor IκB-α. Mechanistically, we show that physiological concentrations of butyrate induces reactive oxygen species that transiently alters the intracellular redox balance and results in inactivation of the NEDD8-conjugating enzyme Ubc12 in a manner similar to effects mediated by viable bacteria. Because the normal flora produces significant amounts of butyrate and other short chain fatty acids, these data provide a functional link between a natural product of the intestinal normal flora and important epithelial inflammatory and proliferative signaling pathways. PMID:19109186

  7. Reactive oxygen species produced upon photoexcitation of sunscreens containing titanium dioxide (an EPR study).

    PubMed

    Brezová, Vlasta; Gabcová, Sona; Dvoranová, Dana; Stasko, Andrej

    2005-05-13

    Commercial sunscreen products containing titanium dioxide were irradiated with lambda>300 nm and the formation of oxygen- (.OH, O2.-/.OOH) and carbon-centered radicals was monitored by EPR spectroscopy and spin trapping technique using 5,5-dimethyl-1-pyrroline N-oxide, alpha-phenyl-N-tert-butylnitrone (PBN), alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone as spin traps, and free nitroxide radical 4-hydroxy-2,2,6,6-tetramethylpiperidine N-oxyl. The photoinduced production of singlet oxygen was shown by 4-hydroxy-2,2,6,6-piperidine. The generation of reactive oxygen radical species upon irradiation of sunscreens significantly depends on their composition, as the additives present (antioxidants, radical-scavengers, solvents) can transform the reactive radicals formed to less harmful products. The continuous in situ irradiation of titanium dioxide powder, recommended for cosmetic application, investigated in different solvents (water, dimethyl sulfoxide, isopropyl myristate) resulted in the generation of oxygen-centered reactive radical species (superoxide anion radical, hydroxyl and alkoxyl radicals). PMID:15878117

  8. 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

  9. Direct and indirect inactivation of tumor cell protective catalase by salicylic acid and anthocyanidins reactivates intercellular ROS signaling and allows for synergistic effects.

    PubMed

    Scheit, Katrin; Bauer, Georg

    2015-03-01

    Salicylic acid and anthocyanidins are known as plant-derived antioxidants, but also can provoke paradoxically seeming prooxidant effects in vitro. These prooxidant effects are connected to the potential of salicylic acid and anthocyanidins to induce apoptosis selectively in tumor cells in vitro and to inhibit tumor growth in animal models. Several epidemiological studies have shown that salicylic acid and its prodrug acetylsalicylic acid are tumor-preventive for humans. The mechanism of salicylic acid- and anthocyanidin-dependent antitumor effects has remained enigmatic so far. Extracellular apoptosis-inducing reactive oxygen species signaling through the NO/peroxynitrite and the HOCl signaling pathway specifically induces apoptosis in transformed cells. Tumor cells have acquired resistance against intercellular reactive oxygen species signaling through expression of membrane-associated catalase. Here, we show that salicylic acid and anthocyanidins inactivate tumor cell protective catalase and thus reactive apoptosis-inducing intercellular reactive oxygen species signaling of tumor cells and the mitochondrial pathway of apoptosis Salicylic acid inhibits catalase directly through its potential to transform compound I of catalase into the inactive compound II. In contrast, anthocyanidins provoke a complex mechanism for catalase inactivation that is initiated by anthocyanidin-mediated inhibition of NO dioxygenase. This allows the formation of extracellular singlet oxygen through the reaction between H(2)O(2) and peroxynitrite, amplification through a caspase8-dependent step and subsequent singlet oxygen-mediated inactivation of catalase. The combination of salicylic acid and anthocyanidins allows for a remarkable synergistic effect in apoptosis induction. This effect may be potentially useful to elaborate novel therapeutic approaches and crucial for the interpretation of epidemiological results related to the antitumor effects of secondary plant compounds. PMID

  10. Serratia Secondary Metabolite Prodigiosin Inhibits Pseudomonas aeruginosa Biofilm Development by Producing Reactive Oxygen Species that Damage Biological Molecules

    PubMed Central

    Kimyon, Önder; Das, Theerthankar; Ibugo, Amaye I.; Kutty, Samuel K.; Ho, Kitty K.; Tebben, Jan; Kumar, Naresh; Manefield, Mike

    2016-01-01

    Prodigiosin is a heterocyclic bacterial secondary metabolite belonging to the class of tripyrrole compounds, synthesized by various types of bacteria including Serratia species. Prodigiosin has been the subject of intense research over the last decade for its ability to induce apoptosis in several cancer cell lines. Reports suggest that prodigiosin promotes oxidative damage to double-stranded DNA (dsDNA) in the presence of copper ions and consequently leads to inhibition of cell-cycle progression and cell death. However, prodigiosin has not been previously implicated in biofilm inhibition. In this study, the link between prodigiosin and biofilm inhibition through the production of redox active metabolites is presented. Our study showed that prodigiosin (500 μM) (extracted from Serratia marcescens culture) and a prodigiosin/copper(II) (100 μM each) complex have strong RNA and dsDNA cleaving properties while they have no pronounced effect on protein. Results support a role for oxidative damage to biomolecules by H2O2 and hydroxyl radical generation. Further, it was demonstrated that reactive oxygen species scavengers significantly reduced the DNA and RNA cleaving property of prodigiosin. P. aeruginosa cell surface hydrophobicity and biofilm integrity were significantly altered due to the cleavage of nucleic acids by prodigiosin or the prodigiosin/copper(II) complex. In addition, prodigiosin also facilitated the bactericidal activity. The ability of prodigiosinto cause nucleic acid degradation offers novel opportunities to interfere with extracellular DNA dependent bacterial biofilms. PMID:27446013

  11. Serratia Secondary Metabolite Prodigiosin Inhibits Pseudomonas aeruginosa Biofilm Development by Producing Reactive Oxygen Species that Damage Biological Molecules.

    PubMed

    Kimyon, Önder; Das, Theerthankar; Ibugo, Amaye I; Kutty, Samuel K; Ho, Kitty K; Tebben, Jan; Kumar, Naresh; Manefield, Mike

    2016-01-01

    Prodigiosin is a heterocyclic bacterial secondary metabolite belonging to the class of tripyrrole compounds, synthesized by various types of bacteria including Serratia species. Prodigiosin has been the subject of intense research over the last decade for its ability to induce apoptosis in several cancer cell lines. Reports suggest that prodigiosin promotes oxidative damage to double-stranded DNA (dsDNA) in the presence of copper ions and consequently leads to inhibition of cell-cycle progression and cell death. However, prodigiosin has not been previously implicated in biofilm inhibition. In this study, the link between prodigiosin and biofilm inhibition through the production of redox active metabolites is presented. Our study showed that prodigiosin (500 μM) (extracted from Serratia marcescens culture) and a prodigiosin/copper(II) (100 μM each) complex have strong RNA and dsDNA cleaving properties while they have no pronounced effect on protein. Results support a role for oxidative damage to biomolecules by H2O2 and hydroxyl radical generation. Further, it was demonstrated that reactive oxygen species scavengers significantly reduced the DNA and RNA cleaving property of prodigiosin. P. aeruginosa cell surface hydrophobicity and biofilm integrity were significantly altered due to the cleavage of nucleic acids by prodigiosin or the prodigiosin/copper(II) complex. In addition, prodigiosin also facilitated the bactericidal activity. The ability of prodigiosinto cause nucleic acid degradation offers novel opportunities to interfere with extracellular DNA dependent bacterial biofilms. PMID:27446013

  12. The roles of polycarboxylates in Cr(VI)/sulfite reaction system: Involvement of reactive oxygen species and intramolecular electron transfer.

    PubMed

    Jiang, Bo; Wang, Xianli; Liu, Yukun; Wang, Zhaohui; Zheng, Jingtang; Wu, Mingbo

    2016-03-01

    In this study, the effects of polycarboxylates on both Cr(VI) reduction and S(IV) consumption in Cr(VI)/S(IV) system was investigated in acidic solution. Under aerobic condition, the productions of reactive oxygen species (ROS), i.e., SO4(-) and OH, have been confirmed in S(IV) reducing Cr(VI) process by using electron spin resonance and fluorescence spectrum techniques, leading to the excess consumption of S(IV). However, when polycarboxylates (oxalic, citric, malic and tartaric acid) were present in Cr(VI)/S(IV) system, the affinity of polycarboxylates to CrSO6(2-) can greatly promote the reduction of Cr(VI) via expanding the coordination of Cr(VI) species from tetrahedron to hexahedron. Besides, as alternatives to S(IV), these polycarboxylates can also act as electron donors for Cr(VI) reduction via intramolecular electron transfer reaction, which is dependent on the energies of the highest occupied molecular orbital of these polycarboxylates. Notably, the variant electron donating capacity of these polycarboxylates resulted in different yield of ROS and therefore the oxidation efficiencies of other pollutants, e.g., rhodamine B and As(III). Generally, this study does not only shed light on the mechanism of S(IV) reducing Cr(VI) process mediated by polycarboxylates, but also provides an escalated, cost-effective and green strategy for the remediation of Cr(VI) using sulfite as a reductant. PMID:26610099

  13. Reactivity of the glutathione species towards the reduction of ormaplatin (or tetraplatin).

    PubMed

    Dong, Jingran; Huo, Shuying; Shen, Shigang; Xu, Jianzhong; Shi, Tiesheng; Elding, Lars I

    2016-09-01

    The reduction of ormaplatin (tetraplatin), a prototype for Pt(IV) anticancer prodrugs, by glutathione (GSH) was kinetically characterized over a wide pH range at 25.0°C and 1.0M ionic strength. The reduction follows overall second-order kinetics, giving rise to the oxidized glutathione as the oxidation product, which was identified by high-resolution mass spectrometry. The reaction mechanism put forward involves parallel attacks by all the GSH species on the Pt(IV) prodrug as rate-determining steps. All rate constants for the rate-determining steps have been derived for the first time, enabling the construction of the reactivity of GSH species versus their pH distribution diagram. The diagram clearly displays that only one out of the five GSH species is the mainly responsible for the reduction of ormaplatin at the physiological pH of 7.4. PMID:27481559

  14. Enhancing the reactivity of bimetallic Bi/Fe(0) by citric acid for remediation of polluted water.

    PubMed

    Gong, Jianyu; Lee, Chung-Seop; Kim, Eun-Ju; Chang, Yoon-Young; Chang, Yoon-Seok

    2016-06-01

    In this study, the environmentally benign citric acid (CA) was utilized to improve the aerobic degradation of 4-chlorophenol (4-CP) over bismuth modified nanoscale zero-valent iron (Bi/Fe(0)). The characterization results revealed the existence of bismuth covering on the Fe(0) surface under zero-valent state. And, the Bi/Fe(0)-CA+O2 system performed excellent reactivity in degradation of 4-CP due to the generation of reactive oxygen species (ROS), which was confirmed by electron spin resonance (ESR) spectroscopy. After 30min of reaction, 80% of 4-CP was removed using Bi/Fe(0)-CA+O2 accompanying with high dechlorination rate. The oxidative degradation intermediates were analyzed by HPLC and LC-MS. We found that CA could promote the bismuth-iron system to produce much reactive oxygen species ROS under both aerobic and anaerobic conditions due to its ligand function, which could react with Fe(3+) to form a ligand complex (Fe(III)Cit), accompanying with a considerable production of Fe(2+) and H2O2. This study provides a new strategy for generating ROS on nZVI and suggests its application for the mineralization of many recalcitrant pollutants. PMID:26905611

  15. 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.

  16. Chemical cross-linking with NHS esters: a systematic study on amino acid reactivities.

    PubMed

    Mädler, Stefanie; Bich, Claudia; Touboul, David; Zenobi, Renato

    2009-05-01

    Structure elucidation of tertiary or quaternary protein structures by chemical cross-linking and mass spectrometry (MS) has recently gained importance. To locate the cross-linker modification, dedicated software is applied to analyze the mass or tandem mass spectra (MS/MS). Such software requires information on target amino acids to limit the data analysis time. The most commonly used homobifunctional N-hydroxy succinimide (NHS) esters are often described as reactive exclusively towards primary amines, although side reactions with tyrosine and serine have been reported. Our goal was to systematically study the reactivity of NHS esters and derive some general rules for their attack of nucleophilic amino acid side chains in peptides. We therefore studied the cross-linking reactions of synthesized and commercial model peptides with disuccinimidyl suberate (DSS). The first reaction site in all cases was expectedly the alpha-NH(2)-group of the N-terminus or the epsilon-NH(2)-group of lysine. As soon as additional cross-linkers were attached or loops were formed, other amino acids were also involved in the reaction. In addition to the primary amino groups, serine, threonine and tyrosine showed significant reactivity due to the effect of neighboring amino acids by intermediate or permanent Type-1 cross-link formation. The reactivity is highly dependent on the pH and on adjacent amino acids. PMID:19132714

  17. Degradation State, Sources, and Reactivity of Dissolved Organic Matter from an Amino Acid Time Series in an Agricultural Watershed

    NASA Astrophysics Data System (ADS)

    Matiasek, S. J.; Pellerin, B. A.; Spencer, R. G.; Bergamaschi, B. A.; Hernes, P.

    2015-12-01

    A detailed time series of dissolved amino acids was obtained in an agricultural watershed in the northern Central Valley, California, USA to investigate the roles of hydrologic and seasonal changes on the composition of dissolved organic matter (DOM). Total hydrolysable amino acid (THAA) concentrations ranged from 0.55 to 9.96 μM (mean 3.76 ± 1.80 μM) and not only peaked with discharge during winter storms, but also remained elevated throughout the irrigation season when discharge was low. Summer irrigation was a critical hydrologic regime for DOM cycling, since it mobilized DOM similar in concentration and reactivity to DOM released during winter storms for an extended period of time, with the largest amino acid contributions to the dissolved organic carbon (DOC) and the dissolved organic nitrogen (DON) pools (3.4 ‒ 3.7 % DOC-AA, 17.4 ‒ 22.5 % DON-AA), the largest proportion of basic amino acids (B/(B+A) = 0.19 ‒ 0.22), and the largest degradation index values (mean 1.37 ± 0.96). The mole percent of non-protein amino acids, commonly considered as an indicator of microbial degradation, decreased with DOM processing and was highest during summer (mean 4.1 ± 1.1%). A lack of correlation between THAA concentrations and UV-Vis absorbance and fluorescence proxies (including "protein-like" fluorophores B and T) indicated that optical properties may be limited in representing amino acid dynamics in this system. A new parameter for DOM processing derived from trends in individual amino acids demonstrated strong potential for inferring the extent of DOM degradation in freshwater systems. The biogeochemical relevance of irrigation practices is heightened by timing, since the additional export of reactive DOM coincides with enhanced downstream DOM processing in the Sacramento-San Joaquin River Delta, a critical habitat for endangered species serving as water source for 25 million Californians.

  18. Furfural induces reactive oxygen species accumulation and cellular damage in Saccharomyces cerevisiae

    PubMed Central

    2010-01-01

    Background Biofuels offer a viable alternative to petroleum-based fuel. However, current methods are not sufficient and the technology required in order to use lignocellulosic biomass as a fermentation substrate faces several challenges. One challenge is the need for a robust fermentative microorganism that can tolerate the inhibitors present during lignocellulosic fermentation. These inhibitors include the furan aldehyde, furfural, which is released as a byproduct of pentose dehydration during the weak acid pretreatment of lignocellulose. In order to survive in the presence of furfural, yeast cells need not only to reduce furfural to the less toxic furan methanol, but also to protect themselves and repair any damage caused by the furfural. Since furfural tolerance in yeast requires a functional pentose phosphate pathway (PPP), and the PPP is associated with reactive oxygen species (ROS) tolerance, we decided to investigate whether or not furfural induces ROS and its related cellular damage in yeast. Results We demonstrated that furfural induces the accumulation of ROS in Saccharomyces cerevisiae. In addition, furfural was shown to cause cellular damage that is consistent with ROS accumulation in cells which includes damage to mitochondria and vacuole membranes, the actin cytoskeleton and nuclear chromatin. The furfural-induced damage is less severe when yeast are grown in a furfural concentration (25 mM) that allows for eventual growth after an extended lag compared to a concentration of furfural (50 mM) that prevents growth. Conclusion These data suggest that when yeast cells encounter the inhibitor furfural, they not only need to reduce furfural into furan methanol but also to protect themselves from the cellular effects of furfural and repair any damage caused. The reduced cellular damage seen at 25 mM furfural compared to 50 mM furfural may be linked to the observation that at 25 mM furfural yeast were able to exit the furfural-induced lag phase and resume

  19. 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

  20. Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma.

    PubMed

    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 invasion

  1. Detection of saccharides by reactive desorption electrospray ionization (DESI) using modified phenylboronic acids

    NASA Astrophysics Data System (ADS)

    Zhang, Yun; Chen, Hao

    2010-01-01

    We have reported previously a method for the detection of sugars via in-situ derivatization with phenylboronic acid PhB(OH)2 using reactive desorption electrospray ionization (DESI, Chen et al., Chem. Commun. (2006) 597-599). The present study describes an improved method that employs modified phenylboronic acids including 3-nitrophenylboronic acid and N-methyl-4-pyridineboronic acid iodide. In contrast to using PhB(OH)2, enhanced sensitivity of using 3-nitrophenylboronic acid was observed due to the stabilization of the resulting boronate ester anion by the electron-withdrawing nitro group and the limit of detections (LODs) for glucose in water using 3-nitrophenylbornic acid and phenylboronic acid were determined to be 0.11 mM and 0.40 mM, respectively. In the case of N-methyl-4-pyridineboronic acid iodide, the corresponding LOD is 6.9 [mu]M and the higher sensitivity obtained is attributed to the efficient ionization of both the reactive DESI reagent and reaction product since the precursor acid with a quaternary ammonium group is pre-charged. In this case, additional important features are found: (i) unlike using phenylboronic acid or 3-nitrophenylbornic acid, the experiment, performed in the positive ion mode, is applicable to neutral and acidic saccharide solutions, facilitating the analysis of biological fluids without the need to adjust pH; (ii) simply by changing the spray solvent from water to acetonitrile, the method can be used for direct glucose analyses of both urine and serum samples via online desalting, due to the low solubility of salts of these biofluids in the sprayed organic solvent; (iii) in comparison with other sugar derivatizing reagents such as the Girard's reagent T, the N-methyl-4-pyridineboronic acid iodide shows higher reactivity in the reactive DESI; and (iv) the ions of saccharide DESI reaction products undergo extensive ring or glycosidic bond cleavage upon CID, a feature that might be useful in the structure elucidation of

  2. Multilayer Heterojunction Anodes for Saline Wastewater Treatment: Design Strategies and Reactive Species Generation Mechanisms.

    PubMed

    Yang, Yang; Shin, Jieun; Jasper, Justin T; Hoffmann, Michael R

    2016-08-16

    Multilayer heterojunction SbSn/CoTi/Ir anodes, which consist of Ir0.7Ta0.3O2 bottom layers coated onto a titanium base, Co-TiO2 interlayers, and overcoated discrete Sb-SnO2 islands, were prepared by spray pyrolysis. The Ir0.7Ta0.3O2 bottom layer serves as an Ohmic contact to facilitate electron transfer from semiconductor layers to the Ti base. The Co-TiO2 interlayer and overcoated Sb-SnO2 islands enhance the evolution of reactive chlorine. The surficial Sb-SnO2 islands also serve as the reactive sites for free radical generation. Experiments coupled with computational kinetic simulations show that while ·OH and Cl· are initially produced on the SbSn/CoTi/Ir anode surface, the dominant radical formed in solution is the dichlorine radical anion, Cl2·(-). The steady-state concentration of reactive radicals is 10 orders of magnitude lower than that of reactive chlorine. The SbSn/CoTi/Ir anode was applied to electrochemically treat human wastewater. These test results show that COD and NH4(+) can be removed after 2 h of electrolysis with minimal energy consumption (370 kWh/kg COD and 383 kWh/kg NH4(+)). Although free radical species contribute to COD removal, anodes designed to enhance reactive chlorine production are more effective than those designed to enhance free radical production. PMID:27402194

  3. Influence of coffee genotype on bioactive compounds and the in vitro capacity to scavenge reactive oxygen and nitrogen species.

    PubMed

    Rodrigues, Naira Poerner; Salva, Terezinha de Jesus Garcia; Bragagnolo, Neura

    2015-05-20

    The influence of green coffee genotype on the bioactive compounds and the in vitro antioxidant capacity against the principal reactive oxygen (ROO(•), H2O2, HO(•), and HOCl) and nitrogen (NO(•) and ONOO(-)) species of biological relevance was investigated. This is the first report on the capacity of green coffee to scavenge H2O2, HOCl, and NO(•). Variations in the contents of total chlorogenic acids (22.9-37.9 g/100 g), cinnamoyl-amino acid conjugates (0.03-1.12 g/100 g), trigonelline (3.1-6.7 g/100 g), and caffeine (3.9-11.8 g/100 g) were found. Hydrophilic extracts of Coffea canephora and Coffea kapakata were the most potent scavengers of ROO(•), H2O2, HO(•), NO(•), and ONOO(-) due to their chlorogenic acid contents, which were, on average, 30% higher than those found in Coffea arabica and Coffea racemosa. The results showed that genotype is a determinant characteristic in the bioactive compound contents and consequently in the antioxidant capacity of green coffee. PMID:25910038

  4. A novel biointerface that suppresses cell morphological changes by scavenging excess reactive oxygen species.

    PubMed

    Ikeda, Yutaka; Yoshinari, Tomoki; Nagasaki, Yukio

    2015-09-01

    During cell cultivation on conventional culture dishes, various events results in strong stresses that lead to the production of bioactive species such as reactive oxygen species (ROS) and nitric oxide. These reactive species cause variable damage to cells and stimulate cellular responses. Here, we report the design of a novel biocompatible surface that decreases stress by not only morphologically modifying the dish surface by using poly(ethylene glycol) tethered chains, but also actively scavenging oxidative stress by using our novel nitroxide radical-containing polymer. A block copolymer, poly(ethylene glycol)-b-poly[(2,2,6,6-tetramethylpiperidine-N-oxyl)aminomethylstyrene] (PEG-b-PMNT) was used to coat the surface of a dish. Differentiation of undifferentiated human leukemia (HL-60) cells was found to be suppressed on the polymer-coated dish. Notably, HL-60 cell cultivation caused apoptosis under high-density conditions, while spontaneous apoptosis was suppressed in cells plated on the PEG-b-PMNT-modified surface, because a healthy mitochondrial membrane potential was maintained. In contrast, low molecular weight antioxidants did not have apparent effects on the maintenance of mitochondria. We attribute this to the lack of cellular internalization of our immobilized polymer and selective scavenging of excessive ROS generated outside of cells. These results demonstrate the utility of our novel biocompatible material for actively scavenging ROS and thus maintaining cellular morphology. PMID:25691268

  5. Evidence for reactive reduced phosphorus species in the early Archean ocean

    PubMed Central

    Pasek, Matthew A.; Harnmeijer, Jelte P.; Buick, Roger; Gull, Maheen; Atlas, Zachary

    2013-01-01

    It has been hypothesized that before the emergence of modern DNA–RNA–protein life, biology evolved from an “RNA world.” However, synthesizing RNA and other organophosphates under plausible early Earth conditions has proved difficult, with the incorporation of phosphorus (P) causing a particular problem because phosphate, where most environmental P resides, is relatively insoluble and unreactive. Recently, it has been proposed that during the Hadean–Archean heavy bombardment by extraterrestrial impactors, meteorites would have provided reactive P in the form of the iron–nickel phosphide mineral schreibersite. This reacts in water, releasing soluble and reactive reduced P species, such as phosphite, that could then be readily incorporated into prebiotic molecules. Here, we report the occurrence of phosphite in early Archean marine carbonates at levels indicating that this was an abundant dissolved species in the ocean before 3.5 Ga. Additionally, we show that schreibersite readily reacts with an aqueous solution of glycerol to generate phosphite and the membrane biomolecule glycerol–phosphate under mild thermal conditions, with this synthesis using a mineral source of P. Phosphite derived from schreibersite was, hence, a plausible reagent in the prebiotic synthesis of phosphorylated biomolecules and was also present on the early Earth in quantities large enough to have affected the redox state of P in the ocean. Phosphorylated biomolecules like RNA may, thus, have first formed from the reaction of reduced P species with the prebiotic organic milieu on the early Earth. PMID:23733935

  6. Antigenic cross-reactivity and species-specific identification of Pseudocerastes persicus fieldi snake venom.

    PubMed

    Ibrahim, Nihal M; El-Kady, Ebtsam M

    2016-09-01

    In the present study, we recognized progressively high immunological cross-reactivity between Pseudocerastes persicus fieldi (Pf) venom and six other medically important Egyptian snake venoms belonging to families Viperidae and Elapidae. Antibodies with a range of bonding strengths were shown to be involved in such cross-reactivity. Two strategies have been tried to access specificity; (i) using affinity purified species-specific anti-Pf antivenom antibodies, (ii) conducting the assay in the presence of ammonium thiocyanate (NH4SCN). The discrimination power of the prepared species-specific antivenom was demonstrated by its ability to detect Pf venom over a range of Pf concentrations (2.5 ng-2.5 μg) in a variety of body fluids. The assay could distinguish circulating Pf antigens from other viper antigens in the whole blood of experimentally envenomed mice. What seems promising in our work is the use of the chaotrope, NH4SCN, which renders the reaction medium more favorable for the specific homologous antigen-antibody interactions, primarily via preventing lower avid antibodies to share and, to a bit lesser extent, by decreasing non-specific absorbance signals frequently encountered with ELISA assays. The ELISA described herein may be useful for clinicians for identification of snake bites inflicted by Pf snake species. Balancing between specificity and sensitivity has to be considered for best results. PMID:27319296

  7. Multiscale Reactive Molecular Dynamics for Absolute pK a Predictions and Amino Acid Deprotonation.

    PubMed

    Nelson, J Gard; Peng, Yuxing; Silverstein, Daniel W; Swanson, Jessica M J

    2014-07-01

    Accurately calculating a weak acid's pK a from simulations remains a challenging task. We report a multiscale theoretical approach to calculate the free energy profile for acid ionization, resulting in accurate absolute pK a values in addition to insights into the underlying mechanism. Importantly, our approach minimizes empiricism by mapping electronic structure data (QM/MM forces) into a reactive molecular dynamics model capable of extensive sampling. Consequently, the bulk property of interest (the absolute pK a) is the natural consequence of the model, not a parameter used to fit it. This approach is applied to create reactive models of aspartic and glutamic acids. We show that these models predict the correct pK a values and provide ample statistics to probe the molecular mechanism of dissociation. This analysis shows changes in the solvation structure and Zundel-dominated transitions between the protonated acid, contact ion pair, and bulk solvated excess proton. PMID:25061442

  8. Beneficial effects of fructose 1,6-biphosphate on hypothermia-induced reactive oxygen species injury in rats.

    PubMed

    Gámez, Antonio; Alva, Norma; Roig, Teresa; Bermúdez, Jordi; Carbonell, Teresa

    2008-08-20

    The release of reactive oxygen species has been described in hypothermic cells and tissues. Fructose 1,6-biphosphate (F1,6-BP) protects tissue stored at cold temperatures. We study the effect of F1,6-BP in vivo administration on anaesthetized rats exposed to cold stress (4 degrees C chamber for 30 min) and rewarming, to see if it alters cold-induced oxidative injury. Body temperatures show that the animals reached moderate hypothermia (26.80+/-0.62 degrees C) after 30 min of cold exposition. A decrease in mean arterial pressure was found. One group of animals was then rewarmed. Both hypothermia and rewarming increased the production of thiobarbituric acid-reactive substances, an index of lipid peroxidation, and reduced the antioxidant levels of plasmatic sulfhydryl groups, as well as decreasing the enzymatic activities of Cu,Zn-superoxide dismutase (Cu,Zn-SOD), catalase and GSH peroxidase in erythrocytes. Administration of F1,6-BP increased sulfhydryl groups and limited lipid peroxidation in plasma. It furthermore enhanced Cu,Zn-SOD and GSH peroxidase antioxidant activity in erythrocytes and preserved mean arterial pressure. Therefore, F1,6-BP has therapeutic potential based on its ability to reduce free-radical injury resulting from acute cold exposure and rewarming in vivo. PMID:18602097

  9. Contribution of reactive oxygen species to cartilage degradation in rheumatic diseases: molecular pathways, diagnosis and potential therapeutic strategies.

    PubMed

    Schiller, J; Fuchs, B; Arnhold, J; Arnold, K

    2003-10-01

    Inflammatory joint diseases are of considerable socio-economic significance. However, mechanisms of cartilage destruction are so far only poorly understood. This review is dedicated to reactive oxygen species (ROS) like superoxide anion radicals, hydrogen peroxide, singlet oxygen, hypochlorous acid, hydroxyl radicals and nitric oxide that are generated under inflammatory conditions and also to their potential contribution to cartilage degradation. First, the relevance of rheumatic diseases and potential mechanisms of cartilage degradation are discussed in this review, followed by the description of the chemical constituents and the molecular architecture of articular cartilage as well as the different cell types that play a role in inflammation and cartilage destruction. Methods of the assessment of cartilage degeneration are also shortly discussed. In the main chapter of this review the characteristics of individual ROS, their generation under in vivo conditions as well as their reactivities with individual cartilage components are discussed. Because of the low selectivity of ROS, useful "markers" of cartilage degradation allowing the differentiation of effects induced by individual ROS are also discussed. In the last chapter current therapeutic concepts of the treatment of rheumatic diseases are reviewed. The recently developed "anti-TNF-alpha" therapy that is primarily directed against neutrophilic granulocytes that are powerful sources of ROS and, therefore, important mediators of joint degeneration are emphasised. PMID:12871089

  10. Sensing atmospheric reactive species using light emitting diode by incoherent broadband cavity enhanced absorption spectroscopy.

    PubMed

    Yi, Hongming; Wu, Tao; Wang, Guishi; Zhao, Weixiong; Fertein, Eric; Coeur, Cécile; Gao, Xiaoming; Zhang, Weijun; Chen, Weidong

    2016-05-16

    We overview our recent progress in the developments and applications of light emitting diode-based incoherent broadband cavity enhanced absorption spectroscopy (LED-IBBCEAS) techniques for real-time optical sensing chemically reactive atmospheric species (HONO, NO3, NO2) in intensive campaigns and in atmospheric simulation chamber. New application of optical monitoring of NO3 concentration-time profile for study of the NO3-initiated oxidation process of isoprene in a smog chamber is reported. PMID:27409951

  11. Generation of reactive oxygen species by interaction between antioxidants used as food additive and metal ions.

    PubMed

    Iwasaki, Yusuke; Oda, Momoko; Tsukuda, Yuri; Nagamori, Yuki; Nakazawa, Hiroyuki; Ito, Rie; Saito, Koichi

    2014-01-01

    Food additives, such as preservatives, sweeteners, coloring agents, and flavoring agents, are widely used in food manufacturing. However, their combined effects on the human body are not known. The purpose of this study was to examine whether combinations of antioxidants and metal ions generate reactive oxygen species (ROS) under in vitro conditions using electron spin resonance (ESR). Among the metal ions examined, only iron and copper generated ROS in the presence of antioxidants. Moreover, certain phenolic antioxidants having pro-oxidant activity induced DNA oxidation and degradation via the generation of high levels of ROS in the presence of copper ion, resulting in complete degradation of DNA in vitro. PMID:25212818

  12. Superparamagnetic iron oxide nanoparticles as radiosensitizer via enhanced reactive oxygen species formation.

    PubMed

    Klein, Stefanie; Sommer, Anja; Distel, Luitpold V R; Neuhuber, Winfried; Kryschi, Carola

    2012-08-24

    Internalization of citrate-coated and uncoated superparamagnetic iron oxide nanoparticles by human breast cancer (MCF-7) cells was verified by transmission electron microscopy imaging. Cytotoxicity studies employing metabolic and trypan blue assays manifested their excellent biocompatibility. The production of reactive oxygen species in iron oxide nanoparticle loaded MCF-7 cells was explained to originate from both, the release of iron ions and their catalytically active surfaces. Both initiate the Fenton and Haber-Weiss reaction. Additional oxidative stress caused by X-ray irradiation of MCF-7 cells was attributed to the increase of catalytically active iron oxide nanoparticle surfaces. PMID:22842461

  13. Functional implications of mitochondrial reactive oxygen species generated by oncogenic viruses

    PubMed Central

    Choi, Young Bong; Harhaj, Edward William

    2014-01-01

    Between 15–20% of human cancers are associated with infection by oncogenic viruses. Oncogenic viruses, including HPV, HBV, HCV and HTLV-1, target mitochondria to influence cell proliferation and survival. Oncogenic viral gene products also trigger the production of reactive oxygen species which can elicit oxidative DNA damage and potentiate oncogenic host signaling pathways. Viral oncogenes may also subvert mitochondria quality control mechanisms such as mitophagy and metabolic adaptation pathways to promote virus replication. Here, we will review recent progress on viral regulation of mitophagy and metabolic adaptation and their roles in viral oncogenesis. PMID:25580106

  14. Beyond oxidative stress: an immunologist’s guide to reactive oxygen species

    PubMed Central

    Nathan, Carl; Cunningham-Bussel, Amy

    2014-01-01

    Reactive oxygen species (ROS) react preferentially with certain atoms to modulate functions ranging from cell homeostasis to cell death. Molecular actions include both inhibition and activation of proteins, mutagenesis of DNA and activation of gene transcription. Cellular actions include promotion or suppression of inflammation, immunity and carcinogenesis. ROS help the host to compete against microorganisms and are also involved in intermicrobial competition. ROS chemistry and their pleiotropy make them difficult to localize, to quantify and to manipulate — challenges we must overcome to translate ROS biology into medical advances. PMID:23618831

  15. Reactive oxygen species controllable non-thermal helium plasmas for evaluation of plasmid DNA strand breaks

    NASA Astrophysics Data System (ADS)

    Young Kim, Jae; Lee, Dong-Hoon; Ballato, John; Cao, Weiguo; Kim, Sung-O.

    2012-11-01

    Non-thermal, oxygen-rich helium plasmas were investigated to achieve an enhanced reactive oxygen species concentration at low voltage driving conditions. A non-thermal plasma device was fabricated based on a theta-shaped tube, and its potential was investigated for use in topological alteration of plasmid DNA. The optical emission spectra of the plasma showed that the oxygen flow affected the plasma properties, even though an oxygen plasma was not produced. The plasmid DNA strand breaks became more significant with the addition of oxygen flow to the helium in a single hollow, theta-shaped tube with other experimental conditions being unchanged.

  16. Reactive oxygen species and nitric oxide mediate plasticity of neuronal calcium signaling

    PubMed Central

    Yermolaieva, Olena; Brot, Nathan; Weissbach, Herbert; Heinemann, Stefan H.; Hoshi, Toshinori

    2000-01-01

    Reactive oxygen species (ROS) and nitric oxide (NO) are important participants in signal transduction that could provide the cellular basis for activity-dependent regulation of neuronal excitability. In young rat cortical brain slices and undifferentiated PC12 cells, paired application of depolarization/agonist stimulation and oxidation induces long-lasting potentiation of subsequent Ca2+ signaling that is reversed by hypoxia. This potentiation critically depends on NO production and involves cellular ROS utilization. The ability to develop the Ca2+ signal potentiation is regulated by the developmental stage of nerve tissue, decreasing markedly in adult rat cortical neurons and differentiated PC12 cells. PMID:10618438

  17. 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.

  18. Induced reactive oxygen species improve enzyme production from Aspergillus niger cultivation.

    PubMed

    Sahoo, Susmita; Rao, K Krishnamurthy; Suraishkumar, G K

    2003-05-01

    Intracellular reactive oxygen species (iROS) induction by HOCl was used as a novel strategy to improve enzyme productivities in Aspergillus niger growing in a bioreactor. With induced iROS, the specific intracellular activities of alpha-amylase, protease, catalase, and glucose oxidase were increased by about 170%, 250%, 320%, and 260%, respectively. The optimum specific iROS level for achieving maximum cell concentration and enzyme production was about 15 mmol g cell-1. The type of iROS inducing the enzyme production was identified to be a derivative of the superoxide radical. PMID:12882014

  19. Color removal from acid and reactive dye solutions by electrocoagulation and electrocoagulation/adsorption processes.

    PubMed

    Bellebia, S; Kacha, S; Bouberka, Z; Bouyakoub, A Z; Derriche, Z

    2009-04-01

    In this study, electrocoagulation of Marine Blue Erionyl MR (acid dye) and electrocoagulation followed by adsorption of Brilliant Blue Levafix E-BRA (reactive dye) from aqueous solutions were investigated, using aluminum electrodes and granular activated carbon (GAC). In the electrocoagulation and adsorption of dyestuff solutions, the effects of current density, loading charge, pH, conductivity, stirring velocity, contact time, and GAC concentration were examined. The optimum conditions for the electrocoagulation process were identified as loading charges 7.46 and 1.49 F/m3, for a maximum abatement of 200 mg/L reactive and acid dye, respectively. The residual reactive dye concentration was completely removed with 700 mg/L GAC. The results of this investigation provide important data for the development of a combined process to remove significant concentrations of recalcitrant dyes from water, using moderate activated carbon energy and aluminum consumption, and thereby lowering the cost of treatment. PMID:19445327

  20. Biosynthesis of Jasmonic Acid by Several Plant Species 1

    PubMed Central

    Vick, Brady A.; Zimmerman, Don C.

    1984-01-01

    Six plant species metabolized 18O-labeled 12-oxo-cis,cis-10,15-phytodienoic acid (12-oxo-PDA) to short chain cyclic fatty acids. The plant species were corn (Zea mays L.), eggplant (Solanum melongena L.), flax (Linum usitatissimum L.), oat (Avena sativa L.), sunflower (Helianthus annuus L.), and wheat (Triticum aestivum L.). Among the products was jasmonic acid, a natural plant constituent with growth-regulating properties. The pathway is the same as the one recently reported by us for jasmonic acid synthesis in Vicia faba L. pericarp. First, the ring double bond of 12-oxo-PDA is saturated; then β-oxidation enzymes remove six carbons from the carboxyl side chain of the ring. Substrate specificity studies indicated that neither the stereochemistry of the side chain at carbon 13 of 12-oxo-PDA nor the presence of the double bond at carbon 15 was crucial for either enzyme step. The presence of enzymes which convert 12-oxo-PDA to jasmonic acid in several plant species indicates that this may be a general metabolic pathway in plants. PMID:16663643

  1. The complex interplay of iron metabolism, reactive oxygen species, and reactive nitrogen species: insights into the potential of various iron therapies to induce oxidative and nitrosative stress.

    PubMed

    Koskenkorva-Frank, Taija S; Weiss, Günter; Koppenol, Willem H; Burckhardt, Susanna

    2013-12-01

    Production of minute concentrations of superoxide (O2(*-)) and nitrogen monoxide (nitric oxide, NO*) plays important roles in several aspects of cellular signaling and metabolic regulation. However, in an inflammatory environment, the concentrations of these radicals can drastically increase and the antioxidant defenses may become overwhelmed. Thus, biological damage may occur owing to redox imbalance-a condition called oxidative and/or nitrosative stress. A complex interplay exists between iron metabolism, O2(*-), hydrogen peroxide (H2O2), and NO*. Iron is involved in both the formation and the scavenging of these species. Iron deficiency (anemia) (ID(A)) is associated with oxidative stress, but its role in the induction of nitrosative stress is largely unclear. Moreover, oral as well as intravenous (iv) iron preparations used for the treatment of ID(A) may also induce oxidative and/or nitrosative stress. Oral administration of ferrous salts may lead to high transferrin saturation levels and, thus, formation of non-transferrin-bound iron, a potentially toxic form of iron with a propensity to induce oxidative stress. One of the factors that determine the likelihood of oxidative and nitrosative stress induced upon administration of an iv iron complex is the amount of labile (or weakly-bound) iron present in the complex. Stable dextran-based iron complexes used for iv therapy, although they contain only negligible amounts of labile iron, can induce oxidative and/or nitrosative stress through so far unknown mechanisms. In this review, after summarizing the main features of iron metabolism and its complex interplay with O2(*-), H2O2, NO*, and other more reactive compounds derived from these species, the potential of various iron therapies to induce oxidative and nitrosative stress is discussed and possible underlying mechanisms are proposed. Understanding the mechanisms, by which various iron formulations may induce oxidative and nitrosative stress, will help us

  2. Influence of the sulfur species reactivity on biofilm conformation during pyrite colonization by Acidithiobacillus thiooxidans.

    PubMed

    Lara, René H; García-Meza, J Viridiana; Cruz, Roel; Valdez-Pérez, Donato; González, Ignacio

    2012-08-01

    Massive pyrite (FeS₂) electrodes were potentiostatically modified by means of variable oxidation pulse to induce formation of diverse surface sulfur species (S(n)²⁻, S⁰). The evolution of reactivity of the resulting surfaces considers transition from passive (e.g., Fe(1-x )S₂) to active sulfur species (e.g., Fe(1-x )S(2-y ), S⁰). Selected modified pyrite surfaces were incubated with cells of sulfur-oxidizing Acidithiobacillus thiooxidans for 24 h in a specific culture medium (pH 2). Abiotic control experiments were also performed to compare chemical and biological oxidation. After incubation, the attached cells density and their exopolysaccharides were analyzed by confocal laser scanning microscopy (CLMS) and atomic force microscopy (AFM) on bio-oxidized surfaces; additionally, S(n)²⁻/S⁰ speciation was carried out on bio-oxidized and abiotic pyrite surfaces using Raman spectroscopy. Our results indicate an important correlation between the evolution of S(n)²⁻/S⁰ surface species ratio and biofilm formation. Hence, pyrite surfaces with mainly passive-sulfur species were less colonized by A. thiooxidans as compared to surfaces with active sulfur species. These results provide knowledge that may contribute to establishing interfacial conditions that enhance or delay metal sulfide (MS) dissolution, as a function of the biofilm formed by sulfur-oxidizing bacteria. PMID:22113561

  3. Real-Time Discrimination and Versatile Profiling of Spontaneous Reactive Oxygen Species in Living Organisms with a Single Fluorescent Probe.

    PubMed

    Zhang, Ruilong; Zhao, Jun; Han, Guangmei; Liu, Zhengjie; Liu, Cui; Zhang, Cheng; Liu, Bianhua; Jiang, Changlong; Liu, Renyong; Zhao, Tingting; Han, Ming-Yong; Zhang, Zhongping

    2016-03-23

    Fluorescent probes are powerful tools for the investigations of reactive oxygen species (ROS) in living organisms by visualization and imaging. However, the multiparallel assays of several ROS with multiple probes are often limited by the available number of spectrally nonoverlapping chromophores together with large invasive effects and discrepant biological locations. Meanwhile, the spontaneous ROS profilings in various living organs/tissues are also limited by the penetration capability of probes across different biological barriers and the stability in reactive in vivo environments. Here, we report a single fluorescent probe to achieve the effective discrimination and profiling of hydroxyl radicals (•OH) and hypochlorous acid (HClO) in living organisms. The probe is constructed by chemically grafting an additional five-membered heterocyclic ring and a lateral triethylene glycol chain to a fluorescein mother, which does not only turn off the fluorescence of fluorescein, but also create the dual reactive sites to ROS and the penetration capability in passing through various biological barriers. The reactions of probe with •OH and HClO simultaneously result in cyan and green emissions, respectively, providing the real-time discrimination and quantitative analysis of the two ROS in cellular mitochondria. Surprisingly, the accumulation of probes in the intestine and liver of a normal-state zebrafish and the transfer pathway from intestine-to-blood-to-organ/tissue-to-kidney-to-excretion clearly present the profiling of spontaneous •OH and HClO in these metabolic organs. In particular, the stress generation of •OH at the fresh wound of zebrafish is successfully visualized for the first time, in spite of its extremely short lifetime. PMID:26938117

  4. Heavy-metal-induced reactive oxygen species: phytotoxicity and physicochemical changes in plants.

    PubMed

    Shahid, Muhammad; Pourrut, Bertrand; Dumat, Camille; Nadeem, Muhammad; Aslam, Muhammad; Pinelli, Eric

    2014-01-01

    As a result of the industrial revolution, anthropogenic activities have enhanced there distribution of many toxic heavy metals from the earth's crust to different environmental compartments. Environmental pollution by toxic heavy metals is increasing worldwide, and poses a rising threat to both the environment and to human health.Plants are exposed to heavy metals from various sources: mining and refining of ores, fertilizer and pesticide applications, battery chemicals, disposal of solid wastes(including sewage sludge), irrigation with wastewater, vehicular exhaust emissions and adjacent industrial activity.Heavy metals induce various morphological, physiological, and biochemical dysfunctions in plants, either directly or indirectly, and cause various damaging effects. The most frequently documented and earliest consequence of heavy metal toxicity in plants cells is the overproduction of ROS. Unlike redox-active metals such as iron and copper, heavy metals (e.g, Pb, Cd, Ni, AI, Mn and Zn) cannot generate ROS directly by participating in biological redox reactions such as Haber Weiss/Fenton reactions. However, these metals induce ROS generation via different indirect mechanisms, such as stimulating the activity of NADPH oxidases, displacing essential cations from specific binding sites of enzymes and inhibiting enzymatic activities from their affinity for -SH groups on the enzyme.Under normal conditions, ROS play several essential roles in regulating the expression of different genes. Reactive oxygen species control numerous processes like the cell cycle, plant growth, abiotic stress responses, systemic signalling, programmed cell death, pathogen defence and development. Enhanced generation of these species from heavy metal toxicity deteriorates the intrinsic antioxidant defense system of cells, and causes oxidative stress. Cells with oxidative stress display various chemical,biological and physiological toxic symptoms as a result of the interaction between ROS and

  5. Mechanism of artemisinin phytotoxicity action: induction of reactive oxygen species and cell death in lettuce seedlings.

    PubMed

    Yan, Zhi-Qiang; Wang, Dan-Dan; Ding, Lan; Cui, Hai-Yan; Jin, Hui; Yang, Xiao-Yan; Yang, Jian-She; Qin, Bo

    2015-03-01

    Artemisinin has been recognized as an allelochemical that inhibits growth of several plant species. However, its mode of action is not well clarified. In this study, the mechanism of artemisinin phytotoxicity on lettuce seedlings was investigated. Root and shoot elongation of lettuce seedlings were inhibited by artemisinin in a concentration-dependent manner. The compound effectively arrested cell division and caused loss of cell viability in root tips of lettuce. Overproduction of reactive oxygen species (ROS) was induced by artemisinin. Lipid peroxidation, proline overproduction and reduction of chlorophyll content in lettuce seedlings were found after treatments. These results suggested that artemisinin could induce ROS overproduction, which caused membrane lipids peroxidation and cell death, and impacted mitosis and physiological processes, resulting in growth inhibition of receptor plants. PMID:25658194

  6. Two-photon or higher-order absorbing optical materials for generation of reactive species

    NASA Technical Reports Server (NTRS)

    Cumpston, Brian (Inventor); Lipson, Matthew (Inventor); Marder, Seth R. (Inventor); Perry, Joseph W. (Inventor)

    2003-01-01

    Disclosed are highly efficient multiphoton absorbing compounds and methods of their use. The compounds generally include a bridge of pi-conjugated bonds connecting electron donating groups or electron accepting groups. The bridge may be substituted with a variety of substituents as well. Solubility, lipophilicity, absorption maxima and other characteristics of the compounds may be tailored by changing the electron donating groups or electron accepting groups, the substituents attached to or the length of the pi-conjugated bridge. Numerous photophysical and photochemical methods are enabled by converting these compounds to electronically excited states upon simultaneous absorption of at least two photons of radiation. The compounds have large two-photon or higher-order absorptivities such that upon absorption, one or more Lewis acidic species, Lewis basic species, radical species or ionic species are formed.

  7. Two-photon or higher-order absorbing optical materials for generation of reactive species

    NASA Technical Reports Server (NTRS)

    Cumpston, Brian (Inventor); Lipson, Matthew (Inventor); Marder, Seth R (Inventor); Perry, Joseph W (Inventor)

    2007-01-01

    Disclosed are highly efficient multiphoton absorbing compounds and methods of their use. The compounds generally include a bridge of pi-conjugated bonds connecting electron donating groups or electron accepting groups. The bridge may be substituted with a variety of substituents as well. Solubility, lipophilicity, absorption maxima and other characteristics of the compounds may be tailored by changing the electron donating groups or electron accepting groups, the substituents attached to or the length of the pi-conjugated bridge. Numerous photophysical and photochemical methods are enabled by converting these compounds to electronically excited states upon simultaneous absorption of at least two photons of radiation. The compounds have large two-photon or higher-order absorptivities such that upon absorption, one or more Lewis acidic species, Lewis basic species, radical species or ionic species are formed.

  8. Two-Photon or Higher-Order Absorbing Optical Materials for Generation of Reactive Species

    NASA Technical Reports Server (NTRS)

    Cumpston, Brian (Inventor); Lipson, Matthew (Inventor); Marder, Seth R. (Inventor); Perry, Joseph W. (Inventor)

    2013-01-01

    Disclosed are highly efficient multiphoton absorbing compounds and methods of their use. The compounds generally include a bridge of pi-conjugated bonds connecting electron donating groups or electron accepting groups. The bridge may be substituted with a variety of substituents as well. Solubility, lipophilicity, absorption maxima and other characteristics of the compounds may be tailored by changing the electron donating groups or electron accepting groups, the substituents attached to or the length of the pi-conjugated bridge. Numerous photophysical and photochemical methods are enabled by converting these compounds to electronically excited states upon simultaneous absorption of at least two photons of radiation. The compounds have large two-photon or higher-order absorptivities such that upon absorption, one or more Lewis acidic species, Lewis basic species, radical species or ionic species are formed.

  9. Calcium influx through TRP channels induced by short-lived reactive species in plasma-irradiated solution.

    PubMed

    Sasaki, Shota; Kanzaki, Makoto; Kaneko, Toshiro

    2016-01-01

    Non-equilibrium helium atmospheric-pressure plasma (He-APP), which allows for a strong non-equilibrium chemical reaction of O2 and N2 in ambient air, uniquely produces multiple extremely reactive products, such as reactive oxygen species (ROS), in plasma-irradiated solution. We herein show that relatively short-lived unclassified reactive species (i.e., deactivated within approximately 10 min) generated by the He-APP irradiation can trigger physiologically relevant Ca(2+) influx through ruthenium red- and SKF 96365-sensitive Ca(2+)-permeable channel(s), possibly transient receptor potential channel family member(s). Our results provide novel insight into understanding of the interactions between cells and plasmas and the mechanism by which cells detect plasma-induced chemically reactive species, in addition to facilitating development of plasma applications in medicine. PMID:27169489

  10. Calcium influx through TRP channels induced by short-lived reactive species in plasma-irradiated solution

    PubMed Central

    Sasaki, Shota; Kanzaki, Makoto; Kaneko, Toshiro

    2016-01-01

    Non-equilibrium helium atmospheric-pressure plasma (He-APP), which allows for a strong non-equilibrium chemical reaction of O2 and N2 in ambient air, uniquely produces multiple extremely reactive products, such as reactive oxygen species (ROS), in plasma-irradiated solution. We herein show that relatively short-lived unclassified reactive species (i.e., deactivated within approximately 10 min) generated by the He-APP irradiation can trigger physiologically relevant Ca2+ influx through ruthenium red- and SKF 96365-sensitive Ca2+-permeable channel(s), possibly transient receptor potential channel family member(s). Our results provide novel insight into understanding of the interactions between cells and plasmas and the mechanism by which cells detect plasma-induced chemically reactive species, in addition to facilitating development of plasma applications in medicine. PMID:27169489

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

    SciTech Connect

    Chibli, H.; Carlini, L.; Park, S.; Dimitrijevic, N. M.; Nadeau, J. L.

    2011-01-01

    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.

  12. Reactive Oxygen Species in the Paraventricular Nucleus of the Hypothalamus Alter Sympathetic Activity During Metabolic Syndrome

    PubMed Central

    Cruz, Josiane C.; Flôr, Atalia F. L.; França-Silva, Maria S.; Balarini, Camille M.; Braga, Valdir A.

    2015-01-01

    The paraventricular nucleus of the hypothalamus (PVN) contains heterogeneous populations of neurons involved in autonomic and neuroendocrine regulation. The PVN plays an important role in the sympathoexcitatory response to increasing circulating levels of angiotensin II (Ang-II), which activates AT1 receptors in the circumventricular organs (OCVs), mainly in the subfornical organ (SFO). Circulating Ang-II induces a de novo synthesis of Ang-II in SFO neurons projecting to pre-autonomic PVN neurons. Activation of AT1 receptors induces intracellular increases in reactive oxygen species (ROS), leading to increases in sympathetic nerve activity (SNA). Chronic sympathetic nerve activation promotes a series of metabolic disorders that characterizes the metabolic syndrome (MetS): dyslipidemia, hyperinsulinemia, glucose intolerance, hyperleptinemia and elevated plasma hormone levels, such as noradrenaline, glucocorticoids, leptin, insulin, and Ang-II. This review will discuss the contribution of our laboratory and others regarding the sympathoexcitation caused by peripheral Ang-II-induced reactive oxygen species along the subfornical organ and paraventricular nucleus of the hypothalamus. We hypothesize that this mechanism could be involved in metabolic disorders underlying MetS. PMID:26779026

  13. Amaranth peptides from simulated gastrointestinal digestion: antioxidant activity against reactive species.

    PubMed

    Delgado, María C Orsini; Galleano, Mónica; Añón, María C; Tironi, Valeria A

    2015-03-01

    We evaluated the capacity of simulated gastrointestinal digests or alcalase hydrolysates of protein isolates from amaranth to scavenge diverse physiologically relevant reactive species. The more active hydrolysate was obtained with the former method. Moreover, a prior alcalase treatment of the isolate followed by the same simulated gastrointestinal digestion did not improve the antioxidant capacity in any of the assays performed and even produced a negative effect under some conditions. Gastrointestinal digestion produced a strong increment in the scavenging capacity against peroxyl radicals (ORAC assay), hydroxyl radicals (ESR-OH assay), and peroxynitrites; thus decreasing the IC50 values to approximately 20, 25, and 20%, respectively, of the levels attained with the nonhydrolyzed proteins. Metal chelation (HORAC assay) also enhanced respect to isolate levels, but to a lesser extent (decreasing IC50 values to only 50%). The nitric-oxide- and superoxide-scavenging capacities of the digests were not relevant with respect to the methodologies used. The gastrointestinal digests from amaranth proteins acted against reactive species by different mechanisms, thus indicating the protein isolate to be a potential polyfunctional antioxidant ingredient. PMID:25577328

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

    PubMed

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

    2016-06-01

    As plants are sessile organisms that have to attune their physiology and morphology continuously to varying environmental challenges in order to survive and reproduce, they have evolved complex and integrated environment-cell, cell-cell, and cell-organelle signalling circuits that regulate and trigger the required adjustments (such as alteration of gene expression). Although reactive oxygen species (ROS) are essential components of this network, their pathways are not yet completely unravelled. In addition to the intrinsic chemical properties that define the array of interaction partners, mobility, and stability, ROS signalling specificity is obtained via the spatiotemporal control of production and scavenging at different organellar and subcellular locations (e.g. chloroplasts, mitochondria, peroxisomes, and apoplast). Furthermore, these cellular compartments may crosstalk to relay and further fine-tune the ROS message. Hence, plant cells might locally and systemically react upon environmental or developmental challenges by generating spatiotemporally controlled dosages of certain ROS types, each with specific chemical properties and interaction targets, that are influenced by interorganellar communication and by the subcellular location and distribution of the involved organelles, to trigger the suitable acclimation responses in association with other well-established cellular signalling components (e.g. reactive nitrogen species, phytohormones, and calcium ions). Further characterization of this comprehensive ROS signalling matrix may result in the identification of new targets and key regulators of ROS signalling, which might be excellent candidates for engineering or breeding stress-tolerant plants. PMID:26976816

  15. Overexpression of stanniocalcin-1 inhibits reactive oxygen species and renal ischemia/reperfusion injury in mice.

    PubMed

    Huang, Luping; Belousova, Tatiana; Chen, Minyi; DiMattia, Gabriel; Liu, Dajun; Sheikh-Hamad, David

    2012-10-01

    Reactive oxygen species, endothelial dysfunction, inflammation, and mitogen-activated protein kinases have important roles in the pathogenesis of ischemia/reperfusion kidney injury. Stanniocalcin-1 (STC1) suppresses superoxide generation in many systems through the induction of mitochondrial uncoupling proteins and blocks the cytokine-induced rise in endothelial permeability. Here we tested whether transgenic overexpression of STC1 protects from bilateral ischemia/reperfusion kidney injury. This injury in wild-type mice caused a halving of the creatinine clearance; severe tubular vacuolization and cast formation; increased infiltration of macrophages and T cells; higher vascular permeability; greater production of superoxide and hydrogen peroxide; and higher ratio of activated extracellular regulated kinase/activated Jun-N-terminal kinase and p38, all compared to sham-treated controls. Mice transgenic for human STC1 expression, however, had resistance to equivalent ischemia/reperfusion injury indicated as no significant change from controls in any of these parameters. Tubular epithelial cells in transgenic mice expressed higher mitochondrial uncoupling protein 2 and lower superoxide generation. Pre-treatment of transgenic mice with paraquat, a generator of reactive oxygen species, before injury restored the susceptibility to ischemia/reperfusion kidney injury, suggesting that STC1 protects by an anti-oxidant mechanism. Thus, STC1 may be a therapeutic target for ischemia/reperfusion kidney injury. PMID:22695329

  16. Khat (Catha edulis) generates reactive oxygen species and promotes hepatic cell apoptosis via MAPK activation.

    PubMed

    Abid, Morad Dirhem Naji; Chen, Juan; Xiang, Min; Zhou, Jie; Chen, Xiaoping; Gong, Feili

    2013-08-01

    A number of studies have suggested an association between khat (Catha edulis) chewing and acute liver lesions or chronic liver disease. However, little is known about the effects of khat on hepatic cells. In the current study, we investigated the mechanism behind khat-induced apoptosis in the L02 human hepatic cell line. We used cell growth inhibition assay, flow cytometry and Hoechst 33258 staining to measure hepatocyte apoptosis induced by khat. Western blot analysis was used to detect the expression levels of caspase-8 and -9, as well as those of Bax and Bcl-2. We also measured reactive oxygen species production. The results indicated that khat induced significant hepatocyte apoptosis in L02 cells. We found that khat activated caspase-8 and -9, upregulated Bax protein expression and downregulated Bcl-2 expression levels, which resulted in the coordination of apoptotic signals. Khat-induced hepatocyte apoptosis is primarily regulated through the sustained activation of the c-Jun NH2-terminal kinase (JNK) pathway and only partially via the extracellular signal-regulated kinase (ERK) cascade. Furthermore, the khat-induced reactive oxygen species (ROS) production and the activation of the ROS scavenger, N-acetyl-L-cysteine (NAC), attenuated the khat-induced activation of JNK and ERK. Our results demonstrate that khat triggers the generation of intracellular ROS and sequentially induces the sustainable activation of JNK, which in turn results in a decrease in cell viability and an increase in cell apoptosis. PMID:23708648

  17. Extensive Dark Biological Production of Reactive Oxygen Species in Brackish and Freshwater Ponds.

    PubMed

    Zhang, Tong; Hansel, Colleen M; Voelker, Bettina M; Lamborg, Carl H

    2016-03-15

    Within natural waters, photodependent processes are generally considered the predominant source of reactive oxygen species (ROS), a suite of biogeochemically important molecules. However, recent discoveries of dark particle-associated ROS production in aquatic environments and extracellular ROS production by various microorganisms point to biological activity as a significant source of ROS in the absence of light. Thus, the objective of this study was to explore the occurrence of dark biological production of the ROS superoxide (O2(-)) and hydrogen peroxide (H2O2) in brackish and freshwater ponds. Here we show that the ROS superoxide and hydrogen peroxide were present in dark waters at comparable concentrations as in sunlit waters. This suggests that, at least for the short-lived superoxide species, light-independent processes were an important control on ROS levels in these natural waters. Indeed, we demonstrated that dark biological production of ROS extensively occurred in brackish and freshwater environments, with greater dark ROS production rates generally observed in the aphotic relative to the photic zone. Filtering and formaldehyde inhibition confirmed the biological nature of a majority of this dark ROS production, which likely involved phytoplankton, particle-associated heterotrophic bacteria, and NADH-oxidizing enzymes. We conclude that biological ROS production is widespread, including regions devoid of light, thereby expanding the relevance of these reactive molecules to all regions of our oxygenated global habit. PMID:26854358

  18. The role of reactive oxygen species in mesenchymal stem cell adipogenic and osteogenic differentiation: a review.

    PubMed

    Atashi, Fatemeh; Modarressi, Ali; Pepper, Michael S

    2015-05-15

    Mesenchymal stromal cells (MSCs) are promising candidates for tissue engineering and regenerative medicine. The multipotent stem cell component of MSC isolates is able to differentiate into derivatives of the mesodermal lineage including adipocytes, osteocytes, chondrocytes, and myocytes. Many common pathways have been described in the regulation of adipogenesis and osteogenesis. However, stimulation of osteogenesis appears to suppress adipogenesis and vice-versa. Increasing evidence implicates a tight regulation of these processes by reactive oxygen species (ROS). ROS are short-lived oxygen-containing molecules that display high chemical reactivity toward DNA, RNA, proteins, and lipids. Mitochondrial complexes I and III, and the NADPH oxidase isoform NOX4 are major sources of ROS production during MSC differentiation. ROS are thought to interact with several pathways that affect the transcription machinery required for MSC differentiation including the Wnt, Hedgehog, and FOXO signaling cascades. On the other hand, elevated levels of ROS, defined as oxidative stress, lead to arrest of the MSC cell cycle and apoptosis. Tightly regulated levels of ROS are therefore critical for MSC terminal differentiation, although the precise sources, localization, levels and the exact species of ROS implicated remain to be determined. This review provides a detailed overview of the influence of ROS on adipogenic and osteogenic differentiation in MSCs. PMID:25603196

  19. Modeling non-isothermal multiphase multi-species reactive chemical transport in geologic media

    SciTech Connect

    Tianfu Xu; Gerard, F.; Pruess, K.; Brimhall, G.

    1997-07-01

    The assessment of mineral deposits, the analysis of hydrothermal convection systems, the performance of radioactive, urban and industrial waste disposal, the study of groundwater pollution, and the understanding of natural groundwater quality patterns all require modeling tools that can consider both the transport of dissolved species as well as their interactions with solid (or other) phases in geologic media and engineered barriers. Here, a general multi-species reactive transport formulation has been developed, which is applicable to homogeneous and/or heterogeneous reactions that can proceed either subject to local equilibrium conditions or kinetic rates under non-isothermal multiphase flow conditions. Two numerical solution methods, the direct substitution approach (DSA) and sequential iteration approach (SIA) for solving the coupled complex subsurface thermo-physical-chemical processes, are described. An efficient sequential iteration approach, which solves transport of solutes and chemical reactions sequentially and iteratively, is proposed for the current reactive chemical transport computer code development. The coupled flow (water, vapor, air and heat) and solute transport equations are also solved sequentially. The existing multiphase flow code TOUGH2 and geochemical code EQ3/6 are used to implement this SIA. The flow chart of the coupled code TOUGH2-EQ3/6, required modifications of the existing codes and additional subroutines needed are presented.

  20. Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation

    SciTech Connect

    Meeran, Syed M.; Katiyar, Suchitra; Katiyar, Santosh K.

    2008-05-15

    Phytochemicals show promise as potential chemopreventive or chemotherapeutic agents against various cancers. Here we report the chemotherapeutic effects of berberine, a phytochemical, on human prostate cancer cells. The treatment of human prostate cancer cells (PC-3) with berberine induced dose-dependent apoptosis but this effect of berberine was not seen in non-neoplastic human prostate epithelial cells (PWR-1E). Berberine-induced apoptosis was associated with the disruption of the mitochondrial membrane potential, release of apoptogenic molecules (cytochrome c and Smac/DIABLO) from mitochondria and cleavage of caspase-9,-3 and PARP proteins. This effect of berberine on prostate cancer cells was initiated by the generation of reactive oxygen species (ROS) irrespective of their androgen responsiveness, and the generation of ROS was through the increased induction of xanthine oxidase. Treatment of cells with allopurinol, an inhibitor of xanthine oxidase, inhibited berberine-induced oxidative stress in cancer cells. Berberine-induced apoptosis was blocked in the presence of antioxidant, N-acetylcysteine, through the prevention of disruption of mitochondrial membrane potential and subsequently release of cytochrome c and Smac/DIABLO. In conclusion, the present study reveals that the berberine-mediated cell death of human prostate cancer cells is regulated by reactive oxygen species, and therefore suggests that berberine may be considered for further studies as a promising therapeutic candidate for prostate cancer.

  1. Formation of reactive oxygen species in rat epithelial cells upon stimulation with fly ash.

    PubMed

    Voelkel, K; Krug, H F; Diabaté, S

    2003-02-01

    Fly ash was used as a model for ambient particulate matter which is under suspicion to cause adverse pulmonary health effects. The fly ash was pre-sized and contained only particles < 20 microm including an ultrafine fraction (< 100 nm) that contributed 31% to the particle number. In our study, we investigated the influence of fly ash on the promotion of early inflammatory reactions like the formation of reactive oxygen species (ROS) in rat lung epithelial cells (RLE-6TN). Furthermore, we determined the formation of nitric oxide (NO). The cells show a clear dose-response relationship concerning the formation of ROS with regard to the mass of particles applied. Lipopolysaccharide (LPS) added as a co-stimulus did not increase the formation of ROS induced by fly ash. Furthermore, in LPS (0.1 microg/ml) and tumour necrosis factor-alpha (TNF-alpha; 1 ng/ml) pre-treated cells no increase in reactive oxygen species comparable to fly ash alone is observable. In presence of the metal chelator, desferrioxamine (DFO), ROS formation can be significantly reduced. Neither fly ash nor LPS induced a significant NO release in RLE-6TN cells. PMID:12682424

  2. The Role of Reactive Oxygen Species in Mesenchymal Stem Cell Adipogenic and Osteogenic Differentiation: A Review

    PubMed Central

    Atashi, Fatemeh; Modarressi, Ali

    2015-01-01

    Mesenchymal stromal cells (MSCs) are promising candidates for tissue engineering and regenerative medicine. The multipotent stem cell component of MSC isolates is able to differentiate into derivatives of the mesodermal lineage including adipocytes, osteocytes, chondrocytes, and myocytes. Many common pathways have been described in the regulation of adipogenesis and osteogenesis. However, stimulation of osteogenesis appears to suppress adipogenesis and vice-versa. Increasing evidence implicates a tight regulation of these processes by reactive oxygen species (ROS). ROS are short-lived oxygen-containing molecules that display high chemical reactivity toward DNA, RNA, proteins, and lipids. Mitochondrial complexes I and III, and the NADPH oxidase isoform NOX4 are major sources of ROS production during MSC differentiation. ROS are thought to interact with several pathways that affect the transcription machinery required for MSC differentiation including the Wnt, Hedgehog, and FOXO signaling cascades. On the other hand, elevated levels of ROS, defined as oxidative stress, lead to arrest of the MSC cell cycle and apoptosis. Tightly regulated levels of ROS are therefore critical for MSC terminal differentiation, although the precise sources, localization, levels and the exact species of ROS implicated remain to be determined. This review provides a detailed overview of the influence of ROS on adipogenic and osteogenic differentiation in MSCs. PMID:25603196

  3. The Role of Reactive Species in Epileptogenesis and Influence of Antiepileptic Drug Therapy on Oxidative Stress

    PubMed Central

    Martinc, Boštjan; Grabnar, Iztok; Vovk, Tomaž

    2012-01-01

    Epilepsy is considered one of the most common neurological disorders. The focus of this review is the acquired form of epilepsy, with the development process consisting of three major phases, the acute injury phase, the latency epileptogenesis phase, and the phase of spontaneous recurrent seizures. Nowadays, an increasing attention is paid to the possible interrelationship between oxidative stress resulting in disturbance of physiological signalling roles of calcium and free radicals in neuronal cells and mitochondrial dysfunction, cell damage, and epilepsy. The positive stimulation of mitochondrial calcium signals by reactive oxygen species and increased reactive oxygen species generation resulting from increased mitochondrial calcium can lead to a positive feedback loop. We propose that calcium can pose both, physiological and pathological effects of mitochondrial function, which can lead in neuronal cell death and consequent epileptic seizures. Various antiepileptic drugs may impair the endogenous antioxidative ability to prevent oxidative stress. Therefore, some antiepileptic drugs, especially from the older generation, may trigger oxygen-dependent tissue injury. The prooxidative effects of these antiepileptic drugs might lead to enhancement of seizure activity, resulting in loss of their efficacy or apparent functional tolerance and undesired adverse effects. Additionally, various reactive metabolites of antiepileptic drugs are capable of covalent binding to macromolecules which may lead to deterioration of the epileptic seizures and systemic toxicity. Since neuronal loss seems to be one of the major neurobiological abnormalities in the epileptic brain, the ability of antioxidants to attenuate seizure generation and the accompanying changes in oxidative burden, further support an important role of antioxidants as having a putative antiepileptic potential. PMID:23730257

  4. Efficient transformation of DDT by peroxymonosulfate activated with cobalt in aqueous systems: Kinetics, products, and reactive species identification.

    PubMed

    Qin, Wenxiu; Fang, Guodong; Wang, Yujun; Wu, Tongliang; Zhu, Changyin; Zhou, Dongmei

    2016-04-01

    Recently, sulfate radical ( [Formula: see text] ) based-advanced oxidation technologies (AOTs) have been attracted great attention in the remediation of contaminated soil and groundwater. In the present study, Co(2+) ions activated peroxymonosulfate (PMS) system was used to degrade 1, 1, 1-trichloro-2, 2'bis(p-chlorophenyl) ethane (DDT) in aqueous solutions. It was found that DDT was efficiently degraded in the PMS/Co(II) solutions within several hours, and the degradation efficiency of DDT was dependent on the concentrations of PMS and Co(II), and the optimum molar ratio of PMS and Co(II) was 50:1. The degradation kinetics of DDT were well described with pseudo-first-order equations over a range of temperature (10-40 °C), and the activation energy that was calculated with Arrhenius equation was 72.3 ± 2.6 kJ/mol. Electron paramagnetic resonance (EPR) and GC-MS techniques were applied to identify the intermediates and reactive species for DDT degradation. The results indicated that [Formula: see text] and OH were the main reactive species accounting for DDT degradation. Dichlorobenzophenone, 4-chlorobenzoic acid and benzylalcohol were the dominant intermediates for DDT degradation, and the likely degradation pathway of DDT was proposed on the basis of these identified products. Increasing pH inhibited the formation of [Formula: see text] and OH, and thus decreased the catalytic degradation of DDT. Cl(-) ion was found to significantly inhibit, while [Formula: see text] and dissolved oxygen had limited effects on DDT degradation. PMID:26802265

  5. Radiolytic Modification and Reactivity of Amino Acid Residues Serving as Structural Probes for Protein Footprinting

    SciTech Connect

    Xu,G.; Chance, M.

    2005-01-01

    Hydroxyl radical-mediated protein footprinting is a convenient and sensitive technique for mapping solvent-accessible surfaces of proteins and examining the structure and dynamics of biological assemblies. In this study, the reactivities and tendencies to form easily detectible products for all 20 (common) amino acid side chains along with cystine are directly compared using various standards. Although we have previously reported on the oxidation of many of these residues, this study includes a detailed examination of the less reactive residues and better defines their usefulness in hydroxyl radical-mediated footprinting experiments. All 20 amino amides along with cystine and a few tripeptides were irradiated by -rays, the products were analyzed by electrospray mass spectrometry, and rate constants of modification were measured. The reactivities of amino acid side chains were compared based on their loss of mass spectral signal normalized to the rate of loss for Phe or Pro that were radiolyzed simultaneously to serve as internal standards. In this way, accurate quantitation of relative rates could be assured. A reactivity order of amino acid side chains was obtained as Cys > Met > Trp > Tyr > Phe > cystine > His > Leu, Ile > Arg, Lys, Val > Ser, Thr, Pro > Gln, Glu > Asp, Asn > Ala > Gly. Ala and Gly are far too unreactive to be useful probes in typical experiments and Asp and Asn are unlikely to be useful as well. Although Ser and Thr are more reactive than Pro, which is known to be a useful probe, their oxidation products are not easily detectible. Thus, it appears that 14 of the 20 side chains (plus cystine) are most likely to be useful in typical experiments. Since these residues comprise 65% of the sequence of a typical protein, the footprinting approach provides excellent coverage of the side-chain reactivity for proteins.

  6. Laser mass-spectrometry for online diagnosis of reactive plasmas with many species

    SciTech Connect

    Feng Chunlei; Gao Liang; Liu Jiahong; Zhang Lei; Ding Hongbin

    2011-06-15

    The purpose of this study is to design a diagnostic system for reactive plasma environment by combining molecular-beam time-of-flight (TOF) mass spectroscopy with laser spectroscopy technique. The combination of TOF mass spectrometers and pulsed lasers is favorable in the diagnosis of intermediate species distribution since they allow the simultaneous but separate recording of the spectra of different species. In the plasma system, the intermediate species in electronic ground state or low lying excited state is pumped to higher energy level with resonant laser excitation, and then, the ionization with a second laser system is possible which can readily be detected by the TOF analyzer. The ionization itself is only used as a detection mechanism for the observation of the excitation of these states. In this manner, the population distribution of intermediate species can be determined with state-selective and mass-selective feature. Also, in this article, a flexible data acquisition and automatic control system based on LABVIEW was designed to integrate all the stand-alone measurement instruments including a TOF spectrometer, a laser system, a high performance oscilloscope, and a digital delay generator into a single personal computer-based control unit. Moreover, a virtual Boxcar integrator with hundreds of channels has been developed to enhance the signal while filtering out the random noises. Finally, the many potentials of this technique in the application of plasma diagnosis will be discussed.

  7. The positive response of Ty1 retrotransposition test to carcinogens is due to increased levels of reactive oxygen species generated by the genotoxins.

    PubMed

    Dimitrov, Martin; Venkov, Pencho; Pesheva, Margarita

    2011-01-01

    In previous laboratory and environmental studies, the Ty1 short-term test showed positive responses (i.e. induced mobility of the Ty1 retrotransposon) to carcinogenic genotoxins. Here, we provide evidence for a causal relationship between increased level of reactive oxygen species and induction the mobility of the Ty1 retrotransposon. Results obtained in concentration and time-dependent experiments after treatment, the tester cells with carcinogenic genotoxins [benzo(a)pyrene, benzo(a)anthracene, ethylmethanesulfonate, formamide], free bile acids (chenodeoxycholic, lithocholic acids) and metals (arsenic, hexavelant chromium, lead) showed a simultaneous increase in both cellular level of the superoxide anions and Ty1 retrotransposition rates. Treatment with the noncarcinogenic genotoxins [benzo(e)pyrene, benzo(b)anthracen, anthracene], conjugated bile acids (taurodeoxycholic, glycodeoxycholic acids) and metals (zinc, trivalent chromium) did not change significantly superoxide anions level and Ty1 retrotransposition rate. The induction by carcinogens of the Ty1 mobility seems to depend on the accumulation of superoxide anions, since the addition of the scavenger N-acetylcysteine resulted in loss of both increased amount of superoxide anions and induced Ty1 retrotransposition. Increased hydrogen peroxide levels are also involved in the induction of Ty1 retrotransposition rates in response to treatment with carcinogenic genotoxins, as evidenced by disruption of YAP1 gene in the tester cells. It is concluded that the carcinogen-induced high level of reactive oxygen species play a primary and key role in determination the selective response of Ty1 test to carcinogenic genotoxins. PMID:20401468

  8. A Role for Reactive Oxygen Species Produced by NADPH Oxidases in the Embryo and Aleurone Cells in Barley Seed Germination

    PubMed Central

    Ishibashi, Yushi; Kasa, Shinsuke; Sakamoto, Masatsugu; Aoki, Nozomi; Kai, Kyohei; Yuasa, Takashi; Hanada, Atsushi; Yamaguchi, Shinjiro; Iwaya-Inoue, Mari

    2015-01-01

    Reactive oxygen species (ROS) promote the germination of several seeds, and antioxidants suppress it. However, questions remain regarding the role and production mechanism of ROS in seed germination. Here, we focused on NADPH oxidases, which produce ROS. After imbibition, NADPH oxidase mRNAs were expressed in the embryo and in aleurone cells of barley seed; these expression sites were consistent with the sites of ROS production in the seed after imbibition. To clarify the role of NADPH oxidases in barley seed germination, we examined gibberellic acid (GA) / abscisic acid (ABA) metabolism and signaling in barley seeds treated with diphenylene iodonium chloride (DPI), an NADPH oxidase inhibitor. DPI significantly suppressed germination, and suppressed GA biosynthesis and ABA catabolism in embryos. GA, but not ABA, induced NADPH oxidase activity in aleurone cells. Additionally, DPI suppressed the early induction of α-amylase by GA in aleurone cells. These results suggest that ROS produced by NADPH oxidases promote GA biosynthesis in embryos, that GA induces and activates NADPH oxidases in aleurone cells, and that ROS produced by NADPH oxidases induce α-amylase in aleurone cells. We conclude that the ROS generated by NADPH oxidases regulate barley seed germination through GA / ABA metabolism and signaling in embryo and aleurone cells. PMID:26579718

  9. A Role for Reactive Oxygen Species Produced by NADPH Oxidases in the Embryo and Aleurone Cells in Barley Seed Germination.

    PubMed

    Ishibashi, Yushi; Kasa, Shinsuke; Sakamoto, Masatsugu; Aoki, Nozomi; Kai, Kyohei; Yuasa, Takashi; Hanada, Atsushi; Yamaguchi, Shinjiro; Iwaya-Inoue, Mari

    2015-01-01

    Reactive oxygen species (ROS) promote the germination of several seeds, and antioxidants suppress it. However, questions remain regarding the role and production mechanism of ROS in seed germination. Here, we focused on NADPH oxidases, which produce ROS. After imbibition, NADPH oxidase mRNAs were expressed in the embryo and in aleurone cells of barley seed; these expression sites were consistent with the sites of ROS production in the seed after imbibition. To clarify the role of NADPH oxidases in barley seed germination, we examined gibberellic acid (GA) / abscisic acid (ABA) metabolism and signaling in barley seeds treated with diphenylene iodonium chloride (DPI), an NADPH oxidase inhibitor. DPI significantly suppressed germination, and suppressed GA biosynthesis and ABA catabolism in embryos. GA, but not ABA, induced NADPH oxidase activity in aleurone cells. Additionally, DPI suppressed the early induction of α-amylase by GA in aleurone cells. These results suggest that ROS produced by NADPH oxidases promote GA biosynthesis in embryos, that GA induces and activates NADPH oxidases in aleurone cells, and that ROS produced by NADPH oxidases induce α-amylase in aleurone cells. We conclude that the ROS generated by NADPH oxidases regulate barley seed germination through GA / ABA metabolism and signaling in embryo and aleurone cells. PMID:26579718

  10. Reactive Oxygen Species Play a Role in the Infection of the Necrotrophic Fungi, Rhizoctonia solani in Wheat.

    PubMed

    Foley, Rhonda C; Kidd, Brendan N; Hane, James K; Anderson, Jonathan P; Singh, Karam B

    2016-01-01

    Rhizoctonia solani is a nectrotrophic fungal pathogen that causes billions of dollars of damage to agriculture worldwide and infects a broad host range including wheat, rice, potato and legumes. In this study we identify wheat genes that are differentially expressed in response to the R. solani isolate, AG8, using microarray technology. A significant number of wheat genes identified in this screen were involved in reactive oxygen species (ROS) production and redox regulation. Levels of ROS species were increased in wheat root tissue following R. solani infection as determined by Nitro Blue Tetrazolium (NBT), 3,3'-diaminobenzidine (DAB) and titanium sulphate measurements. Pathogen/ROS related genes from R. solani were also tested for expression patterns upon wheat infection. TmpL, a R. solani gene homologous to a gene associated with ROS regulation in Alternaria brassicicola, and OAH, a R. solani gene homologous to oxaloacetate acetylhydrolase which has been shown to produce oxalic acid in Sclerotinia sclerotiorum, were highly induced in R. solani when infecting wheat. We speculate that the interplay between the wheat and R. solani ROS generating proteins may be important for determining the outcome of the wheat/R. solani interaction. PMID:27031952

  11. Reactive Oxygen Species Play a Role in the Infection of the Necrotrophic Fungi, Rhizoctonia solani in Wheat

    PubMed Central

    Foley, Rhonda C.; Kidd, Brendan N.; Hane, James K.; Anderson, Jonathan P.; Singh, Karam B.

    2016-01-01

    Rhizoctonia solani is a nectrotrophic fungal pathogen that causes billions of dollars of damage to agriculture worldwide and infects a broad host range including wheat, rice, potato and legumes. In this study we identify wheat genes that are differentially expressed in response to the R. solani isolate, AG8, using microarray technology. A significant number of wheat genes identified in this screen were involved in reactive oxygen species (ROS) production and redox regulation. Levels of ROS species were increased in wheat root tissue following R. solani infection as determined by Nitro Blue Tetrazolium (NBT), 3,3'-diaminobenzidine (DAB) and titanium sulphate measurements. Pathogen/ROS related genes from R. solani were also tested for expression patterns upon wheat infection. TmpL, a R. solani gene homologous to a gene associated with ROS regulation in Alternaria brassicicola, and OAH, a R. solani gene homologous to oxaloacetate acetylhydrolase which has been shown to produce oxalic acid in Sclerotinia sclerotiorum, were highly induced in R. solani when infecting wheat. We speculate that the interplay between the wheat and R. solani ROS generating proteins may be important for determining the outcome of the wheat/R. solani interaction. PMID:27031952

  12. Differential accumulation of reactive oxygen and nitrogen species in maize lines with contrasting drought tolerance and aflatoxin resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Abiotic stresses such as drought stress can exacerbate aflatoxin contamination of maize kernels. Previous studies showed that maize lines resistance to aflatoxin contamination tend to exhibit enhanced drought tolerance and accumulate lower levels of reactive oxygen species (ROS) and nitrogen species...

  13. Elusive Sulfurous Acid: Gas-Phase Basicity and IR Signature of the Protonated Species.

    PubMed

    Sinha, Rajeev K; Scuderi, Debora; Maitre, Philippe; Chiavarino, Barbara; Crestoni, Maria Elisa; Fornarini, Simonetta

    2015-05-01

    The ion corresponding to protonated sulfurous acid, H3SO3(+), has been successfully delivered into the gas phase by electrospray ionization of the solution of a suitable precursor and an in-source fragmentation process. The neutral acid is a highly elusive molecule. However, its gas-phase basicity has been ascertained by means of a kinetic study of proton-transfer reactivity. The structure of the H3SO3(+) sampled ion has been probed by IRMPD spectroscopy in two complementary IR frequency ranges in conjunction with density functional theory calculations and found to conform to a trihydroxosulfonium ion. The characteristic IR signatures may aid in deciphering the presence of this species in extraterrestrial atmospheres. PMID:26263321

  14. Micrurus snake species: Venom immunogenicity, antiserum cross-reactivity and neutralization potential.

    PubMed

    Tanaka, Gabriela D; Sant'Anna, Osvaldo Augusto; Marcelino, José Roberto; Lustoza da Luz, Ana Cristina; Teixeira da Rocha, Marisa Maria; Tambourgi, Denise V

    2016-07-01

    Micrurus snakebites can cause death by muscle paralysis and respiratory arrest a few hours after envenomation. The specific treatment for these snake envenomations is the intravenous application of heterologous antivenom. In Brazil, this antivenom is produced from horses that are immunized with a mixture of Micrurus corallinus and Micrurus frontalis venoms, which are snakes that inhabit the south and southeastern regions of the country. Previously, we demonstrated that the coral antivenom, which is used in human therapy, was not able to neutralize several of the toxic venom effects from some Micrurus species that inhabit the country, as measured by in vitro and in vivo assays. The present study aimed to investigate the immunogenic properties of Micrurus spp. venoms, as well as the cross-reactivity and neutralization potential of experimental monovalent and polyvalent sera that were produced in different animal species. The present data showed that Micrurus venoms exhibited the same immunogenicity pattern in the three utilized animal species and that the specific antisera presented a large cross-reactivity when analyzed with ELISA and Western blot assays. Nonetheless, these positive results were not well correlated with the neutralizing potential of the antisera. Thus, the establishment of a new antigenic mixture to produce novel more efficient therapeutic Micrurus antivenom is not a simple task. Further studies, particularly with the Micrurus lemniscatus, Micrurus altirostris and Micrurus surinamensis venoms, are necessary to establish new strategies for the production of antivenoms with broad neutralizing activity for the treatment of accidents involving coral snakes throughout the country. PMID:27045363

  15. 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.

  16. A Modular Computer Code for Simulating Reactive Multi-Species Transport in 3-Dimensional Groundwater Systems

    SciTech Connect

    TP Clement

    1999-06-24

    RT3DV1 (Reactive Transport in 3-Dimensions) is computer code that solves the coupled partial differential equations that describe reactive-flow and transport of multiple mobile and/or immobile species in three-dimensional saturated groundwater systems. RT3D is a generalized multi-species version of the US Environmental Protection Agency (EPA) transport code, MT3D (Zheng, 1990). The current version of RT3D uses the advection and dispersion solvers from the DOD-1.5 (1997) version of MT3D. As with MT3D, RT3D also requires the groundwater flow code MODFLOW for computing spatial and temporal variations in groundwater head distribution. The RT3D code was originally developed to support the contaminant transport modeling efforts at natural attenuation demonstration sites. As a research tool, RT3D has also been used to model several laboratory and pilot-scale active bioremediation experiments. The performance of RT3D has been validated by comparing the code results against various numerical and analytical solutions. The code is currently being used to model field-scale natural attenuation at multiple sites. The RT3D code is unique in that it includes an implicit reaction solver that makes the code sufficiently flexible for simulating various types of chemical and microbial reaction kinetics. RT3D V1.0 supports seven pre-programmed reaction modules that can be used to simulate different types of reactive contaminants including benzene-toluene-xylene mixtures (BTEX), and chlorinated solvents such as tetrachloroethene (PCE) and trichloroethene (TCE). In addition, RT3D has a user-defined reaction option that can be used to simulate any other types of user-specified reactive transport systems. This report describes the mathematical details of the RT3D computer code and its input/output data structure. It is assumed that the user is familiar with the basics of groundwater flow and contaminant transport mechanics. In addition, RT3D users are expected to have some experience in

  17. Assessment of electrochemical potentiokinetic reactivation tests to qualify stainless steel for nitric acid service

    SciTech Connect

    Olsen, A.R.; Dillon, J.J.; Peters, A.H.; Clift, T.L.

    1986-12-31

    To minimize the costs and delivery time delays associated with purchasing type 304L stainless steel materials for service in nitric-acid-containing media, an alternative to the current Oak Ridge Y-12 Plant requirement of testing in accordance with American Society for Testing and Materials (ASTM) A 262, Practice C (the boiling nitric acid test), is being sought. A possible candidate is the electrochemical potentiokinetic reactivation (EPR) test being developed for the nuclear industry and under consideration for acceptance as an ASTM standard. Based on a review of the literature and some limited screening tests, this test, as currently proposed, is not a suitable substitute for the nitric acid test. However, with additional development the EPR test is a likely candidate for providing a quantitative substitute for the current qualitative oxalic acid etching (ASTM A 282, Practice A) often used to accept, but not reject, materials for use in a nitric acid medium.

  18. Kinetic dissolution of carbonates and Mn oxides in acidic water: Measurement of in situ field rates and reactive transport modeling

    USGS Publications Warehouse

    Brown, J.G.; Glynn, P.D.

    2003-01-01

    The kinetics of carbonate and Mn oxide dissolution under acidic conditions were examined through the in situ exposure of pure phase samples to acidic ground water in Pinal Creek Basin, Arizona. The average long-term calculated in situ dissolution rates for calcite and dolomite were 1.65??10-7 and 3.64??10-10 mmol/(cm2 s), respectively, which were about 3 orders of magnitude slower than rates derived in laboratory experiments by other investigators. Application of both in situ and lab-derived calcite and dolomite dissolution rates to equilibrium reactive transport simulations of a column experiment did not improve the fit to measured outflow chemistry: at the spatial and temporal scales of the column experiment, the use of an equilibrium model adequately simulated carbonate dissolution in the column. Pyrolusite (MnO2) exposed to acidic ground water for 595 days increased slightly in weight despite thermodynamic conditions that favored dissolution. This result might be related to a recent finding by another investigator that the reductive dissolution of pyrolusite is accompanied by the precipitation of a mixed Mn-Fe oxide species. In PHREEQC reactive transport simulations, the incorporation of Mn kinetics improved the fit between observed and simulated behavior at the column and field scales, although the column-fitted rate for Mn-oxide dissolution was about 4 orders of magnitude greater than the field-fitted rate. Remaining differences between observed and simulated contaminant transport trends at the Pinal Creek site were likely related to factors other than the Mn oxide dissolution rate, such as the concentration of Fe oxide surface sites available for adsorption, the effects of competition among dissolved species for available surface sites, or reactions not included in the model.

  19. Experimental Study and Reactive Transport Modeling of Boric Acid Leaching of Concrete

    NASA Astrophysics Data System (ADS)

    Pabalan, R. T.; Chiang, K.-T. K.

    2013-07-01

    Borated water leakage through spent fuel pools (SFPs) at pressurized water reactors is a concern because it could cause corrosion of reinforcement steel in the concrete structure, compromise the integrity of the structure, or cause unmonitored releases of contaminated water to the environment. Experimental data indicate that pH is a critical parameter that determines the corrosion susceptibility of rebar in borated water and the degree of concrete degradation by boric acid leaching. In this study, reactive transport modeling of concrete leaching by borated water was performed to provide information on the solution pH in the concrete crack or matrix and the degree of concrete degradation at different locations of an SFP concrete structure exposed to borated water. Simulations up to 100 years were performed using different boric acid concentrations, crack apertures, and solution flow rates. Concrete cylinders were immersed in boric acid solutions for several months and the mineralogical changes and boric acid penetration in the concrete cylinder were evaluated as a function of time. The depths of concrete leaching by boric acid solution derived from the reactive transport simulations were compared with the measured boric acid penetration depth.

  20. Properties of Copolymers of Aspartic Acid and Aliphatic Dicarboxylic Acids Prepared by Reactive Extrusion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aspartic acid may be prepared chemically or by the fermentation of carbohydrates. Currently, low molecular weight polyaspartic acids are prepared commercially by heating aspartic acid at high temperatures (greater than 220 degrees C) for several hours in the solid state. In an effort to develop a ...

  1. Contrasted resistance of stone-dwelling Geodermatophilaceae species to stresses known to give rise to reactive oxygen species.

    PubMed

    Gtari, Maher; Essoussi, Imen; Maaoui, Radhi; Sghaier, Haïtham; Boujmil, Rabeb; Gury, Jérôme; Pujic, Petar; Brusetti, Lorenzo; Chouaia, Bessem; Crotti, Elena; Daffonchio, Daniele; Boudabous, Abdellatif; Normand, Philippe

    2012-06-01

    Stones in arid environments are inhabited by actinobacteria of the family Geodermatophilaceae like the genera Blastococcus and Modestobacter frequently isolated from altered calcarenites. Their habitat requires adaptation to light-induced and other stresses that generate reactive oxygen species. Here, we show that representative members of the species Blastococcus saxobsidens, Geodermatophilus obscurus, and Modestobacter multiseptatus are differentially adapted to stresses associated with arid environments. Whereas B. saxobsidens was found to be sensitive to gamma radiation (D(10)  = 900 Gy; 10% survival at 900 Gy), M. multiseptatus was moderately (D(10)  = 6000 Gy) and G. obscurus was highly tolerant (D(10)  = 9000 Gy). A difference in resistance to high-frequency (λ value = 254 nm) UV was shown by B. saxobsidens, M. multiseptatus, and G. obscurus, being sensitive, tolerant, and highly tolerant (D(10) of 6, 900, and > 3500 kJ m(-2) , respectively). Tolerance to desiccation, mitomycin C and hydrogen peroxide correlated with the ionizing radiation and UV resistance profiles of the three species and were correlated with the pigments synthesized. Resistance to heavy metals/metalloids did not follow the same pattern, with resistance to Ag(2+) and Pb(2+) being similar for B. saxobsidens, M. multiseptatus, and G. obscurus, whereas resistance to AsO4 3-, Cr(2+) , or Cu(2+) was greater for B. saxobsidens than for the other two species. The stress resistance profiles of M. multiseptatus and B. saxobsidens were reflected in different calcarenite colonization patterns. While M. multiseptatus was predominantly isolated from the first two millimeters of stone surface, B. saxobsidens was predominantly isolated from the deeper part of the stone where it is better protected from sun irradiation, suggesting that the response to light- and desiccation-induced oxidative stress is an important driver for niche colonization in the stone biotope. PMID:22296311

  2. Relative kinetic reactivity of boronic acid and boronate ion towards Tiron, 2,2'-biphenol, and propylene glycol.

    PubMed

    Watanabe, Eisuke; Miyamoto, Chiaki; Tanaka, Asumi; Iizuka, Kenzo; Iwatsuki, Satoshi; Inamo, Masahiko; Takagi, Hideo D; Ishihara, Koji

    2013-06-21

    Reaction systems of boronic acid (RB(OH2), R = phenyl or 3-fluorophenyl) with diols and no proton ambiguity were elaborately set up, and kinetic measurements were conducted to elucidate the relative reactivities of RB(OH)2 and RB(OH)3(-). In the reactions of phenylboronic and 3-fluorophenylboronic acids with propylene glycol, the reactivity order was: RB(OH)2 > RB(OH)3(-), whereas in the reactions of 3-pyridylboronic acid with Tiron and 2,2'-biphenol, the reactivity of RB(OH)2 was comparable to that of RB(OH)3(-). These results are in contrast to those that have been previously reported, and widely accepted for over thirty years, that concluded that the reactivity of RB(OH)3(-) is several orders of magnitude higher than that of RB(OH)2. The reactivity of Tiron with 3-pyridylboronic acid is affected by the protonation of one of its sulfonate groups. PMID:23625094

  3. Acid dew and the role of chemistry in the dry deposition of reactive gases to wetted surfaces

    NASA Technical Reports Server (NTRS)

    Chameides, William L.

    1987-01-01

    A formalism is developed to describe the dry deposition of soluble reactive gases to wetted surfaces in terms of the relevant meteorological conditions, the surface roughness, the total amount of liquid water present on the surface, the rate of accumulation of this water, and the species' solubility and reactivity in the surface water. This formulation is then incorporated into a model designed to simulate the generation of acidic dew from the deposition of HNO3, SO2, S(IV) oxidants, H2O2, and O3. Similar to the observations of dew in the continental U.S., the model generates a dewdrop pH of about 4 by the end of the night; the pH can rapidly fall to toxic levels due to rapid evaporation after sunrise. Relatively low deposition velocities are predicted for the SO2 and O3 because of their lower solubilities and hence larger surface resistances than those of the other oxidants. Because the chemical lifetime of the SO2 in the dew is influenced by the atmospheric levels of H2O2, O3, and SO2, the SO2 deposition velocity is a strong function of these species' atmospheric abundances.

  4. Exploring the Reactivity of Flavonoid Compounds with Metal-Associated Amyloid-β Species

    PubMed Central

    He, Xiaoming; Park, Hyun Min; Hyung, Suk-Joon; DeToma, Alaina S.; Kim, Cheal; Ruotolo, Brandon T.; Lim, Mi Hee

    2016-01-01

    Metal ions associated with amyloid-β (Aβ) peptides have been suggested to be involved in the development of Alzheimer’s disease (AD), but this remains unclear and controversial. Some attempts to rationally design or select small molecules with structural moieties for metal chelation and Aβ interaction (i.e., bifunctionality) have been made to gain a better understanding of the hypothesis. In order to contribute to these efforts, four synthetic flavonoid derivatives FL1 – FL4 were rationally selected according to the principles of bifunctionality and their abilities to chelate metal ions, interact with Aβ, inhibit metal-induced Aβ aggregation, scavenge radicals, and regulate the formation of reactive oxygen species (ROS) were studied using physical methods and biological assays. The compounds FL1 – FL3 were able to chelate metal ions, but showed limited solubility in aqueous buffered solutions. In the case of FL4, which was most compatible with aqueous conditions, its binding affinities for Cu2+ and Zn2+ (nM and μM, respectively) were obtained through solution speciation studies. The direct interaction between FL4 and Aβ monomer was weak, which was monitored by NMR spectroscopy and mass spectrometry. Employing FL1 – FL4, no noticeable inhibitory effect on metal-mediated Aβ aggregation was observed. Among FL1 – FL4, FL3, having 3-OH, 4-oxo, and 4′-N(CH3)2 groups, exhibited similar antioxidant activity to the vitamin E analogue, Trolox, and ca. 60% reduction in the amount of hydrogen peroxide (H2O2) generated by Cu2+-Aβ in the presence of dioxygen (O2) and a reducing agent. Overall, the studies here suggest that although four flavonoid molecules were selected based on expected bifunctionality, their properties and metal-Aβ reactivity were varied depending on the structure differences, demonstrating that bifunctionality must be well tuned to afford desirable reactivity. PMID:22437427

  5. A monobromobimane-based assay to measure the pharmacokinetic profile of reactive sulphide species in blood

    PubMed Central

    Wintner, Edward A; Deckwerth, Thomas L; Langston, William; Bengtsson, Asa; Leviten, Dina; Hill, Paul; Insko, Michael A; Dumpit, Ronald; VandenEkart, Emily; Toombs, Christopher F; Szabo, Csaba

    2010-01-01

    Background and purpose: Hydrogen sulphide (H2S) is a labile, endogenous metabolite of cysteine, with multiple biological roles. The development of sulphide-based therapies for human diseases will benefit from a reliable method of quantifying H2S in blood and tissues. Experimental approach: Concentrations of reactive sulphide in saline and freshly drawn whole blood were quantified by reaction with the thio-specific derivatization agent monobromobimane, followed by reversed-phase fluorescence HPLC and/or mass spectrometry. In pharmacokinetic studies, male rats were exposed either to intravenous infusions of sodium sulphide or to H2S gas inhalation, and levels of available blood sulphide were measured. Levels of dissolved H2S/HS- were concomitantly measured using an amperometric sensor. Key results: Monobromobimane was found to rapidly and quantitatively derivatize sulphide in saline or whole blood to yield the stable small molecule sulphide dibimane. Extraction and quantification of this bis-bimane derivative were validated via reversed-phase HPLC separation coupled to fluorescence detection, and also by mass spectrometry. Baseline levels of sulphide in blood were in the range of 0.4–0.9 µM. Intravenous administration of sodium sulphide solution (2–20 mg·kg−1·h−1) or inhalation of H2S gas (50–400 ppm) elevated reactive sulphide in blood in a dose-dependent manner. Each 1 mg·kg−1·h−1 of sodium sulphide infusion into rats was found to be pharmacokinetically equivalent to approximately 30 ppm of H2S gas inhalation. Conclusions and implications: The monobromobimane derivatization method is a sensitive and reliable means to measure reactive sulphide species in whole blood. Using this method, we have established a bioequivalence between infused sodium sulphide and inhaled H2S gas. PMID:20590590

  6. Mechanisms Underlying Interferon-γ-Induced Priming of Microglial Reactive Oxygen Species Production.

    PubMed

    Spencer, Nicholas G; Schilling, Tom; Miralles, Francesc; Eder, Claudia

    2016-01-01

    Microglial priming and enhanced reactivity to secondary insults cause substantial neuronal damage and are hallmarks of brain aging, traumatic brain injury and neurodegenerative diseases. It is, thus, of particular interest to identify mechanisms involved in microglial priming. Here, we demonstrate that priming of microglia with interferon-γ (IFN γ) substantially enhanced production of reactive oxygen species (ROS) following stimulation of microglia with ATP. Priming of microglial ROS production was substantially reduced by inhibition of p38 MAPK activity with SB203580, by increases in intracellular glutathione levels with N-Acetyl-L-cysteine, by blockade of NADPH oxidase subunit NOX2 activity with gp91ds-tat or by inhibition of nitric oxide production with L-NAME. Together, our data indicate that priming of microglial ROS production involves reduction of intracellular glutathione levels, upregulation of NADPH oxidase subunit NOX2 and increases in nitric oxide production, and suggest that these simultaneously occurring processes result in enhanced production of neurotoxic peroxynitrite. Furthermore, IFNγ-induced priming of microglial ROS production was reduced upon blockade of Kir2.1 inward rectifier K+ channels with ML133. Inhibitory effects of ML133 on microglial priming were mediated via regulation of intracellular glutathione levels and nitric oxide production. These data suggest that microglial Kir2.1 channels may represent novel therapeutic targets to inhibit excessive ROS production by primed microglia in brain pathology. PMID:27598576

  7. 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. PMID:19483186

  8. Sodium channels as gateable non-photonic sensors for membrane-delimited reactive species

    PubMed Central

    Ojha, Navin K.; Nematian-Ardestani, Ehsan; Neugebauer, Sophie; Borowski, Benjamin; El-Hussein, Ahmed; Hoshi, Toshinori; Leipold, Enrico; Heinemann, Stefan H.

    2014-01-01

    Reactive oxygen species (ROS) and reactive oxygen intermediates (ROI) play crucial roles in physiological processes. While excessive ROS damages cells, small fluctuations in ROS levels represent physiological signals important for vital functions. Despite the physiological importance of ROS, many fundamental questions remain unanswered, such as which types of ROS occur in cells, how they distribute inside cells, and how long they remain in an active form. The current study presents a ratiometric sensor of intracellular ROS levels based on genetically engineered voltage-gated sodium channels (roNaV). roNaV can be used for detecting oxidative modification that occurs near the plasma membrane with a sensitivity similar to existing fluorescence-based ROS sensors. Moreover, roNaV has several advantages over traditional sensors because it does not need excitation light for sensing, and thus, can be used to detect phototoxic cellular modifications. In addition, the ROS dynamic range of roNaV is easily manipulated in real time by means of the endogenous channel inactivation mechanism. Measurements on ROS liberated from intracellular Lucifer Yellow and genetically encoded KillerRed has revealed an assessment of ROS lifetime in individual mammalian cells. Flashlight-induced ROS concentration decayed with two major time constants of about 10 and 1000 ms. PMID:24513256

  9. 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

  10. Reactive oxygen species scavenging activity of Jixueteng evaluated by electron spin resonance (ESR) and photon emission.

    PubMed

    Toyama, Toshizo; Wada-Takahashi, Satoko; Takamichi, Maomi; Watanabe, Kiyoko; Yoshida, Ayaka; Yoshino, Fumihiko; Miyamoto, Chihiro; Maehata, Yojiro; Sugiyama, Shuta; Takahashi, Shun-Suke; Todoki, Kazuo; Lee, Masaichi-Chang-Il; Hamada, Nobushiro

    2014-12-01

    Jixueteng, the dried stem of Spatholobus suberectus Dunn (Leguminosae), is a traditional Chinese herbal medicine that is commonly classified as a herb that promotes blood circulation and can be used to treat blood stasis. The aim of this study was to examine the reactive oxygen species (ROS) scavenging activity of Jixueteng and other herbal medicines. The ROS scavenging activities of the water extracts of Jixueteng, Cnidium officinale and Salvia miltiorrhiza were examined using an electron spin resonance (ESR) technique and faint luminescence measurement. The ESR signal intensities of the superoxide anion (O2·) and hydroxyl radical (HO·) were reduced more by Jixueteng than the other herbal medicines we tested. High photon emission intensity to hydrogen peroxide (H202) and HO· was observed in Jixueteng using the XYZ chemiluminescence system that was used as faint luminescence measurement and analysis. The results of the present study revealed that the ROS scavenging activity of 8% Jixueteng was the strongest among the herbal medicines we tested. It has been reported that Jixueteng includes various polyphenols. In the ROS scavenging activity by Jixueteng, it is supposed that the antioxidant activity caused by these polyphenols would contribute greatly. In conclusion, a water extract component of Jixueteng had potent free radical scavenging activity and an antioxidative effect that inhibited the oxidative actions of O2·⁻, H2O2 and HO·. Therefore, Jixueteng represents a promising therapeutic drug for reactive oxygen-associated pathologies. PMID:25632478

  11. Detecting, Visualizing and Quantitating the Generation of Reactive Oxygen Species in an Amoeba Model System

    PubMed Central

    Zhang, Xuezhi; Soldati, Thierry

    2013-01-01

    Reactive oxygen species (ROS) comprise a range of reactive and short-lived, oxygen-containing molecules, which are dynamically interconverted or eliminated either catalytically or spontaneously. Due to the short life spans of most ROS and the diversity of their sources and subcellular localizations, a complete picture can be obtained only by careful measurements using a combination of protocols. Here, we present a set of three different protocols using OxyBurst Green (OBG)-coated beads, or dihydroethidium (DHE) and Amplex UltraRed (AUR), to monitor qualitatively and quantitatively various ROS in professional phagocytes such as Dictyostelium. We optimised the beads coating procedures and used OBG-coated beads and live microscopy to dynamically visualize intraphagosomal ROS generation at the single cell level. We identified lipopolysaccharide (LPS) from E. coli as a potent stimulator for ROS generation in Dictyostelium. In addition, we developed real time, medium-throughput assays using DHE and AUR to quantitatively measure intracellular superoxide and extracellular H2O2 production, respectively. PMID:24300479

  12. Hydrogen sulfide signaling: interactions with nitric oxide and reactive oxygen species.

    PubMed

    Hancock, John T; Whiteman, Matthew

    2016-02-01

    Signaling in cells involving reactive compounds is well established. Reactive oxygen species (ROS) and nitric oxide (NO) are known to be extremely influential in the control of a range of physiological responses in many organisms, from animals to plants. Often, their generation is triggered in reaction to stress, and it is common for ROS and NO metabolism to interact to give a coordinated response. Recently, hydrogen sulfide (H2 S) has also been found to be an important signaling molecule, being shown to be involved in vascular tone in animals. Of relevance to respiration, in plants, H2 S has been shown to affect stomatal apertures and the transpiration stream, while, in animals, H2 S has been shown to be a source of electrons for ATP synthesis in mitochondria. However, in signaling, H2 S does not work in isolation, and it is likely that it will interact with both ROS and NO. This may occur at a variety of levels, from influencing the generation of such molecules, interacting directly, or competing for control of downstream signaling events. A full understanding of the impact of this toxic molecule in the control of cells requires all these factors to be taken into account. PMID:25782612

  13. Sodium channels as gateable non-photonic sensors for membrane-delimited reactive species.

    PubMed

    Ojha, Navin K; Nematian-Ardestani, Ehsan; Neugebauer, Sophie; Borowski, Benjamin; El-Hussein, Ahmed; Hoshi, Toshinori; Leipold, Enrico; Heinemann, Stefan H

    2014-05-01

    Reactive oxygen species (ROS) and reactive oxygen intermediates (ROI) play crucial roles in physiological processes. While excessive ROS damages cells, small fluctuations in ROS levels represent physiological signals important for vital functions. Despite the physiological importance of ROS, many fundamental questions remain unanswered, such as which types of ROS occur in cells, how they distribute inside cells, and how long they remain in an active form. The current study presents a ratiometric sensor of intracellular ROS levels based on genetically engineered voltage-gated sodium channels (roNaV). roNaV can be used for detecting oxidative modification that occurs near the plasma membrane with a sensitivity similar to existing fluorescence-based ROS sensors. Moreover, roNaV has several advantages over traditional sensors because it does not need excitation light for sensing, and thus, can be used to detect phototoxic cellular modifications. In addition, the ROS dynamic range of roNaV is easily manipulated in real time by means of the endogenous channel inactivation mechanism. Measurements on ROS liberated from intracellular Lucifer Yellow and genetically encoded KillerRed have revealed an assessment of ROS lifetime in individual mammalian cells. Flashlight-induced ROS concentration decayed with two major time constants of about 10 and 1000 ms. PMID:24513256

  14. Reactivity, Selectivity, and Reaction Mechanisms of Aminoguanidine, Hydralazine, Pyridoxamine, and Carnosine as Sequestering Agents of Reactive Carbonyl Species: A Comparative Study.

    PubMed

    Colzani, Mara; De Maddis, Danilo; Casali, Gaia; Carini, Marina; Vistoli, Giulio; Aldini, Giancarlo

    2016-08-19

    Reactive carbonyl species (RCS) are endogenous or exogenous byproducts involved in the pathogenic mechanisms of different oxidative-based disorders. Detoxification of RCS by carbonyl quenchers is a promising therapeutic strategy. Among the most studied quenchers are aminoguanidine, hydralazine, pyridoxamine, and carnosine; their quenching activity towards four RCS (4-hydroxy-trans-2-nonenal, methylglyoxal, glyoxal, and malondialdehyde) was herein analyzed and compared. Their ability to prevent protein carbonylation was evaluated in vitro by using an innovative method based on high-resolution mass spectrometry (HRMS). The reactivity of the compounds was RCS dependent: carnosine efficiently quenched 4-hydroxy-trans-2-nonenal, pyridoxamine was particularly active towards malondialdehyde, aminoguanidine was active towards methylglyoxal and glyoxal, and hydralazine efficiently quenched all RCS. Reaction products were generated in vitro and were characterized by HRMS. Molecular modeling studies revealed that the reactivity was controlled by specific stereoelectronic parameters that could be used for the rational design of improved carbonyl quenchers. PMID:26891408

  15. Tks5-dependent, Nox-mediated Generation of Reactive Oxygen Species is Necessary for Invadopodia Formation*

    PubMed Central

    Diaz, Begoña; Shani, Gidon; Pass, Ian; Anderson, Diana; Quintavalle, Manuela; Courtneidge, Sara A.

    2009-01-01

    Invadopodia are actin-rich membrane protrusions of cancer cells which facilitate pericellular proteolysis and invasive behavior. We show here that reactive oxygen species (ROS) generated by the NADPH oxidase (Nox) system are necessary for invadopodia formation and function. The invadopodia protein Tks5 is structurally related to p47phox, a Nox component in phagocytic cells. Knockdown of Tks5 reduces total ROS levels in cancer cells. Furthermore, Tks5 and p22phox can associate with each other, suggesting that Tks5 is part of the Nox complex. Tyrosine phosphorylation of Tks5 and Tks4, but not other Src substrates, is reduced by Nox inhibition. We propose that Tks5 facilitates the production of ROS necessary for invadopodia formation, and that in turn ROS modulates Tks5 tyrosine phosphorylation in a positive feedback loop. PMID:19755709

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

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

  17. Reactive oxygen species generated from skeletal muscles are required for gecko tail regeneration.

    PubMed

    Zhang, Qing; Wang, Yingjie; Man, Lili; Zhu, Ziwen; Bai, Xue; Wei, Sumei; Liu, Yan; Liu, Mei; Wang, Xiaochuan; Gu, Xiaosong; Wang, Yongjun

    2016-01-01

    Reactive oxygen species (ROS) participate in various physiological and pathological functions following generation from different types of cells. Here we explore ROS functions on spontaneous tail regeneration using gecko model. ROS were mainly produced in the skeletal muscle after tail amputation, showing a temporal increase as the regeneration proceeded. Inhibition of the ROS production influenced the formation of autophagy in the skeletal muscles, and as a consequence, the length of the regenerating tail. Transcriptome analysis has shown that NADPH oxidase (NOX2) and the subunits (p40(phox) and p47(phox)) are involved in the ROS production. ROS promoted the formation of autophagy through regulation of both ULK and MAPK activities. Our results suggest that ROS produced by skeletal muscles are required for the successful gecko tail regeneration. PMID:26853930

  18. Reactive Oxygen Species Modulate the Differentiation of Neurons in Clonal Cortical Cultures.

    PubMed Central

    Tsatmali, Marina; Walcott, Elisabeth C.; Makarenkova, Helen; Crossin, Kathryn L.

    2007-01-01

    Reactive oxygen species (ROS) are important regulators of intracellular signaling. We examined the expression of ROS during rat brain development and explored their role in differentiation using cortical cultures. High levels of ROS were found in newborn neurons. Neurons produced ROS, not connected with cell death, throughout embryogenesis and postnatal stages. By P20, ROS-producing cells were found only in neurogenic regions. Cells with low levels of ROS, isolated from E15 brains by FACS, differentiated into neurons, oligodendrocytes, and astrocytes in clonal cultures. Neurons produced high ROS early in culture and later differentiated into two types: large pyramidal-like neurons that fired no or only a single action potential and smaller neurons that expressed nuclear calretinin and fired repeated action potentials. Antioxidant treatment did not alter neuron number but increased the ratio of small to large neurons. These findings suggest that modulation of ROS levels influences multiple aspects of neuronal differentiation. PMID:17000118

  19. Reactive Oxygen Species and Autophagy Modulation in Non-Marine Drugs and Marine Drugs

    PubMed Central

    Farooqi, Ammad Ahmad; Fayyaz, Sundas; Hou, Ming-Feng; Li, Kun-Tzu; Tang, Jen-Yang; Chang, Hsueh-Wei

    2014-01-01

    It is becoming more understandable that an existing challenge for translational research is the development of pharmaceuticals that appropriately target reactive oxygen species (ROS)-mediated molecular networks in cancer cells. In line with this approach, there is an overwhelmingly increasing list of many non-marine drugs and marine drugs reported to be involved in inhibiting and suppressing cancer progression through ROS-mediated cell death. In this review, we describe the strategy of oxidative stress-based therapy and connect the ROS modulating effect to the regulation of apoptosis and autophagy. Finally, we focus on exploring the function and mechanism of cancer therapy by the autophagy modulators including inhibitors and inducers from non-marine drugs and marine drugs. PMID:25402829

  20. Nitrotyrosine-modified SERCA2: a cellular sensor of reactive nitrogen species

    SciTech Connect

    Bigelow, Diana J.

    2009-01-19

    The SERCA2 isoform of the sarco/endoplasmic reticulum Ca2+-ATPase is sensitive to cellular conditions of inflammation and oxidative stress as evidenced by the common appearance of 3-nitrotyrosine modified forms of SERCA2 in aging and disease in both striated and smooth muscle of humans and several rodent models. Structural-functional studies of nitrated SERCA2 in aging heart and skeletal muscle demonstrate stoichiometric nitration of vicinal tyrosines, Tyr-294 and Tyr-295, on the lumenal side of the membrane-spanning helix, M4 that correlates with partial inhibition of its Ca2+-ATPase activity suggesting a possible regulatory function in down-regulating mitochondrial energy production and the associated generation of reactive oxygen/nitrogen species. This review discusses recent work regarding the nitrative and redox sensitivity of SERCA2 in muscle with respect to general cellular mechanisms of turnover and repair of modified proteins.

  1. Hemoglobin fructation promotes heme degradation through the generation of endogenous reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Goodarzi, M.; Moosavi-Movahedi, A. A.; Habibi-Rezaei, M.; Shourian, M.; Ghourchian, H.; Ahmad, F.; Farhadi, M.; Saboury, A. A.; Sheibani, N.

    2014-09-01

    Protein glycation is a cascade of nonenzymatic reactions between reducing sugars and amino groups of proteins. It is referred to as fructation when the reducing monosaccharide is fructose. Some potential mechanisms have been suggested for the generation of reactive oxygen species (ROS) by protein glycation reactions in the presence of glucose. In this state, glucose autoxidation, ketoamine, and oxidative advance glycation end products (AGEs) formation are considered as major sources of ROS and perhaps heme degradation during hemoglobin glycation. However, whether fructose mediated glycation produces ROS and heme degradation is unknown. Here we report that ROS (H2O2) production occurred during hemoglobin fructation in vitro using chemiluminescence methods. The enhanced heme exposure and degradation were determined using UV-Vis and fluorescence spectrophotometry. Following accumulation of ROS, heme degradation products were accumulated reaching a plateau along with the detected ROS. Thus, fructose may make a significant contribution to the production of ROS, glycation of proteins, and heme degradation during diabetes.

  2. UVB dependence of quantum dot reactive oxygen species generation in common skin cell models

    PubMed Central

    MORTENSEN, LUKE J.; FAULKNOR, RENEA; RAVICHANDRAN, SUPRIYA; ZHENG, HONG; DELOUISE, LISA A.

    2015-01-01

    Studies have shown that UVB can slightly increase the penetration of nanoparticles through skin and significantly alter skin cell biology, thus it is important to understand if and how UVB may impact subsequent nanoparticle skin cell interactions. The research presented herein evaluates the effect of UVB on quantum dot (QD) uptake and reactive oxygen species (ROS) generation in primary keratinocytes, primary melanocytes, and related cell lines. QD exposure induced cell type dependent ROS responses increased by pre-exposing cells to UVB and correlated with the level of QD uptake. Our results suggest that keratinocytes may be at greater risk for QD induced ROS generation than melanocytes, and raise awareness about the differential cellular effects that topically applied nanomaterials may have on UVB exposed skin. PMID:26485933

  3. The Role of Heme and Reactive Oxygen Species in Proliferation and Survival of Trypanosoma cruzi

    PubMed Central

    Paes, Marcia Cristina; Cosentino-Gomes, Daniela; de Souza, Cíntia Fernandes; Nogueira, Natália Pereira de Almeida; Meyer-Fernandes, José Roberto

    2011-01-01

    Trypanosoma cruzi, the protozoan responsible for Chagas disease, has a complex life cycle comprehending two distinct hosts and a series of morphological and functional transformations. Hemoglobin degradation inside the insect vector releases high amounts of heme, and this molecule is known to exert a number of physiological functions. Moreover, the absence of its complete biosynthetic pathway in T. cruzi indicates heme as an essential molecule for this trypanosomatid survival. Within the hosts, T. cruzi has to cope with sudden environmental changes especially in the redox status and heme is able to increase the basal production of reactive oxygen species (ROS) which can be also produced as byproducts of the parasite aerobic metabolism. In this regard, ROS sensing is likely to be an important mechanism for the adaptation and interaction of these organisms with their hosts. In this paper we discuss the main features of heme and ROS susceptibility in T. cruzi biology. PMID:22007287

  4. Hyaluronan coated cerium oxide nanoparticles modulate CD44 and reactive oxygen species expression in human fibroblasts.

    PubMed

    Lord, Megan S; Farrugia, Brooke L; Yan, Claudia M Y; Vassie, James A; Whitelock, John M

    2016-07-01

    Cerium oxide nanoparticles are being widely explored for cell therapies. In this study, nanoceria was functionalized with hyaluronan (HA) using the organosilane linker, 3-aminopropyltriethoxysilane. HA-nanoceria was found to be cytocompatible and to reduce intracellular reactive oxygen species in human fibroblasts. The HA-nanoceria was found to colocalize with CD44 on the surface of the cells and once internalized traffic to the lysosomes, be degraded and induce markers of autophagy. These particles were also effective in reducing the cell surface expression of CD44. Together these data suggest that HA-nanoceria is a promising drug delivery material to target CD44-expressing cells through a variety of mechanisms. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1736-1746, 2016. PMID:26946213

  5. Fast, Ultrasensitive Detection of Reactive Oxygen Species Using a Carbon Nanotube Based-Electrocatalytic Intracellular Sensor.

    PubMed

    Rawson, Frankie J; Hicks, Jacqueline; Dodd, Nicholas; Abate, Wondwossen; Garrett, David J; Yip, Nga; Fejer, Gyorgy; Downard, Alison J; Baronian, Kim H R; Jackson, Simon K; Mendes, Paula M

    2015-10-28

    Herein, we report a highly sensitive electrocatalytic sensor-cell construct that can electrochemically communicate with the internal environment of immune cells (e.g., macrophages) via the selective monitoring of a particular reactive oxygen species (ROS), hydrogen peroxide. The sensor, which is based on vertically aligned single-walled carbon nanotubes functionalized with an osmium electrocatalyst, enabled the unprecedented detection of a local intracellular "pulse" of ROS on a short second time scale in response to bacterial endotoxin (lipopolysaccharide-LPS) stimulation. Our studies have shown that this initial pulse of ROS is dependent on NADPH oxidase (NOX) and toll like receptor 4 (TLR4). The results suggest that bacteria can induce a rapid intracellular pulse of ROS in macrophages that initiates the classical innate immune response of these cells to infection. PMID:26438964

  6. Reactive oxygen species production in single cells following laser irradiation (Presentation Recording)

    NASA Astrophysics Data System (ADS)

    Duquette, Michelle L.; Kim, Justine; Shi, Linda Z.; Berns, Michael W.

    2015-08-01

    Region specific DNA breaks can be created in single cells using laser light that damages DNA but does not directly generate reactive oxygen species (ROS). We have examined the cellular response to directly generated DNA breaks in single cells. Using a combination of ROS specific dyes and oxidase inhibitors we have found that the oxidase and chromatin remodeling protein Lysine demethylase I (LSD1) generates detectable ROS as a byproduct of its chromatin remodeling activity during the initial DNA damage response. ROS is produced at detectable amounts primarily within the first 3 minutes post irradiation. LSD1 activity has been previously associated with transcriptional regulation therefore these findings have implications for regulation of gene expression following DNA damage particularly in cells with altered redox states.

  7. The Emerging Immunological Role of Post-Translational Modifications by Reactive Nitrogen Species in Cancer Microenvironment

    PubMed Central

    De Sanctis, Francesco; Sandri, Sara; Ferrarini, Giovanna; Pagliarello, Irene; Sartoris, Silvia; Ugel, Stefano; Marigo, Ilaria; Molon, Barbara; Bronte, Vincenzo

    2014-01-01

    Under many inflammatory contexts, such as tumor progression, systemic and peripheral immune response is tailored by reactive nitrogen species (RNS)-dependent post-translational modifications, suggesting a biological function for these chemical alterations. RNS modify both soluble factors and receptors essential to induce and maintain a tumor-specific immune response, creating a “chemical barrier” that impairs effector T cell infiltration and functionality in tumor microenvironment and supports the escape phase of cancer. RNS generation during tumor growth mainly depends on nitric oxide production by both tumor cells and tumor-infiltrating myeloid cells that constitutively activate essential metabolic pathways of l-arginine catabolism. This review provides an overview of the potential immunological and biological role of RNS-induced modifications and addresses new approaches targeting RNS either in search of novel biomarkers or to improve anti-cancer treatment. PMID:24605112

  8. The regulatory roles of ethylene and reactive oxygen species (ROS) in plant salt stress responses.

    PubMed

    Zhang, Ming; Smith, J Andrew C; Harberd, Nicholas P; Jiang, Caifu

    2016-08-01

    Soil salinity is one of the most commonly encountered environmental stresses affecting plant growth and crop productivity. Accordingly, plants have evolved a variety of morphological, physiological and biochemical strategies that enable them to adapt to saline growth conditions. For example, it has long been known that salinity-stress increases both the production of the gaseous stress hormone ethylene and the in planta accumulation of reactive oxygen species (ROS). Recently, there has been significant progress in understanding how the fine-tuning of ethylene biosynthesis and signaling transduction can promote salinity tolerance, and how salinity-induced ROS accumulation also acts as a signal in the mediation of salinity tolerance. Furthermore, recent advances have indicated that ethylene signaling modulates salinity responses largely via regulation of ROS-generating and ROS-scavenging mechanisms. This review focuses on these recent advances in understanding the linked roles of ethylene and ROS in salt tolerance. PMID:27233644

  9. Development of a Sensitive Bioluminogenic Probe for Imaging Highly Reactive Oxygen Species in Living Rats.

    PubMed

    Kojima, Ryosuke; Takakura, Hideo; Kamiya, Mako; Kobayashi, Eiji; Komatsu, Toru; Ueno, Tasuku; Terai, Takuya; Hanaoka, Kenjiro; Nagano, Tetsuo; Urano, Yasuteru

    2015-12-01

    A sensitive bioluminogenic probe for highly reactive oxygen species (hROS), SO3 H-APL, was developed based on the concept of dual control of bioluminescence emission by means of bioluminescent enzyme-induced electron transfer (BioLeT) and modulation of cell-membrane permeability. This probe enables non-invasive visualization of physiologically relevant amounts of hROS generated deep inside the body of living rats for the first time. It is expected to serve as a practical analytical tool for investigating a wide range of biological functions of hROS in vivo. The design concept should be applicable to other in vivo bioluminogenic probes. PMID:26474404

  10. Polyglutamine expansion inhibits respiration by increasing reactive oxygen species in isolated mitochondria

    SciTech Connect

    Puranam, Kasturi L.; Wu, Guanghong; Strittmatter, Warren J.; Burke, James R. . E-mail: james.burke@duke.edu

    2006-03-10

    Huntington's disease results from expansion of the polyglutamine (PolyQ) domain in the huntingtin protein. Although the cellular mechanism by which pathologic-lengt