Sample records for exogenous reactive oxygen

  1. Differential effects of Bcl-2 and caspases on mitochondrial permeabilization during endogenous or exogenous reactive oxygen species-induced cell death: a comparative study of H?O?, paraquat, t-BHP, etoposide and TNF-?-induced cell death.

    PubMed

    Rincheval, Vincent; Bergeaud, Marie; Mathieu, Lise; Leroy, Jacqueline; Guillaume, Arnaud; Mignotte, Bernard; Le Floch, Nathalie; Vayssière, Jean-Luc

    2012-08-01

    In this study, we have compared several features of cell death triggered by classical inducers of apoptotic pathways (etoposide and tumour necrosis factor (TNF)-?) versus exogenous reactive oxygen species (ROS; hydrogen peroxide (H?O?), tert-butyl hydroperoxide (t-BHP)) or a ROS generator (paraquat). Our aim was to characterize relationships that exist between ROS, mitochondrial perturbations, Bcl-2 and caspases, depending on source and identity of ROS. First, we have found that these five inducers trigger oxidative stress, mitochondrial membrane permeabilization (MMP), cytochrome c (cyt c) release from mitochondria and cell death. In each case, cell death could be inhibited by several antioxidants, showing that it is primarily ROS dependent. Second, we have highlighted that during etoposide or TNF-? treatments, intracellular ROS level, MMP and cell death are all regulated by caspases and Bcl-2, with caspases acting early in the process. Third, we have demonstrated that H?O?-induced cell death shares many of these characteristics with etoposide and TNF-?, whereas t-BHP induces both caspase-dependent and caspase-independent cell death. Surprisingly, paraquat-induced cell death, which harbours some characteristics of apoptosis such as cyt c release and caspase-3 activation, is not modulated by Bcl-2 and caspase inhibitors, suggesting that paraquat also triggers non-apoptotic cell death signals. On the one hand, these results show that endogenous or exogenous ROS can trigger multiple cell death pathways with Bcl-2 and caspases acting differentially. On the other hand, they suggest that H?O? could be an important mediator of etoposide and TNF-?-dependent cell death since these inducers trigger similar phenotypes. PMID:22491967

  2. Mitochondrial reactive oxygen species and cancer

    E-print Network

    Chandel, Navdeep S

    Mitochondria produce reactive oxygen species (mROS) as a natural by-product of electron transport chain activity. While initial studies focused on the damaging effects of reactive oxygen species, a recent paradigm shift ...

  3. Reactive oxygen species and hematopoietic stem cell senescence

    Microsoft Academic Search

    Lijian Shao; Hongliang Li; Senthil K. Pazhanisamy; Aimin Meng; Yong Wang; Daohong Zhou

    Hematopoietic stem cells (HSCs) are responsible for sustaining hematopoietic homeostasis and regeneration after injury for\\u000a the entire lifespan of an organism through self-renewal, proliferation, differentiation, and mobilization. Their functions\\u000a can be affected by reactive oxygen species (ROS) that are produced endogenously through cellular metabolism or after exposure\\u000a to exogenous stress. At physiological levels, ROS function as signal molecules which can

  4. 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

  5. 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

  6. Reactive oxygen metabolites and upper gastrointestinal diseases.

    PubMed

    Kountouras, J; Chatzopoulos, D; Zavos, C

    2001-01-01

    Reactive oxygen metabolites play an important role in the pathogenesis of gastroduodenal mucosal inflammation (mucosal ischemic injury and other models of mucosal damage induced by nonsteroidal anti-inflammatory drugs, ethanol, or H. pylori), peptic ulcer disease, and gastric cancer. H. pylori achieves its pathogenetic role by triggering an intense leukocyte infiltration of the gastric mucosa, and neutrophil activation provides a major source of reactive oxygen metabolites which can cause tissue damage mainly in the absence of antioxidants. H. pylori virulence factors promote release of a variety of chemoattractants/inflammatory mediators. Circulating leukocytes are recruited to sites of inflammation by a well-regulated and coordinated process that largely occurs in postcapillary venules. Adhesion molecules are expressed on the surface of endothelial cells and leukocytes serve to ensure an orderly sequence of cell-to-cell interactions that sustain leukocyte adherence to vascular endothelium and the subsequent transendothelial migration into inflamed tissue. Transcriptional factors are involved in the expression of endothelial adhesion molecules, and regulation of activity of these factors (i.e., NF-kappa B) is a very attractive target for therapeutic interventions. Longstanding H. pylori-associated gastritis predisposes to gastric cancer development and reactive oxygen metabolites play a part in H. pylori-related gastric carcinogenesis. Various regimens of reactive oxygen metabolite scavengers appear to be new treatment strategies for upper gastrointestinal diseases. PMID:11462918

  7. Cytochemistry and reactive oxygen species: a retrospective

    Microsoft Academic Search

    Morris J. Karnovsky

    1994-01-01

    This retrospective reviews the methodology we have developed over several decades for detecting reactive oxygen species (ROS), using the activated polymorphonuclear leukocyte (PMN) as the paradigm of a cell which vigorously generates ROS through activation of NADPH oxidase. In the seventies, the sites of ROS generation by PMN were not clear from biochemical data, and we sought to develop new

  8. Reactive oxygen species and superoxide dismutases: role in joint diseases.

    PubMed

    Afonso, Valéry; Champy, Romuald; Mitrovic, Dragoslav; Collin, Pascal; Lomri, Abderrahim

    2007-07-01

    Reactive oxygen species (ROS) are produced in many normal and abnormal processes in humans, including atheroma, asthma, joint diseases, aging, and cancer. The superoxide anion O(2)(-) is the main ROS. Increased ROS production leads to tissue damage associated with inflammation. Superoxide dismutases (SODs) convert superoxide to hydrogen peroxide, which is then removed by glutathione peroxidase or catalase. Thus, SODs prevent the formation of highly aggressive ROS, such as peroxynitrite or the hydroxyl radical. Experimental models involving SOD knockout or overexpression are beginning to shed light on the pathophysiological role of SOD in humans. Although the antiinflammatory effects of exogenous native SOD (orgotein) are modest, synthetic SOD mimetics hold considerable promise for modulating the inflammatory response. In this review, we discuss new knowledge about the role of the superoxide anion and its derivates as mediators of inflammation and the role of SODs and SOD mimetics as antioxidant treatments in joint diseases such as rheumatoid arthritis, osteoarthritis, and crystal-induced arthropathies. PMID:17590367

  9. Signal transduction by reactive oxygen species

    PubMed Central

    2011-01-01

    Although historically viewed as purely harmful, recent evidence suggests that reactive oxygen species (ROS) function as important physiological regulators of intracellular signaling pathways. The specific effects of ROS are modulated in large part through the covalent modification of specific cysteine residues found within redox-sensitive target proteins. Oxidation of these specific and reactive cysteine residues in turn can lead to the reversible modification of enzymatic activity. Emerging evidence suggests that ROS regulate diverse physiological parameters ranging from the response to growth factor stimulation to the generation of the inflammatory response, and that dysregulated ROS signaling may contribute to a host of human diseases. PMID:21746850

  10. 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

  11. 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 ...

  12. Metabolic Stress, Reactive Oxygen Species, and Arrhythmia

    PubMed Central

    Jeong, Euy-Myoung; Liu, Man; Sturdy, Megan; Gao, Ge; Sovari, Ali A.; Dudley, Samuel C.

    2011-01-01

    Cardiac arrhythmias can cause sudden cardiac death (SCD) and add to the current heart failure (HF) health crisis. Nevertheless, the pathological processes underlying arrhythmias are unclear. Arrhythmic conditions are associated with systemic and cardiac oxidative stress caused by reactive oxygen species (ROS). In excitable cardiac cells, ROS regulate both cellular metabolism and ion homeostasis. Increasing evidence suggests that elevated cellular ROS can cause alterations of the cardiac sodium channel (Nav1.5), abnormal Ca2+ handling, changes of mitochondrial function, and gap junction remodeling, leading to arrhythmogenesis. This review summarizes our knowledge of the mechanisms by which ROS may cause arrhythmias and discusses potential therapeutic strategies to prevent arrhythmias by targeting ROS and its consequences. PMID:21978629

  13. Characterization of reactive oxygen species in diaphragm.

    PubMed

    Zuo, L; Best, T M; Roberts, W J; Diaz, P T; Wagner, P D

    2015-03-01

    Reactive oxygen species (ROS) exist as natural mediators of metabolism to maintain cellular homeostasis. However, ROS production may significantly increase in response to environmental stressors, resulting in extensive cellular damage. Although several potential sources of increased ROS have been proposed, exact mechanisms of their generation have not been completely elucidated. This is particularly true for diaphragmatic skeletal muscle, the key muscle used for respiration. Several experimental models have focused on detection of ROS generation in rodent diaphragm tissue under stressful conditions, including hypoxia, exercise, and heat, as well as ROS formation in single myofibres. Identification methods include direct detection of ROS with confocal or fluorescent microscopy and indirect detection of ROS through end product analysis. This article explores implications of ROS generation and oxidative stress, and also evaluates potential mechanisms of cellular ROS formation in diaphragmatic skeletal muscle. PMID:25330121

  14. [Reactive oxygen forms and luminescence of intact microspore cells].

    PubMed

    Roshchina, V V; Miller, A V; Safronova, V G; Karnaukhov, V N

    2003-01-01

    The participation of reactive oxygen species (ROS) in luminescence (chemiluminescence and autofluorescence induced by ultraviolet light of 360-380 nm) was analyzed. Microspores, the pollen (male gametophyte) of Hippeastrum hybridum, Philadelphus grandiflorus, and Betula verrucosa and vegetative microspores of the spore-breeding plant Equisetum arvense served as models. It was found that the addition of the chemiluminescent probe lucigenin, which luminesces in the presence of superoxide anionradicals, leads to intensive chemiluminescence of microspores. No emission was observed in the absence of lucigenin and in the presence of the dye luminol as a chemiluminescent probe. The emission decreased significantly if superoxide dismutase, an enzyme of the superoxide anionradical dismutation during which this radical disappeared, was added before the dye addition. The autofluorescence intensity of microspores decreased in the presence of both superoxide dismutase and peroxidase, an enzyme destroying hydrogen peroxide and organic peroxides. The most significant effect was noted after the addition of peroxidase, which indicates a greater contribution of peroxides to this type of emission. The fumigation with ozone, which increases the amount of ROS on the cell surface, enhanced the intensity of the chemiluminescence of microspores with lucigenin, but decreased the intensity of the autofluorescence of microspores. Exogenous peroxides (hydrogen peroxide and tert-butylhydroperoxide) stimulated the autofluorescence of pollen and vegetative spores in a concentration-dependent manner. It was shown that the formation of ROS contributes to the luminescence of plant microspores, which reflects their functional state. PMID:12723352

  15. Reactive oxygen species in pulmonary vascular remodeling.

    PubMed

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

    2013-07-01

    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 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 antioxidant 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 cofactor 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

  16. 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

  17. Reactive Oxygen Species in Skeletal Muscle Signaling

    PubMed Central

    Barbieri, Elena; Sestili, Piero

    2012-01-01

    Generation of reactive oxygen species (ROS) is a ubiquitous phenomenon in eukaryotic cells' life. Up to the 1990s of the past century, ROS have been solely considered as toxic species resulting in oxidative stress, pathogenesis and aging. However, there is now clear evidence that ROS are not merely toxic species but also—within certain concentrations—useful signaling molecules regulating physiological processes. During intense skeletal muscle contractile activity myotubes' mitochondria generate high ROS flows: this renders skeletal muscle a tissue where ROS hold a particular relevance. According to their hormetic nature, in muscles ROS may trigger different signaling pathways leading to diverging responses, from adaptation to cell death. Whether a “positive” or “negative” response will prevail depends on many variables such as, among others, the site of ROS production, the persistence of ROS flow or target cells' antioxidant status. In this light, a specific threshold of physiological ROS concentrations above which ROS exert negative, toxic effects is hard to determine, and the concept of “physiologically compatible” levels of ROS would better fit with such a dynamic scenario. In this review these concepts will be discussed along with the most relevant signaling pathways triggered and/or affected by ROS in skeletal muscle. PMID:22175016

  18. 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

  19. Indoor particulate reactive oxygen species concentrations.

    PubMed

    Khurshid, Shahana S; Siegel, Jeffrey A; Kinney, Kerry A

    2014-07-01

    Despite the fact that precursors to reactive oxygen species (ROS) are prevalent indoors, the concentration of ROS inside buildings is unknown. ROS on PM2.5 was measured inside and outside twelve residential buildings and eleven institutional and retail buildings. The mean (± s.d.) concentration of ROS on PM2.5 inside homes (1.37 ± 1.2 nmoles/m(3)) was not significantly different from the outdoor concentration (1.41 ± 1.0 nmoles/m(3)). Similarly, the indoor and outdoor concentrations of ROS on PM2.5 at institutional buildings (1.16 ± 0.38 nmoles/m(3) indoors and 1.68 ± 1.3 nmoles/m(3) outdoors) and retail stores (1.09 ± 0.93 nmoles/m(3) indoors and 1.12 ± 1.1 nmoles/m(3) outdoors) were not significantly different and were comparable to those in residential buildings. The indoor concentration of particulate ROS cannot be predicted based on the measurement of other common indoor pollutants, indicating that it is important to separately assess the concentration of particulate ROS in air quality studies. Daytime indoor occupational and residential exposure to particulate ROS dominates daytime outdoor exposure to particulate ROS. These findings highlight the need for further study of ROS in indoor microenvironments. PMID:24742727

  20. Effect of exogenous adenosine triphosphate on the oxygen uptake of skeletal muscle and liver slices and homogenate of albino rats

    Microsoft Academic Search

    H. M. Tahani; M. Ibrahim Khairia; Y. A. Habib; M. Talaat

    1979-01-01

    Summary The effect of exogenous adenosine triphosphate on the oxygen uptake of rat diaphragm and liver slices and homogenate were studied in normal rats using Warburg Manometric Technique. Five concentrations of ATP were used, namely 0.275, 0.55, 1.1, 2.75, and 5.5 mM ATP.

  1. Antioxidant combination inhibits reactive oxygen species mediated damage.

    PubMed

    Yanai, Nobuya; Shiotani, Shigenobu; Hagiwara, Shoji; Nabetani, Hiroshi; Nakajima, Mitsutoshi

    2008-12-01

    We examined the preventive activity of naturally occurring antioxidants against three reactive oxygen species using a protein degradation assay. The hydroxyl, hypochlorite, and peroxynitrite radicals are typical reactive oxygen species generated in human body. Previously, we found that hydrophobic botanical antioxidants exhibited specific antioxidant activity against hydroxyl radicals, whereas anserine and carnosine mixture, purified from chicken extract and vitamin C, exhibited antioxidant activities against hypochlorite and peroxynitrite radicals respectively. Since ethanol, used as a solvent in the experiments, also showed an antioxidant action against the hydroxyl radical, we re-assessed antioxidant activities using aqueous solutions of botanical antioxidants. Among the seven hydrophobic antioxidants examined, ferulic acid exhibited the strongest antioxidant activity against the hydroxyl radical. An antioxidant preparation of anserine-carnosine mixture, vitamin C, and ferulic acid prevented oxidative stress by reactive oxygen species. Loss of deformability in human erythrocytes and protein degradation caused by reactive oxygen species were completely inhibited. PMID:19060409

  2. Reactive oxygen species in vascular biology: implications in hypertension

    Microsoft Academic Search

    R. M. Touyz; E. L. Schiffrin

    2004-01-01

    Reactive oxygen species (ROS), including superoxide (·O 2 ?), hydrogen peroxide (H 2O 2), and hydroxyl anion (OH-), and reactive nitrogen species, such as nitric oxide (NO) and peroxynitrite (ONOO ?), are biologically important O 2 derivatives that are increasingly recognized to be important in vascular biology through their oxidation\\/reduction (redox) potential. All vascular cell types (endothelial cells, vascular smooth

  3. Impaired Endothelial Regulation of Ventricular Relaxation in Cardiac Hypertrophy Role of Reactive Oxygen Species and NADPH Oxidase

    Microsoft Academic Search

    Philip A. MacCarthy; David J. Grieve; Jian-Mei Li; Christina Dunster

    Background—Endothelium-derived nitric oxide (NO) selectively enhances myocardial relaxation. In experimental left ventricular hypertrophy (LVH), this endothelium-dependent LV relaxant response is impaired despite a preserved response to exogenous NO. We investigated the potential role of reactive oxygen species (ROS) in this defect. Methods and Results—Short-term treatment with the antioxidants vitamin C (10 mol\\/L) or deferoxamine (500 mol\\/L) restored LV relaxant responses

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

    SciTech Connect

    Koontz, S.; Leger, L.; Albyn, K.; Cross, J. (NASA, Johnson Space Center, Houston, TX (USA) Los Alamos National Laboratory, NM (USA))

    1990-06-01

    Experimental results are presented which indicate that low fluxes of vacuum UV (VUV) radiation exert a pronounced influence on the atomic oxygen reactivity of such fluorocarbon and fluorocarbon spacecraft materials as the FEP Teflon and PCTFE that are under consideration for the Space Station Freedom. With simultaneous exposure to VUV fluxes comparable to those experienced in LEO, the reactivity of these materials becomes comparable to that of Kapton; VUV radiation has also been shown to increase the reactivity of Kapton with thermal-energy oxygen atoms. 8 refs.

  5. Generation of reactive oxygen species by the faecal matrix

    PubMed Central

    Owen, R; Spiegelhalder, B; Bartsch, H

    2000-01-01

    BACKGROUND—Reactive oxygen species are implicated in the aetiology of a range of human diseases and there is increasing interest in their role in the development of cancer.?AIM—To develop a suitable method for the detection of reactive oxygen species produced by the faecal matrix.?METHODS—A refined high performance liquid chromatography system for the detection of reactive oxygen species is described.?RESULTS—The method allows baseline separation of the products of hydroxyl radical attack on salicylic acid in the hypoxanthine/xanthine oxidase system, namely 2,5-dihydroxybenzoic acid, 2,3-dihydroxybenzoic acid, and catechol. The increased efficiency and precision of the method has allowed a detailed evaluation of the dynamics of reactive oxygen species generation in the faecal matrix. The data show that the faecal matrix is capable of generating reactive oxygen species in abundance. This ability cannot be attributed to the bacteria present, but rather to a soluble component within the matrix. As yet, the nature of this soluble factor is not entirely clear but is likely to be a reducing agent.?CONCLUSIONS—The soluble nature of the promoting factor renders it amenable to absorption, and circumstances may exist in which either it comes into contact with either free or chelated iron in the colonocyte, leading to direct attack on cellular DNA, or else it initiates lipid peroxidation processes whereby membrane polyunsaturated fatty acids are attacked by reactive oxygen species propagating chain reactions leading to the generation of promutagenic lesions such as etheno based DNA adducts.???Keywords: colorectal cancer; faecal matrix; hypoxanthine; phytic acid; reactive oxygen species; xanthine oxidase PMID:10644317

  6. Blood Radicals: Reactive Nitrogen Species, Reactive Oxygen Species, Transition Metal Ions, and the Vascular System

    Microsoft Academic Search

    Victor Darley-Usmar; Barry Halliwell

    1996-01-01

    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

  7. 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

  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. Oxygen Reactivity of a Carbon Fiber Composite

    SciTech Connect

    Marshall, Theron Devol; Pawelko, Robert James; Anderl, Robert Andrew; Smolik, Galen Richard

    2002-09-01

    Carbon Fiber Composites (CFCs) are often suggested as armor material for the first wall of a fusion plasma chamber due to carbon's low atomic number, high thermal conductivity, and high melting point. However, carbon is chemically reactive in air and will react with ingress air during a Loss of Vacuum Accident and release tritium fuel that has been retained in the carbon. Tritium mobilization and carbon monoxide generation via CFC oxidation are both safety concerns. This paper discusses chemical reactivity experiments that were performed using the state-of-the-art 3-dimensional NB31 CFC produced by SNECMA and a laminar reaction gas of Ar–21 vol% O2. Oxidation reaction rates were measured for CFC temperatures of 525, 600, 700, 800, 900, and 1000 °C and a 100 standard cubic centimeters per minute (sccm) Ar–O2 flow rate. Experiments were also performed at CFC temperatures of 700 and 1000 °C and a 1000 sccm Ar–O2 flow rate. Mass spectral analyses of the exhaust reaction gas suggested that carbon monoxide was the primary reaction at the CFC surface and carbon dioxide was readily produced in the exiting reaction gas. The measured reaction rates compare well with the literature and were used to produce a CFC oxidation curve that is recommended for use in fusion safety analyses.

  10. Reactive oxygen species and superoxide dismutases: Role in joint diseases

    Microsoft Academic Search

    Valéry Afonso; Romuald Champy; Dragoslav Mitrovic; Pascal Collin; Abderrahim Lomri

    2007-01-01

    Reactive oxygen species (ROS) are produced in many normal and abnormal processes in humans, including atheroma, asthma, joint diseases, aging, and cancer. The superoxide anion O2? is the main ROS. Increased ROS production leads to tissue damage associated with inflammation. Superoxide dismutases (SODs) convert superoxide to hydrogen peroxide, which is then removed by glutathione peroxidase or catalase. Thus, SODs prevent

  11. 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...

  12. Engineering of Pyranose Dehydrogenase for Increased Oxygen Reactivity

    PubMed Central

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

    2014-01-01

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

  13. Modulation of Vascular Smooth Muscle Signaling by Reactive Oxygen Species

    NSDL National Science Digital Library

    Alicia N. Lyle (Emory University Department of Medicine, Division of Cardiology)

    2006-08-01

    Modulation of signaling in vascular cells by reactive oxygen species (ROS) affects many aspects of cellular function, including growth, migration, and contraction. NADPH oxidases, important sources of ROS, regulate many growth-specific and migration-related signaling pathways. Identifying the precise intracellular targets of ROS enhances understanding of their role in cardiovascular physiology and pathophysiology.

  14. Antimicrobial reactive oxygen and nitrogen species: concepts and controversies

    Microsoft Academic Search

    Ferric C. Fang

    2004-01-01

    Phagocyte-derived reactive oxygen and nitrogen species are of crucial importance for host resistance to microbial pathogens. Decades of research have provided a detailed understanding of the regulation, generation and actions of these molecular mediators, as well as their roles in resisting infection. However, differences of opinion remain with regard to their host specificity, cell biology, sources and interactions with one

  15. 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 ...

  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. Engineering Pyranose 2-Oxidase for Modified Oxygen Reactivity

    PubMed Central

    Brugger, Dagmar; Krondorfer, Iris; Shelswell, Christopher; Huber-Dittes, Benjamin; Haltrich, Dietmar; Peterbauer, Clemens K.

    2014-01-01

    Pyranose 2-oxidase (POx), a member of the GMC family of flavoproteins, catalyzes the regioselective oxidation of aldopyranoses at position C2 to the corresponding 2-ketoaldoses. During the first half-reaction, FAD is reduced to FADH2 and reoxidized in the second half-reaction by reducing molecular oxygen to H2O2. Alternative electron acceptors including quinones, radicals or chelated metal ions show significant and in some cases even higher activity. While oxygen as cheap and abundantly available electron acceptor is favored for many processes, reduced oxygen reactivity is desirable for some applications such as in biosensors/biofuel cells because of reduced oxidative damages to the biocatalyst from concomitant H2O2 production as well as reduced electron “leakage” to oxygen. The reactivity of flavoproteins with oxygen is of considerable scientific interest, and the determinants of oxygen activation and reactivity are the subject of numerous studies. We applied site-saturation mutagenesis on a set of eleven amino acids around the active site based on the crystal structure of the enzyme. Using microtiter plate screening assays with peroxidase/2,2?-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and 2,6-dichlorophenolindophenol, variants of POx with decreased oxidase activity and maintained dehydrogenase activity were identified. Variants T166R, Q448H, L545C, L547R and N593C were characterized with respect to their apparent steady-state constants with oxygen and the alternative electron acceptors DCPIP, 1,4-benzoquinone and ferricenium ion, and the effect of the mutations was rationalized based on structural properties. PMID:25296188

  18. Generation of reactive oxygen species by leukocytes of Prochilodus lineatus.

    PubMed

    de Faria, Marcos Tucunduva; Cury-Boaventura, Maria Fernanda; Lopes, Lucia Rossetti; da Silva, José Roberto Machado Cunha

    2014-04-01

    Prochilodus lineatus (curimbatá), from the Procholodontidae family, is a Brazilian freshwater fish, which is important commercially, nutritionally and ecologically. It is encountered in the Rio da Prata Bay in Southern South America. Studies on the immune system of this fish are scarce, but the physiological mechanisms of the species are analogous to those of other vertebrates. Thus, this work discusses the present study, which correlates P. lineatus leukocytes and the generation of reactive oxygen species after modulatory stimuli. Leukocytes were characterized by light and electron transmission microscopy and investigated by the generation of H2O2 and O2 (-), using phenol red, flow-cytometry and electron transmission histochemistry. The study determined that monocytes and neutrophils are the main cells responsible for generating O2 after stimulation with phorbol myristate acetate. Superoxide dismutase successfully inhibited the generation of reactive oxygen species in neutrophils and monocytes, but stimulated generation when in association with phorbol myristate acetate. Fish leukocyte samples from P. lineatus showed cross-reactivity with antibodies directed against human NADPH-oxidase antibody subunits (p47(phox) and p67(phox)). Thus, catalase enhanced the presence of p47(phox). Neutrophil mitochondria were shown to be generators of H2O2 (charged by cerium precipitate), being enlarged and changing their format. The present study contributes to a better understanding of the respiratory burst pathways in this species and suggests mitochondria as the organelle responsible for generation of reactive oxygen species. PMID:24068363

  19. Mechanisms that Regulate Production of Reactive Oxygen Species by Cytochrome P450

    SciTech Connect

    Zangar, Richard C.; Davydov, Dmitri R.; Verma, Seema

    2004-09-15

    Mammalian cytochromes P450 (P450) are a family of heme-thiolate enzymes involved in the oxidative metabolism of a variety of endogenous and exogenous lipophilic compounds. Poor coupling of the P450 catalytic cycle results in continuous production of reactive oxygen species (ROS), which affect signaling pathways and other cellular functions. P450 generation of ROS is tightly controlled by regulation of gene transcription, as well as by modulation of interactions between protein constituents of the monooxygenase that affects its activity, coupling and stability. Malfunction of these mechanisms may result in a burst of ROS production, which can cause lipid peroxidation and oxidative stress. In turn, oxidative stress downregulates P450 levels by a variety of feedback mechanisms. This review provides an overview of recent advances in our understanding of these feedback mechanisms that serve to limit P450 production of ROS. Some of the more likely physiological and cellular effects of P450 generation of ROS are also discussed.

  20. Mitochondria and Reactive Oxygen Species: Physiology and Pathophysiology

    PubMed Central

    Bolisetty, Subhashini; Jaimes, Edgar A.

    2013-01-01

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

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

    PubMed Central

    Porter, Kristi M.; Sutliff, Roy L.

    2012-01-01

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

  2. Reactive Oxygen Species, Oxidative Stress and Plant Ion Channels

    Microsoft Academic Search

    Vadim Demidchik

    \\u000a Reactive oxygen species (ROS) are important toxic and regulatory agents in plants. They are produced in response to a number\\u000a of stimuli, including major biotic and abiotic stresses. Disruption of respiratory and photosynthetic electron transport chains,\\u000a as well as activation of NADPH oxidases (NOXs) and peroxidases, is a major reason for ROS generation and accumulation during\\u000a stress conditions. ROS production

  3. Reactive oxygen radical levels in caustic esophageal burns

    Microsoft Academic Search

    Engin Günel; Fatma Ça?layan; Osman Ça?layan; Ishak Akillio?lu

    1999-01-01

    Purpose: This study was designed to determine the tissue levels of reactive oxygen radicals in caustic esophageal burns in a rat model.Methods: Forty rats were divided into four groups of 10 animals each. The control rats were uninjured in group A, and the others were injured rats in groups B, C, and D. Through a medial laparatomy incision, a 1.5-cm

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

    NASA Technical Reports Server (NTRS)

    Yen, A. S.

    2002-01-01

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

  5. Reactive oxygen species in the neuropathogenesis of hypertension

    Microsoft Academic Search

    Jeffrey R. Peterson; Ram V. Sharma; Robin L. Davisson

    2006-01-01

    New evidence that has emerged during the past several years clearly demonstrates that reactive oxygen species (ROS) in the\\u000a brain play a crucial role in blood pressure regulation by serving as signaling molecules within neurons of cardiovascular\\u000a control regions. In the forebrain, midbrain, and hindbrain, a key role for oxidant stress in the pathogenesis of angiotensin\\u000a II-dependent and various other

  6. Mitochondrial Reactive Oxygen Species in Myocardial Pre and Postconditioning

    Microsoft Academic Search

    Ariel R. Cardoso; Bruno B. Queliconi; Alicia J. Kowaltowski

    \\u000a Myocardial ischemia followed by reperfusion is a well established condition of medical importance in which reactive oxygen\\u000a species (ROS) are determinant for the pathological outcome. Indeed, oxidative damage during reperfusion is causative of many\\u000a of the complications found after ischemia. ROS leading to postischemic myocardial damage come from many sources, including\\u000a mitochondria, NADPH oxidase, xanthine oxidase, and infiltrated phagocytes [1].

  7. Reactive Oxygen Species in Plant–Pathogen Interactions

    Microsoft Academic Search

    G. Paul Bolwell; Arsalan Daudi

    Reactive oxygen species (ROS), superoxide, hydrogen peroxide and nitric oxide are produced at all levels of resistance reactions\\u000a in plants. In basal resistance, they are linked to papilla formation and the assembly of barriers. In the hypersensitive response,\\u000a they may be linked to programmed cell death, and in systemic acquired resistance, they interact with salicylate in signalling.\\u000a Despite this importance,

  8. REACTIVE OXYGEN SPECIES: Metabolism, Oxidative Stress, and Signal Transduction

    Microsoft Academic Search

    Klaus Apel; Heribert Hirt

    2004-01-01

    ? Abstract Several reactive oxygen,species (ROS) are continuously,produced,in plants as byproducts,of aerobic metabolism. Depending,on the nature of the ROS species, some are highly toxic and rapidly detoxified by various cellular enzymatic and,nonenzymatic,mechanisms.,Whereas,plants are surfeited with mechanisms,to combat increased ROS levels during abiotic stress conditions, in other circumstances plants appear to purposefully,generate ROS as signaling molecules,to control various processes including pathogen

  9. Focus Issue: Reactive Oxygen Species--Friend or Foe?

    NSDL National Science Digital Library

    Nancy R. Gough (DC; American Association for the Advancement of Science, Washington REV)

    2006-04-25

    Science’s STKE focuses on the signaling pathways activated in response to pathological accumulation of reactive oxygen species (ROS), as well as on mechanisms by which cells have harnessed these reactive molecules as active participants in signaling that leads to a desirable cellular response. ROS are chemically reactive because they contain unpaired electrons and, depending on the location of their production and the molecules with which they interact, they can cause cellular damage or trigger specific signaling events. Indeed, kinases and phosphatases are now recognized as key molecules that can be modified by interaction with ROS, and the Protocol by Wu and Terada describes a method for detecting oxidatively modified protein tyrosine phosphatases. In a Perspective, Michel et al. discuss how susceptibility to elevated ROS contributes to death of specific neurons and in a Review, Storz discusses the signaling pathways activated to detoxify ROS and how mitochondrial ROS may contribute to aging.

  10. Properties of Reactive Oxygen Species by Quantum Monte Carlo

    E-print Network

    Andrea Zen; Bernhardt L. Trout; Leonardo Guidoni

    2014-06-16

    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.

  11. Properties of reactive oxygen species by quantum Monte Carlo

    SciTech Connect

    Zen, Andrea [Dipartimento di Fisica, La Sapienza - Università di Roma, Piazzale Aldo Moro 2, 00185 Rome (Italy); Trout, Bernhardt L. [Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, Massachusetts 02139 (United States); Guidoni, Leonardo, E-mail: leonardo.guidoni@univaq.it [Dipartimento di Scienze Fisiche e Chimiche, Università degli studi de L'Aquila, Via Vetoio, 67100 Coppito, L'Aquila (Italy)

    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.

  12. 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.

  13. Hypoxia-mediated degradation of Na,K-ATPase via mitochondrial reactive oxygen species and the ubiquitin-conjugating system.

    PubMed

    Comellas, Alejandro P; Dada, Laura A; Lecuona, Emilia; Pesce, Liuska M; Chandel, Navdeep S; Quesada, Nancy; Budinger, G R Scott; Strous, Ger J; Ciechanover, Aaron; Sznajder, Jacob I

    2006-05-26

    We set out to determine whether cellular hypoxia, via mitochondrial reactive oxygen species, promotes Na,K-ATPase degradation via the ubiquitin-conjugating system. Cells exposed to 1.5% O2 had a decrease in Na,K-ATPase activity and oxygen consumption. The total cell pool of alpha1 Na,K-ATPase protein decreased on exposure to 1.5% O2 for 30 hours, whereas the plasma membrane Na,K-ATPase was 50% degraded after 2 hours of hypoxia, which was prevented by lysosome and proteasome inhibitors. When Chinese hamster ovary cells that exhibit a temperature-sensitive defect in E1 ubiquitin conjugation enzyme were incubated at 40 degrees C and 1.5% O2, the degradation of the alpha1 Na,K-ATPase was prevented. Exogenous reactive oxygen species increased the plasma membrane Na,K-ATPase degradation, whereas, in mitochondrial DNA deficient rho(0) cells and in cells transfected with small interfering RNA against Rieske iron sulfur protein, the hypoxia-mediated Na,K-ATPase degradation was prevented. The catalase/superoxide dismutase (SOD) mimetic (EUK-134) and glutathione peroxidase overexpression prevented the hypoxia-mediated Na,K-ATPase degradation and overexpression of SOD1, but not SOD2, partially inhibited the Na+ pump degradation. Accordingly, we provide evidence that during hypoxia, mitochondrial reactive oxygen species are necessary to degrade the plasma membrane Na,K-ATPase via the ubiquitin-conjugating system. PMID:16614303

  14. Lactone-derived carbon-centered radicals: formation and reactivity with oxygen.

    PubMed

    Bejan, E V; Font-Sanchis, E; Scaiano, J C

    2001-12-13

    [reaction: see text] Several lactones were examined to test the reactivity of carbon-centered radicals toward oxygen. Notably, the radical derived from 2-coumaranone (4) is unreactive toward oxygen, while 2-cuomaranone itself shows enhanced reactivity toward hydrogen abstraction by alkoxyl radicals. We propose that five parameters influence diminished reactivity toward oxygen, i.e., (a) benzylic resonance stabilization, (b) unpaired spin delocalization on oxygen, (c) favorable stereoelectronic effects, (d) electron-withdrawing effects, and (e) steric effects. PMID:11735584

  15. Manganese Neurotoxicity and the Role of Reactive Oxygen Species

    PubMed Central

    Martinez-Finley, Ebany J.; Gavin, Claire E; Aschner, Michael; Gunter, Thomas E.

    2013-01-01

    Manganese (Mn) is an essential dietary nutrient but excess or accumulations can be toxic. Disease states, like manganism, are associated with overexposure or accumulation of Mn and are due to the production of reactive oxygen species, free radicals and toxic metabolites, alteration of mitochondrial function and ATP production and depletion of cellular antioxidant defense mechanisms. This review focuses on all of the preceding mechanisms and the scientific studies that support them as well as provides an overview of the absorption, distribution, and excretion of Mn and the stability and transport of Mn compounds in the body. PMID:23395780

  16. In situ reactive oxygen species production for tertiary wastewater treatment.

    PubMed

    Guitaya, Léa; Drogui, Patrick; Blais, Jean François

    2014-12-01

    The goal of this research was to develop a new approach for tertiary water treatment, particularly disinfection and removal of refractory organic compounds, without adding any chemical. Hydrogen peroxide can indeed be produced from dissolved oxygen owing to electrochemical processes. Using various current intensities (1.0 to 4.0 A), it was possible to in situ produce relatively high concentration of H2O2 with a specific production rate of 0.05?×?10(-5) M/min/A. Likewise, by using ultraviolet-visible absorption spectroscopy method, it was shown that other reactive oxygen species (ROS) including HO(*) radical and O3 could be simultaneously formed during electrolysis. The ROS concentration passed from 0.45?×?10(-5) M after 20 min of electrolysis to a concentration of 2.87?×?10(-5) M after 100 min of electrolysis. The disinfection and the organic matter removal were relatively high during the tertiary treatment of municipal and domestic wastewaters. More than 90 % of organic compounds (chemical oxygen demand) can be removed, whereas 99 % of faecal coliform abatement can be reached. Likewise, the process was also effective in removing turbidity (more than 90 % of turbidity was removed) so that the effluent became more and more transparent. PMID:25483973

  17. Diagnostics of reactive oxygen species produced by microplasmas

    NASA Astrophysics Data System (ADS)

    Sousa, J. S.; Puech, V.

    2013-11-01

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

  18. Reactive oxygen species induce procalcitonin expression in trigeminal ganglia glia

    PubMed Central

    Raddant, Ann C.; Russo, Andrew F.

    2014-01-01

    Objective To examine calcitonin gene-related peptide (CGRP) gene expression under inflammatory conditions using trigeminal ganglia organ cultures as an experimental system. These cultures have increased proinflammatory signaling that may mimic neurogenic inflammation in the migraine state. Background The trigeminal nerve sends peripheral pain signals to the central nervous system during migraine. Understanding the dynamic processes that occur within the trigeminal nerve and ganglion may provide insights into events that contribute to migraine pain. A neuropeptide of particular interest is CGRP, which can be elevated and play a causal role in migraine. However, most studies have overlooked a second splice product of the CALCA gene, which encodes calcitonin (CT), a peptide hormone involved in calcium homeostasis. Importantly, a precursor form of calcitonin called procalcitonin (proCT) can act as a partial agonist at the CGRP receptor and elevated proCT has recently been reported during migraine. Methods We used a trigeminal ganglion whole organ explant model, which has previously been demonstrated to induce pro-inflammatory agents in vitro. Quantitative PCR and immunohistochemistry were used to evaluate changes in mRNA and protein levels of CGRP and proCT. Results Whole mouse trigeminal ganglia cultured for 24 h showed a 10-fold increase in CT mRNA, with no change in CGRP mRNA. A similar effect was observed in ganglia from adult rats. ProCT immunoreactivity was localized in glial cells. Cutting the tissue blunted the increase in CT, suggesting that induction required the close environment of the intact ganglia. Consistent with this prediction, there were increased reactive oxygen species in the ganglia and the elevated CT mRNA was reduced by antioxidant treatment. Surprisingly, reactive oxygen species were increased in neurons, not glia. Conclusions These results demonstrate that reactive oxygen species can activate proCT expression from the CGRP gene in trigeminal glia by a paracrine regulatory mechanism. We propose that this glial recruitment pathway may occur following cortical spreading depression and neurogenic inflammation to increase CGRP nociceptive actions in migraine. PMID:24512072

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. Reactive oxygen species, ageing and the hormesis police

    PubMed Central

    Ludovico, Paula; Burhans, William C.

    2013-01-01

    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

  5. 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

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

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  7. Soot-driven reactive oxygen species formation from incense burning.

    PubMed

    Chuang, Hsiao-Chi; Jones, Tim P; Lung, Shih-Chun C; BéruBé, Kelly A

    2011-10-15

    This study investigated the effects of reactive oxygen species (ROS) generated as a function of the physicochemistry of incense particulate matter (IPM), diesel exhaust particles (DEP) and carbon black (CB). Microscopical and elemental analyses were used to determine particle morphology and inorganic compounds. ROS was determined using the reactive dye, Dichlorodihydrofluorescin (DCFH), and the Plasmid Scission Assay (PSA), which determine DNA damage. Two common types of soot were observed within IPM, including nano-soot and micro-soot, whereas DEP and CB mainly consisted of nano-soot. These PM were capable of causing oxidative stress in a dose-dependent manner, especially IPM and DEP. A dose of IPM (36.6-102.3?g/ml) was capable of causing 50% oxidative DNA damage. ROS formation was positively correlated to smaller nano-soot aggregates and bulk metallic compounds, particularly Cu. These observations have important implications for respiratory health given that inflammation has been recognised as an important factor in the development of lung injury/diseases by oxidative stress. This study supports the view that ROS formation by combustion-derived PM is related to PM physicochemistry, and also provides new data for IPM. PMID:21889784

  8. Influence of Induced Reactive Oxygen Species in p53-Mediated Cell Fate Decisions

    PubMed Central

    Macip, Salvador; Igarashi, Makoto; Berggren, Petra; Yu, Jian; Lee, Sam W.; Aaronson, Stuart A.

    2003-01-01

    The p53 tumor suppressor gene can induce either apoptosis or a permanent growth arrest (also termed senescence) phenotype in response to cellular stresses. We show that the increase in intracellular reactive oxygen species (ROS) associated with the magnitude of p53 protein expression correlated with the induction of either senescence or apoptosis in both normal and cancer cells. ROS inhibitors ameliorated both p53-dependent cell fates, implicating ROS accumulation as an effector in each case. The absence of Bax or PUMA strongly inhibited both p53-induced apoptosis and ROS increase, indicating an important role these p53 targets affecting mitochondrial function genes in p53-mediated ROS accumulation. Moreover, physiological p53 levels in combination with an exogenous ROS source were able to convert a p53 senescence response into apoptosis. All of these findings establish a critical role of ROS accumulation and mitochondrial function in p53-dependent cell fates and show that other ROS inducers can collaborate with p53 to influence these fate decisions. Thus, our studies imply that therapeutic agents that generate ROS are more likely to be toxic for normal cells than p53-negative tumor cells and provide a rationale for identifying therapeutic agents that do not complement p53 in ROS generation to ameliorate the cytotoxic side effects in normal cells. PMID:14612402

  9. Induction of apoptosis in NK cells by monocyte-derived reactive oxygen metabolites.

    PubMed

    Hansson, M; Asea, A; Ersson, U; Hermodsson, S; Hellstrand, K

    1996-01-01

    Human NK cells (with CD3-/56+ phenotype) acquired features characteristic of apoptosis after incubation with autologous monocytes, as revealed by apoptotic nuclear morphology, degradation of DNA into oligonucleosomal fragments, and reduced nuclear interchalation of propidium iodide. In contrast, T cells (CD3+/56-) remained non-apoptotic. The monocyte-induced apoptosis in NK cells was prevented by catalase, a scavenger of hydrogen peroxide; whereas superoxide dismutase (a scavenger of superoxide anion), hydroxyl radical scavengers such as mannitol and deferoxamine, or the hypochlorus acid scavenger taurine did not prevent apoptosis. Sodium azide, a myeloperoxidase inhibitor, substantially reduced the monocyte-induced apoptosis in NK cells. Exogenous hydrogen peroxide, at concentrations exceeding 1 microns, induced apoptosis in both NK and T cells. Apoptosis induced by hydrogen peroxide occurred independently of synthesis of protein or mRNA and was blocked by the endonuclease inhibitor aurin tricarboxylic acid. Furthermore, oxidatively induced apoptosis in NK cells was inhibited by herbimycin A, indicating that apoptosis was dependent on protein kinases. Two to five times more hydrogen peroxide was required to induce apoptosis in T cells compared with NK cells. Similarly, NK cells were considerably more susceptible to apoptosis induced by the topoisomerase II inhibitor etoposide or by gamma-irradiation than were T cells. We conclude that monocyte-derived reactive oxygen metabolites kill NK cells by apoptosis and that NK cells are unusually sensitive to oxidatively as well as non-oxidatively induced apoptosis. PMID:8598491

  10. Oxidative stress-induced necrotic cell death via mitochondira-dependent burst of reactive oxygen species.

    PubMed

    Choi, Kyungsun; Kim, Jinho; Kim, Gyung W; Choi, Chulhee

    2009-11-01

    Oxidative stress is deeply involved in various brain diseases, including neurodegenerative diseases, stroke, and ischemia/reperfusion injury. Mitochondria are thought to be the target and source of oxidative stress. We investigated the role of mitochondria in oxidative stress-induced necrotic neuronal cell death in a neuroblastoma cell line and a mouse model of middle cerebral artery occlusion. The exogenous administration of hydrogen peroxide was used to study the role of oxidative stress on neuronal cell survival and mitochondrial function in vitro. Hydrogen peroxide induced non-apoptotic neuronal cell death in a c-Jun N-terminal kinase- and poly(ADP-ribosyl) polymerase-dependent manner. Unexpectedly, hydrogen peroxide treatment induced transient hyperpolarization of the mitochondrial membrane potential and a subsequent delayed burst of endogenous reactive oxygen species (ROS). The inhibition of mitochondrial hyperpolarization by diphenylene iodonium or rotenone, potent inhibitors of mitochondrial respiratory chain complex I, resulted in reduced ROS production and subsequent neuronal cell death in vitro and in vivo. The inhibition of mitochondrial hyperpolarization can protect neuronal cells from oxidative stress-induced necrotic cell death, suggesting a novel method of therapeutic intervention in oxidative stress-induced neurological disease. PMID:19807658

  11. Oxygenation of zinc dialkyldithiocarbamate complexes: isolation, characterization, and reactivity of the stoichiometric oxygenates.

    PubMed

    Brayton, Daniel F; Tanabe, Kristine; Khiterer, Mariya; Kolahi, Kian; Ziller, Joseph; Greaves, John; Farmer, Patrick J

    2006-07-24

    S-oxygenation of dithiocarbamate (DTC) complexes has been implicated in their function as industrial anti-oxidants, as well as in their use as pesticides and most recently in their cumulative toxicity, but little is known of the species generated. Several S-oxygenated derivatives of N,N-disubstituted DTCs have been synthesized, characterized by a variety of methods, and their structure and reactivity examined. Low-temperature reaction of bis(N,N-diethyldithiocarbamato)zinc(II), Zn(deDTC)2 1, with oxygenating reagents (hydrogen peroxide, m-chloroperbenzoic acid, urea hydrogen peroxide) yields mono-oxygenated DTC complexes (N,N-peroxydiethyldithiocarbamato)(N,N-diethyldithiocarbamato)zin(II), Zn(O-deDTC)(deDTC), 2 and bis(N,N-peroxydiethyldithiocarbamato)zinc(II), Zn(O-deDTC)2, 3. The tetraoxygenated derivative bis(N,N-diethylthiocarbamoylsulfinato)zinc(II), Zn(O(2)-deDTC)2, 4, was cleanly obtained by initial reaction of the DTC salts with stoichiometric oxidant prior to complexation with Zn(II). X-ray crystallographic analysis of 2, 3, and 4 show that the peroxydithiocarbamate ligands are S,O-bound. Similar derivatives were obtained from the homoleptic dimethyl and pyrollidine DTC Zn complexes. These oxygenated species display unique 1H and 13C NMR variable-temperature spectra, as the symmetry of DTC ligand is broken upon oxygenation; total line shape analysis (TLSA) was used to compare the energetic parameters for rotation about the C-N bond in several derivatives. Compounds 2, 3, and 4 were deoxygenated by alkyl phosphine, regenerating the parent dithiocarbamate 1. The peroxydithiocarbamate complexes were susceptible to base-catalyzed hydrolytic decomposition, giving ligand-based products indicative of S-oxidation and S-extrusion. PMID:16842015

  12. 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 for this disease. PMID:22401856

  13. Reactive oxygen species, apoptosis, antimicrobial peptides and human inflammatory diseases.

    PubMed

    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

  14. REACTIVE OXYGEN SPECIES, CELLULAR REDOX SYSTEMS AND APOPTOSIS

    PubMed Central

    Circu, Magdalena L.; Aw, Tak Yee

    2010-01-01

    Reactive oxygen species (ROS) are products of normal metabolism and xenobiotic exposure, and depending on concentrations, ROS can be beneficial or harmful to cells and tissues. At physiological low levels, ROS function as “redox messengers” in intracellular signaling and regulation while excess ROS induce oxidative modification of cellular macromolecules, inhibit protein function and promote cell death. Additionally, various redox systems, such as the glutathione, thioredoxin, and pyridine nucleotide redox couples, participate in cell signaling and modulation of cell function, including apoptotic cell death. Cell apoptosis is initiated by extracellular and intracellular signals via two main pathways, the death receptor- or mitochondria-mediated pathways. Various pathologies can result from oxidative stress induced apoptotic signaling that is consequent to ROS increases and/or antioxidant decreases, disruption of intracellular redox homeostasis, and irreversible oxidative modifications of lipid, protein or DNA. In the current review, we focused on several key aspects of ROS and redox mechanisms in apoptotic signaling, and highlighted the gaps in knowledge and potential avenues for further investigation. A full understanding of redox control of apoptotic initiation and execution could underpin the development of therapeutic interventions targeted at oxidative stress associated disorders. PMID:20045723

  15. Simvastatin inhibits osteoclast differentiation by scavenging reactive oxygen species

    PubMed Central

    Moon, Ho-Jin; Kim, Sung Eun; Yun, Young Pil; Hwang, Yu-Shik; Bang, Jae Beum

    2011-01-01

    Osteoclasts, together with osteoblasts, control the amount of bone tissue and regulate bone remodeling. Osteoclast differentiation is an important factor related to the pathogenesis of bone-loss related diseases. Reactive oxygen species (ROS) acts as a signal mediator in osteoclast differentiation. Simvastatin, which inhibits 3-hydroxy-3-methylglutaryl coenzyme A, is a hypolipidemic drug which is known to affect bone metabolism and suppresses osteoclastogenesis induced by receptor activator of nuclear factor-?B ligand (RANKL). In this study, we analyzed whether simvastatin can inhibit RANKL-induced osteoclastogenesis through suppression of the subsequently formed ROS and investigated whether simvastatin can inhibit H2O2-induced signaling pathways in osteoclast differentiation. We found that simvastatin decreased expression of tartrate-resistant acid phosphatase (TRAP), a genetic marker of osteoclast differentiation, and inhibited intracellular ROS generation in RAW 264.7 cell lines. ROS generation activated NF-?B, protein kinases B (AKT), mitogen-activated protein kinases signaling pathways such as c-JUN N-terminal kinases, p38 MAP kinases as well as extracellular signal-regulated kinase. Simvastatin was found to suppress these H2O2-induced signaling pathways in osteoclastogenesis. Together, these results indicate that simvastatin acts as an osteoclastogenesis inhibitor through suppression of ROS-mediated signaling pathways. This indicates that simvastatin has potential usefulness for osteoporosis and pathological bone resorption. PMID:21832867

  16. Hemodynamic Regulation of Reactive Oxygen Species: Implications for Vascular Diseases

    PubMed Central

    Raaz, Uwe; Toh, Ryuji; Maegdefessel, Lars; Adam, Matti; Nakagami, Futoshi; Emrich, Fabian C.; Spin, Joshua M.

    2014-01-01

    Abstract Significance: Arterial blood vessels functionally and structurally adapt to altering hemodynamic forces in order to accommodate changing needs and to provide stress homeostasis. This ability is achieved at the cellular level by converting mechanical stimulation into biochemical signals (i.e., mechanotransduction). Physiological mechanical stress helps maintain vascular structure and function, whereas pathologic or aberrant stress may impair cellular mechano-signaling, and initiate or augment cellular processes that drive disease. Recent Advances: Reactive oxygen species (ROS) may represent an intriguing class of mechanically regulated second messengers. Chronically enhanced ROS generation may be induced by adverse mechanical stresses, and is associated with a multitude of vascular diseases. Although a causal relationship has clearly been demonstrated in large numbers of animal studies, an effective ROS-modulating therapy still remains to be established by clinical studies. Critical Issues and Future Directions: This review article focuses on the role of various mechanical forces (in the form of laminar shear stress, oscillatory shear stress, or cyclic stretch) as modulators of ROS-driven signaling, and their subsequent effects on vascular biology and homeostasis, as well as on specific diseases such as arteriosclerosis, hypertension, and abdominal aortic aneurysms. Specifically, it highlights the significance of the various NADPH oxidase (NOX) isoforms as critical ROS generators in the vasculature. Directed targeting of defined components in the complex network of ROS (mechano-)signaling may represent a key for successful translation of experimental findings into clinical practice. Antioxid. Redox Signal. 20, 914–928. PMID:23879326

  17. 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

  18. Tamoxifen reduces fat mass by boosting reactive oxygen species.

    PubMed

    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

  19. Reactive oxygen metabolites produced by the carcinogenic fibrous mineral erionite

    SciTech Connect

    Urano, Naoko; Yano, Eiji (Teikyo Univ. (Japan)); Evans, P.H. (MRC Dunn Nutrition Unit, Cambridge (United Kingdom))

    1991-02-01

    Erionite, a fibrous mineral and the causative agent of the endemic outbreak of mesothelioma in Turkey, has been shown to generate reactive oxygen metabolites (ROM) from polymorphonuclear leukocytes (PMN). In order to investigate the mechanism of the production of ROM by erionite from PMN, a luminol-dependent chemiluminescence (CL) method was utilized. Human peripheral blood PMN were incubated with 50-800 {mu}g/ml of erionite. PMN CL was produced immediately after the addition of erionite; the maximal CL production was reached within 2 to 6 minutes and the CL response increased with the dose of erionite. Superoxide dismutase, catalase, and dimethyl sulfoxide were utilized as scavengers of O{sub 2}, H{sub 2}O{sub 2}, and OH, respectively. These scavengers inhibited the production of erionite-stimulated PMN CL dose dependently, thus indicating the production of O{sub 2}{sup {minus}}, H{sub 2}O{sub 2}, and OH by erionite-stimulated PMN. The less phagocytically active cells, namely, mononuclear cells and erythrocytes, produced CL immediately after the addition of erionite or phorbol myristate acetate and displayed a significant delay period after the addition of zymosan. Therefore, the direct interaction between the cell surface membrane and erionite would appear to be more important than phagocytosis, per se, for the production of ROM by erionite.

  20. Reactive Oxygen Species and Antioxidants in Pulmonary Hypertension

    PubMed Central

    Wong, Chi-Ming; Bansal, Geetanjali; Pavlickova, Ludmila; Marcocci, Lucia

    2013-01-01

    Abstract Significance: Pulmonary hypertension is a devastating disorder without any available treatment strategies that satisfactorily promote the survival of patients. The identification of new therapeutic strategies to treat patients with pulmonary hypertension is warranted. Recent Advances: Human studies have provided evidence that there is increased oxidative stress (lipid peroxidation, protein oxidation, DNA oxidation, and the depletion of small-molecule antioxidants) in patients with pulmonary hypertension. A variety of compounds with antioxidant properties have been shown to have beneficial therapeutic effects in animal models of pulmonary hypertension, possibly supporting the hypothesis that reactive oxygen species (ROS) are involved in the progression of pulmonary hypertension. Thus, understanding the molecular mechanisms of ROS actions could contribute to the development of optimal, antioxidant-based therapy for human pulmonary hypertension. One such mechanism includes action as a second messenger during cell-signaling events, leading to the growth of pulmonary vascular cells and right ventricular cells. Critical Issues: The molecular mechanisms behind promotion of cell signaling for pulmonary vascular cell growth and right ventricular hypertrophy by ROS are not well understood. Evidence suggests that iron-catalyzed protein carbonylation may be involved. Future Directions: Understanding precise mechanisms of ROS actions should be useful for designing preclinical animal experiments and human clinical trials of the use of antioxidants and/or other redox compounds in the treatment of pulmonary hypertension. Antioxid. Redox Signal. 18, 1789–1796. PMID:22657091

  1. Reactive oxygen species in pulmonary inflammation by ambient particulates.

    PubMed

    Tao, Florence; Gonzalez-Flecha, Beatriz; Kobzik, Lester

    2003-08-15

    Exposure to ambient air pollution particles (PM) has been associated with increased cardiopulmonary morbidity and mortality, particularly in individuals with pre-existing disease. Exacerbation of pulmonary inflammation in susceptible people (e.g., asthmatics, COPD patients) appears to be a central mechanism by which PM exert their toxicity. Health effects are seen most consistently with PM with aerodynamic diameter < 2.5 micrometers (PM(2.5)), although 10 micrometers < PM < 2.5 micrometers can also be toxic. Through its metal, semi-quinone, lipopolysaccaride, hydrocarbon, and ultrafine constituents, PM may exert oxidative stress on cells in the lung by presenting or by stimulating the cells to produce reactive oxygen (ROS). In vivo, PM increase cytokine and chemokine release, lung injury, and neutrophil influx. In vitro analysis of PM effects on the critical cellular targets, alveolar macrophages, epithelial cells, and neutrophils, demonstrates PM- and oxidant-dependent responses consistent with in vivo data. These effects have been observed with PM samples collected over years as well as concentrated PM(2.5) (CAPs) collected in real time. Oxidative stress mediated by ROS is an important mechanism of PM-induced lung inflammation. PMID:12899936

  2. Light and Dark of Reactive Oxygen Species for Vascular Function.

    PubMed

    Shimokawa, Hiroaki; Satoh, Kimio

    2014-08-26

    Vascular-derived hydrogen peroxide (H2O2) serves as an important signaling molecule in the cardiovascular system and contributes to vascular homeostasis. H2O2 is a second messenger, transducing the oxidative signal into biological responses through post-translational protein modification. The balance between oxidant and antioxidant systems regulates intracellular redox status, and their imbalance causes oxidative or reductive stress, leading to cellular damage in cardiovascular systems. Excessive H2O2 deteriorates vascular functions and promotes vascular disease through multiple pathways. The RhoA/Rho-kinase pathway plays an important role in various fundamental cellular functions, including production of excessive reactive oxygen species (ROS), leading to the development of cardiovascular diseases. Rho-kinase (ROCK1 and ROCK2) belongs to the family of serine/threonine kinases and is an important downstream effector of the small GTP-binding protein RhoA. Rho-kinase plays a crucial role in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, stroke and heart failure. Thus, Rho-kinase inhibitors may be useful for the treatment of cardiovascular diseases in humans. In this review, we will briefly discuss the roles of vascular-derived H2O2 and review the recent progress in the translational research on the therapeutic importance of the Rho-kinase pathway in cardiovascular medicine. PMID:25162437

  3. Reactive Oxygen Species prime Drosophila haematopoietic progenitors for differentiation

    PubMed Central

    Owusu-Ansah, Edward; Banerjee, Utpal

    2009-01-01

    Reactive Oxygen Species (ROS), produced during various electron transfer reactions in vivo are generally considered to be deleterious to cells1. In the mammalian haematopoietic system, haematopoietic stem cells (HSCs) contain low ROS levels, but unexpectedly, the common myeloid progenitors (CMPs), produce significantly elevated levels of ROS2. The functional significance of this difference in ROS level in the two progenitor types remains unresolved2,3. Here, we show that Drosophila multipotent haematopoietic progenitors which are largely akin to the mammalian myeloid progenitors4 display elevated levels of ROS under in vivo physiological conditions, which is downregulated upon differentiation. Scavenging the ROS from these haematopoietic progenitors using in vivo genetic tools, retards their differentiation into mature blood cells. Conversely, increasing the haematopoietic progenitor ROS beyond their basal level triggers precocious differentiation into all three mature blood cell types found in Drosophila, through a signaling pathway that involves JNK and FoxO activation as well as Polycomb downregulation. We conclude that the developmentally regulated, moderately high ROS level in the progenitor population sensitizes them to differentiation, and establishes a signaling role for ROS in the regulation of haematopoietic cell fate. Our results lead to a model that could be extended to reveal a probable signaling role for ROS in the differentiation of CMPs in mammalian haematopoietic development and oxidative stress response. PMID:19727075

  4. Mitochondrial reactive oxygen species in cell death signaling.

    PubMed

    Fleury, Christophe; Mignotte, Bernard; Vayssière, Jean-Luc

    2002-01-01

    During apoptosis, mitochondrial membrane permeability (MMP) increases and the release into the cytosol of pro-apoptotic factors (procaspases, caspase activators and caspase-independent factors such as apoptosis-inducing factor (AIF)) leads to the apoptotic phenotype. Apart from this pivotal role of mitochondria during the execution phase of apoptosis (documented in other reviews of this issue), it appears that reactive oxygen species (ROS) produced by the mitochondria can be involved in cell death. These toxic compounds are normally detoxified by the cells, failing which oxidative stress occurs. However, ROS are not only dangerous molecules for the cell, but they also display a physiological role, as mediators in signal transduction pathways. ROS participate in early and late steps of the regulation of apoptosis, according to different possible molecular mechanisms. In agreement with this role of ROS in apoptosis signaling, inhibition of apoptosis by anti-apoptotic Bcl-2 and Bcl-x(L) is associated with a protection against ROS and/or a shift of the cellular redox potential to a more reduced state. Furthermore, the fact that active forms of cell death in yeast and plants also involve ROS suggests the existence of an ancestral redox-sensitive death signaling pathway that has been independent of caspases and Bcl-2. PMID:12022944

  5. Role of GLUT1 in regulation of reactive oxygen species

    PubMed Central

    Andrisse, Stanley; Koehler, Rikki M.; Chen, Joseph E.; Patel, Gaytri D.; Vallurupalli, Vivek R.; Ratliff, Benjamin A.; Warren, Daniel E.; Fisher, Jonathan S.

    2014-01-01

    In skeletal muscle cells, GLUT1 is responsible for a large portion of basal uptake of glucose and dehydroascorbic acid, both of which play roles in antioxidant defense. We hypothesized that conditions that would decrease GLUT1-mediated transport would cause increased reactive oxygen species (ROS) levels in L6 myoblasts, while conditions that would increase GLUT1-mediated transport would result in decreased ROS levels. We found that the GLUT1 inhibitors fasentin and phloretin increased the ROS levels induced by antimycin A and the superoxide generator pyrogallol. However, indinavir, which inhibits GLUT4 but not GLUT1, had no effect on ROS levels. Ataxia telangiectasia mutated (ATM) inhibitors and activators, previously shown to inhibit and augment GLUT1-mediated transport, increased and decreased ROS levels, respectively. Mutation of an ATM target site on GLUT1 (GLUT1-S490A) increased ROS levels and prevented the ROS-lowering effect of the ATM activator doxorubicin. In contrast, expression of GLUT1-S490D lowered ROS levels during challenge with pyrogallol, prevented an increase in ROS when ATM was inhibited, and prevented the pyrogallol-induced decrease in insulin signaling and insulin-stimulated glucose transport. Taken together, the data suggest that GLUT1 plays a role in regulation of ROS and could contribute to maintenance of insulin action in the presence of ROS. PMID:25101238

  6. 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

  7. 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

  8. Free radicals, reactive oxygen species, oxidative stress and its classification.

    PubMed

    Lushchak, Volodymyr I

    2014-10-28

    Reactive oxygen species (ROS) initially considered as only damaging agents in living organisms further were found to play positive roles also. This paper describes ROS homeostasis, principles of their investigation and technical approaches to investigate ROS-related processes. Especial attention is paid to complications related to experimental documentation of these processes, their diversity, spatiotemporal distribution, relationships with physiological state of the organisms. Imbalance between ROS generation and elimination in favor of the first with certain consequences for cell physiology has been called "oxidative stress". Although almost 30years passed since the first definition of oxidative stress was introduced by Helmut Sies, to date we have no accepted classification of oxidative stress. In order to fill up this gape here classification of oxidative stress based on its intensity is proposed. Due to that oxidative stress may be classified as basal oxidative stress (BOS), low intensity oxidative stress (LOS), intermediate intensity oxidative stress (IOS), and high intensity oxidative stress (HOS). Another classification of potential interest may differentiate three categories such as mild oxidative stress (MOS), temperate oxidative stress (TOS), and finally severe (strong) oxidative stress (SOS). Perspective directions of investigations in the field include development of sophisticated classification of oxidative stresses, accurate identification of cellular ROS targets and their arranged responses to ROS influence, real in situ functions and operation of so-called "antioxidants", intracellular spatiotemporal distribution and effects of ROS, deciphering of molecular mechanisms responsible for cellular response to ROS attacks, and ROS involvement in realization of normal cellular functions in cellular homeostasis. PMID:25452175

  9. 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-1? 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

  10. How reactive oxygen species and proline face stress together.

    PubMed

    Ben Rejeb, Kilani; Abdelly, Chedly; Savouré, Arnould

    2014-07-01

    Reactive oxygen species (ROS) are continuously generated as a consequence of plant metabolic processes due to incomplete reduction of O2. Previously considered to be only toxic by-products of metabolism, ROS are now known to act as second messengers in intracellular signalling cascades to trigger tolerance of various abiotic and biotic stresses. The accumulation of proline is frequently observed during the exposure of plants to adverse environmental conditions. Interestingly proline metabolism may also contribute to ROS formation in mitochondria, which play notably a role in hypersensitive response in plants, life-span extension in worms and tumor suppression in animals. Here we review current knowledge about the regulation of proline metabolism in response to environmental constraints and highlight the key role of ROS in the regulation of this metabolism. The impact of proline on ROS generation is also investigated. Deciphering and integrating these relationships at the whole plant level will bring new perspectives on how plants adapt to environmental stresses. PMID:24813727

  11. 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

  12. 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

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

    SciTech Connect

    Lee, Boram; Kim, Ki Hyun; Jung, Hye Jin [Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)] [Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Kwon, Ho Jeong, E-mail: kwonhj@yonsei.ac.kr [Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

    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.

  14. Carbon-Oxygen Bond Activation in Esters by Platinum(0): Cleavage of the Less Reactive Bond

    E-print Network

    Jones, William D.

    Carbon-Oxygen Bond Activation in Esters by Platinum(0): Cleavage of the Less Reactive Bond Kimberly, they typically exchange the OR group for another incoming nucleophile by acyl-oxygen cleavage: e.g., in acidic hydrolysis reactions. SN1 cleavage of the alkyl-oxygen RCOO-R bond is seen only when the ester is protonated

  15. Sunlight-mediated inactivation of MS2 coliphage via exogenous singlet oxygen produced by sensitizers in natural waters.

    PubMed

    Kohn, Tamar; Nelson, Kara L

    2007-01-01

    Pathogens in sunlit surface waters can be damaged directly by UVB light. Indirect inactivation by reactive oxygen species (ROS) generated by sunlight interacting with external sensitizer molecules may also be important, but this mechanism has not been conclusively demonstrated. To better understand the role of ROS, we investigated the inactivation of MS2 coliphage, a commonly used surrogate for human enteric viruses, in water samples irradiated with a solar simulator and containing different types of sensitizers: waste stabilization pond (WSP) constituents, Fluka humic acid (FHA), and Suwannee River humic acid (SRHA). Inactivation of MS2 by the indirect mechanism was significant for all three sensitizers, and the efficiency of the sensitizers at inactivating MS2 was FHA > SRHA > WSP. Both dissolved and particulate fractions in the WSP water contributed to inactivation. In the WSP water, the indirect process was quantitatively more importantthan direct damage by UVB light, due to the rapid attenuation of UVB compared to the longer wavelengths that may initiate the indirect mechanism. Singlet oxygen (1O2) was the most important ROS involved in the inactivation of MS2. The addition of histidine, a 1O2 quencher, decreased inactivation, whereas inactivation rate constants increased in solutions of D20. Selective quenchers for other ROS showed little or no protective effect. Inactivation in WSP water was a function of the steady-state 102 concentration and could be described by a second-order rate expression. PMID:17265947

  16. Reactive oxygen species and human spermatozoa: analysis of the cellular mechanisms involved in luminol- and lucigenin-dependent chemiluminescence.

    PubMed

    Aitken, R J; Buckingham, D W; West, K M

    1992-06-01

    We have shown that human spermatozoa generate and release reactive oxygen species that can be detected by chemiluminescence techniques. Analysis of the cellular mechanisms responsible for this activity suggests that the probe, luminol, undergoes an intracellular dioxygenation reaction mediated by hydrogen peroxide and a sperm peroxidase located within the acrosome. Support for this model included the following observations: (1) the luminol-dependent signal could be suppressed with peroxidase inhibitors, phenylhydrazine and sodium azide; (2) this suppression could be reversed by the addition of an azide-insensitive peroxidase, horse radish peroxidase (HRP); (3) inhibition of intracellular superoxide dismutase (SOD) with potassium cyanide (KCN) suppressed the luminol signal; (4) peroxidase activity could be detected in purified populations of human spermatozoa with 3,3',5,5' tetramethylbenzidine (TMB); (5) this peroxidase was active at the pH prevailing within the acrosomal vesicle; and (6) peroxidase activity and luminol-dependent chemiluminescence were minimal in spermatozoa exhibiting a congenital absence of acrosomes. Human spermatozoa could also generate lucigenin-dependent chemiluminescent signals that could neither be suppressed with peroxidase inhibitors nor enhanced by the addition of peroxidase. However, these signals could be enhanced by suppression of intracellular SOD with KCN or inhibited by exogenous SOD, suggesting that lucigenin was responding to superoxide anion released into the extracellular space. The ability of chemiluminescent techniques to detect and discriminate the production of superoxide and hydrogen peroxide by spermatozoa should facilitate the further analysis of reactive oxygen species as mediators of normal and abnormal human sperm function. PMID:1338331

  17. 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.

  18. Reactive Oxygen Production Induced by the Gut Microbiota: Pharmacotherapeutic Implications

    PubMed Central

    Jones, R.M.; Mercante, J.W.; Neish, A.S.

    2014-01-01

    The resident prokaryotic microbiota of the mammalian intestine influences diverse homeostatic functions, including regulation of cellular growth, maintenance of barrier function, and modulation of immune responses. However, it is unknown how commensal prokaryotic organisms mechanistically influence eukaryotic signaling networks. Recent data has demonstrated that gut epithelia contacted by enteric commensal bacteria rapidly generate reactive oxygen species (ROS). While the induced generation of ROS via stimulation of formyl peptide receptors is a cardinal feature of the cellular response of phagocytes to pathogenic or commensal bacteria, evidence is accumulating that ROS are also similarly elicited in other cell types, including intestinal epithelia, in response to microbial signals. Additionally, ROS have been shown to serve as critical second messengers in multiple signal transduction pathways stimulated by proinflammatory cytokines and growth factors. This physiologically-generated ROS is known to participate in cellular signaling via the rapid and transient oxidative inactivation of a defined class of sensor proteins bearing oxidant-sensitive thiol groups. These proteins include tyrosine phosphatases that serve as regulators of MAP kinase pathways, cytoskeletal dynamics, as well as components involved in control of ubiquitination-mediated NF-?B activation. Consistently, microbial-elicited ROS has been shown to mediate increased cellular proliferation and motility and to modulate innate immune signaling. These results demonstrate how enteric microbiota influence regulatory networks of the mammalian intestinal epithelia. We hypothesize that many of the known effects of the normal microbiota on intestinal physiology, and potential beneficial effects of candidate probiotic bacteria, may be at least partially mediated by this ROS-dependent mechanism. PMID:22360484

  19. Role of Reactive Oxygen Species-Mediated Signaling in Aging

    PubMed Central

    Labunskyy, Vyacheslav M.

    2013-01-01

    Abstract Significance: Redox biology is a rapidly developing area of research due to the recent evidence for general importance of redox control for numerous cellular functions under both physiological and pathophysiological conditions. Understanding of redox homeostasis is particularly relevant to the understanding of the aging process. The link between reactive oxygen species (ROS) and accumulation of age-associated oxidative damage to macromolecules is well established, but remains controversial and applies only to a subset of experimental models. In addition, recent studies show that ROS may function as signaling molecules and that dysregulation of this process may also be linked to aging. Recent Advances: Many protein factors and pathways that control ROS production and scavenging, as well as those that regulate cellular redox homeostasis, have been identified. However, much less is known about the mechanisms by which redox signaling pathways influence longevity. In this review, we discuss recent advances in the understanding of the molecular basis for the role of redox signaling in aging. Critical Issues: Recent studies allowed identification of previously uncharacterized redox components and revealed complexity of redox signaling pathways. It would be important to identify functions of these components and elucidate how distinct redox pathways are integrated with each other to maintain homeostatic balance. Future Directions: Further characterization of processes that coordinate redox signaling, redox homeostasis, and stress response pathways should allow researchers to dissect how their dysregulation contributes to aging and pathogenesis of various age-related diseases, such as diabetes, cancer and neurodegeneration. Antioxid. Redox Signal. 19, 1362–1372. PMID:22901002

  20. Roles of reactive oxygen species and antioxidants in ovarian toxicity.

    PubMed

    Devine, Patrick J; Perreault, Sally D; Luderer, Ulrike

    2012-02-01

    Proper functioning of the ovary is critical to maintain fertility and overall health, and ovarian function depends on the maintenance and normal development of ovarian follicles. This review presents evidence about the potential impact of oxidative stress on the well-being of primordial, growing and preovulatory follicles, as well as oocytes and early embryos, examining cell types and molecular targets. Limited data from genetically modified mouse models suggest that several antioxidant enzymes that protect cells from reactive oxygen species (ROS) may play important roles in follicular development and/or survival. Exposures to agents known to cause oxidative stress, such as gamma irradiation, chemotherapeutic drugs, or polycyclic aromatic hydrocarbons, induce rapid primordial follicle loss; however, the mechanistic role of ROS has received limited attention. In contrast, ROS may play an important role in the initiation of apoptosis in antral follicles. Depletion of glutathione leads to atresia of antral follicles in vivo and apoptosis of granulosa cells in cultured antral follicles. Chemicals, such as cyclophosphamide, dimethylbenzanthracene, and methoxychlor, increase proapoptotic signals, preceded by increased ROS and signs of oxidative stress, and cotreatment with antioxidants is protective. In oocytes, glutathione levels change rapidly during progression of meiosis and early embryonic development, and high oocyte glutathione at the time of fertilization is required for male pronucleus formation and for embryonic development to the blastocyst stage. Because current evidence suggests that oxidative stress can have significant negative impacts on female fertility and gamete health, dietary or pharmacological intervention may prove to be effective strategies to protect female fertility. PMID:22034525

  1. Carbon Monoxide Activates Autophagy via Mitochondrial Reactive Oxygen Species Formation

    PubMed Central

    Lee, Seon-Jin; Ryter, Stefan W.; Xu, Jin-Fu; Nakahira, Kiichi; Kim, Hong Pyo; Kim, Young Sam

    2011-01-01

    Autophagy, an autodigestive process that degrades cellular organelles and protein, plays an important role in maintaining cellular homeostasis during environmental stress. Carbon monoxide (CO), a toxic gas and candidate therapeutic molecule, confers cytoprotection in animal models of acute lung injury. The mechanisms underlying CO-dependent lung cell protection and the role of autophagy in this process remain unclear. Here, we demonstrate that CO exposure time-dependently increased the expression and activation of the autophagic protein, microtubule-associated protein–1 light chain-3B (LC3B) in mouse lung, and in cultured human alveolar (A549) or human bronchial epithelial cells. Furthermore, CO increased autophagosome formation in epithelial cells by electron microscopy and green fluorescent protein (GFP)-LC3 puncta assays. Recent studies indicate that reactive oxygen species (ROS) play an important role in the activation of autophagy. CO up-regulated mitochondria-dependent generation of ROS in epithelial cells, as assayed by MitoSOX fluorescence. Furthermore, CO-dependent induction of LC3B expression was inhibited by N-acetyl-L-cysteine and the mitochondria-targeting antioxidant, Mito-TEMPO. These data suggest that CO promotes the autophagic process through mitochondrial ROS generation. We investigated the relationships between autophagic proteins and CO-dependent cytoprotection using a model of hyperoxic stress. CO protected against hyperoxia-induced cell death, and inhibited hyperoxia-associated ROS production. The ability of CO to protect against hyperoxia-induced cell death and caspase-3 activation was compromised in epithelial cells infected with LC3B-small interfering (si)RNA, indicating a role for autophagic proteins. These studies uncover a new mechanism for the protective action of CO, in support of potential therapeutic application of this gas. PMID:21441382

  2. Laser irradiation of mouse spermatozoa enhances in-vitro fertilization and Ca2+ uptake via reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Cohen, Natalie; Lubart, Rachel; Rubinstein, Sara; Breitbart, Haim

    1996-11-01

    630 nm He-Ne laser irradiation was found to have a profound influence on Ca2+ uptake in mouse spermatozoa and the fertilizing potential of these cells. Laser irradiation affected mainly the mitochondrial Ca2+ transport mechanisms. Furthermore, the effect of light was found to be Ca2+-dependent. We demonstrate that reactive oxygen species (ROS) are involved in the cascade of biochemical events evoked by laser irradiation. A causal association between laser irradiation, ROS generation, and sperm function was indicated by studies with ROS scavengers, superoxide dismutase (SOD) and catalase, and exogenous hydrogen peroxide. SOD treatment resulted in increased Ca2+ uptake and in enhanced fertilization rate. Catalase treatment impaired the light-induced stimulation in Ca2+ uptake and fertilization rate. Exogenous hydrogen peroxide was found to enhance Ca2+ uptake in mouse spermatozoa and the fertilizing capability of these cells in a dose-dependent manner. These results suggest that the effect of 630 nm He-Ne laser irradiation is mediated through the generation of hydrogen peroxide by the spermatozoa and that this effect plays a significant role in the augmentation of the sperm cells' capability to fertilize metaphase II-arrested eggs in-vitro.

  3. Reactive Oxygen Species-Driven Transcription in Arabidopsis under Oxygen Deprivation1[W

    PubMed Central

    Pucciariello, Chiara; Parlanti, Sandro; Banti, Valeria; Novi, Giacomo; Perata, Pierdomenico

    2012-01-01

    Reactive oxygen species (ROS) play an important role as triggers of gene expression during biotic and abiotic stresses, among which is low oxygen (O2). Previous studies have shown that ROS regulation under low O2 is driven by a RHO-like GTPase that allows tight control of hydrogen peroxide (H2O2) production. H2O2 is thought to regulate the expression of heat shock proteins, in a mechanism that is common to both O2 deprivation and to heat stress. In this work, we used publicly available Arabidopsis (Arabidopsis thaliana) microarray datasets related to ROS and O2 deprivation to define transcriptome convergence pattern. Our results show that although Arabidopsis response to anoxic and hypoxic treatments share a common core of genes related to the anaerobic metabolism, they differ in terms of ROS-related gene response. We propose that H2O2 production under O2 deprivation is a trait present in a very early phase of anoxia, and that ROS are needed for the regulation of a set of genes belonging to the heat shock protein and ROS-mediated groups. This mechanism, likely not regulated via the N-end rule pathway for O2 sensing, is probably mediated by a NADPH oxidase and it is involved in plant tolerance to the stress. PMID:22415514

  4. Rat colonic reactive oxygen species production and DNA damage are mediated by diet and age

    E-print Network

    Henderson, Cara Aletha Everett

    2001-01-01

    Colon cancer is the second leading cause of death from cancer in the United States. Studies suggest that oxidative damage to DNA caused by reactive oxygen species (ROS) is a critical initiating event in carcinogenesis. Rates of colon cancer...

  5. 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...

  6. 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...

  7. VARICOCELE IS ASSOCIATED WITH ELEVATED SPERMATOZOAL REACTIVE OXYGEN SPECIES PRODUCTION AND DIMINISHED SEMINAL PLASMA ANTIOXIDANT CAPACITY

    Microsoft Academic Search

    BENJAMIN N. HENDIN; PETER N. KOLETTIS; RAKESH K. SHARMA; ANTHONY J. THOMAS; ASHOK AGARWAL

    1999-01-01

    PurposeBecause varicocele is seen often in infertile men and oxidative stress has been implicated in sperm dysfunction, we assessed spermatozoal reactive oxygen species and seminal total antioxidant capacity in men with and without varicocele.

  8. S-nitrosothiols and reactive oxygen species in plant disease resistance and development 

    E-print Network

    Brzezek, Kerstin

    2014-06-28

    Nitric oxide (NO) as well as reactive oxygen species (ROS) play an important role in defence signalling in plants. After successful recognition of an invading pathogen, an increase in ROS occurs, the ’oxidative burst’; ...

  9. The control of reactive oxygen species influences porcine oocyte in vitro maturation.

    PubMed

    Alvarez, G M; Morado, S A; Soto, M P; Dalvit, G C; Cetica, P D

    2015-04-01

    The aim of this study was to examine the effect of varying intracellular reactive oxygen species (ROS) levels during oocyte in vitro maturation with enzymatic ROS production systems (xanthine + xanthine oxidase or xanthine + xanthine oxidase + catalase), scavenger systems (catalase or superoxide dismutase + catalase) or cysteine on porcine oocyte maturation. Oocyte ROS levels showed an increase when H2 O2 or O2 ?(-) production systems were added to the culture medium (p < 0.05). On the other hand, the presence of ROS scavengers in the maturation medium did not modify oocyte ROS levels compared with the control after 48 h of maturation, but the addition of cysteine induced a decrease in oocyte ROS levels (p < 0.05). The ROS production systems used in this work did not modified the percentage of oocyte nuclear maturation, but increased the decondensation of sperm head (p < 0.05) and decreased the pronuclear formation (p < 0.05). In turn, the addition of O2 ?(-) and H2 O2 scavenging systems during in vitro maturation did not modify the percentage of oocytes reaching metaphase II nor the oocytes with decondensed sperm head or pronuclei after fertilization. However, both parameters increased in the presence of cysteine (p < 0.05). The exogenous generation of O2 ?(-) and H2 O2 during oocyte in vitro maturation would not affect nuclear maturation or later sperm penetration, but most of the spermatozoa cannot progress to form the pronuclei after fusion with the oocyte. The decrease in endogenous ROS levels by the addition of cysteine would improve pronuclear formation after sperm penetration. PMID:25522082

  10. Telomeric DNA Induces p53-Dependent Reactive Oxygen Species And Protects Against Oxidative Damage

    PubMed Central

    Lee-Bellantoni, Margaret S.; Yaar, Mina; Eller, Mark S.; Rünger, Thomas M.; Gao, Ying; Gilchrest, Barbara A.

    2009-01-01

    Background Reactive oxygen species (ROS) are generated by cellular metabolism as well as by exogenous agents. While ROS can promote cellular senescence, they can also act as signaling molecules for processes that do not lead to senescence. Telomere homolog oligonucleotides (T-oligos) induce adaptive DNA damage responses including increased DNA repair capacity and these effects are mediated, at least in part, through p53. Objective Studies were undertaken to determine whether such p53-mediated protective responses include enhanced antioxidant defenses. Methods Normal human fibroblasts as well as R2F fibroblasts expressing wild type or dominant negative p53 were treated with an 11-base T-oligo, a complementary control oligo or diluents alone and then examined by western blot analysis, immunofluorescence microscopy and various biochemical assays. Results We now report that T-oligo increases the level of the antioxidant enzymes superoxide dismutase 1 and 2 and protects cells from oxidative damage; and that telomere-based ?H2AX (DNA damage) foci that form in response to T-oligos contain phosphorylated ATM and Chk2, proteins known to activate p53 and to mediate cell cycle arrest in response to oxidative stress. Further, T-oligo increases cellular ROS levels via a p53-dependent pathway, and these increases are abrogated by the NAD(P)H oxidase inhibitor diphenyliodonium chloride. Conclusion These results suggest the existence of innate telomere-based protective responses that act to reduce oxidative damage to cells. T-oligo treatment induces the same responses and offers a new model for studying intracellular ROS signaling and the relationships between DNA damage, ROS, oxidative stress, and cellular defense mechanisms. PMID:19906512

  11. The phytoalexin camalexin mediates cytotoxicity towards aggressive prostate cancer cells via reactive oxygen species

    PubMed Central

    Smith, Basil A.; Neal, Corey L.; Chetram, Mahandranauth; Vo, BaoHan; Mezencev, Roman; Hinton, Cimona

    2013-01-01

    Camalexin is a phytoalexin that accumulates in various cruciferous plants upon exposure to environmental stress and plant pathogens. Besides moderate antibacterial and antifungal activity, camalexin was reported to also exhibit antiproliferative and cancer chemopreventive effects in breast cancer and leukemia. We studied the cytotoxic effects of camalexin treatment on prostate cancer cell lines and whether this was mediated by reactive oxygen species (ROS) generation. As models, we utilized LNCaP and its aggressive subline, C4-2, as well as ARCaP cells stably transfected with empty vector (Neo) control or constitutively active Snail cDNA that represents an epithelial to mesenchymal transition (EMT) model and displays increased cell migration and tumorigenicity. We confirmed previous studies showing that C4-2 and ARCaP-Snail cells express more ROS than LNCaP and ARCaP-Neo, respectively. Camalexin increased ROS, decreased cell proliferation, and increased apoptosis more significantly in C4-2 and ARCaP-Snail cells as compared to LNCaP and ARCaP-Neo cells, respectively, while normal prostate epithelial cells (PrEC) were unaffected. Increased caspase-3/7 activity and increased cleaved PARP protein shown by Western blot analysis was suggestive of increased apoptosis. The ROS scavenger N-acetyl cysteine (NAC) antagonized the effects of camalexin, whereas the addition of exogenous hydrogen peroxide potentiated the effects of camalexin, showing that camalexin is mediating its effects through ROS. In conclusion, camalexin is more potent in aggressive prostate cancer cells that express high ROS levels, and this phytoalexin has a strong potential as a novel therapeutic agent for the treatment of especially metastatic prostate cancer. PMID:23179315

  12. Sitagliptin attenuates sympathetic innervation via modulating reactive oxygen species and interstitial adenosine in infarcted rat hearts

    PubMed Central

    Lee, Tsung-Ming; Chen, Wei-Ting; Yang, Chen-Chia; Lin, Shinn-Zong; Chang, Nen-Chung

    2015-01-01

    We investigated whether sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, attenuates arrhythmias through inhibiting nerve growth factor (NGF) expression in post-infarcted normoglycemic rats, focusing on adenosine and reactive oxygen species production. DPP-4 bound adenosine deaminase has been shown to catalyse extracellular adenosine to inosine. DPP-4 inhibitors increased adenosine levels by inhibiting the complex formation. Normoglycemic male Wistar rats were subjected to coronary ligation and then randomized to either saline or sitagliptin in in vivo and ex vivo studies. Post-infarction was associated with increased oxidative stress, as measured by myocardial superoxide, nitrotyrosine and dihydroethidium fluorescent staining. Measurement of myocardial norepinephrine levels revealed a significant elevation in vehicle-treated infarcted rats compared with sham. Compared with vehicle, infarcted rats treated with sitagliptin significantly increased interstitial adenosine levels and attenuated oxidative stress. Sympathetic hyperinnervation was blunted after administering sitagliptin, as assessed by immunofluorescent analysis and western blotting and real-time quantitative RT-PCR of NGF. Arrhythmic scores in the sitagliptin-treated infarcted rats were significantly lower than those in vehicle. Ex vivo studies showed a similar effect of erythro-9-(2-hydroxy-3-nonyl) adenine (an adenosine deaminase inhibitor) to sitagliptin on attenuated levels of superoxide and NGF. Furthermore, the beneficial effects of sitagliptin on superoxide anion production and NGF levels can be reversed by 8-cyclopentyl-1,3-dipropulxanthine (adenosine A1 receptor antagonist) and exogenous hypoxanthine. Sitagliptin protects ventricular arrhythmias by attenuating sympathetic innervation via adenosine A1 receptor and xanthine oxidase-dependent pathways, which converge through the attenuated formation of superoxide in the non-diabetic infarcted rats. PMID:25388908

  13. 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-?B], activator protein-1, hypoxia-inducible factor-1?, 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, ?-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-?, inflammation, and NF-?B, 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

  14. Bcl2 Inhibition of Neural Death: Decreased Generation of Reactive Oxygen Species

    Microsoft Academic Search

    Darci J. Kane; Theodore A. Sarafian; Rein Anton; Hejin Hahn; Edith Butler Gralla; Joan Selverstone Valentine; Tonis Ord; Dale E. Bredesen

    1993-01-01

    The proto-oncogene bcl-2 inhibits apoptotic and necrotic neural cell death. Expression of Bcl-2 in the GT1-7 neural cell line prevented death as a result of glutathione depletion. Intracellular reactive oxygen species and lipid peroxides rose rapidly in control cells depleted of glutathione, whereas cells expressing Bcl-2 displayed a blunted increase and complete survival. Modulation of the increase in reactive oxygen

  15. Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis

    PubMed Central

    Khan, Saeed R.

    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 at the basal side. In addition endothelial cells lining the blood vessels may also become osteogenic producing membrane vesicles. Calcification of the vesicles gives rise to RPs. The growth of the RP’s is sustained by mineralization of collagen laid down as result of inflammation and fibrosis. PMID:25383321

  16. 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 the basal side. In addition endothelial cells lining the blood vessels may also become osteogenic producing membrane vesicles. Calcification of the vesicles gives rise to RPs. The growth of the RP's is sustained by mineralization of collagen laid down as result of inflammation and fibrosis. PMID:25383321

  17. Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens

    Microsoft Academic Search

    Carl Nathan; Michael U. Shiloh

    2000-01-01

    This review summarizes recent evidence from knock-out mice on the role of reactive oxygen intermediates and reactive nitrogen intermediates (RNI) in mammalian immunity. Reflections on redundancy in immunity help explain an apparent paradox: the phagocyte oxidase and inducible nitric oxide synthase are each nonredundant, and yet also mutually redundant, in host defense. In combination, the contribution of these two enzymes

  18. BUTYRIC ACID INCREASES INVASIVENESS OF HL-60 LEUKEMIA CELLS: ROLE OF REACTIVE OXYGEN SPECIES

    E-print Network

    Paris-Sud XI, Université de

    1 BUTYRIC ACID INCREASES INVASIVENESS OF HL-60 LEUKEMIA CELLS: ROLE OF REACTIVE OXYGEN SPECIES differentiation of human leukemia, including HL-60 cells. By using a fluorescent probe, we showed that reactive and increased invasiveness. Keywords: butyrate, differentiation, invasion, leukemia, matrix metalloproteinase

  19. Modulation of neuronal stem cell differentiation by hypoxia and reactive oxygen species

    Microsoft Academic Search

    Helena L. A. Vieira; Paula M. Alves; Alessandro Vercelli

    2011-01-01

    Low oxygen concentrations (hypoxia) occur in several physiological and pathological cellular situations such as embryogenesis and stem cell modulation (in terms of differentiation\\/proliferation), or ischemic stroke and cancer. On the other side of the coin, the generation of reactive oxygen species (ROS) is tightly controlled by the cell. ROS control redox sensitive signaling pathways and thus regulate cell physiology, such

  20. Association of reactive oxygen species levels and radioresistance in cancer stem cells

    Microsoft Academic Search

    Maximilian Diehn; Robert W. Cho; Neethan A. Lobo; Tomer Kalisky; Mary Jo Dorie; Angela N. Kulp; Dalong Qian; Jessica S. Lam; Laurie E. Ailles; Manzhi Wong; Benzion Joshua; Michael J. Kaplan; Irene Wapnir; Frederick M. Dirbas; George Somlo; Carlos Garberoglio; Benjamin Paz; Jeannie Shen; Sean K. Lau; Stephen R. Quake; J. Martin Brown; Irving L. Weissman; Michael F. Clarke

    2009-01-01

    The metabolism of oxygen, although central to life, produces reactive oxygen species (ROS) that have been implicated in processes as diverse as cancer, cardiovascular disease and ageing. It has recently been shown that central nervous system stem cells and haematopoietic stem cells and early progenitors contain lower levels of ROS than their more mature progeny, and that these differences are

  1. Oxygen Pathway Modeling Estimates High Reactive Oxygen Species Production above the Highest Permanent Human Habitation

    PubMed Central

    Cano, Isaac; Selivanov, Vitaly; Gomez-Cabrero, David; Tegnér, Jesper; Roca, Josep; Wagner, Peter D.; Cascante, Marta

    2014-01-01

    The production of reactive oxygen species (ROS) from the inner mitochondrial membrane is one of many fundamental processes governing the balance between health and disease. It is well known that ROS are necessary signaling molecules in gene expression, yet when expressed at high levels, ROS may cause oxidative stress and cell damage. Both hypoxia and hyperoxia may alter ROS production by changing mitochondrial Po2 (). Because depends on the balance between O2 transport and utilization, we formulated an integrative mathematical model of O2 transport and utilization in skeletal muscle to predict conditions to cause abnormally high ROS generation. Simulations using data from healthy subjects during maximal exercise at sea level reveal little mitochondrial ROS production. However, altitude triggers high mitochondrial ROS production in muscle regions with high metabolic capacity but limited O2 delivery. This altitude roughly coincides with the highest location of permanent human habitation. Above 25,000 ft., more than 90% of exercising muscle is predicted to produce abnormally high levels of ROS, corresponding to the “death zone” in mountaineering. PMID:25375931

  2. Generation and reactivity toward oxygen of carbon-centered radicals containing indane, indene, and fluorenyl moieties.

    PubMed

    Font-Sanchis, Enrique; Aliaga, Carolina; Bejan, Elena V; Cornejo, Raecca; Scaiano, J C

    2003-04-18

    Resonance-stabilized radicals containing indane, indene, and fluorenyl moieties exhibit attenuated reactivity toward oxygen. Rate constants of approximately 10(5) M(-1) s(-1) were observed for the most stabilized radicals. The dependence of k(OX) (rate constant for radical trapping by oxygen) on the corresponding bond dissociation energies revealed that stereoelectronic effects are more important than steric effects in determining the low radical reactivity with oxygen. Scavenging by the nitroxide TEMPO was also examined, and revealed that in this case steric effects are more important than in the case of oxygen. The rate constants for the hydrogen abstraction by cumyloxyl and tert-butoxyl radicals generated thermally and photochemically have been determined in benzene, and were in the range of ca. (1-13) x 10(6) M(-1) s(-1), showing that benzylic stabilization has a modest effect on substrate reactivity as a hydrogen donor toward alkoxyl radicals. PMID:12688791

  3. Reactive oxygen species and Udx1 during early sea urchin development Julian L. Wong, Gary M. Wessel*

    E-print Network

    Wessel, Gary M.

    Reactive oxygen species and Udx1 during early sea urchin development Julian L. Wong, Gary M. Wessel Abstract Sea urchin fertilization is marked by a massive conversion of molecular oxygen to hydrogen of these defective embryos. We also report an unequal distribution of reactive oxygen species between sister

  4. Dense ceramic membranes for reactive separation of oxygen

    SciTech Connect

    Balachandran, U.; Dusek, J.T.; Maiya, P.S. [Argonne National Lab., IL (United States)] [and others

    1995-12-01

    Oxides in the system Sr-Fe-Co exhibit mixed (electronic/ionic) conductivity. These mixed-conducting oxides can operate without external circuitry to separate oxygen from oxygen-containing gases. We have used these oxides for partial oxygenation of methane, with air as source of oxygen. The ceramics are fabricated in the form of dense tubes. Methane and air are passed over the shell and core side of the membrane tube, respectively. Membrane performance is evaluated in a conversion reactor operated at {approx}850{degrees}C to directly convert methane into synthesis gas (CO + H{sub 2}). Methane conversion efficiencies of >98% have been observed. Some of the tubes have been operated for more than 1000 h. In this talk, we describe processing and fabrication of the membrane tubes, their characterization, and performance in the conversion reactor.

  5. Stabilization of nitrosyls by surface oxygen: Structure and reactivity of NO on oxygen-modified Mo(110)

    SciTech Connect

    Queeney, K.T.; Friend, C.M. [Harvard Univ., Cambridge, MA (United States). Dept. of Chemistry] [Harvard Univ., Cambridge, MA (United States). Dept. of Chemistry

    1998-11-12

    The effects of preadsorbed atomic oxygen on nitric oxide (NO) structure and reactivity on Mo(110) are studied via temperature programmed reaction, high-resolution electron energy loss spectroscopy, and infrared reflectance absorbance spectroscopy. NO reaction on two different oxygen overlayers--a saturated low-temperature surface overlayer and a thin-film oxide--is studied in detail. The dissociation of NO to atomic nitrogen and oxygen, the predominant pathway for NO reaction on clean Mo(110), is inhibited by surface oxygen, even though NO dissociation displaces surface oxygen from high- to low-coordination sites. The same low-temperature pathways observed for N-N bond formation on clean Mo(110)--N{sub 2}O formation from dinitrosyl coupling and N{sub 2} formation from reaction of molecular NO with atomic nitrogen--are observed on the oxygen-modified surfaces, but in lesser relative and absolute amounts than on clean Mo(110). As oxygen coverage is increased, NO desorption becomes the dominant reaction pathway and occurs at increasingly higher temperatures. Vibrational spectroscopy is used to correlate desorption features with distinct NO species, which vary qualitatively with oxygen coverage. The authors find that, in contrast to earlier studies on other oxygen-modified transition metal surfaces, NO desorption temperature cannot be correlated with the strength of the metal-NO interaction as judged by the internal N-O stretch frequency.

  6. Asymmetric dimethylarginine and reactive oxygen species: unwelcome twin visitors to the cardiovascular and kidney disease tables.

    PubMed

    Wilcox, Christopher S

    2012-02-01

    Plasma levels of asymmetric dimethylarginine or markers of reactive oxygen species are increased in subjects with risk factors for cardiovascular disease or chronic kidney disease. We tested the hypothesis that reactive oxygen species generate cellular asymmetric dimethylarginine that together cause endothelial dysfunction that underlies the risk of subsequent disease. Rat preglomerular vascular smooth muscle cells transfected with p22(phox) had increased NADPH oxidase activity, enhanced activity and expression of protein arginine methyltransferase, and reduced activity and protein expression of dimethylarginine dimethylaminotransferase and of cationic amino acid transferase 1 resulting in increased cellular levels of asymmetric dimethylarginine. Rats infused with angiotensin II had oxidative stress. The endothelial function of their mesenteric arterioles was changed from vasodilatation to vasoconstriction, accompanied by increased vascular asymmetric dimethylarginine. All of these changes were prevented by Tempol. In vivo silencing of dimethylarginine dimethylaminotransferase 1 increased plasma levels of asymmetric dimethylarginine, whereas silencing of dimethylarginine dimethylaminotransferase 2 impaired endothelial function. We suggest that initiation factors, such as angiotensin II, expressed in blood vessels or tissues of subjects with cardiovascular and kidney disease risk factors generate reactive oxygen species from NADPH oxidase that enhances cellular asymmetric dimethylarginine in an amplification loop. This leads to adverse changes in vascular and organ functions, as a consequence of reduced tissue levels of NO and increased reactive oxygen species. Thus, we conclude that reactive oxygen species and asymmetric dimethylarginine form a tightly coupled amplification system that translates cardiovascular/kidney risk into overt disease. PMID:22215715

  7. Frequency effects on the production of reactive oxygen species in atmospheric radio frequency helium-oxygen discharges

    SciTech Connect

    Zhang, Yuantao T.; He Jin [Shandong Provincial Key Lab of UHV Technology and Gas Discharge Physics, School of Electrical Engineering, Shandong University, Jinan, Shandong Province 250061 (China)

    2013-01-15

    Several experimental and computational studies have shown that increasing frequency can effectively enhance the discharge stability in atmospheric radio-frequency (rf) discharges, but the frequency effects on the reactivity of rf discharges, represented by the densities of reactive oxygen species (ROS), are still far from fully understood. In this paper, a one-dimensional fluid model with 17 species and 65 reactions taken into account is used to explore the influences of the driving frequency on the production and destruction of ROS in atmospheric rf helium-oxygen discharges. From the computational results, with an increase in the frequency the densities of ROS decrease always at a constant power density, however, in the relatively higher frequency discharges the densities of ROS can be effectively improved by increasing the input power density with an expanded oxygen admixture range, while the discharges operate in the {alpha} mode, and the numerical data also show the optimal oxygen admixture for ground state atomic oxygen, at which the peak atomic oxygen density can be obtained, increases with the driving frequency.

  8. [Effects of water and light interaction on reactive oxygen metabolism in ginger leaves].

    PubMed

    Zhang, Yong-Zheng; Li, Hai-Dong; Li, Xiu; Xiao, Jing; Xu, Kun

    2013-12-01

    To explore the relationship between water supply in roots, light intensity on leaves and reactive oxygen metabolism, the effects of various treatments including natural light plus normal watering (T1), 50% shading plus normal watering (T2), natural light plus PEG-6000 simulated drought (T3), 50% shading plus simulated drought (T4) on reactive oxygen level and antioxidant enzyme activity in ginger leaves were studied. The results showed that, 6 days after treatment, the O2* production rate and H2O2 and MDA contents remarkably increased in ginger leaves at midday. Treatment T3 showed the greatest increment, followed by T4, T1 and T2 in order. In addition, the activities of SOD and POD in all treatments and CAT in T3 and T4 noticeably decreased, while CAT in T1 and T2 exhibited a high activity at midday. Throughout the whole treatment, reactive oxygen level and antioxidant enzyme activities of ginger leaves in T1 and T2 remained stable, with a higher activity in T1 than in T2. However, the reactive oxygen level kept increasing in leaves exposed to treatments T3 and T4. Meanwhile, the activities of antioxidant enzymes increased firstly and then decreased. Taken together, this study demonstrated that drought stress, especially drought plus light stress, led to an increased accumulation of reactive oxygen in ginger leaves, while shading was conducive to maintaining high activity of protective enzymes, and therefore to reducing reactive oxygen level and alleviate drought-induced injury. PMID:24697065

  9. NecroX as a novel class of mitochondrial reactive oxygen species and ONOO ? scavenger

    Microsoft Academic Search

    Hyoung Jin Kim; Sun Young Koo; Bong-Hyun Ahn; Doo Hoe Park; Dong Ook Seo; Jong Heon Won; Hyeon Joo Yim; Hyo-Shin Kwak; Heui Sul Park; Chul Woong Chung; Young Leem Oh; Soon Ha Kim

    2010-01-01

    Mitochondrial reactive oxygen species and reactive nitrogen species are proven to be major sources of oxidative stress in\\u000a the cell; they play a prominent role in a wide range of human disorders resulting from nonapoptotic cell death. The aim of\\u000a this study is to examine the cytoprotective effect of the NecroX series against harmful stresses, including pro-oxidant (tertiarybutylhydroperoxide),\\u000a doxorubicin, CCl4,

  10. The Role of Mitochondrial Reactive Oxygen Species Formation for Age-Induced Vascular Dysfunction

    Microsoft Academic Search

    Andreas Daiber; Joachim Kienhoefer; Rebecca Zee; Philip Wenzel; Volker Ullrich; Bernd van der Loo; Markus Bachschmid

    \\u000a Aging is an important risk factor for the development of cardiovascular diseases, which can be accelerated by atherosclerosis,\\u000a diabetes, hypercholesterolemia, or obesity. Vascular aging is mainly characterized by endothelial dysfunction, an alteration\\u000a of endothelium-dependent signaling processes, and vascular remodeling. The underlying mechanisms include increased production\\u000a of reactive oxygen species (ROS), inactivation of nitric oxide (•NO), and subsequent formation of reactive

  11. Reactive Oxygen Species-Dependent Nitric Oxide Production Contributes to Hydrogen-Promoted Stomatal Closure in Arabidopsis.

    PubMed

    Xie, Yanjie; Mao, Yu; Zhang, Wei; Lai, Diwen; Wang, Qingya; Shen, Wenbiao

    2014-04-14

    The signaling role of hydrogen gas (H2) has attracted increasing attention from animals to plants. However, the physiological significance and molecular mechanism of H2 in drought tolerance are still largely unexplored. In this article, we report that abscisic acid (ABA) induced stomatal closure in Arabidopsis (Arabidopsis thaliana) by triggering intracellular signaling events involving H2, reactive oxygen species (ROS), nitric oxide (NO), and the guard cell outward-rectifying K(+) channel (GORK). ABA elicited a rapid and sustained H2 release and production in Arabidopsis. Exogenous hydrogen-rich water (HRW) effectively led to an increase of intracellular H2 production, a reduction in the stomatal aperture, and enhanced drought tolerance. Subsequent results revealed that HRW stimulated significant inductions of NO and ROS synthesis associated with stomatal closure in the wild type, which were individually abolished in the nitric reductase mutant nitrate reductase1/2 (nia1/2) or the NADPH oxidase-deficient mutant rbohF (for respiratory burst oxidase homolog). Furthermore, we demonstrate that the HRW-promoted NO generation is dependent on ROS production. The rbohF mutant had impaired NO synthesis and stomatal closure in response to HRW, while these changes were rescued by exogenous application of NO. In addition, both HRW and hydrogen peroxide failed to induce NO production or stomatal closure in the nia1/2 mutant, while HRW-promoted ROS accumulation was not impaired. In the GORK-null mutant, stomatal closure induced by ABA, HRW, NO, or hydrogen peroxide was partially suppressed. Together, these results define a main branch of H2-regulated stomatal movement involved in the ABA signaling cascade in which RbohF-dependent ROS and nitric reductase-associated NO production, and subsequent GORK activation, were causally involved. PMID:24733882

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

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  14. Oxygen-sulfur exchange and the gas-phase reactivity of cobalt sulfide cluster anions with molecular oxygen.

    PubMed

    Jia, Mei-Ye; Luo, Zhixun; He, Sheng-Gui; Ge, Mao-Fa

    2014-09-18

    We present here a study of gas-phase reactivity of cobalt sulfide cluster anions Co(m)S(n)(-) with molecular oxygen. Nascent Co(m)S(n)(-) clusters were prepared via a laser ablation source and reacted with oxygen in a fast flow reactor under thermal collision conditions. We chose (18)O2 in place of (16)O2 to avoid mass degeneration with sulfur, and a time-of-flight (TOF) mass spectrometer was used to detect the cluster distributions in the absence and presence of the reactant. It was found that oxygen-sulfur exchange occurs in the reactions for those with specific compositions (CoS)(n)(-) and (CoS)(n)S(-) (n = 2-5) according to a consistent pathway, "Co(m)S(n)(-) + (18)O2 ? Co(m)S(n-1)(18)O(-) + S(18)O". Typically, for "Co2S2(-) + (18)O2" we have calculated the reaction coordinates by employing the density functional theory (DFT), where both the oxygen-sulfur exchange and SO molecule release are thermodynamically and kinetically favorable. It is noteworthy that the reaction with molecular oxygen (triplet ground state) needs to overcome a spin excitation as well as a large O-O activation energy. This study sheds light on the activation of molecular oxygen by cobalt sulfides on one hand and also provides insight into the regeneration mechanism of cobalt oxides from the counterpart sulfides in the presence of oxygen gas on the other hand. PMID:24588651

  15. Oxygen therapy does not increase production and damage induced by reactive oxygen species in focal cerebral ischemia.

    PubMed

    Sun, Li; Wolferts, Guido; Veltkamp, Roland

    2014-08-01

    Oxygen therapy with hyperbaric oxygen (HBO) or normobaric hyperoxia (NBO) improves outcome in experimental cerebral ischemia. However, an increased formation of reactive oxygen species (ROS) may be an undesirable side effect of oxygen therapy. We investigated the effect of both oxygen therapies on ROS production and adverse effects in murine focal ischemia. 25 min after 90 min filament-induced middle cerebral artery occlusion (MCAO), mice breathed either air, 100% O2 (NBO), or 100% O2 at 3 ata (HBO) for 60 min. ROS were depicted on tissue sections after preischemic injection of hydroethidine, a marker of in vivo superoxide production. Moreover, infarct sizes were quantified in experiments using peroxybutinitrite (PBN) in mice treated with HBO. Effects of oxygen therapy were also tested in superoxide 2 knock-out mice. Both NBO and HBO significantly reduced superoxide radicals compared to air. Application of PBN had no additional protective effect when combined with HBO. Infarct volumes did not differ among SOD2 knock-out mice receiving air (34.0 ± 19.6mm(3)), NBO (35.4 ± 14.3mm(3)) or HBO (33.4 ± 12.2mm(3)). In conclusion, brief episodes of oxygen therapy do not appear to promote damage inflicted by ROS in experimental stroke. PMID:24909618

  16. Impact reactivity of materials at very high oxygen pressure

    NASA Technical Reports Server (NTRS)

    Connor, H. W.; Minchey, J. G.; Crowder, R.; Davidson, R.

    1983-01-01

    The requirements for impact testing of materials in an oxygen atmosphere at pressures from 82.7 MPa (12,000 psi) to 172 MPa (25,000 psi) were evaluated. The impact tester system was evaluated for potential pressure increases from 69 MPa (10,000 psi) to 82.7 MPa (12,000 psi). The low pressure oxygen and nitrogen systems, the impact tower, the impact test cell, and the high pressure oxygen system were evaluated individually. Although the structural integrity of the impact test cell and the compressor were sufficient for operation at 82.7 MPa (12,000 psi), studies revealed possible material incompatibility at that pressure and above. It was recommended that if a component should be replaced for 82.7 MPa (12,000 psi) operation the replacement should meet the final objectives of 172 MPa (25,000 psi). Recommended changes in the system include; use of Monel 400 for pressures above 82.7 MPa (12,000 psi), use of bellows to replace the seal in the impact tester, use of a sapphire window attached to a fiber optic for event sensing, and use of a three diaphragm compressor.

  17. Nitric oxide affects the production of reactive oxygen species in hepatoma cells: implications for the process of oxygen sensing

    Microsoft Academic Search

    Just Genius; Joachim Fandrey

    2000-01-01

    Treatment of human hepatoma cells (HepG2) with NO-donors for 24 h inhibited hypoxia-induced erythropoietin (EPO) gene activation. NO was found to increase the production of reactive oxygen species (ROS), the putative signaling molecules between a cellular O2-sensor and hypoxia inducible factor 1 (HIF-1). HIF-1 is the prime regulator of O2-dependent genes such as EPO. NO-treatment for more than 20 h

  18. Murine Glia Cells in Culture Can be Stimulated to Generate Reactive Oxygen

    Microsoft Academic Search

    Bruno Sonderer; Peter Wild; Robert Wyler; Adriano Fontana; Ernst Peterhans; Martin Schwyzer

    1987-01-01

    Induction of luminol-enhanced chemiluminescence (CL) Indicative of reactive oxygen formation was studied in glia cell cultures from newborn mice. A burst of CL could be induced by phorbol myrlstate acetate, zymosan, and antibody-coated bovine red blood cells, whereas Sendai virus and several other agents known to induce CL In myeloid cells were ineffective. Sodium azide failed to inhibit CL, Indicating

  19. Roles of Reactive Oxygen Species: Signaling and Regulation of Cellular Functions

    Microsoft Academic Search

    I. A. Gamaley; I. V. Klyubin

    1999-01-01

    Reactive oxygen species (ROS) are the side products (H2O2•? and O2•) of general metabolism and are also produced specifically by the NADPH oxidase system in most cell types. Cells have a very efficient antioxidant defense to counteract the toxic effect of ROS. The physiological significance of ROS is that ROS at low concentrations are able to mediate cellular functions through

  20. Original Article The increase of reactive oxygen species and their inhibition in an isolated

    E-print Network

    Shi, Riyi

    of spinal cord traumatic injury. Spinal Cord (2002) 40, 656 ± 665. doi:10.1038/sj.sc.3101363 Keywords: spinal cord injury; reactive oxygen species (ROS); in vitro; ascorbic acid; hypothermia; ¯ow cytometry Introduction Traumatic spinal cord injury (SCI) is the consequence of a primary physical injury and a secondary

  1. Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production

    Microsoft Academic Search

    Javier Martinez; Juan J Moreno

    2000-01-01

    Resveratrol is a natural molecule with antioxidant action. Moreover, resveratrol is also considered to be a molecule with anti-inflammatory action, an effect attributed to suppression of prostaglandin (PG) biosynthesis. The aim of the present study was to investigate the effects of resveratrol, a polyphenol present in most red wines, on reactive oxygen species formation as well as on arachidonic acid

  2. Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses

    Microsoft Academic Search

    Stephen S Leonard; Chang Xia; Bin-Hua Jiang; Beth Stinefelt; Hillar Klandorf; Gabriel K Harris; Xianglin Shi

    2003-01-01

    Scavenging or quenching of the reactive oxygen species (ROS) involved in oxidative stress has been the subject of many recent studies. Resveratrol, found in various natural food products, has been linked to decreased coronary artery disease and preventing cancer development. The present study measured the effect of resveratrol on several different systems involving the hydroxyl, superoxide, metal\\/enzymatic-induced, and cellular generated

  3. Increased levels of thiols protect antimony unresponsive Leishmania donovani field isolates against reactive oxygen

    E-print Network

    Schnaufer, Achim

    Increased levels of thiols protect antimony unresponsive Leishmania donovani field isolates against reactive oxygen species generated by trivalent antimony G. MANDAL1 , S. WYLLIE2 , N. SINGH3 , S. SUNDAR4 (Received 28 February 2007; revised 8 May 2007; accepted 10 May 2007) SUMMARY The current trend of antimony

  4. 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...

  5. Redundant Catalases Detoxify Phagocyte Reactive Oxygen and Facilitate Histoplasma capsulatum Pathogenesis

    PubMed Central

    Holbrook, Eric D.; Smolnycki, Katherine A.; Youseff, Brian H.

    2013-01-01

    Histoplasma capsulatum is a respiratory pathogen that infects phagocytic cells. The mechanisms allowing Histoplasma to overcome toxic reactive oxygen molecules produced by the innate immune system are an integral part of Histoplasma's ability to survive during infection. To probe the contribution of Histoplasma catalases in oxidative stress defense, we created and analyzed the virulence defects of mutants lacking CatB and CatP, which are responsible for extracellular and intracellular catalase activities, respectively. Both CatB and CatP protected Histoplasma from peroxide challenge in vitro and from antimicrobial reactive oxygen produced by human neutrophils and activated macrophages. Optimal protection required both catalases, as the survival of a double mutant lacking both CatB and CatP was lower than that of single-catalase-deficient cells. Although CatB contributed to reactive oxygen species defenses in vitro, CatB was dispensable for lung infection and extrapulmonary dissemination in vivo. Loss of CatB from a strain also lacking superoxide dismutase (Sod3) did not further reduce the survival of Histoplasma yeasts. Nevertheless, some catalase function was required for pathogenesis since simultaneous loss of both CatB and CatP attenuated Histoplasma virulence in vivo. These results demonstrate that Histoplasma's dual catalases comprise a system that enables Histoplasma to efficiently overcome the reactive oxygen produced by the innate immune system. PMID:23589579

  6. The Significance of Testicular Reactive Oxygen Species on Testicular Histology in Infertile Patients

    Microsoft Academic Search

    Ö. Yaman; T. Soygür; E. Yilmaz; S. Elgün; A. Keskine?e; O. Gö?ü?

    1999-01-01

    This study was designed to investigate the relationship between the effects of testicular reactive oxygen species (ROS) levels and testicular histology on infertile patients with the aid of xanthine oxidase system and testicular tissue malondialdehyde levels. Forty patients with idiopathic infertility constituted our study group. Bilateral testicular biopsies were performed and spermatogenesis was assessed histopathologically. Patients were divided into 4

  7. An inducible release of reactive oxygen radicals in four species of gorgonian corals

    Microsoft Academic Search

    Laura D. Mydlarz; Robert S. Jacobs

    2006-01-01

    The capability for physical injury or heat stress to elicit the production of reactive oxygen species was examined in four species of gorgonian corals. The sea plumes Pseudopterogorgia elisabethae, Pseudopterogorgia americana, the sea rod Eunicea fusca and the azooxanthellate red branching gorgonian Lophogorgia chilensis were physically injured using sonic sound cavitations and heat shocked by incubation in 33°C sea water.

  8. The Possible Role of Reactive Oxygen Species Generated by Neutrophils in Mediating Acne Inflammation

    Microsoft Academic Search

    H. Akamatsu; T. Horio

    1998-01-01

    The purpose of this study was to investigate the possible role of reactive oxygen species (ROS) generated by neutrophils in mediating acne inflammation. Antibiotics used for the treatment of acne significantly inhibited ROS generated by neutrophils, when compared to other antibiotics. Metronidazole, which is effective in the treatment of acne, markedly inhibited ROS generated by neutrophils. The drug is known

  9. Reactive Oxygen Intermediates Mediate a Systemic Signal Network in the Establishment of Plant Immunity

    Microsoft Academic Search

    Mar??a E Alvarez; Roger I Pennell; Per-Johan Meijer; Atsushi Ishikawa; Richard A Dixon; Chris Lamb

    1998-01-01

    Recognition of an avirulent pathogen stimulates an oxidative burst generating O2? and H2O2, and these reactive oxygen intermediates (ROIs) cue the induction of defense genes and cell death in the development of a restricted lesion. This localized hypersensitive response (HR) is accompanied by the development of systemic acquired resistance to virulent pathogens. Here we show that inoculation of Arabidopsis leaves

  10. Detection of reactive oxygen species in mainstream cigarette smoke by a fluorescent probe

    Microsoft Academic Search

    Li Liu; Shi-Jie Xu; Song-Zhan Li

    2009-01-01

    A mass of reactive oxygen species(ROS) are produced in the process of smoking. Superfluous ROS can induce the oxidative stress in organism, which will cause irreversible damage to cells. Fluorescent probe is taken as a marker of oxidative stress in biology and has been applied to ROS detection in the field of biology and chemistry for high sensitivity, high simplicity

  11. Elicitor effects on reactive oxygen species in liquid cultures of Penicillium chrysogenum

    Microsoft Academic Search

    R. Radman; C. Bucke; T. Keshavarz

    2004-01-01

    Activity of reactive oxygen species (ROS) was investigated in liquid cultures of Penicillium chrysogenum P2 supplemented with carbohydrates. Oligosaccharides lowered the ROS activity in all samples. The greatest effect occurred when oligosaccharides were added to samples 48 h after inoculation. The ROS decrease in the presence of oligoguluronate, oligomannuronate and mannan oligosaccharides was 18%, 36% and 54%, respectively (ROS levels

  12. Is there a role for reactive oxygen species in arterial medial elastocalcinosis?

    Microsoft Academic Search

    Moulay Zyad Lalaoui; Adil El Midaoui; Jacques de Champlain; Pierre Moreau

    2007-01-01

    Isolated systolic hypertension results from a gradual stiffening of large arteries, to which medial elastocalcinosis (calcification of elastic lamellae) contributes. There is compelling evidence that reactive oxygen species (ROS) are associated with several disease processes affecting the cardiovascular system, including hypertension. The present study was designed to investigate whether the inhibition of ROS production by alpha-lipoic acid can prevent vascular

  13. When antioxidants Reactive oxygen species (ROS) get a bad press, as evidenced by the notable trend

    E-print Network

    Cai, Long

    levels of reactive oxygen species (ROS) have been considered to pro- motecancer1,2 .YetthelevelsofNrf2 oncogenes actively induce transcription of Nrf2, promoting a ROS detoxification program that is required is genetic targeting of the KEAP1­NRF2 pathway in humans. Under normal con- ditions, the repressor protein

  14. Eccentric exercise, isokinetic muscle torque and delayed onset muscle soreness: the role of reactive oxygen species

    Microsoft Academic Search

    Graeme L. Close; Tony Ashton; Tim Cable; Dominic Doran; Don P. M. MacLaren

    2004-01-01

    There is growing evidence that reactive oxygen species (ROS) are involved in the muscular damage and soreness that is observed following strenuous or unaccustomed exercise. This study investigated the relationship between delayed onset muscle soreness (DOMS), muscle function and ROS following downhill running using electron spin resonance (ESR) spectroscopy and plasma malonaldehyde (MDA) concentrations. Eight physically active male subjects participated

  15. Carvacrol has the priming effects of reactive oxygen species (ROS) production in C6 glioma cells

    Microsoft Academic Search

    Tzou Chi Huang; Ya Ting Lin; Kuo Pin Chuang

    2010-01-01

    Carvacrol (5-isopropyl-2-methylphenol) is the major component of Plectranthus amboinicus. Several studies have shown that carvacrol has antibacterial, antifungal and insecticidal effects, but the mechanisms that govern these processes are unclear. Reactive oxygen species (ROS) play a major role in host defence eradication of microorganisms. In this study, we provide evidence that carvacrol has priming effects on ROS production in C6

  16. 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...

  17. A review of the interaction among dietary antioxidants and reactive oxygen species

    Microsoft Academic Search

    Harold E. Seifried; Darrell E. Anderson; Evan I. Fisher; John A. Milner

    2007-01-01

    During normal cellular activities, various processes inside of cells produce reactive oxygen species (ROS). Some of the most common ROS are hydrogen peroxide (H2O2), superoxide ion (O2?), and hydroxide radical (OH?). These compounds, when present in a high enough concentration, can damage cellular proteins and lipids or form DNA adducts that may promote carcinogenic activity. The purpose of antioxidants in

  18. 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...

  19. ROLE OF THE REACTIVE OXYGEN SPECIES PEROXYNITRITE IN TRAUMATIC BRAIN INJURY

    Microsoft Academic Search

    Ying Deng

    2008-01-01

    Reactive oxygen species (ROS) is cytotoxic to the cell and is known to contribute to secondary cell death following primary traumatic brain injury (TBI). We described in our study that PN is the main mediator for both lipid peroxidation and protein nitration, and occurred almost immediately after injury. As a downstream factor to oxidative damage, the peak of Ca2+-dependent, calpainmediated

  20. Quality Control of Reactive Oxygen Species Measurement by Luminol-Dependent Chemiluminescence Assay

    Microsoft Academic Search

    HIROSHI KOBAYASHI; ENRIQUE GIL-GUZMAN; AYMAN M. MAHRAN; RAKESH K. SHARMA; DAVID R. NELSON; ANTHONY J. THOMAS JR; ASHOK AGARWAL

    A total of 28 donor semen samples were used to eval- uate the characteristics of laboratory variability in measuring reactive oxygen species (ROS). The objectives of this study were to assess the interassay (same sample observed on different days by the same observers) variability; interdonor, intraobserver (replications of the same sample on the same day) variability; and interobserver (multiple observers

  1. Chemiluminescent Detection and Imaging of Reactive Oxygen Species in Live Mouse Skin Exposed to UVA

    Microsoft Academic Search

    Hiroyuki Yasui; Hiromu Sakurai

    2000-01-01

    The recent increase of ultraviolet (UV) rays on Earth due to the increasing size of the ozone hole is suggested to be harmful to life and to accelerate premature photoaging of the skin. The detrimental effects of UV radiation on the skin are associated with the generation of reactive oxygen species (ROS) such as superoxide anion radical (•O?2), hydrogen peroxide

  2. Anthralin stimulates keratinocyte-derived proinflammatory cytokines via generation of reactive oxygen species

    Microsoft Academic Search

    R. W. Lange; P. J. Hayden; C. F. Chignell; M. I. Luster

    1998-01-01

    Objective and Design: Topical application of anthralin, used in the treatment of psoriasis, is often accompanied by severe skin inflammation, presumably due to free radical products of the drug. The role of inflammatory cytokines and their induction by anthralin-derived reactive oxygen species were studied in cultures of normal human keratinocytes (NHKs).¶Materials and Methods: Anthralin was added to cultures of NHKs

  3. Involvement of reactive oxygen species in endosperm cap weakening and embryo elongation growth during lettuce seed germination.

    PubMed

    Zhang, Yu; Chen, Bingxian; Xu, Zhenjiang; Shi, Zhaowan; Chen, Shanli; Huang, Xi; Chen, Jianxun; Wang, Xiaofeng

    2014-07-01

    Endosperm cap (CAP) weakening and embryo elongation growth are prerequisites for the completion of lettuce seed germination. Although it has been proposed that the cell wall loosening underlying these processes results from an enzymatic mechanism, it is still unclear which enzymes are involved. Here it is shown that reactive oxygen species (ROS), which are non-enzymatic factors, may be involved in the two processes. In Guasihong lettuce seeds imbibed in water, O2·(-) and H2O2 accumulated and peroxidase activity increased in the CAP, whereas its puncture force decreased. In addition, in the radicle, the increase in embryo growth potential was accompanied by accumulation of O2·(-) and an increase in peroxidase activity. Imbibing seeds in 0.3% sodium dichloroisocyanurate (SDIC) reduced endosperm viability and the levels of O2·(-), H2O2, and peroxidase activity in the CAP, whereas the decrease in its puncture force was inhibited. However, in the embryo, SDIC did not affect the accumulation of O2·(-), peroxidase activity, and the embryo growth potential. As a result, SDIC caused atypical germination, in which the endosperm ruptured at the boundary between the CAP and lateral endosperm. ROS scavengers and ROS generation inhibitors inhibited the CAP weakening and also decreased the embryo growth potential, thus decreasing the percentage of seed germination. Exogenous ROS and ROS generation inducers increased the percentage of CAP rupture to some extent, and the addition of H2O2 to 0.3% SDIC enabled some seeds to undergo typical germination. PMID:24744430

  4. Involvement of reactive oxygen species in endosperm cap weakening and embryo elongation growth during lettuce seed germination

    PubMed Central

    Zhang, Yu; Chen, Bingxian; Xu, Zhenjiang; Shi, Zhaowan; Chen, Shanli; Huang, Xi; Chen, Jianxun; Wang, Xiaofeng

    2014-01-01

    Endosperm cap (CAP) weakening and embryo elongation growth are prerequisites for the completion of lettuce seed germination. Although it has been proposed that the cell wall loosening underlying these processes results from an enzymatic mechanism, it is still unclear which enzymes are involved. Here it is shown that reactive oxygen species (ROS), which are non-enzymatic factors, may be involved in the two processes. In Guasihong lettuce seeds imbibed in water, O2·– and H2O2 accumulated and peroxidase activity increased in the CAP, whereas its puncture force decreased. In addition, in the radicle, the increase in embryo growth potential was accompanied by accumulation of O2·– and an increase in peroxidase activity. Imbibing seeds in 0.3% sodium dichloroisocyanurate (SDIC) reduced endosperm viability and the levels of O2·–, H2O2, and peroxidase activity in the CAP, whereas the decrease in its puncture force was inhibited. However, in the embryo, SDIC did not affect the accumulation of O2·–, peroxidase activity, and the embryo growth potential. As a result, SDIC caused atypical germination, in which the endosperm ruptured at the boundary between the CAP and lateral endosperm. ROS scavengers and ROS generation inhibitors inhibited the CAP weakening and also decreased the embryo growth potential, thus decreasing the percentage of seed germination. Exogenous ROS and ROS generation inducers increased the percentage of CAP rupture to some extent, and the addition of H2O2 to 0.3% SDIC enabled some seeds to undergo typical germination. PMID:24744430

  5. Effects of shear stresses and antioxidant concentrations on the production of reactive oxygen species in lung cancer cells

    PubMed Central

    Lo, Kai-Yin; Zhu, Yun; Tsai, Hsieh-Fu; Sun, Yung-Shin

    2013-01-01

    Reactive oxygen species (ROS) are known to be a key factor in the development of cancer, and many exogenous sources are supposed to be related to the formation of ROS. In this paper, a microfluidic chip was developed for studying the production of ROS in lung cancer cells under different chemical and physical stimuli. This chip has two unique features: (1) five relative concentrations of 0, 1/8, 1/2, 7/8, and 1 are achieved in the culture regions; (2) a shear stress gradient is produced inside each of the five culture areas. Lung cancer cells were seeded inside this biocompatible chip for investigating their response to different concentrations of H2O2, a chemical stimulus known to increase the production of ROS. Then the effect of shear stress, a physical stimulus, on lung cancer cells was examined, showing that the production of ROS was increased in response to a larger shear stress. Finally, two antioxidants, ?-tocopherol and ferulic acid, were used to study their effects on reducing ROS. It was found that high-dose ?-tocopherol was not able to effectively eliminate the ROS produced inside cells. This counter effect was not observed in cells cultured in a traditional chamber slide, where no shear stress was present. This result suggests that the current microfluidic chip provides an in vitro platform best mimicking the physiological condition where cells are under circulating conditions. PMID:24396542

  6. Increased resistin may suppress reactive oxygen species production and inflammasome activation in type 2 diabetic patients with pulmonary tuberculosis infection.

    PubMed

    Chao, Wen-Cheng; Yen, Chia-Liang; Wu, Ying-Hsun; Chen, Shin-Yi; Hsieh, Cheng-Yuan; Chang, Tsung-Chain; Ou, Horng-Yih; Shieh, Chi-Chang

    2015-03-01

    Although it has been known for decades that patients with type 2 diabetes mellitus (DM) are more susceptible to severe tuberculosis (TB) infection, the underlying immunological mechanisms remain unclear. Resistin, a protein produced by immune cells in humans, causes insulin resistance and has been implicated in inhibiting reactive oxygen species (ROS) production in leukocytes. Recent studies suggested that IL-1? production in patients with Mycobacteria tuberculosis infection correlates with inflammasome activation which may be regulated by ROS production in the immune cells. By investigating the level of resistin in different patient groups, we found that serum resistin levels were significantly higher in severe TB and DM-only groups when compared with mild TB cases and healthy controls. Moreover, elevation of serum resistin correlated with impairment of ROS production of neutrophils in patients with both DM and TB. In human macrophages, exogenous resistin inhibits the production of ROS which are important in the mycobacterium-induced inflammasome activation. Moreover, macrophages with defective ROS production had poor IL-1? production and ineffective control of mycobacteria growth. Our results suggest that increased resistin in severe TB and DM patients may suppress the mycobacterium-induced inflammasome activation through inhibiting ROS production by leukocytes. PMID:25528597

  7. An Inherited Heteroplasmic Mutation in Mitochondrial Gene COI in a Patient with Prostate Cancer Alters Reactive Oxygen, Reactive Nitrogen and Proliferation

    PubMed Central

    Arnold, Rebecca S.; Sun, Qian; Sun, Carrie Q.; Richards, Jendai C.; O'Hearn, Sean; Osunkoya, Adeboye O.; Wallace, Douglas C.; Petros, John A.

    2013-01-01

    Mitochondrial DNA (mtDNA) mutations have been found in many cancers but the physiological derangements caused by such mutations have remained elusive. Prostate cancer is associated with both inherited and somatic mutations in the cytochrome c oxidase (COI) gene. We present a prostate cancer patient-derived rare heteroplasmic mutation of this gene, part of mitochondrial respiratory complex IV. Functional studies indicate that this mutation leads to the simultaneous decrease in cytochrome oxidation, increase in reactive oxygen, and increased reactive nitrogen. These data suggest that mitochondrial DNA mutations resulting in increased reactive oxygen and reactive nitrogen generation may be involved in prostate cancer biology. PMID:23509693

  8. Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens

    PubMed Central

    Nathan, Carl; Shiloh, Michael U.

    2000-01-01

    This review summarizes recent evidence from knock-out mice on the role of reactive oxygen intermediates and reactive nitrogen intermediates (RNI) in mammalian immunity. Reflections on redundancy in immunity help explain an apparent paradox: the phagocyte oxidase and inducible nitric oxide synthase are each nonredundant, and yet also mutually redundant, in host defense. In combination, the contribution of these two enzymes appears to be greater than previously appreciated. The remainder of this review focuses on a relatively new field, the basis of microbial resistance to RNI. Experimental tuberculosis provides an important example of an extended, dynamic balance between host and pathogen in which RNI play a major role. In diseases such as tuberculosis, a molecular understanding of host–pathogen interactions requires characterization of the defenses used by microbes against RNI, analogous to our understanding of defenses against reactive oxygen intermediates. Genetic and biochemical approaches have identified candidates for RNI-resistance genes in Mycobacterium tuberculosis and other pathogens. PMID:10922044

  9. Chemistry and biology of reactive oxygen species in signaling or stress responses

    PubMed Central

    dickinson, Bryan C; Chang, Christopher J

    2012-01-01

    Reactive oxygen species (ROS) are a family of molecules that are continuously generated, transformed and consumed in all living organisms as a consequence of aerobic life. The traditional view of these reactive oxygen metabolites is one of oxidative stress and damage that leads to decline of tissue and organ systems in aging and disease. However, emerging data show that ROS produced in certain situations can also contribute to physiology and increased fitness. This Perspective provides a focused discussion on what factors lead ROS molecules to become signal and/or stress agents, highlighting how increasing knowledge of the underlying chemistry of ROS can lead to advances in understanding their disparate contributions to biology. An important facet of this emerging area at the chemistry-biology interface is the development of new tools to study these small molecules and their reactivity in complex biological systems. PMID:21769097

  10. 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 ?-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

  11. 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.

  12. The Interplay of Light and Oxygen in the Reactive Oxygen Stress Response of Chlamydomonas reinhardtii Dissected by Quantitative Mass Spectrometry*

    PubMed Central

    Barth, Johannes; Bergner, Sonja Verena; Jaeger, Daniel; Niehues, Anna; Schulze, Stefan; Scholz, Martin; Fufezan, Christian

    2014-01-01

    Light and oxygen are factors that are very much entangled in the reactive oxygen species (ROS) stress response network in plants, algae and cyanobacteria. The first obligatory step in understanding the ROS network is to separate these responses. In this study, a LC-MS/MS based quantitative proteomic approach was used to dissect the responses of Chlamydomonas reinhardtii to ROS, light and oxygen employing an interlinked experimental setup. Application of novel bioinformatics tools allow high quality retention time alignment to be performed on all LC-MS/MS runs increasing confidence in protein quantification, overall sequence coverage and coverage of all treatments measured. Finally advanced hierarchical clustering yielded 30 communities of co-regulated proteins permitting separation of ROS related effects from pure light effects (induction and repression). A community termed redoxII was identified that shows additive effects of light and oxygen with light as the first obligatory step. Another community termed 4-down was identified that shows repression as an effect of light but only in the absence of oxygen indicating ROS regulation, for example, possibly via product feedback inhibition because no ROS damage is occurring. In summary the data demonstrate the importance of separating light, O2 and ROS responses to define marker genes for ROS responses. As revealed in this study, an excellent candidate is DHAR with strong ROS dependent induction profiles. PMID:24482124

  13. Reactive oxygen species, lipid peroxidation and enzymatic defence systems in human spermatozoa.

    PubMed

    Griveau, J F; Dumont, E; Renard, P; Callegari, J P; Le Lannou, D

    1995-01-01

    The reactive oxygen species, hydrogen peroxide (H2O2) and superoxide anion (O2o-), were generated with a xanthine-xanthine oxidase system and their effect on human sperm function was studied. The action of reactive oxygen species on selected human spermatozoa resulted in a decreased capacity for ionophore-induced acrosome reaction, a decrease in sperm motility, an increase in the concentration of lipid hydroperoxides and a loss of membrane polyunsaturated fatty acids. H2O2 was the key intermediate of the deleterious effects exerted by the xanthine and xanthine oxidase. Among these parameters, the acrosome reaction appeared most susceptible to the reactive oxygen species generated by the xanthine-xanthine oxidase system, and was decreased without sperm motility being affected. Treatment with H2O2 was shown to inactivate several enzymatic activities involved in the antioxidant defence of spermatozoa: glutathione peroxidase, superoxide dismutase and glucose-6-phosphate dehydrogenase. H2O2 and O2o- were shown to be involved in the lipid alterations triggered by the xanthine-xanthine oxidase system. Singlet oxygen is proposed to intervene in the lipoperoxidation process. The inefficacy of mannitol in protecting spermatozoa suggests that hydroxyl radicals were not produced in the extracellular medium. PMID:7707295

  14. 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

  15. Photo-Irradiation of Proanthocyanidin as a New Disinfection Technique via Reactive Oxygen Species Formation

    PubMed Central

    Nakamura, Keisuke; Shirato, Midori; Ikai, Hiroyo; Kanno, Taro; Sasaki, Keiichi; Kohno, Masahiro; Niwano, Yoshimi

    2013-01-01

    In the present study, the bactericidal effect of photo-irradiated proanthocyanidin was evaluated in relation to reactive oxygen species formation. Staphylococcus aureus suspended in proanthocyanidin aqueous solution was irradiated with light from a laser at 405 nm. The bactericidal effect of photo-irradiated proanthocyanidin depended on the concentration of proanthocyanidin, the laser irradiation time, and the laser output power. When proanthocyanidin was used at the concentration of 1 mg/mL, the laser irradiation of the bacterial suspension could kill the bacteria with a >5-log reduction of viable cell counts. By contrast, bactericidal effect was not observed when proanthocyanidin was not irradiated. In electron spin resonance analysis, reactive oxygen species, such as hydroxyl radicals, superoxide anion radicals, and hydrogen peroxide, were detected in the photo-irradiated proanthocyanidin aqueous solution. The yields of the reactive oxygen species also depended on the concentration of proanthocyanidin, the laser irradiation time, and the laser output power as is the case with the bactericidal assay. Thus, it is indicated that the bactericidal effect of photo-irradiated proanthocyanidin is exerted via the reactive oxygen species formation. The bactericidal effect as well as the yield of the oxygen radicals increased with the concentration of proanthocyanidin up to 4 mg/mL, and then decreased with the concentration. These findings suggest that the antioxidative activity of proanthocyanidin might prevail against the radical generation potency of photo-irradiated proanthocyanidin resulting in the decreased bactericidal effect when the concentration is over 4 mg/mL. The present study suggests that photo-irradiated proanthocyanidin whenever used in an optimal concentration range can be a new disinfection technique. PMID:23527299

  16. Neuroprotection by genipin against reactive oxygen and reactive nitrogen species-mediated injury in organotypic hippocampal slice cultures.

    PubMed

    Hughes, Rebecca H; Silva, Victoria A; Ahmed, Ijaz; Shreiber, David I; Morrison, Barclay

    2014-01-16

    Genipin, the multipotent ingredient in Gardenia jasmenoides fruit extract (GFE), may be an effective candidate for treatment following stroke or traumatic brain injury (TBI). Secondary injury includes damage mediated by reactive oxygen species (ROS) and reactive nitrogen species (RNS), which can alter the biological function of key cellular structures and eventually lead to cell death. In this work, we studied the neuroprotective potential of genipin against damage stemming from ROS and RNS production in organotypic hippocampal slice cultures (OHSC), as well as its potential as a direct free radical scavenger. A 50 µM dose of genipin provided significant protection against tert-butyl hydroperoxide (tBHP), a damaging organic peroxide. This dosage of genipin significantly reduced cell death at 48 h compared to vehicle control (0.1% DMSO) when administered 0, 1, 6, and 24 h after addition of tBHP. Similarly, genipin significantly reduced cell death at 48 h when administered 0, 1, 2, and 6h after addition of rotenone, which generates reactive oxygen species via a more physiologically relevant mechanism. Furthermore, genipin significantly reduced both cell death and nitrite levels at 24 h caused by S-nitroso-N-acetylpenicillamine (SNAP), a direct nitric oxide (NO) donor, and successfully quenched 1,1-Diphenyl-2-picryl-hydrazyl (DPPH), a stable free radical, suggesting that genipin may act as a direct free radical scavenger. Our encouraging findings suggest that genipin should be tested in animal models of CNS injury with a significant component of ROS- and RNS-mediated damage, such as TBI and stroke, to assess its in vivo efficacy. PMID:24275198

  17. Annato extract and ?-carotene modulate the production of reactive oxygen species/nitric oxide in neutrophils from diabetic rats

    PubMed Central

    Rossoni-Júnior, Joamyr Victor; Araújo, Glaucy Rodrigues; Pádua, Bruno da Cruz; Chaves, Míriam Martins; Pedrosa, Maria Lúcia; Silva, Marcelo Eustáquio; Costa, Daniela Caldeira

    2012-01-01

    Annatto has been identified as carotenoids that have antioxidative effects. It is well known that one of the key elements in the development of diabetic complications is oxidative stress. The immune system is especially vulnerable to oxidative damage because many immune cells, such as neutrophils, produce reactive oxygen species and reactive nitrogen species as part of the body’s defense mechanisms to destroy invading pathogens. Reactive oxygen species/reactive nitrogen species are excessively produced by active peripheral neutrophils, and may damage essential cellular components, which in turn can cause vascular complications in diabetes. The present study was undertaken to evaluate the possible protective effects of annatto on the reactive oxygen species and nitric oxide (NO) inhibition in neutrophils from alloxan-induced diabetic rats. Adult female rats were divided into six groups based on receiving either a standard diet with or without supplementation of annatto extract or beta carotene. All animals were sacrificed 30 days after treatment and the neutrophils were isolated using two gradients of different densities. The reactive oxygen species and NO were quantified by a chemiluminescence and spectrophotometric assays, respectively. Our results show that neutrophils from diabetic animals produce significantly more reactive oxygen species and NO than their respective controls and that supplementation with beta carotene and annatto is able to modulate the production of these species. Annatto extract may have therapeutic potential for modulation of the balance reactive oxygen species/NO induced by diabetes. PMID:22573917

  18. Annato extract and ?-carotene modulate the production of reactive oxygen species/nitric oxide in neutrophils from diabetic rats.

    PubMed

    Rossoni-Júnior, Joamyr Victor; Araújo, Glaucy Rodrigues; Pádua, Bruno da Cruz; Chaves, Míriam Martins; Pedrosa, Maria Lúcia; Silva, Marcelo Eustáquio; Costa, Daniela Caldeira

    2012-05-01

    Annatto has been identified as carotenoids that have antioxidative effects. It is well known that one of the key elements in the development of diabetic complications is oxidative stress. The immune system is especially vulnerable to oxidative damage because many immune cells, such as neutrophils, produce reactive oxygen species and reactive nitrogen species as part of the body's defense mechanisms to destroy invading pathogens. Reactive oxygen species/reactive nitrogen species are excessively produced by active peripheral neutrophils, and may damage essential cellular components, which in turn can cause vascular complications in diabetes. The present study was undertaken to evaluate the possible protective effects of annatto on the reactive oxygen species and nitric oxide (NO) inhibition in neutrophils from alloxan-induced diabetic rats. Adult female rats were divided into six groups based on receiving either a standard diet with or without supplementation of annatto extract or beta carotene. All animals were sacrificed 30 days after treatment and the neutrophils were isolated using two gradients of different densities. The reactive oxygen species and NO were quantified by a chemiluminescence and spectrophotometric assays, respectively. Our results show that neutrophils from diabetic animals produce significantly more reactive oxygen species and NO than their respective controls and that supplementation with beta carotene and annatto is able to modulate the production of these species. Annatto extract may have therapeutic potential for modulation of the balance reactive oxygen species/NO induced by diabetes. PMID:22573917

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

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

  20. Oxidases and reactive oxygen species during hematopoiesis: a focus on megakaryocytes

    PubMed Central

    Eliades, Alexia; Matsuura, Shinobu; Ravid, Katya

    2012-01-01

    Reactive oxygen species (ROS), generated as a result of various reactions, control an array of cellular processes. The role of ROS during megakaryocyte (MK) development has been a subject of interest and research. The bone marrow niche is the major site of MK differentiation and maturation. In this environment, a gradient of oxygen tension, from normoxia to hypoxia results in different levels of ROS, impacting cellular physiology. This article provides an overview of major sources of ROS, their implication in different signaling pathways, and their effect on cellular physiology, with a focus on megakaryopoiesis. The importance of ROS-generating oxidases in MK biology and pathology, including myelofibrosis, is also described. PMID:22331622

  1. Small-molecule screen identifies reactive oxygen species as key regulators of neutrophil chemotaxis

    PubMed Central

    Hattori, Hidenori; Subramanian, Kulandayan K.; Sakai, Jiro; Jia, Yonghui; Li, Yitang; Porter, Timothy F.; Loison, Fabien; Sarraj, Bara; Kasorn, Anongnard; Jo, Hakryul; Blanchard, Catlyn; Zirkle, Dorothy; McDonald, Douglas; Pai, Sung-Yun; Serhan, Charles N.; Luo, Hongbo R.

    2010-01-01

    Neutrophil chemotaxis plays an essential role in innate immunity, but the underlying cellular mechanism is still not fully characterized. Here, using a small-molecule functional screening, we identified NADPH oxidase–dependent reactive oxygen species as key regulators of neutrophil chemotactic migration. Neutrophils with pharmacologically inhibited oxidase, or isolated from chronic granulomatous disease (CGD) patients and mice, formed more frequent multiple pseudopodia and lost their directionality as they migrated up a chemoattractant concentration gradient. Knocking down NADPH oxidase in differentiated neutrophil-like HL60 cells also led to defective chemotaxis. Consistent with the in vitro results, adoptively transferred CGD murine neutrophils showed impaired in vivo recruitment to sites of inflammation. Together, these results present a physiological role for reactive oxygen species in regulating neutrophil functions and shed light on the pathogenesis of CGD. PMID:20142487

  2. 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.

  3. Relationship of Metabolism of Reactive Oxygen Species with Cytoplasmic Male Sterility in Pepper( Capsicum annuum L.)

    Microsoft Academic Search

    Ming-Hua DENG; Jin-Fen WEN; Jin-Long HUO; Hai-Shan ZHU; Xiong-Ze DAI; Zhu-Qing ZHANG; Hui ZHOU; Xue-Xiao ZOU

    Pepper cytoplasmic male sterility (CMS) line 9704A is one of the CMS types used for hybrid pepper (Capsicum annuum L.) production in China. Our previous studies suggested that CMS-9704A may suffer from oxidative stress as its cyanide-resistant respiration is lower than that of the maintainer line. To elucidate the metabolic mechanism of reactive oxygen species (ROS) in the CMS-pepper anthers,

  4. Reactive oxygen species and inflammatory mediators enhance muscle spindles mechanosensitivity in rats

    Microsoft Academic Search

    Stéphane Delliaux; Christelle Brerro-Saby; Jean Guillaume Steinberg; Yves Jammes

    2009-01-01

    We tested the hypothesis that reactive oxygen species (ROS) and inflammatory mediators affect transduction properties of muscle\\u000a spindles. In rats, muscle spindles response to high-frequency vibration (HFV) was recorded before and after (1) injection\\u000a of hydrogen peroxide (H2O2) in control rats and animals pre-treated with diclofenac (anti-inflammatory substance), (2) injection of bradykinin and (3)\\u000a fatigue induced by muscle stimulation (MS)

  5. Protein Kinase D Mediates Mitochondrion-to-Nucleus Signaling and Detoxification from Mitochondrial Reactive Oxygen Species

    Microsoft Academic Search

    Peter Storz; Heike Doppler; Alex Toker

    2005-01-01

    Efficient elimination of mitochondrial reactive oxygen species (mROS) correlates with increased cellular survival and organism life span. Detoxification of mitochondrial ROS is regulated by induction of the nuclear SOD2 gene, which encodes the manganese-dependent superoxide dismutase (MnSOD). However, the mecha- nisms by which mitochondrial oxidative stress activates cellular signaling pathways leading to induction of nuclear genes are not known. Here

  6. Liposomalization of hydroxyphenyl fluorescein as a reagent for detecting highly reactive oxygen species

    Microsoft Academic Search

    Ikumi Sugiyama; Saki Kojima; Naoto Oku; Yasuyuki Sadzuka

    2010-01-01

    It has been shown that lifestyle-related diseases and aging are related to reactive oxygen species (ROS), and many studies\\u000a have reported on the direct detection of ROS. The topical fluorescence reagent 2,7-dichlorodihydrofluorescein (DCDHF) is used\\u000a to measure oxidation. However, there are problems regarding its stability, and its similar sensitivity to ROS cannot be easily\\u000a distinguished. In this study, we used

  7. Zinc protects Ceratophyllum demersum L. (free-floating hydrophyte) against reactive oxygen species induced by cadmium

    Microsoft Academic Search

    P. Aravind; M. N. V. Prasad; P. Malec; A. Waloszek; K. Strza?ka

    2009-01-01

    Evidence for Zn protection against Cd-induced reactive oxygen species in the free-floating hydrophyte Ceratophyllum demersum L. is presented in this paper. Metal treatments of 10?mol\\/L Cd, 10 Cd?mol\\/L supplemented with Zn (10, 50, 100 and 200?mol\\/L) and Zn-alone treatments of the same concentrations were used. Using 5,5 dimethyl pyrroline-N-oxide as the spin-probe, electron spin resonance spectra indicated a drastic increase

  8. Reactive oxygen species regulate hypoxia-inducible factor 1alpha differentially in cancer and ischemia.

    PubMed

    Qutub, Amina A; Popel, Aleksander S

    2008-08-01

    In exercise, as well as cancer and ischemia, hypoxia-inducible factor 1 (HIF1) transcriptionally activates hundreds of genes vital for cell homeostasis and angiogenesis. While potentially beneficial in ischemia, upregulation of the HIF1 transcription factor has been linked to inflammation, poor prognosis in many cancers, and decreased susceptibility of tumors to radiotherapy and chemotherapy. Considering HIF1's function, HIF1alpha protein and its hydroxylation cofactors look increasingly attractive as therapeutic targets. Independently, antioxidants have shown promise in lowering the risk of some cancers and improving neurological and cardiac function following ischemia. The mechanism of how different antioxidants and reactive oxygen species influence HIF1alpha expression has drawn interest and intense debate. Here we present an experimentally based computational model of HIF1alpha protein degradation that represents how reactive oxygen species and antioxidants likely affect the HIF1 pathway differentially in cancer and ischemia. We use the model to demonstrate effects on HIF1alpha expression from combined doses of five potential therapeutically targeted compounds (iron, ascorbate, hydrogen peroxide, 2-oxoglutarate, and succinate) influenced by cellular oxidation-reduction and involved in HIF1alpha hydroxylation. Results justify the hypothesis that reactive oxygen species work by two opposite ways on the HIF1 system. We also show how tumor cells and cells under ischemic conditions would differentially respond to reactive oxygen species via changes to HIF1alpha expression over the course of hours to days, dependent on extracellular hydrogen peroxide levels and largely independent of initial intracellular levels, during hypoxia. PMID:18559422

  9. Copper increases the damage to DNA and proteins caused by reactive oxygen species

    Microsoft Academic Search

    Martha Patricia Cervantes-Cervantes; J. Víctor Calderón-Salinas; Arnulfo Albores; José Luis Muñoz-Sánchez

    2005-01-01

    Copper [Cu(II)] is an ubiquitous transition and trace element in living organisms. It increases reactive oxygen species (ROS)\\u000a and free-radical generation that might damage biomolecules like DNA, proteins, and lipids. Furthermore, ability of Cu(II)\\u000a greatly increases in the presence of oxidants. ROS, like hydroxyl (·OH) and superoxide (·O2) radicals, alter both the structure of the DNA double helix and the

  10. Generation of reactive oxygen species induced by gold nanoparticles under x-ray and UV Irradiations

    Microsoft Academic Search

    Masaki Misawa; Junko Takahashi

    2011-01-01

    The radiosensitizing effect of 5--250 nm diameter Au nanoparticles (AuNPs) in water was investigated under irradiations of diagnostic x-ray and UV light. Enhanced generations of hydroxyl radical (OH) and superoxide anion (O2?) were confirmed from their dependencies on the absorbed energy, ethanol concentration and AuNPs' concentration. Two kinds of fluorescent probes revealed that the reactive oxygen species (ROS) generation rate

  11. Analysis of Reactive Oxygen Species Generated by Neutrophils Using a Chemiluminescence Probe L-012

    Microsoft Academic Search

    Isuke Imada; Eisuke F. Sato; Masafumi Miyamoto; Yuzo Ichimori; Yukiko Minamiyama; Ryusei Konaka; Masayasu Inoue

    1999-01-01

    Reactive oxygen species (ROS) play important roles in the defense mechanism against infection and in the pathogenesis of various diseases. Although chemical properties of ROS generated by leukocytes have been studied extensively, methods available for their analysis are not sufficiently sensitive. We found that 8-amino-5-chloro-7-phenylpyrido[3,4-d]pyridazine-1,4-(2H,3H)dione (L-012) reacted with various types of ROS generated by activated neutrophils in human blood and

  12. Cell death and reactive oxygen species metabolism during accelerated ageing of soybean axes

    Microsoft Academic Search

    X. Tian; S. Song; Y. Lei

    2008-01-01

    In this paper, Glycine max L. seeds under accelerated ageing condition (40°C and 100% relative humidity) were used as experimental material to study\\u000a the relationships between seed viability and cell death, production and scavenging of reactive oxygen species (ROS) during\\u000a accelerated ageing. Water content of seeds gradually increased, while the final germination percentage, germination rate of\\u000a seeds and fresh weight

  13. Endogenous Reactive Oxygen Species Is an Important Mediator of Miconazole Antifungal Effect

    Microsoft Academic Search

    Daisuke Kobayashi; Kei Kondo; Nobuyuki Uehara; Seiko Otokozawa; Naoki Tsuji; Atsuhito Yagihashi; Naoki Watanabe

    2002-01-01

    We investigated the significance of endogenous reactive oxygen species (ROS) produced by fungi treated with miconazole. ROS production in Candida albicans was measured by a real-time fluorogenic assay. The level of ROS production was increased by miconazole at the MIC (0.125 g\\/ml) and was enhanced further in a dose-dependent manner, with a fourfold increase detected when miconazole was used at

  14. Reactive oxygen intermediates in plant-microbe interactions: Who is who in powdery mildew resistance?

    Microsoft Academic Search

    Ralph Hückelhoven; Karl-Heinz Kogel

    2003-01-01

    Reactive oxygen intermediates (ROIs) such as hydrogen peroxide (H2O2) and the superoxide anion radical (O2·m) accumulate in many plants during attack by microbial pathogens. Despite a huge number of studies, the complete picture of the role of ROIs in the host-pathogen interaction is not yet fully understood. This situation is reflected by the controversially discussed question as to whether ROIs

  15. In vitro scavenging capacity of annatto seed extracts against reactive oxygen and nitrogen species.

    PubMed

    Chisté, Renan Campos; Mercadante, Adriana Zerlotti; Gomes, Ana; Fernandes, Eduarda; Lima, José Luís Fontes da Costa; Bragagnolo, Neura

    2011-07-15

    Bixa orellana L. (annatto), from Bixaceae family, is a native plant of tropical America, which accumulates several carotenoids (including bixin and norbixin), terpenoids, tocotrienols and flavonoids with potential antioxidant activity. In the present study, the in vitro scavenging capacity of annatto seed extracts against reactive oxygen species (ROS) and reactive nitrogen species (RNS) was evaluated and compared to the bixin standard. Annatto extracts were obtained using solvents with different polarities and their phenolic compounds and bixin levels were determined by high performance liquid chromatography coupled to diode array detector. All annatto extracts were able to scavenge all the reactive species tested at the low ?g/mL range, with the exception of superoxide radical. The ethanol:ethyl acetate and ethyl acetate extracts of annatto seeds, which presented the highest levels of hypolaetin and bixin, respectively, were the extracts with the highest antioxidant capacity, although bixin standard presented the lowest IC(50) values. PMID:23140681

  16. 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

  17. [Effects of allelochemical dibutyl phthalate on Gymnodinium breve reactive oxygen species].

    PubMed

    Bie, Cong-Cong; Li, Feng-Min; Li, Yuan-Yuan; Wang, Zhen-Yu

    2012-02-01

    The purpose of this study was to investigate the mechanism of inhibitory action of dibutyl phthalate (DBP) on red tide algae Gymnodinium breve. Reactive oxygen species (ROS) level, contents of *OH and H2O2, and O2*(-) production rate were investigated, and also for the effects of electron transfer inhibitors on the ROS induction of DBP. The results showed that DBP triggered the synthesis of reactive oxygen species ROS, and with the increase of concentration of DBP, *OH and H2O2 contents in cells accumulated, as for the 3 mg x L(-1) DBP treated algae cultures, OH showed a peak of 33 U x mL(-1) at 48 h, which was about 2. 4 times higher than that in the controlled, and H2O2 contents was about 250 nmol x (10(7) cells)(-1) at 72 h, which was about 5 times higher and also was the highest during the whole culture. Rotenone (an inhibitor of complex I in the mitochondria electron transport chain) decreased the DBP induced ROS production, and dicumarol (an inhibitor of the redox enzyme system in the plasma membrane) stimulated the DBP induced ROS production. Taken all together, the results demonstrated DBP induced over production of reactive oxygen species in G. breve, which is the main inhibitory mechanism, and mitochondria and plasma membrane seem to be the main target site of DBP. These conclusions were of scientific meaning on uncovering the inhibitory mechanism of allelochemical on algae. PMID:22509579

  18. Inhibition of astrocyte glutamate uptake by reactive oxygen species: role of antioxidant enzymes.

    PubMed Central

    Sorg, O.; Horn, T. F.; Yu, N.; Gruol, D. L.; Bloom, F. E.

    1997-01-01

    BACKGROUND: The recent literature suggests that free radicals and reactive oxygen species may account for many pathologies, including those of the nervous system. MATERIALS AND METHODS: The influence of various reactive oxygen species on the rate of glutamate uptake by astrocytes was investigated on monolayers of primary cultures of mouse cortical astrocytes. RESULTS: Hydrogen peroxide and peroxynitrite inhibited glutamate uptake in a concentration-dependent manner. Addition of copper ions and ascorbate increased the potency and the efficacy of the hydrogen peroxide effect, supporting the potential neurotoxicity of the hydroxyl radical. The free radical scavenger dimethylthiourea effectively eliminated the inhibitory potential of a mixture containing hydrogen peroxide, copper sulphate, and ascorbate on the rate of glutamate transport into astrocytes. The inhibitory effect of hydrogen peroxide on glutamate uptake was not altered by the inhibition of glutathione peroxidase, whereas the inhibition of catalase by sodium azide clearly potentiated this effect. Superoxide and nitric oxide had no effect by themselves on the rate of glutamate uptake by astrocytes. The absence of an effect of nitric oxide is not due to an inability of astrocytes to respond to this substance, since the same cultures did respond to nitric oxide with a sustained increase in cytoplasmic free calcium. CONCLUSION: These results confirm that reactive oxygen species have a potential neurotoxicity by means of impairing glutamate transport into astrocytes, and they suggest that preventing the accumulation of hydrogen peroxide in the extracellular space of the brain, especially during conditions that favor hydroxyl radical formation, could be therapeutic. PMID:9260155

  19. Impairment of epithelium-dependent relaxation in coaxial bioassay by reactive oxygen species.

    PubMed

    Burcin, I U; Sahin-Erdemli, I; Arzu, S; Ilhan, M

    1999-07-28

    The purpose of the present study was to investigate the effects of reactive oxygen species on the activity of epithelium-derived relaxant factor (EpDRF) released by guinea-pig tracheal epithelium. Reactive oxygen species were generated by the electrolysis of the physiological buffer in which the tissues were bathed. Epithelium-dependent relaxation induced by acetylcholine in precontracted rat anococcygeus muscle that was placed in epithelium-intact guinea-pig trachea (coaxial bioassay system) was significantly attenuated when the tissues were exposed to electrolysis. Impairment of the acetylcholine response was prevented by incubation with free radical scavengers prior to electrolysis. In isolated rings of guinea-pig trachea, the contractile responses elicited by acetylcholine, histamine and 5-hydroxytryptamine were not altered after electrolysis of the bathing solution. The results of the present study suggested that exposure to reactive oxygen species impaired EpDRF release from guinea-pig trachea epithelium but did not alter the contractility of tracheal smooth muscle. PMID:10478570

  20. [Reactive oxygen forms and Ca ions as possible intermediaries under the induction of heat resistance of plant cells by jasmonic acid].

    PubMed

    Karpets, Iu V; Kolupaev, Iu E; Iastreb, T O; Obozny?, A I; Shvidenko, N V; Lugovaia, A A; Va?ner, A A

    2013-01-01

    The participation of reactive oxygen species (ROS) and calcium ions in realization of influence of exogenous jasmonic acid (JA) on the heat resistance of wheat coleoptiles has been investigated. Influence of 1 microM JA caused the transitional intensifying of generation of superoxide anion-radical (O2*-) and hydrogen peroxide in coleoptiles with the maximum within 15-30 minutes after the treatment beginning. Within the first hour after the beginning of coleoptiles treatment with JA the increase of superoxide dismutase (SOD) activity was noted. Later on (within 5-24 hours after the treatment beginning) there was the lowering of ROS generation by coleoptiles of experimental variant, and the SOD activity approached the control value. Intensifying of generation of superoxide radical induced by JA was suppressed by the antioxidant ionol and was partially levelled by imidazole (inhibitor of NADPH-oxidase), EGTA (chelator of extracellular calcium) and lanthanum chloride (calcium channels blocker). Pretreatment of coleoptiles with the ionol, imidazole, EGTA and LaC3l3 also partially removed the effect of increase of their resistance to the damaging heating caused by exogenous JA. It is supposed that the ROS generated with participation NADPH-oxidase, which activity depends on the receipt of calcium ions from extracellular space in the cytosol, are involved in realization of physiological effects of JA. PMID:23937049

  1. Long-chain bases and their phosphorylated derivatives differentially regulate cryptogein-induced production of reactive oxygen species in tobacco (Nicotiana tabacum) BY-2 cells.

    PubMed

    Coursol, Sylvie; Fromentin, Jérôme; Noirot, Elodie; Brière, Christian; Robert, Franck; Morel, Johanne; Liang, Yun-Kuan; Lherminier, Jeannine; Simon-Plas, Françoise

    2015-02-01

    The proteinaceous elicitor cryptogein triggers defence reactions in Nicotiana tabacum (tobacco) through a signalling cascade, including the early production of reactive oxygen species (ROS) by the plasma membrane (PM)-located tobacco respiratory burst oxidase homologue D (NtRbohD). Sphingolipid long-chain bases (LCBs) are emerging as potent positive regulators of plant defence-related mechanisms. This led us to question whether both LCBs and their phosphorylated derivatives (LCB-Ps) are involved in the early signalling process triggered by cryptogein in tobacco BY-2 cells. Here, we showed that cryptogein-induced ROS production was inhibited by LCB kinase (LCBK) inhibitors. Additionally, Arabidopsis thaliana sphingosine kinase 1 and exogenously supplied LCB-Ps increased cryptogein-induced ROS production, whereas exogenously supplied LCBs had a strong opposite effect, which was not driven by a reduction in cellular viability. Immunogold-electron microscopy assay also revealed that LCB-Ps are present in the PM, which fits well with the presence of a high LCBK activity associated with this fraction. Our data demonstrate that LCBs and LCB-Ps differentially regulate cryptogein-induced ROS production in tobacco BY-2 cells, and support a model in which a cooperative synergism between LCBK/LCB-Ps and NtRbohD/ROS in the cryptogein signalling pathway is likely at the PM in tobacco BY-2 cells. PMID:25303640

  2. Low oxygen and 1-MCP pretreatments delay superficial scald development by reducing reactive oxygen species (ROS) accumulation in stored ‘Granny Smith’ apples

    Microsoft Academic Search

    Revital Sabban-Amin; Oleg Feygenberg; Eduard Belausov; Edna Pesis

    2011-01-01

    ‘Granny Smith’ apples are highly susceptible to superficial scald, a symptom of chilling injury. For many crops, low temperature storage results in oxidative stress and chilling injury, caused by increased production of superoxide anions which in turn leads to the generation of other dangerous reactive oxygen species (ROS). Application, prior to cold storage, of low oxygen (LO2, <0.5%) atmospheres, ethanol

  3. Intermittent hypoxia augments pulmonary vascular smooth muscle reactivity to NO: regulation by reactive oxygen species.

    PubMed

    Norton, Charles E; Jernigan, Nikki L; Kanagy, Nancy L; Walker, Benjimen R; Resta, Thomas C

    2011-10-01

    Intermittent hypoxia (IH) resulting from sleep apnea can lead to pulmonary hypertension. IH causes oxidative stress that may limit bioavailability of the endothelium-derived vasodilator nitric oxide (NO) and thus contribute to this hypertensive response. We therefore hypothesized that increased vascular superoxide anion (O(2)(-)) generation reduces NO-dependent pulmonary vasodilation following IH. To test this hypothesis, we examined effects of the O(2)(-) scavenger tiron on vasodilatory responses to the endothelium-dependent vasodilator ionomycin and the NO donor S-nitroso-N-acetylpenicillamine in isolated lungs from hypocapnic-IH (H-IH; 3 min cycles of 5% O(2)/air flush, 7 h/day, 4 wk), eucapnic-IH (E-IH; cycles of 5% O(2), 5% CO(2)/air flush), and sham-treated (air/air cycled) rats. Next, we assessed effects of endogenous O(2)(-) on NO- and cGMP-dependent vasoreactivity and measured O(2)(-) levels using the fluorescent indicator dihydroethidium (DHE) in isolated, endothelium-disrupted small pulmonary arteries from each group. Both E-IH and H-IH augmented NO-dependent vasodilation; however, enhanced vascular smooth muscle (VSM) reactivity to NO following H-IH was masked by an effect of endogenous O(2)(-). Furthermore, H-IH and E-IH similarly increased VSM sensitivity to cGMP, but this response was independent of either O(2)(-) generation or altered arterial protein kinase G expression. Finally, both H-IH and E-IH increased arterial O(2)(-) levels, although this response was more pronounced following H-IH, and H-IH exposure resulted in greater protein tyrosine nitration indicative of increased NO scavenging by O(2)(-). We conclude that IH increases pulmonary VSM sensitivity to NO and cGMP. Furthermore, endogenous O(2)(-) limits NO-dependent vasodilation following H-IH through an apparent reduction in bioavailable NO. PMID:21757577

  4. Reactive ion beam machining of diamond using an ECR-type oxygen source

    NASA Astrophysics Data System (ADS)

    Kiyohara, Shuji; Miyamoto, Iwao

    1996-09-01

    Reactive ion beam machining of diamond chips with oxygen ions using a Kaufman-type apparatus has been investigated. This paper reports machining characteristics of single crystal diamond chips processed with an oxygen ion beam using an electron cyclotron resonance (ECR)-type apparatus. The specific machining rate increases with increase in ion energy, reaches a maximum rate at an ion energy of 300 eV, then decreases gradually with further increase in ion energy. The specific machining rate obtained with 1000 eV oxygen ions increases with increase in ion incident angle and reaches a maximum rate at an ion incident angle of 0957-4484/7/3/017/img1, then decreases with increase in ion incident angle. The specific machining rate obtained with 500 eV oxygen ions decreases with increase in ion incident angle. The specific machining rate for 500 eV oxygen ions at an ion incident angle of 0957-4484/7/3/017/img2 is 12 times greater than that for argon ions. Futhermore, the surface roughness of diamond chips before and after oxygen ion beam machining was evaluated using an atomic force microscope (AFM) and a scanning electron microscope (SEM). It was found that the surface roughness increases with increase in ion incident angle, and decreases with increase in ion energy.

  5. Effect of oxygen deficiency on the photoresponse and reactivity of mixed phase titania thin films

    SciTech Connect

    DeSario, Paul A.; Chen Le; Graham, Michael E.; Gray, Kimberly A. [Department of Civil and Environmental Engineering, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208 (United States); Department of Materials Science and Engineering, Northwestern University, 2220 Campus Drive, Evanston, Illinois 60208 (United States); Department of Civil and Environmental Engineering, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208 (United States)

    2011-05-15

    Nonstoichiometric mixed phased titania nanocomposites (TiO{sub 2-x}) were deposited by reactive direct current magnetron sputtering. The authors explored the role of nonstoichiometry (as defined by oxygen deficiency in synthesis) in mixed phase titania thin films and its effects on the photoresponse and photocatalytic performance for CO{sub 2} reduction to methane under UV and visible light. Oxygen partial pressure was varied during film deposition, yielding different levels of oxygen deficiency in the films. Optimized nonstoichiometric films showed a strong redshift. The authors have identified an optimum set of synthesis conditions for TiO{sub 2-x} films that produce a relative maximum in photocatalytically produced methane under both UV and visible light.

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

    EPA Science Inventory

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

  7. A Permeable Cuticle Is Associated with the Release of Reactive Oxygen Species and Induction of Innate Immunity

    E-print Network

    Angélique Besson-bard ¤a; Matteo Binda; Mario Serrano; Eliane Abou-mansour; Francine Balet; Henk-jan Schoonbeek ¤b; Stephane Hess; Ricardo Mir ¤c; José Léon ¤c; Olivier Lamotte ¤a

    Wounded leaves of Arabidopsis thaliana show transient immunity to Botrytis cinerea, the causal agent of grey mould. Using a fluorescent probe, histological staining and a luminol assay, we now show that reactive oxygen species (ROS), including H2O2 and O2 2, are produced within minutes after wounding. ROS are formed in the absence of the enzymes Atrboh D and F and can be prevented by diphenylene iodonium (DPI) or catalase. H2O2 was shown to protect plants upon exogenous application. ROS accumulation and resistance to B. cinerea were abolished when wounded leaves were incubated under dry conditions, an effect that was found to depend on abscisic acid (ABA). Accordingly, ABA biosynthesis mutants (aba2 and aba3) were still fully resistant under dry conditions even without wounding. Under dry conditions, wounded plants contained higher ABA levels and displayed enhanced expression of ABA-dependent and ABA-reporter genes. Mutants impaired in cutin synthesis such as bdg and lacs2.3 are already known to display a high level of resistance to B. cinerea and were found to produce ROS even when leaves were not wounded. An increased permeability of the cuticle and enhanced ROS production were detected in aba2 and aba3 mutants as described for bdg and lacs2.3. Moreover, leaf surfaces treated with cutinase produced ROS and became more protected to B. cinerea. Thus, increased permeability of the cuticle is strongly linked with ROS formation and resistance to B. cinerea. The amount of oxalic acid, an inhibitor of ROS secreted by B. cinerea could be reduced using plants over expressing a fungal oxalate decarboxylase of Trametes versicolor. Infection of such

  8. A permeable cuticle is associated with the release of reactive oxygen species and induction of innate immunity.

    PubMed

    L'Haridon, Floriane; Besson-Bard, Angélique; Binda, Matteo; Serrano, Mario; Abou-Mansour, Eliane; Balet, Francine; Schoonbeek, Henk-Jan; Hess, Stephane; Mir, Ricardo; Léon, José; Lamotte, Olivier; Métraux, Jean-Pierre

    2011-07-01

    Wounded leaves of Arabidopsis thaliana show transient immunity to Botrytis cinerea, the causal agent of grey mould. Using a fluorescent probe, histological staining and a luminol assay, we now show that reactive oxygen species (ROS), including H(2)O(2) and O(2) (-), are produced within minutes after wounding. ROS are formed in the absence of the enzymes Atrboh D and F and can be prevented by diphenylene iodonium (DPI) or catalase. H(2)O(2) was shown to protect plants upon exogenous application. ROS accumulation and resistance to B. cinerea were abolished when wounded leaves were incubated under dry conditions, an effect that was found to depend on abscisic acid (ABA). Accordingly, ABA biosynthesis mutants (aba2 and aba3) were still fully resistant under dry conditions even without wounding. Under dry conditions, wounded plants contained higher ABA levels and displayed enhanced expression of ABA-dependent and ABA-reporter genes. Mutants impaired in cutin synthesis such as bdg and lacs2.3 are already known to display a high level of resistance to B. cinerea and were found to produce ROS even when leaves were not wounded. An increased permeability of the cuticle and enhanced ROS production were detected in aba2 and aba3 mutants as described for bdg and lacs2.3. Moreover, leaf surfaces treated with cutinase produced ROS and became more protected to B. cinerea. Thus, increased permeability of the cuticle is strongly linked with ROS formation and resistance to B. cinerea. The amount of oxalic acid, an inhibitor of ROS secreted by B. cinerea could be reduced using plants over expressing a fungal oxalate decarboxylase of Trametes versicolor. Infection of such plants resulted in a faster ROS accumulation and resistance to B. cinerea than that observed in untransformed controls, demonstrating the importance of fungal suppression of ROS formation by oxalic acid. Thus, changes in the diffusive properties of the cuticle are linked with the induction ROS and attending innate defenses. PMID:21829351

  9. Cancer-derived immunoglobulin G promotes tumor cell growth and proliferation through inducing production of reactive oxygen species

    PubMed Central

    Wang, J; Lin, D; Peng, H; Huang, Y; Huang, J; Gu, J

    2013-01-01

    Cancer cells have been found to express immunoglobulin G (IgG), but the exact functions and underlying mechanisms of cancer-derived IgG remain elusive. In this study, we first confirmed that downregulation of IgG restrained the growth and proliferation of cancer cells in vitro and in vivo. To elucidate its mechanism, we carried out a co-immunoprecipitation assay in HeLa cells and identified 27 potential IgG-interacting proteins. Among them, receptor of activated protein kinase C 1 (RACK1), ras-related nuclear protein (RAN) and peroxiredoxin 1 (PRDX1) are closely related to cell growth and oxidative stress, which prompted us to investigate the mechanism of action of IgG in the above phenomena. Upon confirmation of the interactions between IgG and the three proteins, further experiments revealed that downregulation of cancer-derived IgG lowered levels of intracellular reactive oxygen species (ROS) by enhancing cellular total antioxidant capacity. In addition, a few ROS scavengers, including catalase (CAT), dimethylsulfoxide (DMSO), n-acetylcysteine (NAC) and superoxide dismutase (SOD), further inhibited the growth of IgG-deficient cancer cells through suppressing mitogen-activated protein kinase/extracellular-regulated kinase (MAPK/ERK) signaling pathway induced by a low level of intracellular ROS, whereas exogenous hydrogen peroxide (H2O2) at low concentration promoted their survival via increasing intracellular ROS levels. Similar results were obtained in an animal model and human tissues. Taken together, our results demonstrate that cancer-derived IgG can enhance the growth and proliferation of cancer cells via inducing the production of ROS at low level. These findings provide new clues for understanding tumor proliferation and designing cancer therapy. PMID:24309932

  10. Green tea polyphenols potentiate the action of nerve growth factor to induce neuritogenesis: possible role of reactive oxygen species.

    PubMed

    Gundimeda, Usha; McNeill, Thomas H; Schiffman, Jason E; Hinton, David R; Gopalakrishna, Rayudu

    2010-12-01

    Exogenously administered nerve growth factor (NGF) repairs injured axons, but it does not cross the blood-brain barrier. Thus, agents that could potentiate the neuritogenic ability of endogenous NGF would be of great utility in treating neurological injuries. Using the PC12 cell model, we show here that unfractionated green tea polyphenols (GTPP) at low concentrations (0.1 ?g/ml) potentiate the ability of low concentrations of NGF (2 ng/ml) to induce neuritogenesis at a level comparable to that induced by optimally high concentrations of NGF (50 ng/ml) alone. In our experiments, GTPP by itself did not induce neuritogenesis or increase immunofluorescent staining for ?-tubulin III; however, it increased expression of mRNA and proteins for the neuronal markers neurofilament-L and GAP-43. Among the polyphenols present in GTPP, epigallocatechin-3-gallate (EGCG) alone appreciably potentiated NGF-induced neurite outgrowth. Although other polyphenols present in GTPP, particularly epigallocatechin and epicatechin, lack this activity, they synergistically promoted this action of EGCG. GTPP also induced an activation of extracellular signal-regulated kinases (ERKs). PD98059, an inhibitor of the ERK pathway, blocked the expression of GAP-43. K252a, an inhibitor of TrkA-associated tyrosine kinase, partially blocked the expression of these genes and ERK activation. Antioxidants, catalase (cell-permeable form), and N-acetylcysteine (both L and D-forms) inhibited these events and abolished the GTPP potentiation of NGF-induced neuritogenesis. Taken together, these results show for the first time that GTPP potentiates NGF-induced neuritogenesis, likely through the involvement of sublethal levels of reactive oxygen species, and suggest that unfractionated GTPP is more effective in this respect than its fractionated polyphenols. PMID:20936703

  11. 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

  12. Oleic acid increases mitochondrial reactive oxygen species production and decreases endothelial nitric oxide synthase activity in cultured endothelial cells.

    PubMed

    Gremmels, Hendrik; Bevers, Lonneke M; Fledderus, Joost O; Braam, Branko; Jan van Zonneveld, Anton; Verhaar, Marianne C; Joles, Jaap A

    2015-03-15

    Elevated plasma levels of free fatty acids (FFA) are associated with increased cardiovascular risk. This may be related to FFA-induced elevation of oxidative stress in endothelial cells. We hypothesized that, in addition to mitochondrial production of reactive oxygen species, endothelial nitric oxide synthase (eNOS)-mediated reactive oxygen species production contributes to oleic acid (OA)-induced oxidative stress in endothelial cells, due to eNOS uncoupling. We measured reactive oxygen species production and eNOS activity in cultured endothelial cells (bEnd.3) in the presence of OA bound to bovine serum albumin, using the CM-H2DCFDA assay and the l-arginine/citrulline conversion assay, respectively. OA induced a concentration-dependent increase in reactive oxygen species production, which was inhibited by the mitochondrial complex II inhibitor thenoyltrifluoroacetone (TTFA). OA had little effect on eNOS activity when stimulated by a calcium-ionophore, but decreased both basal and insulin-induced eNOS activity, which was restored by TTFA. Pretreatment of bEnd.3 cells with tetrahydrobiopterin (BH4) prevented OA-induced reactive oxygen species production and restored inhibition of eNOS activity by OA. Elevation of OA levels leads to both impairment in receptor-mediated stimulation of eNOS and to production of mitochondrial-derived reactive oxygen species and hence endothelial dysfunction. PMID:25595727

  13. Adsorption removal of reactive dyes from aqueous solution by modified basic oxygen furnace slag: Isotherm and kinetic study

    Microsoft Academic Search

    Yongjie Xue; Haobo Hou; Shujing Zhu

    2009-01-01

    The utilization of treated basic oxygen furnace slag (BOF slag) was successfully carried out to remove three synthetic textile dyes (Reactive Blue 19 (RB19), Reactive Black 5 (RB5) and Reactive Red 120 (RR120)) by adsorption from aqueous solutions. Batch studies were carried out to address various experimental parameters such as pH, contact time, temperature and ionic strength. In the batch

  14. NecroX as a novel class of mitochondrial reactive oxygen species and ONOO? scavenger.

    PubMed

    Kim, Hyoung Jin; Koo, Sun Young; Ahn, Bong-Hyun; Park, Oeuk; Park, Doo Hoe; Seo, Dong Ook; Won, Jong Heon; Yim, Hyeon Joo; Kwak, Hyo-Shin; Park, Heui Sul; Chung, Chul Woong; Oh, Young Leem; Kim, Soon Ha

    2010-11-01

    Mitochondrial reactive oxygen species and reactive nitrogen species are proven to be major sources of oxidative stress in the cell; they play a prominent role in a wide range of human disorders resulting from nonapoptotic cell death. The aim of this study is to examine the cytoprotective effect of the NecroX series against harmful stresses, including pro-oxidant (tertiarybutylhydroperoxide), doxorubicin, CCl?, and hypoxic injury. In this study, these novel chemical molecules inhibited caspase-independent cell death with necrotic morphology, which is distinctly different from apoptosis, autophagy, and necroptosis. In addition, they displayed strong mitochondrial reactive oxygen species and ONOO? scavenging activity. Further, oral administration of these molecules in C57BL/6 mice attenuated streptozotocin-induced pancreatic islet ?-cell destruction as well as CCl?-induced hepatotoxicity in vivo. Taken together, these results demonstrate that the NecroX series are involved in the blockade of nonapoptotic cell death against mitochondrial oxidative stresses. Thus, these chemical molecules are potential therapeutic agents in mitochondria-related human diseases involving necrotic tissue injury. PMID:21116785

  15. The Escherichia coli BtuE Protein Functions as a Resistance Determinant against Reactive Oxygen Species

    PubMed Central

    Arenas, Felipe A.; Covarrubias, Paulo C.; Sandoval, Juan M.; Pérez-Donoso, José M.; Imlay, James A.; Vásquez, Claudio C.

    2011-01-01

    This work shows that the recently described Escherichia coli BtuE peroxidase protects the bacterium against oxidative stress that is generated by tellurite and by other reactive oxygen species elicitors (ROS). Cells lacking btuE (?btuE) displayed higher sensitivity to K2TeO3 and other oxidative stress-generating agents than did the isogenic, parental, wild-type strain. They also exhibited increased levels of cytoplasmic reactive oxygen species, oxidized proteins, thiobarbituric acid reactive substances, and lipoperoxides. E. coli ?btuE that was exposed to tellurite or H2O2 did not show growth changes relative to wild type cells either in aerobic or anaerobic conditions. Nevertheless, the elimination of btuE from cells deficient in catalases/peroxidases (Hpx?) resulted in impaired growth and resistance to these toxicants only in aerobic conditions, suggesting that BtuE is involved in the defense against oxidative damage. Genetic complementation of E. coli ?btuE restored toxicant resistance to levels exhibited by the wild type strain. As expected, btuE overexpression resulted in decreased amounts of oxidative damage products as well as in lower transcriptional levels of the oxidative stress-induced genes ibpA, soxS and katG. PMID:21264338

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

    PubMed

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

    2015-02-23

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

  17. The behaviour of negative oxygen ions in the afterglow of a reactive HiPIMS discharge

    NASA Astrophysics Data System (ADS)

    Bowes, M.; Bradley, J. W.

    2014-07-01

    Using a single Langmuir probe, the temporal evolution of the oxygen negative ion, n-, and electron, ne, densities in the afterglow of a reactive HiPIMS discharge operating in argon-oxygen gas mixtures have been determined. The magnetron was equipped with a titanium target and operated in ‘poisoned’ mode at a frequency of 100 Hz with a pulse width of 100 µs for a range of oxygen partial pressures, {p_{O_{2}}}/{p_{total}} = 0.0{{-}}0.5 . In the initial afterglow, the density of the principle negative ion in the discharge (O-) was of the order of 1016 m-3 for all conditions. The O- concentration was found to decay slowly with characteristic decay times between 585 µs and 1.2 ms over the oxygen partial pressure range. Electron densities were observed to fall more rapidly, resulting in long-lived highly electronegative afterglow plasmas where the ratio, ? = n-/ne, was found to reach values up to 672 (±100) for the highest O2 partial pressure. By comparing results to a simple plasma-chemical model, we speculate that with increased {p_{O_{2}}}/{p_{total}} ratio, more O- ions are formed in the afterglow via dissociative electron attachment to highly excited metastable oxygen molecules, with the latter being formed during the active phase of the discharge. After approximately 2.5 ms into the off-time, the afterglow degenerates into an ion-ion plasma and negative ions are free to impinge upon the chamber walls and grounded substrates with flux densities of the order of 1018 m-2 s-1, which is around 10% of the positive ion flux measured during the on-time. This illustrates the potential importance of the long afterglow in reactive HiPIMS, which can act as a steady source of low energy O- ions to a growing thin film at the substrate during periods of reduced positive ion bombardment.

  18. Light-responsive polymer nanoreactors: a source of reactive oxygen species on demand.

    PubMed

    Baumann, Patric; Balasubramanian, Vimalkumar; Onaca-Fischer, Ozana; Sienkiewicz, Andrzej; Palivan, Cornelia G

    2013-01-01

    Various domains present the challenges of responding to stimuli in a specific manner, with the desired sensitivity or functionality, and only when required. Stimuli-responsive systems that are appropriately designed can effectively meet these challenges. Here, we introduce nanoreactors that encapsulate photosensitizer-protein conjugates in polymer vesicles as a source of "on demand" reactive oxygen species. Vesicles made of poly(2-methyloxazoline)-poly(dimethylsiloxane)-poly(2-methyloxazoline) successfully encapsulated the photosensitizer Rose Bengal-bovine serum albumin conjugate (RB-BSA) during a self-assembly process, as demonstrated by UV-Vis spectroscopy. A combination of light scattering and transmission electron microscopy indicated that the nanoreactors are stable over time. They serve a dual role: protecting the photosensitizer in the inner cavity and producing in situ reactive oxygen species (ROS) upon irradiation with appropriate electromagnetic radiation. Illumination with appropriate wavelength light allows us to switch on/off and to control the production of ROS. Because of the oxygen-permeable nature of the polymer membrane of vesicles, ROS escape into the environment around vesicles, as established by electron paramagnetic resonance. The light-sensitive nanoreactor is taken up by HeLa cells in a Trojan horse fashion: it is nontoxic and, when irradiated with the appropriate laser light, produces ROS that induce cell death in a precise area corresponding to the irradiation zone. These nanoreactors can be used in theranostic approaches because they can be detected via the fluorescent photosensitizer signal and simultaneously produce ROS efficiently "on demand". PMID:23154601

  19. Deconvoluting the role of reactive oxygen species and autophagy in human diseases.

    PubMed

    Wen, Xin; Wu, Jinming; Wang, Fengtian; Liu, Bo; Huang, Canhua; Wei, Yuquan

    2013-12-01

    Reactive oxygen species (ROS), chemically reactive molecules containing oxygen, can form as a natural byproduct of the normal metabolism of oxygen and also have their crucial roles in cell homeostasis. Of note, the major intracellular sources including mitochondria, endoplasmic reticulum (ER), peroxisomes and the NADPH oxidase (NOX) complex have been identified in cell membranes to produce ROS. Interestingly, autophagy, an evolutionarily conserved lysosomal degradation process in which a cell degrades long-lived proteins and damaged organelles, has recently been well-characterized to be regulated by different types of ROS. Accumulating evidence has demonstrated that ROS-modulated autophagy has numerous links to a number of pathological processes, including cancer, ageing, neurodegenerative diseases, type-II diabetes, cardiovascular diseases, muscular disorders, hepatic encephalopathy and immunity diseases. In this review, we focus on summarizing the molecular mechanisms of ROS-regulated autophagy and their relevance to diverse diseases, which would shed new light on more ROS modulators as potential therapeutic drugs for fighting human diseases. PMID:23872397

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

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

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

  1. 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. (Industrial Toxicology Research Centre, Lucknow (India))

    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.

  2. Characterizing semen parameters and their association with reactive oxygen species in infertile men

    PubMed Central

    2014-01-01

    Background A routine semen analysis is a first step in the laboratory evaluation of the infertile male. In addition, other tests such as measurement of reactive oxygen species can provide additional information regarding the etiology of male infertility. The objective of this study was to investigate the association of semen parameters with reactive oxygen species (ROS) in two groups: healthy donors of unproven and proven fertility and infertile men. In addition, we sought to establish an ROS cutoff value in seminal plasma at which a patient may be predicted to be infertile. Methods Seminal ejaculates from 318 infertile patients and 56 donors, including those with proven fertility were examined for semen parameters and ROS levels. Correlations were determined between traditional semen parameters and levels of ROS among the study participants. ROS levels were measured using chemiluminescence assay. Receiver operating characteristic curves were obtained to calculate a cutoff value for these tests. Results Proven Donors (n?=?28) and Proven Donors within the past 2 years (n?=?16) showed significantly better semen parameters than All Patients group (n?=?318). Significantly lower ROS levels were seen in the two Proven Donor groups compared with All Patients. The cutoff value of ROS in Proven Donors was determined to be 91.9 RLU/s with a specificity of 68.8% and a sensitivity of 93.8%. Conclusions Infertile men, irrespective of their clinical diagnoses, have reduced semen parameters and elevated ROS levels compared to proven fertile men who have established a pregnancy recently or in the past. Reactive oxygen species are negatively correlated with traditional semen parameters such as concentration, motility and morphology. Measuring ROS levels in the seminal ejaculates provides clinically-relevant information to clinicians. PMID:24885775

  3. Effect of different intravenous iron preparations on lymphocyte intracellular reactive oxygen species generation and subpopulation survival

    PubMed Central

    2010-01-01

    Background Infections in hemodialysis (HD) patients lead to high morbidity and mortality rates and are associated with early cardiovascular mortality, possibly related to chronic inflammation. Intravenous (IV) iron is widely administered to HD patients and has been associated with increased oxidative stress and dysfunctional cellular immunity. The purpose of this study was to examine the effect of three commercially available IV iron preparations on intracellular reactive oxygen species generation and lymphocyte subpopulation survival. Methods Peripheral blood mononuclear cells (PBMC) were isolated from healthy donor buffy coat. PBMC were cultured and incubated with 100 ?g/mL of sodium ferric gluconate (SFG), iron sucrose (IS) or iron dextran (ID) for 24 hours. Cells were then probed for reactive oxygen species (ROS) with dichlorofluorescein-diacetate. In separate studies, isolated PBMCs were incubated with the 25, 50 or 100 ?g/mL iron concentrations for 72 hours and then stained with fluorescein conjugated monoclonal antibodies for lymphocyte subpopulation identification. Untreated PBMCs at 24 hours and 72 hours served as controls for each experiment. Results All three IV iron preparations induced time dependent increases in intracellular ROS with SFG and IS having a greater maximal effect than ID. The CD4+ lymphocytes were most affected by IV iron exposure, with statistically significant reduction in survival after incubation with all three doses (10, 25 and 100 ?g/mL) of SFG, IS and ID. Conclusion These data indicate IV iron products induce differential deleterious effects on CD4+ and CD16+ human lymphocytes cell populations that may be mediated by intracellular reactive oxygen species generation. Further studies are warranted to determine the potential clinical relevance of these findings. PMID:20716362

  4. A review of the interaction among dietary antioxidants and reactive oxygen species.

    PubMed

    Seifried, Harold E; Anderson, Darrell E; Fisher, Evan I; Milner, John A

    2007-09-01

    During normal cellular activities, various processes inside of cells produce reactive oxygen species (ROS). Some of the most common ROS are hydrogen peroxide (H(2)O(2)), superoxide ion (O(2)(-)), and hydroxide radical (OH(-)). These compounds, when present in a high enough concentration, can damage cellular proteins and lipids or form DNA adducts that may promote carcinogenic activity. The purpose of antioxidants in a physiological setting is to prevent ROS concentrations from reaching a high-enough level within a cell that damage may occur. Cellular antioxidants may be enzymatic (catalase, glutathione peroxidase, superoxide dismutase) or nonenzymatic (glutathione, thiols, some vitamins and metals, or phytochemicals such as isoflavones, polyphenols, and flavanoids). Reactive oxygen species are a potential double-edged sword in disease prevention and promotion. Whereas generation of ROS once was viewed as detrimental to the overall health of the organism, advances in research have shown that ROS play crucial roles in normal physiological processes including response to growth factors, the immune response, and apoptotic elimination of damaged cells. Notwithstanding these beneficial functions, aberrant production or regulation of ROS activity has been demonstrated to contribute to the development of some prevalent diseases and conditions, including cancer and cardiovascular disease (CVD). The topic of antioxidant usage and ROS is currently receiving much attention because of studies linking the use of some antioxidants with increased mortality in primarily higher-risk populations and the lack of strong efficacy data for protection against cancer and heart disease, at least in populations with adequate baseline dietary consumption. In normal physiological processes, antioxidants effect signal transduction and regulation of proliferation and the immune response. Reactive oxygen species have been linked to cancer and CVD, and antioxidants have been considered promising therapy for prevention and treatment of these diseases, especially given the tantalizing links observed between diets high in fruits and vegetables (and presumably antioxidants) and decreased risks for cancer. PMID:17360173

  5. Synthesis and reactivity of compounds containing ruthenium-carbon, -nitrogen, and -oxygen bonds

    SciTech Connect

    Hartwig, J.F.

    1990-12-01

    The products and mechanisms of the thermal reactions of several complexes of the general structure (PMe{sub 3}){sub 4}Ru(X)(Y) and (DMPM){sub 2}Ru(X)(Y) where X and Y are hydride, aryl, and benzyl groups, have been investigated. The mechanism of decomposition depends critically on the structure of the complex and the medium in which the thermolysis is carried out. The alkyl hydride complexes are do not react with alkane solvent, but undergo C-H activation processes with aromatic solvents by several different mechanisms. Thermolysis of (PMe{sub 3}){sub 4}Ru(Ph)(Me) or (PMe{sub 3}){sub 4}Ru(Ph){sub 2} leads to the ruthenium benzyne complex (PMe{sub 3}){sub 4}Ru({eta}{sup 2}-C{sub 6}H{sub 4}) (1) by a mechanism which involves reversible dissociation of phosphine. In many ways its chemistry is analogous to that of early rather than late organo transition metal complexes. The synthesis, structure, variable temperature NMR spectroscopy and reactivity of ruthenium complexes containing aryloxide or arylamide ligands are reported. These complexes undergo cleavage of a P-C bond in coordinated trimethylphosphine, insertion of CO and CO{sub 2} and hydrogenolysis. Mechanistic studies on these reactions are described. The generation of a series of reactive ruthenium complexes of the general formula (PMe{sub 3}){sub 4}Ru(R)(enolate) is reported. Most of these enolates have been shown to bind to the ruthenium center through the oxygen atom. Two of the enolate complexes 8 and 9 exist in equilibrium between the O- and C-bound forms. The reactions of these compounds are reported, including reactions to form oxygen-containing metallacycles. The structure and reactivity of these ruthenium metallacycles is reported, including their thermal chemistry and reactivity toward protic acids, electrophiles, carbon monoxide, hydrogen and trimethylsilane. 243 refs., 10 tabs.

  6. Damaged DNA Binding Protein 2 in Reactive Oxygen Species (ROS) Regulation and Premature Senescence

    PubMed Central

    Roy, Nilotpal; Bagchi, Srilata; Raychaudhuri, Pradip

    2012-01-01

    Premature senescence induced by DNA damage or oncogene is a critical mechanism of tumor suppression. Reactive oxygen species (ROS) have been implicated in the induction of premature senescence response. Several pathological disorders such as cancer, aging and age related neurological abnormalities have been linked to ROS deregulation. Here, we discuss how Damaged DNA binding Protein-2 (DDB2), a nucleotide excision repair protein, plays an important role in ROS regulation by epigenetically repressing the antioxidant genes MnSOD and Catalase. We further revisit a model in which DDB2 plays an instrumental role in DNA damage induced ROS accumulation, ROS induced premature senescence and inhibition of skin tumorigenesis. PMID:23109835

  7. Reactive oxygen species and antioxidant enzymes activity of Anabaena sp. PCC 7120 (Cyanobacterium) under simulated microgravity

    NASA Astrophysics Data System (ADS)

    Li, Gen-bao; Liu, Yong-ding; Wang, Gao-hong; Song, Li-rong

    2004-12-01

    It was found that reactive oxygen species in Anabaena cells increased under simulated microgravity provided by clinostat. Activities of intracellular antioxidant enzymes, such as superoxide dismutase, catalase were higher than those in the controlled samples during the 7 days' experiment. However, the contents of gluathione, an intracellular antioxidant, decreased in comparison with the controlled samples. The results suggested that microgravity provided by clinostat might break the oxidative/antioxidative balance. It indicated a protective mechanism in algal cells, that the total antioxidant system activity increased, which might play an important role for algal cells to adapt the environmental stress of microgravity.

  8. 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

  9. Mitochondrial reactive oxygen species generation in obese non-diabetic and type 2 diabetic participants

    Microsoft Academic Search

    M. A. Abdul-Ghani; R. Jani; A. Chavez; M. Molina-Carrion; D. Tripathy; R. A. DeFronzo

    2009-01-01

    Aims\\/hypothesis  The aim of this study was to measure mitochondrial reactive oxygen species (ROS) production directly from skeletal muscle\\u000a biopsies obtained from obese insulin-resistant non-diabetic and type 2 diabetic participants.\\u000a \\u000a \\u000a \\u000a Methods  Ten lean healthy, ten obese non-diabetic and ten type 2 diabetic participants received a euglycaemic–hyperinsulinaemic clamp\\u000a to measure whole body insulin sensitivity. Mitochondria were isolated from skeletal muscle biopsies, and mitochondrial

  10. A comparative kinetic and mechanistic study between tetrahydrozoline and naphazoline toward photogenerated reactive oxygen species.

    PubMed

    Criado, Susana; García, Norman A

    2010-01-01

    Kinetic and mechanistic aspects of the vitamin B2 (riboflavin [Rf])-sensitized photo-oxidation of the imidazoline derivates (IDs) naphazoline (NPZ) and tetrahydrozoline (THZ) were investigated in aqueous solution. The process appears as important on biomedical grounds, considering that the vitamin is endogenously present in humans, and IDs are active components of ocular medicaments of topical application. Under aerobic visible light irradiation, a complex picture of competitive interactions between sensitizer, substrates and dissolved oxygen takes place: the singlet and triplet ((3)Rf*) excited states of Rf are quenched by the IDs: with IDs concentrations ca. 5.0 mM and 0.02 mM Rf, (3)Rf* is quenched by IDs, in a competitive fashion with dissolved ground state oxygen. Additionally, the reactive oxygen species: O(2)((1)Delta(g)), O(2)(*-), HO(*) and H(2)O(2), generated from (3)Rf* and Rf(*-), were detected with the employment of time-resolved methods or specific scavengers. Oxygen uptake experiments indicate that, for NPZ, only H(2)O(2) was involved in the photo-oxidation. In the case of THZ, O(2)(*-), HO(*) and H(2)O(2) were detected, whereas only HO(*) was unambiguously identified as THZ oxidative agents. Upon direct UV light irradiation NPZ and THZ generate O(2)((1)Delta(g)), with quantum yields of 0.2 (literature value, employed as a reference) and 0.08, respectively, in acetonitrile. PMID:19709378

  11. Quantification of reactive oxygen species generation by photoexcitation of PEGylated quantum dots.

    PubMed

    Yaghini, Elnaz; Pirker, Katharina F; Kay, Christopher W M; Seifalian, Alexander M; MacRobert, Alexander J

    2014-12-29

    Photocatalytic generation of reactive oxygen species (ROS) from quantum dots (QDs) has been widely reported yet quantitative studies of ROS formation and their quantum yields are lacking. This study investigates the generation of ROS by water soluble PEGylated CdSe/ZnS QDs with red emission. PEGylation of QDs is commonly used to confer water solubility and minimise uptake by organs of the reticuloendothelial system; therefore studies of ROS formation are of biomedical relevance. Using non-photolytic visible wavelength excitation, the superoxide anion radical is shown to be the primary ROS species generated with a quantum efficiency of 0.35%. The yield can be significantly enhanced in the presence of the electron donor, nicotinamide adenine dinucleotide (NADH), as demonstrated by oxygen consumption measurements and electron paramagnetic resonance spectroscopy with in situ illumination. Direct production of singlet oxygen is not detectable from the QDs alone. A comparison is made with ROS generation by the same QDs complexed with a sulfonated phthalocyanine which can generate singlet oxygen via Förster resonance energy transfer between the QDs and the phthalocyanine. PMID:25164061

  12. 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

  13. [Relationship between breaking of dormancy and reactive oxygen species metabolism in flower buds of pear].

    PubMed

    Shao, Hao; Ma, Feng-Wang

    2004-12-01

    The metabolism of reactive oxygen species in pear (Pyrus bretschneideri Rehd.) flower buds changes greatly during their natural dormancy in winter. The O(-.)(2) production rate increases rapidly during the period of dormancy, but decreases when dormancy finishes (Fig. 5). H(2)O(2) content goes up significantly at the early stage of dormancy, but afterwards falls gradually (Fig. 5). However, ascorbic acid (AsA) and reduced glutathione (GSH) contents show a different changing trend: descending at first and keeping at relatively low levels during the process of dormancy, but rising during breaking of dormancy (Fig. 4). The activities of superoxide dismutase (SOD), ascorbic peroxidase (APX) and glutathione reductase (GR) descend during the process of dormancy, but rise during breaking of dormancy, although at different rates for different enzymes (Figs. 1, 3). On the contrary, the activity of catalase (CAT) increases sharply at the beginning of dormancy, keeps at a stable high level during dormancy, and gradually decreases at the end of dormancy period (Fig. 2). The activity of peroxidase (POD) even keeps increasing during dormancy and breaking of dormancy (Fig. 1). The results show that the metabolism of reactive oxygen species has certain strong correlation with the natural dormancy of pear flower buds in winter. PMID:15643086

  14. Induction of the human oxidized base-specific DNA glycosylase NEIL1 by reactive oxygen species.

    PubMed

    Das, Aditi; Hazra, Tapas K; Boldogh, Istvan; Mitra, Sankar; Bhakat, Kishor K

    2005-10-21

    NEIL1, a mammalian DNA glycosylase and ortholog of Escherichia coli Nei/Fpg, is involved in the repair of oxidatively damaged bases in mammalian cells. Exposure of HCT116 human colon carcinoma cells to reactive oxygen species, generated by glucose oxidase (GO), enhanced the levels of NEIL1 mRNA and polypeptide by 2-4-fold by 6 h after GO treatment. A similar oxidative stress-induced increase in human NEIL1 (hNEIL1) promoter-dependent luciferase expression in HCT116 cells indicates that reactive oxygen species activates NEIL1 transcription. The transcriptional start site of hNEIL1 was mapped, and the upstream promoter sequence was characterized via luciferase reporter assay. Two identical CRE/AP-1-binding sites were identified in the promoter that binds transcription factors c-Jun and CREB/ATF2. This binding was significantly enhanced in extracts of cells treated with GO. Furthermore, a simultaneous increase in the level of phosphorylated c-Jun suggests its involvement in up-regulating the NEIL1 promoter. Oxidative stress-induced activation of NEIL1 appears to be involved in the feedback regulation of cellular repair activity needed to handle an increase in the level of oxidative base damage. PMID:16118226

  15. Dynamic Aspect of Reactive Oxygen and Nitric Oxide in Oral Cavity

    PubMed Central

    Sato, Eisuke F.; Choudhury, Tina; Nishikawa, Tomoko; Inoue, Masayasu

    2008-01-01

    Oral mucosa is a critical protective interface between external and internal environments. Therefore, it must serve as a barrier to a huge number of microbial species present in the environment. Saliva is an important factor that provides for the environment in the oral cavity, and it is indispensable to the host defense reaction in this manner. Oral neutrophils are also important contributors to maintaining the balance between health and disease in this complex environment. These produce reactive oxygen species, nitric oxide, and several antimicrobial peptides, and enzymes. Neutrophils and saliva all contribute to the maintaining the health of the oral cavity in overlapping but independent ways. In addition to production by neutrophils and macrophage, some bacteria can also generate superoxide, hydrogen peroxide, and nitric oxide. Dietary intake of nitrate-enriched vegetables might play important roles in the protection of the oral and stomach against hazardous pathogens via the gastro-intestinal-salivary cycle of nitric oxide (NO) and related metabolites. This review will focus on defense system of the human oral cavity and metabolism of reactive oxygen and NO. PMID:18231624

  16. Measurement of reactive oxygen metabolites produced by human monocyte-derived macrophages exposed to mineral dusts.

    PubMed Central

    Nyberg, P.; Klockars, M.

    1990-01-01

    The aim of the present work was to develop an in-vitro model for studying mineral dust-induced production of reactive oxygen metabolites by human macrophages. Monocytes isolated from human buffy coats were cultured in vitro for 1-6 days. Quartz particles induced both luminol- and lucigenin-dependent chemiluminescence (CL) by the adherent cells. However, the luminol response decreased form day to day, obviously due to a decrease in the myeloperoxidase (MPO) activity of the cells, whereas the lucigenin response showed no such MPO dependence. The luminol response was inhibited by superoxide dismutase (SOD), catalase, and the MPO-inhibitor azide, while the lucigenin response was inhibited by SOD and catalase but stimulated by azide. There was a positive correlation between the lucigenin responses and the results obtained with the established cytochrome c assay for superoxide, when opsonized zymosan was used as a stimulant. The effects of quartz, titanium dioxide, chrysotile asbestos, and wollastonite particles were investigated with the lucigenin assay. Quartz and chrysotile caused prominent light emission by 6-day-old macrophages, whereas titanium dioxide and wollastonite caused weak responses. We conclude that mineral dusts induce production of reactive oxygen metabolites by human monocyte-derived macrophages, and that the quantitative responses depend on both physical and physicochemical dust properties, the nature of which are still to be defined. PMID:2169299

  17. Novel Approach to Reactive Oxygen Species in Nontransfusion-Dependent Thalassemia

    PubMed Central

    Tyan, Paul I.; Radwan, Amr H.; Eid, Assaad; Haddad, Anthony G.; Wehbe, David; Taher, Ali T.

    2014-01-01

    The term Nontransfusion dependent thalassaemia (NTDT) was suggested to describe patients who had clinical manifestations that are too severe to be termed minor yet too mild to be termed major. Those patients are not entirely dependent on transfusions for survival. If left untreated, three main factors are responsible for the clinical sequelae of NTDT: ineffective erythropoiesis, chronic hemolytic anemia, and iron overload. Reactive oxygen species (ROS) generation in NTDT patients is caused by 2 major mechanisms. The first one is chronic hypoxia resulting from chronic anemia and ineffective erythropoiesis leading to mitochondrial damage and the second is iron overload also due to chronic anemia and tissue hypoxia leading to increase intestinal iron absorption in thalassemic patients. Oxidative damage by reactive oxygen species (generated by free globin chains and labile plasma iron) is believed to be one of the main contributors to cell injury, tissue damage, and hypercoagulability in patients with thalassemia. Independently increased ROS has been linked to a myriad of pathological outcomes such as leg ulcers, decreased wound healing, pulmonary hypertension, silent brain infarcts, and increased thrombosis to count a few. Interestingly many of those complications overlap with those found in NTDT patients. PMID:25121095

  18. Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation

    SciTech Connect

    Meeran, Syed M.; Katiyar, Suchitra [Department of Dermatology, University of Alabama at Birmingham (United States); Katiyar, Santosh K. [Department of Dermatology, University of Alabama at Birmingham (United States); Department of Environmental Health Sciences, University of Alabama at Birmingham (United States); Clinical Nutrition Research Center, University of Alabama at Birmingham (United States); Comprehensive Cancer Center, University of Alabama at Birmingham (United States); Birmingham VA Medical Center, Birmingham, AL, 35294 (United States)], E-mail: skatiyar@uab.edu

    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.

  19. Reactive oxygen species exacerbate autoimmune hemolytic anemia in New Zealand Black mice.

    PubMed

    Konno, Tasuku; Otsuki, Noriyuki; Kurahashi, Toshihiro; Kibe, Noriko; Tsunoda, Satoshi; Iuchi, Yoshihito; Fujii, Junichi

    2013-12-01

    Elevated reactive oxygen species (ROS) and oxidative damage occur in the red blood cells (RBCs) of SOD1-deficient C57BL/6 mice. This leads to autoimmune responses against RBCs in aged mice that are similar to autoimmune hemolytic anemia (AIHA). We examined whether a SOD1 deficiency and/or the human SOD1 transgene (hSOD1) would affect phenotypes of AIHA-prone New Zealand Black (NZB) mice by establishing three congenic strains: those lacking SOD1, those expressing hSOD1 under a GATA-1 promoter, and those lacking mouse SOD1 but expressing hSOD1. Levels of intracellular ROS and oxidative stress markers increased, and the severity of the AIHA phenotype was aggravated by a SOD1 deficiency. In contrast, the transgenic expression of hSOD1 in an erythroid cell-specific manner averted most of the AIHA phenotype evident in the SOD1-deficient mice and also ameliorated the AIHA phenotype in the mice possessing intrinsic SOD1. These data suggest that oxidative stress in RBCs may be an underlying mechanism for autoimmune responses in NZB mice. These results were consistent with the hypothetical role of reactive oxygen species in triggering the autoimmune reaction in RBCs and may provide a novel approach to mitigating the progression of AIHA by reducing oxidative stress. PMID:24095725

  20. Production of Reactive Oxygen Species from Dissolved Organic Matter Photolysis in Ice

    NASA Astrophysics Data System (ADS)

    Fede, A.; Grannas, A. M.

    2012-12-01

    Dissolved natural organic matter (DOM) is a ubiquitous component of natural waters and an important photosensitizer. A variety of reactive oxygen species (ROS) are known to be produced from DOM photolysis including singlet oxygen, hydroxyl radical, peroxyl radical, etc. Recently, it has been determined that organic material is one of the largest contributors to sunlight absorption in snowpack, however DOM photochemistry in snow/ice has received little attention in the literature. The production of ROS from DOM photolysis in snow/ice could play an important role in snowpack photochemical processes, degradation of pollutants in snowpack, and generation of volatile organic compounds emitted from snowpack. We have investigated ROS production from DOM in frozen aqueous solutions, using commercially available humic and fulvic acids. Here we will discuss the rates of ROS production in both liquid and frozen systems, differences in reactivity amongst the DOM sources studied (Suwannee River Humic Acid, Suwannee River Fulvic Acid, and Pony Lake Fulvic Acid), and the potential implications for snowpack photochemical processes.

  1. 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(^1?) 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.

  2. Reactive oxygen species as universal constraints in life-history evolution

    PubMed Central

    Dowling, Damian K.; Simmons, Leigh W.

    2009-01-01

    Evolutionary theory is firmly grounded on the existence of trade-offs between life-history traits, and recent interest has centred on the physiological mechanisms underlying such trade-offs. Several branches of evolutionary biology, particularly those focusing on ageing, immunological and sexual selection theory, have implicated reactive oxygen species (ROS) as profound evolutionary players. ROS are a highly reactive group of oxygen-containing molecules, generated as common by-products of vital oxidative enzyme complexes. Both animals and plants appear to intentionally harness ROS for use as molecular messengers to fulfil a wide range of essential biological processes. However, at high levels, ROS are known to exert very damaging effects through oxidative stress. For these reasons, ROS have been suggested to be important mediators of the cost of reproduction, and of trade-offs between metabolic rate and lifespan, and between immunity, sexual ornamentation and sperm quality. In this review, we integrate the above suggestions into one life-history framework, and review the evidence in support of the contention that ROS production will constitute a primary and universal constraint in life-history evolution. PMID:19324792

  3. Hypoxia-Induced Reactive Oxygen Species Cause Chromosomal Abnormalities in Endothelial Cells in the Tumor Microenvironment

    PubMed Central

    Hida, Yasuhiro; Maishi, Nako; Towfik, Alam Mohammad; Inoue, Nobuo; Shindoh, Masanobu; Hida, Kyoko

    2013-01-01

    There is much evidence that hypoxia in the tumor microenvironment enhances tumor progression. In an earlier study, we reported abnormal phenotypes of tumor-associated endothelial cells such as those resistant to chemotherapy and chromosomal instability. Here we investigated the role of hypoxia in the acquisition of chromosomal abnormalities in endothelial cells. Tumor-associated endothelial cells isolated from human tumor xenografts showed chromosomal abnormalities, >30% of which were aneuploidy. Aneuploidy of the tumor-associated endothelial cells was also shown by simultaneous in-situ hybridization for chromosome 17 and by immunohistochemistry with anti-CD31 antibody for endothelial staining. The aneuploid cells were surrounded by a pimonidazole-positive area, indicating hypoxia. Human microvascular endothelial cells expressed hypoxia-inducible factor 1 and vascular endothelial growth factor A in response to either hypoxia or hypoxia-reoxygenation, and in these conditions, they acquired aneuploidy in 7 days. Induction of aneuploidy was inhibited by either inhibition of vascular endothelial growth factor signaling with vascular endothelial growth factor receptor 2 inhibitor or by inhibition of reactive oxygen species by N-acetyl-L-cysteine. These results indicate that hypoxia induces chromosomal abnormalities in endothelial cells through the induction of reactive oxygen species and excess signaling of vascular endothelial growth factor in the tumor microenvironment. PMID:24260373

  4. Spontaneous generation of reactive oxygen species in the mixture of cyanide and glycerol.

    PubMed

    Chun, Yang-Sook; Yeo, Eun-Jin; Suh, Hwa-Jin; Park, Jong-Wan

    2004-12-01

    Reactive oxygen species are involved in tumor promotion or apoptosis. In assaying prooxidant or antioxidant activities, cyanide has been commonly used as an inhibitor of mitochondrial oxidases, peroxidases, or Cu,Zn-superoxide dismutase, which have an influence on intracellular levels of reactive oxygen species. It has also been used to chemically mimic hypoxia. On the other hand, glycerol has been widely used as a stabilizer of various enzymes. In particular, glycerol is required to maintain the enzymatic activities of membrane-bound NAD(P)H oxidases extracted from surrounding phospholipids. Since both cyanide and glycerol are relatively inert, they have been used concomitantly regardless of any mutual interference. In this study, we demonstrate that a mixture of glycerol and cyanide reduced cytochrome c and nitroblue tetrazolium, both of which are superoxide anion indicators. The mixture also enhanced the production of superoxide anion in the presence of redox-cycling compounds. Superoxide production by the mixture was confirmed by electron spin resonance spectra. Moreover, the mixture induced lipid peroxidation and hemolysis in human erythrocytes. These results suggest that cyanide and glycerol should be used carefully in reaction systems used to measure superoxide production or antioxidant activity. However, sucrose and sodium azide in combination do not produce such artifacts and thus may be used as an alternative. PMID:15659779

  5. Oxygen-17 NMR, Electronic, and Vibrational Spectroscopy of Transition Metal Peroxo Complexes: Correlation with Reactivity.

    PubMed

    Reynolds, Martha S.; Butler, Alison

    1996-04-10

    The (17)O NMR chemical shifts of several previously characterized mono- and diperoxo complexes of vanadium(V), molybdenum(VI), tungsten(VI), and titanium(IV) were measured. Compilation of NMR, electronic, and vibrational spectroscopic data and metric parameters for these and other complexes permits us to draw correlations among (17)O peroxo chemical shift, the electronic charge transfer band, the O-O vibrational frequency, and the length of the oxygen-oxygen bond. Monoperoxo complexes exhibit (17)O chemical shifts of 500-660 ppm, while those of diperoxo complexes fall in the range 350-460 ppm. The correlation of chemical shift with the inverse ligand-to-metal charge transfer energy from electronic spectra is consistent with a formalism developed by Ramsey, despite the variations in the metals, the number of peroxo ligands, and the nature of the remaining ligands in the coordination sphere. Vibrational frequency and length of the oxygen-oxygen bond also correlate with the inverse ligand-to-metal charge transfer energy. Monoperoxo complexes show values of nu(O)(-)(O) above 900 cm(-)(1) and O-O distances in the range 1.43-1.46 Å. Diperoxo complexes have values of nu(O)(-)(O) below 900 cm(-)(1) and O-O distances of 1.46-1.53 Å. The assignment of nu(O)(-)(O) = 910 cm(-)(1) for the infrared spectrum of ammonium aquaoxoperoxo(pyridine-2,6-dicarboxylato)vanadium(V), NH(4)[VO(O(2))(dipic)(H(2)O)], was made by isotopic substitution. The stretching frequency and length of the O-O bond for peroxo complexes are explained in terms of sigma-bonding between a metal d orbital and a peroxo pi orbital. A comparison of the spectroscopic properties of these complexes with their reactivity as oxidizing agents suggests that the strength of the O-O bond is an important factor. The most reactive species exhibit lambda(max) values below 400 nm, stretching frequencies below 900 cm(-)(1), and (17)O chemical shifts below 600 nm. These generalizations may permit the prediction of peroxometal reactivity from spectroscopic information. PMID:11666439

  6. Reactive oxygen species and serum antioxidant defense in juvenile idiopathic arthritis.

    PubMed

    Lipi?ska, Joanna; Lipi?ska, Stanis?awa; Sta?czyk, Jerzy; Sarniak, Agata; Przymi?ska Vel Prymont, Anna; Kasielski, Marek; Smolewska, El?bieta

    2015-03-01

    In autoimmune inflammatory diseases, including juvenile idiopathic arthritis (JIA), which leads to joint destruction, there is an imbalance between production of reactive oxygen species (ROS) and their neutralization which, as a consequence, leads to "oxidative stress." The aim of the study was to assess the concentration of oxidative stress markers: nitric oxide (NO), a degree of lipid membrane damage, and total antioxidant plasma capacity in children with JIA. Thirty-four children with JIA were included into the study. A degree of lipid membrane damage (lipid peroxidation products) was estimated as thiobarbituric acid-reactive substances (TBARs), NO concentration as NO end-products: nitrite/nitrate (NO2 (-)/NO3 (-)) and total antioxidant plasma capacity as ferric reducing ability of plasma (FRAP). NO2 (-)/NO3 (-) serum concentration in children with JIA was statistically significantly higher than that in healthy children (p?=?0.00069). There was no significant difference in TBAR levels between children with JIA and the control group. FRAP in sera of children with JIA was lower than that in healthy children, but the difference was not statistically significant. A statistically significant positive correlation was observed between NO end products and the 27-joint juvenile arthritis disease activity score (JADAS-27) and ESR, and a negative correlation was observed between FRAP and C-reactive protein (CRP) and white blood cell count (WBC). Our results confirm the increased oxidative stress in children with JIA. Overproduction of NO and decrease in the antioxidant plasma capacity may be involved in JIA pathogenesis. PMID:24651913

  7. Light-responsive polymer nanoreactors: a source of reactive oxygen species on demand

    NASA Astrophysics Data System (ADS)

    Baumann, Patric; Balasubramanian, Vimalkumar; Onaca-Fischer, Ozana; Sienkiewicz, Andrzej; Palivan, Cornelia G.

    2012-12-01

    Various domains present the challenges of responding to stimuli in a specific manner, with the desired sensitivity or functionality, and only when required. Stimuli-responsive systems that are appropriately designed can effectively meet these challenges. Here, we introduce nanoreactors that encapsulate photosensitizer-protein conjugates in polymer vesicles as a source of ``on demand'' reactive oxygen species. Vesicles made of poly(2-methyloxazoline)-poly(dimethylsiloxane)-poly(2-methyloxazoline) successfully encapsulated the photosensitizer Rose Bengal-bovine serum albumin conjugate (RB-BSA) during a self-assembly process, as demonstrated by UV-Vis spectroscopy. A combination of light scattering and transmission electron microscopy indicated that the nanoreactors are stable over time. They serve a dual role: protecting the photosensitizer in the inner cavity and producing in situ reactive oxygen species (ROS) upon irradiation with appropriate electromagnetic radiation. Illumination with appropriate wavelength light allows us to switch on/off and to control the production of ROS. Because of the oxygen-permeable nature of the polymer membrane of vesicles, ROS escape into the environment around vesicles, as established by electron paramagnetic resonance. The light-sensitive nanoreactor is taken up by HeLa cells in a Trojan horse fashion: it is nontoxic and, when irradiated with the appropriate laser light, produces ROS that induce cell death in a precise area corresponding to the irradiation zone. These nanoreactors can be used in theranostic approaches because they can be detected via the fluorescent photosensitizer signal and simultaneously produce ROS efficiently ``on demand''.Various domains present the challenges of responding to stimuli in a specific manner, with the desired sensitivity or functionality, and only when required. Stimuli-responsive systems that are appropriately designed can effectively meet these challenges. Here, we introduce nanoreactors that encapsulate photosensitizer-protein conjugates in polymer vesicles as a source of ``on demand'' reactive oxygen species. Vesicles made of poly(2-methyloxazoline)-poly(dimethylsiloxane)-poly(2-methyloxazoline) successfully encapsulated the photosensitizer Rose Bengal-bovine serum albumin conjugate (RB-BSA) during a self-assembly process, as demonstrated by UV-Vis spectroscopy. A combination of light scattering and transmission electron microscopy indicated that the nanoreactors are stable over time. They serve a dual role: protecting the photosensitizer in the inner cavity and producing in situ reactive oxygen species (ROS) upon irradiation with appropriate electromagnetic radiation. Illumination with appropriate wavelength light allows us to switch on/off and to control the production of ROS. Because of the oxygen-permeable nature of the polymer membrane of vesicles, ROS escape into the environment around vesicles, as established by electron paramagnetic resonance. The light-sensitive nanoreactor is taken up by HeLa cells in a Trojan horse fashion: it is nontoxic and, when irradiated with the appropriate laser light, produces ROS that induce cell death in a precise area corresponding to the irradiation zone. These nanoreactors can be used in theranostic approaches because they can be detected via the fluorescent photosensitizer signal and simultaneously produce ROS efficiently ``on demand''. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr32380j

  8. Enhancement of reactive oxygen species and induction of apoptosis in streptozotocin-induced diabetic rats under hyperbaric oxygen exposure

    PubMed Central

    Matsunami, Tokio; Sato, Yukita; Hasegawa, Yuki; Ariga, Satomi; Kashimura, Haruka; Sato, Takuya; Yukawa, Masayoshi

    2011-01-01

    An important source of reactive oxygen species (ROS) production is nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which on activation induces superoxide production via oxidation in the mitochondria, inflammation and stress; such ROS are implicated in the pathogenesis of diabetic complications, including neuropathy. Hyperbaric oxygen (HBO) treatments are applied various diseases including diabetic patients with unhealing foot ulcers, however, and also increases the formation of ROS. In a previous study, we showed that a clinically recommended HBO treatment significantly enhanced oxidative stress of pancreatic tissue in the diabetic rats. However, no study has been undertaken with regard to the effects of HBO on the activity and gene expression of the NADPH oxidase complex and on apoptosis in the pancreas of diabetic animals. The purpose of this study was to investigate the effect of HBO exposure on gene expression of the NADPH complex, and pancreatic expression of genes related to apoptosis via the mitochondria, using the NADPH oxidase inhibitor apocynin. The mRNA expression of genes related to NADPH oxidase complex and apoptosis increased significantly (P < 0.05) in the pancreas of diabetic rats under HBO exposure. Similarly, activities of NADPH oxidase and caspase-3 changed in parallel with mRNA levels. These results suggest that oxidative stress caused by HBO exposure in diabetic animals induces further ROS production and apoptosis, potentially through the up-regulation of NADPH oxidase complex. Thus, this study can contribute to development of a better understanding of the molecular mechanisms of apoptosis via the mitochondria in diabetes, under HBO exposure. PMID:21487521

  9. Reactive oxygen species mediated diaphragm fatigue in a rat model of chronic intermittent hypoxia.

    PubMed

    Shortt, Christine M; Fredsted, Anne; Chow, Han Bing; Williams, Robert; Skelly, J Richard; Edge, Deirdre; Bradford, Aidan; O'Halloran, Ken D

    2014-04-01

    Respiratory muscle dysfunction documented in sleep apnoea patients is perhaps due to oxidative stress secondary to chronic intermittent hypoxia (CIH). We sought to explore the effects of different CIH protocols on respiratory muscle form and function in a rodent model. Adult male Wistar rats were exposed to CIH (n = 32) consisting of 90 s normoxia-90 s hypoxia (either 10 or 5% oxygen at the nadir; arterial O2 saturation ? 90 or 80%, respectively] for 8 h per day or to sham treatment (air-air, n = 32) for 1 or 2 weeks. Three additional groups of CIH-treated rats (5% O2 for 2 weeks) had free access to water containing N-acetyl cysteine (1% NAC, n = 8), tempol (1 mM, n = 8) or apocynin (2 mM, n = 8). Functional properties of the diaphragm muscle were examined ex vivo at 35 °C. The myosin heavy chain and sarco(endo)plasmic reticulum Ca(2+)-ATPase isoform distribution, succinate dehydrogenase and glyercol phosphate dehydrogenase enzyme activities, Na(+)-K(+)-ATPase pump content, concentration of thiobarbituric acid reactive substances, DNA oxidation and antioxidant capacity were determined. Chronic intermittent hypoxia (5% oxygen at the nadir; 2 weeks) decreased diaphragm muscle force and endurance. All three drugs reversed the deleterious effects of CIH on diaphragm endurance, but only NAC prevented CIH-induced diaphragm weakness. Chronic intermittent hypoxia increased diaphragm muscle myosin heavy chain 2B areal density and oxidized glutathione/reduced glutathione (GSSG/GSH) ratio. We conclude that CIH-induced diaphragm dysfunction is reactive oxygen species dependent. N-Acetyl cysteine was most effective in reversing CIH-induced effects on diaphragm. Our results suggest that respiratory muscle dysfunction in sleep apnoea may be the result of oxidative stress and, as such, antioxidant treatment could prove a useful adjunctive therapy for the disorder. PMID:24443349

  10. Age-related increase of reactive oxygen generation in the brains of mammals and birds: is reactive oxygen a signaling molecule to determine the aging process and life span?

    PubMed

    Sasaki, Toru; Unno, Keiko; Tahara, Shoichi; Kaneko, Takao

    2010-07-01

    Since Harman proposed the "free-radical theory of aging", oxidative stress has been postulated to be a major causal factor of senescence. The accumulation of oxidative stress-induced oxidatively modified macromolecules, including protein, DNA and lipid, were found in tissues during the aging process; however, it is not necessarily clear which factor is more critical, an increase in endogenous reactive oxygen and/or a decrease in anti-oxidative defense, to the age-related increase in oxidative damage. To clarify the increasing production of reactive oxygen with age, we examined reactive oxygen-dependent chemiluminescent (CL) signals in ex vivo brain slices prepared from different-aged animal brains during hypoxia-reoxygenation treatment using a novel photonic imaging method. The CL signal was intensified during reoxygenation. The signals in SAMP10 (short-life strain) and SAMR1 (control) brain slices increased with aging. The slope of the increase of CL intensity with age in P10 was steeper than in R1. Age-dependent increase of CL intensity was also observed in C57BL/6 mice, Wistar rats and pigeons; however, superoxide dismutase (SOD) activity in the brain did not change with age. These results suggest that reactive oxygen production itself increased with aging. The rate of age-related increases of CL intensity was inversely related to the maximum lifespan of animals. We speculate that reactive oxygen might be a signaling molecule and its levels in tissue might determine the aging process and lifespan. Decelerating age-related increases of reactive oxygen production are expected to be a potent strategy for anti-aging interventions. PMID:20590825

  11. Role of reactive oxygen species in Escherichia coli inactivation by cupric ion.

    PubMed

    Park, Hee-Jin; Nguyen, Thuy T M; Yoon, Jeyong; Lee, Changha

    2012-10-16

    This study demonstrated Escherichia coli inactivation by cupric ion (Cu[II]), focusing on intracellular generation and consumption of reactive oxygen species (ROS) including superoxide and hydroxyl radials. In the presence of Cu(II), intracellular superoxide levels of E. coli decreased in a concentration-dependent manner, indicating that superoxide radical was used to reduce Cu(II) to Cu(I) in cells. The variation in the hydroxyl radical level by adding Cu(II) was negligible. Molecular oxygen and hydroxyl radical scavengers did not affect the inactivation efficacy of E. coli by Cu(II), excluding the possibility that hydroxyl radicals induced by the copper-mediated reduction of oxygen contributed to the microbiocidal action of Cu(II). However, the inactivation of E. coli by Cu(II) was considerably inhibited and accelerated by a Cu(I)-chelating agent and a Cu(II)-reducing agent, respectively. Our results suggest that the microbiocidal action of Cu(II) is attributable to the cytotoxicity of cellularly generated Cu(I), which does not appear to be associated with oxidative damage by Cu(I)-driven ROS. PMID:22998466

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

    PubMed Central

    Waris, Gulam; Ahsan, Haseeb

    2006-01-01

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

  13. Hypoxia-inducible Factor ? Subunit Stabilization by NEDD8 Conjugation Is Reactive Oxygen Species-dependent*

    PubMed Central

    Ryu, Ji-Hye; Li, Shan-Hua; Park, Hyoung-Sook; Park, Jong-Wan; Lee, ByungLan; Chun, Yang-Sook

    2011-01-01

    Hypoxia-inducible factor ? proteins (HIF-?s) are regulated oxygen dependently and transactivate numerous genes essential for cellular adaptation to hypoxia. NEDD8, a member of the ubiquitin-like family, covalently binds to its substrate proteins, and thus, regulates their stabilities and functions. In the present study, we examined the possibility that the HIF signaling is regulated by the neddylation. HIF-1? expression and activity were inhibited by knocking down APPBP1 E1 enzyme for NEDD8 conjugation but enhanced by ectopically expressing NEDD8. HIF-1? and HIF-2? were identified to be covalently modified by NEDD8. NEDD8 stabilized HIF-1? even in normoxia and further increased its level in hypoxia, which also occurred in von Hippel-Lindau (VHL) protein- or p53-null cell lines. The HIF-1?-stabilizing effect of NEDD8 was diminished by antioxidants and mitochondrial respiratory chain blockers. This suggests that the NEDD8 effect is concerned with reactive oxygen species driven from mitochondria rather than with the prolyl hydroxylase (PHD)/VHL-dependent oxygen-sensing system. Based on these findings, we propose that NEDD8 is an ancillary player to regulate the stability of HIF-1?. Furthermore, given the positive role played by HIF-?s in cancer promotion, the NEDD8 conjugation process could be a potential target for cancer therapy. PMID:21193393

  14. Iron-induced tissue damage and cancer: the role of reactive oxygen species-free radicals.

    PubMed

    Okada, S

    1996-05-01

    Oxygen is poisonous, but we cannot live without it. The high oxidizing potential of oxygen molecules (dioxygen) is a valuable source of energy for the organism and its reactivity is low; that is, spin forbidden. However, the dioxygen itself is a 'free radical' and, especially in the presence of transition metals, it is a major promoter of radical reactions in the cell. Humans survive only by virtue of their elaborate defense mechanisms against oxygen toxicity. Iron is the most abundant transition metal in the human body. Because iron shows wide variation in redox potential with different co-ordination ligands, it may be used as a redox intermediate in many biological mechanism. However, it is precisely this redox activeness that makes iron a key participant in free radical production. The current research on the relationship between iron and cancer is briefly reviewed. Research results are reported here which indicate that iron, when bound to certain ligands, can cause free-radical mediated tissue damage and become carcinogenic. The present study also suggests that iron may also have a significant role in spontaneous human cancer. PMID:8809878

  15. [Microcirculatory hemodynamics in oral tissues with reference to neurogenic response and reactive oxygen species interaction].

    PubMed

    Okabe, E; Todoki, K

    1999-04-01

    The primary purpose of the microcirculation is to transport nutrients and oxygen and to remove metabolic waste products from tissues. It is also well known that the fundamental mechanism for vascular control is the local regulation of the basal vascular tone, which is reinforced by blood pressure and counteracted by tissue metabolites. Thus, the well-being of the tissue depends on the circulatory transport process, which is governed by many functional parameters of the microcirculation such as blood flow, blood volume, intravascular and extravascular pressures, and capillary permeability. Inflammatory reactions in oral tissues can be initiated by many different insults to the tissues, and the reaction itself can be expressed in various ways. In addition, the tissues seem to have many "backup" systems, so that any one response can be produced in several ways, which is important for a reaction that has a survival value. A recent concept is that repeated stimulation of sensitive teeth may induce pulpal changes; this could occur through induction of neurogenic inflammation and alteration of pulpal blood flow. One possibility is that production of reactive oxygen species, as well as release of the sensory neuropeptides, at sites of inflammation contributes to alterations in local blood flow. In addition to the part played by the neurogenic mediators, nitric oxide participation and its interaction with oxygen-derived free radicals in oral tissue hemodynamics are also discussed. PMID:10412160

  16. Reactivity in oxygen and carbon dioxide of char formed in the pyrolysis of refuse-derived fuel

    SciTech Connect

    Cozzani, V.

    2000-04-01

    The reactivity in oxygen and carbon dioxide of chars obtained from the pyrolysis of a refuse-derived fuel (RDF) was investigated. RDF chars were obtained in a fixed-bed pyrolysis reactor at low heating rates (60 C/min) and temperatures between 500 and 800 C. The heterogeneous gasification kinetics of the chars were studied using thermogravimetric methods and were compared to data available in the literature. The RDF chars were found to have a reactivity quite similar to that of chars obtained from municipal solid wastes and wood, but higher than that of graphite of about 5 orders of magnitude in oxygen. Raising the final temperature of the pyrolysis process from 500 to 800 C resulted in the decrease of the H/C ratio and in a significantly lower reactivity in oxygen of the char.

  17. 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

  18. Glutathione, Glutathione S-Transferase and Reactive Oxygen Species of Human Scalp Sebaceous Glands in Male Pattern Baldness

    Microsoft Academic Search

    Montserrat Giralt; Isabel Cervello; María Rosa Nogues; Antonia María Puerto; Francesca Ortin; Núria Argany; Jordi Mallol

    1996-01-01

    We investigated the contribution of reactive oxygen species to the development of sebaceous gland hyperplasia and the characteristics of the glutathione S-transferase\\/glutathione system in male pattern baldness. Glutathione S-transferase, glutathione, and thiobarbituric acid-reactive substances were determined in sebaceous gland-enriched scalp skin of men affected by male pattern baldness and were subjected to hair autotransplantation. In comparison with the hairy occipital-donor

  19. Chemical kinetics and reactive species in atmospheric pressure helium-oxygen plasmas with humid-air impurities

    NASA Astrophysics Data System (ADS)

    Murakami, Tomoyuki; Niemi, Kari; Gans, Timo; O'Connell, Deborah; Graham, William G.

    2013-02-01

    In most applications helium-based plasma jets operate in an open-air environment. The presence of humid air in the plasma jet will influence the plasma chemistry and can lead to the production of a broader range of reactive species. We explore the influence of humid air on the reactive species in radio frequency (rf)-driven atmospheric-pressure helium-oxygen mixture plasmas (He-O2, helium with 5000 ppm admixture of oxygen) for wide air impurity levels of 0-500 ppm with relative humidities of from 0% to 100% using a zero-dimensional, time-dependent global model. Comparisons are made with experimental measurements in an rf-driven micro-scale atmospheric pressure plasma jet and with one-dimensional semi-kinetic simulations of the same plasma jet. These suggest that the plausible air impurity level is not more than hundreds of ppm in such systems. The evolution of species concentration is described for reactive oxygen species, metastable species, radical species and positively and negatively charged ions (and their clusters). Effects of the air impurity containing water humidity on electronegativity and overall plasma reactivity are clarified with particular emphasis on reactive oxygen species.

  20. Impact of oxygen addition during enological fermentation on sterol contents in yeast lees and their reactivity towards oxygen

    Microsoft Academic Search

    Caroline Fornairon-Bonnefond; Evelyne Aguera; Christelle Deytieux; Jean-Marie Sablayrolles; Jean-Michel Salmon

    2003-01-01

    During enological fermentations, superfluous oxygen consumption by yeast cells is observed. The superfluous oxygen consumed by the yeast cells is mainly related to the operation of non-respiratory oxygen consumption pathways resulting in an overall decrease in the total sterol fraction in yeast. On the other hand, yeast lees remaining at the end of alcoholic fermentations exhibit specific oxygen utilization rates

  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. The Requirement of Reactive Oxygen Intermediates for Lymphocytic Choriomeningitis Virus Binding and Growth1

    PubMed Central

    Michalek, Ryan D.; Pellom, S. Troy; Holbrook, Beth C.; Grayson, Jason M.

    2008-01-01

    Multiple viruses induce reactive oxygen intermediate (ROI) generation during infection that plays an important role in growth. We have examined the importance of ROI during lymphocytic choriomeningitis virus (LCMV) infection of immortalized BHK-21 cells and murine peritoneal macrophages. Within 15 minutes of virus addition, intracellular ROI levels increased. To examine the contribution of ROI to LCMV infection, cells were pretreated with antioxidant prior to virus addition. Antioxidant treatment inhibited low and high MOI growth of virus. The requirement for ROI was greatest during the initial phase of infection, as antioxidant treatment after six hours post infection had a weaker inhibitory effect. Furthermore, antioxidant treatment of cells inhibited virus binding, while treatment of virus stocks with N-ethyl malemide, which blocks free thiols, eliminated infectious virus. This illustrates that ROI are critical to the regulation of virus binding and growth and has important implications for understanding the infectivity of related viruses. PMID:18691729

  3. Pharmacology of Free Radicals and the Impact of Reactive Oxygen Species on the Testis

    PubMed Central

    Aprioku, Jonah Sydney

    2013-01-01

    The role of free radicals in normal cellular functions and different pathological conditions has been a focus of pharmacological studies in the recent past. Reactive oxygen species (ROS) and free radicals in general are essential for cell signaling and other vital physiological functions; however, excessive amounts can cause alteration in cellular reduction-oxidation (redox) balance, and disrupt normal biological functions. When there is an imbalance between activities of ROS and antioxidant/scavenging defense systems, oxidative stress (OS) occurs. A good number of studies have shown OS is involved in the development of several disease conditions, including male infertility. In the present article, generation of free radicals and their effects, as well as the mechanisms of antioxidant/scavenging defense systems are discussed, with particular focus on the testis. The review also discusses the contribution of OS on testicular dysfunction and briefly focuses on some OS-induced conditions that will alter testicular function. PMID:24551570

  4. 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.

  5. Symbiotic lactobacilli stimulate gut epithelial proliferation via Nox-mediated generation of reactive oxygen species

    PubMed Central

    Jones, Rheinallt M; Luo, Liping; Ardita, Courtney S; Richardson, Arena N; Kwon, Young Man; Mercante, Jeffrey W; Alam, Ashfaqul; Gates, Cymone L; Wu, Huixia; Swanson, Phillip A; Lambeth, J David; Denning, Patricia W; Neish, Andrew S

    2013-01-01

    The resident prokaryotic microbiota of the metazoan gut elicits profound effects on the growth and development of the intestine. However, the molecular mechanisms of symbiotic prokaryotic–eukaryotic cross-talk in the gut are largely unknown. It is increasingly recognized that physiologically generated reactive oxygen species (ROS) function as signalling secondary messengers that influence cellular proliferation and differentiation in a variety of biological systems. Here, we report that commensal bacteria, particularly members of the genus Lactobacillus, can stimulate NADPH oxidase 1 (Nox1)-dependent ROS generation and consequent cellular proliferation in intestinal stem cells upon initial ingestion into the murine or Drosophila intestine. Our data identify and highlight a highly conserved mechanism that symbiotic microorganisms utilize in eukaryotic growth and development. Additionally, the work suggests that specific redox-mediated functions may be assigned to specific bacterial taxa and may contribute to the identification of microbes with probiotic potential. PMID:24141879

  6. Reactive oxygen species (ROS) production by amoebocytes of Asterias rubens (Echinodermata).

    PubMed

    Coteur, Geoffroy; Warnau, Michel; Jangoux, Michel; Dubois, Philippe

    2002-03-01

    An adapted peroxidase, luminol-enhanced chemiluminescence method in an EDTA-free, Ca++-containing medium is described and used to characterise reactive oxygen species (ROS) production by starfish immunocytes using a standard microplate reader luminometer. ROS production was stimulated by direct interaction of immunocytes with bacteria or bacterial wall components, but not by the soluble stimulant PMA nor the lectin concanavalin A. Produced ROS detected by this method are apparently superoxide anions, hydrogen peroxide and peroxynitrite. Comparison with other chemiluminescence methods indicates that the described method is the only one to detect the stimulation of starfish immunocytes by the Gram-positive bacteria, Micrococcus luteus, a fact that questions previous reports indicating a lack of stimulation by pathogens. The adapted method provides a rapid determination of the overall ROS production, which is suitable for both disease control and immunotoxicological studies in echinoderms. PMID:11931015

  7. Angiotensin-II-derived reactive oxygen species on baroreflex sensitivity during hypertension: new perspectives

    PubMed Central

    de Queiroz, Thyago M.; Monteiro, Matheus M. O.; Braga, Valdir A.

    2013-01-01

    Hypertension is a multifactorial disorder, which has been associated with the reduction in baroreflex sensitivity (BRS) and autonomic dysfunction. Several studies have revealed that increased reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase, following activation of type 1 receptor (AT1R) by Angiotensin-(Ang) II, the main peptide of the Renin–Angiotensin–Aldosterone System (RAAS), is the central mechanism involved in Ang-II-derived hypertension. In the present review, we will discuss the role of Ang II and oxidative stress in hypertension, the relationship between the BRS and the genesis of hypertension and how the oxidative stress triggers baroreflex dysfunction in several models of hypertension. Finally, we will describe some novel therapeutic drugs for improving the BRS during hypertension. PMID:23717285

  8. Reversible inactivation of deubiquitinases by reactive oxygen species in vitro and in cells

    PubMed Central

    Lee, Jin-Gu; Baek, Kheewoong; Soetandyo, Nia; Ye, Yihong

    2013-01-01

    In eukaryotes, deubiquitinases (DUBs) remove ubiquitin conjugates from diverse substrates, altering their stabilities, localizations or activities. Here we show that many DUBs of the USP and UCH subfamilies can be reversibly inactivated upon oxidation by reactive oxygen species in vitro and in cells. Oxidation occurs preferentially on the catalytic cysteine, abrogating the isopeptide-cleaving activity without affecting these enzymes’ affinity to ubiquitin. Sensitivity to oxidative inhibition is associated with DUB activation wherein the active site cysteine is converted to a deprotonated state prone to oxidation. We demonstrate that this redox regulation is essential for mono-ubiquitination of proliferating-cell nuclear antigen in response to oxidative DNA damage, which initiates a DNA damage-tolerance programme. These findings establish a novel mechanism of DUB regulation that may be integrated with other redox-dependent signalling circuits to govern cellular adaptation to oxidative stress, a process intimately linked to aging and cancer. PMID:23463011

  9. Effects of Surface Chemistry on the Generation of Reactive Oxygen Species by Copper Nanoparticles

    PubMed Central

    Shi, Miao; Kwon, Hyun Soo; Peng, Zhenmeng; Elder, Alison; Yang, Hong

    2012-01-01

    Mercaptocarboxylic acids with different carbon chain lengths were used for stabilizing uniform 15 nm copper nanoparticles. The effects of surface chemistry such as ligand type and surface oxidation on the reactive oxygen species (ROS) generated by the copper nanoparticles were examined. Transmission electron microscopy (TEM), Powder X-ray diffraction (PXRD), UV-vis spectroscopy, and an acellular ROS assay show that ROS generation is closely related to the surface oxidation of copper nanoparticles. It was found that the copper nanoparticles with longer chain ligands had surfaces that were better protected from oxidation and a corresponding lower ROS generating capacity than did particles with shorter chain ligands. Conversely, the copper nanoparticles with greater surface oxidation also had higher ROS generating capacity. PMID:22390268

  10. Mitochondrial reactive oxygen species regulate the strength of inhibitory GABA-mediated synaptic transmission

    NASA Astrophysics Data System (ADS)

    Accardi, Michael V.; Daniels, Bryan A.; Brown, Patricia M. G. E.; Fritschy, Jean-Marc; Tyagarajan, Shiva K.; Bowie, Derek

    2014-01-01

    Neuronal communication imposes a heavy metabolic burden in maintaining ionic gradients essential for action potential firing and synaptic signalling. Although cellular metabolism is known to regulate excitatory neurotransmission, it is still unclear whether the brain’s energy supply affects inhibitory signalling. Here we show that mitochondrial-derived reactive oxygen species (mROS) regulate the strength of postsynaptic GABAA receptors at inhibitory synapses of cerebellar stellate cells. Inhibition is strengthened through a mechanism that selectively recruits ?3-containing GABAA receptors into synapses with no discernible effect on resident ?1-containing receptors. Since mROS promotes the emergence of postsynaptic events with unique kinetic properties, we conclude that newly recruited ?3-containing GABAA receptors are activated by neurotransmitter released onto discrete postsynaptic sites. Although traditionally associated with oxidative stress in neurodegenerative disease, our data identify mROS as a putative homeostatic signalling molecule coupling cellular metabolism to the strength of inhibitory transmission.

  11. Salicylic acid and reactive oxygen species interplay in the transcriptional control of defense genes expression

    PubMed Central

    Herrera-Vásquez, Ariel; Salinas, Paula; Holuigue, Loreto

    2015-01-01

    It is well established that salicylic acid (SA) plays a critical role in the transcriptional reprograming that occurs during the plant defense response against biotic and abiotic stress. In the course of the defense response, the transcription of different sets of defense genes is controlled in a spatio-temporal manner via SA-mediated mechanisms. Interestingly, different lines of evidence indicate that SA interplays with reactive oxygen species (ROS) and glutathione (GSH) in stressed plants. In this review we focus on the evidence that links SA, ROS, and GSH signals to the transcriptional control of defense genes. We discuss how redox modifications of regulators and co-regulators involved in SA-mediated transcriptional responses control the temporal patterns of gene expression in response to stress. Finally, we examine how these redox sensors are coordinated with the dynamics of cellular redox changes occurring in the defense response to biotic and abiotic stress. PMID:25852720

  12. Reactive oxygen intermediates metabolizing enzymes in Ancylostoma ceylanicum and Nippostrongylus brasiliensis.

    PubMed

    Batra, S; Singh, S P; Gupta, S; Katiyar, J C; Srivastava, V M

    1990-01-01

    Adult worms of Ancylostoma ceylanicum and Nippostronglyus brasiliensis were found to possess an active system for the detoxification of reactive oxygen intermediates. Xanthine oxidase, which is known to produce superoxide anion, was detected in both the nematode parasites in significant activities. Superoxide anion, thus produced, may quickly be eliminated by superoxide dismutase. Both parasites also exhibited the presence of catalase, peroxidase, and glutathione peroxidase for efficient removal of hydrogen peroxide. Glutathione reductase and glucose-6-phosphate dehydrogenase were, however, detected in low levels of activities. Endowment of A. ceylanicum and N. brasiliensis with these antioxidant enzymes, therefore, enables them to evade the host's effector mechanism for their survival. Superoxide dismutase of both these nematodes showed marked inhibition by KCN and, hence, the enzyme appears to be of copper-zinc type. PMID:2341058

  13. Superhydrophilic TiO{sub 2} surfaces generated by reactive oxygen treatment

    SciTech Connect

    Ishida, Nobuyuki; Fujita, Daisuke [Global Research Center for Environment and Energy based on Nanomaterials Science (GREEN), National Institute for Materials Science, 1-2-1 Sengen, Tsukuba, Ibaraki 305-0047 (Japan); Global Research Center for Environment and Energy based on Nanomaterials Science (GREEN), National Institute for Materials Science, 1-2-1 Sengen, Tsukuba, Ibaraki 305-0047 (Japan) and Advanced Nanocharacterization Unit, National Institute for Materials Science, 1-2-1 Sengen, Tsukuba, Ibaraki 305-0047 (Japan)

    2012-09-15

    The authors show that superhydrophilic TiO{sub 2} can be obtained without irradiation of the surface with ultraviolet (UV) light and concomitant excitation of electron-hole pairs. The authors demonstrate that the treatment of TiO{sub 2} surfaces with reactive oxygen species generated by air plasma removes the surface organic contaminants, leading to almost 0 Degree-Sign contact-angle wetting of the surface. The superhydrophilicity can be explained by the positive spreading coefficient calculated using the effective surface tensions. Our results point toward UV-light irradiation as an indirect cause of the superhydrophilicity of TiO{sub 2} and support the hypothesis that this property arises from a self-cleaning effect based on the photo-oxidation and decomposition of organic contaminants at the surface.

  14. Reactive oxygen species-inducing antifungal agents and their activity against fungal biofilms.

    PubMed

    Delattin, Nicolas; Cammue, Bruno P A; Thevissen, Karin

    2014-01-01

    Invasive fungal infections are associated with very high mortality rates ranging from 20-90% for opportunistic fungal pathogens such as Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. Fungal resistance to antimycotic treatment can be genotypic (due to resistant strains) as well as phenotypic (due to more resistant fungal lifestyles, such as biofilms). With regard to the latter, biofilms are considered to be critical in the development of invasive fungal infections. However, there are only very few antimycotics, such as miconazole (azoles), echinocandins and liposomal formulations of amphotericin B (polyenes), which are also effective against fungal biofilms. Interestingly, these antimycotics all induce reactive oxygen species (ROS) in fungal (biofilm) cells. This review provides an overview of the different classes of antimycotics and novel antifungal compounds that induce ROS in fungal planktonic and biofilm cells. Moreover, different strategies to further enhance the antibiofilm activity of such ROS-inducing antimycotics will be discussed. PMID:24358949

  15. Role of Reactive Oxygen Species in Pathogenesis of Radiocontrast-Induced Nephropathy

    PubMed Central

    Pisani, Antonio; Faga, Teresa; Ashour, Michael; Di Nuzzi, Antonella; Mancini, Aldo

    2013-01-01

    In vitro and in vivo studies have demonstrated enhanced hypoxia and formation of reactive oxygen species (ROS) in the kidney following the administration of iodinated contrast media, which play a relevant role in the development of contrast media-induced nephropathy. Many studies indeed support this possibility, suggesting a protective effect of ROS scavenging or reduced ROS formation with the administration of N-acetylcysteine and bicarbonate infusion, respectively. Furthermore, most risk factors, predisposing to contrast-induced nephropathy, are prone to enhanced renal parenchymal hypoxia and ROS formation. In this review, the association of renal hypoxia and ROS-mediated injury is outlined. Generated during contrast-induced renal parenchymal hypoxia, ROS may exert direct tubular and vascular endothelial injury and might further intensify renal parenchymal hypoxia by virtue of endothelial dysfunction and dysregulation of tubular transport. Preventive strategies conceivably should include inhibition of ROS generation or ROS scavenging. PMID:24459673

  16. Reactive oxygen species and upregulation of NADPH oxidases in mechanotransduction of embryonic stem cells.

    PubMed

    Sauer, Heinrich; Ruhe, Carola; Müller, Jörg P; Schmelter, Maike; D'Souza, Rochelle; Wartenberg, Maria

    2008-01-01

    Deciphering the differentiation pathway of embryonic stem (ES) cells is a challenging task not only for basic research, but also for clinicians who intend to use ES cells for cell transplantation approaches. We have shown that reactive oxygen species (ROS) play a primordial role in the differentiation of mouse ES cells toward the cardiovascular cell lineage. During differentiation, ES cells robustly generate ROS, which interfere with signaling pathways that direct cardiac and vascular commitment. Differentiating ES cells expression of Nox-1, Nox-2, and Nox-4 has been demonstrated. We have shown that mechanical strain application to embyoid bodies grown from ES cells initiates the cardiovascular differentiation program. Under these conditions, a burst of ROS generation occurs which is followed by induction of Nox-1 and Nox-4 and a feed-forward upregulation of ROS production. PMID:19082963

  17. Polyglutamine expansion inhibits respiration by increasing reactive oxygen species in isolated mitochondria

    SciTech Connect

    Puranam, Kasturi L. [Deane Laboratory, Department of Medicine, Division of Neurology, Duke University Medical Center, Durham, NC 27710 (United States); Wu, Guanghong [Deane Laboratory, Department of Medicine, Division of Neurology, Duke University Medical Center, Durham, NC 27710 (United States); Strittmatter, Warren J. [Deane Laboratory, Department of Medicine, Division of Neurology, Duke University Medical Center, Durham, NC 27710 (United States); Burke, James R. [Deane Laboratory, Department of Medicine, Division of Neurology, Duke University Medical Center, Durham, NC 27710 (United States)]. 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-length PolyQ protein causes neurodegeneration is unclear, mitochondria appear central in pathogenesis. We demonstrate in isolated mitochondria that pathologic-length PolyQ protein directly inhibits ADP-dependent (state 3) mitochondrial respiration. Inhibition of mitochondrial respiration by PolyQ protein is not due to reduction in the activities of electron transport chain complexes, mitochondrial ATP synthase, or the adenine nucleotide translocase. We show that pathologic-length PolyQ protein increases the production of reactive oxygen species in isolated mitochondria. Impairment of state 3 mitochondrial respiration by PolyQ protein is reversed by addition of the antioxidants N-acetyl-L-cysteine or cytochrome c. We propose a model in which pathologic-length PolyQ protein directly inhibits mitochondrial function by inducing oxidative stress.

  18. Chemical reactivity of hydrogen, nitrogen, and oxygen atoms at temperatures below 100 k

    NASA Technical Reports Server (NTRS)

    Mcgee, H. A., Jr.

    1973-01-01

    The synthesis of unusual compounds by techniques employing cryogenic cooling to retard their very extreme reactivity was investigated. Examples of such species that were studied are diimide (N2H2), cyclobutadiene (C4H4), cyclopropanone (C3H4O), oxirene (C2H2O), and many others. Special purpose cryogenically cooled inlet arrangements were designed such that the analyses incurred no warm-up of the cold, and frequently explosively unstable, compounds. Controlled energy electron impact techniques were used to measure critical potentials and to develop the molecular energetics and thermodynamics of these molecules and to gain some insight into their kinetic characteristics as well. Three and four carbon strained ring molecules were studied. Several reactions of oxygen and hydrogen atoms with simple molecules of H, N, C, and O in hard quench configurations were studied. And the quench stabilization of BH3 was explored as a model system in cryochemistry.

  19. Selection of functional human sperm with higher DNA integrity and fewer reactive oxygen species.

    PubMed

    Asghar, Waseem; Velasco, Vanessa; Kingsley, James L; Shoukat, Muhammad S; Shafiee, Hadi; Anchan, Raymond M; Mutter, George L; Tüzel, Erkan; Demirci, Utkan

    2014-10-01

    Fertilization and reproduction are central to the survival and propagation of a species. Couples who cannot reproduce naturally have to undergo in vitro clinical procedures. An integral part of these clinical procedures includes isolation of healthy sperm from raw semen. Existing sperm sorting methods are not efficient and isolate sperm having high DNA fragmentation and reactive oxygen species (ROS), and suffer from multiple manual steps and variations between operators. Inspired by in vivo natural sperm sorting mechanisms where vaginal mucus becomes less viscous to form microchannels to guide sperm towards egg, a chip is presented that efficiently sorts healthy, motile and morphologically normal sperm without centrifugation. Higher percentage of sorted sperm show significantly lesser ROS and DNA fragmentation than the conventional swim-up method. The presented chip is an easy-to-use high-throughput sperm sorter that provides standardized sperm sorting assay with less reliance on operators's skills, facilitating reliable operational steps. PMID:24753434

  20. 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

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

    PubMed Central

    Schillinger, Kurt J.; Patel, Vickas V.

    2012-01-01

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

  2. Symbiotic lactobacilli stimulate gut epithelial proliferation via Nox-mediated generation of reactive oxygen species.

    PubMed

    Jones, Rheinallt M; Luo, Liping; Ardita, Courtney S; Richardson, Arena N; Kwon, Young Man; Mercante, Jeffrey W; Alam, Ashfaqul; Gates, Cymone L; Wu, Huixia; Swanson, Phillip A; Lambeth, J David; Denning, Patricia W; Neish, Andrew S

    2013-11-27

    The resident prokaryotic microbiota of the metazoan gut elicits profound effects on the growth and development of the intestine. However, the molecular mechanisms of symbiotic prokaryotic-eukaryotic cross-talk in the gut are largely unknown. It is increasingly recognized that physiologically generated reactive oxygen species (ROS) function as signalling secondary messengers that influence cellular proliferation and differentiation in a variety of biological systems. Here, we report that commensal bacteria, particularly members of the genus Lactobacillus, can stimulate NADPH oxidase 1 (Nox1)-dependent ROS generation and consequent cellular proliferation in intestinal stem cells upon initial ingestion into the murine or Drosophila intestine. Our data identify and highlight a highly conserved mechanism that symbiotic microorganisms utilize in eukaryotic growth and development. Additionally, the work suggests that specific redox-mediated functions may be assigned to specific bacterial taxa and may contribute to the identification of microbes with probiotic potential. PMID:24141879

  3. Generation of reactive oxygen species by lethal attacks from competing microbes.

    PubMed

    Dong, Tao G; Dong, Shiqi; Catalano, Christy; Moore, Richard; Liang, Xiaoye; Mekalanos, John J

    2015-02-17

    Whether antibiotics induce the production of reactive oxygen species (ROS) that contribute to cell death is an important yet controversial topic. Here, we report that lethal attacks from bacterial and viral species also result in ROS production in target cells. Using soxS as an ROS reporter, we found soxS was highly induced in Escherichia coli exposed to various forms of attacks mediated by the type VI secretion system (T6SS), P1vir phage, and polymyxin B. Using a fluorescence ROS probe, we found enhanced ROS levels correlate with induced soxS in E. coli expressing a toxic T6SS antibacterial effector and in E. coli treated with P1vir phage or polymyxin B. We conclude that both contact-dependent and contact-independent interactions with aggressive competing bacterial species and viruses can induce production of ROS in E. coli target cells. PMID:25646446

  4. Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species

    PubMed Central

    Akhtar, Mohd Javed; Ahamed, Maqusood; Kumar, Sudhir; Khan, MA Majeed; Ahmad, Javed; Alrokayan, Salman A

    2012-01-01

    Background Zinc oxide nanoparticles (ZnO NPs) have received much attention for their implications in cancer therapy. It has been reported that ZnO NPs induce selective killing of cancer cells. However, the underlying molecular mechanisms behind the anticancer response of ZnO NPs remain unclear. Methods and results We investigated the cytotoxicity of ZnO NPs against three types of cancer cells (human hepatocellular carcinoma HepG2, human lung adenocarcinoma A549, and human bronchial epithelial BEAS-2B) and two primary rat cells (astrocytes and hepatocytes). Results showed that ZnO NPs exert distinct effects on mammalian cell viability via killing of all three types of cancer cells while posing no impact on normal rat astrocytes and hepatocytes. The toxicity mechanisms of ZnO NPs were further investigated using human liver cancer HepG2 cells. Both the mRNA and protein levels of tumor suppressor gene p53 and apoptotic gene bax were upregulated while the antiapoptotic gene bcl-2 was downregulated in ZnO NP-treated HepG2 cells. ZnO NPs were also found to induce activity of caspase-3 enzyme, DNA fragmentation, reactive oxygen species generation, and oxidative stress in HepG2 cells. Conclusion Overall, our data demonstrated that ZnO NPs selectively induce apoptosis in cancer cells, which is likely to be mediated by reactive oxygen species via p53 pathway, through which most of the anticancer drugs trigger apoptosis. This study provides preliminary guidance for the development of liver cancer therapy using ZnO NPs. PMID:22393286

  5. Role of Reactive Oxygen Species in Hypertension Produced by Reduced Uterine Perfusion in Pregnant Rats

    PubMed Central

    Sedeek, Mona; Gilbert, Jeffrey S.; LaMarca, Babbette B.; Sholook, Myssara; Chandler, Derrick L.; Wang, Yuping; Granger, Joey P.

    2009-01-01

    BACKGROUND Although recent studies indicate preeclampsia (PE) is associated with increased oxidative stress, the role of reactive oxygen species in the hypertension associated with PE remains unclear. We sought to test the hypothesis that placental ischemia increases oxidative stress which in turn, contributes to hypertension. METHODS Reduction in uterine perfusion pressure (RUPP) was induced by placing silver clips on the abdominal aorta and the ovarian arteries on day 14 of pregnancy. On day 20 of pregnancy, mean arterial pressure (MAP) was measured and oxidative stress was assessed in renal and placental tissues whereas systemic administration of tempol, a superoxide dismutase (SOD) mimetic, was used to evaluate the contribution of reactive oxygen species on RUPP-induced hypertension. RESULTS MAP (120 ± 2 mm Hg vs.106 ± 3 mm Hg), placental levels of 8-isoprostane (1.9 ± 0.4 ng/g tissue vs. 0.8 ± 0.1 ng/g tissue), and malondialdehyde (MDA) (6.9 ± 0.6 ?mol/g tissue vs. 3.9 ± 0.4 ?mol/g tissue) were increased, whereas renal cortical SOD activity was decreased in RUPP rats (1.2 ± 0.1 units/mg protein vs. 1.6 ± 0.1 units/ mg protein) at day 20 of gestation (20 dG) compared to controls. Chronic treatment with tempol attenuated the hypertension (RUPP + tempol 112 ± 2 mm Hg vs. RUPP, 120 ± 2 mm Hg) associated with RUPP, whereas tempol had no effect on MAP (NP, 106 ± 3 vs. NP + tempol, 108 ± 2) in control rats. CONCLUSION The results of this study indicate that placental ischemia decreases innate antioxidant activity resulting in elevated oxidative stress which appears to play a role in mediating hypertension associated with chronic RUPP in pregnant rats. PMID:18670418

  6. Evidence that 4-aminobiphenyl, benzidine, and benzidine congeners produce genotoxicity through reactive oxygen species.

    PubMed

    Makena, Patrudu; Chung, King-Thom

    2007-06-01

    4-Aminobyphenyl (4-Ab), benzidine (Bz), and Bz congeners were evaluated for their ability to induce genotoxicity through an oxidative mechanism. The mutagenicity of these compounds was tested in the presence and absence of Aroclor 1254-induced rat S9 mix using Salmonella typhimurium tester strain TA102, which is sensitive to agents producing reactive oxygen species (ROS). In the presence of S9, 4-Ab, Bz, N-acetyl-benzidine, and 3,3-dimethoxybenzidine were strongly mutagenic in TA102, whereas, 3,3,5,5-tetra-methylbenzidine, 3,3-dimethylbenzidine (O-tolidine), and N,N-diacetylbenzidine were not mutagenic. In addition, 3,3-dichlorobenzidine and 4,4-dinitro-2-biphenylamine were directly mutagenic in TA102. Incorporation of the free radical and metal scavengers, catalase, superoxide dismutase (SOD), butylated hydroxytolune (BHT), and ethylenediamine tetraacetic acid (EDTA) reduced the mutagenic responses of 4-Ab and Bz, whereas heat-inactivated catalase and SOD had no effect. 4-Ab and Bz also induced lipid peroxidation in the presence of S9 mix as shown using the thiobarbituric acid reactive substances assay. The results of this study indicate that 4-Ab and Bz induce mutations through the induction of ROS. PMID:17370336

  7. Methylglyoxal induces apoptosis mediated by reactive oxygen species in bovine retinal pericytes.

    PubMed

    Kim, Jaetaek; Son, Jang-Won; Lee, Jeong-An; Oh, Yeon-Sahng; Shinn, Soon-Hyun

    2004-02-01

    One of the histopathologic hallmarks of early diabetic retinopathy is the loss of pericytes. Evidences suggest that the pericyte loss in vivo is mediated by apoptosis. However, the underlying cause of pericyte apoptosis is not fully understood. This study investigated the influence of methylglyoxal (MGO), a reactive alpha-dicarbonyl compound of glucose metabolism, on apoptotic cell death in bovine retinal pericytes. Analysis of internucleosomal DNA fragmentation by ELISA showed that MGO (200 to 800 microM) induced apoptosis in a concentration-dependent manner. Intracellular reactive oxygen species were generated earlier and the antioxidant, N-acetyl cysteine, inhibited the MGO-induced apoptosis. NF-kappaB activation and increased caspase-3 activity were detected. Apoptosis was also inhibited by the caspase-3 inhibitor, Z-DEVD-fmk, or the NF-kappaB inhibitor, pyrrolidine dithiocarbamate. These data suggest that elevated MGO levels observed in diabetes may cause apoptosis in bovine retinal pericytes through an oxidative stress mechanism and suggests that the nuclear activation of NF-kappaB are involved in the apoptotic process. PMID:14966349

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

    PubMed

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

    2014-01-01

    In developing cost-effective complex oxide materials for the oxygen evolution reaction, it is critical to establish the missing links between structure and function at the atomic level. The fundamental and practical implications of the relationship on any oxide surface are prerequisite to the design of new stable and active materials. Here we report an intimate relationship between the stability and reactivity of oxide catalysts in exploring the reaction on strontium ruthenate single-crystal thin films in alkaline environments. We determine that for strontium ruthenate films with the same conductance, the degree of stability, decreasing in the order (001)>(110)>(111), is inversely proportional to the activity. Both stability and reactivity are governed by the potential-induced transformation of stable Ru(4+) to unstable Ru(n>4+). This ordered(Ru(4+))-to-disordered(Ru(n>4+)) transition and the development of active sites for the reaction are determined by a synergy between electronic and morphological effects. PMID:24939393

  9. Formation, Reactivity, and Properties of Nondative Late Transition Metal–Oxygen and–Nitrogen Bonds

    PubMed Central

    FULTON, J. ROBIN; HOLLAND, ANDREW W.; FOX, DANIEL J.; BERGMAN*, ROBERT G.

    2005-01-01

    Complexes containing bonds between heteroatoms such as nitrogen and oxygen and “late” transition metals (i.e., those located on the right side of the transition series) have been implicated as reactive intermediates in numerous important catalytic systems. Despite this, our understanding of such M–X linkages still lags behind that of their M–H and M–C analogues. New synthetic strategies have now made possible the isolation and study of a variety of monomeric late-metal alkoxide, aryloxide, and amide complexes, including parent hydroxide and amide species. The heteroatoms in these materials form surprisingly strong bonds to their metal centers, and their bond energies do not necessarily correlate with the energies of the corresponding H–X bonds. The M–X complexes typically exhibit nucleophilic reactivity, in some cases form strong hydrogen bonds to proton donors, and even deprotonate relatively weak acids. These observations, as well as thermodynamic investigations, suggest that late metal–heteroatom bonds are strongly polarized and possess significant ionic character, properties that play an important role in their interactions with organic compounds. PMID:11790088

  10. Inelastic and reactive scattering of hyperthermal atomic oxygen from amorphous carbon

    NASA Technical Reports Server (NTRS)

    Minton, Timothy K.; Nelson, Christine M.; Brinza, David E.; Liang, Ranty H.

    1991-01-01

    The reaction of hyperthermal oxygen atoms with an amorphous carbon-13 surface was studied using a modified universal crossed molecular beams apparatus. Time-of-flight distributions of inelastically scattered O-atoms and reactively scattered CO-13 and CO2-13 were measured with a rotatable mass spectrometer detector. Two inelastic scattering channels were observed, corresponding to a direct inelastic process in which the scattered O-atoms retain 20 to 30 percent of their initial kinetic energy and to a trapping desorption process whereby O-atoms emerge from the surface at thermal velocities. Reactive scattering data imply the formation of two kinds of CO products, slow products whose translational energies are determined by the surface temperature and hyperthermal (Approx. 3 eV) products with translational energies comprising roughly 30 percent of the total available energy (E sub avl), where E sub avl is the sum of the collision energy and the reaction exothermicity. Angular data show that the hyperthermal CO is scattered preferentially in the specular direction. CO2 product was also observed, but at much lower intensities than CO and with only thermal velocities.

  11. Reactive oxygen species and related haem pathway components as possible epigenetic modifiers in neurobehavioural pathology.

    PubMed

    Gericke, G S

    2006-01-01

    The neuroendocrine response to stress utilizes several bio-communicative pathways which also play a role in neurodevelopmental plasticity. The mechanism of action of steroidal compounds includes DNA alteration by reactive oxygen species (ROS) arising through redox cycling of reactive hormone derivatives. ROS and reactive nitrogen species play a significant role in signaling networks affecting gene transcriptional regulation during normal as well as stress-induced responses. ROS-associated synaptic and regulatory region plasticity may have been important for normal brain evolution, but probably simultaneously lowered the threshold for inducing neuropathology. A shift from 'plasticity' to 'instability' is likely to be associated with the emergence of complex effects depending on the timing, duration and intensity of the ROS insult, and is suggested to include heritable epigenetic chromatin/regulatory region remodeling differentially influencing expression levels of significant neuropsychiatric genes and their variant alleles. Neurobehavioural disorder clinical manifestations have been linked with ROS effects. The concepts discussed here relate to ROS-associated instability of DNA regulatory region sequences and a proposal that it may play an important modifying role in brain and neuro-behaviourally related gene expression. Genes encoding key steps in mitochondrial, haem, iron and bilirubin ROS metabolic pathways have been used as examples to illustrate how ROS-modified regulatory networks could possibly alter the context within which (even ostensibly unrelated) neuropsychiatric gene candidates may sometimes be recruited. Furthermore, reactions of certain radicals release sufficient energy to generate UV-photons. DNA conformational changes accompanied by changes in photon emission suggest that functional neuroimaging findings probably reflect interaction on the level of ROS/biophoton/genome regulatory region domains rather than the signatures of individual neurobehavioural disorder candidate genes. PMID:16183208

  12. Targeting and Regulation of Reactive Oxygen Species Generation by Nox Family NADPH Oxidases

    PubMed Central

    Morand, Stanislas; Hurt, Darrell; Ueyama, Takehiko

    2009-01-01

    Abstract Nox family NADPH oxidases serve a variety of functions requiring reactive oxygen species (ROS) generation, including antimicrobial defense, biosynthetic processes, oxygen sensing, and redox-based cellular signaling. We explored targeting, assembly, and activation of several Nox family oxidases, since ROS production appears to be regulated both spatially and temporally. Nox1 and Nox3 are similar to the phagocytic (Nox2-based) oxidase, functioning as multicomponent superoxide-generating enzymes. Factors regulating their activities include cytosolic activator and organizer proteins and GTP-Rac. Their regulation varies, with the following rank order: Nox2?>?Nox1?>?Nox3. Determinants of subcellular targeting include: (a) formation of Nox-p22phox heterodimeric complexes allowing plasma membrane translocation, (b) phospholipids-binding specificities of PX domain-containing organizer proteins (p47phox or Nox organizer 1 (Noxo1 and p40phox), and (c) variably splicing of Noxo1 PX domains directing them to nuclear or plasma membranes. Dual oxidases (Duox1 and Duox2) are targeted by different mechanisms. Plasma membrane targeting results in H2O2 release, not superoxide, to support extracellular peroxidases. Human Duox1 and Duox2 have no demonstrable peroxidase activity, despite their extensive homology with heme peroxidases. The dual oxidases were reconstituted by Duox activator 2 (Duoxa2) or two Duoxa1 variants, which dictate maturation, subcellular localization, and the type of ROS generated by forming stable complexes with Duox. Antioxid Redox Signal. 11, 2607–2619. PMID:19438290

  13. Rheumatoid arthritis: the role of reactive oxygen species in disease development and therapeutic strategies.

    PubMed

    Gelderman, Kyra A; Hultqvist, Malin; Olsson, Lina M; Bauer, Kristin; Pizzolla, Angela; Olofsson, Peter; Holmdahl, Rikard

    2007-10-01

    Autoimmune diseases such as rheumatoid arthritis (RA) are chronic diseases that cannot be prevented or cured If the pathologic basis of such disease would be known, it might be easier to develop new drugs interfering with critical pathway. Genetic analysis of animal models for autoimmune diseases can result in discovery of proteins and pathways that play key function in pathogenesis, which may provide rationales for new therapeutic strategies. Currently, only the MHC class II is clearly associated with human RA and animal models for RA. However, recent data from rats and mice with a polymorphism in Ncf1, a member of the NADPH oxidase complex, indicate a role for oxidative burst in protection from arthritis. Oxidative burst-activating substances can treat and prevent arthritis in rats, as efficiently as clinically applied drugs, suggesting a novel pathway to a therapeutic target in human RA. Here, the authors discuss the role of oxygen radicals in regulating the immune system and autoimmune disease. It is proposed that reactive oxygen species set the threshold for T cell activation and thereby regulate chronic autoimmune inflammatory diseases like RA. In the light of this new hypothesis, new possibilities for preventive and therapeutic treatment of chronic inflammatory diseases are discussed. PMID:17678439

  14. Hypoxia-Dependent Reactive Oxygen Species Signaling in the Pulmonary Circulation: Focus on Ion Channels

    PubMed Central

    Veit, Florian; Pak, Oleg; Brandes, Ralf P.

    2015-01-01

    Abstract Significance: An acute lack of oxygen in the lung causes hypoxic pulmonary vasoconstriction, which optimizes gas exchange. In contrast, chronic hypoxia triggers a pathological vascular remodeling causing pulmonary hypertension, and ischemia can cause vascular damage culminating in lung edema. Recent Advances: Regulation of ion channel expression and gating by cellular redox state is a widely accepted mechanism; however, it remains a matter of debate whether an increase or a decrease in reactive oxygen species (ROS) occurs under hypoxic conditions. Ion channel redox regulation has been described in detail for some ion channels, such as Kv channels or TRPC6. However, in general, information on ion channel redox regulation remains scant. Critical Issues and Future Directions: In addition to the debate of increased versus decreased ROS production during hypoxia, we aim here at describing and deciphering why different oxidants, under different conditions, can cause both activation and inhibition of channel activity. While the upstream pathways affecting channel gating are often well described, we need a better understanding of redox protein modifications to be able to determine the complexity of ion channel redox regulation. Against this background, we summarize the current knowledge on hypoxia-induced ROS-mediated ion channel signaling in the pulmonary circulation. Antioxid. Redox Signal. 22, 537–552 PMID:25545236

  15. Silver-ion-mediated reactive oxygen species generation affecting bactericidal activity.

    PubMed

    Park, Hee-Jin; Kim, Jee Yeon; Kim, Jaeeun; Lee, Joon-Hee; Hahn, Ji-Sook; Gu, Man Bock; Yoon, Jeyong

    2009-03-01

    Silver ions have been widely used as disinfectants that inhibit bacterial growth by inhibiting the essential enzymatic functions of the microorganism via interaction with the thiol-group of l-cysteine. However, silver-ion-mediated perturbation of the bacterial respiratory chain has raised the possibility of reactive oxygen species (ROS) generation. We used bacterial reporter strains specifically responding to superoxide radicals and found that silver-ion-mediated ROS-generation affected bactericidal activity. Almost half the log reduction in Escherichia coli and Staphylococcus aureus populations (model strains for gram negative and positive bacteria, respectively) caused by silver-ion disinfection was attributed to ROS-mediated bactericidal activity. The major form of ROS generated was the superoxide-radical; H(2)O(2) was not induced. Furthermore, silver ions strongly enhanced paraquat-induced oxidative stress, indicating close correlation and synergism between the conventional and ROS-mediated silver toxicity. Our results suggest that further studies in silver-based disinfection systems should consider the oxygen concentration and ROS reaction. PMID:19073336

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

    PubMed Central

    Klann, Eric

    2011-01-01

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

  17. Reactive oxygen species initiate a metabolic collapse in hippocampal slices: potential trigger of cortical spreading depression.

    PubMed

    Malkov, Anton; Ivanov, Anton I; Popova, Irina; Mukhtarov, Marat; Gubkina, Olena; Waseem, Tatsiana; Bregestovski, Piotr; Zilberter, Yuri

    2014-09-01

    Excessive accumulation of reactive oxygen species (ROS) underlies oxidative damage. We find that in hippocampal slices, decreased activity of glucose-based antioxidant system induces a massive, abrupt, and detrimental change in cellular functions. We call this phenomenon metabolic collapse (MC). This collapse manifested in long-lasting silencing of synaptic transmission, abnormal oxidation of NAD(P)H and FADH2 associated with immense oxygen consumption, and massive neuronal depolarization. MC occurred without any preceding deficiency in neuronal energy supply or disturbances of ionic homeostasis and spread throughout the hippocampus. It was associated with a preceding accumulation of ROS and was largely prevented by application of an efficient antioxidant Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl). The consequences of MC resemble cortical spreading depression (CSD), a wave of neuronal depolarization that occurs in migraine, brain trauma, and stroke, the cellular initiation mechanisms of which are poorly understood. We suggest that ROS accumulation might also be the primary trigger of CSD. Indeed, we found that Tempol strongly reduced occurrence of CSD in vivo, suggesting that ROS accumulation may be a key mechanism of CSD initiation. PMID:25027308

  18. Mammalian mitochondrial complex I: biogenesis, regulation, and reactive oxygen species generation.

    PubMed

    Koopman, Werner J H; Nijtmans, Leo G J; Dieteren, Cindy E J; Roestenberg, Peggy; Valsecchi, Federica; Smeitink, Jan A M; Willems, Peter H G M

    2010-06-15

    Virtually every mammalian cell contains mitochondria. These double-membrane organelles continuously change shape and position and contain the complete metabolic machinery for the oxidative conversion of pyruvate, fatty acids, and amino acids into ATP. Mitochondria are crucially involved in cellular Ca2+ and redox homeostasis and apoptosis induction. Maintenance of mitochondrial function and integrity requires an inside-negative potential difference across the mitochondrial inner membrane. This potential is sustained by the electron-transport chain (ETC). NADH:ubiquinone oxidoreductase or complex I (CI), the first and largest protein complex of the ETC, couples the oxidation of NADH to the reduction of ubiquinone. During this process, electrons can escape from CI and react with ambient oxygen to produce superoxide and derived reactive oxygen species (ROS). Depending on the balance between their production and removal by antioxidant systems, ROS may function as signaling molecules or induce damage to a variety of biomolecules or both. The latter ultimately leads to a loss of mitochondrial and cellular function and integrity. In this review, we discuss (a) the role of CI in mitochondrial functioning; (b) the composition, structure, and biogenesis of CI; (c) regulation of CI function; (d) the role of CI in ROS generation; and (e) adaptive responses to CI deficiency. PMID:19803744

  19. Growth properties and reactivity of oxygen phases on platinum (111) and palladiium (111)

    NASA Astrophysics Data System (ADS)

    Devarajan, Sunil Poondi

    Oxidation reactions of Pt and Pd under lean burn or oxygen rich conditions are crucial to heterogeneous catalysis systems used in oxidation of hydrocarbons, fabrication of specialty chemicals, power generation through catalytic oxidation, fuel cells and most significantly pollution control through remediation of industrial and automotive exhaust. In spite of their tremendous appeal and widespread use in many important applications, knowledge used to formulate catalytic systems based on the transition metals has chiefly been derived from empirical data, because of their low reactivity towards molecular oxygen under experimental conditions of Ultra High Vacuum (UHV). Thanks to recent advances in surface science techniques, path breaking research through innovative experimental methods coupled with a renewed vigor towards computational ab-initio simulations, have opened avenues for fundamental understanding of this important class of reactions. We utilized strong oxidizing agents like nitrogen di-oxide and atomic oxygen beams to grow oxygen phases on platinum and palladium single crystals and studied their characteristics using various surface analytic techniques. Our STM work on Pt(111), ends a long standing debate on whether the oxygen atoms continue filling up fcc hollow sites or start filling up hcp hollow sites beyond the well understood 0.25 ML coverage. We also present evidence to demonstrate formation of a Pt oxide chain compound which appears as protrusions on the surface and arrange themselves into a well networked superstructure during initial oxidation. Our work on Pd(111) using TPRS, reveals for the first time that C-H bond cleavage of propane occurs on a PdO(101) thin film at temperatures below 200 K under UHV conditions. It is also observed that the hydrogen, and propyl fragments resulting from the bond cleavage react with the thin film oxide to undergo complete oxidation releasing H2O and CO2 at higher temperatures. The C-H bond cleavage occurs only because of the formation of a strongly bound molecular state, which in turn is facilitated by the unique local bonding environment of the PdO(101) surface.

  20. Mitochondrial respiration deficits driven by reactive oxygen species in experimental temporal lobe epilepsy.

    PubMed

    Rowley, Shane; Liang, Li-Ping; Fulton, Ruth; Shimizu, Takahiko; Day, Brian; Patel, Manisha

    2015-03-01

    Metabolic alterations have been implicated in the etiology of temporal lobe epilepsy (TLE), but whether or not they have a functional impact on cellular energy producing pathways (glycolysis and/or oxidative phosphorylation) is unknown. The goal of this study was to determine if alterations in cellular bioenergetics occur using real-time analysis of mitochondrial oxygen consumption and glycolytic rates in an animal model of TLE. We hypothesized that increased steady-state levels of reactive oxygen species (ROS) initiated by epileptogenic injury result in impaired mitochondrial respiration. We established methodology for assessment of bioenergetic parameters in isolated synaptosomes from the hippocampus of Sprague-Dawley rats at various times in the kainate (KA) model of TLE. Deficits in indices of mitochondrial respiration were observed at time points corresponding with the acute and chronic phases of epileptogenesis. We asked if mitochondrial bioenergetic dysfunction occurred as a result of increased mitochondrial ROS and if it could be attenuated in the KA model by pharmacologically scavenging ROS. Increased steady-state ROS in mice with forebrain-specific conditional deletion of manganese superoxide dismutase (Sod2(fl/fl)NEX(Cre/Cre)) in mice resulted in profound deficits in mitochondrial oxygen consumption. Pharmacological scavenging of ROS with a catalytic antioxidant restored mitochondrial respiration deficits in the KA model of TLE. Together, these results demonstrate that mitochondrial respiration deficits occur in experimental TLE and ROS mechanistically contribute to these deficits. Furthermore, this study provides novel methodology for assessing cellular metabolism during the entire time course of disease development. PMID:25600213

  1. Antibody-induced generation of reactive oxygen radicals by brain macrophages in canine distemper encephalitis: a mechanism for bystander demyelination

    Microsoft Academic Search

    C. Griot; T. Biirge; M. Vandevelde; E. Peterhans

    1989-01-01

    The mechanism of inflammatory demyelination in canine distemper encephalitis (CDE) is uncertain but macrophages are thought to play an important effector role in this lesion. Serum and cerebrospinal fluid (CSF), containing anti-canine distemper virus and anti-myelin antibodies from dogs with CDE were tested for their ability to generate reactive oxygen species (ROS) in macrophages in primary dog brain cell cultures

  2. Aging: Functional Metabolic Balance among cAMP, cGMP and Reactive Oxygen Intermediate Generation by Human Granulocytes

    Microsoft Academic Search

    Bernardo Coelho Horta; Cecília Steinberg Perilo; Daniela Caldeira Costa; José Augusto Nogueira-Machado; Míriam Martins Chaves

    2005-01-01

    Background: The nature of the aging process has been the subject of considerable speculation. It has been reported that in the aging process several components of the signal transduction pathways, including phosphoinositide, protein kinase C, protein kinase A and reactive oxygen intermediate (ROI) generation, are altered. Objective: The aim of our study was to evaluate the functional metabolic balance among

  3. Analysis of the relationship between histologic alterations and the generation of reactive oxygen species in vasectomized rat testes

    Microsoft Academic Search

    Kaan Aydos; Bora Kupeli; Tarkan Soygur; Ali Unsal; Esra Erden; Ozden Tulunay; Sadettin Kupeli

    1998-01-01

    Objectives. To evaluate the effects of vasal obstruction on testicular structure, to determine if tissue and\\/or cell damage can cause significant reactive oxygen species (ROS) generation, and to correlate the histologic alterations to the measured levels of ROS products.Methods. To evaluate the effects of ROS generation in vasectomized testes, unilateral vasectomy was performed on 17 rats and tissue samples were

  4. Intracellular Reactive Oxygen Species Mediate the Linkage of Na /K -ATPase to Hypertrophy and Its Marker Genes in

    E-print Network

    Brand, Paul H.

    Intracellular Reactive Oxygen Species Mediate the Linkage of Na /K -ATPase to Hypertrophy and Its hypertrophy and transcrip- tional regulations of growth-related marker genes through multiple Ca2 -dependent. A phorbol ester that also causes myocyte hypertrophy did not increase ROS generation, and its effects

  5. Upper control limit of reactive oxygen species in follicular fluid beyond which viable embryo formation is not favorable

    Microsoft Academic Search

    Saikat K. Jana; Narendra Babu K; Ratna Chattopadhyay; Baidyanath Chakravarty; Koel Chaudhury

    2010-01-01

    Though the role of reactive oxygen species (ROS) in female infertility has been a subject of rigorous research worldwide, there is inadequate information on the cut-off value of ROS in the oocyte microenvironment beyond which ART outcome may be adversely affected. An upper ROS level in follicular fluid (FF) samples of women undergoing IVF beyond which good quality embryo formation

  6. Intracellular Reactive Oxygen Species Activate Src Tyrosine Kinase during Cell Adhesion and Anchorage-Dependent Cell Growth

    Microsoft Academic Search

    Elisa Giannoni; Francesca Buricchi; Giovanni Raugei; Giampietro Ramponi; Paola Chiarugi

    2005-01-01

    Src tyrosine kinases are central components of adhesive responses and are required for cell spreading onto the extracellular matrix. Among other intracellular messengers elicited by integrin ligation are reactive oxygen species, which act as synergistic mediators of cytoskeleton rearrangement and cell spreading. We report that after integrin ligation, the tyrosine kinase Src is oxidized and activated. Src displays an early

  7. Regulation of Murine Intestinal Inflammation by Reactive Metabolites of Oxygen and Nitrogen: Divergent Roles of Superoxide and Nitric Oxide

    Microsoft Academic Search

    Christian F. Krieglstein; Wolfgang H. Cerwinka; F. Stephen Laroux; James W. Salter; Janice M. Russell; Guido Schuermann; Matthew B. Grisham; Christopher R. Ross; D. Neil Granger

    2001-01-01

    Several reports have implicated reactive oxygen and nitrogen metabolites (RONS) in the initi- ation and\\/or progression of inflammatory bowel diseases (IBDs). We have investigated the role of three key RONS-metabolizing enzymes (inducible nitric oxide synthase (iNOS), superox- ide dismutase (SOD), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase) in a murine model of IBD. Mice genetically deficient ( ? \\/ ? )

  8. In vitro and in vivo generation of reactive oxygen species, DNA damage and lactate dehydrogenase leakage by selected pesticides

    Microsoft Academic Search

    D. Bagchi; M. Bagchi; E. A. Hassoun; S. J. Stohs

    1995-01-01

    Reactive oxygen species may be involved in the toxicity of various pesticides and we have, therefore, examined the in vivo effects of structurally dissimilar polyhalogenated cyclic hydrocarbons (PCH), such as endrin and chlordane, chlorinated acetamide herbicides (CAH), such as alachlor, and organophosphate pesticides (OPS), such as chlorpyrifos and fenthion, on the production of hepatic and brain lipid peroxidation and DNA-single

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    EPA Science Inventory

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

  11. Calcium Homeostasis and Reactive Oxygen Species Production in Cells Transformed by Mitochondria from Individuals with Sporadic Alzheimer's Disease

    Microsoft Academic Search

    Jason P. Sheehan; Russel H. Swerdlow; Scott W. Miller; Robert E. Davis; Jan K. Parks; W. Davis

    1997-01-01

    Alzheimer's disease (AD) is associated with defects in mito- chondrial function. Mitochondrial-based disturbances in cal- cium homeostasis, reactive oxygen species (ROS) generation, and amyloid metabolism have been implicated in the patho- physiology of sporadic AD. The cellular consequences of mito- chondrial dysfunction, however, are not known. To examine these consequences, mitochondrially transformed cells (cy- brids) were created from AD patients

  12. Generation of Reactive Oxygen and Anti-Oxidant Species by Hydrodynamically-Stressed Suspensions of Morinda citrofolia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The generation of reactive oxygen species (ROS) by plant cell suspension cultures, in response to the imposition of both biotic and abiotic stress, is well-documented. This study investigated the generation of hydrogen peroxide by hydrodynamically-stressed cultures of Morinda citrifolia, over a 5-ho...

  13. Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain

    PubMed Central

    Yoshino, Fumihiko; Yoshida, Ayaka; Umigai, Naofumi; Kubo, Koya; Lee, Masaichi-Chang-il

    2011-01-01

    Crocetin is a natural carotenoid compound of gardenia fruits and saffron, which has various effects in biological systems. In this study, we investigated the antioxidant effects of crocetin on reactive oxygen species such as hydroxyl radical using in vitro X-band electron spin resonance and spin trapping. Crocetin significantly inhibited hydroxyl radical generation compared with the control. Moreover, we performed electron spin resonance computed tomography ex vivo with the L-band electron spin resonance imaging system and determined the electron spin resonance signal decay rate in the isolated brain of stroke-prone spontaneously hypertensive rats, a high-oxidative stress model. Crocetin significantly reduced oxidative stress in the isolated brain by acting as a scavenger of reactive oxygen species, especially hydroxyl radical, as demonstrated by in vitro and ex vivo electron spin resonance analysis. The distribution of crocetin was also determined in the plasma and the brain of stroke-prone spontaneously hypertensive rats using high-performance liquid chromatography. After oral administration, crocetin was detected at high levels in the plasma and the brain. Our results suggest that crocetin may participate in the prevention of reactive oxygen species-induced disease due to a reduction of oxidative stress induced by reactive oxygen species in the brain. PMID:22128217

  14. Mitochondrial membrane potential and reactive oxygen species content of endothelial and smooth muscle cells cultured on poly( ?-caprolactone) films

    Microsoft Academic Search

    M. Concepción Serrano; Raffaella Pagani; Miguel Manzano; Juan V. Comas; M. Teresa Portolés

    2006-01-01

    A transitory but significant stimulation of mitochondrial activity, increase of reactive oxygen species (ROS) and oxidative stress were previously observed in L929 fibroblasts cultured on poly(?-caprolactone) (PCL) films. ROS, mainly formed in mitochondria, play a physiological role but an excessive production can promote endothelial dysfunction, cause oxidative injury to vascular cells, oxidize lipoproteins and accelerate atherothrombogenesis. On the other hand,

  15. Reactive Oxygen Species in Tumor Necrosis Factor-?-Activated Primary Human Keratinocytes: Implications for Psoriasis and Inflammatory Skin Disease

    Microsoft Academic Search

    Chen N Young; Jay I Koepke; Laura J Terlecky; Michael S Borkin; Savoy L Boyd; Stanley R Terlecky

    2008-01-01

    The multifunctional cytokine tumor necrosis factor-? (TNF-?) is known to play an important role in inflammatory and immunological responses in human skin. Although it has been documented that reactive oxygen species (ROS) are involved in TNF-?-induced signaling pathways associated with certain inflammatory diseases, their role in TNF-? signaling cascades has not been examined in primary human keratinocytes used as a

  16. Nutrient Acquisition and Generation of Reactive Oxygen Species Via CREA, AREA, and NOXa are Important in Pathogenicity in Mycosphaerella Graminicola

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycosphaerella graminicola is an important wheat pathogen causing significant economic loss. M. graminicola is a hemibiotroph, indicating that a biotrophic stage with nutrient uptake and a necrotrophic stage associated with a possible toxin or reactive oxygen species (ROS) are important to pathogeni...

  17. Cadmium-Induced Hydrogen Sulfide Synthesis Is Involved in Cadmium Tolerance in Medicago sativa by Reestablishment of Reduced (Homo)glutathione and Reactive Oxygen Species Homeostases

    PubMed Central

    Cui, Weiti; Chen, Huiping; Zhu, Kaikai; Jin, Qijiang; Xie, Yanjie; Cui, Jin; Xia, Yan; Zhang, Jing; Shen, Wenbiao

    2014-01-01

    Until now, physiological mechanisms and downstream targets responsible for the cadmium (Cd) tolerance mediated by endogenous hydrogen sulfide (H2S) have been elusive. To address this gap, a combination of pharmacological, histochemical, biochemical and molecular approaches was applied. The perturbation of reduced (homo)glutathione homeostasis and increased H2S production as well as the activation of two H2S-synthetic enzymes activities, including L-cysteine desulfhydrase (LCD) and D-cysteine desulfhydrase (DCD), in alfalfa seedling roots were early responses to the exposure of Cd. The application of H2S donor sodium hydrosulfide (NaHS), not only mimicked intracellular H2S production triggered by Cd, but also alleviated Cd toxicity in a H2S-dependent fashion. By contrast, the inhibition of H2S production caused by the application of its synthetic inhibitor blocked NaHS-induced Cd tolerance, and destroyed reduced (homo)glutathione and reactive oxygen species (ROS) homeostases. Above mentioned inhibitory responses were further rescued by exogenously applied glutathione (GSH). Meanwhile, NaHS responses were sensitive to a (homo)glutathione synthetic inhibitor, but reversed by the cotreatment with GSH. The possible involvement of cyclic AMP (cAMP) signaling in NaHS responses was also suggested. In summary, LCD/DCD-mediated H2S might be an important signaling molecule in the enhancement of Cd toxicity in alfalfa seedlings mainly by governing reduced (homo)glutathione and ROS homeostases. PMID:25275379

  18. Simvastatin inhibits lipopolysaccharide-induced tumor necrosis factor-alpha expression in neonatal rat cardiomyocytes: The role of reactive oxygen species.

    PubMed

    Shang, Fujun; Zhao, Lianyou; Zheng, Qiangsun; Wang, Jiepin; Xu, Zhe; Liang, Wenbing; Liu, Hui; Liu, Shaowei; Zhang, Lijuan

    2006-12-29

    Tumor necrosis factor-alpha (TNF-alpha) is implicated in heart failure and cardiomyocytes themselves can express TNF-alpha. Nevertheless, the mechanisms and regulations of TNF-alpha expression in cardiomyocytes remain poorly understood. The present study was to investigate the effects of simvastatin on TNF-alpha expression in cardiomyocytes and the underlying molecular mechanisms. In neonatal rat cardiomyocytes, RT-PCR and ELISA showed lipopolysaccharide (LPS)-induced TNF-alpha expression was attenuated by simvastatin pretreatment in a dose-dependent manner. The reactive oxygen species (ROS) scavenger N-acetylcysteine and the NADPH oxidase inhibitor diphenyleneiodonium also inhibited the LPS-induced expression of TNF-alpha. Dichlorofluorescein-fluorescence and cytochrome c reduction assay indicated LPS increased ROS generation and NADPH oxidase activity in cardiomyocytes, which were abrogated by simvastatin. Furthermore, similar to LPS, exogenous hydrogen peroxide also increased TNF-alpha secretion, but simvastatin did not significantly affect the hydrogen peroxide-induced TNF-alpha secretion. All the effects of simvastatin as mentioned above were completely reversed by concomitant pretreatment with mevalonate, a key intermediate during cholesterol synthesis. These results suggest that simvastatin attenuates LPS-induced TNF-alpha expression in cardiomyocytes via inhibition of activation of NADPH oxidase and subsequent ROS generation. PMID:17094942

  19. Mechanical and photo-fragmentation processes for nanonization of melanin to improve its efficacy in protecting cells from reactive oxygen species stress

    NASA Astrophysics Data System (ADS)

    Liu, Yi-Cheng; Chen, Sih-Min; Liu, Jhong-Han; Hsu, Hsiang-Wei; Lin, Hoang-Yan; Chen, Szu-yuan

    2015-02-01

    It has been well established ex vivo that melanin has the ability of scavenging free radicals and reactive oxygen species (ROS), besides other functions. Therefore, we propose to utilize nanonized melanin as medication against acute oxidative stress. For this purpose, we developed and characterized two techniques based on mechanical stir and photo-fragmentation using femtosecond laser pulses, respectively, for disintegration of suspended melanin powder to produce nanometer-sized and water-dispersible melanin. This resolves a major obstacle in the medical and industrial applications of melanin. The viabilities of cultured retinal pigment epithelium (RPE) cells exposed to exogenous H2O2 stress and treated with various conditions of melanin and irradiation were compared. It was found that melanin could be nanonized very effectively with the techniques, and nanonized melanin exhibited a much stronger effect than unprocessed melanin on raising the viability of cultured RPE cells under acute ROS stress. The effect was even more prominent without simultaneous light irradiation, promising for effective in vivo application to the whole body.

  20. Studies on the inhibitory effects of curcumin and eugenol on the formation of reactive oxygen species and the oxidation of ferrous iron

    Microsoft Academic Search

    A. Ch. Pulla Reddy; Belur R. Lokesh

    1994-01-01

    The spice principles curcumin (from turmeric) and eugenol (from cloves) are good inhibitors of lipid peroxidation. Lipid peroxidation is known to be initiated by reactive oxygen species. The effect of curcumin and eugenol on the generation of reactive oxygen species in model systems were investigated. Both curcumin and eugenol inhibited superoxide anion generation in xanthine-xanthine oxidase system to an extent

  1. An example of molecular co-evolution: reactive oxygen species (ROS) and ROS scavenger levels in Schistosoma mansoni/Biomphalaria glabrata interactions

    E-print Network

    Paris-Sud XI, Université de

    An example of molecular co-evolution: reactive oxygen species (ROS) and ROS scavenger levels ROS scavengers in order to survive. In this context, ROS and ROS scavengers are involved in a co, Reactive oxygen species (ROS), ROS scavengers halsde-00580768,version1-29Mar2011 #12;1. Introduction44 45

  2. In vitro generation of reactive oxygen species by free coelomic cells of the annelid Eisenia fetida andrer: An analysis by chemiluminescence and nitro blue tetrazolium reduction

    Microsoft Academic Search

    Pierre Valembois; Maguy Lassègues

    1995-01-01

    Coelomocytes of the earthworm Eisenia fetida andrei were activated in vitro with various stimulants in order to investigate their capacity to produce reactive oxygen species. Analysis by luminol-enhanced chemiluminescence and nitro blue tetrazolium reduction suggests the production in vitro of reactive oxygen species by both categories of free coelomocytes, leucocytes and chloragocytes, while affecting different modalities: a respiratory burst-like reaction

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

    PubMed

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

    2010-03-01

    Redox evolution in sparsely fractured crystalline rocks is a key, and largely unresolved, issue when assessing the geochemical suitability of deep geological repositories for nuclear waste. Redox zonation created by the influx of oxygenated waters has previously been simulated using reactive transport models that have incorporated a variety of processes, resulting in predictions for the depth of oxygen penetration that may vary greatly. An assessment and direct comparison of the various underlying conceptual models are therefore needed. In this work a reactive transport model that considers multiple processes in an integrated manner is used to investigate the ingress of oxygen for both single fracture and fracture zone scenarios. It is shown that the depth of dissolved oxygen migration is greatly influenced by the a priori assumptions that are made in the conceptual models. For example, the ability of oxygen to access and react with minerals in the rock matrix may be of paramount importance for single fracture conceptual models. For fracture zone systems, the abundance and reactivity of minerals within the fractures and thin matrix slabs between the fractures appear to provide key controls on O(2) attenuation. The findings point to the need for improved understanding of the coupling between the key transport-reaction feedbacks to determine which conceptual models are most suitable and to provide guidance for which parameters should be targeted in field and laboratory investigations. PMID:19926162

  4. Benzene's metabolites alter c-MYB activity via reactive oxygen species in HD3 cells

    SciTech Connect

    Wan, Joanne [Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario (Canada); Winn, Louise M. [Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario (Canada) and School of Environmental Studies, Queen's University, Kingston, Ontario (Canada)]. E-mail: winnl@queensu.ca

    2007-07-15

    Benzene is a known leukemogen that is metabolized to form reactive intermediates and reactive oxygen species (ROS). The c-Myb oncoprotein is a transcription factor that has a critical role in hematopoiesis. c-Myb transcript and protein have been overexpressed in a number of leukemias and cancers. Given c-Myb's role in hematopoiesis and leukemias, it is hypothesized that benzene interferes with the c-Myb signaling pathway and that this involves ROS. To investigate our hypothesis, we evaluated whether benzene, 1,4-benzoquinone, hydroquinone, phenol, and catechol generated ROS in chicken erythroblast HD3 cells, as measured by 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (DCFDA) and dihydrorhodamine-123 (DHR-123), and whether the addition of 100 U/ml of the antioxidating enzyme superoxide dismutase (SOD) could prevent ROS generation. Reduced to oxidized glutathione ratios (GSH:GSSG) were also assessed as well as hydroquinone and benzoquinone's effects on c-Myb protein levels and activation of a transiently transfected reporter construct. Finally we attempted to abrogate benzene metabolite mediated increases in c-Myb activity with the use of SOD. We found that benzoquinone, hydroquinone, and catechol increased DCFDA fluorescence, increased DHR-123 fluorescence, decreased GSH:GSSG ratios, and increased reporter construct expression after 24 h of exposure. SOD was able to prevent DCFDA fluorescence and c-Myb activity caused by benzoquinone and hydroquinone only. These results are consistent with other studies, which suggest metabolite differences in benzene-mediated toxicity. More importantly, this study supports the hypothesis that benzene may mediate its toxicity through ROS-mediated alterations in the c-Myb signaling pathway.

  5. Negative feedback regulation of reactive oxygen species on AT1 receptor gene expression

    PubMed Central

    Nickenig, Georg; Strehlow, Kerstin; Bäumer, Anselm T; Baudler, Stefanie; Waßmann, Sven; Sauer, Heinrich; Böhm, Michael

    2000-01-01

    Free radicals as well as the AT1 receptor are involved in the pathogenesis of cardiovascular disease. Both the intracellular mechanisms of AT1 receptor regulation and the effect of free radicals on AT1 receptor expression are currently unknown. This study investigates the role of free radicals in the modulation of AT1 receptor expression and in the angiotensin II-induced AT1 receptor regulation. AT1 receptor mRNA was assessed by Northern blotting and AT1 receptor density by radioligand binding assays, respectively, in vascular smooth muscle cells (VSMC). Free radical release was measured by confocal laser scanning microscopy. AT1 receptor mRNA transcription rate was determined by nuclear run-on assays and AT1 receptor mRNA half-life was measured under transcriptional blockade. Angiotensin II caused a time-dependent decrease of AT1 receptor mRNA expression in rat VSMC in culture (30±6% at 4?h with 100?nM angiotensin II). This was followed by a consistent decrease in AT1 receptor density. Angiotensin II caused release of reactive oxygen species in VSMC which was abolished by preincubation with 100??M diphenylene iodonium (DPI). DPI inhibited partially the down-regulating effect of angiotensin II on the AT1 receptor. Incubation of VSMC with either hydrogen peroxide or xanthine/xanthine oxidase caused a dose-dependent decrease in AT1 receptor mRNA expression which was not mediated by a decreased rate of transcription but rather through destabilization of AT1 receptor mRNA. Experiments which included preincubation of VSMC with various intracellular inhibitors suggested that free radicals caused AT1 receptor downregulation through activation of p38-MAP kinase and intracellular release of calcium. However, angiotensin II-induced AT1 receptor expression was not inhibited by blockade of p38-MAP kinase activation or intracellular calcium release. Free radicals may at least in part mediate angiotensin II-induced AT1 receptor regulation through direct post-transcriptional effects on AT1 receptor mRNA expression which involves intracellular release of calcium and activation of p38-MAP kinase. These findings may help to clarify the intracellular mechanisms involved in AT1 receptor regulation and reveal a novel biological feature for reactive oxygen species. PMID:11030730

  6. Green tea polyphenols precondition against cell death induced by oxygen-glucose deprivation via stimulation of laminin receptor, generation of reactive oxygen species, and activation of protein kinase C?.

    PubMed

    Gundimeda, Usha; McNeill, Thomas H; Elhiani, Albert A; Schiffman, Jason E; Hinton, David R; Gopalakrishna, Rayudu

    2012-10-01

    As the development of synthetic drugs for the prevention of stroke has proven challenging, utilization of natural products capable of preconditioning neuronal cells against ischemia-induced cell death would be a highly useful complementary approach. In this study using an oxygen-glucose deprivation and reoxygenation (OGD/R) model in PC12 cells, we show that 2-day pretreatment with green tea polyphenols (GTPP) and their active ingredient, epigallocatechin-3-gallate (EGCG), protects cells from subsequent OGD/R-induced cell death. A synergistic interaction was observed between GTPP constituents, with unfractionated GTPP more potently preconditioning cells than EGCG. GTPP-induced preconditioning required the 67-kDa laminin receptor (67LR), to which EGCG binds with high affinity. 67LR also mediated the generation of reactive oxygen species (ROS) via activation of NADPH oxidase. An exogenous ROS-generating system bypassed 67LR to induce preconditioning, suggesting that sublethal levels of ROS are indeed an important mediator in GTPP-induced preconditioning. This role for ROS was further supported by the fact that antioxidants blocked GTPP-induced preconditioning. Additionally, ROS induced an activation and translocation of protein kinase C (PKC), particularly PKC? from the cytosol to the membrane/mitochondria, which was also blocked by antioxidants. The crucial role of PKC in GTPP-induced preconditioning was supported by use of its specific inhibitors. Preconditioning was increased by conditional overexpression of PKC? and decreased by its knock-out with siRNA. Collectively, these results suggest that GTPP stimulates 67LR and thereby induces NADPH oxidase-dependent generation of ROS, which in turn induces activation of PKC, particularly prosurvival isoenzyme PKC?, resulting in preconditioning against cell death induced by OGD/R. PMID:22879598

  7. Phospholipase D signaling mediates reactive oxygen species-induced lung endothelial barrier dysfunction

    PubMed Central

    Usatyuk, Peter V.; Kotha, Sainath R.; Parinandi, Narasimham L.; Natarajan, Viswanathan

    2013-01-01

    Reactive oxygen species (ROS) have emerged as critical players in the pathophysiology of pulmonary disorders and diseases. Earlier, we have demonstrated that ROS stimulate lung endothelial cell (EC) phospholipase D (PLD) that generates phosphatidic acid (PA), a second messenger involved in signal transduction. In the current study, we investigated the role of PLD signaling in the ROS-induced lung vascular EC barrier dysfunction. Our results demonstrated that hydrogen peroxide (H2O2), a typical physiological ROS, induced PLD activation and altered the barrier function in bovine pulmonary artery ECs (BPAECs). 1-Butanol, the quencher of PLD, generated PA leading to the formation of physiologically inactive phosphatidyl butanol but not its biologically inactive analog, 2-butanol, blocked the H2O2-mediated barrier dysfunction. Furthermore, cell permeable C2 ceramide, an inhibitor of PLD but not the C2 dihydroceramide, attenuated the H2O2-induced PLD activation and enhancement of paracellular permeability of Evans blue conjugated albumin across the BPAEC monolayers. In addition, transfection of BPAECs with adenoviral constructs of hPLD1 and mPLD2 mutants attenuated the H2O2-induced barrier dysfunction, cytoskeletal reorganization and distribution of focal adhesion proteins. For the first time, this study demonstrated that the PLD-generated intracellular bioactive lipid signal mediator, PA, played a critical role in the ROS-induced barrier dysfunction in lung vascular ECs. This study also underscores the importance of PLD signaling in vascular leak and associated tissue injury in the etiology of lung diseases among critically ill patients encountering oxygen toxicity and excess ROS production during ventilator-assisted breathing. PMID:23662182

  8. Oxygen diffusion and reactivity at low temperature on bare amorphous olivine-type silicate

    SciTech Connect

    Minissale, M., E-mail: marco.minissale@obspm.fr; Congiu, E.; Dulieu, F. [LERMA-LAMAp, Université de Cergy-Pontoise, Observatoire de Paris, ENS, UPMC, UMR 8112 du CNRS, 5 Mail Gay Lussac, 95000 Cergy Pontoise Cedex (France)] [LERMA-LAMAp, Université de Cergy-Pontoise, Observatoire de Paris, ENS, UPMC, UMR 8112 du CNRS, 5 Mail Gay Lussac, 95000 Cergy Pontoise Cedex (France)

    2014-02-21

    The mobility of O atoms at very low temperatures is not generally taken into account, despite O diffusion would add to a series of processes leading to the observed rich molecular diversity in space. We present a study of the mobility and reactivity of O atoms on an amorphous silicate surface. Our results are in the form of reflection absorption infrared spectroscopy and temperature-programmed desorption spectra of O{sub 2} and O{sub 3} produced via two pathways: O + O and O{sub 2} + O, investigated in a submonolayer regime and in the range of temperature between 6.5 and 30 K. All the experiments show that ozone is formed efficiently on silicate at any surface temperature between 6.5 and 30 K. The derived upper limit for the activation barriers of O + O and O{sub 2} + O reactions is ?150 K/k{sub b}. Ozone formation at low temperatures indicates that fast diffusion of O atoms is at play even at 6.5 K. Through a series of rate equations included in our model, we also address the reaction mechanisms and show that neither the Eley–Rideal nor the hot atom mechanisms alone can explain the experimental values. The rate of diffusion of O atoms, based on modeling results, is much higher than the one generally expected, and the diffusive process proceeds via the Langmuir-Hinshelwood mechanism enhanced by tunnelling. In fact, quantum effects turn out to be a key factor that cannot be neglected in our simulations. Astrophysically, efficient O{sub 3} formation on interstellar dust grains would imply the presence of huge reservoirs of oxygen atoms. Since O{sub 3} is a reservoir of elementary oxygen, and also of OH via its hydrogenation, it could explain the observed concomitance of CO{sub 2} and H{sub 2}O in the ices.

  9. Reactive Oxygen Species Prevent Imiquimod-Induced Psoriatic Dermatitis through Enhancing Regulatory T Cell Function

    PubMed Central

    Choi, Eun-Jeong; Hong, Min-Pyo; Kie, Jeong-Hae; Lim, Woosung; Lee, Hyeon Kook; Moon, Byung-In; Seoh, Ju-Young

    2014-01-01

    Psoriasis is a chronic inflammatory skin disease resulting from immune dysregulation. Regulatory T cells (Tregs) are important in the prevention of psoriasis. Traditionally, reactive oxygen species (ROS) are known to be implicated in the progression of inflammatory diseases, including psoriasis, but many recent studies suggested the protective role of ROS in immune-mediated diseases. In particular, severe cases of psoriasis vulgaris have been reported to be successfully treated by hyperbaric oxygen therapy (HBOT), which raises tissue level of ROS. Also it was reported that Treg function was closely associated with ROS level. However, it has been only investigated in lowered levels of ROS so far. Thus, in this study, to clarify the relationship between ROS level and Treg function, as well as their role in the pathogenesis of psoriasis, we investigated imiquimod-induced psoriatic dermatitis (PD) in association with Treg function both in elevated and lowered levels of ROS by using knockout mice, such as glutathione peroxidase-1?/? and neutrophil cytosolic factor-1?/? mice, as well as by using HBOT or chemicals, such as 2,3-dimethoxy-1,4-naphthoquinone and N-acetylcysteine. The results consistently showed Tregs were hyperfunctional in elevated levels of ROS, whereas hypofunctional in lowered levels of ROS. In addition, imiquimod-induced PD was attenuated in elevated levels of ROS, whereas aggravated in lowered levels of ROS. For the molecular mechanism that may link ROS level and Treg function, we investigated the expression of an immunoregulatory enzyme, indoleamine 2,3-dioxygenase (IDO) which is induced by ROS, in PD lesions. Taken together, it was implied that appropriately elevated levels of ROS might prevent psoriasis through enhancing IDO expression and Treg function. PMID:24608112

  10. Reactive oxygen species are involved in nickel inhibition of dna repair

    SciTech Connect

    Lynn, S.; Yew, F.H.; Chen, K.S.; Jan, K.Y.

    1997-06-01

    Nickel has been shown to inhibit DNA repair in a way that may play a role in its toxicity. Since nickel treatment increases cellular reactive oxygen species (ROS), we have investigated the involvement of ROS in nickel inhibition of DNA repair. Inhibition of glutathione synthesis or catalase activity increased the enhancing effect of nickel on the cytotoxicity of ultraviolet (UV) light. Inhibition of catalase and glutathione peroxidase activities also enhanced the retardation effect of nickel on the rejoining of DNA strand breaks accumulated by hydroxyurea plus cytosine-{beta}-D-arabinofuranoside in UV-irradiated cells. Since DNA polymerization and ligation are involved in the DNA-break rejoining, we have investigated the effect of ROS on these two steps in an extract of Chinese hamster ovary cells. Nickel inhibition of the incorporation of ({sup 3}H)dTTP into the DNase l-activated calf thymus DNA was stronger than the ligation of poly(dA){center_dot}oligo(dT), whereas H{sub 2}O{sub 2} was more potent in inhibiting DNA ligation than DNA polymerization. Nickel, in the presence of H{sub 2}O{sub 2}, exhibited a synergistic inhibition on both DNA polymerization and ligation and caused protein fragmentation. In addition, glutathione could completely recover the inhibition by nickel or H{sub 2}O{sub 2} alone but only partially recover the inhibition by nickel plus H{sub 2}O{sub 2}. Therefore, nickel may bind to DNA-repair enzymes and generate oxygen-free radicals to cause protein degradation in situ. This irreversible damage to the proteins involved in DNA repair, replication, recombination, and transcription could be important for the toxic effects of nickel. 60 refs., 6 figs., 4 tabs.

  11. Photochemically induced formation of reactive oxygen species (ROS) from effluent organic matter.

    PubMed

    Zhang, Danning; Yan, Shuwen; Song, Weihua

    2014-11-01

    The formation of reactive oxygen species (ROS) from effluent organic matter (EfOM) was investigated under simulated solar irradiation. In this study, EfOM was isolated into three different fractions based on hydrophobicity. The productivity of ROS in EfOM was measured and compared with that of natural organic matter (NOM) isolates, including Suwannee River humic acid/fulvic acid (SRHA/FA) and Pony Lake fulvic acid (PLFA). The hydrophilic (HPI) component had a greater quantum yield of 1O2 than those of the hydrophobic (HPO) and transphilic (TPI) fractions because the HPI contained peptides and proteins. Regarding O2•-, the phenolic moieties acted as electron donating species after photochemical excitation and therefore electron transfer to oxygen. A positive correlation was found between the phenolic concentrations and the steady state O2•-concentrations. H2O2 accumulated during the irradiation process from superoxide as precursor. Potentially, due to the presence of proteins or other organic species in the HPI fraction, the decay rates of H2O2 in the dark for both the effluent wastewater and the HPI fraction were significantly faster than the rates observed in the standard NOM isolates, the HPO and TPI fractions. Autochthonous NOM showed a higher •OH productivity than terrestrial NOM. The [•OH]ss was lowest in the HPI fraction due to the lack of humic fraction and existence of soluble microbial products (SMPs), which easily reacted with •OH. Overall, the HPO and TPI fractions were the major sources of superoxide, H2O2 and •OH under simulated solar irradiation. The HPI fraction dominated the production of 1O2 and acted as a sink for H2O2 and •OH. PMID:25314220

  12. Phospholipase D signaling mediates reactive oxygen species-induced lung endothelial barrier dysfunction.

    PubMed

    Usatyuk, Peter V; Kotha, Sainath R; Parinandi, Narasimham L; Natarajan, Viswanathan

    2013-01-01

    Reactive oxygen species (ROS) have emerged as critical players in the pathophysiology of pulmonary disorders and diseases. Earlier, we have demonstrated that ROS stimulate lung endothelial cell (EC) phospholipase D (PLD) that generates phosphatidic acid (PA), a second messenger involved in signal transduction. In the current study, we investigated the role of PLD signaling in the ROS-induced lung vascular EC barrier dysfunction. Our results demonstrated that hydrogen peroxide (H2O2), a typical physiological ROS, induced PLD activation and altered the barrier function in bovine pulmonary artery ECs (BPAECs). 1-Butanol, the quencher of PLD, generated PA leading to the formation of physiologically inactive phosphatidyl butanol but not its biologically inactive analog, 2-butanol, blocked the H2O2-mediated barrier dysfunction. Furthermore, cell permeable C2 ceramide, an inhibitor of PLD but not the C2 dihydroceramide, attenuated the H2O2-induced PLD activation and enhancement of paracellular permeability of Evans blue conjugated albumin across the BPAEC monolayers. In addition, transfection of BPAECs with adenoviral constructs of hPLD1 and mPLD2 mutants attenuated the H2O2-induced barrier dysfunction, cytoskeletal reorganization and distribution of focal adhesion proteins. For the first time, this study demonstrated that the PLD-generated intracellular bioactive lipid signal mediator, PA, played a critical role in the ROS-induced barrier dysfunction in lung vascular ECs. This study also underscores the importance of PLD signaling in vascular leak and associated tissue injury in the etiology of lung diseases among critically ill patients encountering oxygen toxicity and excess ROS production during ventilator-assisted breathing. PMID:23662182

  13. Oxygen diffusion and reactivity at low temperature on bare amorphous olivine-type silicate.

    PubMed

    Minissale, M; Congiu, E; Dulieu, F

    2014-02-21

    The mobility of O atoms at very low temperatures is not generally taken into account, despite O diffusion would add to a series of processes leading to the observed rich molecular diversity in space. We present a study of the mobility and reactivity of O atoms on an amorphous silicate surface. Our results are in the form of reflection absorption infrared spectroscopy and temperature-programmed desorption spectra of O2 and O3 produced via two pathways: O + O and O2 + O, investigated in a submonolayer regime and in the range of temperature between 6.5 and 30 K. All the experiments show that ozone is formed efficiently on silicate at any surface temperature between 6.5 and 30 K. The derived upper limit for the activation barriers of O + O and O2 + O reactions is ?150 K/kb. Ozone formation at low temperatures indicates that fast diffusion of O atoms is at play even at 6.5 K. Through a series of rate equations included in our model, we also address the reaction mechanisms and show that neither the Eley-Rideal nor the hot atom mechanisms alone can explain the experimental values. The rate of diffusion of O atoms, based on modeling results, is much higher than the one generally expected, and the diffusive process proceeds via the Langmuir-Hinshelwood mechanism enhanced by tunnelling. In fact, quantum effects turn out to be a key factor that cannot be neglected in our simulations. Astrophysically, efficient O3 formation on interstellar dust grains would imply the presence of huge reservoirs of oxygen atoms. Since O3 is a reservoir of elementary oxygen, and also of OH via its hydrogenation, it could explain the observed concomitance of CO2 and H2O in the ices. PMID:24559358

  14. 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.

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

    PubMed Central

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

    2013-01-01

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

  16. Superparamagnetic iron oxide nanoparticles as radiosensitizer via enhanced reactive oxygen species formation

    SciTech Connect

    Klein, Stefanie; Sommer, Anja [Department of Chemistry and Pharmacy, Physical Chemistry I and ICMM, Friedrich-Alexander University of Erlangen-Nuremberg, Egerlandstr. 3, D-91058 Erlangen (Germany)] [Department of Chemistry and Pharmacy, Physical Chemistry I and ICMM, Friedrich-Alexander University of Erlangen-Nuremberg, Egerlandstr. 3, D-91058 Erlangen (Germany); Distel, Luitpold V.R. [Department of Radiation Oncology, Friedrich Alexander University Erlangen-Nuremberg, Universitaetsstrasse 27, D-91054 Erlangen (Germany)] [Department of Radiation Oncology, Friedrich Alexander University Erlangen-Nuremberg, Universitaetsstrasse 27, D-91054 Erlangen (Germany); Neuhuber, Winfried [Department of Anatomy, Chair of Anatomy I, Friedrich Alexander University Erlangen-Nuremberg, Krankenhausstr. 9, D-91054 Erlangen (Germany)] [Department of Anatomy, Chair of Anatomy I, Friedrich Alexander University Erlangen-Nuremberg, Krankenhausstr. 9, D-91054 Erlangen (Germany); Kryschi, Carola, E-mail: kryschi@chemie.uni-erlangen.de [Department of Chemistry and Pharmacy, Physical Chemistry I and ICMM, Friedrich-Alexander University of Erlangen-Nuremberg, Egerlandstr. 3, D-91058 Erlangen (Germany)] [Department of Chemistry and Pharmacy, Physical Chemistry I and ICMM, Friedrich-Alexander University of Erlangen-Nuremberg, Egerlandstr. 3, D-91058 Erlangen (Germany)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Ultrasmall citrate-coated SPIONs with {gamma}Fe{sub 2}O{sub 3} and Fe{sub 3}O{sub 4} structure were prepared. Black-Right-Pointing-Pointer SPIONs uptaken by MCF-7 cells increase the ROS production for about 240%. Black-Right-Pointing-Pointer The SPION induced ROS production is due to released iron ions and catalytically active surfaces. Black-Right-Pointing-Pointer Released iron ions and SPION surfaces initiate the Fenton and Haber-Weiss reaction. Black-Right-Pointing-Pointer X-ray irradiation of internalized SPIONs leads to an increase of catalytically active surfaces. -- Abstract: 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.

  17. Administration of an Antioxidant Prevents Lymphoma Development in Transmitochondrial Mice Overproducing Reactive Oxygen Species

    PubMed Central

    Yamanashi, Haruka; Hashizume, Osamu; Yonekawa, Hiromichi; Nakada, Kazuto; Hayashi, Jun-Ichi

    2014-01-01

    Because of the difficulty to exclude possible involvement of nuclear DNA mutations, it has been a controversial issue whether pathogenic mutations in mitochondrial DNA (mtDNA) and the resultant respiration defects are involved in tumor development. To address this issue, our previous study generated transmitochondrial mice (mito-mice-ND613997), which possess the nuclear and mtDNA backgrounds derived from C57BL/6J (B6) strain mice except that they carry B6 mtDNA with a G13997A mutation in the mt-Nd6 gene. Because aged mito-mice-ND613997 simultaneously showed overproduction of reactive oxygen species (ROS) in bone marrow cells and high frequency of lymphoma development, current study examined the effects of administrating a ROS scavenger on the frequency of lymphoma development. We used N-acetylcysteine (NAC) as a ROS scavenger, and showed that NAC administration prevented lymphoma development. Moreover, its administration induced longevity in mito-mice-ND613997. The gene expression profiles in bone marrow cells indicated the upregulation of the Fasl gene, which can be suppressed by NAC administration. Given that natural-killer (NK) cells mediate the apoptosis of various tumor cells via enhanced expression of genes encoding apoptotic ligands including Fasl gene, its overexpression would reflect the frequent lymphoma development in bone marrow cells. These observations suggest that continuous administration of an antioxidant would be an effective therapeutics to prevent lymphoma development enhanced by ROS overproduction. PMID:25048265

  18. Characterization of springtime airborne particulate matter-bound reactive oxygen species in Beijing.

    PubMed

    Liu, Qingyang; Zhang, Yuanxun; Liu, Yanju; Zhang, Meigen

    2014-08-01

    Epidemiologic studies have suggested that particulate matter (PM)-associated adverse health effects are related to particle composition. To study the toxicological characteristics of dust storm, airborne PM10 was collected at two sites in Beijing from March to May 2012. The production of reactive oxygen species (ROS), quantified by dithiothreitol (DTT), was used to measure the PM-induced oxidative potential. Two dust storm (DS) samples were monitored during the sampling period: one happened on March 28th (DS1) and the other one was on April 28th (DS2). The backward trajectory results showed that both events originated from Inner Mongolia and Mongolia, respectively. The increased trends of ROS activities during the dust storm episode in PM10 were observed for all the dust storms owing to a higher concentration of water-soluble components for all the PM10 samples compared to nondust storm ones. Interestingly, the correlations between DTT consumption with water-soluble species yield interesting results about the spatial variability of redox activity between sites. In particular, a tracer of soil suspension, namely Fe, contributed the most fraction to ROS variability in the urban background site. Water-soluble organic carbon (WSOC) made the highest contribution to ROS variability, suggesting that vehicle emission might be important driving factors of the PM-induced oxidative stress in the urban site. PMID:24728573

  19. Neferine induces reactive oxygen species mediated intrinsic pathway of apoptosis in HepG2 cells.

    PubMed

    Poornima, Paramasivan; Quency, Robin Sheeba; Padma, Viswandha Vijaya

    2013-01-15

    Evidence has accumulated concerning the medicinal application of Nelumbo nucifera in the treatment of various diseases. Neferine, an alkaloid from N. nucifera was found to exert cytotoxicity on liver cancer cells HepG2 in a dose-dependent manner. We evaluated its anticancer potential by studying its effect on mitochondrial membrane potential, intracellular calcium levels [Ca(2+)](i), cell membrane integrity, apoptotic body formation and DNA fragmentation in cultured HepG2 cells. The reactive oxygen species level has been increased upon neferine treatment with concomitant decrease in reduced glutathione. Our data further indicate reduction of ??M and increased [Ca(2+)](i) during apoptosis induction by neferine with increased expression of apoptotic proteins such as Bax, Bad, cleaved forms of caspase 3, caspase 9 and PARP, with the downregulation of anti-apoptotic protein Bcl2 in HepG2 cells. Moreover, the expressions of tumour suppressor proteins p53 and PTEN were upregulated along with the downregulation of P-Akt. In addition, expression levels of TNF-?, p38 and ERK1/2 MAP kinases were increased upon neferine treatment. These results imply that mitochondrial-mediated ROS generation induced by neferine leads to caspase-dependent apoptosis in HepG2 cells. PMID:23122111

  20. Mitochondria-derived reactive oxygen species drive GANT61-induced mesothelioma cell apoptosis.

    PubMed

    Lim, Chuan Bian; Prêle, Cecilia M; Baltic, Svetlana; Arthur, Peter G; Creaney, Jenette; Watkins, D Neil; Thompson, Philip J; Mutsaers, Steven E

    2015-01-30

    Gli transcription factors of the Hedgehog (Hh) pathway have been reported to be drivers of malignant mesothelioma (MMe) cell survival. The Gli inhibitor GANT61 induces apoptosis in various cancer cell models, and has been associated directly with Gli inhibition. However various chemotherapeutics can induce cell death through generation of reactive oxygen species (ROS) but whether ROS mediates GANT61-induced apoptosis is unknown. In this study human MMe cells were treated with GANT61 and the mechanisms regulating cell death investigated. Exposure of MMe cells to GANT61 led to G1 phase arrest and apoptosis, which involved ROS but not its purported targets, GLI1 or GLI2. GANT61 triggered ROS generation and quenching of ROS protected MMe cells from GANT61-induced apoptosis. Furthermore, we demonstrated that mitochondria are important in mediating GANT61 effects: (1) ROS production and apoptosis were blocked by mitochondrial inhibitor rotenone; (2) GANT61 promoted superoxide formation in mitochondria; and (3) mitochondrial DNA-deficient LO68 cells failed to induce superoxide, and were more resistant to apoptosis induced by GANT61 than wild-type cells. Our data demonstrate for the first time that GANT61 induces apoptosis by promoting mitochondrial superoxide generation independent of Gli inhibition, and highlights the therapeutic potential of mitochondrial ROS-mediated anticancer drugs in MMe. PMID:25544756

  1. TNF Dually Mediates Resistance and Susceptibility to Mycobacteria Through Mitochondrial Reactive Oxygen Species

    PubMed Central

    Roca, Francisco J.; Ramakrishnan, Lalita

    2013-01-01

    Summary Tumor Necrosis Factor (TNF) constitutes a critical host defense against tuberculosis but its excess is also implicated in tuberculosis pathogenesis in zebrafish and humans. We elucidate the pathways by which TNF mediates tuberculosis pathogenesis using the zebrafish. TNF excess induces mitochondrial reactive oxygen species (ROS) in infected macrophages through RIP1–RIP3-dependent pathways. While initially increasing macrophage microbicidal activity, ROS rapidly induce programmed necrosis (necroptosis) and, release mycobacteria into the growth-permissive extracellular milieu. TNF-induced necroptosis occurs through two pathways: modulation of mitochondrial cyclophilin D, implicated in mitochondrial permeability transition pore formation, and acid sphingomyelinase-mediated ceramide production. Combined genetic blockade of cyclophilin D and acid sphingomyelinase renders the high TNF state hyperresistant by preventing macrophage necrosis while preserving increased microbicidal activity. Similarly, the cyclophilin D-inhibiting drug alisporivir and the acid sphingomyelinase-inactivating drug, desipramine, synergize to reverse susceptibility, suggesting the therapeutic potential of these orally-active drugs against tuberculosis and possibly other TNF-mediated diseases. PMID:23582643

  2. Ciclopirox induces autophagy through reactive oxygen species-mediated activation of JNK signaling pathway

    PubMed Central

    Zhou, Hongyu; Shen, Tao; Shang, Chaowei; Luo, Yan; Liu, Lei; Yan, Juming; Li, Yan; Huang, Shile

    2014-01-01

    Ciclopirox olamine (CPX), a fungicide, has been demonstrated as a potential anticancer agent. However, the underlying anticancer mechanism is not well understood. Here, we found that CPX induced autophagy in human rhabdomyosarcoma (Rh30 and RD) cells. It appeared that CPX-induced autophagy was attributed to induction of reactive oxygen species (ROS), as N-acetyl-L-cysteine (NAC), a ROS scavenger and antioxidant, prevented this process. Furthermore, we observed that CPX induced activation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 MAPK, which was also blocked by NAC. However, only inhibition of JNK (with SP600125) or expression of dominant negative c-Jun partially prevented CPX-induced autophagy, indicating that ROS-mediated activation of JNK signaling pathway contributed to CPX-induced autophagy. Of interest, inhibition of autophagy by chloroquine (CQ) enhanced CPX-induced cell death, indicating that CPX-induced autophagy plays a pro-survival role in human rhabdomyosarcoma cells. Our finding suggests that the combination with autophagy inhibitors may be a novel strategy in potentiating the anticancer activity of CPX for treatment of rhabdomyosarcoma. PMID:25294812

  3. Mitochondrial reactive oxygen species: a double edged sword in ischemia/reperfusion vs preconditioning.

    PubMed

    Kalogeris, Theodore; Bao, Yimin; Korthuis, Ronald J

    2014-01-01

    Reductions in the blood supply produce considerable injury if the duration of ischemia is prolonged. Paradoxically, restoration of perfusion to ischemic organs can exacerbate tissue damage and extend the size of an evolving infarct. Being highly metabolic organs, the heart and brain are particularly vulnerable to the deleterious effects of ischemia/reperfusion (I/R). While the pathogenetic mechanisms contributing to I/R-induced tissue injury and infarction are multifactorial, the relative importance of each contributing factor remains unclear. However, an emerging body of evidence indicates that the generation of reactive oxygen species (ROS) by mitochondria plays a critical role in damaging cellular components and initiating cell death. In this review, we summarize our current understanding of the mechanisms whereby mitochondrial ROS generation occurs in I/R and contributes to myocardial infarction and stroke. In addition, mitochondrial ROS have been shown to participate in preconditioning by several pharmacologic agents that target potassium channels (e.g., ATP-sensitive potassium (mKATP) channels or large conductance, calcium-activated potassium (mBKCa) channels) to activate cell survival programs that render tissues and organs more resistant to the deleterious effects of I/R. Finally, we review novel therapeutic approaches that selectively target mROS production to reduce postischemic tissue injury, which may prove efficacious in limiting myocardial dysfunction and infarction and abrogating neurocognitive deficits and neuronal cell death in stroke. PMID:24944913

  4. Glutamate mobilizes [Zn2+]i through Ca2+-dependent reactive oxygen species accumulation

    PubMed Central

    Dineley, Kirk E.; Devinney, Michael J.; Zeak, Jennifer A.; Rintoul, Gordon L.; Reynolds, Ian J.

    2013-01-01

    Liberation of zinc from intracellular stores contributes to oxidant-induced neuronal injury. However, little is known regarding how endogenous oxidant systems regulate intracellular free zinc ([Zn2+]i). Here we simultaneously imaged [Ca2+]i and [Zn2+]i to study acute [Zn2+]i changes in cultured rat forebrain neurons after glutamate receptor activation. Neurons were loaded with fura-2FF and FluoZin-3 to follow [Ca2+]i and [Zn2+]i, respectively. Neurons treated with glutamate (100 ?M) for ten minutes gave large Ca2+ responses that did not recover after termination of the glutamate stimulus. Glutamate also increased [Zn2+]i, however glutamate-induced [Zn2+]i changes were completely dependent on Ca2+ entry, appeared to arise entirely from internal stores, and were substantially reduced by co-application of the membrane-permeant chelator TPEN during the glutamate treatment. Pharmacological maneuvers revealed that a number of endogenous oxidant producing systems, including nitric oxide synthase, phospholipase A2, and mitochondria all contributed to glutamate-induced [Zn2+]i changes. We found no evidence that mitochondria buffered [Zn2+]i during acute glutamate receptor activation. We conclude that glutamate-induced [Zn2+]i transients are caused in part by [Ca2+]i -induced reactive oxygen species that arises from both cytosolic and mitochondrial sources. PMID:18624907

  5. A luminol-based micro-flow-injection electrochemiluminescent system to determine reactive oxygen species.

    PubMed

    Chen, Ming; Wei, Xiuhua; Tu, Yifeng

    2011-09-15

    A flow injection analysis (FIA) system with electrochemiluminescent (ECL) detection has been established. Based on a specially designed flow-through ECL cell with a very simple structure, the system possesses rapid response and high sensitivity. With luminol as the ECL reagent, the response of hydrogen peroxide (H(2)O(2)) was investigated on the developed FIA-ECL system. After optimizing the experimental conditions, such as the electric parameters, the buffer condition and the flow rate, it was demonstrated that the developed FIA-ECL system works well for quantified assays. Compared with reported works, the present results indicate that the developed FIA-ECL system has the lowest limit of detection (S/N=3) of 3.0×10(-9) mol/L for H(2)O(2), which is equal to the level of chemiluminescence (CL). The developed system was successfully used to monitor the yield of reactive oxygen species (ROSs) in water vapour during the work of an ultrasonic humidifier with H(2)O(2) as index. And the amount of ROSs in some other real samples, including tap water, drinking water and river water was detected with recoveries from 92.0% to 106%. PMID:21807187

  6. Iron- and ferritin-dependent reactive oxygen species distribution: impact on Arabidopsis root system architecture.

    PubMed

    Reyt, Guilhem; Boudouf, Soukaina; Boucherez, Jossia; Gaymard, Frédéric; Briat, Jean-Francois

    2015-03-01

    Iron (Fe) homeostasis is integrated with the production of reactive oxygen species (ROS), and distribution at the root tip participates in the control of root growth. Excess Fe increases ferritin abundance, enabling the storage of Fe, which contributes to protection of plants against Fe-induced oxidative stress. AtFer1 and AtFer3 are the two ferritin genes expressed in the meristematic zone, pericycle and endodermis of the Arabidopsis thaliana root, and it is in these regions that we observe Fe stained dots. This staining disappears in the triple fer1-3-4 ferritin mutant. Fe excess decreases primary root length in the same way in wild-type and in fer1-3-4 mutant. In contrast, the Fe-mediated decrease of lateral root (LR) length and density is enhanced in fer1-3-4 plants due to a defect in LR emergence. We observe that this interaction between excess Fe, ferritin, and root system architecture (RSA) is in part mediated by the H2O2/O2·(-) balance between the root cell proliferation and differentiation zones regulated by the UPB1 transcription factor. Meristem size is also decreased in response to Fe excess in ferritin mutant plants, implicating cell cycle arrest mediated by the ROS-activated SMR5/SMR7 cyclin-dependent kinase inhibitors pathway in the interaction between Fe and RSA. PMID:25624148

  7. Reactive oxygen species are involved in plant defense against a gall midge.

    PubMed

    Liu, Xuming; Williams, Christie E; Nemacheck, Jill A; Wang, Haiyan; Subramanyam, Subhashree; Zheng, Cheng; Chen, Ming-Shun

    2010-02-01

    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 (Triticum aestivum) and rice (Oryza sativa) against Hessian fly (Mayetiola destructor) larvae. Rapid and prolonged accumulation of hydrogen peroxide (H(2)O(2)) was detected in wheat plants at the attack site during incompatible interactions. Increased accumulation of both H(2)O(2) and superoxide was detected in rice plants during nonhost interactions with the larvae. No increase in accumulation of either H(2)O(2) or superoxide was observed in wheat plants during compatible interactions. A global analysis revealed changes in the abundances of 250 wheat transcripts and 320 rice transcripts encoding proteins potentially involved in ROS homeostasis. A large number of transcripts encoded class III peroxidases that increased in abundance during both incompatible and nonhost interactions, whereas the levels of these transcripts decreased in susceptible wheat during compatible interactions. The higher levels of class III peroxidase transcripts were associated with elevated enzymatic activity of peroxidases at the attack site in plants during incompatible and nonhost interactions. Overall, our data indicate that class III peroxidases may play a role in ROS generation in resistant wheat and nonhost rice plants during response to Hessian fly attacks. PMID:19965963

  8. Reactive oxygen species generation is not different during isometric and lengthening contractions of mouse muscle

    PubMed Central

    Sloboda, Darcée D.

    2013-01-01

    Skeletal muscles can be injured by lengthening contractions, when the muscles are stretched while activated. Lengthening contractions produce structural damage that leads to the degeneration and regeneration of damaged muscle fibers by mechanisms that have not been fully elucidated. Reactive oxygen species (ROS) generated at the time of injury may initiate degenerative or regenerative processes. In the present study we hypothesized that lengthening contractions that damage the muscle would generate more ROS than isometric contractions that do not cause damage. To test our hypothesis, we subjected muscles of mice to lengthening contractions or isometric contractions and simultaneously monitored intracellular ROS generation with the fluorescent indicator 5-(and-6)-chloromethyl-2?,7?-dichlorodihydrofluorescein (CM-DCFH), which is oxidized by ROS to form the fluorescent product CM-DCF. We found that CM-DCF fluorescence was not different during or shortly after lengthening contractions compared with isometric controls, regardless of the amount of stretch and damage that occurred during the lengthening contractions. The only exception was that after severe stretches, the increase in CM-DCF fluorescence was impaired. We conclude that lengthening contractions that damage the muscle do not generate more ROS than isometric contractions that do not cause damage. The implication is that ROS generated at the time of injury are not the initiating signals for subsequent degenerative or regenerative processes. PMID:23948772

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

    PubMed

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

    2007-03-01

    We previously showed that long-term exposure of anterior pituitary cells to nitric oxide (NO) induces apoptosis. The intracellular signals underlying this effect remained unclear. In this study, we searched for possible mechanisms involved in the early stages of the NO apoptotic cascade. Caspase 3 was activated by NO with no apparent disruption of mitochondrial membrane potential. NO caused a rapid increase of reactive oxygen species (ROS), and this increase seems to be dependent of mitochondrial electron transport chain. The antioxidant N-acetyl-cysteine avoided ROS increase, prevented the NO-induced caspase 3 activation, and reduced the NO apoptotic effect. Catalase was inactivated by NO, while glutathione peroxidase (GPx) activity and reduced glutathione (GSH) were not modified at first, but increased at later times of NO exposure. The increase of GSH level is important for the scavenging of the NO-induced ROS overproduction. Our results indicate that ROS have an essential role as a trigger of the NO apoptotic cascade in anterior pituitary cells. The permanent inhibition of catalase may strengthen the oxidative damage induced by NO. GPx activity and GSH level augment in response to the oxidative damage, though this increase seems not to be enough to rescue the cells from the NO effect. PMID:16996755

  10. Reactive oxygen species involved cancer cellular specific 5-aminolevulinic acid uptake in gastric epithelial cells

    PubMed Central

    Ito, Hiromu; Tamura, Masato; Matsui, Hirofumi; Majima, Hideyuki J.; Indo, Hiroko P.; Hyodo, Ichinosuke

    2014-01-01

    Photodynamic therapy and photodynamic diagnosis using 5-aminolevulinic acid (ALA) are clinically useful for cancer treatments. Cancer cells have been reported that 5-aminolevulinic acid is incorporated via peptide transporter 1, which is one of the membrane transport proteins, and has been reported to be significantly expressed in various gastrointestinal cancer cells such as Caco-2. However, the mechanism of this protein expression has not been elucidated. Concentration of reactive oxygen species (ROS) is higher in cancer cells in comparison with that of normal cells. We have previously reported that ROS derived from mitochondria is likely related to invasions and proliferations of cancer cells. Since 5-aminolevulinic acid is the most important precursor of heme which is necessary protein for cellular proliferations, mitochondrial ROS (mitROS) may be also related to peptide transporter 1 expressions. In this study, we used a rat gastric mucosal cell line RGM1 and its cancer-like mutated cell line RGK1, and we clarified the ALA uptake mechanism and its relations between mitROS and peptide transporter 1 expression in RGK1. We also used our self-established stable clone of cell which over-expresses manganese superoxide dismutase, a mitROS scavenger. We studied differences of the photodynamic therapy effects in these cells after ALA administrations to clear the influence of mitROS. PMID:24688215

  11. Autophagy proteins control goblet cell function by potentiating reactive oxygen species production

    PubMed Central

    Patel, Khushbu K; Miyoshi, Hiroyuki; Beatty, Wandy L; Head, Richard D; Malvin, Nicole P; Cadwell, Ken; Guan, Jun-Lin; Saitoh, Tatsuya; Akira, Shizuo; Seglen, Per O; Dinauer, Mary C; Virgin, Herbert W; Stappenbeck, Thaddeus S

    2013-01-01

    Delivery of granule contents to epithelial surfaces by secretory cells is a critical physiologic process. In the intestine, goblet cells secrete mucus that is required for homeostasis. Autophagy proteins are required for secretion in some cases, though the mechanism and cell biological basis for this requirement remain unknown. We found that in colonic goblet cells, proteins involved in initiation and elongation of autophagosomes were required for efficient mucus secretion. The autophagy protein LC3 localized to intracellular multi-vesicular vacuoles that were consistent with a fusion of autophagosomes and endosomes. Using cultured intestinal epithelial cells, we found that NADPH oxidases localized to and enhanced the formation of these LC3-positive vacuoles. Both autophagy proteins and endosome formation were required for maximal production of reactive oxygen species (ROS) derived from NADPH oxidases. Importantly, generation of ROS was critical to control mucin granule accumulation in colonic goblet cells. Thus, autophagy proteins can control secretory function through ROS, which is in part generated by LC3-positive vacuole-associated NADPH oxidases. These findings provide a novel mechanism by which autophagy proteins can control secretion. PMID:24185898

  12. Role of Reactive Oxygen Species and Redox in Regulating the Function of Transient Receptor Potential Channels

    PubMed Central

    Song, Michael Y.; Makino, Ayako

    2011-01-01

    Abstract Cellular redox status, regulated by production of reactive oxygen species (ROS), greatly contributes to the regulation of vascular smooth muscle cell contraction, migration, proliferation, and apoptosis by modulating the function of transient receptor potential (TRP) channels in the plasma membrane. ROS functionally interact with the channel protein via oxidizing the redox-sensitive residues, whereas nitric oxide (NO) regulates TRP channel function by cyclic GMP/protein kinase G-dependent and -independent pathways. Based on the structural differences among different TRP isoforms, the effects of ROS and NO are also different. In addition to regulating TRP channels in the plasma membrane, ROS and NO also modulate Ca2+ release channels (e.g., IP3 and ryanodine receptors) on the sarcoplasmic/endoplasmic reticulum membrane. This review aims at briefly describing (a) the role of TRP channels in receptor-operated and store-operated Ca2+ entry, and (b) the role of ROS and redox status in regulating the function and structure of TRP channels. Antioxid. Redox Signal. 15, 1549–1565. PMID:21126186

  13. 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

  14. Reactive oxygen species mediates homocysteine-induced mitochondrial biogenesis in human endothelial cells: Modulation by antioxidants

    SciTech Connect

    Perez-de-Arce, Karen [Departamento de Nutricion, Diabetes y Metabolismo, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago (Chile); Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago (Chile); Foncea, Rocio [Departamento de Nutricion, Diabetes y Metabolismo, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago (Chile)]. E-mail: rfoncea@med.puc.cl; Leighton, Federico [Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago (Chile)

    2005-12-16

    It has been proposed that homocysteine (Hcy)-induces endothelial dysfunction and atherosclerosis by generation of reactive oxygen species (ROS). A previous report has shown that Hcy promotes mitochondrial damage. Considering that oxidative stress can affect mitochondrial biogenesis, we hypothesized that Hcy-induced ROS in endothelial cells may lead to increased mitochondrial biogenesis. We found that Hcy-induced ROS (1.85-fold), leading to a NF-{kappa}B activation and increase the formation of 3-nitrotyrosine. Furthermore, expression of the mitochondrial biogenesis factors, nuclear respiratory factor-1 and mitochondrial transcription factor A, was significantly elevated in Hcy-treated cells. These changes were accompanied by increase in mitochondrial mass and higher mRNA and protein expression of the subunit III of cytochrome c oxidase. These effects were significantly prevented by pretreatment with the antioxidants, catechin and trolox. Taken together, our results suggest that ROS is an important mediator of mitochondrial biogenesis induced by Hcy, and that modulation of oxidative stress by antioxidants may protect against the adverse vascular effects of Hcy.

  15. A ‘tissue model’ to study the plasma delivery of reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Szili, Endre J.; Bradley, James W.; Short, Robert D.

    2014-04-01

    We demonstrate the utility of a ‘tissue model’ to monitor the delivery of plasma jet-generated reactive oxygen species (ROS). We report on helium plasma jet interactions both across the surface and into the subsurface (defined as 150 µm to 1.5 mm) of the tissue model. The model comprises a gelatin gel encapsulating a homogeneously dispersed chemical or biological reporter molecule. Jet-surface interactions result in (i) star shaped patterns that resemble those previously reported for surface-plasma streamers on insulators (as imaged by Pockels sensing) and (ii) ‘filled’ or hollow circular surface features, which resemble the ‘killing’ patterns seen in plasma jet treatments of bacterial lawns. The use of reporter molecules show that plasma can deliver ROS from 150 µm to 1.5 mm below the tissue surface. Subsurface delivery of ROS is consistent with the use of plasma to decontaminate wounds (covered by wound exudate and clotted blood), the deactivation of whole biofilms, plasma-enhanced drug delivery through skin and the destruction of solid tumours. From the data presented, we argue that in these four cases (and others) ROS may be capable of directly accessing a tissue's subsurface, as opposed to other proposed mechanisms, which involve stimulating surface reactions that trigger a cascade of biomolecular signalling events (into the tissue).

  16. Functional manipulation of dendritic cells by photoswitchable generation of intracellular reactive oxygen species.

    PubMed

    Cheong, Taek-Chin; Shin, Eon Pil; Kwon, Eun-Kyung; Choi, Ji-Hye; Wang, Kang-Kyun; Sharma, Prashant; Choi, Kyong Hoon; Lim, Jin-Muk; Kim, Hong-Gee; Oh, Keunhee; Jeon, Ju-Hong; So, Insuk; Kim, In-Gyu; Choi, Myung-Sik; Kim, Young Keun; Seong, Seung-Yong; Kim, Yong-Rok; Cho, Nam-Hyuk

    2015-03-20

    Reactive oxygen species (ROS) play an important role in cellular signaling as second messengers. However, studying the role of ROS in physiological redox signaling has been hampered by technical difficulties in controlling their generation within cells. Here, we utilize two inert components, a photosensitizer and light, to finely manipulate the generation of intracellular ROS and examine their specific role in activating dendritic cells (DCs). Photoswitchable generation of intracellular ROS rapidly induced cytosolic mobilization of Ca(2+), differential activation of mitogen-activated protein kinases, and nuclear translocation of NF-?B. Moreover, a transient intracellular ROS surge could activate immature DCs to mature and potently enhance migration in vitro and in vivo. Finally, we observed that intracellular ROS-stimulated DCs enhanced antigen specific T-cell responses in vitro and in vivo, which led to delayed tumor growth and prolonged survival of tumor-bearing mice when immunized with a specific tumor antigen. Therefore, a transient intracellular ROS surge alone, if properly manipulated, can cause immature DCs to differentiate into a motile state and mature forms that are sufficient to initiate adaptive T cell responses in vivo. PMID:25458073

  17. Anti-colorectal cancer activity of macrostemonoside A mediated by reactive oxygen species.

    PubMed

    Wang, Yihui; Tang, Qingchao; Jiang, Shixiong; Li, Mingqi; Wang, Xishan

    2013-11-29

    Macrostemonoside A (MSS.A), an active steroidal saponin from Allium macrostemon Bung has been shown to possess anti-coagulation and anti-obesity effects. However, the functional role of MSS.A on tumor growth has not been elucidated. We found that MSS.A significantly inhibited human colorectal cancer cell growth in Caco2 and SW480 cells. Incubation of SW480 cells with MSS.A for 48 h resulted in cell cycle arrest. Moreover, MSS.A dose-dependently induced apoptosis in SW480 cells as shown by increased AnnexinV positively stained cell population, caspase activation, increased pro-apoptotic and reduced anti-apoptotic Bcl-2 family protein levels. Treatment of SW480 cells with MSS.A resulted in increased reactive oxygen species (ROS) generation. However, pre-incubation of SW480 cells with antioxidant N-acetylcysteine (NAC) attenuated the ROS generation and anti-colorectal cancer activities of MSS.A. Lastly, intra-peritoneal injections of MSS.A significantly inhibited tumor formation in BALB/c nude mice carcinogenesis xenograft model by reduced tumor volume and tumor weight when treated at dosages of 10, 50 or 100mg/kg daily for 35 days compared with PBS control. Taken together, our results indicate that MSS.A suppressed colorectal cancer growth and induced cell apoptosis by inducing ROS production, and that MSS.A may have therapeutic relevance in the treatment of human colorectal cancer. PMID:24211203

  18. Isoalantolactone Induces Reactive Oxygen Species Mediated Apoptosis in Pancreatic Carcinoma PANC-1 Cells

    PubMed Central

    Khan, Muhammad; Ding, Chuan; Rasul, Azhar; Yi, Fei; Li, Ting; Gao, Hongwen; Gao, Rong; Zhong, Lili; Zhang, Kun; Fang, Xuedong; Ma, Tonghui

    2012-01-01

    Isoalantolactone, a sesquiterpene lactone compound possesses antifungal, antibacteria, antihelminthic and antiproliferative activities. In the present study, we found that isoalantolactone inhibits growth and induces apoptosis in pancreatic cancer cells. Further mechanistic studies revealed that induction of apoptosis is associated with increased generation of reactive oxygen species, cardiolipin oxidation, reduced mitochondrial membrane potential, release of cytochrome c and cell cycle arrest at S phase. N-Acetyl Cysteine (NAC), a specific ROS inhibitor restored cell viability and completely blocked isoalantolactone-mediated apoptosis in PANC-1 cells indicating that ROS are involved in isoalantolactone-mediated apoptosis. Western blot study showed that isoalantolactone increased the expression of phosphorylated p38 MAPK, Bax, and cleaved caspase-3 and decreased the expression of Bcl-2 in a dose-dependent manner. No change in expression of phosphorylated p38 MAPK and Bax was found when cells were treated with isoalantolactone in the presence of NAC, indicating that activation of these proteins is directly dependent on ROS generation. The present study provides evidence for the first time that isoalantolactone induces ROS-dependent apoptosis through intrinsic pathway. Furthermore, our in vivo toxicity study demonstrated that isoalantolactone did not induce any acute or chronic toxicity in liver and kidneys of CD1 mice at dose of 100 mg/kg body weight. Therefore, isoalantolactone may be a safe chemotherapeutic candidate for the treatment of human pancreatic carcinoma. PMID:22532787

  19. Effects of various physical stress factors on mitochondrial function and reactive oxygen species in rat spermatozoa

    PubMed Central

    Kim, Suhee; Agca, Cansu; Agca, Yuksel

    2013-01-01

    The aim of the present study was to evaluate the effects of various physical interventions on the function of epididymal rat spermatozoa and determine whether there are correlations among these functional parameters. Epididymal rat spermatozoa were subjected to various mechanical (pipetting, centrifugation and Percoll gradient separation) and anisotonic conditions, and sperm motility, plasma membrane integrity (PMI), mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) were evaluated. Repeated pipetting caused a loss in motility, PMI and MMP (P < 0.05). Minimal centrifugation force (200g) had no effect on motility, PMI and MMP, whereas an increase in the centrifugation force to 400g or 600g decreased sperm function (P < 0.005). Percoll gradient separation increased total motility, PMI and MMP (P < 0.05). However, the spermatozoa that were subjected to mechanical interventions showed high susceptibility to a ROS stimulant (P < 0.005). Anisotonic conditions decreased motility, PMI and MMP, and hypotonic conditions in particular increased basal ROS (P < 0.05). In correlation tests, there were strong positive correlations among total motility, PMI and MMP, whereas ROS showed no or negatively weak correlations with the other parameters. In conclusion, the physical interventions may act as important variables, affecting functional parameters of epididymal rat spermatozoa. Therefore, careful consideration and proper protocols for handling of rat spermatozoa and osmotic conditions are required to achieve reliable results and minimise damage. PMID:23140582

  20. Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes

    SciTech Connect

    Radogna, Flavia [Dipartimento di Biologia, Universita di Roma Tor Vergata, via Ricerca Scientifica, 1, 00133 Roma (Italy); Paternoster, Laura [Dipartimento di Biologia, Universita di Roma Tor Vergata, via Ricerca Scientifica, 1, 00133 Roma (Italy); Istitututo di Chimica Biologica, Universita di Urbino Carlo Bo (Italy); De Nicola, Milena; Cerella, Claudia [Dipartimento di Biologia, Universita di Roma Tor Vergata, via Ricerca Scientifica, 1, 00133 Roma (Italy); Ammendola, Sergio [Ambiotec (Italy); Bedini, Annalida; Tarzia, Giorgio [Istituto di Chimica Farmaceutica, Universita di Urbino Carlo Bo (Italy); Aquilano, Katia; Ciriolo, Maria [Dipartimento di Biologia, Universita di Roma Tor Vergata, via Ricerca Scientifica, 1, 00133 Roma (Italy); Ghibelli, Lina [Dipartimento di Biologia, Universita di Roma Tor Vergata, via Ricerca Scientifica, 1, 00133 Roma (Italy)], E-mail: ghibelli@uniroma2.it

    2009-08-15

    Melatonin is a modified tryptophan with potent biological activity, exerted by stimulation of specific plasma membrane (MT1/MT2) receptors, by lower affinity intracellular enzymatic targets (quinone reductase, calmodulin), or through its strong anti-oxidant ability. Scattered studies also report a perplexing pro-oxidant activity, showing that melatonin is able to stimulate production of intracellular reactive oxygen species (ROS). Here we show that on U937 human monocytes melatonin promotes intracellular ROS in a fast (< 1 min) and transient (up to 5-6 h) way. Melatonin equally elicits its pro-radical effect on a set of normal or tumor leukocytes; intriguingly, ROS production does not lead to oxidative stress, as shown by absence of protein carbonylation, maintenance of free thiols, preservation of viability and regular proliferation rate. ROS production is independent from MT1/MT2 receptor interaction, since a) requires micromolar (as opposed to nanomolar) doses of melatonin; b) is not contrasted by the specific MT1/MT2 antagonist luzindole; c) is not mimicked by a set of MT1/MT2 high affinity melatonin analogues. Instead, chlorpromazine, the calmodulin inhibitor shown to prevent melatonin-calmodulin interaction, also prevents melatonin pro-radical effect, suggesting that the low affinity binding to calmodulin (in the micromolar range) may promote ROS production.

  1. Effects of combined radiofrequency radiation exposure on levels of reactive oxygen species in neuronal cells.

    PubMed

    Kang, Kyoung Ah; Lee, Hyung Chul; Lee, Je-Jung; Hong, Mi-Na; Park, Myung-Jin; Lee, Yun-Sil; Choi, Hyung-Do; Kim, Nam; Ko, Young-Gyu; Lee, Jae-Seon

    2014-03-01

    The objective of this study was to investigate the effects of the combined RF radiation (837 MHz CDMA plus 1950 MHz WCDMA) signal on levels of intracellular reactive oxygen species (ROS) in neuronal cells. Exposure of the combined RF signal was conducted at specific absorption rate values of 2 W/kg of CDMA plus 2 W/kg of WCDMA for 2 h. Co-exposure to combined RF radiation with either H2O2 or menadione was also performed. The experimental exposure groups were incubator control, sham-exposed, combined RF radiation-exposed with or without either H2O2 or menadione groups. The intracellular ROS level was measured by flow cytometry using the fluorescent probe dichlorofluorescein diacetate. Intracellular ROS levels were not consistently affected by combined RF radiation exposure alone in a time-dependent manner in U87, PC12 or SH-SY5Y cells. In neuronal cells exposed to combined RF radiation with either H2O2 or menadione, intracellular ROS levels showed no statically significant alteration compared with exposure to menadione or H2O2 alone. These findings indicate that neither combined RF radiation alone nor combined RF radiation with menadione or H2O2 influences the intracellular ROS level in neuronal cells such as U87, PC12 or SH-SY5Y. PMID:24105709

  2. Vibrio parahaemolyticus strengthens their virulence through modulation of cellular reactive oxygen species in vitro

    PubMed Central

    El-Malah, Shimaa S.; Yang, Zhenquan; Hu, Maozhi; Li, Qiuchun; Pan, Zhiming; Jiao, Xinan

    2014-01-01

    Vibrio parahaemolyticus (Vp) is one of the emergent food-borne pathogens that are commensally associated with various shellfish species throughout the world. It is strictly environmental and many strains are pathogenic to humans. The virulent strains cause distinct diseases, including wound infections, septicemia, and most commonly, acute gastroenteritis, which is acquired through the consumption of raw or undercooked seafood, especially shellfish. Vp has two type three secretion systems (T3SSs), which triggering its cytotoxicity and enterotoxicity via their effectors. To better understand the pathogenesis of Vp, we established a cell infection model in vitro using a non-phagocytic cell line. Caco-2 cells were infected with different strains of Vp (pandemic and non-pandemic strains) and several parameters of cytotoxicity were measured together with adhesion and invasion indices, which reflect the pathogen's virulence. Our results show that Vp adheres to cell monolayers and can invade non-phagocytic cells. It also survives and persists in non-phagocytic cells by modulating reactive oxygen species (ROS), allowing its replication, and resulting in complete cellular destruction. We conclude that the pathogenicity of Vp is based on its capacities for adhesion and invasion. Surprisingly's; enhanced of ROS resistance period could promote the survival of Vp inside the intestinal tract, facilitating tissue infection by repressing the host's oxidative stress response. PMID:25566508

  3. Cryptococcus neoformans capsule protects cell from oxygen reactive species generated by antimicrobial photodynamic inactivation

    NASA Astrophysics Data System (ADS)

    Prates, Renato Araujo; Hamblin, Michael R.; Kato, Ilka T.; Fuchs, Beth; Mylonakis, Eleytherios; Simões Ribeiro, Martha; Tegos, George

    2011-03-01

    Antimicrobial photodynamic inactivation (APDI) is based on the utilization of substances that can photosensitize biological tissues and are capable of being activated in the presence of light. Cryptococcus neoformans is an yeast surrounded by a capsule composed primarily of glucoronoxylomannan that plays an important role in its virulence. This yeast causes infection on skin, lungs and brain that can be associated with neurological sequelae and neurosurgical interventions, and its conventional treatment requires prolonged antifungal therapy, which presents important adverse effects. The aim of this study was to evaluate the protective effect of Cryptococcus neoformans capsule against reactive oxygen species generated by APDI. Cryptococcus neoformans KN99?, which is a strain able to produce capsule, and CAP59 that does not present capsule production were submitted to APDI using methylene blue (MB), rose bengal (RB), and pL-ce6 as photosensitizers (PS). Then microbial inactivation was evaluated by counting colony form units following APDI and confocal laser scanning microscopy (CLSM) illustrated localization as well as the preferential accumulation of PS into the fungal cells. C. neoformans KN99? was more resistant to APDI than CAP59 for all PSs tested. CLSM showed incorporation of MB and RB into the cytoplasm and a preferential uptake in mitochondria. A nuclear accumulation of MB was also observed. Contrarily, pL-ce6 appears accumulated in cell wall and cell membrane and minimal florescence was observed inside the fungal cells. In conclusion, the ability of C. neoformans to form capsule enhances survival following APDI.

  4. A Computational Model of Reactive Oxygen Species and Redox Balance in Cardiac Mitochondria

    PubMed Central

    Gauthier, Laura D.; Greenstein, Joseph L.; Cortassa, Sonia; O’Rourke, Brian; Winslow, Raimond L.

    2013-01-01

    Elevated levels of reactive oxygen species (ROS) play a critical role in cardiac myocyte signaling in both healthy and diseased cells. Mitochondria represent the predominant cellular source of ROS, specifically the activity of complexes I and III. The model presented here explores the modulation of electron transport chain ROS production for state 3 and state 4 respiration and the role of substrates and respiratory inhibitors. Model simulations show that ROS production from complex III increases exponentially with membrane potential (??m) when in state 4. Complex I ROS release in the model can occur in the presence of NADH and succinate (reverse electron flow), leading to a highly reduced ubiquinone pool, displaying the highest ROS production flux in state 4. In the presence of ample ROS scavenging, total ROS production is moderate in state 3 and increases substantially under state 4 conditions. The ROS production model was extended by combining it with a minimal model of ROS scavenging. When the mitochondrial redox status was oxidized by increasing the proton permeability of the inner mitochondrial membrane, simulations with the combined model show that ROS levels initially decline as production drops off with decreasing ??m and then increase as scavenging capacity is exhausted. Hence, this mechanistic model of ROS production demonstrates how ROS levels are controlled by mitochondrial redox balance. PMID:23972856

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

    PubMed Central

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

    2013-01-01

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

  6. Cytotoxicity and reactive oxygen species generation from aggregated carbon and carbonaceous nanoparticulate materials

    PubMed Central

    Garza, Kristine M; Soto, Karla F; Murr, Lawrence E

    2008-01-01

    We have investigated the cytotoxicity and reactive oxygen species (ROS) generation for indoor and outdoor soots: candle, wood, diesel, tire, and natural gas burner soots – along with surrogate black carbon, various multiwall carbon nanotube aggregate materials, TiO2 (anatase) and chrysotile asbestos as reference materials. All soots were observed utilizing TEM and FESEM to be composed of aggregated, primary spherules (20–80 nm diameter) forming complex, branched fractal structures. These spherules were composed of intercalated, turbostratic arrangements of curved graphene fragments with varying concentrations of polycyclic aromatic hydrocarbon (PAH) isomers. In vitro cultures with an immortalized human lung epithelial carcinoma cell line (A549) treated with these materials showed decreased cell viability and variations in ROS production, with no correlations to PAH content. The data demonstrate that soots are cytotoxic and that cytotoxicity is not related to PAH content but is related to ROS generation, suggesting that soot induces cellular oxidative stress and that cell viability assays can be indicators of ROS production. PMID:18488419

  7. Reactive oxygen species and cytotoxicity in rainbow trout hepatocytes: effects of medium and incubation time.

    PubMed

    Yazdani, Mazyar; Paulsen, Ragnhild Elisabeth; Gjøen, Tor; Hylland, Ketil

    2015-02-01

    This study evaluated the effects of exposure medium and culture age on intracellular reactive oxygen species (ROS) development and cytotoxicity in fish hepatocytes following exposure to copper (Cu). ROS was quantified using the fluorescent probes DHR 123 and CM-H2DCFDA following exposure to Cu in Leibovitz' medium (L-15) or Tris-buffered saline (TBS). Similarly, culture age effects were investigated using 1-, 2- and 4-day-old cultured hepatocytes by exposing them to Cu in TBS. The exposure in L-15 resulted in significantly higher ROS compared to TBS using CM-H2DCFDA, but not DHR 123. The age of the primary cultures significantly affected the development of ROS for both probes. None of the exposures caused cytotoxicity in the hepatocytes. The results showed that both factors may affect responses to stressors, and suggested that the use of a simple medium such as TBS may be preferable for some applications. It is also preferable to use 1-day-old primary hepatocyte cultures. PMID:25432295

  8. Reactive oxygen species have a causal role in multiple forms of insulin resistance.

    PubMed

    Houstis, Nicholas; Rosen, Evan D; Lander, Eric S

    2006-04-13

    Insulin resistance is a cardinal feature of type 2 diabetes and is characteristic of a wide range of other clinical and experimental settings. Little is known about why insulin resistance occurs in so many contexts. Do the various insults that trigger insulin resistance act through a common mechanism? Or, as has been suggested, do they use distinct cellular pathways? Here we report a genomic analysis of two cellular models of insulin resistance, one induced by treatment with the cytokine tumour-necrosis factor-alpha and the other with the glucocorticoid dexamethasone. Gene expression analysis suggests that reactive oxygen species (ROS) levels are increased in both models, and we confirmed this through measures of cellular redox state. ROS have previously been proposed to be involved in insulin resistance, although evidence for a causal role has been scant. We tested this hypothesis in cell culture using six treatments designed to alter ROS levels, including two small molecules and four transgenes; all ameliorated insulin resistance to varying degrees. One of these treatments was tested in obese, insulin-resistant mice and was shown to improve insulin sensitivity and glucose homeostasis. Together, our findings suggest that increased ROS levels are an important trigger for insulin resistance in numerous settings. PMID:16612386

  9. Detection of reactive oxygen species in mainstream cigarette smoke by a fluorescent probe

    NASA Astrophysics Data System (ADS)

    Liu, Li; Xu, Shi-jie; Li, Song-zhan

    2009-07-01

    A mass of reactive oxygen species(ROS) are produced in the process of smoking. Superfluous ROS can induce the oxidative stress in organism, which will cause irreversible damage to cells. Fluorescent probe is taken as a marker of oxidative stress in biology and has been applied to ROS detection in the field of biology and chemistry for high sensitivity, high simplicity of data collection and high resolution. As one type of fluorescent probe, dihydrorhodamine 6G (dR6G) will be oxidized to the fluorescent rhodamine 6G, which could be used to detect ROS in mainstream cigarette smoke. We investigated the action mechanism of ROS on dR6G, built up the standard curve of R6G fluorescence intensity with its content, achieved the variation pattern of R6G fluorescence intensity with ROS content in mainstream cigarette smoke and detected the contents of ROS from the 4 types of cigarettes purchased in market. The result shows that the amount of ROS has close relationship with the types of tobacco and cigarette production technology. Compared with other detecting methods such as electronic spin resonance(ESR), chromatography and mass spectrometry, this detection method by the fluorescent probe has higher efficiency and sensitivity and will have wide applications in the ROS detection field.

  10. Interactions Between Reactive Oxygen Species Generated by Contractile Activity and Aging in Skeletal Muscle?

    PubMed Central

    2013-01-01

    Abstract Significance: Aging leads to a loss of skeletal muscle mass and function that causes instability, increased risk of falls, and need for residential care. This is due to a reduction in the muscle mass and strength that is primarily due caused by a decrease in the number of muscle fibers, particularly, type II fibers, and atrophy and weakening of those remaining. Recent Advances: Although increased oxidative damage was originally thought to be the key to the aging process, data now indicate that reactive oxygen species (ROS) may be one of the several components of the degenerative processes in aging. The skeletal muscle shows important rapid adaptations to the ROS generated by contractions that are attenuated in aged organisms and transgenic studies have indicated that overcoming these attenuated responses can prevent the age-related loss of muscle mass and function. Critical Issues: Elucidation of the mechanisms by which the skeletal muscle adapts to the ROS generated to contractions and the way in which these processes are attenuated by aging is critical to the development of logical approaches to prevent age-related loss of muscle mass and function. Future Directions: Future studies are likely to focus on the redox regulation of adaptive pathways and their maintenance during aging as an approach to maintain and improve muscle function. Antioxid. Redox Signal. 19, 804–812. PMID:23682926

  11. Effects of oligosaccharides and polysaccharides on the generation of reactive oxygen species in different biological systems.

    PubMed

    Radman, Romeo; Bland, Elliot James; Sangworachat, Nuntaka; Bucke, Christopher; Keshavarz, Tajalli

    2006-06-01

    Use of carbohydrates as elicitors is a novel technique for enhancement of the production of industrially important microbial products. The relation between the levels of ROS (reactive oxygen species) and overproduction of antibiotics in microbial cultures has already been established. In the present study, we aimed to exploit the ROS response to develop a fast technique to assess the potential of oligosaccharides [oligoguluronate, oligomannuronate and MO (mannan oligosaccharides)] and polysaccharides [alginate and LBG (locust-bean gum)] as elicitors for overproduction of secondary metabolites in Streptomyces rimosus and Penicillium chrysogenum. We have also investigated changes in the production of ROS in neutrophils as a result of the action of the same elicitors. LBG-derived oligosaccharides (MO) were most potent inhibitors of ROS in all systems investigated. This correlates with overproduction of secondary metabolites in microbes and enhancement of a number of mammalian systems. We believe that the effects of oligosaccharides and polysaccharides on ROS production by mammalian and microbial cells can be correlated predicatively with overproduction. The underlying methodology offers a fast screening of elicitors that can be applied across the different systems. PMID:16483254

  12. Mitochondrial reactive oxygen species regulate spatial profile of proinflammatory responses in lung venular capillaries.

    PubMed

    Parthasarathi, Kaushik; Ichimura, Hideo; Quadri, Sadiqa; Issekutz, Andrew; Bhattacharya, Jahar

    2002-12-15

    Cytokine-induced lung expression of the endothelial cell (EC) leukocyte receptor P-selectin initiates leukocyte rolling. To understand the early EC signaling that induces the expression, we conducted real-time digital imaging studies in lung venular capillaries. To compare receptor- vs nonreceptor-mediated effects, we infused capillaries with respectively, TNF-alpha and arachidonate. At concentrations adjusted to give equipotent increases in the cytosolic Ca(2+), both agents increased reactive oxygen species (ROS) production and EC P-selectin expression. Blocking the cytosolic Ca(2+) increases abolished ROS production; blocking ROS production abrogated P-selectin expression. TNF-alpha, but not arachidonate, released Ca(2+) from endoplasmic stores and increased mitochondrial Ca(2+). Furthermore, Ca(2+) depletion abrogated TNF-alpha responses partially, but arachidonate responses completely. These differences in Ca(2+) mobilization by TNF-alpha and arachidonate were reflected in spatial patterning in the capillary in that the TNF-alpha effects were localized at branch points, while the arachidonate effects were nonlocalized and extensive. Furthermore, mitochondrial blockers inhibited the TNF-alpha- but not the arachidonate-induced responses. These findings indicate that the different modes of Ca(2+) mobilization determined the spatial patterning of the proinflammatory response in lung capillaries. Responses to TNF-alpha revealed that EC mitochondria regulate the proinflammatory process by generating ROS that activate P-selectin expression. PMID:12471144

  13. ?-lipoic acid protects dopaminergic neurons against MPP+-induced apoptosis by attenuating reactive oxygen species formation.

    PubMed

    Li, Da-Wei; Li, Guang-Ren; Lu, Yan; Liu, Zhi-Qiang; Chang, Ming; Yao, Ming; Cheng, Wei; Hu, Lin-Sen

    2013-07-01

    Reactive oxygen species (ROS) elicited by oxidative stress are widely recognized as a major initiator in the dege-neration of dopaminergic neurons distinctive of Parkinson's disease (PD). The interaction of ROS with mitochondria triggers sequential events in the mitochondrial cell death pathway, which is thought to be responsible for ROS-mediated neurodegeneration in PD. ?-lipoic acid (LA) is a pleiotropic compound with potential pharmacotherapeutic value against a range of pathophysiological insults. Its protective actions against oxidative damage by scavenging ROS and reducing production of free radicals have been reported in various in vitro and in vivo systems. This study analyzed the ability of LA to protect PC12 neuronal cells from toxicity of 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which is known to kill dopaminergic neurons selectively and to cause severe parkinsonism-like symptoms in humans and primate animals. Our results demonstrate that the apoptosis of PC12 cells elicited by MPP+ could be significantly prevented by pretreatment with LA for 1 h. In addition, LA inhibits intercellular ROS levels and the mitochondrial transmembrane permeability, the key players in the pathogenesis of PD, thereby protecting dopaminergic neuronal cells against oxidative damage. PMID:23615851

  14. The role of mitochondrial reactive oxygen species in cartilage matrix destruction.

    PubMed

    Reed, Kendra N; Wilson, Glenn; Pearsall, Albert; Grishko, Valentina I

    2014-12-01

    Upregulation of matrix metalloproteinases (MMPs) is a hallmark of osteoarthritis progression; along with the role reactive oxygen species (ROS) may play in this process. Moreover, mitochondrial DNA damage and dysfunction are also present in osteoarthritic chondrocytes. However, there are no studies published investigating the direct relationship between mitochondrial ROS, mitochondrial DNA damage, and MMP expression. Therefore, the purpose of the present study was to evaluate whether mitochondrial DNA damage and mitochondrial-originated oxidative stress modulates matrix destruction through the upregulation of MMP protein levels. MitoSox red was utilized to observe mitochondrial ROS production while a Quantitative Southern blot technique was conducted to analyze mitochondrial DNA damage. Additionally, Western blot analysis was used to determine MMP protein levels. The results of the present study show that menadione augmented mitochondrial-generated ROS and increased mitochondrial DNA damage. This increase in mitochondrial-generated ROS led to an increase in MMP levels. When a mitochondrial ROS scavenger was added, there was a subsequent reduction in MMP levels. These studies reveal that mitochondrial integrity is essential for maintaining the cartilage matrix by altering MMP levels. This provides new and important insights into the role of mitochondria in chondrocyte function and its potential importance in therapeutic approaches. PMID:25129057

  15. The Emerging Role of Reactive Oxygen Species Signaling during Lateral Root Development.

    PubMed

    Manzano, Concepción; Pallero-Baena, Mercedes; Casimiro, Ilda; De Rybel, Bert; Orman-Ligeza, Beata; Van Isterdael, Gert; Beeckman, Tom; Draye, Xavier; Casero, Pedro; Del Pozo, Juan C

    2014-05-30

    Overall root architecture is the combined result of primary and lateral root growth and is influenced by both intrinsic genetic programs and external signals. One of the main questions for root biologists is how plants control the number of lateral root primordia and their emergence through the main root. We recently identified S-phase kinase-associated protein2 (SKP2B) as a new early marker for lateral root development. Here, we took advantage of its specific expression pattern in Arabidopsis (Arabidopsis thaliana) in a cell-sorting and transcriptomic approach to generate a lateral root-specific cell sorting SKP2B data set that represents the endogenous genetic developmental program. We first validated this data set by showing that many of the identified genes have a function during root growth or lateral root development. Importantly, genes encoding peroxidases were highly represented in our data set. Thus, we next focused on this class of enzymes and showed, using genetic and chemical inhibitor studies, that peroxidase activity and reactive oxygen species signaling are specifically required during lateral root emergence but, intriguingly, not for primordium specification itself. PMID:24879433

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

    PubMed Central

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

    2014-01-01

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

  17. Mitochondrial uncoupling does not decrease reactive oxygen species production after ischemia-reperfusion.

    PubMed

    Quarrie, Ricardo; Lee, Daniel S; Reyes, Levy; Erdahl, Warren; Pfeiffer, Douglas R; Zweier, Jay L; Crestanello, Juan A

    2014-10-01

    Cardiac ischemia-reperfusion (IR) leads to myocardial dysfunction by increasing production of reactive oxygen species (ROS). Mitochondrial H(+) leak decreases ROS formation; it has been postulated that increasing H(+) leak may be a mechanism of decreasing ROS production after IR. Ischemic preconditioning (IPC) decreases ROS formation after IR, but the mechanism is unknown. We hypothesize that pharmacologically increasing mitochondrial H(+) leak would decrease ROS production after IR. We further hypothesize that IPC would be associated with an increase in the rate of H(+) leak. Isolated male Sprague-Dawley rat hearts were subjected to either control or IPC. Mitochondria were isolated at end equilibration, end ischemia, and end reperfusion. Mitochondrial membrane potential (m??) was measured using a tetraphenylphosphonium electrode. Mitochondrial uncoupling was achieved by adding increasing concentrations of FCCP. Mitochondrial ROS production was measured by fluorometry using Amplex-Red. Pyridine dinucleotide levels were measured using HPLC. Before IR, increasing H(+) leak decreased mitochondrial ROS production. After IR, ROS production was not affected by increasing H(+) leak. H(+) leak increased at end ischemia in control mitochondria. IPC mitochondria showed no change in the rate of H(+) leak throughout IR. NADPH levels decreased after IR in both IPC and control mitochondria while NADH increased. Pharmacologically, increasing H(+) leak is not a method of decreasing ROS production after IR. Replenishing the NADPH pool may be a means of scavenging the excess ROS thereby attenuating oxidative damage after IR. PMID:25085966

  18. Antimalarial action of artesunate involves DNA damage mediated by reactive oxygen species.

    PubMed

    Gopalakrishnan, Anusha M; Kumar, Nirbhay

    2015-01-01

    Artemisinin-based combination therapy (ACT) is the recommended first-line treatment for Plasmodium falciparum malaria. It has been suggested that the cytotoxic effect of artemisinin is mediated by free radicals followed by the alkylation of P. falciparum proteins. The endoperoxide bridge, the active moiety of artemisinin derivatives, is cleaved in the presence of ferrous iron, generating reactive oxygen species (ROS) and other free radicals. However, the emergence of resistance to artemisinin in P. falciparum underscores the need for new insights into the molecular mechanisms of antimalarial activity of artemisinin. Here we show that artesunate (ART) induces DNA double-strand breaks in P. falciparum in a physiologically relevant dose- and time-dependent manner. DNA damage induced by ART was accompanied by an increase in the intracellular ROS level in the parasites. Mannitol, a ROS scavenger, reversed the cytotoxic effect of ART and reduced DNA damage, and modulation of glutathione (GSH) levels was found to impact ROS and DNA damage induced by ART. Accumulation of ROS, increased DNA damage, and the resulting antiparasite effect suggest a causal relationship between ROS, DNA damage, and parasite death. Finally, we also show that ART-induced ROS production involves a potential role for NADPH oxidase, an enzyme involved in the production of superoxide anions. Our results with P. falciparum provide novel insights into previously unknown molecular mechanisms underlying the antimalarial activity of artemisinin derivatives and may help in the design of next-generation antimalarial drugs against the most virulent Plasmodium species. PMID:25348537

  19. Apogossypolone induces reactive oxygen species accumulation and controls cell cycle progression in Raji Burkkit's lymphoma cells.

    PubMed

    Hu, Zhe-Yu; Xu, Fei; Sun, Rui; Chen, Yan-Feng; Zhang, Dong-Sheng; Fan, Yu-Hua; Sun, Jian

    2015-07-01

    Burkitt's lymphoma (BL) is a highly aggressive type of non?Hodgkin's lymphoma, with marked rates of proliferation and metabolism. The expression levels of the translocated cellular Myc (c?Myc) oncogene and Epstein?Barr virus infection have an oncogenic role in facilitating tumor progression and maintaining a malignant phenotype in BL Raji cells. The present study identified that more reactive oxygen species (ROS) were produced in Raji cells compared with other types of malignant B cells. Cells exhibiting higher ROS levels suggested facilitation of the induction of cell death by ROS?induction compounds. In the present study, apogossypolone (ApoG2) was observed to induce marked accumulation in the levels of ROS in the Raji cells, which damaged the cells and suppressed cell proliferation. Within 12 h following ApoG2 treatment, the Raji cells were prominently arrested in the G1 phase of the cell cycle. Immunoblotting analysis indicated that the chromodomain?helicase?DNA?binding protein 1, checkpoint kinase 1 and c?Myc proteins were significantly downregulated at 3, 6 and 12 h, respectively, following treatment. Following treatment with ApoG2 for 48 h, ApoG2 induced significant apoptosis in the Raji cells. This findings, together with our previous studies, which demonstrated ApoG2 as a potent inhibitor of anti?apoptotic B cell lymphoma 2 proteins, indicated that the ROS stimulatory effect of ApoG2 increased the antitumor activity of ApoG2. PMID:25738577

  20. A small molecule that induces reactive oxygen species via cellular glutathione depletion.

    PubMed

    Kawamura, Tatsuro; Kondoh, Yasumitsu; Muroi, Makoto; Kawatani, Makoto; Osada, Hiroyuki

    2014-10-01

    Induction of excessive levels of reactive oxygen species (ROS) by small-molecule compounds has been considered a potentially effective therapeutic strategy against cancer cells, which are often subjected to chronic oxidative stress. However, to elucidate the mechanisms of action of bioactive compounds is generally a time-consuming process. We have recently identified NPD926, a small molecule that induces rapid cell death in cancer cells. Using a combination of two comprehensive and complementary approaches, proteomic profiling and affinity purification, together with the subsequent biochemical assays, we have elucidated the mechanism of action underlying NPD926-induced cell death: conjugation with glutathione mediated by GST, depletion of cellular glutathione and subsequent ROS generation. NPD926 preferentially induced effects in KRAS-transformed fibroblast cells, compared with their untransformed counterparts. Furthermore, NPD926 sensitized cells to inhibitors of system x(c)?, a cystine-glutamate antiporter considered to be a potential therapeutic target in cancers including cancer stem cells. These data show the effectiveness of a newly identified ROS inducer, which targets glutathione metabolism, in cancer treatment. PMID:25011393

  1. Apoptosis and autophagy in rat cerebellar granule neuron death: Role of reactive oxygen species.

    PubMed

    Maycotte, Paola; Guemez-Gamboa, Alicia; Moran, Julio

    2010-01-01

    Programmed cell death (PCD) has been defined as an active, controlled process in which cells participate in their own demise. Apoptosis, or type I PCD, has been widely characterized, both morphologically and biochemically. More recently, autophagy, the self-digesting mechanism involved in the removal of cytoplasmic long-lived proteins, has been involved in cell death, and type II PCD is defined as cell death occurring with autophagic features. Neurons can undergo more than one type of PCD as a backup mechanism when the traditional death pathway is inhibited or in response to a particular death-inducing stimulus. Reactive oxygen species (ROS) have been shown to be important signaling molecules in the execution of apoptosis and, more recently, in the autophagic pathway. In this work, we characterize apoptotic and autophagic cell death in rat cerebellar granule neuron (CGN) culture, a widespread model for the study of neuronal death. Potassium deprivation (K5) and staurosporine (STS) were used for death induction. We found apoptotic and autophagic features under both conditions. Caspase inhibition as well as autophagy inhibition by 3-methyl adenine decreased cell death. Moreover, CGN can undergo the alternative type of cell death when the other one is inhibited. An antioxidant or NADPH oxidase inhibitors delayed apoptosis and had no effect in autophagic features. Thus, we found that autophagy plays a role in cell death of CGN and that, when cells are treated with K5 or STS, both autophagy and ROS seem to promote apoptosis by independent mechanisms. PMID:19598251

  2. Reactive oxygen species scavenging by catalase is important for female Lutzomyia longipalpis fecundity and mortality.

    PubMed

    Diaz-Albiter, Hector; Mitford, Roanna; Genta, Fernando A; Sant'Anna, Mauricio R V; Dillon, Rod J

    2011-01-01

    The phlebotomine sand fly Lutzomyia longipalpis is the most important vector of American visceral leishmaniasis (AVL), the disseminated and most serious form of the disease in Central and South America. In the natural environment, most female L. longipalpis are thought to survive for less than 10 days and will feed on blood only once or twice during their lifetime. Successful transmission of parasites occurs when a Leishmania-infected female sand fly feeds on a new host. Knowledge of factors affecting sand fly longevity that lead to a reduction in lifespan could result in a decrease in parasite transmission. Catalase has been found to play a major role in survival and fecundity in many insect species. It is a strong antioxidant enzyme that breaks down toxic reactive oxygen species (ROS). Ovarian catalase was found to accumulate in the developing sand fly oocyte from 12 to 48 hours after blood feeding. Catalase expression in ovaries as well as oocyte numbers was found to decrease with age. This reduction was not found in flies when fed on the antioxidant ascorbic acid in the sugar meal, a condition that increased mortality and activation of the prophenoloxidase cascade. RNA interference was used to silence catalase gene expression in female Lu. longipalpis. Depletion of catalase led to a significant increase of mortality and a reduction in the number of developing oocytes produced after blood feeding. These results demonstrate the central role that catalase and ROS play in the longevity and fecundity of phlebotomine sand flies. PMID:21408075

  3. TOR complex 2–Ypk1 signaling regulates actin polarization via reactive oxygen species

    PubMed Central

    Niles, Brad J.; Powers, Ted

    2014-01-01

    The evolutionarily conserved mTOR complex 2 (mTORC2) signaling pathway is an important regulator of actin cytoskeletal architecture and, as such, is a candidate target for preventing cancer cell motility and invasion. Remarkably, the precise mechanism(s) by which mTORC2 regulates the actin cytoskeleton have remained elusive. Here we show that in budding yeast, TORC2 and its downstream kinase Ypk1 regulate actin polarization by controlling reactive oxygen species (ROS) accumulation. Specifically, we find that TORC2-Ypk1 regulates actin polarization both by vacuole-related ROS, controlled by the phospholipid flippase kinase Fpk1 and sphingolipids, and by mitochondria-mediated ROS, controlled by the PKA subunit Tpk3. In addition, we find that the protein kinase C (Pkc1)/MAPK cascade, a well-established regulator of actin, acts downstream of Ypk1 to regulate ROS, in part by promoting degradation of the oxidative stress responsive repressor, cyclin C. Furthermore, we show that Ypk1 regulates Pkc1 activity through proper localization of Rom2 at the plasma membrane, which is also dependent on Fpk1 and sphingolipids. Together these findings demonstrate important links between TORC2/Ypk1 signaling, Fpk1, sphingolipids, Pkc1, and ROS as regulators of actin and suggest that ROS may play an important role in mTORC2-dependent dysregulation of the actin cytoskeleton in cancer cells. PMID:25253719

  4. Regulation of Murine Intestinal Inflammation by Reactive Metabolites of Oxygen and Nitrogen

    PubMed Central

    Krieglstein, Christian F.; Cerwinka, Wolfgang H.; Laroux, F. Stephen; Salter, James W.; Russell, Janice M.; Schuermann, Guido; Grisham, Matthew B.; Ross, Christopher R.; Granger, D. Neil

    2001-01-01

    Several reports have implicated reactive oxygen and nitrogen metabolites (RONS) in the initiation and/or progression of inflammatory bowel diseases (IBDs). We have investigated the role of three key RONS-metabolizing enzymes (inducible nitric oxide synthase [iNOS], superoxide dismutase [SOD], nicotinamide adenine dinucleotide phosphate [NADPH] oxidase) in a murine model of IBD. Mice genetically deficient (?/?) in either iNOS or the p47phox subunit of NADPH oxidase, transgenic (Tg) mice that overexpress SOD, and their respective wild-type (WT) littermates were fed dextran sulfate sodium (DSS) in drinking water for 7 days to induce colitis. In addition, the specific iNOS inhibitor 1400W was used in DSS-treated WT and p47phox?/? mice. WT mice responded to DSS feeding with progressive weight loss, bloody stools, elevated serum NOX and colonic mucosal injury with neutrophil infiltration. Both the onset and severity of colitis were significantly attenuated in iNOS?/? and 1400W-treated WT mice. While the responses to DSS did not differ between WT and p47phox?/? mice, enhanced protection was noted in 1400W-treated p47phox?/? mice. Interestingly, SODTg mice exhibited more severe colitis than their WT littermates. These findings reveal divergent roles for superoxide and iNOS-derived NO in intestinal inflammation. PMID:11696587

  5. Nicorandil prevents sirolimus-induced production of reactive oxygen species, endothelial dysfunction, and thrombus formation.

    PubMed

    Aizawa, Ken; Takahari, Youko; Higashijima, Naoko; Serizawa, Kenichi; Yogo, Kenji; Ishizuka, Nobuhiko; Endo, Koichi; Fukuyama, Naoto; Hirano, Katsuya; Ishida, Hideyuki

    2015-03-01

    Sirolimus (SRL) is widely used to prevent restenosis after percutaneous coronary intervention. However, its beneficial effect is hampered by complications of thrombosis. Several studies imply that reactive oxygen species (ROS) play a critical role in endothelial dysfunction and thrombus formation. The present study investigated the protective effect of nicorandil (NIC), an anti-angina agent, on SRL-associated thrombosis. In human coronary artery endothelial cells (HCAECs), SRL stimulated ROS production, which was prevented by co-treatment with NIC. The preventive effect of NIC on ROS was abolished by 5-hydroxydecanoate but not by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. NIC also inhibited SRL-induced up-regulation of NADPH oxidase subunit p22(phox) mRNA. Co-treatment with NIC and SRL significantly up-regulated superoxide dismutase 2. NIC treatment significantly improved SRL-induced decrease in viability of HCAECs. The functional relevance of the preventive effects of NIC on SRL-induced ROS production and impairment of endothelial viability was investigated in a mouse model of thrombosis. Pretreatment with NIC inhibited the SRL-induced acceleration of FeCl3-initiated thrombus formation and ROS production in the testicular arteries of mice. In conclusion, NIC prevented SRL-induced thrombus formation, presumably due to the reduction of ROS and to endothelial protection. The therapeutic efficacy of NIC could represent an additional option in the prevention of SRL-related thrombosis. PMID:25837924

  6. Zinc protects Ceratophyllum demersum L. (free-floating hydrophyte) against reactive oxygen species induced by cadmium.

    PubMed

    Aravind, P; Prasad, M N V; Malec, P; Waloszek, A; Strza?ka, K

    2009-01-01

    Evidence for Zn protection against Cd-induced reactive oxygen species in the free-floating hydrophyte Ceratophyllum demersum L. is presented in this paper. Metal treatments of 10 micromol/L Cd, 10 Cd micromol/L supplemented with Zn (10, 50, 100 and 200 micromol/L) and Zn-alone treatments of the same concentrations were used. Using 5,5 dimethyl pyrroline-N-oxide as the spin-probe, electron spin resonance spectra indicated a drastic increase in hydroxyl radicals (OH()) in Cd-10 micromol/L treatments, which was closely correlating with the enhanced formation of hydrogen peroxide (H(2)O(2)) and generation of superoxide radical (O(2)(-)) triggered by the oxidation of NADPH. The supplementation of adding Zn (10-200 micromol/L) to the Cd-10 micromol/L treatments significantly decreased the production of free radicals especially by eliminating the precursors of OH() through inhibition of NADPH oxidation. Cd-enhanced ROS production which substantially increased the oxidative products of proteins measured as carbonyls was effectively inhibited by Zn supplementation. PMID:19203717

  7. Perfluoroalkylated compounds induce cell death and formation of reactive oxygen species in cultured cerebellar granule cells.

    PubMed

    Reistad, Trine; Fonnum, Frode; Mariussen, Espen

    2013-03-27

    The present communication investigates the effects of different perfluoroalkylated compounds (PFCs) on formation of reactive oxygen species (ROS) and cell death in cultured cerebellar granule cells. This allows direct comparison with similar effects found for other environmental contaminants like polychlorinated biphenyls and brominated flame-retardants. The increase in ROS formation and cell death was assayed using the fluorescent probe 2,7-dichlorofluorescin diacetate (DCFH-DA) and the trypan blue exclusion assay. The effects of the PFCs were structure dependent. Cell death was induced at relatively low concentrations by perfluorooctyl sulfonate (PFOS), perfluorooctane sulfonylamide (PFOSA) and the fluorotelomer alcohol 1H, 1H, 2H, 2H-perfluorodecanol (FTOH 8:2) with EC(50)-values of 62 ± 7.6, 13 ± 1.8 and 15 ± 4.2 ?M (mean ± SD) respectively. PFOS, perfluorooctanoic acid (PFOA) and PFOSA induced a concentration dependent increase in ROS formation with EC(50)-values of 27 ± 9.0, 25 ± 11 and 57 ± 19?M respectively. Reduced cell viability and ROS formation were observed at concentration level close to what is found in serum of occupationally exposed workers. The effect of PFCs on ROS formation and cell viability was compared with other halogenated compounds and future investigations should emphasize effects of mixtures and how physical chemical properties of the compounds influence their toxicity. PMID:23340305

  8. Reactive Oxygen Species Are Involved in Plant Defense against a Gall Midge[C][W][OA

    PubMed Central

    Liu, Xuming; Williams, Christie E.; Nemacheck, Jill A.; Wang, Haiyan; Subramanyam, Subhashree; Zheng, Cheng; Chen, Ming-Shun

    2010-01-01

    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 (Triticum aestivum) and rice (Oryza sativa) against Hessian fly (Mayetiola destructor) larvae. Rapid and prolonged accumulation of hydrogen peroxide (H2O2) was detected in wheat plants at the attack site during incompatible interactions. Increased accumulation of both H2O2 and superoxide was detected in rice plants during nonhost interactions with the larvae. No increase in accumulation of either H2O2 or superoxide was observed in wheat plants during compatible interactions. A global analysis revealed changes in the abundances of 250 wheat transcripts and 320 rice transcripts encoding proteins potentially involved in ROS homeostasis. A large number of transcripts encoded class III peroxidases that increased in abundance during both incompatible and nonhost interactions, whereas the levels of these transcripts decreased in susceptible wheat during compatible interactions. The higher levels of class III peroxidase transcripts were associated with elevated enzymatic activity of peroxidases at the attack site in plants during incompatible and nonhost interactions. Overall, our data indicate that class III peroxidases may play a role in ROS generation in resistant wheat and nonhost rice plants during response to Hessian fly attacks. PMID:19965963

  9. Endotoxin Priming of Neutrophils Requires Endocytosis and NADPH Oxidase-dependent Endosomal Reactive Oxygen Species*

    PubMed Central

    Lamb, Fred S.; Hook, Jessica S.; Hilkin, Brieanna M.; Huber, Jody N.; Volk, A. Paige Davis; Moreland, Jessica G.

    2012-01-01

    NADPH oxidase 2 (Nox2)-generated reactive oxygen species (ROS) are critical for neutrophil (polymorphonuclear leukocyte (PMN)) microbicidal function. Nox2 also plays a role in intracellular signaling, but the site of oxidase assembly is unknown. It has been proposed to occur on secondary granules. We previously demonstrated that intracellular NADPH oxidase-derived ROS production is required for endotoxin priming. We hypothesized that endotoxin drives Nox2 assembly on endosomes. Endotoxin induced ROS generation within an endosomal compartment as quantified by flow cytometry (dihydrorhodamine 123 and Oxyburst Green). Inhibition of endocytosis by the dynamin-II inhibitor Dynasore blocked endocytosis of dextran, intracellular generation of ROS, and priming of PMN by endotoxin. Confocal microscopy demonstrated a ROS-containing endosomal compartment that co-labeled with gp91phox, p40phox, p67phox, and Rab5, but not with the secondary granule marker CD66b. To further characterize this compartment, PMNs were fractionated by nitrogen cavitation and differential centrifugation, followed by free flow electrophoresis. Specific subfractions made superoxide in the presence of NADPH by cell-free assay (cytochrome c). Subfraction content of membrane and cytosolic subunits of Nox2 correlated with ROS production. Following priming, there was a shift in the light membrane subfractions where ROS production was highest. CD66b was not mobilized from the secondary granule compartment. These data demonstrate a novel, nonphagosomal intracellular site for Nox2 assembly. This compartment is endocytic in origin and is required for PMN priming by endotoxin. PMID:22235113

  10. Copper chelation selectively kills colon cancer cells through redox cycling and generation of reactive oxygen species

    PubMed Central

    2014-01-01

    Background Metals including iron, copper and zinc are essential for physiological processes yet can be toxic at high concentrations. However the role of these metals in the progression of cancer is not well defined. Here we study the anti-tumor activity of the metal chelator, TPEN, and define its mechanism of action. Methods Multiple approaches were employed, including cell viability, cell cycle analysis, multiple measurements of apoptosis, and mitochondrial function. In addition we measured cellular metal contents and employed EPR to record redox cycling of TPEN–metal complexes. Mouse xenografts were also performed to test the efficacy of TPEN in vivo. Results We show that metal chelation using TPEN (5?M) selectively induces cell death in HCT116 colon cancer cells without affecting the viability of non-cancerous colon or intestinal cells. Cell death was associated with increased levels of reactive oxygen species (ROS) and was inhibited by antioxidants and by prior chelation of copper. Interestingly, HCT116 cells accumulate copper to 7-folds higher levels than normal colon cells, and the TPEN-copper complex engages in redox cycling to generate hydroxyl radicals. Consistently, TPEN exhibits robust anti-tumor activity in vivo in colon cancer mouse xenografts. Conclusion Our data show that TPEN induces cell death by chelating copper to produce TPEN-copper complexes that engage in redox cycling to selectively eliminate colon cancer cells. PMID:25047035

  11. 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

  12. Seminal reactive oxygen species-antioxidant relationship in fertile males with and without varicocele.

    PubMed

    Mostafa, T; Anis, T; Imam, H; El-Nashar, A R; Osman, I A

    2009-04-01

    The aim of this study was to assess seminal reactive oxygen species (ROS)-antioxidants relationship in fertile and infertile men with and without varicocele. One hundred and seventy six males were studied; fertile healthy volunteers (n = 45), fertile men with varicocele (n = 45), infertile oligoasthenozoospermia (OA, n = 44) without varicocele and infertile OA with varicocele (n = 42). In their seminal plasma, two ROS parameters (malondialdehyde, hydrogen peroxide) and five antioxidants (superoxide dismutase, catalase, glutathione peroxidase, vitaminE, vitaminC) were estimated. Compared with fertile healthy men, in all other studied groups, estimated seminal ROS were significantly higher and estimated antioxidants were significantly lower. Infertile men with varicocele showed the same relationship as infertile men without varicocele. Sperm concentration, total sperm motility as well as sperm normal forms were negatively correlated with seminal malondialdehyde and were positively correlated with vitaminC. It is concluded that varicocele has an oxidative stress (OS) in fertile normozoospermic bearing conditions. This may allow understanding that, within men with varicocele, there is a threshold value of OS over which male fertility may be impaired. PMID:19260850

  13. Mitochondria-derived reactive oxygen species drive GANT61-induced mesothelioma cell apoptosis

    PubMed Central

    Lim, Chuan Bian; Prêle, Cecilia M.; Baltic, Svetlana; Arthur, Peter G.; Creaney, Jenette; Watkins, D. Neil; Thompson, Philip J.; Mutsaers, Steven E.

    2015-01-01

    Gli transcription factors of the Hedgehog (Hh) pathway have been reported to be drivers of malignant mesothelioma (MMe) cell survival. The Gli inhibitor GANT61 induces apoptosis in various cancer cell models, and has been associated directly with Gli inhibition. However various chemotherapeutics can induce cell death through generation of reactive oxygen species (ROS) but whether ROS mediates GANT61-induced apoptosis is unknown. In this study human MMe cells were treated with GANT61 and the mechanisms regulating cell death investigated. Exposure of MMe cells to GANT61 led to G1 phase arrest and apoptosis, which involved ROS but not its purported targets, GLI1 or GLI2. GANT61 triggered ROS generation and quenching of ROS protected MMe cells from GANT61-induced apoptosis. Furthermore, we demonstrated that mitochondria are important in mediating GANT61 effects: (1) ROS production and apoptosis were blocked by mitochondrial inhibitor rotenone; (2) GANT61 promoted superoxide formation in mitochondria; and (3) mitochondrial DNA-deficient LO68 cells failed to induce superoxide, and were more resistant to apoptosis induced by GANT61 than wild-type cells. Our data demonstrate for the first time that GANT61 induces apoptosis by promoting mitochondrial superoxide generation independent of Gli inhibition, and highlights the therapeutic potential of mitochondrial ROS-mediated anticancer drugs in MMe. PMID:25544756

  14. Mitochondrial metabolic suppression in fasting and daily torpor: consequences for reactive oxygen species production.

    PubMed

    Brown, Jason C L; Staples, James F

    2011-01-01

    Abstract Daily torpor results in an ?70% decrease in metabolic rate (MR) and a 20%-70% decrease in state 3 (phosphorylating) respiration rate of isolated liver mitochondria in both dwarf Siberian hamsters and mice even when measured at 37°C. This study investigated whether mitochondrial metabolic suppression also occurs in these species during euthermic fasting, when MR decreases significantly but torpor is not observed. State 3 respiration rate measured at 37°C was 20%-30% lower in euthermic fasted animals when glutamate but not succinate was used as a substrate. This suggests that electron transport chain complex I is inhibited during fasting. We also investigated whether mitochondrial metabolic suppression alters mitochondrial reactive oxygen species (ROS) production. In both torpor and euthermic fasting, ROS production (measured as H(2)O(2) release rate) was lower with glutamate in the presence (but not absence) of rotenone when measured at 37°C, likely reflecting inhibition at or upstream of the complex I ROS-producing site. ROS production with succinate (with rotenone) increased in torpor but not euthermic fasting, reflecting complex II inhibition during torpor only. Finally, mitochondrial ROS production was twofold more temperature sensitive than mitochondrial respiration (as reflected by Q(10) values). These data suggest that electron leak from the mitochondrial electron transport chain, which leads to ROS production, is avoided more efficiently at the lower body temperatures experienced during torpor. PMID:21897084

  15. Reactive oxygen species involved in CT26 immunogenic cell death induced by Clostridium difficile toxin B.

    PubMed

    Sun, Chunli; Wang, Haiying; Mao, Shuang; Liu, Ji; Li, Shan; Wang, Jufang

    2015-04-01

    Immunogenic cell death (ICD) is a new concept appeared in recent years. Despite growing interests of research on ICD, the circumstances that trigger immune responses against dying tumor cells remain largely unknown. It was demonstrated that recombinant Clostridium difficile toxin B (rTcdB) can induce ICD in intoxicated cells, but its mechanism remains unclear. This work aims at exploring whether reactive oxygen species (ROS) involved in rTcdB induced ICD using the chemical agent N-acetyl cysteine (NAC), diphenylene iodonium (DPI) and Antimycin A (Anti.A). The results suggested that ROS involved in rTcdB induced apoptosis and autophagy. DPI and Anti.A successfully inhibited the antitumor immune effect induced by rTcdB. As ICD is determined by a variety of factors, rTcdB is a potential tool for further exploring the circumstances that trigger ICD, which may offer us a good choice for designing the new chemotherapeutic drugs with immunogenic properties. PMID:25721381

  16. Reactive oxygen products in heterologous anti-glomerular basement membrane nephritis in rats.

    PubMed Central

    Birtwistle, R. J.; Michael, J.; Howie, A. J.; Adu, D.

    1989-01-01

    The effect of 'scavengers' of reactive oxygen products (ROPs) was studied in the heterologous phase of anti-glomerular basement (anti-GBM) nephritis induced in rats. Glomerulonephritis was induced by the intravenous administration of sheep anti-GBM antibody (5 mg/100 g) to rats on day 0. The intraperitoneal administration of superoxide dismutase (SOD) 30 mg/kg/day or 150 mg/kg/day leads to a significant reduction in proteinuria on day 1 and also on day 3 in animals given SOD 30 mg/kg/day. Proteinuria was not significantly reduced by the intraperitoneal administration of inactivated SOD (150 mg/kg/day). In rats given polyethylene glycol coupled catalase (PEG-catalase) intraperitoneally at a dose of 10,000 iu/kg/day and 100,000 iu/kg/day proteinuria was lower than in rats with unmodified anti-GBM nephritis. These differences were significant on day 1 (P less than 0.05) in rats given PEG-catalase 100,000 iu/kg/day and on days 3 and 5 in rats treated with either dose of PEG-catalase (P less than 0.01). These data suggest a role for superoxide anion and hydrogen peroxide, or a product of their interaction such as hydroxyl radical, in glomerular injury induced by anti-GBM antibody. PMID:2786425

  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. 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.

  19. Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)

    PubMed Central

    Ristow, Michael; Schmeisser, Kathrin

    2014-01-01

    Increasing evidence indicates that reactive oxygen species (ROS), consisting of superoxide, hydrogen peroxide, and multiple others, do not only cause oxidative stress, but rather may function as signaling molecules that promote health by preventing or delaying a number of chronic diseases, and ultimately extend lifespan. While high levels of ROS are generally accepted to cause cellular damage and to promote aging, low levels of these may rather improve systemic defense mechanisms by inducing an adaptive response. This concept has been named mitochondrial hormesis or mitohormesis. We here evaluate and summarize more than 500 publications from current literature regarding such ROS-mediated low-dose signaling events, including calorie restriction, hypoxia, temperature stress, and physical activity, as well as signaling events downstream of insulin/IGF-1 receptors, AMP-dependent kinase (AMPK), target-of-rapamycin (TOR), and lastly sirtuins to culminate in control of proteostasis, unfolded protein response (UPR), stem cell maintenance and stress resistance. Additionally, consequences of interfering with such ROS signals by pharmacological or natural compounds are being discussed, concluding that particularly antioxidants are useless or even harmful. PMID:24910588

  20. Reactive oxygen species in cell wall metabolism and development in plants.

    PubMed

    Kärkönen, Anna; Kuchitsu, Kazuyuki

    2015-04-01

    Although reactive oxygen species (ROS) are highly toxic substances that are produced during aerobic respiration and photosynthesis, many studies have demonstrated that ROS, such as superoxide anion radical (O2(-)) and hydrogen peroxide (H2O2), are produced in the plant cell wall in a highly regulated manner. These molecules are important signalling messengers playing key roles in controlling a broad range of physiological processes, such as cellular growth and development, as well as adaptation to environmental changes. Given the toxicity of ROS, especially of hydroxyl radical (OH), the enzymatic ROS production needs to be tightly regulated both spatially and temporally. Respiratory burst oxidase homologues (Rboh) have been identified as ROS-producing NADPH oxidases, which act as key signalling nodes integrating multiple signal transduction pathways in plants. Also other enzyme systems, such as class III peroxidases, amine oxidases, quinone reductases and oxalate oxidases contribute to apoplastic ROS production, some especially in certain plant taxa. Here we discuss the interrelationship among different enzymes producing ROS in the plant cell wall, as well as the physiological roles of the ROS produced. PMID:25446232

  1. Controllable generation of reactive oxygen species by femtosecond-laser irradiation

    SciTech Connect

    Yan, Wei; He, Hao, E-mail: haohe@tju.edu.cn; Wang, Yintao; Wang, Yisen; Hu, Minglie; Wang, Chingyue [Ultrafast Laser Laboratory, Key Laboratory of Optoelectronic Information Technology (Ministry of Education), College of Precision Instrument and Optoelectronics Engineering, Tianjin University, Tianjin (China)

    2014-02-24

    Femtosecond lasers have been advancing Biophotonics research in the past two decades with multiphoton microscopy, microsurgery, and photodynamic therapy. Nevertheless, laser irradiation is identified to bring photodamage to cells via reactive oxygen species (ROS) generation with unclear mechanism. Meanwhile, currently in biological researches, there is no effective method to provide controllable ROS production precisely, which originally is leaked from mitochondria during respiration and plays a key role in a lot of important cellular processes and cellular signaling pathways. In this study, we show the process of how the tightly focused femtosecond-laser induces ROS generation solely in mitochondria at the very beginning and then release to cytosol if the stimulus is intense enough. At certain weak power levels, the laser pulses induce merely moderate Ca{sup 2+} release but this is necessary for the laser to generate ROS in mitochondria. Cellular original ROS are also involved with a small contribution. When the power is above a threshold, ROS are then released to cytosol, indicating photodamage overwhelming cellular repair ability. The mechanisms in those two cases are quite different. Those results clarify parts of the mechanism in laser-induced ROS generation. Hence, it is possible to further this optical scheme to provide controllable ROS generation for ROS-related biological researches including mitochondrial diseases and aging.

  2. Controllable generation of reactive oxygen species by femtosecond-laser irradiation

    NASA Astrophysics Data System (ADS)

    Yan, Wei; He, Hao; Wang, Yintao; Wang, Yisen; Hu, Minglie; Wang, Chingyue

    2014-02-01

    Femtosecond lasers have been advancing Biophotonics research in the past two decades with multiphoton microscopy, microsurgery, and photodynamic therapy. Nevertheless, laser irradiation is identified to bring photodamage to cells via reactive oxygen species (ROS) generation with unclear mechanism. Meanwhile, currently in biological researches, there is no effective method to provide controllable ROS production precisely, which originally is leaked from mitochondria during respiration and plays a key role in a lot of important cellular processes and cellular signaling pathways. In this study, we show the process of how the tightly focused femtosecond-laser induces ROS generation solely in mitochondria at the very beginning and then release to cytosol if the stimulus is intense enough. At certain weak power levels, the laser pulses induce merely moderate Ca2+ release but this is necessary for the laser to generate ROS in mitochondria. Cellular original ROS are also involved with a small contribution. When the power is above a threshold, ROS are then released to cytosol, indicating photodamage overwhelming cellular repair ability. The mechanisms in those two cases are quite different. Those results clarify parts of the mechanism in laser-induced ROS generation. Hence, it is possible to further this optical scheme to provide controllable ROS generation for ROS-related biological researches including mitochondrial diseases and aging.

  3. Reactive oxygen species inhibitors block priming, but not activation of the NLRP3 inflammasome

    PubMed Central

    Bauernfeind, Franz; Bartok, Eva; Rieger, Anna; Franchi, Luigi; Núñez, Gabriel; Hornung, Veit

    2011-01-01

    A common denominator among the multiple damage-inducing agents that ultimately lead to the activation of NLRP3 has not yet been identified. Recently, the production of reactive oxygen species (ROS) has been suggested to act as a common event upstream of the NLRP3 inflammasome machinery. Since de novo translation of NLRP3 is an essential step in the activation of NLRP3, we investigated the role of substances that either inhibit ROS production or its oxidative activity. While we observe that NLRP3 inflammasome activation is unique amongst other known inflammasomes due to its sensitivity to ROS inhibition, we have found that this phenomenon is attributable to the fact that NLRP3 strictly requires priming by a pro-inflammatory signal, a step that is blocked by ROS inhibitors. While these data do not exclude a general role of ROS production in the process of NLRP3-triggered inflammation, they put ROS upstream of NLRP3 induction, but not activation. PMID:21677136

  4. Helicobacter pylori protects oncogenically transformed cells from reactive oxygen species-mediated intercellular induction of apoptosis.

    PubMed

    Bauer, Georg; Bereswill, Stefan; Aichele, Peter; Glocker, Erik

    2014-07-01

    Malignant transformation of gastric epithelial cells by chronic Helicobacter pylori infection is caused by several mechanisms including attraction of reactive oxygen species (ROS)-producing neutrophils and cytotoxin-associated antigen A-mediated dysplastic alterations. Here we show that H.pylori protects transformed cells from ROS-mediated intercellular induction of apoptosis. This potential control step in oncogenesis depends on the HOCl and NO/peroxynitrite (PON) signaling pathways. Helicobacter pylori-associated catalase and superoxide dismutase (SOD) efficiently cooperate in the inhibition of HOCl and the NO/PON signaling pathways. Helicobacter pylori catalase prevents HOCl synthesis through decomposition of hydrogen peroxide. Helicobacter pylori-associated SOD interferes with the crucial interactions between superoxide anions and HOCl, as well as superoxide anions and NO. The ratio of bacteria to malignant cells is critical for sufficient protection of transformed cells. Low concentrations of H.pylori more efficiently inhibited ROS-mediated destruction of transformed cells when compared with high concentrations of bacteria. Our data demonstrate the critical role of H.pylori antioxidant enzymes in the survival of transformed cells, modulating an early step of oncogenesis that is distinct from the transformation process per se. PMID:24662971

  5. Mitochondrial reactive oxygen species as a mystery voice in hepatitis C.

    PubMed

    Hino, Keisuke; Hara, Yuichi; Nishina, Sohji

    2014-02-01

    There are several lines of evidence suggesting that oxidative stress is present in hepatitis C to a greater degree than in other inflammatory liver diseases and is closely related to disease progression. The main production site of reactive oxygen species (ROS) is assumed to be mitochondria, which concept is supported by evidence that hepatitis C virus (HCV) core protein is directly associated with them. The detoxification of ROS also is an important function of the cellular redox homeostasis system. These results draw our attention to how HCV-induced mitochondrial ROS production is beyond redox regulation and affects the disease progression and development of hepatocellular carcinoma (HCC) in chronic hepatitis C. On the other hand, HCV-related chronic liver diseases are characterized by metabolic alterations such as insulin resistance, hepatic steatosis and/or iron accumulation in the liver. These metabolic disorders also are relevant to the development of HCC in HCV-related chronic liver diseases. Here, we review the mechanisms by which HCV increases mitochondrial ROS production and offer new insights as to how mitochondrial ROS are linked to metabolic disorders such as insulin resistance, hepatic steatosis and hepatic iron accumulation that are observed in HCV-related chronic liver diseases. PMID:24112394

  6. Interplays between nitric oxide and reactive oxygen species in cryptogein signalling.

    PubMed

    Kulik, Anna; Noirot, Elodie; Grandperret, Vincent; Bourque, Stéphane; Fromentin, Jérôme; Salloignon, Pauline; Truntzer, Caroline; Dobrowolska, Gra?yna; Simon-Plas, Françoise; Wendehenne, David

    2015-02-01

    Nitric oxide (NO) has many functions in plants. Here, we investigated its interplays with reactive oxygen species (ROS) in the defence responses triggered by the elicitin cryptogein. The production of NO induced by cryptogein in tobacco cells was partly regulated through a ROS-dependent pathway involving the NADPH oxidase NtRBOHD. In turn, NO down-regulated the level of H2O2. Both NO and ROS synthesis appeared to be under the control of type-2 histone deacetylases acting as negative regulators of cell death. Occurrence of an interplay between NO and ROS was further supported by the finding that cryptogein triggered a production of peroxynitrite (ONOO(-)). Next, we showed that ROS, but not NO, negatively regulate the intensity of activity of the cryptogein-induced protein kinase NtOSAK. Furthermore, using a DNA microarray approach, we identified 15 genes early induced by cryptogein via NO. A part of these genes was also modulated by ROS and encoded proteins showing sequence identity to ubiquitin ligases. Their expression appeared to be negatively regulated by ONOO(-), suggesting that ONOO(-) mitigates the effects of NO and ROS. Finally, we provided evidence that NO required NtRBOHD activity for inducing cell death, thus confirming previous assumption that ROS channel NO through cell death pathways. PMID:24506708

  7. Diminished Macrophage Apoptosis and Reactive Oxygen Species Generation after Phorbol Ester Stimulation in Crohn's Disease

    PubMed Central

    Palmer, Christine D.; Rahman, Farooq Z.; Sewell, Gavin W.; Ahmed, Afshan; Ashcroft, Margaret; Bloom, Stuart L.; Segal, Anthony W.; Smith, Andrew M.

    2009-01-01

    Background Crohn's Disease (CD) is a chronic relapsing disorder characterized by granulomatous inflammation of the gastrointestinal tract. Although its pathogenesis is complex, we have recently shown that CD patients have a systemic defect in macrophage function, which results in the defective clearance of bacteria from inflammatory sites. Methodology/Principal Findings Here we have identified a number of additional macrophage defects in CD following diacylglycerol (DAG) homolog phorbol-12-myristate-13-acetate (PMA) activation. We provide evidence for decreased DNA fragmentation, reduced mitochondrial membrane depolarization, impaired reactive oxygen species production, diminished cytochrome c release and increased IL-6 production compared to healthy subjects after PMA exposure. The observed macrophage defects in CD were stimulus-specific, as normal responses were observed following p53 activation and endoplasmic reticulum stress. Conclusion These findings add to a growing body of evidence highlighting disordered macrophage function in CD and, given their pivotal role in orchestrating inflammatory responses, defective apoptosis could potentially contribute to the pathogenesis of CD. PMID:19907654

  8. Accelerating neuronal aging in in vitro model brain disorders: a focus on reactive oxygen species

    PubMed Central

    Campos, Priscila Britto; Paulsen, Bruna S.; Rehen, Stevens K.

    2014-01-01

    In this review, we discuss insights gained through the use of stem cell preparations regarding the modeling of neurological diseases, the need for aging neurons derived from pluripotent stem cells to further advance the study of late-onset adult neurological diseases, and the extent to which mechanisms linked to the mismanagement of reactive oxygen species (ROS). The context of these issues can be revealed using the three disease states of Parkinson’s (PD), Alzheimer’s (AD), and schizophrenia, as considerable insights have been gained into these conditions through the use of stem cells in terms of disease etiologies and the role of oxidative stress. The latter subject is a primary area of interest of our group. After discussing the molecular models of accelerated aging, we highlight the role of ROS for the three diseases explored here. Importantly, we do not seek to provide an extensive account of all genetic mutations for each of the three disorders discussed in this review, but we aim instead to provide a conceptual framework that could maximize the gains from merging the approaches of stem cell microsystems and the study of oxidative stress in disease in order to optimize therapeutics and determine new molecular targets against oxidative stress that spare stem cell proliferation and development. PMID:25386139

  9. Emerging Roots Alter Epidermal Cell Fate through Mechanical and Reactive Oxygen Species Signaling[C][W

    PubMed Central

    Steffens, Bianka; Kovalev, Alexander; Gorb, Stanislav N.; Sauter, Margret

    2012-01-01

    A central question in biology is how spatial information is conveyed to locally establish a developmental program. Rice (Oryza sativa) can survive flash floods by the emergence of adventitious roots from the stem. Epidermal cells that overlie adventitious root primordia undergo cell death to facilitate root emergence. Root growth and epidermal cell death are both controlled by ethylene. This study aimed to identify the signal responsible for the spatial control of cell death. Epidermal cell death correlated with the proximity to root primordia in wild-type and ADVENTITIOUS ROOTLESS1 plants, indicating that the root emits a spatial signal. Ethylene-induced root growth generated a mechanical force of ?18 millinewtons within 1 h. Force application to epidermal cells above root primordia caused cell death in a dose-dependent manner and was inhibited by 1-methylcyclopropene or diphenylene iodonium, an inhibitor of NADPH oxidase. Exposure of epidermal cells not overlying a root to either force and ethylene or force and the catalase inhibitor aminotriazole induced ectopic cell death. Genetic downregulation of the reactive oxygen species (ROS) scavenger METALLOTHIONEIN2b likewise promoted force-induced ectopic cell death. Hence, reprogramming of epidermal cell fate by the volatile plant hormone ethylene requires two signals: mechanosensing for spatial resolution and ROS for cell death signaling. PMID:22904148

  10. Emerging roots alter epidermal cell fate through mechanical and reactive oxygen species signaling.

    PubMed

    Steffens, Bianka; Kovalev, Alexander; Gorb, Stanislav N; Sauter, Margret

    2012-08-01

    A central question in biology is how spatial information is conveyed to locally establish a developmental program. Rice (Oryza sativa) can survive flash floods by the emergence of adventitious roots from the stem. Epidermal cells that overlie adventitious root primordia undergo cell death to facilitate root emergence. Root growth and epidermal cell death are both controlled by ethylene. This study aimed to identify the signal responsible for the spatial control of cell death. Epidermal cell death correlated with the proximity to root primordia in wild-type and ADVENTITIOUS ROOTLESS1 plants, indicating that the root emits a spatial signal. Ethylene-induced root growth generated a mechanical force of ~18 millinewtons within 1 h. Force application to epidermal cells above root primordia caused cell death in a dose-dependent manner and was inhibited by 1-methylcyclopropene or diphenylene iodonium, an inhibitor of NADPH oxidase. Exposure of epidermal cells not overlying a root to either force and ethylene or force and the catalase inhibitor aminotriazole induced ectopic cell death. Genetic downregulation of the reactive oxygen species (ROS) scavenger METALLOTHIONEIN2b likewise promoted force-induced ectopic cell death. Hence, reprogramming of epidermal cell fate by the volatile plant hormone ethylene requires two signals: mechanosensing for spatial resolution and ROS for cell death signaling. PMID:22904148

  11. Nanoelectrodes for determination of reactive oxygen and nitrogen species inside murine macrophages

    PubMed Central

    Wang, Yixian; Noël, Jean-Marc; Velmurugan, Jeyavel; Nogala, Wojciech; Mirkin, Michael V.; Lu, Cong; Guille Collignon, Manon; Lemaître, Frédéric; Amatore, Christian

    2012-01-01

    Reactive oxygen and nitrogen species (ROS and RNS) produced by macrophages are essential for protecting a human body against bacteria and viruses. Micrometer-sized electrodes coated with Pt black have previously been used for selective and sensitive detection of ROS and RNS in biological systems. To determine ROS and RNS inside macrophages, one needs smaller (i.e., nanometer-sized) sensors. In this article, the methodologies have been extended to the fabrication and characterization of Pt/Pt black nanoelectrodes. Electrodes with the metal surface flush with glass insulator, most suitable for quantitative voltammetric experiments, were fabricated by electrodeposition of Pt black inside an etched nanocavity under the atomic force microscope control. Despite a nanometer-scale radius, the true surface area of Pt electrodes was sufficiently large to yield stable and reproducible responses to ROS and RNS in vitro. The prepared nanoprobes were used to penetrate cells and detect ROS and RNS inside macrophages. Weak and very short leaks of ROS/RNS from the vacuoles into the cytoplasm were detected, which a macrophage is equipped to clean within a couple of seconds, while higher intensity oxidative bursts due to the emptying of vacuoles outside persist on the time scale of tens of seconds. PMID:22615353

  12. Mitochondrial reactive oxygen species: A double edged sword in ischemia/reperfusion vs preconditioning

    PubMed Central

    Kalogeris, Theodore; Bao, Yimin; Korthuis, Ronald J.

    2014-01-01

    Reductions in the blood supply produce considerable injury if the duration of ischemia is prolonged. Paradoxically, restoration of perfusion to ischemic organs can exacerbate tissue damage and extend the size of an evolving infarct. Being highly metabolic organs, the heart and brain are particularly vulnerable to the deleterious effects of ischemia/reperfusion (I/R). While the pathogenetic mechanisms contributing to I/R-induced tissue injury and infarction are multifactorial, the relative importance of each contributing factor remains unclear. However, an emerging body of evidence indicates that the generation of reactive oxygen species (ROS) by mitochondria plays a critical role in damaging cellular components and initiating cell death. In this review, we summarize our current understanding of the mechanisms whereby mitochondrial ROS generation occurs in I/R and contributes to myocardial infarction and stroke. In addition, mitochondrial ROS have been shown to participate in preconditioning by several pharmacologic agents that target potassium channels (e.g., ATP-sensitive potassium (mKATP) channels or large conductance, calcium-activated potassium (mBKCa) channels) to activate cell survival programs that render tissues and organs more resistant to the deleterious effects of I/R. Finally, we review novel therapeutic approaches that selectively target mROS production to reduce postischemic tissue injury, which may prove efficacious in limiting myocardial dysfunction and infarction and abrogating neurocognitive deficits and neuronal cell death in stroke. PMID:24944913

  13. Use of potentiometric fluorophores in the measurement of mitochondrial reactive oxygen species.

    PubMed

    Polster, Brian M; Nicholls, David G; Ge, Shealinna X; Roelofs, Brian A

    2014-01-01

    Mitochondrial reactive oxygen species (ROS) are implicated in signal transduction, inflammation, neurodegenerative disorders, and normal aging. Net ROS release by isolated brain mitochondria derived from a mixture of neurons and glia is readily quantified using fluorescent dyes. Measuring intracellular ROS in intact neurons or glia and assigning the origin to mitochondria are far more difficult. In recent years, the proton-motive force crucial to mitochondrial function has been exploited to target a variety of compounds to the highly negative mitochondrial matrix using the lipophilic triphenylphosphonium cation (TPP(+)) as a "delivery" conjugate. Among these, MitoSOX Red, also called mito-hydroethidine or mito-dihydroethidium, is prevalently used for mitochondrial ROS estimation. Although the TPP(+) moiety of MitoSOX enables the manyfold accumulation of ROS-sensitive hydroethidine in the mitochondrial matrix, the membrane potential sensitivity conferred by TPP(+) creates a daunting set of challenges not often considered in the application of this dye. This chapter provides recommendations and cautionary notes on the use of potentiometric fluorescent indicators for the approximation of mitochondrial ROS in live neurons, with principles that can be extrapolated to nonneuronal cell types. It is concluded that mitochondrial membrane potential changes render accurate estimation of mitochondrial ROS using MitoSOX difficult to impossible. Consequently, knowledge of mitochondrial membrane potential is essential to the application of potentiometric fluorophores for the measurement of intramitochondrial ROS. PMID:25416361

  14. Candida albicans Induces Arginine Biosynthetic Genes in Response to Host-Derived Reactive Oxygen Species

    PubMed Central

    Jiménez-López, Claudia; Collette, John R.; Brothers, Kimberly M.; Shepardson, Kelly M.; Cramer, Robert A.; Wheeler, Robert T.

    2013-01-01

    The interaction of Candida albicans with phagocytes of the host's innate immune system is highly dynamic, and its outcome directly impacts the progression of infection. While the switch to hyphal growth within the macrophage is the most obvious physiological response, much of the genetic response reflects nutrient starvation: translational repression and induction of alternative carbon metabolism. Changes in amino acid metabolism are not seen, with the striking exception of arginine biosynthesis, which is upregulated in its entirety during coculture with macrophages. Using single-cell reporters, we showed here that arginine biosynthetic genes are induced specifically in phagocytosed cells. This induction is lower in magnitude than during arginine starvation in vitro and is driven not by an arginine deficiency within the phagocyte but instead by exposure to reactive oxygen species (ROS). Curiously, these genes are induced in a narrow window of sublethal ROS concentrations. C. albicans cells phagocytosed by primary macrophages deficient in the gp91phox subunit of the phagocyte oxidase do not express the ARG pathway, indicating that the induction is dependent on the phagocyte oxidative burst. C. albicans arg pathway mutants are retarded in germ tube and hypha formation within macrophages but are not notably more sensitive to ROS. We also find that the ARG pathway is regulated not by the general amino acid control response but by transcriptional regulators similar to the Saccharomyces cerevisiae ArgR complex. In summary, phagocytosis induces this single amino acid biosynthetic pathway in an ROS-dependent manner. PMID:23143683

  15. Cyclopentenone isoprostanes induced by reactive oxygen species trigger defense gene activation and phytoalexin accumulation in plants.

    PubMed

    Thoma, Ingeborg; Loeffler, Christiane; Sinha, Alok K; Gupta, Meetu; Krischke, Markus; Steffan, Bert; Roitsch, Thomas; Mueller, Martin J

    2003-05-01

    Lipid peroxidation may be initiated either by lipoxygenases or by reactive oxygen species (ROS). Enzymatic oxidation of alpha-linolenate can result in the biosynthesis of cyclic oxylipins of the jasmonate type while free-radical-catalyzed oxidation of alpha-linolenate may yield several classes of cyclic oxylipins termed phytoprostanes in vivo. Previously, we have shown that one of these classes, the E1-phytoprostanes (PPE1), occurs ubiquitously in plants. In this work, it is shown that PPE1 are converted to novel cyclopentenone A1- and B1-phytoprostanes (PPA1 and PPB1) in planta. Enhanced formation of PPE1, PPA1, and PPB1 is observed after peroxide stress in tobacco cell cultures as well as after infection of tomato plants with a necrotrophic fungus, Botrytis cinerea. PPA1 and PPB1 display powerful biologic activities including activation of mitogen-activated protein kinase (MAPK) and induction of glutathione-S-transferase (GST), defense genes, and phytoalexins. Data collected so far infer that enhanced phytoprostane formation is a general consequence of oxidative stress in plants. We propose that phytoprostanes are components of an oxidant-injury-sensing, archaic signaling system that serves to induce several plant defense mechanisms. PMID:12713542

  16. Accelerating neuronal aging in in vitro model brain disorders: a focus on reactive oxygen species.

    PubMed

    Campos, Priscila Britto; Paulsen, Bruna S; Rehen, Stevens K

    2014-01-01

    In this review, we discuss insights gained through the use of stem cell preparations regarding the modeling of neurological diseases, the need for aging neurons derived from pluripotent stem cells to further advance the study of late-onset adult neurological diseases, and the extent to which mechanisms linked to the mismanagement of reactive oxygen species (ROS). The context of these issues can be revealed using the three disease states of Parkinson's (PD), Alzheimer's (AD), and schizophrenia, as considerable insights have been gained into these conditions through the use of stem cells in terms of disease etiologies and the role of oxidative stress. The latter subject is a primary area of interest of our group. After discussing the molecular models of accelerated aging, we highlight the role of ROS for the three diseases explored here. Importantly, we do not seek to provide an extensive account of all genetic mutations for each of the three disorders discussed in this review, but we aim instead to provide a conceptual framework that could maximize the gains from merging the approaches of stem cell microsystems and the study of oxidative stress in disease in order to optimize therapeutics and determine new molecular targets against oxidative stress that spare stem cell proliferation and development. PMID:25386139

  17. The impact of reactive oxygen species and genetic mitochondrial mutations in Parkinson's disease.

    PubMed

    Zuo, Li; Motherwell, Michael S

    2013-12-10

    The exact pathogenesis of Parkinson's disease (PD) is still unknown and proper mechanisms that correspond to the disease remain unidentified. It is understood that PD is age-related; as age increases, the chance of onset responds accordingly. Although there are no current means of curing PD, the understanding of reactive oxygen species (ROS) provides significant insight to possible treatments. Complex I deficiencies of the respiratory chain account for the majority of unfavorable neural apoptosis generation in PD. Dopaminergic neurons are severely damaged as a result of the deficiency. Symptoms such as inhibited cognitive ability and loss of smooth motor function are the results of such impairment. The genetic mutations of Parkinson's related proteins such as PINK1 and LRRK2 contribute to mitochondrial dysfunction which precedes ROS formation. Various pathways are inhibited by these mutations, and inevitably causing neural cell damage. Antioxidants are known to negate the damaging effects of free radical overexpression. This paper expands on the specific impact of mitochondrial genetic change and production of free radicals as well as its correlation to the neurodegeneration in Parkinson's disease. PMID:23954870

  18. Oncogene-induced reactive oxygen species fuel hyperproliferation and DNA damage response activation

    PubMed Central

    Ogrunc, M; Di Micco, R; Liontos, M; Bombardelli, L; Mione, M; Fumagalli, M; Gorgoulis, V G; d'Adda di Fagagna, F

    2014-01-01

    Oncogene-induced reactive oxygen species (ROS) have been proposed to be signaling molecules that mediate proliferative cues. However, ROS may also cause DNA damage and proliferative arrest. How these apparently opposite roles can be reconciled, especially in the context of oncogene-induced cellular senescence, which is associated both with aberrant mitogenic signaling and DNA damage response (DDR)-mediated arrest, is unclear. Here, we show that ROS are indeed mitogenic signaling molecules that fuel oncogene-driven aberrant cell proliferation. However, by their very same ability to mediate cell hyperproliferation, ROS eventually cause DDR activation. We also show that oncogenic Ras-induced ROS are produced in a Rac1 and NADPH oxidase (Nox4)-dependent manner. In addition, we show that Ras-induced ROS can be detected and modulated in a living transparent animal: the zebrafish. Finally, in cancer we show that Nox4 is increased in both human tumors and a mouse model of pancreatic cancer and specific Nox4 small-molecule inhibitors act synergistically with existing chemotherapic agents. PMID:24583638

  19. 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

  20. Homeostatic generation of reactive oxygen species protects the zebrafish liver from steatosis

    PubMed Central

    Nussbaum, Justin M.; Liu, Liuhong J.; Hasan, Syeda A.; Schaub, Madeline; McClendon, Allyson; Stainier, Didier Y.R.; Sakaguchi, Takuya F.

    2013-01-01

    Nonalcoholic fatty liver disease is the most common liver disease in both adults and children. The earliest stage of this disease is hepatic steatosis, in which triglycerides are deposited as cytoplasmic lipid droplets in hepatocytes. Through a forward genetic approach in zebrafish, we found that guanosine monophosphate (GMP) synthetase mutant larvae develop hepatic steatosis. We further demonstrate that activity of the small GTPase Rac1 and Rac1-mediated production of reactive oxygen species (ROS) are down-regulated in GMP synthetase mutant larvae. Inhibition of Rac1 activity or ROS production in wild-type larvae by small molecule inhibitors was sufficient to induce hepatic steatosis. More conclusively, treating larvae with hydrogen peroxide, a diffusible ROS that has been implicated as a signaling molecule, alleviated hepatic steatosis in both GMP synthetase mutant and Rac1 inhibitor-treated larvae, indicating that homeostatic production of ROS is required to prevent hepatic steatosis. We further found that ROS positively regulate the expression of the triglyceride hydrolase gene, which is responsible for the mobilization of stored triglycerides in hepatocytes. Consistently, inhibition of triglyceride hydrolase activity in wild-type larvae by a small molecule inhibitor was sufficient to induce hepatic steatosis. Conclusion: de novo GMP synthesis influences the activation of the small GTPase Rac1, which controls hepatic lipid dynamics through ROS-mediated regulation of triglyceride hydrolase expression in hepatocytes. PMID:23744565

  1. Spin Biochemistry Modulates Reactive Oxygen Species (ROS) Production by Radio Frequency Magnetic Fields

    PubMed Central

    Usselman, Robert J.; Hill, Iain; Singel, David J.; Martino, Carlos F.

    2014-01-01

    The effects of weak magnetic fields on the biological production of reactive oxygen species (ROS) from intracellular superoxide (O2•?) and extracellular hydrogen peroxide (H2O2) were investigated in vitro with rat pulmonary arterial smooth muscle cells (rPASMC). A decrease in O2•? and an increase in H2O2 concentrations were observed in the presence of a 7 MHz radio frequency (RF) at 10 ?TRMS and static 45 ?T magnetic fields. We propose that O2•? and H2O2 production in some metabolic processes occur through singlet-triplet modulation of semiquinone flavin (FADH•) enzymes and O2•? spin-correlated radical pairs. Spin-radical pair products are modulated by the 7 MHz RF magnetic fields that presumably decouple flavin hyperfine interactions during spin coherence. RF flavin hyperfine decoupling results in an increase of H2O2 singlet state products, which creates cellular oxidative stress and acts as a secondary messenger that affects cellular proliferation. This study demonstrates the interplay between O2•? and H2O2 production when influenced by RF magnetic fields and underscores the subtle effects of low-frequency magnetic fields on oxidative metabolism, ROS signaling, and cellular growth. PMID:24681944

  2. Mitochondrial Respiratory Supercomplex Association Limits Production of Reactive Oxygen Species from Complex I

    PubMed Central

    Maranzana, Evelina; Barbero, Giovanna; Falasca, Anna Ida; Lenaz, Giorgio

    2013-01-01

    Abstract Aims: The mitochondrial respiratory chain is recognized today to be arranged in supramolecular assemblies (supercomplexes). Besides conferring a kinetic advantage (substrate channeling) and being required for the assembly and stability of Complex I, indirect considerations support the view that supercomplexes may also prevent excessive formation of reactive oxygen species (ROS) from the respiratory chain. In the present study, we have directly addressed this issue by testing the ROS generation by Complex I in two experimental systems in which the supramolecular organization of the respiratory assemblies is impaired by: (i) treatment either of bovine heart mitochondria or liposome-reconstituted supercomplex I-III with dodecyl maltoside; (ii) reconstitution of Complexes I and III at high phospholipids to protein ratio. Results: The results of our investigation provide experimental evidence that the production of ROS is strongly increased in either model, supporting the view that disruption or prevention of the association between Complex I and Complex III by different means enhances the generation of superoxide from Complex I. Innovation: Dissociation of supercomplexes may link oxidative stress and energy failure in a vicious circle. Conclusion: Our findings support a central role of mitochondrial supramolecular structure in the development of the aging process and in the etiology and pathogenesis of most major chronic diseases. Antioxid. Redox Signal. 19, 1469–1480. PMID:23581604

  3. Acrosome reaction in bovine spermatozoa: role of reactive oxygen species and lactate dehydrogenase C4.

    PubMed

    O'Flaherty, C; Breininger, E; Beorlegui, N; Beconi, M T

    2005-10-30

    After capacitation, mammalian spermatozoa accomplish the acrosome reaction (AR), a well-controlled exocytosis process crucial to fertilize mature oocytes that involves several protein kinases such as protein kinase A (PKA), C (PKC), and tyrosine kinase (PTK). Reactive oxygen species (ROS) are involved in both bovine sperm capacitation and AR. Lactate dehydrogenase C4 (LDH-C4) was associated with bovine and mouse sperm capacitation. Our aims were to study the participation of LDH-C4 to contribute with the status redox required for AR and the role of ROS in the regulation of PKA, PKC, and PTK involved in the exocytotic event. Sodium oxamate, an inhibitor of LDH-C4, prevented the AR induced by lysophosphatidylcholine (LPC) or NADH. Hydrogen peroxide promoted and superoxide dismutase (scavenger of superoxide), catalase (scavenger of hydrogen peroxide), diphenyleneiodinum, diphenyliodonium, cibacron blue, and lapachol (inhibitors of NADPH oxidase) prevented the AR, suggesting that ROS and a sperm oxidase are involved in the AR induced by these compounds. Inhibitors of PKA, PKC, and PTK also prevented the AR induced by LPC or NADH, suggesting the involvement of these kinases in the process. These results suggest that LDH-C4 may participate in the regulation of the redox status required to achieve the AR in bovine spermatozoa and that ROS are key elements in the regulation of protein kinases associated with the AR process. PMID:16112812

  4. Effect of polyunsaturated fatty acids on the reactive oxygen and nitrogen species production by raw 264.7 macrophages

    Microsoft Academic Search

    Gabriela Ambrozova; Michaela Pekarova; Antonin Lojek

    2010-01-01

    Background  Polyunsaturated fatty acids (PUFAs) can affect various functions of the immune system including inflammatory responses. An\\u000a oxidative burst of phagocytes accompanied by reactive oxygen species (ROS) and reactive nitrogen species (RNS) formation is\\u000a one of the phagocyte functions that could be modulated by PUFAs.\\u000a \\u000a \\u000a \\u000a \\u000a Aim of the study  To investigate the effects of ?-3 (?-linolenic, docosahexaenoic, eicosapentaenoic) and ?-6 (arachidonic, linoleic)

  5. Stability of fluorinated parylenes to oxygen reactive-ion etching under aluminum, aluminum oxide, and tantalum nitride overlayers

    Microsoft Academic Search

    Jay J. Senkevich; B. Wang; J. B. Fortin; M. C. Nielsen; J. F. McDonald; T.-M. Lu; G. M. Nuesca; G. G. Peterson; S. C. Selbrede; M. T. Weise

    2003-01-01

    The fluorine stability of two parylenes, aliphatic-fluorinated AF-4 (?, ?, ??, ?? poly(p-tetrafluoroxylylene) and aromatic-fluorinated\\u000a VT-4 (2, 3, 5, 6 poly(p-tetrafluoroxylylene), were investigated underneath Al, Al2O3, and TaNX overlayers with and without exposure to oxygen reactive-ion etching (RIE). No fluorine diffusion was observed for Al films\\u000a deposited onto the as-received parylenes. However, after oxygen RIE, x-ray photoelectron spectroscopy (XPS) depth

  6. Reactive oxygen species: re-evaluation of generation, monitoring and role in stress-signaling in phototrophic organisms.

    PubMed

    Schmitt, Franz-Josef; Renger, Gernot; Friedrich, Thomas; Kreslavski, Vladimir D; Zharmukhamedov, Sergei K; Los, Dmitry A; Kuznetsov, Vladimir V; Allakhverdiev, Suleyman I

    2014-06-01

    This review provides an overview about recent developments and current knowledge about monitoring, generation and the functional role of reactive oxygen species (ROS) - H2O2, HO2, HO, OH(-), (1)O2 and O2(-) - in both oxidative degradation and signal transduction in photosynthetic organisms including microscopic techniques for ROS detection and controlled generation. Reaction schemes elucidating formation, decay and signaling of ROS in cyanobacteria as well as from chloroplasts to the nuclear genome in eukaryotes during exposure of oxygen-evolving photosynthetic organisms to oxidative stress are discussed that target the rapidly growing field of regulatory effects of ROS on nuclear gene expression. PMID:24530357

  7. Exogenous acetaldehyde as a tool for modulating wine color and astringency during fermentation.

    PubMed

    Sheridan, Marlena K; Elias, Ryan J

    2015-06-15

    Wine tannins undergo modifications during fermentation and storage that can decrease their perceived astringency and increase color stability. Acetaldehyde acts as a bridging compound to form modified tannins and polymeric pigments that are less likely to form tannin-protein complexes than unmodified tannins. Red wines are often treated with oxygen in order to yield acetaldehyde, however this approach can lead to unintended consequences due to the generation of reactive oxygen species. The present study employs exogenous acetaldehyde at relatively low and high treatment concentrations during fermentation to encourage tannin modification without promoting potentially deleterious oxidation reactions. The high acetaldehyde treatment significantly increased polymeric pigments in the wine without increasing concentrations of free and sulfite-bound acetaldehyde. Protein-tannin precipitation was also significantly decreased with the addition of exogenous acetaldehyde. These results indicate a possible treatment of wines early in their production to increase color stability and lower astringency of finished wines. PMID:25660852

  8. Angiotensin-II-induced reactive oxygen species along the SFO-PVN-RVLM pathway: implications in neurogenic hypertension.

    PubMed

    Braga, V A; Medeiros, I A; Ribeiro, T P; França-Silva, M S; Botelho-Ono, M S; Guimarães, D D

    2011-09-01

    Neurogenic hypertension has been the subject of extensive research worldwide. This review is based on the premise that some forms of neurogenic hypertension are caused in part by the formation of angiotensin-II (Ang-II)-induced reactive oxygen species along the subfornical organ-paraventricular nucleus of the hypothalamus-rostral ventrolateral medulla pathway (SFO-PVN-RVLM pathway). We will discuss the recent contribution of our laboratory and others regarding the mechanisms by which neurons in the SFO (an important circumventricular organ) are activated by Ang-II, how the SFO communicates with two other important areas involved in sympathetic activity regulation (PVN and RVLM) and how Ang-II-induced reactive oxygen species participate along the SFO-PVN-RVLM pathway in the pathogenesis of neurogenic hypertension. PMID:21755262

  9. Comparison of stainless and mild steel welding fumes in generation of reactive oxygen species

    PubMed Central

    2010-01-01

    Background Welding fumes consist of a wide range of complex metal oxide particles which can be deposited in all regions of the respiratory tract. The welding aerosol is not homogeneous and is generated mostly from the electrode/wire. Over 390,000 welders were reported in the U.S. in 2008 while over 1 million full-time welders were working worldwide. Many health effects are presently under investigation from exposure to welding fumes. Welding fume pulmonary effects have been associated with bronchitis, metal fume fever, cancer and functional changes in the lung. Our investigation focused on the generation of free radicals and reactive oxygen species from stainless and mild steel welding fumes generated by a gas metal arc robotic welder. An inhalation exposure chamber located at NIOSH was used to collect the welding fume particles. Results Our results show that hydroxyl radicals (.OH) were generated from reactions with H2O2 and after exposure to cells. Catalase reduced the generation of .OH from exposed cells indicating the involvement of H2O2. The welding fume suspension also showed the ability to cause lipid peroxidation, effect O2 consumption, induce H2O2 generation in cells, and cause DNA damage. Conclusion Increase in oxidative damage observed in the cellular exposures correlated well with .OH generation in size and type of welding fumes, indicating the influence of metal type and transition state on radical production as well as associated damage. Our results demonstrate that both types of welding fumes are able to generate ROS and ROS-related damage over a range of particle sizes; however, the stainless steel fumes consistently showed a significantly higher reactivity and radical generation capacity. The chemical composition of the steel had a significant impact on the ROS generation capacity with the stainless steel containing Cr and Ni causing more damage than the mild steel. Our results suggest that welding fumes may cause acute lung injury. Since type of fume generated, particle size, and elapsed time after generation of the welding exposure are significant factors in radical generation and particle deposition these factors should be considered when developing protective strategies. PMID:21047424

  10. Reactive Oxygen Metabolites are Closely Associated With the Diagnosis and Prognosis of Coronary Artery Disease

    PubMed Central

    Hirata, Yoshihiro; Yamamoto, Eiichiro; Tokitsu, Takanori; Kusaka, Hiroaki; Fujisue, Koichiro; Kurokawa, Hirofumi; Sugamura, Koichi; Maeda, Hirofumi; Tsujita, Kenichi; Kaikita, Koichi; Hokimoto, Seiji; Sugiyama, Seigo; Ogawa, Hisao

    2015-01-01

    Background Reactive oxygen species (ROS) are associated with development of coronary artery disease (CAD). However, there's no useful biomarker of ROS in CAD. Methods and Results We recruited 395 consecutive CAD patients who were performed coronary angiography (262 male and 133 female, age 70.2±10), and we measured serum derivatives of reactive oxidative metabolites (DROM) were measured. Two hundred twenty?seven non?CAD patients were also enrolled. We performed follow?up study in these 395 CAD patients and case?control study after risk factor and 1:1 pair matching (both, n=163). As subgroup analysis, DROM were also measured at the aortic root and the coronary sinus in 59 CAD patients. DROM were significantly higher in CAD patients (n=163, median [inter?quartile range, IQR]=338 [302 to 386]) than in risk factor?matched non?CAD patients (n=163, 311 [282 to 352.5], effect size=0.33, P<0.001). During a mean follow?up period of 20 months of 395 CAD patients, 83 cardiovascular events were recorded. Kaplan?Meier analysis showed a higher probability of cardiovascular events in the high?DROM group (>346 U.CARR) than in the low?DROM group (?346 U.CARR) (P=0.001 [log?rank test]). Multivariate Cox hazard analysis identified ln?DROM as an independent predictor for cardiovascular events (hazard ratio: 10.8, 95% confidence interval: 2.76 to 42.4, P=0.001). The transcardiac gradient of DROM was significantly higher in CAD patients than in non?CAD patients (?2.0 [?9.0 to 9.0] versus 8 [?8.0 to 28.3], effect size=0.21, P=0.04), indicating that DROM production in coronary circulation is associated with development of CAD. Conclusion DROM are increased in CAD patients and associated with future cardiovascular events. DROM might provide clinical benefits for risk stratification of CAD. Clinical Trial Registration URL: http://www.umin.ac.jp/ctr/. Unique identifier: UMIN000012990. PMID:25630910

  11. Rapid evaluation of the durability of cortical neural implants using accelerated aging with reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Takmakov, Pavel; Ruda, Kiersten; Phillips, K. Scott; Isayeva, Irada S.; Krauthamer, Victor; Welle, Cristin G.

    2015-04-01

    Objective. A challenge for implementing high bandwidth cortical brain–machine interface devices in patients is the limited functional lifespan of implanted recording electrodes. Development of implant technology currently requires extensive non-clinical testing to demonstrate device performance. However, testing the durability of the implants in vivo is time-consuming and expensive. Validated in vitro methodologies may reduce the need for extensive testing in animal models. Approach. Here we describe an in vitro platform for rapid evaluation of implant stability. We designed a reactive accelerated aging (RAA) protocol that employs elevated temperature and reactive oxygen species (ROS) to create a harsh aging environment. Commercially available microelectrode arrays (MEAs) were placed in a solution of hydrogen peroxide at 87 °C for a period of 7 days. We monitored changes to the implants with scanning electron microscopy and broad spectrum electrochemical impedance spectroscopy (1 Hz–1 MHz) and correlated the physical changes with impedance data to identify markers associated with implant failure. Main results. RAA produced a diverse range of effects on the structural integrity and electrochemical properties of electrodes. Temperature and ROS appeared to have different effects on structural elements, with increased temperature causing insulation loss from the electrode microwires, and ROS concentration correlating with tungsten metal dissolution. All array types experienced impedance declines, consistent with published literature showing chronic (>30 days) declines in array impedance in vivo. Impedance change was greatest at frequencies <10 Hz, and smallest at frequencies 1 kHz and above. Though electrode performance is traditionally characterized by impedance at 1 kHz, our results indicate that an impedance change at 1 kHz is not a reliable predictive marker of implant degradation or failure. Significance. ROS, which are known to be present in vivo, can create structural damage and change electrical properties of MEAs. Broad-spectrum electrical impedance spectroscopy demonstrates increased sensitivity to electrode damage compared with single-frequency measurements. RAA can be a useful tool to simulate worst-case in vivo damage resulting from chronic electrode implantation, simplifying the device development lifecycle.

  12. Exogenous antioxidants—Double-edged swords in cellular redox state

    PubMed Central

    Bohn, Torsten

    2010-01-01

    The balance between oxidation and antioxidation is believed to be critical in maintaining healthy biological systems. Under physiological conditions, the human antioxidative defense system including e.g., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) and others, allows the elimination of excess reactive oxygen species (ROS) including, among others superoxide anions (O2.-), hydroxyl radicals (OH.), alkoxyl radicals (RO.) and peroxyradicals (ROO.). However, our endogenous antioxidant defense systems are incomplete without exogenous originating reducing compounds such as vitamin C, vitamin E, carotenoids and polyphenols, playing an essential role in many antioxidant mechanisms in living organisms. Therefore, there is continuous demand for exogenous antioxidants in order to prevent oxidative stress, representing a disequilibrium redox state in favor of oxidation. However, high doses of isolated compounds may be toxic, owing to prooxidative effects at high concentrations or their potential to react with beneficial concentrations of ROS normally present at physiological conditions that are required for optimal cellular functioning. This review aims to examine the double-edged effects of dietary originating antioxidants with a focus on the most abundant compounds, especially polyphenols, vitamin C, vitamin E and carotenoids. Different approaches to enrich our body with exogenous antioxidants such as via synthetic antioxidants, diets rich in fruits and vegetables and taking supplements will be reviewed and experimental and epidemiological evidences discussed, highlighting that antioxidants at physiological doses are generally safe, exhibiting interesting health beneficial effects. PMID:20972369

  13. Role of Reactive Oxygen Species and Glutathione in Inorganic Mercury-Induced Injury in Human Glioma Cells

    Microsoft Academic Search

    YoungWoo Lee; MiSuk Ha; YongKeun Kim

    2001-01-01

    The present study was undertaken to examine the role of reactive oxygen species (ROS) and glutathione (GSH) in glia cells using human glioma cell line A172 cells. HgCl2 caused the loss of cell viability in a dose-dependent manner. HgCl2-induced loss of cell viability was not affected by H2O2 scavengers catalase and pyruvate, a superoxide scavenger superoxide dismutase, a peroxynitrite scavenger

  14. Characterization by Electron Spin Resonance Spectroscopy of Reactive Oxygen Species Generated by Titanium Dioxide and Hydrogen Peroxide

    Microsoft Academic Search

    M.-C. Lee; F. Yoshino; H. Shoji; S. Takahashi; K. Todoki; S. Shimada; K. Kuse-Barouch

    2005-01-01

    The influence of reactive oxygen species (ROS) on the surface modification of titanium implants and osseointegration is unclear. The aim of this study was to evaluate the ability of titanium dioxide (TiO2) to generate ROS in the presence of H2O2 and to determine whether any ROS thus generated play a role in osseointegration, as measured by electron spin resonance (ESR)

  15. Reactive oxygen species mediates the apoptosis induced by transforming growth factor ? 2 in human lens epithelial cells

    Microsoft Academic Search

    Ke Yao; Jian Tan; Wei-zhong Gu; Pan-Pan Ye; Kai-jun Wang

    2007-01-01

    Transforming growth factor ?2 (TGF-?2), a growth regulator of human lens epithelial cells (HLECs), also regulates the death of these cells. Dose-response analysis showed that the TGF-?2 concentration needed to induce HLECs death (100pg\\/ml) was 10 times that needed to inhibit growth in these cells (10pg\\/ml). TGF-?2-induced apoptosis in HLECs was preceded by an induction of reactive oxygen species (ROS)

  16. Localisation and metabolism of reactive oxygen species during Bremia lactucae pathogenesis in Lactuca sativa and wild Lactuca spp

    Microsoft Academic Search

    Michaela Sedlá?ová; Lenka Luhová; Marek Pet?ivalský; Aleš Lebeda

    2007-01-01

    A plant's physiology is modified simultaneously with Oomycete pathogen penetration, starting with release and accumulation of reactive oxygen species (ROS). Localisation of superoxide, hydrogen peroxide, peroxidase and variation in their activity, and the isoenzyme profile of antioxidant enzymes peroxidase (1.11.1.7), catalase (EC 1.11.1.6), superoxide dismutase (EC 1.15.1.1) were studied in six genotypes of four Lactuca spp. (L. sativa, L. serriola,

  17. Role of the ArcAB two-component system in the resistance of Escherichia coli to reactive oxygen stress

    Microsoft Academic Search

    Cindy Loui; Alexander C Chang; Sangwei Lu

    2009-01-01

    BACKGROUND: The global regulatory system ArcAB controls the anaerobic growth of E. coli, however, its role in aerobic conditions is not well characterized. We have previously reported that ArcA was necessary for Salmonella to resist reactive oxygen species (ROS) in aerobic conditions. RESULTS: To investigate the mechanism of ROS resistance mediated by ArcAB, we generated deletion mutants of ArcA and

  18. Reactive Oxygen and Nitrogen Species, Oxidative and Nitrosative Stress, and Their Role in the Pathogenesis of Acute Kidney Injury

    Microsoft Academic Search

    Eisei Noiri; Francesco Addabbo; Michael S. Goligorsky

    \\u000a This chapter briefly summarizes the existing evidence implicating reactive oxygen (ROS) and nitrogen (RNS) species in renal\\u000a injury and offers insights into the mitochondrial generation of ROS, signaling functions of ROS necessary for survival as\\u000a well as death decisions, the role of ROS in hormesis, and therapeutic strategies attenuating ROS- and RNS-induced renal injury.\\u000a Along with this discussion we emphasize

  19. Modulation of leukocyte–endothelial interactions by reactive metabolites of oxygen and nitrogen: relevance to ischemic heart disease

    Microsoft Academic Search

    Matthew B. Grisham; D. Neil Granger; David J. Lefer

    1998-01-01

    Ischemia and reperfusion (I\\/R) are thought to play an important role in the pathophysiology of ischemic diseases of the heart. It is now well appreciated that leukocyte–endothelial cell interactions are important determinants for I\\/R-induced microvascular injury and dysfunction. There is a growing body of experimental data to suggest that reactive metabolites of oxygen and nitrogen are important physiological modulators of

  20. Homocysteine-Induced Endothelin1 Release Is Dependent on Hyperglycaemia and Reactive Oxygen Species Production in Bovine Aortic Endothelial Cells

    Microsoft Academic Search

    Amarjit S. Sethi; Delphine M. Lees; Julie A. Douthwaite; Anne B. Dawnay; Roger Corder

    2006-01-01

    Background: Elevated plasma homocysteine (Hcy) is a risk factor for coronary disease. The objective of this study was to investigate whether Hcy either alone or in high glucose conditions induces endothelin-1 (ET-1) synthesis via the production of reactive oxygen species (ROS). Methods: Bovine aortic endothelial cells were grown in high (25 mmol\\/l) and low (5 mmol\\/l) glucose medium. Results: In

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

    Microsoft Academic Search

    Michael J. Smietana; Ellen M. Arruda; John A. Faulkner; Susan V. Brooks; Lisa M. Larkin

    2010-01-01

    Reactive oxygen species (ROS) play a role in a number of degenerative conditions including osteoporosis. Mice deficient in Cu,Zn-superoxide dismutase (Sod1) (Sod1?\\/? mice) have elevated oxidative stress and decreased muscle mass and strength compared to wild-type mice (WT) and appear to have an accelerated muscular aging phenotype. Thus, Sod1?\\/? mice may be a good model for evaluating the effects of

  2. Induction of Reactive Oxygen Species by Bisphenol A and Abrogation of Bisphenol A-Induced Cell Injury by DJ1

    Microsoft Academic Search

    Hiromasa Ooe; Takahiro Taira; Sanae M. M. Iguchi-Ariga; Hiroyoshi Ariga

    2005-01-01

    DJ-1 was first identified as an activated ras-dependent onco- gene. DJ-1 is related to male fertility, and its expression in sperm decreases in response to exposure to a number of reproductive toxicants. DJ-1 has been associated with the onset of familial Parkinson's disease (PD) in humans, and has been found to have activity against oxidative damage by eliminating reactive oxygen

  3. Microbial communities and biodegradation in lab-scale BTEX-contaminated groundwater remediation using an oxygen-releasing reactive barrier

    Microsoft Academic Search

    Chi-Wen Lin; Li-Hsuan Chen; Yet-Pole I; Chi-Yung Lai

    2010-01-01

    To remediate benzene, toluene, ethylbenzene and xylene (BTEX) -contaminated groundwater, a biotreatment process including\\u000a biostimulation and bioaugmentation was simulated using oxygen-releasing reactive barriers (ORRB) and water with added BTEX\\u000a in a lab-scale system. The results showed that the capability for BTEX removal decreases in the order of benzene, toluene,\\u000a p-xylene, ethylbenzene for both added-nitrogen and no-added-nitrogen under BTEX concentrations at

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

    PubMed

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

    2015-04-01

    Increased levels of reactive oxygen species (ROS) are a crucial pathogenic factor of osteoporosis. Gastrodin, isolated from the traditional Chinese herbal agent Gastrodia elata, is a potent antioxidant. We hypothesized that gastrodin demonstrates protective effects against osteoporosis by partially reducing reactive oxygen species in human bone marrow mesenchymal stem cells (hBMMSCs) and a macrophage cell line (RAW264.7 cells). We investigated gastrodin on osteogenic and adipogenic differentiation under oxidative stress in hBMMSCs. We also tested gastrodin on osteoclastic differentiation in RAW264.7 cells. Hydrogen peroxide (H2O2) was used to establish an oxidative cell injury model. Our results showed that gastrodin significantly promoted the proliferation of hBMMSCs, improved some osteogenic markers, reduced lipid generation and inhibited the mRNA expression of several adipogenic genes in hBMMSCs. Moreover, gastrodin reduced the number of osteoclasts, TRAP activity and the expression of osteoclast-specific genes in RAW264.7 cells. Gastrodin suppressed the production of reactive oxygen species in both hBMMSCs and RAW264.7 cells. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Our data revealed that gastrodin treatment reduced the activity of serum bone degradation markers, such as CTX-1 and TRAP. Importantly, it ameliorated the micro-architecture of trabecular bones. Gastrodin decreased osteoclast numbers in vivo by TRAP staining. To conclude, these results indicated that gastrodin shows protective effects against osteoporosis linking to a reduction in reactive oxygen species, suggesting that gastrodin may be useful in the prevention and treatment of osteoporosis. PMID:25554600

  5. Estrogen-Induced Generation of Reactive Oxygen and Nitrogen Species, Gene Damage, and Estrogen-Dependent Cancers

    Microsoft Academic Search

    Deodutta Roy; Qiuyin Cai; Quentin Felty; Satya Narayan

    2007-01-01

    In addition to the direct effect of estrogen on mitochondria and the redox cycling of catechol estrogen, estrogen-induced proinflammatory cytokines, such as interleukin-1 beta (IL-1?) and tumor necrosis factor alpha (TNF-?), also generate reactive oxygen and nitrogen species (RO\\/NS). Different cellular signaling pathways may operate in response to varying levels of estrogen-induced RO\\/NS, leading to genotoxic damage, cell apoptosis, or

  6. The Extracellular A-loop of Dual Oxidases Affects the Specificity of Reactive Oxygen Species Release.

    PubMed

    Ueyama, Takehiko; Sakuma, Megumi; Ninoyu, Yuzuru; Hamada, Takeshi; Dupuy, Corinne; Geiszt, Miklós; Leto, Thomas L; Saito, Naoaki

    2015-03-01

    NADPH oxidase (Nox) family proteins produce superoxide (O2 (?)) directly by transferring an electron to molecular oxygen. Dual oxidases (Duoxes) also produce an O2 (?) intermediate, although the final species secreted by mature Duoxes is H2O2, suggesting that intramolecular O2 (?) dismutation or other mechanisms contribute to H2O2 release. We explored the structural determinants affecting reactive oxygen species formation by Duox enzymes. Duox2 showed O2 (?) leakage when mismatched with Duox activator 1 (DuoxA1). Duox2 released O2 (?) even in correctly matched combinations, including Duox2 + DuoxA2 and Duox2 + N-terminally tagged DuoxA2 regardless of the type or number of tags. Conversely, Duox1 did not release O2 (?) in any combination. Chimeric Duox2 possessing the A-loop of Duox1 showed no O2 (?) leakage; chimeric Duox1 possessing the A-loop of Duox2 released O2 (?). Moreover, Duox2 proteins possessing the A-loops of Nox1 or Nox5 co-expressed with DuoxA2 showed enhanced O2 (?) release, and Duox1 proteins possessing the A-loops of Nox1 or Nox5 co-expressed with DuoxA1 acquired O2 (?) leakage. Although we identified Duox1 A-loop residues (His(1071), His(1072), and Gly(1074)) important for reducing O2 (?) release, mutations of these residues to those of Duox2 failed to convert Duox1 to an O2 (?)-releasing enzyme. Using immunoprecipitation and endoglycosidase H sensitivity assays, we found that the A-loop of Duoxes binds to DuoxA N termini, creating more stable, mature Duox-DuoxA complexes. In conclusion, the A-loops of both Duoxes support H2O2 production through interaction with corresponding activators, but complex formation between the Duox1 A-loop and DuoxA1 results in tighter control of H2O2 release by the enzyme complex. PMID:25586178

  7. 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 the environment, but they can also originate endogenously, initiated by electron reduction of molecular oxygen. These molecules have important biological signaling activities, but they cause oxidative stress when dysfunction within the antioxidant system occurs. Excess ROS in living organisms can lead to problems, such as protein oxidation-through either cleavage of the polypeptide chain or modification of amino acid side chains-and lipid oxidation. PMID:25688469

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

    PubMed

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

    2013-04-01

    The aim of the present study was to determine whether the levels of reactive oxygen species (ROS) substances production and the levels of lipid peroxidation of the sperm membrane were related to the quality that the ejaculates exhibited after cryopreservation in boars. Ejaculates from 42 healthy boars were used in this study and they were cryopreserved with the lactose-egg yolk extender (LEY). Several sperm quality parameters were assessed by flow cytometry in samples incubated for 30 and 150 min at 37 °C after thawing: the percentage of sperm with intact plasma membrane (SIPM), intracellular reactive oxygen substances production through mean of DCF fluorescence intensity of total sperm (mean-DCF) and the percentage of viable and non-viable sperm containing oxidized BODIPY (VSOB and NVSOB). In addition, the percentages of total motile (TMS) and progressively motile sperm (PMS) were assessed at the same incubation times with a computer-assisted sperm analysis system. The classification of the ejaculates into good or bad freezers was performed through hierarchical cluster analysis from SIPM and TMS at 150 min post-thawing. The ejaculates of those males classified as good freezers exhibited higher (p < 0.05) SPIM, TMS and PMS than the bad freezers, although both groups presented similar (p > 0.05) VSOB, NVSOB and mean-DCF. Therefore, these results show that lipid peroxidation and the amount of reactive oxygen substances in the sperm after cryopreservation are similar between boars classified as good or bad freezers. PMID:22681414

  9. Flow cytometric assessment of reactive oxygen species generations that are directly related to cellular ZnO nanoparticle uptake.

    PubMed

    Yoo, Hyun Ju; Yoon, Tae Hyun

    2014-07-01

    In this study, a simple flow cytometry protocol to evaluate nanoparticle associated biological response was proposed. Particularly, we have evaluated the effect of surface charge on the cellular nanoparticle associations and nanoparticle-induced apoptosis. Significant enhancement in side scattering intensity was observed for the HeLa cells treated with positively charged (PLL)ZnO nanoparticles, suggesting that the (PLL)ZnO nanoparticles may induce cell death via adsorption and endocytosis of the nanoparticles. On the other hand, the negatively charged (PAA)ZnO nanoparticle seems to cause cell death process indirectly via the released Zn ions, with less contribution from cellular association of nanoparticles. Time- and dose-dependent studies on cellular association of ZnO nanoparticles, and ZnO associated reactive oxygen species generation were also performed for the HeLa cells exposed to the (PLL)ZnO nanoparticle. For those cells associated with (PLL)ZnO nanoparticle, a significant enhancement in reactive oxygen species generation was observed even at a lower concentration (10 ppm), which was not observable for the results with the whole cell population. By using this approach, we are able to distinguish biological responses (e.g., reactive oxygen species (ROS) generation) directly related to the cellular associations of NPs from those indirectly related to the cellular associations of NPs, such as the cytotoxicity caused by the NP released metal ions. PMID:24758038

  10. Enhanced reactive oxygen species overexpression by CuO nanoparticles in poorly differentiated hepatocellular carcinoma cells

    NASA Astrophysics Data System (ADS)

    Kung, Mei-Lang; Hsieh, Shu-Ling; Wu, Chih-Chung; Chu, Tian-Huei; Lin, Yu-Chun; Yeh, Bi-Wen; Hsieh, Shuchen

    2015-01-01

    Copper oxide nanoparticles (CuO NPs) are known to exhibit toxic effects on a variety of cell types and organs. To determine the oxidative impact of CuO NPs on hepatocellular carcinoma (HCC) cells, well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) cells were exposed to CuO NPs. Cell viability assay showed that the median inhibition concentration (IC50) for SK-Hep-1 and HepG2 cells was 25 ?g ml-1 and 85 ?g ml-1, respectively. Cellular fluorescence intensity using DCFH-DA staining analysis revealed significant intracellular reactive oxygen species (ROS) generation of up to 242% in SK-Hep-1 cells, compared with 86% in HepG2 cells. HPLC analysis demonstrated that a CuO NP treatment caused cellular GSH depletion of 58% and a GSH/GSSG ratio decrease to ~0.1 in SK-Hep-1 cells. The oxidative stress caused by enhanced superoxide anion production was observed in both HepG2 (146%) and SK-Hep-1 (192%) cells. The Griess assay verified that CuO NPs induced NO production (170%) in SK-Hep-1 cells. Comet assay and western blot further demonstrated that CuO NPs induced severe DNA strand breakage (70%) in SK-Hep-1 cells and caused DNA damage via increased ?-H2AX levels. These results suggest that well-differentiated HepG2 cells possess a robust antioxidant defense system against CuO NP-induced ROS stress and exhibit more tolerance to oxidative stress. Conversely, poorly differentiated SK-Hep-1 cells exhibited a deregulated antioxidant defense system that allowed accumulation of CuO NP-induced ROS and resulted in severe cytotoxicity.Copper oxide nanoparticles (CuO NPs) are known to exhibit toxic effects on a variety of cell types and organs. To determine the oxidative impact of CuO NPs on hepatocellular carcinoma (HCC) cells, well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) cells were exposed to CuO NPs. Cell viability assay showed that the median inhibition concentration (IC50) for SK-Hep-1 and HepG2 cells was 25 ?g ml-1 and 85 ?g ml-1, respectively. Cellular fluorescence intensity using DCFH-DA staining analysis revealed significant intracellular reactive oxygen species (ROS) generation of up to 242% in SK-Hep-1 cells, compared with 86% in HepG2 cells. HPLC analysis demonstrated that a CuO NP treatment caused cellular GSH depletion of 58% and a GSH/GSSG ratio decrease to ~0.1 in SK-Hep-1 cells. The oxidative stress caused by enhanced superoxide anion production was observed in both HepG2 (146%) and SK-Hep-1 (192%) cells. The Griess assay verified that CuO NPs induced NO production (170%) in SK-Hep-1 cells. Comet assay and western blot further demonstrated that CuO NPs induced severe DNA strand breakage (70%) in SK-Hep-1 cells and caused DNA damage via increased ?-H2AX levels. These results suggest that well-differentiated HepG2 cells possess a robust antioxidant defense system against CuO NP-induced ROS stress and exhibit more tolerance to oxidative stress. Conversely, poorly differentiated SK-Hep-1 cells exhibited a deregulated antioxidant defense system that allowed accumulation of CuO NP-induced ROS and resulted in severe cytotoxicity. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr05843g

  11. Reactivity of oxygen radical anions bound to scandia nanoparticles in the gas phase: C-H bond activation.

    PubMed

    Tian, Li-Hua; Meng, Jing-Heng; Wu, Xiao-Nan; Zhao, Yan-Xia; Ding, Xun-Lei; He, Sheng-Gui; Ma, Tong-Mei

    2014-01-20

    The activation of C-H bonds in alkanes is currently a hot research topic in chemistry. The atomic oxygen radical anion (O(-·)) is an important species in C-H activation. The mechanistic details of C-H activation by O(-·) radicals can be well understood by studying the reactions between O(-·) containing transition metal oxide clusters and alkanes. Here the reactivity of scandium oxide cluster anions toward n-butane was studied by using a high-resolution time-of-flight mass spectrometer coupled with a fast flow reactor. Hydrogen atom abstraction (HAA) from n-butane by (Sc2O3)(N)O(-) (N=1-18) clusters was observed. The reactivity of (Sc2O3)(N)O(-) (N=1-18) clusters is significantly sizedependent and the highest reactivity was observed for N=4 (Sc8O13(-)) and 12 (Sc24O37(-)). Larger (Sc2O3)(N)O(-) clusters generally have higher reactivity than the smaller ones. Density functional theory calculations were performed to interpret the reactivity of (Sc2O3)(N)O(-) (N=1-5) clusters, which were found to contain the O(-·) radicals as the active sites. The local charge environment around the O(-·) radicals was demonstrated to control the experimentally observed size-dependent reactivity. This work is among the first to report HAA reactivity of cluster anions with dimensions up to nanosize toward alkane molecules. The anionic O(-·) containing scandium oxide clusters are found to be more reactive than the corresponding cationic ones in the C-H bond activation. PMID:24338790

  12. Measurements of UV-generated free radicals/reactive oxygen species (ROS) in skin

    NASA Astrophysics Data System (ADS)

    Herrling, Th.; Jung, K.; Fuchs, J.

    2006-03-01

    Free radicals/reactive oxygen species (ROS) generated in skin by UV irradiation were measured by electron spin resonance (ESR). To increase the sensitivity of measurement the short life free radicals/ROS were scavenged and accumulated by using the nitroxyl probe 3-carboxy-2,2,5,5-tetrametylpyrrolidine-1-oxyl (PCA). The spatial distribution of free radicals/ROS measured in pig skin biopsies with ESR imaging after UV irradiation corresponds to the intensity decay of irradiance in the depth of the skin. The main part of free radicals/ROS were generated by UVA (320-400 nm) so that the spatial distribution of free radicals reaches up to the lower side of the dermis. In vivo measurements on human skin were performed with a L-band ESR spectrometer and a surface coil integrating the signal intensities from all skin layers to get a sufficient signal amplitude. Using this experimental arrangement the protection of UVB and UVA/B filter against the generation of free radicals/ROS in skin were measured. The protection against ROS and the repair of damages caused by them can be realized with active antioxidants characterized by a high antioxidative power (AP). The effect of UV filter and antioxidants corresponding to their protection against free radicals/ROS in skin generated by UVAB irradiation can be quantified by the new radical sun protection factor (RSF). The RSF indicates the increase of time for staying in the sun to generate the same number of free radicals/ROS in the skin like for the unprotected skin. Regarding the amount of generated free radicals/ROS in skin as an biophysical endpoint the RSF characterizes both the protection against UVB and UVA radiation.

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

    SciTech Connect

    Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan)] [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Takahashi, Yutaka, E-mail: takahash@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan)] [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan)

    2012-08-24

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

  14. Superparamagnetic iron oxide nanoparticles exacerbate the risks of reactive oxygen species-mediated external stresses.

    PubMed

    Luo, Cheng; Li, Yan; Yang, Liang; Wang, Xun; Long, Jiangang; Liu, Jiankang

    2015-03-01

    Superparamagnetic iron oxide nanoparticles (IONPs) have been widely applied in numerous biomedical fields. The evaluation of the toxicity of IONPs to the environment and human beings is indispensable to guide their applications. IONPs are usually considered to have good biocompatibility; however, some literatures have reported the toxicity of IONPs in vitro and in vivo. The controversy surrounding the biocompatibility of IONPs prompted us to carefully consider the biological effects of IONPs, especially under stress conditions. However, the potential risks of IONPs under stress conditions have not yet been evaluated in depth. Acrolein is widespread in the environment and modulates stress-induced gene activation and cell death in many organs and tissues. In this study, we assessed the sensitivity of H9c2 cardiomyocyte cells embedded with IONPs to acrolein and investigated the possible molecular mechanisms involved in this sensitivity. IONPs, which alone exhibited no toxicity, sensitized the H9c2 cardiomyocytes to acrolein-induced dysfunction. The IONP/acrolein treatment induced a loss of viability, membrane disruption, reactive oxygen species (ROS) generation, Erk activation, mitochondrial and lysosomal dysfunction, and necrosis in H9c2 cells. Treatment with an ROS generation inhibitor (diphenyleneiodonium) or an iron chelator (deferoxamine) prevented the IONP/acrolein-induced loss of viability, suggesting that ROS and IONP degradation facilitated the toxicity of the IONP/acrolein treatment in H9c2 cells. Our data suggest that cells embedded in IONPs are more vulnerable to oxidative stress, which confirms the hypothesis that nanoparticles can sensitize cells to the adverse effects of external stimulation. The present work provides a new perspective from which to evaluate the interactions between nanoparticles and cells. PMID:24847785

  15. Curcumin inhibits reactive oxygen species formation and vascular hyperpermeability following haemorrhagic shock.

    PubMed

    Tharakan, Binu; Hunter, Felicia A; Smythe, W Roy; Childs, Ed W

    2010-09-01

    1. Oxidative stress induced by reactive oxygen species (ROS) is a key mediator of haemorrhagic shock (HS)-induced vascular hyperpermeability. In the present study, curcumin, a natural anti-oxidant obtained from turmeric (Curcuma longa), was tested against HS-induced hyperpermeability and associated ROS formation in rat mesenteric post-capillary venules in vivo and in rat lung microvascular endothelial cells (RLMEC) in vitro. 2. In rats, HS was induced by withdrawing blood to reduce mean arterial pressure to 40 mmHg for 60 min, followed by resuscitation for 60 min. To investigate vascular permeability, rats were given fluorescein isothiocyanate (FITC)-albumin (50 mg/kg, i.v.). The FITC-albumin flux was measured in mesenteric post-capillary venules by determining optical intensity intra- and extravascularly under intravital microscopy. Mitochondrial ROS formation was determined using dihydrorhodamine 123 in vivo. Parallel studies were conducted in vitro using serum collected after HS. The serum was tested on rat lung microvascular endothelial cell RLMEC monolayers. 3. In rats, HS induced a significant increase in vascular hyperpermeability and ROS formation in vivo (P < 0.05). Treatment with curcumin (20 micromol/L) attenuated both these effects (P < 0.05). In RLMEC in vitro, HS serum induced monolayer permeability and ROS formation. Curcumin (10 micromol/L) attenuated HS serum-induced monolayer hyperpermeability and ROS formation. Curcumin (2-100 micromol/L) scavenged 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and 1,1-diphenyl-2-picrylhydrazyl radicals in vitro, indicating its potential as a free radical scavenger. 4. The present study demonstrates that curcumin is an inhibitor of vascular hyperpermeability following HS, with its protective effects mediated through its anti-oxidant properties. PMID:20528978

  16. Surface functionalization of titanium dioxide nanoparticles: Photo-stability and reactive oxygen species (ROS) generation

    NASA Astrophysics Data System (ADS)

    Louis, Kacie M.

    Metal oxide nanoparticles are becoming increasingly prevalent in society for applications of sunscreens, cosmetics, paints, biomedical imaging, and photovoltaics. Due to the increased surface area to volume ratio of nanoparticles compared to bulk materials, it is important to know the health and safety impacts of these materials. One mechanism of toxicity of nominally "safe" materials such as TiO 2 is through the photocatalytic generation of reactive oxygen species (ROS). ROS production and ligand degradation can affect the bioavailability of these particles in aqueous organisms. We have investigated ROS generation by functionalized TiO2 nanoparticles and its influence on aggregation and bioavailability and toxicity to zebrafish embryos/larvae. For these studies we investigated anatase TiO2 nanoparticles. For application purposes and solution stability, the TiO2 nanoparticles were functionalized with a variety of ligands such as citrate, 3,4-dihydroxybenzaldehyde, and ascorbate. We quantitatively examined the amount of ROS produced in aqueous solution using fluorescent probes and see that more ROS is produced under UV light than in the dark control. Our measurements show that TiO2 toxicity reaches a maximum for nanoparticles with smaller diameters, and is correlated with surface area dependent changes in ROS generation. In an effort to reduce toxicity through control of the surface and surface ligands, we synthesized anatase nanoparticles of different sizes, functionalized them with different ligands, and examined the resulting ROS generation and ligand stability. Using a modular ligand containing a hydrophobic inner region and a hydrophilic outer region, we synthesized water-stable nanoparticles, via two different chemical reactions, having much-reduced ROS generation and thus reduced toxicity. These results suggest new strategies for making safer nanoparticles while still retaining their desired properties. We also examine the degradation of the different ligands on the surface of the particles using XPS and FTIR. The combination of ROS production and ligand degradation can affect the bioavailability of these particles in aqueous species.

  17. Non-thermal Plasma Induces Apoptosis in Melanoma Cells via Production of Intracellular Reactive Oxygen Species

    PubMed Central

    Sensenig, Rachel; Kalghatgi, Sameer; Cerchar, Ekaterina; Fridman, Gregory; Shereshevsky, Alexey; Torabi, Behzad; Arjunan, Krishna Priya; Podolsky, Erica; Fridman, Alexander; Friedman, Gary; Azizkhan-Clifford, Jane; Brooks, Ari D.

    2012-01-01

    Non-thermal atmospheric pressure dielectric barrier discharge (DBD) plasma may provide a novel approach to treat malignancies via induction of apoptosis. The purpose of this study was to evaluate the potential of DBD plasma to induce apoptosis in melanoma cells. Melanoma cells were exposed to plasma at doses that did not induce necrosis, and cell viability and apoptotic activity were evaluated by Trypan blue exclusion test, Annexin-V/PI staining, caspase-3 cleavage, and TUNEL® analysis. Trypan blue staining revealed that non-thermal plasma treatment significantly decreased the viability of cells in a dose-dependent manner 3 and 24 h after plasma treatment. Annexin-V/PI staining revealed a significant increase in apoptosis in plasma-treated cells at 24, 48, and 72 h post-treatment (p<0.001). Caspase-3 cleavage was observed 48 h post-plasma treatment at a dose of 15 J/cm2. TUNEL® analysis of plasma-treated cells demonstrated an increase in apoptosis at 48 and 72 h post-treatment (p<0.001) at a dose of 15 J/cm2. Pre-treatment with N-acetyl-L-cysteine (NAC), an intracellular reactive oxygen species (ROS) scavenger, significantly decreased apoptosis in plasma-treated cells at 5 and 15 J/cm2. Plasma treatment induces apoptosis in melanoma cells through a pathway that appears to be dependent on production of intracellular ROS. DBD plasma production of intracellular ROS leads to dose-dependent DNA damage in melanoma cells, detected by ?-H2AX, which was completely abrogated by pre-treating cells with ROS scavenger, NAC. Plasma-induced DNA damage in turn may lead to the observed plasma-induced apoptosis. Since plasma is non-thermal, it may be used to selectively treat malignancies. PMID:21046465

  18. JP-8 induces immune suppression via a reactive oxygen species NF-kappabeta-dependent mechanism.

    PubMed

    Ramos, Gerardo; Limon-Flores, Alberto Y; Ullrich, Stephen E

    2009-03-01

    Applying jet fuel (JP-8) to the skin of mice induces immune suppression. JP-8-treated keratinocytes secrete prostaglandin E(2), which is essential for activating immune suppressive pathways. The molecular pathway leading to the upregulation of the enzyme that controls prostaglandin synthesis, cyclooxygenase (COX)-2, is unclear. Because JP-8 activates oxidative stress and because reactive oxygen species (ROS) turn on nuclear factor kappa B (NF-kappabeta), which regulates the activity of COX-2, we asked if JP-8-induced ROS and NF-kappabeta contributes to COX-2 upregulation and immune suppression in vivo. JP-8 induced the production of ROS in keratinocytes as measured with the ROS indicator dye, aminophenyl fluorescein. Fluorescence was diminished in JP-8-treated keratinocytes overexpressing catalase or superoxide dismutase (SOD) genes. JP-8-induced COX-2 expression was also reduced to background in the catalase and SOD transfected cells, or in cultures treated with N-acetylcysteine (NAC). When NAC was injected into JP-8-treated mice, dermal COX-2 expression, and JP-8-induced immune suppression was inhibited. Because ROS activates NF-kappabeta, we asked if this transcriptional activator played a role in the enhanced COX-2 expression and JP-8-induced immune suppression. When JP-8-treated mice, or JP-8-treated keratinocytes were treated with a selective NF-kappabeta inhibitor, parthenolide, COX-2 expression, and immune suppression were abrogated. Similarly, when JP-8-treated keratinocytes were treated with small interfering RNA specific for the p65 subunit of NF-kappabeta, COX-2 upregulation was blocked. These data indicate that ROS and NF-kappabeta are activated by JP-8, and these pathways are involved in COX-2 expression and the induction of immune suppression by jet fuel. PMID:19095747

  19. Reactive oxygen species and IRF1 stimulate IFN? production by proximal tubules during ischemic AKI

    PubMed Central

    Winterberg, Pamela D.; Wang, Yanxia; Lin, Keng-Mean; Hartono, John R.; Nagami, Glenn T.; Zhou, Xin J.; Shelton, John M.; Richardson, James A.

    2013-01-01

    We previously reported that expression of the transcription factor interferon regulatory factor 1 (IRF1) is an early, critical maladaptive signal expressed by renal tubules during murine ischemic acute kidney injury (AKI). We now show that IRF1 mediates signals from reactive oxygen species (ROS) generated during ischemic AKI and that these signals ultimately result in production of ?-subtypes of type I interferons (IFN?s). We found that genetic knockout of the common type I IFN receptor (IFNARI?/?) improved kidney function and histology during AKI. There are major differences in the spatial-temporal production of the two major IFN subtypes, IFN? and IFN?s: IFN? expression peaks at 4 h, earlier than IFN?s, and continues at the same level at 24 h; expression of IFN?s also increases at 4 h but continues to increase through 24 h. The magnitude of the increase in IFN?s relative to baseline is much greater than that of IFN?. We show by immunohistology and study of isolated cells that IFN? is produced by renal leukocytes and IFN?s are produced by renal tubules. IRF1, IFN?s, and IFNARI were found on the same renal tubules during ischemic AKI. Furthermore, we found that ROS induced IFN? expression by renal tubules in vitro. This expression was inhibited by small interfering RNA knockdown of IRF1. Overexpression of IRF1 resulted in the production of IFN?s. Furthermore, we found that IFN? stimulated production of maladaptive proinflammatory CXCL2 by renal tubular cells. Altogether our data support the following autocrine pathway in renal tubular cells: ROS > IRF1 > IFN? > IFNARI > CXCL2. PMID:23657854

  20. 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 polyester-based biomaterials and provide a robust, cell-degradable substrate for guiding new tissue formation. PMID:24491510

  1. Localized TRPA1 channel Ca2+ signals stimulated by reactive oxygen species promote cerebral artery dilation.

    PubMed

    Sullivan, Michelle N; Gonzales, Albert L; Pires, Paulo W; Bruhl, Allison; Leo, M Dennis; Li, Wencheng; Oulidi, Agathe; Boop, Frederick A; Feng, Yumei; Jaggar, Jonathan H; Welsh, Donald G; Earley, Scott

    2015-01-01

    Reactive oxygen species (ROS) can have divergent effects in cerebral and peripheral circulations. We found that Ca(2+)-permeable transient receptor potential ankyrin 1 (TRPA1) channels were present and colocalized with NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase 2 (NOX2), a major source of ROS, in the endothelium of cerebral arteries but not in other vascular beds. We recorded and characterized ROS-triggered Ca(2+) signals representing Ca(2+) influx through single TRPA1 channels, which we called "TRPA1 sparklets." TRPA1 sparklet activity was low under basal conditions but was stimulated by NOX-generated ROS. Ca(2+) entry during a single TRPA1 sparklet was twice that of a TRPV4 sparklet and ~200 times that of an L-type Ca(2+) channel sparklet. TRPA1 sparklets representing the simultaneous opening of two TRPA1 channels were more common in endothelial cells than in human embryonic kidney (HEK) 293 cells expressing TRPA1. The NOX-induced TRPA1 sparklets activated intermediate-conductance, Ca(2+)-sensitive K(+) channels, resulting in smooth muscle hyperpolarization and vasodilation. NOX-induced activation of TRPA1 sparklets and vasodilation required generation of hydrogen peroxide and lipid-peroxidizing hydroxyl radicals as intermediates. 4-Hydroxy-nonenal, a metabolite of lipid peroxidation, also increased TRPA1 sparklet frequency and dilated cerebral arteries. These data suggest that in the cerebral circulation, lipid peroxidation metabolites generated by ROS activate Ca(2+) influx through TRPA1 channels in the endothelium of cerebral arteries to cause dilation. PMID:25564678

  2. Low Po2 conditions induce reactive oxygen species formation during contractions in single skeletal muscle fibers

    PubMed Central

    Shiah, Amy; Roberts, William J.; Chien, Michael T.; Wagner, Peter D.; Hogan, Michael C.

    2013-01-01

    Contractions in whole skeletal muscle during hypoxia are known to generate reactive oxygen species (ROS); however, identification of real-time ROS formation within isolated single skeletal muscle fibers has been challenging. Consequently, there is no convincing evidence showing increased ROS production in intact contracting fibers under low Po2 conditions. Therefore, we hypothesized that intracellular ROS generation in single contracting skeletal myofibers increases during low Po2 compared with a value approximating normal resting Po2. Dihydrofluorescein was loaded into single frog (Xenopus) fibers, and fluorescence was used to monitor ROS using confocal microscopy. Myofibers were exposed to two maximal tetanic contractile periods (1 contraction/3 s for 2 min, separated by a 60-min rest period), each consisting of one of the following treatments: high Po2 (30 Torr), low Po2 (3–5 Torr), high Po2 with ebselen (antioxidant), or low Po2 with ebselen. Ebselen (10 ?M) was administered before the designated contractile period. ROS formation during low Po2 treatment was greater than during high Po2 treatment, and ebselen decreased ROS generation in both low- and high-Po2 conditions (P < 0.05). ROS accumulated at a faster rate in low vs. high Po2. Force was reduced >30% for each condition except low Po2 with ebselen, which only decreased ?15%. We concluded that single myofibers under low Po2 conditions develop accelerated and more oxidative stress than at Po2 = 30 Torr (normal human resting Po2). Ebselen decreases ROS formation in both low and high Po2, but only mitigates skeletal muscle fatigue during reduced Po2 conditions. PMID:23576612

  3. Reactive Oxygen Species Promote Caspase-12 Expression and Tubular Apoptosis in Diabetic Nephropathy

    PubMed Central

    Brezniceanu, Marie-Luise; Lau, Cara J.; Godin, Nicolas; Chénier, Isabelle; Duclos, Alain; Éthier, Jean; Filep, Janos G.; Ingelfinger, Julie R.; Zhang, Shao-Ling

    2010-01-01

    Apoptosis of tubular epithelial cells contributes to the tubular atrophy that accompanies diabetic nephropathy. Reactive oxygen species (ROS) promote tubular apoptosis, but the mechanisms by which this occurs are incompletely understood. Here, we sought proapoptotic genes that ROS differentially upregulate in renal proximal tubular cells of diabetic (db/db) mice. We performed microarray analysis using total RNA from freshly isolated renal proximal tubules of nondiabetic, diabetic, and diabetic transgenic mice overexpressing catalase in the proximal tubule (thereby attenuating ROS). We observed greater expression of caspase-12 in the proximal tubules of the diabetic mice compared with the nondiabetic and diabetic transgenic mice. Quantitative PCR and immunohistochemistry confirmed the enhanced expression of caspase-12, as well as members of the endoplasmic reticulum stress–induced apoptotic pathway. Ex vivo, albumin induced caspase-12 activity and expression (protein and mRNA) and mRNA expression of the CCAT/enhancer-binding protein homologous protein in freshly isolated wild-type proximal tubules but not in catalase-overexpressing proximal tubules. In vitro, albumin stimulated activity of both caspase-12 and caspase-3 as well as expression of caspase-12 and CCAT/enhancer-binding protein homologous protein in a human proximal tubule cell line (HK-2). The free radical scavenger tiron inhibited these effects. Furthermore, knockdown of caspase-12 with small interfering RNA reduced albumin-induced apoptosis in HK-2 cells. Taken together, these studies demonstrate that albuminuria may induce tubular apoptosis through generation of ROS and the subsequent expression and activation of endoplasmic reticulum stress genes in the diabetic kidney. PMID:20299359

  4. Reactive oxygen species in the presence of high glucose alter ureteric bud morphogenesis.

    PubMed

    Zhang, Shao-Ling; Chen, Yun-Wen; Tran, Stella; Chenier, Isabelle; Hébert, Marie-Josée; Ingelfinger, Julie R

    2007-07-01

    Renal malformations are a major cause of childhood renal failure. During the development of the kidney, ureteric bud (UB) branching morphogenesis is critical for normal nephrogenesis. These studies investigated whether renal UB branching morphogenesis is altered by a high ambient glucose environment and studied underlying mechanism(s). Kidney explants that were isolated from different periods of gestation (embryonic days 12 to 18) from Hoxb7-green fluorescence protein mice were cultured for 24 h in either normal d-glucose (5 mM) or high d-glucose (25 mM) medium with or without various inhibitors. Alterations in renal morphogenesis were assessed by fluorescence microscopy. Paired-homeobox 2 (Pax-2) gene expression was determined by real-time quantitative PCR, Western blotting, and immunohistology. The results revealed that high d-glucose (25 mM) specifically stimulates UB branching morphogenesis via Pax-2 gene expression, whereas other glucose analogs, such as d-mannitol, l-glucose, and 2-deoxy-d-glucose, had no effect. The stimulatory effect of high glucose on UB branching was blocked in the presence of catalase and inhibitors of NADPH oxidase, mitochondrial electron transport chain complex I, and Akt signaling. Moreover, in in vivo studies, it seems that high glucose induces, via Pax-2 (mainly localized in UB), acceleration of UB branching but not nephron formation. Taken together, these data demonstrate that high glucose alters UB branching morphogenesis. This occurs, at least in part, via reactive oxygen species generation, activation of Akt signaling, and upregulation of Pax-2 gene expression. PMID:17538188

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

    PubMed Central

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

    2014-01-01

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

  6. Live Candida albicans Suppresses Production of Reactive Oxygen Species in Phagocytes? †

    PubMed Central

    Wellington, Melanie; Dolan, Kristy; Krysan, Damian J.

    2009-01-01

    Production of reactive oxygen species (ROS) is an important aspect of phagocyte-mediated host responses. Since phagocytes play a crucial role in the host response to Candida albicans, we examined the ability of Candida to modulate phagocyte ROS production. ROS production was measured in the murine macrophage cell line J774 and in primary phagocytes using luminol-enhanced chemiluminescence. J774 cells, murine polymorphonuclear leukocytes (PMN), human monocytes, and human PMN treated with live C. albicans produced significantly less ROS than phagocytes treated with heat-killed C. albicans. Live C. albicans also suppressed ROS production in murine bone marrow-derived macrophages from C57BL/6 mice, but not from BALB/c mice. Live C. albicans also suppressed ROS in response to external stimuli. C. albicans and Candida glabrata suppressed ROS production by phagocytes, whereas Saccharomyces cerevisiae stimulated ROS production. The cell wall is the initial point of contact between Candida and phagocytes, but isolated cell walls from both heat-killed and live C. albicans stimulated ROS production. Heat-killed C. albicans has increased surface exposure of 1,3-?-glucan, a cell wall component that can stimulate phagocytes. To determine whether surface 1,3-?-glucan exposure accounted for the difference in ROS production, live C. albicans cells were treated with a sublethal dose of caspofungin to increase surface 1,3-?-glucan exposure. Caspofungin-treated C. albicans was fully able to suppress ROS production, indicating that suppression of ROS overrides stimulatory signals from 1,3-?-glucan. These studies indicate that live C. albicans actively suppresses ROS production in phagocytes in vitro, which may represent an important immune evasion mechanism. PMID:18981256

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

    PubMed

    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-?B 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. PMID:25576385

  8. Generation of reactive oxygen species mediated by humic-like substances in atmospheric aerosols.

    PubMed

    Lin, Peng; Yu, Jian Zhen

    2011-12-15

    Particulate matter (PM)-mediated reactive oxygen species (ROS) generation has been implicated in health effects posed by PM. Humic-like substances (HULIS) are an unresolved mixture of water-extracted organic compounds from atmospheric aerosol particles or isolated from fog/cloudwater samples. In this study, we use a cell-free dithiothreitol (DTT) assay to measure ROS production mediated by HULIS. The HULIS samples are isolated from aerosols collected at a rural location and a suburban location in the Pearl River Delta, China. In our experiments, ROS activities by residue metal ions in the HULIS fraction are suppressed by including a strong chelating agent in the DTT assay. Under conditions of DTT consumption not exceeding 90%, the HULIS-catalyzed oxidation of DTT follows the zero-order kinetics with respect to DTT concentration, and the rate of DTT oxidation is proportional to the dose of HULIS. The ROS activity of the aerosol HULIS, on a per unit mass basis is 2% of the ROS activity by a reference quinone compound, 1,4-naphthoquinone and exceeds that of two aquatic fulvic acids. The HULIS fraction in the ambient samples tested exhibits comparable ROS activities to the organic solvent extractable fraction, which would contain compounds such as quinones, a known organic compound class capable of catalyzing generation of ROS in cells. HULIS was found to be the major redox active constituent of the water-extractable organic fraction in PM. It is plausible that HULIS contains reversible redox sites, thereby serving as electron carriers to catalyze the formation of ROS. Our work suggests that HULIS could be an active PM component in generating ROS and further work is warranted to characterize its redox properties. PMID:22044074

  9. Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species.

    PubMed

    Ro, Seung-Hyun; Nam, Myeongjin; Jang, Insook; Park, Hwan-Woo; Park, Haeli; Semple, Ian A; Kim, Myungjin; Kim, Jeong Sig; Park, Haewon; Einat, Paz; Damari, Golda; Golikov, Maya; Feinstein, Elena; Lee, Jun Hee

    2014-05-27

    Uncoupling protein 1 (Ucp1), which is localized in the mitochondrial inner membrane of mammalian brown adipose tissue (BAT), generates heat by uncoupling oxidative phosphorylation. Upon cold exposure or nutritional abundance, sympathetic neurons stimulate BAT to express Ucp1 to induce energy dissipation and thermogenesis. Accordingly, increased Ucp1 expression reduces obesity in mice and is correlated with leanness in humans. Despite this significance, there is currently a limited understanding of how Ucp1 expression is physiologically regulated at the molecular level. Here, we describe the involvement of Sestrin2 and reactive oxygen species (ROS) in regulation of Ucp1 expression. Transgenic overexpression of Sestrin2 in adipose tissues inhibited both basal and cold-induced Ucp1 expression in interscapular BAT, culminating in decreased thermogenesis and increased fat accumulation. Endogenous Sestrin2 is also important for suppressing Ucp1 expression because BAT from Sestrin2(-/-) mice exhibited a highly elevated level of Ucp1 expression. The redox-inactive mutant of Sestrin2 was incapable of regulating Ucp1 expression, suggesting that Sestrin2 inhibits Ucp1 expression primarily through reducing ROS accumulation. Consistently, ROS-suppressing antioxidant chemicals, such as butylated hydroxyanisole and N-acetylcysteine, inhibited cold- or cAMP-induced Ucp1 expression as well. p38 MAPK, a signaling mediator required for cAMP-induced Ucp1 expression, was inhibited by either Sestrin2 overexpression or antioxidant treatments. Taken together, these results suggest that Sestrin2 and antioxidants inhibit Ucp1 expression through suppressing ROS-mediated p38 MAPK activation, implying a critical role of ROS in proper BAT metabolism. PMID:24825887

  10. DJ-1 mediates the resistance of cancer cells to dihydroartemisinin through reactive oxygen species removal.

    PubMed

    Zhu, Hong; Liao, Si-Da; Shi, Jia-Jie; Chang, Lin-Lin; Tong, Yun-Guang; Cao, Ji; Fu, Ying-Ying; Chen, Xiu-Ping; Ying, Mei-Dan; Yang, Bo; He, Qiao-Jun; Lu, Jin-Jian

    2014-06-01

    Dihydroartemisinin (DHA), one of the main metabolites of artemisinin and its derivatives, presents anti-cancer potential in vitro and in vivo. To explore the mechanisms of resistance toward DHA, a DHA-resistant cell line, HeLa/DHA, was established with a resistance factor of 7.26 in vitro. Upon DHA treatment, apoptotic cells were significantly elicited in parental HeLa cells but minimally induced in HeLa/DHA cells. HeLa/DHA cells also displayed much less sensitivity to DHA-induced tumor suppression in cancer xenograft models than HeLa cells. Intriguingly, DHA-resistant cells did not display a multidrug-resistant phenotype. Based on a proteomic study employing LC-ESI-MS/MS together with pathway analysis, DJ-1 (PARK7) was found to be highly expressed in HeLa/DHA cells. Western blot and immunofluorescence assays confirmed the higher expression of DJ-1 in HeLa/DHA cells than in parental cells in both cell line and xenograft models. DJ-1 is translocated to the mitochondria of HeLa/DHA cells and oxidized, providing DJ-1 with stronger cytoprotection activity. Further study revealed that DJ-1 knockdown in HeLa/DHA cells abolished the observed resistance, whereas overexpression of DJ-1 endowed the parental HeLa cells with resistance toward DHA. Reactive oxygen species (ROS) were also significantly induced by either DHA or hydrogen peroxide in HeLa cells but not in resistant HeLa/DHA cells. When the cells were pretreated with N-acetyl-l-cysteine, the effect of DJ-1 knockdown on sensitizing HeLa/DHA cells to DHA was significantly attenuated. In summary, our study suggests that overexpression and mitochondrial translocation of DJ-1 provides HeLa/DHA cells with resistance to DHA-induced ROS and apoptosis. PMID:24681255

  11. Increased effectiveness of carbon ions in the production of reactive oxygen species in normal human fibroblasts.

    PubMed

    Dettmering, Till; Zahnreich, Sebastian; Colindres-Rojas, Miriam; Durante, Marco; Taucher-Scholz, Gisela; Fournier, Claudia

    2015-01-01

    The production of reactive oxygen species (ROS), especially superoxide anions (O2 (·-)), is enhanced in many normal and tumor cell types in response to ionizing radiation. The influence of ionizing radiation on the regulation of ROS production is considered as an important factor in the long-term effects of irradiation (such as genomic instability) that might contribute to the development of secondary cancers. In view of the increasing application of carbon ions in radiation therapy, we aimed to study the potential impact of ionizing density on the intracellular production of ROS, comparing photons (X-rays) with carbon ions. For this purpose, we used normal human cells as a model for irradiated tissue surrounding a tumor. By quantifying the oxidization of Dihydroethidium (DHE), a fluorescent probe sensitive to superoxide anions, we assessed the intracellular ROS status after radiation exposure in normal human fibroblasts, which do not show radiation-induced chromosomal instability. After 3-5 days post exposure to X-rays and carbon ions, the level of ROS increased to a maximum that was dose dependent. The maximum ROS level reached after irradiation was specific for the fibroblast type. However, carbon ions induced this maximum level at a lower dose compared with X-rays. Within ?1 week, ROS decreased to control levels. The time-course of decreasing ROS coincides with an increase in cell number and decreasing p21 protein levels, indicating a release from radiation-induced growth arrest. Interestingly, radiation did not act as a trigger for chronically enhanced levels of ROS months after radiation exposure. PMID:25304329

  12. Effects of reactive oxygen species and neutrophils on endothelium-dependent relaxation of rat thoracic aorta

    PubMed Central

    Bauer, Viktor; Sotníková, Ružena; Drábiková, Katarína

    2011-01-01

    Reactive oxygen species (ROS) are produced in different metabolic processes including the respiratory burst of neutrophils accompanying local inflammation. The aim of this study was to analyze the effects of N-formyl-methionyl-leucyl-phenylalanine (FMLP)-activated neutrophils, isolated from the guinea pig peritoneal cavity, on isolated rings of a large (conduit) artery, the rat thoracic aorta. FMLP-activated neutrophils enhanced the basal tension increased by ?1-adrenergic stimulation. In phenylephrine-precontracted aortae, they elicited marked contraction, while in noradrenaline-precontracted rat aortal rings they caused a biphasic response (contraction-relaxation). To eliminate interaction of activated neutrophils with catecholamines, in the subsequent experiments the basal tension was increased by KCl-induced depolarization. Activated neutrophils evoked a low-amplitude biphasic response (relaxation-contraction) on the KCl-induced contraction. Not only the acetylcholine- and A23187-induced relaxations but also the catalase sensitive hydrogen peroxide (H2O2) elicited contractions were endothelium-dependent. Even though the acetylcholine-induced relaxation was changed by activated neutrophils and by the ROS studied, their effects differed significantly, yet none of them did eliminate fully the endothelium-dependent acetylcholine relaxation. The effect of activated neutrophils resembled the effect of superoxide anion radical (O2 •–) produced by xanthine/xanthine oxidase (X/XO) and differed from the inhibitory effects of Fe2SO4/H2O2-produced hydroxyl radical (•OH) and H2O2. Thus O2 •– produced either by activated neutrophils or X/XO affected much less the endothelium-dependent acetylcholine-activated relaxation mechanisms than did •OH and H2O2. In the large (conduit) artery, the effects of activated neutrophils and various ROS (O2 •–, •OH and H2O2) seem to be more dependent on muscle tension than on endothelial mechanisms. PMID:22319253

  13. Reactive oxygen species alters the electrophysiological properties and raises [Ca2+]i in intracardiac ganglion neurons.

    PubMed

    Dyavanapalli, Jhansi; Rimmer, Katrina; Harper, Alexander A

    2010-07-01

    We have investigated the effects of the reactive oxygen species (ROS) donors hydrogen peroxide (H(2)O(2)) and tert-butyl hydroperoxide (t-BHP) on the intrinsic electrophysiological characteristics: ganglionic transmission and resting [Ca(2+)](i) in neonate and adult rat intracardiac ganglion (ICG) neurons. Intracellular recordings were made using sharp microelectrodes filled with either 0.5 M KCl or Oregon Green 488 BAPTA-1, allowing recording of electrical properties and measurement of [Ca(2+)](i). H(2)O(2) and t-BHP both hyperpolarized the resting membrane potential and reduced membrane resistance. In adult ICG neurons, the hyperpolarizing action of H(2)O(2) was reversed fully by Ba(2+) and partially by tetraethylammonium, muscarine, and linopirdine. H(2)O(2) and t-BHP reduced the action potential afterhyperpolarization (AHP) amplitude but had no impact on either overshoot or AHP duration. ROS donors evoked an increase in discharge adaptation to long depolarizing current pulses. H(2)O(2) blocked ganglionic transmission in most ICG neurons but did not alter nicotine-evoked depolarizations. By contrast, t-BHP had no significant action on ganglionic transmission. H(2)O(2) and t-BHP increased resting intracellular Ca(2+) levels to 1.6 ( +/- 0.6, n = 11, P < 0.01) and 1.6 ( +/- 0.3, n = 8, P < 0.001), respectively, of control value (1.0, approximately 60 nM). The ROS scavenger catalase prevented the actions of H(2)O(2), and this protection extended beyond the period of application. Superoxide dismutase partially shielded against the action of H(2)O(2), but this was limited to the period of application. These data demonstrate that ROS decreases the excitability and ganglionic transmission of ICG neurons, attenuating parasympathetic control of the heart. PMID:20445155

  14. Reactive oxygen species induce a Ca(2+)-spark increase in sensitized murine airway smooth muscle cells.

    PubMed

    Tuo, Qing-Rong; Ma, Yun-Fei; Chen, Weiwei; Luo, Xiao-Jing; Shen, Jinhua; Guo, Donglin; Zheng, Yun-Min; Wang, Yong-Xiao; Ji, Guangju; Liu, Qing-Hua

    2013-05-10

    The level of reactive oxygen species (ROS) and the activity of spontaneous, transient, localized Ca(2+) increases (known as Ca(2+) sparks) in tracheal smooth muscle cells (TSMCs) in an experimental allergic asthma mouse model has not yet been investigated. We used laser confocal microscopy and fluorescent dyes to measure ROS levels and Ca(2+) sparks, and we found that both events were significantly increased in TSMCs obtained from ovalbumin (OVA)-sensitized/-challenged mice compared with control mice. ROS levels began to increase in TSMCs after the first OVA challenge, and this increase was sustained. However, this elevation and Ca(2+)-spark increase was abolished after the administration of the ROS scavenger N-acetylcysteine amide (NACA) for 5days. Furthermore, a similar inhibition was also observed following the direct perfusion of NACA into cells isolated from the (OVA)-sensitized mice that were not treated with NACA. Moreover, we used 0.1-mM caffeine treatment to increase the Ca(2+) sparks in single TSMCs and observed cell shortening. In addition, we did not find increases in the mRNA levels of ryanodine (RyRs) and inositol 1,4,5-trisphosphate (IP3Rs) receptors in the tracheal smooth muscle cells of (OVA)-sensitized mice compared with controls. We concluded that ROS and Ca(2+) sparks increased in (OVA)-sensitized TSMCs. We found that ROS induces Ca(2+) sparks, and increased Ca(2+) sparks resulted in the contraction of (OVA)-sensitized TSMCs, resulting in the generation of airway hyperresponsiveness (AHR). This effect may represent a novel mechanism for AHR pathogenesis and might provide insight into new methods for the clinical prevention and treatment of asthma and asthmatic AHR. PMID:23583396

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

    SciTech Connect

    Haase, Hajo; Engelhardt, Gabriela; Hebel, Silke; Rink, Lothar, E-mail: LRink@ukaachen.de

    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.

  16. Impact of hypothalamic reactive oxygen species in the regulation of energy metabolism and food intake

    PubMed Central

    Drougard, Anne; Fournel, Audren; Valet, Philippe; Knauf, Claude

    2015-01-01

    Hypothalamus is a key area involved in the control of metabolism and food intake via the integrations of numerous signals (hormones, neurotransmitters, metabolites) from various origins. These factors modify hypothalamic neurons activity and generate adequate molecular and behavioral responses to control energy balance. In this complex integrative system, a new concept has been developed in recent years, that includes reactive oxygen species (ROS) as a critical player in energy balance. ROS are known to act in many signaling pathways in different peripheral organs, but also in hypothalamus where they regulate food intake and metabolism by acting on different types of neurons, including proopiomelanocortin (POMC) and agouti-related protein (AgRP)/neuropeptide Y (NPY) neurons. Hypothalamic ROS release is under the influence of different factors such as pancreatic and gut hormones, adipokines (leptin, apelin,…), neurotransmitters and nutrients (glucose, lipids,…). The sources of ROS production are multiple including NADPH oxidase, but also the mitochondria which is considered as the main ROS producer in the brain. ROS are considered as signaling molecules, but conversely impairment of this neuronal signaling ROS pathway contributes to alterations of autonomic nervous system and neuroendocrine function, leading to metabolic diseases such as obesity and type 2 diabetes. In this review we focus our attention on factors that are able to modulate hypothalamic ROS release in order to control food intake and energy metabolism, and whose deregulations could participate to the development of pathological conditions. This novel insight reveals an original mechanism in the hypothalamus that controls energy balance and identify hypothalamic ROS signaling as a potential therapeutic strategy to treat metabolic disorders. PMID:25759638

  17. Antioxidant enzymes regulate reactive oxygen species during pod elongation in Pisum sativum and Brassica chinensis.

    PubMed

    Liu, Nan; Lin, Zhifang; Guan, Lanlan; Gaughan, Gerald; Lin, Guizhu

    2014-01-01

    Previous research has focused on the involvement of reactive oxygen species (ROS) in cell wall loosening and cell extension in plant vegetative growth, but few studies have investigated ROS functions specifically in plant reproductive organs. In this study, ROS levels and antioxidant enzyme activities were assessed in Pisum sativum and Brassica chinensis pods at five developmental stages. In juvenile pods, the high levels of O2.- and .OH indicates that they had functions in cell wall loosening and cell elongation. In later developmental stages, high levels of .OH were also related to increases in cell wall thickness in lignified tissues. Throughout pod development, most of the O2.- was detected on plasma membranes of parenchyma cells and outer epidermis cells of the mesocarp, while most of the H2O2 was detected on plasma membranes of most cells throughout the mesocarp. This suggests that these sites are presumably the locations of ROS generation. The antioxidant enzymes superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) apparently contributed to ROS accumulation in pod wall tissues. Furthermore, specifically SOD and POD were found to be associated with pod growth through the regulation of ROS generation and transformation. Throughout pod development, O2.- decreases were associated with increased SOD activity, while changes in H2O2 accumulation were associated with changes in CAT and POD activities. Additionally, high POD activity may contribute to the generation of(.)OH in the early development of pods. It is concluded that the ROS are produced in different sites of plasma membranes with the regulation of antioxidant enzymes, and that substantial ROS generation and accumulation are evident in cell elongation and cell wall loosening in pod wall cells. PMID:24503564

  18. Nox2-derived reactive oxygen species mediate neurovascular dysregulation in the aging mouse brain.

    PubMed

    Park, Laibaik; Anrather, Josef; Girouard, Helene; Zhou, Ping; Iadecola, Costantino

    2007-12-01

    Aging is associated with cerebrovascular dysregulation, which may underlie the increased susceptibility to ischemic stroke and vascular cognitive impairment occurring in the elder individuals. Although it has long been known that oxidative stress is responsible for the cerebrovascular dysfunction, the enzymatic system(s) generating the reactive oxygen species (ROS) have not been identified. In this study, we investigated whether the superoxide-producing enzyme NADPH oxidase is involved in alterations of neurovascular regulation induced by aging. Cerebral blood flow (CBF) was recorded by laser-Doppler flowmetry in anesthetized C57BL/6 mice equipped with a cranial window (age=3, 12, and 24 months). In 12-month-old mice, the CBF increases evoked by whisker stimulation or by the endothelium-dependent vasodilators acetylcholine and bradykinin were attenuated by 42, 36, and 53%, respectively (P<0.05). In contrast, responses to the nitric oxide donor S-nitroso-D-penicillamine or adenosine were not attenuated (P>0.05). These cerebrovascular effects were associated with increased production of ROS in neurons and cerebral blood vessels, assessed by hydroethidine microfluorography. The cerebrovascular impairment present in 12-month-old mice was reversed by the ROS scavenger Mn (III) tetrakis (4-benzoic acid) porphyrin chloride or by the NADPH oxidase peptide inhibitor gp91ds-tat, and was not observed in mice lacking the Nox2 subunit of NADPH oxidase. These findings establish Nox2 as a critical source of the neurovascular oxidative stress mediating the deleterious cerebrovascular effects associated with increasing age. PMID:17429347

  19. Naturally and stimulated levels of reactive oxygen species in cooled stallion semen destined for artificial insemination.

    PubMed

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

    2014-10-01

    The decrease in foaling rates after artificial insemination with cooled semen warrants the search for new predictors of fertility. The objectives were to investigate levels of naturally occurring reactive oxygen species (ROS) in cooled, stored stallion semen doses for artificial insemination (AI), and their relationship with parameters of semen quality and with pregnancy rate. Semen was collected from warmblood stallions (n=15) and used to prepare commercial semen doses for AI. Sperm quality was evaluated after cooled transport to the laboratory overnight. The results were correlated with observed foaling and pregnancy rates. Hydroethidine and dichlorodihydrofluorescein diacetate were used as indicators for the ROS superoxide and hydrogen peroxide, respectively. Sperm morphology, motility, plasma membrane integrity and chromatin integrity were also evaluated. These variables were correlated with each other and with pregnancy rates. We found a high inter-individual variation in the ROS levels between stallions. The proportion of live, hydrogen peroxide-negative spermatozoa was correlated with progressive motility, whereas live hydrogen peroxide-negative spermatozoa and chromatin damage were negatively correlated, indicating that low levels of hydrogen peroxide were correlated with good chromatin integrity. The percentage of dead hydrogen peroxide-positive sperm was negatively related to the foaling rate. The negative relationships were stronger when combining results from both assays for ROS. These results for stored semen samples indicate that high individual variation exists for superoxide and hydrogen peroxide measurements, and that ROS status can influence sperm quality. Thus, ROS may be some of the factors influencing fertility. Moreover, combinations of ROS variables improved the correlation with fertility, indicating the usefulness of including these variables in a future model for prediction of the fertility of a semen sample. PMID:24916995

  20. Antioxidant Enzymes Regulate Reactive Oxygen Species during Pod Elongation in Pisum sativum and Brassica chinensis

    PubMed Central

    Liu, Nan; Lin, Zhifang; Guan, Lanlan; Gaughan, Gerald; Lin, Guizhu

    2014-01-01

    Previous research has focused on the involvement of reactive oxygen species (ROS) in cell wall loosening and cell extension in plant vegetative growth, but few studies have investigated ROS functions specifically in plant reproductive organs. In this study, ROS levels and antioxidant enzyme activities were assessed in Pisum sativum and Brassica chinensis pods at five developmental stages. In juvenile pods, the high levels of O2.? and.OH indicates that they had functions in cell wall loosening and cell elongation. In later developmental stages, high levels of.OH were also related to increases in cell wall thickness in lignified tissues. Throughout pod development, most of the O2.? was detected on plasma membranes of parenchyma cells and outer epidermis cells of the mesocarp, while most of the H2O2 was detected on plasma membranes of most cells throughout the mesocarp. This suggests that these sites are presumably the locations of ROS generation. The antioxidant enzymes superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) apparently contributed to ROS accumulation in pod wall tissues. Furthermore, specifically SOD and POD were found to be associated with pod growth through the regulation of ROS generation and transformation. Throughout pod development, O2.? decreases were associated with increased SOD activity, while changes in H2O2 accumulation were associated with changes in CAT and POD activities. Additionally, high POD activity may contribute to the generation of.OH in the early development of pods. It is concluded that the ROS are produced in different sites of plasma membranes with the regulation of antioxidant enzymes, and that substantial ROS generation and accumulation are evident in cell elongation and cell wall loosening in pod wall cells. PMID:24503564

  1. Endogenous reactive oxygen species modulates voltage-gated sodium channels in dorsal root ganglia of rats

    PubMed Central

    Wang, Han-Jun; Li, Yu-Long; Zhang, Li-Bin; Zucker, Irving H.; Gao, Lie; Zimmerman, Matthew C.

    2011-01-01

    We recently reported that reactive oxygen species (ROS) plays an excitatory role in modulation of the exercise pressor reflex (EPR) in normal rats. In this study, we further tested two independent hypotheses: 1) ROS interacts with EPR-related ionotropic receptors such as the purinergic receptors (P2) and transient receptor potential vanilloid 1 receptors (TRPV1) to indirectly modulate the EPR function; 2) ROS directly affects excitability of muscle afferents by modulating the voltage-gated sodium (Nav) channels. To test the first hypothesis, we performed animal experiments to investigate the effect of the SOD mimetic 4-hydroxy-2,2,6,6-tetramethyl piperidine 1-oxyl (Tempol) on the pressor response to hindlimb intra-arterial (IA) injection of either ?,?-methylene ATP (a P2X agonist) or capsaicin (a TRPV1 agonist) in decerebrate rats. To test the second hypothesis, we used the patch-clamp technique to determine the effect of ROS on Nav channels on the soma of muscle afferents. We also performed local microinjection of a sodium channel blocker, tetrodotoxin (TTX), into ipsilateral L4/L5 dorsal root ganglia (DRGs) to investigate whether the blockade of Nav channels by TTX affects the EPR function. We found that Tempol did not affect the pressor response to injection of either capsaicin or ?,?-methylene ATP but significantly decreased the Nav current in small and medium-sized 1,1?-dioctadecyl-3,3,3?,3?-tetramethylindocarbocyanine perchlorate (DiI)-labeled DRG neurons. A membrane-permeant superoxide dismutase, polyethylene glycol (PEG)-SOD, had an effect on the Nav current in these neurons similar to that of Tempol. Microinjection of TTX into L4/L5 DRGs dramatically attenuated the pressor response to static contraction induced by electrical stimulation of L4/L5 ventral roots. These data suggest that ROS modulates the EPR by affecting the activity of the Nav channels on muscle afferents. PMID:21292836

  2. Withaferin A-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species.

    PubMed

    Hahm, Eun-Ryeong; Moura, Michelle B; Kelley, Eric E; Van Houten, Bennett; Shiva, Sruti; Singh, Shivendra V

    2011-01-01

    Withaferin A (WA), a promising anticancer constituent of Ayurvedic medicinal plant Withania somnifera, inhibits growth of MDA-MB-231 and MCF-7 human breast cancer cells in culture and MDA-MB-231 xenografts in vivo in association with apoptosis induction, but the mechanism of cell death is not fully understood. We now demonstrate, for the first time, that WA-induced apoptosis is mediated by reactive oxygen species (ROS) production due to inhibition of mitochondrial respiration. WA treatment caused ROS production in MDA-MB-231 and MCF-7 cells, but not in a normal human mammary epithelial cell line (HMEC). The HMEC was also resistant to WA-induced apoptosis. WA-mediated ROS production as well as apoptotic histone-associated DNA fragment release into the cytosol was significantly attenuated by ectopic expression of Cu,Zn-superoxide dismutase in both MDA-MB-231 and MCF-7 cells. ROS production resulting from WA exposure was accompanied by inhibition of oxidative phosphorylation and inhibition of complex III activity. Mitochondrial DNA-deficient Rho-0 variants of MDA-MB-231 and MCF-7 cells were resistant to WA-induced ROS production, collapse of mitochondrial membrane potential, and apoptosis compared with respective wild-type cells. WA treatment resulted in activation of Bax and Bak in MDA-MB-231 and MCF-7 cells, and SV40 immortalized embryonic fibroblasts derived from Bax and Bak double knockout mouse were significantly more resistant to WA-induced apoptosis compared with fibroblasts derived from wild-type mouse. In conclusion, the present study provides novel insight into the molecular circuitry of WA-induced apoptosis involving ROS production and activation of Bax/Bak. PMID:21853114

  3. GASA14 regulates leaf expansion and abiotic stress resistance by modulating reactive oxygen species accumulation.

    PubMed

    Sun, Shulan; Wang, Haoxiang; Yu, Hongmei; Zhong, Chunmei; Zhang, Xiaoxia; Peng, Jianzong; Wang, Xiaojing

    2013-04-01

    Gibberellic acid (GA) can regulate many plant developmental processes. GAST1 has been identified as a GA-stimulated transcript, and Arabidopsis GAST-like genes are known to constitute the GASA family. However, the functions of most GASA genes are not clear at present. In this study, the function of GASA14, a member of the GASA family, was investigated. GASA14 expression was upregulated by GA and downregulated by the transcriptional regulators that repress GA responses, the DELLA proteins GAI and RGA. Phenotypic analysis showed that growth of the GASA14 null mutant (gasa14-1) line was retarded, and the growth of the 35S::GASA14 lines were promoted in young plants. Furthermore, seed germination of the gasa14-1 plants showed more sensitivity to paclobutrazol (an inhibitor of GA biosynthesis) than Columbia (Col) plants, suggesting that GASA14 is required for GA-dependent responses. Analysis of the responses of the gasa14-1 and 35S::GASA14 lines to abscisic acid (ABA) and salt revealed that germination and seedling establishment of gasa14-1 were poorer than those of Col plants and that the 35S::GASA14 lines were more resistant to ABA and salt. Further analysis showed that overexpression of GASA14 could suppress reactive oxygen species (ROS) accumulation. Taken together, these results demonstrated that GASA14 regulates leaf expansion and abiotic stress resistance by modulating ROS accumulation. Because GASA14 contains both GASA (GA-stimulated in Arabidopsis) and PRP (proline-rich protein) domains, the PRP domain coding sequence was overexpressed in Col plants and it was found that the growth of the transgenic plants and the responses to ABA and salt were not altered. These results thus suggest that the GASA domain is necessary for the functions of GASA14. PMID:23378382

  4. Mechanotransduction Drives Post Ischemic Revascularization Through KATP Channel Closure and Production of Reactive Oxygen Species

    PubMed Central

    Browning, Elizabeth; Wang, Hui; Hong, Nankang; Yu, Kevin; Buerk, Donald G.; DeBolt, Kristine; Gonder, Daniel; Sorokina, Elena M.; Patel, Puja; De Leon, Diva D.; Feinstein, Sheldon I.; Fisher, Aron B.

    2014-01-01

    Abstract Aims: We reported earlier that ischemia results in the generation of reactive oxygen species (ROS) via the closure of a KATP channel which causes membrane depolarization and NADPH oxidase 2 (NOX2) activation. This study was undertaken to understand the role of ischemia-mediated ROS in signaling. Results: Angiogenic potential of pulmonary microvascular endothelial cells (PMVEC) was studied in vitro and in the hind limb in vivo. Flow adapted PMVEC injected into a Matrigel matrix showed significantly higher tube formation than cells grown under static conditions or cells from mice with knockout of KATP channels or the NOX2. Blocking of hypoxia inducible factor-1 alpha (HIF-1?) accumulation completely abrogated the tube formation in wild-type (WT) PMVEC. With ischemia in vivo (femoral artery ligation), revascularization was high in WT mice and was significantly decreased in mice with knockout of KATP channel and in mice orally fed with a KATP channel agonist. In transgenic mice with endothelial-specific NOX2 expression, the revascularization observed was intermediate between that of WT and knockout of KATP channel or NOX2. Increased HIF-1? activation and vascular endothelial growth factor (VEGF) expression was observed in ischemic tissue of WT mice but not in KATP channel and NOX2 null mice. Revascularization could be partially rescued in KATP channel null mice by delivering VEGF into the hind limb. Innovation: This is the first report of a mechanosensitive ion channel (KATP channel) initiating endothelial signaling that drives revascularization. Conclusion: The KATP channel responds to the stop of flow and activates signals for revascularization to restore the impeded blood flow. Antioxid. Redox Signal. 20, 872–886. PMID:23758611

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

    PubMed Central

    Montezano, Augusto C.

    2014-01-01

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

  6. Enhanced reactive oxygen species overexpression by CuO nanoparticles in poorly differentiated hepatocellular carcinoma cells.

    PubMed

    Kung, Mei-Lang; Hsieh, Shu-Ling; Wu, Chih-Chung; Chu, Tian-Huei; Lin, Yu-Chun; Yeh, Bi-Wen; Hsieh, Shuchen

    2015-02-01

    Copper oxide nanoparticles (CuO NPs) are known to exhibit toxic effects on a variety of cell types and organs. To determine the oxidative impact of CuO NPs on hepatocellular carcinoma (HCC) cells, well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) cells were exposed to CuO NPs. Cell viability assay showed that the median inhibition concentration (IC50) for SK-Hep-1 and HepG2 cells was 25 ?g ml(-1) and 85 ?g ml(-1), respectively. Cellular fluorescence intensity using DCFH-DA staining analysis revealed significant intracellular reactive oxygen species (ROS) generation of up to 242% in SK-Hep-1 cells, compared with 86% in HepG2 cells. HPLC analysis demonstrated that a CuO NP treatment caused cellular GSH depletion of 58% and a GSH/GSSG ratio decrease to ?0.1 in SK-Hep-1 cells. The oxidative stress caused by enhanced superoxide anion production was observed in both HepG2 (146%) and SK-Hep-1 (192%) cells. The Griess assay verified that CuO NPs induced NO production (170%) in SK-Hep-1 cells. Comet assay and western blot further demonstrated that CuO NPs induced severe DNA strand breakage (70%) in SK-Hep-1 cells and caused DNA damage via increased ?-H2AX levels. These results suggest that well-differentiated HepG2 cells possess a robust antioxidant defense system against CuO NP-induced ROS stress and exhibit more tolerance to oxidative stress. Conversely, poorly differentiated SK-Hep-1 cells exhibited a deregulated antioxidant defense system that allowed accumulation of CuO NP-induced ROS and resulted in severe cytotoxicity. PMID:25521936

  7. Monochloramine produces reactive oxygen species in liver by converting xanthine dehydrogenase into xanthine oxidase

    SciTech Connect

    Sakuma, Satoru [Laboratory of Physiological Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)], E-mail: sakuma@gly.oups.ac.jp; Miyoshi, Emi; Sadatoku, Namiko; Fujita, Junko; Negoro, Miki [Laboratory of Physiological Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Arakawa, Yukio [Clinical Laboratory of Practical Pharmacy, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Fujimoto, Yohko [Laboratory of Physiological Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)

    2009-09-15

    In the present study, we assessed the influence of monochloramine (NH{sub 2}Cl) on the conversion of xanthine dehydrogenase (XD) into xanthine oxidase (XO) in rat liver in vitro. When incubated with the partially purified cytosolic fraction from rat liver, NH{sub 2}Cl (2.5-20 {mu}M) dose-dependently enhanced XO activity concomitant with a decrease in XD activity, implying that NH{sub 2}Cl can convert XD into the reactive oxygen species (ROS) producing form XO. The NH{sub 2}Cl (5 {mu}M)-induced XD/XO interconversion in the rat liver cytosol was completely inhibited when added in combination with an inhibitor of NH{sub 2}Cl methionine (25 {mu}M). A sulfhydryl reducing agent, dithiothreitol at concentrations of 0.1, 1 and 5 mM also dose-dependently reversed the NH{sub 2}Cl (5 {mu}M)-induced XD/XO interconversion. These imply that NH{sub 2}Cl itself acts on the XD/XO interconversion, and that this conversion occurs at the cysteine residues in XD. Furthermore, using the fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate, it was found that NH{sub 2}Cl could increase ROS generation in the cytoplasm of rat primary hepatocyte cultures, and that this increase might be reversed by an XO inhibitor, allopurinol. These results suggest that NH{sub 2}Cl has the potential to convert XD into XO in the liver, which in turn may induce the ROS generation in this region.

  8. Acrolein activates matrix metalloproteinases by increasing reactive oxygen species in macrophages

    SciTech Connect

    O'Toole, Timothy E. [Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, KY 40202 (United States)], E-mail: teotoo01@gwise.louisville.edu; Zheng Yuting; Hellmann, Jason; Conklin, Daniel J.; Barski, Oleg; Bhatnagar, Aruni [Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, KY 40202 (United States)

    2009-04-15

    Acrolein is a ubiquitous component of environmental pollutants such as automobile exhaust, cigarette, wood, and coal smoke. It is also a natural constituent of several foods and is generated endogenously during inflammation or oxidation of unsaturated lipids. Because increased inflammation and episodic exposure to acrolein-rich pollutants such as traffic emissions or cigarette smoke have been linked to acute myocardial infarction, we examined the effects of acrolein on matrix metalloproteinases (MMPs), which destabilize atherosclerotic plaques. Our studies show that exposure to acrolein resulted in the secretion of MMP-9 from differentiated THP-1 macrophages. Acrolein-treatment of macrophages also led to an increase in reactive oxygen species (ROS), free intracellular calcium ([Ca{sup 2+}]{sub i}), and xanthine oxidase (XO) activity. ROS production was prevented by allopurinol, but not by rotenone or apocynin and by buffering changes in [Ca{sup 2+}]{sub I} with BAPTA-AM. The increase in MMP production was abolished by pre-treatment with the antioxidants Tiron and N-acetyl cysteine (NAC) or with the xanthine oxidase inhibitors allopurinol or oxypurinol. Finally, MMP activity was significantly stimulated in aortic sections from apoE-null mice containing advanced atherosclerotic lesions after exposure to acrolein ex vivo. These observations suggest that acrolein exposure results in MMP secretion from macrophages via a mechanism that involves an increase in [Ca{sup 2+}]{sub I}, leading to xanthine oxidase activation and an increase in ROS production. ROS-dependent activation of MMPs by acrolein could destabilize atherosclerotic lesions during brief episodes of inflammation or pollutant exposure.

  9. A High Precision Method for Quantitative Measurements of Reactive Oxygen Species in Frozen Biopsies

    PubMed Central

    Lindgren, Mikael; Gustafsson, Håkan

    2014-01-01

    Objective An electron paramagnetic resonance (EPR) technique using the spin probe cyclic hydroxylamine 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH) was introduced as a versatile method for high precision quantification of reactive oxygen species, including the superoxide radical in frozen biological samples such as cell suspensions, blood or biopsies. Materials and Methods Loss of measurement precision and accuracy due to variations in sample size and shape were minimized by assembling the sample in a well-defined volume. Measurement was carried out at low temperature (150 K) using a nitrogen flow Dewar. The signal intensity was measured from the EPR 1st derivative amplitude, and related to a sample, 3-carboxy-proxyl (CP•) with known spin concentration. Results The absolute spin concentration could be quantified with a precision and accuracy better than ±10 µM (k?=?1). The spin concentration of samples stored at ?80°C could be reproduced after 6 months of storage well within the same error estimate. Conclusion The absolute spin concentration in wet biological samples such as biopsies, water solutions and cell cultures could be quantified with higher precision and accuracy than normally achievable using common techniques such as flat cells, tissue cells and various capillary tubes. In addition; biological samples could be collected and stored for future incubation with spin probe, and also further stored up to at least six months before EPR analysis, without loss of signal intensity. This opens for the possibility to store and transport incubated biological samples with known accuracy of the spin concentration over time. PMID:24603936

  10. Lapatinib and obatoclax kill breast cancer cells through re