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1

Silymarin protection against major reactive oxygen species released by environmental toxins: exogenous H2O2 exposure in erythrocytes.  

PubMed

Silymarin is a polyphenolic plant flavonoid (a mixture of flavonoid isomers such as silibinin, isosilibinin, silidianin and silichristin) derived from Silymarin marianum that has anti-inflammatory, hepatoprotective and anticarcinogenic effects. Our earlier studies have shown that silymarin plays a protective role against the oxidative damage induced by environmental contaminants like benzo(a)pyrene in erythrocyte haemolysates. During the detoxification of these environmental contaminants, the major reactive oxygen species generated is hydrogen peroxide (H(2)O(2)). Because H(2)O(2 )can easily penetrate into the cell and cause damage to biomolecules, the protective role of silymarin was further assessed against this cytotoxic agent in vitro in erythrocyte haemolysates. The protective effect was monitored by assessing the levels of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-s-transferase, glutathione peroxidase and malondialdehyde (LPO) in three groups: vehicle control, H(2)O(2)-exposed groups and drug co-incubation group (H(2)O(2) + silymarin). The protective effect of silymarin on the non-enzymic antioxidant glutathione and haemolysis, methaemoglobin content and protein carbonyl content were also assessed. It was observed that the activities of antioxidant enzymes and glutathione were reduced and the malondialdehyde levels were elevated after H(2)O(2 )exposure. There were also alterations in haemolysis, methaemoglobin content and protein carbonyl content, whereas after the administration of silymarin, the antioxidant enzyme activities reversed to near normal with reduced malondialdehyde content and normalized haemolysis, methaemoglobin content and protein carbonyl content. The results suggest that silymarin possesses substantial protective effect and free radical scavenging mechanism against exogenous H(2)O(2)-induced oxidative stress damages, hence, can be used as a protective drug against toxicity induced by environmental contaminants. PMID:17516996

Kiruthiga, P V; Shafreen, R Beema; Pandian, S Karutha; Devi, K Pandima

2007-06-01

2

Catalytic therapy of cancer by ascorbic acid involves redox cycling of exogenous/endogenous copper ions and generation of reactive oxygen species.  

PubMed

Catalytic therapy is a cancer treatment modality based on the generation of reactive oxygen species (ROS) through administration of ascorbate/medicinal herbal extracts and copper. It is known that antioxidants such as ascorbate also exhibit prooxidant activity in the presence of transition metals such as copper. Based on our work and that in the literature, in this review we propose a mechanism for the cytotoxic action of ascorbate against cancer cells. It involves redox cycling of exogenous/endogenous copper ions and the consequent generation of ROS leading to oxidative DNA breakage. Using human peripheral lymphocytes and the Comet assay, we have shown that ascorbic acid is able to cause oxidative breakage in cellular DNA. Such DNA degradation is inhibited by neocuproine (a Cu(I) sequestering agent) and scavengers of ROS indicating that the cellular DNA breakage involves the generation of Cu(I) and formation of ROS. Similar results are also obtained with plant polyphenol antioxidants that are important constituents of medicinal herbal extracts. Copper is an essential component of chromatin and can take part in redox reactions. It is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies. Therefore, cancer cells may be more subject to electron transfer between copper ions and ascorbate/plant polyphenols to generate ROS. In this review we cite evidence to indicate that in catalytic therapy cytotoxic action against cancer cells involves redox cycling of exogenous/endogenous copper ions. PMID:20714144

Hadi, S M; Ullah, M F; Shamim, U; Bhatt, S H; Azmi, A S

2010-01-01

3

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

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

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

2012-08-01

4

Reactive oxygen species and hematopoietic stem cell senescence  

Microsoft Academic Search

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

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

5

Reactive Oxygen Species in Cancer Stem Cells  

PubMed Central

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

Shi, Xiaoke; Zhang, Yan; Zheng, Junheng

2012-01-01

6

Reactive oxygen species in cancer  

PubMed Central

Elevated rates of reactive oxygen species (ROS) have been detected in almost all cancers, where they promote many aspects of tumor development and progression. However, tumor cells also express increased levels of antioxidant proteins to detoxify from ROS, suggesting that a delicate balance of intracellular ROS levels is required for cancer cell function. Further, the radical generated, the location of its generation, as well as the local concentration is important for the cellular functions of ROS in cancer. A challenge for novel therapeutic strategies will be the fine tuning of intracellular ROS signaling to effectively deprive cells from ROS-induced tumor promoting events, towards tipping the balance to ROS-induced apoptotic signaling. Alternatively, therapeutic antioxidants may prevent early events in tumor development, where ROS are important. However, to effectively target cancer cells specific ROS-sensing signaling pathways that mediate the diverse stress-regulated cellular functions need to be identified. This review discusses the generation of ROS within tumor cells, their detoxification, their cellular effects, as well as the major signaling cascades they utilize, but also provides an outlook on their modulation in therapeutics. PMID:20370557

Liou, Geou-Yarh; Storz, Peter

2013-01-01

7

Reactive oxygen species: the unavoidable environmental insult?  

Microsoft Academic Search

Reactive oxygen species (ROS) are generated by a variety of sources from the environment (e.g., photo-oxidations and emissions) and normal cellular functions (e.g., mitochondrial metabolism and neutrophil activation). ROS include free radicals (e.g., superoxide and hydroxyl radicals), nonradical oxygen species (e.g., hydrogen peroxide and peroxynitrite) and reactive lipids and carbohydrates (e.g., ketoaldehydes, hydroxynonenal). Oxidative damage to DNA can occur by

R. W Gracy; J. M Talent; Y Kong; C. C Conrad

1999-01-01

8

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

9

Formation and Detoxification of Reactive Oxygen Species  

ERIC Educational Resources Information Center

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

Kuciel, Radoslawa; Mazurkiewicz, Aleksandra

2004-01-01

10

On the Oxygen Reactivity of Flavoprotein Oxidases  

PubMed Central

The flavoprotein cholesterol oxidase from Brevibacterium sterolicum (BCO) possesses a narrow channel that links the active center containing the flavin to the outside solvent. This channel has been proposed to serve for the access of dioxygen; it contains at its “bottom” a Glu-Arg pair (Glu-475—Arg-477) that was found by crystallographic studies to exist in two forms named “open” and “closed,” which in turn was suggested to constitute a gate functioning in the control of oxygen access. Most mutations of residues that flank the channel have minor effects on the oxygen reactivity. Mutations of Glu-311, however, cause a switch in the basic kinetic mechanism of the reaction of reduced BCO with dioxygen; wild-type BCO and most mutants show a saturation behavior with increasing oxygen concentration, whereas for Glu-311 mutants a linear dependence is found that is assumed to reflect a “simple” second order process. This is taken as support for the assumption that residue Glu-311 finely tunes the Glu-475—Arg-477 pair, forming a gate that functions in modulating the access/reactivity of dioxygen. PMID:18614534

Piubelli, Luciano; Pedotti, Mattia; Molla, Gianluca; Feindler-Boeckh, Susanne; Ghisla, Sandro; Pilone, Mirella S.; Pollegioni, Loredano

2008-01-01

11

Influence of reactive oxygen species on the sterilization of microbes  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

12

REACTIVE OXYGEN SPECIES AND COLORECTAL CANCER  

PubMed Central

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

Sreevalsan, Sandeep; Safe, Stephen

2013-01-01

13

Characterization of reactive oxygen species in diaphragm.  

PubMed

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

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

2015-03-01

14

Reactive oxygen species and hematopoietic stem cell senescence  

PubMed Central

Hematopoietic stem cells (HSCs) are responsible for sustaining hematopoietic homeostasis and regeneration after injury for the entire lifespan of an organism through self-renewal, proliferation, differentiation, and mobilization. Their functions can be affected by reactive oxygen species (ROS) that are produced endogenously through cellular metabolism or after exposure to exogenous stress. At physiological levels, ROS function as signal molecules which can regulate a variety of cellular functions, including HSC proliferation, differentiation, and mobilization. However, an abnormal increase in ROS production occurs under various pathological conditions, which can inhibit HSC self-renewal and induce HSC senescence, resulting in premature exhaustion of HSCs and hematopoietic dysfunction. This review aims to provide a summary of a number of recent findings regarding the cellular sources of ROS in HSCs and the mechanisms of action whereby ROS induce HSC senescence. In particular, we highlight the roles of the p38 mitogen-activated protein kinase (p38)-p16Ink4a (p16) pathway in mediating ROS-induced HSC senescence. PMID:21567162

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

2012-01-01

15

REACTIVE OXYGEN SPECIES IN PULMONARY VASCULAR REMODELING  

PubMed Central

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

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

2014-01-01

16

Generation of reactive oxygen species by the faecal matrix  

Microsoft Academic Search

BACKGROUNDReactive 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.AIMTo develop a suitable method for the detection of reactive oxygen species produced by the faecal matrix.METHODSA refined high performance liquid chromatography system for the detection of reactive oxygen species is described.RESULTSThe method allows

R W Owen; B Spiegelhalder; H Bartsch

2000-01-01

17

Reactive oxygen species and redox compartmentalization  

PubMed Central

Reactive oxygen species (ROS) formation and signaling are of major importance and regulate a number of processes in physiological conditions. A disruption in redox status regulation, however, has been associated with numerous pathological conditions. In recent years it has become increasingly clear that oxidative and reductive modifications are confined in a spatio-temporal manner. This makes ROS signaling similar to that of Ca2+ or other second messengers. Some subcellular compartments are more oxidizing (such as lysosomes or peroxisomes) whereas others are more reducing (mitochondria, nuclei). Moreover, although more reducing, mitochondria are especially susceptible to oxidation, most likely due to the high number of exposed thiols present in that compartment. Recent advances in the development of redox probes allow specific measurement of defined ROS in different cellular compartments in intact living cells or organisms. The availability of these tools now allows simultaneous spatio-temporal measurements and correlation between ROS generation and organelle and/or cellular function. The study of ROS compartmentalization and microdomains will help elucidate their role in physiology and disease. Here we will examine redox probes currently available and how ROS generation may vary between subcellular compartments. Furthermore, we will discuss ROS compartmentalization in physiological and pathological conditions focusing our attention on mitochondria, since their vulnerability to oxidative stress is likely at the basis of several diseases. PMID:25161621

Kaludercic, Nina; Deshwal, Soni; Di Lisa, Fabio

2014-01-01

18

Indoor particulate reactive oxygen species concentrations.  

PubMed

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

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

2014-07-01

19

Reactive oxygen species in leaf abscission signaling  

PubMed Central

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

Sakamoto, Masaru; Munemura, Ikuko; Tomita, Reiko

2008-01-01

20

How mitochondria produce reactive oxygen species  

PubMed Central

The production of ROS (reactive oxygen species) by mammalian mitochondria is important because it underlies oxidative damage in many pathologies and contributes to retrograde redox signalling from the organelle to the cytosol and nucleus. Superoxide (O2•?) is the proximal mitochondrial ROS, and in the present review I outline the principles that govern O2•? production within the matrix of mammalian mitochondria. The flux of O2•? is related to the concentration of potential electron donors, the local concentration of O2 and the second-order rate constants for the reactions between them. Two modes of operation by isolated mitochondria result in significant O2•? production, predominantly from complex I: (i) when the mitochondria are not making ATP and consequently have a high ?p (protonmotive force) and a reduced CoQ (coenzyme Q) pool; and (ii) when there is a high NADH/NAD+ ratio in the mitochondrial matrix. For mitochondria that are actively making ATP, and consequently have a lower ?p and NADH/NAD+ ratio, the extent of O2•? production is far lower. The generation of O2•? within the mitochondrial matrix depends critically on ?p, the NADH/NAD+ and CoQH2/CoQ ratios and the local O2 concentration, which are all highly variable and difficult to measure in vivo. Consequently, it is not possible to estimate O2•? generation by mitochondria in vivo from O2•?-production rates by isolated mitochondria, and such extrapolations in the literature are misleading. Even so, the description outlined here facilitates the understanding of factors that favour mitochondrial ROS production. There is a clear need to develop better methods to measure mitochondrial O2•? and H2O2 formation in vivo, as uncertainty about these values hampers studies on the role of mitochondrial ROS in pathological oxidative damage and redox signalling. PMID:19061483

Murphy, Michael P.

2008-01-01

21

Reactive Oxygen Species in Combustion Aerosols  

NASA Astrophysics Data System (ADS)

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

Balasubramanian, R.; See, S.

2007-12-01

22

Exogenous augmenter of liver regeneration (ALR) attenuates inflammatory response in renal hypoxia re-oxygenation injury.  

PubMed

Recent studies have highlighted the role of the innate immune system in initiating the inflammatory cascade which leads to detrimental changes in renal ischemia reperfusion (I/R) injury. The augmenter of liver regeneration (ALR) is an anti-apoptosis factor which is highly expressed in renal tubulars of renal cortex and medulla after inducing renal I/R injury in rats. It has been shown that exogenous ALR can enhance renal tubular regeneration. However, whether ALR's protective effect against renal I/R injury results from its immune regulatory function remains unknown. Using rat renal tubular epithelial cell (NRK-52E), we investigate the effect of recombinant rat ALR (rrALR) on immune inflammatory response in hypoxia re-oxygenation (H/R) injury in vitro, and further discuss the possible mechanisms. Cultured NRK-52E cells subjected to hypoxia for 6?h followed by re-oxygenation for 12, 24 and 72?h are administered with different doses of rrALR. Expression of Toll-like receptor 4 (TLR4) and transcription nuclear factor-?B (NF-?B) is assessed by reverse-transcriptase polymerase chain reaction (RT-PCR) and western blot. Expression of interleukin (IL)-6 and IL-1? are determined by enzyme-linked immunosorbent assay (ELISA). In rrALR intervened H/R cells, TLR4 and NF-?B are down regulated at both mRNA and protein levels compare with those in control cells. Also, rrALR appears to downregulate IL-6 and IL-1? expression in concentration-dependent manners. In conclusion, rrALR protects NRK-52E cells from H/R injury possibly by relieving the inflammatory response through regulation of TLR4-NF-?B signaling pathway. PMID:24392837

Li, Ying; Zhang, Ling; Liu, Qi; Chen, Guo-Tao; Sun, Hang

2014-04-01

23

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

Microsoft Academic Search

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

Victor Darley-Usmar; Barry Halliwell

1996-01-01

24

Reactive oxygen species production by catechol stabilized copper nanoparticles  

NASA Astrophysics Data System (ADS)

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

Chen, Cheng; Ahmed, Ishtiaq; Fruk, Ljiljana

2013-11-01

25

Comparison of two strategies for detection of reactive oxygen species  

NASA Astrophysics Data System (ADS)

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.

Gao, Weidong; Zhou, Yuanshu; Gu, Yueqing

2014-09-01

26

Inflammation, reactive oxygen species and cytochrome P450  

Microsoft Academic Search

Inflammation may ultimately result from damage to membrane lipids by reactive oxygen species (ROS) such as peroxide, superoxide anion, hydroxyl radical and singlet oxygen. This study compares some of the methods used to determine ROS—ethane exhalation, malondialdehyde quantified as thiobarbituric acid-reacting materials, and luminol-activated chemiluminescence (LAC)—and explores possible relationships with oedema formation in the rat foot-pad model. Iron nitrilotriacetate was

Andrew M. Symons; Laurence J. King

2003-01-01

27

Infections in the male genital tract and reactive oxygen species  

Microsoft Academic Search

In the male genital tract, reactive oxygen species (ROS) are generated by spermatozoa and leukocytes including neutrophils and macrophages. ROS are involved in the regulation of sperm functions such as capacitation and the acrosome reaction. Infections lead to an excessive ROS production, resulting in an 'oxidative burst' from neutrophils\\/macrophages as a first-line defence mechanism. This is modulated by several cytokines

F. R. Ochsendorf

1999-01-01

28

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...

29

Muscle characterization of reactive oxygen species in oral diseases.  

PubMed

Abstract Importance and objective. Reactive Oxygen Species (ROS) are oxygen-derived molecules that are unstable and highly reactive. They are important signaling mediators of biological processes. In contrast, excessive ROS generation, defective oxidant scavenging or both have been implicated in the pathogenesis of several conditions. This biological paradox of ROS function contributes to the integrity of cells and tissues. So, the aim of this review was examined for published literature related to 'reactive oxygen species and dentistry and muscle'. Materials and methods. A PubMed search was performed by using the following key words: 'reactive oxygen species and dentistry and muscle'. Results. Involvement of ROS in pathologic conditions can be highlighted in oral diseases like periodontitis, orofacial pain, temporomandibular disorders and oral cancer. Also, several studies have correlated the increase in ROS production with the initiation of the muscle fatigue process and the process of muscle injury. However, studies evaluating the relation of ROS and orofacial muscles, which can prove very important to understand the fatigue muscle in this region during oral movements, have not yet been conducted. Conclusions. It is concluded that the data on skeletal muscles, especially those of mastication, are not commonly published in this data source; therefore, further studies in this field are strongly recommended. PMID:25205230

Pereira, Yamba Carla Lara; Nascimento, Glauce Crivelaro do; Iyomasa, Daniela Mizusaki; Iyomasa, Mamie Mizusaki

2015-02-01

30

Reactive oxygen species and vascular biology: implications in human hypertension  

Microsoft Academic Search

Increased vascular production of reactive oxygen species (ROS; termed oxidative stress) has been implicated in various chronic diseases, including hypertension. Oxidative stress is both a cause and a consequence of hypertension. Although oxidative injury may not be the sole etiology, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors. Oxidative stress is a multisystem phenomenon in hypertension

Rhian M Touyz; Ana M Briones

2011-01-01

31

A role for reactive oxygen species in postharvest biocontrol  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

32

Engineering of Pyranose Dehydrogenase for Increased Oxygen Reactivity  

PubMed Central

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

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

2014-01-01

33

Cell signaling by reactive nitrogen and oxygen species in atherosclerosis  

Microsoft Academic Search

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

Rakesh P Patel; Douglas Moellering; Joanne Murphy-Ullrich; Hanjoong Jo; Joseph S Beckman; Victor M Darley-Usmar

2000-01-01

34

Properties of reactively sputtered tungsten films in nitrogen and oxygen  

Microsoft Academic Search

Tungsten films reactively sputtered in nitrogen or oxygen were characterized by measurements of electrical resistivity and microstructure. The deposition rate of W--N films is slightly reduced with increasing nitrogen partial pressure accompanied by an increase in electrical resistivity. For example, the nominal resistivity of pure tungsten films increases from 11 to 16 ..mu cap omega.. cm as the nitrogen partial

K. Y. Ahn; S. B. Brodsky; C. Y. Ting; J. Kim

1986-01-01

35

The protistan parasite Perkinsus marinus is resistant to selected reactive oxygen species.  

PubMed

The parasite Perkinsus marinus has devastated natural and farmed oyster populations along the Atlantic and Gulf coasts of North America. When viable P. marinus trophozoites are engulfed by oyster hemocytes, the typical accumulation of reactive oxygen species (ROS) normally associated with phagocyte activity is not observed. One hypothesis to explain this is that the parasite rapidly removes ROS. A manifestation of efficient ROS removal should be a high level of resistance to exogenous ROS. We investigated the in vitro susceptibility of P. marinus to ROS as compared to the estuarine bacterium Vibrio splendidus. We find that P. marinus is markedly less susceptible than V. splendidus to superoxide and hydrogen peroxide (H(2)O(2)), but equally sensitive to hypochlorite. Viable P. marinus trophozoites degrade H(2)O(2) in vitro, but lack detectable catalase activity. However, extracts contain an ascorbate dependent peroxidase activity that may contribute to H(2)O(2) removal in vitro and in vivo. PMID:14990317

Schott, Eric J; Pecher, Wolf T; Okafor, Florence; Vasta, Gerardo R

2003-01-01

36

Mitochondria and Reactive Oxygen Species: Physiology and Pathophysiology  

PubMed Central

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

Bolisetty, Subhashini; Jaimes, Edgar A.

2013-01-01

37

Reactive oxygen species generation and signaling in plants  

PubMed Central

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

Tripathy, Baishnab Charan; Oelmüller, Ralf

2012-01-01

38

HIV-1, Reactive Oxygen Species and Vascular Complications  

PubMed Central

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

Porter, Kristi M.; Sutliff, Roy L.

2012-01-01

39

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

NSDL National Science Digital Library

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.

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

2006-04-25

40

Superoxide dismutase and catalase in Photobacterium damselae subsp. piscicida and their roles in resistance to reactive oxygen species.  

PubMed

Photobacterium damselae subsp. piscicida (formerly Pasteurella piscicida) is the causative agent of pasteurellosis or pseudotuberculosis in warm water marine fish. Enzymes which neutralize reactive oxygen species, produced during aerobic metabolism or during respiratory burst in fish macrophages, are important virulence factors in many pathogens. This study characterizes a periplasmic superoxide dismutase (SOD) and a cytoplasmic catalase in P. damselae. Purification and partial amino-terminal sequencing confirmed the SOD to be iron-cofactored, with a high degree of homology to other bacterial FeSODs. The SOD was common to all strains analysed in terms of type, location and activity, whilst the catalase varied in activity between strains. The catalase was constitutively expressed, but the SOD appeared to be repressed under low oxygen conditions. In spite of the presence of a periplasmic SOD, P. damselae was susceptible to killing by exogenous superoxide anion generated in a cell-free system. Addition of exogenous SOD to this system did not abolish the bactericidal effect; however, addition of catalase was protective. These results suggest that lack of periplasmic catalase may be implicated in susceptiblity to killing by reactive oxygen species. PMID:10075430

Barnes, A C; Balebona, M C; Horne, M T; Ellis, A E

1999-02-01

41

Properties of Reactive Oxygen Species by Quantum Monte Carlo  

E-print Network

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.

Andrea Zen; Bernhardt L. Trout; Leonardo Guidoni

2014-06-16

42

Properties of reactive oxygen species by quantum Monte Carlo  

NASA Astrophysics Data System (ADS)

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.

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

2014-07-01

43

Applications of Electron Spin Resonance Spectrometry for Reactive Oxygen Species and Reactive Nitrogen Species Research  

PubMed Central

Electron spin resonance (ESR) spectroscopy has been widely applied in the research of biological free radicals for quantitative and qualitative analyses of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The ESR spin-trapping method was developed in the early 1970s and enabled the analysis of short-lived free radicals. This method is now widely used as one of the most powerful tools for free radical studies. In this report, some of the studies that applied ESR for the measurement of ROS and RNS during oxidative stress are discussed. PMID:20664724

Kohno, Masahiro

2010-01-01

44

Exogenous insulin augments in healthy volunteers the cardiovascular reactivity to noradrenaline but not to angiotensin II.  

PubMed Central

Hyperinsulinemia has been implicated in the pathogenesis of the blood pressure elevation in patients with noninsulin-dependent diabetes mellitus, obesity, but also essential hypertension. In these conditions an increased cardiovascular reactivity to noradrenaline (NA) and angiotensin II (AII) can be observed. Using the euglycemic clamp technique, we determined the cardiovascular reactivity to graded infusions of NA and AII in nine healthy males before (Bas), and 1 and 6 h after infusion of insulin (50 mU/kg per h) was started. On separate days control experiments were carried out to control for any circadian variation. Insulin led to a decrease of the amount of circulating NA necessary to increase the diastolic blood pressure (DBP) 20 mmHg (actual experiment [mean +/- SEM]: Bas, 23.1 +/- 5.0; 1 h, 14.8 +/- 3.0; and 6 h, 12.3 +/- 3.1; and control experiment: Bas, 20.7 +/- 5.0; 1 h, 18.6 +/- 3.5; and 6 h, 17.3 +/- 3.3 nmol/liter; Bas vs. 1 and 6 h: P less than 0.05). Although the amount of NA infused to raise DBP 20 mmHg showed a similar decline after 1 h of insulin infusion, no such change from baseline could be observed at 6 h. This appeared to be due to an increase in NA clearance with more prolonged insulin infusion. Insulin exerted no effect on the amount of AII infused to increase DBP 20 mmHg (actual experiment: Bas, 27.6 +/- 6.4; 1 h, 28.8 +/- 10.0; and 6 h, 21.2 +/- 5.3; and control experiment: Bas, 33.6 +/- 5.7; 1 h, 34.2 +/- 6.1; and 6 h, 23.4 +/- 4.7 ng/kg/min; NS). We did observe a circadian variation in AII reactivity. Whether the increase in cardiovascular responsiveness to NA after administration of insulin contributes to the elevation in blood pressure frequently observed in patients with insulin resistance remains to be proven. PMID:1864961

Gans, R O; Bilo, H J; von Maarschalkerweerd, W W; Heine, R J; Nauta, J J; Donker, A J

1991-01-01

45

Sulfur, oxygen, and nitrogen mustards: stability and reactivity.  

PubMed

Mustard gas, bis(?-chloroethyl) sulfide (HD), is highly toxic and harmful to humans and the environment. It comprises one class of chemical warfare agents (CWAs) that was used in both World Wars I and II. The three basic analogues or surrogates are: the monochloro derivative, known as the half mustard, 2-chloroethyl ethyl sulfide (CEES); an oxygen analogue, bis(?-chloroethyl) ether (BCEE); and several nitrogen analogues based on the 2,2'-dichlorodiethylamine framework (e.g., HN1, HN2, and HN3). The origin of their toxicity is considered to be from the formation of three-membered heterocyclic ions, a reaction that is especially accelerated in aqueous solution. The reaction of these cyclic ion intermediates with a number of important biological species such as DNA, RNA and proteins causes cell toxicity and is responsible for the deleterious effects of the mustards. While a number of studies have been performed over the last century to determine the chemistry of these compounds, early studies suffered from a lack of more sophisticated NMR and X-ray techniques. It is now well-established that the sulfur and nitrogen mustards are highly reactive in water, while the oxygen analog is much more stable. In this study, we review and summarize results from previous studies, and add results of our own studies of the reactivity of these mustards toward various nonaqueous solvents and nucleophiles. In this manner a more comprehensive evaluation of the stability and reactivity of these related mustard compounds is achieved. PMID:23070251

Wang, Qi-Qiang; Begum, Rowshan Ara; Day, Victor W; Bowman-James, Kristin

2012-11-28

46

Manganese Neurotoxicity and the Role of Reactive Oxygen Species  

PubMed Central

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

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

2013-01-01

47

Reactive Oxygen Species Driven Angiogenesis by Inorganic Nanorods  

PubMed Central

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

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

2011-01-01

48

AIF, reactive oxygen species, and neurodegeneration: a "complex" problem.  

PubMed

Apoptosis-inducing factor (AIF) is a flavin-binding mitochondrial intermembrane space protein that is implicated in diverse but intertwined processes that include maintenance of electron transport chain function, reactive oxygen species regulation, cell death, and neurodegeneration. In acute brain injury, AIF acquires a pro-death role upon translocation from the mitochondria to the nucleus, where it initiates chromatin condensation and large-scale DNA fragmentation. Although harlequin mice exhibiting an 80-90% global reduction in AIF protein are resistant to numerous forms of acute brain injury, they paradoxically undergo slow, progressive neurodegeneration beginning at three months of age. Brain deterioration, accompanied by markers of oxidative stress, is most pronounced in the cerebellum and retina, although it also occurs in the cortex, striatum, and thalamus. Loss of an AIF pro-survival function linked to assembly or stabilization of electron transport chain complex I underlies chronic neurodegeneration. To date, most studies of neurodegeneration have failed to adequately separate the relative importance of the mitochondrial and nuclear functions of AIF in determining the extent of injury, or whether oxidative stress plays a causative role. This review explores the complicated relationship among AIF, complex I, and the regulation of mitochondrial reactive oxygen species levels. It also discusses the controversial role of complex I deficiency in Parkinson's disease, and what can be learned from the AIF- and complex I-depleted harlequin mouse. PMID:23246553

Polster, Brian M

2013-04-01

49

The known and unknown sources of reactive oxygen and nitrogen species in haemocytes of marine bivalve molluscs.  

PubMed

Reactive oxygen and nitrogen species (ROS and RNS) are naturally produced in all cells and organisms. Modifications of standard conditions alter reactive species generation and may result in oxidative stress. Because of the degradation of marine ecosystems, massive aquaculture productions, global change and pathogenic infections, oxidative stress is highly prevalent in marine bivalve molluscs. Haemocytes of bivalve molluscs produce ROS and RNS as part of their basal metabolism as well as in response to endogenous and exogenous stimuli. However, sources and pathways of reactive species production are currently poorly deciphered in marine bivalves, potentially leading to misinterpretations. Although sources and pathways of ROS and RNS productions are highly conserved between vertebrates and invertebrates, some uncommon pathways seem to only exist in marine bivalves. To understand the biology and pathobiology of ROS and RNS in haemocytes of marine bivalves, it is necessary to characterise their sources and pathways of production. The aims of the present review are to discuss the currently known and unknown intracellular sources of reactive oxygen and nitrogen species in marine bivalve molluscs, in light of terrestrial vertebrates, and to expose principal pitfalls usually encountered. PMID:25449373

Donaghy, Ludovic; Hong, Hyun-Ki; Jauzein, Cécile; Choi, Kwang-Sik

2015-01-01

50

Fumarate reductase is a major contributor to the generation of reactive oxygen species in the anaerobe Bacteroides fragilis.  

PubMed

Despite the detrimental role that endogenously generated reactive oxygen species (ROS) may play in bacteria exposed to aerobic environments, very few sources of ROS have been identified in vivo. Such studies are often precluded by the presence of efficient ROS-scavenging pathways, like those found in the aerotolerant anaerobe Bacteroides fragilis. Here we demonstrate that deletion of the genes encoding catalase (Kat), alkylhydroperoxide reductase (AhpC) and thioredoxin-dependent peroxidase (Tpx) strongly inhibits H(2)O(2) detoxification in B. fragilis, thereby allowing for the quantification of ROS production. Exogenous fumarate significantly reduced H(2)O(2) production in a ?ahpC?kat?tpx B. fragilis strain, as did deletion of fumarate reductase subunit c (frdC). Deletion of frdC also increased the aerotolerance of a strain lacking superoxide dismutase, indicating that fumarate reductase is a major contributor to ROS formation in B. fragilis exposed to oxygen. PMID:22075026

Meehan, Brian M; Malamy, Michael H

2012-02-01

51

In situ reactive oxygen species production for tertiary wastewater treatment.  

PubMed

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

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

2014-12-01

52

Diagnostics of reactive oxygen species produced by microplasmas  

NASA Astrophysics Data System (ADS)

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.

Sousa, J. S.; Puech, V.

2013-11-01

53

Role of Reactive Oxygen Species in Antibiotic Action and Resistance  

PubMed Central

The alarming spread of bacterial strains exhibiting resistance to current antibiotic therapies necessitates that we elucidate the specific genetic and biochemical responses underlying drug-mediated cell killing, so as to increase the efficacy of available treatments and develop new antibacterials. Recent research aimed at identifying such cellular contributions has revealed that antibiotics induce changes in metabolism that promote the formation of reactive oxygen species, which play a role in cell death. Here we discuss the relationship between drug-induced oxidative stress, the SOS response and their potential combined contribution to resistance development. Additionally, we describe ways in which these responses are being taken advantage of to combat bacterial infections and arrest the rise of resistant strains. PMID:19647477

Dwyer, Daniel J; Kohanski, Michael A; Collins, James J

2009-01-01

54

Reactive oxygen species, cell signaling, and cell injury.  

PubMed

Oxidative stress has traditionally been viewed as a stochastic process of cell damage resulting from aerobic metabolism, and antioxidants have been viewed simply as free radical scavengers. Only recently has it been recognized that reactive oxygen species (ROS) are widely used as second messengers to propagate proinflammatory or growth-stimulatory signals. With this knowledge has come the corollary realization that oxidative stress and chronic inflammation are related, perhaps inseparable phenomena. New pharmacological strategies aimed at supplementing antioxidant defense systems while antagonizing redox-sensitive signal transduction may allow improved clinical management of chronic inflammatory or degenerative conditions, including Alzheimer's disease. Introduction of antioxidant therapies into mainstream medicine is possible and promising, but will require significant advances in basic cell biology, pharmacology, and clinical bioanalysis. PMID:10927169

Hensley, K; Robinson, K A; Gabbita, S P; Salsman, S; Floyd, R A

2000-05-15

55

The Role of Reactive Oxygen Species in Microvascular Remodeling  

PubMed Central

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

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

2014-01-01

56

Aminoferrocene-based prodrugs activated by reactive oxygen species.  

PubMed

Cancer cells generally generate higher amounts of reactive oxygen species than normal cells. On the basis of this difference, prodrugs have been developed (e.g., hydroxyferrocifen), which remain inactive in normal cells, but become activated in cancer cells. In this work we describe novel aminoferrocene-based prodrugs, which, in contrast to hydroxyferrocifen, after activation form not only quinone methides (QMs), but also catalysts (iron or ferrocenium ions). The released products act in a concerted fashion. In particular, QMs alkylate glutathione, thereby inhibiting the antioxidative system of the cell, whereas the iron species induce catalytic generation of hydroxyl radicals. Since the catalysts are formed as products of the activation reaction, it proceeds autocatalytically. The most potent prodrug described here is toxic toward cancer cells (human promyelocytic leukemia (HL-60), IC(50) = 9 ?M, and human glioblastoma-astrocytoma (U373), IC(50) = 25 ?M), but not toxic (up to 100 ?M) toward representative nonmalignant cells (fibroblasts). PMID:22185340

Hagen, Helen; Marzenell, Paul; Jentzsch, Elmar; Wenz, Frederik; Veldwijk, Marlon R; Mokhir, Andriy

2012-01-26

57

Reactive oxygen species, ageing and the hormesis police  

PubMed Central

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

Ludovico, Paula; Burhans, William C.

2013-01-01

58

Moving forward with reactive oxygen species involvement in antimicrobial lethality.  

PubMed

Support for the contribution of reactive oxygen species (ROS) to antimicrobial lethality has been refined and strengthened. Killing by diverse antimicrobials is enhanced by defects in genes that protect against ROS, inhibited by compounds that block hydroxyl radical accumulation, and is associated with surges in intracellular ROS. Moreover, support has emerged for a genetic pathway that controls the level of ROS. Since some antimicrobials kill in the absence of ROS, ROS must add to, rather than replace, known killing mechanisms. New work has addressed many of the questions concerning the specificity of dyes used to detect intracellular ROS and the specificity of perturbations that influence ROS surges. However, complexities associated with killing under anaerobic conditions remain to be resolved. Distinctions among primary lesion formation, resistance, direct lesion-mediated killing and a self-destructive stress response are discussed to facilitate efforts to potentiate ROS-mediated bacterial killing and improve antimicrobial efficacy. PMID:25422287

Zhao, Xilin; Hong, Yuzhi; Drlica, Karl

2015-03-01

59

Reactive Oxygen Species in Inflammation and Tissue Injury  

PubMed Central

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

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

2014-01-01

60

Reactive Oxygen Species in Normal and Tumor Stem Cells  

PubMed Central

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

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

2014-01-01

61

The role of reactive oxygen species in microvascular remodeling.  

PubMed

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

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

2014-01-01

62

Transcriptomic Footprints Disclose Specificity of Reactive Oxygen Species Signaling in Arabidopsis1[W  

PubMed Central

Reactive oxygen species (ROS) are key players in the regulation of plant development, stress responses, and programmed cell death. Previous studies indicated that depending on the type of ROS (hydrogen peroxide, superoxide, or singlet oxygen) or its subcellular production site (plastidic, cytosolic, peroxisomal, or apoplastic), a different physiological, biochemical, and molecular response is provoked. We used transcriptome data generated from ROS-related microarray experiments to assess the specificity of ROS-driven transcript expression. Data sets obtained by exogenous application of oxidative stress-causing agents (methyl viologen, Alternaria alternata toxin, 3-aminotriazole, and ozone) and from a mutant (fluorescent) and transgenic plants, in which the activity of an individual antioxidant enzyme was perturbed (catalase, cytosolic ascorbate peroxidase, and copper/zinc superoxide dismutase), were compared. In total, the abundance of nearly 26,000 transcripts of Arabidopsis (Arabidopsis thaliana) was monitored in response to different ROS. Overall, 8,056, 5,312, and 3,925 transcripts showed at least a 3-, 4-, or 5-fold change in expression, respectively. In addition to marker transcripts that were specifically regulated by hydrogen peroxide, superoxide, or singlet oxygen, several transcripts were identified as general oxidative stress response markers because their steady-state levels were at least 5-fold elevated in most experiments. We also assessed the expression characteristics of all annotated transcription factors and inferred new candidate regulatory transcripts that could be responsible for orchestrating the specific transcriptomic signatures triggered by different ROS. Our analysis provides a framework that will assist future efforts to address the impact of ROS signals within environmental stress conditions and elucidate the molecular mechanisms of the oxidative stress response in plants. PMID:16603662

Gadjev, Ilya; Vanderauwera, Sandy; Gechev, Tsanko S.; Laloi, Christophe; Minkov, Ivan N.; Shulaev, Vladimir; Apel, Klaus; Inzé, Dirk; Mittler, Ron; Van Breusegem, Frank

2006-01-01

63

Cell signaling by reactive nitrogen and oxygen species in atherosclerosis  

NASA Technical Reports Server (NTRS)

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.

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

2000-01-01

64

p38? inhibits liver fibrogenesis and consequent hepatocarcinogenesis by curtailing accumulation of reactive oxygen species.  

PubMed

Most hepatocellular carcinomas (HCC) develop in the context of severe liver fibrosis and cirrhosis caused by chronic liver inflammation, which also results in accumulation of reactive oxygen species (ROS). In this study, we examined whether the stress-activated protein kinase p38? (Mapk14) controls ROS metabolism and development of fibrosis and cancer in mice given thioacetamide to induce chronic liver injury. Liver-specific p38? ablation was found to enhance ROS accumulation, which appears to be exerted through the reduced expression of antioxidant protein HSP25 (Hspb1), a mouse homolog of HSP27. Its reexpression in p38?-deficient liver prevents ROS accumulation and thioacetamide-induced fibrosis. p38? deficiency increased expression of SOX2, a marker for cancer stem cells and the liver oncoproteins c-Jun (Jun) and Gankyrin (Psmd10) and led to enhanced thioacetamide-induced hepatocarcinogenesis. The upregulation of SOX2 and c-Jun was prevented by administration of the antioxidant butylated hydroxyanisole. Intriguingly, the risk of human HCC recurrence is positively correlated with ROS accumulation in liver. Thus, p38? and its target HSP25/HSP27 appear to play a conserved and critical hepatoprotective function by curtailing ROS accumulation in liver parenchymal cells engaged in oxidative metabolism of exogenous chemicals. Augmented oxidative stress of liver parenchymal cells may explain the close relationship between liver fibrosis and hepatocarcinogenesis. PMID:23271722

Sakurai, Toshiharu; Kudo, Masatoshi; Umemura, Atsushi; He, Guobin; Elsharkawy, Ahmed M; Seki, Ekihiro; Karin, Michael

2013-01-01

65

Modulation of reactive oxygen species by salicylic acid in arabidopsis seed germination under high salinity  

PubMed Central

Potential roles of salicylic acid (SA) on seed germination have been explored in many plant species. However, it is still controversial how SA regulates seed germination, mainly because the results have been somewhat variable, depending on plant genotypes used and experimental conditions employed. We found that SA promotes seed germination under high salinity in Arabidopsis. Seed germination of the sid2 mutant, which has a defect in SA biosynthesis, is hypersensitive to high salinity, but the inhibitory effects are reduced in the presence of physiological concentrations of SA. Abiotic stresses, including high salinity, impose oxidative stress on plants. Endogenous contents of H2O2 are higher in the sid2 mutant seeds. However, exogenous application of SA reduces endogenous level of reactive oxygen species (ROS), indicating that SA is involved in plant responses to ROS-mediated damage under abiotic stress conditions. Gibberellic acid (GA), a plant hormone closely associated with seed germination, also reverses the inhibitory effects of high salinity on seed germination and seedling establishment. Under high salinity, GA stimulates SA biosynthesis by inducing the SID2 gene. Notably, SA also induces genes encoding GA biosynthetic enzymes. These observations indicate that SA promotes seed germination under high salinity by modulating antioxidant activity through signaling crosstalks with GA. PMID:21150285

Lee, Sangmin

2010-01-01

66

REACTIVE OXYGEN AND NITROGEN SPECIES IN PULMONARY HYPERTENSION  

PubMed Central

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

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

2013-01-01

67

Reactive Oxygen Species-Inducible ECF ? Factors of Bradyrhizobium japonicum  

PubMed Central

Extracytoplasmic function (ECF) ? factors control the transcription of genes involved in different cellular functions, such as stress responses, metal homeostasis, virulence-related traits, and cell envelope structure. The genome of Bradyrhizobium japonicum, the nitrogen-fixing soybean endosymbiont, encodes 17 putative ECF ? factors belonging to nine different ECF ? factor families. The genes for two of them, ecfQ (bll1028) and ecfF (blr3038), are highly induced in response to the reactive oxygen species hydrogen peroxide (H2O2) and singlet oxygen (1O2). The ecfF gene is followed by the predicted anti-? factor gene osrA (blr3039). Mutants lacking EcfQ, EcfF plus OsrA, OsrA alone, or both ? factors plus OsrA were phenotypically characterized. While the symbiotic properties of all mutants were indistinguishable from the wild type, they showed increased sensitivity to singlet oxygen under free-living conditions. Possible target genes of EcfQ and EcfF were determined by microarray analyses, and candidate genes were compared with the H2O2-responsive regulon. These experiments disclosed that the two ? factors control rather small and, for the most part, distinct sets of genes, with about half of the genes representing 13% of the members of H2O2-responsive regulon. To get more insight into transcriptional regulation of both ? factors, the 5? ends of ecfQ and ecfF mRNA were determined. The presence of conserved sequence motifs in the promoter region of ecfQ and genes encoding EcfQ-like ? factors in related ?-proteobacteria suggests regulation via a yet unknown transcription factor. By contrast, we have evidence that ecfF is autoregulated by transcription from an EcfF-dependent consensus promoter, and its product is negatively regulated via protein-protein interaction with OsrA. Conserved cysteine residues 129 and 179 of OsrA are required for normal function of OsrA. Cysteine 179 is essential for release of EcfF from an EcfF-OsrA complex upon H2O2 stress while cysteine 129 is possibly needed for EcfF-OsrA interaction. PMID:22916258

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

2012-01-01

68

Reactive oxygen species delay control of lymphocytic choriomeningitis virus.  

PubMed

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

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

2013-04-01

69

Male infertility testing: reactive oxygen species and antioxidant capacity.  

PubMed

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

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

2014-12-01

70

Mitochondrial reactive oxygen species in cell death signaling.  

PubMed

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

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

2002-01-01

71

Metformin reduces endogenous reactive oxygen species and associated DNA damage.  

PubMed

Pharmacoepidemiologic studies provide evidence that use of metformin, a drug commonly prescribed for type II diabetes, is associated with a substantial reduction in cancer risk. Experimental models show that metformin inhibits the growth of certain neoplasms by cell autonomous mechanisms such as activation of AMP kinase with secondary inhibition of protein synthesis or by an indirect mechanism involving reduction in gluconeogenesis leading to a decline in insulin levels and reduced proliferation of insulin-responsive cancers. Here, we show that metformin attenuates paraquat-induced elevations in reactive oxygen species (ROS), and related DNA damage and mutations, but has no effect on similar changes induced by H(2)0(2), indicating a reduction in endogenous ROS production. Importantly, metformin also inhibited Ras-induced ROS production and DNA damage. Our results reveal previously unrecognized inhibitory effects of metformin on ROS production and somatic cell mutation, providing a novel mechanism for the reduction in cancer risk reported to be associated with exposure to this drug. PMID:22262811

Algire, Carolyn; Moiseeva, Olga; Deschênes-Simard, Xavier; Amrein, Lilian; Petruccelli, Luca; Birman, Elena; Viollet, Benoit; Ferbeyre, Gerardo; Pollak, Michael N

2012-04-01

72

Light and Dark of Reactive Oxygen Species for Vascular Function.  

PubMed

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

Shimokawa, Hiroaki; Satoh, Kimio

2014-08-26

73

Methods for Detection of Mitochondrial and Cellular Reactive Oxygen Species  

PubMed Central

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

Harrison, David G.

2014-01-01

74

Reactive oxygen metabolites produced by the carcinogenic fibrous mineral erionite  

SciTech Connect

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.

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

1991-02-01

75

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

PubMed

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

Lushchak, Volodymyr I

2014-10-28

76

Reactive Oxygen Species Signaling in Cancer: Comparison with Aging  

PubMed Central

This work considers reactive oxygen species (ROS) signaling in solid tumors. Most (probably all) cancer cells are characterized by ROS overproduction that is they exist under conditions of incessant oxidative stress. For example ROS overproduction has been shown in prostate, pancreatic, melanoma, and glioma cells. ROS overproduction has been also demonstrated in breast, liver, bladder, colon, and ovarian cancers. Although these examples probably do not incorporate all the described data concerning ROS overproduction in cancer cells, they clearly support a proposal about enhanced oxidative stress in these cells. Therefore the mechanisms of ROS signaling in the survival and death of cancer cells and comparison with ROS signaling in senescent cells ought to be considered. It might be suggested that ROS overproduction in cancer cells is a major origin of their survival and resistance to anticancer treatment while the enhanced oxidative stress responsible for aging development. However it is of particular interest that additional ROS production by prooxidants can induce apoptosis in cancer cells. We suggest that moderate oxidative stress can stimulate proliferation and survival of cancer sells by conditioning mechanism while the enhancement of ROS overproduction by prooxidants under severe oxidative stress results in apoptosis and cell death. Aging development is always characterized by harmful ROS overproduction although the moderate increase in ROS formation in senescent cells might be not dangerous. Similar double-edged sword effects of ROS might be observed during the development of other pathologies for example diabetes mellitus. PMID:22396874

Afanas’ev, Igor

2011-01-01

77

Reactive oxygen species at the crossroads of inflammasome and inflammation  

PubMed Central

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

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

2014-01-01

78

Are Reactive Oxygen Species Always Detrimental to Pathogens?  

PubMed Central

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

Bozza, Marcelo T.

2014-01-01

79

Tamoxifen reduces fat mass by boosting reactive oxygen species.  

PubMed

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

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

2015-01-01

80

Degradative action of reactive oxygen species on hyaluronan.  

PubMed

Many human diseases are associated with harmful action of reactive oxygen species (ROS). These species are involved in the degradation of essential tissue or related components. One of such components is synovial fluid that contains a high-molecular-weight polymer--hyaluronan (HA). Uninhibited and/or inhibited hyaluronan degradation by the action of various ROS has been studied in many in vitro models. In these studies, the change of the molecular weight of HA or a related parameter, such as HA solution viscosity, has been used as a marker of inflicted damage. The aim of the presented review is to briefly summarize the available data. Their correct interpretation could contribute to the implementation of modern methods of evaluation of the antioxidative capacity of natural and synthetic substances and prospective drugs--potential inflammatory disease modifying agents. Another focus of this review is to evaluate briefly the impact of different available analytical techniques currently used to investigate the structure of native high-molecular-weight hyaluronan and/or of its fragments. PMID:16529395

Soltés, L; Mendichi, R; Kogan, G; Schiller, J; Stankovska, M; Arnhold, J

2006-03-01

81

Generator-specific targets of mitochondrial reactive oxygen species.  

PubMed

To understand the role of reactive oxygen species (ROS) in oxidative stress and redox signaling it is necessary to link their site of generation to the oxidative modification of specific targets. Here we have studied the selective modification of protein thiols by mitochondrial ROS that have been implicated as deleterious agents in a number of degenerative diseases and in the process of biological aging, but also as important players in cellular signal transduction. We hypothesized that this bipartite role might be based on different generator sites for "signaling" and "damaging" ROS and a directed release into different mitochondrial compartments. Because two main mitochondrial ROS generators, complex I (NADH:ubiquinone oxidoreductase) and complex III (ubiquinol:cytochrome c oxidoreductase; cytochrome bc1 complex), are known to predominantly release superoxide and the derived hydrogen peroxide (H2O2) into the mitochondrial matrix and the intermembrane space, respectively, we investigated whether these ROS generators selectively oxidize specific protein thiols. We used redox fluorescence difference gel electrophoresis analysis to identify redox-sensitive targets in the mitochondrial proteome of intact rat heart mitochondria. We observed that the modified target proteins were distinctly different when complex I or complex III was employed as the source of ROS. These proteins are potential targets involved in mitochondrial redox signaling and may serve as biomarkers to study the generator-dependent dual role of mitochondrial ROS in redox signaling and oxidative stress. PMID:25451644

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

2015-01-01

82

Roles of Reactive Oxygen and Nitrogen Species in Pain  

PubMed Central

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

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

2011-01-01

83

Reactive Oxygen Species and Antioxidants in Pulmonary Hypertension  

PubMed Central

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

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

2013-01-01

84

Reactive Oxygen Species Production by the Spermatozoa of Patients With Idiopathic Infertility: Relationship to Seminal Plasma Antioxidants  

Microsoft Academic Search

PurposeWe attempted to determine reactive oxygen species production by the spermatozoa of patients with idiopathic infertility and healthy donors, and observe whether increased production was due to decreased seminal plasma reactive oxygen species scavengers.

Ilter Alkan; Ferruh Simsek; Goncagul Haklar; Ertan Kervancioglu; Hakan Ozveri; Suha Yalcin; Atif Akdas

1997-01-01

85

Reactive Oxygen Species Regulate F-actin Dynamics in Neuronal Growth Cones and Neurite Outgrowth  

PubMed Central

Reactive oxygen species are well known for their damaging effects due to oxidation of lipids, proteins and DNA that ultimately result in cell death. Accumulating evidence indicates that reactive oxygen species also have important signaling functions in cell proliferation, differentiation, cell motility and apoptosis. Here, we tested the hypothesis whether reactive oxygen species play a physiological role in regulating F-actin structure and dynamics in neuronal growth cones. Lowering cytoplasmic levels of reactive oxygen species with a free radical scavenger, N-tert-butyl-?-phenylnitrone, or by inhibiting specific sources of reactive oxygen species, such as NADPH oxidases or lipoxygenases, reduced the F-actin content in the peripheral domain of growth cones. Fluorescent speckle microscopy revealed that these treatments caused actin assembly inhibition, reduced retrograde actin flow and increased contractility of actin structures in the transition zone referred to as arcs, possibly by activating the Rho pathway. Reduced levels of reactive oxygen species ultimately resulted in disassembly of the actin cytoskeleton. When neurons were cultured overnight in conditions of reduced free radicals, growth cone formation and neurite outgrowth were severely impaired. Therefore, we conclude that physiological levels of reactive oxygen species are critical for maintaining a dynamic F-actin cytoskeleton and controlling neurite outgrowth. PMID:19054285

Munnamalai, Vidhya; Suter, Daniel M.

2010-01-01

86

Eat-Me: Autophagy, Phagocytosis, and Reactive Oxygen Species Signaling  

PubMed Central

Abstract Significance: Phagocytosis is required for the clearance of dying cells. The subsequent regulation of inflammatory responses by phagocytic cells is mediated by both innate and adaptive immune responses. Autophagy, an evolutionarily ancient process of lysosomal self-digestion of organelles, protein aggregates, apoptotic corpses, and cytosolic pathogens, has only recently become appreciated for its dynamic relationship with phagocytosis, including newly discovered autophagic-phagocytosis “hybrid” processes such as microtubule-associated protein 1 light chain 3-associated phagocytosis (LAP). Recent Advances: Signal transduction by reactive oxygen species (ROS) plays a critical role in the modulation of autophagy, phagocytosis, and LAP, and serves as both a link and an additional layer of regulation between these processes. Furthermore, specific targets for oxidation by ROS molecules have recently begun to become identified in each of these processes, as have “shared” proteins that facilitate the successful completion of both autophagy and phagocytosis. High mobility group box 1 is at the crossroads of autophagy, phagocytosis, and oxidative stress. Critical Issues: In this review, we discuss the most recent findings that link elements of autophagy and phagocytosis, specifically through redox-dependent signal transduction. These interconnected cellular processes are placed in the context of cell death and immunity in both health and disease. Future Directions: Given the broad roles that autophagy, phagocytosis, and ROS signaling play in human health, disease, and the maintenance of cellular and organismal homeostatic balance, it is important to delineate intersections between these pathways and uncover targets for potential therapeutic intervention in the setting of autoimmune and inflammatory diseases. Antioxid. Redox Signal. 18, 677–691. PMID:22871044

Vernon, Philip J.

2013-01-01

87

The impact of reactive oxygen species on anticancer therapeutic strategies.  

PubMed

Over 50 years of experience in free radical biology and medicine shows that normal cells of healthy mammals are characterized by a low steady-state level of reactive oxygen species (ROS) and a constant (reference) level of reducing equivalents. A lasting increase of ROS above the critical level leads to permanent oxidative stress in the cells. This could cause genomic instability and mutations, which are responsible for adaptation of cells to oxidative stress and their survival in an oxidative environment. In turn, these events could provoke malignancy. It is widely accepted that the balance between ROS and reducing equivalents in cells and tissues determines their redox status. The evaluation of tissue redox status has great diagnostic potential in cancer, as well as prognostic potential for cancer therapy, and could significantly contribute to the planning of appropriate treatment and to increasing the patients' quality of life. The conventional therapeutic strategy is based on drugs that increase ROS generation and induce apoptosis in cancer cells. However, this therapeutic approach has serious disadvantages: the expression of various toxic side effects in normal (non-cancer) tissues. The current review describes the basics of free radical biology in carcinogenesis. The authors emphasize the different redox status of normal and cancer cells, which permits the use of this parameter as a new therapeutic target. The authors also outline some directions for the development of promising therapeutic strategies based on the regulation of redox signaling using combined therapy. The review is intended for a broad readership - from non-specialists to researchers in the field of cancer biochemistry and pharmacy. PMID:24431321

Ivanova, Donika; Bakalova, Rumiana; Lazarova, Dessisslava; Gadjeva, Veselina; Zhelev, Zhivko

2013-01-01

88

Reactive oxygen species signaling in plants under abiotic stress.  

PubMed

Abiotic stresses like heavy metals, drought, salt, low temperature, etc. are the major factors that limit crop productivity and yield. These stresses are associated with production of certain deleterious chemical entities called reactive oxygen species (ROS), which include hydrogen peroxide (H?O?), superoxide radical (O?(-)), hydroxyl radical (OH(-)), etc. ROS are capable of inducing cellular damage by degradation of proteins, inactivation of enzymes, alterations in the gene and interfere in various pathways of metabolic importance. Our understanding on ROS in response to abiotic stress is revolutionized with the advancements in plant molecular biology, where the basic understanding on chemical behavior of ROS is better understood. Understanding the molecular mechanisms involved in ROS generation and its potential role during abiotic stress is important to identify means by which plant growth and metabolism can be regulated under acute stress conditions. ROS mediated oxidative stress, which is the key to understand stress related toxicity have been widely studied in many plants and the results in those studies clearly revealed that oxidative stress is the main symptom of toxicity. Plants have their own antioxidant defense mechanisms to encounter ROS that is of enzymic and non-enzymic nature . Coordinated activities of these antioxidants regulate ROS detoxification and reduces oxidative load in plants. Though ROS are always regarded to impart negative impact on plants, some reports consider them to be important in regulating key cellular functions; however, such reports in plant are limited. Molecular approaches to understand ROS metabolism and signaling have opened new avenues to comprehend its critical role in abiotic stress. ROS also acts as secondary messenger that signals key cellular functions like cell proliferation, apoptosis and necrosis. In higher eukaryotes, ROS signaling is not fully understood. In this review we summarize our understanding on ROS and its signaling behavior in plants under abiotic stress. PMID:23425848

Choudhury, Shuvasish; Panda, Piyalee; Sahoo, Lingaraj; Panda, Sanjib Kumar

2013-04-01

89

Reactive Oxygen Production Induced by the Gut Microbiota: Pharmacotherapeutic Implications  

PubMed Central

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

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

2014-01-01

90

Role of Reactive Oxygen Species-Mediated Signaling in Aging  

PubMed Central

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

Labunskyy, Vyacheslav M.

2013-01-01

91

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

NASA Astrophysics Data System (ADS)

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.

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

1996-11-01

92

Endogenous reactivation followed by exogenous re-infection with drug resistant strains, a new challenge for tuberculosis control in Saudi Arabia.  

PubMed

Endogenous reactivation and exogenous reinfection of tuberculosis were studied for the first time in Saudi Arabia after enrolling a total of 39 patients with multiple episodes of tuberculosis between 2009 and 2010. All of the primary and subsequent isolates enrolled were subjected to spoligotyping, 24 loci based MIRU-VNTR typing and first line anti-tuberculosis drug susceptibility testing. The primary episode isolates from patients born outside Saudi Arabia were dominated by lineages which are prevalent in their country of origin (e.g. Ghana, Cameroon, Uganda-I, among African patients/Delhi/CAS and EAI among Asian patients). On the other hand, in Saudi Arabian patients, (median age of 67 years) Delhi/CAS, TUR and S lineages were predominant. The second episode of infection was mainly caused by the lineages Delhi/CAS, EAI, Uganda-I, Haarlem, and LAM which are currently disseminating in the country. Surprisingly, all of the first episode isolates were pan-susceptible, while 35.9% of the re-infected cases were drug resistant. Reactivation of a remote infection eventually followed by an exogenous reinfection was confirmed among patients, particularly those of African origin. Immediate actions to break the cycle of transmission of drug resistant tuberculosis are greatly needed in Saudi Arabia. PMID:23313023

Varghese, Bright; al-Omari, Ruba; Grimshaw, Ceilidh; Al-Hajoj, Sahal

2013-03-01

93

Properties of reactive oxygen species by quantum Monte Carlo  

E-print Network

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 ...

Zen, Andrea

94

The ATX1 gene of Saccharomyces cerevisiae encodes a small metal homeostasis factor that protects cells against reactive oxygen toxicity.  

PubMed Central

In aerobic organisms, protection against oxidative damage involves the combined action of highly specialized antioxidant enzymes, such as superoxide dismutase (SOD) and catalase. Here we describe the isolation and characterization of another gene in the yeast Saccharomyces cerevisiae that plays a critical role in detoxification of reactive oxygen species. This gene, named ATX1, was originally isolated by its ability to suppress oxygen toxicity in yeast lacking SOD. ATX1 encodes a 8.2-kDa polypeptide exhibiting significant similarity and identity to various bacterial metal transporters. Potential ATX1 homologues were also identified in multicellular eukaryotes, including the plants Arabidopsis thaliana and Oryza sativa and the nematode Caenorhabditis elegans. In yeast cells, ATX1 evidently acts in the transport and/or partitioning of copper, and this role in copper homeostasis appears to be directly relevant to the ATX1 suppression of oxygen toxicity: ATX1 was incapable of compensating for SOD when cells were depleted of exogenous copper. Strains containing a deletion in the chromosomal ATX1 locus were generated. Loss of ATX1 function rendered both mutant and wild-type SOD strains hypersensitive toward paraquat (a generator of superoxide anion) and was also associated with an increased sensitivity toward hydrogen peroxide. Hence, ATX1 protects cells against the toxicity of both superoxide anion and hydrogen peroxide. Images Fig. 2 Fig. 3 PMID:7731983

Lin, S J; Culotta, V C

1995-01-01

95

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

E-print Network

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...

Henderson, Cara Aletha Everett

2012-06-07

96

Inhibition of Pyruvate Kinase M2 by Reactive Oxygen Species Contributes to Cellular Antioxidant Responses  

E-print Network

Control of intracellular reactive oxygen species (ROS) concentrations is critical for cancer cell survival. We show that, in human lung cancer cells, acute increases in intracellular concentrations of ROS caused inhibition ...

Vander Heiden, Matthew G.

97

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...

98

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

PubMed

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

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

2015-02-01

99

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

PubMed Central

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

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

2012-01-01

100

Analytica Chimica Acta 437 (2001) 183190 Re-activation of an all solid state oxygen sensor  

E-print Network

Analytica Chimica Acta 437 (2001) 183­190 Re-activation of an all solid state oxygen sensor W/SiO2/Si3N4/LaF3/Pt can be used as a potentiometric oxygen sensor working at room temperature. A thermal can be applied. A heating time as short as 300 ns was sufficient for the re-activation of the sensor

Moritz, Werner

101

Modulation of protein kinases and protein phosphatases by reactive oxygen species: Implications for hippocampal synaptic plasticity  

Microsoft Academic Search

1.1. Reactive oxygen species are known for their role in neurotoxicity. However, recent studies indicate that reactive oxygen species also play a role in cell function under physiological conditions.2.2. Both Superoxide and hydrogen peroxide alter the activity of various protein kinases and protein phosphatases, some of which are involved in hippocampal synaptic plasticity. Specifically, the activity of protein kinase C,

Eric Klann; Edda Thiels

1999-01-01

102

KRIT1 Regulates the Homeostasis of Intracellular Reactive Oxygen Species  

PubMed Central

KRIT1 is a gene responsible for Cerebral Cavernous Malformations (CCM), a major cerebrovascular disease characterized by abnormally enlarged and leaky capillaries that predispose to seizures, focal neurological deficits, and fatal intracerebral hemorrhage. Comprehensive analysis of the KRIT1 gene in CCM patients has suggested that KRIT1 functions need to be severely impaired for pathogenesis. However, the molecular and cellular functions of KRIT1 as well as CCM pathogenesis mechanisms are still research challenges. We found that KRIT1 plays an important role in molecular mechanisms involved in the maintenance of the intracellular Reactive Oxygen Species (ROS) homeostasis to prevent oxidative cellular damage. In particular, we demonstrate that KRIT1 loss/down-regulation is associated with a significant increase in intracellular ROS levels. Conversely, ROS levels in KRIT1?/? cells are significantly and dose-dependently reduced after restoration of KRIT1 expression. Moreover, we show that the modulation of intracellular ROS levels by KRIT1 loss/restoration is strictly correlated with the modulation of the expression of the antioxidant protein SOD2 as well as of the transcriptional factor FoxO1, a master regulator of cell responses to oxidative stress and a modulator of SOD2 levels. Furthermore, we show that the KRIT1-dependent maintenance of low ROS levels facilitates the downregulation of cyclin D1 expression required for cell transition from proliferative growth to quiescence. Finally, we demonstrate that the enhanced ROS levels in KRIT1?/? cells are associated with an increased cell susceptibility to oxidative DNA damage and a marked induction of the DNA damage sensor and repair gene Gadd45?, as well as with a decline of mitochondrial energy metabolism. Taken together, our results point to a new model where KRIT1 limits the accumulation of intracellular oxidants and prevents oxidative stress-mediated cellular dysfunction and DNA damage by enhancing the cell capacity to scavenge intracellular ROS through an antioxidant pathway involving FoxO1 and SOD2, thus providing novel and useful insights into the understanding of KRIT1 molecular and cellular functions. PMID:20668652

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

2010-01-01

103

Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis  

PubMed Central

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

Khan, Saeed R.

2014-01-01

104

Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology  

Microsoft Academic Search

Reactive Oxygen Species (ROS) are produced during normal cellular function. ROS include hydroxyl radicals, superoxide anion, hydrogen peroxide and nitric oxide. They are very transient species due to their high chemical reactivity that leads to lipid peroxidation and oxidation of DNA and proteins. Under normal conditions, antioxidant systems of the cell minimize the perturbations caused by ROS. When ROS generation

2000-01-01

105

Production of reactive oxygen species in mitochondria of HeLa cells under oxidative stress  

Microsoft Academic Search

Mitochondria can be a source of reactive oxygen species (ROS) and a target of oxidative damage during oxidative stress. In this connection, the effect of photodynamic treatment (PDT) with Mitotracker Red (MR) as a mitochondria-targeted photosensitizer has been studied in HeLa cells. It is shown that MR produces both singlet oxygen and superoxide anion upon photoactivation and causes photoinactivation of

Boris V. Chernyak; Denis S. Izyumov; Konstantin G. Lyamzaev; Alina A. Pashkovskaya; Olga Y. Pletjushkina; Yuri N. Antonenko; Dmitrii V. Sakharov; Karel W. A. Wirtz; Vladimir P. Skulachev

2006-01-01

106

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

E-print Network

1 BUTYRIC ACID INCREASES INVASIVENESS OF HL-60 LEUKEMIA CELLS: ROLE OF REACTIVE OXYGEN SPECIES oxygen species (ROS) were generated in BA-treated cells. BA-induced differentiation was accompanied. In addition, migratory and invasive properties of HL-60 cells were enhanced by BA, but differently affected

Paris-Sud XI, Université de

107

Nanoparticle Inhalation Impairs Coronary Microvascular Reactivity via a Local Reactive Oxygen Species-Dependent Mechanism  

PubMed Central

We have shown that nanoparticle inhalation impairs endothelium-dependent vasodilation in coronary arterioles. It is unknown whether local reactive oxygen species (ROS) contribute to this effect. Rats were exposed to TiO2 nanoparticles via inhalation to produce a pulmonary deposition of 10 µg. Coronary arterioles were isolated from the left anterior descending artery distribution, and responses to acetylcholine, arachidonic acid, and U46619 were assessed. Contributions of nitric oxide synthase and prostaglandin were assessed via competitive inhibition with NG-Monomethyl-L-Arginine (L-NMMA) and indomethacin. Microvascular wall ROS were quantified via dihydroethidium (DHE) fluorescence. Coronary arterioles from rats exposed to nano-TiO2 exhibited an attenuated vasodilator response to ACh, and this coincided with a 45% increase in DHE fluorescence. Coincubation with 2,2,6,6-tetramethylpiperidine-N-oxyl and catalase ameliorated impairments in ACh-induced vasodilation from nanoparticle exposed rats. Incubation with either L-NMMA or indomethacin significantly attenuated Ach-induced vasodilation in sham-control rats, but had no effect in rats exposed to nano-TiO2. Arachidonic acid induced vasoconstriction in coronary arterioles from rats exposed to nano-TiO2, but dilated arterioles from sham-control rats. These results suggest that nanoparticle exposure significantly impairs endothelium-dependent vasoreactivity in coronary arterioles, and this may be due in large part to increases in microvascular ROS. Furthermore, altered prostanoid formation may also contribute to this dysfunction. Such disturbances in coronary microvascular function may contribute to the cardiac events associated with exposure to particles in this size range. PMID:20033351

LeBlanc, A. J.; Moseley, A. M.; Chen, B. T.; Frazer, D.; Castranova, V.

2010-01-01

108

Reactive oxygen species produced by irradiation of some phthalocyanine derivatives  

Microsoft Academic Search

A comparative study of the reliability of methods used for the determination of singlet oxygen was carried out. The water iodide method, as well as the methods using 9,10-dimethylanthracene (DMA) and 1,3-diphenylisobenzofuran (DPIBF) in dimethylformamide (DMF) solutions, was used for the detection of singlet oxygen 1O2 production in eight phthalocyanine photosensitizers. The iodide method is not only selective for the

Ji?í ?erný; Marie Karásková; Jan Rakušan; Stanislav Nešp?rek

2010-01-01

109

Lycopene cyclase paralog CruP protects against reactive oxygen species in oxygenic photosynthetic organisms.  

PubMed

In photosynthetic organisms, carotenoids serve essential roles in photosynthesis and photoprotection. A previous report designated CruP as a secondary lycopene cyclase involved in carotenoid biosynthesis [Maresca J, et al. (2007) Proc Natl Acad Sci USA 104:11784-11789]. However, we found that cruP KO or cruP overexpression plants do not exhibit correspondingly reduced or increased production of cyclized carotenoids, which would be expected if CruP was a lycopene cyclase. Instead, we show that CruP aids in preventing accumulation of reactive oxygen species (ROS), thereby reducing accumulation of ?-carotene-5,6-epoxide, a ROS-catalyzed autoxidation product, and inhibiting accumulation of anthocyanins, which are known chemical indicators of ROS. Plants with a nonfunctional cruP accumulate substantially higher levels of ROS and ?-carotene-5,6-epoxide in green tissues. Plants overexpressing cruP show reduced levels of ROS, ?-carotene-5,6-epoxide, and anthocyanins. The observed up-regulation of cruP transcripts under photoinhibitory and lipid peroxidation-inducing conditions, such as high light stress, cold stress, anoxia, and low levels of CO(2), fits with a role for CruP in mitigating the effects of ROS. Phylogenetic distribution of CruP in prokaryotes showed that the gene is only present in cyanobacteria that live in habitats characterized by large variation in temperature and inorganic carbon availability. Therefore, CruP represents a unique target for developing resilient plants and algae needed to supply food and biofuels in the face of global climate change. PMID:22706644

Bradbury, Louis M T; Shumskaya, Maria; Tzfadia, Oren; Wu, Shi-Biao; Kennelly, Edward J; Wurtzel, Eleanore T

2012-07-01

110

Effects of rank and calcium catalysis on oxygen chemisorption and gasification reactivity of coal chars  

NASA Astrophysics Data System (ADS)

The effects of coal rank and calcium catalysis on oxygen gasification of coal chars have been investigated. Five different coals, from lignite to anthracite were used. Coals were demineralized and a calcium catalyst was deposited on the carbon in different amounts, by ion exchange for lignite and subbituminous coals and by impregnation for the others. Chars from all coals were obtained by both slow and rapid pyrolysis. Oxygen chemisorption studies conducted under conditions far away from gasification and measured oxygen uptakes during gasification revealed that large amounts of oxygen are chemisorbed. The lower the coal rank, the greater the amount of chemisorbed oxygen in both cases. The presence of a calcium catalyst additionally increased the oxygen uptake by solid carbons. The chemisorption tests also showed the influence of diffusion inside the smallest micropores on the kinetics of the process. Reactivity profiles were investigated in detail. Demineralized coal chars showed monotonic, linear increases with burn-off for a broad range of conversion (20-80%). The higher the coal rank, the greater the reactivity increase per unit burn-off. A comparison of reactivities of the demineralized form of coal chars confirmed that the reactivity is affected by diffusion inside the smallest micropores for experiments in the intermediate temperature range, usually 700-800 K. A comparison of reactivities of the calcium-loaded and demineralized coal chars prepared and subsequently reacted at the same conditions has confirmed that the catalytic effect of calcium is the greatest for lower-rank coals, and that it decreases with increasing coal rank. Comparable reactivities for as-received and calcium-loaded lignite and subbituminous char were about two orders of magnitude greater than for a corresponding demineralized char. For higher ranks of coal the effect of calcium loading is smaller than one order of magnitude. For the lower ranks of coal, where calcium is very well dispersed, reactivity profiles are confirmed to be dominated by the catalytic effect. Based on the reactivity and oxygen chemisorption studies, it was concluded that the effect of oxygen diffusion on char reactivity is much greater for higher-rank coals than for lower-rank coals. For the lignite char the diffusion effect is only important at the beginning of gasification and it decreases with increasing burn-off. For the anthracite char it is about 3 times greater at the very low burn-offs than at 85% burn-off. In addition, for demineralized anthracite char this diffusion effect lasts longer in terms of time and conversion.

Piotrowski, Andrzej

111

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

PubMed

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

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

2014-04-14

112

Reactive oxygen species in the aerobic decomposition of sodium hydroxymethanesulfinate.  

PubMed

Sodium hydroxymethanesulfinate, (HOCH2SO2Na, HMS) is relatively stable in aqueous alkaline environments, but rapidly decomposes in acidic medium to give a variety of products that include sulfur dioxide. A detailed kinetic and mechanistic study of the decomposition of HMS in slightly acidic medium has shown a process that produces dithionite, S2O2-4, which is preceded by an induction period which persists for as long as molecular oxygen is present in the reaction solution. The complete consumption of molecular oxygen is a prerequisite for the formation of S2O2-4. Among some of the intermediates detected in the decomposition of HMS is the sulfite radical, SO-3. Comparisons are made between the decomposition mechanisms of thiourea dioxide (aminoiminomethanesulfinic acid) and HMS. PMID:10395746

Makarov, S V; Mundoma, C; Svarovsky, S A; Shi, X; Gannett, P M; Simoyi, R H

1999-07-15

113

Impact reactivity of materials at very high oxygen pressure  

NASA Technical Reports Server (NTRS)

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.

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

1983-01-01

114

[Oxidised dextrans influence on reactive oxygen species generation by murine peritoneal exudate phagocytic cells].  

PubMed

The effects of oxidized dextrans of different molecular weight on reactive oxygen species production and transmembrane mitochondrial potential of macrophages and neutrophils have been studied in vivo and in vitro. Oxidised dextrans demonstrated moderate direct antioxidant ability but induced intracellular oxidative stress through the increase of oxygen radical generation. This effect of the investigated compounds amplifies the cytotoxic and bactericidal potential of phagocytes and can influence isoniazid metabolism, thus increasing its efficiency in therapy of infectious diseases. PMID:23650725

Tkachev, V O; Za?kovskaia, M V; Troitski?, A V; Luzgina, N G; Shkurupi?, V A

2013-01-01

115

Reactive oxygen species-dependent RhoA activation mediates collagen synthesis in hyperoxic lung fibrosis  

Microsoft Academic Search

Lung fibrosis is an ultimate consequence of pulmonary oxygen toxicity in human and animal models. Excessive production and deposition of extracellular matrix proteins, e.g., collagen-I, is the most important feature of pulmonary fibrosis in hyperoxia-induced lung injury. In this study, we investigated the roles of RhoA and reactive oxygen species (ROS) in collagen-I synthesis in hyperoxic lung fibroblasts and in

Dmitry Kondrikov; Ruth B. Caldwell; Zheng Dong; Yunchao Su

2011-01-01

116

Anoxia-induced changes in reactive oxygen species and cyclic nucleotides in the painted turtle  

Microsoft Academic Search

The Western painted turtle survives months without oxygen. A key adaptation is a coordinated reduction of cellular ATP production\\u000a and utilization that may be signaled by changes in the concentrations of reactive oxygen species (ROS) and cyclic nucleotides\\u000a (cAMP and cGMP). Little is known about the involvement of cyclic nucleotides in the turtle’s metabolic arrest and ROS have\\u000a not been

Matthew Edward Pamenter; Michael David Richards; Leslie Thomas Buck

2007-01-01

117

The reactivity of ?-oxoaldehyde with reactive oxygen species in diabetes complications  

PubMed Central

The reactions of three ?-oxoaldehydes (methylglyoxal, glyoxal, and pyruvic acid) with hydroxyl radicals generated by sonolysis of water were investigated using an electron spin resonance (electron paramagnetic resonance) spin-trapping method, and their reaction kinetics were investigated. It is apparent from our experimental results that methylglyoxal exhibits the highest reactivity of the three ?-oxoaldehydes. These ?-oxoaldehydes can react with hydroxyl radicals faster than other well-known antioxidants can. The reactivity of hydroxyl radicals is higher than that of hydrogen peroxides. PMID:23526048

Matsumura, Yuriko; Iwasawa, Atsuo; Kobayashi, Toshihiro; Kamachi, Toshiaki; Ozawa, Toshihiko; Kohno, Masahiro

2013-01-01

118

Induction of Apoptosis in Human Multiple Myeloma Cell Lines by Ebselen via Enhancing the Endogenous Reactive Oxygen Species Production  

PubMed Central

Ebselen a selenoorganic compound showing glutathione peroxidase like activity is an anti-inflammatory and antioxidative agent. Its cytoprotective activity has been investigated in recent years. However, experimental evidence also shows that ebselen causes cell death in several cancer cell types whose mechanism has not yet been elucidated. In this study, we examined the effect of ebselen on multiple myeloma (MM) cell lines in vitro. The results showed that ebselen significantly enhanced the production of reactive oxygen species (ROS) accompanied by cell viability decrease and apoptosis rate increase. Further studies revealed that ebselen can induce Bax redistribution from the cytosol to mitochondria leading to mitochondrial membrane potential ??m changes and cytochrome C release from the mitochondria to cytosol. Furtherly, we found that exogenous addition of N-acetyl cysteine (NAC) completely diminished the cell damage induced by ebselen. This result suggests that relatively high concentration of ebselen can induce MM cells apoptosis in culture by enhancing the production of endogenous ROS and triggering mitochondria mediated apoptotic pathway. PMID:24587987

Du, Jia; Li, Mengxia; Qian, Chengyuan; Cheng, Yi; Peng, Yang; Xie, Jiayin; Wang, Dong

2014-01-01

119

Reactive Oxygen Species-mediated Immunity against Leishmania mexicana and Serratia marcescens in the Phlebotomine Sand Fly Lutzomyia longipalpis*  

PubMed Central

Phlebotomine sand flies are the vectors of medically important Leishmania. The Leishmania protozoa reside in the sand fly gut, but the nature of the immune response to the presence of Leishmania is unknown. Reactive oxygen species (ROS) are a major component of insect innate immune pathways regulating gut-microbe homeostasis. Here we show that the concentration of ROS increased in sand fly midguts after they fed on the insect pathogen Serratia marcescens but not after feeding on the Leishmania that uses the sand fly as a vector. Moreover, the Leishmania is sensitive to ROS either by oral administration of ROS to the infected fly or by silencing a gene that expresses a sand fly ROS-scavenging enzyme. Finally, the treatment of sand flies with an exogenous ROS scavenger (uric acid) altered the gut microbial homeostasis, led to an increased commensal gut microbiota, and reduced insect survival after oral infection with S. marcescens. Our study demonstrates a differential response of the sand fly ROS system to gut microbiota, an insect pathogen, and the Leishmania that utilize the sand fly as a vehicle for transmission between mammalian hosts. PMID:22645126

Diaz-Albiter, Hector; Sant'Anna, Mauricio R. V.; Genta, Fernando A.; Dillon, Rod J.

2012-01-01

120

EPR detection of reactive oxygen species in hemolymph of Galleria mellonella and Dendrolimus superans sibiricus (Lepidoptera) larvae.  

PubMed

The formation of reactive oxygen species (ROS) in hemolymph and hemocytes of Galleria mellonella and Dendrolimus superans sibiricus larvae was studied by ESR spectroscopy using spin-trap 1-hydroxy-3-carboxy-pyrrolidine (CP-H). The background level of ROS formation was detected in the intact hemolymph. The addition of dihydroxyphenylalanine (DOPA) into free cells of the hemolymph increased CP-H oxidation about two times for G. mellonella and about four times for D. superans sibiricus. This increase was completely inhibited by a specific inhibitor of phenoloxidase, phenylthiourea. The presence of exogenous superoxide dismutase (SOD) did not change CP-H oxidation in the hemolymph. The data obtained in hemocytes showed only a DOPA-induced increase in CP-H oxidation. Phagocytosis activators did not affect ROS formation in hemocytes of both insect species. SOD decreased DOPA-induced CP-H oxidation 20-30% in suspension of hemocytes of D. superans sibiricus only. Our results are in agreement with the contribution of superoxide radical and DOPA-derived quinones/semiquinones in the immune response of insects. PMID:10527867

Slepneva, I A; Glupov, V V; Sergeeva, S V; Khramtsov, V V

1999-10-14

121

Scavenging of reactive oxygen species by letosteine, a molecule with two blocked SH groups  

Microsoft Academic Search

Acute production of reactive oxygen species by polymorphonuclear neutrophils during the respiratory burst may induce tissue injuries. In thisin vitro study, it was demonstrated that letosteine, a mucolytic agent containing two blocked thiol groups, had antioxidant activity, but only when it was first submitted to alkaline hydrolysis. In a cell-free system, hydrogen peroxide, hypochlorous acid and hydroxyl radical concentrations were

B. Gressier; N. Lebegue; C. Brunet; M. Luyckx; T. Dine; M. Cazin; J. C. Cazin

1995-01-01

122

Involvement of reactive oxygen species in aflatoxin B 1-induced cell injury in cultured rat hepatocytes  

Microsoft Academic Search

The role of reactive oxygen species (ROS) in AFB1-induced cell injury was investigated using cultured rat hepatocytes. Malonaldehyde (MDA) generation and lactate dehydrogenase (LDH) release were determined as indices of lipid peroxidation and cell injury, respectively. Exposure to AFB1 for up to 72 h resulted in significantly elevated levels of LDH being released into the medium as well as the

Han-Ming Shen; Choon-Nam Ong; Chen-Yang Shi

1995-01-01

123

Reactive Oxygen Species—Induced Apoptosis and Necrosis in Bovine Corneal Endothelial Cells  

Microsoft Academic Search

PURPOSE. The loss of corneal endothelial cells associated with aging and possibly other causes has been speculated to be related to exposure to reactive oxygen species (ROS). The current study was conducted to investigate, by use of photosensitizers, the underlying mechanisms involved in the death of bovine corneal endothelial cells (BCENs) caused by ROS. METHODS. BCEN cells in primary culture

Kyung-Sun Cho; Eunjoo H. Lee; Jun-Sub Choi; Choun-Ki Joo

1999-01-01

124

Regulation of Gene Expression in the Nervous System by Reactive Oxygen and Nitrogen Species  

Microsoft Academic Search

Reactive oxygen and nitrogen species function as direct and indirect modulators of gene expression through their interactions with transcription factors and also key enzymes in receptor-activated signalling pathways. This regulatory role may become displaced under certain circumstances such as aging, autoimmune responses and viral infection, leading to the pathological outcome associated with inflammatory and degenerative diseases in the CNS.

Jean E. Merrill; Sean P. Murphy

1997-01-01

125

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

Microsoft Academic Search

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

I. A. Gamaley; I. V. Klyubin

1999-01-01

126

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

Microsoft Academic Search

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

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

2009-01-01

127

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

E-print Network

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

Schnaufer, Achim

128

Spatiotemporal Patterning of Reactive Oxygen Production and Ca2+ Wave Propagation in Fucus Rhizoid Cells  

Microsoft Academic Search

Both Ca 2 ? and reactive oxygen species (ROS) play critical signaling roles in plant responses to biotic and abiotic stress. However, the positioning of Ca 2 ? and ROS (in particular H 2 O 2 ) after a stress stimulus and their subcellular interactions are poorly understood. Moreover, although information can be encoded in different patterns of cellular Ca

Susana M. Coelho; Alison R. Taylor; Keith P. Ryan; Isabel Sousa-Pinto; Murray T. Brown; Colin Brownlee; Drake Circus

2002-01-01

129

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

E-print Network

CANCER When antioxidants are bad Reactive oxygen species (ROS) get a bad press, as evidenced by the notable trend in the use of dietary and cosmetic antioxidants. New work suggests, however, that ROS might-- the transcription factor that mainly regulates physiological antioxidant pathways -- is also increased in some

Cai, Long

130

Redundant Catalases Detoxify Phagocyte Reactive Oxygen and Facilitate Histoplasma capsulatum Pathogenesis  

PubMed Central

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

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

2013-01-01

131

Two Distinct Sources of Elicited Reactive Oxygen Species in Tobacco Epidermal Cells  

Microsoft Academic Search

Reactive oxygen species (ROS) play a prominent role in early and later stages of the plant pathogenesis response, pu- tatively acting as both cellular signaling molecules and direct antipathogen agents. A single-cell assay, based on the fluorescent probe dichlorofluorescein, was used to scrutinize the generation and movement of ROS in tobacco epider- mal tissue. ROS, generated within cells, quickly moved

Andrew C. Allan; Robert Fluhr

1997-01-01

132

Molecular evolution of the reactive oxygen-generating NADPH oxidase (Nox\\/Duox) family of enzymes  

Microsoft Academic Search

BACKGROUND: NADPH-oxidases (Nox) and the related Dual oxidases (Duox) play varied biological and pathological roles via regulated generation of reactive oxygen species (ROS). Members of the Nox\\/Duox family have been identified in a wide variety of organisms, including mammals, nematodes, fruit fly, green plants, fungi, and slime molds; however, little is known about the molecular evolutionary history of these enzymes.

Tsukasa Kawahara; Mark T Quinn; J David Lambeth

2007-01-01

133

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

Microsoft Academic Search

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

Hiroyuki Yasui; Hiromu Sakurai

2000-01-01

134

Detection of reactive oxygen species by flow cytometry after spinal cord injury  

E-print Network

that reactive oxygen species (ROS) are important mediators of secondary injury in CNS trauma (Hall, 1989; Coyle the mechanism of secondary damage and evaluating the effectiveness of antioxidants. Flow cytometry trauma in live animals (Hall, 1989). The inhibition of ROS has been shown to provide behavioral

Shi, Riyi

135

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

E-print Network

Introduction Traumatic spinal cord injury (SCI) is the consequence of a primary physical injury and a secondary profound and mediated by a series of secondary injury mechanisms. Among these secondary injury mechan- isms, reactive oxygen species (ROS) have been postulated to play a critical role in CNS trauma.6 ± 8 It is well

Shi, Riyi

136

Reactive Oxygen Species and Root Hairs in Arabidopsis Root Response to Nitrogen, Phosphorus and Potassium Deficiency  

Microsoft Academic Search

; Plant root sensing and adaptation to changes in the nutrient status of soils is vital for long-term productivity and growth. Reactive oxygen species (ROS) have been shown to play a role in root response to potassium depriva- tion. To determine the role of ROS in plant response to nitrogen and phosphorus deficiency, studies were con- ducted using wild-type Arabidopsis

Ryoung Shin; R. Howard Berg; Daniel P. Schachtman

2005-01-01

137

Redox regulation of anoikis: reactive oxygen species as essential mediators of cell survival  

Microsoft Academic Search

Proper attachment to the extracellular matrix (ECM) is essential for cell survival. The loss of integrin-mediated cell–ECM contact results in an apoptotic process termed anoikis. However, mechanisms involved in regulation of cell survival are poorly understood and mediators responsible for anoikis have not been well characterized. Here, we demonstrate that reactive oxygen species (ROS) produced through the involvement of the

E Giannoni; F Buricchi; G Grimaldi; M Parri; F Cialdai; M L Taddei; G Raugei; G Ramponi; P Chiarugi

2008-01-01

138

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

Microsoft Academic Search

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

Tzou Chi Huang; Ya Ting Lin; Kuo Pin Chuang

2010-01-01

139

Role of Auxin-Induced Reactive Oxygen Species in Root Gravitropism  

Microsoft Academic Search

We report our studies on root gravitropism indicating that reactive oxygen species (ROS) may function as a downstream component in auxin-mediated signal transduction. A transient increase in the intracellular concentration of ROS in the convex endodermis resulted from either gravistimulation or unilateral application of auxin to vertical roots. Root bending was also brought about by unilateral application of ROS to

Jung Hee Joo; Yun Soo Bae; June Seung Lee

2001-01-01

140

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

Microsoft Academic Search

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.

Laura D. Mydlarz; Robert S. Jacobs

2006-01-01

141

Reactive Oxygen Species and Acute Modulation of Albumin Microvascular Leakage in the Microcirculation of Diabetic Rats in vivo  

Microsoft Academic Search

Endothelial cells have been reported to generate reactive oxygen species such as the superoxide anion, hydrogen peroxide, and the hydroxyl radical. The aim of this work was to evaluate the role of reactive oxygen species in diabetes-induced changes in vascular permeability. Intravital videomicroscopy was used to study albumin microvascular leakage in the cremaster muscle. The extravasation of a fluorescent macromolecular

E. Bonnardel-Phu; E. Vicaut

2000-01-01

142

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

PubMed Central

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

2014-01-01

143

Cell death from antibiotics without the involvement of reactive oxygen species  

PubMed Central

Recent observations have suggested that classic antibiotics kill bacteria by stimulating the formation of reactive oxygen species. If true, this notion might guide new strategies to improve antibiotic efficacy. In this study the model was directly tested. Contrary to the hypothesis, antibiotic treatment did not accelerate the formation of hydrogen peroxide in Escherichia coli and did not elevate intracellular free iron, an essential reactant for the production of lethal damage. Lethality persisted in the absence of oxygen, and DNA repair mutants were not hypersensitive, undermining the idea that toxicity arose from oxidative DNA lesions. We conclude that these antibiotic exposures did not produce reactive oxygen species and that lethality more likely resulted from the direct inhibition of cell-wall assembly, protein synthesis, and DNA replication. PMID:23471409

Liu, Yuanyuan; Imlay, James A.

2013-01-01

144

Reactive Oxygen Species on the Early Earth and Survival of Bacteria  

NASA Technical Reports Server (NTRS)

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.

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

2011-01-01

145

The Contributions of Reactive Oxygen Intermediates and Reactive Nitrogen Intermediates to Listericidal Mechanisms Differ in Macrophages Activated Pre- and Postinfection  

PubMed Central

The contribution of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) to the killing of Listeria monocytogenes by macrophages activated by addition of spleen cells from listeria-immune mice plus specific antigen was examined. When macrophages were infected with L. monocytogenes and then spleen cells were added, there was not as big a difference in listericidal activity between macrophages cultured with normal spleen cells and those cultured with immune spleen cells as expected. In this culture system, RNI was mainly involved in the macrophage intracellular killing. In macrophages first activated and then infected, a significant level of enhanced killing was observed. Blockade of ROI production drastically affected the enhanced killing ability, while inhibition of RNI production had a negligible effect. Thus, the contributions of ROI and RNI to listericidal mechanisms of macrophages were different between macrophages activated at pre- and postinfection stages. PMID:9712745

Ohya, Satoshi; Tanabe, Yoshinari; Makino, Masato; Nomura, Takamasa; Xiong, Huabao; Arakawa, Masaaki; Mitsuyama, Masao

1998-01-01

146

Responses of corn root protoplasts to exogenous reduced nicotinamide adenine dinucleotide: Oxygen consumption, ion uptake, and membrane potential  

PubMed Central

Addition of 1.5 mM NADH tripled the O2 consumption in corn root protoplasts. The stimulation was temperature and pH dependent, specific to NADH, and accompanied by a 2- to 3-fold increase in K+ and Pi uptake into protoplasts. The increase in ion uptake was not due to the accumulation of NADH into protoplasts. The effect of exogenous NADH on O2 consumption and ion uptake was also evident in corn root segments but to a lesser extent. A 20-mV hyperpolarization of protoplast membrane potential occurred on addition of NADH and was abolished by the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone. Increases in cell volume of 30% and 40% were detected in response to NADH/H+ and NADH/H+/K+, respectively. The data are discussed in terms of a transmembrane redox reaction and the possibility that some part of the energy-linked ion transport may be driven by a NADH ? O2 electron-transport system in the plasmalemma. PMID:16593197

Lin, Willy

1982-01-01

147

Pump administration of exogenous surfactant: effects on oxygenation, heart rate, and chest wall movement of premature infants.  

PubMed

Adverse reactions of infants to surfactant administration include loss of chest wall movement and decrease in oxygen saturation and heart rate. We are aware of no previous studies addressing the administration of surfactant. We studied 22 infants with respiratory distress syndrome to determine whether these adverse reactions could be reduced by giving surfactant slowly by microinfusion syringe pump. Loss of chest wall movement was significantly greater in infants receiving surfactant by the hand-dosing method as compared with administration of surfactant by pump. A significant increase in ventilator pressure interventions was observed when surfactant was given by standard hand bolus method compared with pump infusion. Heart rate and oxygen saturation did not differ significantly between the two techniques. These findings suggest that pump administration of surfactant minimized potential airway obstruction; thus it may be an alternative to standard bolus dosing techniques. PMID:8345382

Sitler, C G; Turnage, C S; McFadden, B E; Smith, E O; Adams, J M

1993-01-01

148

Exogenous ochronosis.  

PubMed

A 55-year-old woman with melasma develops biopsy-proved exogenous ochronosis in the setting of prolonged topical hydroquinone use. A limited number of similar reports exist in the US literature and are the basis for an FDA call to review hydroquinone-based products. This case underscores the difficult therapeutic dilemma which this diagnosis presents to dermatologists. PMID:19061605

Merola, Joseph F; Meehan, Shane; Walters, Ruth F; Brown, Lance

2008-01-01

149

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

PubMed Central

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

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

150

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

NASA Astrophysics Data System (ADS)

The atomic oxygen metastable dynamics in a Reactive High-Power Impulse Magnetron Sputtering (R-HiPIMS) discharge has been characterized using time-resolved diode laser absorption in an Ar/O2 gas mixture with a Ti target. Two plasma regions are identified: the ionization region (IR) close to the target and further out the diffusion region (DR), separated by a transition region. The ?s temporal resolution allows identifying the main atomic oxygen production and destruction routes, which are found to be very different during the pulse as compared to the afterglow as deduced from their evolution in space and time.

Vitelaru, Catalin; Lundin, Daniel; Brenning, Nils; Minea, Tiberiu

2013-09-01

151

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

NASA Technical Reports Server (NTRS)

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.

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

1998-01-01

152

Probing oxidative stress: Small molecule fluorescent sensors of metal ions, reactive oxygen species, and thiols  

PubMed Central

Oxidative stress is a common feature shared by many diseases, including neurodegenerative diseases. Factors that contribute to cellular oxidative stress include elevated levels of reactive oxygen species, diminished availability of detoxifying thiols, and the misregulation of metal ions (both redox-active iron and copper as well as non-redox active calcium and zinc). Deciphering how each of these components interacts to contribute to oxidative stress presents an interesting challenge. Fluorescent sensors can be powerful tools for detecting specific analytes within a complicated cellular environment. Reviewed here are several classes of small molecule fluorescent sensors designed to detect several molecular participants of oxidative stress. We focus our review on describing the design, function and application of probes to detect metal cations, reactive oxygen species, and intracellular thiol-containing compounds. In addition, we highlight the intricacies and complications that are often faced in sensor design and implementation. PMID:23440254

Hyman, Lynne M.; Franz, Katherine J.

2013-01-01

153

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

PubMed Central

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

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

154

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

NASA Astrophysics Data System (ADS)

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.

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

2014-01-01

155

Fluorescence-based assay for reactive oxygen species: A protective role for creatinine  

Microsoft Academic Search

Attack by reactive oxygen species leads to a decay in phycoerythrin fluorescence emission. This phenomenon provides a versatile new assay for small molecules and macromolecules that can function as protective compounds. With 1-2 à 10⁻⁸ M phycoerythrin, under conditions where peroxyl radical generation is rate-limiting, the fluorescence decay follows apparent zero-order kinetics. On reaction with HO{center dot}, generated with the

ALEXANDER N. GLAZER

1988-01-01

156

Detection of elevated reactive oxygen species level in cultured rat hepatocytes treated with aflatoxin B 1  

Microsoft Academic Search

Accumulating evidence demonstrates that oxidative damage is one of the underlying mechanisms to the cytotoxicity and carcinogenicity of AFB1. The main objective of this study is to show that AFB, increases reactive oxygen species (ROS) formation in hepatocytes. The ROS level was detected using a fluorescence probe, 2?,7?-dichlorofluorescin diacetate (DCFH-DA), which could be converted to highly fluorescent dichlorofluorescein (DCF) with

Han-Ming Shen; Chen-Yang Shi; Yi Shen; Choon-Nam Ong

1996-01-01

157

Nitric oxide counteracts cytotoxic processes mediated by reactive oxygen species in plant tissues  

Microsoft Academic Search

.   Many environmental conditions subject plants to oxidative stress, in which reactive oxygen species (ROS) are overproduced.\\u000a These ROS act as transduction signals in plant defense responses, but also cause effects that result in cellular damage. Since\\u000a nitric oxide (NO) is a bioactive molecule able to scavenge ROS, we analyzed its effect on some cytotoxic processes produced\\u000a by ROS in

María Verónica Beligni; Lorenzo Lamattina

1999-01-01

158

Pathophysiological and pharmacological implications of mitochondria-targeted reactive oxygen species generation in astrocytes  

Microsoft Academic Search

Astrocytes, in addition to passively supporting neurons, have recently been shown to be actively involved in synaptic transmission and neurovascular coupling in the central nervous system (CNS). This review summarizes briefly our previous observations using fluorescent probes coupled with laser scanning digital imaging microscopy to visualize spatio-temporal alteration of mitochondrial reactive oxygen species (mROS) generation in intact astrocytes. mROS formation

Mei-Jie Jou

2008-01-01

159

Optical imaging of intracellular reactive oxygen species for the assessment of the cytotoxicity of nanoparticles  

Microsoft Academic Search

The generation of intracellular reactive oxygen species (ROS) was optically monitored using ROS-sensitive gold nanoprobes in response to an exposure of nanoparticles (NPs). Fluorescent dye-labeled hyaluronic acid was grafted onto the surface of gold nanoparticles (HF-AuNPs) for imaging intracellular ROS. The ultrasensitive detection of intracellular ROS was utilized as a powerful analytical tool to assess early cellular toxicities of monodisperse

Kyuri Lee; Hyukjin Lee; Kun Woo Lee; Tae Gwan Park

2011-01-01

160

Induced reactive oxygen species improve enzyme production from Aspergillus niger cultivation  

Microsoft Academic Search

Intracellular reactive oxygen species (iROS) induction by HOCl was used as a novel strategy to improve enzyme productivities in Aspergillus niger growing in a bioreactor. With induced iROS, the specific intracellular activities of a-amylase, protease, catalase, and glucose oxidase were increased by about 170%, 250%, 320%, and 260%, respectively. The optimum specific iROS level for achieving maximum cell concentration and

Susmita Sahoo; K. Krishnamurthy Rao; G. K. Suraishkumar

2003-01-01

161

Biocompatible Reactive Oxygen Species (ROS)-Responsive Nanoparticles as Superior Drug Delivery Vehicles.  

PubMed

A novel reactive oxygen species (ROS)-responsive nanoplatform can be successfully manufactured from a ROS-triggerable ?-cyclodextrin material. Extensive in vitro and in vivo studies validate that this nanoscaled system may serve as a new drug delivery vehicle with well-defined ROS-sensitivity and superior biocompatibility. This nanocarrier can be used for ROS-triggered transport of diverse therapeutics and imaging agents. PMID:25147049

Zhang, Dinglin; Wei, Yanling; Chen, Kai; Zhang, Xiangjun; Xu, Xiaoqiu; Shi, Qing; Han, Songling; Chen, Xin; Gong, Hao; Li, Xiaohui; Zhang, Jianxiang

2015-01-01

162

Roles of the reactive oxygen species-generating peroxidase reactions in plant defense and growth induction  

Microsoft Academic Search

Extracellularly secreted plant peroxidases (POXs) are considered to catalyze the generation of reactive oxygen species (ROS) coupled to oxidation of plant hormone indole-3-acetic acid (IAA) and defense-related compounds salicylic acid (SA), aromatic monoamines (AMAs) and chitooligosaccharides (COSs). This review article consists of two parts, which describe H2O2-dependent and H2O2-independent mechanisms for ROS generation, respectively. Recent studies have shown that plant

T. Kawano

2003-01-01

163

Role of reactive oxygen species and antioxidants on pathophysiology of male reproduction  

Microsoft Academic Search

The excessive generation of reactive oxygen species (ROS) by abnormal spermatozoa and contaminating leukocytes has been defined\\u000a as one of the few etiologies for male infertility. Administration of antioxidants in patients with ‘male factor’ infertility\\u000a has begun to attract considerable interest. The main difficulty of such an approach is our incomplete understanding of the\\u000a role of free radicals in normal

M Maneesh; H Jayalekshmi

2006-01-01

164

Role of reactive oxygen species in brainstem in neural mechanisms of hypertension.  

PubMed

The involvement of reactive oxygen species such as superoxide is implicated in the pathogenesis of hypertension. The brain contains a high concentration of polyunsaturated fatty acids in its cell membranes. These fatty acids are targets of oxygen-derived free radicals. Thiobarbituric acid-reactive substances (TBARS), an indirect marker of oxidative stress, are increased in the brainstem of stroke-prone spontaneously hypertensive rats (SHRSP) compared with those of Wistar-Kyoto rats (WKY). In addition, the intensity of electron spin resonance signals taken from the rostral ventrolateral medulla (RVLM), a cardiovascular center, decreases more rapidly in SHRSP than in WKY. To confirm the role of reactive oxygen species in the RVLM or the nucleus tractus solitarius (NTS) in SHRSP, we transfected adenovirus vectors encoding the manganese superoxide dismutase (MnSOD) gene (AdMnSOD) or Cu/Zn-SOD gene (AdCu/ZnSOD) bilaterally into the RVLM or the NTS. After the gene transfer, blood pressure and heart rate of SHRSP, monitored by radio-telemetry system, were significantly decreased compared with non-treated SHRSP, but not WKY. Urinary norepinephrine excretion was significantly decreased in AdMnSOD- or AdCu/ZnSOD-transfected SHRSP, but not in WKY. Furthermore, we found that activation of NAD(P)H oxidase via Rac1 is a source of reactive oxygen species generation in the brain of hypertensive rats. Taken together, these results suggest that the increased oxidative stress in the RVLM and the NTS contribute to the central nervous system mechanisms underlying hypertension in SHRSP. We also found that atorvastatin has actions of reducing oxidative stress in the brain associated with sympatho-inhibitory effects. PMID:18650132

Hirooka, Yoshitaka

2008-11-01

165

Differential Reactivity of [beta]-Carotene Isomers from Dunaliella bardawil Toward Oxygen Radicals.  

PubMed

Dunaliella bardawil accumulates massive amounts of [beta]-carotene in two isoforms, a 9-cis and an all-trans stereoisomer, when grown under high irradiance, as a means to protect the cells against photoinhibition (A. Ben-Amotz, A. Shaish, M. Avron [1989] Plant Physiol 91: 1040-1043). The purpose of this work has been to find out if the mechanism of protection involves scavenging of reactive oxygen species. For this purpose high- and low-[beta]-carotene-containing cells were compared with respect to their sensitivity to several external oxidants [H2O2, methyl viologen, rose bengal, and 2,2[prime]-azobis(2-amidinopropane)HCl]. All oxidants induce a light-stimulated degradation of [beta]-carotene and of chlorophyll. The degradation of [beta]-carotene precedes that of chlorophyll, indicating that it is more reactive toward oxidants. The 9-cis [beta]-carotene is degraded faster than the all-trans stereoisomer when exposed to oxidants, both in intact cells and in isolated [beta]-carotene globules, indicating that it is a more effective scavenger of reactive oxygen species. Comparison of the sensitivity to different oxidants, between high- and low-[beta]-carotene-containing cells, reveals similar rates of chlorophyll and [beta]-carotene degradation in the two populations. Survival tests toward H2O2 and rose bengal show that high-[beta]-carotene cells have a similar sensitivity toward H2O2 but are more resistant toward rose bengal, a photoactivated generator of singlet oxygen, possibly due to masking of the latter by [beta]-carotene. These results suggest that the protection mechanism of massively accumulated [beta]-carotene in Dunaliella against photoinhibition is not due to scavenging of reactive oxygen species. PMID:12231693

Jimenez, C.; Pick, U.

1993-02-01

166

Differential Reactivity of [beta]-Carotene Isomers from Dunaliella bardawil Toward Oxygen Radicals.  

PubMed Central

Dunaliella bardawil accumulates massive amounts of [beta]-carotene in two isoforms, a 9-cis and an all-trans stereoisomer, when grown under high irradiance, as a means to protect the cells against photoinhibition (A. Ben-Amotz, A. Shaish, M. Avron [1989] Plant Physiol 91: 1040-1043). The purpose of this work has been to find out if the mechanism of protection involves scavenging of reactive oxygen species. For this purpose high- and low-[beta]-carotene-containing cells were compared with respect to their sensitivity to several external oxidants [H2O2, methyl viologen, rose bengal, and 2,2[prime]-azobis(2-amidinopropane)HCl]. All oxidants induce a light-stimulated degradation of [beta]-carotene and of chlorophyll. The degradation of [beta]-carotene precedes that of chlorophyll, indicating that it is more reactive toward oxidants. The 9-cis [beta]-carotene is degraded faster than the all-trans stereoisomer when exposed to oxidants, both in intact cells and in isolated [beta]-carotene globules, indicating that it is a more effective scavenger of reactive oxygen species. Comparison of the sensitivity to different oxidants, between high- and low-[beta]-carotene-containing cells, reveals similar rates of chlorophyll and [beta]-carotene degradation in the two populations. Survival tests toward H2O2 and rose bengal show that high-[beta]-carotene cells have a similar sensitivity toward H2O2 but are more resistant toward rose bengal, a photoactivated generator of singlet oxygen, possibly due to masking of the latter by [beta]-carotene. These results suggest that the protection mechanism of massively accumulated [beta]-carotene in Dunaliella against photoinhibition is not due to scavenging of reactive oxygen species. PMID:12231693

Jimenez, C.; Pick, U.

1993-01-01

167

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

PubMed

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

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

2011-07-15

168

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

PubMed Central

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

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

1997-01-01

169

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

PubMed

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 in molecular oxygen. Four major ROS are recognized comprising superoxide (O2•-), hydrogen peroxide (H2O2), hydroxyl radical (•OH), and singlet oxygen ((1)O2), but they display very different kinetics and levels of activity. The effects of O2•- and H2O2 are less acute than those of •OH and (1)O2, because the former are much less reactive and can be detoxified by endogenous antioxidants (both enzymatic and nonenzymatic) that are induced by oxidative stress. In contrast, no enzyme can detoxify •OH or (1)O2, 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 nonpharmacological 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

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

2013-11-01

170

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

PubMed

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

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

2015-02-01

171

Divergent effects of Sulforaphane on Basal and Glucose-Stimulated Insulin Secretion in ?-Cells: Role of Reactive Oxygen Species and Induction of Endogenous Antioxidants  

PubMed Central

Purpose Oxidative stress is implicated in pancreatic ?-cell dysfunction, yet clinical outcomes of antioxidant therapies on diabetes are inconclusive. Since reactive oxygen species (ROS) can function as signaling intermediates for glucose-stimulated insulin secretion (GSIS), we hypothesize that exogenously boosting cellular antioxidant capacity dampens signaling ROS and GSIS. Methods To test the hypothesis, we formulated a mathematical model of redox homeostatic control circuit comprising known feedback and feedforward loops and validated model predictions with plant-derived antioxidant sulforaphane (SFN). Results SFN acutely (30-min treatment) stimulated basal insulin secretion in INS-1(832/13) cells and cultured mouse islets, which could be attributed to SFN-elicited ROS as N-acetylcysteine or glutathione ethyl ester suppressed SFN-stimulated insulin secretion. The mathematical model predicted an adapted redox state characteristic of strong induction of endogenous antioxidants but marginally increased ROS under prolonged SFN exposure, a state that attenuates rather than facilitates glucose-stimulated ROS and GSIS. We validated the prediction by demonstrating that although 24-h treatment of INS-1(832/13) cells with low, non-cytotoxic concentrations of SFN (2-10 ?M) protected the cells from cytotoxicity by oxidative insult, it markedly suppressed insulin secretion stimulated by 20 mM glucose. Conclusions Our study indicates that adaptive induction of endogenous antioxidants by exogenous antioxidants, albeit cytoprotective, inhibits GSIS in ?-cells. PMID:23468051

Fu, Jingqi; Zhang, Qiang; Woods, Courtney G.; Zheng, Hongzhi; Yang, Bei; Qu, Weidong; Andersen, Melvin E.; Pi, Jingbo

2013-01-01

172

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

PubMed

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

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

173

Comparison of sensitizers by detecting reactive oxygen species after photodynamic reaction in vitro.  

PubMed

The production of reactive oxygen species (ROS) has a crucial effect on the result of photodynamic therapy (PDT). Because of this fact, we examined the ROS formation by means of three porphyrin sensitizers (TPPS(4), ZnTPPS(4) and PdTPPS(4)) and compared their effectivity for induction of cell death in the G361 (human melanoma) cell line. The porphyrins used are very efficient water-soluble aromatic dyes with a potential application in photomedicine and have a high tendency to accumulate in the membranes of intracellular organelles such as lysosomes and mitochondria. Interaction between the triplet excited state of the sensitizer and molecular oxygen leads to the production singlet oxygen and other reactive oxygen species to induce cell death. Production of ROS was investigated by molecular probe CM-H(2)DCFDA. Our results demonstrated that ZnTPPS(4) induces the highest ROS production in the cell line compared to TPPS(4) and PdTPPS(4) at concentrations of 1, 10, and 100 microM and light dose of 1 J cm(-2). We also observed a consequence between ROS production and cell survival. In conclusion, these results demonstrate that photodynamic effect depends on sensitizer type, its concentration and light dose. PMID:17561369

Kolarova, H; Bajgar, R; Tomankova, K; Nevrelova, P; Mosinger, J

2007-10-01

174

Reactive oxygen species as second messengers? Induction of the expression of yeast catalase T gene by heat and hyperosmotic stress does not require oxygen.  

PubMed

It is shown that oxygen is not absolutely needed for stress-induced synthesis of catalase T in the yeast Saccharomyces cerevisiae. Yeast cells develop heat resistance after exposure to elevated temperatures in anoxia. The levels of catalase activity and thermotolerance are comparable to those in aerobically stressed cells. While these results obviously do not exclude a stress signaling role of reactive oxygen species in some systems, as postulated by other authors, they suggest that the question of the obligatory requirement for reactive oxygen species in other stress signaling systems should be rigorously re-investigated. PMID:10961694

Krawiec, Z; Bili?ski, T; Schüller, C; Ruis, H

2000-01-01

175

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...

176

Modification of 5-hydroxytryptophan-evoked 5-hydroxytryptamine formation of guinea pig colonic mucosa by reactive oxygen species.  

PubMed

We studied whether reactive oxygen species (ROS) generated by normal colonic mucosa affect 5-hydroxytryptophan (5-HTP)-evoked 5-HT formation (measured as the sum of 5-HT plus 5-hydroxyindole acetic acid (5-HIAA) accumulation) of guinea pig's isolated colonic mucosa. Catalase (3000-6000 U/ml), a hydrogen peroxide (H2O2) scavenger or diphenylene iodonium (DPI, 10-100 microM), an NADPH oxidase inhibitor, concentration-dependently caused an increase of the sum of 5-HT plus 5-HIAA accumulation in the presence of 5-HTP (10 microM), but these drugs did not significantly affect the 5-HT-metabolite in the colonic mucosa measured as the ratio of 5-HIAA/5-HT. Exogenously applied H2O2 (10-100 microM) concentration-dependently inhibited the sum of 5-HT plus 5-HIAA accumulation. In contrast, neither superoxide dismutase (SOD, 100-300 U/ml), superoxide anion scavenger, nor dimetyl sulfoxide (1-5%, DMSO), a hydroxyl radical scavenger affected the sum of 5-HT plus 5-HIAA accumulation. Moreover, mucosa ROS generation was estimated using the chemiluminescence technique. SOD (100-300 U/ml), catalase (3000-6000 U/ml) or DPI (10-100 microM), concentration-dependently reduced luminol-enhanced chemiluminescence signal from the colonic mucosa, while allopurinol (10-100 microM), a xanthine oxidase inhibitor, did not affect the chemiluminescence signal. These results suggest that ROS is formed through an NADPH oxidase system in the guinea pig colonic mucosa, where it exerts a modulatory effect on mucosal 5-HT formation upon addition of 5-HTP. Thus, ROS formation from normal colonic mucosa could be considered to contribute to the control of 5-HT production in mucosa enterochromaffin cells. PMID:11855670

Kojim, Shu-ichi; Ikeda, Masashi; Shibukawa, Asako; Kamikawa, Yuichiro

2002-01-01

177

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

PubMed Central

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

Kvietys, Peter R.; Granger, D. Neil

2012-01-01

178

[Effects of exogenous silicon on physiological characteristics of cucumber seedlings under ammonium stress].  

PubMed

The present study evaluated the effects of exogenous silicon on growth and physiological characteristics of hydroponically cultured cucumber seedlings under ammonium stress. The results showed that the growth, especially the aerial part growth of cucumber seedlings cultured with ammonium were significantly inhibited than those with nitrate, especially after treatment for 10 d, the aerial part fresh mass of cucumber seedlings were reduced 6.17 g per plant. The accumulation of reactive oxygen species (ROS) was also promoted in cucumber seedlings under ammonium, and the contents of O2*- and H2O2 were significantly increased in cucumber leaves. With the exogenous silicon treatment, the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX) were significantly improved, the ability to remove reactive oxygen species was enhanced, the contents of O2*- and H2O2 were significantly reduced in cucumber leaves, decreasing the reactive oxygen damage to the cell membrane, and the ratio of electrolyte leakage and the content of MDA in cucumber leaves. Also, with exogenous silicon treatment, the plasma membrane and activity of vacuolar membrane H(+)-ATP was significantly increased, transport capacity of intracellular proton was improved, and the level of ammonium in cucumber body was significantly reduced, thereby reducing the toxicity of ammonium. In conclusion, exogenous silicon could relieve ammonium stress, by increasing the antioxidant enzyme activity, H(+)-ATP activity, and decreasing the ammonium content in cucumber seedlings. PMID:25129941

Gao, Qing-Hai; Wang, Ya-Kun; Lu, Xiao-Min; Jia, Shuang-Shuang

2014-05-01

179

Distinct Roles of Reactive Nitrogen and Oxygen Species To Control Infection with the Facultative Intracellular Bacterium Francisella tularensis  

Microsoft Academic Search

Reactive nitrogen species (RNS) and reactive oxygen species (ROS) are important mediators of the bacte- ricidal host response. We investigated the contribution of these two mediators to the control of infection with the facultative intracellular bacterium Francisella tularensis. When intradermally infected with the live vaccine strain F. tularensis LVS, mice deficient in production of RNS (iNOS\\/ mice) or in production

Helena Lindgren; Stephan Stenmark; Wangxue Chen; Arne Tarnvik; Anders Sjostedt

2004-01-01

180

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

SciTech Connect

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

Chibli, H.; Carlini, L.; Park, S.; Dimitrijevic, N. M.; Nadeau, J. L. (Center for Nanoscale Materials); ( CSE); (McGill Univ.)

2011-01-01

181

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

PubMed

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

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

2013-12-01

182

Proximal ligand control of heme iron coordination structure and reactivity with hydrogen peroxide: investigations of the myoglobin cavity mutant H93G with unnatural oxygen donor proximal ligands.  

PubMed

The role of the proximal heme iron ligand in activation of hydrogen peroxide and control of spin state and coordination number in heme proteins is not yet well understood. Although there are several examples of amino acid sidechains with oxygen atoms which can act as potential heme iron ligands, the occurrence of protein-derived oxygen donor ligation in natural protein systems is quite rare. The sperm whale myoglobin cavity mutant H93G Mb (D. Barrick, Biochemistry 33 (1994) 6546) has its proximal histidine ligand replaced by glycine, a mutation which leaves an open cavity capable of accommodation of a variety of unnatural potential proximal ligands. This provides a convenient system for studying ligand-protein interactions. Molecular modeling of the proximal cavity in the active site of H93G Mb indicates that the cavity is of sufficient size to accommodate benzoate and phenolate in conformations that allow their oxygen atoms to come within binding distance of the heme iron. In addition, benzoate may occupy the cavity in an orientation which allows one carboxylate oxygen atom to ligate to the heme iron while the other carboxylate oxygen is within hydrogen bonding distance of serine 92. The ferric phenolate and benzoate complexes have been prepared and characterized by UV-visible and MCD spectroscopies. The benzoate adduct shows characteristics of a six-coordinate high-spin complex. To our knowledge, this is the first known example of a six-coordinate high-spin heme complex with an anionic oxygen donor proximal ligand. The benzoate ligand is displaced at alkaline pH and upon reaction with hydrogen peroxide. The phenolate adduct of H93G Mb is a five-coordinate high-spin complex whose UV-visible and MCD spectra are distinct from those of the histidine 93 to tyrosine (H93Y Mb) mutant of sperm whale myoglobin. The phenolate adduct is stable at alkaline pH and exhibits a reduced reactivity with hydrogen peroxide relative to that of both native ferric myoglobin, and the exogenous ligand-free derivative of ferric H93G Mb. These observations indicate that the identity of the proximal oxygen donor ligand has an important influence on both the heme iron coordination number and the reactivity of the complex with hydrogen peroxide. PMID:11051562

Roach, M P; Puspita, W J; Watanabe, Y

2000-08-31

183

Reactive Oxygen Species-dependent RhoA Activation Mediates Collagen Synthesis in Hyperoxic Lung Fibrosis  

PubMed Central

Lung fibrosis is an ultimate consequence of pulmonary oxygen toxicity in human and animal models. Excessive production and deposition of extracellular matrix proteins, e. g. collagen-I, is the most important feature of pulmonary fibrosis in hyperoxia-induced lung injury. In the present study, we investigated the role of RhoA and reactive oxygen species (ROS) in collagen-I synthesis in hyperoxic lung fibroblasts and in a mouse model of oxygen toxicity. Exposure of human lung fibroblasts to hyperoxia resulted in RhoA activation and increase in collagen-I synthesis and cell proliferation. Inhibition of RhoA by C3 transferase CT-04, dominant-negative RhoA mutant T19N, or RhoA siRNA prevented hyperoxia-induced collagen-I synthesis. Constitutively active RhoA mutant Q63L mimicked the effect of hyperoxia on collagen-I expression. Moreover, Rho kinase (ROCK) inhibitor Y27632 inhibited collagen-I synthesis in hyperoxic lung fibroblasts and fibrosis in mouse lungs after oxygen toxicity. Furthermore, ROS scavenger tiron attenuated hyperoxia-induced increases in RhoA activation and collagen-I synthesis in lung fibroblasts and mouse lungs after oxygen toxicity. More importantly, we found that hyperoxia induced separation of guanine nucleotide dissociation inhibitor (GDI) from RhoA in lung fibroblasts and mouse lungs. Further, tiron prevented the separation of GDI from RhoA in hyperoxic lung fibroblasts and mouse lungs with oxygen toxicity. Together, these results indicate that ROS-induced separation of GDI from RhoA leads to RhoA activation with oxygen toxicity. ROS-dependent RhoA activation is responsible for the increase in collagen-I synthesis in hyperoxic lung fibroblasts and mouse lungs. PMID:21439370

Kondrikov, Dmitry; Caldwell, Ruth B.; Dong, Zheng; Su, Yunchao

2011-01-01

184

Reactive oxygen species-dependent RhoA activation mediates collagen synthesis in hyperoxic lung fibrosis.  

PubMed

Lung fibrosis is an ultimate consequence of pulmonary oxygen toxicity in human and animal models. Excessive production and deposition of extracellular matrix proteins, e.g., collagen-I, is the most important feature of pulmonary fibrosis in hyperoxia-induced lung injury. In this study, we investigated the roles of RhoA and reactive oxygen species (ROS) in collagen-I synthesis in hyperoxic lung fibroblasts and in a mouse model of oxygen toxicity. Exposure of human lung fibroblasts to hyperoxia resulted in RhoA activation and an increase in collagen-I synthesis and cell proliferation. Inhibition of RhoA by C3 transferase CT-04, dominant-negative RhoA mutant T19N, or RhoA siRNA prevented hyperoxia-induced collagen-I synthesis. The constitutively active RhoA mutant Q63L mimicked the effect of hyperoxia on collagen-I expression. Moreover, the Rho kinase inhibitor Y27632 inhibited collagen-I synthesis in hyperoxic lung fibroblasts and fibrosis in mouse lungs after oxygen toxicity. Furthermore, the ROS scavenger tiron attenuated hyperoxia-induced increases in RhoA activation and collagen-I synthesis in lung fibroblasts and mouse lungs after oxygen toxicity. More importantly, we found that hyperoxia induced separation of guanine nucleotide dissociation inhibitor (GDI) from RhoA in lung fibroblasts and mouse lungs. Further, tiron prevented the separation of GDI from RhoA in hyperoxic lung fibroblasts and mouse lungs with oxygen toxicity. Together, these results indicate that ROS-induced separation of GDI from RhoA leads to RhoA activation with oxygen toxicity. ROS-dependent RhoA activation is responsible for the increase in collagen-I synthesis in hyperoxic lung fibroblasts and mouse lungs. PMID:21439370

Kondrikov, Dmitry; Caldwell, Ruth B; Dong, Zheng; Su, Yunchao

2011-06-01

185

A targeted antioxidant reveals the importance of mitochondrial reactive oxygen species in the hypoxic signaling of HIF-1?  

Microsoft Academic Search

Exposure to limiting oxygen in cells and tissues induce the stabilization and transcriptional activation of the hypoxia-inducible factor 1 alpha (HIF-1?) protein, a key regulator of the hypoxic response. Reactive oxygen species (ROS) generation has been implicated in the stabilization of HIF-1? during this response, but this is still a matter of some debate. In this study we utilize a

Alejandra Sanjuán-Pla; Ana M. Cervera; Nadezda Apostolova; Remedios Garcia-Bou; Víctor M. Víctor; Michael P. Murphy; Kenneth J. McCreath

2005-01-01

186

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

E-print Network

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 peroxide by a sea urchin dual oxidase, Udx1. This enzyme is essential for completing the physical block

Wessel, Gary M.

187

Optical mapping of myocardial reactive oxygen species production throughout the reperfusion of global ischemia  

NASA Astrophysics Data System (ADS)

Reactive oxygen species (ROS) are short-lived, highly reactive chemical entities that play significant roles in all levels of biology. However, their measurement requires destructive preparation, thereby limiting the continuous measurement of ROS in a living tissue. We develop an optical mapping system to visualize ROS production in an isolated and perfused rat heart. By staining the heart with dihydroethidium (DHE), a 532-nm laser beam is directed to the epicardial surface, where we collect the red fluorescence (>600 nm) for semiquantitative analysis. With this system, ROS production as well as ventricular pressure and ECG in isolated perfused rat hearts are monitored throughout the reperfusion of global ischemia. Ischemia would decrease myocardial ROS production, while reperfusion would immediately result in sustained ROS overproduction. Optical mapping would provide information regarding the spatial distribution and temporal evolution of myocardial ROS production, which would enhance knowledge of the role of free radicals in cardiovascular biology.

Lu, Long-sheng; Liu, Yen-Bin; Sun, Chia-Wei; Lin, Lung-Chun; Su, Ming-jia; Wu, Chau-Chung

2006-03-01

188

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

PubMed Central

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

2014-01-01

189

Induced reactive oxygen species improve enzyme production from Aspergillus niger cultivation.  

PubMed

Intracellular reactive oxygen species (iROS) induction by HOCl was used as a novel strategy to improve enzyme productivities in Aspergillus niger growing in a bioreactor. With induced iROS, the specific intracellular activities of alpha-amylase, protease, catalase, and glucose oxidase were increased by about 170%, 250%, 320%, and 260%, respectively. The optimum specific iROS level for achieving maximum cell concentration and enzyme production was about 15 mmol g cell-1. The type of iROS inducing the enzyme production was identified to be a derivative of the superoxide radical. PMID:12882014

Sahoo, Susmita; Rao, K Krishnamurthy; Suraishkumar, G K

2003-05-01

190

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

PubMed Central

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

2014-01-01

191

Different tobacco retrotransposons are specifically modulated by the elicitor cryptogein and reactive oxygen species.  

PubMed

Interactions of plant retrotransposons with different steps of biotic and abiotic stress-associated signaling cascades are still poorly understood. We perform here a finely tuned comparison of four tobacco retrotransposons (Tnt1, Tnt2, Queenti, and Tto1) responses to the plant elicitor cryptogein. We demonstrate that basal transcript levels in cell suspensions and plant leaves as well as the activation during the steps of defense signaling events are specific to each retrotransposon. Using antisense NtrbohD lines, we show that NtrbohD-dependent reactive oxygen species (ROS) production might act as negative regulator of retrotransposon activation. PMID:25128785

Anca, Iulia-Andra; Fromentin, Jérôme; Bui, Quynh Trang; Mhiri, Corinne; Grandbastien, Marie-Angèle; Simon-Plas, Françoise

2014-10-15

192

Characterization of reactive oxygen species generated by protoporphyrin IX under X-ray irradiation  

NASA Astrophysics Data System (ADS)

As a possible radiosensitizer candidate having biological compatibility, oncotropic property, and X-ray activation capability, contribution of protoporphyrin IX (PpIX) to enhanced generation of reactive oxygen species (ROS) under X-ray and UV irradiations were examined. To identify the kinds of ROS, 2-[6-(4-amino)phenoxy-3 H-xanthen-3-on-9-yl] benzoic acid (APF) and dihydroethidium (DHE) were used together with ethanol as a hydroxyl radical (OH rad ) quencher. All of the three species of our interest (OH rad , superoxide radical (O 2rad - ), and singlet oxygen ( 1O 2)) were enhanced by PpIX under X-ray and UV irradiations in addition to those by radiolysis and photolysis. Its enhancement factors exceeded 1.7 depending on the concentrations of PpIX from 1.5 to 15.0 ?g/ml.

Takahashi, Junko; Misawa, Masaki

2009-11-01

193

Inhibition of Legionella pneumophila growth by gamma interferon in permissive A/J mouse macrophages: role of reactive oxygen species, nitric oxide, tryptophan, and iron(III).  

PubMed Central

A/J mouse macrophages infected with Legionella pneumophila and treated with gamma interferon (IFN-gamma) in vitro developed potent antimicrobial activity. This antilegionella activity was independent of the macrophage capacity to generate reactive oxygen intermediates, since the oxygen radical scavengers catalase, superoxide dismutase, mannitol, and thiourea had no effect on the antilegionella activity of IFN-gamma-activated macrophages. Likewise, whereas the ability of IFN-gamma-activated macrophages to synthesize reactive nitrogen intermediates was markedly inhibited by the L-arginine (Arg) analogs, NG-monomethyl-L-arginine and L-aminoguanidine, as well as by incubation in L-Arg-free medium, their ability to inhibit the intracellular growth of L. pneumophila remained intact. The intracellular growth of L. pneumophila in A/J macrophages was inhibited by the iron(III) chelator desferrioxamine and reversed by Fe-transferrin as well as by ferric salts. Additionally, IFN-gamma-activated macrophages incorporated 28% less 59Fe(III) compared with nonactivated cells. Nonetheless, only partial blocking of growth restriction was observed when IFN-gamma-stimulated macrophages were saturated with iron(III). Indole-propionic acid, which appears to inhibit the biosynthesis of L-tryptophan (L-Trp), was an L-Trp-reversible growth inhibitor of L. pneumophila in macrophages, implying that the intracellular replication of this pathogen is also L-Trp dependent. However, an excess of exogenous L-Trp did not reverse the growth inhibition due to IFN-gamma, though a small synergistic effect was observed when the culture medium was supplemented with both iron(III) and L-Trp. We conclude that IFN-gamma-activated macrophages inhibit the intracellular proliferation of L. pneumophila by reactive oxygen intermediate- and reactive nitrogen intermediate-independent mechanisms and just partially by nutritionally dependent mechanisms. We also suggest that additional mechanisms, still unclear, may be involved, since complete reversion was never obtained and since at higher concentrations of IFN-gamma, iron(III) did not induce any significant reversion in the L. pneumophila growth inhibition. PMID:8039889

Gebran, S J; Yamamoto, Y; Newton, C; Klein, T W; Friedman, H

1994-01-01

194

Role of mitochondrial reactive oxygen species in age-related inflammatory activation of endothelium.  

PubMed

Vascular aging is accompanied by increases in circulatory proinflammatory cytokines leading to inflammatory endothelial response implicated in early atherogenesis. To study the possible role of mitochondria-derived reactive oxygen species (ROS) in this phenomenon, we applied the effective mitochondria-targeted antioxidant SkQ1, the conjugate of plastoquinone with dodecyltriphenylphosphonium. Eight months treatment of (CBAxC57BL/6) F1 mice with SkQ1 did not prevent age-related elevation of the major proinflammatory cytokines TNF and IL-6 in serum, but completely abrogated the increase in adhesion molecule ICAM1 expression in aortas of 24-month-old animals. In endothelial cell culture, SkQ1 also attenuated TNF-induced increase in ICAM1, VCAM, and E-selectin expression and secretion of IL-6 and IL-8, and prevented neutrophil adhesion to the endothelial monolayer. Using specific inhibitors to transcription factor NF-?B and stress-kinases p38 and JNK, we demonstrated that TNF-induced ICAM1 expression depends mainly on NF-?B activity and, to a lesser extent, on p38. SkQ1 had no effect on p38 phosphorylation (activation) but significantly reduced NF-?B activation by inhibiting phosphorylation and proteolytic cleavage of the inhibitory subunit I?B?. The data indicate an important role of mitochondrial reactive oxygen species in regulation of the NF-?B pathway and corresponding age-related inflammatory activation of endothelium. PMID:25239871

Zinovkin, Roman A; Romaschenko, Valeria P; Galkin, Ivan I; Zakharova, Vlada V; Pletjushkina, Olga Yu; Chernyak, Boris V; Popova, Ekaterina N

2014-08-01

195

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

NASA Astrophysics Data System (ADS)

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.

Fede, A.; Grannas, A. M.

2012-12-01

196

Snail-Mediated Regulation of Reactive Oxygen Species in ARCaP Human Prostate Cancer Cells  

PubMed Central

Reactive oxygen species increases in various diseases including cancer and has been associated with induction of epithelial-mesenchymal transition (EMT), as evidenced by decrease in cell adhesion-associated molecules like E-cadherin, and increase in mesenchymal markers like vimentin. We investigated the molecular mechanisms by which Snail transcription factor, an inducer of EMT, promotes tumor aggressiveness utilizing ARCaP prostate cancer cell line. An EMT model created by Snail overexpression in ARCaP cells was associated with decreased E-cadherin and increased vimentin. Moreover, Snail-expressing cells displayed increased concentration of reactive oxygen species (ROS), specifically, superoxide and hydrogen peroxide, in vitro and in vivo. Real time PCR profiling demonstrated increased expression of oxidative stress-responsive genes, such as aldeyhyde oxidase I, in response to Snail. The ROS scavenger, N-acetyl cysteine partially reversed Snail-mediated EMT after 7 days characterized by increased E-cadherin levels and decreased ERK activity, while treatment with the MEK inhibitor, UO126, resulted in a more marked effect by 3 days, characterized by cells returning back to the epithelial morphology and increased E-cadherin. In conclusion, this study shows for the first time that Snail transcription factor can regulate oxidative stress enzymes and increase ROS-mediated EMT regulated in part by ERK activation. Therefore, Snail may be an attractive molecule for therapeutic targeting to prevent tumor progression in human prostate cancer. PMID:21093414

Barnett, Petrina; Arnold, Rebecca S.; Mezencev, Roman; Chung, Leland W. K.; Zayzafoon, Majd; Odero-Marah, Valerie

2010-01-01

197

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

PubMed

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

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

2009-08-01

198

Reactive oxygen species as universal constraints in life-history evolution  

PubMed Central

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

Dowling, Damian K.; Simmons, Leigh W.

2009-01-01

199

Role of reactive oxygen species in the response of barley to necrotrophic pathogens.  

PubMed

The interactions between Hordeum vulgare(barley) and two fungal necrotrophs, Rhynchosporium secalis and Pyrenophora teres (causal agents of barley leaf scald and net blotch), were investigated in a detached-leaf system. An early oxidative burst specific to epidermal cells was observed in both the susceptible and resistant responses to R. secalis, and later on, a second susceptible-specific burst was observed. Time points of the first and the second burst correlated closely with pathogen contact to the plasma membrane and subsequent cell death, respectively. HO(2)(*)/O(2)(-) levels in resistant and susceptible responses to P. teres were limited in comparison. During later stages, HO(2)(*)/O(2)(-) was only detected in 2 to 3 epidermal cells immediately adjacent to phenolic browning and cell death observed during the susceptible response. However, H(2)O(2) was detected in the majority of mesophyll cells adjacent to the observed lesion caused by P. teres. In contrast to observations during challenge with R. secalis, no direct contact between P. teres and the plasma membrane at sites of reactive oxygen species production was evident. Preinfiltration of leaves with antioxidants prior to challenge with either pathogen had no effect on resistance responses but did limit the growth of the pathogens and inhibit the extent of cell death during susceptible responses. These results suggest a possible role for reactive oxygen species in the induction of cell death during the challenge of a susceptible plant cell with a necrotrophic fungal leaf pathogen. PMID:12768351

Able, Amanda J

2003-05-01

200

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

SciTech Connect

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.

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

201

Capacity of circulating neutrophils to produce reactive oxygen species after exhaustive exercise.  

PubMed

To investigate the cause of disagreement within the large body of literature concerning the effect of exercise on the capacity of circulating neutrophils to produce reactive oxygen species (ROS), 10 male endurance-trained athletes underwent maximal exercise. The generation of superoxide radical (O2-.) by neutrophils was first detected on a cell-by-cell basis by using histochemical nitro blue tetrazolium tests performed directly on fresh unseparated blood, which showed that responsive neutrophils under several stimulatory conditions relatively decreased after exercise. Similarly, O2-. detected with bis-N-methylacridinium nitrate (lucigenin)-dependent chemiluminescence (CL) of a fixed number of purified neutrophils on stimulation with opsonized zymosan was decreased slightly after exercise. In contrast, the 5-amino-2,3-dihydro-1,4-phthalazinedione (luminol)-dependent CL response of the neutrophils indicative of the myeloperoxidase (MPO)-mediated formation of highly reactive oxidants was significantly enhanced after exercise. It therefore suggests that the pathway of neutrophil ROS metabolism might be forwarded from the precursor O2-. production to the stages of more reactive oxidant formation due to the facilitation of MPO degranulation. In addition, these phenomena were closely associated with the exercise-induced mobilization of neutrophils from the marginated pool into the circulation, which was mediated by the overshooting of catecholamines during exercise. These findings indicate that the use of different techniques for detecting ROS or the different stages of neutrophil ROS metabolism could explain some of the disparate findings of the previous studies. PMID:8889756

Suzuki, K; Sato, H; Kikuchi, T; Abe, T; Nakaji, S; Sugawara, K; Totsuka, M; Sato, K; Yamaya, K

1996-09-01

202

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal  

PubMed Central

During the past several years, major advances have been made in understanding how reactive oxygen species (ROS) and nitrogen species (RNS) participate in signal transduction. Identification of the specific targets and the chemical reactions involved still remains to be resolved with many of the signaling pathways in which the involvement of reactive species has been determined. Our understanding is that ROS and RNS have second messenger roles. While cysteine residues in the thiolate (ionized) form found in several classes of signaling proteins can be specific targets for reaction with H2O2 and RNS, better understanding of the chemistry, particularly kinetics, suggests that for many signaling events in which ROS and RNS participate, enzymatic catalysis is more likely to be involved than non-enzymatic reaction. Due to increased interest in how oxidation products, particularly lipid peroxidation products, also are involved with signaling, a review of signaling by 4-hydroxy-2-nonenal (HNE) is included. This article focuses on the chemistry of signaling by ROS, RNS, and HNE and will describe reactions with selected target proteins as representatives of the mechanisms rather attempt to comprehensively review the many signaling pathways in which the reactive species are involved. PMID:18602883

Forman, Henry Jay; Fukuto, Jon M.; Miller, Tom; Zhang, Hongqiao; Rinna, Alessandra; Levy, Smadar

2008-01-01

203

Role of reactive oxygen species in ultra-weak photon emission in biological systems.  

PubMed

Ultra-weak photon emission originates from the relaxation of electronically excited species formed in the biological systems such as microorganisms, plants and animals including humans. Electronically excited species are formed during the oxidative metabolic processes and the oxidative stress reactions that are associated with the production of reactive oxygen species (ROS). The review attempts to overview experimental evidence on the involvement of superoxide anion radical, hydrogen peroxide, hydroxyl radical and singlet oxygen in both the spontaneous and the stress-induced ultra-weak photon emission. The oxidation of biomolecules comprising either the hydrogen abstraction by superoxide anion and hydroxyl radicals or the cycloaddition of singlet oxygen initiate a cascade of oxidative reactions that lead to the formation of electronically excited species such as triplet excited carbonyl, excited pigments and singlet oxygen. The photon emission of these electronically excited species is in the following regions of the spectrum (1) triplet excited carbonyl in the near UVA and blue-green areas (350-550nm), (2) singlet and triplet excited pigments in the green-red (550-750nm) and red-near IR (750-1000nm) areas, respectively and (3) singlet oxygen in the red (634 and 703nm) and near IR (1270nm) areas. The understanding of the role of ROS in photon emission allows us to use the spontaneous and stress-induced ultra-weak photon emission as a non-invasive tool for monitoring of the oxidative metabolic processes and the oxidative stress reactions in biological systems in vivo, respectively. PMID:24674863

Pospíšil, Pavel; Prasad, Ankush; Rác, Marek

2014-10-01

204

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

PubMed

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

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

2014-04-01

205

The role of reactive oxygen species in immunopathogenesis of rheumatoid arthritis.  

PubMed

Rheumatoid arthritis is a disease associated with painful joints that affects approximately 1% of the population worldwide, and for which no effective cure is available. It is characterized by chronic joint inflammation and variable degrees of bone and cartilage erosion. Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. Reactive oxygen species (ROS) are produced in many normal and abnormal processes in humans, including atheroma, asthma, joint diseases, aging, and cancer. TNF-alpha overproduction is thought to be the main contributor to increased ROS release in patients with RA. Increased ROS production leads to tissue damage associated with inflammation. The prevailing hypothesis that ROS promote inflammation was recently challenged when polymorphisms in Neutrophil cytosolic factor 1(Ncf1), that decrease oxidative burst, were shown to increase disease severity in mouse and rat arthritis models. It has been shown that oxygen radicals might also be important in controlling disease severity and reducing joint inflammation and connective tissue damage. In this review article, our aim is to clarify the role of ROS in immunopathogenesis of Rheumatoid arthritis. PMID:19052348

Mirshafiey, Abbas; Mohsenzadegan, Monireh

2008-12-01

206

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

PubMed Central

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

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

2011-01-01

207

Production of reactive oxygen species after photodynamic therapy by porphyrin sensitizers.  

PubMed

The objectives of this study was to investigate the production of reactive oxygen species (ROS) after photodynamic therapy (PDT) in vitro. We examined second generation sensitizers, porphyrines (TPPS4, ZnTPPS4 and PdTPPS4) and compared their effectivity on ROS generation in G361 cell line. Used porphyrines are very efficient water-soluble aromatic dyes with potential to use in photomedicine and have a high propensity to accumulate in the membranes of intracellular organelles like lysosomes and mitochondria. Interaction between the triplet excited state of the sensitizer and molecular oxygen leads to produce singlet oxygen and other ROS to induce cell death. Production of ROS was verificated by molecular probe CM-H2DCFDA and viability of cells was determined by MTT assay. Our results demonstrated that ZnTPPS4 induces the highest ROS production in cell line compared to TPPS4 and PdTPPS4 at each used concentration and light dose. These results consist with a fact that photodynamic effect depends on sensitizer type, its concentration and light dose. PMID:18645224

Kolarova, H; Nevrelova, P; Tomankova, K; Kolar, P; Bajgar, R; Mosinger, J

2008-06-01

208

Correlation Between Jugular Bulb Oxygen Saturation and Partial Pressure of Brain Tissue Oxygen During CO 2 and O 2 Reactivity Tests in Severely Head-Injured Patients  

Microsoft Academic Search

Summary  ?Purpose. To correlate the jugular bulb oxygen saturation (SjvO2) and brain tissue oxygen pressure (PbtO2) during carbon dioxide (CO2) and oxygen (O2) reactivity tests in severely head-injured patients.\\u000a \\u000a ?Methods and Results. In nine patients (7 men, 2 women, age: 26?6.5 years, GCS of 6.5?2.9), a polarographic microcatheter (Clark-type) was inserted\\u000a into nonlesioned white matter (frontal lobe). PbtO2 and SjvO2 were

J. Fandino; R. Stocker; S. Prokop; H.-G. Imhof

1999-01-01

209

Changes in the Vascular Reactivity of the Isolated Tail Arteries of Spontaneous and Renovascular Hypertensive Rats to Endogenous and Exogenous Noradrenaline  

Microsoft Academic Search

We have investigated the changes in the responses to noradrenaline of isolated tail arteries of spontaneously hypertensive (SHR) and renovascular hypertensive rats (Wistar-Kyoto: two-kidney, one-clip model, WKY:2K1C) compared with normotensive (Wistar-Kyoto, WKY) rats. Renovascular hypertension was induced by 4 weeks’ unilateral renal artery clipping. Arteries were vasoconstricted with exogenous noradrenaline, electrical field stimulation or high potassium. The effects of the

Abdel-Kader Fouda; Alfio Marazzi; Nicole Boillat; Mireille Sonnay; Hervé Guillain; Jeffrey Atkinson

1987-01-01

210

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

NASA Astrophysics Data System (ADS)

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.

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

2013-02-01

211

Electron spin resonance spectroscopy for the study of nanomaterial-mediated generation of reactive oxygen species.  

PubMed

Many of the biological applications and effects of nanomaterials are attributed to their ability to facilitate the generation of reactive oxygen species (ROS). Electron spin resonance (ESR) spectroscopy is a direct and reliable method to identify and quantify free radicals in both chemical and biological environments. In this review, we discuss the use of ESR spectroscopy to study ROS generation mediated by nanomaterials, which have various applications in biological, chemical, and materials science. In addition to introducing the theory of ESR, we present some modifications of the method such as spin trapping and spin labeling, which ultimately aid in the detection of short-lived free radicals. The capability of metal nanoparticles in mediating ROS generation and the related mechanisms are also presented. PMID:24673903

He, Weiwei; Liu, Yitong; Wamer, Wayne G; Yin, Jun-Jie

2014-03-01

212

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

PubMed

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

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

2014-01-01

213

Reactive oxygen species as transducers of sphinganine-mediated cell death pathway  

PubMed Central

Long chain bases or sphingoid bases are building blocks of complex sphingolipids that display a signaling role in programmed cell death in plants. So far, the type of programmed cell death in which these signaling lipids have been demonstrated to participate is the cell death that occurs in plant immunity, known as the hypersensitive response. The few links that have been described in this pathway are: MPK6 activation, increased calcium concentrations and reactive oxygen species (ROS) generation. The latter constitute one of the more elusive loops because of the chemical nature of ROS, the multiple possible cell sites where they can be formed and the ways in which they influence cell structure and function. PMID:21921699

Saucedo-García, Mariana; González-Solís, Ariadna; Rodríguez-Mejía, Priscila; de Jesús Olivera-Flores, Teresa; Vázquez-Santana, Sonia; Cahoon, Edgar B

2011-01-01

214

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

PubMed

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

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

2015-02-17

215

Hemoglobin fructation promotes heme degradation through the generation of endogenous reactive oxygen species  

NASA Astrophysics Data System (ADS)

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.

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

216

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

PubMed Central

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

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

217

Regulatory mechanisms of nitric oxide and reactive oxygen species generation and their role in plant immunity.  

PubMed

Rapid production of nitric oxide (NO) and reactive oxygen species (ROS) has been implicated in diverse physiological processes, such as programmed cell death, development, cell elongation and hormonal signaling, in plants. Much attention has been paid to the regulation of plant innate immunity by these signal molecules. Recent studies provide evidence that an NADPH oxidase, respiratory burst oxidase homolog, is responsible for pathogen-responsive ROS burst. However, we still do not know about NO-producing enzymes, except for nitrate reductase, although many studies suggest the existence of NO synthase-like activity responsible for NO burst in plants. Here, we introduce regulatory mechanisms of NO and ROS bursts by mitogen-activated protein kinase cascades, calcium-dependent protein kinase or riboflavin and its derivatives, flavin mononucleotide and flavin adenine dinucleotide, and we discuss the roles of the bursts in defense responses against plant pathogens. PMID:21195205

Yoshioka, Hirofumi; Mase, Keisuke; Yoshioka, Miki; Kobayashi, Michie; Asai, Shuta

2011-08-01

218

The association between microenvironmental reactive oxygen species and embryo development in assisted reproduction technology cycles.  

PubMed

This study was designed to determine the relevance between the levels of reactive oxygen species (ROS) in microenvironment (follicular fluid or culture media) and the embryo development in IVF/ICSI cycles. A total of 466 follicles from 174 IVF/ICSI cycles were collected for this study. The ROS levels in monofollicular fluid and spent culture media were evaluated by chemiluminescence assay with luminol as a probe. The results demonstrated that it is in ICSI cycles that elevated ROS levels in follicular fluid were associated with day 3 poor embryo quality. The ROS levels in spent culture media were correlated with advanced degree of fragmentation. In addition, ROS levels in culture media, instead of in follicular fluid, were negatively correlated with implantation potential of embryos. The ROS levels in culture media may be viewed as an embryo metabolic marker and function as an adjuvant criterion for embryo selection. PMID:22378864

Lee, Tsung-Hsien; Lee, Maw-Sheng; Liu, Chung-Hsien; Tsao, Hui-Mei; Huang, Chun-Chia; Yang, Yu-Shih

2012-07-01

219

Effects of Hepatitis C core protein on mitochondrial electron transport and production of reactive oxygen species  

PubMed Central

Viral infections frequently alter mitochondrial function with suppression or induction of apoptosis and enhanced generation of reactive oxygen species. The mechanisms of these effects are varied and mitochondria are affected by both direct interactions with viral proteins as well as by secondary effects of viral activated signaling cascades. This chapter describes methods used in our laboratory to assess the effects of the Hepatitis C virus core protein on mitochondrial ROS production, electron transport and Ca2+ uptake. These include measurements of the effects of in vitro incubation of liver mitochondria with purified core protein as well as assessment of the function of mitochondria in cells and tissues expressing core and other viral proteins. These methods are generally applicable to the study of viral-mitochondrial interactions. PMID:19348899

Campbell, Roosevelt V.; Yang, Yuanzheng; Wang, Ting; Rachamallu, Aparna; Li, Yanchun; Watowich, Stanley J.; Weinman, Steven A.

2014-01-01

220

The roles of reactive oxygen metabolism in drought: not so cut and dried.  

PubMed

Drought is considered to cause oxidative stress, but the roles of oxidant-induced modifications in plant responses to water deficit remain obscure. Key unknowns are the roles of reactive oxygen species (ROS) produced at specific intracellular or apoplastic sites and the interactions between the complex, networking antioxidative systems in restricting ROS accumulation or in redox signal transmission. This Update discusses the physiological aspects of ROS production during drought, and analyzes the relationship between oxidative stress and drought from different but complementary perspectives. We ask to what extent redox changes are involved in plant drought responses and discuss the roles that different ROS-generating processes may play. Our discussion emphasizes the complexity and the specificity of antioxidant systems, and the likely importance of thiol systems in drought-induced redox signaling. We identify candidate drought-responsive redox-associated genes and analyze the potential importance of different metabolic pathways in drought-associated oxidative stress signaling. PMID:24715539

Noctor, Graham; Mhamdi, Amna; Foyer, Christine H

2014-04-01

221

The Role of Heme and Reactive Oxygen Species in Proliferation and Survival of Trypanosoma cruzi  

PubMed Central

Trypanosoma cruzi, the protozoan responsible for Chagas disease, has a complex life cycle comprehending two distinct hosts and a series of morphological and functional transformations. Hemoglobin degradation inside the insect vector releases high amounts of heme, and this molecule is known to exert a number of physiological functions. Moreover, the absence of its complete biosynthetic pathway in T. cruzi indicates heme as an essential molecule for this trypanosomatid survival. Within the hosts, T. cruzi has to cope with sudden environmental changes especially in the redox status and heme is able to increase the basal production of reactive oxygen species (ROS) which can be also produced as byproducts of the parasite aerobic metabolism. In this regard, ROS sensing is likely to be an important mechanism for the adaptation and interaction of these organisms with their hosts. In this paper we discuss the main features of heme and ROS susceptibility in T. cruzi biology. PMID:22007287

Paes, Marcia Cristina; Cosentino-Gomes, Daniela; de Souza, Cíntia Fernandes; Nogueira, Natália Pereira de Almeida; Meyer-Fernandes, José Roberto

2011-01-01

222

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

PubMed

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

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

223

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

NASA Technical Reports Server (NTRS)

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.

Mcgee, H. A., Jr.

1973-01-01

224

Signaling Networks Involving Reactive Oxygen Species and Ca2+ in Plants  

NASA Astrophysics Data System (ADS)

Although plants never evolved central information processing organs such as brains, plants have evolved distributed information processing systems and are able to sense various environmental changes and reorganize their body plan coordinately without moving. Recent molecular biological studies revealed molecular bases for elementary processes of signal transduction in plants. Though reactive oxygen species (ROS) are highly toxic substances produced through aerobic respiration and photosynthesis, plants possess ROS-producing enzymes whose activity is highly regulated by binding of Ca2+. In turn, Ca2+- permeable channel proteins activated by ROS are shown to be localized to the cell membrane. These two components are proposed to constitute a positive feedback loop to amplify cellular signals. Such molecular physiological studies should be important steps to understand information processing systems in plants and future application for technology related to environmental, energy and food sciences.

Kuchitsu, Kazuyuki

2013-01-01

225

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

SciTech Connect

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.

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

226

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

PubMed Central

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

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

2013-01-01

227

Reactive oxygen species production and activation mechanism of the rice NADPH oxidase OsRbohB.  

PubMed

Reactive oxygen species (ROS) produced by plant NADPH oxidases (NOXes) are important in plant innate immunity. The Oryza sativa respiratory burst oxidase homologue B (OsRbohB) gene encodes a NOX the regulatory mechanisms of which are largely unknown. Here, we used a heterologous expression system to demonstrate that OsRbohB shows ROS-producing activity. Treatment with ionomycin, a Ca(2+) ionophore, and calyculin A, a protein phosphatase inhibitor, activated ROS-producing activity; it was thus OsRbohB activated by both Ca(2+) and protein phosphorylation. Mutation analyses revealed that not only the first EF-hand motif but also the upstream amino-terminal region were necessary for Ca(2+)-dependent activation, while these regions are not required for phosphorylation-induced ROS production. PMID:22528669

Takahashi, Shinya; Kimura, Sachie; Kaya, Hidetaka; Iizuka, Ayako; Wong, Hann Ling; Shimamoto, Ko; Kuchitsu, Kazuyuki

2012-07-01

228

Reactive oxygen species, cell growth, cell cycle progression and vascular remodeling in hypertension.  

PubMed

Reactive oxygen species (ROS) include superoxide, hygrogen peroxide and hydroxyl radical. Under physiological conditions, all vascular cell types produce ROS in a controlled and regulated fashion, mainly through nonphagocyte NADPH oxidase. An imbalance between pro-oxidants and antioxidants results in oxidative stress. ROS are important intracellular signaling molecules. There is growing evidence that increased oxidative stress and associated oxidative damage are mediators of vascular injury in hypertension, as well as in other cardiovascular diseases. Oxidative stress causes vascular injury by reducing nitric oxide bioavailability, altering endothelial function and vascular contraction/dilation, promoting vascular smooth muscle cell proliferation and hypertrophy, and increasing extracellular matrix deposition and inflammation. The present review focuses on the regulatory role of ROS on cell growth and cell cycle progression and discusses implications of these events in vascular remodeling in hypertension. PMID:19804207

Vokurkova, Martina; Xu, Shaoping; Touyz, Rhian M

2007-01-01

229

Reactive oxygen species (ROS) is not a promotor of taxol-induced cytoplasmic vacuolization  

NASA Astrophysics Data System (ADS)

we have previously reported that taxol, a potent anticancer agent, induces caspase-independent cell death and cytoplasmic vacuolization in human lung adenocarcinoma (ASTC-a-1) cells. However, the mechanisms of taxol-induced cytoplasmic vacuolization are poorly understood. Reactive oxygen species (ROS) has been reported to be involved in the taxol-induced cell death. Here, we employed confocal fluorescence microscopy imaging to explore the role of ROS in taxol-induced cytoplasmic vacuolization. We found that ROS inhibition by addition of N-acetycysteine (NAC), a total ROS scavenger, did not suppress these vacuolization but instead increased vacuolization. Take together, our results showed that ROS is not a promotor of the taxol-induced cytoplasmic vacuolization.

Sun, Qingrui; Chen, Tongsheng

2009-02-01

230

Current Progress in Reactive Oxygen Species (ROS)-Responsive Materials for Biomedical Applications  

PubMed Central

Recently, significant progress has been made in developing “stimuli-sensitive” biomaterials as a new therapeutic approach to interact with dynamic physiological conditions. Reactive oxygen species (ROS) production has been implicated in important pathophysiological events, such as atherosclerosis, aging, and cancer. ROS are often overproduced locally in diseased cells and tissues, and they individually and synchronously contribute to many of the abnormalities associated with local pathogenesis. Therefore, the advantages of developing ROS-responsive materials extend beyond site-specific targeting of therapeutic delivery, and potentially include navigating, sensing, and repairing the cellular damages via programmed changes in material properties. Here we review the mechanism and development of biomaterials with ROS-induced solubility switch or degradation, as well as their performance and potential for future biomedical applications. PMID:25136729

Lee, Sue Hyun; Gupta, Mukesh K.; Bang, Jae Beum; Bae, Hojae

2013-01-01

231

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

NASA Astrophysics Data System (ADS)

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.

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

2014-01-01

232

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

PubMed

Nano-iron metal and nano-iron oxides are among the most widely used engineered and naturally occurring nanostructures, and the increasing incidence of biological exposure to these nanostructures has raised concerns about their biotoxicity. Reactive oxygen species (ROS)-induced oxidative stress is one of the most accepted toxic mechanisms and, in the past decades, considerable efforts have been made to investigate the ROS-related activities of iron nanostructures. In this review, we summarize activities of nano-iron metal and nano-iron oxides in ROS-related redox processes, addressing in detail the known homogeneous and heterogeneous redox mechanisms involved in these processes, intrinsic ROS-related properties of iron nanostructures (chemical composition, particle size, and crystalline phase), and ROS-related bio-microenvironmental factors, including physiological pH and buffers, biogenic reducing agents, and other organic substances. PMID:24673906

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

2014-03-01

233

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

NASA Astrophysics Data System (ADS)

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.

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

2014-09-01

234

Generation of Reactive Oxygen Species Contributes to the Development of Carbon Black Cytotoxicity to Vascular Cells  

PubMed Central

Carbon black, a particulate form of pure elemental carbon, is an industrial chemical with the high potential of occupational exposure. Although the relationship between exposure to particulate matters (PM) and cardiovascular diseases is well established, the cardiovascular risk of carbon black has not been characterized clearly. In this study, the cytotoxicity of carbon black to vascular smooth muscle and endothelial cells were examined to investigate the potential vascular toxicity of carbon black. Carbon black with distinct particle size, N330 (primary size, 28~36 nm) and N990 (250~350 nm) were treated to A-10, rat aortic smooth muscle cells and human umbilical vein endothelial cell line, ECV304, and cell viability was assessed by lactate dehydrogenase (LDH) leakage assay. Treatment of carbon black N990 resulted in the significant reduction of viability in A-10 cells at 100 ?g/ml, the highest concentration tested, while N330 failed to cause cell death. Cytotoxicity to ECV304 cells was induced only by N330 at higher concentration, 200 ?g/ml, suggesting that ECV304 cells were relatively resistant to carbon black. Treatment of 100 ?g/ml N990 led to the elevation of reactive oxygen species (ROS) detected by dichlorodihydrofluorescein (DCF) in A-10 cells. Pretreatment of antioxidants, N-acetylcysteine (NAC) and sulforaphane restored decreased viability of N990-treated A-10 cells, and N-acetylcysteine, but not sulforaphane, attenuated N990-induced ROS generation in A-10 cells. Taken together, present study shows that carbon black is cytotoxic to vascular cells, and the generation of reactive oxygen contributes to the development of cytotoxicity. ROS scavenging antioxidant could be a potential strategy to attenuate the toxicity induced by carbon black exposure. PMID:24278567

Lee, Jong Gwan; Noh, Won Jun; Kim, Hwa

2011-01-01

235

Exendin-4 Protects Mitochondria from Reactive Oxygen Species Induced Apoptosis in Pancreatic Beta Cells  

PubMed Central

Objective Mitochondrial oxidative stress is the basis for pancreatic ?-cell apoptosis and a common pathway for numerous types of damage, including glucotoxicity and lipotoxicity. We cultivated mice pancreatic ?-cell tumor Min6 cell lines in vitro and observed pancreatic ?-cell apoptosis and changes in mitochondrial function before and after the addition of Exendin-4. Based on these observations, we discuss the protective role of Exendin-4 against mitochondrial oxidative damage and its relationship with Ca2+-independent phospholipase A2. Methods We established a pancreatic ?-cell oxidative stress damage model using Min6 cell lines cultured in vitro with tert-buty1 hydroperoxide and hydrogen peroxide. We then added Exendin-4 to observe changes in the rate of cell apoptosis (Annexin-V-FITC-PI staining flow cytometry and DNA ladder). We detected the activity of the caspase 3 and 8 apoptotic factors, measured the mitochondrial membrane potential losses and reactive oxygen species production levels, and detected the expression of cytochrome c and Smac/DLAMO in the cytosol and mitochondria, mitochondrial Ca2-independent phospholipase A2 and Ca2+-independent phospholipase A2 mRNA. Results The time-concentration curve showed that different percentages of apoptosis occurred at different time-concentrations in tert-buty1 hydroperoxide- and hydrogen peroxide-induced Min6 cells. Incubation with 100 µmol/l of Exendin-4 for 48 hours reduced the Min6 cell apoptosis rate (p<0.05). The mitochondrial membrane potential loss and total reactive oxygen species levels decreased (p<0.05), and the release of cytochrome c and Smac/DLAMO from the mitochondria was reduced. The study also showed that Ca2+-independent phospholipase A2 activity was positively related to Exendin-4 activity. Conclusion Exendin-4 reduces Min6 cell oxidative damage and the cell apoptosis rate, which may be related to Ca2-independent phospholipase A2. PMID:24204601

Li, Zhen; Zhou, Zhiguang; Huang, Gan; Hu, Fang; Xiang, Yufei; He, Lining

2013-01-01

236

Inelastic and reactive scattering of hyperthermal atomic oxygen from amorphous carbon  

NASA Technical Reports Server (NTRS)

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.

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

1991-01-01

237

Probing the magic numbers of aluminum-magnesium cluster anions and their reactivity toward oxygen.  

PubMed

We report a joint experimental and theoretical investigation into the geometry, stability, and reactivity with oxygen of alloy metal clusters Al(n)Mg(m)(-) (4 ? n+m ? 15; 0 ? m ? 3). Considering that Al and Mg possess three and two valence electrons, respectively, clusters with all possible valence electron counts from 11 to 46 are studied to probe the magic numbers predicted by the spherical jellium model, and to determine whether enhanced stability and reduced reactivity may be found for some Al(n)Mg(m)(-) at non-magic numbers. Al5Mg2(-) and Al11Mg3(-) exhibit enhanced stability corresponding to the expected magic numbers of 20 and 40 electrons, respectively; while Al7Mg3(-), Al11Mg(-), and Al11Mg2(-) turn out to be unexpectedly stable at electron counts of 28, 36, and 38, respectively. The enhanced stability at non-magic numbers is explained through a crystal-field-like splitting of degenerate shells by the geometrical distortions of the clusters. Al(n)Mg(m)(-) clusters appear to display higher oxidation than pure Al(n)(-) clusters, suggesting that the addition of Mg atoms enhances the combustion of pure aluminum clusters. PMID:23432202

Luo, Zhixun; Grover, Cameron J; Reber, Arthur C; Khanna, Shiv N; Castleman, A W

2013-03-20

238

Ambient Particulates Alter Vascular Function through Induction of Reactive Oxygen and Nitrogen Species  

PubMed Central

Previous studies have shown a link between inhaled particulate matter (PM) exposure in urban areas and susceptibility to cardiovascular diseases. Although an oxidative stress pathway is strongly implicated, the locus of generation of reactive oxygen species (ROS) and the mechanisms by which these radicals exert their effects remain to be characterized. To test the hypothesis that exposure to environmentally relevant inhaled concentrated ambient PM (CAPs) enhances atherosclerosis through induction of vascular ROS and reactive nitrogen species. High-fat chow fed apolipoprotein E–/– mice were exposed to CAPs of less than 2.5 ?m (PM2.5) or filtered air (FA), for 6 h/day, 5 days/week, for 4 months in Manhattan, NY. Atherosclerotic lesions were analyzed by histomorphometricly. Vascular reactivity, superoxide generation, mRNA expression of NADPH (nicotinamide adenine dinucleotide phosphate, reduced) oxidase subunits, inducible nitric oxide synthase, endothelial nitric oxide synthase, and GTP cyclohydrolase I were also assessed. Manhattan PM2.5 CAPs were characterized by higher concentrations of organic and elemental carbon. Analysis of vascular responses revealed significantly decreased phenylephrine constriction in CAPs-exposed mice, which was restored by a soluble guanine cyclase inhibitor 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one. Vascular relaxation to A23187, but not to acetylcholine, was attenuated in CAPs mice. Aortic expression of NADPH oxidase subunits (p47phox and rac1) and iNOS were markedly increased, paralleled by increases in superoxide generation and extensive protein nitration in the aorta. The composite plaque area of thoracic aorta was significantly increased with pronounced macrophage infiltration and lipid deposition in the CAPs mice. CAPs exposure in Manhattan alters vasomotor tone and enhances atherosclerosis through NADPH oxidase dependent pathways. PMID:19182107

Ying, Zhekang; Kampfrath, Thomas; Thurston, George; Farrar, Britten; Lippmann, Mort; Wang, Aixia; Sun, Qinghua; Chen, Lung Chi; Rajagopalan, Sanjay

2009-01-01

239

Inhibition of ultraviolet-induced formation of reactive oxygen species, lipid peroxidation, erythema and skin photosensitization by polypodium leucotomos.  

PubMed

The acute reactions of human skin to solar ultraviolet radiation (290-400 nm) are recognized as a form of inflammation reactions that are mediated by several possible mechanisms including (a) direct action of photons on DNA, (b) generation of reactive free radicals and reactive oxygen species involving the formation of O2.-, 1O2, H2O2, OH, etc., (c) generation of prostaglandins (PGD2, PGE2, etc.), histamine, leucotrienes, and other inflammatory mediators. It is conceivable that UV-induced reactions represent oxidative stress mediated by the formation of free radicals, reactive oxygen, lipid peroxidation, liberation of membrane phospholipids, and subsequent formation of prostaglandins by cyclo-oxygenase pathway. In this study, we examined the role of reactive oxygen species and lipid peroxidation in in vitro reactions as well as in vivo skin inflammation reactions induced by (a) UVB radiation (290-320 nm), and (b) skin photosensitization reaction by PUVA treatment involving 8-methoxypsoralen and UVA (320-400 nm) radiation and presented data for the generation of superoxide anion O2.-) and lipid peroxides. We have also evaluated, both in vitro as well as in vivo systems, the quenching or the inhibition of O2.- by a plant extract known as Polypodium leucotomos. The P. leucotomos extract was found to exhibit interesting antioxidant and anti-inflammatory as well as photoprotective properties against photo-oxidative stress involving the generation of reactive oxygen, lipid peroxidation under in vitro reactions as well as in vivo experimental conditions. Significant inhibition of UVB-induced erythemal response, and 8-methoxypsoralen plus UVA-induced phototoxic reaction after topical application or oral administration of the photosensitizer could be demonstrated in guinea pig skin and human skin following the topical application of P. leucotomos extract. The photoprotective mechanism of P.leucotomos involving interaction with reactive oxygen species or free radicals appears to have potential clinical usefulness in preventing sunburn and inhibiting phototoxic reaction. PMID:8897589

González, S; Pathak, M A

1996-04-01

240

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

PubMed

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

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

2002-05-31

241

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

PubMed

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

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

2007-10-01

242

Environmentally Persistent Free Radicals (EPFRs). 1. Generation of Reactive Oxygen Species in Aqueous Solutions  

PubMed Central

Reactive oxygen species (ROS) generated by environmentally persistent free radicals (EPFRs) of 2-monochlorophenol, associated with CuO/silica particles, were detected using the chemical spin trap, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), in conjunction with Electron Paramagnetic Resonance (EPR) spectroscopy. Yields of hydroxyl radical (.OH), superoxide anion radical (O2.?), and hydrogen peroxide (H2O2) generated by EPFR-particle systems are reported. Failure to trap superoxide radicals in aqueous solvent, formed from the reaction of EPFRs with molecular oxygen, results from the fast transformation of the superoxide to hydrogen peroxide. However, formation of superoxide as an intermediate product in hydroxyl radical formation in aprotic solutions of dimethyl sulfoxide (DMSO) and acetonitrile (AcN) was observed. Experiments with superoxide dismutase (SOD) and catalase (CAT) confirmed the formation of superoxide and hydrogen peroxide, respectively, in the presence of EPFRs. The large number of hydroxyl radicals formed per EPFR and monotonic increase of the DMPO-OH spin adduct concentration with the incubation time suggest a catalytic cycle of ROS formation. PMID:21823585

Khachatryan, Lavrent; Vejerano, Eric; Lomnicki, Slawo; Dellinger, Barry

2011-01-01

243

Reactive Oxygen Species in the Regulation of Synaptic Plasticity and Memory  

PubMed Central

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

Klann, Eric

2011-01-01

244

Modulation of the production of reactive oxygen species by pre-activated neutrophils by aminoadamantane derivatives.  

PubMed

Aminoadamantane derivatives (AAD) such as amantadine or memantine have been used for the treatment of Morbus Parkinson and Morbus Alzheimer. In this communication, we report on the immunomodulatory activities of AAD. Luminol-dependent chemiluminescence of zymosan-, N-formylmethionylleucylphenylalanine(FMLP)- or experimental Ca2+-ionophore(A 231879)-preactivated polymorphonuclear leukocytes (PMN) was strongly enhanced by submicromolar concentrations of AAD and inhibited at higher concentrations than 0.1 mM. Light emission by phorbol-12-myristate-acetate(PMA)-preactivated cells was not further stimulated but inhibited by the elevated concentrations, just as with the other, above-mentioned activators. Ethylene formation from alpha-keto-methylthiobutyrate (KMB) as an indicator for production of OH.-type reactive oxygen species by the NADPH-oxidase ("respiratory burst") was augmented by AAD and completely inhibited by superoxide dismutase. In contrast, ethylene release from 1-amino-cyclopropyl-l-carboxylic acid (ACC) as relatively specific indicator for the myeloperoxidase reaction after degranulation was not influenced by AAD. As documented by several model reactions, AAD per se did not act as scavengers or quenchers of activated oxygen species such as superoxide, OH.-radical, hydrogen peroxide or hypochlorite. Altogether, these results suggest that submicromolar concentrations of AAD upregulate the respiratory burst, but apparently not the degranulation of prestimulated polymorphonuclear leukocytes. At higher concentrations of AAD, both respiratory burst and degranulation are inhibited, however. These effects can also be shown in complete blood samples. PMID:9698098

Albrecht-Goepfert, E; Schempp, H; Elstner, E F

1998-07-01

245

Peroxisome proliferation in Foraminifera inhabiting the chemocline: an adaptation to reactive oxygen species exposure?  

PubMed

Certain foraminiferal species are abundant within the chemocline of marine sediments. Ultrastructurally, most of these species possess numerous peroxisomes complexed with the endoplasmic reticulum (ER); mitochondria are often interspersed among these complexes. In the Santa Barbara Basin, pore-water bathing Foraminifera and co-occurring sulfur-oxidizing microbial mats had micromolar levels of hydrogen peroxide (H(2)O(2)), a reactive oxygen species that can be detrimental to biological membranes. Experimental results indicate that adenosine triphosphate concentrations are significantly higher in Foraminifera incubated in 16 microM H(2)O(2) than in specimens incubated in the absence of H(2)O(2). New ultrastructural and experimental observations, together with published results, lead us to propose that foraminiferans can utilize oxygen derived from the breakdown of environmentally and metabolically produced H(2)O(2). Such a capability could explain foraminiferal adaptation to certain chemically inhospitable environments; it would also force us to reassess the role of protists in biogeochemistry, especially with respect to hydrogen and iron. The ecology of these protists also appears to be tightly linked to the sulfur cycle. Finally, given that some Foraminifera bearing peroxisome-ER complexes belong to evolutionarily basal groups, an early acquisition of the capability to use environmental H(2)O(2) could have facilitated diversification of foraminiferans during the Neoproterozoic. PMID:18460150

Bernhard, Joan M; Bowser, Samuel S

2008-01-01

246

Effects of Autoregulation and CO2 Reactivity on Cerebral Oxygen Transport  

PubMed Central

Both autoregulation and CO2 reactivity are known to have significant effects on cerebral blood flow and thus on the transport of oxygen through the vasculature. In this paper, a previous model of the autoregulation of blood flow in the cerebral vasculature is expanded to include the dynamic behavior of oxygen transport through binding with hemoglobin. The model is used to predict the transfer functions for both oxyhemoglobin and deoxyhemoglobin in response to fluctuations in arterial blood pressure and arterial CO2 concentration. It is shown that only six additional nondimensional groups are required in addition to the five that were previously found to characterize the cerebral blood flow response. A resonant frequency in the pressure-oxyhemoglobin transfer function is found to occur in the region of 0.1 Hz, which is a frequency of considerable physiological interest. The model predictions are compared with results from the published literature of phase angle at this frequency, showing that the effects of changes in breathing rate can significantly alter the inferred phase dynamics between blood pressure and hemoglobin. The question of whether dynamic cerebral autoregulation is affected under conditions of stenosis or stroke is then examined. PMID:19629692

Payne, S. J.; Selb, J.; Boas, D. A.

2009-01-01

247

Photolysis of atrazine in aqueous solution: role of process variables and reactive oxygen species.  

PubMed

Photochemical advanced oxidation processes have been considered for the treatment of water and wastewater containing the herbicide atrazine (ATZ), a possible human carcinogen and endocrine disruptor. In this study, we investigated the effects of the photon emission rate and initial concentration on ATZ photolysis at 254 nm, an issue not usually detailed in literature. Moreover, the role of reactive oxygen species (ROS) is discussed. Photon emission rates in the range 0.87?×?10(18)-3.6?×?10(18) photons L(-1) s(-1) and [ATZ]0?=?5 and 20 mg L(-1) were used. The results showed more than 65 % of ATZ removal after 30 min. ATZ photolysis followed apparent first-order kinetics with k values and percent removals decreasing with increasing herbicide initial concentration. A fivefold linear increase in specific degradation rate constants with photon emission rate was observed. Also, regardless the presence of persistent degradation products, toxicity was efficiently removed after 60-min exposure to UV radiation. Experiments confirmed a noticeable contribution of singlet oxygen and radical species to atrazine degradation during photolysis. These results may help understand the behavior of atrazine in different UV-driven photochemical degradation treatment processes. PMID:24764010

Silva, Marcela Prado; Batista, Ana Paula dos Santos; Borrely, Sueli Ivone; Silva, Vanessa Honda Ogihara; Teixeira, Antonio Carlos Silva Costa

2014-11-01

248

Enterovirus 71 Induces Mitochondrial Reactive Oxygen Species Generation That is Required for Efficient Replication  

PubMed Central

Redox homeostasis is an important host factor determining the outcome of infectious disease. Enterovirus 71 (EV71) infection has become an important endemic disease in Southeast Asia and China. We have previously shown that oxidative stress promotes viral replication, and progeny virus induces oxidative stress in host cells. The detailed mechanism for reactive oxygen species (ROS) generation in infected cells remains elusive. In the current study, we demonstrate that mitochondria were a major ROS source in EV71-infected cells. Mitochondria in productively infected cells underwent morphologic changes and exhibited functional anomalies, such as a decrease in mitochondrial electrochemical potential ??m and an increase in oligomycin-insensitive oxygen consumption. Respiratory control ratio of mitochondria from infected cells was significantly lower than that of normal cells. The total adenine nucleotide pool and ATP content of EV71-infected cells significantly diminished. However, there appeared to be a compensatory increase in mitochondrial mass. Treatment with mito-TEMPO reduced eIF2? phosphorylation and viral replication, suggesting that mitochondrial ROS act to promote viral replication. It is plausible that EV71 infection induces mitochondrial ROS generation, which is essential to viral replication, at the sacrifice of efficient energy production, and that infected cells up-regulate biogenesis of mitochondria to compensate for their functional defect. PMID:25401329

Cheng, Mei-Ling; Weng, Shiue-Fen; Kuo, Chih-Hao; Ho, Hung-Yao

2014-01-01

249

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

NASA Astrophysics Data System (ADS)

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.

Devarajan, Sunil Poondi

250

Reactive oxygen species production by potato tuber mitochondria is modulated by mitochondrially bound hexokinase activity.  

PubMed

Potato tuber (Solanum tuberosum) mitochondria (PTM) have a mitochondrially bound hexokinase (HK) activity that exhibits a pronounced sensitivity to ADP inhibition. Here we investigated the role of mitochondrial HK activity in PTM reactive oxygen species generation. Mitochondrial HK has a 10-fold higher affinity for glucose (Glc) than for fructose (KMGlc=140 microM versus KMFrc=1,375 microM). Activation of PTM respiration by succinate led to an increase in hydrogen peroxide (H2O2) release that was abrogated by mitochondrial HK activation. Mitochondrial HK activity caused a decrease in the mitochondrial membrane potential and an increase in oxygen consumption by PTM. Inhibition of Glc phosphorylation by mannoheptulose or GlcNAc induced a rapid increase in H2O2 release. The blockage of H2O2 release sustained by Glc was reverted by oligomycin and atractyloside, indicating that ADP recycles through the adenine nucleotide translocator and F0F1ATP synthase is operative during the mitochondrial HK reaction. Inhibition of mitochondrial HK activity by 60% to 70% caused an increase of 50% in the maximal rate of H2O2 release. Inhibition in H2O2 release by mitochondrial HK activity was comparable to, or even more potent, than that observed for StUCP (S. tuberosum uncoupling protein) activity. The inhibition of H2O2 release in PTM was two orders of magnitude more selective for the ADP produced from the mitochondrial HK reaction than for that derived from soluble yeast (Saccharomyces cerevisiae) HK. Modulation of H2O2 release and oxygen consumption by Glc and mitochondrial HK inhibitors in potato tuber slices shows that hexoses and mitochondrial HK may act as a potent preventive antioxidant mechanism in potato tubers. PMID:19109413

Camacho-Pereira, Juliana; Meyer, Laudiene Evangelista; Machado, Lilia Bender; Oliveira, Marcus Fernandes; Galina, Antonio

2009-02-01

251

Maize ABP9 enhances tolerance to multiple stresses in transgenic Arabidopsis by modulating ABA signaling and cellular levels of reactive oxygen species.  

PubMed

The phytohormone abscisic acid (ABA) and reactive oxygen species (ROS) play critical roles in mediating abiotic stress responses in plants. It is well known that ABA is involved in the modulation of ROS levels by regulating ROS-producing and ROS-scavenging genes, but the molecular mechanisms underlying this regulation are poorly understood. Here we show that the expression of maize ABP9 gene, which encodes a bZIP transcription factor capable of binding to the ABRE2 motif in the maize Cat1 promoter, is induced by ABA, H(2)O(2), drought and salt. Constitutive expression of ABP9 in transgenic Arabidopsis leads to remarkably enhanced tolerance to multiple stresses including drought, high salt, freezing temperature and oxidative stresses. ABP9 expressing Arabidopsis plants also exhibit increased sensitivity to exogenously applied ABA during seed germination, root growth and stomatal closure and improved water-conserving capacity. Moreover, constitutive expression of ABP9 causes reduced cellular levels of ROS, alleviated oxidative damage and reduced cell death, accompanied by elevated expression of many stress/ABA responsive genes including those for scavenging and regulating ROS. Taken together, these results suggest that ABP9 may play a pivotal role in plant tolerance to abiotic stresses by fine tuning ABA signaling and control of ROS accumulation. PMID:21327835

Zhang, Xia; Wang, Lei; Meng, Hui; Wen, Hongtao; Fan, Yunliu; Zhao, Jun

2011-03-01

252

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

Microsoft Academic Search

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

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

1989-01-01

253

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

PubMed Central

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

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

2011-01-01

254

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

PubMed

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

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

2011-11-01

255

Protection of Mycobacterium tuberculosis from Reactive Oxygen Species Conferred by the mel2 Locus Impacts Persistence and Dissemination  

Microsoft Academic Search

Persistence of Mycobacterium tuberculosis in humans represents a major roadblock to elimination of tuber- culosis. We describe identification of a locus in M. tuberculosis, mel2, that displays similarity to bacterial bioluminescent loci and plays an important role during persistence in mice. We constructed a deletion of the mel2 locus and found that the mutant displays increased susceptibility to reactive oxygen

Suat L. G. Cirillo; Selvakumar Subbian; Bing Chen; Torin R. Weisbrod; William R. Jacobs; Jeffrey D. Cirillo

2009-01-01

256

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...

257

Aclarubicin-induced differentiation and invasiveness Involvement of reactive oxygen species in aclarubicin-induced diferentiation and  

E-print Network

Aclarubicin-induced differentiation and invasiveness 1 Involvement of reactive oxygen species in aclarubicin-induced diferentiation and invasiveness of HL-60 leukemia cells Doriane Richard, Patrick Hollender-induced differentiation and invasiveness. hal-00422906,version1-8Oct2009 Author manuscript, published in "International

Paris-Sud XI, Université de

258

INHIBITION OF CASPASE-LIKE ACTIVITIES PREVENTS THE APPEARANCE OF REACTIVE OXYGEN SPECIES AND DARK-INDUCED APOPTOSIS  

E-print Network

-INDUCED APOPTOSIS IN THE UNICELLULAR CHLOROPHYTE DUNALIELLA TERTIOLECTA1 Mari´a Segovia2 Department of Ecology, Wisconsin 53201, USA When the chlorophyte alga Dunaliella tertiolecta Butcher is placed in darkness, a form viability; Dunaliella tertiolecta; phosphatidylserine; phytoplankton; reactive oxygen species; unicellular

Berges, John A.

259

HYR1-Mediated Detoxification of Reactive Oxygen Species Is Required for Full Virulence in the Rice Blast Fungus  

Microsoft Academic Search

During plant-pathogen interactions, the plant may mount several types of defense responses to either block the pathogen completely or ameliorate the amount of disease. Such responses include release of reactive oxygen species (ROS) to attack the pathogen, as well as formation of cell wall appositions (CWAs) to physically block pathogen penetration. A successful pathogen will likely have its own ROS

Kun Huang; Kirk J. Czymmek; Jeffrey L. Caplan; James A. Sweigard; Nicole M. Donofrio

2011-01-01

260

The reactive oxygen species—total antioxidant capacity score is a new measure of oxidative stress to predict male infertility  

Microsoft Academic Search

There is growing evidence that oxidative stress significantly impairs sperm function, and plays a major role in the aetiology The imbalance between reactive oxygen species (ROS) of defective sperm function. This may lead to the onset of production and total antioxidant capacity (TAC) in seminal male infertility via mechanisms involving the induction of fluid indicates oxidative stress and is correlated

Rakesh K. Sharma; Fabio F. Pasqualotto; David R. Nelson; Anthony J. Thomas Jr; Ashok Agarwal

261

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

Microsoft Academic Search

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

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

1995-01-01

262

Generation of DNA-Damaging Reactive Oxygen Species via the Autoxidation of Hydrogen Sulfide under Physiologically Relevant  

E-print Network

Generation of DNA-Damaging Reactive Oxygen Species via the Autoxidation of Hydrogen Sulfide under found that micromolar concentrations of H2S generated single-strand DNA cleavage. Mechanistic studies indicate that this process involved autoxidation of H2S to generate superoxide, hydrogen peroxide, and

Gates, Kent. S.

263

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...

264

Screening for the Formation of Reactive Oxygen Species and of NO in Muscle Tissue and Remote Organs upon Mechanical Trauma to the Mouse Hind Limb  

Microsoft Academic Search

Background: Until now, no systematic surveys exist in the literature on the early local and systemic generation of reactive oxygen species and of nitric oxide in response to muscle crush injury. Therefore, this study aims to evaluate the formation of reactive oxygen species and nitric oxide in different tissues (injured and contralateral muscle, liver, kidney, spleen and blood) that is

Uta Kerkweg; Daniel Schmitz; Herbert de Groot

2006-01-01

265

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

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

A. Ch. Pulla Reddy; Belur R. Lokesh

1994-01-01

266

Detection of reactive oxygen species in isolated, perfused lungs by electron spin resonance spectroscopy  

PubMed Central

Background The sources and measurement of reactive oxygen species (ROS) in intact organs are largely unresolved. This may be related to methodological problems associated with the techniques currently employed for ROS detection. Electron spin resonance (ESR) with spin trapping is a specific method for ROS detection, and may address some these technical problems. Methods We have established a protocol for the measurement of intravascular ROS release from isolated buffer-perfused and ventilated rabbit and mouse lungs, combining lung perfusion with the spin probe l-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine (CPH) and ESR spectroscopy. We then employed this technique to characterize hypoxia-dependent ROS release, with specific attention paid to NADPH oxidase-dependent superoxide formation as a possible vasoconstrictor pathway. Results While perfusing lungs with CPH over a range of inspired oxygen concentrations (1–21 %), the rate of CP• formation exhibited an oxygen-dependence, with a minimum at 2.5 % O2. Addition of superoxide dismutase (SOD) to the buffer fluid illustrated that a minor proportion of this intravascular ROS leak was attributable to superoxide. Stimulation of the lungs by injection of phorbol-12-myristate-13-acetate (PMA) into the pulmonary artery caused a rapid increase in CP• formation, concomitant with pulmonary vasoconstriction. Both the PMA-induced CPH oxidation and the vasoconstrictor response were largely suppressed by SOD. When the PMA challenge was performed at different oxygen concentrations, maximum superoxide liberation and pulmonary vasoconstriction occurred at 5 % O2. Using a NADPH oxidase inhibitor and NADPH-oxidase deficient mice, we illustrated that the PMA-induced superoxide release was attributable to the stimulation of NADPH oxidases. Conclusion The perfusion of isolated lungs with CPH is suitable for detection of intravascular ROS release by ESR spectroscopy. We employed this technique to demonstrate that 1) PMA-induced vasoconstriction is caused "directly" by superoxide generated from NADPH oxidases and 2) this pathway is pronounced in hypoxia. NADPH oxidases thus may contribute to the hypoxia-dependent regulation of pulmonary vascular tone. PMID:16053530

Weissmann, Norbert; Kuzkaya, Nermin; Fuchs, Beate; Tiyerili, Vedat; Schäfer, Rolf U; Schütte, Hartwig; Ghofrani, Hossein A; Schermuly, Ralph T; Schudt, Christian; Sydykov, Akylbek; Egemnazarow, Bakytbek; Seeger, Werner; Grimminger, Friedrich

2005-01-01

267

The role of reactive oxygen species and proinflammatory cytokines in type 1 diabetes pathogenesis  

PubMed Central

Type 1 diabetes (T1D) is a T cell–mediated autoimmune disease characterized by the destruction of insulin-secreting pancreatic ? cells. In humans with T1D and in nonobese diabetic (NOD) mice (a murine model for human T1D), autoreactive T cells cause ?-cell destruction, as transfer or deletion of these cells induces or prevents disease, respectively. CD4+ and CD8+ T cells use distinct effector mechanisms and act at different stages throughout T1D to fuel pancreatic ?-cell destruction and disease pathogenesis. While these adaptive immune cells employ distinct mechanisms for ?-cell destruction, one central means for enhancing their autoreactivity is by the secretion of proinflammatory cytokines, such as IFN-?, TNF-?, and IL-1. In addition to their production by diabetogenic T cells, proinflammatory cytokines are induced by reactive oxygen species (ROS) via redox-dependent signaling pathways. Highly reactive molecules, proinflammatory cytokines are produced upon lymphocyte infiltration into pancreatic islets and induce disease pathogenicity by directly killing ? cells, which characteristically possess low levels of antioxidant defense enzymes. In addition to ?-cell destruction, proinflammatory cytokines are necessary for efficient adaptive immune maturation, and in the context of T1D they exacerbate autoimmunity by intensifying adaptive immune responses. The first half of this review discusses the mechanisms by which autoreactive T cells induce T1D pathogenesis and the importance of ROS for efficient adaptive immune activation, which, in the context of T1D, exacerbates autoimmunity. The second half provides a comprehensive and detailed analysis of (1) the mechanisms by which cytokines such as IL-1 and IFN-? influence islet insulin secretion and apoptosis and (2) the key free radicals and transcription factors that control these processes. PMID:23323860

Padgett, Lindsey E; Broniowska, Katarzyna A; Hansen, Polly A; Corbett, John A; Tse, Hubert M

2013-01-01

268

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

SciTech Connect

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.

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

269

Oxidized LDL activates STAT1 and STAT3 transcription factors: possible involvement of reactive oxygen species.  

PubMed

The effect of cupric ion-oxidized low density lipoprotein (Cu-LDL) or endothelial cell-oxidized LDL (E-LDL) on STAT1 and STAT3 (signal transducers and activators of transcription) DNA binding activity was investigated by electrophoretic mobility shift assay in human endothelial cells. Both oxidized LDL enhanced STAT1 and STAT3 binding to their respective consensus binding sites. Furthermore, the activation of STATs was proportional to the oxidation degree of LDL in that the highly oxidized Cu-LDL exhibited a more marked effect than E-LDL. Oxidized LDL induced an intracellular oxidative stress, as shown by the increase in the intracellular level of lipid peroxidation products (thiobarbituric acid-reactive substances) and in the level of reactive oxygen species, measured by the fluorescence of dichlorofluorescein diacetate. The binding activity of STAT1 and STAT3 paralleled these two parameters, which suggests that it is dependent upon the redox state of the cell. The activation of STATs by oxidized LDL was almost completely inhibited by the lipophilic antioxidant vitamin E, and partially antagonized by the hydrophilic thiol-containing compound N-acetylcysteine, suggesting that the oxidative stress induced by oxidized LDL is involved in the observed phenomenon. Furthermore, the lipid extract of Cu-LDL also activated STAT1 and STAT3. Since the STAT pathway plays a key role in cytokine and growth factor signal transduction, the activation of STATs by oxidized LDL might be related to their proinflammatory and fibroproliferative effect in the atherosclerotic plaque. PMID:10217408

Mazière, C; Alimardani, G; Dantin, F; Dubois, F; Conte, M A; Mazière, J C

1999-04-01

270

Uncoupling-mediated generation of reactive oxygen by halogenated aromatic hydrocarbons in mouse liver microsomes.  

PubMed

Studying liver microsomes from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced or vehicle-treated (noninduced) mice, we evaluated the in vitro effects of added chemicals on the production of reactive oxygen due to substrate/P450-mediated uncoupling. The catalase-inhibited NADPH-dependent H(2)O(2) production (luminol assay) was lower in induced than noninduced microsomes. The effects of adding chemicals (2.5 microM) in vitro could be divided into three categories: Group 1, highly halogenated and coplanar compounds that increased H(2)O(2) production at least 5-fold in induced, but not in noninduced, microsomes; Group 2, non-coplanar halogenated biphenyls that did not affect H(2)O(2) production; Group 3, minimally halogenated biphenyls and benzo[a]pyrene that decreased H(2)O(2) production. Molar consumption of NADPH and O(2) and molar H(2)O(2) production (o-dianisidine oxidation) revealed that Group 1 compounds mostly increased, Group 2 had no effect, and Group 3 decreased the H(2)O(2)/O(2) and H(2)O(2)/NADPH ratios. Microsomal lipid peroxidation (thiobarbituric acid-reactive substances) was proportional to H(2)O(2) production. Although TCDD induction decreased microsomal production of H(2)O(2), addition of Group 1 compounds to TCDD-induced microsomes in vitro stimulated the second-electron reduction of cytochrome P450 and subsequent release of H(2)O(2) production. This pathway is likely to contribute to the oxidative stress response and associated toxicity produced by many of these environmental chemicals. PMID:14980705

Shertzer, Howard G; Clay, Corey D; Genter, Mary Beth; Chames, Mark C; Schneider, Scott N; Oakley, Greg G; Nebert, Daniel W; Dalton, Timothy P

2004-03-01

271

Mobile Phone Radiation Induces Reactive Oxygen Species Production and DNA Damage in Human Spermatozoa In Vitro  

PubMed Central

Background In recent times there has been some controversy over the impact of electromagnetic radiation on human health. The significance of mobile phone radiation on male reproduction is a key element of this debate since several studies have suggested a relationship between mobile phone use and semen quality. The potential mechanisms involved have not been established, however, human spermatozoa are known to be particularly vulnerable to oxidative stress by virtue of the abundant availability of substrates for free radical attack and the lack of cytoplasmic space to accommodate antioxidant enzymes. Moreover, the induction of oxidative stress in these cells not only perturbs their capacity for fertilization but also contributes to sperm DNA damage. The latter has, in turn, been linked with poor fertility, an increased incidence of miscarriage and morbidity in the offspring, including childhood cancer. In light of these associations, we have analyzed the influence of RF-EMR on the cell biology of human spermatozoa in vitro. Principal Findings Purified human spermatozoa were exposed to radio-frequency electromagnetic radiation (RF-EMR) tuned to 1.8 GHz and covering a range of specific absorption rates (SAR) from 0.4 W/kg to 27.5 W/kg. In step with increasing SAR, motility and vitality were significantly reduced after RF-EMR exposure, while the mitochondrial generation of reactive oxygen species and DNA fragmentation were significantly elevated (P<0.001). Furthermore, we also observed highly significant relationships between SAR, the oxidative DNA damage bio-marker, 8-OH-dG, and DNA fragmentation after RF-EMR exposure. Conclusions RF-EMR in both the power density and frequency range of mobile phones enhances mitochondrial reactive oxygen species generation by human spermatozoa, decreasing the motility and vitality of these cells while stimulating DNA base adduct formation and, ultimately DNA fragmentation. These findings have clear implications for the safety of extensive mobile phone use by males of reproductive age, potentially affecting both their fertility and the health and wellbeing of their offspring. PMID:19649291

De Iuliis, Geoffry N.; Newey, Rhiannon J.; King, Bruce V.; Aitken, R. John

2009-01-01

272

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

PubMed Central

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

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

2014-01-01

273

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

PubMed

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

Zhang, Danning; Yan, Shuwen; Song, Weihua

2014-11-01

274

Release of Proteins from Intact Chloroplasts Induced by Reactive Oxygen Species during Biotic and Abiotic Stress  

PubMed Central

Plastids sustain life on this planet by providing food, feed, essential biomolecules and oxygen. Such diverse metabolic and biosynthetic functions require efficient communication between plastids and the nucleus. However, specific factors, especially large molecules, released from plastids that regulate nuclear genes have not yet been fully elucidated. When tobacco and lettuce transplastomic plants expressing GFP within chloroplasts, were challenged with Erwinia carotovora (biotic stress) or paraquat (abiotic stress), GFP was released into the cytoplasm. During this process GFP moves gradually towards the envelope, creating a central red zone of chlorophyll fluorescence. GFP was then gradually released from intact chloroplasts into the cytoplasm with an intact vacuole and no other visible cellular damage. Different stages of GFP release were observed inside the same cell with a few chloroplasts completely releasing GFP with detection of only red chlorophyll fluorescence or with no reduction in GFP fluorescence or transitional steps between these two phases. Time lapse imaging by confocal microscopy clearly identified sequence of these events. Intactness of chloroplasts during this process was evident from chlorophyll fluorescence emanated from thylakoid membranes and in vivo Chla fluorescence measurements (maximum quantum yield of photosystem II) made before or after infection with pathogens to evaluate their photosynthetic competence. Hydrogen peroxide and superoxide anion serve as signal molecules for generation of reactive oxygen species and Tiron, scavenger of superoxide anion, blocked release of GFP from chloroplasts. Significant increase in ion leakage in the presence of paraquat and light suggests changes in the chloroplast envelope to facilitate protein release. Release of GFP-RC101 (an antimicrobial peptide), which was triggered by Erwinia infection, ceased after conferring protection, further confirming this export phenomenon. These results suggest a novel signaling mechanism, especially for participation of chloroplast proteins (e.g. transcription factors) in retrograde signaling, thereby offering new opportunities to regulate pathways outside chloroplasts. PMID:23799142

Singh, Nameirakpam D.; Daniell, Henry

2013-01-01

275

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

SciTech Connect

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.

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

276

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

PubMed Central

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

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

2013-01-01

277

Anoxia-induced changes in reactive oxygen species and cyclic nucleotides in the painted turtle.  

PubMed

The Western painted turtle survives months without oxygen. A key adaptation is a coordinated reduction of cellular ATP production and utilization that may be signaled by changes in the concentrations of reactive oxygen species (ROS) and cyclic nucleotides (cAMP and cGMP). Little is known about the involvement of cyclic nucleotides in the turtle's metabolic arrest and ROS have not been previously measured in any facultative anaerobes. The present study was designed to measure changes in these second messengers in the anoxic turtle. ROS were measured in isolated turtle brain sheets during a 40-min normoxic to anoxic transition. Changes in cAMP and cGMP were determined in turtle brain, pectoralis muscle, heart and liver throughout 4 h of forced submergence at 20-22 degrees C. Turtle brain ROS production decreased 25% within 10 min of cyanide or N(2)-induced anoxia and returned to control levels upon reoxygenation. Inhibition of electron transfer from ubiquinol to complex III caused a smaller decrease in [ROS]. Conversely, inhibition of complex I increased [ROS] 15% above controls. In brain [cAMP] decreased 63%. In liver [cAMP] doubled after 2 h of anoxia before returning to control levels with prolonged anoxia. Conversely, skeletal muscle and heart [cAMP] remained unchanged; however, skeletal muscle [cGMP] became elevated sixfold after 4 h of submergence. In liver and heart [cGMP] rose 41 and 127%, respectively, after 2 h of anoxia. Brain [cGMP] did not change significantly during 4 h of submergence. We conclude that turtle brain ROS production occurs primarily between mitochondrial complexes I and III and decreases during anoxia. Also, cyclic nucleotide concentrations change in a manner suggestive of a role in metabolic suppression in the brain and a role in increasing liver glycogenolysis. PMID:17347830

Pamenter, Matthew Edward; Richards, Michael David; Buck, Leslie Thomas

2007-05-01

278

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

PubMed

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

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

2007-03-01

279

Knockdown of GDCH gene reveals reactive oxygen species-induced leaf senescence in rice.  

PubMed

Glycine decarboxylase complex (GDC) is a multi-protein complex, comprising P-, H-, T- and L-protein subunits, which plays a major role in photorespiration in plants. While structural analysis has demonstrated that the H subunit of GDC (GDCH) plays a pivotal role in GDC, research on the role of GDCH in biological processes in plants is seldom reported. Here, the function of GDCH, stresses resulting from GDCH-knockdown and the interactions of these stresses with other cellular processes were studied in rice plants. Under high CO(2), the OsGDCH RNA interference (OsGDCH-RNAi) plants grew normally, but under ambient CO(2), severely suppressed OsGDCH-RNAi plants (SSPs) were non-viable, which displayed a photorespiration-deficient phenotype. Under ambient CO(2), chlorophyll loss, protein degradation, lipid peroxidation and photosynthesis decline occurred in SSPs. Electron microscopy studies showed that chloroplast breakdown and autophagy took place in these plants. Reactive oxygen species (ROS), including O2(-) and H(2)O(2), accumulated and the antioxidant enzyme activities decreased in the leaves of SSPs under ambient CO(2). The expression of transcription factors and senescence-associated genes (SAGs), which was up-regulated in SSPs after transfer to ambient CO(2), was enhanced in wild-type plants treated with H(2)O(2). Evidences demonstrate ROS induce senescence in SSPs, and transcription factors OsWRKY72 may mediate the ROS-induced senescence. PMID:23421602

Zhou, Qiying; Yu, Qian; Wang, Zhanqi; Pan, Yufang; Lv, Wentang; Zhu, Lili; Chen, Rongzhi; He, Guangcun

2013-08-01

280

Involvement of reactive oxygen species in the cytotoxic effect of acid-electrolyzed water.  

PubMed

Acid-electrolyzed water (AEW) is commonly used as a disinfectant in the agricultural and medical fields. Although several studies have been conducted to examine its toxicity in vitro and in vivo, the cytotoxic mechanism of AEW has never been verified. The purpose of the present study was to elucidate the underlying mechanism by which AEW exerts its in vitro cytotoxic effect. Mouse fibroblasts treated with AEW experienced dilution rate-dependent cytotoxic effects in the 100% confluent phase as well as in the mitotic phase. The levels of intracellular reactive oxygen species (ROS) increased significantly in fully-confluent cells treated with undiluted and four times diluted AEW. In both of these treatments, cytotoxicity was also observed. It is thus concluded that the in vitro cytotoxicity of AEW is attributable to increased intracellular ROS. Additionally, the ROS responsible for these effects appears to be, at least in part, hydroxyl radical because the increase in intracellular ROS was attenuated by post-treatment with dimethyl sulfoxide, a hydroxyl radical scavenger, and with the antioxidant polyphenol, proanthocyanidin. PMID:25560392

Mokudai, Takayuki; Kanno, Taro; Niwano, Yoshimi

2015-01-01

281

Controllable generation of reactive oxygen species by femtosecond-laser irradiation  

SciTech Connect

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.

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

282

Reactive oxygen species inhibitors block priming, but not activation of the NLRP3 inflammasome  

PubMed Central

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

Bauernfeind, Franz; Bartok, Eva; Rieger, Anna; Franchi, Luigi; Núñez, Gabriel; Hornung, Veit

2011-01-01

283

Reactive oxygen species scavenging activity during periodontal mucoperiosteal healing: an experimental study in dogs.  

PubMed

Excessive release of reactive oxygen species (ROS) in wounded tissue due to inflammation and ischaemia is a deleterious and destructive phenomenon for the healing process. Hence, scavenging of ROS is one of the essential steps in normal wound repair. In this study, we presented a profile of free radical scavenging enzyme (FRSE) activity of periodontal mucoperiosteal wounds in order to investigate ROS activity during periodontal wound healing. Mucoperiosteal periodontal flaps were elevated in the mandibular buccal region of seven dogs between the first premolar and first molar teeth, creating acute incisional wounds in the inner side of the flaps and they were replaced 30 min after elevation. Gingival samples taken from certain biopsy regions at baseline (before flap elevation), day 3, 12, 21 and 30 were processed for detection of active amounts of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). All enzyme activities had increased by more than 100% of their baseline levels by day 3. SOD activity decreased gradually from days 3 to 30 and reached a level lower than the baseline value. The increase in CAT activity continued until day 21, and decreased to a level higher than the baseline value by day 30. GPX also decreased from day 3, and reached a level less than its baseline value by day 30. Our results suggest that FRSEs may contribute to the detoxification of ROS during periodontal mucoperiosteal healing. This relationship may be utilized to facilitate soft tissue and/or flap management in periodontal or intra-oral treatments. PMID:15939395

Sakallio?lu, Umur; Aliyev, Eldar; Eren, Zafer; Ak?im?ek, Gülhan; Keskiner, Ilker; Yavuz, Umit

2005-12-01

284

Behind the scenes: the roles of reactive oxygen species in guard cells.  

PubMed

Guard cells regulate stomatal pore size through integration of both endogenous and environmental signals; they are widely recognized as providing a key switching mechanism that maximizes both the efficient use of water and rates of CO? exchange for photosynthesis; this is essential for the adaptation of plants to water stress. Reactive oxygen species (ROS) are widely considered to be an important player in guard cell signalling. In this review, we focus on recent progress concerning the role of ROS as signal molecules in controlling stomatal movement, the interaction between ROS and intrinsic and environmental response pathways, the specificity of ROS signalling, and how ROS signals are sensed and relayed. However, the picture of ROS-mediated signalling is still fragmented and the issues of ROS sensing and the specificity of ROS signalling remain unclear. Here, we review some recent advances in our understanding of ROS signalling in guard cells, with an emphasis on the main players known to interact with abscisic acid signalling. PMID:24188383

Song, Yuwei; Miao, Yuchen; Song, Chun-Peng

2014-03-01

285

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

PubMed Central

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

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

2014-01-01

286

Reactive Oxygen Species Production in Energized Cardiac Mitochondria During Hypoxia/Reoxygenation: Modulation by Nitric Oxide  

PubMed Central

Mitochondria are an important source of reactive oxygen species (ROS) implicated in ischemia/reperfusion injury. When isolated from ischemic myocardium, mitochondria demonstrate increased ROS production as a result of damage to electron transport complexes. To investigate the mechanisms, we studied effects of hypoxia/reoxygenation on ROS production by isolated energized heart mitochondria. ROS production, tracked using Fe2+-catalyzed, H2O2-dependent H2DCF oxidation or Amplex Red, was similar during normoxia and hypoxia, but markedly increased during reoxygenation, in proportion to the duration of hypoxia. In contrast, if mitochondria were rapidly converted from normoxia to near-anoxia ([O2]< 1 ?M), the increase in H2DCF oxidation rate during reoxygenation was markedly blunted. To elicit the robust increase in H2DCF oxidation rate during reoxygenation, hypoxia had to be severe enough to cause partial, but not complete, respiratory chain inhibition (as shown by partial dissipation of membrane potential and increased NADH auto-fluorescence). Consistent with its cardioprotective actions, nitric oxide (•NO) abrogated increased H2DCF oxidation under these conditions, as well as attenuating ROS-induced increases in matrix [Fe2+] and aconitase inhibition caused by antimycin. Collectively, these results suggest that a) hypoxia sufficient to cause partial respiratory inhibition is more damaging to mitochondria than near-anoxia; b) •NO suppresses ROS-induced damage to electron transport complexes, probably by forming •NO-Fe2+ complexes in the presence of glutathione which inhibit hydroxyl radical formation. PMID:18776040

Korge, Paavo; Ping, Peipei; Weiss, James N

2009-01-01

287

Mitochondria-derived reactive oxygen species mediate caspase-dependent and -independent neuronal deaths.  

PubMed

Mitochondrial dysfunction and oxidative stress are implicated in many neurodegenerative diseases. Mitochondria-targeted drugs that effectively decrease oxidative stress, protect mitochondrial energetics, and prevent neuronal loss may therefore lend therapeutic benefit to these currently incurable diseases. To investigate the efficacy of such drugs, we examined the effects of mitochondria-targeted antioxidants MitoQ10 and MitoE2 on neuronal death induced by neurotrophin deficiency. Our results indicate that MitoQ10 blocked apoptosis by preventing increased mitochondria-derived reactive oxygen species (ROS) and subsequent cytochrome c release, caspase activation, and mitochondrial damage in nerve growth factor (NGF)-deprived sympathetic neurons, while MitoE2 was largely ineffective. In this paradigm, the most proximal point of divergence was the ability of MitoQ10 to scavenge mitochondrial superoxide (O2(-)). MitoQ10 also prevented caspase-independent neuronal death in these cells demonstrating that the mitochondrial redox state significantly influences both apoptotic and nonapoptotic pathways leading to neuronal death. We suggest that mitochondria-targeted antioxidants may provide tools for delineating the role and significance of mitochondrial ROS in neuronal death and provide a new therapeutic approach for neurodegenerative conditions involving trophic factor deficits and multiple modes of cell death. PMID:25239010

McManus, Meagan J; Murphy, Michael P; Franklin, James L

2014-11-01

288

Metabolism of reactive oxygen species in cytoplasmic male sterility of rice by marking upmost pulvinus interval.  

PubMed

Reactive oxygen species (ROS) and malondialdehyde (MDA) in plant cell are thought to be important inducible factors of cell apoptosis if excessively accumulated in cells. To elucidate the metabolic mechanism of MDA production and scavenging in the cytoplasmic male-sterile (CMS) rice, CMS line and maintainer were employed for studying the relationship at different developmental stages by marking upmost pulvinus interval method of experiment. The results showed that the panicles and leaves of the CMS line had a noticeable higher MDA content than those of maintainer line at all five stages that had been investigated (p?

Li, Jianxin; Dai, Ximei; Li, Linyu; Jiao, Zhen; Huang, Qunce

2015-02-01

289

Cytotoxicity and reactive oxygen species generation from aggregated carbon and carbonaceous nanoparticulate materials  

PubMed Central

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

Garza, Kristine M; Soto, Karla F; Murr, Lawrence E

2008-01-01

290

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

NASA Astrophysics Data System (ADS)

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.

Liu, Li; Xu, Shi-jie; Li, Song-zhan

2009-07-01

291

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

PubMed Central

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

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

2013-01-01

292

Reactive oxygen species scavenging ability of a new compound derived from weathered coal  

NASA Astrophysics Data System (ADS)

The scavenging activity of three fulvic acids (named XWCS-1, XWCS-4, and XWCS-8 according to time taken for ozonolysis) obtained by ozonolysis of humic acid extracted from Xinjiang (China) weathered coal and a fulvic acid (named XWCFA) extracted from the same coal towards reactive oxygen species such as superoxide radical (O 2rad -) and hydroxyl radical ( rad OH) was investigated with an electron spin resonance (ESR)-spin trapping method using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trap. O 2rad - was generated with a hypoxanthine-xanthine oxidase system. rad OH was generated by three different methods; (i) FeSO 4-hydrogen peroxide (H 2O 2) system, (ii) Cu(en) 2-H 2O 2 system, and (iii) UVB photolysis of H 2O 2. At physiological pH, XWCS-1 had the greatest O 2rad - scavenging activity, followed by XWCS-4, XWCS-8 and XWCFA. XWCFA had the greatest rad OH scavenging activity among the four fulvic acids, whereas XWCS-1 and XWCS-4 enhanced the production of rad OH from a metal-catalyzed hydroxyl radical generating system, suggesting that these molecules act as prooxidants in the presence of metal ion.

Ueda, Jun-ichi; Ikota, Nobuo; Shinozuka, Toshiyuki; Yamaguchi, Tatsuaki

2004-09-01

293

Reactive oxygen species enhance differentiation of human embryonic stem cells into mesendodermal lineage.  

PubMed

Recently, reactive oxygen species (ROS) have been studied as a regulator of differentiation into specific cell types in embryonic stem cells (ESCs). However, ROS role in human ESCs (hESCs) is unknown because mouse ESCs have been used mainly for most studies. Herein we suggest that ROS generation may play a critical role in differentiation of hESCs; ROS enhances differentiation of hESCs into bi-potent mesendodermal cell lineage via ROS-involved signaling pathways. In ROS-inducing conditions, expression of pluripotency markers (Oct4, Tra 1-60, Nanog, and Sox2) of hESCs was decreased, while expression of mesodermal and endodermal markers was increased. Moreover, these differentiation events of hESCs in ROS-inducing conditions were decreased by free radical scavenger treatment. hESC-derived embryoid bodies (EBs) also showed similar differentiation patterns by ROS induction. In ROS-related signaling pathway, some of the MAPKs family members in hESCs were also affected by ROS induction. p38 MAPK and AKT (protein kinases B, PKB) were inactivated significantly by buthionine sulfoximine (BSO) treatment. JNK and ERK phosphorylation levels were increased at early time of BSO treatment but not at late time point. Moreover, MAPKs family-specific inhibitors could prevent the mesendodermal differentiation of hESCs by ROS induction. Our results demonstrate that stemness and differentiation of hESCs can be regulated by environmental factors such as ROS. PMID:20164681

Ji, Ae-Ri; Ku, Seung-Yup; Cho, Myung Soo; Kim, Yoon Young; Kim, Yong Jin; Oh, Sun Kyung; Kim, Seok Hyun; Moon, Shin Yong; Choi, Young Min

2010-03-31

294

Ornithine decarboxylase prevents dibenzoylmethane-induced apoptosis through repressing reactive oxygen species generation.  

PubMed

Dibenzoylmethane (DBM) belongs to the flavonoid family and is a minor constituent of the root extract of licorice and the ?-diketone analogue of curcumin. It exhibits antimutagenic, anticancer, and chemopreventive effects. Ornithine decarboxylase (ODC), the rate-limiting enzyme of the polyamine biosynthetic pathway, plays an important role in growth, proliferation, and transformation. Our previous studies showed ODC overexpression prevented etoposide-, paclitaxel-, and cisplatin-induced apoptosis. Here, we investigated one mechanism of DBM-induced apoptosis and the antiapoptotic effects of ODC during DBM treatment. We found that DBM induced apoptosis, promoted reactive oxygen species (ROS) generation, and disrupted the mitochondrial membrane potential (??(m). N-acetylcysteine, a ROS scavenger, reduced DBM-induced apoptosis, which led to the loss of ??(m) due to reduced ROS. Overexpression of ODC in parental cells had the same effects as the ROS scavenger. The results demonstrated that DBM-induced apoptosis was a ROS-dependent pathway and ODC overexpression blocked DBM-induced apoptosis by inhibiting intracellular ROS production. PMID:21523861

Wu, Chih-Lung; Liao, Ya-Fan; Hung, Ying-Cheng; Lu, Ko-Hsiu; Hung, Hui-Chih; Liu, Guang-Yaw

2011-01-01

295

Mitochondrial reactive oxygen species regulate spatial profile of proinflammatory responses in lung venular capillaries.  

PubMed

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

Parthasarathi, Kaushik; Ichimura, Hideo; Quadri, Sadiqa; Issekutz, Andrew; Bhattacharya, Jahar

2002-12-15

296

Copper compound induces autophagy and apoptosis of glioma cells by reactive oxygen species and jnk activation  

PubMed Central

Background Glioblastoma multiforme (GBM) is the most aggressive of the primary brain tumors, with a grim prognosis despite intensive treatment. In the past decades, progress in research has not significantly increased overall survival rate. Methods The in vitro antineoplastic effect and mechanism of action of Casiopeina III-ia (Cas III-ia), a copper compound, on rat malignant glioma C6 cells was investigated. Results Cas III-ia significantly inhibited cell proliferation, inducing autophagy and apoptosis, which correlated with the formation of autophagic vacuoles, overexpression of LC3, Beclin 1, Atg 7, Bax and Bid proteins. A decrease was detected in the mitochondrial membrane potential and in the activity of caspase 3 and 8, together with the generation of intracellular reactive oxygen species (ROS) and increased activity of c-jun NH2-terminal kinase (JNK). The presence of 3-methyladenine (as selective autophagy inhibitor) increased the antineoplastic effect of Cas III-ia, while Z-VAD-FMK only showed partial protection from the antineoplastic effect induced by Cas III-ia, and ROS antioxidants (N-acetylcysteine) decreased apoptosis, autophagy and JNK activity. Moreover, the JNK –specific inhibitor SP600125 prevented Cas III-ia-induced cell death. Conclusions Our data suggest that Cas III-ia induces cell death by autophagy and apoptosis, in part due to the activation of ROS –dependent JNK signaling. These findings support further studies of Cas III-ia as candidate for treatment of human malignant glioma. PMID:22540380

2012-01-01

297

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

SciTech Connect

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.

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

298

Inhibition of ERK Oscillations by Ionizing Radiation and Reactive Oxygen Species  

SciTech Connect

The shuttling of activated protein kinases between the cytoplasm and nucleus is an essential feature of normal growth factor signaling cascades. Here we demonstrate that transforming growth factor alpha (TGF?) induces oscillations in extracellular signal regulated kinase (ERK) cytoplasmic-nuclear translocations in human keratinocytes. TGF?-dependent ERK oscillations mediated through the epidermal growth factor receptor (EGFR) are inhibited by low dose X-irradiation (10?cGy) and low concentrations of hydrogen peroxide (0.32–3.26?µM H2O2) used as a model reactive oxygen species (ROS). A fluorescent indicator dye (H2-DCFDA) was used to measure cellular ROS levels following X-irradiation, 12-O-tetradecanoyl phorbol-13-acetate (TPA) and H2O2. X-irradiation did not generate significant ROS production while 0.32?µM H2O2 and TPA induced significant increases in ROS levels with H2O2? >?TPA. TPA alone induced transactivation of the EGFR but did not induce ERK oscillations. TPA as a cotreatment did not inhibit TGF?-stimulated ERK oscillations but qualitatively altered TGF?-dependent ERK oscillation characteristics (amplitude, time-period). Collectively, these observations demonstrate that TGF?-induced ERK oscillations are inhibited by ionizing radiation/ROS and perturbed by epigenetic carcinogen in human keratinocytes. © 2010 Wiley-Liss, Inc.

Shankaran, Harish; Chrisler, William B.; Sontag, Ryan L.; Weber, Thomas J.

2010-12-28

299

Targeting cancer cells with reactive oxygen and nitrogen species generated by atmospheric-pressure air plasma.  

PubMed

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

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

2014-01-01

300

Mechanism of Action of Phenethylisothiocyanate and Other Reactive Oxygen Species-Inducing Anticancer Agents  

PubMed Central

Reactive oxygen species (ROS)-inducing anticancer agents such as phenethylisothiocyanate (PEITC) activate stress pathways for killing cancer cells. Here we demonstrate that PEITC-induced ROS decreased expression of microRNA 27a (miR-27a)/miR-20a:miR-17-5p and induced miR-regulated ZBTB10/ZBTB4 and ZBTB34 transcriptional repressors, which, in turn, downregulate specificity protein (Sp) transcription factors (TFs) Sp1, Sp3, and Sp4 in pancreatic cancer cells. Decreased expression of miR-27a/miR-20a:miR-17-5p by PEITC-induced ROS is a key step in triggering the miR-ZBTB Sp cascade leading to downregulation of Sp TFs, and this is due to ROS-dependent epigenetic effects associated with genome-wide shifts in repressor complexes, resulting in decreased expression of Myc and the Myc-regulated miRs. Knockdown of Sp1 alone by RNA interference also induced apoptosis and decreased pancreatic cancer cell growth and invasion, indicating that downregulation of Sp transcription factors is an important common mechanism of action for PEITC and other ROS-inducing anticancer agents. PMID:24732804

Jutooru, Indira; Guthrie, Aaron S.; Chadalapaka, Gayathri; Pathi, Satya; Kim, KyoungHyun; Burghardt, Robert; Jin, Un-Ho

2014-01-01

301

Role of Reactive Oxygen Intermediates in Cellular Responses to Dietary Cancer Chemopreventive Agents  

PubMed Central

Epidemiological studies continue to support the premise that diets rich in fruits and vegetables may offer protection against cancer of various anatomical sites. This correlation is quite persuasive for some vegetables including Allium (e.g., garlic) and cruciferous (e.g., broccoli and watercress) vegetables. The bioactive food components responsible for cancer chemopreventive effects of various edible plants have been identified. For instance, anticancer effects of Allium and cruciferous vegetables are attributed to organosulfur compounds (e.g., diallyl trisulfide) and isothiocyanates (e.g., sulforaphane and phenethyl isothiocyanate), respectively. Bioactive food components with anticancer activity are generally considered antioxidants due to their ability to modulate expression/activity of anti-oxidative and phase 2 drug metabolizing enzymes and scavenging free radicals. At the same time, more recent studies have provided convincing evidence to indicate that certain dietary cancer chemopreventive agents cause generation of reactive oxygen species to trigger signal transduction culminating in cell cycle arrest and/or programmed cell death (apoptosis). Interestingly, the ROS generation by some dietary anticancer agents is tumor cell specific and does not occur in normal cells. This review summarizes experimental evidence supporting involvement of ROS in cellular responses to cancer chemopreventive agents derived from common edible plants. PMID:18671201

Antosiewicz, Jedrzej; Ziolkowski, Wieslaw; Kar, Siddhartha; Powolny, Anna A.; Singh, Shivendra V.

2008-01-01

302

p75NTR-dependent modulation of cellular handling of reactive oxygen species  

PubMed Central

Our previous studies demonstrated that p75NTR confers protection against oxidative stress-induced apoptosis upon PC12 cells; however, the mechanisms responsible for this effect are not known. The present studies reveal decreased mitochondrion membrane potential and increased generation of reactive oxygen species (ROS) in p75NTR-deficient PC12 cells as well as diminution of ROS generation after transfection of a full-length p75NTR construct into these cells. They also show that p75NTR deficiency attenuates activation of the phosphatidylinositol 3-kinase ? phospho-Akt/protein kinase B pathway in PC12 cells by oxidative stress or neurotrophic ligands and inhibition of Akt phosphorylation decreases the glutathione (GSH) content in PC12 cells. In addition, decreased de novo GSH synthesis and increased GSH consumption are observed in p75NTR-deficient cells. These findings indicate that p75NTR regulates cellular handling of ROS to effect a survival response to oxidative stress. PMID:19457114

Mi, Zhiping; Rogers, Danny A.; Mirnics, Zeljka Korade; Schor, Nina Felice

2015-01-01

303

Baicalin scavenges reactive oxygen species and protects human keratinocytes against UVC-induced cytotoxicity.  

PubMed

Long-term exposure to solar ultraviolet (UV) radiation can cause multiple skin disorders, including skin cancer. Protection against UV-induced damage is, therefore, a worldwide concern. Baicalin, a major component of traditional Chinese medicine Scutellaria baicalensis, has been reported to have antioxidant and cytostatic effects on normal epithelial and normal peripheral blood and myeloid cells. In the current study, we examined whether baicalin could also effectively protect human keratinocytes from damaging short-wave UVC irradiation. Baicalin-scavenged reactive oxygen species increased within 2 h after UVC radiation. Baicalin also abrogated UVC-induced apoptosis. In addition, we identified the major products after UVC radiation with T4 UV endonuclease, finding that baicalin prevented cyclobutane pyrimidine dimer formation induced by UVC. Furthermore, baicalin also prevented formation of oxidative adducts induced by UVC. Our results demonstrated the utility of baicalin in assessing the potential contribution of traditional Chinese medicinal agents in therapy of UVC-induced genomic damage to skin and suggest potential application of these agents as pharmaceuticals in prevention of solar-induced skin damage. PMID:24292572

Wang, Shou-Cheng; Chen, Sue-Fung; Lee, Yi-Min; Chuang, Chin-Liang; Bau, Da-Tian; Lin, Song-Shei

2013-01-01

304

Irradiation of skin with visible light induces reactive oxygen species and matrix-degrading enzymes.  

PubMed

Daily skin exposure to solar radiation causes cells to produce reactive oxygen species (ROS), which are a primary factor in skin damage. Although the contribution of the UV component to skin damage has been established, few studies have examined the effects of non-UV solar radiation on skin physiology. Solar radiation comprises <10% of UV, and thus the purpose of this study was to examine the physiological response of skin to visible light (400-700 nm). Irradiation of human skin equivalents with visible light induced production of ROS, proinflammatory cytokines, and matrix metalloproteinase (MMP)-1 expression. Commercially available sunscreens were found to have minimal effects on reducing visible light-induced ROS, suggesting that UVA/UVB sunscreens do not protect the skin from visible light-induced responses. Using clinical models to assess the generation of free radicals from oxidative stress, higher levels of free radical activity were found after visible light exposure. Pretreatment with a photostable UVA/UVB sunscreen containing an antioxidant combination significantly reduced the production of ROS, cytokines, and MMP expression in vitro, and decreased oxidative stress in human subjects after visible light irradiation. Taken together, these findings suggest that other portions of the solar spectrum aside from UV, particularly visible light, may also contribute to signs of premature photoaging in skin. PMID:22318388

Liebel, Frank; Kaur, Simarna; Ruvolo, Eduardo; Kollias, Nikiforos; Southall, Michael D

2012-07-01

305

Brain infarction correlates more closely with acrolein than with reactive oxygen species.  

PubMed

Although it is thought that the major factor responsible for cell damage is reactive oxygen species (ROS), our recent studies have shown that acrolein is more toxic than ROS. Thus, the relative importance of acrolein and ROS in cell damage during brain infarction was compared using photochemically induced thrombosis model mice. The levels of acrolein-conjugated albumin, and of 4-hydroxynonenal (HNE)-conjugated albumin and 8-OHdG were evaluated as indicators of damage produced by acrolein and ROS, respectively. The increase in acrolein-conjugated albumin was much greater than the increase in HNE-conjugated albumin or 8-OHdG, suggesting that acrolein is more strongly involved in cell damage than ROS during brain infarction. It was also shown that infarction led more readily to RNA damage than to DNA or phospholipid damage. As a consequence, polyamines were released from RNA, and acrolein was produced from polyamines, especially from spermine by spermine oxidase. Production of acrolein from spermine by spermine oxidase was clarified using spermine synthase-deficient Gy mice and transglutaminase 2-knockout mice, in which spermine content is negligible or spermidine/spermine N(1)-acetyltransferase activity is elevated. PMID:21187074

Saiki, Ryotaro; Park, Hyerim; Ishii, Itsuko; Yoshida, Madoka; Nishimura, Kazuhiro; Toida, Toshihiko; Tatsukawa, Hideki; Kojima, Soichi; Ikeguchi, Yoshihiko; Pegg, Anthony E; Kashiwagi, Keiko; Igarashi, Kazuei

2011-01-28

306

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

NASA Astrophysics Data System (ADS)

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).

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

2014-04-01

307

Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers  

PubMed Central

There are multiple sources of reactive oxygen species (ROS) in the cell. As a major site of ROS production, mitochondria have drawn considerable interest because it was recently discovered that mitochondrial ROS (mtROS) directly stimulate the production of proinflammatory cytokines and pathological conditions as diverse as malignancies, autoimmune diseases, and cardiovascular diseases all share common phenotype of increased mtROS production above basal levels. Several excellent reviews on this topic have been published, but ever-changing new discoveries mandated a more up-to-date and comprehensive review on this topic. Therefore, we update recent understanding of how mitochondria generate and regulate the production of mtROS and the function of mtROS both in physiological and pathological conditions. In addition, we describe newly developed methods to probe or scavenge mtROS and compare these methods in detail. Thorough understanding of this topic and the application of mtROS-targeting drugs in the research is significant towards development of better therapies to combat inflammatory diseases and inflammatory malignancies. PMID:23442817

2013-01-01

308

Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)  

PubMed Central

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

Ristow, Michael; Schmeisser, Kathrin

2014-01-01

309

Protective effect of lecithinized SOD on reactive oxygen species-induced xerostomia.  

PubMed

Reactive oxygen species (ROS) are believed to be involved in radiation-induced xerostomia, and the application of antioxidants may be a promising method for treating patients suffering from salivary gland dysfunction. In this study, we examined the ability of the antioxidant superoxide dismutase (SOD) to restore radiation-induced salivary gland dysfunction using a mouse model of radiation-induced salivary gland hypofunction and ultraviolet B (UVB)-irradiated human salivary gland cells. We administered lecithinized SOD (PC-SOD) prior to and after irradiation and measured the amount of saliva secreted. To confirm ROS generation, flow cytometry was performed using an oxidant-sensitive fluorescent dye, dihydroethidium, and CM-H(2)DCFDA. While no significant decrease in saliva secretion was observed after irradiation in the mice that were treated with PC-SOD, a significant reduction in saliva secretion was noted in the irradiated mice that were not treated with PC-SOD. Furthermore, flow cytometry clearly revealed that PC-SOD eliminated superoxide (O(2)(-)) induced by UVB radiation. These results suggested that PC-SOD may protect against exocrine gland dysfunction induced by radiation, presumably by rapidly converting O(2)(-) to hydrogen peroxide. We believe that our results may advance the potential application of antioxidants for the prevention of ROS-induced xerostomia. PMID:19708782

Tai, Yoshinori; Inoue, Hiroko; Sakurai, Takashi; Yamada, Hiroyuki; Morito, Mitsuhiko; Ide, Fumio; Mishima, Kenji; Saito, Ichiro

2009-09-01

310

Amputation-induced reactive oxygen species (ROS) are required for successful Xenopus tadpole tail regeneration  

PubMed Central

Understanding the molecular mechanisms that promote successful tissue regeneration is critical for continued advancements in regenerative medicine. Vertebrate amphibian tadpoles of the species Xenopus laevis and Xenopus tropicalis have remarkable abilities to regenerate their tails following amputation 1, 2, via the coordinated activity of numerous growth factor signaling pathways, including the Wnt, Fgf, BMP, notch, and TGF? pathways 3-6. Little is known, however, about the events that act upstream of these signalling pathways following injury. Here, we show that Xenopus tadpole tail amputation induces a sustained production of reactive oxygen species (ROS) during tail regeneration. Lowering ROS levels, via pharmacological or genetic approaches, reduces cell proliferation and impairs tail regeneration. Genetic rescue experiments restored both ROS production and the initiation of the regenerative response. Sustained increased ROS levels are required for Wnt/?-catenin signaling and the activation of one of its major downstream targets, fgf20 7, which, in turn, is essential for proper tail regeneration. These findings demonstrate that injury-induced ROS production is an important regulator of tissue regeneration. PMID:23314862

Love, Nick R.; Chen, Yaoyao; Ishibashi, Shoko; Kritsiligkou, Paraskevi; Lea, Robert; Koh, Yvette; Gallop, Jennifer L.; Dorey, Karel; Amaya, Enrique

2013-01-01

311

The molecular basis for adhesion-mediated suppression of reactive oxygen species generation by human neutrophils  

PubMed Central

Human neutrophil adherence to ECMs induces an initial inhibition of stimulated reactive oxygen species (ROS) formation, followed by an enhanced phase of oxidant production. The initial integrin-mediated suppression of ROS constitutes a mechanism to prevent inappropriate tissue damage as leukocytes migrate to inflammatory sites. The Rac2 guanosine 5?-triphosphatase (GTPase) is a critical regulatory component of the phagocyte NADPH oxidase. We show that activation of Rac2 is inhibited in adherent neutrophils, correlating with inhibition of ROS formation. Conversely, NADPH oxidase components p47 and p67 assemble normally, suggesting a specific action of adhesion on the Rac2 molecular switch. Reconstitution with activated Rac2 restored rapid NADPH oxidase activation kinetics to adherent neutrophils, establishing that inhibition was due to defective Rac2 activity. We provide evidence that integrins inhibit Rac2 activation via a membrane-associated guanine nucleotide exchange factor, likely to be Vav1. Activation of Vav1, but not its upstream activator, Syk, is suppressed by cell adhesion. Vav1 activity is inhibited due to dephosphorylation of the regulatory Tyr174 via enhanced tyrosine phosphatase activity in adherent cells. These studies identify an integrin-mediated pathway in which Vav1 is as a strong candidate for the critical regulatory point in suppression of Rac2 activation and ROS generation during inflammatory responses. PMID:14660749

Zhao, Tieming; Benard, Valerie; Bohl, Benjamin P.; Bokoch, Gary M.

2003-01-01

312

Mitochondrial uncoupling does not decrease reactive oxygen species production after ischemia-reperfusion.  

PubMed

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

Quarrie, Ricardo; Lee, Daniel S; Reyes, Levy; Erdahl, Warren; Pfeiffer, Douglas R; Zweier, Jay L; Crestanello, Juan A

2014-10-01

313

Mitochondrial metabolic suppression in fasting and daily torpor: consequences for reactive oxygen species production.  

PubMed

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

Brown, Jason C L; Staples, James F

2011-01-01

314

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

NASA Astrophysics Data System (ADS)

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

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

2013-02-01

315

Ethylene Response Factor 6 Is a Regulator of Reactive Oxygen Species Signaling in Arabidopsis  

PubMed Central

Reactive oxygen species (ROS) are produced in plant cells in response to diverse biotic and abiotic stresses as well as during normal growth and development. Although a large number of transcription factor (TF) genes are up- or down-regulated by ROS, currently very little is known about the functions of these TFs during oxidative stress. In this work, we examined the role of ERF6 (ETHYLENE RESPONSE FACTOR6), an AP2/ERF domain-containing TF, during oxidative stress responses in Arabidopsis. Mutant analyses showed that NADPH oxidase (RbohD) and calcium signaling are required for ROS-responsive expression of ERF6. erf6 insertion mutant plants showed reduced growth and increased H2O2 and anthocyanin levels. Expression analyses of selected ROS-responsive genes during oxidative stress identified several differentially expressed genes in the erf6 mutant. In particular, a number of ROS responsive genes, such as ZAT12, HSFs, WRKYs, MAPKs, RBOHs, DHAR1, APX4, and CAT1 were more strongly induced by H2O2 in erf6 plants than in wild-type. In contrast, MDAR3, CAT3, VTC2 and EX1 showed reduced expression levels in the erf6 mutant. Taken together, our results indicate that ERF6 plays an important role as a positive antioxidant regulator during plant growth and in response to biotic and abiotic stresses. PMID:23940555

Sewelam, Nasser; Kazan, Kemal; Thomas-Hall, Skye R.; Kidd, Brendan N.; Manners, John M.; Schenk, Peer M.

2013-01-01

316

Chondrocyte cell death mediated by reactive oxygen species-dependent activation of PKC-?I  

PubMed Central

Signals generated by the extracellular matrix (ECM) promote cell survival. We have shown that chondrocytes detached from their native ECM and plated without serum at low density on poly-l-lysine undergo significant cell death that is associated with the production of reactive oxygen species (ROS). No cell death or ROS production was observed when cells were plated on fibronectin under the same conditions. Cell death on poly-l-lysine could be completely inhibited with the addition of either antioxidants or inhibitors of specific protein kinase C (PKC) isoforms including PKC-?I. PKC-?I was noted to translocate from the cytosol to the particulate membrane after plating on poly-l-lysine, and this translocation was inhibited by the addition of an antioxidant. Time-course analyses implicated endogenous ROS production as a secondary messenger leading to PKC-?I activation and subsequent chondrocyte cell death. Cell survival on poly-l-lysine was significantly improved in the presence of oligomycin or DIDS, suggesting that ROS production occurred via complex V of the electron transport chain of the mitochondria and that ROS were released to the cytosol via voltage-dependent anion channels. Together, these results represent a novel mechanism by which ROS can initiate cell death through the activation of PKC-?I. PMID:16236825

DelCarlo, Marcello; Loeser, Richard F.

2006-01-01

317

Hyperthermia Induces Apoptosis through Endoplasmic Reticulum and Reactive Oxygen Species in Human Osteosarcoma Cells  

PubMed Central

Osteosarcoma (OS) is a relatively rare form of cancer, but OS is the most commonly diagnosed bone cancer in children and adolescents. Chemotherapy has side effects and induces drug resistance in OS. Since an effective adjuvant therapy was insufficient for treating OS, researching novel and adequate remedies is critical. Hyperthermia can induce cell death in various cancer cells, and thus, in this study, we investigated the anticancer method of hyperthermia in human OS (U-2 OS) cells. Treatment at 43 °C for 60 min induced apoptosis in human OS cell lines, but not in primary bone cells. Furthermore, hyperthermia was associated with increases of intracellular reactive oxygen species (ROS) and caspase-3 activation in U-2 OS cells. Mitochondrial dysfunction was followed by the release of cytochrome c from the mitochondria, and was accompanied by decreased anti-apoptotic Bcl-2 and Bcl-xL, and increased pro-apoptotic proteins Bak and Bax. Hyperthermia triggered endoplasmic reticulum (ER) stress, which was characterized by changes in cytosolic calcium levels, as well as increased calpain expression and activity. In addition, cells treated with calcium chelator (BAPTA-AM) blocked hyperthermia-induced cell apoptosis in U-2 OS cells. In conclusion, hyperthermia induced cell apoptosis substantially via the ROS, ER stress, mitochondria, and caspase pathways. Thus, hyperthermia may be a novel anticancer method for treating OS. PMID:25268613

Hou, Chun-Han; Lin, Feng-Ling; Hou, Sheng-Mon; Liu, Ju-Fang

2014-01-01

318

Cryptococcus neoformans capsule protects cell from oxygen reactive species generated by antimicrobial photodynamic inactivation  

NASA Astrophysics Data System (ADS)

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.

Prates, Renato Araujo; Hamblin, Michael R.; Kato, Ilka T.; Fuchs, Beth; Mylonakis, Eleytherios; Simões Ribeiro, Martha; Tegos, George

2011-03-01

319

Antimalarial action of artesunate involves DNA damage mediated by reactive oxygen species.  

PubMed

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

Gopalakrishnan, Anusha M; Kumar, Nirbhay

2015-01-01

320

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

PubMed Central

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

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

2014-01-01

321

Phenolic extract of Dialium guineense pulp enhances reactive oxygen species detoxification in aflatoxin B? hepatocarcinogenesis.  

PubMed

This study investigated the effect of Dialium guineense pulp phenolic extract on aflatoxin B1 (AFB1)-induced oxidative imbalance in rat liver. Reactive oxygen species (ROS) scavenging potentials of free and bound phenolic extract of D. guineense (0.2-1.0?mg/mL) were investigated in vitro using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, superoxide ion (O2(-)), hydrogen peroxide (H2O2), hydroxyl radical, and ferric ion reducing system. In the in vivo study, 35 animals were randomized into seven groups of five rats each. Free and bound phenolic extract (1?mg/mL) produced 66.42% and 93.08%, 57.1% and 86.0%, 62.0% and 90.05%, and 60.11% and 72.37% scavenging effect on DPPH radical, O2(-) radical, H2O2, and hydroxyl radical, while ferric ion was significantly reduced. An AFB1-mediated decrease in the activities of ROS detoxifying enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose 6 phosphate dehydrogenase) was significantly attenuated (P<.05). AFB1-mediated elevation in the concentrations of oxidative stress biomarkers; malondialdehyde, conjugated dienes, lipid hydroperoxides, protein carbonyl, and percentage DNA fragmentation were significantly lowered by D. guineense phenolic extract (P<.05). Overall, the in vitro and in vivo effects suggest that D. guineense phenolic extract elicited ROS scavenging and detoxification potentials, as well as the capability of preventing lipid peroxidation, protein oxidation, and DNA fragmentation. PMID:24892362

Adeleye, Abdulwasiu O; Ajiboye, Taofeek O; Iliasu, Ganiyat A; Abdussalam, Folakemi A; Balogun, Abdulazeez; Ojewuyi, Oluwayemisi B; Yakubu, Musa T

2014-08-01

322

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

PubMed Central

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

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

323

Chemiluminescent detection of induced reactive oxygen metabolite production of human polymorphonuclear leucocytes by anthophyllite asbestos.  

PubMed

Incidences of lung cancer and pleural plaque have been reported in relation to exposure to anthophyllite asbestos. To investigate the pathogenic mechanisms of anthophyllite, chemiluminescence (CL) detection of reactive oxygen metabolite (ROM) generation of human polymorphonuclear leucocytes (PMN) stimulated by anthophyllite asbestos was determined and compared with that of other asbestos and mineral fiber samples. When anthophyllite fiber sample was mixed with the luminol-primed PMN, high levels of CL which exhibited a specific time course characterized by two separate peaks were induced. The CL induced by anthophyllite sample was greater than that induced by chrysotile, crocidolite, and amosite asbestos. We further investigated the two peaks of CL using specific inhibitors of signal transduction mechanisms. The two peaks of CL by anthophyllite sample were different in sensitivity to cytochalasin B and genistein; the former relates to the cytoskeleton-dependent mechanism and the latter has been shown to inhibit tyrosine kinase, which resides in the pathway to cause PMN activation. The strong ROM reaction of PMN by anthophyllite suggests that the surface characteristics of the fiber may participate in the pathogenic mechanisms of anthophyllite asbestos. PMID:11896666

Iwata, Toyoto; Kohyama, Norihiko; Yano, Eiji

2002-01-01

324

Emerging Roots Alter Epidermal Cell Fate through Mechanical and Reactive Oxygen Species Signaling[C][W  

PubMed Central

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

Steffens, Bianka; Kovalev, Alexander; Gorb, Stanislav N.; Sauter, Margret

2012-01-01

325

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

NASA Astrophysics Data System (ADS)

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.

Zhang, WeiNa; Chen, WenLi

2010-02-01

326

Comparison of reactive oxygen species in neat and washed semen of infertile men  

PubMed Central

Background: Male are involved in near 50% of cases of infertility and reactive oxygen species (ROS) playing an important role in decreasing fertility potential. Accurate measurement of ROS seems to be important in evaluation of infertile male patients. Objective: To compare ROS measurement in neat and washed semen samples of infertile men and define the best method for evaluation of ROS in these patients. Materials and Methods: We measured the level of ROS in semen samples of thirty five non-azoospermic men with infertility. The semen samples were divided into two parts and the semen parameters and ROS levels in neat and washed samples were evaluated. We also evaluated the presence of pyospermia using peroxidase test. Results: The differences regarding sperm count and quick motility were significant in neat and washed semen samples. The mean ROS level was significantly higher in neat samples compared with washed spermatozoa (7.50 RLU vs. 1.20 RLU respectively). Difference in ROS levels was more significant in patients with pyospermia compared to whom with no pyospermia (378.67 RLU vs. 9.48 RLU respectively). Conclusion: Our study confirmed that neat or unprocessed samples are better index of normal oxidative status of semen samples. Because we do not artificially add or remove factors that may play an important role in oxidative equilibrium status. PMID:25031573

Moein, Mohammad Reza; Vahidi, Serajedin; Ghasemzadeh, Jalal; Tabibnejad, Nasim

2014-01-01

327

Fluorescent approach to quantitation of reactive oxygen species in mainstream cigarette smoke.  

PubMed

A novel approach to monitoring of mainstream smoke reactive oxygen species (ROS) has been developed and applied to the quantitation of smoke oxidants. Redox-active fluorescent probe dihydrorhodamine 6G (DHR-6G) was selected as the molecular probe because it is sensitive to typical smoke ROS. The experimental system couples an automatic cigarette smoke machine fiber-optic fluorometer for real-time monitoring of the reaction progress between cigarette smoke and DHR-6G. Quantitation was achieved based on the amount of rhodamine 6G, which is the sole product from DHR-6G oxidation. With the optimization of the trapping efficiency, we detected 391 nmol of ROS/cigarette in the mainstream CS for a standard cigarette 2R4F under standard Federal Trade Commission smoking protocol. Applying this method, we quantified the ROS of selected cigarettes and found that the cigarettes made of burley tobacco have much ( approximately 10 times) higher ROS content in the smoke than that in the tobacco made of bright tobacco. The smokeless cigarette, Eclipse, has comparable ROS with cigarettes made of bright tobacco. PMID:16642999

Ou, Boxin; Huang, Dejian

2006-05-01

328

Wogonin Induces Reactive Oxygen Species Production and Cell Apoptosis in Human Glioma Cancer Cells  

PubMed Central

Glioma is the most common primary adult brain tumor with poor prognosis because of the ease of spreading tumor cells to other regions of the brain. Cell apoptosis is frequently targeted for developing anti-cancer drugs. In the present study, we have assessed wogonin, a flavonoid compound isolated from Scutellaria baicalensis Georgi, induced ROS generation, endoplasmic reticulum (ER) stress and cell apoptosis. Wogonin induced cell death in two different human glioma cells, such as U251 and U87 cells but not in human primary astrocytes (IC 50 > 100 ?M). Wogonin-induced apoptotic cell death in glioma cells was measured by propidine iodine (PI) analysis, Tunnel assay and Annexin V staining methods. Furthermore, wogonin also induced caspase-9 and caspase-3 activation as well as up-regulation of cleaved PARP expression. Moreover, treatment of wogonin also increased a number of signature ER stress markers glucose-regulated protein (GRP)-78, GRP-94, Calpain I, and phosphorylation of eukaryotic initiation factor-2? (eIF2?). Treatment of human glioma cells with wogonin was found to induce reactive oxygen species (ROS) generation. Wogonin induced ER stress-related protein expression and cell apoptosis was reduced by the ROS inhibitors apocynin and NAC (N-acetylcysteine). The present study provides evidence to support the fact that wogonin induces human glioma cell apoptosis mediated ROS generation, ER stress activation and cell apoptosis. PMID:22949836

Tsai, Cheng-Fang; Yeh, Wei-Lan; Huang, Ssu Ming; Tan, Tzu-Wei; Lu, Dah-Yuu

2012-01-01

329

Mitochondrial reactive oxygen species: A double edged sword in ischemia/reperfusion vs preconditioning  

PubMed Central

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

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

2014-01-01

330

Correlation of the intracellular reactive oxygen species levels with textural properties of functionalized mesostructured silica.  

PubMed

Mesostructured silica is frequently used in biomedical applications, being considered nontoxic and biocompatible material, suitable for the development of drug delivery systems (DDS). Four functionalized MCM-41 silica materials with hydrophobic (methyl and vinyl) and hydrophilic (3-aminopropyl and 3-mercaptopropyl) groups were obtained by post-synthesis functionalization and characterized by small-angle X-ray diffraction, infrared spectroscopy, thermal analysis, and nitrogen adsorption-desorption isotherms. The main structural and textural parameters of the obtained silica were determined. The effect of the functionalized silica on fibroblast (NIH3T3) and melanocyte cells (B16F10) was studied with respect to the proliferation rate and the levels of reactive oxygen species (ROS). It was found that the textural properties of all samples influenced the levels of intracellular ROS and consequently, the proliferation rate. Both, healthy and malignant cells exhibited linear dependence of ROS levels with the specific surface area values, but with different response. The contribution of the methyl functionalized silica to the ROS level is apart to the general trend. PMID:24677796

Bajenaru, Laura; Berger, Daniela; Miclea, Luminita; Matei, Cristian; Nastase, Silviu; Andronescu, Cristian; Moisescu, Mihaela G; Savopol, Tudor

2014-12-01

331

Conversion of Natively Unstructured ?-Synuclein to Its ?-Helical Conformation Significantly Attenuates Production of Reactive Oxygen Species  

PubMed Central

The intracellular ?-synuclein (?-syn) protein, whose conformational change and aggregation have been closely linked to the pathology of Parkingson’s disease (PD), is highly populated at the presynaptic termini and remains there in the ?-helical conformation. In this study, circular dichroism confirmed that natively unstructured ?-syn in aqueous solution was transformed to its ?-helical conformation upon addition of trifluoroethanol (TFE). Electrochemical and UV–visible spectroscopic experiments reveal that both Cu(I) and Cu(II) are stabilized, with the former being stabilized by about two orders of magnitude. Compared to unstructured ?-syn (Binolfi et al., J. Am. Chem. Soc. 133 (2011) 194–196), ?-helical ?-syn stabilizes Cu(I) by more than three orders of magnitude. Through the measurements of H2O2 and hydroxyl radicals (OH•) in solutions containing different forms of Cu(II) (free and complexed by unstructured or ?-helical ?-syn), we demonstrate that the significantly enhanced Cu(I) binding affinity helps inhibit the production of highly toxic reactive oxygen species, especially the hydroxyl radicals. Our study provides strong evidence that, as a possible means to prevent neuronal cell damage, conversion of the natively unstructured ?-syn to its ?-helical conformation in vivo could significantly attenuate the copper-modulated ROS production. PMID:23123341

Zhou, Binbin; Hao, Yuanqiang; Wang, Chengshan; Li, Ding; Liu, You-Nian; Zhou, Feimeng

2012-01-01

332

Apolipoprotein A-I expression suppresses COX-2 expression by reducing reactive oxygen species in hepatocytes.  

PubMed

Abnormal lipid metabolism may contribute to the increase of reactive oxygen species (ROS) and inflammation in the pathogenesis of non-alcoholic steatohepatitis (NASH). Apolipoprotein A-I (apoA-I) accepts cellular cholesterol and phospholipids transported by ATP-binding cassette transporter A1 to generate nascent high density lipoprotein particles. Previous studies revealed that the overexpression of ABCA1 or apoA-I alleviated hepatic lipid levels by modifying lipid transport. Here, we examined the effect of apoA-I overexpression on ROS and genes involved in inflammation in both BEL-7402 hepatocytes and mice. Human apoA-I was overexpressed by transfection in BEL-7402 hepatocytes and by an adenoviral vector in C57BL/6J mice fed a methionine choline-deficient diet. The overexpression of apoA-I in both models resulted in decreased ROS and lipid peroxidation levels, as well as a reduced MAPK phosphorylation and decreased expression levels of c-Fos and COX-2. These results suggest that apoA-I overexpression can reduce steatosis by decreasing ROS levels and suppressing COX-2-induced inflammation in hepatocytes. MAPK and c-Fos are involved in this regulatory process. PMID:25451254

Mao, Jing; Liu, Wei; Wang, Yutong

2014-10-24

333

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

PubMed

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

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

2015-02-01

334

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

PubMed

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

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

2013-09-01

335

Interplays between nitric oxide and reactive oxygen species in cryptogein signalling.  

PubMed

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 H2 O2 . 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

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

336

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

PubMed Central

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

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

2014-01-01

337

Oncogene-induced reactive oxygen species fuel hyperproliferation and DNA damage response activation  

PubMed Central

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

Ogrunc, M; Di Micco, R; Liontos, M; Bombardelli, L; Mione, M; Fumagalli, M; Gorgoulis, V G; d'Adda di Fagagna, F

2014-01-01

338

H2S cytotoxicity mechanism involves reactive oxygen species formation and mitochondrial depolarisation.  

PubMed

A number of scavengers of reactive oxygen species (ROS) were found to be protective against cell death induced by hydrogen sulfide (H2S) in isolated hepatocytes. The H2O2 scavengers alpha-ketoglutarate and pyruvate, which also act as energy substrate metabolites, were more protective against H2S toxicity than lactate which is only an energy substrate metabolite. All of these results suggest that H2S toxicity is dependent on ROS production. We measured ROS formation directly in hepatocytes using the fluorogenic dichlorofluorescin method. H2S-induced ROS formation was dose dependent and pyruvate inhibited this ROS production. Non-toxic concentrations of H2S enhanced the cytotoxicity of H2O2 generated by glucose/glucose oxidase, which was inhibited by CYP450 inibitors. Furthermore, hepatocyte ROS formation induced by H2S was decreased by CYP450 inhibitors cimetidine and benzylimidazole. These results suggest that CYP450-dependant metabolism of H2S is responsible for inducing ROS production. H2S-induced cytotoxicity was preceded by mitochondrial depolarization as measured by rhodamine 123 fluorescence. Mitochondrial depolarization induced by H2S was prevented by zinc, methionine and pyruvate all of which decreased H2S-induced cell death. Treatment of H2S poisoning may benefit from interventions aimed at minimizing ROS-induced damage and reducing mitochondrial damage. PMID:15363583

Eghbal, Mohammad A; Pennefather, Peter S; O'Brien, Peter J

2004-10-15

339

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

PubMed Central

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

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

2014-01-01

340

Mitochondrial reactive oxygen species induces NLRP3-dependent lysosomal damage and inflammasome activation.  

PubMed

The nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome drives many inflammatory processes and mediates IL-1 family cytokine release. Inflammasome activators typically damage cells and may release lysosomal and mitochondrial products into the cytosol. Macrophages triggered by the NLRP3 inflammasome activator nigericin show reduced mitochondrial function and decreased cellular ATP. Release of mitochondrial reactive oxygen species (ROS) leads to subsequent lysosomal membrane permeabilization (LMP). NLRP3-deficient macrophages show comparable reduced mitochondrial function and ATP loss, but maintain lysosomal acidity, demonstrating that LMP is NLRP3 dependent. A subset of wild-type macrophages undergo subsequent mitochondrial membrane permeabilization and die. Both LMP and mitochondrial membrane permeabilization are inhibited by potassium, scavenging mitochondrial ROS, or NLRP3 deficiency, but are unaffected by cathepsin B or caspase-1 inhibitors. In contrast, IL-1? secretion is ablated by potassium, scavenging mitochondrial ROS, and both cathepsin B and caspase-1 inhibition. These results demonstrate interplay between lysosomes and mitochondria that sustain NLRP3 activation and distinguish cell death from IL-1? release. PMID:24089192

Heid, Michelle E; Keyel, Peter A; Kamga, Christelle; Shiva, Sruti; Watkins, Simon C; Salter, Russell D

2013-11-15

341

[Production of reactive oxygen species and scavenger treatment in nephrotoxic nephritis].  

PubMed

Role of reactive oxygen species (ROS) was studied in accelerated nephrotoxic nephritis (NTN) in rats. In this experimental model, histological examination, and luminol amplified chemiluminescence (CL) assay of peripheral polymorphonuclear neutrophils (PMN), peritoneal macrophages (M phi), and isolated glomeruli were performed time-sequentially. Effect of ROS scavengers were also examined in this experiment. Daily dosages of bovine liver catalase and SOD were 550,000 and 1,000 units respectively. After nephrotoxic IgG injection, CL of glomeruli increased strikingly attaining peak at day 1, and remained high until the end of the experiment. This increase of CL may have reflected the release of ROS by glomerular cells and/or infiltrating cells stimulated in situ. In fact, peripheral PMN and peritoneal M phi showed no increase of CL after nephrotoxic IgG injection. Glomerular cells increased as early as 3 hours after induction of nephritis. Accumulation of PMN was noted for the first three days, whereas that of M phi became prominent after 4 days. Favourable effect was obtained in terms of proteinuria by administration of catalase, only when catalase was given at initial 3 days of nephritis. The data suggest that generation of ROS reflected by increase of CL in glomeruli of NTN rats is attributable to the PMN and M phi infiltrated in glomeruli as well as glomerular resident cells per se. It is also suggested that glomerular PMN increasing in the early phase of NTN plays a considerable role in glomerular injury. PMID:1479715

Nakamura, K

1992-07-01

342

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

SciTech Connect

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.

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

343

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

SciTech Connect

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.

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

344

Identification and biological activities of a new antiangiogenic small molecule that suppresses mitochondrial reactive oxygen species  

SciTech Connect

Research highlights: {yields} YCG063 was screened as a new angiogenesis inhibitor which suppresses mitochondrial ROS generation in a phenotypic cell-based screening of a small molecule-focused library. {yields} The compound inhibited in vitro and in vivo angiogenesis in a dose-dependent manner. {yields} This new small molecule tool will provide a basis for a better understanding of angiogenesis driven under hypoxic conditions. -- Abstract: Mitochondrial reactive oxygen species (ROS) are associated with multiple cellular functions such as cell proliferation, differentiation, and apoptosis. In particular, high levels of mitochondrial ROS in hypoxic cells regulate many angiogenesis-related diseases, including cancer and ischemic disorders. Here we report a new angiogenesis inhibitor, YCG063, which suppressed mitochondrial ROS generation in a phenotypic cell-based screening of a small molecule-focused library with an ArrayScan HCS reader. YCG063 suppressed mitochondrial ROS generation under a hypoxic condition in a dose-dependent manner, leading to the inhibition of in vitro angiogenic tube formation and chemoinvasion as well as in vivo angiogenesis of the chorioallantoic membrane (CAM) at non-toxic doses. In addition, YCG063 decreased the expression levels of HIF-1{alpha} and its target gene, VEGF. Collectively, a new antiangiogenic small molecule that suppresses mitochondrial ROS was identified. This new small molecule tool will provide a basis for a better understanding of angiogenesis driven under hypoxic conditions.

Kim, Ki Hyun; Park, Ju Yeol; 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)

2011-01-07

345

Regulation of Reactive Oxygen Species Homeostasis by Peroxiredoxins and c-Myc*S?  

PubMed Central

Peroxiredoxins (Prxs) are highly conserved proteins found in most organisms, where they function primarily to scavenge reactive oxygen species (ROS). Loss of the most ubiquitous member of the family, Prx1, is associated with the accumulation of oxidatively damaged DNA and a tumor-prone phenotype. Prx1 interacts with the transcriptional regulatory domain of the c-Myc oncoprotein and suppresses its transforming activity. The DNA damage in tissues of prx1-/- mice is associated in some cases with only modest increases in total ROS levels. However, these cells show dramatic increases in nuclear ROS and reduced levels of cytoplasmic ROS, which explains their mutational susceptibility. In the current work, we have investigated whether changes in other ROS scavengers might account for the observed ROS redistribution pattern in prx1-/- cells. We show ?5-fold increases in Prx5 levels in prx1-/- embryo fibroblasts relative to prx1+/+ cells. Moreover, Prx5 levels normalize when Prx1 expression is restored. Prx5 levels also appear to be highly dependent on c-Myc, and chromatin immunoprecipitation experiments showed differential occupancy of c-Myc and Prx1 complexes at E-box elements in the prx5 gene proximal promoter. This study represents a heretofore unreported mechanism for the c-Myc-dependent regulation of one Prx family member by another and identifies a novel means by which cells reestablish ROS homeostasis when one of these family members is compromised. PMID:19098005

Graves, J. Anthony; Metukuri, Mallikarjuna; Scott, Donald; Rothermund, Kristi; Prochownik, Edward V.

2009-01-01

346

Inactive ERBB Receptors Cooperate With Reactive Oxygen Species To Suppress Cancer Progression  

PubMed Central

The ERBB receptors are a family of heterodimerization partners capable of driving transformation and metastasis. While the therapeutic targeting of single receptors has proven efficacious, optimal targeting of this receptor family should target all oncogenic members simultaneously. The juxtamembrane domains of ERBB1, ERBB2, and ERBB3 are highly conserved and control various aspects of ERBB-dependent biology. In an effort to block those functions, we have targeted this domain with decoy peptides synthesized in tandem with a cell-penetrating peptide, termed EJ1. Treatment with EJ1 induces cell death, promotes the formation of inactive ERBB multimers, and results in simultaneous reduction of ERBB1, ERBB2, and ERBB3 activation. Treatment also results in the activation of myosin light chain–dependent cell blebbing while inactivating CaMKII signaling, coincident with the induction of cell death. EJ1 also directly translocates to mitochondria, correlating with a loss of mitochondrial membrane potential and production of reactive oxygen species. Finally, treatment of a mouse model of breast cancer with EJ1 results in the inhibition of tumor growth and metastasis without associated toxicities in normal cells. Overall, these data demonstrate that a portion of the ERBB jxm domain, when used as an intracellular decoy, can inhibit tumor growth and metastasis, representing a novel anticancer therapeutic. PMID:24081029

Hart, Matthew R; Su, Hsin-Yuan; Broka, Derrick; Goverdhan, Aarthi; Schroeder, Joyce A

2013-01-01

347

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

PubMed Central

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

Kim, Suhee; Agca, Cansu; Agca, Yuksel

2013-01-01

348

Reactive oxygen species mediate IL-8 expression in Down syndrome candidate region-1-overexpressed cells.  

PubMed

Reactive oxygen species (ROS) have been considered to mediate inflammation in Down syndrome (DS). The present study is purposed to examine the mechanism of increased ROS levels and inflammatory cytokine IL-8 expression in Down syndrome candidate region-1 (DSCR1)-transfected cells, by determining ROS levels, IL-8 expression, NF-?B activation, and SOD1 levels in human embryonic kidney (HEK) 293 cells. The cells were treated with an antioxidant N-acetyl cysteine (NAC) or a calcium chelator BAPTA and stimulated with or without IL-1?. As a result, basal levels of ROS, IL-8, and NF-?B-DNA binding activity were higher, and basal SOD1 levels were higher in DSCR1-transfected cells than pcDNA-transfected cells. BAPTA and NAC inhibited increase in ROS (intracellular and mitochondrial levels) in DSCR-1-transfected cells without treatment of IL-1?. DSCR1 transfection-induced changes were increased by treatment with IL-1?, which was suppressed by NAC and BAPTA. Transfection of SOD1 inhibited ROS levels in DSCR1-transfected cells. In conclusion, ROS activate NF-?B and IL-8 induction in DSCR1-transfected cells in a calcium-dependent manner, which is augmented by IL-1? since IL-1? increases calcium and ROS levels in the cells. Reducing ROS levels by treatment of antioxidants may be beneficial for preventing DS-associated inflammation by suppressing cytokine expression. PMID:25218171

Ko, Je Won; Lim, Sei Young; Chung, Kwang Chul; Lim, Joo Weon; Kim, Hyeyoung

2014-10-01

349

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

PubMed Central

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

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

2014-01-01

350

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

PubMed

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

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

2014-10-30

351

Feedback between p21 and reactive oxygen production is necessary for cell senescence  

PubMed Central

Cellular senescence—the permanent arrest of cycling in normally proliferating cells such as fibroblasts—contributes both to age-related loss of mammalian tissue homeostasis and acts as a tumour suppressor mechanism. The pathways leading to establishment of senescence are proving to be more complex than was previously envisaged. Combining in-silico interactome analysis and functional target gene inhibition, stochastic modelling and live cell microscopy, we show here that there exists a dynamic feedback loop that is triggered by a DNA damage response (DDR) and, which after a delay of several days, locks the cell into an actively maintained state of ‘deep' cellular senescence. The essential feature of the loop is that long-term activation of the checkpoint gene CDKN1A (p21) induces mitochondrial dysfunction and production of reactive oxygen species (ROS) through serial signalling through GADD45-MAPK14(p38MAPK)-GRB2-TGFBR2-TGF?. These ROS in turn replenish short-lived DNA damage foci and maintain an ongoing DDR. We show that this loop is both necessary and sufficient for the stability of growth arrest during the establishment of the senescent phenotype. PMID:20160708

Passos, João F; Nelson, Glyn; Wang, Chunfang; Richter, Torsten; Simillion, Cedric; Proctor, Carole J; Miwa, Satomi; Olijslagers, Sharon; Hallinan, Jennifer; Wipat, Anil; Saretzki, Gabriele; Rudolph, Karl Lenhard; Kirkwood, Tom B L; von Zglinicki, Thomas

2010-01-01

352

Commensal bacteria modulate cullin-dependent signaling via generation of reactive oxygen species  

PubMed Central

The resident prokaryotic microflora of the mammalian intestine influences diverse homeostatic functions of the gut, including regulation of cellular growth and immune responses; however, it is unknown how commensal prokaryotic organisms mechanistically influence eukaryotic signaling networks. We have shown that bacterial coculture with intestinal epithelial cells modulates ubiquitin-mediated degradation of important signaling intermediates, including ?-catenin and the NF-?B inhibitor I?B-?. Ubiquitination of these proteins as well as others is catalyzed by the SCF?TrCP ubiquitin ligase, which itself requires regulated modification of the cullin-1 subunit by the ubiquitin-like protein NEDD8. Here we show that epithelia contacted by enteric commensal bacteria in vitro and in vivo rapidly generate reactive oxygen species (ROS). Bacterially induced ROS causes oxidative inactivation of the catalytic cysteine residue of Ubc12, the NEDD8-conjugating enzyme, resulting in complete but transient loss of cullin-1 neddylation and consequent effects on NF-?B and ?-catenin signaling. Our results demonstrate that commensal bacteria directly modulate a critical control point of the ubiquitin–proteasome system, and suggest how enteric commensal bacterial flora influences the regulatory pathways of the mammalian intestinal epithelia. PMID:17914462

Kumar, Amrita; Wu, Huixia; Collier-Hyams, Lauren S; Hansen, Jason M; Li, Tengguo; Yamoah, Kosj; Pan, Zhen-Qiang; Jones, Dean P; Neish, Andrew S

2007-01-01

353

?,?-Dimethylacrylshikonin sensitizes human colon cancer cells to ionizing radiation through the upregulation of reactive oxygen species  

PubMed Central

Shikonin, a naphthoquinone derivative, has been shown to possess antitumor activity. In the present study, the effects of shikonin and its analog, ?,?-dimethylacrylshikonin, were investigated as radiosensitizers on the human colon cancer cell line, HCT-116. Shikonin and, to a greater extent, its analog-induced apoptosis of HCT-116 cells further synergistically potentiated the induction of apoptosis when combined with ionizing radiation (IR) treatment. Shikonins also stimulated an increase in reactive oxygen species (ROS) production and IR-induced DNA damage. Pre-treatment with the ROS scavenger, N-acetylcysteine, suppressed the enhancement of IR-induced DNA damage and apoptosis stimulated by shikonins, indicating that shikonins exert their radiosensitizing effects through ROS upregulation. The radiosensitizing effect of shikonins was also examined in vivo using the xenograft mouse model. Consistent with the in vitro results, injection of ?,?-dimethylacrylshikonin combined with IR treatment significantly suppressed tumor growth of the HCT-116 xenograft. Taken together, the results show that ?,?-dimethylacrylshikonin is a promising agent for developing an improved strategy for radiotherapy against tumors. PMID:24932238

KWAK, SEO-YOUNG; JEONG, YOUN KYOUNG; KIM, BU-YEON; LEE, JI YOUNG; AHN, HYUN-JOO; JEONG, JAE-HOON; KIM, MI-SOOK; KIM, JOON; HAN, YOUNG-HOON

2014-01-01

354

?,?-Dimethylacrylshikonin sensitizes human colon cancer cells to ionizing radiation through the upregulation of reactive oxygen species.  

PubMed

Shikonin, a naphthoquinone derivative, has been shown to possess antitumor activity. In the present study, the effects of shikonin and its analog, ?,?-dimethylacrylshikonin, were investigated as radiosensitizers on the human colon cancer cell line, HCT-116. Shikonin and, to a greater extent, its analog-induced apoptosis of HCT-116 cells further synergistically potentiated the induction of apoptosis when combined with ionizing radiation (IR) treatment. Shikonins also stimulated an increase in reactive oxygen species (ROS) production and IR-induced DNA damage. Pre-treatment with the ROS scavenger, N-acetylcysteine, suppressed the enhancement of IR-induced DNA damage and apoptosis stimulated by shikonins, indicating that shikonins exert their radiosensitizing effects through ROS upregulation. The radiosensitizing effect of shikonins was also examined in vivo using the xenograft mouse model. Consistent with the in vitro results, injection of ?,?-dimethylacrylshikonin combined with IR treatment significantly suppressed tumor growth of the HCT-116 xenograft. Taken together, the results show that ?,?-dimethylacrylshikonin is a promising agent for developing an improved strategy for radiotherapy against tumors. PMID:24932238

Kwak, Seo-Young; Jeong, Youn Kyoung; Kim, Bu-Yeon; Lee, Ji Young; Ahn, Hyun-Joo; Jeong, Jae-Hoon; Kim, Mi-Sook; Kim, Joon; Han, Young-Hoon

2014-06-01

355

Effects of Sanionia uncinata extracts in protecting against and inducing DNA cleavage by reactive oxygen species.  

PubMed

When mosses are exposed to increased quantities of ultraviolet (UV) radiation, they produce more secondary metabolites. Antarctica moss Sanionia uncinata (Hedw.) Loeske has presented high carotenoid contents in response to an increase in UVB radiation. This moss has been recommended as a potential source of antioxidants. In the present work, the protective and enhancing effects of aqueous (AE) and hydroalcoholic (HE) extracts of S. uncinata on the cleavage of supercoiled DNA were evaluated through topological modifications, quantified by densitometry after agarose gel electrophoresis. Total phenolic contents reached 5.89 mg/g. Our data demonstrated that the extract does not induce DNA cleavage. Furthermore, both extracts showed antioxidant activity that protected the DNA against cleavage induced by (i) O(2)(•-), 89% (AE) and 94% (HE) (P<0.05), and (ii) (.)OH, 17% (AE) and 18% (HE). However, the extracts intensified cleavage induced by Fenton-like reactions: (i) Cu(2+)/H(2)O(2), 94% (AE) and 100% (HE) (P<0.05), and (ii) SnCl(2), 62% (AE) and 56% (HE). DNA damages seem to follow different ways: (i) in the presence of Fenton-like reactions could be via reactive oxygen species generation and (ii) with HE/Cu(2+) could have also been triggered by other mechanisms. PMID:22005340

Fernandes, Andréia da Silva; Mazzei, José Luiz; de Alencar, Alexandre Santos; Evangelista, Heitor; Felzenszwalb, Israel

2011-01-01

356

Reactive oxygen species promote heat shock protein 90-mediated HBV capsid assembly.  

PubMed

Hepatitis B virus (HBV) infection induces reactive oxygen species (ROS) production and has been associated with the development of hepatocellular carcinoma (HCC). ROS are also an important factor in HCC because the accumulated ROS leads to abnormal cell proliferation and chromosome mutation. In oxidative stress, heat shock protein 90 (Hsp90) and glutathione (GSH) function as part of the defense mechanism. Hsp90 prevents cellular component from oxidative stress, and GSH acts as antioxidants scavenging ROS in the cell. However, it is not known whether molecules regulated by oxidative stress are involved in HBV capsid assembly. Based on the previous study that Hsp90 facilitates HBV capsid assembly, which is an important step for the packing of viral particles, here, we show that ROS enrich Hsp90-driven HBV capsid formation. In cell-free system, HBV capsid assembly was facilitated by ROS with Hsp90, whereas it was decreased without Hsp90. In addition, GSH inhibited the function of Hsp90 to decrease HBV capsid assembly. Consistent with the result of cell-free system, ROS and buthionine sulfoximine (BS), an inhibitor of GSH synthesis, increased HBV capsid formation in HepG2.2.15 cells. Thus, our study uncovers the interplay between ROS and Hsp90 during HBV capsid assembly. PMID:25576869

Kim, Yoon Sik; Seo, Hyun Wook; Jung, Guhung

2015-02-13

357

Interactions Between Reactive Oxygen Species Generated by Contractile Activity and Aging in Skeletal Muscle?  

PubMed Central

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

2013-01-01

358

Antioxidant properties of UCP1 are evolutionarily conserved in mammals and buffer mitochondrial reactive oxygen species.  

PubMed

Mitochondrial uncoupling reduces reactive oxygen species (ROS) production and appears to be important for cellular signaling/protection, making it a focus for the treatment of metabolic and age-related diseases. Whereas the physiological role of uncoupling protein 1 (UCP1) of brown adipose tissue is established for thermogenesis, the function of UCP1 in the reduction of ROS in cold-exposed animals is currently under debate. Here, we investigated the role of UCP1 in mitochondrial ROS handling in the Lesser hedgehog tenrec (Echinops telfairi), a unique protoendothermic Malagasy mammal with recently identified brown adipose tissue (BAT). We show that the reduction of ROS by UCP1 activity also occurs in BAT mitochondria of the tenrec, suggesting that the antioxidative role of UCP1 is an ancient mammalian trait. Our analysis shows that the quantity of UCP1 displays strong control over mitochondrial hydrogen peroxide release, whereas other factors, such as mild cold, nonshivering thermogenesis, oxidative capacity, and mitochondrial respiration, do not correlate. Furthermore, hydrogen peroxide release from recoupled BAT mitochondria was positively associated with mitochondrial membrane potential. These findings led to a model of UCP1 controlling mitochondrial ROS release and, presumably, being controlled by high membrane potential, as proposed in the canonical model of "mild uncoupling". Our study further promotes a conserved role for UCP1 in the prevention of oxidative stress, which was presumably established during evolution before UCP1 was physiologically integrated into nonshivering thermogenesis. PMID:25224037

Oelkrug, Rebecca; Goetze, Nadja; Meyer, Carola W; Jastroch, Martin

2014-12-01

359

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

PubMed

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

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

2014-07-01

360

Copper chelation selectively kills colon cancer cells through redox cycling and generation of reactive oxygen species  

PubMed Central

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

2014-01-01

361

Diminished Macrophage Apoptosis and Reactive Oxygen Species Generation after Phorbol Ester Stimulation in Crohn's Disease  

PubMed Central

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

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

362

Mitochondrial production of reactive oxygen species contributes to the ?-adrenergic stimulation of mouse cardiomycytes  

PubMed Central

Abstract The sympathetic adrenergic system plays a central role in stress signalling and stress is often associated with increased production of reactive oxygen species (ROS). Furthermore, the sympathetic adrenergic system is intimately involved in the regulation of cardiomyocyte Ca2+ handling and contractility. In this study we hypothesize that endogenously produced ROS contribute to the inotropic mechanism of ?-adrenergic stimulation in mouse cardiomyocytes. Cytoplasmic Ca2+ transients, cell shortening and ROS production were measured in freshly isolated cardiomyocytes using confocal microscopy and fluorescent indicators. As a marker of oxidative stress, malondialdehyde (MDA) modification of proteins was detected with Western blotting. Isoproterenol (ISO), a ?-adrenergic agonist, increased mitochondrial ROS production in cardiomyocytes in a concentration- and cAMP–protein kinase A-dependent but Ca2+-independent manner. Hearts perfused with ISO showed a twofold increase in MDA protein adducts relative to control. ISO increased Ca2+ transient amplitude, contraction and L-type Ca2+ current densities (measured with whole-cell patch-clamp) in cardiomyocytes and these increases were diminished by application of the general antioxidant N-acetylcysteine (NAC) or the mitochondria-targeted antioxidant SS31. In conclusion, increased mitochondrial ROS production plays an integral role in the acute inotropic response of cardiomyocytes to ?-adrenergic stimulation. On the other hand, chronically sustained adrenergic stress is associated with the development of heart failure and cardiac arrhythmias and prolonged increases in ROS may contribute to these defects. PMID:21486840

Andersson, Daniel C; Fauconnier, Jérémy; Yamada, Takashi; Lacampagne, Alain; Zhang, Shi-Jin; Katz, Abram; Westerblad, Håkan

2011-01-01

363

Acute ethanol exposure disrupts actin cytoskeleton and generates reactive oxygen species in c6 cells.  

PubMed

Central nervous system dysfunctions are among the most significant effects of exposure to ethanol and the glial cells that play an important role in maintaining neuronal function, are extremely involved with these effects. The actin cytoskeleton plays a crucial role in a wide variety of cellular functions, especially when there is some injury. Therefore the aim of the present study was to analyze the short-term effects of ethanol (50, 100 and 200 mM) on the cytoskeleton of C6 glioma cells. Here we report that acute ethanol exposure profoundly disrupts the actin cytoskeleton in C6 cells decreasing stress fiber formation and downregulating RhoA and vinculin immunocontent. In contrast, microtubule and GFAP networks were not altered. We further demonstrate that anti-oxidants prevent ethanol-induced actin alterations, suggesting that the actions of ethanol on the actin cytoskeleton are related with generation of reactive oxygen species (ROS) in these cells. Our results show that ethanol at concentrations described to be toxic to the central nervous system was able to target the cytoskeleton of C6 cells and this effect could be related with increased ROS generation. Therefore, we propose that the dynamic restructuring of the cytoskeleton of glial cells might contribute to the response to the injury provoked by binge-like ethanol exposure in brain. PMID:20837132

Loureiro, Samanta Oliveira; Heimfarth, Luana; Reis, Karina; Wild, Luiza; Andrade, Cláudia; Guma, Fátima Theresinha Costa Rodrigues; Gonçalves, Carlos Alberto; Pessoa-Pureur, Regina

2011-02-01

364

Reactive oxygen species activity and lipid peroxidation in Helicobacter pylori associated gastritis: relation to gastric mucosal ascorbic acid concentrations and effect of H pylori eradication  

PubMed Central

Background—Helicobacter pylori is an independent risk factor for gastric cancer, and this association may be due to the bacterium causing reactive oxygen species mediated damage to DNA in the gastric epithelium. High dietary ascorbic acid intake may protect against gastric cancer by scavenging reactive oxygen species. ?Aims—To assess reactive oxygen species activity and damage in gastric mucosa in relation to gastric pathology and mucosal ascorbic acid level, and to determine the effect of H pylori eradication on these parameters. ?Patients—Gastric biopsy specimens were obtained for analysis from 161 patients undergoing endoscopy for dyspepsia. ?Methods—Reactive oxygen species activity and damage was assessed by luminol enhanced chemiluminescence and malondialdehyde equivalent estimation respectively. Ascorbic acid concentrations were measured using HPLC. ?Results—Chemiluminescence and malondialdehyde levels in gastric mucosa were higher in patients with H pylori gastritis than in those with normal histology. Successful eradication of the bacterium led to decreases in both parameters four weeks after treatment was completed. Gastric mucosal ascorbic acid and total vitamin C concentrations were not related to mucosal histology, but correlated weakly with reactive oxygen species activity (chemiluminescence and malodialdehyde levels). ?Conclusions—Data suggest that reactive oxygen species play a pathological role in H pylori gastritis, but mucosal ascorbic acid is not depleted in this condition. ?? Keywords: Helicobacter pylori; gastric cancer; reactive oxygen species; ascorbic acid PMID:9691912

Drake, I; Mapstone, N; Schorah, C; White, K; Chalmers, D; Dixon, M; Axon, A

1998-01-01

365

Exogenous acetaldehyde as a tool for modulating wine color and astringency during fermentation.  

PubMed

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

Sheridan, Marlena K; Elias, Ryan J

2015-06-15

366

Exogenous antioxidants—Double-edged swords in cellular redox state  

PubMed Central

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

Bohn, Torsten

2010-01-01

367

Combined effect of X-ray radiation and static magnetic fields on reactive oxygen species in rat lymphocytes in vitro.  

PubMed

The aim of this study was to investigate the effect of static magnetic fields (SMF) on reactive oxygen species induced by X-ray radiation. The experiments were performed on lymphocytes from male albino Wistar rats. After exposure to 3?Gy X-ray radiation (with a dose rate of 560?mGy/min) the measurement of intracellular reactive oxygen species in lymphocytes, using a fluorescent probe, was done before exposure to the SMF, and after 15?min, 1 and 2?h of exposure to the SMF or a corresponding incubation time. For SMF exposure, 0?mT (50?µT magnetic field induction opposite to the geomagnetic field) and 5?mT fields were chosen. The trend of SMF effects for 0?mT was always opposite that of 5?mT. The first one decreased the rate of fluorescence change, while the latter one increased it. PMID:23184469

Polita?ski, Piotr; Rajkowska, El?bieta; Brodecki, Marcin; Bednarek, Andrzej; Zmy?lony, Marek

2013-05-01

368

Angiotensin-II-induced reactive oxygen species along the SFO-PVN-RVLM pathway: implications in neurogenic hypertension.  

PubMed

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

Braga, V A; Medeiros, I A; Ribeiro, T P; França-Silva, M S; Botelho-Ono, M S; Guimarães, D D

2011-09-01

369

Comparison of stainless and mild steel welding fumes in generation of reactive oxygen species  

PubMed Central

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

2010-01-01

370

Role of angiotensin II and reactive oxygen species in cyclosporine A-dependent hypertension.  

PubMed

Treatment with cyclosporine A (CysA), a potent immunosuppressive agent, is associated with systemic and renal vasoconstriction, leading to hypertension. The present study was conducted to elucidate the contribution of angiotensin II (Ang II) to CysA-induced hypertension and reactive oxygen species (ROS) generation. CysA (30 mg/kg per day SC), given for 3 weeks in rats, increased systolic blood pressure (SBP) from 119+/-2 to 145+/-3 mm Hg (n=7). Plasma and kidney Ang II levels were significantly higher in CysA-treated rats (136+/-10 fmol/mL and 516+/-70 fmol/g) than in vehicle-treated (1 mL olive oil) rats (76+/-10 fmol/mL and 222+/-21 fmol/g, n=7). CysA treatment increased AT1 receptor protein expression in the aorta (by 251+/-35%), whereas it was reduced in the kidney (by -32+/-4%). Superoxide anion production in aortic segments and kidney thiobarbituric acid-reactive substance (TBARS) contents were higher in CysA-treated rats (26+/-2 counts/min per milligram and 37+/-3 nmol/g) than in vehicle-treated rats (17+/-1 counts/min per milligram and 24+/-3 nmol/g). Concurrent administration of an AT1 receptor antagonist, valsartan (30 mg/kg per day, in drinking water), to CysA-treated rats (n=7) significantly decreased SBP (113+/-4 mm Hg) and prevented increases in vascular superoxide (16+/-2 counts/min per milligram) and kidney TBARS contents (21+/-3 nmol/g). Similarly, treatment with a superoxide dismutase mimetic, 4-hydroxy-2,2,6,6,-tetramethylpiperidine-N-oxyl (Tempol; 3 mmol/L in drinking water, n=7), prevented CysA-induced increases in SBP (115+/-3 mm Hg), vascular superoxide (16+/-1 counts/min per milligram), and kidney TBARS contents (19+/-2 nmol/g). These data suggest that ROS generation induced by augmented Ang II levels contributes to the development of CysA-induced hypertension. PMID:12874088

Nishiyama, Akira; Kobori, Hiroyuki; Fukui, Toshiki; Zhang, Guo-Xing; Yao, Li; Rahman, Matlubur; Hitomi, Hirofumi; Kiyomoto, Hideyasu; Shokoji, Takatomi; Kimura, Shoji; Kohno, Masakazu; Abe, Youichi

2003-10-01

371

Effect of reactive oxygen species on NH4+ permeation in Xenopus laevis oocytes.  

PubMed

To investigate the effects of reactive oxygen species (ROS) on NH4+ permeation in Xenopus laevis oocytes, we used intracellular double-barreled microelectrodes to monitor the changes in membrane potential (V(m)) and intracellular pH (pH(i)) induced by a 20 mM NH4Cl-containing solution. Under control conditions, NH4Cl exposure induced a large membrane depolarization (to V(m) = 4.0 +/- 1.5 mV; n = 21) and intracellular acidification [reaching a change in pH(i) (DeltapH(i)) of 0.59 +/- 0.06 pH units in 12 min]; the initial rate of cell acidification (dpH(i)/dt) was 0.06 +/- 0.01 pH units/min. Incubation of the oocytes in the presence of H2O2 or beta-amyloid protein had no marked effect on the NH4Cl-induced DeltapH(i). By contrast, in the presence of photoactivated rose bengal (RB), tert-butyl-hydroxyperoxide (t-BHP), or xanthine/xanthine oxidase (X/XO), the same experimental maneuver induced significantly greater DeltapH(i) and dpH(i)/dt. These increases in DeltapH(i) and dpH(i)/dt were prevented by the ROS scavengers histidine and desferrioxamine, suggesting involvement of the reactive species (1)DeltagO2 and.OH. Using the voltage-clamp technique to identify the mechanism underlying the ROS-measured effects, we found that RB induced a large increase in the oocyte membrane conductance (G(m)). This RB-induced G(m) increase was prevented by 1 mM diphenylamine-2-carboxylate (DPC) and by a low Na+ concentration in the bath. We conclude that RB, t-BHP, and X/XO enhance NH4+ influx into the oocyte via activation of a DPC-sensitive nonselective cation conductance pathway. PMID:11997259

Cougnon, Marc; Benammou, Samia; Brouillard, Franck; Hulin, Philippe; Planelles, Gabrielle

2002-06-01

372

Characterization by Electron Spin Resonance Spectroscopy of Reactive Oxygen Species Generated by Titanium Dioxide and Hydrogen Peroxide  

Microsoft Academic Search

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)

M.-C. Lee; F. Yoshino; H. Shoji; S. Takahashi; K. Todoki; S. Shimada; K. Kuse-Barouch

2005-01-01

373

Tacrine-induced Reactive Oxygen Species in a Human Liver Cell Line: The Role of Anethole Dithiolethione as a Scavenger  

Microsoft Academic Search

The mechanisms leading to tacrine (THA) hepatotoxic effects are not yet fully understood. Reactive oxygen species (ROS) overproduction and intracellular reduced glutathione (GSH) depletion are common mechanisms involved in drug toxicity. The aim of this study was to investigate, on the human liver cell line HepG2, whether THA at human blood concentrations induces ROS production stimulation and\\/or GSH depletion. A

R. A Osseni; C Debbasch; M.-O Christen; P Rat; J.-M Warnet

1999-01-01

374

EPR Detection of Reactive Oxygen Species in Hemolymph of Galleria mellonella and Dendrolimus superans sibiricus (Lepidoptera) Larvae  

Microsoft Academic Search

The formation of reactive oxygen species (ROS) in hemolymph and hemocytes of Galleria mellonella and Dendrolimus superans sibiricus larvae was studied by ESR spectroscopy using spin-trap 1-hydroxy-3-carboxy-pyrrolidine (CP-H). The background level of ROS formation was detected in the intact hemolymph. The addition of dihydroxyphenylalanine (DOPA) into free cells of the hemolymph increased CP-H oxidation about two times for G. mellonella

I. A. Slepneva; V. V. Glupov; S. V. Sergeeva; V. V. Khramtsov

1999-01-01

375

In vitro alachlor effects on reactive oxygen species generation, motility patterns and apoptosis markers in human spermatozoa  

Microsoft Academic Search

Due to its extensive production and application, the toxicity of chloracetanilide herbicide alachlor[2-chloro-2?,6?-diethyl-N-(methoxymethyl)-acetanilide] should be evaluated to establish minimum effects. In this study, we have examined the in vitro effects of alachlor on human sperm motion using a compunter-assisted sperm analyser (CASA). An evaluation of both reactive oxygen species (ROS) and markers of apoptosis was also performed to investigate the

Geneviève Grizard; Lemlih Ouchchane; Héléne Roddier; Christine Artonne; Benoît Sion; Marie-Paule Vasson; Laurent Janny

2007-01-01

376

Localisation and metabolism of reactive oxygen species during Bremia lactucae pathogenesis in Lactuca sativa and wild Lactuca spp  

Microsoft Academic Search

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,

Michaela Sedlá?ová; Lenka Luhová; Marek Pet?ivalský; Aleš Lebeda

2007-01-01

377

Reactive oxygen intermediates and glutathione regulate the expression of cytosolic ascorbate peroxidase during iron-mediated oxidative stress in bean  

Microsoft Academic Search

Excess of free iron is thought to harm plant cells by enhancing the intracellular production of reactive oxygen intermediates (ROI). Cytosolic ascorbate peroxidase (cAPX) is an iron-containing, ROI-detoxifying enzyme induced in response to iron overload or oxidative stress. We studied the expression of cAPX in leaves of de-rooted bean plants in response to iron overload. cAPX expression, i.e., mRNA and

Irena Pekker; Elisha Tel-Or; Ron Mittler

2002-01-01

378

G Protein-Coupled Receptor Ca2+Linked Mitochondrial Reactive Oxygen Species Are Essential for Endothelial\\/Leukocyte Adherence  

Microsoft Academic Search

Received 21 March 2007\\/Returned for modification 20 June 2007\\/Accepted 16 August 2007 Receptor-mediated signaling is commonly associated with multiple functions, including the production of reactive oxygen species. However, whether mitochondrion-derived superoxide (mROS) contributes directly to physiological signaling is controversial. Here we demonstrate a previously unknown mechanism in which physiologic Ca2-evoked mROS production plays a pivotal role in endothelial cell (EC)

Brian J. Hawkins; Laura A. Solt; Ibrul Chowdhury; Altaf S. Kazi; M. Ruhul Abid; William C. Aird; Michael J. May; J. Kevin Foskett; Muniswamy Madesh

2007-01-01

379

Reactive oxygen species production and antioxidative defense system in pea root tissues treated with lead ions: the whole roots level  

Microsoft Academic Search

The lead absorbed by the roots induce oxidative stress conditions through the Reactive oxygen species (ROS) production for\\u000a the pea plants cultivated hydroponically for 96 h on a Hoagland medium with the addition of 0.1 and 0.5 mM of Pb(NO3)2. The alterations in $$ {\\\\text{O}}_{2}^{ - \\\\cdot } $$ and H2O2 concentrations were monitored spectrophotometrically which show a rapid increase in $$

Arleta Malecka; Aneta Piechalak; Barbara Tomaszewska

2009-01-01

380

Reactive oxygen species are involved in the apoptosis induced by nonsteroidal anti-inflammatory drugs in cultured gastric cells.  

PubMed

We previously reported the induction of apoptotic DNA fragmentation by nonsteroidal anti-inflammatory drugs (NSAIDs) in cultured rat gastric cells, and indicated that prostaglandin-synthesis is only marginally involved in the apoptotic process. In the present study, we examined whether the generation of reactive oxygen species is critically involved in NSAID-induced apoptosis. Indomethacin, sodium diclofenac, flurbiprofen, zaltoprofen, etodolac, but not mofezolac, enhanced apoptotic DNA fragmentation and mRNA expression for cyclooxygenase-2 in AGS cells, a cell line derived from human gastric epithelium. The apoptotic effect of indomethacin was then confirmed by fluorescent staining of the cells with annexin V. Apoptotic DNA fragmentation induced by indomethacin and flurbiprofen was suppressed by incubation of the cells with the anti-oxidants pyrrolidine dithiocarbamate, diphenyleneiodonium chloride, and N-acetyl-L-cysteine. These two NSAIDs also enhanced release from the cells of 8-isoprostane, a nonenzymatic product by free-radical-mediated peroxidation of arachidonic acid. Further, lucigenin chemiluminescence showed that the intracellular production of reactive oxygen species increased in cells treated with indomethacin. The present data thus indicate a crucial association between the generation of reactive oxygen species and NSAID-induced apoptosis in gastric epithelial cells. PMID:10594327

Kusuhara, H; Komatsu, H; Sumichika, H; Sugahara, K

1999-11-01

381

Enhanced reactive oxygen species overexpression by CuO nanoparticles in poorly differentiated hepatocellular carcinoma cells  

NASA Astrophysics Data System (ADS)

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

Kung, Mei-Lang; Hsieh, Shu-Ling; Wu, Chih-Chung; Chu, Tian-Huei; Lin, Yu-Chun; Yeh, Bi-Wen; Hsieh, Shuchen

2015-01-01

382

Mesenchymal stem/stromal cells inhibit the NLRP3 inflammasome by decreasing mitochondrial reactive oxygen species.  

PubMed

Mesenchymal stem/stromal cells (MSCs) control excessive inflammatory responses by modulating a variety of immune cells including monocytes/macrophages. However, the mechanisms by which MSCs regulate monocytes/macrophages are unclear. Inflammasomes in macrophages are activated upon cellular "danger" signals and initiate inflammatory responses through the maturation and secretion of proinflammatory cytokines such as interleukin 1? (IL-1?). Here we demonstrate that human MSCs (hMSCs) negatively regulate NLRP3 inflammasome activation in human or mouse macrophages stimulated with LPS and ATP. Caspase-1 activation and subsequent IL-1? release were decreased in macrophages by direct or transwell coculture with hMSCs. Addition of hMSCs to macrophages either at a LPS priming or at a subsequent ATP step similarly inhibited the inflammasome activation. The hMSCs had no effect on NLRP3 and IL-1? expression at mRNA levels during LPS priming. However, MSCs markedly suppressed the generation of mitochondrial reactive oxygen species (ROS) in macrophages. Further analysis showed that NLRP3-activated macrophages stimulated hMSCs to increase the expression and secretion of stanniocalcin (STC)-1, an antiapoptotic protein. Addition of recombinant protein STC-1 reproduced the effects of hMSCs in inhibiting NLRP3 inflammasome activation and ROS production in macrophages. Conversely, the effects of hMSCs on macrophages were largely abrogated by an small interfering RNA (siRNA) knockdown of STC-1. Together, our results reveal that hMSCs inhibit NLRP3 inflammasome activation in macrophages primarily by secreting STC-1 in response to activated macrophages and thus by decreasing mitochondrial ROS. PMID:24307525

Oh, Joo Youn; Ko, Jung Hwa; Lee, Hyun Ju; Yu, Ji Min; Choi, Hosoon; Kim, Mee Kum; Wee, Won Ryang; Prockop, Darwin J

2014-06-01

383

Mice producing less reactive oxygen species are relatively resistant to collagen glycopeptide vaccination against arthritis.  

PubMed

The bottleneck for the induction of collagen-induced arthritis in mice is the recognition of immunodominant type II collagen (CII) peptide (CII259-273) bound to the MHC class II molecule A(q). We have shown previously that the posttranslationally glycosylated lysine at position 264 in this epitope is of great importance for T cell recognition and tolerance induction to CII as well as for arthritis development. The Ncf1 gene, controlling oxidative burst, has been shown to play an important role for immune tolerance to CII. To investigate the effect of oxidation on the efficiency of immune-specific vaccination with MHC class II/glycosylated-CII peptide complexes, we used Ncf1 mutated mice. We demonstrate that normal reactive oxygen species (ROS) levels contribute to the establishment of tolerance and arthritis protection, because only mice with a functional oxidative burst were completely protected from arthritis after administration of the glycosylated CII259-273 peptide in complex with MHC class II. Transfer of T cells from vaccinated mice with functional Ncf1 protein resulted in strong suppression of clinical signs of arthritis in B10.Q mice, whereas the Ncf1 mutated mice as recipients had a weaker suppressive effect, suggesting that ROS modified the secondary rather than the primary immune response. A milder but still significant effect was also observed in ROS deficient mice. During the primary vaccination response, regulatory T cells, upregulation of negative costimulatory molecules, and increased production of anti-inflammatory versus proinflammatory cytokines in both Ncf1 mutated and wild type B10.Q mice was observed, which could explain the vaccination effect independent of ROS. PMID:20686129

Batsalova, Tsvetelina; Dzhambazov, Balik; Klaczkowska, Dorota; Holmdahl, Rikard

2010-09-01

384

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

NASA Astrophysics Data System (ADS)

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

Jadko, Sergiy

385

Reactive Oxygen Species in Unstimulated Hemocytes of the Pacific Oyster Crassostrea gigas: A Mitochondrial Involvement  

PubMed Central

The Pacific oyster Crassostrea gigas is a sessile bivalve mollusc whose homeostasis relies, at least partially, upon cells circulating in hemolymph and referred to as hemocytes. Oyster’s hemocytes have been reported to produce reactive oxygen species (ROS), even in absence of stimulation. Although ROS production in bivalve molluscs is mostly studied for its defence involvement, ROS may also be involved in cellular and tissue homeostasis. ROS sources have not yet been described in oyster hemocytes. The objective of the present work was to characterize the ROS sources in unstimulated hemocytes. We studied the effects of chemical inhibitors on the ROS production and the mitochondrial membrane potential (??m) of hemocytes. First, this work confirmed the specificity of JC-10 probe to measure ??m in oyster hemocytes, without being affected by ?pH, as reported in mammalian cells. Second, results show that ROS production in unstimulated hemocytes does not originate from cytoplasmic NADPH-oxidase, nitric oxide synthase or myeloperoxidase, but from mitochondria. In contrast to mammalian cells, incubation of hemocytes with rotenone (complex I inhibitor) had no effect on ROS production. Incubation with antimycin A (complex III inhibitor) resulted in a dose-dependent ROS production decrease while an over-production is usually reported in vertebrates. In hemocytes of C. gigas, the production of ROS seems similarly dependent on both ??m and ?pH. These findings point out differences between mammalian models and bivalve cells, which warrant further investigation about the fine characterization of the electron transfer chain and the respective involvement of mitochondrial complexes in ROS production in hemocytes of bivalve molluscs. PMID:23056359

Donaghy, Ludovic; Kraffe, Edouard; Le Goïc, Nelly; Lambert, Christophe; Volety, Aswani K.; Soudant, Philippe

2012-01-01

386

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

SciTech Connect

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.

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

387

Contractile protein expression is upregulated by reactive oxygen species in aorta of Goto-Kakizaki rat  

PubMed Central

Although it is known that blood vessels undergo remodeling in type 2 diabetes (T2D), the signaling pathways that underlie the structural and functional changes seen in diabetic arteries remain unclear. Our objective was to determine whether the remodeling in type 2 diabetic Goto-Kakizaki (GK) rats is evoked by elevated reactive oxygen species (ROS). Our results show that aortas from GK rats produced greater force (P < 0.05) in response to stimulation with KCl and U46619 than aortas from Wistar rats. Associated with these changes, aortic expression of contractile proteins (measured as an index of remodeling) and the microRNA (miR-145), which act to upregulate transcription of contractile protein genes, was twofold higher (P < 0.05) in GK than Wistar (age-matched control) rats, and there was a corresponding increase in ROS and decrease in nitric oxide signaling. Oral administration of the antioxidant Tempol (1 mmol/l) to Wistar and GK rats reduced (P < 0.05) myocardin and calponin expression. Tempol (1 mmol/l) decreased expression of miR-145 in Wistar and GK rat aorta. To elucidate the mechanism through which ROS increases miR-145, we measured their levels in freshly isolated aorta and cultured aortic smooth muscle cells incubated for 12 h in the presence of H2O2 (300 ?mol/l). H2O2 increased expression of miR-145, and there were corresponding nuclear increases in myocardin, a miR-145 target protein. Intriguingly, H2O2-induced expression of miR-145 was decreased by U0126 (10 ?mol/l), a MEK1/2 inhibitor, and myocardin was decreased by anti-miR-145 (50 nmol/l) and U0126 (10 ?mol/l). Our novel findings demonstrate that ROS evokes vascular wall remodeling and dysfunction by enhancing expression of contractile proteins in T2D. PMID:24213617

Chettimada, Sukrutha; Ata, Hirotaka; Rawat, Dhwajbahadur K.; Gulati, Salil; Kahn, Andrea G.; Edwards, John G.

2013-01-01

388

Enhanced reactive oxygen species overexpression by CuO nanoparticles in poorly differentiated hepatocellular carcinoma cells.  

PubMed

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

Kung, Mei-Lang; Hsieh, Shu-Ling; Wu, Chih-Chung; Chu, Tian-Huei; Lin, Yu-Chun; Yeh, Bi-Wen; Hsieh, Shuchen

2015-01-22

389

Reactive oxygen species production and redox state in parthenogenetic and sperm-mediated bovine oocyte activation.  

PubMed

The knowledge concerning redox and reactive oxygen species (ROS)-mediated regulation of early embryo development is scarce and remains controversial. The aim of this work was to determine ROS production and redox state during early in vitro embryo development in sperm-mediated and parthenogenetic activation of bovine oocytes. Sperm-mediated oocyte activation was carried out in IVF-modified synthetic oviductal fluid (mSOF) with frozen-thawed semen. Parthenogenetic activation was performed in TALP plus ionomycin and then in IVF-mSOF with 6-dimethylaminopurine plus cytochalasin B. Embryos were cultured in IVF-mSOF. ROS and redox state were determined at each 2-h interval (7-24?h from activation) by 2',7'-dichlorodihydrofluorescein diacetate and RedoxSensor Red CC-1 fluorochromes respectively. ROS levels and redox state differed between activated and non-activated oocytes (P<0.05 by ANOVA). In sperm-activated oocytes, an increase was observed between 15 and 19?h (P<0.05). Conversely, in parthenogenetically activated oocytes, we observed a decrease at 9?h (P<0.05). In sperm-activated oocytes, ROS fluctuated throughout the 24?h, presenting peaks around 7, 19, and 24?h (P<0.05), while in parthenogenetic activation, peaks were detected at 7, 11, and 17?h (P<0.05). In the present work, we found clear distinctive metabolic patterns between normal and parthenogenetic zygotes. Oxidative activity and ROS production are an integral part of bovine zygote behavior, and defining a temporal pattern of change may be linked with developmental competence. PMID:23630331

Morado, S; Cetica, P; Beconi, M; Thompson, J G; Dalvit, G

2013-05-01

390

Roles of Reactive Oxygen Species and Antioxidants in Ovarian Toxicity1  

PubMed Central

ABSTRACT 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

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

2011-01-01

391

Elevated generation of reactive oxygen/nitrogen species in hantavirus cardiopulmonary syndrome.  

PubMed

Hantavirus cardiopulmonary syndrome (HCPS) is a life-threatening respiratory disease characterized by profound pulmonary edema and myocardial depression. Most cases of HCPS in North America are caused by Sin Nombre virus (SNV), which is carried asymptomatically by deer mice (Peromyscus maniculatus). The underlying pathophysiology of HCPS is poorly understood. We hypothesized that pathogenic SNV infection results in increased generation of reactive oxygen/nitrogen species (RONS), which contribute to the morbidity and mortality of HCPS. Human disease following infection with SNV or Andes virus was associated with increased nitrotyrosine (NT) adduct formation in the lungs, heart, and plasma and increased expression of inducible nitric oxide synthase (iNOS) in the lungs compared to the results obtained for normal human volunteers. In contrast, NT formation was not increased in the lungs or cardiac tissue from SNV-infected deer mice, even at the time of peak viral antigen expression. In a murine (Mus musculus) model of HCPS (infection of NZB/BLNJ mice with lymphocytic choriomeningitis virus clone 13), HCPS-like disease was associated with elevated expression of iNOS in the lungs and NT formation in plasma, cardiac tissue, and the lungs. In this model, intraperitoneal injection of 1400W, a specific iNOS inhibitor, every 12 h during infection significantly improved survival without affecting intrapulmonary fluid accumulation or viral replication, suggesting that cardiac damage may instead be the cause of mortality. These data indicate that elevated production of RONS is a feature of pathogenic New World hantavirus infection and that pharmacologic blockade of iNOS activity may be of therapeutic benefit in HCPS cases, possibly by ameliorating the myocardial suppressant effects of RONS. PMID:12134039

Davis, Ian C; Zajac, Allan J; Nolte, Kurt B; Botten, Jason; Hjelle, Brian; Matalon, Sadis

2002-08-01

392

Monochloramine produces reactive oxygen species in liver by converting xanthine dehydrogenase into xanthine oxidase  

SciTech Connect

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.

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

393

Relationship between reactive oxygen species and autophagy in dormant mouse blastocysts during delayed implantation  

PubMed Central

Objective Under estrogen deficiency, blastocysts cannot initiate implantation and enter dormancy. Dormant blastocysts live longer in utero than normal blastocysts, and autophagy has been suggested as a mechanism underlying the sustained survival of dormant blastocysts during delayed implantation. Autophagy is a cellular degradation pathway and a central component of the integrated stress response. Reactive oxygen species (ROS) are produced within cells during normal metabolism, but their levels increase dramatically under stressful conditions. We investigated whether heightened autophagy in dormant blastocysts is associated with the increased oxidative stress under the unfavorable condition of delayed implantation. Methods To visualize ROS production, day 8 (short-term dormancy) and day 20 (long-term dormancy) dormant blastocysts were loaded with 1-µM 5-(and-6)-chloromethyl-2', 7'-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA). To block autophagic activation, 3-methyladenine (3-MA) and wortmannin were used in vivo and in vitro, respectively. Results We observed that ROS production was not significantly affected by the status of dormancy; in other words, both dormant and activated blastocysts showed high levels of ROS. However, ROS production was higher in the dormant blastocysts of the long-term dormancy group than in those of the short-term group. The addition of wortmannin to dormant blastocysts in vitro and 3-MA injection in vivo significantly increased ROS production in the short-term dormant blastocysts. In the long-term dormant blastocysts, ROS levels were not significantly affected by the treatment of the autophagy inhibitor. Conclusion During delayed implantation, heightened autophagy in dormant blastocysts may be operative as a potential mechanism to reduce oxidative stress. Further, ROS may be one of the potential causes of compromised developmental competence of long-term dormant blastocysts after implantation. PMID:25309857

Shin, Hyejin; Choi, Soyoung

2014-01-01

394

Acrolein activates matrix metalloproteinases by increasing reactive oxygen species in macrophages  

SciTech Connect

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.

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

395

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

SciTech Connect

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.

Haase, Hajo; Engelhardt, Gabriela; Hebel, Silke; Rink, Lothar, E-mail: LRink@ukaachen.de

2011-01-01

396

Antioxidant Enzymes Regulate Reactive Oxygen Species during Pod Elongation in Pisum sativum and Brassica chinensis  

PubMed Central

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

Liu, Nan; Lin, Zhifang; Guan, Lanlan; Gaughan, Gerald; Lin, Guizhu

2014-01-01

397

Measurements of UV-generated free radicals/reactive oxygen species (ROS) in skin  

NASA Astrophysics Data System (ADS)

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.

Herrling, Th.; Jung, K.; Fuchs, J.

2006-03-01

398

Localized TRPA1 channel Ca2+ signals stimulated by reactive oxygen species promote cerebral artery dilation.  

PubMed

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