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1

Protection against reactive oxygen species by selenoproteins  

Microsoft Academic Search

Reactive oxygen species (ROS) are derived from cellular oxygen metabolism and from exogenous sources. An excess of ROS results in oxidative stress and may eventually cause cell death. ROS levels within cells and in extracellular body fluids are controlled by concerted action of enzymatic and non-enzymatic antioxidants. The essential trace element selenium exerts its antioxidant function mainly in the form

Holger Steinbrenner; Helmut Sies

2009-01-01

2

Fluoranthene fumigation and exogenous scavenging of reactive oxygen intermediates (ROI) in evergreen Japanese red pine seedlings (Pinus densiflora Sieb. et. Zucc.).  

PubMed

Generation of reactive oxygen intermediates (ROI) such as O(2)(-), H(2)O(2), and *OH is known to be a major mechanism of damage in biological systems. This study investigated and compared effectiveness of scavenging ROI generated in fluoranthene (FLU) pre-fumigated Japanese red pine seedlings. Three kinds of eco-physiological assessments were used to express the impact of the different fumigants used inside the green house. Gas exchange measurements showed negative changes induced by 10 microM FLU on Japanese pine seedlings during a 10 d exposure period whilst no negative change was found during a 5 d exposure period. Moreover, during a 14 d FLU exposure incorporating ROI scavengers, results revealed that chlorophyll fluorescence, needle chemical contents and needle dry mass per unit area of the seedlings were affected. The negative effects of FLU on the conifer were dependent on both the dose and period of FLU fumigation. Peroxidase (PERO), superoxide dismutase (SOD) and mannitol (MANN) were all effective scavengers of ROI. MANN scavenged *OH, the most lethal of the ROI. For practicable use, MANN is more economical, and may be the best ROI scavenger among the three considered. It can be concluded that efficient scavenging of ROI in biological systems is important to mitigate the negative effects of FLU on Japanese red pine trees. PMID:18442844

Oguntimehin, Ilemobayo; Sakugawa, Hiroshi

2008-06-01

3

Reactive oxygen molecules, oxidant injury and renal disease  

Microsoft Academic Search

Oxidant injury has been implicated in the pathogenesis of inflammotory, metabolic and toxic insults, in ischemic-reperfusion injury, and in carcinogenesis, aging and atherosclerosis. Oxidant injury is initiated by free radicals and reactive oxygen molecules which are generated by activated neutrophils, monocytes, and mesangial cells, during normal and abnormal metabolic processes, and from the metabolism of exogenous drugs and toxins. When

Sharon P. Andreoli

1991-01-01

4

Catalase and Superoxide Dismutase Conjugated with Platelet-Endothelial Cell Adhesion Molecule Antibody Distinctly Alleviate Abnormal Endothelial Permeability Caused by Exogenous Reactive Oxygen Species and Vascular Endothelial Growth Factor  

PubMed Central

Reactive oxygen species (ROS) superoxide anion (O2?) and hydrogen peroxide (H2O2) produced by activated leukocytes and endothelial cells in sites of inflammation or ischemia cause endothelial barrier dysfunction that may lead to tissue edema. Antioxidant enzymes (AOEs) catalase and superoxide dismutase (SOD) conjugated with antibodies to platelet-endothelial cell adhesion molecule-1 (PECAM-1) specifically bind to endothelium, quench the corresponding ROS, and alleviate vascular oxidative stress and inflammation. In the present work, we studied the effects of anti-PECAM/catalase and anti-PECAM/SOD conjugates on the abnormal permeability manifested by transendothelial electrical resistance decline, increased fluorescein isothiocyanate-dextran influx, and redistribution of vascular endothelial-cadherin in human umbilical vein endothelial cell (HUVEC) monolayers. Anti-PECAM/catalase protected HUVEC monolayers against H2O2-induced endothelial barrier dysfunction. Polyethylene glycol-conjugated catalase exerted orders of magnitude lower endothelial uptake and no protective effect, similarly to IgG/catalase. Anti-PECAM/catalase, but not anti-PECAM/SOD, alleviated endothelial hyperpermeability caused by exposure to hypoxanthine/xanthine oxidase, implicating primarily H2O2 in the disruption of the endothelial barrier in this model. Thrombin-induced endothelial permeability was not affected by treatment with anti-PECAM/AOEs or the NADPH oxidase inhibitor apocynin or overexpression of AOEs, indicating that the endogenous ROS play no key role in thrombin-mediated endothelial barrier dysfunction. In contrast, anti-PECAM/SOD, but not anti-PECAM/catalase, inhibited a vascular endothelial growth factor (VEGF)-induced increase in endothelial permeability, identifying a key role of endogenous O2? in the VEGF-mediated regulation of endothelial barrier function. Therefore, AOEs targeted to endothelial cells provide versatile molecular tools for testing the roles of specific ROS in vascular pathology and may be translated into remedies for these ROS-induced abnormalities. PMID:21474567

Han, Jingyan; Shuvaev, Vladimir V.

2011-01-01

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 periodontitis  

PubMed Central

Recent epidemiological studies reveal that more than two-third of the world's population suffers from one of the chronic forms of periodontal disease. The primary etiological agent of this inflammatory disease is a polymicrobial complex, predominantly Gram negative anaerobic or facultative bacteria within the sub-gingival biofilm. These bacterial species initiate the production of various cytokines such as interleukin-8 and TNF-?, further causing an increase in number and activity of polymorphonucleocytes (PMN) along with these cytokines, PMNs also produce reactive oxygen species (ROS) superoxide via the respiratory burst mechanism as the part of the defence response to infection. ROS just like the interleukins have deleterious effects on tissue cells when produced in excess. To counter the harmful effects of ROS, human body has its own defence mechanisms to eliminate them as soon as they are formed. The aim of this review is to focus on the role of different free radicals, ROS, and antioxidants in the pathophysiology of periodontal tissue destruction. PMID:24174716

Dahiya, Parveen; Kamal, Reet; Gupta, Rajan; Bhardwaj, Rohit; Chaudhary, Karun; Kaur, Simerpreet

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

Phytate, reactive oxygen species and colorectal cancer.  

PubMed

Reproducible high-performance liquid chromatography methods have been developed and validated which allow an accurate quantification of phytic acid in faeces and food and reactive oxygen species in an in vitro model system and in faecal specimens. When applied to the evaluation of reactive oxygen species generation by faeces, this method has shown that 1:100 dilutions of matrix obtained from stool samples of adenoma patients are capable of generating significant quantities of reactive oxygen species as evinced by the production of diphenols from salicylic acid. Moreover, it has been shown that the major product of HO. attack on salicylic acid is 2,5-dihydroxy benzoic acid and not 2, 3-dihydroxy benzoic acid as previously reported. In the presence of the antioxidant ascorbic acid the inhibitory capacity of phytic acid on the generation of reactive oxygen species is completely subverted. Therefore, the kinetics of reactive oxygen species production by faeces is currently under further investigation by high-performance liquid chromatography and chemiluminescence in various patient groups and may give an insight into the role of reactive oxygen species in the aetiology of colorectal cancer. PMID:9696942

Owen, R W; Spiegelhalder, B; Bartsch, H

1998-05-01

9

Rosacea, Reactive Oxygen Species, and Azelaic Acid  

PubMed Central

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

2009-01-01

10

Signal transduction by reactive oxygen species  

PubMed Central

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

2011-01-01

11

Reactive Oxygen Species in Plant Cell Walls  

Microsoft Academic Search

Plant cell walls are dynamic structures composed of polysaccharides, phenolics, and proteins. The plant cell wall is important\\u000a not only for maintaining cell shape, but it also responds to endogenous and environmental clues through the release of signaling\\u000a molecules, such as H2O2, which may act following autocrine and paracrine pathways. However, the primary function of reactive oxygen species (ROS)\\u000a production

Alfonso Ros Barceló; V. Gómez Ros Laura

12

REACTIVE OXYGEN SPECIES: IMPACT ON SKELETAL MUSCLE  

PubMed Central

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

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

2014-01-01

13

Reactive oxygen species and sperm cells  

PubMed Central

There is a dynamic interplay between pro- and anti-oxidant substances in human ejaculate. Excessive reactive oxygen species (ROS) generation can overwhelm protective mechanism and initiate changes in lipid and/or protein layers of sperm plasma membranes. Additionally, changes in DNA can be induced. The essential steps of lipid peroxidation have been listed as well as antioxidant substances of semen. A variety of detection techniques of lipid peroxidation have been summarized together with the lipid components of sperm membranes that can be subjected to stress. It is unsolved, a threshold for ROS levels that may induce functional sperm ability or may lead to male infertility. PMID:15038829

Sanocka, Dorota; Kurpisz, Maciej

2004-01-01

14

Reactive Oxygen Species and Tumor Metastasis  

PubMed Central

The migration and invasion of cancer cells are the first steps in metastasis. Through a series of cellular responses, including cytoskeletal reorganization and degradation of the extracellular matrix, cancer cells are able to separate from the primary tumor and metastasize to distant locations in the body. In cancer cells, reactive oxygen species (ROS) play important roles in the migration and invasion of cells. Stimulation of cell surface receptors with growth factors and integrin assembly generates ROS, which relay signals from the cell surface to important signaling proteins. ROS then act within cells to promote migration and invasion. In this review, we collect recent evidence pointing towards the involvement of ROS in tumor metastasis and discuss the roles of ROS at different stages during the process of cancer cell migration, invasion and epithelial-mesenchymal transition. PMID:23456330

Lee, Doo Jae; Kang, Sang Won

2013-01-01

15

Reactive Oxygen Species in Health and Disease  

PubMed Central

During the past decades, it became obvious that reactive oxygen species (ROS) exert a multitude of biological effects covering a wide spectrum that ranges from physiological regulatory functions to damaging alterations participating in the pathogenesis of increasing number of diseases. This review summarizes the key roles played by the ROS in both health and disease. ROS are metabolic products arising from various cells; two cellular organelles are intimately involved in their production and metabolism, namely, the endoplasmic reticulum and the mitochondria. Updates on research that tremendously aided in confirming the fundamental roles of both organelles in redox regulation will be discussed as well. Although not comprehensive, this review will provide brief perspective on some of the current research conducted in this area for better understanding of the ROS actions in various conditions of health and disease. PMID:22927725

Alfadda, Assim A.; Sallam, Reem M.

2012-01-01

16

Metabolic Stress, Reactive Oxygen Species, and Arrhythmia  

PubMed Central

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

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

2011-01-01

17

Production and Consumption of Reactive Oxygen Species by Fullerenes  

EPA Science Inventory

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

18

Reactive Oxygen Species and the Cardiovascular System  

PubMed Central

Ever since the discovery of free radicals, many hypotheses on the deleterious actions of reactive oxygen species (ROS) have been proposed. However, increasing evidence advocates the necessity of ROS for cellular homeostasis. ROS are generated as inherent by-products of aerobic metabolism and are tightly controlled by antioxidants. Conversely, when produced in excess or when antioxidants are depleted, ROS can inflict damage to lipids, proteins, and DNA. Such a state of oxidative stress is associated with many pathological conditions and closely correlated to oxygen consumption. Although the deleterious effects of ROS can potentially be reduced by restoring the imbalance between production and clearance of ROS through administration of antioxidants (AOs), the dosage and type of AOs should be tailored to the location and nature of oxidative stress. This paper describes several pathways of ROS signaling in cellular homeostasis. Further, we review the function of ROS in cardiovascular pathology and the effects of AOs on cardiovascular outcomes with emphasis on the so-called oxidative paradox. PMID:23738043

Taverne, Yannick J. H. J.; Bogers, Ad J. J. C.; Duncker, Dirk J.; Merkus, Daphne

2013-01-01

19

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

PubMed

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

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

2003-01-01

20

Mitochondrial reactive oxygen species accelerate gastric cancer cell invasion  

PubMed Central

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

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

2014-01-01

21

Reactive oxygen species, antioxidants and fish mitochondria.  

PubMed

In fishes, irrespective of their thermoregulatory capacity or metabolic rate, the main physiological source of reactive oxygen species (ROS) is mitochondria. During active swimming, ROS is by an large provided by red muscle mitochondria. Other tissues such as lens, liver, heart, swimbladder, roe and blood also afford important ROS production and antioxidant levels in resting fish. A close relationship between structure and function is evident in fish mitochondrion with a surface-to-volume optimization by the size of cristae to maximize electron transfer. The mechanism of fish mitochondrial superoxide anion (O2*-) and ROS production as well as the mechanism of mitochondrial coupling and proton leak seems similar to that of mammals. Contrary to mammalian red cells, fish erythrocytes possess nuclei and mitochondria. The presence of cardiolipin and the absence of cholesterol in fish mitochondrial membranes confer a high structural flexibility. The difference in phospholipid unsaturation may explain the greater proton leak in endotherms compared to thermoconformers. The present review summarizes our current understanding in respect to comparative aspects of fish mitochondrial function, with an emphasis on the adaptations to changes in temperature, O2 availability and O2 consumption, which are generally coupled to changes in antioxidant status and ROS production. Nevertheless, most work on this fascinating area has yet to be done. The literature on the effect of xenobiotics, aquatic contamination, and aquaculture issues are not reviewed. Data on the production of NO and reactive nitrogen species (RNS), on O2 sensing and on the role of ROS and RNS in cell signalling involving fish mitochondria are almost completely lacking in the literature. PMID:17127376

Wilhelm Filho, Danilo

2007-01-01

22

Human Cytomegalovirus Induces Multiple Means To Combat Reactive Oxygen Species?  

PubMed Central

Reactive oxygen species (ROS) are generated as by-products of many cellular processes and can modulate cellular signaling pathways. However, high ROS levels are toxic; thus, intracellular ROS need to be tightly controlled. Therefore, cells use a group of antioxidant molecules and detoxifying enzymes that remove or detoxify reactive species. We found that the level of the antioxidant glutathione is greatly increased in human cytomegalovirus (HCMV)-infected cells due to activation of glutathione synthetic enzymes. In addition, our data suggest that virus-specific mechanisms are used to induce the expression of target antioxidant and detoxifying enzymes critical for the success of the infection. As a result of this virus-induced anti-ROS environment, key signaling kinases, such as the mammalian target of rapamycin (mTOR) kinase in mTOR complex 1 (mTORC1), are protected from inhibition by exogenous hydrogen peroxide (H2O2). In this regard, we found that phosphorylation of mTOR kinase at serine 2448 (suggested to be activating) was maintained during infection even under ROS stress conditions that inhibited it in uninfected cells. We also show that AMP-dependent kinase (AMPK)-mediated phosphorylation of serine 792 of raptor, the specificity subunit of mTORC1, increases in infected cells after H2O2 treatment. This phosphorylation is normally inhibitory for mTORC1. However, in infected cells this did not result in inhibition of mTORC1 activity, suggesting that inhibitory effects of raptor phosphorylation are circumvented. Overall, our data suggest that HCMV utilizes virus-specific mechanisms to activate a variety of means to protect the cell and mTORC1 from the effects of ROS. PMID:21937645

Tilton, Carisa; Clippinger, Amy J.; Maguire, Tobi; Alwine, James C.

2011-01-01

23

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

24

Effect of reactive oxygen species on the erythrocyte calcium-pump function in protein-energy malnutrition.  

PubMed

The presence of detectable amounts of non-heme iron in erythrocyte ghost membranes have been postulated to lead to the initiation of membrane lipid peroxidation and the attendant perturbation of membrane functions. We have investigated the presence of non-heme iron and endogenous products of lipid peroxidation in erythrocyte membranes of normal and kwashiorkor (KWA) subjects and assessed the susceptibility of the membranes to exogenously generated reactive oxygen species. The modulation of the basal and calmodulin-stimulated calcium-pumping activity of these membranes by reactive oxygen species was also assessed. The results show the presence of significant amounts of non-heme iron and endogenous free radical reaction products in the red cell membranes of KWA subjects compared with that of normal children. Estimation of the extent of lipid peroxidation in the presence of exogenously generated reactive oxygen species further revealed that erythrocyte ghost membranes of KWA subjects are more susceptible to oxidative stress than those of normal individuals. Although both the basal and calmodulin-stimulated activities of the membrane-bound Ca(2+)-pump enzyme in normal and KWA subjects were inhibited by oxygen-free radicals, the erythrocyte enzyme in KWA subjects showed higher susceptibility to inhibition by oxygen free radicals than that of normal individuals. We propose that the reduced erythrocyte calcium-pump function in KWA is not unconnected with excessive generation of reactive oxygen species. PMID:1338495

Okunade, W G; Olorunsogo, O O

1992-12-01

25

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

26

Reactive Oxygen Emission from Microwave Discharge Plasmas  

NASA Astrophysics Data System (ADS)

Metastable oxygen atoms and molecules have received increased interest because of their function in surface modification, bio-decontamination and many other industrial applications, in addition to the role in the upper atmospheric layer chemistry. We review work on production and detection of metastable oxygen and we describe our experiments, including the development of techniques for measurement of metastable molecular oxygen. We show that either metastable oxygen molecules or metastable oxygen atoms can be produced in large quantities in electrical discharges, carefully tailored to promote the required kinetics. Although the two species may coexist, colder discharge regimes favor production of molecules, while at higher temperature conditions atomic oxygen prevails. We found that microwave cavity discharges in He/O2 mixtures favor molecular production, but that an arc-seeded microwave torch in air shows preference of atomic production. Result on the specific yield of molecular oxygen in the microwave cavity discharge shows qualitative agreement with the models.

Popovi?, S.; Raškovi?, M.; Kuo, S. P.; Vuškovi?, L.

2007-10-01

27

Role of reactive oxygen species in low level light therapy  

E-print Network

This review will focus on the role of reactive oxygen species in the cellular and tissue effects of low level light therapy (LLLT). Coincidentally with the increase in electron transport and in ATP, there has also been ...

Hamblin, Michael R.

28

Reactive Oxygen Species Driven Angiogenesis by Inorganic Nanorods  

E-print Network

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·?) is involved in redox signaling pathways during angiogenesis, ...

Patra, Chitta Ranjan

29

Reactive oxygen species: toxic molecules or spark of life?  

Microsoft Academic Search

Increases in reactive oxygen species (ROS) and tissue evidence of oxidative injury are common in patients with inflammatory processes or tissue injury. This has led to many clinical attempts to scavenge ROS and reduce oxidative injury. However, we live in an oxygen rich environment and ROS and their chemical reactions are part of the basic chemical processes of normal metabolism.

Sheldon Magder

2006-01-01

30

Vacuum ultraviolet radiation/atomic oxygen synergism in materials reactivity  

NASA Technical Reports Server (NTRS)

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

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

1990-01-01

31

Generation of reactive oxygen species by the faecal matrix  

PubMed Central

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

Owen, R; Spiegelhalder, B; Bartsch, H

2000-01-01

32

Differential patterns of reactive oxygen species and antioxidative mechanisms during atrazine injury and sucrose-induced tolerance in Arabidopsis thaliana plantlets  

Microsoft Academic Search

ABSTRACT: BACKGROUND: Besides being essential for plant structure and metabolism, soluble carbohydrates play important roles in stress responses. Sucrose has been shown to confer to Arabidopsis seedlings a high level of tolerance to the herbicide atrazine, which causes reactive oxygen species (ROS) production and oxidative stress. The effects of atrazine and of exogenous sucrose on ROS patterns and ROS-scavenging systems

Fanny Ramel; Cécile Sulmon; Matthieu Bogard; Ivan Couée; Gwenola Gouesbet

2009-01-01

33

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

34

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

35

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

36

Biochemical Studies on Hemoglobin Modified with Reactive Oxygen Species (ROS)  

Microsoft Academic Search

Hemoglobin is the iron-containing oxygen transporting metalloprotein in the red cells of blood in mammals and other animals.\\u000a Hemoprotein-mediated oxidative stress is thought to play a major role in pathophysiology of cerebral hemorrhage, blast pressure\\u000a injury, crush injury, myocardial ischemia reperfusion injury. Hemoglobin undergoes oxidation–reduction reactions that lead\\u000a to both generation and consumption of highly reactive oxygen and nitrogen species.

Tejinder Pal Khaket; Rizwan Ahmad

2011-01-01

37

Demyelination: the role of reactive oxygen and nitrogen species.  

PubMed

This review summarises the role that reactive oxygen and nitrogen species play in demyelination, such as that occurring in the inflammatory demyelinating disorders multiple sclerosis and Guillain-Barré syndrome. The concentrations of reactive oxygen and nitrogen species (e.g. superoxide, nitric oxide and peroxynitrite) can increase dramatically under conditions such as inflammation, and this can overwhelm the inherent antioxidant defences within lesions. Such oxidative and/or nitrative stress can damage the lipids, proteins and nucleic acids of cells and mitochondria, potentially causing cell death. Oligodendrocytes are more sensitive to oxidative and nitrative stress in vitro than are astrocytes and microglia, seemingly due to a diminished capacity for antioxidant defence, and the presence of raised risk factors, including a high iron content. Oxidative and nitrative stress might therefore result in vivo in selective oligodendrocyte death, and thereby demyelination. The reactive species may also damage the myelin sheath, promoting its attack by macrophages. Damage can occur directly by lipid peroxidation, and indirectly by the activation of proteases and phospholipase A2. Evidence for the existence of oxidative and nitrative stress within inflammatory demyelinating lesions includes the presence of both lipid and protein peroxides, and nitrotyrosine (a marker for peroxynitrite formation). The neurological deficit resulting from experimental autoimmune demyelinating disease has generally been reduced by trial therapies intended to diminish the concentration of reactive oxygen species. However, therapies aimed at diminishing reactive nitrogen species have had a more variable outcome, sometimes exacerbating disease. PMID:9989453

Smith, K J; Kapoor, R; Felts, P A

1999-01-01

38

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

39

Role of reactive oxygen species in cell signalling pathways  

Microsoft Academic Search

Reactive oxygen species (ROS) were originally thought to only be released by phagocytic cells during their role in host defence. It is now clear that ROS have a cell signalling role in many biological systems, both in animals and in plants. ROS induce programmed cell death or necrosis, induce or suppress the expression of many genes, and activate cell signalling

J. T. Hancock; R. Desikan; S. J. Neill

2001-01-01

40

Plasmodium berghei Resists Killing by Reactive Oxygen Species  

Microsoft Academic Search

Reactive oxygen species (ROS) are widely believed to kill malarial parasites. C57BL\\/6 mice injected with P. berghei inocula incubated with supraphysiological doses of NO (<150 M) or with peroxynitrite (220 M), however, exhibited parasitemia similar to that seen with those given control inocula, and there was no difference in disease development. Only treatment of inocula with NO doses nearing saturation

Peter Sobolewski; Irene Gramaglia; John A. Frangos; Marcos Intaglietta; Henri van der Heyde

2005-01-01

41

Crosstalk of reactive oxygen species and NF-?B signaling  

Microsoft Academic Search

NF-?B proteins are a family of transcription factors that are of central importance in inflammation and immunity. NF-?B also plays important roles in other processes, including development, cell growth and survival, and proliferation, and is involved in many pathological conditions. Reactive Oxygen Species (ROS) are created by a variety of cellular processes as part of cellular signaling events. While certain

Michael J Morgan; Zheng-gang Liu

2011-01-01

42

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...

43

Engineering Pyranose 2-Oxidase for Modified Oxygen Reactivity  

PubMed Central

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

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

2014-01-01

44

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

45

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 ...

Zen, Andrea; Guidoni, Leonardo

2014-01-01

46

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; Oelmuller, Ralf

2012-01-01

47

Telomeres, sex, reactive oxygen species, and human cardiovascular aging.  

PubMed

By undergoing erosion with each replicative cycle, telomeres chronicle the replicative history of human somatic cells in vitro and in vivo. In human beings the telomere is relatively short, inversely correlated with age, highly heritable, and longer in women than men. However, it is not established whether the dynamics of telomere attrition in vivo has a role in the biology of human aging. Telomere attrition may be modified by reactive oxygen species, the biology of which is governed by processes that are influenced by sex. Indices of cardiovascular aging in humans are correlated with telomere length and this relationship is characterized by sexual dimorphism. In the final analysis, the biology of reactive oxygen species may offer a common explanation for some interindividual variation in cardiovascular aging and age-dependent telomere attrition in humans. PMID:12436345

Aviv, Abraham

2002-11-01

48

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

49

Unusual Reactivity of the Martian Soil: Oxygen Release Upon Humidification  

NASA Technical Reports Server (NTRS)

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

Yen, A. S.

2002-01-01

50

Reactive Oxygen Species, Oxidative Stress and Plant Ion Channels  

Microsoft Academic Search

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

Vadim Demidchik

51

Reactive Oxygen Species in Plant–Pathogen Interactions  

Microsoft Academic Search

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

G. Paul Bolwell; Arsalan Daudi

52

Mitochondrial respiration and reactive oxygen species in mitochondrial aging mutants.  

PubMed

A powerful approach to understanding a complex process such as aging is to study the process in model organisms that are amenable to genetic dissection. Several mutant strains in different organisms have been identified that affect lifespan; data from these organisms indicate that mitochondrial function is a major factor affecting lifespan. Mutations which affect some aspect of mitochondrial function and affect lifespan have been isolated in yeast, nematodes, flies and mice. These results have revealed a general pattern that decreased metabolic rates are associated with increased lifespans. However, it is also clear that some strains with decreased metabolic rates have shortened lifespans. The emerging data is most consistent with the effects of reactive oxygen species also playing a major role in determining lifespan. Mitochondrial mutations are apparently capable of slowing metabolism with resulting increases or decreases in production of reactive oxygen species. In this review, we discuss the effects of mitochondrial mutations of lifespan with an emphasis on the role of reactive oxygen species. PMID:16497463

Sedensky, Margaret M; Morgan, Philip G

2006-03-01

53

Susceptibility of cloned K+ channels to reactive oxygen species.  

PubMed Central

Free radical-induced oxidant stress has been implicated in a number of physiological and pathophysiological states including ischemia and reperfusion-induced dysrhythmia in the heart, apoptosis of T lymphocytes, phagocytosis, and neurodegeneration. We have studied the effects of oxidant stress on the native K+ channel from T lymphocytes and on K+ channels cloned from cardiac, brain, and T-lymphocyte cells and expressed in Xenopus oocytes. The activity of three Shaker K+ channels (Kv1.3, Kv1.4, and Kv1.5), one Shaw channel (Kv3.4), and one inward rectifier K+ channel (IRK3) was drastically inhibited by photoactivation of rose bengal, a classical generator of reactive oxygen species. Other channel types (such as Shaker K+ channel Kv1.2, Shab channels Kv2.1 and Kv2.2, Shal channel Kv4.1, inward rectifiers IRK1 and ROMK1, and hIsK) were completely resistant to this treatment. On the other hand tert-butyl hydroperoxide, another generator of reactive oxygen species, removed the fast inactivation processes of Kv1.4 and Kv3.4 but did not alter other channels. Xanthine/xanthine oxidase system had no effect on all channels studied. Thus, we show that different types of K+ channels are differently modified by reactive oxygen species, an observation that might be of importance in disease states. PMID:8524851

Duprat, F; Guillemare, E; Romey, G; Fink, M; Lesage, F; Lazdunski, M; Honore, E

1995-01-01

54

Reactive oxygen species produced by NADPH oxidase are involved in pollen tube growth.  

PubMed

Tip-localized reactive oxygen species (ROS) were detected in growing pollen tubes by chloromethyl dichlorodihydrofluorescein diacetate oxidation, while tip-localized extracellular superoxide production was detected by nitroblue tetrazolium (NBT) reduction. To investigate the origin of the ROS we cloned a fragment of pollen specific tobacco NADPH oxidase (NOX) closely related to a pollen specific NOX from Arabidopsis. Transfection of tobacco pollen tubes with NOX-specific antisense oligodeoxynucleotides (ODNs) resulted in decreased amount of NtNOX mRNA, lower NOX activity and pollen tube growth inhibition. The ROS scavengers and the NOX inhibitor diphenylene iodonium chloride (DPI) inhibited growth and ROS formation in tobacco pollen tube cultures. Exogenous hydrogen peroxide (H2O2) rescued the growth inhibition caused by NOX antisense ODNs. Exogenous CaCl2 increased NBT reduction at the pollen tube tip, suggesting that Ca2+ increases the activity of pollen NOX in vivo. The results show that tip-localized ROS produced by a NOX enzyme is needed to sustain the normal rate of pollen tube growth and that this is likely to be a general mechanism in the control of tip growth of polarized plant cells. PMID:17504458

Potocký, Martin; Jones, Mark A; Bezvoda, Radek; Smirnoff, Nicholas; Zárský, Viktor

2007-01-01

55

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

2014-03-11

56

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

57

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

58

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

59

Redox processes in neurodegenerative disease involving reactive oxygen species.  

PubMed

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

Kovacic, Peter; Somanathan, Ratnasamy

2012-12-01

60

Reactive oxygen species in regulation of fungal development.  

PubMed

Reactive oxygen species (ROS) are formed by fungi in the course of metabolic activity. ROS production increases in fungi due to various stress agents such as starvation, light, mechanical damage, and interactions with some other living organisms. Regulation of ROS level appears to be very important during development of the fungal organism. ROS sources in fungal cells, their sensors, and ROS signal transduction pathways are discussed in this review. Antioxidant defense systems in different classes of fungi are characterized in detail. Particular emphasis is placed on ROS functions in interactions of phytopathogenic fungi with plant cells. PMID:18021067

Gessler, N N; Aver'yanov, A A; Belozerskaya, T A

2007-10-01

61

Reactive oxygen species in aerobic methane formation from vegetation  

PubMed Central

The first report of aerobic methane emissions from vegetation by an unknown mechanism1 suggested that this potential new source may make a significant contribution to global methane emissions. We recently investigated possible mechanisms and reported2,3 experiments in which UV-irradiation caused methane emissions from pectin, a major plant cell wall polysaccharide. Our findings also suggest that UV-generated reactive oxygen species (ROS) release methane from pectin. This has implications for all other, UV-independent processes which may generate ROS in or close to the plant cell wall and suggests a need to evaluate additional systems for ROS-generated methane emissions in leaves. PMID:19820327

Messenger, David J; McLeod, Andy R

2009-01-01

62

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

63

Redox Processes in Neurodegenerative Disease Involving Reactive Oxygen Species  

PubMed Central

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

Kovacic, Peter; Somanathan, Ratnasamy

2012-01-01

64

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

PubMed Central

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

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

2014-01-01

65

Biochemical studies on hemoglobin modified with reactive oxygen species (ROS).  

PubMed

Hemoglobin is the iron-containing oxygen transporting metalloprotein in the red cells of blood in mammals and other animals. Hemoprotein-mediated oxidative stress is thought to play a major role in pathophysiology of cerebral hemorrhage, blast pressure injury, crush injury, myocardial ischemia reperfusion injury. Hemoglobin undergoes oxidation-reduction reactions that lead to both generation and consumption of highly reactive oxygen and nitrogen species. In the present study, hemoglobin molecule was treated with hydrogen peroxide and the modification so incurred was analyzed by UV spectra, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and detection of carbonyl content. Our observations suggest that carbonyl content increases with increase in concentration of hydrogen peroxide. Production of hydroxyl radical was assessed by using benzoate degradation analysis. Our results was in tandem with the fact that hemoglobin on treatment with hydrogen peroxide rapidly generates free-radical species that can degrade benzoate to thiobarbituric acid reactive material which on reacting with thiobarbituric acid gives color. The increase in absorbance of ROS-modified hemoglobin at 532 nm shows the increase in benzoate degradation, which is a parameter of hydroxyl radical formation with increase in concentration of hydrogen peroxide. Modified hemoglobin was treated with catalase, mannitol, thiourea, glutathion, sodium benzoate and their effect were detected by spectroscopy and SDS-PAGE (12%). Substantial scavenging effect of aforementioned antioxidants reiterates the formation of hydroxyl radical. Catalase shows the maximum scavenging effect followed by thiourea and mannitol. PMID:21416337

Khaket, Tejinder Pal; Ahmad, Rizwan

2011-08-01

66

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

PubMed Central

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 H2O2 detoxification in B. fragilis, thereby allowing for the quantification of ROS production. Exogenous fumarate significantly reduced H2O2 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.

2012-01-01

67

Reactive oxygen species-targeted therapeutic interventions for atrial fibrillation  

PubMed Central

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

Sovari, Ali A.; Dudley, Samuel C.

2012-01-01

68

Reactive oxygen species in inflammation and tissue injury.  

PubMed

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. PMID:23991888

Mittal, Manish; Siddiqui, Mohammad Rizwan; Tran, Khiem; Reddy, Sekhar P; Malik, Asrar B

2014-03-01

69

Reactive Oxygen Species: The Achilles' Heel of Cancer Cells?  

PubMed Central

Abstract Cancer development, progression, and metastasis are multistep processes. Accumulating evidence suggests that reactive oxygen species (ROS) are critically involved in cancer cell functions. This Forum reviews our current understanding of the important and paradoxical role of ROS in the regulation of tumor-associated cell properties, genes, and signaling pathways. The six reviews in this Forum showcase the up-to-date knowledge on how ROS modulate or interact with the p53 protein, epithelial–mesenchymal transition, tumor stromal cells, angiogenesis, and cancer stem cells, which are essential factors in cancer development and metastasis. The contributions demonstrate that ROS levels in cancer cells are tightly controlled, which brings promises and challenges in the development of novel ROS-targeted anticancer therapies. Further understanding of the biological mechanisms underlying the effects of oxidative stress on tumor growth and metastasis will contribute to the advancement of cancer biology and cancer treatment. Antioxid. Redox Signal. 16, 1212–1214. PMID:22304673

2012-01-01

70

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

71

Oxidative depolymerization of polysaccharides by reactive oxygen/nitrogen species  

PubMed Central

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are constantly produced and are tightly regulated to maintain a redox balance (or homeostasis) together with antioxidants (e.g. superoxide dismutase and glutathione) under normal physiological circumstances. These ROS/RNS have been shown to be critical for various biological events including signal transduction, aging, apoptosis, and development. Despite the known beneficial effects, an overproduction of ROS/RNS in the cases of receptor-mediated stimulation and disease-induced oxidative stress can inflict severe tissue damage. In particular, these ROS/RNS are capable of degrading macromolecules including proteins, lipids and nucleic acids as well as polysaccharides, and presumably lead to their dysfunction. The purpose of this review is to highlight (1) chemical mechanisms related to cell-free and cell-based depolymerization of polysaccharides initiated by individual oxidative species; (2) the effect of ROS/RNS-mediated depolymerization on the successive cleavage of the glycosidic linkage of polysaccharides by glycoside hydrolases; and (3) the potential biological outcome of ROS/RNS-mediated depolymerization of polysaccharides. PMID:21030538

Duan, Jinyou; Kasper, Dennis L

2011-01-01

72

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

73

Oxygen versus Reactive Oxygen in the Regulation of HIF-1?: The Balance Tips  

PubMed Central

Hypoxia inducible factor (HIF) is known as the master regulator of the cellular response to hypoxia and is of pivotal importance during development as well as in human disease, particularly in cancer. It is composed of a constitutively expressed ? subunit (HIF-1?) and an oxygen-regulated ? subunit (HIF-1? and HIF-2?), whose stability is tightly controlled by a family of oxygen- and iron-dependent prolyl hydroxylase enzymes. Whether or not mitochondria-derived reactive oxygen species (ROS) are involved in the regulation of Hypoxia Inducible Factor-1? has been a matter of contention for the last 10 years, with equally compelling evidence in favor and against their contribution. A number of recent papers appear to tip the balance against a role for ROS. Thus, it has been demonstrated that HIF prolyl hydroxylases are unlikely to be physiological targets of ROS and that the increase in ROS that is associated with downregulation of Thioredoxin Reductase in hypoxia does not affect HIF-1? stabilization. Finally, the protein CHCHD4, which modulates cellular HIF-1? concentrations by promoting mitochondrial electron transport chain activity, has been proposed to exert its regulatory effect by affecting cellular oxygen availability. These reports are consistent with the hypothesis that mitochondria play a critical role in the regulation of HIF-1? by controlling intracellular oxygen concentrations. PMID:23091723

Hagen, Thilo

2012-01-01

74

Acute and chronic modulation of placental chorionic plate artery reactivity by reactive oxygen species.  

PubMed

Control of vascular resistance and blood flow in the fetoplacental circulation is incompletely understood. Reactive oxygen species (ROS), physiological and pathophysiological regulators of vascular tone, are elevated in preeclampsia (PE), a disease of pregnancy characterized by increased fetoplacental vascular resistance. We tested the hypothesis that ROS modulate vascular reactivity in placental chorionic plate arteries. Wire myography was used to examine (1) the effects of acute exposure to ROS on arterial function in normal pregnancy and (2) the effects of maternal antioxidant supplementation on arterial reactivity in women at high risk for PE participating in the Vitamins in Pre-eclampsia (VIP) trial. ROS generated by xanthine plus xanthine oxidase enhanced basal tension, vasoconstriction in response to the thromboxane mimetic U46619, and relaxation in response to sodium nitroprusside. Hydrogen peroxide and peroxynitrite increased basal tone and relaxed preconstricted arteries (U44619), respectively. In women at risk for PE, chorionic plate artery constriction in response to U46619 was greater in the women receiving placebo compared to the women supplemented with the antioxidant vitamins C and E. ROS may regulate fetoplacental vascular resistance and blood flow in the short term, and chronic exposure to raised ROS could contribute to elevated fetoplacental vascular resistance in PE and fetal growth restriction (FGR). PMID:19389471

Mills, Tracey A; Wareing, Mark; Shennan, Andrew H; Poston, Lucilla; Baker, Philip N; Greenwood, Susan L

2009-07-15

75

Reactive Oxygen Species Modulate the Barrier Function of the Human Glomerular Endothelial Glycocalyx  

PubMed Central

Reactive oxygen species (ROS) play a key role in the pathogenesis of proteinuria in glomerular diseases like diabetic nephropathy. Glomerular endothelial cell (GEnC) glycocalyx covers the luminal aspect of the glomerular capillary wall and makes an important contribution to the glomerular barrier. ROS are known to depolymerise glycosaminoglycan (GAG) chains of proteoglycans, which are crucial for the barrier function of GEnC glycocalyx. The aim of this study is to investigate the direct effects of ROS on the structure and function of GEnC glycocalyx using conditionally immortalised human GEnC. ROS were generated by exogenous hydrogen peroxide. Biosynthesis and cleavage of GAG chains was analyzed by radiolabelling (S35 and 3H-glucosamine). GAG chains were quantified on GEnC surface and in the cell supernatant using liquid chromatography and immunofluorescence techniques. Barrier properties were estimated by measuring trans-endothelial passage of albumin. ROS caused a significant loss of WGA lectin and heparan sulphate staining from the surface of GEnC. This lead to an increase in trans-endothelial albumin passage. The latter could be inhibited by catalase and superoxide dismutase. The effect of ROS on GEnC was not mediated via the GAG biosynthetic pathway. Quantification of radiolabelled GAG fractions in the supernatant confirmed that ROS directly caused shedding of HS GAG. This finding is clinically relevant and suggests a mechanism by which ROS may cause proteinuria in clinical conditions associated with high oxidative stress. PMID:23457483

Singh, Anurag; Ramnath, Raina D.; Foster, Rebecca R.; Wylie, Emma C.; Fridén, Vincent; Dasgupta, Ishita; Haraldsson, Borje; Welsh, Gavin I.; Mathieson, Peter W.; Satchell, Simon C.

2013-01-01

76

Reactive oxygen species modulate the barrier function of the human glomerular endothelial glycocalyx.  

PubMed

Reactive oxygen species (ROS) play a key role in the pathogenesis of proteinuria in glomerular diseases like diabetic nephropathy. Glomerular endothelial cell (GEnC) glycocalyx covers the luminal aspect of the glomerular capillary wall and makes an important contribution to the glomerular barrier. ROS are known to depolymerise glycosaminoglycan (GAG) chains of proteoglycans, which are crucial for the barrier function of GEnC glycocalyx. The aim of this study is to investigate the direct effects of ROS on the structure and function of GEnC glycocalyx using conditionally immortalised human GEnC. ROS were generated by exogenous hydrogen peroxide. Biosynthesis and cleavage of GAG chains was analyzed by radiolabelling (S(35) and (3)H-glucosamine). GAG chains were quantified on GEnC surface and in the cell supernatant using liquid chromatography and immunofluorescence techniques. Barrier properties were estimated by measuring trans-endothelial passage of albumin. ROS caused a significant loss of WGA lectin and heparan sulphate staining from the surface of GEnC. This lead to an increase in trans-endothelial albumin passage. The latter could be inhibited by catalase and superoxide dismutase. The effect of ROS on GEnC was not mediated via the GAG biosynthetic pathway. Quantification of radiolabelled GAG fractions in the supernatant confirmed that ROS directly caused shedding of HS GAG. This finding is clinically relevant and suggests a mechanism by which ROS may cause proteinuria in clinical conditions associated with high oxidative stress. PMID:23457483

Singh, Anurag; Ramnath, Raina D; Foster, Rebecca R; Wylie, Emma C; Fridén, Vincent; Dasgupta, Ishita; Haraldsson, Borje; Welsh, Gavin I; Mathieson, Peter W; Satchell, Simon C

2013-01-01

77

Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability  

E-print Network

Rac1b and reactive oxygen species mediate MMP-3- induced EMT and genomic instability Derek C. Bissell1 The tumour microenvironment can be a potent carcinogen, not only by facilitating cancer causes an increase in cellular reactive oxygen species (ROS). The ROS stimulate the expression

Nelson, Celeste M.

78

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

79

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

80

Role of GLUT1 in regulation of reactive oxygen species.  

PubMed

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

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

2014-01-01

81

Reactive oxygen metabolites produced by the carcinogenic fibrous mineral erionite.  

PubMed

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 micrograms/ml of erionite. PMN CL was produced immediately after the addition of erionite; the maximal CL production was reached within 2 to 6 min and the CL response increased with the dose of erionite. Superoxide dismutase, catalase, and dimethyl sulfoxide were utilized as scavengers of O2-, H2O2, and OH., respectively. These scavengers inhibited the production of erionite-stimulated PMN CL dose dependently, thus indicating the production of O2-, H2O2, 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. PMID:1848514

Urano, N; Yano, E; Evans, P H

1991-02-01

82

Generation of Reactive Oxygen Species from Silicon Nanowires  

PubMed Central

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

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

2014-01-01

83

Role of Reactive Oxygen Species and Antioxidants in Atopic Dermatitis  

PubMed Central

Background: In humans, oxidative stress is involved in many diseases such as atherosclerosis, Parkinson’s disease, heart failure, myocardial infarction, Alzheimer’s disease, Fragile X syndrome and chronic fatigue syndrome. Atopic dermatitis (AD), also known as atopic eczema, is a non-contagious, relapsing inflammatory skin disease which is characterized by eczema and pruritus. The skin reacts abnormally to irritants, food and environmental allergens and it becomes very itchy, which leads to scratching, redness and flaky skin. Very little study has been done to find out the relationship between oxidative stress and Atopic dermatitis. Aim: The aim of our work was to evaluate the status of oxidative stress in patients of Atopic dermatitis in comparison with healthy control subjects. Material and Methods: Twenty five patients of known Atopic dermatitis and 25 normal healthy controls of same age group were included in the study. Estimations of oxidants like Malondialdehyde (MDA), enzymatic antioxidants like Superoxide dismutase (SOD), Catalase, Glutathione peroxidase (GPX) and non-enzymatic antioxidants like reduced Glutathione (GSH), Vitamin A, Vitamin E and Vitamin C were done to assess the oxidative stress. Results: Atopic dermatitis patients were more prone to damage caused by Reactive Oxygen Species (ROS) or Oxidants, than controls, which was evident from an increase of Malondialdehyde and a decrease of enzymatic and non enzymatic Antioxidants. Conclusion: Antioxidants may possibly be beneficial in the treatment of Atopic dermatitis, which must be substantiated by further studies. PMID:24551611

Sivaranjani, N.; Rao, S. Venkata; Rajeev, G.

2013-01-01

84

Role of GLUT1 in regulation of reactive oxygen species  

PubMed Central

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

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

2014-01-01

85

Scavenging of reactive oxygen species in mitochondria induces myofibroblast differentiation.  

PubMed

The goal of this study was to investigate the possible role of reactive oxygen species (ROS) in signaling, in modulation of the cytoskeleton, and in differentiation of fibroblasts. For this purpose, we have applied a novel mitochondria-targeted antioxidant: plastoquinone conjugated with decyltriphenylphosphonium (SkQ1). This antioxidant at nanomolar concentration prevented ROS accumulation and cell death induced by H(2)O(2) in fibroblasts. We found that scavenging of ROS produced by mitochondria activated the Rho/ROCK/LIMK signaling pathway that was followed by phosphorylation of cofilin and stabilization of actin stress fibers. The mitochondria-targeted antioxidant induced differentiation of human subcutaneous fibroblasts to myofibroblasts as revealed by expression of fibronectin isoform (EDA-FN) and smooth muscle actin (?-SMA). This effect was shown to be mediated by transforming growth factor ?1 (TGF?1), which was activated by matrix metalloprotease 9 (MMP9) in the culture medium. Scavenging of ROS stimulated secretion of MMP9 rather than its processing. The same effect was achieved by the nontargeted antioxidant Trolox at higher concentration, but the thiol antioxidant N-acetylcysteine (NAC) inhibited MMP activity and was not able to induce myofibroblast differentiation. The myofibroblast phenotype was supported due to autocrine TGF?1-dependent stimulation after removal of SkQ1. It is concluded that ROS scavenging in mitochondria induces TGF?1-dependent myofibroblast differentiation. PMID:20446771

Popova, Ekaterina N; Pletjushkina, Olga Y; Dugina, Vera B; Domnina, Lidia V; Ivanova, Olga Y; Izyumov, Denis S; Skulachev, Vladimir P; Chernyak, Boris V

2010-11-01

86

REACTIVE OXYGEN SPECIES, CELLULAR REDOX SYSTEMS AND APOPTOSIS  

PubMed Central

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

Circu, Magdalena L.; Aw, Tak Yee

2010-01-01

87

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

88

Roles of Reactive Oxygen Species in the Spermatogenesis Regulation  

PubMed Central

Spermatogenesis is a complex process of male germ cells proliferation and maturation from diploid spermatogonia, through meiosis, to mature haploid spermatozoa. The process involves dynamic interactions between the developing germ cells and their supporting Sertoli cells. The gonadal tissue, with abundance of highly unsaturated fatty acids, high rates of cell division, and variety of testis enzymes results very vulnerable to the overexpression of reactive oxygen species (ROS). In order to address this risk, testis has developed a sophisticated array of antioxidant systems comprising both enzymes and free radical scavengers. This chapter sets out the major pathways of testis generation, the metabolism of ROS, and highlights the transcriptional regulation by steroid receptors of antioxidant stress enzymes and their functional implications. It also deals with of the advantages of the system biology for an antioxidant under steroid control, the major selenoprotein expressed by germ cells in the testis, the phospholipid hydroperoxide glutathione peroxidase (PHGPx/GPx4) having multiple functions and representing the pivotal link between selenium, sperm quality, and species preservation. PMID:24795696

Guerriero, Giulia; Trocchia, Samantha; Abdel-Gawad, Fagr K.; Ciarcia, Gaetano

2014-01-01

89

Mitochondrial Reactive Oxygen Species Trigger Hypoxia-Induced Transcription  

NASA Astrophysics Data System (ADS)

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

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

1998-09-01

90

How reactive oxygen species and proline face stress together.  

PubMed

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

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

2014-07-01

91

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

92

Role of mitochondrial reactive oxygen species in osteoclast differentiation.  

PubMed

Previously we showed that hypoxia-induced mitochondrial respiratory stress in RAW 264.7 macrophages and other cells caused activation of retrograde signaling (also known as mitochondrial respiratory stress signaling) and the appearance of tartrate-resistant acid phosphatase (TRAP)-positive cells. In the present study, we used N-acetyl cysteine and ascorbate (general antioxidants) and MitoQ, a mitochondria-specific antioxidant, to investigate the role of intracellular reactive oxygen species (ROS) in osteoclast differentiation. Our results show that hypoxia-mediated mitochondrial dysfunction, as tested by disruption of mitochondrial transmembrane potential, was suppressed by MitoQ as well as by the other antioxidants. These agents also suppressed the activation of mitochondrial retrograde signaling. Interestingly, in terms of molar concentrations, MitoQ was more than 1000-fold more effective than general antioxidants in suppressing the receptor activator of nuclear factor-B ligand-induced differentiation of RAW 264.7 cells into multinucleated and TRAP-positive osteoclasts. We propose that mitochondrial function and intramitochondrial ROS play important roles in osteoclastogenesis. PMID:20392243

Srinivasan, Satish; Koenigstein, Alexander; Joseph, Joy; Sun, Li; Kalyanaraman, B; Zaidi, Mone; Avadhani, Narayan G

2010-03-01

93

Mitochondrial Reactive Oxygen Species Regulate Transforming Growth Factor-? Signaling  

PubMed Central

TGF-? signaling is required for normal tissue repair; however, excessive TGF-? signaling can lead to robust profibrotic gene expression in fibroblasts, resulting in tissue fibrosis. TGF-? binds to cell-surface receptors, resulting in the phosphorylation of the Smad family of transcription factors to initiate gene expression. TGF-? also initiates Smad-independent pathways, which augment gene expression. Here, we report that mitochondrial reactive oxygen species (ROS) generated at complex III are required for TGF-?-induced gene expression in primary normal human lung fibroblasts. TGF-?-induced ROS could be detected in both the mitochondrial matrix and cytosol. Mitochondrially targeted antioxidants markedly attenuated TGF-?-induced gene expression without affecting Smad phosphorylation or nuclear translocation. Genetically disrupting mitochondrial complex III-generated ROS production attenuated TGF-?-induced profibrotic gene expression. Furthermore, inhibiting mitochondrial ROS generation attenuated NOX4 (NADPH oxidase 4) expression, which is required for TGF-? induced myofibroblast differentiation. Lung fibroblasts from patients with pulmonary fibrosis generated more mitochondrial ROS than normal human lung fibroblasts, and mitochondrially targeted antioxidants attenuated profibrotic gene expression in both normal and fibrotic lung fibroblasts. Collectively, our results indicate that mitochondrial ROS are essential for normal TGF-?-mediated gene expression and that targeting mitochondrial ROS might be beneficial in diseases associated with excessive fibrosis. PMID:23204521

Jain, Manu; Rivera, Stephanie; Monclus, Elena A.; Synenki, Lauren; Zirk, Aaron; Eisenbart, James; Feghali-Bostwick, Carol; Mutlu, Gokhan M.; Budinger, G. R. Scott; Chandel, Navdeep S.

2013-01-01

94

Tissue oxygen sensor function of NADPH oxidase isoforms, an unusual cytochrome aa3 and reactive oxygen species  

Microsoft Academic Search

NADPH oxidase isoforms with different gp91phox subunits as well as an unusual cytochrome aa3 with a heme a\\/a3 relationship of 9:91 are discussed as putative oxygen sensor proteins influencing gene expression and ion channel conductivity. Reactive oxygen species (ROS) are important second messengers of the oxygen sensing signal cascade determining the stability of transcription factors or the gating of ion

Torsten Porwol; Wilhelm Ehleben; Verena Brand; Helmut Acker

2001-01-01

95

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. Keywords: Chemical sensor; Thermal treatment; Activation; LaF3; Pt 1. Introduction There are several oxygen

Moritz, Werner

96

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

97

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

98

Mitochondrial reactive oxygen species: which ROS signals cardioprotection?  

PubMed Central

Mitochondria are the major effectors of cardioprotection by procedures that open the mitochondrial ATP-sensitive potassium channel (mitoKATP), including ischemic and pharmacological preconditioning. MitoKATP opening leads to increased reactive oxygen species (ROS), which then activate a mitoKATP-associated PKC?, which phosphorylates mitoKATP and leaves it in a persistent open state (Costa AD, Garlid KD. Am J Physiol Heart Circ Physiol 295, H874–H882, 2008). The ROS responsible for this effect is not known. The present study focuses on superoxide (O2·?), hydrogen peroxide (H2O2), and hydroxyl radical (HO?), each of which has been proposed as the signaling ROS. Feedback activation of mitoKATP provides an ideal setting for studying endogenous ROS signaling. Respiring rat heart mitochondria were preincubated with ATP and diazoxide, together with an agent being tested for interference with this process, either by scavenging ROS or by blocking ROS transformations. The mitochondria were then assayed to determine whether or not the persistent phosphorylated open state was achieved. Dimethylsulfoxide (DMSO), dimethylformamide (DMF), deferoxamine, Trolox, and bromoenol lactone each interfered with formation of the ROS-dependent open state. Catalase did not interfere with this step. We also found that DMF blocked cardioprotection by both ischemic preconditioning and diazoxide. The lack of a catalase effect and the inhibitory effects of agents acting downstream of HO? excludes H2O2 as the endogenous signaling ROS. Taken together, the results support the conclusion that the ROS message is carried by a downstream product of HO? and that it is probably a product of phospholipid oxidation. PMID:23913710

Jaburek, Martin; Jacobs, Jeremy P.; Garlid, Keith D.

2013-01-01

99

Mitochondrial reactive oxygen species: which ROS signals cardioprotection?  

PubMed

Mitochondria are the major effectors of cardioprotection by procedures that open the mitochondrial ATP-sensitive potassium channel (mitoKATP), including ischemic and pharmacological preconditioning. MitoKATP opening leads to increased reactive oxygen species (ROS), which then activate a mitoKATP-associated PKC?, which phosphorylates mitoKATP and leaves it in a persistent open state (Costa AD, Garlid KD. Am J Physiol Heart Circ Physiol 295, H874-H882, 2008). The ROS responsible for this effect is not known. The present study focuses on superoxide (O2(·-)), hydrogen peroxide (H2O2), and hydroxyl radical (HO(·)), each of which has been proposed as the signaling ROS. Feedback activation of mitoKATP provides an ideal setting for studying endogenous ROS signaling. Respiring rat heart mitochondria were preincubated with ATP and diazoxide, together with an agent being tested for interference with this process, either by scavenging ROS or by blocking ROS transformations. The mitochondria were then assayed to determine whether or not the persistent phosphorylated open state was achieved. Dimethylsulfoxide (DMSO), dimethylformamide (DMF), deferoxamine, Trolox, and bromoenol lactone each interfered with formation of the ROS-dependent open state. Catalase did not interfere with this step. We also found that DMF blocked cardioprotection by both ischemic preconditioning and diazoxide. The lack of a catalase effect and the inhibitory effects of agents acting downstream of HO(·) excludes H2O2 as the endogenous signaling ROS. Taken together, the results support the conclusion that the ROS message is carried by a downstream product of HO(·) and that it is probably a product of phospholipid oxidation. PMID:23913710

Garlid, Anders O; Jaburek, Martin; Jacobs, Jeremy P; Garlid, Keith D

2013-10-01

100

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

101

Inflammation and reactive oxygen species in cardiovascular disease.  

PubMed

Reactive oxygen species (ROS) have long been proposed to be mediators of experimental cardiovascular pathology. There is also a wealth of data indicating that ROS are involved in clinical cardiovascular pathology. However, multiple clinical studies have shown little benefit from anti-oxidant treatments, whereas nearly all experimental studies have shown a marked effect of anti-oxidant therapy. One reason for this discrepancy is that ROS are produced through multiple different mechanisms of which some are clinically beneficial; thus, in a defined experimental system where predominately pathological ROS are generated does not mimic a clinical setting where there are likely to be multiple ROS generating systems producing beneficial and pathological ROS. Simple inhibition of ROS would not be expected to have the same result in these two situations; ergo, it is important to understand the molecular mechanism underlying the production of ROS so that clinical treatments can be tailored to target the pathological production of ROS. One such example of this in cardiovascular biology is tissue specific inflammation-mediated ROS generation. This and the following series of articles discuss the current understanding of the role of ROS in cardiovascular disease, specifically focusing on the molecular mechanisms of ROS generation and the actions of ROS within the cardiovascular system. Although there are still many areas with regard to the effects of ROS in the cardiovascular system that are not completely understood, there is a wealth of data suggesting that blocking pathological ROS production is likely to have beneficial clinical effects compared to traditional anti-oxidants. PMID:21191541

Zhang, Nannan; Andresen, Bradley T; Zhang, Cuihua

2010-12-26

102

Carbon monoxide activates autophagy via mitochondrial reactive oxygen species formation.  

PubMed

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

Lee, Seon-Jin; Ryter, Stefan W; Xu, Jin-Fu; Nakahira, Kiichi; Kim, Hong Pyo; Choi, Augustine M K; Kim, Young Sam

2011-10-01

103

HIF and reactive oxygen species regulate oxidative phosphorylation in cancer.  

PubMed

A decrease in oxidative phosphorylation (OXPHOS) is characteristic of many cancer types and, in particular, of clear cell renal carcinoma (CCRC) deficient in von Hippel-Lindau (vhl) gene. In the absence of functional pVHL, hypoxia-inducible factor (HIF) 1-alpha and HIF2-alpha subunits are stabilized, which induces the transcription of many genes including those involved in glycolysis and reactive oxygen species (ROS) metabolism. Transfection of these cells with vhl is known to restore HIF-alpha subunit degradation and to reduce glycolytic genes transcription. We show that such transfection with vhl of 786-0 CCRC (which are devoid of HIF1-alpha) also increased the content of respiratory chain subunits. However, the levels of most transcripts encoding OXPHOS subunits were not modified. Inhibition of HIF2-alpha synthesis by RNA interference in pVHL-deficient 786-0 CCRC also restored respiratory chain subunit content and clearly demonstrated a key role of HIF in OXPHOS regulation. In agreement with these observations, stabilization of HIF-alpha subunit by CoCl(2) decreased respiratory chain subunit levels in CCRC cells expressing pVHL. In addition, HIF stimulated ROS production and mitochondrial manganese superoxide dismutase content. OXPHOS subunit content was also decreased by added H(2)O(2.) Interestingly, desferrioxamine (DFO) that also stabilized HIF did not decrease respiratory chain subunit level. While CoCl(2) significantly stimulates ROS production, DFO is known to prevent hydroxyl radical production by inhibiting Fenton reactions. This indicates that the HIF-induced decrease in OXPHOS is at least in part mediated by hydroxyl radical production. PMID:18515279

Hervouet, Eric; Cízková, Alena; Demont, Jocelyne; Vojtísková, Alena; Pecina, Petr; Franssen-van Hal, Nicole L W; Keijer, Jaap; Simonnet, Hélène; Ivánek, Robert; Kmoch, Stanislav; Godinot, Catherine; Houstek, Josef

2008-08-01

104

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

105

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

PubMed Central

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

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

2013-01-01

106

Modulation of mitochondrial membrane potential and reactive oxygen species production by copper in astrocytes.  

PubMed

In monolayers of cultured rat astrocytes a number of agents that induce oxidative stress act synergistically with exposure to copper leading to rapid depolarization of the mitochondrial membrane potential (Psi m) and increased reactive oxygen species (ROS) production. Copper sensitized astrocytes to the action of menadione, an intracellular generator of superoxide anion radical, exogenous hydrogen peroxide (H2O2) and rotenone, an inhibitor of mitochondrial electron transport chain complex I. However, significant differences were observed in the ability to modulate the copper-enhanced oxidative stress depending on which stressor was used. The inhibitor of mitochondrial permeability transition cyclosporin A attenuated the effect of copper and rotenone, but had no protective action in the case of H2O2/copper and menadione/copper combinations. The H2O2 scavenger pyruvate was effective at protecting mitochondria against damage associated with the combined exposure to H2O2/copper and menadione/copper but not to the rotenone/copper combination. The antioxidant Trolox was ineffective at protecting against any of these actions and indeed had a damaging effect when combined with copper. The membrane-permeable copper chelator neocuproine combined with sensitizing concentrations of menadione caused a decrease in Psi m, mimicking the action of copper. Penicillamine, a membrane-impermeable copper chelator, was effective at reducing copper sensitization. Endogenous copper, mobilized during periods of oxidative stress, may play a role in the pathophysiology of brain injury. Our results suggest that this might be particularly dangerous in dysfunctional conditions in which the mitochondrial electron transport chain is compromised. PMID:14511122

Gyulkhandanyan, Armen V; Feeney, Chris J; Pennefather, Peter S

2003-10-01

107

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

PubMed Central

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

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

2009-01-01

108

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

PubMed

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 is enhanced by exogenous oxidants exposure, Ca2+ stress and endogenous pathological defect of mitochondrial respiratory complexes. In addition, mROS formation can be specifically stimulated by visible light or visible laser irradiation and can be augmented further by photodynamic coupling with photosensitizers, particularly with mitochondria-targeted photosensitizers. "Severe" oxidative insult often results in massive and homogeneous augmentation of mROS formation which causes cessation of mitochondrial movement, pathological fission and irreversible swelling of mitochondria and eventually apoptosis or necrosis of cells. Mitochondria-targeted antioxidants and protectors such as MitoQ, melatonin and nanoparticle C(60) effectively prevent "severe" mROS generation. Intriguingly, "minor" oxidative insults enhance heterogeneity of mROS and mitochondrial dynamics. "Minor" mROS formation-induced fission and fusion of mitochondria relocates mitochondrial network to form a mitochondria free gap, i.e., "firewall", which may play a crucial role in mROS-mediated protective "preconditioning" by preventing propagation of mROS during oxidative insults. These mROS-targeted strategies for either enhancement or prevention of mitochondrial oxidative stress in astrocytes may provide new insights for future development of therapeutic interventions in the treatment of cancer such as astrocytomas and gliomas and astrocyte-associated neurodegeneration, mitochondrial diseases and aging. PMID:18692534

Jou, Mei-Jie

2008-01-01

109

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.

110

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

111

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

112

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

PubMed

We studied the effects of Epithalon (Ala-Glu-Asp-Gly) and Vilon (Lys-Glu) on free radical processes in highly inbred HA(+)line of Drosophila melanogaster. Vilon inhibited generation of reactive oxygen species in mitochondria, but stimulated this process in the cytosol. We found sex- and age-related differences in the generation of reactive oxygen species and cytosol antioxidant activity. PMID:11687853

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

2001-07-01

113

Reactive oxygen species in choline deficiency induced carcinogenesis and nitrone inhibition  

Microsoft Academic Search

Reactive oxygen species and free radical processes have been considered important in cancer development for many years. Much research demonstrates that the choline-deficiency induced hepatocarcinogenesis model prominently involves reactive oxygen species. We present a summary of results obtained in our original studies of this model over the last 4 years. We have shown that ?-phenyl-tert-butyl nitrone (PBN) and some of

Robert A. Floyd; Yashige Kotake; Kenneth Hensley; Dai Nakae; Yoichi Konishi

2002-01-01

114

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

115

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

116

Metabolic rate and reactive oxygen species production in different genotypes of GH-transgenic zebrafish  

Microsoft Academic Search

Growth hormone overexpression increases growth and consequently increases the metabolic rate in fishes. Therefore, the objective of this study was to evaluate the effects of growth hormone overexpression in zebrafish Danio rerio in terms of growth, oxygen consumption, reactive oxygen species production, lipid hydroperoxide content, antioxidant enzyme activity and glutamate-cysteine ligase catalytic subunit gene expression. The employed models were wild

C. E. Rosa; M. A. Figueiredo; C. F. C. Lanes; D. V. Almeida; J. M. Monserrat; L. F. Marins

2008-01-01

117

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

118

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

PubMed Central

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

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

2014-01-01

119

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

120

Effect of sulphasalazine and its metabolites on the generation of reactive oxygen species.  

PubMed Central

The relative in vitro anti-oxidant efficacy of sulphasalazine (salicylazosulphapyridine, SASP) and its metabolites (5-aminosalicylic acid, 5-ASA; sulphapyridine, SP) was examined by studying their effects on the generation of reactive oxygen species (ROS) using zymosan-stimulated polymorphonuclear leucocytes (PMNs) and a cell free, xanthine-xanthine oxidase system. Salicylazosulphapyridine, 5-ASA, and SP showed anti-oxidant effects to the various degrees. In particular, production of OH, which is one of the most potent reactive oxygen species, was remarkably suppressed by 5-ASA dose relatedly. These findings suggest that SASP and its metabolites play an important role in the inhibition of respiratory bursts. As the potent products of the respiratory burst by polymorphonuclear leucocytes are thought to be important inflammatory mediators, suppression of toxic reactive oxygen species generation by these agents may partly explain the therapeutic efficacy of SASP in ulcerative colitis, which is characterised by an acute mucosal inflammation dominated by polymorphonuclear leucocytes accumulation. PMID:2881849

Miyachi, Y; Yoshioka, A; Imamura, S; Niwa, Y

1987-01-01

121

Reactive oxygen species do not cause arsine-induced hemoglobin damage  

SciTech Connect

Previous work suggested that arsine- (AsH{sub 3}-) induced hemoglobin (HbO{sub 2}) damage may lead to hemolysis (Hatlelid et al., 1996). The purpose of the work presented here was to determine whether reactive oxygen species are formed by AsH{sub 3} in solution, in hemoglobin solutions, or in intact red blood cells, and, if so, to determine whether these species are responsible for the observed hemoglobin damage. Hydrogen peroxide (H{sub 2}O{sub 2}) was detected in aqueous solutions containing AsH{sub 3} and HbO{sub 2} or AsH{sub 3} alone but not in intact red blood cells or lysates. Additionally, high-activity catalase (19,200 U/ml) or glutathione peroxidase (68 U/ml) added to solutions of HbO{sub 2} and AsH{sub 3} had only a minor protective effect against AsH{sub 3}-induced damage. Further, the differences between the visible spectra of AsH{sub 3}-treated HbO{sub 2} and H{sub 2}O{sub 2}-treated HbO{sub 2} indicate that two different degradative processes occur. The presence of superoxide anion (O{sub 2}{sup {minus}}) was measured by O{sub 2}{sup {minus}} -dependent reduction of nitro blue tetrazolium (NBT). The results were negative for O{sub 2}{sup {minus}}. Exogenous superoxide dismutase (100 {mu}g/ml) did not affect AsH{sub 3}-induced HbO{sub 2} spectral changes, nor did the hydroxyl radical scavengers, mannitol, and DMSO (20mM each). The general antioxidants ascorbate ({le} 10 mM) and glutathione ({le}1 mM) also had no effect. These results indicate that the superoxide anion and the hydroxyl radical (OH) are not involved in the mechanism of AsH{sub 3}-induced HbO{sub 2} damage. The results also indicate that although AsH{sub 3} contributes to H{sub 2}O{sub 2} production in vitro, cellular defenses are adequate to detoxify the amount formed. An alternative mechanism by which an arsenic species is the hemolytic agent is proposed. 16 refs., 4 figs., 2 tabs.

Hatlelid, K.M.; Carter, D.E. [Univ. of Arizona, AZ (United States)

1997-04-11

122

Peripartum Cardiomyopathy: Role of STAT3 and Reactive Oxygen Species  

Microsoft Academic Search

\\u000a Enhanced oxidative stress related to high metabolic turnover and elevated tissue oxygen requirements are the characteristic\\u000a physiological state in pregnancy. In women with noneventful pregnancy and peripartum periods, this process appears to be paralleled\\u000a by an increase in systemic antioxidant capacity. While these biochemical changes may not have pathophysiological consequences\\u000a in healthy women, they may sensitize women with additional risk

Denise Hilfiker-Kleiner; Arash Haghikia; Andres Hilfiker

123

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

Microsoft Academic Search

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

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

124

Metabolic rate and reactive oxygen species production in different genotypes of GH-transgenic zebrafish.  

PubMed

Growth hormone overexpression increases growth and consequently increases the metabolic rate in fishes. Therefore, the objective of this study was to evaluate the effects of growth hormone overexpression in zebrafish Danio rerio in terms of growth, oxygen consumption, reactive oxygen species production, lipid hydroperoxide content, antioxidant enzyme activity and glutamate-cysteine ligase catalytic subunit gene expression. The employed models were wild type and transgenic (hemizygous and homozygous) zebrafish expressing the Odonthestes argentinensis growth hormone gene directed by the Cyprinus carpio beta-actin promoter. Higher growth parameters were observed in the hemizygous group. The homozygous group possessed higher oxygen consumption and reactive oxygen species production. Growth hormone transgenesis causes a decrease in glutamate-cysteine ligase catalytic subunit expression, an enzyme responsible for glutathione synthesis. Although the lipid hydroperoxide content was similar between groups, we demonstrate that growth hormone overexpression has the potential to generate oxidative stress in fishes. PMID:17931920

Rosa, C E; Figueiredo, M A; Lanes, C F C; Almeida, D V; Monserrat, J M; Marins, L F

2008-01-01

125

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

PubMed

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

Sun, Li; Wolferts, Guido; Veltkamp, Roland

2014-08-01

126

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

127

Single-molecule Detection of Reactive Oxygen Species: Application to Photocatalytic Reactions  

Microsoft Academic Search

In this review, we have focused on the oxidation reactions of single dye molecules by reactive oxygen species (ROS). The methodologies\\u000a for the single-molecule detection of ROS, such as hydroxyl radical (HO•), singlet oxygen (O2(a1?g)), and hydrogen peroxide (H2O2), have been introduced together with examples. In particular, a successful application using the single-molecule fluorescence\\u000a technique for the investigation of the

Takashi Tachikawa; Tetsuro Majima

2007-01-01

128

Ascorbic acid and reactive oxygen species are involved in the inhibition of seed germination by abscisic acid in rice seeds.  

PubMed

The antagonism between abscisic acid (ABA) and gibberellin (GA) plays a key role in controlling seed germination, but the mechanism of antagonism during this process is not known. The possible links among ABA, reactive oxygen species (ROS), ascorbic acid (ASC), and GA during rice seed germination were investigated. Unlike in non-seed tissues where ROS production is increased by ABA, ABA reduced ROS production in imbibed rice seeds, especially in the embryo region. Such reduced ROS also led to an inhibition of ASC production. GA accumulation was also suppressed by a reduced ROS and ASC level, which was indicated by the inhibited expression of GA biosynthesis genes, amylase genes, and enzyme activity. Application of exogenous ASC can partially rescue seed germination from ABA treatment. Production of ASC, which acts as a substrate in GA biosynthesis, was significantly inhibited by lycorine which thus suppressed the accumulation of GA. Consequently, expression of GA biosynthesis genes was suppressed by the low levels of ROS and ASC in ABA-treated seeds. It can be concluded that ABA regulates seed germination in multiple dimensions. ROS and ASC are involved in its inhibition of GA biosynthesis. PMID:22200664

Ye, Nenghui; Zhu, Guohui; Liu, Yinggao; Zhang, Aying; Li, Yingxuan; Liu, Rui; Shi, Lu; Jia, Liguo; Zhang, Jianhua

2012-03-01

129

Induction of apoptosis in human multiple myeloma cell lines by ebselen via enhancing the endogenous reactive oxygen species production.  

PubMed

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

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

2014-01-01

130

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

131

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

E-print Network

and measured with electrophysiological and anatomical technique. Further, ascorbic acid, hypothermia was the most eective when compared with ascorbic acid or hypothermia alone. Conclusion: This in vitro model has: spinal cord injury; reactive oxygen species (ROS); in vitro; ascorbic acid; hypothermia; ¯ow cytometry

Shi, Riyi

132

Cooperation between Reactive Oxygen and Nitrogen Intermediates in Killing of Rhodococcus equi by Activated Macrophages  

Microsoft Academic Search

Rhodococcus equi is a facultative intracellular bacterium of macrophages which can infect immunocompro- mised humans and young horses. In the present study, we examine the mechanism of host defense against R. equi by using a murine model. We show that bacterial killing is dependent upon the presence of gamma interferon (IFN-g), which activates macrophages to produce reactive nitrogen and oxygen

PATRICIA A. DARRAH; MARY K. HONDALUS; QUIPING CHEN; HARRY ISCHIROPOULOS; DAVID M. MOSSER

2000-01-01

133

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

Microsoft Academic Search

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

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

1998-01-01

134

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

135

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

136

Transient Influx of Nickel in Root Mitochondria Modulates Organic Acid and Reactive Oxygen Species Production in  

E-print Network

Transient Influx of Nickel in Root Mitochondria Modulates Organic Acid and Reactive Oxygen Species, Delaware 19711 Background: Mitochondria are important targets of metal toxicity. Results: Our data confirms that nickel is localized in the mitochondria of Alyssum murale root epidermal cells. Conclusion

Sparks, Donald L.

137

Review: Reactive oxygen and nitrogen species and functional adaptation of the placenta  

Microsoft Academic Search

The placenta regulates fetal growth and development via transport of nutrients and gases, and synthesis and secretion of steroid and peptide hormones. These functions are determined by vascular development and blood flow and by growth and differentiation of the trophoblast, which contains receptors, transporters and enzymes. The placenta generates reactive oxygen species which may contribute to the oxidative stress seen

L. Myatt

2010-01-01

138

Reactive Oxygen Metabolite Production Induced by Asbestos and Glass Fibers: Effect of Fiber Milling  

Microsoft Academic Search

Particle stimulated chemiluminescence (CL) production by human polymorphonuclear leucocytes (PMN) has been utilized to evaluate the pathogenicity of mineral and glass fibers with the understanding that reactive oxygen metabolites (ROM) production as measured by CL is etiopathogenically related to fiber toxicity. In the present study to investigate the specific pathogenic role of fiber number and dimensions, CL production from PMN

Toyoto IWATA; Eiji YANO

2003-01-01

139

Role of Reactive Oxygen Species on Diesel Exhaust Particle-Induced Cytotoxicity in Rat Cardiac Myocytes  

Microsoft Academic Search

Exposure to air pollution containing diesel exhaust particles (DEP) is associated with an increase in mortality rate attributed to cardiovascular diseases, but the mechanisms by which DEP produces adverse cardiovascular effects at the cellular level are not elucidated. This study investigated the cytotoxic mechanisms underlying DEP-induced neonatal rat cardiac myocytes effects in vitro, focusing on the role of reactive oxygen

Yuta Okayama; Masayoshi Kuwahara; Akira K. Suzuki; Hirokazu Tsubone

2006-01-01

140

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

Microsoft Academic Search

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

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

2003-01-01

141

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

Microsoft Academic Search

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

Javier Martinez; Juan J Moreno

2000-01-01

142

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

143

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

144

Semiconducting Polymer Nanoprobe for in vivo Imaging of Reactive Oxygen and Nitrogen Species  

PubMed Central

Semiconducting polymer nanoparticles are utilized as a free-radical inert and light-harvesting nanoplatform for in vivo molecular imaging of reactive oxygen and nitrogen species (RONS). With its RONS-sensitive fluorescence, good biodistribution and passive targeting ability to leaky inflammatory vasculature, this nanoprobe permits detection of RONS in the microenvironment of spontaneous bacterial infection following systemic administration. PMID:23943508

Pu, Kanyi; Shuhendler, Adam J.

2014-01-01

145

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

Microsoft Academic Search

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

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

1998-01-01

146

Reactive oxygen and nitrogen species and glutathione: key players in the legume-Rhizobium symbiosis  

Microsoft Academic Search

Several reactive oxygen and nitrogen species (ROS\\/ RNS) are continuously produced in plants as by- products of aerobic metabolism or in response to stresses. Depending on the nature of the ROS and RNS, some of them are highly toxic and rapidly detoxified by various cellular enzymatic and non- enzymatic mechanisms. Whereas plants have many mechanisms with which to combat increased

Nicolas Pauly; Chiara Pucciariello; Karine Mandon; Gilles Innocenti; Alexandre Jamet; Emmanuel Baudouin; Didier Herouart; Pierre Frendo; Alain Puppo

2006-01-01

147

Astrocyte-Enhanced Neuronal Survival is Mediated by Scavenging of Extracellular Reactive Oxygen Species  

Microsoft Academic Search

The survival of cultured neurons is promoted by the presence of antioxidants or astrocytes. This indicates that extracellular reactive oxygen species (ROS) impair neuronal survival and suggests that astrocytes exert their survival-enhancing effect through inactivation of these toxicants. However, to our knowledge, data supporting this hypothesis are lacking. Previously, we showed that loss of the antioxidant glutathione abolishes the neuronal

Benjamin Drukarch; Eric Schepens; Johannes C. Stoof; Cornelis H. Langeveld; Freek L. Van Muiswinkel

1998-01-01

148

Distinct Signaling Pathways Respond to Arsenite and Reactive Oxygen Species in Schizosaccharomyces pombe  

Microsoft Academic Search

Exposure to certain metal and metalloid species, such as arsenic, cadmium, chromium, and nickel, has been associated with an increased risk of cancer in humans. The biological effects of these metals are thought to result from induction of reactive oxygen species (ROS) and inhibition of DNA repair enzymes, although alterations in signal transduction pathways may also be involved in tumor

M. A. Rodriguez-Gabriel; Paul Russell

2005-01-01

149

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

Microsoft Academic Search

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

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

2007-01-01

150

The Alternative Oxidase Lowers Mitochondrial Reactive Oxygen Production in Plant Cells  

Microsoft Academic Search

Besides the cytochrome c pathway, plant mitochondria have an alternative respiratory pathway that is comprised of a single homodimeric protein, alternative oxidase (AOX). Transgenic cultured tobacco cells with altered levels of AOX were used to test the hypothesis that the alternative pathway in plant mitochondria functions as a mechanism to decrease the formation of reactive oxygen species (ROS) produced during

Denis P. Maxwell; Yong Wang; Lee McIntosh

1999-01-01

151

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

152

Reactivity and stability of platinum and platinum alloy catalysts toward the oxygen reduction reaction  

E-print Network

Density functional theory (DFT) is used to study the reactivity of Pt and Pt-M (M: Pd, Co, Ni, V, and Rh) alloy catalysts towards the oxygen reduction reaction (ORR) as a function of the alloy overall composition and surface atomic distribution...

Calvo, Sergio Rafael

2009-05-15

153

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

Microsoft Academic Search

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

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

2007-01-01

154

A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche  

Microsoft Academic Search

A low-oxygenic niche in bone marrow limits reactive oxygen species (ROS) pro- duction, thus providing long-term protec- tion for hematopoietic stem cells (HSCs) from ROS stress. Although many ap- proaches have been used to enrich HSCs, none has been designed to isolate primi- tive HSCs located within the low- oxygenic niche due to difficulties of di- rect physical access. Here

Yoon-Young Jang; Saul J. Sharkis

2007-01-01

155

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

156

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

157

Scavenging of reactive oxygen species by tryptophan metabolites helps Pseudomonas aeruginosa escape neutrophil killing.  

PubMed

Pseudomonas aeruginosa is responsible for persistent infections in cystic fibrosis patients, suggesting an ability to circumvent innate immune defenses. This bacterium uses the kynurenine pathway to catabolize tryptophan. Interestingly, many host cells also produce kynurenine, which is known to control immune system homeostasis. We showed that most strains of P. aeruginosa isolated from cystic fibrosis patients produce a high level of kynurenine. Moreover, a strong transcriptional activation of kynA (the first gene involved in the kynurenine pathway) was observed upon contact with immune cells and particularly with neutrophils. In addition, using coculture of human neutrophils with various strains of P. aeruginosa producing no (?kynA) or a high level of kynurenine (?kynU or ?kynA pkynA), we demonstrated that kynurenine promotes bacterial survival. In addition, increasing the amount kynurenine inhibits reactive oxygen species production by activated neutrophils, as evaluated by chemiluminescence with luminol or isoluminol or SOD-sensitive cytochrome c reduction assay. This inhibition is due neither to a phagocytosis defect nor to direct NADPH oxidase inhibition. Indeed, kynurenine has no effect on oxygen consumption by neutrophils activated by PMA or opsonized zymosan. Using in vitro reactive oxygen species-producing systems, we showed that kynurenine scavenges hydrogen peroxide and, to a lesser extent, superoxide. Kynurenine?s scavenging effect occurs mainly intracellularly after bacterial stimulation, probably in the phagosome. In conclusion, the kynurenine pathway allows P. aeruginosa to circumvent the innate immune response by scavenging neutrophil reactive oxygen species production. PMID:24929180

Genestet, Charlotte; Le Gouellec, Audrey; Chaker, Hichem; Polack, Benoit; Guery, Benoit; Toussaint, Bertrand; Stasia, Marie José

2014-08-01

158

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

PubMed Central

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

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

2013-01-01

159

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

SciTech Connect

The atomic oxygen metastable dynamics in a Reactive High-Power Impulse Magnetron Sputtering (R-HiPIMS) discharge has been characterized using time-resolved diode laser absorption in an Ar/O{sub 2} gas mixture with a Ti target. Two plasma regions are identified: the ionization region (IR) close to the target and further out the diffusion region (DR), separated by a transition region. The ?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 [Laboratoire the Physique de Gaz et Plasmas, UMR 8578 CNRS, Université Paris-Sud, Orsay Cedex 91405 (France) [Laboratoire the Physique de Gaz et Plasmas, UMR 8578 CNRS, Université Paris-Sud, Orsay Cedex 91405 (France); National Institute for Optoelectronics, Magurele-Bucharest, RO 077125 (Romania); Lundin, Daniel [Laboratoire the Physique de Gaz et Plasmas, UMR 8578 CNRS, Université Paris-Sud, Orsay Cedex 91405 (France) [Laboratoire the Physique de Gaz et Plasmas, UMR 8578 CNRS, Université Paris-Sud, Orsay Cedex 91405 (France); Division of Space and Plasma Physics, School of Electrical Engineering, Royal Institute of Technology, Stockholm, SE-100 44 (Sweden); Brenning, Nils [Division of Space and Plasma Physics, School of Electrical Engineering, Royal Institute of Technology, Stockholm, SE-100 44 (Sweden)] [Division of Space and Plasma Physics, School of Electrical Engineering, Royal Institute of Technology, Stockholm, SE-100 44 (Sweden); Minea, Tiberiu [Laboratoire the Physique de Gaz et Plasmas, UMR 8578 CNRS, Université Paris-Sud, Orsay Cedex 91405 (France)] [Laboratoire the Physique de Gaz et Plasmas, UMR 8578 CNRS, Université Paris-Sud, Orsay Cedex 91405 (France)

2013-09-02

160

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

161

[The role of reactive oxygen and nitrogen species in calcium and iron homeostasis dysregulation in anthracycline cardiotoxicity].  

PubMed

Anthracyclines are potent anticancer agents which have been used in therapy for 40 years. However, their activity is very limited due to their cumulative, dose-dependent, chronic cardiotoxicity. The cardiotoxic effect of anthracyclines may lead to irreversible and incurable cardiomyopathy, which impairs quality of live and increases the risk of death. The most prominent feature of this cardiac disease is diminished ejection fraction of the left ventricle, which leads to congestive heart failure. Reactive oxygen species, alcoholic metabolites of anthracycline, and cellular calcium homeostasis dysregulation cause chronic anthracycline cardiotoxicity. Recently, an important role for reactive nitric species and iron homeostasis deregulation was suspected. Some reactive oxygen and nitric species might react with one another to produce new, highly toxic products. It is suggested that after anthracycline administration, reactive oxygen and nitric species affect cellular calcium and iron homeostasis deregulation. The possible connection between reactive oxygen and nitric species and calcium and iron deregulation is presented in the paper. PMID:16641894

Dudka, Jaros?aw

2006-01-01

162

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

163

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

Microsoft Academic Search

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

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

2002-01-01

164

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

Microsoft Academic Search

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

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

2009-01-01

165

Effect of Brazilian green propolis on the production of reactive oxygen species by stimulated neutrophils  

Microsoft Academic Search

The activity of a crude ethanol extract of green propolis and its fractions obtained by partition with hexane, chloroform and n-butanol was assessed on luminol- and lucigenin- enhanced chemiluminescence (CL) produced by rabbit neutrophils (PMNs) stimulated with particles of serum-opsonized zymosan (OZ). The total production of reactive oxygen species (ROS) by PMNs was measured by the luminol-enhanced CL (LumCL) assay

L. M. C Simões; L. E Gregório; A. A Da Silva Filho; M. L de Souza; A. E. C. S Azzolini; J. K Bastos; Y. M Lucisano-Valim

2004-01-01

166

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

167

The production of reactive oxygen species in peripheral blood neutrophils is modulated by airway mucous  

Microsoft Academic Search

Neutrophils are a major source of reactive oxygen species (ROS). The role of airway mucous on ROS production is unknown. The\\u000a aim of our study was to investigate the direct influence of bronchoalveolar lavage fluid (BALF) and induced sputum (IS) alone\\u000a or in combination with chemical\\/biological stimulus on ROS production in peripheral blood neutrophils during chronic obstructive\\u000a pulmonary disease (COPD).

Agne Babusyte; Jolanta Jeroch; Rimantas Stakauskas; Raimundas Sakalauskas

2009-01-01

168

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

Microsoft Academic Search

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

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

169

Metabolism of reactive oxygen species in cotton cytoplasmic male sterility and its restoration  

Microsoft Academic Search

To elucidate reactive oxygen species (ROS) metabolism of cotton cytoplasmic male sterility and the effects of restorer gene\\u000a on the metabolism of ROS, the metabolism changes in the production and scavenging of ROS and gene expression related to ROS-scavenging\\u000a enzymes were investigated in the anther mitochondria of CMS line, maintainer line and hybrid F1. During the abortion preliminary stage (sporogenous

Peidong Jiang; Xiaoquan Zhang; Yunguo Zhu; Wei Zhu; Haiyan Xie; Xuede Wang

2007-01-01

170

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

171

Modification of reactive oxygen species scavenging capacity of chloroplasts through plastid transformation  

Microsoft Academic Search

Reactive oxygen species (ROS), including superoxide anions, hydrogen peroxide and hydroxyl radicals are generated through\\u000a normal biochemical processes, but their production is increased by abiotic stresses. The prospects for enhancing ROS scavenging,\\u000a and hence stress tolerance, by direct gene expression in a vulnerable cell compartment, the chloroplast, have been explored\\u000a in tobacco. Several plastid transformants were generated which contained either

Miranda Poage; Bénédicte Le Martret; Marcel A. K. Jansen; Gregory D. Nugent; Philip J. Dix

2011-01-01

172

Cellular mechanisms and treatment of diabetes vascular complications converge on reactive oxygen species  

Microsoft Academic Search

High glucose activates a myriad of signaling and gene expression pathways in non-insulin-dependent target cells causing diabetes\\u000a complications. One of the earliest responses to high glucose by vascular cells is the generation of reactive oxygen species\\u000a (ROS) that act directly on intracellular proteins and DNA, or indirectly as second messengers, transforming these cells into\\u000a disease phenotypes. ROS are produced by

Catharine I. Whiteside

2005-01-01

173

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

174

Increased Adhesion Molecules Expression and Production of Reactive Oxygen Species in Leukocytes of Sleep Apnea Patients  

Microsoft Academic Search

Obstructive sleep apnea (OSA) is associated with increased cardio- vascular morbidity and mortality. Free radicals and adhesion mole- cules were implicated in the pathogenesis of atherosclerosis lead- ing to cardiovascular disorders. Therefore, we investigated the link between CD15, CD11c, CD11b, and CD64 expression on leukocytes and their ability to generate reactive oxygen species (ROS) in pa- tients with OSA and

LARISSA DYUGOVSKAYA; PERETZ LAVIE; LENA LAVIE

175

Involvement of reactive oxygen species in the UV-B damage to the cyanobacterium Anabaena sp  

Microsoft Academic Search

Reactive oxygen species (ROS) are involved the damage of living organisms under environmental stress including UV radiation. Cyanobacteria, photoautotrophic prokaryotic organisms, also suffer from increasing UV-B due to the depletion of the stratospheric ozone layer. The increased UV-B induces the production of ROS in vivo detected by using the ROS-sensitive probe 2?,7?-dichlorodihydrofluorescein diacetate (DCFH-DA). Ascorbic acid and N-acetyl-l-cysteine (NAC) scavenged

Yu-Ying He; Donat-P Häder

2002-01-01

176

Signaling by carcinogenic metals and metal-induced reactive oxygen species  

Microsoft Academic Search

Epidemiological data indicate that exposure to metal and metalloid species, including arsenic(III), chromium(VI), and nickel(II), increases the risk of cancer, particularly of the lung and skin. Alterations in normal signal transduction as a result of exposure to carcinogenic metals, and to metal-catalyzed reactive oxygen species (ROS) formation, appear to play an important role in the etiology of metal-induced carcinogenesis. Signaling

Gabriel Keith Harris; Xianglin Shi

2003-01-01

177

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

178

Oxygen and nitrogen are pro-carcinogens. Damage to DNA by reactive oxygen, chlorine and nitrogen species: measurement, mechanism and the effects of nutrition  

Microsoft Academic Search

Humans are exposed to many carcinogens, but the most significant may be the reactive species derived from metabolism of oxygen and nitrogen. Nitric oxide seems unlikely to damage DNA directly, but nitrous acid produces deamination and peroxynitrite leads to both deamination and nitration. Scavenging of reactive nitrogen species generated in the stomach may be an important role of flavonoids, flavonoids

Barry Halliwell

1999-01-01

179

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

PubMed Central

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

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

2013-01-01

180

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

PubMed

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

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

2012-02-01

181

Crosstalk between Nitrite, Myoglobin and Reactive Oxygen Species to Regulate Vasodilation under Hypoxia  

PubMed Central

The systemic response to decreasing oxygen levels is hypoxic vasodilation. While this mechanism has been known for more than a century, the underlying cellular events have remained incompletely understood. Nitrite signaling is critically involved in vessel relaxation under hypoxia. This can be attributed to the presence of myoglobin in the vessel wall together with other potential nitrite reductases, which generate nitric oxide, one of the most potent vasodilatory signaling molecules. Questions remain relating to the precise concentration of nitrite and the exact dose-response relations between nitrite and myoglobin under hypoxia. It is furthermore unclear whether regulatory mechanisms exist which balance this interaction. Nitrite tissue levels were similar across all species investigated. We then investigated the exact fractional myoglobin desaturation in an ex vivo approach when gassing with 1% oxygen. Within a short time frame myoglobin desaturated to 58±12%. Given that myoglobin significantly contributes to nitrite reduction under hypoxia, dose-response experiments using physiological to pharmacological nitrite concentrations were conducted. Along all concentrations, abrogation of myoglobin in mice impaired vasodilation. As reactive oxygen species may counteract the vasodilatory response, we used superoxide dismutase and its mimic tempol as well as catalase and ebselen to reduce the levels of reactive oxygen species during hypoxic vasodilation. Incubation of tempol in conjunction with catalase alone and catalase/ebselen increased the vasodilatory response to nitrite. Our study shows that modest hypoxia leads to a significant nitrite-dependent vessel relaxation. This requires the presence of vascular myoglobin for both physiological and pharmacological nitrite levels. Reactive oxygen species, in turn, modulate this vasodilation response. PMID:25148388

Kelm, Malte; Rassaf, Tienush

2014-01-01

182

Crosstalk between nitrite, myoglobin and reactive oxygen species to regulate vasodilation under hypoxia.  

PubMed

The systemic response to decreasing oxygen levels is hypoxic vasodilation. While this mechanism has been known for more than a century, the underlying cellular events have remained incompletely understood. Nitrite signaling is critically involved in vessel relaxation under hypoxia. This can be attributed to the presence of myoglobin in the vessel wall together with other potential nitrite reductases, which generate nitric oxide, one of the most potent vasodilatory signaling molecules. Questions remain relating to the precise concentration of nitrite and the exact dose-response relations between nitrite and myoglobin under hypoxia. It is furthermore unclear whether regulatory mechanisms exist which balance this interaction. Nitrite tissue levels were similar across all species investigated. We then investigated the exact fractional myoglobin desaturation in an ex vivo approach when gassing with 1% oxygen. Within a short time frame myoglobin desaturated to 58±12%. Given that myoglobin significantly contributes to nitrite reduction under hypoxia, dose-response experiments using physiological to pharmacological nitrite concentrations were conducted. Along all concentrations, abrogation of myoglobin in mice impaired vasodilation. As reactive oxygen species may counteract the vasodilatory response, we used superoxide dismutase and its mimic tempol as well as catalase and ebselen to reduce the levels of reactive oxygen species during hypoxic vasodilation. Incubation of tempol in conjunction with catalase alone and catalase/ebselen increased the vasodilatory response to nitrite. Our study shows that modest hypoxia leads to a significant nitrite-dependent vessel relaxation. This requires the presence of vascular myoglobin for both physiological and pharmacological nitrite levels. Reactive oxygen species, in turn, modulate this vasodilation response. PMID:25148388

Totzeck, Matthias; Hendgen-Cotta, Ulrike B; Kelm, Malte; Rassaf, Tienush

2014-01-01

183

[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

184

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

SciTech Connect

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

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

2011-05-15

185

Stimulus-induced downregulation of root water transport involves reactive oxygen species-activated cell signalling and plasma membrane intrinsic protein internalization.  

PubMed

The water uptake capacity of plant roots (i.e. their hydraulic conductivity, Lp(r)) is determined in large part by aquaporins of the plasma membrane intrinsic protein (PIP) subfamily. In the present work, we investigated two stimuli, salicylic acid (SA) and salt, because of their ability to induce an accumulation of reactive oxygen species (ROS) and an inhibition of Lp(r) concomitantly in the roots of Arabidopsis plants. The inhibition of Lp(r) by SA was partially counteracted by preventing the accumulation of hydrogen peroxide (H(2)O(2)) with exogenous catalase. In addition, exogenous H(2)O(2) was able to reduce Lp(r) by up to 90% in <15 min. Based on the lack of effects of H(2)O(2) on the activity of individual aquaporins in Xenopus oocytes, and on a pharmacological dissection of the action of H(2)O(2) on Lp(r), we propose that ROS do not gate Arabidopsis root aquaporins through a direct oxidative mechanism, but rather act through cell signalling mechanisms. Expression in transgenic roots of PIP-GFP fusions and immunogold labelling indicated that external H(2)O(2) enhanced, in <15 min, the accumulation of PIPs in intracellular structures tentatively identified as vesicles and small vacuoles. Exposure of roots to SA or salt also induced an intracellular accumulation of the PIP-GFP fusion proteins, and these effects were fully counteracted by co-treatment with exogenous catalase. In conclusion, the present work identifies SA as a novel regulator of aquaporins, and delineates an ROS-dependent signalling pathway in the roots of Arabidopsis. Several abiotic and biotic stress-related stimuli potentially share this path, which involves an H(2)O(2)-induced internalization of PIPs, to downregulate root water transport. PMID:18573191

Boursiac, Yann; Boudet, Julie; Postaire, Olivier; Luu, Doan-Trung; Tournaire-Roux, Colette; Maurel, Christophe

2008-10-01

186

Reactive oxygen species homeostasis and virulence of the fungal pathogen Cryptococcus neoformans requires an intact proline catabolism pathway.  

PubMed

Degradation of the multifunctional amino acid proline is associated with mitochondrial oxidative respiration. The two-step oxidation of proline is catalyzed by proline oxidase and ?(1)-pyrroline-5-carboxylate (P5C) dehydrogenase, which produce P5C and glutamate, respectively. In animal and plant cells, impairment of P5C dehydrogenase activity results in P5C-proline cycling when exogenous proline is supplied via the actions of proline oxidase and P5C reductase (the enzyme that converts P5C to proline). This proline is oxidized by the proline oxidase-FAD complex that delivers electrons to the electron transport chain and to O2, leading to mitochondrial reactive oxygen species (ROS) overproduction. Coupled activity of proline oxidase and P5C dehydrogenase is therefore important for maintaining ROS homeostasis. In the genome of the fungal pathogen Cryptococcus neoformans, there are two paralogs (PUT1 and PUT5) that encode proline oxidases and a single ortholog (PUT2) that encodes P5C dehydrogenase. Transcription of all three catabolic genes is inducible by the presence of proline. However, through the creation of deletion mutants, only Put5 and Put2 were found to be required for proline utilization. The put2? mutant also generates excessive mitochondrial superoxide when exposed to proline. Intracellular accumulation of ROS is a critical feature of cell death; consistent with this fact, the put2? mutant exhibits a slight, general growth defect. Furthermore, Put2 is required for optimal production of the major cryptococcal virulence factors. During murine infection, the put2? mutant was discovered to be avirulent; this is the first report highlighting the importance of P5C dehydrogenase in enabling pathogenesis of a microorganism. PMID:23564202

Lee, I Russel; Lui, Edmund Y L; Chow, Eve W L; Arras, Samantha D M; Morrow, Carl A; Fraser, James A

2013-06-01

187

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

188

Contributions of reactive oxygen species and mitogen-activated protein kinase signaling in arsenite-stimulated hemeoxygenase-1 production  

SciTech Connect

Hemeoxygenase-1 (HO-1) is an oxidative stress responsive gene upregulated by various physiological and exogenous stimuli. HO-1 has cytoprotective activities and arsenite is a potent inducer of HO-1 in many cell types and tissues, including epidermal keratinocytes. We investigated the potential contributions of reactive oxygen species (ROS) generation and mitogen-activated protein kinase (MAPK) activation to arsenite-dependent regulation of HO-1 in HaCaT cells, an immortalized human keratinocyte line. Both epidermal growth factor (EGF) and arsenite stimulated ROS production was detected by dihydroethidium (DHE) staining and fluorescence microscopy. Arsenite induced HO-1 in a time- and concentration-dependent manner, while HO-1 expression in response to EGF was modest and evident at extended time points (48-72 h). Inhibition of EGF receptor, MEK I/II or Src decreased arsenite-stimulated HO-1 expression by 20-30%. In contrast, addition of a superoxide scavenger or inhibition of p38 activity decreased the arsenite-dependent response by 80-90% suggesting that ROS and p38 are required for HO-1 induction. However, ROS generation alone was insufficient for the observed arsenite-dependent response as use of a xanthine/xanthine oxidase system to generate ROS did not produce an equivalent upregulation of HO-1. Cooperation between ERK signaling and ROS generation was demonstrated by synergistic induction of HO-1 in cells co-treated with EGF and xanthine/xanthine oxidase resulting in a response nearly equivalent to that observed with arsenite. These findings suggest that the ERK/MAPK activation is necessary but not sufficient for optimal arsenite-stimulated HO-1 induction. The robust and persistent upregulation of HO-1 may have a role in cellular adaptation to chronic arsenic exposure.

Cooper, Karen L. [MSC09 5360, 1 University of New Mexico Health Sciences Center, Program in Toxicology, College of Pharmacy, Albuquerque, NM 87131 (United States); Liu, Ke Jian [MSC09 5360, 1 University of New Mexico Health Sciences Center, Program in Toxicology, College of Pharmacy, Albuquerque, NM 87131 (United States); Hudson, Laurie G. [MSC09 5360, 1 University of New Mexico Health Sciences Center, Program in Toxicology, College of Pharmacy, Albuquerque, NM 87131 (United States)]. E-mail: lhudson@salud.unm.edu

2007-01-15

189

Artemisinin dimer anticancer activity correlates with heme-catalyzed reactive oxygen species generation and endoplasmic reticulum stress induction.  

PubMed

Analogs of the malaria therapeutic, artemisinin, possess in vitro and in vivo anticancer activity. In this study, two dimeric artemisinins (NSC724910 and 735847) were studied to determine their mechanism of action. Dimers were >1,000 fold more active than monomer and treatment was associated with increased reactive oxygen species (ROS) and apoptosis induction. Dimer activity was inhibited by the antioxidant L-NAC, the iron chelator desferroxamine and exogenous hemin. Similarly, induction of heme oxygenase (HMOX) with CoPPIX inhibited activity, whereas inhibition of HMOX with SnPPIX enhanced it. These results emphasize the importance of iron, heme and ROS in activity. Microarray analysis of dimer treated cells identified DNA damage, iron/heme and cysteine/methionine metabolism, antioxidant response, and endoplasmic reticulum (ER) stress as affected pathways. Detection of an ER-stress response was relevant because in malaria, artemisinin inhibits pfATP6, the plasmodium orthologue of mammalian sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPases (SERCA). A comparative study of NSC735847 with thapsigargin, a specific SERCA inhibitor and ER-stress inducer showed similar behavior in terms of transcriptomic changes, induction of endogenous SERCA and ER calcium mobilization. However, thapsigargin had little effect on ROS production, modulated different ER-stress proteins and had greater potency against purified SERCA1. Furthermore, an inactive derivative of NSC735847 that lacked the endoperoxide had identical inhibitory activity against purified SERCA1, suggesting that direct inhibition of SERCA has little inference on overall cytotoxicity. In summary, these data implicate indirect ER-stress induction as a central mechanism of artemisinin dimer activity. PMID:19533749

Stockwin, Luke H; Han, Bingnan; Yu, Sherry X; Hollingshead, Melinda G; ElSohly, Mahmoud A; Gul, Waseem; Slade, Desmond; Galal, Ahmed M; Newton, Dianne L; Bumke, Maja A

2009-09-15

190

Green Tea Polyphenols Potentiate the Action of Nerve Growth Factor to Induce Neuritogenesis: Possible Role of Reactive Oxygen Species  

PubMed Central

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

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

2010-01-01

191

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

PubMed Central

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

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

2013-01-01

192

Reactive Oxygen Species Homeostasis and Virulence of the Fungal Pathogen Cryptococcus neoformans Requires an Intact Proline Catabolism Pathway  

PubMed Central

Degradation of the multifunctional amino acid proline is associated with mitochondrial oxidative respiration. The two-step oxidation of proline is catalyzed by proline oxidase and ?1-pyrroline-5-carboxylate (P5C) dehydrogenase, which produce P5C and glutamate, respectively. In animal and plant cells, impairment of P5C dehydrogenase activity results in P5C-proline cycling when exogenous proline is supplied via the actions of proline oxidase and P5C reductase (the enzyme that converts P5C to proline). This proline is oxidized by the proline oxidase-FAD complex that delivers electrons to the electron transport chain and to O2, leading to mitochondrial reactive oxygen species (ROS) overproduction. Coupled activity of proline oxidase and P5C dehydrogenase is therefore important for maintaining ROS homeostasis. In the genome of the fungal pathogen Cryptococcus neoformans, there are two paralogs (PUT1 and PUT5) that encode proline oxidases and a single ortholog (PUT2) that encodes P5C dehydrogenase. Transcription of all three catabolic genes is inducible by the presence of proline. However, through the creation of deletion mutants, only Put5 and Put2 were found to be required for proline utilization. The put2? mutant also generates excessive mitochondrial superoxide when exposed to proline. Intracellular accumulation of ROS is a critical feature of cell death; consistent with this fact, the put2? mutant exhibits a slight, general growth defect. Furthermore, Put2 is required for optimal production of the major cryptococcal virulence factors. During murine infection, the put2? mutant was discovered to be avirulent; this is the first report highlighting the importance of P5C dehydrogenase in enabling pathogenesis of a microorganism. PMID:23564202

Lee, I. Russel; Lui, Edmund Y. L.; Chow, Eve W. L.; Arras, Samantha D. M.; Morrow, Carl A.; Fraser, James A.

2013-01-01

193

The role of oxidized cytochrome c in regulating mitochondrial reactive oxygen species production and its perturbation in ischaemia  

PubMed Central

Oxidized cytochrome c is a powerful superoxide scavenger within the mitochondrial IMS (intermembrane space), but the importance of this role in situ has not been well explored. In the present study, we investigated this with particular emphasis on whether loss of cytochrome c from mitochondria during heart ischaemia may mediate the increased production of ROS (reactive oxygen species) during subsequent reperfusion that induces mPTP (mitochondrial permeability transition pore) opening. Mitochondrial cytochrome c depletion was induced in vitro with digitonin or by 30 min ischaemia of the perfused rat heart. Control and cytochrome c-deficient mitochondria were incubated with mixed respiratory substrates and an ADP-regenerating system (State 3.5) to mimic physiological conditions. This contrasts with most published studies performed with a single substrate and without significant ATP turnover. Cytochrome c-deficient mitochondria produced more H2O2 than control mitochondria, and exogenous cytochrome c addition reversed this increase. In the presence of increasing [KCN] rates of H2O2 production by both pre-ischaemic and end-ischaemic mitochondria correlated with the oxidized cytochrome c content, but not with rates of respiration or NAD(P)H autofluorescence. Cytochrome c loss during ischaemia was not mediated by mPTP opening (cyclosporine-A insensitive), neither was it associated with changes in mitochondrial Bax, Bad, Bak or Bid. However, bound HK2 (hexokinase 2) and Bcl-xL were decreased in end-ischaemic mitochondria. We conclude that cytochrome c loss during ischaemia, caused by outer membrane permeabilization, is a major determinant of H2O2 production by mitochondria under pathophysiological conditions. We further suggest that in hypoxia, production of H2O2 to activate signalling pathways may be also mediated by decreased oxidized cytochrome c and less superoxide scavenging. PMID:21410437

Pasdois, Philippe; Parker, Joanne E.; Griffiths, Elinor J.; Halestrap, Andrew P.

2011-01-01

194

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

PubMed

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

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

2010-11-01

195

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

NASA Astrophysics Data System (ADS)

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

Bowes, M.; Bradley, J. W.

2014-07-01

196

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

PubMed

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. PMID:21509403

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

2011-06-01

197

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

198

Boron substitution in aluminum cluster anions: magic clusters and reactivity with oxygen.  

PubMed

We have studied the size-selective reactivity of AlnBm(-) clusters m = 1,2 with O2 to investigate the effect of congener substitution in energetic aluminum clusters. Mixed-metal clusters offer an additional strategy for tuning the electronic and geometric structure of clusters and by substituting an atom with a congener; we may investigate the effect of structural changes in clusters with similar electronic structures. Using a fast-flow tube mass spectrometer, we formed aluminum boride cluster anions and exposed them to molecular oxygen. We found multiple stable species with Al12B(-) and Al11B2(-) being highly resistant to reactivity with oxygen. These clusters behave in a similar manner as Al13(-), which has previously been found to be stable in oxygen because of its icosahedral geometry and its filled electronic shell. Al13(-) and Al12B(-) have icosahedral structures, while Al11B2(-) forms a distorted icosahedron. All three of these clusters have filled electronic shells, and Al12B(-) has a larger HOMO-LUMO gap due to its compact geometry. Other cluster sizes are investigated, and the structures of the AlnB(-) series are found to have endohedrally doped B atoms, as do many of the AlnB2(-) clusters. The primary etching products are found to be a loss of two Al2O molecules, with boron likely to remain in the cluster. PMID:24725222

Smith, Jordan C; Reber, Arthur C; Khanna, Shiv N; Castleman, A W

2014-09-18

199

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

NASA Astrophysics Data System (ADS)

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

2011-06-01

200

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

SciTech Connect

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

Arif, J.M.; Khan, S.G.; Ashquin, M.; Rahman, Q. (Industrial Toxicology Research Centre, Lucknow (India))

1993-05-01

201

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

202

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

203

In vivo imaging of nitric oxide and reactive oxygen species using laser scanning confocal microscopy.  

PubMed

Both nitric oxide (NO) and reactive oxygen species (ROS) are versatile molecules that mediate a variety of cellular responses in plants. In this chapter, methods for imaging NO and ROS using laser scanning confocal microscopy (LSCM) are presented. Arabidopsis roots, dyed with DAF-FM or H(2)DCF, are observed using the Leica TCS-SP2 LSCM. NO or ROS production are imaged and their kinetic changes monitored with the laser excitation and emission wavelengths at 488 nm and between 500 and 530 nm, respectively. In addition, Leica software is employed to visualize and calculate the fluorescence intensity data. PMID:22895760

Xie, Yan-Jie; Shen, Wen-Biao

2012-01-01

204

Generation of reactive oxygen species by interaction between antioxidants used as food additive and metal ions.  

PubMed

Food additives, such as preservatives, sweeteners, coloring agents, and flavoring agents, are widely used in food manufacturing. However, their combined effects on the human body are not known. The purpose of this study was to examine whether combinations of antioxidants and metal ions generate reactive oxygen species (ROS) under in vitro conditions using electron spin resonance (ESR). Among the metal ions examined, only iron and copper generated ROS in the presence of antioxidants. Moreover, certain phenolic antioxidants having pro-oxidant activity induced DNA oxidation and degradation via the generation of high levels of ROS in the presence of copper ion, resulting in complete degradation of DNA in vitro. PMID:25212818

Iwasaki, Yusuke; Oda, Momoko; Tsukuda, Yuri; Nagamori, Yuki; Nakazawa, Hiroyuki; Ito, Rie; Saito, Koichi

2014-01-01

205

The determination and analysis of site-specific rates of mitochondrial reactive oxygen species production.  

PubMed

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

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

2013-01-01

206

Beyond oxidative stress: an immunologist’s guide to reactive oxygen species  

PubMed Central

Reactive oxygen species (ROS) react preferentially with certain atoms to modulate functions ranging from cell homeostasis to cell death. Molecular actions include both inhibition and activation of proteins, mutagenesis of DNA and activation of gene transcription. Cellular actions include promotion or suppression of inflammation, immunity and carcinogenesis. ROS help the host to compete against microorganisms and are also involved in intermicrobial competition. ROS chemistry and their pleiotropy make them difficult to localize, to quantify and to manipulate — challenges we must overcome to translate ROS biology into medical advances. PMID:23618831

Nathan, Carl; Cunningham-Bussel, Amy

2014-01-01

207

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

NASA Astrophysics Data System (ADS)

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

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

2004-12-01

208

Role of reactive oxygen species and phosphatidylinositol 3-kinase in cardiomyocyte differentiation of embryonic stem cells.  

PubMed

Cardiotypic development in embryonic stem cell-derived embryoid bodies may be regulated by reactive oxygen species (ROS). ROS were generated by a NADPH oxidase-like enzyme which was transiently expressed during the time course of embryoid body development. Incubation with either H(2)O(2) or menadione enhanced cardiomyogenesis, whereas the radical scavengers trolox, pyrrolidinedithiocarbamate and N-acetylcysteine exerted inhibitory effects. The phosphatidylinositol 3-kinase (PI-3-kinase) inhibitors LY294002 and wortmannin abolished cardiac commitment and downregulated ROS in embryoid bodies. Coadministration of LY294002 with prooxidants resumed cardiomyocyte differentiation, indicating a role for PI-3-kinase in the regulation of the intracellular redox state. PMID:10913617

Sauer, H; Rahimi, G; Hescheler, J; Wartenberg, M

2000-07-01

209

Evolving Concepts of Oxidative Stress and Reactive Oxygen Species in Cardiovascular Disease  

PubMed Central

Cardiovascular disease continues to be a substantial health-care burden, despite recent treatment advances. Oxidative stress has long been regarded as a key pathophysiological mediator that ultimately leads to CVD including atherosclerosis, hypertension and heart failure. Over the past decade, emerging evidence has shifted our understanding of reactive oxygen species (ROS) from its harmful role to being signaling molecules. Here, we reviewed recent advances in our understanding of ROS that mediate the complex process of cardiovascular diseases, with a focus on major ROS signaling and sources such as mitochondria and NADPH oxidases. PMID:22956414

Chen, Kai; Keaney, John F.

2013-01-01

210

Oxygen chemisorption on Au (1 1 0) -(1×2) II. Spectroscopic and reactive thermal desorption measurements  

Microsoft Academic Search

Electron bombardment of physisorbed and condensed oxygen molecules on Au(110)-(1×2) at 28 K produces chemisorbed atomic oxygen. The latter was investigated with UV photoelectron spectroscopy (UPS) as well as with work function (??) and reactive thermal desorption measurements (RTDM). UPS reveals that the electronic structure of chemisorbed oxygen bears a strong resemblance to that of gold oxide, Au2O3. At monolayer

J. M. Gottfried; K. J. Schmidt; S. L. M. Schroeder; K. Christmann

2003-01-01

211

Novel Approach to Reactive Oxygen Species in Nontransfusion-Dependent Thalassemia  

PubMed Central

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

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

2014-01-01

212

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

PubMed Central

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

Nyberg, P.; Klockars, M.

1990-01-01

213

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

PubMed

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. PMID:18275980

Meeran, Syed M; Katiyar, Suchitra; Katiyar, Santosh K

2008-05-15

214

Overexpression of stanniocalcin-1 inhibits reactive oxygen species and renal ischemia/reperfusion injury in mice.  

PubMed

Reactive oxygen species, endothelial dysfunction, inflammation, and mitogen-activated protein kinases have important roles in the pathogenesis of ischemia/reperfusion kidney injury. Stanniocalcin-1 (STC1) suppresses superoxide generation in many systems through the induction of mitochondrial uncoupling proteins and blocks the cytokine-induced rise in endothelial permeability. Here we tested whether transgenic overexpression of STC1 protects from bilateral ischemia/reperfusion kidney injury. This injury in wild-type mice caused a halving of the creatinine clearance; severe tubular vacuolization and cast formation; increased infiltration of macrophages and T cells; higher vascular permeability; greater production of superoxide and hydrogen peroxide; and higher ratio of activated extracellular regulated kinase/activated Jun-N-terminal kinase and p38, all compared to sham-treated controls. Mice transgenic for human STC1 expression, however, had resistance to equivalent ischemia/reperfusion injury indicated as no significant change from controls in any of these parameters. Tubular epithelial cells in transgenic mice expressed higher mitochondrial uncoupling protein 2 and lower superoxide generation. Pre-treatment of transgenic mice with paraquat, a generator of reactive oxygen species, before injury restored the susceptibility to ischemia/reperfusion kidney injury, suggesting that STC1 protects by an anti-oxidant mechanism. Thus, STC1 may be a therapeutic target for ischemia/reperfusion kidney injury. PMID:22695329

Huang, Luping; Belousova, Tatiana; Chen, Minyi; DiMattia, Gabriel; Liu, Dajun; Sheikh-Hamad, David

2012-10-01

215

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

216

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

217

Lung surfactant and reactive oxygen-nitrogen species: antimicrobial activity and host-pathogen interactions.  

PubMed

Surfactant protein (SP) A and SP-D are members of the collectin superfamily. They are widely distributed within the lung, are capable of antigen recognition, and can discern self versus nonself. SPs recognize bacteria, fungi, and viruses by binding mannose and N-acetylglucosamine residues on microbial cell walls. SP-A has been shown to stimulate the respiratory burst as well as nitric oxide synthase expression by alveolar macrophages. Although nitric oxide (NO.) is a well-recognized microbicidal product of macrophages, the mechanism(s) by which NO. contributes to host defense remains undefined. The purpose of this symposium was to present current research pertaining to the specific role of SPs and reactive oxygen-nitrogen species in innate immunity. The symposium focused on the mechanisms of NO*-mediated toxicity for bacterial, human, and animal models of SP-A- and NO.-mediated pathogen killing, microbial defense mechanisms against reactive oxygen-nitrogen species, specific examples and signaling pathways involved in the SP-A-mediated killing of pulmonary pathogens, the structure and binding of SP-A and SP-D to bacterial targets, and the immunoregulatory functions of SP-A. PMID:11504674

Hickman-Davis, J M; Fang, F C; Nathan, C; Shepherd, V L; Voelker, D R; Wright, J R

2001-09-01

218

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

219

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

PubMed

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

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

2004-12-01

220

Electron Spin Resonance Spectroscopy for Studying the Generation and Scavenging of Reactive Oxygen Species by Nanomaterials  

NASA Astrophysics Data System (ADS)

One fundamental mechanism widely described for nanotoxicity involves oxidative damage due to generation of free radicals and other reactive oxygen species. Indeed, the ability of nanoscale materials to facilitate the transfer of electrons, and thereby promote oxidative damage or in some instances provide antioxidant protection, may be a fundamental property of these materials. Any assessment of a nanoscale material's safety must therefore consider the potential for toxicity arising from oxidative damage. Therefore, rapid and predictive methods are needed to assess oxidative damage elicited by nanoscale materials. The use of electron spin resonance (ESR) to study free radical related bioactivity of nanomaterials has several advantages for free radical determination and identification. Specifically it can directly assess antioxidant quenching or prooxidant generation of relevant free radicals and reactive oxygen species. In this chapter, we have reported some nonclassical behaviors of the electron spin relaxation properties of unpaired electrons in different fullerenes and the investigation of anti/prooxidant activity by various types of nanomaterials using ESR. In addition, we have reviewed the mechanisms of free radical formation photosensitized by different nanomaterials. This chapter also included the use of spin labels, spin traps and ESR oximetry to systematically examine the enzymatic mimetic activities of nanomaterials.

Yin, Jun-Jie; Zhao, Baozhong; Xia, Qingsu; Fu, Peter P.

2013-09-01

221

?-Glutamylcysteine detoxifies reactive oxygen species by acting as glutathione peroxidase-1 cofactor  

PubMed Central

Reactive oxygen species regulate redox-signaling processes, but in excess they can cause cell damage, hence underlying the aetiology of several neurological diseases. Through its ability to down modulate reactive oxygen species, glutathione is considered an essential thiol-antioxidant derivative, yet under certain circumstances it is dispensable for cell growth and redox control. Here we show, by directing the biosynthesis of ?-glutamylcysteine—the immediate glutathione precursor—to mitochondria, that it efficiently detoxifies hydrogen peroxide and superoxide anion, regardless of cellular glutathione concentrations. Knocking down glutathione peroxidase-1 drastically increases superoxide anion in cells synthesizing mitochondrial ?-glutamylcysteine. In vitro, ?-glutamylcysteine is as efficient as glutathione in disposing of hydrogen peroxide by glutathione peroxidase-1. In primary neurons, endogenously synthesized ?-glutamylcysteine fully prevents apoptotic death in several neurotoxic paradigms and, in an in vivo mouse model of neurodegeneration, ?-glutamylcysteine protects against neuronal loss and motor impairment. Thus, ?-glutamylcysteine takes over the antioxidant and neuroprotective functions of glutathione by acting as glutathione peroxidase-1 cofactor. PMID:22395609

Quintana-Cabrera, Ruben; Fernandez-Fernandez, Seila; Bobo-Jimenez, Veronica; Escobar, Javier; Sastre, Juan; Almeida, Angeles; Bolanos, Juan P.

2012-01-01

222

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

PubMed Central

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.

2014-01-01

223

Apogossypolone targets mitochondria and light enhances its anticancer activity by stimulating generation of singlet oxygen and reactive oxygen species  

PubMed Central

Apogossypolone (ApoG2), a novel derivative of gossypol, has been shown to be a potent inhibitor of antiapoptotic Bcl-2 family proteins and to have antitumor activity in multiple types of cancer cells. Recent reports suggest that gossypol stimulates the generation of cellular reactive oxygen species (ROS) in leukemia and colorectal carcinoma cells; however, gossypol-mediated cell death in leukemia cells was reported to be ROS-independent. This study was conducted to clarify the effect of ApoG2-induced ROS on mitochondria and cell viability, and to further evaluate its utility as a treatment for nasopharyngeal carcinoma (NPC). We tested the photocytotoxicity of ApoG2 to the poorly differentiated NPC cell line CNE-2 using the ROS-generating TL/10 illumination system. The rapid ApoG2-induced cell death was partially reversed by the antioxidant N-acetyl-L-cysteine (NAC), but the ApoG2-induced reduction of mitochondrial membrane potential (MMP) was not reversed by NAC. In the presence of TL/10 illumination, ApoG2 generated massive amounts of singlet oxygen and was more effective in inhibiting cell growth than in the absence of illumination. We also determined the influence of light on the anti-proliferative activity of ApoG2 using a CNE-2–xenograft mouse model. ApoG2 under TL/10 illumination healed tumor wounds and suppressed tumor growth more effectively than ApoG2 treatment alone. These results indicate that the ApoG2-induced CNE-2 cell death is partly ROS-dependent. ApoG2 may be used with photodynamic therapy (PDT) to treat NPC. PMID:21192843

Hu, Zhe-Yu; Wang, Jing; Cheng, Gang; Zhu, Xiao-Feng; Huang, Peng; Yang, Dajun; Zeng, Yi-Xin

2011-01-01

224

Detection of irradiation induced reactive oxygen species production in live cells  

NASA Astrophysics Data System (ADS)

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

Gao, Bo; Zhu, Debin

2006-09-01

225

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

226

Inhibition of respiration extends C. elegans’ lifespan via reactive oxygen species that increase HIF-1 activity  

PubMed Central

Summary A mild inhibition of mitochondrial respiration extends the lifespan of many organisms, including yeast, worms, flies and mice [1–10], but the underlying mechanism is unknown. One environmental condition that reduces rates of respiration is hypoxia (low oxygen). Thus it is possible that mechanisms that sense oxygen play a role in the longevity response to reduced respiration. The hypoxia-inducible factor HIF-1 is a highly-conserved transcription factor that activates genes that promote survival during hypoxia [11–12]. In this study, we show that inhibiting respiration in C. elegans can promote longevity by activating HIF-1. Through genome-wide screening, we found that RNAi knockdown of many genes encoding respiratory-chain components induced hif-1-dependent transcription. Moreover, HIF-1 was required for the extended lifespans of clk-1 and isp-1 mutants, which have reduced rates of respiration [1, 4, 13]. Inhibiting respiration appears to activate HIF-1 by elevating the level of reactive oxygen species (ROS). We found that ROS is increased in respiration mutants, and that mild increases in ROS can stimulate HIF-1 to activate gene expression and promote longevity. In this way, HIF-1 appears to link respiratory stress in the mitochondria to a nuclear transcriptional response that promotes longevity. PMID:21093262

Lee, Seung-Jae; Hwang, Ara B.; Kenyon, Cynthia

2011-01-01

227

Reactive Oxygen Species Mediate Epstein-Barr Virus Reactivation by N-Methyl-N’-Nitro-N-Nitrosoguanidine  

PubMed Central

N-nitroso compounds (NOCs) and Epstein-Barr virus (EBV) reactivation have been suggested to play a role in the development of nasopharyngeal carcinoma (NPC). Although chemicals have been shown to be a risk factor contributing to the carcinogenesis of NPC, the underlying mechanism is not fully understood. We demonstrated recently that N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) enhances the genomic instability and tumorigenicity of NPC cells via induction of EBV reactivation. However, the mechanisms that trigger EBV reactivation from latency remain unclear. Here, we address the role of ROS in induction of EBV reactivation under MNNG treatment. EBV reactivation was induced in over 70% of EBV-positive NA cells and the promoter of Rta (Rp) was activated after MNNG treatment. Inhibitor experiments revealed ATM, p38 MAPK and JNK were activated by ROS and involved in MNNG-induced EBV reactivation. Significantly, ROS scavengers N-acetyl-L-cysteine (NAC), catalase and reduced glutathione inhibited EBV reactivation under MNNG and H2O2 treatment, suggesting ROS mediate EBV reactivation. The p53 was essential for EBV reactivation and the Rp activation by MNNG. Moreover, the p53 was phosphorylated, translocated into nucleus, and bound to Rp following ROS stimulation. The results suggest ROS play an important role in initiation of EBV reactivation by MNNG through a p53-dependent mechanism. Our findings demonstrate novel signaling mechanisms used by NOCs to induce EBV reactivation and provide a novel insight into NOCs link the EBV reactivation in the contribution to the development of NPC. Notably, this study indicates that antioxidants might be effective for inhibiting N-nitroso compound-induced EBV reactivation and therefore could be promising preventive and therapeutic agents for EBV reactivation-associated malignancies. PMID:24376853

Huang, Sheng-Yen; Fang, Chih-Yeu; Wu, Chung-Chun; Tsai, Ching-Hwa; Lin, Su-Fang; Chen, Jen-Yang

2013-01-01

228

Protective effect of Castanea sativa and Quercus robur leaf extracts against oxygen and nitrogen reactive species.  

PubMed

Topical natural antioxidants are a useful strategy for the prevention of photoaging and oxidative stress mediated skin diseases. In view of this underlying principle, the screening of natural plant extracts with scavenging activity for pro-oxidant reactive species is a primary requirement for the development of new topical antioxidant formulations. In the present study, an ethanol:water (7:3) extract from Castanea sativa leaves and a ethanol:water (2:3) extract from Quercus robur leaves were evaluated for their putative in vitro scavenging effects on reactive oxygen species (ROS) namely superoxide radical (O(2)(-)), hydroxyl radical (HO()), peroxyl radical (ROO()), hydrogen peroxide (H(2)O(2)) and singlet oxygen ((1)O(2)) as well as on reactive nitrogen species (RNS) namely nitric oxide (()NO) and peroxynitrite (ONOO(-)). The extracts presented a high potency to scavenge the tested reactive species, all the IC(50)s being found at the microg/mL level. IC(50)s (mean+/-SE) for the ROS O(2)(-),HO(),H(2)O(2) and (1)O(2) were 13.6+/-1.8; 216+/-4; 410+/-8; 12.3+/-0.7 microug/mL, respectively, for C. sativa, and 11.0+/-0.5; 285+/-22; 251+/-32; 7.90+/-0.56 microg/mL, respectively, for Q. robur. The ORAC values obtained for ROO() were 1.24+/-0.13 for C. sativa and 1.09+/-0.06 for Q. robur. The IC(50)s (mean+/-SE) for ()NO and ONOO(-) were 3.10+/-0.14 and 1.49+/-0.10 microg/mL, respectively, for C. sativa and 3.13+/-0.11 and 0.95+/-0.02 microg/mL, respectively, for Q. robur. The content of total phenolics for C. sativa and Q. robur were 284+/-9 and 346+/-4 mg of gallic acid equivalents (GAE)/g of lyophilized extract respectively. The observed effects might be of relevance considering the putative interest of these extracts as topical antioxidants. PMID:18337113

Almeida, Isabel F; Fernandes, Eduarda; Lima, José L F C; Costa, P C; Bahia, M F

2008-05-29

229

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

SciTech Connect

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

Cozzani, V.

2000-04-01

230

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

Microsoft Academic Search

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

I M Drake; N P Mapstone; C J Schorah; K L M White; D M Chalmers; M F Dixon; A T R Axon

1998-01-01

231

Cobalt Protoporphyrin Induces HO-1 Expression Mediated Partially by FOXO1 and Reduces Mitochondria-Derived Reactive Oxygen Species Production  

PubMed Central

Background Reactive oxygen species arise in the mitochondria as byproducts of respiration and oxidase activity and have important roles in many physiological and pathophysiological conditions. The level of reactive oxygen species is regulated by a number of enzymes and physiological antioxidants, including HO-1, Sod2, catalase and COX-2, etc. And HO-1 against oxidative stress requires an increase in stress-responsive genes, such as Sod2 and catalase. Especially for the activity of HO-1, cobalt protoporphyrin is known to be a potent and effective inducer in many tissues. The transcription factor, FOXO1 is resistant to oxidative stress through downregulating reactive oxygen species production. Previous study showed that FOXO1 induces HO-1 expression by binding to HO-1 promoter. The question whether cobalt protoporphyrin induces HO-1 expression mediated by FOXO1 and subsequently lessens reactive oxygen species production remains to be elucidated. Results Cobalt protoporphyrin enhances the expression of FOXO1 and facilitates FOXO1 binding to HO-1 promoter and increasing its transcriptional activity without influencing the FOXO1 protein stability. CoPP induces HO-1 and other oxidative stress-responsive genes expression, such as catalase, cytochrome c, Sod2, and COX-2, and decreases mitochondria-derived reactive oxygen species production, which are mediated partially by FOXO1. Conclusions Cobalt protoporphyrin induces HO-1 and other oxidative stress-responsive genes expression mediated partially by FOXO1, and has an important role in reducing cellular reactive oxygen species level. Cobalt protoporphyrin may be a more promising therapeutic agent to upregulate some antioxidantive genes. PMID:24255720

Li, Meixia; Xu, Haifeng; Zuo, Jin; Fang, Fude; Chang, Yongsheng

2013-01-01

232

Effect of temperature on reduction reactivity of oxygen carrier particles in a fixed bed chemical-looping combustor  

Microsoft Academic Search

In a chemical-looping combustor (CLC), gaseous fuel is oxidized by metal oxide particle, e.g. oxygen carrier, in a reduction\\u000a reactor (combustor), and the greenhouse gas CO2 is separated from the exhaust gases during the combustion. In this study, NiO\\/bentonite particle was examined on the basis\\u000a of reduction reactivity, carbon deposition during reduction, and NOx formation during oxidation. Reactivity data for

Ho-Jung Ryu; Dal-Hee Bae; Gyoung-Tae Jin

2003-01-01

233

Preventing UV induced cell damage by scavenging reactive oxygen species with enzyme-mimic Au-Pt nanocomposites.  

PubMed

We have prepared enzyme-mimic Au-Pt nanocomposites (NCs) for catalyzing the decomposition of reactive oxygen species. After surface modification, the Au-Pt NCs can be readily internalized and retained by human skin cells and also can effectively reduce cellular oxidative stress. We have demonstrated that the active and biocompatible Au-Pt nanocomposites can be applied for preventing cell damages by scavenging cellular reactive oxygen species induced by ultraviolet irradiation, indicating potential uses for the prevention and therapy of ROS-mediated diseases. PMID:24468368

Xiong, Bin; Xu, Ruili; Zhou, Rui; He, Yan; Yeung, Edward S

2014-03-01

234

Early Increase of Reactive Oxygen Species in Pea Seedling Roots Under Hypergravity  

NASA Astrophysics Data System (ADS)

Early increase of intensity of peroxidation and formation of reactive oxygen species (ROS) in plant cells take place under various impacts. The ROS can act as second messengers in mechanism of cell responses (Mittler et al 2006; Jadko et al 2007). Early stages of ROS content (chemiluminescence, ChL) in pea root cells under 3, 5, 10 and 15g during centrifugation have been investigated. After 30 min of centrifugation, especially under 10 and 15g, the intensity of ChL increased and was higher on 40-50% comparing to controls. Than the ChL slowly decreased and reached the controls in 1 hour. The changes of the ChL depend on both the dose and the duration of centrifugation. The role of ROS in mechanism of cell response to hypergravity is discussed.

Jadko, Sergiy; Syvash, Alexander; Klymchuk, Dmytro

235

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

236

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

237

Regulatory volume decrease in cardiomyocytes is modulated by calcium influx and reactive oxygen species.  

PubMed

We investigated the role of Ca(2+) in generating reactive oxygen species (ROS) induced by hyposmotic stress (Hypo) and its relationship to regulatory volume decrease (RVD) in cardiomyocytes. Hypo-induced increases in cytoplasmic and mitochondrial Ca(2+). Nifedipine (Nife) inhibited both Hypo-induced Ca(2+) and ROS increases. Overexpression of catalase (CAT) induced RVD and a decrease in Hypo-induced blebs. Nife prevented CAT-dependent RVD activation. These results show a dual role of Hypo-induced Ca(2+) influx in the control of cardiomyocyte viability. Hypo-induced an intracellular Ca(2+) increase which activated RVD and inhibited necrotic blebbing thus favoring cell survival, while simultaneously increasing ROS generation, which in turn inhibited RVD and induced necrosis. PMID:19818777

Rojas-Rivera, Diego; Díaz-Elizondo, Jessica; Parra, Valentina; Salas, Daniela; Contreras, Ariel; Toro, Barbra; Chiong, Mario; Olea-Azar, Claudio; Lavandero, Sergio

2009-11-01

238

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

239

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

240

Cross-talk of nitric oxide and reactive oxygen species in plant programed cell death  

PubMed Central

In plants, programed cell death (PCD) is an important mechanism to regulate multiple aspects of growth and development, as well as to remove damaged or infected cells during responses to environmental stresses and pathogen attacks. Under biotic and abiotic stresses, plant cells exhibit a rapid synthesis of nitric oxide (NO) and a parallel accumulation of reactive oxygen species (ROS). Frequently, these responses trigger a PCD process leading to an intrinsic execution of plant cells. The accumulating evidence suggests that both NO and ROS play key roles in PCD. These redox active small molecules can trigger cell death either independently or synergistically. Here we summarize the recent progress on the cross-talk of NO and ROS signals in the hypersensitive response, leaf senescence, and other kinds of plant PCD caused by diverse cues. PMID:23967004

Wang, Yiqin; Loake, Gary J.; Chu, Chengcai

2013-01-01

241

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

242

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

243

Human classical monocytes control the intracellular stage of Leishmania braziliensis by reactive oxygen species.  

PubMed

Leishmania braziliensis are intracellular parasites that cause unique clinical forms of cutaneous leishmaniasis. Previous studies with other leishmania species demonstrated that reactive oxygen species (ROS) control promastigotes, the infective stage of the parasite, but not the amastigote form that exists in the mammalian host. Here we show that ROS inhibits growth of L. braziliensis amastigotes in resting monocytes, and that classical monocytes are primarily responsible for this control. ROS, but not nitric oxide, also contributed to killing of L. braziliensis by IFN-? activated monocytes. Furthermore, by gene expression profiling of human lesions we found greater expression of genes associated with ROS, but not nitric oxide, compared to normal skin. This study shows that ROS are important for control of L. braziliensis both at the initial stages of infection, as well as at later time points, and highlights that monocyte subsets may play different roles during leishmaniasis. PMID:24403561

Novais, Fernanda O; Nguyen, Ba T; Beiting, Daniel P; Carvalho, Lucas P; Glennie, Nelson D; Passos, Sara; Carvalho, Edgar M; Scott, Phillip

2014-04-15

244

Fundamental roles of reactive oxygen species and protective mechanisms in the female reproductive system  

PubMed Central

Controlled oxidation, such as disulfide bond formation in sperm nuclei and during ovulation, plays a fundamental role in mammalian reproduction. Excess oxidation, however, causes oxidative stress, resulting in the dysfunction of the reproductive process. Antioxidation reactions that reduce the levels of reactive oxygen species are of prime importance in reproductive systems in maintaining the quality of gametes and support reproduction. While anti-oxidative enzymes, such as superoxide dismutase and peroxidase, play a central role in eliminating oxidative stress, reduction-oxidation (redox) systems, comprised of mainly glutathione and thioredoxin, function to reduce the levels of oxidized molecules. Aldo-keto reductase, using NADPH as an electron donor, detoxifies carbonyl compounds resulting from the oxidation of lipids and proteins. Thus, many antioxidative and redox enzyme genes are expressed and aggressively protect gametes and embryos in reproductive systems. PMID:16137335

Fujii, Junichi; Iuchi, Yoshihito; Okada, Futoshi

2005-01-01

245

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

246

CNS SIRT3 expression is altered by reactive oxygen species and in Alzheimer's disease.  

PubMed

Progressive mitochondrial dysfunction contributes to neuronal degeneration in age-mediated disease. An essential regulator of mitochondrial function is the deacetylase, sirtuin 3 (SIRT3). Here we investigate a role for CNS Sirt3 in mitochondrial responses to reactive oxygen species (ROS)- and Alzheimer's disease (AD)-mediated stress. Pharmacological augmentation of mitochondrial ROS increases Sirt3 expression in primary hippocampal culture with SIRT3 over-expression being neuroprotective. Furthermore, Sirt3 expression mirrors spatiotemporal deposition of ?-amyloid in an AD mouse model and is also upregulated in AD patient temporal neocortex. Thus, our data suggest a role for SIRT3 in mechanisms sensing and tackling ROS- and AD-mediated mitochondrial stress. PMID:23139766

Weir, Heather J M; Murray, Tracey K; Kehoe, Patrick G; Love, Seth; Verdin, Eric M; O'Neill, Michael J; Lane, Jon D; Balthasar, Nina

2012-01-01

247

Reactive Oxygen Species and Autophagy Modulation in Non-Marine Drugs and Marine Drugs  

PubMed Central

It is becoming more understandable that an existing challenge for translational research is the development of pharmaceuticals that appropriately target reactive oxygen species (ROS)-mediated molecular networks in cancer cells. In line with this approach, there is an overwhelmingly increasing list of many non-marine drugs and marine drugs reported to be involved in inhibiting and suppressing cancer progression through ROS-mediated cell death. In this review, we describe the strategy of oxidative stress-based therapy and connect the ROS modulating effect to the regulation of apoptosis and autophagy. Finally, we focus on exploring the function and mechanism of cancer therapy by the autophagy modulators including inhibitors and inducers from non-marine drugs and marine drugs. PMID:25402829

Farooqi, Ammad Ahmad; Fayyaz, Sundas; Hou, Ming-Feng; Li, Kun-Tzu; Tang, Jen-Yang; Chang, Hsueh-Wei

2014-01-01

248

Reactive oxygen species mediate dopamine-induced signaling in renal proximal tubule cells.  

PubMed

Intrarenally-produced dopamine (DA) induces a large increase in urinary sodium excretion mainly due to the inhibition of tubular sodium reabsorption. We aimed to study the participation of reactive oxygen species (ROS) in DA signaling pathway in proximal tubule cells. Our results show that DA increased ROS production in OK cells and indicate the mitochondria as the main source of ROS. DA also increased ERK1/2, superoxide dismutase (SOD) and transcription factor ?B (NF-?B) activity. These findings suggest that DA generates mitochondria-derived ROS that activate ERK1/2 and subsequently NF-?B and SOD activity at concentrations that exert a physiological regulation of renal function. PMID:23994527

Acquier, Andrea B; Mori Sequeiros García, Mercedes; Gorostizaga, Alejandra B; Paz, Cristina; Mendez, Carlos F

2013-10-01

249

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

PubMed Central

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

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

2013-01-01

250

Enhanced phagocytosis, chemotaxis, and production of reactive oxygen intermediates by interstitial lung macrophages following acute endotoxemia.  

PubMed

Endotoxemia is associated with enhanced release of a variety of cytotoxic and/or proinflammatory mediators from locally activated tissue macrophages. The lung is highly sensitive to damage induced by endotoxin, suggesting that pulmonary macrophages are activated by this bacterially derived product to release mediators that contribute to the pathogenesis of tissue injury. In the present studies, we used a rat model of acute endotoxemia induced by a single intravenous injection of animals with lipopolysaccharide (LPS) to determine the extent to which different lung macrophage subpopulations are activated. Alveolar macrophages (AM) and interstitial macrophages (IM) were isolated sequentially from the lung by lavage, followed by digestion with collagenase and selective adherence to tissue culture dishes. Both AM and IM were found to produce superoxide anion, as well as hydrogen peroxide in response to inflammatory stimuli. AM produced greater quantities of these reactive oxygen intermediates than did IM. Treatment of rats with LPS resulted in a significant increase in production of reactive oxygen intermediates by IM, but not by AM. Similarly, while AM from untreated rats phagocytized more opsonized sheep red blood cells than did IM, LPS treatment of rats significantly enhanced phagocytosis only in IM. In addition, this treatment caused a significant increase in chemotaxis of IM towards C5a. In contrast, although LPS treatment of rats had no effect on tumor necrosis factor-alpha release by AM, a significant reduction was observed in IM. Taken together, these data demonstrate that IM play a role in the inflammatory response of the lung to acute endotoxemia. PMID:8086172

Wizemann, T M; Laskin, D L

1994-09-01

251

Iron induces protection and necrosis in cultured cardiomyocytes: Role of reactive oxygen species and nitric oxide.  

PubMed

We investigate here the role of reactive oxygen species and nitric oxide in iron-induced cardiomyocyte hypertrophy or cell death. Cultured rat cardiomyocytes incubated with 20 microM iron (added as FeCl(3)-Na nitrilotriacetate, Fe-NTA) displayed hypertrophy features that included increased protein synthesis and cell size, plus realignment of F-actin filaments along with sarcomeres and activation of the atrial natriuretic factor gene promoter. Incubation with higher Fe-NTA concentrations (100 microM) produced cardiomyocyte death by necrosis. Incubation for 24 h with Fe-NTA (20-40 microM) or the nitric oxide donor Delta-nonoate increased iNOS mRNA but decreased iNOS protein levels; under these conditions, iron stimulated the activity and the dimerization of iNOS. Fe-NTA (20 microM) promoted short- and long-term generation of reactive oxygen species, whereas preincubation with l-arginine suppressed this response. Preincubation with 20 microM Fe-NTA also attenuated the necrotic cell death triggered by 100 microM Fe-NTA, suggesting that these preincubation conditions have cardioprotective effects. Inhibition of iNOS activity with 1400 W enhanced iron-induced ROS generation and prevented both iron-dependent cardiomyocyte hypertrophy and cardioprotection. In conclusion, we propose that Fe-NTA (20 microM) stimulates iNOS activity and that the enhanced NO production, by promoting hypertrophy and enhancing survival mechanisms through ROS reduction, is beneficial to cardiomyocytes. At higher concentrations, however, iron triggers cardiomyocyte death by necrosis. PMID:19969068

Munoz, Juan Pablo; Chiong, Mario; García, Lorena; Troncoso, Rodrigo; Toro, Barbra; Pedrozo, Zully; Diaz-Elizondo, Jessica; Salas, Daniela; Parra, Valentina; Núñez, Marco T; Hidalgo, Cecilia; Lavandero, Sergio

2010-02-15

252

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

PubMed Central

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

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

2009-01-01

253

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

PubMed Central

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

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

2012-01-01

254

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

255

Mitochondrial membrane permeabilization and cell death during myocardial infarction: roles of calcium and reactive oxygen species  

PubMed Central

Excess generation of reactive oxygen species (ROS) and cytosolic calcium accumulation play major roles in the initiation of programmed cell death during acute myocardial infarction. Cell death may include necrosis, apoptosis and autophagy, and combinations thereof. During ischemia, calcium handling between the sarcoplasmic reticulum and myofilament is disrupted and calcium is diverted to the mitochondria causing swelling. Reperfusion, while essential for survival, reactivates energy transduction and contractility and causes the release of ROS and additional ionic imbalance. During acute ischemia–reperfusion, the principal death pathways are programmed necrosis and apoptosis through the intrinsic pathway, initiated by the opening of the mitochondrial permeability transition pore and outer mitochondrial membrane permeabilization, respectively. Despite intense investigation, the mechanisms of action and modes of regulation of mitochondrial membrane permeabilization are incompletely understood. Extrinsic apoptosis, necroptosis and autophagy may also contribute to ischemia–reperfusion injury. In this review, the roles of dysregulated calcium and ROS and the contributions of Bcl-2 proteins, as well as mitochondrial morphology in promoting mitochondrial membrane permeability change and the ensuing cell death during myocardial infarction are discussed. PMID:23176689

Webster, Keith A

2013-01-01

256

Carcinogenic Metals Induce Hypoxia-inducible Factor-stimulated Transcription by Reactive Oxygen Species-independent Mechanism1  

Microsoft Academic Search

Nickel (Ni21) and cobalt (Co21) mimic hypoxia and were used as a tool to study the role of oxygen sensing and signaling cascades in the regulation of hypoxia-inducible gene expression. These metals can produce oxidative stress; therefore, it was conceivable that reactive oxygen species (ROS) may trigger signaling pathways resulting in the activation of the hypoxia- inducible factor (HIF)-1 transcription

Konstantin Salnikow; Weicheng Su; Mikhail V. Blagosklonny; Max Costa

257

Enzymatic and nonenzymatic formation of reactive oxygen species from 6-anilino-5,8-quinolinequinone.  

PubMed

The nonenzymatic and enzymatic formation of reactive oxygen species (ROS) from LY83583 (6-anilino-5,8-quinolinequinone) was investigated by electron paramagnetic resonance (EPR) spectroscopy. In the presence of thiol compounds such as glutathione and L-cysteine, LY83583 underwent a one-electron reduction due to low redox potential (-0.3+/-0.01 V vs. SCE), followed by formation of LY83583 semiquinone anion radical. This species was characterized by EPR spectroscopy under an argon atmosphere at neutral pH. Under an aerobic condition, this species interacts with molecular oxygen to form a superoxide anion radical. GSH-conjugated LY83583 was also identified by NMR and FAB-MS. When LY83583 was applied to PC12 cells, ROS formation was completely inhibited by both the flavoenzyme inhibitor DPI and the DT-diaphorase inhibitor dicumarol. On the other hand, ROS generation occurred independent of intracellular GSH level. These results indicate that LY83583 can generate ROS both enzymatically and nonenzymatically, although the enzymatic formation is dominant over the nonenzymatic system in PC12 cells. PMID:14729138

Hasegawa, Toyoshi; Bando, Atsushi; Tsuchiya, Koichiro; Abe, Shinji; Okamoto, Masumi; Kirima, Kazuyoshi; Ueno, Satoru; Yoshizumi, Masanori; Houchi, Hitoshi; Tamaki, Toshiaki

2004-01-01

258

Involvement of reactive oxygen species in the UV-B damage to the cyanobacterium Anabaena sp.  

PubMed

Reactive oxygen species (ROS) are involved the damage of living organisms under environmental stress including UV radiation. Cyanobacteria, photoautotrophic prokaryotic organisms, also suffer from increasing UV-B due to the depletion of the stratospheric ozone layer. The increased UV-B induces the production of ROS in vivo detected by using the ROS-sensitive probe 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). Ascorbic acid and N-acetyl-L-cysteine (NAC) scavenged ROS effectively, while alpha-tocopherol acetate or pyrrolidine dithiocarbamate (PDTC) did not. The presence of rose bengal and hypocrellin A increased the ROS level by photodynamic action in the visible light. The presence of the herbicide, 3-(3,4-dichlorophenyl)-1,1-dimethyl urea (DCMU), increased ROS production slightly, and ROS formation was greatly enhanced by the addition of methyl viologen due to the fact that this redox system diverts electrons from PSI to oxygen and thus forms ROS. UV-B induces ROS generation by photodynamic action and inhibition of the electron transport by damaging the electron receptors or enzymes associated with the electron transport chain during photosynthesis. PMID:11849986

He, Yu Ying; Häder, Donat P

2002-02-01

259

Embryonic cardiac arrhythmia and generation of reactive oxygen species: common teratogenic mechanism for IKr blocking drugs.  

PubMed

In the adult organism, it is well established that hypoxia followed by reperfusion may be fatal and result in generation of reactive oxygen species (ROS) and subsequent tissue damage. There is also considerable evidence that temporary decrease or interruption in oxygen supply to the embryo and ROS generation during reperfusion result in tissue damage in embryonic tissues. A wide spectrum of different malformations by transient embryonic hypoxia could be produced, depending on the duration, extent, and timing of the hypoxic event. It is the contention of this paper that drugs that block the potassium channel IKr, either as an intended pharmacologic effect or as an unwanted side-effect, are potentially teratogenic by a common ROS related mechanism. Drugs blocking the IKr channel, such as almokalant, dofetilide, phenytoin, cisapride and astemizole, do all produce a similar pattern of hypoxia-related malformations. Mechanistic studies show that the malformations are preceded by embryonic cardiac arrhythmia and periods of hypoxia/reoxygenation in embryonic tissues. Pretreatment or simultaneous treatment with radical scavengers with capacity to capture ROS, markedly decrease the teratogenicity of different IKr blocking drugs. A second aim of this review is to demonstrate that the conventional design of teratology studies is not optimal to detect malformations caused by IKr blocking drugs. Repeated high doses result in high incidences of embryonic death due embryonic cardiac arrhythmia, thus masking their teratogenic potential. Instead, single dosing on specific days is proposed to be a better way to characterize the teratogenic potential of Ikr blocking drugs. PMID:17570632

Danielsson, Bengt R; Danielsson, Christian; Nilsson, Mats F

2007-07-01

260

The role of metals in production and scavenging of reactive oxygen species in photosystem II.  

PubMed

Metal ions play a crucial role in enzymatic reactions in all photosynthetic organisms such as cyanobacteria, algae and plants. It well known that metal ions maintain the binding of substrate in the active site of the metalloenzymes and control the redox activity of the metalloenzyme in the enzymatic reaction. A large pigment-protein complex, PSII, known to serve as a water-plastoquinone oxidoreductase, contains three metal centers comprising non-heme iron, heme iron of Cyt b559 and the water-splitting manganese complex. Metal ions bound to PSII proteins maintain the electron transport from water to plastoquinone and regulate the pro-oxidant and antioxidant activity in PSII. In this review, attention is focused on the role of PSII metal centers in (i) the formation of superoxide anion and hydroxyl radicals by sequential one-electron reduction of molecular oxygen and the formation of hydrogen peroxide by incomplete two-electron oxidation of water; and (ii) the elimination of superoxide anion radical by one-electron oxidation and reduction (superoxide dismutase activity) and of hydrogen peroxide by two-electron oxidation and reduction (catalase activity). The balance between the formation and elimination of reactive oxygen species by PSII metal centers is discussed as an important aspect in the prevention of photo-oxidative damage of PSII proteins and lipids. PMID:24771559

Pospíšil, Pavel

2014-07-01

261

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

262

Circadian Clock Control of Nox4 and Reactive Oxygen Species in the Vasculature  

PubMed Central

Recent studies have shown that circadian clock disruption is associated with pathological remodeling in the arterial structure and vascular stiffness. Moreover, chronic circadian disruption is associated with dysfunction in endothelial responses and signaling. Reactive oxygen species have emerged as key regulators in vascular pathology. Previously, we have demonstrated that circadian clock dysfunction exacerbates superoxide production through eNOS uncoupling. To date, the impact of circadian clock mutation on vascular NADPH oxidase expression and function is not known. The goal in the current study was to determine if the circadian clock controls vascular Nox4 expression and hydrogen peroxide formation in arteries, particularly in endothelial and vascular smooth muscle cells. In aorta, there was an increase in hydrogen peroxide and Nox4 expression in mice with a dysfunctional circadian rhythm (Bmal1-KO mice). In addition, the Nox4 gene promoter is activated by the core circadian transcription factors. Lastly, in synchronized cultured human endothelial cells, Nox4 gene expression exhibited rhythmic oscillations. These data reveal that the circadian clock plays an important role in the control of Nox4 and disruption of the clock leads to subsequent production of reaction oxygen species. PMID:24205282

Chen, Feng; Ali, M. Irfan; Hart, C. Michael M.; Stepp, David W.; Kovalenkov, Yevgeniy O.; Merloiu, Ana-Maria; Pati, Paramita; Fulton, David; Rudic, R. Daniel

2013-01-01

263

Circadian clock control of Nox4 and reactive oxygen species in the vasculature.  

PubMed

Recent studies have shown that circadian clock disruption is associated with pathological remodeling in the arterial structure and vascular stiffness. Moreover, chronic circadian disruption is associated with dysfunction in endothelial responses and signaling. Reactive oxygen species have emerged as key regulators in vascular pathology. Previously, we have demonstrated that circadian clock dysfunction exacerbates superoxide production through eNOS uncoupling. To date, the impact of circadian clock mutation on vascular NADPH oxidase expression and function is not known. The goal in the current study was to determine if the circadian clock controls vascular Nox4 expression and hydrogen peroxide formation in arteries, particularly in endothelial and vascular smooth muscle cells. In aorta, there was an increase in hydrogen peroxide and Nox4 expression in mice with a dysfunctional circadian rhythm (Bmal1-KO mice). In addition, the Nox4 gene promoter is activated by the core circadian transcription factors. Lastly, in synchronized cultured human endothelial cells, Nox4 gene expression exhibited rhythmic oscillations. These data reveal that the circadian clock plays an important role in the control of Nox4 and disruption of the clock leads to subsequent production of reaction oxygen species. PMID:24205282

Anea, Ciprian B; Zhang, Maoxiang; Chen, Feng; Ali, M Irfan; Hart, C Michael M; Stepp, David W; Kovalenkov, Yevgeniy O; Merloiu, Ana-Maria; Pati, Paramita; Fulton, David; Rudic, R Daniel

2013-01-01

264

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

PubMed

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

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

2014-09-01

265

Environmentally persistent free radicals (EPFRs). 1. Generation of reactive oxygen species in aqueous solutions.  

PubMed

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 (O(2)(•-)), and hydrogen peroxide (H(2)O(2)) generated by EPFR-particle systems were reported. Failure to trap superoxide radicals in aqueous solvent, formed from reaction of EPFRs with molecular oxygen, results from 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 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 incubation time suggest a catalytic cycle of ROS formation. PMID:21823585

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

2011-10-01

266

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

2014-11-01

267

Ultraviolet Irradiation-Dependent Fluorescence Enhancement of Hemoglobin Catalyzed by Reactive Oxygen Species  

PubMed Central

Ultraviolet (UV) light has a potent effect on biological organisms. Hemoglobin, an oxygen-transport protein, plays an irreplaceable role in sustaining life of all vertebrates. In this study we scrutinize the effects of ultraviolet irradiation (UVI) as well as visible irradiation on the fluorescence characteristics of bovine hemoglobin (BHb) in vitro. Data show that UVI results in fluorescence enhancement of BHb in a dose-dependant manner. Furthermore, UVI-induced fluorescence enhancement is significantly increased when BHb is pretreated with hydrogen peroxide (H2O2), a type of reactive oxygen species (ROS). Meanwhile, The water-soluble antioxidant vitamin C suppresses this UVI-induced fluorescence enhancement. In contrast, green light irradiation does not lead to fluorescence enhancement of BHb no matter whether H2O2 is acting on the BHb solution or not. Taken together, these results indicate that catalysis of ROS and UVI-dependent irradiation play two key roles in the process of UVI-induced fluorescence enhancement of BHb. PMID:22952902

Pan, Leiting; Wang, Xiaoxu; Yang, Shuying; Wu, Xian; Lee, Imshik; Zhang, Xinzheng; Rupp, Romano A.; Xu, Jingjun

2012-01-01

268

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

269

Observation and quantification of ultraviolet-induced reactive oxygen species in ex vivo human skin.  

PubMed

Two-photon fluorescence imaging is used to detect UV-induced reactive oxygen species (ROS) in ex vivo human skin in this study. ROS (potentially H202, singlet oxygen or peroxynitrite [or all]) are detected after reaction with nonfluorescent dihydrorhodamine-123 (DHR) and the consequent formation of fluorescent rhodamine-123 (R123). The cellular regions at each epidermal stratum that generate ROS are identified. R-123 fluorescence is detected predominately in the lipid matrix of the stratum corneum. In contrast, the strongest R123 fluorescence signal is detected in the intracellular cytoplasm of the viable epidermal keratinocytes. A simple bimolecular one-step kinetic model is used for estimating the upper bound of the number of ROS that are generated in the skin and that react with DHR. After ultraviolet-B radiation (280-320 nm) (UVB) equivalent to 2 h of noonday summer North American solar exposure (1600 J m(-2) UVB), the model finds that 14.70 x 10(-3) mol of ROS that react with DHR are generated in the stratum corneum of an average adult-size face (258 cm(-2)). Approximately 10(-4) mol are potentially generated in the lower epidermal strata. The data show that two-photon fluorescence imaging can be used to detect ROS in UV-irradiated skin. PMID:12126308

Hanson, Kerry M; Clegg, Robert M

2002-07-01

270

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

271

Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage. A review.  

PubMed

Abstract In recent years there has been enormous interest in researching oxidative stress. Reactive oxygen species (ROS) are derived from the metabolism of oxygen as by-products of cell respiration, and are continuously produced in all aerobic organisms. Oxidative stress occurs as a consequence of an imbalance between ROS production and the available antioxidant defence against them. Nowadays, a variety of diseases and degenerative processes such as cancer, Alzheimer's and autoimmune diseases are mediated by oxidative stress. Heat stress was suggested to be an environmental factor responsible for stimulating ROS production because of similarities in responses observed following heat stress compared with that occurring following exposure to oxidative stress. This manuscript describes the main mitochondrial sources of ROS and the antioxidant defences involved to prevent oxidative damage in all the mitochondrial compartments. It also deals with discussions concerning the cytotoxic effect of heat stress, mitochondrial heat-induced alterations, as well as heat shock protein (HSP) expression as a defence mechanism. PMID:25354680

Belhadj Slimen, Imen; Najar, Taha; Ghram, Abdeljelil; Dabbebi, Hajer; Ben Mrad, Moncef; Abdrabbah, Manef

2014-11-01

272

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

273

Reactive oxygen metabolites promote cholesterol crystal formation in model bile: role of lipid peroxidation.  

PubMed

In animal models of gallstone disease inflammatory alterations of the gallbladder mucosa are regularly found before the first appearance of cholesterol monohydrate crystals in bile. At sites of inflammation granulocytes generate reactive oxygen metabolites (ROM). The aim of our study was to investigate whether ROM may influence the cholesterol monohydrate crystal formation in supersaturated model bile. Superoxide anions (O2-), hydrogen peroxide (H2O2), and hydroxyl radicals (.OH) were generated by the interaction of Fe(3+)-EDTA with ascorbic acid (Asc). The influence of ROM on cholesterol crystal formation was studied by measurement of the nucleation time. To check whether lipid peroxidation was induced by the ROM generation, production of malondialdehyde equivalents was measured in bile with the thiobarbituric assay. Furthermore, the lipid pattern of bile after ROM exposure was analyzed by thin layer chromatography. Addition of Fe(3+)-EDTA/Asc to model bile markedly decreased the cholesterol nucleation time (NT) (p < 0.01), caused a significant increase in malonidialdehyde equivalents (p < 0.001) and induced the generation of 4-hydroxy-2,3-trans-nonenal (4-HNE). In an attempt to identify a specific oxygen metabolite responsible for the alterations in bile, the effects of various oxygen radical scavengers were tested. Desferal, which prevents -OH generation by chelation of ferrous iron, completely protected bile against Fe(3+)-EDTA/Asc-induced decrease in NT (p < 0.001), increase in lipid peroxidation (p < 0.001) and generation of 4-HNE. Our results indicate that formation of cholesterol crystals in model bile is enhanced by ROM. Hydroxyl radical induced lipid peroxidation appears to be the mechanism responsible for the crystallisation promoting activity of ROM. PMID:8721618

Eder, M I; Miquel, J F; Jongst, D; Paumgartner, G; von Ritter, C

1996-01-01

274

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

PubMed Central

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

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

2014-01-01

275

Inhibition of ATP citrate lyase induces an anticancer effect via reactive oxygen species: AMPK as a predictive biomarker for therapeutic impact.  

PubMed

De novo lipogenesis is activated in most cancers. Inhibition of ATP citrate lyase (ACLY), the enzyme that catalyzes the first step of de novo lipogenesis, leads to growth suppression and apoptosis in a subset of human cancer cells. Herein, we found that ACLY depletion increases the level of intracellular reactive oxygen species (ROS), whereas addition of an antioxidant reduced ROS and attenuated the anticancer effect. ACLY depletion or exogenous hydrogen peroxide induces phosphorylation of AMP-activated protein kinase (p-AMPK), a crucial regulator of lipid metabolism, independently of energy status. Analysis of various cancer cell lines revealed that cancer cells with a higher susceptibility to ACLY depletion have lower levels of basal ROS and p-AMPK. Mitochondrial-deficient ?(0) cells retained high levels of ROS and p-AMPK and were resistant to ACLY depletion, whereas the replenishment of normal mitochondrial DNA reduced the levels of ROS and p-AMPK and restored the sensitivity to ACLY depletion, indicating that low basal levels of mitochondrial ROS are critical for the anticancer effect of ACLY depletion. Finally, p-AMPK levels were significantly correlated to the levels of oxidative DNA damage in colon cancer tissues, suggesting that p-AMPK reflects cellular ROS levels in vitro and in vivo. Together, these data suggest that ACLY inhibition exerts an anticancer effect via increased ROS, and p-AMPK could be a predictive biomarker for its therapeutic outcome. PMID:23506848

Migita, Toshiro; Okabe, Sachiko; Ikeda, Kazutaka; Igarashi, Saori; Sugawara, Shoko; Tomida, Akihiro; Taguchi, Ryo; Soga, Tomoyoshi; Seimiya, Hiroyuki

2013-05-01

276

The Mechanisms Involved in Seed Dormancy Alleviation by Hydrogen Cyanide Unravel the Role of Reactive Oxygen Species as Key Factors of Cellular Signaling during Germination[C][W  

PubMed Central

The physiological dormancy of sunflower (Helianthus annuus) embryos can be overcome during dry storage (after-ripening) or by applying exogenous ethylene or hydrogen cyanide (HCN) during imbibition. The aim of this work was to provide a comprehensive model, based on oxidative signaling by reactive oxygen species (ROS), for explaining the cellular mode of action of HCN in dormancy alleviation. Beneficial HCN effect on germination of dormant embryos is associated with a marked increase in hydrogen peroxide and superoxide anion generation in the embryonic axes. It is mimicked by the ROS-generating compounds methylviologen and menadione but suppressed by ROS scavengers. This increase results from an inhibition of catalase and superoxide dismutase activities and also involves activation of NADPH oxidase. However, it is not related to lipid reserve degradation or gluconeogenesis and not associated with marked changes in the cellular redox status controlled by the glutathione/glutathione disulfide couple. The expression of genes related to ROS production (NADPHox, POX, AO1, and AO2) and signaling (MAPK6, Ser/ThrPK, CaM, and PTP) is differentially affected by dormancy alleviation either during after-ripening or by HCN treatment, and the effect of cyanide on gene expression is likely to be mediated by ROS. It is also demonstrated that HCN and ROS both activate similarly ERF1, a component of the ethylene signaling pathway. We propose that ROS play a key role in the control of sunflower seed germination and are second messengers of cyanide in seed dormancy release. PMID:19329562

Oracz, Krystyna; El-Maarouf-Bouteau, Hayat; Kranner, Ilse; Bogatek, Renata; Corbineau, Francoise; Bailly, Christophe

2009-01-01

277

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

PubMed

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

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

2014-01-01

278

Reactive oxygen species generated by microbial NADPH oxidase NoxA regulate sexual development in Aspergillus nidulans  

Microsoft Academic Search

Summary NADPH oxidases (Nox) have been characterized as higher eukaryotic enzymes used deliberately to pro- duce reactive oxygen species (ROS). The recent dis- covery of new functional members of the Nox family in plants and animals has led to the recognition of the increasing importance of ROS as signals involved in regulation of diverse cellular processes such as defence, growth

Teresa Lara-Ortíz; Héctor Riveros-Rosas; Jesús Aguirre

279

Serotonin 5-HT2B Receptor Blockade Prevents Reactive Oxygen SpeciesInduced Cardiac Hypertrophy in Mice  

E-print Network

increased superoxide anion concentration ( 32%), NAD(P)H oxidase maximal activity ( 84%), and p47phox NAD be either dismutated spontaneously to hydrogen peroxide or in a reaction involving superoxide dismutase (SOD of reactive oxygen species and tumor necrosis factor- through the activation of reduced nicotinamide

Boyer, Edmond

280

Associations between reactive oxygen species, blood pressure and arterial stiffness in black South Africans: the SABPA study  

Microsoft Academic Search

Many mechanisms, including oxidative stress, contribute to hypertension. This study investigated the possible associations between oxidative stress, blood pressure and arterial stiffness in black South Africans. Ambulatory blood pressure measurements were taken for 101 black South African men and 99 women. The stiffness indices included ambulatory arterial stiffness index (AASI) and pulse pressure (PP). Reactive oxygen species (ROS) levels (P<0.0001)

R Kruger; R Schutte; H W Huisman; J M Van Rooyen; N T Malan; C M T Fourie; R Louw; F H van der Westhuizen; C A van Deventer; L Malan; A E Schutte

2012-01-01

281

Do vitamins C and E attenuate the effects of reactive oxygen species during pulmonary reperfusion and thereby prevent injury?  

Microsoft Academic Search

Background. We established an in vivo pig model of standardized lung ischemia to analyze pulmonary reperfusion injury. Enhanced chemiluminescence measurement (CM) allowed immediate quantification of reactive oxygen species (ROS) and subsequent lipid peroxidation. In such model we analyzed efficacy of vitamins C and E to prevent reperfusion injury.Methods. After left lateral thoracotomy in group I (n = 6), normothermic lung

Florian M Wagner; Andreas T Weber; Katrin Ploetze; Felix Schubert; Steffen Pfeiffer; Steffen Albrecht; Stephan Schueler

2002-01-01

282

Regulation of glycolysis and expression of glucose metabolism-related genes by reactive oxygen species in contracting skeletal muscle cells  

Microsoft Academic Search

Contractile activity induces a marked increase in glycolytic activity and gene expression of enzymes and transporters involved in glucose metabolism in skeletal muscle. Muscle contraction also increases the production of reactive oxygen species (ROS). In this study, the effects of treatment with N-acetylcysteine (NAC), a potent antioxidant compound, on contraction-stimulated glycolysis were investigated in electrically stimulated primary rat skeletal muscle

Carlos Hermano da Justa Pinheiro; Leonardo R. Silveira; Renato Tadeu Nachbar; Kaio Fernando Vitzel; Rui Curi

2010-01-01

283

Involvement of Reactive Oxygen Species in Human Sperm Arcosome Reaction Induced by A23 187, Lysophosphatidyicholine, and Biological Fluid Ultrafiltrates  

Microsoft Academic Search

Although recent evidence indicated that the produc- tion of reactive oxygen species (ROS) by human spermatozoa may be involved in the regulation of capacitation, very little is known about the role of ROS in the acrosome reaction. To address this issue, Percoll-washed spermatozoa were incubated in Ham's F-b medium in the absence (no capacitation) or presence (capacita- tion) of fetal

EVE DE LAMIRANDE; CONYEE TSAI; AZIZ HARAKAT; CLAUDE GAGNON

1998-01-01

284

Reactive oxygen species induce expression of vascular endothelial growth factor in chondrocytes and human articular cartilage explants  

Microsoft Academic Search

Vascular endothelial growth factor (VEGF) promotes cartilage-degrading pathways, and there is evidence for the involvement of reactive oxygen species (ROS) in cartilage degeneration. However, a relationship between ROS and VEGF has not been reported. Here, we investigate whether the expression of VEGF is modulated by ROS. Aspirates of synovial fluid from patients with osteoarthritis (OA) were examined for intra-articular VEGF

Jakob Fay; Deike Varoga; Christoph J Wruck; Bodo Kurz; Mary B Goldring; Thomas Pufe

2006-01-01

285

From the Cover: Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production  

Microsoft Academic Search

The mitochondrial theory of aging proposes that reactive oxygen species (ROS) generated inside the cell will lead, with time, to increasing amounts of oxidative damage to various cell components. The main site for ROS production is the respiratory chain inside the mitochondria and accumulation of mtDNA mutations, and impaired respiratory chain function have been associated with degenerative diseases and aging.

Aleksandra Trifunovic; Anna Hansson; Anna Wredenberg; Anja T. Rovio; Eric Dufour; Ivan Khvorostov; Johannes N. Spelbrink; Rolf Wibom; Howard T. Jacobs; Nils-Göran Larsson

2005-01-01

286

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

Microsoft Academic Search

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

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

2006-01-01

287

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

288

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

289

Mercuric chloride?induced reactive oxygen species and its effect on antioxidant enzymes in different regions of rat brain  

Microsoft Academic Search

The present study was undertaken to determine if in vitro exposure to mercuric chloride produces reactive oxygen species (ROS) in the synaptosomes prepared from various regions of rat brain. The effects of in vivo exposure to mercury on antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in different regions of rat brain were also investigated. Adult

S. Hussain; D. A. Rodgers; H. M. Duhart; S. F. Ali

1997-01-01

290

Levels of Monocyte Reactive Oxygen Species Are Associated with Reduced Natural Killer Cell Activity in Major Depressive Disorder  

Microsoft Academic Search

Major depressive disorder (MDD) is associated with reductions in natural killer cell activity (NKCA), however the mechanism(s) mediating reduced NKCA in MDD has yet to be determined. In light of evidence that MDD is associated with an inflammatory immune response, we propose that reactive oxygen species (ROS), generated by inflammatory leukocytes (monocytes and\\/or neutrophils), may mediate the suppression of NKCA

Matthew G. Frank; Shelton E. Hendricks; Diane Bessette; Donald R. Johnson; Julie L. Wieseler Frank; William J. Burke

2001-01-01

291

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

292

Nox1Based NADPH Oxidase Is the Major Source of UVA-Induced Reactive Oxygen Species in Human Keratinocytes  

Microsoft Academic Search

UVA radiation is a major environmental stress on skin, causing acute and chronic photodamage. These responses are mediated by reactive oxygen species (ROS), although the cellular source of these ROS is unknown. We tested the hypotheses that UVA-induced activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is required for ROS generation in human keratinocytes (HK) and that these ROS initiate

Antonio Valencia; Irene E Kochevar

2008-01-01

293

The role of long-lived reactive oxygen intermediates in the reaction of ozone with aerosol particles  

Microsoft Academic Search

The heterogeneous reactions of O3 with aerosol particles are of central importance to air quality. They are studied extensively, but the molecular mechanisms and kinetics remain unresolved. Based on new experimental data and calculations, we show that long-lived reactive oxygen intermediates (ROIs) are formed. The chemical lifetime of these intermediates exceeds 100 seconds, which is much longer than the surface

Manabu Shiraiwa; Yulia Sosedova; Aurélie Rouvière; Hong Yang; Yingyi Zhang; Jonathan P. D. Abbatt; Markus Ammann; Ulrich Pöschl

2011-01-01

294

Dermal Toxicity and Environmental Contamination: Electron Transfer, Reactive Oxygen Species, Oxidative Stress, Cell Signaling, and Protection by Antioxidants  

Microsoft Academic Search

\\u000a Many papers have addressed the role of electron transfer (ET) (electron movement from one site to another), reactive oxygen\\u000a species (ROS), and oxidative stress (OS) in producing cellular insults and, thereby, toxicity in major organs. The present\\u000a review provides evidence for the same mechanistic theme as it applies to skin toxicants.

Peter Kovacic; Ratnasamy Somanathan

295

Role of mast cells in the pathogenesis of postburn inflammatory response: reactive oxygen species as mast cell stimulators  

Microsoft Academic Search

Thermal trauma has a direct effect on mast cells, triggering the secretion of histamine. This secretion leads to an enhanced xanthine oxidase activity and an increased production of reactive oxygen species (ROS), the latter being produced after burns through differing mechanisms. As ROS have been shown to have deleterious effects on cellular membranes, a lesion of the mast cell membrane

F. X Santos; C Arroyo; I Garc??a; R Blasco; J. M Obispo; C Hamann; L Espejo

2000-01-01

296

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

Microsoft Academic Search

BACKGROUND: Cellular damage caused by reactive oxygen species (ROS) has been implicated in several diseases, and hence natural antioxidants have significant importance in human health. The present study was carried out to evaluate the in vitro antioxidant and reactive oxygen species scavenging activities of Terminalia chebula, Terminalia belerica and Emblica officinalis fruit extracts. METHODS: The 70% methanol extracts were studied

Bibhabasu Hazra; Rhitajit Sarkar; Santanu Biswas; Nripendranath Mandal

2010-01-01

297

The Suppressive Effect of Dietary Restriction and Weight Loss in the Obese on the Generation of Reactive Oxygen Species by Leukocytes, Lipid Peroxidation, and Protein Carbonylation  

Microsoft Academic Search

Increased reactive oxygen species generation by the leukocytes of the obese may be responsible for increased oxidative injury to lipids and proteins and, hence, atherosclerosis. We have investigated whether reactive oxygen species generation by leukocytes and other indexes of oxidative damage in the body fall with short-term dietary restriction and weight loss. Nine nondiabetic obese subjects (body mass index, 32.5-

PARESH DANDONA; PRIYA MOHANTY; HUSAM GHANIM; AHMAD ALJADA; RICHARD BROWNE; WAEL HAMOUDA; ANU PRABHALA; AQEELA AFZAL; RAJESH GARG

2010-01-01

298

Reactive Oxygen and Nitrogen Oxide Species-induced Stress, a Major Intrinsic Factor Involved in Carcinogenic Processes and a Possible Target for Cancer Prevention  

Microsoft Academic Search

Reactive oxygen and nitrogen oxide species and their inducing stress are involved in a variety of physiological and pathological phenomena in aerobes, including humans. For multistage carcinogenic processes, reactive oxygen and nitrogen oxide species-induced stress (RONOSS) serves as a major intrinsic factor and is involved in every step. This means that free radicals, RONOSS and their inducing downstream events may

Dai Nakae; Takashi Umemura; Yuji Kurokawa

2002-01-01

299

Heme oxygenase up-regulation in ultraviolet-B irradiated soybean plants involves reactive oxygen species.  

PubMed

Ultraviolet-B (UV-B) radiation has a negative impact on plant cells, and leads to the generation of reactive oxygen species (ROS). Heme oxygenase (HO, EC 1.14.99.3) plays a protective role against oxidative stress in mammals, but little is known about this issue in plants. Here, we report for the first time the response of HO in leaves of soybean (Glycine max L.) plants subjected to UV-B radiation. Under 7.5 and 15 kJ m(-2 )UV-B doses, HO, catalase (CAT, EC 1.11.1.6) and ascorbate peroxidase (APX, EC 1.11.1.11) activities were increased and the production of thiobarbituric acid reactive substances (TBARS) regain control values after 4 h of plant recuperation. Treatment with 30 kJ m(-2) UV-B provoked a decrease in these antioxidant enzyme activities. Immunoblot analysis showed a 4.3 and 3.7-fold increase in HO-1 protein expression after irradiation with 7.5 and 15 kJ m(-2), respectively. HO-1 transcript levels were enhanced (up to 77%) at these doses, as assessed by semi-quantitative RT-PCR. These data demonstrated that increased HO activity was associated with augmented protein expression and transcript levels. Plants pre-treated with the antioxidant ascorbic acid did not show the UV-B-induced up-regulation of HO-1 mRNA, but hydrogen peroxide treatment could mimic this reaction. Our results indicate that HO is up-regulated in a dose-depending manner as a mechanism of cell protection against oxidative damage and that such response occurred as a consequence of HO-1 mRNA enhancement involving ROS. PMID:16703357

Yannarelli, Gustavo G; Noriega, Guillermo O; Batlle, Alcira; Tomaro, Maria L

2006-10-01

300

Reactive Oxygen and Nitrogen Species and Functional Adaptation of the Placenta  

PubMed Central

The placenta regulates fetal growth and development via transport of nutrients and gases, and synthesis and secretion of steroid and peptide hormones. These functions are determined by vascular development and blood flow and by growth and differentiation of the trophoblast, which contains receptors, transporters and enzymes. The placenta generates reactive oxygen species which may contribute to the oxidative stress seen even in normal pregnancy but this is increased in pregnancies complicated by preeclampsia, IUGR and pregestational diabetes where oxidative and nitrative stress have been clearly documented. Nitrative stress is the covalent modification of proteins and DNA by peroxynitrite formed by the interaction of superoxide and nitric oxide. We have demonstrated nitrative stress by localizing nitrotyrosine residues in these placentas and found increased expression of NADPH oxidase (NOX) enzyme isoforms 1 and 5 as a potential source of superoxide generation. The presence of nitrative stress was associated with diminished vascular reactivity of the fetal placental circulation, a situation that could be reproduced by treatment with peroxynitrite in vitro. We find many nitrated proteins in the placenta, including p38 MAP kinase which has a role in development of the villous vasculature. Nitration of p38 MAPK was increased in the preeclamptic placenta and associated with loss of catalytic activity. We hypothesize that nitration of proteins in the placenta including receptors, transporters, enzymes and structural proteins can alter protein and placental function and this influences fetal growth and development. Increasing nitrative stress but a decrease in oxidative stress, measured as protein carbonylation, is found in the placenta with increasing BMI. Formation of peroxynitrite may then consume superoxide, decreasing nitrative stress. As protein carbonylation is a covalent modification at Lys, Arg, Pro and Thr residues the switch from carbonylation to nitration at tyrosine residues may alter protein function and hence placental function. PMID:20110125

Myatt, Leslie

2009-01-01

301

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

PubMed Central

Objectives: Chronic inflammation and oxidative stress are associated with health and the disease status. The objective of the present study was to investigate the association among white blood cell (WBC) counts, neutrophil counts as a WBC subpopulation, and diacron reactive oxygen metabolites (d-ROMs) levels in an asymptomatic population. Methods: The clinical data, including general cardiovascular risk variables and high-sensitivity C-reactive protein (hs-CRP), were collected from 100 female subjects (mean age, 62 years) in outpatient clinics. The correlation of the d-ROMs with hs-CRP, WBC, and neutrophil counts was examined. Results: The mean/median levels were WBC counts 5.9 × 109/L, neutrophil counts 3.6 × 109/L, hs-CRP 0.06 mg/dL, and d-ROMs 359 CURR U. A simple correlation analysis showed a significant positive correlation of the d-ROMs with the WBC counts, neutrophil counts, or hs-CRP levels. The correlation between d-ROMs and neutrophil counts (? = 0.22, P < 0.05), as well as that between d-ROMs and hs-CRP (? = 0.28, P < 0.01), remained significant and independent in a multiple linear regression analysis adjusted for other variables. A multiple linear regression analysis showed that WBC counts had only a positive correlation tendency to the d-ROMs. Conclusions: Neutrophils may be slightly but more involved in the oxidative stress status, as assessed by d-ROMs, in comparison to the overall WBC. Further studies are needed to clarify the biologic mechanism(s) of the observed relationship. PMID:22783470

Kotani, Kazuhiko; Sakane, Naoki

2012-01-01

302

Contribution of Reactive Oxygen Species to para-Aminophenol Toxicity in LLC-PK1 Cells  

PubMed Central

Para-aminophenol (PAP) causes nephrotoxicity by biochemical mechanisms that have not been fully elucidated. PAP can undergo enzymatic or non-enzymatic oxidation to form reactive intermediates. Using modulators of reactive oxygen species (ROS), the role of ROS in PAP toxicity in LLC-PK1 cells was investigated. ROS formation was determined using a fluorescein derivative and viability using alamarBlue. Following treatment of cells with PAP, ROS formation occurred prior to loss of cell viability. Several modulators of ROS were used to identify the pathways involved in PAP toxicity. Viability was improved with catalase treatment, while viability was decreased when cells were treated with superoxide dismutase (SOD). Both catalase and SOD exert their effects outside of cells in the incubation medium, since there was no evidence of uptake of these enzymes in LLC-PK1 cells. In cell-free incubations, hydrogen peroxide (H2O2) was produced when 0.5 mM PAP was included in the incubation medium. Further, SOD greatly increased and catalase greatly decreased H2O2 production in these cell-free incubations. These data suggest that H2O2 formed in the incubation medium contributes to loss of viability following PAP treatment. When cells were coincubated with 0.5 mM PAP and tiron, pyruvate, bathocuproine, 1, 10-phenanthroline, or dimethylthiourea (DMTU), ROS formation was decreased. However, there was minimal improvement in cell viability. Paradoxically, DMTU exacerbated PAP-induced loss of viability. These data suggest ROS are generated in cells exposed to PAP but these species are not the predominant cause of cellular injury. PMID:18396305

Foreman, Brooke D.; Tarloff, Joan B.

2008-01-01

303

Contribution of reactive oxygen species to para-aminophenol toxicity in LLC-PK1 cells.  

PubMed

para-aminophenol (PAP) causes nephrotoxicity by biochemical mechanisms that have not been fully elucidated. PAP can undergo enzymatic or non-enzymatic oxidation to form reactive intermediates. Using modulators of reactive oxygen species (ROS), the role of ROS in PAP toxicity in LLC-PK(1) cells was investigated. ROS formation was determined using a fluorescein derivative and viability using alamarBlue. Following treatment of cells with PAP, ROS formation occurred prior to loss of cell viability. Several modulators of ROS were used to identify the pathways involved in PAP toxicity. Viability was improved with catalase treatment, while viability was decreased when cells were treated with superoxide dismutase (SOD). Both catalase and SOD exert their effects outside of cells in the incubation medium, since there was no evidence of uptake of these enzymes in LLC-PK(1) cells. In cell-free incubations, hydrogen peroxide (H(2)O(2)) was produced when 0.5 mM PAP was included in the incubation medium. Further, SOD greatly increased and catalase greatly decreased H(2)O(2) production in these cell-free incubations. These data suggest that H(2)O(2) formed in the incubation medium contributes to loss of viability following PAP treatment. When cells were coincubated with 0.5 mM PAP and tiron, pyruvate, bathocuproine, 1, 10-phenanthroline, or dimethylthiourea (DMTU), ROS formation was decreased. However, there was minimal improvement in cell viability. Paradoxically, DMTU exacerbated PAP-induced loss of viability. These data suggest that ROS are generated in cells exposed to PAP but these species are not the predominant cause of cellular injury. PMID:18396305

Foreman, Brooke D; Tarloff, Joan B

2008-07-15

304

Phospholipase A2, reactive oxygen species, and lipid peroxidation in cerebral ischemia.  

PubMed

Ischemic stroke is caused by obstruction of blood flow to the brain, resulting in energy failure that initiates a complex series of metabolic events, ultimately causing neuronal death. One such critical metabolic event is the activation of phospholipase A2 (PLA2), resulting in hydrolysis of membrane phospholipids and release of free fatty acids including arachidonic acid, a metabolic precursor for important cell-signaling eicosanoids. PLA2 enzymes have been classified as calcium-dependent cytosolic (cPLA2) and secretory (sPLA2) and calcium-independent (iPLA2) forms. Cardiolipin hydrolysis by mitochondrial sPLA2 disrupts the mitochondrial respiratory chain and increases production of reactive oxygen species (ROS). Oxidative metabolism of arachidonic acid also generates ROS. These two processes contribute to formation of lipid peroxides, which degrade to reactive aldehyde products (malondialdehyde, 4-hydroxynonenal, and acrolein) that covalently bind to proteins/nucleic acids, altering their function and causing cellular damage. Activation of PLA2 in cerebral ischemia has been shown while other studies have separately demonstrated increased lipid peroxidation. To the best of our knowledge no study has directly shown the role of PLA2 in lipid peroxidation in cerebral ischemia. To date, there are very limited data on PLA2 protein by Western blotting after cerebral ischemia, though some immunohistochemical studies (for cPLA2 and sPLA2) have been reported. Dissecting the contribution of PLA2 to lipid peroxidation in cerebral ischemia is challenging due to multiple forms of PLA2, cardiolipin hydrolysis, diverse sources of ROS arising from arachidonic acid metabolism, catecholamine autoxidation, xanthine oxidase activity, mitochondrial dysfunction, activated neutrophils coupled with NADPH oxidase activity, and lack of specific inhibitors. Although increased activity and expression of various PLA2 isoforms have been demonstrated in stroke, more studies are needed to clarify the cellular origin and localization of these isoforms in the brain, their responses in cerebral ischemic injury, and their role in oxidative stress. PMID:16443152

Muralikrishna Adibhatla, Rao; Hatcher, J F

2006-02-01

305

Reactive oxygen species are involved in nickel inhibition of dna repair  

SciTech Connect

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

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

1997-06-01

306

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 (1)O2 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 (1)O2 and acted as a sink for H2O2 and •OH. PMID:25314220

Zhang, Danning; Yan, Shuwen; Song, Weihua

2014-11-01

307

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

308

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

NASA Astrophysics Data System (ADS)

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

Minissale, M.; Congiu, E.; Dulieu, F.

2014-02-01

309

Influence of particle size and reactive oxygen species on cobalt chrome nanoparticle-mediated genotoxicity.  

PubMed

Patients with cobalt chrome (CoCr) metal-on-metal (MOM) implants may be exposed to a wide size range of metallic nanoparticles as a result of wear. In this study we have characterised the biological responses of human fibroblasts to two types of synthetically derived CoCr particles [(a) from a tribometer (30 nm) and (b) thermal plasma technology (20, 35, and 80 nm)] in vitro, testing their dependence on nanoparticle size or the generation of oxygen free radicals, or both. Metal ions were released from the surface of nanoparticles, particularly from larger (80 nm) particles generated by thermal plasma technology. Exposure of fibroblasts to these nanoparticles triggered rapid (2 h) generation of reactive oxygen species (ROS) that could be eliminated by inhibition of NADPH oxidase, suggesting that it was mediated by phagocytosis of the particles. The exposure also caused a more prolonged, MitoQ sensitive production of ROS (24 h), suggesting involvement of mitochondria. Consequently, we recorded elevated levels of aneuploidy, chromosome clumping, fragmentation of mitochondria and damage to the cytoskeleton particularly to the microtubule network. Exposure to the nanoparticles resulted in misshapen nuclei, disruption of mature lamin B1 and increased nucleoplasmic bridges, which could be prevented by MitoQ. In addition, increased numbers of micronuclei were observed and these were only partly prevented by MitoQ, and the incidence of micronuclei and ion release from the nanoparticles were positively correlated with nanoparticle size, although the cytogenetic changes, modifications in nuclear shape and the amount of ROS were not. These results suggest that cells exhibit diverse mitochondrial ROS-dependent and independent responses to CoCr particles, and that nanoparticle size and the amount of metal ion released are influential. PMID:23433773

Raghunathan, Vijay Krishna; Devey, Michael; Hawkins, Sue; Hails, Lauren; Davis, Sean A; Mann, Stephen; Chang, Isaac T; Ingham, Eileen; Malhas, Ashraf; Vaux, David J; Lane, Jon D; Case, Charles P

2013-05-01

310

Inactivation of Primary Antioxidant Enzymes in Mouse Keratinocytes by Photodynamically Generated Singlet Oxygen  

Microsoft Academic Search

Cellular antioxidant enzymes protect against damage caused by exposure to endogenous or exogenous proox- idants. Singlet oxygen ( 1 O 2 ) is a reactive form of oxygen that can be produced in vivo either in normal and pathophysiologic conditions or by photosensitizing chemicals, as during photodynamic treatment. We hypoth- esized that photodynamically generated 1 O 2 would decrease the

Jun Luo; Ling Li; Yuping Zhang; Douglas R. Spitz; Garry R. Buettner; Larry W. Oberley; Frederick E. Domann

2006-01-01

311

The role of mitochondrial reactive oxygen species in cartilage matrix destruction.  

PubMed

Upregulation of matrix metalloproteinases (MMPs) is a hallmark of osteoarthritis progression; along with the role reactive oxygen species (ROS) may play in this process. Moreover, mitochondrial DNA damage and dysfunction are also present in osteoarthritic chondrocytes. However, there are no studies published investigating the direct relationship between mitochondrial ROS, mitochondrial DNA damage, and MMP expression. Therefore, the purpose of the present study was to evaluate whether mitochondrial DNA damage and mitochondrial-originated oxidative stress modulates matrix destruction through the upregulation of MMP protein levels. MitoSox red was utilized to observe mitochondrial ROS production while a Quantitative Southern blot technique was conducted to analyze mitochondrial DNA damage. Additionally, Western blot analysis was used to determine MMP protein levels. The results of the present study show that menadione augmented mitochondrial-generated ROS and increased mitochondrial DNA damage. This increase in mitochondrial-generated ROS led to an increase in MMP levels. When a mitochondrial ROS scavenger was added, there was a subsequent reduction in MMP levels. These studies reveal that mitochondrial integrity is essential for maintaining the cartilage matrix by altering MMP levels. This provides new and important insights into the role of mitochondria in chondrocyte function and its potential importance in therapeutic approaches. PMID:25129057

Reed, Kendra N; Wilson, Glenn; Pearsall, Albert; Grishko, Valentina I

2014-12-01

312

Mitochondrial Respiratory Supercomplex Association Limits Production of Reactive Oxygen Species from Complex I  

PubMed Central

Abstract Aims: The mitochondrial respiratory chain is recognized today to be arranged in supramolecular assemblies (supercomplexes). Besides conferring a kinetic advantage (substrate channeling) and being required for the assembly and stability of Complex I, indirect considerations support the view that supercomplexes may also prevent excessive formation of reactive oxygen species (ROS) from the respiratory chain. In the present study, we have directly addressed this issue by testing the ROS generation by Complex I in two experimental systems in which the supramolecular organization of the respiratory assemblies is impaired by: (i) treatment either of bovine heart mitochondria or liposome-reconstituted supercomplex I-III with dodecyl maltoside; (ii) reconstitution of Complexes I and III at high phospholipids to protein ratio. Results: The results of our investigation provide experimental evidence that the production of ROS is strongly increased in either model, supporting the view that disruption or prevention of the association between Complex I and Complex III by different means enhances the generation of superoxide from Complex I. Innovation: Dissociation of supercomplexes may link oxidative stress and energy failure in a vicious circle. Conclusion: Our findings support a central role of mitochondrial supramolecular structure in the development of the aging process and in the etiology and pathogenesis of most major chronic diseases. Antioxid. Redox Signal. 19, 1469–1480. PMID:23581604

Maranzana, Evelina; Barbero, Giovanna; Falasca, Anna Ida; Lenaz, Giorgio

2013-01-01

313

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

314

The role of intraplatelet reactive oxygen species in the regulation of platelet glycoprotein Ib? ectodomain shedding.  

PubMed

Glycoprotein (GP) Ib? ectodomain shedding has become a generally accepted negative regulatory mechanism of platelet function. Stimulation of platelet with either physiological or chemical compound results in GPIb? ectodomain shedding in vitro and in vivo, the mechanism, however, is not totally understood. Here we show, collagen, thrombin, and calcium ionophore A23187 induce reactive oxygen species (ROS) generation, and simultaneously incur GPIb? ectodomain shedding. ROS scavengers N-acetylcysteine (NAC) and dithiothreitol (DTT) abolish not only collagen, thrombin, and A23187 induced ROS production, but also GPIb? ectodomain shedding. Interestingly, a recognized calpain activator, dibucaine, induces both ROS production and GPIb? shedding, which are also obviously reduced by NAC and DTT. Furthermore, calpain inhibitors calpain inhibitor I and carbobenzoxy-valinyl-phenylalaninal, obviously reduce dibucaine, thrombin, and A23187-induced ROS generation. These data indicate that ROS plays a key role in collagen, thrombin, and A23187-induced GPIb? ectodomain shedding. Calpain is an up-stream regulator that regulates ROS-mediated GPIb? shedding. PMID:24120238

Zhang, Pingping; Du, Juan; Zhao, Lili; Wang, Xiujuan; Zhang, Yiwen; Yan, Rong; Dai, Jin; Liu, Guanglei; Zhang, Feng; Dai, Kesheng

2013-01-01

315

Mitochondrial phospholipase A2 activated by reactive oxygen species in heart mitochondria induces mild uncoupling.  

PubMed

Homeostasis of reactive oxygen species (ROS) in cardiomyocytes is critical for elucidation of normal heart physiology and pathology. Mitochondrial phospholipases A2 (mt-PLA2) have been previously suggested to be activated by ROS. Therefore, we have attempted to elucidate physiological role of such activation. We have found that function of a specific i-isoform of mitochondrial phospholipase A2 (mt-iPLA2) is activated by tert-butylhydroperoxide in isolated rat heart mitochondria. Isoform specificity was judged from the inhibition by bromoenol lactone (BEL), a specific iPLA2 inhibitor. Concomitant uncoupling has been caused by free fatty acids, since it was inhibited by bovine serum albumin. The uncoupling was manifested as a respiration burst accompanied by a slight decrease in mitochondrial inner membrane potential. Since this uncoupling was sensitive to carboxyatractyloside and purine nucleotide di- and tri-phosphates, we conclude that it originated from the onset of fatty acid cycling mediated by the adenine nucleotide translocase (major contribution) and mitochondrial uncoupling protein(s) (minor contribution), respectively. Such a mild uncoupling may provide a feedback downregulation of oxidative stress, since it can further attenuate mitochondrial production of ROS. In conclusion, ROS-induced function of cardiac mt-iPLA2 may stand on a pro-survival side of ischemia-reperfusion injury. PMID:20406040

Ježek, J; Jab?rek, M; Zelenka, J; Ježek, P

2010-01-01

316

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

PubMed

Evidence for Zn protection against Cd-induced reactive oxygen species in the free-floating hydrophyte Ceratophyllum demersum L. is presented in this paper. Metal treatments of 10 micromol/L Cd, 10 Cd micromol/L supplemented with Zn (10, 50, 100 and 200 micromol/L) and Zn-alone treatments of the same concentrations were used. Using 5,5 dimethyl pyrroline-N-oxide as the spin-probe, electron spin resonance spectra indicated a drastic increase in hydroxyl radicals (OH()) in Cd-10 micromol/L treatments, which was closely correlating with the enhanced formation of hydrogen peroxide (H(2)O(2)) and generation of superoxide radical (O(2)(-)) triggered by the oxidation of NADPH. The supplementation of adding Zn (10-200 micromol/L) to the Cd-10 micromol/L treatments significantly decreased the production of free radicals especially by eliminating the precursors of OH() through inhibition of NADPH oxidation. Cd-enhanced ROS production which substantially increased the oxidative products of proteins measured as carbonyls was effectively inhibited by Zn supplementation. PMID:19203717

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

2009-01-01

317

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

NASA Astrophysics Data System (ADS)

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

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

2014-06-01

318

Mechanism of action of phenethylisothiocyanate and other reactive oxygen species-inducing anticancer agents.  

PubMed

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; Safe, Stephen

2014-07-01

319

Reactive-Oxygen-Species-Mediated P. aeruginosa Killing Is Functional in Human Cystic Fibrosis Macrophages  

PubMed Central

Pseudomonas aeruginosa is the most common pathogen for chronic lung infection in cystic fibrosis (CF) patients. About 80% of adult CF patients have chronic P. aeruginosa infection, which accounts for much of the morbidity and most of the mortality. Both bacterial genetic adaptations and defective innate immune responses contribute to the bacteria persistence. It is well accepted that CF transmembrane conductance regulator (CFTR) dysfunction impairs the airways-epithelium-mediated lung defence; however, other innate immune cells also appear to be affected, such as neutrophils and macrophages, which thus contribute to this infectious pathology in the CF lung. In macrophages, the absence of CFTR has been linked to defective P. aeruginosa killing, increased pro-inflammatory cytokine secretion, and reduced reactive oxygen species (ROS) production. To learn more about macrophage dysfunction in CF patients, we investigated the generation of the oxidative burst and its impact on bacterial killing in CF macrophages isolated from peripheral blood or lung parenchyma of CF patients, after P. aeruginosa infection. Our data demonstrate that CF macrophages show an oxidative response of similar intensity to that of non-CF macrophages. Intracellular ROS are recognized as one of the earliest microbicidal mechanisms against engulfed pathogens that are activated by macrophages. Accordingly, NADPH inhibition resulted in a significant increase in the intracellular bacteria survival in CF and non-CF macrophages, both as monocyte-derived macrophages and as lung macrophages. These data strongly suggest that the contribution of ROS to P. aeruginosa killing is not affected by CFTR mutations. PMID:23977124

Cifani, Noemi; Pompili, Barbara; Anile, Marco; Patella, Miriam; Diso, Daniele; Venuta, Federico; Cimino, Giuseppe; Quattrucci, Serena; Di Domenico, Enea Gino; Ascenzioni, Fiorentina; Porto, Paola Del

2013-01-01

320

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

321

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

322

NF-?B Inhibitors from Brucea javanica Exhibiting Intracellular Effects on Reactive Oxygen Species  

PubMed Central

Aim Brucea javanica was studied to identify Nuclear Factor kappaB (NF-?B) inhibitors exhibiting Reactive Oxygen Species (ROS) intracellular amplification. Material and Methods Eight compounds were evaluated for selective cytotoxicity using HT-29, HeLa, and HL-60 cells, and in a NF-?B assay. Active compounds were then tested using ROS and Mitochondria Transmembrane Potential (MTP) assays. NF-?B and Nuclear Factor Activated T cell (NFAT) translocation were also assessed using their respective whole cell assays. Results Bruceajavanone B, bruceantin, bruceine A, (?)-hydnocarpin, and chrysoeriol exhibited cytotoxic potential and NF-?B p65 inhibition. Chrysoeriol exhibited selective cytotoxicity against leukemia cells with greater potency and also showed an ability to up-regulate NFAT transcriptional pathways through the amplification of intracellular ROS, in the presence of H2O2, to a greater degree than bruceantin and bruceine. Conclusion Chrysoeriol selectively kills leukemic cells and potentiates the amplification of ROS levels. Therefore, chrysoeriol could serve as a potential chemotherapeutic modifier for leukemia chemotherapy since leukemia cells have a higher susceptibility to elevated ROS levels. PMID:20944100

Kim, Jeong-Ah; Lau, Edward K.; Pan, Li; Carcache de Blanco, Esperanza J.

2010-01-01

323

Aryl hydrocarbon receptor protects against bacterial infection by promoting macrophage survival and reactive oxygen species production.  

PubMed

Aryl hydrocarbon receptor (AhR) is crucial for various immune responses. The relationship between AhR and infection with the intracellular bacteria Listeria monocytogenes (LM) is poorly understood. Here, we show that in response to LM infection, AhR is required for bacterial clearance by promoting macrophage survival and reactive oxygen species (ROS) production. AhR-deficient mice were more susceptible to listeriosis, and AhR deficiency enhances bacterial growth in vivo and in vitro. On the other hand, pro-inflammatory cytokines were increased in AhR-deficient macrophages infected with LM despite enhanced susceptibility to LM infection in AhR-deficient mice. Subsequent studies demonstrate that AhR protects against macrophage cell death induced by LM infection through the induction of the antiapoptotic factor, the apoptosis inhibitor of macrophages, which promotes macrophage survival in the setting of LM infection. Furthermore, AhR promotes ROS production for bacterial clearance. Our results demonstrate that AhR is essential to the resistance against LM infection as it promotes macrophage survival and ROS production. This suggests that the activation of AhR by its ligands may be an effective strategy against listeriosis. PMID:24343818

Kimura, Akihiro; Abe, Hiromi; Tsuruta, Sanae; Chiba, Sayuri; Fujii-Kuriyama, Yoshiaki; Sekiya, Takashi; Morita, Rimpei; Yoshimura, Akihiko

2014-04-01

324

The dynamics of reactive oxygen species in photodynamic therapy with tetra sulfophenyl-porphyrin.  

PubMed

Photodynamic therapy (PDT) is a promising therapy especially in skin cancer, using the systemic administration of a photosensitizer (PS), followed by the local irradiation of the tumor with visible light. The antitumor effects of PDT are determined especially by the generation of cytotoxic reactive oxygen species (ROS). The 5,10,15,20-tetra-sulfo-phenyl-porphyrin (TSPP) is a synthetic photosensitizer, which proved its efficiency in in vitro studies. Our study evaluates the effects of PDT with TSPP upon the tumor levels of ROS and upon the metalloproteinases 2 (MMP2) activities on Wistar male rats bearing 256 Walker carcinosarcoma in correlation with the accumulation of PS in the tumor and with the intratumor histological alterations. The evaluations were performed dynamically, at 3 hours, 6 hours, 24 hours and 14 days after the PDT with TSPP. Our results emphasize that 24 hours after the PDT with TSPP, the ROS generation increases, as revealed by protein carbonyls and malondialdehyde levels and the antioxidant capacity (hydrogen donors, thiol groups) decreases in the tumor tissue. These parameters were correlated with the appearance of the histological disorders. The MMP-2 activity increases exponentially in the 24 hours-14 days post PDT interval. PDT with TSPP offers, in vivo , consistent results regarding ROS generation, MMP2 activation and cytotoxic capacity. PMID:20233689

Clichici, Simona; Filip, A; Daicoviciu, D; Ion, R M; Mocan, T; Tatomir, C; Rogojan, L; Olteanu, D; Muresan, A

2010-03-01

325

Moscatilin Inhibits Lung Cancer Cell Motility and Invasion via Suppression of Endogenous Reactive Oxygen Species  

PubMed Central

Lung cancer is the leading cause of death among cancer patients worldwide, and most of them have died from metastasis. Migration and invasion are prerequisite processes associated with high metastasis potential in cancers. Moscatilin, a bibenzyl derivative isolated from the Thai orchid Dendrobium pulchellum, has been shown to have anticancer effect against numerous cancer cell lines. However, little is known regarding the effect of moscatilin on cancer cell migration and invasion. The present study demonstrates that nontoxic concentrations of moscatilin were able to inhibit human nonsmall cell lung cancer H23 cell migration and invasion. The inhibitory effect of moscatilin was associated with an attenuation of endogenous reactive oxygen species (ROS), in which hydroxyl radical (OH?) was identified as a dominant species in the suppression of filopodia formation. Western blot analysis also revealed that moscatilin downregulated activated focal adhesion kinase (phosphorylated FAK, Tyr 397) and activated ATP-dependent tyrosine kinase (phosphorylated Akt, Ser 473), whereas their parental counterparts were not detectable changed. In conclusion, our results indicate the novel molecular basis of moscalitin-inhibiting lung cancer cell motility and invasion and demonstrate a promising antimetastatic potential of such an agent for lung cancer therapy. PMID:23738332

Kowitdamrong, Akkarawut; Chanvorachote, Pithi; Sritularak, Boonchoo

2013-01-01

326

Reactive Oxygen Species Are Involved in Plant Defense against a Gall Midge[C][W][OA  

PubMed Central

Reactive oxygen species (ROS) play a major role in plant defense against pathogens, but evidence for their role in defense against insects is still preliminary and inconsistent. In this study, we examined the potential role of ROS in defense of wheat (Triticum aestivum) and rice (Oryza sativa) against Hessian fly (Mayetiola destructor) larvae. Rapid and prolonged accumulation of hydrogen peroxide (H2O2) was detected in wheat plants at the attack site during incompatible interactions. Increased accumulation of both H2O2 and superoxide was detected in rice plants during nonhost interactions with the larvae. No increase in accumulation of either H2O2 or superoxide was observed in wheat plants during compatible interactions. A global analysis revealed changes in the abundances of 250 wheat transcripts and 320 rice transcripts encoding proteins potentially involved in ROS homeostasis. A large number of transcripts encoded class III peroxidases that increased in abundance during both incompatible and nonhost interactions, whereas the levels of these transcripts decreased in susceptible wheat during compatible interactions. The higher levels of class III peroxidase transcripts were associated with elevated enzymatic activity of peroxidases at the attack site in plants during incompatible and nonhost interactions. Overall, our data indicate that class III peroxidases may play a role in ROS generation in resistant wheat and nonhost rice plants during response to Hessian fly attacks. PMID:19965963

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

2010-01-01

327

Spontaneous generation of reactive oxygen species and effect on motility and fertilizability of sea urchin spermatozoa.  

PubMed

Summary We investigated the generation of reactive oxygen species (ROS) by spermatozoa in two species of sea urchin. ROS generation was accompanied by the initiation of motility and respiration and influenced the motility and fertilizability of spermatozoa. The sea urchin performs external fertilization in aerobic seawater. Sperm motility was initiated after spawning through Na+/H+ exchange. ROS generation was dependent on the respiration and sperm concentration and its generation was first observed at initiation of motility, via activation of respiration through ATP/ADP transport. The ROS generation rate increased at higher dilution ratios of spermatozoa, in a manner that was synchronous with the respiratory rate. This phenomenon resembled the previously defined 'sperm dilution effect' on respiration. The loss of motility and fertilizability was induced not only by treatment with hydrogen peroxide but also by sperm dilution. Storage of spermatozoa with a higher dilution ratio also accelerated the decrease in fertilizability. Thus, optimum sea urchin fertilizability is maintained by storage of undiluted spermatozoa on ice, in order to minimize oxidative stress and to maximize longevity. PMID:23174027

Kazama, Makoto; Sato, Taizo; Hino, Akiya

2014-05-01

328

Mechanically induced generation of highly reactive excited-state oxygen molecules in cluster scattering.  

PubMed

Molecular electronic excitation in (O(2))(n) clusters induced by mechanical collisions via the "chemistry with a hammer" is investigated by a combination of molecular dynamics simulations and quantum chemistry calculations. Complete active space self-consistent field augmented with triple-zeta polarizable basis set quantum chemistry calculations of a compressed (O(2))(2) cluster model in various configurations reveal the emergence of possible pathways for the generation of electronically excited singlet O(2) molecules upon cluster compression and vibrational excitation, due to electronic curve-crossing and spin-orbit coupling. Extrapolation of the model (O(2))(2) results to larger clusters suggests a dramatic increase in the population of electronically excited O(2) products, and may account for the recently observed cluster-catalyzed oxidation of silicon surfaces, via singlet oxygen generation induced by cluster impact, followed by surface reaction of highly reactive singlet O(2) molecules. Extensive molecular dynamics simulations of (O(2))(n) clusters colliding onto a hot surface indeed reveal that cluster compression is sufficient under typical experimental conditions for nonadiabatic transitions to occur. This work highlights the importance of nonadiabatic effects in the "chemistry with a hammer." PMID:21322678

Nguyen, Tao-Nhân V; Timerghazin, Qadir K; Vach, Holger; Peslherbe, Gilles H

2011-02-14

329

Inhibitory phlorotannins from the edible brown alga Ecklonia stolonifera on total reactive oxygen species (ROS) generation.  

PubMed

Reactive oxygen species (ROS) play an important role in the pathogenesis of many human degenerative diseases such as cancer, aging, arteriosclerosis, and rheumatism. Much attention has been focused on the development of safe and effective antioxidants. To discover sources of antioxidative activity in marine algae, extracts from 17 kinds of seaweed were screened for their inhibitory effect on total ROS generation in kidney homogenate using 2',7'-dichlorofluorescein diacetate (DCFH-DA). ROS inhibition was seen in three species: Ulva pertusa, Symphyocladia latiuscula, and Ecklonia stolonifera. At a final concentration of 25 microg/mL, U. pertusa inhibited 85.65+/-20.28% of total ROS generation, S. latiscula caused 50.63+/-0.09% inhibitory, and the Ecklonia species was 44.30+/-7.33% inhibition. E. stolonifera Okamura (Laminariaceae), which belongs to the brown algae, has been further investigated because it is commonly used as a foodstuff in Korea. Five compounds, phloroglucinol (1), eckstolonol (2), eckol (3), phlorofucofuroeckol A (4), and dieckol (5), isolated from the ethyl acetate soluble fraction of the methanolic extract of E. stolonifera inhibited total ROS generation. PMID:15022722

Kang, Hye Sook; Chung, Hae Young; Kim, Ji Young; Son, Byeng Wha; Jung, Hyun Ah; Choi, Jae Sue

2004-02-01

330

Modulation of reactive oxygen species by Rac1 or catalase prevents asbestos-induced pulmonary fibrosis  

PubMed Central

The release of reactive oxygen species (ROS) and cytokines by alveolar macrophages has been demonstrated in asbestos-induced pulmonary fibrosis, but the mechanism linking alveolar macrophages to the pathogenesis is not known. The GTPase Rac1 is a second messenger that plays an important role in host defense. In this study, we demonstrate that Rac1 null mice are protected from asbestos-induced pulmonary fibrosis, as determined by histological and biochemical analysis. We hypothesized that Rac1 induced pulmonary fibrosis via generation of ROS. Asbestos increased TNF-? and ROS in a Rac1-dependent manner. TNF-? was elevated only 1 day after exposure, whereas ROS generation progressively increased in bronchoalveolar lavage cells obtained from wild-type (WT) mice. To determine whether ROS generation contributed to pulmonary fibrosis, we overexpressed catalase in WT monocytes and observed a decrease in ROS generation in vitro. More importantly, administration of catalase to WT mice attenuated the development of fibrosis in vivo. For the first time, these results demonstrate that Rac1 plays a crucial role in asbestos-induced pulmonary fibrosis. Moreover, it suggests that a simple intervention may be useful to prevent progression of the disease. PMID:19684199

Murthy, Shubha; Adamcakova-Dodd, Andrea; Perry, Sarah S.; Tephly, Linda A.; Keller, Richard M.; Metwali, Nervana; Meyerholz, David K.; Wang, Yongqiang; Glogauer, Michael; Thorne, Peter S.

2009-01-01

331

The essential oil of bergamot stimulates reactive oxygen species production in human polymorphonuclear leukocytes.  

PubMed

Bergamot (Citrus aurantium L. subsp. bergamia) essential oil (BEO) is used in folk medicine as an antiseptic and anthelminthic and to facilitate wound healing. Evidence indicates that BEO has substantial antimicrobial activity; however its effects on immunity have never been examined. We studied the effects of BEO on reactive oxygen species (ROS) production in human polymorphonuclear leukocytes (PMN) and the role of Ca(2+) in the functional responses evoked by BEO in these cells. Results show that BEO increased intracellular ROS production in human PMN, an effect that required the contribution of extracellular (and, to a lesser extent, of intracellular) Ca(2+) . Bergamot essential oil also significantly increased ROS production induced by the chemotactic peptide N-formyl-Met-Leu-Phe and reduced the response to the protein kinase C activator phorbol myristate acetate. In conclusion, this is the first report showing the ability of BEO to increase ROS production in human PMN. This effect could both contribute to the activity of BEO in infections and in tissue healing as well as underlie an intrinsic proinflammatory potential. The relevance of these findings for the clinical uses of BEO needs careful consideration. PMID:24458921

Cosentino, Marco; Luini, Alessandra; Bombelli, Raffaella; Corasaniti, Maria T; Bagetta, Giacinto; Marino, Franca

2014-08-01

332

Accelerating neuronal aging in in vitro model brain disorders: a focus on reactive oxygen species  

PubMed Central

In this review, we discuss insights gained through the use of stem cell preparations regarding the modeling of neurological diseases, the need for aging neurons derived from pluripotent stem cells to further advance the study of late-onset adult neurological diseases, and the extent to which mechanisms linked to the mismanagement of reactive oxygen species (ROS). The context of these issues can be revealed using the three disease states of Parkinson’s (PD), Alzheimer’s (AD), and schizophrenia, as considerable insights have been gained into these conditions through the use of stem cells in terms of disease etiologies and the role of oxidative stress. The latter subject is a primary area of interest of our group. After discussing the molecular models of accelerated aging, we highlight the role of ROS for the three diseases explored here. Importantly, we do not seek to provide an extensive account of all genetic mutations for each of the three disorders discussed in this review, but we aim instead to provide a conceptual framework that could maximize the gains from merging the approaches of stem cell microsystems and the study of oxidative stress in disease in order to optimize therapeutics and determine new molecular targets against oxidative stress that spare stem cell proliferation and development. PMID:25386139

Campos, Priscila Britto; Paulsen, Bruna S.; Rehen, Stevens K.

2014-01-01

333

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

334

Crocidolite-induced reactive oxygen metabolites generation from human polymorphonuclear leukocytes.  

PubMed

In order to study the mechanism of carcinogenicity of crocidolite asbestos, we have investigated the species of reactive oxygen metabolites (ROM) induced by crocidolite from human polymorphonuclear leukocytes (PMN) utilizing both an electron spin resonance (ESR) spin trapping method with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), and a luminol-dependent chemiluminescence (CL) method. The present study confirms the generation of OH. from human peripheral blood PMN stimulated by UICC crocidolite utilizing ESR. In addition, PMN incubated with 25-400 micrograms/ml of crocidolite produced CL, the intensity of CL increasing in a dose-dependent manner. Superoxide dismutase, catalase, and dimethyl sulfoxide, which are scavengers of O2-, H2O2, and OH., respectively, inhibited the production of crocidolite-stimulated CL from PMN, also in a dose-dependent manner. Sodium azide, an inhibitor of myeloperoxidase (MPO) to produce OCl-, also inhibited CL production. These results suggest the involvement of O2-, H2O2, OH., and OCl- in the production of CL by crocidolite-stimulated PMN. In conclusion, it is proposed that OH. is a key ROM species in the mechanism of crocidolite-induced carcinogenesis. PMID:8055842

Ishizaki, T; Yano, E; Urano, N; Evans, P H

1994-08-01

335

Regulation of reactive oxygen species homeostasis by peroxiredoxins and c-Myc.  

PubMed

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 approximately 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

2009-03-01

336

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

NASA Technical Reports Server (NTRS)

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

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

2002-01-01

337

The role of mitochondrial bioenergetics and reactive oxygen species in coronary collateral growth  

PubMed Central

Coronary collateral growth is a process involving coordination between growth factors expressed in response to ischemia and mechanical forces. Underlying this response is proliferation of vascular smooth muscle and endothelial cells, resulting in an enlargement in the caliber of arterial-arterial anastomoses, i.e., a collateral vessel, sometimes as much as an order of magnitude. An integral element of this cell proliferation is the process known as phenotypic switching in which cells of a particular phenotype, e.g., contractile vascular smooth muscle, must change their phenotype to proliferate. Phenotypic switching requires that protein synthesis occurs and different kinase signaling pathways become activated, necessitating energy to make the switch. Moreover, kinases, using ATP to phosphorylate their targets, have an energy requirement themselves. Mitochondria play a key role in the energy production that enables phenotypic switching, but under conditions where mitochondrial energy production is constrained, e.g., mitochondrial oxidative stress, this switch is impaired. In addition, we discuss the potential importance of uncoupling proteins as modulators of mitochondrial reactive oxygen species production and bioenergetics, as well as the role of AMP kinase as an energy sensor upstream of mammalian target of rapamycin, the master regulator of protein synthesis. PMID:23997092

Pung, Yuh Fen; Sam, Wai Johnn; Hardwick, James P.; Yin, Liya; Ohanyan, Vahagn; Logan, Suzanna; Di Vincenzo, Lola

2013-01-01

338

A small molecule that induces reactive oxygen species via cellular glutathione depletion.  

PubMed

Induction of excessive levels of reactive oxygen species (ROS) by small-molecule compounds has been considered a potentially effective therapeutic strategy against cancer cells, which are often subjected to chronic oxidative stress. However, to elucidate the mechanisms of action of bioactive compounds is generally a time-consuming process. We have recently identified NPD926, a small molecule that induces rapid cell death in cancer cells. Using a combination of two comprehensive and complementary approaches, proteomic profiling and affinity purification, together with the subsequent biochemical assays, we have elucidated the mechanism of action underlying NPD926-induced cell death: conjugation with glutathione mediated by GST, depletion of cellular glutathione and subsequent ROS generation. NPD926 preferentially induced effects in KRAS-transformed fibroblast cells, compared with their untransformed counterparts. Furthermore, NPD926 sensitized cells to inhibitors of system x(c)?, a cystine-glutamate antiporter considered to be a potential therapeutic target in cancers including cancer stem cells. These data show the effectiveness of a newly identified ROS inducer, which targets glutathione metabolism, in cancer treatment. PMID:25011393

Kawamura, Tatsuro; Kondoh, Yasumitsu; Muroi, Makoto; Kawatani, Makoto; Osada, Hiroyuki

2014-10-01

339

Paradoxical action of reactive oxygen species in creation and therapy of cancer.  

PubMed

A great number of comprehensive literature believe that reactive oxygen species (ROS) and their products play a significant role in cell homeostasis maintenance, tissue protection against further insults by controlling cells proliferation through inducing apoptosis, and defending against cancer. ROS is believed to be like a potential double-edged sword in both cancer progression and prevention. Although at low and moderate levels ROS affect some of the most essential mechanisms of cell survival such as proliferation, angiogenesis and tumor invasion, at higher levels these agents can expose cells to detrimental consequences of oxidative stress including DNA damage and apoptosis that result in therapeutic effects on cancer. Understanding the new aspects on molecular mechanisms and signaling pathways modulating creation and therapy of cancers by ROS is critical in development of therapeutic strategies for patients suffering from cancer. This paper presents a general overview and rationale of paradoxical action of ROS in creation and therapy of cancer, tests to be used, and examples of how it may be applied. PMID:24780648

Kardeh, Sina; Ashkani-Esfahani, Soheil; Alizadeh, Ali Mohammad

2014-07-15

340

Heterogeneous assembled nanocomplexes for ratiometric detection of highly reactive oxygen species in vitro and in vivo.  

PubMed

Probes for detecting highly reactive oxygen species (hROS) are critical to both understanding the etiology of the disease and optimizing therapeutic interventions. However, problems such as low stability due to autoxidation and photobleaching and unsuitability for biological application in vitro and in vivo, as well as the high cost and complex procedure in synthesis and modification, largely limit their application. In this work, binary heterogeneous nanocomplexes (termed as C-dots-AuNC) constructed from gold clusters and carbon dots were reported. The fabrication takes full advantages of the inherent active groups on the surface of the nanoparticles to avoid tedious modification and chemical synthetic processes. Additionally, the assembly endowed C-dots-AuNC with improved performance such as the fluorescence enhancement of AuNCs and stability of C-dots to hROS. Moreover, the dual-emission property allows sensitive imaging and monitoring of the hROS signaling in living cells with high contrast. Importantly, with high physiological stability and excellent biocompatibility, C-dots-AuNC allows for the detection of hROS in the model of local ear inflammation. PMID:24873414

Ju, Enguo; Liu, Zhen; Du, Yingda; Tao, Yu; Ren, Jinsong; Qu, Xiaogang

2014-06-24

341

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

342

Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling  

PubMed Central

SUMMARY It is widely appreciated that T cells increase glycolytic flux during activation, however the role of mitochondrial flux is unclear. Here we have shown that mitochondrial metabolism, in the absence of glucose metabolism, was sufficient to support interleukin-2 (IL-2) induction. Furthermore, we used mice with reduced mitochondrial reactive oxygen species (mROS) production in T cells (T-Uqcrfs?/? mice) to show that mitochondria are required for T cell activation to produce mROS for activation of nuclear factor of activated T cells (NFAT) and subsequent IL-2 induction. These mice could not induce antigen-specific expansion of T cells in vivo, however Uqcrfs1?/? T cells retained the ability to proliferate in vivo under lymphopenic conditions. This suggests that Uqcrfs1?/? T cells were not lacking bioenergetically, but rather lacked specific ROS-dependent signaling events needed for antigen-specific expansion. Thus, mitochondrial metabolism is a critical component of T cell activation through production of complex III ROS. PMID:23415911

Sena, Laura A.; Li, Sha; Jairaman, Amit; Prakriya, Murali; Ezponda, Teresa; Hildeman, David A.; Wang, Chyung-Ru; Schumacker, Paul T.; Licht, Jonathan D.; Perlman, Harris; Bryce, Paul J.; Chandel, Navdeep S.

2013-01-01

343

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

PubMed

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

2014-05-01

344

The effect of electromagnetic field on reactive oxygen species production in human neutrophils in vitro.  

PubMed

The present study was undertaken in order to determine the effect of low frequency electromagnetic field (EMF) on reactive oxygen species (ROS) production in human neutrophils in peripheral blood in vitro. We investigated how differently generated EMF and several levels of magnetic induction affect ROS production. To evaluate the level of ROS production, two fluorescent dyes were used: 2'7'-dichlorofluorscein-diacetate and dihydrorhodamine. Phorbol 12-myristate 13-acetate (PMA), known as strong stimulator of the respiratory burst, was also used. Alternating magnetic field was generated by means of Viofor JPS apparatus. Three different levels of magnetic induction have been analyzed (10, 40 and 60 ?T). Fluorescence of dichlorofluorescein and 123 rhodamine was measured by flow cytometry. The experiments demonstrated that only EMF tuned to the calcium ion cyclotron resonance frequency was able to affect ROS production in neutrophils. Statistical analysis showed that this effect depended on magnetic induction value of applied EMF. Incubation in EMF inhibited cell activity slightly in unstimulated neutrophils, whereas the activity of PMA-stimulated neutrophils has increased after incubation in EMF. PMID:23137127

Poniedzialek, Barbara; Rzymski, Piotr; Nawrocka-Bogusz, Honorata; Jaroszyk, Feliks; Wiktorowicz, Krzysztof

2013-09-01

345

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

PubMed

In the advancement of green syntheses and sustainable reactions, enzymatic biocatalysis offers extremely high reaction rates and selectivity that goes far beyond the reach of chemical catalysts; however, these enzymes suffer from typical environmental constraints, e.g. operational temperature, pH and tolerance to oxidative environments. A common hydrolase enzyme, diisopropylfluorophosphatase (DFPase, EC 3.1.8.2), has demonstrated a pronounced efficacy for the hydrolysis of a variety of substrates for potential toxin remediation, but suffers from the aforementioned limitations. As a means to enhance DFPase's stability in oxidative environments, enzymatic covalent immobilization within the polymeric matrix of poly(propylene sulfide) (PPS) nanoparticles was performed. By modifying the enzyme's exposed lysine residues via thiolation, DFPase is utilized as a comonomer/crosslinker in a mild emulsion polymerization. The resultant polymeric polysulfide shell acts as a 'sacrificial barrier' by first oxidizing to polysulfoxides and polysulfones, rendering DFPase in an active state. DFPase-PPS nanoparticles thus retain activity upon exposure to as high as 50 parts per million (ppm) of hypochlorous acid (HOCl), while native DFPase is observed as inactive at 500 parts per billion (ppb). This trend is also confirmed by enzyme-generated (chloroperoxidase (CPO), EC 1.11.1.10) reactive oxygen species (ROS) including both HOCl (3 ppm) and ClO(2) (100 ppm). PMID:22743846

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

2012-07-27

346

Reactive oxygen species promote ovarian cancer progression via the HIF-1?/LOX/E-cadherin pathway.  

PubMed

Reactive oxygen species (ROS) can drive the de?differentiation of tumor cells leading to the process of epithelial-to-mesenchymal transition (EMT) to enhance invasion and metastasis. The invasive and metastatic phenotype of malignant cells is often linked to loss of E-cadherin expression, a hallmark of EMT. Recent studies have demonstrated that hypoxic exposure causes HIF-1-dependent repression of E-cadherin. However, the mechanism by which ROS and/or HIF suppresses E-cadherin expression remains less clear. In the present study, we found that ROS accumulation in ovarian carcinoma cells upregulated HIF-1? expression and subsequent transcriptional induction of lysyl oxidase (LOX) which repressed E-cadherin. Loss of E-cadherin facilitated ovarian cancer (OC) cell migration in vitro and promoted tumor growth in vivo. E-cadherin immunoreactivity correlated with International Federation of Gynecology and Obstetrics (FIGO) stage, tumor differentiation and metastasis. Negative E-cadherin expression along with FIGO stage, tumor differentiation and metastasis significantly predicted for a lower 5-year survival rate. These findings suggest that ROS play an important role in the initiation of metastatic growth of OC cells and support a molecular pathway from ROS to aggressive transformation which involves upregulation of HIF-1? and its downstream target LOX to suppress E-cadherin expression leading to an increase in cell motility and invasiveness. PMID:25174950

Wang, Yu; Ma, Jun; Shen, Haoran; Wang, Chengjie; Sun, Yueping; Howell, Stephen B; Lin, Xinjian

2014-11-01

347

Licochalcone A inhibiting proliferation of bladder cancer T24 cells by inducing reactive oxygen species production.  

PubMed

The aim of this study was to determine the relationship between proliferation inhibition and the production of reactive oxygen species (ROS) induced by Licochalcone A (LCA). Cell viability was evaluated using sulforhodamine B (SRB) assay. Intracellular ROS level was assessed using the 2, 7-dichlorofluorescein diacetate (H2DCFDA) probe and dihydroethidium (DHE) probe assay. The results indicate that LCA inhibits human bladder cancer T24 proliferation in a concentration-dependent manner, with an IC50 value of approximately 55 ?M. The LCA-induced ROS production is inhibited by the co-treatment of LCA and free radical scavenger N-acetyl-cysteine (NAC), on the contrary, the proliferation rate and ROS production increase when treated by the combination of LCA and L-buthionine-(S,R)-sulfoximine (BSO). The ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) decreases in a concentration-dependent manner. The results suggest that LCA inhibits proliferation by increasing intracellular ROS levels resulted in an oxidative stress status in T24 cells. PMID:24211992

Jiang, Jiangtao; Yuan, Xuan; Zhao, Hong; Yan, Xinyan; Sun, Xiling; Zheng, Qiusheng

2014-01-01

348

Role of reactive oxygen species in the defective regeneration seen in aging muscle.  

PubMed

The ability of muscles to regenerate successfully following damage diminishes with age and this appears to be a major contributor to the development of muscle weakness and physical frailty. Successful muscle regeneration is dependent on appropriate reinnervation of regenerating muscle. Age-related changes in the interactions between nerve and muscle are poorly understood but may play a major role in the defective regeneration. During aging there is defective redox homeostasis and an accumulation of oxidative damage in nerve and muscle that may contribute to defective regeneration. The aim of this review is to summarise the evidence that abnormal reactive oxygen species (ROS) generation in nerve and/or muscle may be responsible for the defective regeneration that contributes to the degeneration of skeletal muscle observed during aging. Identifying the importance of ROS generation in skeletal muscle during aging could have fundamental implications for interventions to prevent muscle degeneration and treatments to reverse the age-related decline in muscle mass and function. PMID:23851030

Vasilaki, Aphrodite; Jackson, Malcolm J

2013-12-01

349

Administration of an antioxidant prevents lymphoma development in transmitochondrial mice overproducing reactive oxygen species.  

PubMed

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-ND6(13997)), 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-ND6(13997) 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-ND6(13997). 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

2014-10-30

350

Controllable generation of reactive oxygen species by femtosecond-laser irradiation  

NASA Astrophysics Data System (ADS)

Femtosecond lasers have been advancing Biophotonics research in the past two decades with multiphoton microscopy, microsurgery, and photodynamic therapy. Nevertheless, laser irradiation is identified to bring photodamage to cells via reactive oxygen species (ROS) generation with unclear mechanism. Meanwhile, currently in biological researches, there is no effective method to provide controllable ROS production precisely, which originally is leaked from mitochondria during respiration and plays a key role in a lot of important cellular processes and cellular signaling pathways. In this study, we show the process of how the tightly focused femtosecond-laser induces ROS generation solely in mitochondria at the very beginning and then release to cytosol if the stimulus is intense enough. At certain weak power levels, the laser pulses induce merely moderate Ca2+ release but this is necessary for the laser to generate ROS in mitochondria. Cellular original ROS are also involved with a small contribution. When the power is above a threshold, ROS are then released to cytosol, indicating photodamage overwhelming cellular repair ability. The mechanisms in those two cases are quite different. Those results clarify parts of the mechanism in laser-induced ROS generation. Hence, it is possible to further this optical scheme to provide controllable ROS generation for ROS-related biological researches including mitochondrial diseases and aging.

Yan, Wei; He, Hao; Wang, Yintao; Wang, Yisen; Hu, Minglie; Wang, Chingyue

2014-02-01

351

Mechanisms underlying reductant-induced reactive oxygen species formation by anticancer copper(II) compounds  

PubMed Central

Intracellular generation of reactive oxygen species (ROS) via thiol-mediated reduction of copper(II) to copper(I) has been assumed as the major mechanism underlying the anticancer activity of copper(II) complexes. The aim of this study was to compare the anticancer potential of copper(II) complexes of Triapine (3-amino-pyridine-2-carboxaldehyde thiosemicarbazone; currently in phase II clinical trials) and its terminally dimethylated derivative with that of 2-formylpyridine thiosemicarbazone and that of 2,2?-bipyridyl-6-carbothioamide. Experiments on generation of oxidative stress and the influence of biologically relevant reductants (glutathione, ascorbic acid) on the anticancer activity of the copper complexes revealed that reductant-dependent redox cycling occurred mainly outside the cells, leading to generation and dismutation of superoxide radicals resulting in cytotoxic amounts of H2O2. However, without extracellular reductants only weak intracellular ROS generation was observed at IC50 levels, suggesting that cellular thiols are not involved in copper-complex-induced oxidative stress. Taken together, thiol-induced intracellular ROS generation might contribute to the anticancer activity of copper thiosemicarbazone complexes but is not the determining factor. PMID:22189939

2012-01-01

352

Oleoyl-Lysophosphatidylcholine Limits Endothelial Nitric Oxide Bioavailability by Induction of Reactive Oxygen Species  

PubMed Central

Previously we reported modulation of endothelial prostacyclin and interleukin-8 production, cyclooxygenase-2 expression and vasorelaxation by oleoyl- lysophosphatidylcholine (LPC 18:1). In the present study, we examined the impact of this LPC on nitric oxide (NO) bioavailability in vascular endothelial EA.hy926 cells. Basal NO formation in these cells was decreased by LPC 18:1. This was accompanied with a partial disruption of the active endothelial nitric oxide synthase (eNOS)- dimer, leading to eNOS uncoupling and increased formation of reactive oxygen species (ROS). The LPC 18:1-induced ROS formation was attenuated by the superoxide scavenger Tiron, as well as by the pharmacological inhibitors of eNOS, NADPH oxidases, flavin-containing enzymes and superoxide dismutase (SOD). Intracellular ROS-formation was most prominent in mitochondria, less pronounced in cytosol and undetectable in endoplasmic reticulum. Importantly, Tiron completely prevented the LPC 18:1-induced decrease in NO bioavailability in EA.hy926 cells. The importance of the discovered findings for more in vivo like situations was analyzed by organ bath experiments in mouse aortic rings. LPC 18:1 attenuated the acetylcholine-induced, endothelium dependent vasorelaxation and massively decreased NO bioavailability. We conclude that LPC 18:1 induces eNOS uncoupling and unspecific superoxide production. This results in NO scavenging by ROS, a limited endothelial NO bioavailability and impaired vascular function. PMID:25419657

Kozina, Andrijana; Opresnik, Stefan; Wong, Michael Sze Ka; Hallström, Seth; Graier, Wolfgang F.; Malli, Roland; Schröder, Katrin; Schmidt, Kurt; Frank, Saša

2014-01-01

353

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

354

Spin Biochemistry Modulates Reactive Oxygen Species (ROS) Production by Radio Frequency Magnetic Fields  

PubMed Central

The effects of weak magnetic fields on the biological production of reactive oxygen species (ROS) from intracellular superoxide (O2•?) and extracellular hydrogen peroxide (H2O2) were investigated in vitro with rat pulmonary arterial smooth muscle cells (rPASMC). A decrease in O2•? and an increase in H2O2 concentrations were observed in the presence of a 7 MHz radio frequency (RF) at 10 ?TRMS and static 45 ?T magnetic fields. We propose that O2•? and H2O2 production in some metabolic processes occur through singlet-triplet modulation of semiquinone flavin (FADH•) enzymes and O2•? spin-correlated radical pairs. Spin-radical pair products are modulated by the 7 MHz RF magnetic fields that presumably decouple flavin hyperfine interactions during spin coherence. RF flavin hyperfine decoupling results in an increase of H2O2 singlet state products, which creates cellular oxidative stress and acts as a secondary messenger that affects cellular proliferation. This study demonstrates the interplay between O2•? and H2O2 production when influenced by RF magnetic fields and underscores the subtle effects of low-frequency magnetic fields on oxidative metabolism, ROS signaling, and cellular growth. PMID:24681944

Usselman, Robert J.; Hill, Iain; Singel, David J.; Martino, Carlos F.

2014-01-01

355

Reactive oxygen species and the structural remodeling of the visual system after ocular enucleation.  

PubMed

Redox processes associated with controlled generation of reactive oxygen species (ROS) by NADPH oxidase (Nox) add an essential level of regulation to signaling pathways underlying physiological processes. We evaluated the ROS generation in the main visual relays of the mammalian brain, namely the superior colliculus (SC) and the dorsal lateral geniculate nucleus (DLG), after ocular enucleation in adult rats. Dihydroethidium (DHE) oxidation revealed increased ROS generation in SC and DLG between 1 and 30 days postlesion. ROS generation was decreased by the Nox inhibitors diphenyleneiodonium chloride (DPI) and apocynin. Real-time PCR results revealed that Nox 2 was upregulated in both retinorecipient structures after deafferentation, whereas Nox 1 and Nox 4 were upregulated only in the SC. To evaluate the role of ROS in structural remodeling after the lesions, apocynin was given to enucleated rats and immunohistochemistry was conducted for markers of neuronal remodeling into SC and DLG. Immunohistochemical data showed that ocular enucleation produces an increase of neurofilament and microtubule-associated protein-2 immunostaining in both SC and DLG, which was markedly attenuated by apocynin treatment. Taken together, the findings of the present study suggest a novel role for Nox-induced ROS signaling in mediating neuronal remodeling in visual areas after ocular enucleation. PMID:20728508

Hernandes, M S; Britto, L R G; Real, C C; Martins, D O; Lopes, L R

2010-11-10

356

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

357

Reactive Oxygen Species Scavenging by Catalase Is Important for Female Lutzomyia longipalpis Fecundity and Mortality  

E-print Network

The phlebotomine sand fly Lutzomyia longipalpis is the most important vector of American visceral leishmaniasis (AVL), the disseminated and most serious form of the disease in Central and South America. In the natural environment, most female L. longipalpis are thought to survive for less than 10 days and will feed on blood only once or twice during their lifetime. Successful transmission of parasites occurs when a Leishmania-infected female sand fly feeds on a new host. Knowledge of factors affecting sand fly longevity that lead to a reduction in lifespan could result in a decrease in parasite transmission. Catalase has been found to play a major role in survival and fecundity in many insect species. It is a strong antioxidant enzyme that breaks down toxic reactive oxygen species (ROS). Ovarian catalase was found to accumulate in the developing sand fly oocyte from 12 to 48 hours after blood feeding. Catalase expression in ovaries as well as oocyte numbers was found to decrease with age. This reduction was not found in flies when fed on the antioxidant ascorbic acid in the sugar meal, a condition that increased mortality and activation of the prophenoloxidase cascade. RNA interference was used to silence catalase gene expression in female Lu. longipalpis. Depletion of catalase led to a significant increase of mortality and a reduction in the number of developing oocytes produced after blood feeding. These results demonstrate the central role

Hector Diaz-albiter; Roanna Mitford; O A. Genta; Mauricio R. V. Sant’anna; Rod J. Dillon

2010-01-01

358

Reactive oxygen species production in mitochondria of human gingival fibroblast induced by blue light irradiation.  

PubMed

In recent years, it has become well known that the production of reactive oxygen species (ROS) induced by blue-light irradiation causes adverse effects of photo-aging, such as age-related macular degeneration of the retina. Thus, orange-tinted glasses are used to protect the retina during dental treatment involving blue-light irradiation (e.g., dental resin restorations or tooth bleaching treatments). However, there are few studies examining the effects of blue-light irradiation on oral tissue. For the first time, we report that blue-light irradiation by quartz tungsten halogen lamp (QTH) or light-emitting diode (LED) decreased cell proliferation activity of human gingival fibroblasts (HGFs) in a time-dependent manner (<5 min). Additionally, in a morphological study, the cytotoxic effect was observed in the cell organelles, especially the mitochondria. Furthermore, ROS generation induced by the blue-light irradiation was detected in mitochondria of HGFs using fluorimetry. In all analyses, the cytotoxicity was significantly higher after LED irradiation compared with cytotoxicity after QTH irradiation. These results suggest that blue light irradiation, especially by LED light sources used in dental aesthetic treatment, might have adverse effects on human gingival tissue. Hence, this necessitates the development of new dental aesthetic treatment methods and/or techniques to protect HGFs from blue light irradiation during dental therapy. PMID:24141287

Yoshida, Ayaka; Yoshino, Fumihiko; Makita, Tetsuya; Maehata, Yojiro; Higashi, Kazuyoshi; Miyamoto, Chihiro; Wada-Takahashi, Satoko; Takahashi, Shun-suke; Takahashi, Osamu; Lee, Masaichi Chang-il

2013-12-01

359

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

NASA Astrophysics Data System (ADS)

In the advancement of green syntheses and sustainable reactions, enzymatic biocatalysis offers extremely high reaction rates and selectivity that goes far beyond the reach of chemical catalysts; however, these enzymes suffer from typical environmental constraints, e.g. operational temperature, pH and tolerance to oxidative environments. A common hydrolase enzyme, diisopropylfluorophosphatase (DFPase, EC 3.1.8.2), has demonstrated a pronounced efficacy for the hydrolysis of a variety of substrates for potential toxin remediation, but suffers from the aforementioned limitations. As a means to enhance DFPase’s stability in oxidative environments, enzymatic covalent immobilization within the polymeric matrix of poly(propylene sulfide) (PPS) nanoparticles was performed. By modifying the enzyme’s exposed lysine residues via thiolation, DFPase is utilized as a comonomer/crosslinker in a mild emulsion polymerization. The resultant polymeric polysulfide shell acts as a ‘sacrificial barrier’ by first oxidizing to polysulfoxides and polysulfones, rendering DFPase in an active state. DFPase-PPS nanoparticles thus retain activity upon exposure to as high as 50 parts per million (ppm) of hypochlorous acid (HOCl), while native DFPase is observed as inactive at 500 parts per billion (ppb). This trend is also confirmed by enzyme-generated (chloroperoxidase (CPO), EC 1.11.1.10) reactive oxygen species (ROS) including both HOCl (3 ppm) and ClO2 (100 ppm).

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

2012-07-01

360

Role of NADPH Oxidase-Mediated Reactive Oxygen Species in Podocyte Injury  

PubMed Central

Proteinuria is an independent risk factor for end-stage renal disease (ESRD) (Shankland, 2006). Recent studies highlighted the mechanisms of podocyte injury and implications for potential treatment strategies in proteinuric kidney diseases (Zhang et al., 2012). Reactive oxygen species (ROS) are cellular signals which are closely associated with the development and progression of glomerular sclerosis. NADPH oxidase is a district enzymatic source of cellular ROS production and prominently expressed in podocytes (Zhang et al., 2010). In the last decade, it has become evident that NADPH oxidase-derived ROS overproduction is a key trigger of podocyte injury, such as renin-angiotensin-aldosterone system activation (Whaley-Connell et al., 2006), epithelial-to-mesenchymal transition (Zhang et al., 2011), and inflammatory priming (Abais et al., 2013). This review focuses on the mechanism of NADPH oxidase-mediated ROS in podocyte injury under different pathophysiological conditions. In addition, we also reviewed the therapeutic perspectives of NADPH oxidase in kidney diseases related to podocyte injury. PMID:24319690

Chen, Shan; Meng, Xian-Fang; Zhang, Chun

2013-01-01

361

Hypoxia induces adipocyte differentiation of adipose-derived stem cells by triggering reactive oxygen species generation.  

PubMed

Generation of reactive oxygen species (ROS) by NADPH oxidase 4 (Nox4) induces the proliferation and migration of adipose-derived stem cells (ASCs). However, the functional role of mitochondrial ROS (mtROS) generation in ASCs is unknown. Therefore, we have investigated whether hypoxia induces the differentiation of ASCs via ROS generation. We also have tried to identify the cellular mechanisms of ROS generation underlying adipocyte differentiation. Hypoxia (2%) and ROS generators, such as antimycin and rotenone, induced adipocyte differentiation, which was attenuated by an ROS scavenger. Although Nox4 generates ROS and regulates proliferation of ASCs, Nox4 inhibition or Nox4 silencing did not inhibit adipocyte differentiation; indeed fluorescence intensity of mito-SOX increased in hypoxia, and treatment with mito-CP, a mtROS scavenger, significantly reduced hypoxia-induced adipocyte differentiation. Phosphorylation of Akt and mTOR was induced by hypoxia, while inhibition of these molecules prevented adipocyte differentiation. Thus hypoxia induces adipocyte differentiation by mtROS generation, and the PI3K/Akt/mTOR pathway is involved. PMID:23956071

Kim, Ji Hye; Kim, Seok-Ho; Song, Seung Yong; Kim, Won-Serk; Song, Sun U; Yi, TacGhee; Jeon, Myung-Shin; Chung, Hyung-Min; Xia, Ying; Sung, Jong-Hyuk

2014-01-01

362

NRROS negatively regulates reactive oxygen species during host defence and autoimmunity.  

PubMed

Reactive oxygen species (ROS) produced by phagocytes are essential for host defence against bacterial and fungal infections. Individuals with defective ROS production machinery develop chronic granulomatous disease. Conversely, excessive ROS can cause collateral tissue damage during inflammatory processes and therefore needs to be tightly regulated. Here we describe a protein, we termed negative regulator of ROS (NRROS), which limits ROS generation by phagocytes during inflammatory responses. NRROS expression in phagocytes can be repressed by inflammatory signals. NRROS-deficient phagocytes produce increased ROS upon inflammatory challenges, and mice lacking NRROS in their phagocytes show enhanced bactericidal activity against Escherichia coli and Listeria monocytogenes. Conversely, these mice develop severe experimental autoimmune encephalomyelitis owing to oxidative tissue damage in the central nervous system. Mechanistically, NRROS is localized to the endoplasmic reticulum, where it directly interacts with nascent NOX2 (also known as gp91(phox) and encoded by Cybb) monomer, one of the membrane-bound subunits of the NADPH oxidase complex, and facilitates the degradation of NOX2 through the endoplasmic-reticulum-associated degradation pathway. Thus, NRROS provides a hitherto undefined mechanism for regulating ROS production--one that enables phagocytes to produce higher amounts of ROS, if required to control invading pathogens, while minimizing unwanted collateral tissue damage. PMID:24739962

Noubade, Rajkumar; Wong, Kit; Ota, Naruhisa; Rutz, Sascha; Eidenschenk, Celine; Valdez, Patricia A; Ding, Jiabing; Peng, Ivan; Sebrell, Andrew; Caplazi, Patrick; DeVoss, Jason; Soriano, Robert H; Sai, Tao; Lu, Rongze; Modrusan, Zora; Hackney, Jason; Ouyang, Wenjun

2014-05-01

363

Reactive Oxygen Species in the Signaling and Adaptation of Multicellular Microbial Communities  

PubMed Central

One of the universal traits of microorganisms is their ability to form multicellular structures, the cells of which differentiate and communicate via various signaling molecules. Reactive oxygen species (ROS), and hydrogen peroxide in particular, have recently become well-established signaling molecules in higher eukaryotes, but still little is known about the regulatory functions of ROS in microbial structures. Here we summarize current knowledge on the possible roles of ROS during the development of colonies and biofilms, representatives of microbial multicellularity. In Saccharomyces cerevisiae colonies, ROS are predicted to participate in regulatory events involved in the induction of ammonia signaling and later on in programmed cell death in the colony center. While the latter process seems to be induced by the total ROS, the former event is likely to be regulated by ROS-homeostasis, possibly H2O2-homeostasis between the cytosol and mitochondria. In Candida albicans biofilms, the predicted signaling role of ROS is linked with quorum sensing molecule farnesol that significantly affects biofilm formation. In bacterial biofilms, ROS induce genetic variability, promote cell death in specific biofilm regions, and possibly regulate biofilm development. Thus, the number of examples suggesting ROS as signaling molecules and effectors in the development of microbial multicellularity is rapidly increasing. PMID:22829965

Cap, Michal; Vachova, Libuse; Palkova, Zdena

2012-01-01

364

Mitochondrial Dysfunction and Increased Reactive Oxygen Species Impair Insulin Secretion in Sphingomyelin Synthase 1-null Mice*  

PubMed Central

Sphingomyelin synthase 1 (SMS1) catalyzes the conversion of ceramide to sphingomyelin. Here, we generated and analyzed SMS1-null mice. SMS1-null mice exhibited moderate neonatal lethality, reduced body weight, and loss of fat tissues mass, suggesting that they might have metabolic abnormality. Indeed, analysis on glucose metabolism revealed that they showed severe deficiencies in insulin secretion. Isolated mutant islets exhibited severely impaired ability to release insulin, dependent on glucose stimuli. Further analysis indicated that mitochondria in mutant islet cells cannot up-regulate ATP production in response to glucose. We also observed additional mitochondrial abnormalities, such as hyperpolarized membrane potential and increased levels of reactive oxygen species (ROS) in mutant islets. Finally, when SMS1-null mice were treated with the anti-oxidant N-acetyl cysteine, we observed partial recovery of insulin secretion, indicating that ROS overproduction underlies pancreatic ?-cell dysfunction in SMS1-null mice. Altogether, our data suggest that SMS1 is important for controlling ROS generation, and that SMS1 is required for normal mitochondrial function and insulin secretion in pancreatic ?-cells. PMID:21115496

Yano, Masato; Watanabe, Ken; Yamamoto, Tadashi; Ikeda, Kazutaka; Senokuchi, Takafumi; Lu, Meihong; Kadomatsu, Tsuyoshi; Tsukano, Hiroto; Ikawa, Masahito; Okabe, Masaru; Yamaoka, Shohei; Okazaki, Toshiro; Umehara, Hisanori; Gotoh, Tomomi; Song, Wen-Jie; Node, Koichi; Taguchi, Ryo; Yamagata, Kazuya; Oike, Yuichi

2011-01-01

365

Low Po? conditions induce reactive oxygen species formation during contractions in single skeletal muscle fibers.  

PubMed

Contractions in whole skeletal muscle during hypoxia are known to generate reactive oxygen species (ROS); however, identification of real-time ROS formation within isolated single skeletal muscle fibers has been challenging. Consequently, there is no convincing evidence showing increased ROS production in intact contracting fibers under low Po? conditions. Therefore, we hypothesized that intracellular ROS generation in single contracting skeletal myofibers increases during low Po? compared with a value approximating normal resting Po?. Dihydrofluorescein was loaded into single frog (Xenopus) fibers, and fluorescence was used to monitor ROS using confocal microscopy. Myofibers were exposed to two maximal tetanic contractile periods (1 contraction/3 s for 2 min, separated by a 60-min rest period), each consisting of one of the following treatments: high Po? (30 Torr), low Po? (3-5 Torr), high Po? with ebselen (antioxidant), or low Po? with ebselen. Ebselen (10 ?M) was administered before the designated contractile period. ROS formation during low Po? treatment was greater than during high Po? treatment, and ebselen decreased ROS generation in both low- and high-Po? conditions (P < 0.05). ROS accumulated at a faster rate in low vs. high Po?. Force was reduced >30% for each condition except low Po? with ebselen, which only decreased ~15%. We concluded that single myofibers under low Po? conditions develop accelerated and more oxidative stress than at Po? = 30 Torr (normal human resting Po?). Ebselen decreases ROS formation in both low and high Po?, but only mitigates skeletal muscle fatigue during reduced Po? conditions. PMID:23576612

Zuo, Li; Shiah, Amy; Roberts, William J; Chien, Michael T; Wagner, Peter D; Hogan, Michael C

2013-06-01

366

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

367

A Mitogen-activated protein kinase kinase kinase mediates reactive oxygen species homeostasis in Arabidopsis.  

PubMed

Mitogen-activated protein kinase kinase kinases (MAPKKKs) play key roles in intra- and extracellular signaling in eukaryotes. Here we report that the MAPKKK MEKK1 regulates redox homeostasis in Arabidopsis. We show that MEKK1-deficient plants are misregulated in the expression of a number of genes involved in cellular redox control and accumulate reactive oxygen species (ROS). Most strikingly, homozygous mekk1 mutant plants exhibit a lethal phenotype when developing true leaves. MEKK1 kinase activity and protein stability was regulated by H(2)O(2) in a proteasome-dependent manner and mekk1 plants were compromised in ROS-induced MAPK MPK4 activation. Whereas mpk3 and mpk6 knock out plants showed no defects in development or changes in redox control genes, mpk4 null mutant shared several phenotypic and transcript profile features with mekk1 plants. In agreement with the concept that ROS negatively regulates auxin responses in plants, mekk1 and mpk4 mutants show reduced expression of several auxin-inducible marker genes. Overall, our data defines MPK4 as downstream target of MEKK1 and show that MEKK1 functions in integrating ROS homeostasis with plant development and hormone signaling. PMID:17043356

Nakagami, Hirofumi; Soukupová, Hanka; Schikora, Adam; Zárský, Viktor; Hirt, Heribert

2006-12-15

368

Emerging roots alter epidermal cell fate through mechanical and reactive oxygen species signaling.  

PubMed

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

2012-08-01

369

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

370

The influence of reactive oxygen species on cell cycle progression in mammalian cells.  

PubMed

Cell cycle regulation is performed by cyclins and cyclin dependent kinases (CDKs). Recently, it has become clear that reactive oxygen species (ROS) influence the presence and activity of these enzymes and thereby control cell cycle progression. In this review, we first describe the discovery of enzymes specialized in ROS production: the NADPH oxidase (NOX) complexes. This discovery led to the recognition of ROS as essential players in many cellular processes, including cell cycle progression. ROS influence cell cycle progression in a context-dependent manner via phosphorylation and ubiquitination of CDKs and cell cycle regulatory molecules. We show that ROS often regulate ubiquitination via intermediate phosphorylation and that phosphorylation is thus the major regulatory mechanism influenced by ROS. In addition, ROS have recently been shown to be able to activate growth factor receptors. We will illustrate the diverse roles of ROS as mediators in cell cycle regulation by incorporating phosphorylation, ubiquitination and receptor activation in a model of cell cycle regulation involving EGF-receptor activation. We conclude that ROS can no longer be ignored when studying cell cycle progression. PMID:22981713

Verbon, Eline Hendrike; Post, Jan Andries; Boonstra, Johannes

2012-12-10

371

Lonidamine extends lifespan of adult Caenorhabditis elegans by increasing the formation of mitochondrial reactive oxygen species.  

PubMed

Compounds that delay aging in model organisms may be of significant interest to antiaging medicine, since these substances potentially provide pharmaceutical approaches to promote healthy lifespan in humans. The aim of the study was to test whether pharmaceutical concentrations of the glycolytic inhibitor lonidamine are capable of extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans. Several hundreds of adult C. elegans roundworms were maintained on agar plates and fed E. coli strain OP50 bacteria. Lonidamine was applied to test whether it may promote longevity by quantifying survival in the presence and absence of the compound. In addition, several biochemical and metabolic assays were performed with nematodes exposed to lonidamine. Lonidamine significantly extends both median and maximum lifespan of C. elegans when applied at a concentration of 5 micromolar by 8% each. Moreover, the compound increases paraquat stress resistance, and promotes mitochondrial respiration, culminating in increased formation of reactive oxygen species (ROS). Extension of lifespan requires activation of pmk-1, an orthologue of p38 MAP kinase, and is abolished by co-application of an antioxidant, indicating that increased ROS formation is required for the extension of lifespan by lonidamine. Consistent with the concept of mitohormesis, lonidamine is capable of promoting longevity in a pmk-1 sensitive manner by increasing formation of ROS. PMID:21932172

Schmeisser, S; Zarse, K; Ristow, M

2011-09-01

372

Mitochondrial calcium and reactive oxygen species regulate agonist-initiated platelet phosphatidylserine exposure  

PubMed Central

Objective To study the interactions of cytoplasmic calcium (Ca2+cyt) elevation, mitochondrial permeability transition pore (mPTP) formation, and reactive oxygen species (ROS) formation in the regulation of phosphatidylserine (PS) exposure in platelets. Methods and results mPTP formation, but not the degree of Ca2+cyt elevation, was associated with PS exposure in wild-type, CypD null, ionomycin-treated and ROS-treated platelets. In the absence of the mPTP regulator cyclophilin D agonist-initiated mPTP formation and high-level PS exposure were markedly blunted, but Ca2+cyt transients were unchanged. Mitochondrial calcium (Ca2+mit) transients and ROS, key regulators of mPTP formation, were examined in strongly-stimulated platelets. Increased ROS production occurred in strongly-stimulated platelets and was dependent on extracellular calcium entry, but not the presence of CypD. Ca2+mit increased significantly in strongly-stimulated platelets. Abrogation of Ca2+mit entry either by inhibition of the mitochondrial calcium uniporter or mitochondrial depolarization prevented mPTP formation and exposure, but not platelet aggregation or granule release. Conclusions Sustained Ca2+cyt levels are necessary, but not sufficient, for high-level PS exposure in response to agonists. Increased Ca2+mit levels are a key signal initiating mPTP formation and PS exposure. Blockade of Ca2+mit entry allows the specific inhibition of platelet procoagulant activity. PMID:23087357

Choo, Hyo-Jung; Saafir, Talib B.; Mkumba, Laura; Wagner, Mary B.; Jobe, Shawn M.

2012-01-01

373

Silver nanoparticle-algae interactions: oxidative dissolution, reactive oxygen species generation and synergistic toxic effects.  

PubMed

The short-term toxicity of citrate-stabilized silver nanoparticles (AgNPs) and ionic silver Ag(I) to the ichthyotoxic marine raphidophyte Chattonella marina has been examined using the fluorometric indicator alamarBlue. Aggregation and dissolution of AgNPs occurred after addition to GSe medium while uptake of dissolved Ag(I) occurred in the presence of C. marina. Based on total silver mass, toxicity was much higher for Ag(I) than for AgNPs. Cysteine, a strong Ag(I) ligand, completely removed the inhibitory effects of Ag(I) and AgNPs on the metabolic activity of C. marina, suggesting that the toxicity of AgNPs was due to the release of Ag(I). Synergistic toxic effects of AgNPs/Ag(I) and C. marina to fish gill cells were observed with these effects possibly attributable to enhancement in the generation of reactive oxygen species by C. marina on exposure of the organism to silver. PMID:22816991

He, Di; Dorantes-Aranda, Juan José; Waite, T David

2012-08-21

374

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

375

Regulation of reactive-oxygen-species generation in fibroblasts by Rac1.  

PubMed Central

In a variety of non-phagocytic cell types, there is a marked increase in intracellular levels of reactive oxygen species (ROS), including superoxide and H2O2, after ligand stimulation. We demonstrate that in NIH 3T3 cells transient expression of constitutively activated forms of the small GTP-binding proteins Ras or Rac1 leads to a significant increase in intracellular ROS. An increase in intracellular ROS is also demonstrated after growth factor [platelet-derived growth factor (PDGF) or epidermal growth factor (EGF)] or cytokine [tumour necrosis factor-alpha (TNF-alpha) or interleukin (IL)-1 beta] stimulation of NIH 3T3 cells. Expression of a dominant negative allele of Rac1 inhibits the rise in ROS seen after Ras expression or after stimulation by either growth factors or cytokines. These results provide the first demonstration of the pathway by which ligand stimulation of ROS occurs in non-phagocytic cells and suggest that the family of Ras-related small GTP-binding proteins may function as regulators of the intracellular redox state. PMID:8809022

Sundaresan, M; Yu, Z X; Ferrans, V J; Sulciner, D J; Gutkind, J S; Irani, K; Goldschmidt-Clermont, P J; Finkel, T

1996-01-01

376

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

377

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

378

Digital Image Analysis of Reactive Oxygen Species and CA2+ in Mouse 3T3 Fibroblasts  

NASA Astrophysics Data System (ADS)

Recently, analysis of digital images with confocal microscope has become a routine technique and indispensable tool for cell biological studies and molecular investigations. Because the light emitted from the point out-of-focus is blocked by the pinhole and can not reach the detector, thus only an image of the fluorescence from the focal plane is imaged. In present studies, we use the probes 2', 7'-dichlorof luorescein diacetate (H2DCF-DA) and Fluo-3 AM to research reactive oxygen species (ROS) and Ca2+ in mouse 3T3 fibroblasts, respectively. Our results indicate that the distribution of ROS and Ca2+ were clearly seen in mouse 3T3 fibroblasts. Moreover, we acquired and quantified the fluorescence intensity of ROS and Ca2+ with Leica Confocal Software. It was found that the quantified fluorescence intensity of ROS and Ca2+ was 123.30.26±8.99 and 125.13±12.16, respectively. Taken together, our results indicate that it is a good method to research the distribution and fluorescence intensity of ROS and Ca2+ in cultured cells with confocal microscope.

Xu, Hongzhi; Liu, Dongwu; Chen, Zhiwei

379

Hyperthermia induces apoptosis through endoplasmic reticulum and reactive oxygen species in human osteosarcoma cells.  

PubMed

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

380

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

381

?-lipoic acid protects dopaminergic neurons against MPP+-induced apoptosis by attenuating reactive oxygen species formation.  

PubMed

Reactive oxygen species (ROS) elicited by oxidative stress are widely recognized as a major initiator in the dege-neration of dopaminergic neurons distinctive of Parkinson's disease (PD). The interaction of ROS with mitochondria triggers sequential events in the mitochondrial cell death pathway, which is thought to be responsible for ROS-mediated neurodegeneration in PD. ?-lipoic acid (LA) is a pleiotropic compound with potential pharmacotherapeutic value against a range of pathophysiological insults. Its protective actions against oxidative damage by scavenging ROS and reducing production of free radicals have been reported in various in vitro and in vivo systems. This study analyzed the ability of LA to protect PC12 neuronal cells from toxicity of 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which is known to kill dopaminergic neurons selectively and to cause severe parkinsonism-like symptoms in humans and primate animals. Our results demonstrate that the apoptosis of PC12 cells elicited by MPP+ could be significantly prevented by pretreatment with LA for 1 h. In addition, LA inhibits intercellular ROS levels and the mitochondrial transmembrane permeability, the key players in the pathogenesis of PD, thereby protecting dopaminergic neuronal cells against oxidative damage. PMID:23615851

Li, Da-Wei; Li, Guang-Ren; Lu, Yan; Liu, Zhi-Qiang; Chang, Ming; Yao, Ming; Cheng, Wei; Hu, Lin-Sen

2013-07-01

382

Repetition rate dependency of reactive oxygen species formation during femtosecond laser-based cell surgery  

NASA Astrophysics Data System (ADS)

Femtosecond (fs) laser-based cell surgery is typically done in two different regimes, at kHz or MHz repetition rate. Formation of reactive oxygen species (ROS) is an often predicted effect due to illumination with short laser pulses in biological tissue. We present our study on ROS formation in single cells in response to irradiation with fs laser pulses depending on the repetition rate while focusing into the cell nucleus. We observed a significant increase of ROS concentration directly after manipulation followed by a decrease in both regimes at kHz and MHz repetition rate. In addition, effects of consecutive exposures at MHz and kHz repetition rate and vice versa on ROS production were studied. Irradiation with a MHz pulse train followed by a kHz pulse train resulted in a significantly higher increase of ROS concentration than in the reversed case and often caused cell death. In the presence of the antioxidant ascorbic acid, accumulation of ROS and cell death were strongly reduced. Therefore, addition of antioxidants during fs laser-based cell surgery experiments could be advantageous in terms of suppressing photochemical damage to the cell.

Baumgart, Judith; Kuetemeyer, Kai; Bintig, Willem; Ngezahayo, Anaclet; Ertmer, Wolfgang; Lubatschowski, Holger; Heisterkamp, Alexander

2009-09-01

383

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

384

PKC? Regulates T-Cell Leukemia-Initiating Activity via Reactive Oxygen Species  

PubMed Central

Reactive oxygen species (ROS), a by-product of cellular metabolism, damage intracellular macromolecules and, in excess, can promote normal hematopoietic stem cell differentiation and exhaustion1–3. However, mechanisms that regulate ROS levels in leukemia-initiating cells (LICs) and the biological role of ROS in these cells remain largely unknown. We show here the ROSlow subset of CD44+ cells in T-cell acute lymphoblastic leukemia (T-ALL), a malignancy of immature T-cell progenitors, to be highly enriched in the most aggressive LICs, and that ROS are maintained at low levels by downregulation of protein kinase C theta (PKC?). Strikingly, primary mouse T-ALLs lacking PKC? show improved LIC activity whereas enforced PKC? expression in both mouse and human primary T-ALLs compromised LIC activity. We also demonstrate that PKC? is positively regulated by RUNX1, and that NOTCH1, which is frequently activated by mutation in T-ALL4–6 and required for LIC activity in both mouse and human models7,8, downregulates PKC? and ROS via a novel pathway involving induction of RUNX3 and subsequent repression of RUNX1. These results reveal key functional roles for PKC? and ROS in T-ALL and suggest that aggressive biological behavior in vivo could be limited by therapeutic strategies that promote PKC? expression/activity or ROS accumulation. PMID:23086478

Giambra, Vincenzo; Jenkins, Christopher R.; Wang, Hongfang; Lam, Sonya H.; Shevchuk, Olena O.; Nemirovsky, Oksana; Wai, Carol; Gusscott, Sam; Chiang, Mark Y.; Aster, Jon C.; Humphries, R. Keith; Eaves, Connie; Weng, Andrew P.

2013-01-01

385

Reactive Oxygen Species Production in Peripheral Blood Neutrophils of Obstructive Sleep Apnea Patients  

PubMed Central

Obstructive sleep apnea (OSA) as well as obesity is associated with increased production of reactive oxygen species (ROS). Neutrophils produce great amounts of ROS. The aim was to evaluate peripheral blood neutrophils ROS production in men with OSA and to establish relations with disease severity and obesity. Methods. Forty-six men with OSA and 10 controls were investigated. OSA was confirmed by polysomnography (PSG), when apnea/hypopnea index was >5/h. Body mass index (BMI) was evaluated. Neutrophils were isolated from peripheral blood in the morning after PSG. Dihydrorhodamine-123 was used for ROS detection. Data is presented as median (25th and 75th percentiles). All subjects were divided into four groups: nonobese mild-to-moderate OSA, obese mild-to-moderate OSA, nonobese severe OSA, and obese severe OSA. Results. Neutrophil ROS production was higher in nonobese severe OSA group compared to nonobese mild-to-moderate OSA (mean fluorescence intensity (MFI) 213.4 (89.0–238.9) versus 44.5 (20.5–58.4), P < 0.05). In obese patient groups, ROS production was more increased in severe OSA compared to mild-to-moderate OSA group (MFI 74.5 (47.9–182.4) versus 31.0 (14.8–53.8), P < 0.05). It did not differ in the groups with different BMI and the same severity of OSA. Conclusion. Increased neutrophil ROS production was related to more severe OSA but not obesity. PMID:23766689

Miliauskas, Skaidrius; Sakalauskas, Raimundas

2013-01-01

386

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

PubMed

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

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

2014-08-01

387

Antioxidant effects of antioxidant biofactor on reactive oxygen species in human gingival fibroblasts  

PubMed Central

The purpose of this study was to investigate the effects of antioxidant biofactor (AOB) on reactive oxygen species (ROS). Generation of superoxide radical (O2•?) and hydroxyl radical (•OH) was determined using an electron spin resonance (ESR) spin-trapping method. AOB was added at different concentrations to these free radical generating systems. The generation of both O2•? and •OH was scavenged by the addition of AOB in a dose-dependent manner. These results indicate that AOB has strong antioxidant properties against these radicals. We further investigated the anti-oxidative effect of AOB on human gingival fibroblasts (HGFs). HGFs were treated for 3 h with ?-MEM containing a combination of AOB and H2O2 (AOB + H2O2 group), containing H2O2 (H2O2 group), or containing AOB alone (AOB group). Non-stimulated HGFs were used as a control group. The number of surviving cells was in the order of the AOB group > control group > AOB + H2O2 group > H2O2 group. The level of expression of type I collagen mRNA and production of collagen were also in the order of the AOB group > control group > AOB + H2O2 group > H2O2 group. In conclusion, our results suggest that AOB may protect HGFs against oxidative stress by reducing stress-induced ROS. PMID:21562640

Matsui, Satoshi; Tsujimoto, Yasuhisa; Ozawa, Toshihiko; Matsushima, Kiyoshi

2011-01-01

388

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

389

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

390

Fine tuning of reactive oxygen species homeostasis regulates primed immune responses in Arabidopsis.  

PubMed

Selected stimuli can prime the plant immune system for a faster and stronger defense reaction to pathogen attack. Pretreatment of Arabidopsis with the chemical agent ?-aminobutyric acid (BABA) augmented H2O2 and callose production after induction with the pathogen-associated molecular pattern (PAMP) chitosan, or inoculation with the necrotrophic fungus Plectosphaerella cucumerina. However, BABA failed to prime H2O2 and callose production after challenge with the bacterial PAMP Flg22. Analysis of Arabidopsis mutants in reactive oxygen species (ROS) production (rbohD) or ROS scavenging (pad2, vtc1, and cat2) suggested a regulatory role for ROS homeostasis in priming of chitosan- and P. cucumerina-inducible callose and ROS. Moreover, rbohD and pad2 were both impaired in BABA-induced resistance against P. cucumerina. Gene expression analysis revealed direct induction of NADPH/respiratory burst oxidase protein D (RBOHD), ?-glutamylcysteine synthetase 1 (GSH1), and vitamin C defective 1 (VTC1) genes after BABA treatment. Conversely, ascorbate peroxidase 1 (APX1) transcription was repressed by BABA after challenge with chitosan or P. cucumerina, probably to provide a more oxidized environment in the cell and facilitate augmented ROS accumulation. Measuring ratios between reduced and oxidized glutathione confirmed that augmented defense expression in primed plants is associated with a more oxidized cellular status. Together, our data indicate that an altered ROS equilibrium is required for augmented defense expression in primed plants. PMID:24088017

Pastor, Victoria; Luna, Estrella; Ton, Jurriaan; Cerezo, Miguel; García-Agustín, Pilar; Flors, Victor

2013-11-01

391

Evaluation of Inflammatory Response to Acute Ischemia using Near Infrared Fluorescent Reactive Oxygen Sensors  

PubMed Central

Ischemia-related processes associated with generation of inflammatory molecules such as reactive oxygen species (ROS) are difficult to detect at the acute stage before physiologic and anatomic evidence of tissue damage is present. Evaluation of the inflammatory and healing response early after an ischemic event in vivo will aid in treatment selection and patient outcomes. We introduce a novel near-infrared hydrocyanine molecular probe for detection of ROS as a marker of tissue response to ischemia and a precursor to angiogenesis and remodeling. The synthesized molecular probe, initially a non-fluorescent hydrocyanine conjugated to polyethyleneglycol, converts to a highly fluorescent cyanine reporter upon oxidation. The probe was applied in a preclinical mouse model for myocardial infarction, where ligation and removal of a portion of the femoral artery in the hindlimb resulted in temporary ischemia followed by angiogenesis and healing. The observed increase in fluorescence intensity was approximately 6-fold over 24 h in the ischemic tissue relative to the uninjured control limb and was attributed to the higher concentration of ROS in the ischemic tissue. These results demonstrate the potential for non-invasive sensing for interrogating the inflammatory and healing response in ischemic tissue. PMID:23378226

Magalotti, Selena; Gustafson, Tiffany; Cao, Qian; Abendschein, Dana; Pierce, Richard; Berezin, Mikhail Y.; Akers, Walter J.

2014-01-01

392

Superoxide flashes reveal novel properties of mitochondrial reactive oxygen species excitability in cardiomyocytes.  

PubMed

Superoxide flash represents quantal and bursting production of mitochondrial reactive oxygen species (ROS) instigated by transient opening of the mitochondrial permeability transition pore (mPTP). Given their critical role in metabolism, ischemia-reperfusion injury, and apoptosis, characterization of flash properties would be valuable to further mechanistic and physiological studies of this newly discovered mitochondrial phenomenon. Here we developed the flash detector FlashSniper based on segmentation of two-dimensional feature maps extracted from time-lapse confocal image stacks, and on the theory for correcting optical distortion of flash-amplitude histograms. Through large-scale analysis of superoxide flashes in cardiomyocytes, we demonstrated uniform mitochondrial ROS excitability among subsarcolemmal and intermyofibrillar mitochondria, and exponential distribution of intervals between consecutive flash events. Flash ignition displayed three different patterns: an abrupt rise from quiescence (44%), a rise with an exponential foot (27%), or a rise occurring after a pedestal precursor (29%), closely resembling action-potential initiation in excitable cells. However, the optical blurring-corrected amplitudes of superoxide flashes were highly variable, as were their durations, indicating stochastic automaticity of single-mitochondrion ROS excitation. Simultaneous measurement of mitochondrial membrane potential revealed that graded, rather than all-or-none, depolarization mirrored the precursor and the primary peak of the flash. We propose that superoxide flash production is a regenerative process dominated by stochastic, autonomous recruitment of a limited number of units (e.g., mPTPs) in single mitochondria. PMID:22404923

Li, Kaitao; Zhang, Wanrui; Fang, Huaqiang; Xie, Wenjun; Liu, Jie; Zheng, Ming; Wang, Xianhua; Wang, Wang; Tan, Wenchang; Cheng, Heping

2012-03-01

393

Synergistic triggering of superoxide flashes by mitochondrial Ca2+ uniport and basal reactive oxygen species elevation.  

PubMed

Mitochondrial superoxide flashes reflect a quantal, bursting mode of reactive oxygen species (ROS) production that arises from stochastic, transient opening of the mitochondrial permeability transition pore (mPTP) in many types of cells and in living animals. However, the regulatory mechanisms and the exact nature of the flash-coupled mPTP remain poorly understood. Here we demonstrate a profound synergistic effect between mitochondrial Ca(2+) uniport and elevated basal ROS production in triggering superoxide flashes in intact cells. Hyperosmotic stress potently augmented the flash activity while simultaneously elevating mitochondrial Ca(2+) and ROS. Blocking mitochondrial Ca(2+) transport by knockdown of MICU1 or MCU, newly identified components of the mitochondrial Ca(2+) uniporter, or scavenging mitochondrial basal ROS markedly diminished the flash response. More importantly, whereas elevating Ca(2+) or ROS production alone was inefficacious in triggering the flashes, concurrent physiological Ca(2+) and ROS elevation served as the most powerful flash activator, increasing the flash incidence by an order of magnitude. Functionally, superoxide flashes in response to hyperosmotic stress participated in the activation of JNK and p38. Thus, physiological levels of mitochondrial Ca(2+) and ROS synergistically regulate stochastic mPTP opening and quantal ROS production in intact cells, marking the flash as a coincidence detector of mitochondrial Ca(2+) and ROS signals. PMID:23283965

Hou, Tingting; Zhang, Xing; Xu, Jiejia; Jian, Chongshu; Huang, Zhanglong; Ye, Tao; Hu, Keping; Zheng, Ming; Gao, Feng; Wang, Xianhua; Cheng, Heping

2013-02-15

394

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

PubMed Central

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

Roca, Francisco J.; Ramakrishnan, Lalita

2013-01-01

395

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. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 4435-4442, 2014. PMID:24677796

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

2014-12-01

396

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

397

A reporter system for the individual detection of hydrogen peroxide and singlet oxygen: its use for the assay of reactive oxygen species produced in vivo.  

PubMed

A reporter system for the assay of reactive oxygen species (ROS) was developed in Chlamydomonas reinhardtii, a plant model organism well suited for the application of inhibitors and generators of various types of ROS. This system employs various HSP70A promoter segments fused to a Renilla reniformis luciferase gene as a reporter. Transformants with the complete HSP70A promoter were inducible by both hydrogen peroxide and singlet oxygen. Constructs that lacked upstream heat-shock elements (HSEs) were inducible by hydrogen peroxide, indicating that this induction does not require such HSEs. Rather, downstream elements located between positions -81 to -149 with respect to the translation start site appear to be involved. In contrast, upstream sequences are essential for the response to singlet oxygen. Thus, activation by singlet oxygen appears to require promoter elements that are different from those used by hydrogen peroxide. ROS generated endogenously by treatment of the alga with metronidazole, protoporphyrin IX, dinoterb or high light intensities were detected by this reporter system, and distinguished as production of hydrogen peroxide (metronidazole) and singlet oxygen (protoporphyrin IX, dinoterb, high light). This system thus makes it possible to test whether, under varying environmental conditions including the application of abiotic stress, hydrogen peroxide or singlet oxygen or both are produced. PMID:17376156

Shao, Ning; Krieger-Liszkay, Anja; Schroda, Michael; Beck, Christoph F

2007-05-01

398

The roles of reactive oxygen species and autophagy in mediating the tolerance of tumor cells to cycling hypoxia.  

PubMed

Tumor hypoxia (low oxygenation) causes treatment resistance and poor patient outcome. A substantial fraction of tumor cells experience cycling hypoxia, characterized by transient episodes of hypoxia and reoxygenation. These cells are under a unique burden of stress, mediated by excessive production of reactive oxygen species (ROS). Cellular components damaged by ROS can be cleared by autophagy, rendering cycling hypoxic tumor cells particularly vulnerable to inhibition of autophagy and its upstream regulatory pathways. Activation of the PERK-mediated signaling arm of the unfolded protein response during hypoxia plays a critical role in the defense against ROS, both by stimulating glutathione synthesis pathways and through promoting autophagy. PMID:24012339

Koritzinsky, Marianne; Wouters, Bradly G

2013-10-01

399

Mitochondrial Reactive Oxygen Species Production in Excitable Cells: Modulators of Mitochondrial and Cell Function  

PubMed Central

Abstract The mitochondrion is a major source of reactive oxygen species (ROS). Superoxide (O2•?) is generated under specific bioenergetic conditions at several sites within the electron-transport system; most is converted to H2O2 inside and outside the mitochondrial matrix by superoxide dismutases. H2O2 is a major chemical messenger that, in low amounts and with its products, physiologically modulates cell function. The redox state and ROS scavengers largely control the emission (generation scavenging) of O2•?. Cell ischemia, hypoxia, or toxins can result in excess O2•? production when the redox state is altered and the ROS scavenger systems are overwhelmed. Too much H2O2 can combine with Fe2+ complexes to form reactive ferryl species (e.g., Fe(IV)?=?O•). In the presence of nitric oxide (NO•), O2•? forms the reactant peroxynitrite (ONOO?), and ONOOH-induced nitrosylation of proteins, DNA, and lipids can modify their structure and function. An initial increase in ROS can cause an even greater increase in ROS and allow excess mitochondrial Ca2+ entry, both of which are factors that induce cell apoptosis and necrosis. Approaches to reduce excess O2•? emission include selectively boosting the antioxidant capacity, uncoupling of oxidative phosphorylation to reduce generation of O2•? by inducing proton leak, and reversibly inhibiting electron transport. Mitochondrial cation channels and exchangers function to maintain matrix homeostasis and likely play a role in modulating mitochondrial function, in part by regulating O2•? generation. Cell-signaling pathways induced physiologically by ROS include effects on thiol groups and disulfide linkages to modify posttranslationally protein structure to activate/inactivate specific kinase/phosphatase pathways. Hypoxia-inducible factors that stimulate a cascade of gene transcription may be mediated physiologically by ROS. Our knowledge of the role played by ROS and their scavenging systems in modulation of cell function and cell death has grown exponentially over the past few years, but we are still limited in how to apply this knowledge to develop its full therapeutic potential. Antioxid. Redox Signal. 11, 1373–1414. PMID:19187004

Camara, Amadou K. S.

2009-01-01

400

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