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1

Enhanced reactive oxygen species scavenging by overproduction of superoxide dismutase and catalase delays postharvest physiological deterioration of cassava storage roots.  

PubMed

Postharvest physiological deterioration (PPD) of cassava (Manihot esculenta) storage roots is the result of a rapid oxidative burst, which leads to discoloration of the vascular tissues due to the oxidation of phenolic compounds. In this study, coexpression of the reactive oxygen species (ROS)-scavenging enzymes copper/zinc superoxide dismutase (MeCu/ZnSOD) and catalase (MeCAT1) in transgenic cassava was used to explore the intrinsic relationship between ROS scavenging and PPD occurrence. Transgenic cassava plants integrated with the expression cassette p54::MeCu/ZnSOD-35S::MeCAT1 were confirmed by Southern-blot analysis. The expression of MeCu/ZnSOD and MeCAT1 was verified by quantitative reverse transcription-polymerase chain reaction and enzymatic activity analysis both in the leaves and storage roots. Under exposure to the ROS-generating reagent methyl viologen or to hydrogen peroxide (H2O2), the transgenic plants showed higher enzymatic activities of SOD and CAT than the wild-type plants. Levels of malondialdehyde, chlorophyll degradation, lipid peroxidation, and H2O2 accumulation were dramatically reduced in the transgenic lines compared with the wild type. After harvest, the storage roots of transgenic cassava lines show a delay in their PPD response of at least 10 d, accompanied by less mitochondrial oxidation and H2O2 accumulation, compared with those of the wild type. We hypothesize that this is due to the combined ectopic expression of Cu/ZnSOD and CAT leading to an improved synergistic ROS-scavenging capacity of the roots. Our study not only sheds light on the mechanism of the PPD process but also develops an effective approach for delaying the occurrence of PPD in cassava. PMID:23344905

Xu, Jia; Duan, Xiaoguang; Yang, Jun; Beeching, John R; Zhang, Peng

2013-03-01

2

Insulin improves osteogenesis of titanium implants under diabetic conditions by inhibiting reactive oxygen species overproduction via the PI3K-Akt pathway.  

PubMed

Clinical evidence indicates that insulin therapy improves implant survival rates in diabetic patients; however, the mechanisms responsible for this effect are unknown. Here, we test if insulin exerts anti-oxidative effects, thereby improving diabetes-associated impaired osteoblast behavior on titanium implants. To test this hypothesis, we cultured primary rabbit osteoblasts in the presence of titanium implants and studied the impact of treatment with normal serum (NS), diabetic serum (DS), DS + insulin, DS + tempol (a superoxide dismutase mimetic), DS + insulin + tempol, and DS + insulin + wortmannin. We analyzed cell function, apoptosis, and reactive oxygen species (ROS) production in osteoblasts following the various treatments. Treatment with DS induced osteoblast dysfunction, evidenced by impaired cell attachment and morphology, decreased cell proliferation and ALP activity, and decreased expression of osteogenesis-related genes. We also observed a significant increase in apoptosis. Importantly, treatment with DS resulted in increased production of ROS in osteoblasts. In contrast, treatment with insulin inhibited ROS production, alleviated cell dysfunction, and decreased apoptosis of osteoblasts on the implants. Scavenging ROS with tempol also attenuated cell dysfunction. Compared to insulin treatment alone, the combination of insulin and tempol failed to further improve osteoblast functional recovery. Moreover, the anti-oxidative and pro-osteogenic effects afforded by insulin were almost completely abolished by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin. These results demonstrate, for the first time, that insulin treatment alleviates the impaired osteogenesis of titanium implants under diabetic conditions by inhibiting ROS overproduction via a PI3K/Akt-dependent mechanism. Both the anti-oxidative and metabolic properties of insulin should make it a viable therapeutic option to combat diabetic implant failure. PMID:25308835

Wang, Lin; Zhao, Xiong; Wei, Bo-Yuan; Liu, Yi; Ma, Xiang-Yu; Wang, Jian; Cao, Peng-Chong; Zhang, Yang; Yan, Ya-Bo; Lei, Wei; Feng, Ya-Fei

2015-01-01

3

Reactive Oxygen Species Signaling in Cancer: Comparison with Aging  

PubMed Central

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

Afanas’ev, Igor

2011-01-01

4

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

Microsoft Academic Search

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

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

1999-01-01

5

Reactive oxygen species in cancer  

PubMed Central

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

Liou, Geou-Yarh; Storz, Peter

2013-01-01

6

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

7

Formation and Detoxification of Reactive Oxygen Species  

ERIC Educational Resources Information Center

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

Kuciel, Radoslawa; Mazurkiewicz, Aleksandra

2004-01-01

8

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

PubMed Central

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

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

2014-01-01

9

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

NASA Astrophysics Data System (ADS)

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

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

2006-03-01

10

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

11

REACTIVE OXYGEN SPECIES AND COLORECTAL CANCER  

PubMed Central

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

Sreevalsan, Sandeep; Safe, Stephen

2013-01-01

12

Characterization of reactive oxygen species in diaphragm.  

PubMed

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

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

2015-03-01

13

Influence of reactive oxygen species on the sterilization of microbes  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

14

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

PubMed

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

Mirshafiey, Abbas; Mohsenzadegan, Monireh

2008-12-01

15

Generation of reactive oxygen species by the faecal matrix  

Microsoft Academic Search

BACKGROUNDReactive oxygen species are implicated in the aetiology of a range of human diseases and there is increasing interest in their role in the development of cancer.AIMTo develop a suitable method for the detection of reactive oxygen species produced by the faecal matrix.METHODSA refined high performance liquid chromatography system for the detection of reactive oxygen species is described.RESULTSThe method allows

R W Owen; B Spiegelhalder; H Bartsch

2000-01-01

16

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

17

Reactive oxygen species and redox compartmentalization  

PubMed Central

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

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

2014-01-01

18

Indoor particulate reactive oxygen species concentrations.  

PubMed

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

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

2014-07-01

19

Reactive oxygen species in leaf abscission signaling  

PubMed Central

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

Sakamoto, Masaru; Munemura, Ikuko; Tomita, Reiko

2008-01-01

20

How mitochondria produce reactive oxygen species  

PubMed Central

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

Murphy, Michael P.

2008-01-01

21

REACTIVE OXYGEN SPECIES IN PULMONARY VASCULAR REMODELING  

PubMed Central

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

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

2014-01-01

22

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

23

Microcystin-LR Induced Reactive Oxygen Species Mediate Cytoskeletal Disruption and Apoptosis of Hepatocytes in Cyprinus carpio L.  

PubMed Central

Microcystins (MCs) are a group of cyclic hepatotoxic peptides produced by cyanobacteria. Microcystin-LR (MC-LR) contains Leucine (L) and Arginine (R) in the variable positions, and is one of the most common and potently toxic peptides. MC-LR can inhibit protein phosphatase type 1 and type 2A (PP1 and PP2A) activities and induce excessive production of reactive oxygen species (ROS). The underlying mechanism of the inhibition of PP1 and PP2A has been extensively studied. The over-production of ROS is considered to be another main mechanism behind MC-LR toxicity; however, the detailed toxicological mechanism involved in over-production of ROS in carp (Cyprinus carpio L.) remains largely unclear. In our present study, the hydroxyl radical (•OH) was significantly induced in the liver of carp after a relatively short-term exposure to MC-LR. The elevated reactive oxygen species (ROS) production may play an important role in the disruption of microtubule structure. Pre-injection of the antioxidant N-acetyl-cysteine (NAC) provided significant protection to the cytoskeleton, however buthionine sulfoximine (BSO) exacerbated cytoskeletal destruction. In addition, the elevated ROS formation induced the expression of apoptosis-related genes, including p38, JNKa, and bcl-2. A significant increase in apoptotic cells was observed at 12 - 48 hours. Our study further supports evidence that ROS are involved in MC-LR induced damage to liver cells in carp, and indicates the need for further study of the molecular mechanisms behind MC-LR toxicity. PMID:24376844

Jiang, Jinlin; Shan, Zhengjun; Xu, Weili; Wang, Xiaorong; Zhou, Junying; Kong, Deyang; Xu, Jing

2013-01-01

24

Growth stress triggers riboflavin overproduction in Ashbya gossypii.  

PubMed

The filamentous fungus Ashbya gossypii is used for riboflavin biosynthesis on an industrial scale, but even the wild type displays overproduction. Because riboflavin overproduction was known to start at the transition between growth and stationary phase, it was suspected that overproduction was induced at low growth rates. However, chemostatic cultivations performed at different growth rates did not result in any detectable riboflavin formation. In this study, we report that it was not the final growth rate that triggered riboflavin overproduction but a decline in growth rate. Therefore, continuous fermenter cultivations with dilution rate shifts were performed. Peaks of riboflavin overproduction were observed in the wild type and in a RIB3placZ reporter strain after downshifts in dilution rate. Accumulation of riboflavin correlated with an increased expression of lacZ reporter activity. The step size of the downshifts corresponded to the peak size of riboflavin formation and reporter activity. Expression of further RIB genes encoding riboflavin biosynthetic enzymes was analyzed by RT-PCR. RIB mRNA levels of the ribulose-5-phosphate branch of the divided riboflavin biosynthesis pathway (RIB3, RIB4, and RIB5) were found to increase in the riboflavin production phase, whereas the RIB2 and RIB7 mRNA levels belonging to the GTP branch remained constant. We propose that a decline in growth rate triggers the increased expression of RIB3, RIB4, and RIB5 resulting in riboflavin overproduction. Because although a reduction in oxygen supply, temperature increase or decrease, or salt stress did affect growth, but neither did lead to riboflavin overproduction nor did induce RIB3 reporter expression, we conclude that declining nutrition must be the stress stimulus. Because about half of the cells in the hyphae of Ashbya gossypii did not accumulate riboflavin, the regulatory response on the cellular level can be estimated to be at least twice as great in comparison to what we detected as overall signals. PMID:17639374

Schlösser, Thomas; Wiesenburg, Andreas; Gätgens, Cornelia; Funke, Andreas; Viets, Ulrike; Vijayalakshmi, Swaminathan; Nieland, Susanne; Stahmann, K-Peter

2007-09-01

25

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

PubMed

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

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

2007-03-01

26

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

EPA Science Inventory

ARSENIC SPECIES. CAUSE RELEASE OF IRON , FROM FERRITIN GENERATING REACTIVE OXYGEN SPECIES Arsenic-associated cancer (lung, bladder, skin, liver, kidney) remains a significant world- wide public health problem (e.g., Taiwan, Chile, Bangladesh, India, China and Thailand). R...

27

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

EPA Science Inventory

ARSENIC SPECIES CAUSE RELEASE OF IRON FROM FERRITIN GENERATING REACTIVE OXYGEN SPECIES Arsenic-associated cancer (lung, bladder, skin, liver, kidney) remains a significant world- wide public health problem (e.g., Taiwan, Chile, Bangladesh, India, China and Thailand). Rece...

28

Direct observation of the oxygenated species during oxygen reduction on a platinum fuel cell cathode  

NASA Astrophysics Data System (ADS)

The performance of polymer electrolyte membrane fuel cells is limited by the reduction at the cathode of various oxygenated intermediates in the four-electron pathway of the oxygen reduction reaction. Here we use ambient pressure X-ray photoelectron spectroscopy, and directly probe the correlation between the adsorbed species on the surface and the electrochemical potential. We demonstrate that, during the oxygen reduction reaction, hydroxyl intermediates on the cathode surface occur in several configurations with significantly different structures and reactivities. In particular, we find that near the open-circuit potential, non-hydrated hydroxyl is the dominant surface species. On the basis of density functional theory calculations, we show that the removal of hydration enhances the reactivity of oxygen species. Tuning the hydration of hydroxyl near the triple phase boundary will be crucial for designing more active fuel cell cathodes.

Casalongue, Hernan Sanchez; Kaya, Sarp; Viswanathan, Venkatasubramanian; Miller, Daniel J.; Friebel, Daniel; Hansen, Heine A.; Nørskov, Jens K.; Nilsson, Anders; Ogasawara, Hirohito

2013-12-01

29

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

30

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

31

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

32

Oxygen chemistry of shocked interstellar clouds. III - Sulfur and oxygen species in dense clouds  

NASA Technical Reports Server (NTRS)

The chemical evolution of oxygen and sulfur species in shocked dense clouds is studied. Reaction rate constants for several important neutral reactions are examined, and revised values are suggested. The one-fluid magnetohydrodynamic shock structure and postshock chemical evolution are calculated for shocks of velocity v(s) = 10 km/s through clouds of initial number density n(0) = 100,000/cu cm and of molecule/atom ratios H2/H = 10, 1000, and 100,000 with most sulfur contained initially in molecules SO2 and SO. Abundances of SO2, SO, CS, and OCS remain near their preshock values, except in clouds containing substantial amounts of atomic hydrogen, where significant destruction of sulfur-oxygen species occurs. Abundances of shock-enhanced molecules HS and H2O are sensitive to the molecule/atom ratio. Nonthermal oxygen-hydrogen chemistry has a minor effect on oxygen-sulfur molecules in the case H2/H = 10.

Leen, T. M.; Graff, M. M.

1988-01-01

33

Infections in the male genital tract and reactive oxygen species  

Microsoft Academic Search

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

F. R. Ochsendorf

1999-01-01

34

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...

35

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

36

A role for reactive oxygen species in postharvest biocontrol  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

37

Cell signaling by reactive nitrogen and oxygen species in atherosclerosis  

Microsoft Academic Search

The production of reactive oxygen and nitrogen species has been implicated in atherosclerosis principally as means of damaging low-density lipoprotein that in turn initiates the accumulation of cholesterol in macrophages. The diversity of novel oxidative modifications to lipids and proteins recently identified in atherosclerotic lesions has revealed surprising complexity in the mechanisms of oxidative damage and their potential role in

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

2000-01-01

38

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

PubMed Central

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

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

2012-01-01

39

Muscle characterization of reactive oxygen species in oral diseases.  

PubMed

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

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

2015-02-01

40

Properties of Reactive Oxygen Species by Quantum Monte Carlo  

E-print Network

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

Andrea Zen; Bernhardt L. Trout; Leonardo Guidoni

2014-06-16

41

Properties of reactive oxygen species by quantum Monte Carlo  

NASA Astrophysics Data System (ADS)

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

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

2014-07-01

42

Reactive oxygen species generation and signaling in plants  

PubMed Central

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

Tripathy, Baishnab Charan; Oelmüller, Ralf

2012-01-01

43

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

Microsoft Academic Search

Free radicals, such as superoxide, hydroxyl and nitric oxide, and other “reactive species”, such as hydrogen peroxide, hypochlorous acid and peroxynitrite, are formed in vivo. Some of these molecules, e.g. superoxide and nitric oxide, can be physiologically useful, but they can also cause damage under certain circumstances. Excess production of reactive oxygen or nitrogen species (ROS, RNS), their production in

Victor Darley-Usmar; Barry Halliwell

1996-01-01

44

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

45

Multi-species simulation of Trichel pulses in oxygen  

NASA Astrophysics Data System (ADS)

The development of negative corona Trichel pulses in oxygen between a spherical cathode and a plane is investigated using a plasma chemical model of ten selected species, which includes electrons, ions and neutrals. The interaction among these species is described by a model that incorporates the most important plasma chemical processes, such as ionization, electron attachment and detachment, electron impact dissociation and excitation, and clustering. The spatio-temporal evolution of charged and neutral species and their reaction rates are evaluated along different moments during the pulses. The case of the first Trichel pulse is considered separately, since its characteristics clearly differ from the subsequent pulses. The results show that the negative space charge is constituted of different types of ions, depending on the stage of the pulse. Moreover, a spatial segregation of negative ions is observed during the post-pulse period. Regarding neutral species, ozone increases linearly with time, without being considerably affected by the occurrence of pulses.

Durán-Olivencia, F. J.; Pontiga, F.; Castellanos, A.

2014-10-01

46

Reactive oxygen species and hematopoietic stem cell senescence  

Microsoft Academic Search

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

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

47

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

48

Oxygen consumption in six species of chitons in relation to their position on the shore  

Microsoft Academic Search

Aerial and aquatic oxygen consumption rates have been measured in six species of intertidal chi tons with respect to zonation, size and oxygen concentration of the external medium. Those species occurring highest on the shore were found to have a lower rate of aquatic oxygen consumption than those ~i'eeies occurring lowest on the shore, with mid-shore species showing intermediate rates.

Robin C. Murdoch; Sandra E. Shumway

1980-01-01

49

Oxygen limitation and thermal tolerance in two terrestrial arthropod species.  

PubMed

Recent studies of marine invertebrates and fish have suggested that lower and upper critical temperatures (CT(min) and CT(max)) are coupled by a common mechanism: oxygen and capacity limitation of thermal tolerance (OCLT). Using thermolimit respirometry, we tested the predictions of this theory for terrestrial arthropods by measuring maxima and minima for both critical temperatures and metabolic rate in two arthropods, the isopod Porcellio scaber and the beetle Tenebrio molitor, at 40%, 21%, 10% and 2.5% ambient O(2). Critical temperatures were identified as particular points on both activity and traces in four ways. In the first two instances, we identified the inflection points in regressions of absolute difference sum (ADS) residuals calculated for activity (aADS) and (VI), respectively. In the third, we visually identified the lowest point before the post-mortal peak in CO(2) release (PMV). Finally, we pinpointed the sudden drop in at death, where fell outside the 95% confidence intervals of the 5 min period immediately preceding the drop-off (CI). Minimum and maximum metabolic rates were determined using CO(2) traces, and the temperatures corresponding to these identified as T(MetMin) and T(MetMax). For both species, ambient oxygen concentration did not influence CT(min), minimum metabolic rate, or T(MetMin). By contrast, severe hypoxia (2.5% O(2)) caused a 6.9 degrees C decline in activity-based CT(max) for T. molitor and a 10.6 degrees C decline for P. scaber, relative to normoxia (21% O(2)). The magnitude of this decrease differed between methods used to estimated critical thermal limits, highlighting the need for a standard method to determine these endpoints during thermolimit respirometry. Maximum metabolic rate also declined with decreasing ambient oxygen in both species. The combination of increasing metabolic rate and oxygen limitation affected upper thermal limits in these arthropods only in severe hypoxia (2.5% O(2)). In both species, CT(min) and CT(max) responded differently to oxygen limitation, suggesting that this is not a common mechanism coupling upper and lower limits in terrestrial arthropods. PMID:20543119

Stevens, Meagan M; Jackson, Sue; Bester, Susan A; Terblanche, John S; Chown, Steven L

2010-07-01

50

Spermine metabolism and radiation-derived reactive oxygen species for future therapeutic implications in cancer: an additive or adaptive response.  

PubMed

Destruction of cells by irradiation-induced radical formation is one of the most frequent interventions in cancer therapy. An alternative to irradiation-induced radical formation is in principle drug-induced formation of radicals, and the formation of toxic metabolites by enzyme catalyzed reactions. Thus, combination therapy targeting polyamine metabolism could represent a promising strategy to fight hyper-proliferative disease. The aim of this work is to discuss and evaluate whether the presence of a DNA damage provoked by enzymatic ROS overproduction may act as an additive or adaptive response upon radiation and combination of hyperthermia with lysosomotropic compounds may improve the cytocidal effect of polyamines oxidation metabolites. Low level of X-irradiations delivers challenging dose of damage and an additive or adaptive response with the chronic damage induced by spermine oxidase overexpression depending on the deficiency of the DNA repair mechanisms. Since reactive oxygen species lead to membrane destabilization and cell death, we discuss the effects of BSAO and spermine association in multidrug resistant cells that resulted more sensitive to spermine metabolites than their wild-type counterparts, due to an increased mitochondrial activity. Since mammal spermine oxidase is differentially activated in a tissue specific manner, and cancer cells can differ in term of DNA repair capability, it could be of interest to open a scientific debate to use combinatory treatments to alter spermine metabolism and deliver differential response. PMID:23999645

Amendola, Roberto; Cervelli, Manuela; Tempera, Giampiero; Fratini, Emiliano; Varesio, Luigi; Mariottini, Paolo; Agostinelli, Enzo

2014-03-01

51

Angiotensin II-Induced Production of Mitochondrial Reactive Oxygen Species: Potential Mechanisms and Relevance for Cardiovascular Disease  

PubMed Central

Abstract Significance: The role of reactive oxygen species (ROS) in angiotensin II (AngII) induced endothelial dysfunction, cardiovascular and renal remodeling, inflammation, and fibrosis has been well documented. The molecular mechanisms of AngII pathophysiological activity involve the stimulation of NADPH oxidases, which produce superoxide and hydrogen peroxide. AngII also increases the production of mitochondrial ROS, while the inhibition of AngII improves mitochondrial function; however, the specific molecular mechanisms of the stimulation of mitochondrial ROS is not clear. Recent Advances: Interestingly, the overexpression of mitochondrial thioredoxin 2 or mitochondrial superoxide dismutase attenuates AngII-induced hypertension, which demonstrates the importance of mitochondrial ROS in AngII-mediated cardiovascular diseases. Critical Issues: Although mitochondrial ROS plays an important role in normal physiological cell signaling, AngII, high glucose, high fat, or hypoxia may cause the overproduction of mitochondrial ROS, leading to the feed-forward redox stimulation of NADPH oxidases. This vicious cycle may contribute to the development of pathological conditions and facilitate organ damage in hypertension, atherosclerosis, and diabetes. Future Directions: The development of antioxidant strategies specifically targeting mitochondria could be therapeutically beneficial in these disease conditions. Antioxid. Redox Signal. 19, 1085–1094. PMID:22443458

Nazarewicz, Rafal R.

2013-01-01

52

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

53

Reactive Oxygen Species Driven Angiogenesis by Inorganic Nanorods  

PubMed Central

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

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

2011-01-01

54

Aminoferrocene-based prodrugs activated by reactive oxygen species.  

PubMed

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

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

2012-01-26

55

In situ reactive oxygen species production for tertiary wastewater treatment.  

PubMed

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

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

2014-12-01

56

Diagnostics of reactive oxygen species produced by microplasmas  

NASA Astrophysics Data System (ADS)

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

Sousa, J. S.; Puech, V.

2013-11-01

57

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

PubMed

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

Polster, Brian M

2013-04-01

58

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

59

Role of Reactive Oxygen Species in Antibiotic Action and Resistance  

PubMed Central

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

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

2009-01-01

60

Reactive oxygen species, cell signaling, and cell injury.  

PubMed

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

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

2000-05-15

61

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

NSDL National Science Digital Library

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

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

2006-04-25

62

The Role of Reactive Oxygen Species in Microvascular Remodeling  

PubMed Central

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

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

2014-01-01

63

Reactive oxygen species, ageing and the hormesis police  

PubMed Central

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

Ludovico, Paula; Burhans, William C.

2013-01-01

64

Moving forward with reactive oxygen species involvement in antimicrobial lethality.  

PubMed

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

Zhao, Xilin; Hong, Yuzhi; Drlica, Karl

2015-03-01

65

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

66

Reactive Oxygen Species in Normal and Tumor Stem Cells  

PubMed Central

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

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

2014-01-01

67

The role of reactive oxygen species in microvascular remodeling.  

PubMed

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

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

2014-01-01

68

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

69

Degradative action of reactive oxygen species on hyaluronan.  

PubMed

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

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

2006-03-01

70

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

71

Characterization of superoxide overproduction by the D-LoopNox4-Nox2 cytochrome b558 in phagocytes – Differential sensitivity to calcium and phosphorylation events  

PubMed Central

NADPH oxidase is a crucial element of phagocytes involved in microbicidal mechanisms. It becomes active when membrane-bound cytochrome b558, the redox core, is assembled with cytosolic p47phox, p67phox, p40phox, and rac proteins to produce superoxide, the precursor for generation of toxic reactive oxygen species. In a previous study, we demonstrated that the potential second intracellular loop of Nox2 was essential to maintaining NADPH oxidase activity by controlling electron transfer from FAD to O2. Moreover, replacement of this loop by the Nox4-D-loop (D-loopNox4-Nox2) in PLB-985 cells induced superoxide overproduction. In the present investigation, we demonstrated that both soluble and particulate stimuli were able to induce this superoxide overproduction. Superoxide overproduction was also observed after phosphatidic acid activation in a purified cell-free-system assay. The highest oxidase activity was obtained after ionomycin and fMLF stimulation. In addition, enhanced sensitivity to Ca2+ influx was shown by thapsigargin, EDTA, or BTP2 treatment before fMLF activation. Mutated cytochrome b558 was less dependent on phosphorylation triggered by ERK1/2 during fMLF or PMA stimulation and by PI3K during OpZ stimulation. The superoxide overproduction of the D-loopNox4-Nox2 mutant may come from a change of responsiveness to intracellular Ca2+ level and to phosphorylation events during oxidase activation. Finally the D-loopNox4-Nox2 -PLB-985 cells were more effective against an attenuated strain of Pseudomonas aeruginosa compared to WT-Nox2 cells. The killing mechanism was biphasic, an early step of ROS production that was directly bactericidal, and a second oxidase-independent step related to the amount of ROS produced in the first step. PMID:20708598

Carrichon, Laure; Picciocchi, Antoine; Debeurme, Franck; Defendi, Federica; Beaumel, Sylvain; Jesaitis, Algirdas J.; Dagher, Marie-Claire; Stasia, Marie-José

2010-01-01

72

Properties of reactive oxygen species by quantum Monte Carlo  

E-print Network

The electronic properties of the oxygen molecule, in its singlet and triplet states, and of many small oxygen-containing radicals and anions have important roles in different fields of chemistry, biology, and atmospheric ...

Zen, Andrea

73

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

74

Reactive oxygen species delay control of lymphocytic choriomeningitis virus.  

PubMed

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

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

2013-04-01

75

Male infertility testing: reactive oxygen species and antioxidant capacity.  

PubMed

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

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

2014-12-01

76

Mitochondrial reactive oxygen species in cell death signaling.  

PubMed

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

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

2002-01-01

77

Metformin reduces endogenous reactive oxygen species and associated DNA damage.  

PubMed

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

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

2012-04-01

78

Light and Dark of Reactive Oxygen Species for Vascular Function.  

PubMed

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

Shimokawa, Hiroaki; Satoh, Kimio

2014-08-26

79

Methods for Detection of Mitochondrial and Cellular Reactive Oxygen Species  

PubMed Central

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

Harrison, David G.

2014-01-01

80

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

PubMed

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

Lushchak, Volodymyr I

2014-10-28

81

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

82

Are Reactive Oxygen Species Always Detrimental to Pathogens?  

PubMed Central

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

Bozza, Marcelo T.

2014-01-01

83

Tamoxifen reduces fat mass by boosting reactive oxygen species.  

PubMed

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

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

2015-01-01

84

Generator-specific targets of mitochondrial reactive oxygen species.  

PubMed

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

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

2015-01-01

85

Reactive oxygen species and hematopoietic stem cell senescence  

PubMed Central

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

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

2012-01-01

86

Reactive Oxygen Species and Antioxidants in Pulmonary Hypertension  

PubMed Central

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

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

2013-01-01

87

Electrolyzed–Reduced Water Scavenges Active Oxygen Species and Protects DNA from Oxidative Damage  

Microsoft Academic Search

Active oxygen species or free radicals are considered to cause extensive oxidative damage to biological macromolecules, which brings about a variety of diseases as well as aging. The ideal scavenger for active oxygen should be ‘active hydrogen’. ‘Active hydrogen’ can be produced in reduced water near the cathode during electrolysis of water. Reduced water exhibits high pH, low dissolved oxygen

Sanetaka Shirahata; Shigeru Kabayama; Mariko Nakano; Takumi Miura; Kenichi Kusumoto; Miho Gotoh; Hidemitsu Hayashi; Kazumichi Otsubo; Shinkatsu Morisawa; Yoshinori Katakura

1997-01-01

88

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

89

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

PubMed Central

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

Vernon, Philip J.

2013-01-01

90

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

91

Reactive oxygen species signaling in plants under abiotic stress.  

PubMed

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

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

2013-04-01

92

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

93

Dissolved-Oxygen Requirements of Three Species of Fish  

Microsoft Academic Search

Critical dissolved-oxygen levels and standard metabolic rates were determined for the bluegill, Lepomis macrochirus; largemouth bass, Micropterus salmoides; and the channel catfish, Ictalurus punctatus, at 25° C., 30° C., and 35° C. Two types of experiments were conducted: shock tests in which the dissolved oxygen was dropped rapidly from near saturation to a critically low point; and acclimation tests in

D. D. Moss; D. C. Scott

1961-01-01

94

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

95

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

PubMed Central

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

Munnamalai, Vidhya; Suter, Daniel M.

2010-01-01

96

KRIT1 Regulates the Homeostasis of Intracellular Reactive Oxygen Species  

PubMed Central

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

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

2010-01-01

97

Reactive oxygen species produced by irradiation of some phthalocyanine derivatives  

Microsoft Academic Search

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

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

2010-01-01

98

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

PubMed

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

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

2012-07-01

99

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

100

A new species of Glochinema (Epsilonematidae: Nematoda) from the oxygen minimum zone off Baja California,  

E-print Network

A new species of Glochinema (Epsilonematidae: Nematoda) from the oxygen minimum zone off Baja nouvelle espèce du genre Glochinema (Epsilonematidae : Nematoda) de la zone de minimum en oxygène au large

Levin, Lisa

101

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

102

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.

103

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

104

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

Microsoft Academic Search

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

Eric Klann; Edda Thiels

1999-01-01

105

Cadmium effect on oxidative metabolism of pea (Pisum sativum L.) roots. Imaging of reactive oxygen species and nitric oxide accumulation in vivo.  

PubMed

Growth of pea (Pisum sativum L.) plants with 50 microM CdCl2 for 15 d produced a reduction in the number and length of lateral roots, and changes in structure of the principal roots affecting the xylem vessels. Cadmium induced a reduction in glutathione (GSH) and ascorbate (ASC) contents, and catalase (CAT), GSH reductase (GR) and guaiacol peroxidase (GPX) activities. CuZn-superoxide dismutase (SOD) activity was also diminished by the Cd treatment, although Mn-SOD was slightly increased. CAT and CuZn-SOD were down-regulated at transcriptional level, while Mn-SOD, Fe-SOD and GR were up-regulated. Analysis of reactive oxygen species (ROS) and nitric oxide (NO) levels by fluorescence and confocal laser microscopy (CLM) showed an over-accumulation of O2*- and H2O2, and a reduction in the NO content in lateral and principal roots. ROS overproduction was dependent on changes in intracellular Ca+2 content, and peroxidases and NADPH oxidases were involved. Cadmium also produced an increase in salicylic acid (SA), jasmonic acid (JA) and ethylene (ET) contents. The rise of ET and ROS, and the NO decrease are in accordance with senescence processes induced by Cd, and the increase of JA and SA could regulate the cellular response to cope with damages imposed by cadmium. PMID:16898016

Rodríguez-Serrano, María; Romero-Puertas, María C; Zabalza, Ana; Corpas, Francisco J; Gómez, Manuel; Del Río, Luis A; Sandalio, Luisa M

2006-08-01

106

Direct mitochondrial dysfunction precedes reactive oxygen species production in amiodarone-induced toxicity in human peripheral lung epithelial HPL1A cells  

SciTech Connect

Amiodarone (AM), a drug used in the treatment of cardiac dysrrhythmias, can produce severe pulmonary adverse effects, including fibrosis. Although the pathogenesis of AM-induced pulmonary toxicity (AIPT) is not clearly understood, several hypotheses have been advanced, including increased inflammatory mediator release, mitochondrial dysfunction, and free-radical formation. The hypothesis that AM induces formation of reactive oxygen species (ROS) was tested in an in vitro model relevant for AIPT. Human peripheral lung epithelial HPL1A cells, as surrogates for target cells in AIPT, were susceptible to the toxicity of AM and N-desethylamiodarone (DEA), a major AM metabolite. Longer incubations ({>=} 6 h) of HPL1A cells with 100 {mu}M AM significantly increased ROS formation. In contrast, shorter incubations (2 h) of HPL1A cells with AM resulted in mitochondrial dysfunction and cytoplasmic cytochrome c translocation. Preexposure of HPL1A cells to ubiquinone and {alpha}-tocopherol was more effective than that with Trolox C (registered) or 5,5-dimethylpyrolidine N-oxide (DMPO) at preventing AM cytotoxicity. These data suggest that mitochondrial dysfunction, rather than ROS overproduction, represents an early event in AM-induced toxicity in peripheral lung epithelial cells that may be relevant for triggering AIPT, and antioxidants that target mitochondria may potentially have beneficial effects in AIPT.

Nicolescu, Adrian C. [Department of Pharmacology and Toxicology, Queen's University, Kingston, ON, K7L 3N6 (Canada)], E-mail: adrian.nicolescu@ualberta.ca; Ji, Yanbin; Comeau, Jeannette L. [Department of Pharmacology and Toxicology, Queen's University, Kingston, ON, K7L 3N6 (Canada); Hill, Bruce C. [Department of Biochemistry, Queen's University, Kingston, ON, K7L 3N6 (Canada); Takahashi, Takashi [Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Brien, James F.; Racz, William J.; Massey, Thomas E. [Department of Pharmacology and Toxicology, Queen's University, Kingston, ON, K7L 3N6 (Canada)

2008-03-15

107

Reactive oxygen species in the aerobic decomposition of sodium hydroxymethanesulfinate.  

PubMed

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

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

1999-07-15

108

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

109

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

Microsoft Academic Search

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

Laura D. Mydlarz; Robert S. Jacobs

2006-01-01

110

Involvement of reactive oxygen species in brominated diphenyl ether-47-induced inflammatory cytokine release from human extravillous trophoblasts in vitro  

SciTech Connect

Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant compounds. Brominated diphenyl ether (BDE)-47 is one of the most prevalent PBDE congeners found in human breast milk, serum and placenta. Despite the presence of PBDEs in human placenta, effects of PBDEs on placental cell function are poorly understood. The present study investigated BDE-47-induced reactive oxygen species (ROS) formation and its role in BDE-47-stimulated proinflammatory cytokine release in a first trimester human extravillous trophoblast cell line, HTR-8/SVneo. Exposure of HTR-8/SVneo cells for 4 h to 20 ?M BDE-47 increased ROS generation 1.7 fold as measured by the dichlorofluorescein (DCF) assay. Likewise, superoxide anion production increased approximately 5 fold at 10 and 15 ?M and 9 fold at 20 ?M BDE-47 with a 1-h exposure, as measured by cytochrome c reduction. BDE-47 (10, 15 and 20 ?M) decreased the mitochondrial membrane potential by 47–64.5% at 4, 8 and 24 h as assessed with the fluorescent probe Rh123. Treatment with 15 and 20 ?M BDE-47 stimulated cellular release and mRNA expression of IL-6 and IL-8 after 12 and 24-h exposures: the greatest increases were a 35-fold increased mRNA expression at 12 h and a 12-fold increased protein concentration at 24 h for IL-6. Antioxidant treatments (deferoxamine mesylate, (±)?-tocopherol, or tempol) suppressed BDE-47-stimulated IL-6 release by 54.1%, 56.3% and 37.7%, respectively, implicating a role for ROS in the regulation of inflammatory pathways in HTR-8/SVneo cells. Solvent (DMSO) controls exhibited statistically significantly decreased responses compared with non-treated controls for IL-6 release and IL-8 mRNA expression, but these responses were not consistent across experiments and times. Nonetheless, it is possible that DMSO (used to dissolve BDE-47) may have attenuated the stimulatory actions of BDE-47 on cytokine responses. Because abnormal activation of proinflammatory responses can disrupt trophoblast functions necessary for placental development and successful pregnancy, further investigation is warranted of the impact of ROS and BDE-47 on trophoblast cytokine responses. - Highlights: • BDE-47 induced ROS overproduction and mitochondrial dysfunction. • BDE-47 stimulated production of proinflammatory cytokines. • Antioxidant treatment reduced BDE-47-stimulated ROS generation and cytokine release.

Park, Hae-Ryung, E-mail: heaven@umich.edu; Kamau, Patricia W.; Loch-Caruso, Rita

2014-01-15

111

Using oxygen species to measure marine production in Drake Passage  

NASA Astrophysics Data System (ADS)

Marine biological production is key to understanding the global carbon cycle, particularly the role of the Southern Ocean as a sink of CO2. Measurements of oxygen in the surface ocean allow quantifying marine biological productivity, since CO2 and O2 are linked via photosynthesis and respiration. Measurements of O2/Ar ratios and dissolved O2 isotopologues, together with wind-speed gas exchange parameterizations, give estimates of biological oxygen air-sea fluxes (Fbio) and gross photosynthetic production (G) in the mixed layer (zmix). In the absence of vertical mixing, Fbio can be used as a proxy for net community production (N). O2/Ar ratios and O2 concentrations were measured continuously in the uncontaminated seawater supply on board the RRS James Clark Ross along two sections across Drake Passage (DP). The DP1 section (southbound, 27 February-3 March 2007) represented mid-summer; DP2 represented early autumn (northbound, 12-15 April, 2007). The time difference between the two transects was 40 days. Weighted average gas exchange rates were calculated using the WOCE-NODC ocean mixed layer depth climatology and ECMWF wind speeds over 60 days prior to sample collection. The WOCE-NODC climatology shows a deepening of the zmix by on average 46 m within 40 days. The sea surface temperature decreased about 2.4 °C from DP1 to DP2. This reflects the seasonal transition from late summer to early autumn. In agreement with previous observations, we observed a strong north-south gradient of biological oxygen production in the DP. Our results also show high temporal variability over the course of 40 days. During late summer, the physical supersaturation contributes to about 3.6% of the total O2 supersaturation (?O2) for the Subantarctic and Polar Frontal Zones (SAZ and PFZ, respectively). In the other hand, the biological O2 supersaturation (?O2/Ar) showed mainly positive and homogeneous values (~1%) along the Antarctic Zone and Southern Antarctic Circumpolar Current Zone (AZ and SACCZ, respectively). This observation reflects predominantly a biological O2 production, associated with a shallow summer zmix (66 m), rather than due to physical processes (average Fbio of 9 mmol m-2 d-1 and G of 28 mmol m-2 d-1). The situation is inverted 40 days later during early autumn, when sea ice begins to form and zmix deepens (112 m). In AZ and SACCZ, Fbio and G decreased to -7 mmol m-2 d-1 and 10 mmol m-2 d-1, respectively. It is unclear whether net heterotrophy, upwelling of O2 subsaturated waters or increased of zmix and entrainment of low oxygen waters are responsible for the negative biological oxygen flux observed in during late summer in SAZ and PFZ, and in early autumn for AZ and SACCZ. We found a higher correlation between Fbio and zmix for the DP2 section than for DP1 (R2=0.61 and 0.08, respectively). Therefore, the increase of the zmix also plays an important role for the Fbio and G pattern in the DP, suggesting the entrainment of subsurface O2 depleted waters to the upper water column at the end of the growing season. Based on our observations, we argue that seasonal variations in zmix can potentially explain part of the meridional gradients found in the DP.

Castro Morales, Karel; Cassar, Nicolas; Bender, Michael; Kaiser, Jan

2010-05-01

112

Metabolic regulation and overproduction of primary metabolites  

PubMed Central

Summary Overproduction of microbial metabolites is related to developmental phases of microorganisms. Inducers, effectors, inhibitors and various signal molecules play a role in different types of overproduction. Biosynthesis of enzymes catalysing metabolic reactions in microbial cells is controlled by well?known positive and negative mechanisms, e.g. induction, nutritional regulation (carbon or nitrogen source regulation), feedback regulation, etc. The microbial production of primary metabolites contributes significantly to the quality of life. Fermentative production of these compounds is still an important goal of modern biotechnology. Through fermentation, microorganisms growing on inexpensive carbon and nitrogen sources produce valuable products such as amino acids, nucleotides, organic acids and vitamins which can be added to food to enhance its flavour, or increase its nutritive values. The contribution of microorganisms goes well beyond the food and health industries with the renewed interest in solvent fermentations. Microorganisms have the potential to provide many petroleum?derived products as well as the ethanol necessary for liquid fuel. Additional applications of primary metabolites lie in their impact as precursors of many pharmaceutical compounds. The roles of primary metabolites and the microbes which produce them will certainly increase in importance as time goes on. In the early years of fermentation processes, development of producing strains initially depended on classical strain breeding involving repeated random mutations, each followed by screening or selection. More recently, methods of molecular genetics have been used for the overproduction of primary metabolic products. The development of modern tools of molecular biology enabled more rational approaches for strain improvement. Techniques of transcriptome, proteome and metabolome analysis, as well as metabolic flux analysis. have recently been introduced in order to identify new and important target genes and to quantify metabolic activities necessary for further strain improvement. PMID:21261849

Sanchez, Sergio; Demain, Arnold L.

2008-01-01

113

FORUM REVIEW ARTICLE Reactive Oxygen Species in Plant Pathogenesis  

E-print Network

species (ROS) play multiple roles in interactions between plants and microbes, both as host defense as programmed cell death responses are central to plant defenses against invading pathogens. Contact of ROS, in- cluding hydrogen peroxide (H2O2), which diffuses into cells and activates plant defenses (6

Daub, Margaret

114

Reactive Oxygen Species on the Early Earth and Survival of Bacteria  

NASA Technical Reports Server (NTRS)

An oxygen-rich atmosphere appears to have been a prerequisite for complex, multicellular life to evolve on Earth and possibly elsewhere in the Universe. However it remains unclear how free oxygen first became available on the early Earth. A potentially important, and as yet poorly constrained pathway, is the production of oxygen through the weathering of rocks and release into the near-surface environment. Reactive Oxygen Species (ROS), as precursors to molecular oxygen, are a key step in this process, and may have had a decisive impact on the evolution of life, present and past. ROS are generated from minerals in igneous rocks during hydrolysis of peroxy defects, which consist of pairs of oxygen anions oxidized to the valence state -1 and during (bio) transformations of iron sulphide minerals. ROS are produced and consumed by intracellular and extracellular reactions of Fe, Mn, C, N, and S species. We propose that, despite an overall reducing or neutral oxidation state of the macroenvironment and the absence of free O2 in the atmosphere, organisms on the early Earth had to cope with ROS in their microenvironments. They were thus under evolutionary pressure to develop enzymatic and other defences against the potentially dangerous, even lethal effects of oxygen and its derived ROS. Conversely it appears that microorganisms learned to take advantage of the enormous reactive potential and energy gain provided by nascent oxygen. We investigate how oxygen might be released through weathering. We test microorganisms in contact with rock surfaces and iron sulphides. We model bacteria such as Deionococcus radiodurans and Desulfotomaculum, Moorella and Bacillus species for their ability to grow or survive in the presence of ROS. We examine how early Life might have adapted to oxygen.

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

2011-01-01

115

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

PubMed

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

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

2013-01-01

116

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

Microsoft Academic Search

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

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

2011-01-01

117

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

118

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

119

Electron Spin Resonance (ESR) detection of active oxygen species and organic phases in Martian soils  

NASA Technical Reports Server (NTRS)

The presence of active oxygen species (O(-), O2(-), O3(-)) and other strong oxidants (Fe2O3 and Fe3O4) was invoked in interpretations of the Viking biological experiments and a model was also suggested for Martian surface chemistry. The non-biological interpretations of the biological results gain futher support as no organic compounds were detected in the Viking pyrolysis-gas chromatography mass spectrometer (GCSM) experiments at concentrations as low as 10 ppb. Electron spin resonance (ESR) measures the absorption of microwaves by a paramagnetic and/or ferromagnetic center in the presence of an external field. In many instances, ESR has the advantage of detailed submicroscopic identification of the transient species and/or unstable reaction intermediates in their environments. Since the higly active oxygen species (O(-), O2(-), O3(-), and R-O-O(-)) are all paramagnetic in nature, they can be readily detected in native form by the ESR method. Active oxygen species likely to occur in the Martian surface samples were detected by ESR in UV-irradiated samples containing MgO. A miniaturized ESR spectrometer system can be developed for the Mars Rover Sample Return Mission. The instrument can perform the following in situ Martian samples analyses: detection of active oxygen species; characterization of Martian surface chemistry and photooxidation processes; and searching for organic compounds in the form of free radicals preserved in subsoils, and detection of microfossils with Martian carbonate sediments.

Tsay, Fun-Dow; Kim, Soon Sam; Liang, Ranty H.

1989-01-01

120

Adaptations of fish species to oxygen depletion in a central Amazonian floodplain lake  

Microsoft Academic Search

Pronounced seasonal and daily oxygen concentration changes are characteristic for Amazonian floodplain lakes. Studies on the\\u000a fish fauna of the Lago Camaleão, Solimões River, Amazonas, Brazil, showed several fish species which are able to survive prolonged\\u000a periods of heavy hypoxia. Twenty species belonging to eight families were observed in the laboratory in order to determine\\u000a their respiratory adaptations to hypoxic

M. G. M. Soares; N. A. Menezes; W. J. Junk

2006-01-01

121

Dominant Presence of Oxygenated Organic Species in the Remote Southern Hemisphere Troposphere  

NASA Technical Reports Server (NTRS)

Oxygenated organic species are intimately involved with the fate of nitrogen oxides (NO(sub x)) and hydrogen oxides (HO(sub x)), which are necessary for tropospheric ozone formation. A recent airborne experiment (March-April, 1999) focused over the southern hemisphere (SH) Pacific Ocean (PEM-tropics-B) provided a first opportunity for a detailed characterization of the oxygenated organic composition of the remote southern hemisphere troposphere. Three co-located multi-channel airborne instruments measured a dozen key oxygenated species (carbonyls, alcohols, organic nitrates, organic pernitrates, peroxides) along with a comprehensive suite of C2-C8 Nonmethane hydrocarbons (NMHC). These measurements reveal that in the tropical SH (0-30 deg south), oxygenated chemical abundances are extremely large and collectively are nearly five times those of NMHC. Even in the NH remote atmospheres their burden is equal to or greater than that of NMHC. The relatively uniform global distribution oxygenates (EPSILON Ox-org) is indicative of the presence of large natural and distributed sources. A global 3-D model, reflecting the present state of science, is unable to correctly simulate the atmospheric distribution and variability of several of these species.

Singh, H.; Chen, Y.; Staudt, A.; Jacob, D.; Blake, D.; Heikes, B.; Snow, J.; Hipskind, R. Stephen (Technical Monitor)

2000-01-01

122

Cell death from antibiotics without the involvement of reactive oxygen species  

PubMed Central

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

Liu, Yuanyuan; Imlay, James A.

2013-01-01

123

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

Microsoft Academic Search

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

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

1995-01-01

124

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

Microsoft Academic Search

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

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

1995-01-01

125

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

Microsoft Academic Search

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

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

1999-01-01

126

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

127

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

Microsoft Academic Search

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

I. A. Gamaley; I. V. Klyubin

1999-01-01

128

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

129

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

E-print Network

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

Cai, Long

130

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

131

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

Microsoft Academic Search

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

Andrew C. Allan; Robert Fluhr

1997-01-01

132

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

Microsoft Academic Search

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

Hiroyuki Yasui; Hiromu Sakurai

2000-01-01

133

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

E-print Network

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

Shi, Riyi

134

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

E-print Network

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

Shi, Riyi

135

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

Microsoft Academic Search

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

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

2005-01-01

136

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

Microsoft Academic Search

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

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

2008-01-01

137

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

138

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

139

Formation of Active Oxygen Species and Lipid Peroxidation Induced by Hypochlorite  

Microsoft Academic Search

Hypochlorite or its acid, hypochlorous acid, may exert both beneficial and toxic effects in vivo. In order to understand the role and action of hypochlorite, the formation of active oxygen species and its kinetics were studied in the reactions of hypochlorite with peroxides and amino acids. It was found that tert-butyl hydroperoxide and methyl linoleate hydroperoxide reacted with hypochlorite to

Noriko Noguchi; Akihiro Nakada; Yasuhiro Itoh; Akira Watanabe; Etsuo Niki

2002-01-01

140

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

PubMed

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

Pospíšil, Pavel; Prasad, Ankush; Rác, Marek

2014-10-01

141

Low oxygen tolerance of different life stages of temperate freshwater fish species.  

PubMed

Data on low dissolved oxygen (DO?) tolerance of freshwater fish species of north-western Europe were used to create species sensitivity distributions (SSD). Lowest observed effect concentrations (LOEC) and 100% lethal concentrations (LC???) data were collected from the scientific literature. Comparisons were made among life stages as well as between native and exotic species. In addition, lethal DO? concentrations were compared to oxygen concentrations corresponding to maximum tolerable water temperatures of the same species. Fish eggs and embryos were the least tolerant. Juveniles had a significantly lower mean LOEC than adults, but there was no difference in mean LC??? between the two groups. The difference in lethal oxygen concentrations between adults and juveniles was largest for three salmonids, although it remains uncertain if this was a result of smoltification. There were no significant differences between native and exotic species; however, data on exotics are limited. DO? concentrations converted from maximum tolerable water temperatures were 3·9 times higher than the measured lethal DO? concentrations, which may reflect changes in respiration rates (Q??) and may also relate to the simplicity of the model used. PMID:23808700

Elshout, P M F; Dionisio Pires, L M; Leuven, R S E W; Wendelaar Bonga, S E; Hendriks, A J

2013-07-01

142

The role of reactive oxygen species and subsequent DNA-damage response in the emergence of resistance towards resveratrol in colon cancer models.  

PubMed

In spite of the novel strategies to treat colon cancer, mortality rates associated with this disease remain consistently high. Tumour recurrence has been linked to the induction of resistance towards chemotherapy that involves cellular events that enable cancer cells to escape cell death. Treatment of colon cancer mainly implicates direct or indirect DNA-damaging agents and increased repair or tolerances towards subsequent lesions contribute to generate resistant populations. Resveratrol (RSV), a potent chemosensitising polyphenol, might share common properties with chemotherapeutic drugs through its indirect DNA-damaging effects reported in vitro. In this study, we investigated how RSV exerts its anticancer effects in models of colon cancer with a particular emphasis on the DNA-damage response (DDR; PIKKs-Chks-p53 signalling cascade) and its cellular consequences. We showed in vitro and in vivo that colon cancer models could progressively escape the repeated pharmacological treatments with RSV. We observed for the first time that this response was correlated with transient activation of the DDR, of apoptosis and senescence. In vitro, a single treatment with RSV induced a DDR correlated with S-phase delay and apoptosis, but prolonged treatments led to transient micronucleations and senescence phenotypes associated with polyploidisation. Ultimately, stable resistant populations towards RSV displaying higher degrees of ploidy and macronucleation as compared to parental cells emerged. We linked these transient effects and resistance emergence to the abilities of these cells to progressively escape RSV-induced DNA damage. Finally, we demonstrated that this DNA damage was triggered by an overproduction of reactive oxygen species (ROS) against which cancer cells could adapt under prolonged exposure to RSV. This study provides a pre-clinical analysis of the long-term effects of RSV and highlights ROS as main agents in RSV's indirect DNA-damaging properties and consequences in terms of anticancer response and potent resistance emergence. PMID:25412311

Colin, D J; Limagne, E; Ragot, K; Lizard, G; Ghiringhelli, F; Solary, É; Chauffert, B; Latruffe, N; Delmas, D

2014-01-01

143

Oxygen stress reduces zoospore survival of Phytophthora species in a simulated aquatic system  

PubMed Central

Background The genus Phytophthora includes a group of agriculturally important pathogens and they are commonly regarded as water molds. They produce motile zoospores that can move via water currents and on their own locomotion in aquatic environments. However, zoosporic response to dissolved oxygen, an important water quality parameter, is not known. Like other water quality parameters, dissolved oxygen concentration in irrigation reservoirs fluctuates dramatically over time. The aim of this study was to determine whether and how zoospore survival may be affected by elevated and low concentrations of dissolved oxygen in water to better understand the aquatic biology of these pathogens in irrigation reservoirs. Results Zoospores of P. megasperma, P. nicotianae, P. pini and P. tropicalis were assessed for survival in 10% Hoagland’s solution at a range of dissolved concentrations from 0.9 to 20.1 mg L-1 for up to seven exposure times from 0 to 72 h. Zoospore survival was measured by resultant colony counts per ml. Zoospores of these species survived the best in control Hoagland’s solution at dissolved oxygen concentrations of 5.3 to 5.6 mg L-1. Zoospore survival rates decreased with increasing and decreasing concentration of dissolved oxygen, depending upon Phytophthora species and exposure time. Overall, P. megasperma and P. pini are less sensitive than P. nicotianae and P. tropicalis to hyperoxia and hypoxia conditions. Conclusion Zoospores in the control solution declined over time and this natural decline process was enhanced under hyperoxia and hypoxia conditions. These findings suggest that dramatic fluctuations of dissolved oxygen in irrigation reservoirs contribute to the population decline of Phytophthora species along the water path in the same reservoirs. These findings advanced our understanding of the aquatic ecology of these pathogens in irrigation reservoirs. They also provided a basis for pathogen risk mitigation by prolonging the turnover time of runoff water in recycling irrigation systems via better system designs. PMID:24885900

2014-01-01

144

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

145

Oxygen species  

NASA Technical Reports Server (NTRS)

The spatial distribution of ozone, as predicted by numerical models, is compared with observations. A set of reference ozone profiles was developed against which to compare current numerical calculations. Most of the analyses will focus on ozone between 30 and 70 km altitude.

Brasseur, G.; Miller, A. J.; Bhartia, P. K.; Fleig, A.; Froidevaux, L.; Heath, D.; Hilsenrath, E.; Logan, J. A.; Mccormick, P.; Megie, G.

1985-01-01

146

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

147

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

PubMed

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

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

2000-01-01

148

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

NASA Astrophysics Data System (ADS)

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

Takahashi, Junko; Misawa, Masaki

2009-11-01

149

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

PubMed Central

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

Hyman, Lynne M.; Franz, Katherine J.

2013-01-01

150

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

PubMed Central

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

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

2010-01-01

151

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

PubMed

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

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

2007-10-01

152

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

153

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

Microsoft Academic Search

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

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

1996-01-01

154

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

155

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

156

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

Microsoft Academic Search

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

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

2011-01-01

157

Induced reactive oxygen species improve enzyme production from Aspergillus niger cultivation  

Microsoft Academic Search

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

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

2003-01-01

158

Oxygen species scavenging activity of phenolic extracts from hawthorn fresh plant organs and pharmaceutical preparations.  

PubMed

Different extracts of fresh vegetative and reproductive organs from Crataegus monogyna harvested during a whole season and from some pharmaceutical hawthorn preparations exhibit in vitro antioxidant activities using three different models of oxygen reactive species generation (superoxide anion, hydrogen peroxide and hypochlorous acid). All the tested samples show low IC50 values, the most efficient being fresh young leaves, fresh floral buds and pharmaceutical dried flowers. The activities seem to be especially bound to the total phenolic proanthocyanidin and flavonoid contents. PMID:8955870

Bahorun, T; Gressier, B; Trotin, F; Brunet, C; Dine, T; Luyckx, M; Vasseur, J; Cazin, M; Cazin, J C; Pinkas, M

1996-11-01

159

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

PubMed

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

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

2015-01-01

160

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

161

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

Microsoft Academic Search

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

M Maneesh; H Jayalekshmi

2006-01-01

162

Mechanisms of active oxygen species reduction by non-steroidal anti-inflammatory drugs.  

PubMed

Many forms of active oxygen have been suggested to participate in the course of inflammation. Anti-inflammatory drugs have been considered to function as active oxygen inhibitors. However, detailed mechanisms for such inhibitory activity remain unclear because of little well established methods to study inhibitory effect of anti-inflammatory drugs on active oxygen species. In this report, the author investigated four non-steroidal anti-inflammatory drugs, including acetaminophen, sodium salicylate, naproxen and flurbiprofen, their elimination and inhibition ability of active oxygen, using of the electron spin resonance spin-trapping method and the horseradish peroxidase method. In this experiment as active oxygen models, superoxide was evolved from a hypoxanthine-xanthine oxidase reaction system, and hydrogen peroxide by the spontaneous dismutation reaction. The data here show that the amount of superoxide was reduced in the manner of concentration of non-steroidal anti-inflammatory drugs in the reaction. Kinetic studies for these reaction showed that acetaminophen and sodium salicylate reacted with superoxide competitively, whereas naproxen and flurbiprofen did not. Analysis of generation of hydrogen peroxide formed by the spontaneous dismutation of superoxide derived from the reaction system revealed that hydrogen peroxide was increased by acetaminophen and decreased by sodium salicylate, naproxen and flurbiprofen. PMID:9202422

Kimura, K

1997-03-01

163

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

PubMed Central

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

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

2011-01-01

164

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

PubMed

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

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

2011-06-01

165

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

PubMed Central

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

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

2012-01-01

166

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

PubMed Central

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

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

1997-01-01

167

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

PubMed

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

Hirooka, Yoshitaka

2008-11-01

168

A Three Species Model to Simulate Application of Hyperbaric Oxygen Therapy to Chronic Wounds  

PubMed Central

Chronic wounds are a significant socioeconomic problem for governments worldwide. Approximately 15% of people who suffer from diabetes will experience a lower-limb ulcer at some stage of their lives, and 24% of these wounds will ultimately result in amputation of the lower limb. Hyperbaric Oxygen Therapy (HBOT) has been shown to aid the healing of chronic wounds; however, the causal reasons for the improved healing remain unclear and hence current HBOT protocols remain empirical. Here we develop a three-species mathematical model of wound healing that is used to simulate the application of hyperbaric oxygen therapy in the treatment of wounds. Based on our modelling, we predict that intermittent HBOT will assist chronic wound healing while normobaric oxygen is ineffective in treating such wounds. Furthermore, treatment should continue until healing is complete, and HBOT will not stimulate healing under all circumstances, leading us to conclude that finding the right protocol for an individual patient is crucial if HBOT is to be effective. We provide constraints that depend on the model parameters for the range of HBOT protocols that will stimulate healing. More specifically, we predict that patients with a poor arterial supply of oxygen, high consumption of oxygen by the wound tissue, chronically hypoxic wounds, and/or a dysfunctional endothelial cell response to oxygen are at risk of nonresponsiveness to HBOT. The work of this paper can, in some way, highlight which patients are most likely to respond well to HBOT (for example, those with a good arterial supply), and thus has the potential to assist in improving both the success rate and hence the cost-effectiveness of this therapy. PMID:19649306

Flegg, Jennifer A.; McElwain, Donald L. S.; Byrne, Helen M.; Turner, Ian W.

2009-01-01

169

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

PubMed

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

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

2015-02-17

170

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

PubMed

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

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

2011-07-15

171

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

PubMed Central

Inflammation is a complex and potentially life-threatening condition that involves the participation of a variety of chemical mediators, signaling pathways, and cell types. The microcirculation, which is critical for the initiation and perpetuation of an inflammatory response, exhibits several characteristic functional and structural changes in response to inflammation. These include vasomotor dysfunction (impaired vessel dilation and constriction), the adhesion and transendothelial migration of leukocytes, endothelial barrier dysfunction (increased vascular permeability), blood vessel proliferation (angiogenesis), and enhanced thrombus formation. These diverse responses of the microvasculature largely reflect the endothelial cell dysfunction that accompanies inflammation and the central role of these cells in modulating processes as varied as blood flow regulation, angiogenesis, and thrombogenesis. The importance of endothelial cells in inflammation-induced vascular dysfunction is also predicated on the ability of these cells to produce and respond to reactive oxygen and nitrogen species. Inflammation seems to upset the balance between nitric oxide and superoxide within (and surrounding) endothelial cells, which is necessary for normal vessel function. This review is focused on defining the molecular targets in the vessel wall that interact with reactive oxygen species and nitric oxide to produce the characteristic functional and structural changes that occur in response to inflammation. This analysis of the literature is consistent with the view that reactive oxygen and nitrogen species contribute significantly to the diverse vascular responses in inflammation and supports efforts that are directed at targeting these highly reactive species to maintain normal vascular health in pathological conditions that are associated with acute or chronic inflammation. PMID:22154653

Kvietys, Peter R.; Granger, D. Neil

2012-01-01

172

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

SciTech Connect

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

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

2011-01-01

173

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

PubMed

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

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

2013-11-01

174

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

EPA Science Inventory

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

175

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

176

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

177

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

E-print Network

Reactive oxygen species and Udx1 during early sea urchin development Julian L. Wong, Gary M. Wessel Abstract Sea urchin fertilization is marked by a massive conversion of molecular oxygen to hydrogen peroxide by a sea urchin dual oxidase, Udx1. This enzyme is essential for completing the physical block

Wessel, Gary M.

178

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

PubMed

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

Bernhard, Joan M; Bowser, Samuel S

2008-01-01

179

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

PubMed Central

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

2014-01-01

180

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

PubMed

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

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

2003-05-01

181

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

PubMed Central

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

2014-01-01

182

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

183

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

184

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

PubMed Central

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

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

2011-01-01

185

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

PubMed

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

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

2008-06-01

186

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

187

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

188

Protective activity of propofol, Diprivan and intralipid against active oxygen species.  

PubMed Central

We separately studied the antioxidant properties of propofol (PPF), Diprivan (the commercial form of PPF) and intralipid (IL) (the vehicle solution of PPF in Diprivan) on active oxygen species produced by phorbol myristate acetate (10(-6) M)-stimulated human polymorphonuclear leukocytes (PMN: 5 x 10(5) cells/assay), human endothelial cells (5 x 10(5) cells/assay) or cell-free systems (NaOCl or H2O2/peroxidase systems), using luminol (10(-4) M)-enhanced chemiluminescence (CL). We also studied the protective effects of Diprivan on endothelial cells submitted to an oxidant stress induced by H2O2/MPO system: cytotoxicity was assessed by the release of preincorporated 51Cr. Propofol inhibited the CL produced by stimulated PMN in a dose dependent manner (until 5 x 10(-5) M, a clinically relevant concentration), while Diprivan and IL were not dose-dependent inhibitors. The CL produced by endothelial cells was dose-dependently inhibited by Diprivan and PPF, and weakly by IL (not dose-dependent). In cell free systems, dose-dependent inhibitions were obtained for the three products with a lower effect for IL. Diprivan efficaciously protected endothelial cells submitted to an oxidant stress, while IL was ineffective. By HPLC, we demonstrated that PPF was not incorporated into the cells. The drug thus acted by scavenging the active oxygen species released in the extracellular medium. IL acted in the same manner, but was a less powerful antioxidant. PMID:9883967

Mathy-Hartert, M; Deby-Dupont, G; Hans, P; Deby, C; Lamy, M

1998-01-01

189

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

PubMed Central

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

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

2010-01-01

190

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

PubMed

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

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

1998-07-01

191

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

PubMed

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

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

2014-11-01

192

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

193

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

SciTech Connect

Phytochemicals show promise as potential chemopreventive or chemotherapeutic agents against various cancers. Here we report the chemotherapeutic effects of berberine, a phytochemical, on human prostate cancer cells. The treatment of human prostate cancer cells (PC-3) with berberine induced dose-dependent apoptosis but this effect of berberine was not seen in non-neoplastic human prostate epithelial cells (PWR-1E). Berberine-induced apoptosis was associated with the disruption of the mitochondrial membrane potential, release of apoptogenic molecules (cytochrome c and Smac/DIABLO) from mitochondria and cleavage of caspase-9,-3 and PARP proteins. This effect of berberine on prostate cancer cells was initiated by the generation of reactive oxygen species (ROS) irrespective of their androgen responsiveness, and the generation of ROS was through the increased induction of xanthine oxidase. Treatment of cells with allopurinol, an inhibitor of xanthine oxidase, inhibited berberine-induced oxidative stress in cancer cells. Berberine-induced apoptosis was blocked in the presence of antioxidant, N-acetylcysteine, through the prevention of disruption of mitochondrial membrane potential and subsequently release of cytochrome c and Smac/DIABLO. In conclusion, the present study reveals that the berberine-mediated cell death of human prostate cancer cells is regulated by reactive oxygen species, and therefore suggests that berberine may be considered for further studies as a promising therapeutic candidate for prostate cancer.

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

2008-05-15

194

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

PubMed Central

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

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

2008-01-01

195

Stable oxygen and hydrogen isotope composition of leaf water in C 3 and C 4 plant species under field conditions  

Microsoft Academic Search

In this paper we make comparisons between the observed oxygen and hydrogen stable isotope composition of leaf water and the predictions of the Craig-Gordon model of evaporative isotopic enrichment. Comparisons were made among two C3 species (Chenopodium album and Helianthus annuus) and two C4 species (Amaranthus retroflexus and Kochia scoparia), when plants were exposed to natural environmental conditions in the

Lawrence B. Flanagan; John F. Bain; James R. Ehleringer

1991-01-01

196

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

Microsoft Academic Search

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

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

2004-01-01

197

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

PubMed

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

Zhang, Danning; Yan, Shuwen; Song, Weihua

2014-11-01

198

Alginate Overproduction Affects Pseudomonas aeruginosa Biofilm Structure and Function  

Microsoft Academic Search

During the course of chronic cystic fibrosis (CF) infections, Pseudomonas aeruginosa undergoes a conversion to a mucoid phenotype, which is characterized by overproduction of the exopolysaccharide alginate. Chronic P. aeruginosa infections involve surface-attached, highly antibiotic-resistant communities of microorganisms organized in biofilms. Although biofilm formation and the conversion to mucoidy are both important aspects of CF pathogenesis, the relationship between them

M. Hentzer; GAIL M. TEITZEL; GRANT J. BALZER; A. Heydorn; S. Molin; M. Givskov; MATTHEW R. PARSEK

2001-01-01

199

Exploring the Overproduction of Amino Acids Using the Bilevel Optimization  

E-print Network

Exploring the Overproduction of Amino Acids Using the Bilevel Optimization Framework OptKnock Priti of representative amino acids and key precursors for all five families. These strat- egies span not only the central metabolic network genes but also the amino acid biosynthetic and degradation pathways. In addition to gene

Maranas, Costas

200

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

NASA Astrophysics Data System (ADS)

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

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

2013-02-01

201

Diffusion of a multi-species component and its role in oxygen and water transport in silicates  

NASA Technical Reports Server (NTRS)

The diffusion of a multispecies component is complicated by the different diffusion coefficient of each species and the interconversion reactions among the species. A diffusion equation is derived that incorporates the diffusive fluxes of all species contributing to the component's concentration. The effect of speciation on diffusion is investigated experimentally by measuring concentration profiles of all species developed during diffusion experiments. Data on water diffusion in rhyolitic glasses indicate that H2O molecules predominate over OH groups as the diffusing species at very low to high water concentrations. A simple theoretical relationship is drawn between the effective total oxygen diffusion coefficient and the total water concentration of silicates at low water content.

Zhang, Youxue; Stolper, E. M.; Wasserburg, G. J.

1991-01-01

202

Variability of oxygen radical absorbance capacity (ORAC) in different animal species.  

PubMed

The oxygen radical absorbance capacity (ORAC) was measured both in whole (ORAC-T) and deproteinized (ORAC-AS) plasma samples of human, pig, cow, rabbit, dog, cat, sheep, horse, dolphin, turkey, guinea-hen and chicken. In the 12 species, ORAC-T data, expressed as micromoles of peroxyl radicals trapped by 11 of sample, were found scattered between 8,600 and 23,000 micromol/l. The species with the highest ORAC-T values were cat among mammals and chicken among avies. ORAC-AS values ranged between 600 and 2000 micromol/l, with the highest values found in dolphin and sheep among mammals, while chicken was first among avies. In the 12 species, the relative contribution of ORAC-AS in relation to ORAC-T ranged from 5% to 20%. Protein SH-groups and uric acid were measured in plasma of all species, but no significant correlation was found between thiols and ORAC-T values or between uric acid and ORAC-AS values. Our results show that: (1) the ORAC method is reproducible and sensitive enough to be used in the comparison of the peroxyl-radical absorbance capacity of protein and non-protein plasma components in different animal species; (2) both in mammals and in avies, there is a deep intra-class heterogeneity of ORAC-T and ORAC-AS values; (3) by considering most species, plasma proteins and lipoproteins account for about 85-90% of the overall peroxyl-radical trapping capacity. In the dolphin only, the protein contribution decreases to 80%; (4) uric acid accounts for about one-half of the ORAC-AS value in human, guinea-hen and for about one-third in chicken, while it provides a very limited contribution in other species. We conclude that species with the highest ORAC-T, like cat and chicken, or with the highest ORAC-AS, like dolphin, are interesting models to study the reasons of such a marked antioxidant defense in the plasma. PMID:9925032

Ninfali, P; Aluigi, G

1998-11-01

203

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

PubMed Central

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

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

2006-01-01

204

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

PubMed

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

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

2014-04-01

205

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

PubMed

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

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

2009-02-01

206

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

PubMed

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

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

2014-03-01

207

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

208

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

PubMed Central

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

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

2011-01-01

209

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

NASA Astrophysics Data System (ADS)

Protein glycation is a cascade of nonenzymatic reactions between reducing sugars and amino groups of proteins. It is referred to as fructation when the reducing monosaccharide is fructose. Some potential mechanisms have been suggested for the generation of reactive oxygen species (ROS) by protein glycation reactions in the presence of glucose. In this state, glucose autoxidation, ketoamine, and oxidative advance glycation end products (AGEs) formation are considered as major sources of ROS and perhaps heme degradation during hemoglobin glycation. However, whether fructose mediated glycation produces ROS and heme degradation is unknown. Here we report that ROS (H2O2) production occurred during hemoglobin fructation in vitro using chemiluminescence methods. The enhanced heme exposure and degradation were determined using UV-Vis and fluorescence spectrophotometry. Following accumulation of ROS, heme degradation products were accumulated reaching a plateau along with the detected ROS. Thus, fructose may make a significant contribution to the production of ROS, glycation of proteins, and heme degradation during diabetes.

Goodarzi, M.; Moosavi-Movahedi, A. A.; Habibi-Rezaei, M.; Shourian, M.; Ghourchian, H.; Ahmad, F.; Farhadi, M.; Saboury, A. A.; Sheibani, N.

2014-09-01

210

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

PubMed Central

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

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

2013-01-01

211

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

PubMed

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

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

2011-08-01

212

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

PubMed

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

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

2012-07-01

213

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

PubMed Central

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

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

2014-01-01

214

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

PubMed Central

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

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

2011-01-01

215

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

216

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

SciTech Connect

Huntington's disease results from expansion of the polyglutamine (PolyQ) domain in the huntingtin protein. Although the cellular mechanism by which pathologic-length PolyQ protein causes neurodegeneration is unclear, mitochondria appear central in pathogenesis. We demonstrate in isolated mitochondria that pathologic-length PolyQ protein directly inhibits ADP-dependent (state 3) mitochondrial respiration. Inhibition of mitochondrial respiration by PolyQ protein is not due to reduction in the activities of electron transport chain complexes, mitochondrial ATP synthase, or the adenine nucleotide translocase. We show that pathologic-length PolyQ protein increases the production of reactive oxygen species in isolated mitochondria. Impairment of state 3 mitochondrial respiration by PolyQ protein is reversed by addition of the antioxidants N-acetyl-L-cysteine or cytochrome c. We propose a model in which pathologic-length PolyQ protein directly inhibits mitochondrial function by inducing oxidative stress.

Puranam, Kasturi L. [Deane Laboratory, Department of Medicine, Division of Neurology, Duke University Medical Center, Durham, NC 27710 (United States); Wu, Guanghong [Deane Laboratory, Department of Medicine, Division of Neurology, Duke University Medical Center, Durham, NC 27710 (United States); Strittmatter, Warren J. [Deane Laboratory, Department of Medicine, Division of Neurology, Duke University Medical Center, Durham, NC 27710 (United States); Burke, James R. [Deane Laboratory, Department of Medicine, Division of Neurology, Duke University Medical Center, Durham, NC 27710 (United States)]. E-mail: james.burke@duke.edu

2006-03-10

217

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

PubMed Central

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

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

2013-01-01

218

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

PubMed

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

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

2012-07-01

219

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

PubMed

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

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

2003-01-01

220

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

PubMed

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

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

2007-01-01

221

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

NASA Astrophysics Data System (ADS)

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

Sun, Qingrui; Chen, Tongsheng

2009-02-01

222

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

PubMed Central

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

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

2013-01-01

223

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

224

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

225

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

226

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

PubMed

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

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

2002-05-31

227

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

PubMed

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

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

2007-10-01

228

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

NASA Astrophysics Data System (ADS)

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

Fede, A.; Grannas, A. M.

2012-12-01

229

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

230

Antioxidant-photosensitizer dual-loaded polymeric micelles with controllable production of reactive oxygen species.  

PubMed

Poly(ethylene glycol)-b-poly(caprolactone) (PEG-b-PCL) micelles dually loaded with both pheophorbide a (PhA) as a photosensitizer and ?-carotene (CAR) as a singlet oxygen ((1)O2) scavenger were designed to control photodynamic therapy (PDT) activity in cancer treatment. The CAR in the PhA/CAR micelles significantly diminished PhA-generated (1)O2 through direct (1)O2 scavenging, whereas the CAR molecules lost their (1)O2 scavenging activity when the PhA and CAR were spatially isolated by the disintegration of the PEG-b-PCL micelles. In cell-culture systems, light irradiation at a post-treatment time that corresponded to the presence of the micelles in the blood environment induced negligible phototoxicity, whereas light irradiation at a post-treatment time that corresponded to the presence of the micelles in the intracellular environment induced remarkable phototoxicity. In addition, a longer post-treatment time induced greater internalization of PhA/CAR micelles, which resulted in higher phototoxicity, suggesting an increase in photo killing activity against the tumor cells of interest. Thus, the co-loading of a (1)O2 generator and a (1)O2 scavenger into a single micelle is a potential strategy that may be useful in facilitating more accurate and reliable PDT with site-specific controllable production of singlet oxygen species for cancer treatment. PMID:24939615

Li, Li; Cho, Hana; Yoon, Kwon Hyeok; Kang, Han Chang; Huh, Kang Moo

2014-08-25

231

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

232

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

PubMed

Infection with ectomycorrhizal fungi can increase the ability of plants to resist drought stress through morphophysiological and biochemical mechanisms. However, the metabolism of antioxidative enzyme activities in the ectomycorrhizal symbiosis remains poorly understood. This study investigated biomass production, reactive oxygen metabolism (hydrogen peroxide and malondialdehyde concentration) and antioxidant enzyme activity (superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase) in pure cultures of the ectomycorrhizal fungi Descolea antartica Sing. and Pisolithus tinctorius (Pers.) Coker & Couch, and non-mycorrhizal and mycorrhizal roots of Nothofagus dombeyi (Mirb.) roots under well-watered conditions and drought conditions (DC). The studied ectomycorrhizal fungi regulated their antioxidative enzyme metabolism differentially in response to drought, resulting in cellular damage in D. antartica but not in P. tinctorius. Ectomycorrhizal inoculation and water treatment had a significant effect on all parameters studied, including relative water content of the plant. As such, N. dombeyi plants in symbiosis experienced a lower oxidative stress effect than non-mycorrhizal plants under DC. Additionally, ectomycorrhizal N. dombeyi roots showed a greater antioxidant enzyme activity relative to non-mycorrhizal roots, an effect which was further expressed under DC. The association between the non-specific P. tinctorius and N. dombeyi had a more effective reactive oxygen species (ROS) metabolism than the specific D. antartica-N. dombeyi symbiosis. We conclude that the combination of effective ROS prevention and ROS detoxification by ectomycorrhizal plants resulted in reduced cellular damage and increased plant growth relative to non-mycorrhizal plants under drought. PMID:19483186

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

2009-08-01

233

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

234

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

235

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

PubMed Central

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

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

2013-01-01

236

The Effects of Cold Acclimation upon the Oxygen Consumption of Two Species of Free-Living Nematodes  

PubMed Central

Two species of free-living nematodes, Panagrellus redivivus and Turbatrix aceti, were cultured axenically at control (20 C) and cold (10 C) temperatures. Oxygen consumption of worms from each population was measured manometrically on days 2 through 8 after exposure to these temperatures. In both species, the slope of the oxygen consumption curve for the controls was greater than that of the worms exposed to the cold on day 2. The slope of the curve of the cold-exposed worms gradually increased until day 7. At this time, the slope of the oxygen consumption curve from the cold-exposed worms exceeded or equaled that of the controls. This is taken as an indication of the onset of the cold-acclimated state in both species of worms by day 7. PMID:19319343

Cooper, S. C.; Ferguson, J. H.

1973-01-01

237

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

PubMed Central

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

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

2005-01-01

238

The chemical kinetics and thermodynamics of sodium species in oxygen-rich hydrogen flames  

NASA Technical Reports Server (NTRS)

Results are presented which, it is claimed, lead to a correction of previous misconceptions over the relative importance and kinetics of NaO2. It is shown that its rapid conversion to NaO and NaOH is such that it can severely perturb the NaOH/Na ratio and produce significant concentration overshoots over that predicted from the balance of the reaction of Na with H2O. This becomes increasingly the case in flames of large O2 concentrations and temperatures below 2500 K; and the corresponding large rate constants for the termolecular formation of the other alkali peroxides imply that similar considerations will be necessary for them. Depending on the rate constants for the exothermic conversions of MO2 to MO or MOH, the steady-state concentrations of MO2 could be more or less significant than for sodium. Owing to numerous reactions that produce these conversions, the MOH species will probably be the dominant species in all cases in oxygen-rich hydrogen or hydrocarbon flames, with MO concentrations at not greater than 1 percent of the bound metal.

Hynes, A. J.; Steinberg, M.; Schofield, K.

1984-01-01

239

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

PubMed Central

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

Lee, Sangmin

2010-01-01

240

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

PubMed Central

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

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

2013-01-01

241

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

PubMed

Abstract Daily torpor results in an ?70% decrease in metabolic rate (MR) and a 20%-70% decrease in state 3 (phosphorylating) respiration rate of isolated liver mitochondria in both dwarf Siberian hamsters and mice even when measured at 37°C. This study investigated whether mitochondrial metabolic suppression also occurs in these species during euthermic fasting, when MR decreases significantly but torpor is not observed. State 3 respiration rate measured at 37°C was 20%-30% lower in euthermic fasted animals when glutamate but not succinate was used as a substrate. This suggests that electron transport chain complex I is inhibited during fasting. We also investigated whether mitochondrial metabolic suppression alters mitochondrial reactive oxygen species (ROS) production. In both torpor and euthermic fasting, ROS production (measured as H(2)O(2) release rate) was lower with glutamate in the presence (but not absence) of rotenone when measured at 37°C, likely reflecting inhibition at or upstream of the complex I ROS-producing site. ROS production with succinate (with rotenone) increased in torpor but not euthermic fasting, reflecting complex II inhibition during torpor only. Finally, mitochondrial ROS production was twofold more temperature sensitive than mitochondrial respiration (as reflected by Q(10) values). These data suggest that electron leak from the mitochondrial electron transport chain, which leads to ROS production, is avoided more efficiently at the lower body temperatures experienced during torpor. PMID:21897084

Brown, Jason C L; Staples, James F

2011-01-01

242

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

PubMed

Artemisinin-based combination therapy (ACT) is the recommended first-line treatment for Plasmodium falciparum malaria. It has been suggested that the cytotoxic effect of artemisinin is mediated by free radicals followed by the alkylation of P. falciparum proteins. The endoperoxide bridge, the active moiety of artemisinin derivatives, is cleaved in the presence of ferrous iron, generating reactive oxygen species (ROS) and other free radicals. However, the emergence of resistance to artemisinin in P. falciparum underscores the need for new insights into the molecular mechanisms of antimalarial activity of artemisinin. Here we show that artesunate (ART) induces DNA double-strand breaks in P. falciparum in a physiologically relevant dose- and time-dependent manner. DNA damage induced by ART was accompanied by an increase in the intracellular ROS level in the parasites. Mannitol, a ROS scavenger, reversed the cytotoxic effect of ART and reduced DNA damage, and modulation of glutathione (GSH) levels was found to impact ROS and DNA damage induced by ART. Accumulation of ROS, increased DNA damage, and the resulting antiparasite effect suggest a causal relationship between ROS, DNA damage, and parasite death. Finally, we also show that ART-induced ROS production involves a potential role for NADPH oxidase, an enzyme involved in the production of superoxide anions. Our results with P. falciparum provide novel insights into previously unknown molecular mechanisms underlying the antimalarial activity of artemisinin derivatives and may help in the design of next-generation antimalarial drugs against the most virulent Plasmodium species. PMID:25348537

Gopalakrishnan, Anusha M; Kumar, Nirbhay

2015-01-01

243

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

PubMed Central

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

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

2014-01-01

244

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

PubMed

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

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

2014-07-01

245

Titan's photochemical model: Further update, oxygen species, and comparison with Triton and Pluto  

NASA Astrophysics Data System (ADS)

The photochemical model for Titan's atmosphere and ionosphere is improved using the Troe approximation for termolecular reactions and inclusion of four radiative association reactions from those calculated by Vuitton et al. (2012). Proper fitting of eddy diffusion results in a reduction of the mean difference between 63 observed mixing ratios and their calculated values from a factor of 5 in our previous Titan's models to a factor of 3 in the current model. Oxygen chemistry on Titan is initiated by influxes of H2O from meteorites and O+ from magnetospheric interactions with the Saturn rings and Enceladus. Two versions of the model were calculated, with and without the O+ flux. Balances of CO, CO2, H2O, and H2CO are discussed in detail for both versions. The calculated model with the O+ flux agrees with the observations of CO, CO2, and H2O, including recent H2O CIRS limb observations and measurements by the Herschel Space Observatory. Major observational data and photochemical models for Triton and Pluto are briefly discussed. While the basic atmospheric species N2, CH4, and CO are similar on Triton and Pluto, properties of their atmospheres are very different with dominating atomic species and ions in Triton's upper atmosphere and ionosphere opposed to the molecular composition on Pluto. Calculations favor a transition between two types of photochemistry at the CH4 mixing ratio of ~5×10-4. Therefore the current Triton's photochemistry is still similar to that at the Voyager flyby despite the observed increase in N2 and CH4. The meteorite H2O results in precipitation of CO on Triton and CO2 on Pluto near perihelion. Main oxygen species on Titan: observations and the model. Solid lines show the model with both meteorite influx of H2O and magnetospheric flux of O+. Thin lines show the model without flux of O+. Observations: (1) CIRS (de Kok et al. 2007), (2) CIRS at 5°N (Vinatier et al. 2010), (3) ISO (Coustenis et al. 1998), (4) INMS (Cui et al., 2009), (5) CIRS (Cottini et al. 2012), and (6) Herschel (Moreno et al. 2012).

Krasnopolsky, V. A.

2012-12-01

246

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

PubMed

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

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

2015-02-01

247

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

PubMed Central

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

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

2014-01-01

248

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

PubMed Central

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

Singh, Nameirakpam D.; Daniell, Henry

2013-01-01

249

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

250

Oxygen Metabolic Responses of Three Species of Large Benthic Foraminifers with Algal Symbionts to Temperature Stress  

PubMed Central

Water temperature affects the physiology of large benthic foraminifers (LBFs) with algal symbionts dwelling in coral reef environments. However, the detailed physiological responses of LBF holobionts to temperature ranges occurring in their habitats are not known. We report net oxygen (O2) production and respiration rates of three LBF holobionts (Baculogypsina sphaerulata and Calcarina gaudichaudii hosting diatom symbionts, and Amphisorus kudakajimensis hosting dinoflagellate symbionts) measured in the laboratory at water temperatures ranging from 5°C to 45°C in 2.5°C or 5°C intervals and with light saturation levels of ?500 µmol m?2 s?1. In addition, the recovery of net O2 production and respiration rates after exposure to temperature stress was assessed. The net O2 production and respiration rates of the three LBF holobionts peaked at ?30°C, indicating their optimal temperature for a short exposure period. At extreme high temperatures (?40°C), the net O2 production rates of all three LBF holobionts declined to less than zero and the respiration rates slightly decreased, indicating that photosynthesis of algal symbionts was inactivated. At extreme low temperatures (?10°C for two calcarinid species and ?5°C for A. kudakajimensis), the net O2 production and respiration rates were near zero, indicating a weakening of holobiont activity. After exposure to extreme high or low temperature, the net O2 production rates did not recover until the following day, whereas the respiration rates recovered rapidly, suggesting that a longer time (days) is required for recovery from damage to the photosystem by temperature stress compared to the respiration system. These results indicate that the oxygen metabolism of LBF holobionts can generally cope well with conditions that fluctuate diurnally and seasonally in their habitats. However, temporal heat and cold stresses with high light levels may induce severe damage to algal symbionts and also damage to host foraminifers. PMID:24594773

Fujita, Kazuhiko; Okai, Takaaki; Hosono, Takashi

2014-01-01

251

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

252

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

PubMed

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

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

2007-05-01

253

Oxygen metabolic responses of three species of large benthic foraminifers with algal symbionts to temperature stress.  

PubMed

Water temperature affects the physiology of large benthic foraminifers (LBFs) with algal symbionts dwelling in coral reef environments. However, the detailed physiological responses of LBF holobionts to temperature ranges occurring in their habitats are not known. We report net oxygen (O2) production and respiration rates of three LBF holobionts (Baculogypsina sphaerulata and Calcarina gaudichaudii hosting diatom symbionts, and Amphisorus kudakajimensis hosting dinoflagellate symbionts) measured in the laboratory at water temperatures ranging from 5°C to 45°C in 2.5°C or 5°C intervals and with light saturation levels of ?500 µmol m(-2) s(-1). In addition, the recovery of net O2 production and respiration rates after exposure to temperature stress was assessed. The net O2 production and respiration rates of the three LBF holobionts peaked at ?30°C, indicating their optimal temperature for a short exposure period. At extreme high temperatures (?40°C), the net O2 production rates of all three LBF holobionts declined to less than zero and the respiration rates slightly decreased, indicating that photosynthesis of algal symbionts was inactivated. At extreme low temperatures (?10°C for two calcarinid species and ?5°C for A. kudakajimensis), the net O2 production and respiration rates were near zero, indicating a weakening of holobiont activity. After exposure to extreme high or low temperature, the net O2 production rates did not recover until the following day, whereas the respiration rates recovered rapidly, suggesting that a longer time (days) is required for recovery from damage to the photosystem by temperature stress compared to the respiration system. These results indicate that the oxygen metabolism of LBF holobionts can generally cope well with conditions that fluctuate diurnally and seasonally in their habitats. However, temporal heat and cold stresses with high light levels may induce severe damage to algal symbionts and also damage to host foraminifers. PMID:24594773

Fujita, Kazuhiko; Okai, Takaaki; Hosono, Takashi

2014-01-01

254

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

255

Role of oxygen and nitrogen species in experimental uveitis: anti-inflammatory activity of the synthetic antioxidant ebselen  

Microsoft Academic Search

This study was aimed at examining the role of oxygen and nitrogen reactive species in a model of experimental uveitis upon intravitreal injection of bacterial endotoxin to albino New Zealand rabbits. The inflammatory response was evaluated in terms of: (i) the integrity of the blood aqueous barrier (protein and cell content in samples of aqueous humor), (ii) histopathological changes of

Francisco Bosch-Morell; Joaqu??n Romá; Nuria Mar??n; Belén Romero; Antonio Rodriguez-Galietero; Siv Johnsen-Soriano; Manuel D??az-Llopis; Francisco J Romero

2002-01-01

256

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

PubMed

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

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

2011-11-01

257

Abilities of Helophyte Species to Release Oxygen into Rhizospheres with Varying Redox Conditions in Laboratory-Scale Hydroponic Systems  

Microsoft Academic Search

Plantlets of the wetland species cattail (Typha latifolia), reed (Phragmites australis), rush (Juncus effusus), and yellow flag (Iris pseudacorus) grown from seedlings or cuttings were investigated in laboratory-scale hydroponic systems in order to determine the intensity of oxygen release into the rhizosphere under various redox conditions. The initial redox conditions of the rhizosphere were modified by adding different amounts of

A. Wießner; P. Kuschk; M. Kästner; U. Stottmeister

2002-01-01

258

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

259

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

260

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

E-print Network

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

Berges, John A.

261

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

Microsoft Academic Search

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

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

2011-01-01

262

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

263

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

Microsoft Academic Search

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

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

1995-01-01

264

Probing secondary coordination sphere influence on the oxygenation of zinc alkyls: formation of a unique zinc peroxide species.  

PubMed

Reactions of ethylzinc derivatives of o-hydroxybiphenyl with O2 were investigated. The study revealed an essential role in the oxygenation process of intra-molecular interactions involving aromatic rings and provided a unique aryloxide (hydroxide) Zn8(OAr)8(OH)6(O2) cluster with an encapsulated peroxide species. PMID:24080918

Sobota, Piotr; Petrus, Rafa?; Zelga, Karolina; M?kolski, Lukasz; Kubicki, Dominik; Lewi?ski, Janusz

2013-11-18

265

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

E-print Network

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

Gates, Kent. S.

266

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

267

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

PubMed Central

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

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

2009-01-01

268

Mitochondrial Redox Signaling: Interaction of Mitochondrial Reactive Oxygen Species with Other Sources of Oxidative Stress  

PubMed Central

Abstract Significance: Oxidative stress is a well established hallmark of cardiovascular disease and there is strong evidence for a causal role of reactive oxygen and nitrogen species (RONS) therein. Recent Advances: Improvement of cardiovascular complications by genetic deletion of RONS producing enzymes and overexpression of RONS degrading enzymes proved the involvement of these species in cardiovascular disease at a molecular level. Vice versa, overexpression of RONS producing enzymes as well as deletion of antioxidant enzymes was demonstrated to aggravate cardiovascular complications. Critical Issues: With the present overview we present and discuss different pathways how mitochondrial RONS interact (crosstalk) with other sources of oxidative stress, namely NADPH oxidases, xanthine oxidase and an uncoupled nitric oxide synthase. The potential mechanisms of how this crosstalk proceeds are discussed in detail. Several examples from the literature are summarized (including hypoxia, angiotensin II mediated vascular dysfunction, cellular starvation, nitrate tolerance, aging, hyperglycemia, ?-amyloid stress and others) and the underlying mechanisms are put together to a more general concept of redox-based activation of different sources of RONS via enzyme-specific “redox switches”. Mitochondria play a key role in this concept providing redox triggers for oxidative damage in the cardiovascular system but also act as amplifiers to increase the burden of oxidative stress. Future Directions: Based on these considerations, the characterization of the role of mitochondrial RONS formation in cardiac disease as well as inflammatory processes but also the role of mitochondria as potential therapeutic targets in these pathophysiological states should be addressed in more detail in the future. Antioxid. Redox Signal. 20, 308–324. PMID:22657349

Schulz, Eberhard; Wenzel, Philip; Münzel, Thomas

2014-01-01

269

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

PubMed Central

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

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

2009-01-01

270

Differential effects of mitochondrial Complex I inhibitors on production of reactive oxygen species  

PubMed Central

We have investigated the production of reactive oxygen species (ROS) by Complex I in isolated open bovine heart submitochondrial membrane fragments during forward electron transfer in presence of NADH, by means of the probe 2?,7?-Dichlorodihydrofluorescein diacetate. ROS production by Complex I is strictly related to its inhibited state. Our results indicate that different Complex I inhibitors can be grouped into two classes: Class A inhibitors (Rotenone, Piericidin A and Rolliniastatin 1 and 2) increase ROS production; Class B inhibitors (Stigmatellin, Mucidin, Capsaicin and Coenzyme Q2) prevent ROS production also in the presence of Class A inhibitors. Addition of the hydrophilic Coenzyme Q1 as an electron acceptor potentiates the effect of Rotenone-like inhibitors in increasing ROS production, but has no effect in the presence of Stigmatellin-like inhibitors; the effect is not shared by more hydrophobic quinones such as decylubiquinone. This behaviour relates the prooxidant CoQ1 activity to a hydrophilic electron escape site. Moreover the two classes of Complex I inhibitors have an opposite effect on the increase of NADH–DCIP reduction induced by short chain quinones: only Class B inhibitors allow this increase, indicating the presence of a Rotenone-sensitive but Stigmatellin-insensitive semiquinone species in the active site of the enzyme. The presence of this semiquinone was also suggested by preliminary EPR data. The results suggest that electron transfer from the iron–sulphur clusters (N2) to Coenzyme Q occurs in two steps gated by two different conformations, the former being sensitive to Rotenone and the latter to Stigmatellin. PMID:19059197

Fato, Romana; Bergamini, Christian; Bortolus, Marco; Maniero, Anna Lisa; Leoni, Serena; Ohnishi, Tomoko; Lenaz, Giorgio

2009-01-01

271

Arginine decarboxylase expression, polyamines biosynthesis and reactive oxygen species during organogenic nodule formation in hop  

PubMed Central

Hop (Humulus lupulus L.) is an economically important plant species used in beer production and as a health-promoting medicine. Hop internodes develop upon stress treatments organogenic nodules which can be used for genetic transformation and micropropagation. Polyamines are involved in plant development and stress responses. Arginine decarboxylase (ADC; EC 4·1.1·19) is a key enzyme involved in the biosynthesis of putrescine in plants. Here we show that ADC protein was increasingly expressed at early stages of hop internode culture (12 h). Protein continued accumulating until organogenic nodule formation after 28 days, decreasing thereafter. The same profile was observed for ADC transcript suggesting transcriptional regulation of ADC gene expression during morphogenesis. The highest transcript and protein levels observed after 28 days of culture were accompanied by a peak in putrescine levels. Reactive oxygen species accumulate in nodular tissues probably due to stress inherent to in vitro conditions and enhanced polyamine catabolism. Conjugated polyamines increased during plantlet regeneration from nodules suggesting their involvement in plantlet formation and/or in the control of free polyamine levels. Immunogold labeling revealed that ADC is located in plastids, nucleus and cytoplasm of nodular cells. In vacuolated cells, ADC immunolabelling in plastids doubled the signal of proplastids in meristematic cells. Location of ADC in different subcellular compartments may indicate its role in metabolic pathways taking place in these compartments. Altogether these data suggest that polyamines play an important role in organogenic nodule formation and represent a progress towards understanding the role played by these growth regulators in plant morphogenesis. PMID:21415599

Santos, Filipa; Seguí-Simarro, José M; Palme, Klaus; Altabella, Teresa; Tiburcio, Antonio F; Pais, Maria S

2011-01-01

272

The Stimulated Innate Resistance Event in Bordetella pertussis Infection Is Dependent on Reactive Oxygen Species Production  

PubMed Central

The exacerbated induction of innate immune responses in airways can abrogate diverse lung infections by a phenomenon known as stimulated innate resistance (StIR). We recently demonstrated that the enhancement of innate response activation can efficiently impair Bordetella pertussis colonization in a Toll-like receptor 4 (TLR4)-dependent manner. The aim of this work was to further characterize the effect of lipopolysaccharide (LPS) on StIR and to identify the mechanisms that mediate this process. Our results showed that bacterial infection was completely abrogated in treated mice when the LPS of B. pertussis (1 ?g) was added before (48 h or 24 h), after (24 h), or simultaneously with the B. pertussis challenge (107 CFU). Moreover, we detected that LPS completely cleared bacterial infection as soon as 2 h posttreatment. This timing suggests that the observed StIR phenomenon should be mediated by fast-acting antimicrobial mechanisms. Although neutrophil recruitment was already evident at this time point, depletion assays using an anti-GR1 antibody showed that B. pertussis clearance was achieved even in the absence of neutrophils. To evaluate the possible role of free radicals in StIR, we performed animal assays using the antioxidant N-acetyl cysteine (NAC), which is known to inactivate oxidant species. NAC administration blocked the B. pertussis clearance induced by LPS. Nitrite concentrations were also increased in the LPS-treated mice; however, the inhibition of nitric oxide synthetases did not suppress the LPS-induced bacterial clearance. Taken together, our results show that reactive oxygen species (ROS) play an essential role in the TLR4-dependent innate clearance of B. pertussis. PMID:23630952

Zurita, E.; Moreno, G.; Errea, A.; Ormazabal, M.; Rumbo, M.

2013-01-01

273

Ethylene and reactive oxygen species are involved in root aerenchyma formation and adaptation of wheat seedlings to oxygen-deficient conditions  

PubMed Central

Exposing plants to hypoxic conditions greatly improves their anoxic stress tolerance by enhancing the activities of glycolysis and fermentation in roots. Ethylene may also be involved in these adaptive responses because its synthesis is increased in roots under hypoxic conditions. Here it is reported that pre-treatment of wheat seedlings with an ethylene precursor, 1-aminocyclopropanecarboxylic acid (ACC), enhanced accumulation of ethylene in the roots of wheat seedlings, and enhanced their tolerance of oxygen-deficient conditions through increasing the expression of genes encoding ethanol fermentation enzymes, alcohol dehydrogenase and pyruvate decarboxylase, in the roots. Lysigenous aerenchyma formation in root was induced by ACC pre-treatment and was further induced by growth under oxygen-deficient conditions. ACC pre-treatment increased the expression of three genes encoding respiratory burst oxidase homologue (a plant homologue of gp91phox in NADPH oxidase), which has a role in the generation of reactive oxygen species (ROS), in roots of seedlings. Co-treatment with ACC and an NADPH oxidase inhibitor, diphenyleneiodonium, partly suppressed the ACC-induced responses. These results suggest that ethylene and ROS are involved in adaptation of wheat seedlings to oxygen-deficient conditions through controlling lysigenous aerenchyma formation and the expression of genes encoding ethanol fermentation enzymes. PMID:24253196

Yamauchi, Takaki

2014-01-01

274

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

PubMed

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

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

2013-01-01

275

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

276

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

PubMed

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

Mokudai, Takayuki; Kanno, Taro; Niwano, Yoshimi

2015-01-01

277

Controllable generation of reactive oxygen species by femtosecond-laser irradiation  

SciTech Connect

Femtosecond lasers have been advancing Biophotonics research in the past two decades with multiphoton microscopy, microsurgery, and photodynamic therapy. Nevertheless, laser irradiation is identified to bring photodamage to cells via reactive oxygen species (ROS) generation with unclear mechanism. Meanwhile, currently in biological researches, there is no effective method to provide controllable ROS production precisely, which originally is leaked from mitochondria during respiration and plays a key role in a lot of important cellular processes and cellular signaling pathways. In this study, we show the process of how the tightly focused femtosecond-laser induces ROS generation solely in mitochondria at the very beginning and then release to cytosol if the stimulus is intense enough. At certain weak power levels, the laser pulses induce merely moderate Ca{sup 2+} release but this is necessary for the laser to generate ROS in mitochondria. Cellular original ROS are also involved with a small contribution. When the power is above a threshold, ROS are then released to cytosol, indicating photodamage overwhelming cellular repair ability. The mechanisms in those two cases are quite different. Those results clarify parts of the mechanism in laser-induced ROS generation. Hence, it is possible to further this optical scheme to provide controllable ROS generation for ROS-related biological researches including mitochondrial diseases and aging.

Yan, Wei; He, Hao, E-mail: haohe@tju.edu.cn; Wang, Yintao; Wang, Yisen; Hu, Minglie; Wang, Chingyue [Ultrafast Laser Laboratory, Key Laboratory of Optoelectronic Information Technology (Ministry of Education), College of Precision Instrument and Optoelectronics Engineering, Tianjin University, Tianjin (China)

2014-02-24

278

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

PubMed Central

A common denominator among the multiple damage-inducing agents that ultimately lead to the activation of NLRP3 has not yet been identified. Recently, the production of reactive oxygen species (ROS) has been suggested to act as a common event upstream of the NLRP3 inflammasome machinery. Since de novo translation of NLRP3 is an essential step in the activation of NLRP3, we investigated the role of substances that either inhibit ROS production or its oxidative activity. While we observe that NLRP3 inflammasome activation is unique amongst other known inflammasomes due to its sensitivity to ROS inhibition, we have found that this phenomenon is attributable to the fact that NLRP3 strictly requires priming by a pro-inflammatory signal, a step that is blocked by ROS inhibitors. While these data do not exclude a general role of ROS production in the process of NLRP3-triggered inflammation, they put ROS upstream of NLRP3 induction, but not activation. PMID:21677136

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

2011-01-01

279

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

PubMed

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

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

1996-09-01

280

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

PubMed

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

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

2005-12-01

281

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

PubMed

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

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

2014-03-01

282

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

PubMed Central

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

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

2009-01-01

283

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

PubMed

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

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

2014-11-01

284

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

PubMed

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

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

2015-02-01

285

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

PubMed Central

We have investigated the cytotoxicity and reactive oxygen species (ROS) generation for indoor and outdoor soots: candle, wood, diesel, tire, and natural gas burner soots – along with surrogate black carbon, various multiwall carbon nanotube aggregate materials, TiO2 (anatase) and chrysotile asbestos as reference materials. All soots were observed utilizing TEM and FESEM to be composed of aggregated, primary spherules (20–80 nm diameter) forming complex, branched fractal structures. These spherules were composed of intercalated, turbostratic arrangements of curved graphene fragments with varying concentrations of polycyclic aromatic hydrocarbon (PAH) isomers. In vitro cultures with an immortalized human lung epithelial carcinoma cell line (A549) treated with these materials showed decreased cell viability and variations in ROS production, with no correlations to PAH content. The data demonstrate that soots are cytotoxic and that cytotoxicity is not related to PAH content but is related to ROS generation, suggesting that soot induces cellular oxidative stress and that cell viability assays can be indicators of ROS production. PMID:18488419

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

2008-01-01

286

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

287

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

288

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

NASA Astrophysics Data System (ADS)

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

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

2004-09-01

289

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

PubMed

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

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

2010-03-31

290

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

291

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

PubMed

Cytokine-induced lung expression of the endothelial cell (EC) leukocyte receptor P-selectin initiates leukocyte rolling. To understand the early EC signaling that induces the expression, we conducted real-time digital imaging studies in lung venular capillaries. To compare receptor- vs nonreceptor-mediated effects, we infused capillaries with respectively, TNF-alpha and arachidonate. At concentrations adjusted to give equipotent increases in the cytosolic Ca(2+), both agents increased reactive oxygen species (ROS) production and EC P-selectin expression. Blocking the cytosolic Ca(2+) increases abolished ROS production; blocking ROS production abrogated P-selectin expression. TNF-alpha, but not arachidonate, released Ca(2+) from endoplasmic stores and increased mitochondrial Ca(2+). Furthermore, Ca(2+) depletion abrogated TNF-alpha responses partially, but arachidonate responses completely. These differences in Ca(2+) mobilization by TNF-alpha and arachidonate were reflected in spatial patterning in the capillary in that the TNF-alpha effects were localized at branch points, while the arachidonate effects were nonlocalized and extensive. Furthermore, mitochondrial blockers inhibited the TNF-alpha- but not the arachidonate-induced responses. These findings indicate that the different modes of Ca(2+) mobilization determined the spatial patterning of the proinflammatory response in lung capillaries. Responses to TNF-alpha revealed that EC mitochondria regulate the proinflammatory process by generating ROS that activate P-selectin expression. PMID:12471144

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

2002-12-15

292

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

PubMed Central

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

2012-01-01

293

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

294

Inhibition of ERK Oscillations by Ionizing Radiation and Reactive Oxygen Species  

SciTech Connect

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

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

2010-12-28

295

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

PubMed

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

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

2014-01-01

296

Oxygen isotopic analyses of individual planktic foraminifera species: implications for seasonality in the western Arabian Sea  

NASA Astrophysics Data System (ADS)

The variation of stable isotopes between individual shells of planktic foraminifera of a given species and size may provide short-term seasonal insight on Paleoceanography. In this context, oxygen isotope analyses of individual Globigerinoides sacculifer and Neogloboquadrina dutertrei were carried out from the Ocean Drilling Program Site 723A in the western Arabian Sea to unravel the seasonal changes for the last 22 kyr. ?18O values of single shells of G. sacculifer range from of 0.54 to 2.09‰ at various depths in the core which cover a time span of the last 22 kyr. Maximum inter-shell ?18O variability and high standard deviation is noticed from 20 to 10 kyr, whereas from 10 kyr onwards the inter shell ?18O variability decreased. The individual contribution of sea surface temperature (SST) and sea surface salinity (SSS) on the inter shell ?18O values of G. sacculifer were quantified. Maximum seasonal SST between 20 and 14 ka was caused due to weak summer monsoon upwelling and strong cold winter arid continental winds. Maximum SSS differences between 18 and 10 ka is attributed to the increase of net evaporation minus precipitation due to the shift of ITCZ further south. Overall, winter dominated SST signal in Greenland would be responsible to make a teleconnection between Indian monsoon and Greenland temperature. Thus the present study has wider implications in understanding wether the forcing mechanisms of tropical monsoon climate lies in high latitudes or in the tropics.

Naidu, P. D.; Niitsuma, N.; Naik, S.

2014-09-01

297

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

PubMed Central

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

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

2014-01-01

298

p75NTR-dependent modulation of cellular handling of reactive oxygen species  

PubMed Central

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

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

2015-01-01

299

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

300

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

PubMed

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

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

2012-07-01

301

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

PubMed

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

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

2011-01-28

302

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

NASA Astrophysics Data System (ADS)

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

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

2014-04-01

303

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

304

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

305

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

PubMed

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

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

2009-09-01

306

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

307

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

PubMed

Cardiac ischemia-reperfusion (IR) leads to myocardial dysfunction by increasing production of reactive oxygen species (ROS). Mitochondrial H(+) leak decreases ROS formation; it has been postulated that increasing H(+) leak may be a mechanism of decreasing ROS production after IR. Ischemic preconditioning (IPC) decreases ROS formation after IR, but the mechanism is unknown. We hypothesize that pharmacologically increasing mitochondrial H(+) leak would decrease ROS production after IR. We further hypothesize that IPC would be associated with an increase in the rate of H(+) leak. Isolated male Sprague-Dawley rat hearts were subjected to either control or IPC. Mitochondria were isolated at end equilibration, end ischemia, and end reperfusion. Mitochondrial membrane potential (m??) was measured using a tetraphenylphosphonium electrode. Mitochondrial uncoupling was achieved by adding increasing concentrations of FCCP. Mitochondrial ROS production was measured by fluorometry using Amplex-Red. Pyridine dinucleotide levels were measured using HPLC. Before IR, increasing H(+) leak decreased mitochondrial ROS production. After IR, ROS production was not affected by increasing H(+) leak. H(+) leak increased at end ischemia in control mitochondria. IPC mitochondria showed no change in the rate of H(+) leak throughout IR. NADPH levels decreased after IR in both IPC and control mitochondria while NADH increased. Pharmacologically, increasing H(+) leak is not a method of decreasing ROS production after IR. Replenishing the NADPH pool may be a means of scavenging the excess ROS thereby attenuating oxidative damage after IR. PMID:25085966

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

2014-10-01

308

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

NASA Astrophysics Data System (ADS)

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

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

2013-02-01

309

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

PubMed Central

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

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

2013-01-01

310

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

PubMed Central

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

DelCarlo, Marcello; Loeser, Richard F.

2006-01-01

311

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

312

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

NASA Astrophysics Data System (ADS)

Antimicrobial photodynamic inactivation (APDI) is based on the utilization of substances that can photosensitize biological tissues and are capable of being activated in the presence of light. Cryptococcus neoformans is an yeast surrounded by a capsule composed primarily of glucoronoxylomannan that plays an important role in its virulence. This yeast causes infection on skin, lungs and brain that can be associated with neurological sequelae and neurosurgical interventions, and its conventional treatment requires prolonged antifungal therapy, which presents important adverse effects. The aim of this study was to evaluate the protective effect of Cryptococcus neoformans capsule against reactive oxygen species generated by APDI. Cryptococcus neoformans KN99?, which is a strain able to produce capsule, and CAP59 that does not present capsule production were submitted to APDI using methylene blue (MB), rose bengal (RB), and pL-ce6 as photosensitizers (PS). Then microbial inactivation was evaluated by counting colony form units following APDI and confocal laser scanning microscopy (CLSM) illustrated localization as well as the preferential accumulation of PS into the fungal cells. C. neoformans KN99? was more resistant to APDI than CAP59 for all PSs tested. CLSM showed incorporation of MB and RB into the cytoplasm and a preferential uptake in mitochondria. A nuclear accumulation of MB was also observed. Contrarily, pL-ce6 appears accumulated in cell wall and cell membrane and minimal florescence was observed inside the fungal cells. In conclusion, the ability of C. neoformans to form capsule enhances survival following APDI.

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

2011-03-01

313

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

PubMed

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

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

2014-08-01

314

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

PubMed Central

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

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

2013-01-01

315

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

316

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

NASA Astrophysics Data System (ADS)

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

Zhang, WeiNa; Chen, WenLi

2010-02-01

317

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

318

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

PubMed

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

Ou, Boxin; Huang, Dejian

2006-05-01

319

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

PubMed Central

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

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

2012-01-01

320

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

321

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

PubMed

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

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

2014-12-01

322

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

PubMed Central

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

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

2012-01-01

323

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

PubMed

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

Mao, Jing; Liu, Wei; Wang, Yutong

2014-10-24

324

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

PubMed

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

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

2015-02-01

325

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

PubMed

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

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

2013-09-01

326

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

PubMed

Nitric oxide (NO) has many functions in plants. Here, we investigated its interplays with reactive oxygen species (ROS) in the defence responses triggered by the elicitin cryptogein. The production of NO induced by cryptogein in tobacco cells was partly regulated through a ROS-dependent pathway involving the NADPH oxidase NtRBOHD. In turn, NO down-regulated the level of H2 O2 . Both NO and ROS synthesis appeared to be under the control of type-2 histone deacetylases acting as negative regulators of cell death. Occurrence of an interplay between NO and ROS was further supported by the finding that cryptogein triggered a production of peroxynitrite (ONOO(-) ). Next, we showed that ROS, but not NO, negatively regulate the intensity of activity of the cryptogein-induced protein kinase NtOSAK. Furthermore, using a DNA microarray approach, we identified 15 genes early induced by cryptogein via NO. A part of these genes was also modulated by ROS and encoded proteins showing sequence identity to ubiquitin ligases. Their expression appeared to be negatively regulated by ONOO(-) , suggesting that ONOO(-) mitigates the effects of NO and ROS. Finally, we provided evidence that NO required NtRBOHD activity for inducing cell death, thus confirming previous assumption that ROS channel NO through cell death pathways. PMID:24506708

Kulik, Anna; Noirot, Elodie; Grandperret, Vincent; Bourque, Stéphane; Fromentin, Jérôme; Salloignon, Pauline; Truntzer, Caroline; Dobrowolska, Gra?yna; Simon-Plas, Françoise; Wendehenne, David

2015-02-01

327

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

PubMed Central

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

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

2014-01-01

328

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

PubMed Central

Oncogene-induced reactive oxygen species (ROS) have been proposed to be signaling molecules that mediate proliferative cues. However, ROS may also cause DNA damage and proliferative arrest. How these apparently opposite roles can be reconciled, especially in the context of oncogene-induced cellular senescence, which is associated both with aberrant mitogenic signaling and DNA damage response (DDR)-mediated arrest, is unclear. Here, we show that ROS are indeed mitogenic signaling molecules that fuel oncogene-driven aberrant cell proliferation. However, by their very same ability to mediate cell hyperproliferation, ROS eventually cause DDR activation. We also show that oncogenic Ras-induced ROS are produced in a Rac1 and NADPH oxidase (Nox4)-dependent manner. In addition, we show that Ras-induced ROS can be detected and modulated in a living transparent animal: the zebrafish. Finally, in cancer we show that Nox4 is increased in both human tumors and a mouse model of pancreatic cancer and specific Nox4 small-molecule inhibitors act synergistically with existing chemotherapic agents. PMID:24583638

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

2014-01-01

329

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

PubMed

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

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

2004-10-15

330

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

331

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

PubMed

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

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

2013-11-15

332

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

PubMed

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

Nakamura, K

1992-07-01

333

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

SciTech Connect

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

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

2005-12-16

334

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

SciTech Connect

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

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

2009-08-15

335

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

SciTech Connect

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

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

2011-01-07

336

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

337

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

PubMed Central

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

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

2013-01-01

338

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

PubMed Central

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

Kim, Suhee; Agca, Cansu; Agca, Yuksel

2013-01-01

339

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

PubMed

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

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

2014-10-01

340

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

PubMed Central

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

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

2014-01-01

341

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

PubMed

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

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

2014-10-30

342

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

PubMed Central

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

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

2007-01-01

343

Role of extracellular calcium and mitochondrial oxygen species in psychosine-induced oligodendrocyte cell death.  

PubMed

Globoid cell leukodystrophy (GLD) is a metabolic disease caused by mutations in the galactocerebrosidase (GALC) gene. GALC is a lysosomal enzyme whose function is to degrade galacto-lipids, including galactosyl-ceramide and galactosyl-sphingosine (psychosine, PSY). GALC loss of function causes progressive intracellular accumulation of PSY. It is widely held that PSY is the main trigger for the degeneration of myelinating cells and progressive white-matter loss. However, still little is known about the molecular mechanisms by which PSY imparts toxicity. Here, we address the role of calcium dynamics during PSY-induced cell death. Using the human oligodendrocyte cell line MO3.13, we report that cell death by PSY is accompanied by robust cytosolic and mitochondrial calcium (Ca(2+)) elevations, and by mitochondrial reactive oxygen species (ROS) production. Importantly, we demonstrate that the reduction of extracellular calcium content by the chelating agent ethylenediaminetetraacetic acid can decrease intra-mitochondrial ROS production and enhance cell viability. Antioxidant administration also reduces mitochondrial ROS production and cell loss, but this treatment does not synergize with Ca(2+) chelation. Our results disclose novel intracellular pathways involved in PSY-induced death that may be exploited for therapeutic purposes to delay GLD onset and/or slow down its progression. PMID:25412308

Voccoli, V; Tonazzini, I; Signore, G; Caleo, M; Cecchini, M

2014-01-01

344

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

PubMed Central

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

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

2014-01-01

345

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

PubMed

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

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

2014-06-01

346

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

PubMed

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

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

2011-01-01

347

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

PubMed

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

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

2015-02-13

348

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

PubMed Central

Abstract Significance: Aging leads to a loss of skeletal muscle mass and function that causes instability, increased risk of falls, and need for residential care. This is due to a reduction in the muscle mass and strength that is primarily due caused by a decrease in the number of muscle fibers, particularly, type II fibers, and atrophy and weakening of those remaining. Recent Advances: Although increased oxidative damage was originally thought to be the key to the aging process, data now indicate that reactive oxygen species (ROS) may be one of the several components of the degenerative processes in aging. The skeletal muscle shows important rapid adaptations to the ROS generated by contractions that are attenuated in aged organisms and transgenic studies have indicated that overcoming these attenuated responses can prevent the age-related loss of muscle mass and function. Critical Issues: Elucidation of the mechanisms by which the skeletal muscle adapts to the ROS generated to contractions and the way in which these processes are attenuated by aging is critical to the development of logical approaches to prevent age-related loss of muscle mass and function. Future Directions: Future studies are likely to focus on the redox regulation of adaptive pathways and their maintenance during aging as an approach to maintain and improve muscle function. Antioxid. Redox Signal. 19, 804–812. PMID:23682926

2013-01-01

349

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

PubMed

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

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

2014-12-01

350

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

351

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

352

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

PubMed Central

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

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

2011-01-01

353

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

PubMed

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

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

2011-02-01

354

Optimization of bioinsecticides overproduction by Bacillus thuringiensis subsp. kurstaki using linear regression.  

PubMed

A multiple linear regression analyses were performed to screen for the significant factors simultaneously influencing production of deltaendotoxin, proteolytic activities and spore formation by a Bacillus thuringiensis kurstaki strain. Investigated factors included: pH of the medium, available oxygen and inoculum size. It was observed that oxygen availability was the most influencing setting on both deltaendotoxins production and spores counts, followed by initial pH of the medium and inoculum size. On other hand, pH of medium was found to be the most significant parameter for proteolytic activity, followed by inoculum size and dissolved oxygen. Our results suggested that the first order with two-factor interaction model seemed to be more satisfactory than simple first order model for optimization of delta-endotoxin overproduction. The coefficients of determination (R') indicated a better adequacy of the second order models to justify the obtained data. Based on results, relationships between delta-endotoxins production, proteolytic activities and spores counts were established. Our results can help to balance delta-endotoxins production and its stability. PMID:24459834

Ennourri, Karim; Hassen, Hanen Ben; Zouari, Nabil

2013-01-01

355

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

Microsoft Academic Search

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

Uta Kerkweg; Daniel Schmitz; Herbert de Groot

2006-01-01

356

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

Microsoft Academic Search

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

A. Ch. Pulla Reddy; Belur R. Lokesh

1994-01-01

357

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

NASA Astrophysics Data System (ADS)

Copper oxide nanoparticles (CuO NPs) are known to exhibit toxic effects on a variety of cell types and organs. To determine the oxidative impact of CuO NPs on hepatocellular carcinoma (HCC) cells, well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) cells were exposed to CuO NPs. Cell viability assay showed that the median inhibition concentration (IC50) for SK-Hep-1 and HepG2 cells was 25 ?g ml-1 and 85 ?g ml-1, respectively. Cellular fluorescence intensity using DCFH-DA staining analysis revealed significant intracellular reactive oxygen species (ROS) generation of up to 242% in SK-Hep-1 cells, compared with 86% in HepG2 cells. HPLC analysis demonstrated that a CuO NP treatment caused cellular GSH depletion of 58% and a GSH/GSSG ratio decrease to ~0.1 in SK-Hep-1 cells. The oxidative stress caused by enhanced superoxide anion production was observed in both HepG2 (146%) and SK-Hep-1 (192%) cells. The Griess assay verified that CuO NPs induced NO production (170%) in SK-Hep-1 cells. Comet assay and western blot further demonstrated that CuO NPs induced severe DNA strand breakage (70%) in SK-Hep-1 cells and caused DNA damage via increased ?-H2AX levels. These results suggest that well-differentiated HepG2 cells possess a robust antioxidant defense system against CuO NP-induced ROS stress and exhibit more tolerance to oxidative stress. Conversely, poorly differentiated SK-Hep-1 cells exhibited a deregulated antioxidant defense system that allowed accumulation of CuO NP-induced ROS and resulted in severe cytotoxicity.Copper oxide nanoparticles (CuO NPs) are known to exhibit toxic effects on a variety of cell types and organs. To determine the oxidative impact of CuO NPs on hepatocellular carcinoma (HCC) cells, well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) cells were exposed to CuO NPs. Cell viability assay showed that the median inhibition concentration (IC50) for SK-Hep-1 and HepG2 cells was 25 ?g ml-1 and 85 ?g ml-1, respectively. Cellular fluorescence intensity using DCFH-DA staining analysis revealed significant intracellular reactive oxygen species (ROS) generation of up to 242% in SK-Hep-1 cells, compared with 86% in HepG2 cells. HPLC analysis demonstrated that a CuO NP treatment caused cellular GSH depletion of 58% and a GSH/GSSG ratio decrease to ~0.1 in SK-Hep-1 cells. The oxidative stress caused by enhanced superoxide anion production was observed in both HepG2 (146%) and SK-Hep-1 (192%) cells. The Griess assay verified that CuO NPs induced NO production (170%) in SK-Hep-1 cells. Comet assay and western blot further demonstrated that CuO NPs induced severe DNA strand breakage (70%) in SK-Hep-1 cells and caused DNA damage via increased ?-H2AX levels. These results suggest that well-differentiated HepG2 cells possess a robust antioxidant defense system against CuO NP-induced ROS stress and exhibit more tolerance to oxidative stress. Conversely, poorly differentiated SK-Hep-1 cells exhibited a deregulated antioxidant defense system that allowed accumulation of CuO NP-induced ROS and resulted in severe cytotoxicity. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr05843g

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

2015-01-01

358

Reactive oxygen species cause direct damage of Engelbreth-Holm-Swarm matrix.  

PubMed Central

Reactive oxygen species (ROS) are produced and released into the extracellular spaces in numerous diseases and contribute to development and progression, for example, of inflammatory diseases, proteinuria, and tumor invasion. However, little is known about ROS-induced chemical changes of interstitial matrix proteins and their consequences for the integrity of the matrix meshwork. As basement membranes and other matrices are highly cross-linked and complex, the relatively simple matrix produced by Engelbreth-Holm-Swarm (EHS) sarcoma, and proteins isolated therefrom, were incubated in vitro with defined concentrations of ROS that were generated by the Fenton or xanthine oxidase/xanthine reactions. This resulted in two counter-current effects. Although up to approximately 15% of the EHS matrix proteins were released into the supernatant in a ROS dose-response relationship, the residual insoluble matrix was partially cross-linked by ROS. Matrix proteins released into the supernatants were examined by rotary shadowing, quantitative sodium dodecyl sulfate polyacrylamide gel electrophoresis, immunoblotting, and fluorospectrometry for loss of tryptophans and formation of bityrosine residues. At relatively low ROS concentrations, selective liberation of morphologically intact laminin/entactin was found that, however, failed to reassociate and showed oxidative damage of its tryptophan residues. At higher ROS concentrations, laminin and entactin were progressively disintegrated, partially fragmented, and eventually completely degraded. At this point oligomers of type IV collagen predominated in the supernatant, and proteoglycans were not encountered at any concentration of ROS. Similar gradual molecular changes were also obtained when fractions of isolated soluble EHS matrix proteins were incubated with graded concentrations of ROS. In these experiments, the formation of covalently linked oligomers and aggregates paralleled the ROS-dependent formation of cross-linking bityrosine groups. ROS scavengers pinpointed to the hydroxyl radical as the most damaging radical species. Protease inhibitor experiments suggested that degradation of matrix proteins was caused primarily by the direct action of ROS and not by proteolysis by potentially contaminating proteases. Collectively, these results provide evidence that EHS matrix proteins show differential sensitivity to ROS-induced damage in a reproducible, sequential pattern, in the order entactin > laminin > type IV collagen, and that ROS cause partial dissociation and cross-linking of the EHS matrix. Images Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 11 PMID:9212747

Riedle, B.; Kerjaschki, D.

1997-01-01

359

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

PubMed

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

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

2002-06-01

360

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

PubMed

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

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

2014-06-01

361

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

PubMed

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

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

2010-09-01

362

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

NASA Astrophysics Data System (ADS)

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

Jadko, Sergiy

363

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

SciTech Connect

Highlights: Black-Right-Pointing-Pointer Cellular senescence plays an important role in tumorigenesis and aging process. Black-Right-Pointing-Pointer We demonstrated IGF-I enhanced cellular senescence in primary confluent cells. Black-Right-Pointing-Pointer IGF-I enhanced cellular senescence in the ROS and p53-dependent manner. Black-Right-Pointing-Pointer These results may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. -- Abstract: Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated {beta}-galactosidase (SA-{beta}-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, {gamma}H2AX, the increased levels of p53 and p21 proteins, and activated SA-{beta}-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-{beta}-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.

Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan)] [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Takahashi, Yutaka, E-mail: takahash@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan)] [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan)

2012-08-24

364

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

PubMed Central

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

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

2013-01-01

365

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

PubMed

Copper oxide nanoparticles (CuO NPs) are known to exhibit toxic effects on a variety of cell types and organs. To determine the oxidative impact of CuO NPs on hepatocellular carcinoma (HCC) cells, well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) cells were exposed to CuO NPs. Cell viability assay showed that the median inhibition concentration (IC50) for SK-Hep-1 and HepG2 cells was 25 ?g ml(-1) and 85 ?g ml(-1), respectively. Cellular fluorescence intensity using DCFH-DA staining analysis revealed significant intracellular reactive oxygen species (ROS) generation of up to 242% in SK-Hep-1 cells, compared with 86% in HepG2 cells. HPLC analysis demonstrated that a CuO NP treatment caused cellular GSH depletion of 58% and a GSH/GSSG ratio decrease to ?0.1 in SK-Hep-1 cells. The oxidative stress caused by enhanced superoxide anion production was observed in both HepG2 (146%) and SK-Hep-1 (192%) cells. The Griess assay verified that CuO NPs induced NO production (170%) in SK-Hep-1 cells. Comet assay and western blot further demonstrated that CuO NPs induced severe DNA strand breakage (70%) in SK-Hep-1 cells and caused DNA damage via increased ?-H2AX levels. These results suggest that well-differentiated HepG2 cells possess a robust antioxidant defense system against CuO NP-induced ROS stress and exhibit more tolerance to oxidative stress. Conversely, poorly differentiated SK-Hep-1 cells exhibited a deregulated antioxidant defense system that allowed accumulation of CuO NP-induced ROS and resulted in severe cytotoxicity. PMID:25521936

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

2015-01-22

366

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

PubMed

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

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

2013-05-01

367

Roles of Reactive Oxygen Species and Antioxidants in Ovarian Toxicity1  

PubMed Central

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

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

2011-01-01

368

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

PubMed

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

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

2002-08-01

369

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

SciTech Connect

In the present study, we assessed the influence of monochloramine (NH{sub 2}Cl) on the conversion of xanthine dehydrogenase (XD) into xanthine oxidase (XO) in rat liver in vitro. When incubated with the partially purified cytosolic fraction from rat liver, NH{sub 2}Cl (2.5-20 {mu}M) dose-dependently enhanced XO activity concomitant with a decrease in XD activity, implying that NH{sub 2}Cl can convert XD into the reactive oxygen species (ROS) producing form XO. The NH{sub 2}Cl (5 {mu}M)-induced XD/XO interconversion in the rat liver cytosol was completely inhibited when added in combination with an inhibitor of NH{sub 2}Cl methionine (25 {mu}M). A sulfhydryl reducing agent, dithiothreitol at concentrations of 0.1, 1 and 5 mM also dose-dependently reversed the NH{sub 2}Cl (5 {mu}M)-induced XD/XO interconversion. These imply that NH{sub 2}Cl itself acts on the XD/XO interconversion, and that this conversion occurs at the cysteine residues in XD. Furthermore, using the fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate, it was found that NH{sub 2}Cl could increase ROS generation in the cytoplasm of rat primary hepatocyte cultures, and that this increase might be reversed by an XO inhibitor, allopurinol. These results suggest that NH{sub 2}Cl has the potential to convert XD into XO in the liver, which in turn may induce the ROS generation in this region.

Sakuma, Satoru [Laboratory of Physiological Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)], E-mail: sakuma@gly.oups.ac.jp; Miyoshi, Emi; Sadatoku, Namiko; Fujita, Junko; Negoro, Miki [Laboratory of Physiological Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Arakawa, Yukio [Clinical Laboratory of Practical Pharmacy, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Fujimoto, Yohko [Laboratory of Physiological Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)

2009-09-15

370

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

PubMed Central

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

Shin, Hyejin; Choi, Soyoung

2014-01-01

371

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

PubMed

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

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

2015-02-01

372

Acrolein activates matrix metalloproteinases by increasing reactive oxygen species in macrophages  

SciTech Connect

Acrolein is a ubiquitous component of environmental pollutants such as automobile exhaust, cigarette, wood, and coal smoke. It is also a natural constituent of several foods and is generated endogenously during inflammation or oxidation of unsaturated lipids. Because increased inflammation and episodic exposure to acrolein-rich pollutants such as traffic emissions or cigarette smoke have been linked to acute myocardial infarction, we examined the effects of acrolein on matrix metalloproteinases (MMPs), which destabilize atherosclerotic plaques. Our studies show that exposure to acrolein resulted in the secretion of MMP-9 from differentiated THP-1 macrophages. Acrolein-treatment of macrophages also led to an increase in reactive oxygen species (ROS), free intracellular calcium ([Ca{sup 2+}]{sub i}), and xanthine oxidase (XO) activity. ROS production was prevented by allopurinol, but not by rotenone or apocynin and by buffering changes in [Ca{sup 2+}]{sub I} with BAPTA-AM. The increase in MMP production was abolished by pre-treatment with the antioxidants Tiron and N-acetyl cysteine (NAC) or with the xanthine oxidase inhibitors allopurinol or oxypurinol. Finally, MMP activity was significantly stimulated in aortic sections from apoE-null mice containing advanced atherosclerotic lesions after exposure to acrolein ex vivo. These observations suggest that acrolein exposure results in MMP secretion from macrophages via a mechanism that involves an increase in [Ca{sup 2+}]{sub I}, leading to xanthine oxidase activation and an increase in ROS production. ROS-dependent activation of MMPs by acrolein could destabilize atherosclerotic lesions during brief episodes of inflammation or pollutant exposure.

O'Toole, Timothy E. [Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, KY 40202 (United States)], E-mail: teotoo01@gwise.louisville.edu; Zheng Yuting; Hellmann, Jason; Conklin, Daniel J.; Barski, Oleg; Bhatnagar, Aruni [Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, KY 40202 (United States)

2009-04-15

373

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

SciTech Connect

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

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

2011-01-01

374

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

PubMed Central

Previous research has focused on the involvement of reactive oxygen species (ROS) in cell wall loosening and cell extension in plant vegetative growth, but few studies have investigated ROS functions specifically in plant reproductive organs. In this study, ROS levels and antioxidant enzyme activities were assessed in Pisum sativum and Brassica chinensis pods at five developmental stages. In juvenile pods, the high levels of O2.? and.OH indicates that they had functions in cell wall loosening and cell elongation. In later developmental stages, high levels of.OH were also related to increases in cell wall thickness in lignified tissues. Throughout pod development, most of the O2.? was detected on plasma membranes of parenchyma cells and outer epidermis cells of the mesocarp, while most of the H2O2 was detected on plasma membranes of most cells throughout the mesocarp. This suggests that these sites are presumably the locations of ROS generation. The antioxidant enzymes superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) apparently contributed to ROS accumulation in pod wall tissues. Furthermore, specifically SOD and POD were found to be associated with pod growth through the regulation of ROS generation and transformation. Throughout pod development, O2.? decreases were associated with increased SOD activity, while changes in H2O2 accumulation were associated with changes in CAT and POD activities. Additionally, high POD activity may contribute to the generation of.OH in the early development of pods. It is concluded that the ROS are produced in different sites of plasma membranes with the regulation of antioxidant enzymes, and that substantial ROS generation and accumulation are evident in cell elongation and cell wall loosening in pod wall cells. PMID:24503564

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

2014-01-01

375

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

NASA Astrophysics Data System (ADS)

Free radicals/reactive oxygen species (ROS) generated in skin by UV irradiation were measured by electron spin resonance (ESR). To increase the sensitivity of measurement the short life free radicals/ROS were scavenged and accumulated by using the nitroxyl probe 3-carboxy-2,2,5,5-tetrametylpyrrolidine-1-oxyl (PCA). The spatial distribution of free radicals/ROS measured in pig skin biopsies with ESR imaging after UV irradiation corresponds to the intensity decay of irradiance in the depth of the skin. The main part of free radicals/ROS were generated by UVA (320-400 nm) so that the spatial distribution of free radicals reaches up to the lower side of the dermis. In vivo measurements on human skin were performed with a L-band ESR spectrometer and a surface coil integrating the signal intensities from all skin layers to get a sufficient signal amplitude. Using this experimental arrangement the protection of UVB and UVA/B filter against the generation of free radicals/ROS in skin were measured. The protection against ROS and the repair of damages caused by them can be realized with active antioxidants characterized by a high antioxidative power (AP). The effect of UV filter and antioxidants corresponding to their protection against free radicals/ROS in skin generated by UVAB irradiation can be quantified by the new radical sun protection factor (RSF). The RSF indicates the increase of time for staying in the sun to generate the same number of free radicals/ROS in the skin like for the unprotected skin. Regarding the amount of generated free radicals/ROS in skin as an biophysical endpoint the RSF characterizes both the protection against UVB and UVA radiation.

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

2006-03-01

376

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

PubMed

Reactive oxygen species (ROS) can have divergent effects in cerebral and peripheral circulations. We found that Ca(2+)-permeable transient receptor potential ankyrin 1 (TRPA1) channels were present and colocalized with NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase 2 (NOX2), a major source of ROS, in the endothelium of cerebral arteries but not in other vascular beds. We recorded and characterized ROS-triggered Ca(2+) signals representing Ca(2+) influx through single TRPA1 channels, which we called "TRPA1 sparklets." TRPA1 sparklet activity was low under basal conditions but was stimulated by NOX-generated ROS. Ca(2+) entry during a single TRPA1 sparklet was twice that of a TRPV4 sparklet and ~200 times that of an L-type Ca(2+) channel sparklet. TRPA1 sparklets representing the simultaneous opening of two TRPA1 channels were more common in endothelial cells than in human embryonic kidney (HEK) 293 cells expressing TRPA1. The NOX-induced TRPA1 sparklets activated intermediate-conductance, Ca(2+)-sensitive K(+) channels, resulting in smooth muscle hyperpolarization and vasodilation. NOX-induced activation of TRPA1 sparklets and vasodilation required generation of hydrogen peroxide and lipid-peroxidizing hydroxyl radicals as intermediates. 4-Hydroxy-nonenal, a metabolite of lipid peroxidation, also increased TRPA1 sparklet frequency and dilated cerebral arteries. These data suggest that in the cerebral circulation, lipid peroxidation metabolites generated by ROS activate Ca(2+) influx through TRPA1 channels in the endothelium of cerebral arteries to cause dilation. PMID:25564678

Sullivan, Michelle N; Gonzales, Albert L; Pires, Paulo W; Bruhl, Allison; Leo, M Dennis; Li, Wencheng; Oulidi, Agathe; Boop, Frederick A; Feng, Yumei; Jaggar, Jonathan H; Welsh, Donald G; Earley, Scott

2015-01-01

377

Reactive Oxygen Species From Human Astrocytes Induced Functional Impairment and Oxidative Damage  

PubMed Central

Reactive oxygen species (ROS) have been shown to be a contributor to aging and disease. ROS also serve as a trigger switch for signaling cascades leading to corresponding cellular and molecular events. In the central nervous system, microglial cells are likely the main source of ROS production. However, activated astrocytes also appear to be capable of generating ROS. In this study we investigated ROS production in human astrocytes stimulated with interleukin (IL)-1? and interferon (IFN)-? and its potential harmful effects. Although IFN-? alone had no effect, it potentiated IL-1?-induced ROS production in a time-dependent manner. One of the sources of ROS in IL-1?-activated astrocytes was from increased superoxide production in mitochondria accompanied by enhanced manganese superoxide dismutase and inhibited catalase expression. NADPH oxidase (NOX) may also contribute to ROS production as astrocytes express NOX isoforms. Glutamate uptake, which represents one of the most important methods of astrocytes to prevent excitotoxity, was down-regulated in IL-1?-activated astrocytes, and was further suppressed in the presence of IFN-?; IFN-? itself exerted minimal effect. Elevated levels of 8-isoprostane in IL-1? ± IFN-?-activated human astrocytes indicate downstream lipid peroxidation. Pretreatment with DPI (diphenyleneiodonium) abolished the IL-1? ± IFN-?-induced ROS production, restored glutamate uptake function and reduced 8-isoprostane to near control levels suggesting that ROS contributes to the dysfunction of activated astrocytes. These results support the notion that dampening activated human astrocytes to maintain the redox homeostasis is vital to preserve their neuroprotective potential in the CNS. PMID:23918204

Sheng, Wen S; Hu, Shuxian; Feng, Amy; Rock, R. Bryan

2013-01-01

378

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research  

PubMed Central

Abstract Significance: Reactive oxygen species (ROS) are signaling molecules that are important in physiological processes, including host defense, aging, and cellular homeostasis. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in the onset and/or progression of chronic diseases, including hypertension. Recent Advances: Although oxidative stress may not be the only cause of hypertension, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors, such as salt loading, activation of the renin-angiotensin-aldosterone system, and sympathetic hyperactivity, at least in experimental models. A major source for ROS in the cardiovascular-renal system is a family of nicotinamide adenine dinucleotide phosphate oxidases (Noxs), including the prototypic Nox2-based Nox, and Nox family members: Nox1, Nox4, and Nox5. Critical Issues: Although extensive experimental data support a role for increased ROS levels and altered redox signaling in the pathogenesis of hypertension, the role in clinical hypertension is unclear, as a direct causative role of ROS in blood pressure elevation has yet to be demonstrated in humans. Nevertheless, what is becoming increasingly evident is that abnormal ROS regulation and aberrant signaling through redox-sensitive pathways are important in the pathophysiological processes which is associated with vascular injury and target-organ damage in hypertension. Future Directions: There is a paucity of clinical information related to the mechanisms of oxidative stress and blood pressure elevation, and a few assays accurately measure ROS directly in patients. Such further ROS research is needed in humans and in the development of adequately validated analytical methods to accurately assess oxidative stress in the clinic. Antioxid. Redox Signal. 20, 164–182. PMID:23600794

Montezano, Augusto C.

2014-01-01

379

Selenoprotein P Inhibits Radiation-Induced Late Reactive Oxygen Species Accumulation and Normal Cell Injury  

SciTech Connect

Purpose: Radiation is a common mode of cancer therapy whose outcome is often limited because of normal tissue toxicity. We have shown previously that the accumulation of radiation-induced late reactive oxygen species (ROS) precedes cell death, suggesting that metabolic oxidative stress could regulate cellular radiation response. The purpose of this study was to investigate whether selenoprotein P (SEPP1), a major supplier of selenium to tissues and an antioxidant, regulates late ROS accumulation and toxicity in irradiated normal human fibroblasts (NHFs). Methods and Materials: Flow cytometry analysis of cell viability, cell cycle phase distribution, and dihydroethidium oxidation, along with clonogenic assays, were used to measure oxidative stress and toxicity. Human antioxidant mechanisms array and quantitative real-time polymerase chain reaction assays were used to measure gene expression during late ROS accumulation in irradiated NHFs. Sodium selenite addition and SEPP1 overexpression were used to determine the causality of SEPP1 regulating late ROS accumulation and toxicity in irradiated NHFs. Results: Irradiated NHFs showed late ROS accumulation (4.5-fold increase from control; P<.05) that occurs after activation of the cell cycle checkpoint pathways and precedes cell death. The mRNA levels of CuZn- and Mn-superoxide dismutase, catalase, peroxiredoxin 3, and thioredoxin reductase 1 increased approximately 2- to 3-fold, whereas mRNA levels of cold shock domain containing E1 and SEPP1 increased more than 6-fold (P<.05). The addition of sodium selenite before the radiation treatment suppressed toxicity (45%; P<.05). SEPP1 overexpression suppressed radiation-induced late ROS accumulation (35%; P<.05) and protected NHFs from radiation-induced toxicity (58%; P<.05). Conclusion: SEPP1 mitigates radiation-induced late ROS accumulation and normal cell injury.

Eckers, Jaimee C.; Kalen, Amanda L.; Xiao, Wusheng; Sarsour, Ehab H.; Goswami, Prabhat C., E-mail: prabhat-goswami@uiowa.edu

2013-11-01

380

Reactive oxygen species involved in trichosanthin-induced apoptosis of human choriocarcinoma cells.  

PubMed Central

The type-I ribosome-inactivating protein trichosanthin (TCS) has a broad spectrum of biological and pharmacological activities, including abortifacient, anti-tumour and anti-HIV activities. We have found for the first time that TCS stimulated the production of reactive oxygen species (ROS) in JAR cells (a human choriocarcinoma cell line) in a time- and concentration-dependent manner by using the fluorescent probe 2',7'-dichlorofluorescein diacetate with confocal laser scanning microscopy. ESR spectral studies and the inhibition of ROS formation by the superoxide radical anion (O(2)(-.)) scavenger superoxide dismutase, the H(2)O(2) scavenger catalase and the hydroxyl radical (OH(.)) scavenger mannitol suggested the involvement of O(2)(-.), H(2)O(2) and OH(.). TCS-induced ROS formation was shown to be dependent on the presence of both extracellular and intracellular Ca(2+); moreover, ROS production paralleled the intracellular Ca(2+) elevation induced by TCS, suggesting that ROS production might be a consequence of Ca(2+) signalling. TCS-induced activation of caspase-3 was initiated within 2 h; however, TCS-induced production of ROS was initiated within 5 min, suggesting that the production of ROS preceded the activation of caspase-3. Simultaneous observation of the nuclear morphological changes via two-photon laser scanning microscopy and ROS production via confocal laser scanning microscopy revealed that ROS is involved in the apoptosis of JAR cells. The involvement of ROS was also confirmed by the inhibition of TCS-induced cell death by the antioxidant Trolox and the ROS scavengers catalase and mannitol. Diethylenetriaminepenta-acetic acid, an inhibitor of metal-facilitated OH(.) formation, markedly inhibited TCS-induced cell death, suggesting that TCS induced OH(.) formation via the Fenton reaction. The finding that ROS is involved in the TCS-induced apoptosis of JAR cells might provide new insight into the anti-tumour and anti-HIV mechanism of TCS. PMID:11311127

Zhang, C; Gong, Y; Ma, H; An, C; Chen, D; Chen, Z L

2001-01-01

381

Extending cassava root shelf life via reduction of reactive oxygen species production.  

PubMed

One of the major constraints facing the large-scale production of cassava (Manihot esculenta) roots is the rapid postharvest physiological deterioration (PPD) that occurs within 72 h following harvest. One of the earliest recognized biochemical events during the initiation of PPD is a rapid burst of reactive oxygen species (ROS) accumulation. We have investigated the source of this oxidative burst to identify possible strategies to limit its extent and to extend cassava root shelf life. We provide evidence for a causal link between cyanogenesis and the onset of the oxidative burst that triggers PPD. By measuring ROS accumulation in transgenic low-cyanogen plants with and without cyanide complementation, we show that PPD is cyanide dependent, presumably resulting from a cyanide-dependent inhibition of respiration. To reduce cyanide-dependent ROS production in cassava root mitochondria, we generated transgenic plants expressing a codon-optimized Arabidopsis (Arabidopsis thaliana) mitochondrial alternative oxidase gene (AOX1A). Unlike cytochrome c oxidase, AOX is cyanide insensitive. Transgenic plants overexpressing AOX exhibited over a 10-fold reduction in ROS accumulation compared with wild-type plants. The reduction in ROS accumulation was associated with a delayed onset of PPD by 14 to 21 d after harvest of greenhouse-grown plants. The delay in PPD in transgenic plants was also observed under field conditions, but with a root biomass yield loss in the highest AOX-expressing lines. These data reveal a mechanism for PPD in cassava based on cyanide-induced oxidative stress as well as PPD control strategies involving inhibition of ROS production or its sequestration. PMID:22711743

Zidenga, Tawanda; Leyva-Guerrero, Elisa; Moon, Hangsik; Siritunga, Dimuth; Sayre, Richard

2012-08-01

382

Hypothalamic Apelin/Reactive Oxygen Species Signaling Controls Hepatic Glucose Metabolism in the Onset of Diabetes  

PubMed Central

Abstract Aims: We have previously demonstrated that central apelin is implicated in the control of peripheral glycemia, and its action depends on nutritional (fast versus fed) and physiological (normal versus diabetic) states. An intracerebroventricular (icv) injection of a high dose of apelin, similar to that observed in obese/diabetic mice, increase fasted glycemia, suggesting (i) that apelin contributes to the establishment of a diabetic state, and (ii) the existence of a hypothalamic to liver axis. Using pharmacological, genetic, and nutritional approaches, we aim at unraveling this system of regulation by identifying the hypothalamic molecular actors that trigger the apelin effect on liver glucose metabolism and glycemia. Results: We show that icv apelin injection stimulates liver glycogenolysis and gluconeogenesis via an over-activation of the sympathetic nervous system (SNS), leading to fasted hyperglycemia. The effect of central apelin on liver function is dependent of an increased production of hypothalamic reactive oxygen species (ROS). These data are strengthened by experiments using lentiviral vector-mediated over-expression of apelin in hypothalamus of mice that present over-activation of SNS associated to an increase in hepatic glucose production. Finally, we report that mice fed a high-fat diet present major alterations of hypothalamic apelin/ROS signaling, leading to activation of glycogenolysis. Innovation/Conclusion: These data bring compelling evidence that hypothalamic apelin is one master switch that participates in the onset of diabetes by directly acting on liver function. Our data support the idea that hypothalamic apelin is a new potential therapeutic target to treat diabetes. Antioxid. Redox Signal. 20, 557–573. PMID:23879244

Drougard, Anne; Duparc, Thibaut; Brenachot, Xavier; Carneiro, Lionel; Gouazé, Alexandra; Fournel, Audren; Geurts, Lucie; Cadoudal, Thomas; Prats, Anne-Catherine; Pénicaud, Luc; Vieau, Didier; Lesage, Jean; Leloup, Corinne; Benani, Alexandre; Cani, Patrice D.; Valet, Philippe

2014-01-01

383

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

PubMed

Scoparone, one of the bioactive components of Artemisia capillaris Thunb, has various biological properties including immunosuppressive, hepatoprotective, anti-allergic, anti-inflammatory, and antioxidant effects. This study aims at evaluating the anti-osteoporotic effect of scoparone and its underlying mechanism in vitro. Scoparone demonstrated potent cellular antioxidant capacity. It was also found that scoparone inhibited the receptor activator of nuclear factor-?B ligand (RANKL)-induced osteoclast differentiation and suppressed cathepsin K and tartrate-resistant acid phosphatase (TRAP) expression via c-jun N-terminal kinase (JNK)/extracellular signal-regulated kinase (ERK)/p38-mediated c-Fos-nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) signaling pathway. During osteoclast differentiation, the production of general reactive oxygen species (ROS) and superoxide anions was dose-dependently attenuated by scoparone. In addition, scoparone diminished NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 1 (Nox1) expression and activation via the tumor necrosis factor receptor-associated factor 6 (TRAF6)-cSrc-phosphatidylinositol 3-kinase (PI3k) signaling pathway and prevented the disruption of mitochondrial electron transport chain system. Furthermore, scoparone augmented the expression of superoxide dismutase 1 (SOD1) and catalase (CAT). The overall results indicate that the inhibitory effect of scoparone on RANKL-induced osteoclast differentiation is attributed to the suppressive effect on ROS and superoxide anion production by inhibiting Nox1 expression and activation and protecting the mitochondrial electron transport chain system and the scavenging effect of ROS resulting from elevated SOD1 and CAT expression. PMID:25576385

Lee, Sang-Hyun; Jang, Hae-Dong

2015-02-15

384

Endothelial cells negatively modulate reactive oxygen species generation in vascular smooth muscle cells: role of thioredoxin.  

PubMed

In intact vessels, endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) act as an integrated system, possibly through reactive oxygen species (ROS). Using a coculture system we tested whether ECs modulate VSMC redox status by regulating activity of NAD(P)H oxidase and antioxidants. VSMC production of O(2)(*-), H(2)O(2), and NO was assessed using fluoroprobes and amplex-red. NAD(P)H oxidase subunit expression and oxidase activity were determined by Western blotting and chemiluminescence, respectively. Expression of thioredoxin, SOD, growth signaling pathways (PCNA, p21cip1, CDK4, ERK1/2, p38MAPK) was evaluated by immunoblotting. Thioredoxin activity was assessed by the insulin disulfide reduction assay. In cocultured conditions, VSMC ROS production was reduced by approximately 50% without changes in NAD(P)H oxidase expression/activity versus monoculture (P<0.05). This was associated with decreased cell growth (P<0.05). Expression of Cu/Zn SOD and thioredoxin was increased in coculture versus monoculture VSMCs (P<0.01). Pretreatment of ECs with L-NAME (NOS inhibitor), NS-398 (Cox2 inhibitor), and HET0016 (20-HETE inhibitor) did not influence VSMC ROS formation, whereas CDNB, thioredoxin reductase inhibitor, abolished ROS modulating effects of ECs. These findings indicate that in a coculture system recapitulating intact vessels, ECs negatively regulate ROS production in VSMCs through thioredoxin upregulation. Functionally this is associated with growth inhibition. The modulatory actions of ECs are independent of NOS/NO, Cox2, and HETE and do not involve NAD(P)H oxidase. Our data identify novel mechanisms whereby ECs protect against VSMC oxidative stress, a process that may be important in maintaining vascular integrity. PMID:19564543

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

2009-08-01

385

The Role of Reactive Oxygen Species in Anopheles aquasalis Response to Plasmodium vivax Infection  

PubMed Central

Malaria affects millions of people worldwide and hundreds of thousands of people each year in Brazil. The mosquito Anopheles aquasalis is an important vector of Plasmodium vivax, the main human malaria parasite in the Americas. Reactive oxygen species (ROS) have been shown to have a role in insect innate immune responses as a potent pathogen-killing agent. We investigated the mechanisms of free radicals modulation after A. aquasalis infection with P. vivax. ROS metabolism was evaluated in the vector by studying expression and activity of three key detoxification enzymes, one catalase and two superoxide dismutases (SOD3A and SOD3B). Also, the involvement of free radicals in the mosquito immunity was measured by silencing the catalase gene followed by infection of A. aquasalis with P. vivax. Catalase, SOD3A and SOD3B expression in whole A. aquasalis were at the same levels of controls at 24 h and upregulated 36 h after ingestion of blood containing P. vivax. However, in the insect isolated midgut, the mRNA for these enzymes was not regulated by P. vivax infection, while catalase activity was reduced 24 h after the infectious meal. RNAi-mediated silencing of catalase reduced enzyme activity in the midgut, resulted in increased P. vivax infection and prevalence, and decreased bacterial load in the mosquito midgut. Our findings suggest that the interactions between A. aquasalis and P. vivax do not follow the model of ROS-induced parasite killing. It appears that P. vivax manipulates the mosquito detoxification system in order to allow its own development. This can be an indirect effect of fewer competitive bacteria present in the mosquito midgut caused by the increase of ROS after catalase silencing. These findings provide novel information on unique aspects of the main malaria parasite in the Americas interaction with one of its natural vectors. PMID:23441231

Bahia, Ana C.; Oliveira, José Henrique M.; Kubota, Marina S.; Araújo, Helena R. C.; Lima, José B. P.; Ríos-Velásquez, Claudia Maria; Lacerda, Marcus Vinícius G.; Oliveira, Pedro L.

2013-01-01

386

Increased effectiveness of carbon ions in the production of reactive oxygen species in normal human fibroblasts.  

PubMed

The production of reactive oxygen species (ROS), especially superoxide anions (O2 (·-)), is enhanced in many normal and tumor cell types in response to ionizing radiation. The influence of ionizing radiation on the regulation of ROS production is considered as an important factor in the long-term effects of irradiation (such as genomic instability) that might contribute to the development of secondary cancers. In view of the increasing application of carbon ions in radiation therapy, we aimed to study the potential impact of ionizing density on the intracellular production of ROS, comparing photons (X-rays) with carbon ions. For this purpose, we used normal human cells as a model for irradiated tissue surrounding a tumor. By quantifying the oxidization of Dihydroethidium (DHE), a fluorescent probe sensitive to superoxide anions, we assessed the intracellular ROS status after radiation exposure in normal human fibroblasts, which do not show radiation-induced chromosomal instability. After 3-5 days post exposure to X-rays and carbon ions, the level of ROS increased to a maximum that was dose dependent. The maximum ROS level reached after irradiation was specific for the fibroblast type. However, carbon ions induced this maximum level at a lower dose compared with X-rays. Within ?1 week, ROS decreased to control levels. The time-course of decreasing ROS coincides with an increase in cell number and decreasing p21 protein levels, indicating a release from radiation-induced growth arrest. Interestingly, radiation did not act as a trigger for chronically enhanced levels of ROS months after radiation exposure. PMID:25304329

Dettmering, Till; Zahnreich, Sebastian; Colindres-Rojas, Miriam; Durante, Marco; Taucher-Scholz, Gisela; Fournier, Claudia

2015-01-01

387

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

PubMed Central

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

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

2013-01-01

388

Regulation of reactive oxygen species by p53: implications for nitric oxide-mediated apoptosis.  

PubMed

Nitric oxide (NO) induces vascular smooth muscle cell (VSMC) apoptosis in part through activation of p53. Traditionally, p53 has been thought of as the gatekeeper, determining if a cell should undergo arrest and repair or apoptosis following exposure to DNA-damaging agents, depending on the severity of the damage. However, our laboratory previously demonstrated that NO induces apoptosis to a much greater extent in p53(-/-) compared with p53(+/+) VSMC. Increased reactive oxygen species (ROS) within VSMC has been shown to induce VSMC apoptosis, and recently it was found that the absence of, or lack of, functional p53 leads to increased ROS and oxidative stress within different cell types. This study investigated the differences in intracellular ROS levels between p53(-/-) and p53(+/+) VSMC and examined if these differences were responsible for the increased susceptibility to NO-induced apoptosis observed in p53(-/-) VSMC. We found that p53 actually protects VSMC from NO-induced apoptosis by increasing antioxidant protein expression [i.e., peroxiredoxin-3 (PRx-3)], thereby reducing ROS levels and cellular oxidative stress. We also observed that the NO-induced apoptosis in p53(-/-) VSMC was largely abrogated by pretreatment with catalase. Furthermore, when the antioxidant protein PRx-3 and its specific electron acceptor thioredoxin-2 were silenced within p53(+/+) VSMC with small-interfering RNA, not only did these cells exhibit greater ROS production, but they also exhibited increased NO-induced apoptosis similar to that observed in p53(-/-) VSMC. These findings suggest that ROS mediate NO-induced VSMC apoptosis and that p53 protects VSMC from NO-induced apoptosis by decreasing intracellular ROS. This research demonstrates that p53 has antioxidant functions in stressed cells and also suggests that p53 has antiapoptotic properties. PMID:20382856

Popowich, Daniel A; Vavra, Ashley K; Walsh, Christopher P; Bhikhapurwala, Hussein A; Rossi, Nicholas B; Jiang, Qun; Aalami, Oliver O; Kibbe, Melina R

2010-06-01

389

Reactive oxygen species in stallion semen can be affected by season and colloid centrifugation.  

PubMed

There are anecdotal reports that equine fertility may decline towards the end of the breeding season. Previous studies have examined differences in sperm quality between the breeding season and non-breeding season but few studies have investigated the proportions of superoxide or peroxide containing spermatozoa at different times during the breeding season. The purpose of this study was to measure the content of these reactive oxygen species (ROS) at the beginning and end of the Swedish breeding season, using flow cytometric analysis of the fluorescence produced after staining with hydroethidium and dichlorodihydrofluorescein diacetate. In addition, the effects of a new method of selecting good quality spermatozoa by colloid centrifugation, known as Single Layer Centrifugation (SLC), on ROS-content were investigated. Superoxide production by stallion spermatozoa was found to be higher at the start than at the end of the breeding season in Sweden (22±16% versus 9±6%, P<0.05), whereas sperm motility was lower (total motility 80±9% versus 90±6%, P<0.01; progressive motility 55±12% versus 60±8%, P<0.05, at the beginning and end of the breeding season respectively). The mean values of the other parameters of sperm quality measured did not differ with time within the breeding season although differences did occur for individual stallions. SLC was found to select motile spermatozoa that contained less superoxide (16±14% versus 23±18%, P<0.01) and less peroxide (0.3±0.8 versus 1±2%, P<0.01) than uncentrifuged controls, although they were capable of producing ROS when stimulated with menadione. This reduced peroxide production may contribute to the enhanced sperm survival (retention of motility) seen in the SLC samples during storage. PMID:23778304

Morrell, J M; Winblad, C; Georgakas, A; Stuhtmann, G; Humblot, P; Johannisson, A

2013-07-01

390

Production of reactive oxygen species by man-made vitreous fibres in human polymorphonuclear leukocytes.  

PubMed

Human polymorphonuclear leukocytes (PMNL) or erythrocytes, isolated from human blood, were exposed to graded doses of asbestos (chrysotile), quartz, or man-made vitreous fibres (MMVF), i.e. refractory ceramic fibres (RCF), glasswool, or rockwool fibres. None of the MMVF affected either the viability of PMNL, as measured by trypan blue exclusion test, or induced haemolysis, whereas the positive controls, quartz and chrysotile, dose-dependently induced haemolysis in PMNL. MMVF did not increase the release of lactate dehydrogenase (LDH) from the PMNL, whereas the positive controls, chrysotile and quartz, induced a marked and dose-dependent release of LDH. When PMNL were exposed to MMVF, some of the fibre types slightly increased the levels of free intracellular calcium ([Ca2+]i) within the cells in a manner similar to that induced by chrysotile or quartz. All MMVF induced a dose-dependent production of reactive oxygen species (ROS) in PMNL, with RCF-induced production of ROS being the most marked. Production of ROS by MMVF seemed to depend on the availability of extracellular calcium because it could be attenuated with a Ca2+ channel blocker, verapamil, or a Ca2+ chelating agent, EGTA. Production of ROS may be a common pathway through which PMNL respond to MMVF-induced cell activation, but alterations of levels of free intracellular Ca2+ do not seem to be an absolute prerequisite for this effect. Fibre length seemed not to be an important factor in affecting the ability of MMVF to induce ROS production in PMNL. However, the balance between different elements in the fibre seemed importantly to affect the biological activity of a fibre. PMID:10413242

Ruotsalainen, M; Hirvonen, M R; Luoto, K; Savolainen, K M

1999-06-01

391

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

SciTech Connect

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

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

2007-07-15

392

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

PubMed Central

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

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

2010-01-01

393

Magnetosomes eliminate intracellular reactive oxygen species in Magnetospirillum gryphiswaldense MSR-1.  

PubMed

Magnetotactic bacteria synthesize magnetic particles called magnetosomes that cause them to orient to their external magnetic fields. However, the physiological significance and other possible functions of these magnetosomes have not been explored in detail. In this study, we have investigated the biological functions of magnetosomes with respect to their ability to scavenge reactive oxygen species (ROS) in Magnetospirillum gryphiswaldense MSR-1. To assess the changes in ROS levels under different conditions, cells were cultured under aerobic or micro-aerobic conditions in medium containing high and low amounts of iron. To ensure that the observed results were not due to nonspecific interactions, reactions were carried out using a mutant deficient in synthesizing magnetite (mamO-deficient mutant), its complementary strain or the wild-type MSR-1. We observed that the levels of intercellular ROS under micro-aerobic conditions with high-iron medium were much higher when the non-synthetic Fe(3) O(4) crystals mutant Mu21-415 was employed for the assay, compared with the wild-type or complementary strain, or when conditions were aerobic with low-iron medium. These results indicated that magnetosomes function in the scavenging of intracellular ROS. Furthermore, we have demonstrated that the magnetosomes exhibit peroxidase-like properties, by using the earlier reported in vitro horseradish peroxidase assay for artificial magnetic nanoparticles. In addition to possessing peroxidase-like activity, the magnetosomes also exhibited a more enzymatic kinetic response, suggesting that proteins on the membranes of the magnetosomes likely contribute to the enzymatic activity. This is the first study to demonstrate that magnetosomes play an important role in decreasing or eliminating ROS. PMID:22360568

Guo, Fang Fang; Yang, Wei; Jiang, Wei; Geng, Shuang; Peng, Tao; Li, Ji Lun

2012-07-01

394

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

PubMed

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

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

1999-04-01

395

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

PubMed Central

Introduction Recent advances suggest that the cellular redox state may play a significant role in the progression of fibrosis in systemic sclerosis (SSc). Another, and as yet poorly accounted for, feature of SSc is its overlap with thyroid abnormalities. Previous reports demonstrate that hypothyroidism reduces oxidant stress. The aim of this study was therefore to evaluate the effect of propylthiouracil (PTU), and of the hypothyroidism induced by it, on the development of cutaneous and pulmonary fibrosis in the oxidant stress murine model of SSc. Methods Chronic oxidant stress SSc was induced in BALB/c mice by daily subcutaneous injections of hypochlorous acid (HOCl) for 6 weeks. Mice (n = 25) were randomized into three arms: HOCl (n = 10), HOCl plus PTU (n = 10) or veh