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1

Crucial Role of Membrane Potential in Heat Stress-Induced Overproduction of Reactive Oxygen Species in Avian Skeletal Muscle Mitochondria  

PubMed Central

Heat stress is an environmental factor that causes oxidative stress. We found previously that acute heat stress stimulates the production of reactive oxygen species (ROS) in the skeletal muscle mitochondria of birds, and that this was accompanied by an increase of the mitochondrial membrane potential (??) due to increased substrate oxidation by the electron transport chain. We also showed that avian uncoupling protein (avUCP) expression is decreased by the heat exposure. The present study clarifies whether ?? is a major determinant of the overproduction of ROS due to acute heat stress, and if the decrease in avUCP expression is responsible for the elevation in ??. Control (24°C) and acute heat-stressed (34°C for 12 h) birds exhibited increased succinate-driven mitochondrial ROS production as indicated by an elevation of ??, with this increase being significantly higher in the heat-stressed group compared with the control group. In glutamate/malate-energized mitochondria, no difference in the ROS production between the groups was observed, though the mitochondrial ?? was significantly higher in the heat-stressed groups compared with the control group. Furthermore, mitochondria energized with either succinate/glutamate or succinate/malate showed increased ROS production and ?? in the heat-stressed group compared with mitochondria from the control group. These results suggest that succinate oxidation could play an important role in the heat stress-induced overproduction of mitochondrial ROS in skeletal muscle. In agreement with the notion of a decrease in avUCP expression in response to heat stress, proton leak, which was likely mediated by UCP (that part which is GDP-inhibited and arachidonic acid-sensitive), was reduced in the heat-exposed group. We suggest that the acute heat stress-induced overproduction of mitochondrial ROS may depend on ??, which may in turn result not only from increased substrate oxidation but also from a decrease in the mitochondrial avUCP content.

Kikusato, Motoi; Toyomizu, Masaaki

2013-01-01

2

Reduction of reactive oxygen species ameliorates metabolism-secretion coupling in islets of diabetic GK rats by suppressing lactate overproduction.  

PubMed

We previously demonstrated that impaired glucose-induced insulin secretion (IS) and ATP elevation in islets of Goto-Kakizaki (GK) rats, a nonobese model of diabetes, were significantly restored by 30-60-min suppression of endogenous reactive oxygen species (ROS) overproduction. In this study, we investigated the effect of a longer (12 h) suppression of ROS on metabolism-secretion coupling in ?-cells by exposure to tempol, a superoxide (O2(-)) dismutase mimic, plus ebselen, a glutathione peroxidase mimic (TE treatment). In GK islets, both H2O2 and O2(-) were sufficiently reduced and glucose-induced IS and ATP elevation were improved by TE treatment. Glucose oxidation, an indicator of Krebs cycle velocity, also was improved by TE treatment at high glucose, whereas glucokinase activity, which determines glycolytic velocity, was not affected. Lactate production was markedly increased in GK islets, and TE treatment reduced lactate production and protein expression of lactate dehydrogenase and hypoxia-inducible factor 1? (HIF1?). These results indicate that the Warburg-like effect, which is characteristic of aerobic metabolism in cancer cells by which lactate is overproduced with reduced linking to mitochondria metabolism, plays an important role in impaired metabolism-secretion coupling in diabetic ?-cells and suggest that ROS reduction can improve mitochondrial metabolism by suppressing lactate overproduction through the inhibition of HIF1? stabilization. PMID:23349483

Sasaki, Mayumi; Fujimoto, Shimpei; Sato, Yuichi; Nishi, Yuichi; Mukai, Eri; Yamano, Gen; Sato, Hiroki; Tahara, Yumiko; Ogura, Kasane; Nagashima, Kazuaki; Inagaki, Nobuya

2013-06-01

3

Ethylene-induced overproduction of reactive oxygen species is responsible for the development of watersoaking in immature cucumber fruit.  

PubMed

Watersoaking is an ethylene-induced disorder observed in some members of the Cucurbitaceae including cucumber (Cucumis sativus L.), watermelon (Citrullus lanatus Thunb. Matsum and Nakai), and tropical pumpkin (Cucurbita moschata Duch.). Previous studies have found that immature beit-alpha cucumber (cv. Manar) exhibit watersoaking after 6d of continuous exposure to 10 ?LL(-1) ethylene in air (21 kPa O(2)). The present study was designed to investigate the early dynamics of ethylene responses in immature cucumber fruit in order to provide insight into the watersoaking triggering mechanism. Changes in respiration, epidermal color, firmness, reactive oxygen species (ROS) production and electrolyte leakage were evaluated as a function of time under different ethylene concentrations and exposure duration. Ethylene concentrations exceeding 10 ?LL(-1) did not accelerate changes in any of the evaluated responses. The first detectable change was a significant rise in respiration on day 2, followed by a significant rise in ROS on day 4, and significant degreening, mesocap softening, and increased electrolyte leakage on day 6; the latter responses coincident with incipient watersoaking. Varying the duration of exposure to ethylene indicated that the critical exposure time is between 2 and 4d. Notably, all deleterious responses to ethylene were suppressed under a hypoxic atmosphere. A model is proposed in which ethylene induces a sharp increase in respiration with a concomitant sharp rise in ROS, which the immature fruit is incapable of quenching. The resulting production of excess ROS leads to discoloration and membrane deterioration, leading to the release of cytoplasmic content, rapid softening, and the visual symptom of watersoaking. PMID:22999588

Hurr, Brandon M; Huber, Donald J; Vallejos, C Eduardo; Lee, Eunkyung; Sargent, Steven A

2013-01-01

4

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

5

Enhanced Reactive Oxygen Species Scavenging by Overproduction of Superoxide Dismutase and Catalase Delays Postharvest Physiological Deterioration of Cassava Storage Roots1[C][W][OA  

PubMed Central

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.

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

2013-01-01

6

Deficit of complex I activity in human skin fibroblasts with chromosome 21 trisomy and overproduction of reactive oxygen species by mitochondria: involvement of the cAMP/PKA signalling pathway.  

PubMed

DS (Down's syndrome) is the most common human aneuploidy associated with mental retardation and early neurodegeneration. Mitochondrial dysfunction has emerged as a crucial factor in the pathogenesis of numerous neurological disorders including DS, but the cause of mitochondrial damage remains elusive. In the present study, we identified new molecular events involved in mitochondrial dysfunction which could play a role in DS pathogenesis. We analysed mitochondrial respiratory chain function in DS-HSFs (Down's syndrome human foetal skin fibroblasts; human foetal skin fibroblasts with chromosome 21 trisomy) and found a selective deficit in the catalytic efficiency of mitochondrial complex I. The complex I deficit was associated with a decrease in cAMP-dependent phosphorylation of the 18 kDa subunit of the complex, due to a decrease in PKA (protein kinase A) activity related to reduced basal levels of cAMP. Consistently, exposure of DS-HSFs to db-cAMP (dibutyryl-cAMP), a membrane-permeable cAMP analogue, stimulated PKA activity and consequently rescued the deficit of both the cAMP-dependent phosphorylation and the catalytic activity of complex I; conversely H89, a specific PKA inhibitor, suppressed these cAMP-dependent activations. Furthermore, in the present paper we report a 3-fold increase in cellular levels of ROS (reactive oxygen species), in particular superoxide anion, mainly produced by DS-HSF mitochondria. ROS accumulation was prevented by db-cAMP-dependent activation of complex I, suggesting its involvement in ROS production. Taken together, the results of the present study suggest that the drastic decrease in basal cAMP levels observed in DS-HSFs participates in the complex I deficit and overproduction of ROS by DS-HSF mitochondria. PMID:21338338

Valenti, Daniela; Manente, Gabriella Arcangela; Moro, Laura; Marra, Ersilia; Vacca, Rosa Anna

2011-05-01

7

[Reactive oxygen and nitrogen species in inflammatory process].  

PubMed

Reactive oxygen species (ROS) are generated in every cell during normal oxidation. The most important ROS include: superoxide anion (O2*-), hydroxyl radical (OH*), hydroperoxyl radical (HO2*), hydrogen peroxide (H2O2) and singlet oxygen ((1)O2*-). Reactive oxygen species can react with key cellular structures and molecules altering their biological function. Similarly reactive nitrogen species (RNS) such as nitric oxide (NO) or peroxinitrite anion (ONOO-) have physiological activity or reacts with different types of molecules to form toxic products. ROS and RNS are important in process of energy generation, lipids peroxidation, protein and DNA oxidation, nitration, nitrosation or nitrosylation and catecholamine response. Reactive oxygen/nitrogen species are neutralized by enzymatic activity or natural antioxidants that stop the initial formation of radicals. Overproduction of ROS or RNS results in "oxidative" or "nitrosative" stress which contributes to variety of pathological processes typical for different cancer, neurodegenerative, viral, toxic or inflammatory diseases. PMID:18044345

Rutkowski, Ryszard; Pancewicz, S?awomir A; Rutkowski, Krzysztof; Rutkowska, Joanna

2007-08-01

8

Reactive Oxygen Species and Cellular Oxygen Sensing  

PubMed Central

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

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

2008-01-01

9

Measuring mitochondrial reactive oxygen species  

Microsoft Academic Search

This article examines recent methods for measuring reactive oxygen species produced in isolated mitochondria and within live cells, with particular emphasis on the detection of hydrogen peroxide. Protocols for reliable measurements of mitochondrial hydrogen peroxide are presented, while the advantages and pitfalls of these and other methods are discussed. New developments in the detection of lipid peroxidation are outlined. Advice

Mauro Degli Esposti

2002-01-01

10

Mechanisms of nanotoxicity: generation of reactive oxygen species.  

PubMed

Nanotechnology is a rapidly developing field in the 21(st) century, and the commercial use of nanomaterials for novel applications is increasing exponentially. To date, the scientific basis for the cytotoxicity and genotoxicity of most manufactured nanomaterials are not understood. The mechanisms underlying the toxicity of nanomaterials have recently been studied intensively. An important mechanism of nanotoxicity is the generation of reactive oxygen species (ROS). Overproduction of ROS can induce oxidative stress, resulting in cells failing to maintain normal physiological redox-regulated functions. This in turn leads to DNA damage, unregulated cell signaling, change in cell motility, cytotoxicity, apoptosis, and cancer initiation. There are critical determinants that can affect the generation of ROS. These critical determinants, discussed briefly here, include: size, shape, particle surface, surface positive charges, surface-containing groups, particle dissolution, metal ion release from nanometals and nanometal oxides, UV light activation, aggregation, mode of interaction with cells, inflammation, and pH of the medium. PMID:24673904

Fu, Peter P; Xia, Qingsu; Hwang, Huey-Min; Ray, Paresh C; Yu, Hongtao

2014-03-01

11

Reactive oxygen species in periodontitis  

PubMed Central

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

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

2013-01-01

12

[Hemoglobin--source of reactive oxygen species].  

PubMed

Erythrocytes are especially vulnerable to reactive oxygen species because of their direct role in oxygen transport. Moreover, hemoglobin contains iron ions (Fe²?), which catalyze both the Fenton reaction and lipid peroxidation. Reactive oxygen species in erythrocytes are also generated through nonenzymatic and enzymatic processes of heme degradation. The nonenzymatic process of heme degradation is initiated by e.g. hydrogen peroxide, whereas the process of enzymatic degradation is under the influence of heme oxygenase. In both cases biliverdin, carbon monoxide (CO) and iron ions (Fe²?) are generated. These products of heme degradation can initialize the oxidative processes within erythrocytes, but at low concentrations exhibit cytoprotective properties. PMID:23619220

Zapora, Ewa; Jarocka, Iwona

2013-01-01

13

Reactive oxygen species in phagocytic leukocytes  

PubMed Central

Phagocytic leukocytes consume oxygen and generate reactive oxygen species in response to appropriate stimuli. The phagocyte NADPH oxidase, a multiprotein complex, existing in the dissociated state in resting cells becomes assembled into the functional oxidase complex upon stimulation and then generates superoxide anions. Biochemical aspects of the NADPH oxidase are briefly discussed in this review; however, the major focus relates to the contributions of various modes of microscopy to our understanding of the NADPH oxidase and the cell biology of phagocytic leukocytes.

2008-01-01

14

Rosacea, Reactive Oxygen Species, and Azelaic Acid  

PubMed Central

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

2009-01-01

15

The glomerulosclerosis gene Mpv17 encodes a peroxisomal protein producing reactive oxygen species.  

PubMed

The mutant mouse strain Mpv17 carries a retroviral insert in its genome which inactivates the Mpv17 gene. At a young age these mice develop glomerulosclerosis and nephrotic syndrome which resembles human disease. We show here that the Mpv17 gene product is highly conserved and encodes a peroxisomal protein. Loss of the Mpv17 protein does not impair peroxisome biogenesis but instead leads to a reduced ability to produce reactive oxygen species (ROS). In turn, overproduction of the Mpv17 gene in transfected cells results in dramatically enhanced levels of intracellular ROS indicating a direct involvement of Mpv17 in ROS production. These data reveal a role for the Mpv17 protein in peroxisomal reactive oxygen metabolism and establish a novel link between peroxisomal ROS production and glomerulosclerosis. PMID:7957077

Zwacka, R M; Reuter, A; Pfaff, E; Moll, J; Gorgas, K; Karasawa, M; Weiher, H

1994-11-01

16

The glomerulosclerosis gene Mpv17 encodes a peroxisomal protein producing reactive oxygen species.  

PubMed Central

The mutant mouse strain Mpv17 carries a retroviral insert in its genome which inactivates the Mpv17 gene. At a young age these mice develop glomerulosclerosis and nephrotic syndrome which resembles human disease. We show here that the Mpv17 gene product is highly conserved and encodes a peroxisomal protein. Loss of the Mpv17 protein does not impair peroxisome biogenesis but instead leads to a reduced ability to produce reactive oxygen species (ROS). In turn, overproduction of the Mpv17 gene in transfected cells results in dramatically enhanced levels of intracellular ROS indicating a direct involvement of Mpv17 in ROS production. These data reveal a role for the Mpv17 protein in peroxisomal reactive oxygen metabolism and establish a novel link between peroxisomal ROS production and glomerulosclerosis. Images

Zwacka, R M; Reuter, A; Pfaff, E; Moll, J; Gorgas, K; Karasawa, M; Weiher, H

1994-01-01

17

Mitochondrial formation of reactive oxygen species  

PubMed Central

The reduction of oxygen to water proceeds via one electron at a time. In the mitochondrial respiratory chain, Complex IV (cytochrome oxidase) retains all partially reduced intermediates until full reduction is achieved. Other redox centres in the electron transport chain, however, may leak electrons to oxygen, partially reducing this molecule to superoxide anion (O2?•). Even though O2?• is not a strong oxidant, it is a precursor of most other reactive oxygen species, and it also becomes involved in the propagation of oxidative chain reactions. Despite the presence of various antioxidant defences, the mitochondrion appears to be the main intracellular source of these oxidants. This review describes the main mitochondrial sources of reactive species and the antioxidant defences that evolved to prevent oxidative damage in all the mitochondrial compartments. We also discuss various physiological and pathological scenarios resulting from an increased steady state concentration of mitochondrial oxidants.

Turrens, Julio F

2003-01-01

18

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

19

Antimicrobial Actions of Reactive Oxygen Species  

PubMed Central

ABSTRACT Everything should be as simple as it can be, but not simpler.—Attributed to Albert Einstein (1) Reactive oxygen species (ROS) are produced by host phagocytes and exert antimicrobial actions against a broad range of pathogens. The observable antimicrobial actions of ROS are highly dependent on experimental conditions. This perspective reviews recent controversies regarding ROS in Salmonella-phagocyte interactions and attempts to reconcile conflicting observations from different laboratories.

Fang, Ferric C.

2011-01-01

20

Hepatocarcinogenesis in hepatitis C: HCV shrewdly exacerbates oxidative stress by modulating both production and scavenging of reactive oxygen species.  

PubMed

Persistent infection with hepatitis C virus (HCV) is a major risk for the development of hepatocellular carcinoma (HCC). One of the characteristics of HCV infection is the unusual augmentation of oxidative stress, which is exacerbated by iron accumulation in the liver, as observed frequently in hepatitis C patients. Using a transgenic mouse model, in which HCC develops late in life after the preneoplastic steatosis stage, the core protein of HCV was shown to induce the overproduction of reactive oxygen species (ROS) in the liver. In excessive generation of ROS, HCV affects the steady-state levels of a mitochondrial protein chaperone, i.e. prohibitin, leading to an impaired function of the mitochondrial respiratory chain with the overproduction of ROS. Insulin resistance and hepatic steatosis, which frequently accompany HCV infection, exacerbate ROS production. On the other hand, HCV compromises some of the antioxidant systems, including heme oxygenase-1 and NADH dehydrogenase quinone 1, resulting in the provocation of oxidative stress, together with ROS overproduction, in the liver with HCV infection. Thus, HCV infection not only induces ROS but also hampers the antioxidant system in the liver, thereby exacerbating oxidative stress that would facilitate hepatocarcinogenesis. Combination with the other activated pathway, including an alteration in the intracellular signaling cascade of MAP kinase, along with HCV-associated disturbances in lipid and glucose metabolism would lead to the unusual mode of hepatocarcinogenesis, i.e. very frequent and multicentric development of HCC, in persistent HCV infection. PMID:22212930

Fujinaga, Hidetake; Tsutsumi, Takeya; Yotsuyanagi, Hiroshi; Moriya, Kyoji; Koike, Kazuhiko

2011-01-01

21

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

22

Reactive Oxygen Species in Skeletal Muscle Signaling  

PubMed Central

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

Barbieri, Elena; Sestili, Piero

2012-01-01

23

Reactive Oxygen Species in Health and Disease  

PubMed Central

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

Alfadda, Assim A.; Sallam, Reem M.

2012-01-01

24

Reactive Oxygen Species and Tumor Metastasis  

PubMed Central

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

Lee, Doo Jae; Kang, Sang Won

2013-01-01

25

Reactive oxygen species enhance insulin sensitivity  

PubMed Central

SUMMARY Chronic reactive oxygen species (ROS) production by mitochondria may contribute to the development of insulin resistance, a primary feature of type 2 diabetes. In recent years it has become apparent that ROS generation in response to physiological stimuli such as insulin may also facilitate signaling by reversibly oxidizing and inhibiting protein tyrosine phosphatases (PTPs). Here we report that mice lacking one of the key enzymes involved in the elimination of physiological ROS, glutathione peroxidase 1 (Gpx1), were protected from high fat diet-induced insulin resistance. The increased insulin sensitivity in Gpx1?/? mice was attributed to insulin-induced phosphatidylinositol-3-kinase/Akt signaling and glucose uptake in muscle and could be reversed by the anti-oxidant N-acetylcysteine. Increased insulin signaling correlated with enhanced oxidation of the PTP family member PTEN, which terminates signals generated by phosphatidylinositol-3-kinase. These studies provide causal evidence for the enhancement of insulin signaling by ROS in vivo.

Loh, Kim; Deng, Haiyang; Fukushima, Atsushi; Cai, Xiaochu; Boivin, Benoit; Galic, Sandra; Bruce, Clinton; Shields, Benjamin J.; Skiba, Beata; Ooms, Lisa M.; Stepto, Nigel; Wu, Ben; Mitchell, Christina A.; Tonks, Nicholas K.; Watt, Matthew J.; Febbraio, Mark A.; Crack, Peter J.; Andrikopoulos, Sofianos; Tiganis, Tony

2010-01-01

26

Reactive Oxygen Species and the Cardiovascular System  

PubMed Central

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

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

2013-01-01

27

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.

Shi, Xiaoke; Zhang, Yan; Zheng, Junheng

2012-01-01

28

Reactive Oxygen Species, SUMOylation, and Endothelial Inflammation  

PubMed Central

Although the exact mechanism through which NADPH oxidases (Nox's) generate reactive oxygen species (ROS) is still not completely understood, it is widely considered that ROS accumulation is the cause of oxidative stress in endothelial cells. Increasing pieces of evidence strongly indicate the role for ROS in endothelial inflammation and dysfunction and subsequent development of atherosclerotic plaques, which are causes of various pathological cardiac events. An overview for a causative relationship between ROS and endothelial inflammation will be provided in this review. Particularly, a crucial role for specific protein SUMOylation in endothelial inflammation will be presented. Given that SUMOylation of specific proteins leads to increased endothelial inflammation, targeting specific SUMOylated proteins may be an elegant, effective strategy to control inflammation. In addition, the involvement of ROS production in increasing the risk of recurrent coronary events in a sub-group of non-diabetic, post-infarction patients with elevated levels of HDL-cholesterol will be presented with the emphasis that elevated HDL-cholesterol under certain inflammatory conditions can lead to increased incidence of cardiovascular events.

Le, Nhat-Tu; Corsetti, James P.; Dehoff-Sparks, Janet L.; Sparks, Charles E.; Fujiwara, Keigi; Abe, Jun-ichi

2012-01-01

29

Reactive Oxygen Species, SUMOylation, and Endothelial Inflammation.  

PubMed

Although the exact mechanism through which NADPH oxidases (Nox's) generate reactive oxygen species (ROS) is still not completely understood, it is widely considered that ROS accumulation is the cause of oxidative stress in endothelial cells. Increasing pieces of evidence strongly indicate the role for ROS in endothelial inflammation and dysfunction and subsequent development of atherosclerotic plaques, which are causes of various pathological cardiac events. An overview for a causative relationship between ROS and endothelial inflammation will be provided in this review. Particularly, a crucial role for specific protein SUMOylation in endothelial inflammation will be presented. Given that SUMOylation of specific proteins leads to increased endothelial inflammation, targeting specific SUMOylated proteins may be an elegant, effective strategy to control inflammation. In addition, the involvement of ROS production in increasing the risk of recurrent coronary events in a sub-group of non-diabetic, post-infarction patients with elevated levels of HDL-cholesterol will be presented with the emphasis that elevated HDL-cholesterol under certain inflammatory conditions can lead to increased incidence of cardiovascular events. PMID:22991685

Le, Nhat-Tu; Corsetti, James P; Dehoff-Sparks, Janet L; Sparks, Charles E; Fujiwara, Keigi; Abe, Jun-Ichi

2012-01-01

30

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±1.2nmoles/m(3)) was not significantly different from the outdoor concentration (1.41±1.0nmoles/m(3)). Similarly, the indoor and outdoor concentrations of ROS on PM2.5 at institutional buildings (1.16±0.38nmoles/m(3) indoors and 1.68±1.3nmoles/m(3) outdoors) and retail stores (1.09±0.93nmoles/m(3) indoors and 1.12±1.1nmoles/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

31

Skin, reactive oxygen species, and circadian clocks.  

PubMed

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

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

2014-06-20

32

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.

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

2014-01-01

33

Mitochondrial Structure and Reactive Oxygen Species in Mammary Oncogenesis.  

National Technical Information Service (NTIS)

Oxidative stress may play a role in human oncogenesis, including breast cancer. The mitochondria are most common sources of reactive oxygen species (ROS) responsible for most oxidative stress. This project evaluates the role of mitochondrial abnormalities...

Y. C. Lau

2007-01-01

34

Production of Reactive Oxygen Species by Polyhalogenated Cyclic Hydrocarbons (PCH).  

National Technical Information Service (NTIS)

The results of this research strongly support the hypothesis that polyhalogenated cyclic hydrocarbons (PCH) induce production of reactive oxygen species which may contribute to many of the toxic manifestations associated with these xenobiotics. A non-inva...

S. J. Stohs

1992-01-01

35

Mitochondrial Structure and Reactive Oxygen Species in Mammary Oncogenesis.  

National Technical Information Service (NTIS)

Oxidative stress may play a role in human oncogenesis, including breast cancer. The mitochondria are most common sources of reactive oxygen species (ROS) responsible for most oxidative stress. This project evaluates the role of mitochondrial abnormalities...

Y. C. Lau

2006-01-01

36

Mitochondrial Structure and Reactive Oxygen Species in Mammary Oncogenesis.  

National Technical Information Service (NTIS)

Oxidative stress may play a role in human oncogenesis, including breast cancer. The mitochondria are most frequent sources of reactive oxygen species (ROS) responsible for most oxidative stress. This project evaluates the role of mitochondrial abnormaliti...

Y. C. Lau

2004-01-01

37

Mitochondrial Structure and Reactive Oxygen Species in Mammary Oncogenesis.  

National Technical Information Service (NTIS)

Oxidative stress may play a role in human oncogenesis, including breast cancer. The mitochondria are most common sources of reactive oxygen species (ROS) responsible for most oxidative stress. This project evaluates the role of mitochondrial abnormalities...

Y. C. Lau

2005-01-01

38

The oxygen isotope equilibrium fractionation between sulfite species and water  

NASA Astrophysics Data System (ADS)

Sulfite is an important sulfoxy intermediate in oxidative and reductive sulfur cycling in the marine and terrestrial environment. Different aqueous sulfite species exist, such as dissolved sulfur dioxide (SO2), bisulfite (HSO3-), pyrosulfite (S2O52-) and sulfite sensu stricto (SO32-), whereas their relative abundance in solution depends on the concentration and the pH. Conversion of one species into another is rapid and involves in many cases incorporation of oxygen from, or release of oxygen to, water (e.g. SO2 + H2O ? HSO3- + H+), resulting in rapid oxygen isotope exchange between sulfite species and water. Consequently, the oxygen isotope composition of sulfite is strongly influenced by the oxygen isotope composition of water. Since sulfate does not exchange oxygen isotopes with water under most earth surface conditions, it can preserve the sulfite oxygen isotope signature that it inherits via oxidative and reductive sulfur cycling. Therefore, interpretation of ?O values strongly hinges on the oxygen isotope equilibrium fractionation between sulfite and water which is poorly constrained. This is in large part due to technical difficulties in extraction of sulfite from solution for oxygen isotope analysis.

Müller, Inigo A.; Brunner, Benjamin; Breuer, Christian; Coleman, Max; Bach, Wolfgang

2013-11-01

39

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...

40

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...

41

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

PubMed Central

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

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

2013-01-01

42

Reactive oxygen species in vascular biology: implications in hypertension  

Microsoft Academic Search

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

R. M. Touyz; E. L. Schiffrin

2004-01-01

43

Role of reactive oxygen species in cell toxicity.  

PubMed

Several types of compound exert their cytotoxicity by generating reactive oxygen species, notably the superoxide anion radical. These include quinoid and nitroaromatic compounds serving as redox cyclers, i.e. producing superoxide at the expense of NADPH and oxygen catalyzed by cellular reductases. In specialized cell-types employed in defense such as granulocytes, eosinophils and macrophages, myeloperoxidase, NADPH oxidase and nitric oxide synthase have been identified as major sources of reactive oxygen species in cell toxicity. These include hypochlorite, singlet oxygen, superoxide, nitric oxide and hydrogen peroxide. The interaction of superoxide and nitric oxide generates further oxidants such as peroxynitrite. Lumino-amplified chemiluminescence generated by Kupffer cells is partially sensitive to inhibitors of NO synthase. Superoxide dismutase has been found to catalyze a novel reaction, the reversible conversion of nitric oxide to the nitroxyl anion, the latter being viewed as another form of EDRF. In the defense against oxidative damage, there are enzymatic and nonenzymatic antioxidants. Regarding compounds used pharmacologically, we have been interested in ebselen, a seleno-organic compound exhibiting GSH peroxidase activity, which protects against reactive oxygen species generated, for example, at reoxygenation following a period of hypoxia. Further, we have studied lipoate and dihydrolipoate as antioxidant redox system and as singlet oxygen quencher, e.g. protecting against damage of deoxyguanosines in plasmid DNA generated by singlet oxygen. PMID:1335181

Sies, H; de Groot, H

1992-12-01

44

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

Microsoft Academic Search

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

Tejinder Pal Khaket; Rizwan Ahmad

2011-01-01

45

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

Microsoft Academic Search

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

Klaus Apel; Heribert Hirt

2004-01-01

46

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

PubMed

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

Cordeiro, Rodrigo M

2014-01-01

47

Role of reactive oxygen species in low level light therapy  

NASA Astrophysics Data System (ADS)

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

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

2009-02-01

48

Direct detection of reactive oxygen species ex vivo  

Microsoft Academic Search

Direct detection of reactive oxygen species ex vivo. Oxidative stress is thought to play an important role in the initiation and progression of renal, cardiovascular, neoplastic, and neurodegenerative diseases. It is also widely believed that oxidative stress is a main cause of aging. Although considerable progress has been made in the understanding of the sources and actions of oxidative stress,

Ralf P. Brandes; MARIANO JANISZEWSKI

2005-01-01

49

Reactive oxygen species as agents of wood decay by fungi  

Microsoft Academic Search

Although many wood decay basidiomycetes secrete oxidative and hydrolytic enzymes that participate in lignocellulose biodedgradation, it is generally recognized now that these enzymes cannot penetrate sound wood, and that fungi must employ smaller agents to initiate decay. Reactive oxygen species (ROS) are likely candidates, and evidence is accumulating that some wood decay fungi produce these oxidants. For example, we have

Kenneth E. Hammel; Alexander N. Kapich; Kenneth A. Jensen; Zachary C. Ryan

2002-01-01

50

The mystery of reactive oxygen species derived from cell respiration  

Microsoft Academic Search

Mitochondrial respiration is considered to provide reactive oxygen species (ROS) as byproduct of regular electron transfer. Objections were raised since results ob- tained with isolated mitochondria are commonly transferred to activities of mito- chondria in the living cell. High electrogenic membrane potential was reported to trigger formation of mitochondrial ROS involving complex I and III. Suggested bioenergetic parameters, starting ROS

Hans Nohl; Lars Gille; Katrin Staniek

2004-01-01

51

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...

52

Crosstalk of reactive oxygen species and NF-?B signaling  

Microsoft Academic Search

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

Michael J Morgan; Zheng-gang Liu

2011-01-01

53

Participation of Oxygen Species in Periodic Anodic Processes.  

National Technical Information Service (NTIS)

Galvanostatic periodic potential transients of the half element Pt/1M CH2O, 3.75M H2SO4 were measured. A combination of coulometric analysis of the transients and of estimates of surface coverages of the electrodes with organic and oxygen species provided...

H. F. Hunger

1969-01-01

54

Modulation of Vascular Smooth Muscle Signaling by Reactive Oxygen Species  

NSDL National Science Digital Library

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

Alicia N. Lyle (Emory University Department of Medicine, Division of Cardiology); PhD Kathy K. Griendling (Emory University Department of Medicine, Division of Cardiology)

2006-08-01

55

Use of spectroscopic probes for detection of reactive oxygen species  

Microsoft Academic Search

The detection and quantitation of reactive oxygen species (ROS) receives a great deal of interest because of their importance in a wide range of physiological and pathogenic events. Probe-assisted spectroscopy (electron spin resonance, spectrophotometry, fluorescence and luminescence) is the main tool for this application. This review discusses the properties of spectroscopic probes most commonly used for ROS detection and highlights

Grzegorz Bartosz

2006-01-01

56

Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic ?-cells  

Microsoft Academic Search

Pancreatic ?-cells exposed to hyperglycemia produce reactive oxygen species (ROS). Because ?-cells are sensitive to oxidative stress, excessive ROS may cause dysfunction of ?-cells. Here we demonstrate that mitochondrial ROS suppress glucose-induced insulin secretion (GIIS) from ?-cells. Intracellular ROS increased 15min after exposure to high glucose and this effect was blunted by inhibitors of the mitochondrial function. GIIS was also

Koji Sakai; Kazuya Matsumoto; Takeshi Nishikawa; Mihoshi Suefuji; Kazuhiko Nakamaru; Yoshiaki Hirashima; Junji Kawashima; Tetsuya Shirotani; Kenshi Ichinose; Michael Brownlee; Eiichi Araki

2003-01-01

57

Microplasma generation of reactive oxygen species for biological applications  

Microsoft Academic Search

Summary form only given. Reactive oxygen species (ROS) seem to play an important role in several biological systems, and could generate oxidative damage to a variety of biological targets. Fundamental studies examining the cellular components targeted by different ROS generated in low-temperature plasmas are, thus, quite interesting and very promising for biomedical applications. Among other cellular targets, DNA is of

J. S. Sousa; G. Bauville; B. Lacour; V. Puech; M. Touzeau; J. Ravanat

2010-01-01

58

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.

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

2012-01-01

59

Properties of reactive oxygen species by quantum Monte Carlo.  

PubMed

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

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

2014-07-01

60

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.

Tripathy, Baishnab Charan; Oelmuller, Ralf

2012-01-01

61

A Novel Mechanism of Formaldehyde Neurotoxicity: Inhibition of Hydrogen Sulfide Generation by Promoting Overproduction of Nitric Oxide  

PubMed Central

Background Formaldehyde (FA) induces neurotoxicity by overproduction of intracellular reactive oxygen species (ROS). Increasing studies have shown that hydrogen sulfide (H2S), an endogenous gastransmitter, protects nerve cells against oxidative stress by its antioxidant effect. It has been shown that overproduction of nitric oxide (NO) inhibits the activity of cystathionine-beta-synthase (CBS), the predominant H2S-generating enzyme in the central nervous system. Objective We hypothesize that FA-caused neurotoxicity involves the deficiency of this endogenous protective antioxidant gas, which results from excessive generation of NO. The aim of this study is to evaluate whether FA disturbs H2S synthesis in PC12 cells, and whether this disturbance is associated with overproduction of NO. Principal Findings We showed that exposure of PC12 cells to FA causes reduction of viability, inhibition of CBS expression, decrease of endogenous H2S production, and NO production. CBS silencing deteriorates FA-induced decreases in endogenous H2S generation, neurotoxicity, and intracellular ROS accumulation in PC12 cells; while ADMA, a specific inhibitor of NOS significantly attenuates FA-induced decreases in endogenous H2S generation, neurotoxicity, and intracellular ROS accumulation in PC12 cells. Conclusion/Significance Our data indicate that FA induces neurotoxicity by inhibiting the generation of H2S through excess of NO and suggest that strategies to manipulate endogenous H2S could open a suitable novel therapeutic avenue for FA-induced neurotoxicity.

Zhou, Cheng-Fang; Zhuang, Yuan-Yuan; Zhang, Ping; Gu, Hong-Feng; Hu, Bi

2013-01-01

62

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

PubMed Central

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

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

2014-01-01

63

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.

Porter, Kristi M.; Sutliff, Roy L.

2012-01-01

64

Early Elevation of Cochlear Reactive Oxygen Species following Noise Exposure  

Microsoft Academic Search

Reactive oxygen species (ROS) have been implicated in a growing number of neurological disease states, from acute traumatic injury to neurodegenerative conditions such as Alzheimer’s disease. Considerable evidence suggests that ROS also mediate ototoxicant- and noise-induced cochlear injury, although most of this evidence is indirect. To obtain real-time assessment of noise-induced cochlear ROS production in vivo, we adapted a technique

Kevin K. Ohlemiller; James S. Wright; Laura L. Dugan

1999-01-01

65

Reactive Oxygen Species, Oxidative Stress and Plant Ion Channels  

Microsoft Academic Search

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

Vadim Demidchik

66

Production of Ozone and Reactive Oxygen Species After Welding  

Microsoft Academic Search

Many toxic substances including heavy metals, ozone, carbon monoxide, carbon dioxide, and nitrogen oxides are generated during\\u000a welding. Ozone (O3) is a strong oxidant that generates reactive oxygen species (ROS) in tissue, and ambient ROS exposure associated with particles\\u000a has been determined to cause DNA damage. Ozone is produced within 30 seconds during welding. However, the length of time that

H. H. Liu; Y. C. Wu; H. L. Chen

2007-01-01

67

Reactive Oxygen Species in Vascular Formation and Development  

PubMed Central

Reactive oxygen species (ROS) are derived from the metabolism of oxygen and are traditionally viewed as toxic byproducts that cause damage to biomolecules. It is now becoming widely acknowledged that ROS are key modulators in a variety of biological processes and pathological states. ROS mediate key signaling transduction pathways by reversible oxidation of certain signaling components and are involved in the signaling of growth factors, G-protein-coupled receptors, Notch, and Wnt and its downstream cascades including MAPK, JAK-STAT, NF-?B, and PI3K/AKT. Vascular formation and development is one of the most important events during embryogenesis and is vital for postnasal tissue repair. In this paper, we will discuss how ROS regulate different steps in vascular development, including smooth muscle cell differentiation, angiogenesis, endothelial progenitor cells recruitment, and vascular cell migration.

Zhou, Yijiang; Yan, Hui; Guo, Meiqun; Zhu, Jianhua; Xiao, Qingzhong; Zhang, Li

2013-01-01

68

Reactive oxygen species produced from chromate pigments and ascorbate.  

PubMed Central

The reactions of various chromate pigments and ascorbate were investigated by an ESR spin trapping technique. Production of Cr(V) was detected directly and productions of very electrophilic reactive oxygen species (ROS) was detected via the oxidation of formate. We demonstrated previously that both dissolved oxygen and Cr (V) were essential in the production of ROS in this system, and that ROS production was inhibited by catalase. We studied here the effect of solubility of different chromate pigments: sodium, calcium, strontium, basic zinc, basic lead supported on silica, and lead and barium chromates on the production of ROS in buffered medium and cell culture medium (Dublecco's Modified Eagle medium + fetal calf serum). Sodium, calcium, basic zinc, and basic lead chromates were active in the production of ROS in presence of cell culture medium, whereas lead and barium chromates were inactive.

Lefebvre, Y; Pezerat, H

1994-01-01

69

[Reactive oxygen species and bone marrow hematopoietic stem cell senescence].  

PubMed

Reactive oxygen species (ROS) are bioactive oxygen molecules produced after exposure to exogenous oxidants or endogenously through cellular aerobic metabolism. Hematopoietic stem cells (HSC) are multipotent, self-renewing stem cells residing in hematopoietic tissues. Recent studies show that an abnormal increase in ROS production is associated closely with HSC senescence. Many signaling molecules such as FoxOs, ATM, mTOR, TSC1, Bmi1 and AKT play a significant role in ROS-induced HSC senescence. The roles of p53-p21 and p16-Rb pathways can induce hematopoietic dysfunction and lead to ROS-induced HSC senescence. This review summarizes the recent progress of studies on ROS-induced HSC senescence, and further elaborates the potential signaling molecules and pathways, aiming to provide a new target and thread for clinical treatment. PMID:23257465

Chai, Xiao; Zhao, Ming-Feng

2012-12-01

70

VASECTOMY REVERSAL ASSOCIATED WITH INCREASED REACTIVE OXYGEN SPECIES PRODUCTION BY SEMINAL FLUID LEUKOCYTES AND SPERM  

Microsoft Academic Search

PurposeReactive oxygen species, which are primarily produced by leukocytes, are generally detrimental to sperm. High reactive oxygen species levels are found in men with abnormal sperm function. Since men often have poor sperm characteristics and infertility after vasectomy reversal, fertile men to determine if reactive oxygen species were elevated in the former group.

ROBERT H. SHAPIRO; CHARLES H. MULLER; GREGORY CHEN; RICHARD E. BERGER

1998-01-01

71

Evidence for reactive oxygen species inducing mutations in mammalian cells.  

PubMed Central

We have studied the mutagenicity (by selecting for mutants resistant to 6-thioguanine) and cytotoxicity (by determining cellular cloning efficiency) of physical and chemical agents in Chinese hamster ovary (CHO) cells, clone CHO-K1-BH4 (K1-BH4), and its radiation-hypersensitive transformant, AS52. AS52 cells contain a single functional copy of a bacterial gene, the xanthine/guanine phosphoribosyltransferase (gpt) gene instead of its mammalian equivalent, the hypoxanthine/guanine phosphoribosyltransferase (hprt) gene. We found that x-ray and neutron irradiations are equally toxic to both cell types; however, these physical agents are approximately equal to 10 times more mutagenic to AS52 cells than to K1-BH4 cells. Our earlier studies using Southern blot analysis showed that x-irradiation produces mostly or exclusively deletion mutations in both cell types. If reactive oxygen species mediate the mutagenic effects of radiations and chemicals, then radiomimetic compounds such as streptonigrin and bleomycin, which exert their biological effects via reactive oxygen species, and oxidizing compounds such as potassium superoxide and hydrogen peroxide should elicit a similar differential mutagenic response in both cell types. On the other hand, agents such as ethyl methanesulfonate, ICR 191, and UV light, which do not produce reactive oxygen species, should not elicit differential mutagenicity. Our results fulfill such predictions. The apparent hypermutability of AS52 cells probably results from a higher recovery of multilocus deletion mutants in AS52 cells than in K1-BH4 cells, rather than a higher yield of induced mutants.

Hsie, A W; Recio, L; Katz, D S; Lee, C Q; Wagner, M; Schenley, R L

1986-01-01

72

Regulation of Reactive Oxygen Species Generation in Cell Signaling  

PubMed Central

Reactive oxygen species (ROS) including superoxide anion and hydrogen peroxide (H2O2) are thought to be byproducts of aerobic respiration with damaging effects on DNA, protein, and lipid. A growing body of evidence indicates, however, that ROS are involved in the maintenance of redox homeostasis and various cellular signaling pathways. ROS are generated from diverse sources including mitochondrial respiratory chain, enzymatic activation of cytochrome p450, and NADPH oxidases further suggesting involvement in a complex array of cellular processes. This review summarizes the production and function of ROS. In particular, how cytosolic and membrane proteins regulate ROS generation for intracellular redox signaling will be detailed.

Bae, Yun Soo; Oh, Hyunjin; Rhee, Sue Goo; Yoo, Young Do

2011-01-01

73

The role of reactive oxygen species in ocular malignancy.  

PubMed

Increased production of reactive oxygen species (ROS) is an attribute of malignant cells and is linked to the development of many of the characteristics considered "hallmarks of cancer (Hanahan and Weinberg, Cell 144(5), 2011, 646-674)." Among these are sustained proliferative signaling, induction of new vascular growth, promotion of invasion, and metastatic potential. Maintaining the balance between the beneficial biological functions of ROS and the dysregulation seen in human disease such as cancer, presents a daunting conundrum in the future of oncology research. ROS involvement is pervasive throughout the process of tumorigenesis and subsequent cancer growth, yet the response to both pro- and antioxidant based therapy is varied. We will review the ROS species in the pathogenesis of primary ocular malignancy with consideration of potential targets for therapeutic intervention. PMID:24664755

Klump, Kathryn E; McGinnis, James F

2014-01-01

74

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

PubMed

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

Khaket, Tejinder Pal; Ahmad, Rizwan

2011-08-01

75

Regulation of Endothelial Function by Mitochondrial Reactive Oxygen Species  

PubMed Central

Abstract Mitochondria are well known for their central roles in ATP production, calcium homeostasis, and heme and steroid biosynthesis. However, mitochondrial reactive oxygen species (ROS), including superoxide and hydrogen peroxide, once thought to be toxic byproducts of mitochondrial physiologic activities, have recently been recognized as important cell-signaling molecules in the vascular endothelium, where their production, conversion, and destruction are highly regulated. Mitochondrial reactive oxygen species appear to regulate important vascular homeostatic functions under basal conditions in a variety of vascular beds, where, in particular, they contribute to endothelium-dependent vasodilation. On exposure to cardiovascular risk factors, endothelial mitochondria produce excessive ROS in concert with other cellular ROS sources. Mitochondrial ROS, in this setting, act as important signaling molecules activating prothrombotic and proinflammatory pathways in the vascular endothelium, a process that initially manifests itself as endothelial dysfunction and, if persistent, may lead to the development of atherosclerotic plaques. This review concentrates on emerging appreciation of the importance of mitochondrial ROS as cell-signaling molecules in the vascular endothelium under both physiologic and pathophysiologic conditions. Future potential avenues of research in this field also are discussed. Antioxid. Redox Signal. 15, 1517–1530.

Widlansky, Michael E.

2011-01-01

76

Mitochondrial Reactive Oxygen Species Modulate Mosquito Susceptibility to Plasmodium Infection  

PubMed Central

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

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

2012-01-01

77

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.

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

2014-01-01

78

Diabetic peripheral neuropathy: role of reactive oxygen and nitrogen species.  

PubMed

The prevalence of diabetes has reached epidemic proportions. There are two forms of diabetes: type 1 diabetes mellitus is due to auto-immune-mediated destruction of pancreatic ?-cells resulting in absolute insulin deficiency and type 2 diabetes mellitus is due to reduced insulin secretion and or insulin resistance. Both forms of diabetes are characterized by chronic hyperglycemia, leading to the development of diabetic peripheral neuropathy (DPN) and microvascular pathology. DPN is characterized by enhanced or reduced thermal, chemical, and mechanical pain sensitivities. In the long-term, DPN results in peripheral nerve damage and accounts for a substantial number of non-traumatic lower-limb amputations. This review will address the mechanisms, especially the role of reactive oxygen and nitrogen species in the development and progression of DPN. PMID:23722999

Premkumar, Louis S; Pabbidi, Reddy M

2013-11-01

79

Reactive oxygen species mediate growth and death in submerged plants  

PubMed Central

Aquatic and semi-aquatic plants are well adapted to survive partial or complete submergence which is commonly accompanied by oxygen deprivation. The gaseous hormone ethylene controls a number of adaptive responses to submergence including adventitious root growth and aerenchyma formation. Reactive oxygen species (ROS) act as signaling intermediates in ethylene-controlled submergence adaptation and possibly also independent of ethylene. ROS levels are controlled by synthesis, enzymatic metabolism, and non-enzymatic scavenging. While the actors are by and large known, we still have to learn about altered ROS at the subcellular level and how they are brought about, and the signaling cascades that trigger a specific response. This review briefly summarizes our knowledge on the contribution of ROS to submergence adaptation and describes spectrophotometrical, histochemical, and live cell imaging detection methods that have been used to study changes in ROS abundance. Electron paramagnetic resonance (EPR) spectroscopy is introduced as a method that allows identification and quantification of specific ROS in cell compartments. The use of advanced technologies such as EPR spectroscopy will be necessary to untangle the intricate and partially interwoven signaling networks of ethylene and ROS.

Steffens, Bianka; Steffen-Heins, Anja; Sauter, Margret

2013-01-01

80

Production and detection of reactive oxygen species (ROS) in cancers.  

PubMed

Reactive oxygen species include a number of molecules that damage DNA and RNA and oxidize proteins and lipids (lipid peroxydation). These reactive molecules contain an oxygen and include H(2;)O(2;) (hydrogen peroxide), NO (nitric oxide), O(2;)(-) (oxide anion), peroxynitrite (ONOO(-)), hydrochlorous acid (HOCl), and hydroxyl radical (OH(-)). Oxidative species are produced not only under pathological situations (cancers, ischemic/reperfusion, neurologic and cardiovascular pathologies, infectious diseases, inflammatory diseases, autoimmune diseases , etc…) but also during physiological (non-pathological) situations such as cellular metabolism. Indeed, ROS play important roles in many cellular signaling pathways (proliferation, cell activation, migration etc..). ROS can be detrimental (it is then referred to as "oxidative and nitrosative stress") when produced in high amounts in the intracellular compartments and cells generally respond to ROS by upregulating antioxidants such as superoxide dismutase (SOD) and catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) that protects them by converting dangerous free radicals to harmless molecules (i.e. water). Vitamins C and E have also been described as ROS scavengers (antioxidants). Free radicals are beneficial in low amounts. Macrophage and neutrophils-mediated immune responses involve the production and release of NO, which inhibits viruses, pathogens and tumor proliferation. NO also reacts with other ROS and thus, also has a role as a detoxifier (ROS scavenger). Finally NO acts on vessels to regulate blood flow which is important for the adaptation of muscle to prolonged exercise. Several publications have also demonstrated that ROS are involved in insulin sensitivity. Numerous methods to evaluate ROS production are available. In this article we propose several simple, fast, and affordable assays; these assays have been validated by many publications and are routinely used to detect ROS or its effects in mammalian cells. While some of these assays detect multiple ROS, others detect only a single ROS. PMID:22127014

Wu, Danli; Yotnda, Patricia

2011-01-01

81

Proteins Needed to Activate a Transcriptional Response to the Reactive Oxygen Species Singlet Oxygen  

PubMed Central

ABSTRACT Singlet oxygen (1O2) is a reactive oxygen species generated by energy transfer from one or more excited donors to molecular oxygen. Many biomolecules are prone to oxidation by 1O2, and cells have evolved systems to protect themselves from damage caused by this compound. One way that the photosynthetic bacterium Rhodobacter sphaeroides protects itself from 1O2 is by inducing a transcriptional response controlled by ChrR, an anti-? factor which releases an alternative sigma factor, ?E, in the presence of 1O2. Here we report that induction of ?E-dependent gene transcription is decreased in the presence of 1O2 when two conserved genes in the ?E regulon are deleted, including one encoding a cyclopropane fatty acid synthase homologue (RSP2144) or one encoding a protein of unknown function (RSP1091). Thus, we conclude that RSP2144 and RSP1091 are each necessary to increase ?E activity in the presence of 1O2. In addition, we found that unlike in wild-type cells, where ChrR is rapidly degraded when 1O2 is generated, turnover of this anti-? factor is slowed when cells lacking RSP2144, RSP1091, or both of these proteins are exposed to 1O2. Further, we demonstrate that the organic hydroperoxide tert-butyl hydroperoxide promotes ChrR turnover in both wild-type cells and mutants lacking RSP2144 or RSP1091, suggesting differences in the ways different types of oxidants increase ?E activity.

Nam, Tae-Wook; Ziegelhoffer, Eva C.; Lemke, Rachelle A. S.; Donohue, Timothy J.

2013-01-01

82

Activation of the ACE2/Ang-(1-7)/Mas pathway reduces oxygen-glucose deprivation-induced tissue swelling, ROS production, and cell death in mouse brain with angiotensin II overproduction.  

PubMed

We previously demonstrated that mice which overexpress human renin and angiotensinogen (R+A+) show enhanced cerebral damage in both in vivo and in vitro experimental ischemia models. Angiotensin-converting enzyme 2 (ACE2) counteracts the effects of angiotensin (Ang-II) by transforming it into Ang-(1-7), thus reducing the ligand for the AT1 receptor and increasing stimulation of the Mas receptor. Triple transgenic mice, SARA, which specifically overexpress ACE2 in neurons of R+A+ mice were used to study the role of ACE2 in ischemic stroke using oxygen and glucose deprivation (OGD) of brain slices as an in vitro model. We examined tissue swelling, the production of reactive oxygen species (ROS), and cell death in the cerebral cortex (CX) and the hippocampal CA1 region during OGD. Expression levels of NADPH oxidase (Nox) isoforms, Nox2 and Nox4 were measured using western blots. Results show that SARA mice and R+A+ mice treated with the Mas receptor agonist Ang-(1-7) had less swelling, cell death, and ROS production in CX and CA1 areas compared to those in R+A+ animals. Treatment of slices from SARA mice with the Mas antagonist A779 eliminated this protection. Finally, western blots revealed less Nox2 and Nox4 expression in SARA mice compared with R+A+ mice both before and after OGD. We suggest that reduced brain swelling and cell death observed in SARA animals exposed to OGD result from diminished ROS production coupled with lower expression of Nox isoforms. Thus, the ACE2/Ang-(1-7)/Mas receptor pathway plays a protective role in brain ischemic damage by counteracting the detrimental effects of Ang-II-induced ROS production. PMID:24814023

Zheng, J; Li, G; Chen, S; Bihl, J; Buck, J; Zhu, Y; Xia, H; Lazartigues, E; Chen, Y; Olson, J E

2014-07-25

83

Plasma-generated reactive oxygen species for biomedical applications  

NASA Astrophysics Data System (ADS)

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

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

2012-10-01

84

Roles of Reactive Oxygen Species in the Spermatogenesis Regulation  

PubMed Central

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

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

2014-01-01

85

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

86

Reactive oxygen species-driven transcription in Arabidopsis under oxygen deprivation.  

PubMed

Reactive oxygen species (ROS) play an important role as triggers of gene expression during biotic and abiotic stresses, among which is low oxygen (O(2)). Previous studies have shown that ROS regulation under low O(2) is driven by a RHO-like GTPase that allows tight control of hydrogen peroxide (H(2)O(2)) production. H(2)O(2) is thought to regulate the expression of heat shock proteins, in a mechanism that is common to both O(2) deprivation and to heat stress. In this work, we used publicly available Arabidopsis (Arabidopsis thaliana) microarray datasets related to ROS and O(2) deprivation to define transcriptome convergence pattern. Our results show that although Arabidopsis response to anoxic and hypoxic treatments share a common core of genes related to the anaerobic metabolism, they differ in terms of ROS-related gene response. We propose that H(2)O(2) production under O(2) deprivation is a trait present in a very early phase of anoxia, and that ROS are needed for the regulation of a set of genes belonging to the heat shock protein and ROS-mediated groups. This mechanism, likely not regulated via the N-end rule pathway for O(2) sensing, is probably mediated by a NADPH oxidase and it is involved in plant tolerance to the stress. PMID:22415514

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

2012-05-01

87

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.

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

2013-01-01

88

Geochemical production of reactive oxygen species from biogeochemically reduced fe.  

PubMed

The photochemical reduction of Fe(III) complexes to Fe(II) is a well-known initiation step for the production of reactive oxygen species (ROS) in sunlit waters. Here we show a geochemical mechanism for the same in dark environments based on the tidally driven, episodic movement of anoxic groundwaters through oxidized, Fe(III) rich sediments. Sediment samples were collected from the top 5 cm of sediment in a saline tidal creek in the estuary at Murrell's Inlet, South Carolina and characterized with respect to total Fe, acid volatile sulfides, and organic carbon content. These sediments were air-dried, resuspended in aerated solution, then exposed to aqueous sulfide at a range of concentrations chosen to replicate the conditions characteristic of a tidal cycle, beginning with low tide. No detectable ROS production occurred from this process in the dark until sulfide was added. Sulfide addition resulted in the rapid production of hydrogen peroxide, with maximum concentrations of 3.85 ?M. The mechanism of hydrogen peroxide production was tested using a simplified three factor representation of the system based on hydrogen sulfide, Fe(II) and Fe(III). The resulting predictive model for maximum hydrogen peroxide agreed with measured hydrogen peroxide in field-derived samples at the 95% level of confidence, although with a persistent negative bias suggesting a minor undiscovered peroxide source in sediments. PMID:24597860

Murphy, Sarah A; Solomon, Benson M; Meng, Shengnan; Copeland, Justin M; Shaw, Timothy J; Ferry, John L

2014-04-01

89

Mitochondrial Reactive Oxygen Species Regulate Transforming Growth Factor-? Signaling  

PubMed Central

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

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

2013-01-01

90

Obesity Increases Cerebrocortical Reactive Oxygen Species And Impairs Brain Function  

PubMed Central

Nearly two-thirds of the population in the United States is overweight or obese, and this unprecedented level of obesity will undoubtedly have a profound impact on overall health, although little is currently known about the effects of obesity on the brain. The objective of the current study was to investigate cerebral oxidative stress and cognitive decline in the context of diet-induced obesity (DIO). We demonstrate for the first time that DIO induces higher levels of reactive oxygen species (ROS) in the brain, and promotes cognitive impairment. Importantly, we also demonstrate for the first time in these studies that both body weight and adiposity are tightly correlated with the level of ROS. Interestingly, ROS were not correlated with cognitive decline in this model. Alterations in the antioxidant/detoxification Nrf2 pathway, superoxide dismutase, and catalase were not significantly altered in response to DIO. A significant impairment in glutathione peroxidase was observed in response to DIO. Taken together, these data demonstrate for the first time that DIO increases the level of total and individual ROS in the brain, and highlight a direct relationship between the amount of adiposity and the level of oxidative stress within the brain. These data have important implications for understanding the negative effects of obesity on the brain, and are vital to understanding the role of oxidative stress in mediating the effects of obesity on the brain.

Freeman, Linnea R.; Zhang, Le; Nair, Anand; Dasuri, Kalavathi; Francis, Joseph; Fernandez-Kim, Sun-Ok; Bruce-Keller, Annadora J.; Keller, Jeffrey N.

2014-01-01

91

Role of mitochondrial reactive oxygen species in osteoclast differentiation.  

PubMed

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

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

2010-03-01

92

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.

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

2013-01-01

93

Reactive Oxygen Species (Ros-Induced) Ros Release  

PubMed Central

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

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

2000-01-01

94

Phosphate enhances reactive oxygen species production and suppresses osteoblastic differentiation.  

PubMed

Phosphate has been shown to work as a signaling molecule in several cells including endothelial cells and chondrocytes. However, it is largely unknown how phosphate affects osteoblastic cells. In the present study, we investigated the effects of phosphate on reactive oxygen species (ROS) production and osteoblastic differentiation in murine osteoblastic MC3T3-E1 cells. Phosphate increased production of ROS in MC3T3-E1 cells and the inhibitors of sodium-phosphate cotransporter and NADPH oxidase suppressed ROS production by phosphate. Silencing Nox1 and Nox4 also inhibited the increase of ROS by phosphate. Phosphate also decreased alkaline phosphatase activity induced by bone morphogenetic protein 2 and this inhibition was abrogated by an inhibitor of NADPH oxidase. Furthermore, phosphate decreased the expression of osteoblastic marker genes in MC3T3-E1 cells. These results indicate that phosphate suppresses osteoblastic differentiation at least in part by enhancing ROS production in MC3T3-E1 cells. PMID:24052209

Okamoto, Takaaki; Taguchi, Manabu; Osaki, Tomoko; Fukumoto, Seiji; Fujita, Toshiro

2014-07-01

95

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.

Bozza, Marcelo T.

2014-01-01

96

Scavenging of reactive oxygen species in mitochondria induces myofibroblast differentiation.  

PubMed

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

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

2010-11-01

97

Reactive oxygen species delay control of lymphocytic choriomeningitis virus  

PubMed Central

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.

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

2013-01-01

98

Reactive oxygen species-mediated therapeutic control of bladder cancer.  

PubMed

Urinary bladder cancer is the fifth most common cancer in the US and the most costly cancer to manage because it requires life-long surveillance to monitor for recurrence and advanced progression. Urothelial carcinomas account for more than 90% of urinary bladder cancer cases. Transurethral resection and intravesical chemotherapy or immunotherapy are effective short-term treatments of urothelial carcinoma, but long-term management has not yet been optimized. Recent therapeutic strategies emphasize the targeted interference with aberrantly-regulated signaling modulators that result from genomic alterations. However, targeted therapeutic agents might not distinguish cancer cells from their normal counterparts, resulting in undesirable adverse effects. Thus, a new approach for the treatment of urothelial carcinoma has been suggested that differentially augments cancer-associated events, leading to selective death of cancer cells but not normal cells. Many aberrantly-regulated signaling modulators are associated with the elevation of reactive oxygen species (ROS), and an increasing number of studies report agents with the ability to induce ROS in cancer cells. Accordingly, therapeutic augmentation of ROS to a lethal level in cancer cells only would induce selective death of tumor cells but not normal cells, leading to a highly effective chemotherapy strategy for urothelial carcinoma. PMID:21971316

Wang, Hwa-Chain R; Choudhary, Shambhunath

2011-11-01

99

Reactive oxygen species cause endothelial dysfunction in chronic flow overload  

PubMed Central

Although elevation of shear stress increases production of vascular reactive oxygen species (ROS), the role of ROS in chronic flow overload (CFO) has not been well investigated. We hypothesize that CFO increases ROS production mediated in part by NADPH oxidase, which leads to endothelial dysfunction. In six swine, CFO in carotid arteries was induced by contralateral ligation for 1 wk. In an additional group, six swine received apocynin (NADPH oxidase blocker and anti-oxidant) treatment in conjunction with CFO for 1 wk. The blood flow in carotid arteries increased from 189.2 ± 25.3 ml/min (control) to 369.6 ± 61.9 ml/min (CFO), and the arterial diameter increased by 8.6%. The expressions of endothelial nitric oxide synthase (eNOS), p22/p47phox, and NOX2/NOX4 were upregulated. ROS production increased threefold in response to CFO. The endothelium-dependent vasorelaxation was compromised in the CFO group. Treatment with apocynin significantly reduced ROS production in the vessel wall, preserved endothelial function, and inhibited expressions of p22/p47phox and NOX2/NOX4. Although the process of CFO remodeling to restore the wall shear stress has been thought of as a physiological response, the present data implicate NADPH oxidase-produced ROS and eNOS uncoupling in endothelial dysfunction at 1 wk of CFO.

Lu, X.; Guo, X.; Wassall, C. D.; Kemple, M. D.; Unthank, J. L.

2011-01-01

100

How reactive oxygen species and proline face stress together.  

PubMed

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

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

2014-07-01

101

Mitochondrial Reactive Oxygen Species Trigger Hypoxia-Induced Transcription  

NASA Astrophysics Data System (ADS)

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

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

1998-09-01

102

Reactive Oxygen Species Regulate Protrusion Efficiency by Controlling Actin Dynamics  

PubMed Central

Productive protrusions allowing motile cells to sense and migrate toward a chemotactic gradient of reactive oxygen species (ROS) require a tight control of the actin cytoskeleton. However, the mechanisms of how ROS affect cell protrusion and actin dynamics are not well elucidated yet. We show here that ROS induce the formation of a persistent protrusion. In migrating epithelial cells, protrusion of the leading edge requires the precise regulation of the lamellipodium and lamella F-actin networks. Using fluorescent speckle microscopy, we showed that, upon ROS stimulation, the F-actin retrograde flow is enhanced in the lamellipodium. This event coincides with an increase of cofilin activity, free barbed ends formation, Arp2/3 recruitment, and ERK activity at the cell edge. In addition, we observed an acceleration of the F-actin flow in the lamella of ROS-stimulated cells, which correlates with an enhancement of the cell contractility. Thus, this study demonstrates that ROS modulate both the lamellipodium and the lamella networks to control protrusion efficiency.

Taulet, Nicolas; Delorme-Walker, Violaine D.; DerMardirossian, Celine

2012-01-01

103

Salicylic acid signaling inhibits apoplastic reactive oxygen species signaling  

PubMed Central

Background Reactive oxygen species (ROS) are used by plants as signaling molecules during stress and development. Given the amount of possible challenges a plant face from their environment, plants need to activate and prioritize between potentially conflicting defense signaling pathways. Until recently, most studies on signal interactions have focused on phytohormone interaction, such as the antagonistic relationship between salicylic acid (SA)-jasmonic acid and cytokinin-auxin. Results In this study, we report an antagonistic interaction between SA signaling and apoplastic ROS signaling. Treatment with ozone (O3) leads to a ROS burst in the apoplast and induces extensive changes in gene expression and elevation of defense hormones. However, Arabidopsis thaliana dnd1 (defense no death1) exhibited an attenuated response to O3. In addition, the dnd1 mutant displayed constitutive expression of defense genes and spontaneous cell death. To determine the exact process which blocks the apoplastic ROS signaling, double and triple mutants involved in various signaling pathway were generated in dnd1 background. Simultaneous elimination of SA-dependent and SA-independent signaling components from dnd1 restored its responsiveness to O3. Conversely, pre-treatment of plants with SA or using mutants that constitutively activate SA signaling led to an attenuation of changes in gene expression elicited by O3. Conclusions Based upon these findings, we conclude that plants are able to prioritize the response between ROS and SA via an antagonistic action of SA and SA signaling on apoplastic ROS signaling.

2014-01-01

104

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.

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

2010-01-01

105

Damaged mitochondria and overproduction of ROS in Fanconi anemia cells  

PubMed Central

Fanconi anemia (FA) is a heterogeneous disease associated with a bone marrow failure, cancer predisposition and hypersensitivity to DNA crosslinking agents. To date, 15 different genes have been shown to cause FA, all of which have some role in repair of defective DNA interstrand crosslinks. On a biochemical level, many FA individuals display insufficient growth hormone production, abnormal glucose or insulin metabolism. Clinical phenotype may include hydrocephalia, the erythrophagocytosis and diabetes mellitus, thus linking FA with metabolic disorders that involve impaired oxygen metabolism and mitochondrial alterations. Our recent study demonstrates the decrease of FA mitochondrial membrane potential, low ATP production, impaired oxygen uptake and pathological changes in the morphology of FA mitochondria. This is accompanied by inactivation of the enzymes responsible for energy production and detoxification of ROS. We also propose that FA oversensitivity to DNA crosslinkers may be caused by the overproduction of mitochondrial ROS.

Lyakhovich, Alex

2013-01-01

106

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

107

Active species characterization in RF remote oxygen plasma using actinometry OES and electrical probes  

Microsoft Academic Search

Actinometry optical emission spectroscopy (AOES), single cylindrical Langmuir probe and electrostatic planar probe were used to investigate the active species (electrons, ions and atomic oxygen) of remote oxygen plasma in an RF (13.56 MHz) hollow cathode discharge system, as a function of applied power and gas pressure. The electron density and electron temperature were determined from Langmuir probe. The atomic oxygen

S. Saloum; M. Naddaf; B. Alkhaled

2010-01-01

108

NADPH Oxidase Activation Is Required in Reactive Oxygen Species Generation and Cell Transformation Induced by Hexavalent Chromium  

PubMed Central

Hexavalent chromium [Cr(VI)] is a well-known human carcinogen associated with the incidence of lung cancer. Although overproduction of reactive oxygen species (ROS) has been suggested to play a major role in its carcinogenicity, the mechanisms of Cr(VI)-induced ROS production remain unclear. In this study, we investigated the role of NADPH oxidase (NOX), one of the major sources of cellular ROS, in Cr(VI)-induced oxidative stress and carcinogenesis. We found that short-term exposure to Cr(VI) (2?M) resulted in a rapid increase in ROS generation in Beas-2B cells, and concomitantly increased NOX activity and expression of NOX members (NOX1–3 and NOX5) and subunits (p22phox, p47phox, p40phox, and p67phox). Cr(VI) also induced phosphorylation of p47phox and membrane translocation of p47phox and p67phox, further confirming NOX activation. Knockdown of p47phox with a short hairpin RNA attenuated the ROS production induced by Cr(VI). Chronic exposure (up to 3 months) to low doses of Cr(VI) (0.125, 0.25, and 0.5?M) also promoted ROS generation and the expression of NOX subunits, such as p47phox and p67phox, but inhibited the expression of main antioxidant enzymes, such as superoxidase dismutase (SOD) and glutathione peroxidase (GPx). Chronic Cr(VI) exposure resulted in transformation of Beas-2B cells, increasing cell proliferation, anchorage independent growth in soft agar, and forming aggressive tumors in nude mice. Stable knockdown of p47phox or overexpression of SOD1, SOD2, or catalase (CAT) eliminated Cr(VI)-induced malignant transformation. Our results suggest that NOX plays an important role in Cr(VI)-induced ROS generation and carcinogenesis.

Wang, Xin; Son, Young-Ok; Chang, Qingshan; Sun, Lijuan; Hitron, J.Andrew; Budhraja, Amit; Zhang, Zhuo; Ke, Zunji; Chen, Fei; Luo, Jia; Shi, Xianglin

2011-01-01

109

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

PubMed Central

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

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

2013-01-01

110

Radical oxygen species production induced by advanced oxidation protein products predicts clinical evolution and response to treatment in systemic sclerosis  

PubMed Central

Objectives To investigate the role of reactive oxygen species (ROS) in the development of the various patterns of systemic sclerosis (SSc) and the mechanisms of ROS production by endothelial cells and fibroblasts. Methods Production of hydrogen peroxide (H2O2), nitric oxide (NO) and cellular proliferation were determined following incubation of endothelial cells and fibroblasts with 56 SSc and 30 healthy sera. Correlations were established between those markers, the type and the severity of the clinical involvements, and the response to treatment. The factors leading to ROS production were determined. Results H2O2 production by endothelial cells and fibroblasts was higher after incubation with SSc sera than with normal sera (p<0.001) and with sera from SSc patients with severe complications than sera from other patients (p<0.05). Sera from patients with lung fibrosis triggered the proliferation of fibroblasts more than other SSc sera (p<0.001), whereas sera from patients with vascular complications exerted no proliferative effect on fibroblasts, but inhibited endothelial cell growth (p<0.05) and induced NO overproduction (p<0.05). Bosentan reduced NO release by 32%, whereas N?acetylcystein potentiated 5?fluorouracil (5FU) to inhibit fibroblast proliferation by 78%. Those serum?mediated effects did not involve antibodies but advanced oxidation protein products that selectively triggered cells to produce H2O2 or NO. Conclusions SSc sera induce the production of different types of ROS that selectively activate endothelial cells or fibroblasts, leading to vascular or fibrotic complications. Assaying serum?induced ROS production allows clinical activity of the disease to be followed and appropriate treatments to be selected.

Servettaz, A; Guilpain, P; Goulvestre, C; Chereau, C; Hercend, C; Nicco, C; Guillevin, L; Weill, B; Mouthon, L; Batteux, F

2007-01-01

111

Role of reactive oxygen species in apoptosis: implications for cancer therapy  

Microsoft Academic Search

Reactive oxygen species are widely generated in biological systems. Consequently humans have evolved antioxidant defence systems that limit their production. Intracellular production of active oxygen species such as –OH, O2? and H2O2 is associated with the arrest of cell proliferation. Similarly, generation of oxidative stress in response to various external stimuli has been implicated in the activation of transcription factors

José M Matés; Francisca M Sánchez-Jiménez

2000-01-01

112

NO accounts completely for the oxygenated nitrogen species generated by enzymic L-arginine oxygenation.  

PubMed Central

We have assessed the stoichiometry of the nitric oxide (NO) synthase reaction by using a novel e.p.r. technique. NO generated by crude and partially purified NO synthase from endothelial cells and Escherichia coli-lipopolysaccharide-activated macrophages was trapped by a ferrous diethyldithiocarbamate complex dispersed in yeast. The paramagnetic ferrous mononitrosyl dithiocarbamate complex formed exhibited a characteristic e.p.r. signal at g perpendicular = 2.035 and g parallel = 2.02 with a triplet hyperfine structure (hfs) at g perpendicular. NO, 3-morpholinosydnonimine and S-nitroso-L-cysteine, but not nitrite or hydroxylamine, generated a similar e.p.r. signal. NO generated by NO synthase and by SIN-1 accumulated at a constant rate for 1 h, as measured by continuous e.p.r. registration at 37 degrees C. The formation of e.p.r.-detectable NO by NO synthases was inhibited by NG-nitro-L-arginine. Incubation with [15N]NG-L-arginine caused an e.p.r. signal with doublet hfs, indicating that the nitrosyl nitrogen derived exclusively from the guanidino nitrogen. The amount of NO generated by NO synthase as measured by e.p.r. technique was compared with formation of L-[3H]citrulline from L-[3H]arginine. NO and L-citrulline were detected at a 1:1 ratio with both NO synthase preparations. GSH and thiol depletion did not significantly affect NO synthase activity, excluding S-nitrosothiols as intermediates in the NO synthase reaction. We conclude that NO fully accounts for the immediate oxygenated nitrogen species derived from the enzymic oxygenation of L-arginine.

Mulsch, A; Vanin, A; Mordvintcev, P; Hauschildt, S; Busse, R

1992-01-01

113

The connection of monocytes and reactive oxygen species in pain.  

PubMed

The interplay of specific leukocyte subpopulations, resident cells and proalgesic mediators results in pain in inflammation. Proalgesic mediators like reactive oxygen species (ROS) and downstream products elicit pain by stimulation of transient receptor potential (TRP) channels. The contribution of leukocyte subpopulations however is less clear. Local injection of neutrophilic chemokines elicits neutrophil recruitment but no hyperalgesia in rats. In meta-analyses the monocytic chemoattractant, CCL2 (monocyte chemoattractant protein-1; MCP-1), was identified as an important factor in the pathophysiology of human and animal pain. In this study, intraplantar injection of CCL2 elicited thermal and mechanical pain in Wistar but not in Dark Agouti (DA) rats, which lack p47(phox), a part of the NADPH oxidase complex. Inflammatory hyperalgesia after complete Freund's adjuvant (CFA) as well as capsaicin-induced hyperalgesia and capsaicin-induced current flow in dorsal root ganglion neurons in DA were comparable to Wistar rats. Macrophages from DA expressed lower levels of CCR2 and thereby migrated less towards CCL2 and formed limited amounts of ROS in vitro and 4-hydroxynonenal (4-HNE) in the tissue in response to CCL2 compared to Wistar rats. Local adoptive transfer of peritoneal macrophages from Wistar but not from DA rats reconstituted CCL2-triggered hyperalgesia in leukocyte-depleted DA and Wistar rats. A pharmacological stimulator of ROS production (phytol) restored CCL2-induced hyperalgesia in vivo in DA rats. In Wistar rats, CCL2-induced hyperalgesia was completely blocked by superoxide dismutase (SOD), catalase or tempol. Likewise, inhibition of NADPH oxidase by apocynin reduced CCL2-elicited hyperalgesia but not CFA-induced inflammatory hyperalgesia. In summary, we provide a link between CCL2, CCR2 expression on macrophages, NADPH oxidase, ROS and the development CCL2-triggered hyperalgesia, which is different from CFA-induced hyperalgesia. The study further supports the impact of CCL2 and ROS as potential targets in pain therapy. PMID:23658840

Hackel, Dagmar; Pflücke, Diana; Neumann, Annick; Viebahn, Johannes; Mousa, Shaaban; Wischmeyer, Erhard; Roewer, Norbert; Brack, Alexander; Rittner, Heike Lydia

2013-01-01

114

The Connection of Monocytes and Reactive Oxygen Species in Pain  

PubMed Central

The interplay of specific leukocyte subpopulations, resident cells and proalgesic mediators results in pain in inflammation. Proalgesic mediators like reactive oxygen species (ROS) and downstream products elicit pain by stimulation of transient receptor potential (TRP) channels. The contribution of leukocyte subpopulations however is less clear. Local injection of neutrophilic chemokines elicits neutrophil recruitment but no hyperalgesia in rats. In meta-analyses the monocytic chemoattractant, CCL2 (monocyte chemoattractant protein-1; MCP-1), was identified as an important factor in the pathophysiology of human and animal pain. In this study, intraplantar injection of CCL2 elicited thermal and mechanical pain in Wistar but not in Dark Agouti (DA) rats, which lack p47phox, a part of the NADPH oxidase complex. Inflammatory hyperalgesia after complete Freund's adjuvant (CFA) as well as capsaicin-induced hyperalgesia and capsaicin-induced current flow in dorsal root ganglion neurons in DA were comparable to Wistar rats. Macrophages from DA expressed lower levels of CCR2 and thereby migrated less towards CCL2 and formed limited amounts of ROS in vitro and 4-hydroxynonenal (4-HNE) in the tissue in response to CCL2 compared to Wistar rats. Local adoptive transfer of peritoneal macrophages from Wistar but not from DA rats reconstituted CCL2-triggered hyperalgesia in leukocyte-depleted DA and Wistar rats. A pharmacological stimulator of ROS production (phytol) restored CCL2-induced hyperalgesia in vivo in DA rats. In Wistar rats, CCL2-induced hyperalgesia was completely blocked by superoxide dismutase (SOD), catalase or tempol. Likewise, inhibition of NADPH oxidase by apocynin reduced CCL2-elicited hyperalgesia but not CFA-induced inflammatory hyperalgesia. In summary, we provide a link between CCL2, CCR2 expression on macrophages, NADPH oxidase, ROS and the development CCL2-triggered hyperalgesia, which is different from CFA-induced hyperalgesia. The study further supports the impact of CCL2 and ROS as potential targets in pain therapy.

Hackel, Dagmar; Pflucke, Diana; Neumann, Annick; Viebahn, Johannes; Mousa, Shaaban; Wischmeyer, Erhard; Roewer, Norbert; Brack, Alexander; Rittner, Heike Lydia

2013-01-01

115

Respiration in adipocytes is inhibited by reactive oxygen species.  

PubMed

It is a desirable goal to stimulate fuel oxidation in adipocytes and shift the balance toward less fuel storage and more burning. To understand this regulatory process, respiration was measured in primary rat adipocytes, mitochondria, and fat-fed mice. Maximum O(2) consumption, in vitro, was determined with a chemical uncoupler of oxidative phosphorylation (carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP)). The adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio was measured by luminescence. Mitochondria were localized by confocal microscopy with MitoTracker Green and their membrane potential (Delta psi(M)) measured using tetramethylrhodamine ethyl ester perchlorate (TMRE). The effect of N-acetylcysteine (NAC) on respiration and body composition in vivo was assessed in mice. Addition of FCCP collapsed Delta psi(M) and decreased the ATP/ADP ratio. However, we demonstrated the same rate of adipocyte O(2) consumption in the absence or presence of fuels and FCCP. Respiration was only stimulated when reactive oxygen species (ROS) were scavenged by pyruvate or NAC: other fuels or fuel combinations had little effect. Importantly, the ROS scavenging role of pyruvate was not affected by rotenone, an inhibitor of mitochondrial complex I. In addition, mice that consumed NAC exhibited increased O(2) consumption and decreased body fat in vivo. These studies suggest for the first time that adipocyte O(2) consumption may be inhibited by ROS, because pyruvate and NAC stimulated respiration. ROS inhibition of O(2) consumption may explain the difficulty to identify effective strategies to increase fat burning in adipocytes. Stimulating fuel oxidation in adipocytes by decreasing ROS may provide a novel means to shift the balance from fuel storage to fuel burning. PMID:20035277

Wang, Tong; Si, Yaguang; Shirihai, Orian S; Si, Huiqing; Schultz, Vera; Corkey, Richard F; Hu, Liping; Deeney, Jude T; Guo, Wen; Corkey, Barbara E

2010-08-01

116

Reactive oxygen species in bovine oocyte maturation in vitro.  

PubMed

The role of reactive oxygen species (ROS) in the in vitro maturation (IVM) of oocytes remains controversial. The aim of the present study was to determine possible fluctuations in ROS production during bovine oocyte IVM in the presence of different modulators of ROS generation. Cumulus-oocyte complexes were cultured in medium 199 (control) in the absence or presence of 0.6 mM cysteine, 1 mM 1-choro-2,4-dinitro benzene (CDNB), 2 microM diphenyliodonium, 0.5 mM N-nitro-L-arginine methyl ester or 10 microM sodium nitroprusside (SNP) at 39 degrees C, in 5% CO2 in humidified air for 22 h. In addition, the respiratory chain effectors potassium cyanide (KCN; 1 mM) and carbonyl cyanide m-chlorophenylhydrazone (0.42 microM) were used. Meiotic maturation was determined by the presence of MII. ROS production was evaluated in denuded oocytes at different time points as the ratio of 2',7'-dichlorodihydrofluorescein diacetate (DCHF-DA) to fluorescein diacetate (FDA). ROS levels, expressed as DCHF-DA:FDA, fluctuated throughout the 22 h of maturation depending on the treatment applied. At 12 h incubation in the presence of KCN and SNP, ROS levels were increased, whereas ROS levels after 12 h in the presence of cysteine were reduced (P<0.05). Both CDNB and SNP impaired meiotic progression. The higher metabolic activity demand during bovine oocyte maturation coincides with a concomitant reduction in ROS generation. These results suggest that 12 h would be a critical point for bovine oocyte IVM because it is closely related to the production of ROS at this time. PMID:19383267

Morado, Sergio A; Cetica, Pablo D; Beconi, Martha T; Dalvit, Gabriel C

2009-01-01

117

Are mitochondrial reactive oxygen species required for autophagy?  

SciTech Connect

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

Jiang, Jianfei, E-mail: jjf73@pitt.edu [Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh (United States)] [Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh (United States); Maeda, Akihiro; Ji, Jing [Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh (United States)] [Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh (United States); Baty, Catherine J.; Watkins, Simon C. [Center for Biologic Imaging, Department of Cell Biology and Physiology, University of Pittsburgh (United States)] [Center for Biologic Imaging, Department of Cell Biology and Physiology, University of Pittsburgh (United States); Greenberger, Joel S. [Department of Radiation Oncology, University of Pittsburgh (United States)] [Department of Radiation Oncology, University of Pittsburgh (United States); Kagan, Valerian E., E-mail: kagan@pitt.edu [Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh (United States)

2011-08-19

118

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.

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

2012-01-01

119

The induction of reactive oxygen species and loss of mitochondrial Omi/HtrA2 is associated with S-nitrosoglutathione-induced apoptosis in human endothelial cells  

SciTech Connect

The pathophysiological relevance of S-nitrosoglutathione (GSNO)-induced endothelial cell injury remains unclear. The main objective of this study was to elucidate the molecular mechanisms of GSNO-induced oxidative stress in endothelial cells. Morphological evaluation through DAPI staining and propidium iodide (PI) flow cytometry was used to detect apoptosis. In cultured EA.hy926 endothelial cells, exposure to GSNO led to a time- and dose-dependent apoptotic cascade. When intracellular reactive oxygen species (ROS) production was measured in GSNO-treated cells with the fluorescent probes 5-(and-6)-carboxy-2',7'-dichlorofluorescein diacetate, we observed elevated ROS levels and a concomitant loss in mitochondrial membrane potential, indicating that GSNO-induced death signaling is mediated through a ROS-mitochondrial pathway. Importantly, we found that peroxynitrite formation and Omi/HtrA2 release from mitochondria were involved in this phenomenon, whereas changes of death-receptor dependent signaling were not detected in the same context. The inhibition of NADPH oxidase activation and Omi/HtrA2 by a pharmacological approach provided significant protection against caspase-3 activation and GSNO-induced cell death, confirming that GSNO triggers the death cascade in endothelial cells in a mitochondria-dependent manner. Taken together, our results indicate that ROS overproduction and loss of mitochondrial Omi/HtrA2 play a pivotal role in reactive nitrogen species-induced cell death, and the modulation of these pathways can be of significant therapeutic benefit.

Liu Qibing; Liu Lulu [Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, Zhejiang University, Hangzhou, 310058 (China); Lu Yingmei [Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai (Japan); Tao Rongrong; Huang Jiyun [Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, Zhejiang University, Hangzhou, 310058 (China); Shioda, Norifumi; Moriguchi, Shigeki; Fukunaga, Kohji [Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai (Japan); Han Feng, E-mail: changhuahan@zju.edu.c [Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, Zhejiang University, Hangzhou, 310058 (China); Lou Yijia, E-mail: yijialou@zju.edu.c [Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, Zhejiang University, Hangzhou, 310058 (China)

2010-05-01

120

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.

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

2010-01-01

121

Active oxygen species mediate asbestos fiber uptake by tracheal epithelial cells  

SciTech Connect

To examine the mechanism whereby asbestos fibers penetrate tracheal epithelial cells, we exposed rat tracheal explants to amosite asbestos alone, or with varying concentrations of substances that scavenge active oxygen species (catalase and superoxide dismutase) or prevent formation of active oxygen species (deferoxamine). All three agents decreased asbestos fiber uptake in a dose-response fashion, but no agent provided complete protection against fiber penetration. We conclude that uptake of amosite asbestos fibers is mediated in part by active oxygen species (most likely OH.), but that other mechanisms of fiber uptake must also exist.

Hobson, J.; Wright, J.L.; Churg, A. (Univ. of British Columbia, Vancouver (Canada))

1990-10-01

122

A simple chemiluminescence assay for the determination of reactive oxygen species produced by human neutrophils.  

PubMed

We show that phagocyte production of reactive oxygen species can be measured using a microtitre plate based chemiluminescence blotting technique. The production of reactive oxygen species is determined by their ability to catalyze the oxidation of luminol or isoluminol, resulting in light emission which is recorded on a photographic film. The method permits the determination of NADPH oxidase activity from as few as 9000 cells. It could be used to detect NADPH oxidase defects in neutrophils (e.g. from patients suffering from chronic granulomatous disease), and to screen pharmaceuticals with scavenging activity for reactive oxygen species. PMID:8699014

Liu, L; Dahlgren, C; Elwing, H; Lundqvist, H

1996-06-10

123

Genotoxicity of volatile and secondary reactive oxygen species generated by photosensitization  

SciTech Connect

Reactive oxygen species were generated in the gas phase by photosensitization involving illumination of Rose Bengal. Depending on whether the chromophore is dry or solubilized, this system produces either energy-transfer reactions leading to generation of singlet oxygen specifically, or a combination of energy-transfer and electron-transfer reactions, providing both singlet oxygen and reduced forms of oxygen, such as superoxide anion and hydrogen peroxide. In neither case were the reactive species mutagenic in strain TA104 of Salmonella typhimurium, which had been previously shown to be reverted by oxygen species generated by the hypoxanthine-xanthine oxidase system in aqueous medium. However, mixed oxygen species induced an increased lethality in a variety of DNA repair-deficient Escherichia coli strains. This genotoxic effect, mainly reparable by the uvrA and recA mechanisms, was efficiently prevented by the thiol N-acetyl-L-cysteine. Singlet oxygen itself failed to exert direct genotoxic effects, although secondary reactants produced by its reaction with cell components enhanced lethality in some repair-deficient bacteria. Distance-dependence analyses provided measurements of the lifetimes of the oxygen species generated in the gas phase. 35 refs., 7 figs., 2 tabs.

Camoirano, A.; De Flora, S.; Dahl, T.A. (Univ. of Genoa (Italy) Tufts Univ. Veterinary, Boston, MA (United States))

1993-01-01

124

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

125

MEASUREMENT OF REACTIVE OXYGEN SPECIES AFTER PHOTODYNAMIC THERAPY IN VITRO  

Microsoft Academic Search

A b s t r a c t Photodynamic therapy (PDT) is an emerging modality for the treatment of neoplastic and non- neoplastic diseases. It is based on the use of a sensitiser, which is localised in target tissue, light, and molecular oxygen. Sensitisers are activated with the appropriate wavelength of light and then are excited to the long-lived triplet

126

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

PubMed

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

Sun, Li; Wolferts, Guido; Veltkamp, Roland

2014-08-01

127

Formation of reactive oxygen species at increased contraction frequency in rat cardiomyocytes  

Microsoft Academic Search

Objective: Reactive oxygen species (ROS) play an ambivalent role in cardiomyocytes: low concentrations are involved in cellular signaling, while higher concentrations contribute to cellular injury. We studied ROS formation during increases in contraction frequency in isolated cardiomyocytes.

Frank R. Heinzel; Yukun Luo; Giuliano Dodoni; Kerstin Boengler; Frank Petrat; Fabio Di Lisa; Herbert de Groot; Rainer Schulz; Gerd Heusch

2006-01-01

128

COMPARATIVE ANALYSIS OF REACTIVE OXYGEN SPECIES IN HUMAN PLASMA AND BLOOD  

EPA Science Inventory

Reactive oxygen species (ROS) are commonly associated with diseased states (including asthma, cardiovascular disease, cancer) infections, and exposure to various toxicants in humans. It is of interest in epidemiology studies to characterize the association of oxidative stress in...

129

Bradykinin and adenosine receptors mediate desflurane induced postconditioning in human myocardium: role of reactive oxygen species  

Microsoft Academic Search

BACKGROUND: Desflurane during early reperfusion has been shown to postcondition human myocardium, in vitro. We investigated the role of adenosine and bradykinin receptors, and generation of radical oxygen species in desflurane-induced postconditioning in human myocardium. METHODS: We recorded isometric contraction of human right atrial trabeculae hanged in an oxygenated Tyrode's solution (34 degrees Celsius, stimulation frequency 1 Hz). After a

Sandrine Lemoine; Clément Buléon; René Rouet; Calin Ivascau; Gérard Babatasi; Massimo Massetti; Jean-Louis Gérard; Jean-Luc Hanouz

2010-01-01

130

Prostaglandins and Radical Oxygen Species Are Involved in Microvascular Effects of Hyperoxia  

Microsoft Academic Search

Hyperoxia causes vasoconstriction in most tissues, by mechanisms that are not fully understood. We investigated microvascular effects of breathing 100% oxygen in healthy volunteers, using iontophoresis to deliver acetylcholine (ACh) and sodium nitroprusside (SNP). Aspirin and vitamin C were used to test for involvement of prostaglandins and radical oxygen species. Forearm skin perfusion was measured using laser Doppler perfusion imaging.

A. Rousseau; E. Tesselaar; J. Henricson; F. Sjöberg

2010-01-01

131

Participation of Reactive Oxygen Species in Phototoxicity Induced by Quinolone Antibacterial Agents  

Microsoft Academic Search

To elucidate the mechanism of phototoxicity induced as a side effect by some of the new quinolone antibiotics, we studied sparfloxacin (SPFX), lomefloxacin, enoxacin, ofloxacin, and ciprofloxacin. We first examined the photosensitized formation of reactive oxygen species such as singlet oxygen (1O2) and superoxide anion (O?2) mediated by the new quinolones. Although a large number of studies have been reported,

Naoki Umezawa; Kumi Arakane; Akemi Ryu; Shinro Mashiko; Masaaki Hirobe; Tetsuo Nagano

1997-01-01

132

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

Microsoft Academic Search

Reactive oxygen species (ROS) are a family of molecules that are continuously generated, transformed and consumed in all living organisms as a consequence of aerobic life. The traditional view of these reactive oxygen metabolites is one of oxidative stress and damage that leads to decline of tissue and organ systems in aging and disease. However, emerging data show that ROS

Bryan C Dickinson; Christopher J Chang

2011-01-01

133

Reactive oxygen species in choline deficiency induced carcinogenesis and nitrone inhibition  

Microsoft Academic Search

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

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

2002-01-01

134

Reactive oxygen species as glucose signaling molecules in mesangial cells cultured under high glucose  

Microsoft Academic Search

Reactive oxygen species as glucose signaling molecules in mesangial cells cultured under high glucose.BackgroundOxidative stress is one of the important mediators of vascular complications in diabetes including nephropathy. High glucose (HG) generates reactive oxygen species (ROS) as a result of glucose auto-oxidation, metabolism, and formation of advanced glycosylation end products. The concept of ROS-induced tissue injury has recently been revised

Hunjoo Ha; Hi Bahl Lee

2000-01-01

135

Antioxidants from grape seeds protect hair against reactive oxygen species  

Microsoft Academic Search

Summary Oxygen based radicals are predominantly generated in the water phase. Therefore, it is very important to use not only lipophilic antioxidants but also water-soluble radical scavengers in cosmetic formula- tions. Vitamin C, glutathion and different enzymes are natural water-soluble antioxidants. Unfortunately, most of them are not stable in cosmetic formulations. We studied a new water-soluble antioxidant based on procyanidins

F. Zülli; E. Belser; M. Neuenschwander; R. Muggli

136

Peripartum Cardiomyopathy: Role of STAT3 and Reactive Oxygen Species  

Microsoft Academic Search

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

Denise Hilfiker-Kleiner; Arash Haghikia; Andres Hilfiker

137

Activation of molecular oxygen and the nature of the active oxygen species for CO oxidation on oxide supported Au catalysts.  

PubMed

Although highly dispersed Au catalysts with Au nanoparticles (NPs) of a few nanometers in diameter are well-known for their high catalytic activity for several oxidation and reduction reactions already at rather low temperatures for almost 30 years, central aspects of the reaction mechanism are still unresolved. While most studies focused on the active site, the active Au species, and the effect of the support material, the most crucial step during oxidation reactions, the activation of molecular oxygen and the nature of the resulting active oxygen species (Oact), received more attention just recently. This is topic of this Account, which focuses on the formation, location, and nature of the Oact species present on metal oxide supported Au catalysts under typical reaction conditions, at room temperature and above. It is mainly based on quantitative temporal analysis of products (TAP) reactor measurements, which different from most spectroscopic techniques are able to detect and quantify these species even at the extremely low concentrations present under realistic reaction conditions. Different types of pulse experiments were performed, during which the highly dispersed, realistic powder catalysts are exposed to very low amounts of reactants, CO and/or O2, in order to form and reactively remove Oact species and gain information on their formation, nature, and the active site for Oact formation. Our investigations have shown that the active oxygen species for CO oxidation on Au/TiO2 for reaction at 80 °C and higher is a highly stable atomic species, which at 80 °C is formed only at the perimeter of the Au-oxide interface and whose reactive removal by CO is activated, but not its formation. From these findings, it is concluded that surface lattice oxygen represents the Oact species for the CO oxidation. Accordingly, the CO oxidation proceeds via a Au-assisted Mars-van Krevelen mechanism, during which surface lattice oxygen close to the Au NPs is removed by reaction with CO, resulting in a partially reduced TiO2 surface, which is subsequently reoxidized by O2. We demonstrate that this is the dominant reaction pathway for Au catalysts based on reducible metal oxides in general, at typical reaction temperatures, while for less active Au catalysts based on nonreducible metal oxides, this reaction pathway is not possible and the remaining activity must arise from another pathway, most probably a Au-only mechanism. At lower reaction temperature, reactive removal of Oact becomes increasingly inhibited, leading to a change in the dominant reaction pathway. PMID:24555537

Widmann, D; Behm, R J

2014-03-18

138

Non-lattice surface oxygen species implicated in the catalytic partial oxidation of decane to oxygenated aromatics  

NASA Astrophysics Data System (ADS)

The one-step transformation of C7-C12 linear alkanes into more valuable oxygenates provides heterogeneous catalysis with a major challenge. In evaluating the potential of a classic mixed-metal-oxide catalyst, we demonstrate new insights into the reactivity of adsorbed oxygen species. During the aerobic gas-phase conversion of n-decane over iron molybdate, the product distribution correlates with the condition of the catalyst. Selectivity to oxygenated aromatics peaks at 350 °C while the catalyst is in a fully oxidized state, whereas decene and aromatic hydrocarbons dominate at higher temperatures. The high-temperature performance is consistent with an underlying redox mechanism in which lattice oxide ions abstract hydrogen from decane. At lower temperatures, the formation of oxygenated aromatics competes with the formation of CO2, implying that electrophilic adsorbed oxygen is involved in both reactions. We suggest, therefore, that so-called non-selective oxygen is capable of insertion into carbon-rich surface intermediates to generate aromatic partial oxidation products.

Pradhan, Sivaram; Bartley, Jonathan K.; Bethell, Donald; Carley, Albert F.; Conte, Marco; Golunski, Stan; House, Matthew P.; Jenkins, Robert L.; Lloyd, Rhys; Hutchings, Graham J.

2012-02-01

139

Effect of reactive oxygen and carbonyl species on crucial cellular antioxidant enzymes  

Microsoft Academic Search

Numerous reactive oxygen species (ROS) and reactive carbonyl species (RCS) issuing from lipid and sugar oxidation are known to damage a large number of proteins leading to enzyme inhibition and alteration of cellular functions. Whereas studies in literature only focus on the reactivity of one or two of these compounds, we aimed at comparing in the same conditions of incubations

Jean-François Lesgards; Cyrielle Gauthier; Juan Iovanna; Nicolas Vidal; Alain Dolla; Pierre Stocker

2011-01-01

140

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.

Sanchez, Sergio; Demain, Arnold L.

2008-01-01

141

TCDD as a biological response modifier for Mitomycin C: Oxygen tension affects enzyme activation, reactive oxygen species and cell death  

Microsoft Academic Search

TCDD was assessed as a biological response modifier for increasing MMC cytotoxicity through aryl hydrocarbon receptor (AhR) activation and increasing levels of bioreductive enzymes. Human MCF-7 cells were exposed to TCDD, MMC and combinations thereof under aerobic or hypoxic conditions. Cytotoxicity, enzyme activities (NQO1, XO, XDH, CYPR, CYP1A, GST and UGT) and intracellular reactive oxygen species (ROS) were subsequently measured.

Abby C. Collier; Karen L. Pritsos; Chris A. Pritsos

2006-01-01

142

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 rf driven atmospheric-pressure helium-oxygen mixture plasmas (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. The evolution of species concentration is described for reactive oxygen species, metastable species, radical species and positively- and negatively-charged ions (and its clusters). Effects of the air impurity containing water humidity on electronegativity and chemical activity are clarified with particular emphasis on reactive oxygen species.

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

2012-10-01

143

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

144

Roles of reactive oxygen and nitrogen species in pain.  

PubMed

Peroxynitrite (PN; ONOO?) and its reactive oxygen precursor superoxide (SO; O?•?) are critically important in the development of pain of several etiologies including 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 contributions 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 nonnarcotic analgesics that are based upon the unique ability to selectively eliminate SO and/or PN. As we have a better understanding of the roles of SO and PN in pathophysiological settings, targeting PN may be a better therapeutic strategy than targeting SO. This is because, unlike PN, which has no currently known beneficial role, SO may play a significant role in learning and memory. Thus, the best approach may be to spare SO while directly targeting its downstream product, PN. Over the past 15 years, our team has spearheaded research concerning the roles of SO and 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

2011-09-01

145

Radiation induces aerobic glycolysis through reactive oxygen species  

PubMed Central

Background and purpose Although radiation induced reoxygenation has been thought to increase radiosensitivity, we have shown that its associated oxidative stress can have radioprotective effects, including stabilization of the transcription factor hypoxia inducible factor 1 (HIF-1). HIF-1 is known to regulate many of the glycolytic enzymes, thereby promoting aerobic glycolysis, which is known to promote treatment resistance. Thus, we hypothesized that reoxygenation after radiation would increase glycolysis. We previously showed that blockade of oxidative stress using a superoxide dismutase (SOD) mimic during reoxygenation can downregulate HIF-1 activity. Here we tested whether concurrent use of this drug with radiotherapy would reduce the switch to a glycolytic phenotype. Materials and methods 40 mice with skin fold window chambers implanted with 4T1 mammary carcinomas were randomized into (1) no treatment, (2) radiation alone, (3) SOD mimic alone, and (4) SOD mimic with concurrent radiation. All mice were imaged on the ninth day following tumor implantation (30 h following radiation treatment) following injection of a fluorescent glucose analog, 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG). Hemoglobin saturation was measured by using hyperspectral imaging to quantify oxygenation state. Results Mice treated with radiation showed significantly higher 2-NBDG fluorescence compared to controls (p = 0.007). Hemoglobin saturation analysis demonstrated reoxygenation following radiation, coinciding with the observed increase in glycolysis. The concurrent use of the SOD mimic with radiation demonstrated a significant reduction in 2-NBDG fluorescence compared to effects seen after radiation alone, while having no effect on reoxygenation. Conclusions Radiation induces an increase in tumor glucose demand approximately 30 h following therapy during reoxygenation. The use of an SOD mimic can prevent the increase in aerobic glycolysis when used concurrently with radiation, without preventing reoxygenation.

Zhong, Jim; Rajaram, Narasimhan; Brizel, David M.; Frees, Amy E.; Ramanujam, Nirmala; Batinic-Haberle, Ines; Dewhirst, Mark W.

2013-01-01

146

Molecular Cell Biology: Are Reactive Oxygen Species Regulators of Leaf Senescence?  

Microsoft Academic Search

Senescence processes can influence many important agricultural traits; however, our knowledge concerning regulatory mechanisms\\u000a controlling senescence is still limited. Free radicals are thought to play an essential role in senescence, especially those\\u000a derived from oxygen. In addition to their deleterious functions, they might serve as signalling molecules. The critical balance\\u000a between production and scavenging of reactive oxygen species (ROS), which

Ulrike Zentgraf; Vera Hemleben

147

The effect of thymol and its derivatives on reactions generating reactive oxygen species  

Microsoft Academic Search

The effects of thymol (TOH), thymoquinone (TQ) and dithymoquinone (TQ2) on the reactions generating reactive oxygen species (ROS) such as superoxide anion radical (O?2), hydroxyl radical (HO) and singlet oxygen (1O2) were tested using the chemiluminescence (CL) and spectrophotometry methods. All tested compounds acted as scavengers of various ROS. The rate constant of 1O2-dimols quenching by thymol was calculated.

Irena Kruk; Teresa Michalska; Krzysztof Lichszteld; Aleksandra K?adna; Hasan Y. Aboul-Enein

2000-01-01

148

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

Microsoft Academic Search

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

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

1993-01-01

149

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

PubMed Central

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

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

2014-01-01

150

c-Ets1 inhibits the interaction of NF-?B and CREB, and downregulates IL-1?-induced MUC5AC overproduction during airway inflammation  

PubMed Central

Mucin hypersecretion is frequently observed in many inflammatory diseases of the human respiratory tract. As mucin hypersecretion refers to uncontrolled mucin expression and secretion during inflammation, studies examining the negative control mechanisms of mucin hypersecretion are vital in developing novel therapeutic medications. We hypothesized that the c-Ets1 induced by interleukin (IL)-1? would decrease MUC5AC overproduction by inhibiting the interaction of NF-?B with cAMP response element-binding protein (CREB) in vivo. Stimulation with IL-1? caused the direct binding of NF-?B and CREB to the MUC5AC promoter, thus increasing MUC5AC gene expression. However, IL-1?-induced MUC5AC messenger RNA levels were surprizingly downregulated by c-Ets1 (located ?938 to ?930). Interestingly, c-Ets1 also suppressed IL-1?-induced MUC5AC gene expression in vitro and in vivo by disrupting the interaction of NF-?B with CREB on the MUC5AC promoter. In addition, c-Ets1 also inhibited significant morphologic changes and inflammatory cell infiltration after IL-1? exposure in mouse lungs infected with either wild-type or shRNA-c-Ets1. Moreover, reactive oxygen species produced by NOX4 increased c-Ets1 gene expression and MUC5AC gene expression in alveolar macrophages from bronchoalveolar lavage fluid. These results suggest a molecular paradigm for the establishment of a novel mechanism underlying the negative regulation of mucin overproduction, thus enhancing our understanding of airway inflammation.

Song, K S; Yoon, J-H; Kim, K S; Ahn, D W

2012-01-01

151

Influence of a broad temperature range on the oxygen consumption rates of three desert lizard species.  

PubMed

Oxygen consumption rates of three desert lizard species: (Acanthodactylus boskianus, Lacertidae; Scincus mitranus, Scincidae; Diplometopon zarudnyi, Amphisbaenidae) were determined in relation to ambient temperatures ranging from 10 to 35 degrees C using a double-chamber, volumetric closed system. The interspecific differences in the oxygen consumption rates were found to have a close relationship between the characteristics of the M-T curves, the thermoregulatory behaviour and the ecology of the respective species. The M-T curves of the studied lizards were specifically modified and adjusted to their climatic region. PMID:2873932

Al-Sadoon, M K

1986-01-01

152

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

153

Role of reactive nitrogen and reactive oxygen species against MPTP neurotoxicity in mice  

Microsoft Academic Search

There is growing evidence indicating that reactive nitrogen species (RNS) and reactive oxygen species (ROS) are a major contributor\\u000a to the pathogenesis and progression of Parkinson’s disease. Here we investigated whether edaravone (free radical scavenger),\\u000a minocycline (inducible nitric oxide synthase, iNOS inhibitor), 7-nitroindazole (neuronal NOS, nNOS inhibitor), fluvastatin\\u000a (endothelial NOS, eNOS activator) and pitavastatin (eNOS activator) can protect against MPTP

Hironori Yokoyama; Sho Takagi; Yu Watanabe; Hiroyuki Kato; Tsutomu Araki

2008-01-01

154

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.

Liu, Yuanyuan; Imlay, James A.

2013-01-01

155

Deoxyamphimedine, a pyridoacridine alkaloid, damages DNA via the production of reactive oxygen species.  

PubMed

Marine pyridoacridines are a class of aromatic chemicals that share an 11H-pyrido[4,3,2-mn]acridine skeleton. Pyridoacridine alkaloids display diverse biological activities including cytotoxicity, fungicidal and bactericidal properties, production of reactive oxygen species (ROS) and topoisomerase inhibition. These activities are often dependent on slight modifications to the pyridoacridine skeleton. Here we demonstrate that while structurally similar to neoamphimedine and amphimedine, the biological activity of deoxyamphimedine differs greatly. Deoxyamphimedine damages DNA in vitro independent of topoisomerase enzymes through the generation of reactive oxygen species. Its activity was decreased in low oxygen, with the removal of a reducing agent and in the presence of anti-oxidants. Deoxyamphimedine also showed enhanced toxicity in cells sensitive to single or double strand DNA breaks, consistent with the in vitro activity. PMID:19597581

Marshall, Kathryn M; Andjelic, Cynthia D; Tasdemir, Deniz; Concepción, Gisela P; Ireland, Chris M; Barrows, Louis R

2009-01-01

156

Deoxyamphimedine, a Pyridoacridine Alkaloid, Damages DNA via the Production of Reactive Oxygen Species  

PubMed Central

Marine pyridoacridines are a class of aromatic chemicals that share an 11H-pyrido[4,3,2-mn]acridine skeleton. Pyridoacridine alkaloids display diverse biological activities including cytotoxicity, fungicidal and bactericidal properties, production of reactive oxygen species (ROS) and topoisomerase inhibition. These activities are often dependent on slight modifications to the pyridoacridine skeleton. Here we demonstrate that while structurally similar to neoamphimedine and amphimedine, the biological activity of deoxyamphimedine differs greatly. Deoxyamphimedine damages DNA in vitro independent of topoisomerase enzymes through the generation of reactive oxygen species. Its activity was decreased in low oxygen, with the removal of a reducing agent and in the presence of anti-oxidants. Deoxyamphimedine also showed enhanced toxicity in cells sensitive to single or double strand DNA breaks, consistent with the in vitro activity.

Marshall, Kathryn M.; Andjelic, Cynthia D.; Tasdemir, Deniz; Concepcion, Gisela P.; Ireland, Chris M.; Barrows, Louis R.

2009-01-01

157

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

158

Vascular Smooth Muscle Modulates Endothelial Control of Vasoreactivity via Reactive Oxygen Species Production through Myoendothelial Communications  

Microsoft Academic Search

BackgroundEndothelial control of vascular smooth muscle plays a major role in the resulting vasoreactivity implicated in physiological or pathological circulatory processes. However, a comprehensive understanding of endothelial (EC)\\/smooth muscle cells (SMC) crosstalk is far from complete. Here, we have examined the role of gap junctions and reactive oxygen species (ROS) in this crosstalk and we demonstrate an active contribution of

Marie Billaud; Roger Marthan; Jean-Pierre Savineau; Christelle Guibert; Neeraj Vij

2009-01-01

159

Effects of reactive oxygen species on cellular wall disassembly of banana fruit during ripening  

Microsoft Academic Search

Fruit softening is generally attributed to cell wall disassembly. Experiments were conducted to investigate effects of various reactive oxygen species (ROS) on in vitro cellular wall disassembly of harvested banana fruit. The alcohol-extracted insoluble residue (AEIR) was obtained from the pulp tissues of banana fruit at various ripening stages and then used to examine the disassembly of cellular wall polysaccharides

Guiping Cheng; Xuewu Duan; John Shi; Wangjin Lu; Yunbo Luo; Weibo Jiang; Yueming Jiang

2008-01-01

160

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

161

Determination of reactive oxygen species in single human erythrocytes using microfluidic chip electrophoresis  

Microsoft Academic Search

Reactive oxygen species (ROS) are known to not only mediate the damage of cellular constituents but also to regulate cellular signaling. Analysis of ROS is essential if we wish to understand the mechanisms of cellular alterations. In this paper, a microfluidic chip-based approach to the determination of ROS in single erythrocyte was developed by using a simple crossed-channel glass chip

Yue Sun; Xue-Feng Yin; Yun-Yang Ling; Zhao-Lun Fang

2005-01-01

162

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

Microsoft Academic Search

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

Javier Martinez; Juan J Moreno

2000-01-01

163

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

Microsoft Academic Search

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

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

2003-01-01

164

Increased NAD(P)H Oxidase and Reactive Oxygen Species in Coronary Arteries After Balloon Injury  

Microsoft Academic Search

Reactive oxygen species (ROS), produced by cellular constituents of the arterial wall, provide a signaling mechanism involved in vascular remodeling. Because adventitial fibroblasts are actively involved in coronary remodeling, we examined whether the changes in the redox state affect their phenotypic characteristics. To this end, superoxide anion production and NAD(P)H oxidase activity were measured in porcine coronary arteries in vivo,

Yi Shi; Rodica Niculescu; Dian Wang; Sachin Patel; Kelly L. Davenpeck; Andrew Zalewski

165

Role of reactive oxygen species in organophosphate insecticide phosalone toxicity in erythrocytes in vitro  

Microsoft Academic Search

Reactive oxygen species (ROS) caused by organophosphates may be involved in the toxicity of various pesticides. Therefore, in this study we aimed to investigate how an organophosphate insecticide, phosalone, affects lipid peroxidation (LPO) and the antioxidant defence system in vitro. For this purpose, the effects of various doses of phosalone on LPO and the activities of superoxide dismutase (SOD), glutathione

I Altuntas; N Delibas; D. K Doguc; S Ozmen; F Gultekin

2003-01-01

166

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

167

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

Microsoft Academic Search

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

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

2005-01-01

168

Levels of mitochondrial reactive oxygen species increase in rat neuropathic spinal dorsal horn neurons  

Microsoft Academic Search

Reactive oxygen species (ROS) are toxic agents that may be involved in various neurodegenerative diseases. Recent studies indicate that ROS are also involved in persistent pain through a spinal mechanism. Since the major source of ROS in neurons is mitochondria, mitochondrial ROS generation was examined in dorsal horn neurons of neuropathic rats. Neuropathic rats were produced by L5 spinal nerve

Eun-Sung Park; Xiu Gao; Jin Mo Chung; Kyungsoon Chung

2006-01-01

169

Mitochondrial Reactive Oxygen Species Trigger Calcium Increases During Hypoxia in Pulmonary Arterial Myocytes  

Microsoft Academic Search

We hypothesized that mitochondria function as the O2 sensors underlying hypoxic pulmonary vasoconstriction by releasing reactive oxygen species (ROS) from complex III of the electron transport chain (ETC). We have previously found that antioxidants or inhibition of the proximal region of the ETC attenuates hypoxic pulmonary vasoconstriction in rat lungs and blocks hypoxia-induced contraction of isolated pulmonary arterial (PA) myocytes.

Gregory B. Waypa; Jeremy D. Marks; Mathew M. Mack; Chan Boriboun; Paul T. Mungai; Paul T. Schumacker

2009-01-01

170

Induction of microglial reactive oxygen species production by the organochlorinated pesticide dieldrin  

Microsoft Academic Search

Exposure to pesticides has been speculated to contribute to the development of sporadic Parkinson's disease (PD) characterized by a progressive degeneration of the nigrostriatal dopaminergic pathway. Activation of brain microglia that produce various neurotoxic factors including cytokines and reactive oxygen species (ROS) has been increasingly associated with dopaminergic neurodegeneration induced by various toxicants. Dieldrin, a highly persistent organochlorinated pesticide found

Haoyu Mao; Xi Fang; Katon M. Floyd; Jeanette E. Polcz; Ping Zhang; Bin Liu

2007-01-01

171

Oxygen species scavenger activities and phenolic contents of four West African plants  

Microsoft Academic Search

In West Africa, Alchornea cordifolia, Baphia nitida, Cassia occidentalis and Boerhavia diffusa leaves are used in food and drinks, as well as in traditional medicine, to treat rheumatic ailments which incur oxidative stress. First, these plants were evaluated for their antioxidant properties through a scavenger effect on reactive oxygen species (ROS), such as hydrogen peroxide and hypochlorous acid. All of

G. Kouakou-Siransy; S. Sahpaz; G. Irié-Nguessan; Y. J. Datte; J. Kablan; B. Gressier; F. Bailleul

2010-01-01

172

Controlling Tumor Growth by Modulating Endogenous Production of Reactive Oxygen Species  

Microsoft Academic Search

Paradoxically, reactive oxygen species (ROS) can promote normal cellular proliferation and carcinogenesis, and can also induce apoptosis of tumor cells. In this report, we study the contribution of ROS to various cellular signals depending on the nature and the level of ROS produced. In nontransformed NIH 3T3 cells, ROS are at low levels and originate from NADPH oxidase. Hydrogen peroxide

Alexis Laurent; Carole Nicco; Christiane Chereau; Claire Goulvestre; Jerome Alexandre; Arnaud Alves; Eva Levy; Francois Goldwasser; Yves Panis; Olivier Soubrane; Bernard Weill; Frederic Batteux

2005-01-01

173

Role of redox potential and reactive oxygen species in stress signaling  

Microsoft Academic Search

Stress-activated signaling cascades are affected by altered redox potential. Key contributors to altered redox potential are reactive oxygen species (ROS) which are formed, in most cases, by exogenous genotoxic agents including irradiation, inflammatory cytokines and chemical carcinogens. ROS and altered redox potential can be considered as the primary intracellular changes which regulate protein kinases, thereby serving as an important cellular

Victor Adler; Zhimin Yin; Kenneth D Tew; Ze'ev Ronai

1999-01-01

174

Oxygen-derived species: Their relation to human disease and environmental stress  

Microsoft Academic Search

Free radicals and other reactive oxygen species (ROS) are constantly formed in the human body, often for useful metabolic purposes. Antioxidant defenses protect against them, but these defenses are not completely adequate, and systems that repair damage by ROS are also necessary. Mild oxidative stress often induces antioxidant defense enzymes, but severe stress can cause oxidative damage to lipids, proteins,

B. Halliwell; C. E. Cross

1994-01-01

175

Generation of singlet oxygen and other radical species by quantum dot and carbon dot nanosensitizers  

Microsoft Academic Search

Medicinal applications of luminescent semiconductor quantum dots are of growing interest. In spite of the fact that their fabrication and imaging applications have been extensively investigated for the last decade, very little is documented on photodynamic action of quantum dots. In this study we demonstrate generation of singlet oxygen and other radical species upon exposure of quantum dots to blue

Roman Generalov; Ingeborg L. Christensen; Wei Chen; Ya-Ping Sun; Solveig Kristensen; Petras Juzenas

2009-01-01

176

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

177

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

178

TCDD as a biological response modifier for Mitomycin C: oxygen tension affects enzyme activation, reactive oxygen species and cell death.  

PubMed

TCDD was assessed as a biological response modifier for increasing MMC cytotoxicity through aryl hydrocarbon receptor (AhR) activation and increasing levels of bioreductive enzymes. Human MCF-7 cells were exposed to TCDD, MMC and combinations thereof under aerobic or hypoxic conditions. Cytotoxicity, enzyme activities (NQO1, XO, XDH, CYPR, CYP1A, GST and UGT) and intracellular reactive oxygen species (ROS) were subsequently measured. Under aerobic conditions, TCDD alone had no significant toxicity but combinations of TCDD and MMC significantly increased cell death. LD50 values were: MMC alone, 0.89 +/- 0.04 microM; TCDD co-treatment, 0.26 +/- 0.007 microM (P = 0.008 vs. MMC alone) and TCDD pre-treatment, 0.04 +/- 0.01 microM (P = 0.003 vs. MMC alone). Under hypoxia, TCDD itself caused significant cell death, likely due to increased ROS, but no combinations of MMC/TCDD altered the LD50 of MMC. Significant changes in enzyme activities were caused by TCDD under aerobic but not hypoxic conditions while MMC decreased the activity of its activating enzymes regardless of oxygen tension. Greater toxicity of MMC/TCDD combinations in aerobic culture, were most likely mediated by increased levels of bioreductive enzymes caused through AhR activation. Data presented herein also demonstrate that low oxygen tension decreases AhR activation and signaling and increases the inherent toxicity of TCDD. PMID:16226770

Collier, Abby C; Pritsos, Karen L; Pritsos, Chris A

2006-02-23

179

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

180

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

181

Active oxygen species as mediators of plant immunity: three case studies.  

PubMed

A burst of active oxygen species (AOS) is known to be involved in local cell death as part of plant defence against pathogens. It is, however, under dispute to what extent AOS can induce pathogen resistance and immunity throughout the plant. Three experimental strategies that reveal a primary role for AOS and a surprisingly low chemical and spatial specificity are now described for tobacco and Arabidopsis thaliana plants. Ozone is a gaseous AOS that was applied to non-transgenic plants. Hydrogen peroxide or singlet oxygen are AOS that were induced by high-light treatment of transgenic plants that contained antisense constructs inhibiting catalase activity or chlorophyll biosynthetic enzymes. In all cases, activated oxygen species, cellular lesions, ethylene and salicylic acid, and components of major plant defence systems (systemic acquired resistance, hypersensitive response) were induced, as was resistance towards pathogens (tobacco mosaic virus, Pseudomonas syringae or Peronospora parasitica). It is concluded that active oxygen species can act as mediators of plant immunity so that new non-pesticidal plant protection strategies could be developed. PMID:11030422

Sandermann, H

2000-08-01

182

Prooxidant action of rosmarinic acid: transition metal-dependent generation of reactive oxygen species.  

PubMed

Rosmarinic acid and its constituent caffeic acid produced reactive oxygen species in the presence of transition metals. Complex of rosmarinic acid or caffeic acid with iron inactivated aconitase the most sensitive enzyme to oxidative stress. The inactivation of aconitase was iron-dependent, and prevented by TEMPOL, a scavenger of reactive oxygen species, suggesting that the rosmarinic acid/iron-mediated generation of superoxide anion is responsible for the inactivation of aconitase. Direct spectrophotometric determination of hydrogen peroxide and superoxide anion confirmed the rosmarinic acid/iron-dependent production of reactive oxygen species. Treatment of DNA from plasmid pBR322 and calf thymus with rosmarinic acid plus copper caused strand scission and formed 8-hydroxy-2'-deoxyguanosine in DNA. Rosmarinic acid and caffeic acid showed a potent activity that reduces transition metals. These results suggest that transition metals reduced by rosmarinic acid can form superoxide radical by one electron reduction of oxygen molecule: superoxide radical in turn converts to hydrogen peroxide and hydroxyl radical causing the formation of DNA base adduct. Cytotoxicity of rosmarinic acid may be related to the prooxidant action resulting from metal-reducing activity. PMID:17267171

Murakami, Keiko; Haneda, Miyako; Qiao, Shanlou; Naruse, Makoto; Yoshino, Masataka

2007-06-01

183

Mitochondrial reactive oxygen species are required for hypoxia-induced degradation of keratin intermediate filaments.  

PubMed

Hypoxia can cause stress and structural changes to the epithelial cytoskeleton. The intermediate filament (IF) network is known to reorganize in response to stress. We examined whether rats exposed to hypoxia had altered keratin IF expression in their alveolar epithelial type II (ATII) cells. There was a significant decrease in keratin protein levels in hypoxic ATII cells compared with those in ATII cells isolated from normoxic rats. To define the mechanisms regulating this process we studied changes to the keratin IF network in A549 cells (an alveolar epithelial cell line) exposed to 1.5% oxygen. We observed a time-dependent disassembly-degradation of keratin 8 and 18 proteins, which was associated with an increase in reactive oxygen species (ROS). Hypoxia-treated A549 cells deficient in mitochondrial DNA or A549 cells treated with a small interfering RNA against the Rieske iron-sulfur protein of mitochondrial complex III did not have increased levels of ROS nor was the keratin IF network disassembled and degraded. The superoxide dismutase (SOD)/catalase mimetic (EUK-134) prevented the hypoxia-mediated keratin IF degradation as did the overexpression of SOD1 but not of SOD2. Accordingly, we provide evidence that hypoxia promotes the disassembly and degradation of the keratin IF network via mitochondrial complex III-generated reactive oxygen species.-Na, N., Chandel, N. S., Litvan, J., Ridge, K. M. Mitochondrial reactive oxygen species are required for hypoxia-induced degradation of keratin intermediate filaments. PMID:19897662

Na, Ni; Chandel, Navdeep S; Litvan, Juan; Ridge, Karen M

2010-03-01

184

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.

2014-01-01

185

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.

Kvietys, Peter R.; Granger, D. Neil

2012-01-01

186

Pro-metastatic signaling by c-Met through RAC-1 and reactive oxygen species (ROS).  

PubMed

Overexpression of the c-Met/hepatocyte growth factor receptor(HGF-R) proto-oncogene and abnormal generation of intracellular oxygen species (reactive oxygen species (ROS)) have been linked, by independent lines of evidence, to cell transformation and to malignant growth. By comparing two subpopulations of the B16 mouse melanoma (B16-F0 and B16-F10) endowed with different lung metastasis capacities (low and high, respectively) we found that both the expression/phosphorylation of c-Met and the steady-state levels of ROS positively correlated with metastatic growth. shRNA-mediated downregulation of c-Met in F10 cells led to a parallel decrease in the generation of oxygen species and in metastatic capacity, suggesting that oxidants may mediate the pro-metastatic activity of the HGF receptor. c-Met activation by a ligand elicits the formation of oxidant species through the oxidase-coupled small GTPase Rac-1, a relevant downstream target of the HGF-R. Moreover, cell treatment with the catalytic ROS scavengers EUK-134 and EUK-189 attenuates Met signaling to ERKs and inhibits the anchorage-independent growth of F10 cells, consistent with a critical role for oxygen species in HGF signaling and in aggressive cell behavior. Finally, genetic manipulation of the Rac-ROS cascade at different levels demonstrated its crucial role in the pro-metastatic activity of c-Met in vivo. Thus, we have outlined a novel cascade triggered by c-Met and mediated by ROS, linked to metastasis and potentially targetable by new antimetastatic, redox-based therapies. PMID:16462764

Ferraro, D; Corso, S; Fasano, E; Panieri, E; Santangelo, R; Borrello, S; Giordano, S; Pani, G; Galeotti, T

2006-06-22

187

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.

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

188

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.

Hyman, Lynne M.; Franz, Katherine J.

2013-01-01

189

Stability and characterization of oxygen species in alkali molten carbonated: A thermodynamic and electrochemical approach  

SciTech Connect

The study of the chemical and electrochemical properties of molten carbonate has been widely discussed in the last 20 years because of the necessity for optimizing molten carbonate fuel cell (MCFC) performance. The stability and electrochemical behavior of reduced oxygen species were investigated in several alkali molten carbonates at different oxoacidity levels and temperatures. Theoretical predictions and experimental results were in good agreement and show that, in Na-K, Li-Na, Li-K, and Li-Na-K melts, peroxide species can only be stabilized in basic media. Superoxide species, unstable in lithium-containing carbonate, can be stabilized in Na-K under slightly basic conditions. Peroxide/oxide and superoxide/oxide redox systems were characterized by voltammetric and convolution potential sweep techniques. It was shown that CO[sub 2] does not participate in the rate-determining reduction mechanisms of both superoxide and peroxide species. Electrochemical parameters relative to the cited systems (D, [delta], E[sup 0], E[sub 1/2]), as well as the solubility of reduced oxygen species were determined.

Cassir, M.; Moutiers, G.; Devynck, J. (Ecole Nationale Superieure de Chimie, Paris (France). Lab d'Electrochimie)

1993-11-01

190

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

191

Differential production of reactive oxygen species by subsets of human spermatozoa at different stages of maturation  

Microsoft Academic Search

BACKGROUND: Reactive oxygen species (ROS)-mediated damage to human spermatozoa has been implicated in the pathogenesis of male infertility. Although ROS production by human spermatozoa has been extensively studied, the cell-to-cell variation in ROS production by spermatozoa at different stages of maturation has never been investigated. METHODS: In this study, we determined ROS production by subsets of human spermatozoa at different

E. Gil-Guzman; M. Ollero; M. C. Lopez; R. K. Sharma; J. G. Alvarez; A. J. Thomas; A. Agarwal

2001-01-01

192

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

Microsoft Academic Search

Silver ions have been widely used as disinfectants that inhibit bacterial growth by inhibiting the essential enzymatic functions of the microorganism via interaction with the thiol-group of l-cysteine. However, silver-ion-mediated perturbation of the bacterial respiratory chain has raised the possibility of reactive oxygen species (ROS) generation. We used bacterial reporter strains specifically responding to superoxide radicals and found that silver-ion-mediated

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

2009-01-01

193

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

Microsoft Academic Search

Reactive oxygen species (ROS) play an important role in the pathogenesis of many human degenerative diseases such as cancer,\\u000a aging, arteriosclerosis, and rheumatism. Much attention has been focused on the development of safe and effective antioxidants.\\u000a To discover sources of antioxidative activity in marine algae, extracts from 17 kinds of seaweed were screened for their inhibitory\\u000a effect on total ROS

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

2004-01-01

194

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

Microsoft Academic Search

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

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

2011-01-01

195

Reactive Oxygen Species in Molecular Pathways Controlling Aging in the Filamentous Fungus Podospora anserina  

Microsoft Academic Search

\\u000a To generate ATP via different types of respiration, the impact of reactive oxygen species (ROS) as by-products generated at\\u000a the inner mitochondrial membrane is well analyzed and documented. Moreover, other pathways of ROS generation seem to be of\\u000a relevance, but they are currently less explored. It now seems that ROS not only play a key role in the age-related damaging

Heinz D. Osiewacz; Christian Q. Scheckhuber

196

The antioxidant action of Polypodium leucotomos extract and kojic acid: reactions with reactive oxygen species  

Microsoft Academic Search

Two natural products Polypodium leucotomos extract (PL) and kojic acid (KA) were tested for their ability to scavenge reactive oxygen species ( OH, O2 -, H2O2, 1O2) in phosphate buffer. Hydroxyl radicals were generated by the Fenton reaction, and the rate constants of scavenging were 1.6 x 109 M-1 s-1 for KA and 1.0 x 109 M-1 s-1 for PL,

A. J. Gomes; C. N. Lunardi; S. Gonzalez; A. C. Tedesco

2001-01-01

197

Role of hyaluronan and CD44 in reactive oxygen species-induced mucus hypersecretion  

Microsoft Academic Search

Mucus hypersecretion is an important manifestation in patients with chronic inflammatory airway diseases. Mucin 5AC (MUC5AC)\\u000a is a major component of airway mucus. MUC5AC expression is regulated by epidermal growth factor receptor (EGFR) which can\\u000a be activated by reactive oxygen species (ROS). Hyaluronan (HA), a linear glycosaminoglycan with molecular weights ranging\\u000a from 2 × 105 to 1 × 107, is expressed in airway epithelium

Hongmei Yu; Qi Li; Xiangdong Zhou; Victor P. Kolosov; Juliy M. Perelman

2011-01-01

198

Epidermal growth factor rescues trophoblast apoptosis induced by reactive oxygen species  

Microsoft Academic Search

Pre-eclampsia and intrauterine growth restriction are associated with increased apoptosis of placental villous trophoblast.\\u000a This may result from placental hypoperfusion, leading to the generation of reactive oxygen species (ROS). Apoptosis can be\\u000a induced in villous trophoblast following exposure to oxidative stress. Epidermal growth factor (EGF) reduces trophoblast apoptosis\\u000a resulting from exposure to hypoxia. We hypothesised that exposure to hydrogen peroxide,

Sarah J. Moll; Carolyn J. P. Jones; Ian P. Crocker; Philip N. Baker; Alexander E. P. Heazell

2007-01-01

199

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

Microsoft Academic Search

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

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

2004-01-01

200

Concentration of reactive oxygen species (ROS) in mainstream and sidestream cigarette smoke  

Microsoft Academic Search

Reactive Oxygen Species (ROS) have been related to adverse health effects in recent years. Previous studies have reported ROS concentrations in mainstream smoke, but the reports have shown considerable variability and conclusions. There have been no prior measurements on sidestream smoke. In this study, the amounts of gas-phase and particle-bound ROS in tobacco smoke were determined using 2,7-dichlorodihydrofluorescein diacetate (DCFH)

Jiayuan Zhao; Philip K. Hopke

2011-01-01

201

Concentration of Reactive Oxygen Species (ROS) in Mainstream and Sidestream Cigarette Smoke  

Microsoft Academic Search

Reactive oxygen species (ROS) have been related to adverse health effects in recent years. Previous studies have reported ROS concentrations in mainstream smoke, but the reports have shown considerable variability and conclusions. There have been no prior measurements on sidestream smoke. In this study, the amounts of gas-phase and particle-bound ROS in tobacco smoke were determined using 2?,7?-dichlorodihydrofluorescin diacetate (DCFH-DA)

Jiayuan Zhao; Philip K. Hopke

2012-01-01

202

Upregulation of Endothelial and Inducible Nitric Oxide Synthase Expression by Reactive Oxygen Species  

Microsoft Academic Search

BackgroundThe effect of reactive oxygen species (ROS) on nitric oxide synthase (NOS) expression remains uncertain. This study explored the effect of increased ROS activity on NOS expression in vitro in human coronary artery endothelial cells (HCAECs) grown in culture and in intact animals.MethodsEndothelial NOS (eNOS) expression and nuclear factor ?B (NF?B) activation were determined in HCAECs grown in culture and

Junhui Zhen; Hua Lu; Xiu Q Wang; Nosratola D Vaziri; Xin J Zhou

2008-01-01

203

Protective systems against active oxygen species in spinach: response to cold acclimation in excess light  

Microsoft Academic Search

Spinach (Spinacia oleracea L.) plants were acclimated to 1° C or maintained at 18° C under the same light regime (260–300 µmol photons·m-2·s-1). The cold acclimation led to several metabolic and biochemical changes that apparently include improved protection of the photosynthetic apparatus against active oxygen species. In particular, cold-acclimated leaves exhibited a considerably higher ascorbate content and significantly increased activities

Susanne Schöner; G. Heinrich Krause

1990-01-01

204

Diphenyleneiodonium, an NAD(P)H Oxidase Inhibitor, also Potently Inhibits Mitochondrial Reactive Oxygen Species Production  

Microsoft Academic Search

Diphenyleneiodonium (DPI) has frequently been used to inhibit reactive oxygen species (ROS) production mediated by flavoenzymes, particularly NAD(P)H oxidase. This study was undertaken to examine if DPI could also inhibit production of superoxide and H2O2by mitochondria, the major source of cellular ROS. Detection of mitochondrial superoxide by lucigenin-derived chemiluminescence (CL) with unstimulated monocytes\\/macrophages showed that DPI at concentrations that inhibit

Yunbo Li; Michael A. Trush

1998-01-01

205

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

Microsoft Academic Search

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

Peter Storz; Heike Doppler; Alex Toker

2005-01-01

206

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

Microsoft Academic Search

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

Catharine I. Whiteside

2005-01-01

207

Enhancement of NADP-malic enzyme in transgenic rice induced the accumulation of reactive oxygen species  

Microsoft Academic Search

It had been demonstrated that the photosynthetic photodamage, such as photoinhibition and photooxidation, was enhanced in\\u000a transgenic rice plants overexpressing NADP-malic enzyme (ME). However, its physiological base has not been investigated. In\\u000a order to elucidate the physiological elements contributed to the enhancement of photodamage in NADP-ME transgenic rice plants,\\u000a some physiological indices related to reactive oxygen species (ROS) accumulation were

Wei Chi

2006-01-01

208

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

209

Reactive oxygen species in experimental ischemic flow-through venous flaps and effects of antioxidants on reactive oxygen species and flap survival.  

PubMed

We made an experimental study on rabbit ears using an ischemic flow-through venous flap model to determine the changes in levels of reactive oxygen species (ROS) in venous flaps and effects of exogenous antioxidants on endogenous antioxidant superoxide dismutase (SOD) and ROS indicator malonyldialdehyde (MDA) levels and on flap survival. Mean SOD level significantly decreased and the MDA level significantly increased after the flap elevation according to basal levels of untreated flaps. The mean flap survival rates in the exogenous SOD or glutathione (GSH)-treated groups were significantly increased with respect to the untreated group. The SOD level was increased significantly and the MDA level was decreased significantly in the SOD- or GSH-treated groups relative to the control group after the flap elevation. These results have suggested that ROS may have an important role in ischemic flow-through venous flap pathogenesis and additionally, antioxidants could enhance the rate of flap survival. PMID:17522491

Ozyazgan, Irfan; Tuncer, Ali; Yazici, Cevad; Günay, Galip K

2007-06-01

210

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.

Rossoni-Junior, Joamyr Victor; Araujo, Glaucy Rodrigues; Padua, Bruno da Cruz; Chaves, Miriam Martins; Pedrosa, Maria Lucia; Silva, Marcelo Eustaquio; Costa, Daniela Caldeira

2012-01-01

211

Oxygen and hydroxyl species induce multiple reaction pathways for the partial oxidation of allyl alcohol on gold.  

PubMed

Partial oxidation of alcohols is a topic of great interest in the field of gold catalysis. In this work, we provide evidence that the partial oxidation of allyl alcohol to its corresponding aldehyde, acrolein, over oxygen-precovered gold surfaces occurs via multiple reaction pathways. Utilizing temperature-programmed desorption (TPD) with isotopically labeled water and oxygen species, reactive molecular beam scattering, and density functional theory (DFT) calculations, we demonstrate that the reaction mechanism for allyl alcohol oxidation is influenced by the relative proportions of atomic oxygen and hydroxyl species on the gold surface. Both atomic oxygen and hydroxyl species are shown to be active for allyl alcohol oxidation, but each displays a different pathway of oxidation, as indicated by TPD measurements and DFT calculations. The hydroxyl hydrogen of allyl alcohol is readily abstracted by either oxygen adatoms or adsorbed hydroxyl species on the gold surface to generate a surface-bound allyloxide intermediate, which then undergoes ?-dehydrogenation via interaction with an oxygen adatom or surface hydroxyl species to generate acrolein. Mediation of a second allyloxide with the hydroxyl species lowers the activation barrier for the ?-dehydrogenation process. A third pathway exists in which two hydroxyl species recombine to generate water and an oxygen adatom, which subsequently dehydrogenates allyloxide. This work may aid in the understanding of oxidative catalysis over gold and the effect of water therein. PMID:24702503

Mullen, Gregory M; Zhang, Liang; Evans, Edward J; Yan, Ting; Henkelman, Graeme; Mullins, C Buddie

2014-04-30

212

Optimizing Pulse Waveforms in Plasma Jets for Reactive Oxygen Species (ROS) Production  

NASA Astrophysics Data System (ADS)

Reactive oxygen species (ROS) are desired in numerous applications from the destruction of harmful proteins and bacteria for sterilization in the medical field to taking advantage of the metastable characteristics of O2(^1?) to transfer energy to other species. Advances in atmospheric pressure plasma jets in recent years show the possibility of using this application as a source of reactive oxygen species. In this paper, we report on results from a computational investigation of atmospheric pressure plasma jets in a dielectric barrier discharge (DBD) configuration. The computer model used in this study, nonPDPSIM, solves transport equations for charged and neutral species, Poisson's equation for the electric potential, the electron energy conservation equation for the electron temperature, and Navier-Stokes equations for the neutral gas flow. A Monte Carlo simulation is used to track sheath accelerated secondary electrons emitted from surfaces and the energy of ions incident onto surfaces. Rate coefficients and transport coefficients for the bulk plasma are obtained from local solutions of Boltzmann's equation for the electron energy distribution. Radiation transport is addressed using a Green's function approach. Various waveforms for the voltage source were examined in analogy to spiker-sustainer systems used at lower gas pressures.

Norberg, Seth; Babaeva, Natalia Yu.; Kushner, Mark J.

2012-10-01

213

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

PubMed Central

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

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

2011-01-01

214

Visualization of mitochondrial membrane potential and reactive oxygen species via double staining.  

PubMed

Quantitative and qualitative analysis of both generated reactive oxygen species (ROS) and mitochondrial membrane potential cannot be detected simultaneously. We here introduce a simple, new double staining method. We have successfully used this for several years utilizing cerium for ROS detection and JC-1 staining to assess the mitochondrial membrane potential. The resultant signals on laser confocal images can be localized in the same cells and can easily quantify them. We used a confocal microscope along with our new, combined staining method to both visualize mitochondrial membrane potential (DeltaPsim) and imaged ROS. These were quantified by JC-1 staining and by cerium ions with reflectance in a method modified in our laboratory. To test this double labeling technique we used PC 12 cells subjected to 1 h hypoxia and 24h re-oxygenization. We are able to produce a quantitative analysis of red/green signals of JC-1 that reflected the energy state of the cells. Cerium reflectance correlates with the amount of ROS release in the same cells. Significant differences have been calculated after hypoxia and re-oxygenation in both modality of the cell staining. The red/green ratio was 18.2+/-9.3 (n=30) in normoxic cells versus 1.65+/-0.9 (n=30) in the hypoxia/re-oxygenation group (p<0.05). In the same randomly selected cells the average cerium reflectance signal intensity was 2.5+/-1.2 (n=30) in the control group while 5.8+/-3.1 (n=30) in the hypoxia/re-oxygenation group (p<0.05). This assay, by characterizing hypoxic injury and re-oxygenization induced ROS production, offers a qualitative and quantitative method to detect the consequences of oxidative stress in experimental conditions and to detect different cell protective strategies. PMID:16530963

Szilágyi, Géza; Simon, László; Koska, Péter; Telek, Géza; Nagy, Zoltán

2006-05-22

215

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

216

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

NASA Astrophysics Data System (ADS)

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

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

2011-06-01

217

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

PubMed

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

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

2013-01-01

218

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

SciTech Connect

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 {times} 10{sup {minus}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 ascorbate-Cu{sup 2+} system, the fluorescence decays with apparent first-order kinetics. Examination of the major components of human urine in this assay confirms that at physiological concentrations, urate protects against both types of oxygen radicals. A novel finding is that creatinine protects efficiently by a chelation mechanism against radical damage in the ascorbate-Cu{sup 2+} system at creatinine, ascorbate, and Cu{sup 2+} concentrations comparable to those in normal urine. Urate and creatinine provide complementary modes of protection against reactive oxygen species in the urinary tract.

Glazer, A.N. (Univ. of California, Berkeley (USA))

1988-06-01

219

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

PubMed

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

Criado, Susana; García, Norman A

2010-01-01

220

DNA Oxidation by Reactive Oxygen Species Produced by Atmospheric Pressure Microplasmas  

NASA Astrophysics Data System (ADS)

Arrays of microcathode sustained discharges (MCSD's) have been ­developed for the production of high fluxes of singlet delta oxygen (SDO) and ozone (O3) at atmospheric pressure. SDO and O3 densities higher than 1017 and 1016 cm-3, respectively, have been efficiently produced and transported over distances longer than 50 cm. These arrays of MCSD's have been optimized to supply well-quantified and tunable fluxes of either SDO or O3. This plasma source has been found to be very useful for examining the reactivity of these reactive oxygen species with biological components. Preliminary results indicate that both SDO and O3 are able to oxidize DNA, originating great damages in DNA such as single- and double-strand breaks and base oxidation. It has been observed that while all bases of DNA are almost indifferently and quite effectively oxidized by O3, SDO reacts mainly with guanine.

Sousa, Joao Santos; Girard, Pierre-Marie; Sage, Evelyne; Ravanat, Jean-Luc; Puech, Vincent

221

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

PubMed

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 Ca(2+)-dependent process involving Ca(2+) channel activation. Our results provide evidence for a RHO GTPase-based signalling mechanism to mediate sperm release for fertilization in plants. PMID:24451849

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

2014-01-01

222

Chilling-enhanced photooxidation: The production, action and study of reactive oxygen species produced during chilling in the light  

Microsoft Academic Search

Chilling-enhanced photooxidation is the light- and oxygen-dependent bleaching of photosynthetic pigments that occurs upon the exposure of chilling-sensitive plants to temperatures below approximately 10 °C. The oxidants responsible for the bleaching are the reactive oxygen species (ROS) singlet oxygen (1O2), superoxide anion radical (O2?,hydrogen peroxide (H2O2), the hydroxyl radical (OH·), and the monodehydroascorbate radical (MDA) which are generated by a

Robert R. Wise

1995-01-01

223

Electrolyzed Reduced Water Which Can Scavenge Active Oxygen Species Supresses Cell Growth and Regulates Gene Expression of Animal Cells  

Microsoft Academic Search

Active oxygen species are considered to cause extensive oxidative damage to biological macromolecules, which bring about a\\u000a variety of diseases as well as aging. Reduced water produced near cathode during electrolysis of water exhibits high pH, low\\u000a dissolved oxygen, extremely high dissolvedmolecular hydrogen, and extremely negative redox potential values. Recently we found\\u000a that strongly electrolyzed reduced water scavenges active oxygen

S. Shirahata; S. Kabayama; K. Kusumoto; M. Gotoh; K. Teruya; K. Otsubo; J. Morisawa; H. Hayashi; K. Katakura

224

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...

225

Mechanisms and Modifications of Pulmonary and Systemic Epithelia Function and Structure by Reactive Oxygen Species and Proteases.  

National Technical Information Service (NTIS)

A number of pathologic conditions including battlefield injuries, skin burns, decreased organ perfusion, sepsis and hemorrhagic shock, result in the release of reactive oxygen species (ROS) in the circulation. In addition, activated neutrophils, aggregati...

S. Matalon

1991-01-01

226

Involvement of reactive oxygen species in angiotensin II-induced endothelin-1 gene expression in rat cardiac fibroblasts  

Microsoft Academic Search

ObjectivesThe aim of this study was to investigate the effects of angiotensin II (Ang II) on fibroblast proliferation and endothelin-1 (ET-1) gene induction, focusing especially on reactive oxygen species (ROS)-mediated signaling in cardiac fibroblasts.

Tzu-Hurng Cheng; Pao-Yun Cheng; Neng-Lang Shih; Iuan-Bor Chen; Danny Ling Wang; Jin-Jer Chen

2003-01-01

227

Effects of enhanced solar irradiation on chlorophyll fluorescence and photosynthetic oxygen production of five species of phytoplankton  

Microsoft Academic Search

The effects of solar irradiation on chlorophyll a fluorescence and photosynthetic oxygen production of three Cryptomonas species, Euglena gracilis and Scenedesmus cf. quadricauda were investigated in comparative field studies in Erlangen (280 m above sea level) and at Zugspitze (2957 m above sea level). The experiments showed that the decrease of fluorescence and the inhibition of photosynthetic oxygen production occurred

Sabine Gerber; Donat-P. Häder

1995-01-01

228

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

229

Lens Proteins Block the Copper-Mediated Formation of Reactive Oxygen Species during Glycation Reactions in Vitro  

Microsoft Academic Search

The formation of advanced glycation endproducts (AGEs) from glucose in vitro requires both oxygen and a transition metal ion, usually copper. These elements combine to produce reactive oxygen species (ROS) which degrade glucose to AGE-forming compounds. We measured the ability of Cu(2+) to accelerate ROS formation, and the effect of added lens proteins on these reactions. Increasing levels of Cu(2+)

B. J. Ortwerth; Hongying L. James

1999-01-01

230

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.

2014-01-01

231

Is there an important role for reactive oxygen species and redox regulation during floral senescence?  

PubMed

Senescence is a highly regulated process terminating with programmed cell death (PCD). Floral senescence, and in particular petal senescence, forms an interesting model to study this process in that floral lifespan is species specific and linked to biological function. A feature of petal senescence is a rise in reactive oxygen species (ROS) and a change in redox balance. A key question is whether this is merely a consequence of de-regulation of antioxidant systems as cells enter PCD, or whether the rise in ROS may have a regulatory or signalling function. An important division in the physiology of floral senescence is between species in which ethylene is a key regulator, and those in which it appears not to perform an important regulatory role. Another important question we can therefore ask is whether the redox and ROS changes have the same significance in species with different physiologies. Transcriptomic studies in ethylene-sensitive and -insensitive species allow us to further determine whether changes in the activity of ROS-scavenging enzymes are transcriptionally regulated during floral senescence. Finally, it is important to assess how a signalling role for ROS or redox status would fit with known plant growth regulator (PGR) control of floral senescence. PMID:21635270

Rogers, Hilary J

2012-02-01

232

Effects of diabetes, insulin and antioxidants on NO synthase abundance and NO interaction with reactive oxygen species  

Microsoft Academic Search

Effects of diabetes, insulin and antioxidants on NO synthase abundance and NO interaction with reactive oxygen species.BackgroundEarlier studies have provided evidence for increased production of reactive oxygen species (ROS) and altered nitric oxide (NO) metabolism in diabetes. This study was intended to explore the effect of type I diabetes and its treatment with insulin alone or insulin plus antioxidant-fortified diet

Ja-Ryong Koo; Nosratola D Vaziri

2003-01-01

233

The anti-inflammatory effect of honokiol on neutrophils: mechanisms in the inhibition of reactive oxygen species production  

Microsoft Academic Search

Reactive oxygen species produced by neutrophils contribute to the pathogenesis of focal cerebral ischemia\\/reperfusion injury and signal the inflammatory response. We have previously shown that honokiol, an active principle extracted from Magnolia officinalis, has a protective effect against focal cerebral ischemia\\/reperfusion injury in rats that paralleled a reduction in reactive oxygen species production by neutrophils. To elucidate the underlying mechanism(s)

Kuo-Tong Liou; Yuh-Chiang Shen; Chieh-Fu Chen; Cheng-Ming Tsao; Shen-Kou Tsai

2003-01-01

234

Reactive oxygen species and nitric oxide mediate plasticity of neuronal calcium signaling  

NASA Astrophysics Data System (ADS)

Reactive oxygen species (ROS) and nitric oxide (NO) are important participants in signal transduction that could provide the cellular basis for activity-dependent regulation of neuronal excitability. In young rat cortical brain slices and undifferentiated PC12 cells, paired application of depolarization/agonist stimulation and oxidation induces long-lasting potentiation of subsequent Ca2+ signaling that is reversed by hypoxia. This potentiation critically depends on NO production and involves cellular ROS utilization. The ability to develop the Ca2+ signal potentiation is regulated by the developmental stage of nerve tissue, decreasing markedly in adult rat cortical neurons and differentiated PC12 cells.

Yermolaieva, Olena; Brot, Nathan; Weissbach, Herbert; Heinemann, Stefan H.; Hoshi, Toshinori

2000-01-01

235

p66Shc, mitochondria, and the generation of reactive oxygen species.  

PubMed

Reactive oxygen species (ROS), mainly originated from mitochondrial respiration, are critical inducers of oxidative damage and involved in tissue dysfunction. It is not clear, however, whether oxidative stress is the result of an active gene program or it is the by-product of physiological processes. Recent findings demonstrate that ROS are produced by mitochondria in a controlled way through specialized enzymes, including p66Shc, and take part in cellular process aimed to ensure adaptation and fitness. Therefore, genes generating specifically ROS are selected determinants of life span in response to different environmental conditions. PMID:23849861

Trinei, Mirella; Migliaccio, Enrica; Bernardi, Paolo; Paolucci, Francesco; Pelicci, Piergiuseppe; Giorgio, Marco

2013-01-01

236

The Determination and Analysis of Site-Specific Rates of Mitochondrial Reactive Oxygen Species Production  

PubMed Central

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

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

2014-01-01

237

Calcium and Mitochondrial Reactive Oxygen Species Generation: How to Read the Facts  

PubMed Central

A number of recent discoveries indicate that abnormal Ca2+ signaling, oxidative stress, and mitochondrial dysfunction are involved in the neuronal damage in Alzheimer’s disease. However, the literature on the interactions between these factors is controversial especially in the interpretation of the cause-effect relationship between mitochondrial damage induced by Ca2+ overload and the production of reactive oxygen species (ROS). In this review, we survey the experimental observations on the Ca2+-induced mitochondrial ROS production, explain the sources of controversy in interpreting these results, and discuss the different molecular mechanisms underlying the effect of Ca2+ on the ROS emission by brain mitochondria.

Adam-Vizi, Vera; Starkov, Anatoly A.

2011-01-01

238

Detection of oxygen species generated by CNT photosensitized CoS2 nanocomposites  

NASA Astrophysics Data System (ADS)

In the present work, CoS2 and CoS2-CNT were irradiated by visible light respectively. The generation of reactive oxygen species were detected through the oxidation reaction from 1,5-diphenyl carbazide (DPCI) to 1,5-diphenyl carbazone (DPCO). The composite obtained was also characterized by transmission electron microscopy (TEM), Raman and UV-vis analysis. From the photocatalytic results, the excellent activity of the CoS2-CNT composites for degradation of methylene blue under visible irradiation could be attributed to both the effects of charge transfer to carbon nanomaterial, and the introduced CoS2 to enhance the photogenerated electrons transfer.

Meng, Ze-Da; Zhu, Lei; Ullah, Kefayat; Ye, Shu; Oh, Won-Chun

2013-12-01

239

Practical use of chemical probes for reactive oxygen species produced in biological systems by ?-irradiation  

NASA Astrophysics Data System (ADS)

Application of chemical probes, for detection of reactive oxygen species (ROS), was tested during ?-irradiation. The ethanol/?-(4-pyridyl-1-oxide)- N- tert-butylnitrone (4-POBN) and 3,3'-diaminobenzidine (DAB) were structurally stable enough to detect rad OH and H 2O 2, increasingly generated by ?-irradiation up to 1000 Gy. Interestingly, the production rate of H 2O 2, but not rad OH, during ?-irradiation, was significantly different between in vitro systems of lettuce and spinach. These results suggest that 4-POBN and DAB could be utilized as a semi-quantitative probe to quantify rad OH and H 2O 2, produced by ?-irradiation up to 1000 Gy.

Lee, Min Hee; Moon, Yu Ran; Chung, Byung Yeoup; Kim, Jae-Sung; Lee, Kang-Soo; Cho, Jae-Young; Kim, Jin-Hong

2009-05-01

240

Molecular Crosstalk between Integrins and Cadherins: Do Reactive Oxygen Species Set the Talk?  

PubMed Central

The coordinate modulation of the cellular functions of cadherins and integrins plays an essential role in fundamental physiological and pathological processes, including morphogenesis, tissue differentiation and renewal, wound healing, immune surveillance, inflammatory response, tumor progression, and metastasis. However, the molecular mechanisms underlying the fine-tuned functional communication between cadherins and integrins are still elusive. This paper focuses on recent findings towards the involvement of reactive oxygen species (ROS) in the regulation of cell adhesion and signal transduction functions of integrins and cadherins, pointing to ROS as emerging strong candidates for modulating the molecular crosstalk between cell-matrix and cell-cell adhesion receptors.

Goitre, Luca; Pergolizzi, Barbara; Ferro, Elisa; Trabalzini, Lorenza; Retta, Saverio Francesco

2012-01-01

241

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

Microsoft Academic Search

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

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

2009-01-01

242

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

243

Non-canonical ?-catenin degradation mediates reactive oxygen species-induced epidermal cell death  

PubMed Central

?-catenin is constantly degraded through the ubiquitin-proteasomal pathway. We here report that a different type of ?-catenin degradation is causally involved in epidermal cell death. We observed that reactive oxygen species (ROS) caused ?-catenin degradation in the epidermal cells through a caspase-dependent mechanism, which results in disruption of cell adhesion. Disruption of cell adhesion increased ROS and activated caspases. Upregulation of the intact ?-catenin blocked ROS accumulation and caspase activation. These results indicate that a feed-forward loop consisting of ROS, caspases activation and ?-catenin degradation induces epidermal cell death.

Omori, Emily; Matsumoto, Kunihiro; Ninomiya-Tsuji, Jun

2011-01-01

244

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

PubMed Central

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

Chen, Kai; Keaney, John F.

2013-01-01

245

Role of Reactive Oxygen Species in the Progression of Type 2 Diabetes and Atherosclerosis  

PubMed Central

Type 2 diabetes is the most prevalent and serious metabolic disease all over the world, and its hallmarks are pancreatic ?-cell dysfunction and insulin resistance. Under diabetic conditions, chronic hyperglycemia and subsequent augmentation of reactive oxygen species (ROS) deteriorate ?-cell function and increase insulin resistance which leads to the aggravation of type 2 diabetes. In addition, chronic hyperglycemia and ROS are also involved in the development of atherosclerosis which is often observed under diabetic conditions. Taken together, it is likely that ROS play an important role in the development of type 2 diabetes and atherosclerosis.

Kaneto, Hideaki; Katakami, Naoto; Matsuhisa, Munehide; Matsuoka, Taka-aki

2010-01-01

246

Role of reactive oxygen species in the progression of type 2 diabetes and atherosclerosis.  

PubMed

Type 2 diabetes is the most prevalent and serious metabolic disease all over the world, and its hallmarks are pancreatic beta-cell dysfunction and insulin resistance. Under diabetic conditions, chronic hyperglycemia and subsequent augmentation of reactive oxygen species (ROS) deteriorate beta-cell function and increase insulin resistance which leads to the aggravation of type 2 diabetes. In addition, chronic hyperglycemia and ROS are also involved in the development of atherosclerosis which is often observed under diabetic conditions. Taken together, it is likely that ROS play an important role in the development of type 2 diabetes and atherosclerosis. PMID:20182627

Kaneto, Hideaki; Katakami, Naoto; Matsuhisa, Munehide; Matsuoka, Taka-aki

2010-01-01

247

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

PubMed Central

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

Roy, Nilotpal; Bagchi, Srilata; Raychaudhuri, Pradip

2012-01-01

248

Alternative Oxidase Expression in the Mouse Enables Bypassing Cytochrome c Oxidase Blockade and Limits Mitochondrial ROS Overproduction  

PubMed Central

Cyanide-resistant non-phosphorylating respiration is known in mitochondria from plants, fungi, and microorganisms but is absent in mammals. It results from the activity of an alternative oxidase (AOX) that conveys electrons directly from the respiratory chain (RC) ubiquinol pool to oxygen. AOX thus provides a bypath that releases constraints on the cytochrome pathway and prevents the over-reduction of the ubiquinone pool, a major source of superoxide. RC dysfunctions and deleterious superoxide overproduction are recurrent themes in human pathologies, ranging from neurodegenerative diseases to cancer, and may be instrumental in ageing. Thus, preventing RC blockade and excess superoxide production by means of AOX should be of considerable interest. However, because of its energy-dissipating properties, AOX might produce deleterious effects of its own in mammals. Here we show that AOX can be safely expressed in the mouse (MitAOX), with major physiological parameters being unaffected. It neither disrupted the activity of other RC components nor decreased oxidative phosphorylation in isolated mitochondria. It conferred cyanide-resistance to mitochondrial substrate oxidation and decreased reactive oxygen species (ROS) production upon RC blockade. Accordingly, AOX expression was able to support cyanide-resistant respiration by intact organs and to afford prolonged protection against a lethal concentration of gaseous cyanide in whole animals. Taken together, these results indicate that AOX expression in the mouse is innocuous and permits to overcome a RC blockade, while reducing associated oxidative insult. Therefore, the MitAOX mice represent a valuable tool in order to investigate the ability of AOX to counteract the panoply of mitochondrial-inherited diseases originating from oxidative phosphorylation defects.

El-Khoury, Riyad; Dufour, Eric; Rak, Malgorzata; Ramanantsoa, Nelina; Grandchamp, Nicolas; Csaba, Zsolt; Duvillie, Bertrand; Benit, Paule; Gallego, Jorge; Gressens, Pierre; Sarkis, Chamsy; Jacobs, Howard T.; Rustin, Pierre

2013-01-01

249

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

250

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

NASA Astrophysics Data System (ADS)

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

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

2012-12-01

251

The oxygen reactive species of cytochrome-c-oxidase: an alternative view.  

PubMed

In a recent review article Babcok and Wikström (Nature, 1992, 356, 301-309) proposed that the species of cytochrome-c-oxidase which binds molecular oxygen during turnover is the so-called mixed valence enzyme, in which the binuclear center cytochrome a3-CuB is reduced, while the cytochrome a/CuA sites are oxidized. This proposal is based on earlier work (Morgan and Wikström, Biochemistry 1991, 30, 948-958) in which it was found that the steady-state reduction levels of cytochrome c and cytochrome a in respiring rat liver mitochondria (sustained by ascorbate and TMPD) are quite different, the latter being much more oxidized than the former; evaluation of the steady-state reduction levels demanded a large correction due to the optical contribution of oxidized TMPD+ which overlaps with the cytochromes. We report below that application of transient spectroscopy and SVD analysis to respiring rat heart myocytes, under conditions in which the contribution of TMPD+ is very small or absent, allows to show that the steady-state reduction levels of cytochrome c and cytochrome a are comparable at all times accessible to measurement in the rapid-scanning stopped-flow spectrophotometer. Our conclusion, in agreement with previous results, is that mixed valence cytochrome-c-oxidase as defined above is not the prevailing oxygen binding species of cytochrome-c-oxidase, unless electron donation to cytochrome c becomes rate limiting. PMID:1333992

Brunori, M; Antonini, G; Malatesta, F; Sarti, P; Wilson, M T

1992-12-14

252

SENSORY PLASTICITY OF THE CAROTID BODY: ROLE OF REACTIVE OXYGEN SPECIES AND PHYSIOLOGICAL SIGNIFICANCE  

PubMed Central

Recent studies have shown that acute intermittent hypoxia (IH) induces sensory plasticity of the carotid body manifested as sensory long-term facilitation (LTF), which requires prior conditioning with chronic IH and is mediated by reactive oxygen species (ROS). The purpose of this article is to provide a brief review of chronic IH-induced sensory LTF of the carotid body, sources of ROS, mechanisms underlying sensory LTF and its functional significance. Development of sensory LTF requires conditioning with several days of chronic IH. It is completely reversible following re-oxygenation, does not depend on the severity of hypoxia used for IH conditioning, not species specific and is selectively evoked by acute repetitive hypoxia but not by repetitive hypercapnia. Sensory LTF is not associated morphological changes in the carotid body and is expressed in chronic IH treated adult but not in neonatal rat carotid bodies. Chronic IH increases ROS levels in the carotid body involving 5-HT mediated activation of NADPH oxidase-2 (NOX2) and subsequent inhibition of the mitochondrial complex I. Sensory LTF can be prevented by inhibitors of 5-HT receptors, NOX inhibitors as well as by anti-oxidants. The signaling pathways mediating the sensory LTF are summarized in figure 2. It is suggested that sensory LTF contributes to the persistent sympathetic excitation under chronic IH.

Prabhakar, Nanduri R.

2011-01-01

253

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

254

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

PubMed

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

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

2013-12-01

255

Reactive oxygen species are second messengers of neurokinin signaling in peripheral sensory neurons.  

PubMed

Substance P (SP) is a prominent neuromodulator, which is produced and released by peripheral damage-sensing (nociceptive) neurons; these neurons also express SP receptors. However, the mechanisms of peripheral SP signaling are poorly understood. We report a signaling pathway of SP in nociceptive neurons: Acting predominantly through NK1 receptors and G(i/o) proteins, SP stimulates increased release of reactive oxygen species from the mitochondrial electron transport chain. Reactive oxygen species, functioning as second messengers, induce oxidative modification and augment M-type potassium channels, thereby suppressing excitability. This signaling cascade requires activation of phospholipase C but is largely uncoupled from the inositol 1,4,5-trisphosphate sensitive Ca(2+) stores. In rats SP causes sensitization of TRPV1 and produces thermal hyperalgesia. However, the lack of coupling between SP signaling and inositol 1,4,5-trisphosphate sensitive Ca(2+) stores, together with the augmenting effect on M channels, renders the SP pathway ineffective to excite nociceptors acutely and produce spontaneous pain. Our study describes a mechanism for neurokinin signaling in sensory neurons and provides evidence that spontaneous pain and hyperalgesia can have distinct underlying mechanisms within a single nociceptive neuron. PMID:22586118

Linley, John E; Ooi, Lezanne; Pettinger, Louisa; Kirton, Hannah; Boyle, John P; Peers, Chris; Gamper, Nikita

2012-06-12

256

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

PubMed Central

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

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

2013-01-01

257

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

PubMed Central

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

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

2013-01-01

258

Leishmania major: Reactive oxygen species and interferon gamma induction by soluble lipophosphoglycan of stationary phase promastigotes.  

PubMed

Protozoan parasites of the genus Leishmania cause a number of important human diseases. One of the key determinants of parasite infectivity and survival is membrane glycoconjugate lipophosphoglycan (mLPG). In addition, it has been shown that mLPG could be used as a transmission blocking vaccine. Since culture supernatant of parasite promastigotes is a good source of LPG, we attempted to compare the immunological properties of culture supernatant and membrane LPG prepared from stationary phase promastigotes of Leishmania major. The purity of supernatant LPG (sLPG) and membrane LPG (mLPG) was determined by thin layer chromatography. The effect of sLPG and mLPG on the production of reactive oxygen species (ROS) was studied using PBMCs isolated from healthy individuals. In addition, induction of IL-12, IFN-gamma and IL-10 secretion in the presence of sLPG and mLPG was investigated. Reactive oxygen species in addition to IL-10 and IL-12 were induced by both sLPG and mLPG. However, IFN-gamma production was promoted only in response to sLPG suggesting its ability to promote Th1 response and implication in vaccine design. PMID:16759653

Kavoosi, Gholamreza; Ardestani, Sussan K; Kariminia, Amina; Abolhassani, Mohssen; Turco, Salvatore J

2006-12-01

259

Khat (Catha edulis) generates reactive oxygen species and promotes hepatic cell apoptosis via MAPK activation.  

PubMed

A number of studies have suggested an association between khat (Catha edulis) chewing and acute liver lesions or chronic liver disease. However, little is known about the effects of khat on hepatic cells. In the current study, we investigated the mechanism behind khat-induced apoptosis in the L02 human hepatic cell line. We used cell growth inhibition assay, flow cytometry and Hoechst 33258 staining to measure hepatocyte apoptosis induced by khat. Western blot analysis was used to detect the expression levels of caspase-8 and -9, as well as those of Bax and Bcl-2. We also measured reactive oxygen species production. The results indicated that khat induced significant hepatocyte apoptosis in L02 cells. We found that khat activated caspase-8 and -9, upregulated Bax protein expression and downregulated Bcl-2 expression levels, which resulted in the coordination of apoptotic signals. Khat-induced hepatocyte apoptosis is primarily regulated through the sustained activation of the c-Jun NH2-terminal kinase (JNK) pathway and only partially via the extracellular signal-regulated kinase (ERK) cascade. Furthermore, the khat-induced reactive oxygen species (ROS) production and the activation of the ROS scavenger, N-acetyl-L-cysteine (NAC), attenuated the khat-induced activation of JNK and ERK. Our results demonstrate that khat triggers the generation of intracellular ROS and sequentially induces the sustainable activation of JNK, which in turn results in a decrease in cell viability and an increase in cell apoptosis. PMID:23708648

Abid, Morad Dirhem Naji; Chen, Juan; Xiang, Min; Zhou, Jie; Chen, Xiaoping; Gong, Feili

2013-08-01

260

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.

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

1998-01-01

261

Sensory plasticity of the carotid body: role of reactive oxygen species and physiological significance.  

PubMed

Recent studies have shown that acute intermittent hypoxia (IH) induces sensory plasticity of the carotid body manifested as sensory long-term facilitation (LTF), which requires prior conditioning with chronic IH and is mediated by reactive oxygen species (ROS). The purpose of this article is to provide a brief review of chronic IH-induced sensory LTF of the carotid body, sources of ROS, mechanisms underlying sensory LTF and its functional significance. Development of sensory LTF requires conditioning with several days of chronic IH. It is completely reversible following re-oxygenation, does not depend on the severity of hypoxia used for IH conditioning, not species specific and is selectively evoked by acute repetitive hypoxia but not by repetitive hypercapnia. Sensory LTF is not associated morphological changes in the carotid body and is expressed in chronic IH treated adult but not in neonatal rat carotid bodies. Chronic IH increases ROS levels in the carotid body involving 5-HT mediated activation of NADPH oxidase-2 (NOX2) and subsequent inhibition of the mitochondrial complex I. Sensory LTF can be prevented by inhibitors of 5-HT receptors, NOX inhibitors as well as by anti-oxidants. The signaling pathways mediating the sensory LTF are summarized in the second figure. It is suggested that sensory LTF contributes to the persistent sympathetic excitation under chronic IH. PMID:21621009

Prabhakar, Nanduri R

2011-09-30

262

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

PubMed Central

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

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

2012-01-01

263

SUMO1 Negatively Regulates Reactive Oxygen Species Production From NADPH Oxidases  

PubMed Central

Objective Increased protein SUMOylation provides protection from cellular stress including oxidative stress, but the mechanisms involved are incompletely understood. The NADPH oxidases (Nox) are a primary source of reactive oxygen species (ROS) and oxidative stress and thus our goal was to determine whether SUMO regulates NADPH oxidase activity. Methods and Results Increased expression of SUMO1 potently inhibited the activity of Nox1-5. In contrast, inhibition of endogenous SUMOylation with siRNA to SUMO1 or UBC9 or with the inhibitor, anacardic acid, increased ROS production from HEK-Nox5 cells, human vascular smooth muscle cells and neutrophils. The suppression of ROS production was unique to SUMO1, required a C-terminal di-glycine and the SUMO-specific conjugating enzyme, UBC9. SUMO1 did not modify intracellular calcium or Nox5 phosphorylation but reduced ROS output in an isolated enzyme assay suggesting direct effects of SUMOylation on enzyme activity. However, we could not detect the presence of SUMO1-conjugation on Nox5 using a variety of approaches. Moreover the mutation of over 17 predicted and conserved lysine residues on Nox5 did not alter the inhibitory actions of SUMO1. Conclusion Together, these results suggest that SUMO is an important regulatory mechanism that indirectly represses the production of reactive oxygen species to ameliorate cellular stress.

Pandey, D; Chen, F; Patel, A; Wang, CY; Dimitropoulou, C.; Patel, V.S; Rudic, R.D.; Stepp, DW; Fulton, DJR.

2012-01-01

264

Diabetes mellitus increases reactive oxygen species production in the thyroid of male rats.  

PubMed

Diabetes mellitus (DM) disrupts the pituitary-thyroid axis and leads to a higher prevalence of thyroid disease. However, the role of reactive oxygen species in DM thyroid disease pathogenesis is unknown. Dual oxidases (DUOX) is responsible for H(2)O(2) production, which is a cosubstrate for thyroperoxidase, but the accumulation of H(2)O(2) also causes cellular deleterious effects. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is another member of the nicotinamide adenine dinucleotide phosphate oxidase family expressed in the thyroid. Therefore, we aimed to evaluate the thyroid DUOX activity and expression in DM rats in addition to NOX4 expression. In the thyroids of the DM rats, we found increased H(2)O(2) generation due to higher DUOX protein content and DUOX1, DUOX2, and NOX4 mRNA expressions. In rat thyroid PCCL3 cells, both TSH and insulin decreased DUOX activity and DUOX1 mRNA levels, an effect partially reversed by protein kinase A inhibition. Most antioxidant enzymes remained unchanged or decreased in the thyroid of DM rats, whereas only glutathione peroxidase 3 was increased. DUOX1 and NOX4 expression and H(2)O(2) production were significantly higher in cells cultivated with high glucose, which was reversed by protein kinase C inhibition. We conclude that thyroid reactive oxygen species is elevated in experimental rat DM, which is a consequence of low-serum TSH and insulin but is also related to hyperglycemia per se. PMID:23407453

Santos, Maria C S; Louzada, Ruy A N; Souza, Elaine C L; Fortunato, Rodrigo S; Vasconcelos, Andressa L; Souza, Kléber L A; Castro, João P S W; Carvalho, Denise P; Ferreira, Andrea C F

2013-03-01

265

Influenza virus M2 protein inhibits epithelial sodium channels by increasing reactive oxygen species  

PubMed Central

The mechanisms by which replicating influenza viruses decrease the expression and function of amiloride-sensitive epithelial sodium channels (ENaCs) have not been elucidated. We show that expression of M2, a transmembrane influenza protein, decreases ENaC membrane levels and amiloride-sensitive currents in both Xenopus oocytes, injected with human ?-, ?-, and ?-ENaCs, and human airway cells (H441 and A549), which express native ENaCs. Deletion of a 10-aa region within the M2 C terminus prevented 70% of this effect. The M2 ENaC down-regulation occurred at normal pH and was prevented by MG-132, a proteasome and lysosome inhibitor. M2 had no effect on Liddle ENaCs, which have decreased affinity for Nedd4-2. H441 and A549 cells transfected with M2 showed higher levels of reactive oxygen species, as shown by the activation of redox-sensitive dyes. Pretreatment with glutathione ester, which increases intracellular reduced thiol concentrations, or protein kinase C (PKC) inhibitors prevented the deleterious effects of M2 on ENaCs. The data suggest that M2 protein increases steady-state concentrations of reactive oxygen intermediates that simulate PKC and decrease ENaCs by enhancing endocytosis and its subsequent destruction by the proteasome. These novel findings suggest a mechanism for the influenza-induced rhinorrhea and life-threatening alveolar edema in humans.—Lazrak, A., Iles, K. E., Liu, G. Noah, D. L., Noah, J. W., Matalon, S. Influenza virus M2 protein inhibits epithelial sodium channels by increasing reactive oxygen species.

Lazrak, Ahmed; Iles, Karen E.; Liu, Gang; Noah, Diana L.; Noah, James W.; Matalon, Sadis

2009-01-01

266

Light effect and reactive oxygen species in the action of ciprofloxacin on Staphylococcus aureus.  

PubMed

Oxygen consumption by Staphylococcus aureus ATCC 29213 sensitive to ciprofloxacin was determined with an oxygen selective electrode. Increase in the O(2) consumption was observed with 0.45 micromL(-1) ciprofloxacin while higher concentrations gave rise to a reduction of O(2) consumption. Resistant S. aureus strain did not show increase of O(2) consumption in presence of ciprofloxacin. Nitro Blue Tetrazolium assay showed that production of reactive oxygen species (ROS) increased intracellularly in sensitive bacteria incubated with this antibiotic. The exposition to UV light (360 nm) augmented the intracellular oxidative stress of S. aureus and provoked increment of ROS in extracellular media. Generation of singlet oxygen O(2) ((1)Delta(g)) in S. aureus was measured by means of oxidation of methionine. The absorbance of methionine was monitored at 215 nm and a clear decrease was detected when sensitive S. aureus was stressed with ciprofloxacin. Sodium azide and 2,5-dimethylfuran were used to reinforce the evidence of O(2) ((1)Delta(g)) generation during oxidative stress. Assays with methionine and 2,5-dimethylfuran demonstrated that resistant S. aureus did not increase the production of O(2) ((1)Delta(g)) in the presence of antibiotic. DNA oxidation was investigated in presence of O(2) ((1)Delta(g)) generated by laser excitation of perinaphthenone and subsequent energy transfer. Deactivation of O(2) ((1)Delta(g)) by reaction with DNA of sensitive and resistant bacteria was observed. According to the results obtained, the effect of ciprofloxacin in S. aureus led to an increment of O(2) ((1)Delta(g)) generating oxidative stress in the bacteria. PMID:15488711

Becerra, María Cecilia; Sarmiento, Martín; Páez, Paulina Laura; Argüello, Gustavo; Albesa, Inés

2004-10-25

267

Reactive Oxygen Species and Induction of Lignin Peroxidase in Phanerochaete chrysosporium  

PubMed Central

We studied oxidative stress in lignin peroxidase (LIP)-producing cultures (cultures flushed with pure O2) of Phanerochaete chrysosporium by comparing levels of reactive oxygen species (ROS), cumulative oxidative damage, and antioxidant enzymes with those found in non-LIP-producing cultures (cultures grown with free exchange of atmospheric air [control cultures]). A significant increase in the intracellular peroxide concentration and the degree of oxidative damage to macromolecules, e.g., DNA, lipids, and proteins, was observed when the fungus was exposed to pure O2 gas. The specific activities of manganese superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase and the consumption of glutathione were all higher in cultures exposed to pure O2 (oxygenated cultures) than in cultures grown with atmospheric air. Significantly higher gene expression of the LIP-H2 isozyme occurred in the oxygenated cultures. A hydroxyl radical scavenger, dimethyl sulfoxide (50 mM), added to the culture every 12 h, completely abolished LIP expression at the mRNA and protein levels. This effect was confirmed by in situ generation of hydroxyl radicals via the Fenton reaction, which significantly enhanced LIP expression. The level of intracellular cyclic AMP (cAMP) was correlated with the starvation conditions regardless of the oxygenation regimen applied, and similar cAMP levels were obtained at high O2 concentrations and in cultures grown with atmospheric air. These results suggest that even though cAMP is a prerequisite for LIP expression, high levels of ROS, preferentially hydroxyl radicals, are required to trigger LIP synthesis. Thus, the induction of LIP expression by O2 is at least partially mediated by the intracellular ROS.

Belinky, Paula A.; Flikshtein, Nufar; Lechenko, Sergey; Gepstein, Shimon; Dosoretz, Carlos G.

2003-01-01

268

Network Rigidity and Metabolic Engineering in Metabolite Overproduction  

Microsoft Academic Search

In order to enhance the yield and productivity of metabolite production, researchers have focused almost exclusively on enzyme amplification or other modifications of the product pathway. However, overproduction of many metabolites requires significant redirection of flux distributions in the primary metabolism, which may not readily occur following product deregulation because metabolic pathways have evolved to exhibit control architectures that resist

Gregory Stephanopoulos; Joseph J. Vallino

1991-01-01

269

New locus for exopolysaccharide overproduction in Escherichia coli K-12.  

PubMed Central

A new locus for exopolysaccharide overproduction in Escherichia coli K-12 was mapped by insertion mutagenesis. A 66% linkage to serA, which is located at 62 min on the E. coli K-12 linkage map, was shown by P1 transduction. The polysaccharide produced by the mutant was isolated and was shown to be similar to colanic acid.

Zinkewich-Peotti, K; Fraser, J M

1988-01-01

270

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

271

Protective effect of flavonoids against reactive oxygen species production in sickle cell anemia patients treated with hydroxyurea  

PubMed Central

Objective The aim of this study was to evaluate the protective effects of quercetin, rutin, hesperidin and myricetin against reactive oxygen species production with the oxidizing action of tert-butylhydroperoxide in erythrocytes from normal subjects and sickle cell anemia carriers treated with hydroxyurea. Methods Detection of intracellular reactive oxygen species was carried out using a liposoluble probe, 2',7'-dichlorfluorescein-diacetate (DCFH-DA). A 10% erythrocyte suspension was incubated with flavonoids (quercetin, rutin, hesperidin or myricetin; 30, 50, and 100 µmol/L), and then incubated with tert-butylhydroperoxide (75 µmol/L). Untreated samples were used as controls. Results Red blood cell exposure to tert-butylhydroperoxide resulted in significant increases in the generation of intracellular reactive oxygen species compared to basal levels. Reactive oxygen species production was significantly inhibited when red blood cells were pre-incubated with flavonoids, both in normal individuals and in patients with sickle cell anemia. Quercetin and rutin had the highest antioxidant activity, followed by myricetin and hesperidin. CONCLUSION: Flavonoids, in particular quercetin and rutin, showed better antioxidant effects against damage caused by excess reactive oxygen species characteristic of sickle cell anemia. Results obtained with patients under treatment with hydroxyurea suggest an additional protective effect when associated with the use of flavonoids.

Henneberg, Railson; Otuki, Michel Fleith; Furman, Aline Emmer Ferreira; Hermann, Priscila; do Nascimento, Aguinaldo Jose; Leonart, Maria Suely Soares

2013-01-01

272

Oxygen-derived species: their relation to human disease and environmental stress.  

PubMed Central

Free radicals and other reactive oxygen species (ROS) are constantly formed in the human body, often for useful metabolic purposes. Antioxidant defenses protect against them, but these defenses are not completely adequate, and systems that repair damage by ROS are also necessary. Mild oxidative stress often induces antioxidant defense enzymes, but severe stress can cause oxidative damage to lipids, proteins, and DNA within cells, leading to such events as DNA strand breakage and disruption of calcium ion metabolism. Oxidative stress can result from exposure to toxic agents, and by the process of tissue injury itself. Ozone, oxides of nitrogen, and cigarette smoke can cause oxidative damage; but the molecular targets that they damage may not be the same.

Halliwell, B; Cross, C E

1994-01-01

273

Dopamine Induces Ca2+ Signaling in Astrocytes through Reactive Oxygen Species Generated by Monoamine Oxidase  

PubMed Central

Dopamine is a neurotransmitter that plays a major role in a variety of brain functions, as well as in disorders such as Parkinson disease and schizophrenia. In cultured astrocytes, we have found that dopamine induces sporadic cytoplasmic calcium ([Ca2+]c) signals. Importantly, we show that the dopamine-induced calcium signaling is receptor-independent in midbrain, cortical, and hippocampal astrocytes. We demonstrate that the calcium signal is initiated by the metabolism of dopamine by monoamine oxidase, which produces reactive oxygen species and induces lipid peroxidation. This stimulates the activation of phospholipase C and subsequent release of calcium from the endoplasmic reticulum via the inositol 1,4,5-trisphosphate receptor mechanism. These findings have major implications on the function of astrocytes that are exposed to dopamine and may contribute to understanding the physiological role of dopamine.

Vaarmann, Annika; Gandhi, Sonia; Abramov, Andrey Y.

2010-01-01

274

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.

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

2014-01-01

275

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

PubMed Central

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

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

2012-01-01

276

Sunscreen enhancement of UV-induced reactive oxygen species in the skin.  

PubMed

The number of UV-induced (20 mJ cm(-2)) reactive oxygen species (ROS) generated in nucleated epidermis is dependent upon the length of time the UV filter octocrylene, octylmethoxycinnamate, or benzophenone-3 remains on the skin surface. Two-photon fluorescence images acquired immediately after application of each formulation (2 mg cm(-2)) to the skin surface show that the number of ROS produced is dramatically reduced relative to the skin-UV filter control. After each UV filter remains on the skin surface for t=20 min, the number of ROS generated increases, although it remains below the number generated in the control. By t=60 min, the filters generate ROS above the control. The data show that when all three of the UV filters penetrate into the nucleated layers, the level of ROS increases above that produced naturally by epidermal chromophores under UV illumination. PMID:17015167

Hanson, Kerry M; Gratton, Enrico; Bardeen, Christopher J

2006-10-15

277

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

278

Generation of singlet oxygen and other radical species by quantum dot and carbon dot nanosensitizers  

NASA Astrophysics Data System (ADS)

Medicinal applications of luminescent semiconductor quantum dots are of growing interest. In spite of the fact that their fabrication and imaging applications have been extensively investigated for the last decade, very little is documented on photodynamic action of quantum dots. In this study we demonstrate generation of singlet oxygen and other radical species upon exposure of quantum dots to blue light and therapeutic red light. Extent of radical production can be readily modified by antioxidants. Lay and scientific communities are two sites concerning potential hazards and enthusiastic applications of nanotechnology. Synthesis of quantum dots composed of less toxic materials is of great interest. A new candidate is a ubiquitous element carbon, which on nanoscale exhibits strong photoluminescence.

Generalov, Roman; Christensen, Ingeborg L.; Chen, Wei; Sun, Ya-Ping; Kristensen, Solveig; Juzenas, Petras

2009-06-01

279

Reactive Oxygen Species Modulate the Differentiation of Neurons in Clonal Cortical Cultures.  

PubMed Central

Reactive oxygen species (ROS) are important regulators of intracellular signaling. We examined the expression of ROS during rat brain development and explored their role in differentiation using cortical cultures. High levels of ROS were found in newborn neurons. Neurons produced ROS, not connected with cell death, throughout embryogenesis and postnatal stages. By P20, ROS-producing cells were found only in neurogenic regions. Cells with low levels of ROS, isolated from E15 brains by FACS, differentiated into neurons, oligodendrocytes, and astrocytes in clonal cultures. Neurons produced high ROS early in culture and later differentiated into two types: large pyramidal-like neurons that fired no or only a single action potential and smaller neurons that expressed nuclear calretinin and fired repeated action potentials. Antioxidant treatment did not alter neuron number but increased the ratio of small to large neurons. These findings suggest that modulation of ROS levels influences multiple aspects of neuronal differentiation.

Tsatmali, Marina; Walcott, Elisabeth C.; Makarenkova, Helen; Crossin, Kathryn L.

2007-01-01

280

Reactive oxygen species involved in regulating fruit senescence and fungal pathogenicity.  

PubMed

Senescence is a vital aspect of fruit life cycles, and directly affects fruit quality and resistance to pathogens. Reactive oxygen species (ROS), as the primary mediators of oxidative damage in plants, are involved in senescence. Mitochondria are the main ROS and free radical source. Oxidative damage to mitochondrial proteins caused by ROS is implicated in the process of senescence, and a number of senescence-related disorders in a variety of organisms. However, the specific sites of ROS generation in mitochondria remain largely unknown. Recent discoveries have ascertained that fruit senescence is greatly related to ROS and incidental oxidative damage of mitochondrial protein. Special mitochondrial proteins involved in fruit senescence have been identified as the targets of ROS. We focus in discussion on our recent advances in exploring the mechanisms of how ROS regulate fruit senescence and fungal pathogenicity. PMID:23515879

Tian, Shiping; Qin, Guozheng; Li, Boqiang

2013-08-01

281

The Quantitative Analysis of Active Species Generated by Direct Current Plasma within Oxygen Bubbles  

NASA Astrophysics Data System (ADS)

In this research, concentrations of hydrogen peroxide and dissolved ozone generated by direct current plasma within oxygen bubbles in water were measured. The current magnitude and water conductivity were changed from 1 to 7mA, and from 1 to 100 ?S/cm, respectively. The highest efficiency of hydrogen peroxide generation was 0.64g/kWh at 7mA with 100?S/cm solution. The concentration of dissolved ozone decreased with increasing the discharge current, and was almost zero when the current was higher than 5mA. Non-dimensional simulation revealed that the water vapor concentration in bubbles strongly affects the generation of active species. With a large current, the amount of water vaporized into the bubbles enlarged due to a large heat flux from plasma.

Ishii, Yoko; Ando, Mizuki; Takeuchi, Nozomi; Ikeda, Kei; Yasuoka, Koichi

282

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

283

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

284

Oxygen-derived species: Their relation to human disease and environmental stress  

SciTech Connect

Free radicals and other reactive oxygen species (ROS) are constantly formed in the human body, often for useful metabolic purposes. Antioxidant defenses protect against them, but these defenses are not completely adequate, and systems that repair damage by ROS are also necessary. Mild oxidative stress often induces antioxidant defense enzymes, but severe stress can cause oxidative damage to lipids, proteins, and DNA within cells, leading to such events as DNA strand breakage and disruption of calcium ion metabolism. Oxidative stress can result from exposure to toxic agents, and by the process of tissue injury itself. Ozone, oxides of nitrogen, and cigarette smoke can cause oxidative damage; but the molecular targets that they damage may not be the same. 88 refs., 1 fig., 4 tabs.

Halliwell, B. [Univ. of California-Davis Medical Center, Sacramento, CA (United States)]|[Univ. of London Kings College (United Kingdom); Cross, C.E. [Univ. of California-Davis Medical Center, Sacramento, CA (United States)

1994-12-01

285

Oxygen-derived species: their relation to human disease and environmental stress.  

PubMed

Free radicals and other reactive oxygen species (ROS) are constantly formed in the human body, often for useful metabolic purposes. Antioxidant defenses protect against them, but these defenses are not completely adequate, and systems that repair damage by ROS are also necessary. Mild oxidative stress often induces antioxidant defense enzymes, but severe stress can cause oxidative damage to lipids, proteins, and DNA within cells, leading to such events as DNA strand breakage and disruption of calcium ion metabolism. Oxidative stress can result from exposure to toxic agents, and by the process of tissue injury itself. Ozone, oxides of nitrogen, and cigarette smoke can cause oxidative damage; but the molecular targets that they damage may not be the same. PMID:7705305

Halliwell, B; Cross, C E

1994-12-01

286

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.

Saucedo-Garcia, Mariana; Gonzalez-Solis, Ariadna; Rodriguez-Mejia, Priscila; de Jesus Olivera-Flores, Teresa; Vazquez-Santana, Sonia; Cahoon, Edgar B

2011-01-01

287

Genkwadaphnin induces reactive oxygen species (ROS)-mediated apoptosis of squamous cell carcinoma (SCC) cells.  

PubMed

Genkwadaphnin is a daphnane diterpene ester molecule isolated from the flower buds of Daphne genkwa. In the present study, we investigated the apoptosis-inducing effect of genkwadaphnin in squamous cell carcinoma (SCC) cells. Apoptosis was triggered in SCC12 cells following genkwadaphnin treatment in a time- and concentration-dependent manner. Genkwadaphnin treatment increased phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). Knockdown of JNK and p38 MAPK by recombinant adenovirus expressing microRNA (miR) resulted in significant inhibition of genkwadaphnin-induced apoptosis in SCC12 cells. Finally, pretreatment with the reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) markedly reduced SCC12 cell apoptosis, concomitant with significant inhibition of MAPK activation. These results indicate that genkwadaphnin has the potential to induce apoptosis in SCC cells, providing information on which to base further research with the aim of developing a cure for SCC. PMID:24996181

Li, Zheng Jun; Li, Xue Mei; Piao, Yong Jun; Choi, Dae-Kyoung; Kim, Sue Jeong; Kim, Jae Wha; Sohn, Kyung-Cheol; Kim, Chang Deok; Lee, Jeung-Hoon

2014-07-25

288

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.

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

2013-01-01

289

BRCA1 Down-Regulates Cellular Levels of Reactive Oxygen Species  

PubMed Central

Previous studies have shown that the breast cancer suppressor BRCA1 stimulates antioxidant gene expression and protects cells against oxidative stress. To further examine this important function, we tested whether BRCA1 could modulate intracellular levels of reactive oxygen species (ROS). Wild-type BRCA1 (but not a cancer-associated mutant) significantly reduced ROS levels, determined by DCF fluorescence assays by flow cytometry and confocal microscopy. The BRCA1 and REF1 pathways for reduction of ROS levels appear to exhibit cross-talk. BRCA1 also reduced the levels of protein nitration and H2O2-induced oxidative damage to DNA. Thus, BRCA1 may protect cellular macromolecules by reducing intracellular ROS levels.

Saha, Tapas; Rih, Jeong Keun; Rosen, Eliot M.

2009-01-01

290

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

PubMed Central

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

Aprioku, Jonah Sydney

2013-01-01

291

PGC-1? and Reactive Oxygen Species Regulate Human Embryonic Stem Cell-Derived Cardiomyocyte Function  

PubMed Central

Summary Diminished mitochondrial function is causally related to some heart diseases. Here, we developed a human disease model based on cardiomyocytes from human embryonic stem cells (hESCs), in which an important pathway of mitochondrial gene expression was inactivated. Repression of PGC-1?, which is normally induced during development of cardiomyocytes, decreased mitochondrial content and activity and decreased the capacity for coping with energetic stress. Yet, concurrently, reactive oxygen species (ROS) levels were lowered, and the amplitude of the action potential and the maximum amplitude of the calcium transient were in fact increased. Importantly, in control cardiomyocytes, lowering ROS levels emulated this beneficial effect of PGC-1? knockdown and similarly increased the calcium transient amplitude. Our results suggest that controlling ROS levels may be of key physiological importance for recapitulating mature cardiomyocyte phenotypes, and the combination of bioassays used in this study may have broad application in the analysis of cardiac physiology pertaining to disease.

Birket, Matthew J.; Casini, Simona; Kosmidis, Georgios; Elliott, David A.; Gerencser, Akos A.; Baartscheer, Antonius; Schumacher, Cees; Mastroberardino, Pier G.; Elefanty, Andrew G.; Stanley, Ed G.; Mummery, Christine L.

2013-01-01

292

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

PubMed Central

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

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

2012-01-01

293

INTERACTIONS BETWEEN CALCIUM AND REACTIVE OXYGEN SPECIES IN PULMONARY ARTERIAL SMOOTH MUSCLE RESPONSES TO HYPOXIA  

PubMed Central

In contrast to the systemic vasculature, where hypoxia causes vasodilation, pulmonary arteries constrict in response to hypoxia. The mechanisms underlying this unique response have been the subject of investigation for over 50 years, and still remain a topic of great debate. Over the last 20 years, there has emerged a general consensus that both increases in intracellular calcium concentration and changes in reactive oxygen species (ROS) generation play key roles in the pulmonary vascular response to hypoxia. Controversy exists, however, regarding whether ROS increase or decrease during hypoxia, the source of ROS, and the mechanisms by which changes in ROS might impact intracellular calcium, and vice versa. This review will discuss the mechanisms regulating [Ca2+]i and ROS in PASMCs, and the interaction between ROS and Ca2+ signaling during exposure to acute hypoxia.

Shimoda, Larissa A.; Undem, Clark

2010-01-01

294

Detecting, visualizing and quantitating the generation of reactive oxygen species in an amoeba model system.  

PubMed

Reactive oxygen species (ROS) comprise a range of reactive and short-lived, oxygen-containing molecules, which are dynamically interconverted or eliminated either catalytically or spontaneously. Due to the short life spans of most ROS and the diversity of their sources and subcellular localizations, a complete picture can be obtained only by careful measurements using a combination of protocols. Here, we present a set of three different protocols using OxyBurst Green (OBG)-coated beads, or dihydroethidium (DHE) and Amplex UltraRed (AUR), to monitor qualitatively and quantitatively various ROS in professional phagocytes such as Dictyostelium. We optimised the beads coating procedures and used OBG-coated beads and live microscopy to dynamically visualize intraphagosomal ROS generation at the single cell level. We identified lipopolysaccharide (LPS) from E. coli as a potent stimulator for ROS generation in Dictyostelium. In addition, we developed real time, medium-throughput assays using DHE and AUR to quantitatively measure intracellular superoxide and extracellular H2O2 production, respectively. PMID:24300479

Zhang, Xuezhi; Soldati, Thierry

2013-01-01

295

Reactive oxygen species and the bacteriostatic and bactericidal effects of isoconazole nitrate.  

PubMed

Bacterial superinfections often occur in dermatomycoses, resulting in greatly inflamed or eczematous skin. The objective of this study was to evaluate the antibacterial efficacy of isoconazole nitrate (ISN), a broad-spectrum antimicrobial imidazole, commonly used to treat dermatomycoses. Several gram-positive bacteria minimal inhibitory concentrations (MICs) for ISN (ISN solution or ISN-containing creams: Travogen or corticosteroid-containing Travocort) and ampicillin were obtained using the broth-dilution method. Speed of onset of the bactericidal effect was determined with bacterial killing curves. Reactive oxygen species (ROS) were visualised by staining cells with singlet oxygen detector stain. Compared with ampicillin MICs, ISN MICs for Bacillus cereus, Staphylococcus haemolyticus and Staphylococcus hominis were lower and ISN MICs for Corynebacterium tuberculostearicum and Streptococcus salivarius were similar. Incubation with ISN led to a 50% kill rate for Staphylococcus aureus and methicillin-resistant strains (MRSA). Post-ISN incubation, 36% (30 min) and 90% (60 min) of S. aureus cells were positive for ROS. Isoconazole nitrate has a broad bacteriostatic and bactericidal action, also against a MRSA strain that was not reduced by the corticosteroid in the Travocort cream. Data suggest that the antibacterial effect of ISN may be ROS dependent. An antifungal agent with robust antibacterial activity can provide a therapeutic advantage in treating dermatomycoses with suspected bacterial superinfections. PMID:23574020

Czaika, Viktor A; Siebenbrock, Jan; Czekalla, Frank; Zuberbier, Torsten; Sieber, Martin A

2013-05-01

296

Cadmium induces two waves of reactive oxygen species in Glycine max (L.) roots.  

PubMed

Cadmium (Cd) is a non-essential heavy metal that may be toxic or even lethal to plants as it can be easily taken up by the roots and loaded into the xylem to the leaves. Using soybean roots (Glycine max?L.) DM 4800, we have analysed various parameters related to reactive oxygen metabolism and nitric oxide (NO) during a 6 day Cd exposure. A rise in H2 O2 and NO, and to a lesser extent O2 (·-) content was observed after 6?h exposure with a concomitant increase in lipid peroxidation and carbonyl group content. Both oxidative markers were significantly reduced after 24?h. A second, higher wave of O2 (·-) production was also observed after 72?h of exposure followed by a reduction until the end of the treatment. NOX and glicolate oxidase activity might be involved in the initial Cd-induced reactive oxygen species (ROS) production and it appears that other sources may also participate. The analysis of antioxidative enzymes showed an increase in glutathione-S-transferase activity and in transcript levels and activity of enzymes involved in the ascorbate-glutathione cycle and the NADPH-generating enzymes. These results suggest that soybean is able to respond rapidly to oxidative stress imposed by Cd by improving the availability of NADPH necessary for the ascorbate-glutathione cycle. PMID:24433233

Pérez-Chaca, María Verónica; Rodríguez-Serrano, María; Molina, Alicia S; Pedranzani, Hilda E; Zirulnik, Fanny; Sandalio, Luisa M; Romero-Puertas, María C

2014-07-01

297

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.

Klann, Eric

2011-01-01

298

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

PubMed Central

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

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

2012-01-01

299

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

PubMed

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

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

2011-10-01

300

Action of reactive oxygen species in the antifungal mechanism of gemini-pyridinium salts against yeast.  

PubMed

We previously found that the gemini quaternary salt (gemini-QUAT) containing two pyridinium residues per molecule, 3,3'- (2,7-dioxaoctane) bis (1-decylpyridinium bromide) (3DOBP-4,10) , exerted fungicidal activity against Saccharomyces cerevisiae and caused respiration inhibition and the cytoplasmic leakage of ATP, magnesium, and potassium ions. Here, we investigated how the gemini-QUAT, 3DOBP-4,10, exerts more powerful antimicrobial activity than the mono-QUAT N-cetylpyridinium chloride (CPC) and examined the association between reactive oxygen species (ROS) and the antimicrobial mechanism. Antifungal assays showed that the activity of 3DOBP-4,10 against two yeasts, S. cerevisiae and Candida albicans, was significantly elevated under aerobic conditions, and largely reduced under anaerobic conditions (nitrogen atmosphere) . Adding radical scavengers such as superoxide dismutase, catalase and potassium iodide (KI) also decreased the fungicidal activity of 3DOBP-4,10 but negligibly affected that of CPC. We measured survival under static conditions and found that the rapid fungicidal profile of 3DOBP-4,10 was lost, whereas that of CPC was slightly affected in the presence of KI. Our results suggest that 3DOBP-4,10 exerts powerful antimicrobial activity by penetrating the cell wall and membrane, which then allows oxygen to enter the cells, where it participates in the generation of intracellular ROS. The activity could thus be attributable to a synergic antimicrobial combination of the disruption of organelle membranes by the QUAT and oxidative stress imposed by ROS. PMID:22790843

Shirai, Akihiro; Ueta, Shouko; Maseda, Hideaki; Kourai, Hiroki; Omasa, Takeshi

2012-06-01

301

The Role of Metals in Production and Scavenging of Reactive Oxygen Species in Photosystem II.  

PubMed

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

Pospíšil, Pavel

2014-07-01

302

Ultraviolet irradiation-dependent fluorescence enhancement of hemoglobin catalyzed by reactive oxygen species.  

PubMed

Ultraviolet (UV) light has a potent effect on biological organisms. Hemoglobin, an oxygen-transport protein, plays an irreplaceable role in sustaining life of all vertebrates. In this study we scrutinize the effects of ultraviolet irradiation (UVI) as well as visible irradiation on the fluorescence characteristics of bovine hemoglobin (BHb) in vitro. Data show that UVI results in fluorescence enhancement of BHb in a dose-dependent manner. Furthermore, UVI-induced fluorescence enhancement is significantly increased when BHb is pretreated with hydrogen peroxide (H(2)O(2)), a type of reactive oxygen species (ROS). Meanwhile, The water-soluble antioxidant vitamin C suppresses this UVI-induced fluorescence enhancement. In contrast, green light irradiation does not lead to fluorescence enhancement of BHb no matter whether H(2)O(2) is acting on the BHb solution or not. Taken together, these results indicate that catalysis of ROS and UVI-dependent irradiation play two key roles in the process of UVI-induced fluorescence enhancement of BHb. PMID:22952902

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

2012-01-01

303

Iron toxicity in organotypic cultures of hippocampal slices: role of reactive oxygen species.  

PubMed

Free iron has been assumed to potentiate oxygen toxicity by generating reactive oxygen species (ROS) via the iron-catalyzed Haber-Weiss reaction, leading to oxidative stress. ROS-mediated iron cytotoxicity may trigger apoptotic cell death. In the present study, we used iron treatment of organotypic cultures of hippocampal slices to study potential mechanisms involved in iron-induced neuronal damage. Exposure of mature hippocampal slices to ferrous sulfate resulted in concentration- and time-dependent cell death. After iron treatment, markers of ROS formation and lipid peroxidation, i.e. intensity of dichlorofluorescein (DCF) fluorescence and levels of thiobarbiturate reactive substances (TBARS), were significantly increased. Levels of cytochrome c were increased while levels of pro-caspase-9 and pro-caspase-3 were decreased in cytosolic fractions of iron-treated hippocampal slice cultures. Treatment of cultured slices with a synthetic catalytic ROS scavenger, EUK-134, provided between 50 and 70% protection against various parameters of cell damage and markers of oxidative stress. In addition, inhibition of caspase-3 activity by Ac-DEVDcho partially protected cells from iron toxicity. The combination of EUK-134 and Ac-DEVDcho resulted in an almost complete blockade of iron-induced damage. These results indicate that iron elicits cellular damage predominantly by oxidative stress, and that ROS-mediated iron toxicity may involve cytochrome c- and caspase-3-dependent apoptotic pathways. PMID:12675926

Liu, Ruolan; Liu, Wei; Doctrow, Susan R; Baudry, Michel

2003-04-01

304

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.

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

2011-01-01

305

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

306

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

307

Relationship between lignin degradation and production of reduced oxygen species by Phanerochaete chrysosporium  

SciTech Connect

The relationship between the production of reduced oxygen species, hydrogen peroxide (H/sub 2/O/sub 2/), superoxide (O/sub 2//sup -/), and hydroxyl radical (.OH), and the oxidation of synthetic lignin to CO/sub 2/ was studied in whole cultures of the white-rot fungus Phanerochaete chrysosporium Burds. The kinetics of the synthesis of H/sub 2/O/sub 2/ coincided with the appearance of the ligninolytic system; also, H/sub 2/O/sub 2/ production was markedly enhanced by growth under 100% O/sub 2/, mimicing the increase in ligninolytic activity characteristic of cultures grown under elevated oxygen tension. Lignin degradation by whole cultures was inhibited by a specific H/sub 2/O/sub 2/ scavenger, catalase, implying a role for H/sub 2/O/sub 2/ in the degradative process. Superoxide dismutase also inhibited lignin degradation, suggesting that O/sub 2//sup -/ is also involved in the breakdown of lignin. The production of .OH was assayed in whole cultures by a benzoate decarboxylation assay. Neither the kinetics of .OH synthesis nor the final activity of its producing system obtained under 100% O/sub 2/ correlated with that of the lignin-degrading system. However, lignin degradation was inhibited by compounds which react with .OH. It is concluded that H/sub 2/O/sub 2/, and perhaps O/sub 2//sup -/, are involved in lignin degradation; because these species are relatively unreactive per se, their role must be indirect. Conclusions about a role for .OH in ligninolysis could not be reached. (Refs. 28).

Faison, B.D.; Kirk, T.K.

1983-11-01

308

Reactive Oxygen Species Production by Forward and Reverse Electron Fluxes in the Mitochondrial Respiratory Chain  

PubMed Central

Reactive oxygen species (ROS) produced in the mitochondrial respiratory chain (RC) are primary signals that modulate cellular adaptation to environment, and are also destructive factors that damage cells under the conditions of hypoxia/reoxygenation relevant for various systemic diseases or transplantation. The important role of ROS in cell survival requires detailed investigation of mechanism and determinants of ROS production. To perform such an investigation we extended our rule-based model of complex III in order to account for electron transport in the whole RC coupled to proton translocation, transmembrane electrochemical potential generation, TCA cycle reactions, and substrate transport to mitochondria. It fits respiratory electron fluxes measured in rat brain mitochondria fueled by succinate or pyruvate and malate, and the dynamics of NAD+ reduction by reverse electron transport from succinate through complex I. The fitting of measured characteristics gave an insight into the mechanism of underlying processes governing the formation of free radicals that can transfer an unpaired electron to oxygen-producing superoxide and thus can initiate the generation of ROS. Our analysis revealed an association of ROS production with levels of specific radicals of individual electron transporters and their combinations in species of complexes I and III. It was found that the phenomenon of bistability, revealed previously as a property of complex III, remains valid for the whole RC. The conditions for switching to a state with a high content of free radicals in complex III were predicted based on theoretical analysis and were confirmed experimentally. These findings provide a new insight into the mechanisms of ROS production in RC.

Selivanov, Vitaly A.; Votyakova, Tatyana V.; Pivtoraiko, Violetta N.; Zeak, Jennifer; Sukhomlin, Tatiana; Trucco, Massimo; Roca, Josep; Cascante, Marta

2011-01-01

309

Nitric oxide protects against cellular damage and cytotoxicity from reactive oxygen species.  

PubMed Central

Nitric oxide, NO, which is generated by various components of the immune system, has been presumed to be cytotoxic. However, NO has been proposed to be protective against cellular damage resulting during ischemia reperfusion. Along with NO there is often concomitant formation of superoxide/hydrogen peroxide, and hence a synergistic relationship between the cytotoxic effects of nitric oxide and these active oxygen species is frequently assumed. To study more carefully the potential synergy between NO and active oxygen species in mammalian cell cytotoxicity, we utilized either hypoxanthine/xanthine cell cytotoxicity, we utilized either hypoxanthine/xanthine oxidase (a system that generates superoxide/hydrogen peroxide) or hydrogen peroxide itself. NO generation was accomplished by the use of a class of compounds known as "NONOates," which release NO at ambient temperatures without the requirement of enzyme activation or biotransformation. When Chinese hamster lung fibroblasts (V79 cells) were exposed to hypoxanthine/xanthine oxidase for various times or increasing amounts of hydrogen peroxide, there was a dose-dependent decrease in survival of V79 cells as measured by clonogenic assays. However, in the presence of NO released from (C2H5)2N[N(O)NO]-Na+ (DEA/NO), the cytotoxicity resulting from superoxide or hydrogen peroxide was markedly abrogated. Similarly, primary cultures of rat mesencephalic dopaminergic cells exposed either to hydrogen peroxide or to hypoxanthine/xanthine oxidase resulted in the degradation of the dopamine uptake and release mechanism. As was observed in the case of the V79 cells, the presence of NO essentially abrogated this peroxide-mediated cytotoxic effect on mesencephalic cells. Images Fig. 3

Wink, D A; Hanbauer, I; Krishna, M C; DeGraff, W; Gamson, J; Mitchell, J B

1993-01-01

310

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

PubMed Central

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

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

2012-01-01

311

Reactive oxygen species mediate endothelium-dependent relaxations in tetrahydrobiopterin-deficient mice.  

PubMed

(6R)-5,6,7,8-Tetrahydro-biopterin (H(4)B) is essential for the catalytic activity of all NO synthases. The hyperphenylalaninemic mouse mutant (hph-1) displays 90% deficiency of the GTP cyclohydrolase I, the rate-limiting enzyme in H(4)B synthesis. A relative shortage of H(4)B may shift the balance between endothelial NO synthase (eNOS)-catalyzed generation of NO and reactive oxygen species. Therefore, the hph-1 mouse represents a unique model to assess the effect of chronic H(4)B deficiency on endothelial function. Aortas from 8-week-old hph-1 and wild-type mice (C57BLxCBA) were compared. H(4)B levels were determined by high-performance liquid chromatography and NO synthase activity by [(3)H]citrulline assay in homogenized tissue. Superoxide production by the chemiluminescence method was measured. Isometric tension was continuously recorded. The intracellular levels of H(4)B as well as constitutive NO synthase activity were significantly lower in hph-1 compared with wild-type mice. Systolic blood pressure was increased in hph-1 mice. However, endothelium-dependent relaxations to acetylcholine were present in both groups and abolished by inhibition of NO synthase with N(G)-nitro-L-arginine methyl ester as well. Only in hph-1 mice were the relaxations inhibited by catalase and enhanced by superoxide dismutase. After incubation with exogenous H(4)B, the differences between the 2 groups disappeared. Our findings demonstrate that H(4)B deficiency leads to eNOS dysfunction with the formation of reactive oxygen species, which become mediators of endothelium-dependent relaxations. A decreased availability of H(4)B may favor an impaired activity of eNOS and thus contribute to the development of vascular diseases. PMID:11304463

Cosentino, F; Barker, J E; Brand, M P; Heales, S J; Werner, E R; Tippins, J R; West, N; Channon, K M; Volpe, M; Lüscher, T F

2001-04-01

312

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.

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

2013-01-01

313

Extended Hartree-Fock theory of chemical reactions. IX. Diradical and perepoxide mechanisms for oxygenations of ethylene with molecular oxygen and iron-oxo species are revisited  

NASA Astrophysics Data System (ADS)

Symmetry and broken symmetry (BS) in molecular orbital description of transition structures and intermediates in oxygenation reactions have been revisited to elucidate states correlation diagrams and mechanisms for addition reactions of molecular oxygen and metal-oxo M=O (M = Mn(II) and Fe(II)) species to C=C double bonds. Relative stabilities between diradical (DR) and perepoxide (PE) intermediates were thoroughly investigated by several BS hybrid DFT (HDFT) methods and BS CCSD(T) method with and without spin projection. It has been found that recovery of spin symmetry, namely eliminating spin contamination error from the BS solutions, is crucial for the elucidation of reasonable state correlation diagrams and energy differences of the key structures in the oxygenation reactions because the singlet-triplet energy gap for molecular oxygen is large (22 kcal/mol). The BS HDFT followed by spin correction reproduced activation barriers for transition structures along both PE and DR reaction pathways by the use of the CASPT2 method. Basis set dependence on the relative stability between PE and DR intermediates were also examined thoroughly. Solvation effect for DR and PE intermediates was further examined with self-consistent reaction field (SCRF) and SCIPCM methods. Both BS HDFT and CASPT2 have concluded that the DR mechanism is favorable for the addition reaction of singlet oxygen to ethylene, supporting our previous conclusions. The BS HDFT with spin correction was concluded to be useful enough for theoretical investigations of mechanisms of oxygenation reactions. Implications of the computational results were discussed in relation to the theoretical framework (four configuration model) for elucidation of possible mechanisms of epoxidation reactions with Fe(IV)=O cores in metalloenzymes on the basis of isolobal analogies among O, O=O, and Fe(IV)=O. Correspondence between magnetic coupling mode and radical pathway in oxygenations with these species was clarified based on the BS MO interaction diagrams, leading to local singlet and triplet diradical mechanisms for epoxidations.

Yamaguchi, Kizashi; Yamanaka, Syusuke; Shimada, Jiro; Isobe, Hiroshi; Saito, Toru; Shoji, Mitsuo; Kitagawa, Yasutaka; Okumura, Mitsutaka

314

TLR 9 Activation in Dendritic Cells Enhances Salmonella Killing and Antigen Presentation via Involvement of the Reactive Oxygen Species  

PubMed Central

Synthetic CpG containing oligodeoxynucleotide Toll like receptor-9 agonist (CpG DNA) activates innate immunity and can stimulate antigen presentation against numerous intracellular pathogens. It was observed that Salmonella Typhimurium growth can be inhibited by the CpG DNA treatment in the murine dendritic cells. This inhibitory effect was mediated by an increased reactive oxygen species production. In addition, it was noted that CpG DNA treatment of dendritic cells during Salmonella infection leads to an increased antigen presentation. Further this increased antigen presentation was dependent on the enhanced reactive oxygen species production elicited by Toll like receptor-9 activation. With the help of an exogenous antigen it was shown that Salmonella antigen could also be cross-presented in a better way by CpG induction. These data collectively indicate that CpG DNA enhance the ability of murine dendritic cells to contain the growth of virulent Salmonella through reactive oxygen species dependent killing.

Lahiri, Amit; Vani, Janakiraman; Shaila, M. S.; Chakravortty, Dipshikha

2010-01-01

315

Reactive oxygen species and reactive nitrogen species: relevance to cyto(neuro)toxic events and neurologic disorders. An overview.  

PubMed

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are formed under physiological conditions in the human body and are removed by cellular antioxidant defense system. During oxidative stress their increased formation leads to tissue damage and cell death. This process may be especially important in the central nervous system (CNS) which is vulnerable to ROS and RNS damage as the result of the brain high O(2) consumption, high lipid content and the relatively low antioxidant defenses in brain, compared with other tissues. Recently there has been an increased number of reports suggesting the involvement of free radicals and their non-radical derivatives in a variety of pathological events and multistage disorders including neurotoxicity, apoptotic death of neurons and neural disorders: Alzheimer's (AD), Parkinson's disease (PD) and schizophrenia. Taking into consideration the basic molecular chemistry of ROS and RNS, their overall generation and location, in order to control or suppress their action it is essential to understand the fundamental aspects of this problem. In this presentation we review and summarize the basics of all the recently known and important properties, mechanisms, molecular targets, possible involvement in cellular (neural) degeneration and apoptotic death and in pathogenesis of AD, PD and schizophrenia. The aim of this article is to provide an overview of our current knowledge of this problem and to inspire experimental strategies for the evaluation of optimum innovative therapeutic trials. Another purpose of this work is to shed some light on one of the most exciting recent advances in our understanding of the CNS: the realisation that RNS pathway is highly relevant to normal brain metabolism and to neurologic disorders as well. The interactions of RNS and ROS, their interconversions and the ratio of RNS/ROS could be an important neural tissue injury mechanism(s) involved into etiology and pathogenesis of AD, PD and schizophrenia. It might be possible to direct therapeutic efforts at oxidative events in the pathway of neuron degeneration and apoptotic death. From reviewed data, no single substance can be recommended for use in human studies. Some of the recent therapeutic strategies and neuroprotective trials need further development particularly those of antioxidants enhancement. Such an approach should also consider using combinations of radical(s) scavengers rather than a single substance. PMID:12835102

Metodiewa, D; Ko?ka, C

2000-02-01

316

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

PubMed Central

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

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

2013-01-01

317

Reactive oxygen species and sperm function--in sickness and in health.  

PubMed

The ability of spermatozoa to generate reactive oxygen species (ROS) has been appreciated since the 1940s. It is a universal property of mature spermatozoa from all mammalian species and a major contributor to the oxidative stress responsible for defective sperm function. The mechanisms by which oxidative stress limits the functional competence of mammalian spermatozoa involve the peroxidation of lipids, the induction of oxidative DNA damage, and the formation of protein adducts. ROS production in these cells involves electron leakage from the sperm mitochondria, triggered by a multitude of factors that impede electron flow along the electron transport chain. The net result of mitochondrial ROS generation is to damage these organelles and initiate an intrinsic apoptotic cascade, as a consequence of which spermatozoa lose their motility, DNA integrity, and vitality. This pathway of programmed senescence also results in the exteriorization of phosphatidylserine, which may facilitate the silent phagocytosis of these cells in the aftermath of insemination, in turn influencing the female tract immune response to sperm antigens and future fertility. Despite the vulnerability of sperm to oxidative stress, it is also clear that normal sperm function depends on low levels of ROS generation in order to promote the signal transduction pathways associated with capacitation. Modulators of ROS generation by spermatozoa may therefore have clinical utility in regulating the fertilizing capacity of these cells and preventing the development of antisperm immunity. Achievement of these objectives will require a systematic evaluation of pro- and antioxidant strategies in vivo and in vitro. PMID:22879525

Aitken, R John; Jones, Keith T; Robertson, Sarah A

2012-01-01

318

Contrasting reactive oxygen species and transition metal concentrations in combustion aerosols.  

PubMed

The presence of reactive oxygen species (ROS) and 10 transition metals (Ag, Cd, Co, Cu, Fe, Mn, Ni, Ti, V and Zn) in both the acid-soluble and water-soluble fractions of fine particles of combustion origin were determined. ROS was analyzed using the dichlorofluorescin fluorescence technique. Particles emitted from on-road vehicles, gas cooking, incense burning, and cigarette smoke were characterized along with those in the background air of outdoor and indoor environments. In addition, this study evaluated the possible relationships between ROS and individual transition metals. It is found that cigarette smoke which had the highest concentration of metals also contained the highest concentration of ROS. Regression analysis performed showed that water-soluble metals including Cd, Co, Cu, Fe, Mn, and Ni showed better correlation with ROS concentration as compared to acid-soluble (total) metals. The findings demonstrated that water-soluble metals could be one of the species influencing ROS formation in ambient air. PMID:17011545

See, S W; Wang, Y H; Balasubramanian, R

2007-03-01

319

Amputation-induced reactive oxygen species are required for successful Xenopus tadpole tail regeneration.  

PubMed

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, through the coordinated activity of numerous growth factor signalling pathways, including the Wnt, Fgf, Bmp, Notch and TGF-? pathways. 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, using pharmacological or genetic approaches, reduces the level of 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 signalling and the activation of one of its main downstream targets, fgf20 (ref. 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

2013-02-01

320

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

PubMed Central

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

Kowitdamrong, Akkarawut; Chanvorachote, Pithi; Sritularak, Boonchoo

2013-01-01

321

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, H2 O2 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

322

Effect of reactive oxygen and carbonyl species on crucial cellular antioxidant enzymes.  

PubMed

Numerous reactive oxygen species (ROS) and reactive carbonyl species (RCS) issuing from lipid and sugar oxidation are known to damage a large number of proteins leading to enzyme inhibition and alteration of cellular functions. Whereas studies in literature only focus on the reactivity of one or two of these compounds, we aimed at comparing in the same conditions of incubations (4 and 24h at 37°C) the effects of both various RCS (4-hydroxynonenal, 4-hydroxyhexenal, acrolein, methylglyoxal, glyoxal, malondialdehyde) and ROS (H?O?, AAPH) on the activity of key enzymes involved in cellular oxidative stress: superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH). This was realized both in vitro on purified proteins and MIAPaCa-2 cells. Incubation of these enzymes with RCS resulted in a significant time- and concentration-dependent inhibition for both pure enzymes and in cell lysates. Among all RCS and ROS, hydroxynonenal (HNE) was observed as the most toxic for all studied enzymes except for SOD and is followed by hydrogen peroxide. At 100?M, HNE resulted in a 50% reduction of GPx, 56% of GST, 65% of G6PDH, and only 10% of Cu,Zn-SOD. Meanwhile it seems that concentrations used in our study are closer to biological conditions for ROS than for RCS. H?O? and AAPH-induced peroxyl radicals may be probably more toxic towards the studied enzymes in vivo. PMID:21216240

Lesgards, Jean-François; Gauthier, Cyrielle; Iovanna, Juan; Vidal, Nicolas; Dolla, Alain; Stocker, Pierre

2011-03-15

323

Regulation of insulin secretion and reactive oxygen species production by free fatty acids in pancreatic islets.  

PubMed

Free fatty acids regulate insulin secretion through metabolic and intracellular signaling mechanisms such as induction of malonyl-CoA/long-chain CoA pathway, production of lipids, GPRs (G protein-coupled receptors) activation and the modulation of calcium currents. Fatty acids (FA) are also important inducers of ROS (reactive oxygen species) production in ?-cells. Production of ROS for short periods is associated with an increase in GSIS (glucose-stimulated insulin secretion), but excessive or sustained production of ROS is negatively correlated with the insulin secretory process. Several mechanisms for FA modulation of ROS production by pancreatic ?-cells have been proposed, such as the control of mitochondrial complexes and electron transport, induction of uncoupling proteins, NADPH oxidase activation, interaction with the renin-angiotensin system, and modulation of the antioxidant defense system. The major sites of superoxide production within mitochondria derive from complexes I and III. The amphiphilic nature of FA favors their incorporation into mitochondrial membranes, altering the membrane fluidity and facilitating the electron leak. The extra-mitochondrial ROS production induced by FA through the NADPH oxidase complex is also an important source of these species in ?-cells. PMID:21750413

Graciano, Maria Fernanda Rodrigues; Valle, Maíra M R; Kowluru, Anjan; Curi, Rui; Carpinelli, Angelo R

2011-01-01

324

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

325

[Overproduction of noncanonical amino acids by Escherichia coli cells].  

PubMed

Overproduction of noncanonical amino acids norvaline and norleucine by Escherichia coli with inactivated acetohydroxy acid synthases was demonstrated. The cultivation conditions for the overproduction of noncanonical amino acids were studied. The effect of the restoration of acetohydroxy acid synthase activity, increased expression of the leuABCD operon, and inactivation of the biosynthetic threonine deaminase on norvaline and norleucine synthesis was studied. When grown under valine limitation, E. coli cells with inactivated acetohydroxy acid synthases and an elevated level of expression of the valine operon were shown to accumulate norvaline and norleucine (up to 0.8 and 4 g/l, respectively). These results confirm the existing hypothesis of norvaline and norleucine formation from 2-ketobutyrate by leucine biosynthesis enzymes. PMID:18297871

Sycheva, E V; Iampol'skaia, T A; Preobrazhenskaia, E S; Novikova, A E; Matrosov, N G; Sto?nova, N V

2007-01-01

326

Overproduction of Ascorbate Peroxidase in the Tobacco Chloroplast Does Not Provide Protection against Ozone.  

PubMed Central

Transgenic tobacco (Nicotiana tabacum cv Bel W3) plants were used to test the hypothesis that protection from O3 injury could be conferred by overproduction of ascorbate peroxidase (APX) in the chloroplast. The 10-fold increase in soluble APX activity in the chloroplast was expected to alleviate an implied increase in oxidative potential and prevent damage caused by O3. Three different O3 exposure experiments (one acute and two chronic) with two replicates each were conducted. APX activity in nontransgenic plants increased in response to chronic O3 exposure. However, most responses to O3 were similar between transgenic and nontransgenic plants. These included reductions in net photosynthesis and stomatal conductance, increases in ethylene emission and visible injury, and a decline in the level of the small subunit of ribulose-1,5-biphosphate carboxylase/oxygenase mRNA transcripts observed in response to the air pollutant in the acute and/or chronic experiments. No O3-induced effect on ribulose-1,5-biphosphate carboxylase/oxygenase quantity was observed in the chronic experiments. O3 did not induce acceleration of senescence, as expected from studies with most other species; rather, the tobacco plants rapidly developed necrotic lesions. Thus, overproduction of APX in the chloroplast did not protect this cultivar of tobacco from O3.

Torsethaugen, G.; Pitcher, L. H.; Zilinskas, B. A.; Pell, E. J.

1997-01-01

327

Physiological responses to folate overproduction in Lactobacillus plantarum WCFS1  

Microsoft Academic Search

BACKGROUND: Using a functional genomics approach we addressed the impact of folate overproduction on metabolite formation and gene expression in Lactobacillus plantarum WCFS1. We focused specifically on the mechanism that reduces growth rates in folate-overproducing cells. RESULTS: Metabolite formation and gene expression were determined in a folate-overproducing- and wild-type strain. Differential metabolomics analysis of intracellular metabolite pools indicated that the

Arno Wegkamp; Astrid E Mars; Magda Faijes; Douwe Molenaar; Ric CH de Vos; Sebastian MJ Klaus; Andrew D Hanson; Willem M de Vos; Eddy J Smid

2010-01-01

328

Proteolytic regulation of alginate overproduction in Pseudomonas aeruginosa  

PubMed Central

SUMMARY Pseudomonas aeruginosa, a Gram-negative bacterium, is a significant opportunistic pathogen associated with skin and soft tissue infections, nosocomial pneumonia, and sepsis. In addition, it can chronically colonize the lungs of cystic fibrosis (CF) patients. Overproduction of the exopolysaccharide called alginate provides P. aeruginosa with a selective advantage and facilitates survival in the CF lung. The in vitro phenotype of alginate overproduction observed on solid culture media is referred to as mucoid. Expression of the alginate machinery and biosynthetic enzymes are controlled by the extracytoplasmic sigma factor, ?22 (AlgU/T). The key negative regulator of both ?22 activity and the mucoid phenotype is the cognate anti-sigma factor MucA. MucA sequesters ?22 to the inner membrane inhibiting the sigma factor’s transcriptional activity. The well-studied mechanism for transition to the mucoid phenotype is mutation of mucA, leading to loss of MucA function and therefore activation of ?22. Recently, regulated intramembrane proteolysis (RIP) has been recognized as a mechanism whereby proteolysis of the anti-sigma factor MucA leads to active ?22 allowing P. aeruginosa to respond to environmental stress conditions by overproduction of alginate. The goal of this review is to illuminate the pathways leading to RIP that have been identified and proposed.

Damron, F. Heath; Goldberg, Joanna B.

2012-01-01

329

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

PubMed Central

A low-oxygenic niche in bone marrow limits reactive oxygen species (ROS) production, thus providing long-term protection for hematopoietic stem cells (HSCs) from ROS stress. Although many approaches have been used to enrich HSCs, none has been designed to isolate primitive HSCs located within the low-oxygenic niche due to difficulties of direct physical access. Here we show that an early HSC population that might reside in the niche can be functionally isolated by taking advantage of the relative intracellular ROS activity. Many attributes of primitive HSCs in the low-oxygenic osteoblastic niche, such as quiescence, and calcium receptor, N-cadherin, Notch1, and p21 are higher in the ROSlow population. Intriguingly, the ROSlow population has a higher self-renewal potential. In contrast, significant HSC exhaustion in the ROShigh population was observed following serial transplantation, and expression of activated p38 mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) was higher in this population. Importantly, treatment with an antioxidant, a p38 inhibitor, or rapamycin was able to restore HSC function in the ROShigh population. Thus, more potent HSCs associated with the low-oxygenic niche can be isolated by selecting for the low level of ROS expression. The ROS-related signaling pathways together with specific characteristics of niche HSCs may serve as targets for beneficial therapies.

2007-01-01

330

Pyrite-driven reactive oxygen species formation in simulated lung fluid: implications for coal workers' pneumoconiosis.  

PubMed

The origin of coal worker's pneumoconiosis (CWP) has been long debated. A recent epidemiological study shows a correlation between what is essentially the concentration of pyrite within coal and the prevalence of CWP in miners. Hydrogen peroxide and hydroxyl radical, both reactive oxygen species (ROS), form as byproducts of pyrite oxidative dissolution in air-saturated water. Motivated by the possible importance of ROS in the pathogenesis of CWP, we conducted an experimental study to evaluate if ROS form as byproducts in the oxidative dissolution of pyrite in simulated lung fluid (SLF) under biologically applicable conditions and to determine the persistence of pyrite in SLF. While the rate of pyrite oxidative dissolution in SLF is suppressed by 51% when compared to that in air-saturated water, the initial amount of hydrogen peroxide formed as a byproduct in SLF is nearly doubled. Hydroxyl radical is also formed in the experiments with SLF, but at lower concentrations than in the experiments with water. The formation of these ROS indicates that the reaction mechanism for pyrite oxidative dissolution in SLF is no different from that in water. The elevated hydrogen peroxide concentration in SLF suggests that the decomposition, via the Fenton mechanism to hydroxyl radical or with Fe(III) to form water and molecular oxygen, is initially inhibited by the presence of SLF components. On the basis of the oxidative dissolution rate of pyrite measured in this paper, it is calculated that a respirable two micron pyrite particle will take over 3 years to dissolve completely. PMID:21989857

Harrington, Andrea D; Hylton, Shavonne; Schoonen, Martin A A

2012-08-01

331

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.

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

2014-01-01

332

Reactive oxygen species are involved in nickel inhibition of dna repair  

SciTech Connect

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

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

1997-06-01

333

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

PubMed

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

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

2013-05-01

334

Process of aerenchyma formation and reactive oxygen species induced by waterlogging in wheat seminal roots.  

PubMed

The development and regulation of aerenchyma in waterlogged conditions were studied in the seminal roots of wheat. Evans blue staining and the first cell death position indicated that the cortical cell death began at the root mid-cortex cells in flooding conditions. Continuous waterlogging treatment caused the spread of cell death from the mid-cortex to the neighboring cells and well-developed aerenchyma was formed after 72 h. Meanwhile, the formation of radial oxygen loss barrier was observed in the exodermis owing to the induction of Casparian bands and lignin deposition. Analysis of aerenchyma along the wheat root revealed that aerenchyma formed at 10 mm from the root tip, significantly increased toward the center of the roots, and decreased toward the basal region of the root. In situ detection of radial oxygen species (ROS) showed that ROS accumulation started in the mid-cortex cells, where cell death began indicating that cell death was probably accompanied by ROS production. Further waterlogging treatments resulted in the accumulation of ROS in the cortical cells, which were the zone for aerenchyma development. Accumulation and distribution of H?O? at the subcellular level were revealed by ultracytochemical localization, which further verified the involvement of ROS in the cortical cell death process (i.e., aerenchyma formation). Furthermore, gene expression analysis indicated that ROS production might be the result of up-regulation of genes encoding for ROS-producing enzymes and the down-regulation of genes encoding for ROS-detoxifying enzymes. These results suggest that aerenchyma development in wheat roots starts in the mid-cortex cells and its formation is regulated by ROS. PMID:23975011

Xu, Q T; Yang, L; Zhou, Z Q; Mei, F Z; Qu, L H; Zhou, G S

2013-11-01

335

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.

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

2011-01-01

336

Antagonistic cross-talk between Rac and Cdc42 GTPases regulates generation of reactive oxygen species.  

PubMed

Cross-talk between Rho GTPase family members (Rho, Rac, and Cdc42) plays important roles in modulating and coordinating downstream cellular responses resulting from Rho GTPase signaling. The NADPH oxidase of phagocytes and nonphagocytic cells is a Rac GTPase-regulated system that generates reactive oxygen species (ROS) for the purposes of innate immunity and intracellular signaling. We recently demonstrated that NADPH oxidase activation involves sequential interactions between Rac and the flavocytochrome b(558) and p67(phox) oxidase components to regulate electron transfer from NADPH to molecular oxygen. Here we identify an antagonistic interaction between Rac and the closely related GTPase Cdc42 at the level of flavocytochrome b(558) that regulates the formation of ROS. Cdc42 is unable to stimulate ROS formation by NADPH oxidase, but Cdc42, like Rac1 and Rac2, was able to specifically bind to flavocytochrome b(558) in vitro. Cdc42 acted as a competitive inhibitor of Rac1- and Rac2-mediated ROS formation in a recombinant cell-free oxidase system. Inhibition was dependent on the Cdc42 insert domain but not the Switch I region. Transient expression of Cdc42Q61L inhibited ROS formation induced by constitutively active Rac1 in an NADPH oxidase-expressing Cos7 cell line. Inhibition of Cdc42 activity by transduction of the Cdc42-binding domain of Wiscott-Aldrich syndrome protein into human neutrophils resulted in an enhanced fMetLeuPhe-induced oxidative response, consistent with inhibitory cross-talk between Rac and Cdc42 in activated neutrophils. We propose here a novel antagonism between Rac and Cdc42 GTPases at the level of the Nox proteins that modulates the generation of ROS used for host defense, cell signaling, and transformation. PMID:15123662

Diebold, Becky A; Fowler, Bruce; Lu, Justine; Dinauer, Mary C; Bokoch, Gary M

2004-07-01

337

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.

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

2013-01-01

338

Isoform- and species-specific control of inositol 1,4,5-trisphosphate (IP3) receptors by reactive oxygen species.  

PubMed

Reactive oxygen species (ROS) stimulate cytoplasmic [Ca(2+)] ([Ca(2+)]c) signaling, but the exact role of the IP3 receptors (IP3R) in this process remains unclear. IP3Rs serve as a potential target of ROS produced by both ER and mitochondrial enzymes, which might locally expose IP3Rs at the ER-mitochondrial associations. Also, IP3Rs contain multiple reactive thiols, common molecular targets of ROS. Therefore, we have examined the effect of superoxide anion (O2) on IP3R-mediated Ca(2+) signaling. In human HepG2, rat RBL-2H3, and chicken DT40 cells, we observed [Ca(2+)]c spikes and frequency-modulated oscillations evoked by a O2 donor, xanthine (X) + xanthine oxidase (XO), dose-dependently. The [Ca(2+)]c signal was mediated by ER Ca(2+) mobilization. X+XO added to permeabilized cells promoted the [Ca(2+)]c rise evoked by submaximal doses of IP3, indicating that O2 directly sensitizes IP3R-mediated Ca(2+) release. In response to X+XO, DT40 cells lacking two of three IP3R isoforms (DKO) expressing either type 1 (DKO1) or type 2 IP3Rs (DKO2) showed a [Ca(2+)]c signal, whereas DKO expressing type 3 IP3R (DKO3) did not. By contrast, IgM that stimulates IP3 formation, elicited a [Ca(2+)]c signal in every DKO. X+XO also facilitated the Ca(2+) release evoked by submaximal IP3 in permeabilized DKO1 and DKO2 but was ineffective in DKO3 or in DT40 lacking every IP3R (TKO). However, X+XO could also facilitate the effect of suboptimal IP3 in TKO transfected with rat IP3R3. Although in silico studies failed to identify a thiol missing in the chicken IP3R3, an X+XO-induced redox change was documented only in the rat IP3R3. Thus, ROS seem to specifically sensitize IP3Rs through a thiol group(s) within the IP3R, which is probably inaccessible in the chicken IP3R3. PMID:24469450

Bánsághi, Száva; Golenár, Tünde; Madesh, Muniswamy; Csordás, György; RamachandraRao, Satish; Sharma, Kumar; Yule, David I; Joseph, Suresh K; Hajnóczky, György

2014-03-21

339

Accelerated endothelial dysfunction in mild prediabetic insulin resistance: the early role of reactive oxygen species.  

PubMed

Insulin resistance is well established as an independent risk factor for the development of type 2 diabetes and cardiovascular atherosclerosis. Most studies have examined atherogenesis in models of severe insulin resistance or diabetes. However, by the time of diagnosis, individuals with type 2 diabetes already demonstrate a significant atheroma burden. Furthermore, recent studies suggest that, even in adolescence, insulin resistance is a progressive disorder that increases cardiovascular risk. In the present report, we studied early mechanisms of reduction in the bioavailability of the antiatheroscerotic molecule nitric oxide (NO) in very mild insulin resistance. Mice with haploinsufficiency for the insulin receptor (IRKO) are a model of mild insulin resistance with preserved glycemic control. We previously demonstrated that 2-mo-old (Young) IRKO mice have preserved vasorelaxation responses to ACh. This remained the case at 4 mo of age. However, by 6 mo, despite no significant deterioration in glucose homeostasis (Adult), IRKO mice had marked blunting of ACh-mediated vasorelaxation [IRKO maximum contraction response (E(max)) 66 +/- 5% vs. wild type 87 +/- 4%, P < 0.01]. Despite the endothelial dysfunction demonstrated, aortic endothelial nitric oxide synthase (eNOS) mRNA levels were similar in Adult IRKO and wild-type mice, and, interestingly, aortic eNOS protein levels were increased, suggesting a compensatory upregulation in the IRKO. We then examined the potential role of reactive oxygen species in mediating early endothelial dysfunction. The superoxide dismutase mimetic Mn(III)tetrakis(1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP) restored ACh relaxation responses in the Adult IRKO (E(max) to ACh with MnTMPyP 85 +/- 5%). Dihydroethidium fluorescence of aortas and isolated coronary microvascular endothelial cells confirmed a substantial increase in endothelium-derived reactive oxygen species in IRKO mice. These data demonstrate that mild insulin resistance is a potent substrate for accelerated endothelial dysfunction and support a role for endothelial cell superoxide production as a mechanism underlying the early reduction in NO bioavailability. PMID:17711985

Duncan, Edward R; Walker, Simon J; Ezzat, Vivienne A; Wheatcroft, Stephen B; Li, Jian-Mei; Shah, Ajay M; Kearney, Mark T

2007-11-01

340

Glucocorticoids increase the accumulation of reactive oxygen species and enhance adriamycin-induced toxicity in neuronal culture.  

PubMed

Glucocorticoids (GCs), the adrenal steroids secreted during stress, are known to affect diverse processes involving reactive oxygen species, from exacerbation of ischemic damage to alteration of antioxidant enzyme activities. To determine whether GCs have a direct effect on oxidative processes, we constructed a dose-response curve using adriamycin, an oxygen radical generator, in primary neuronal cultures. In cultures derived from the hippocampus, which has the greatest concentration of corticosteroid receptors in the brain, higher levels of GCs significantly increased adriamycin toxicity, while not being toxic themselves. In cortical cultures, which contain lesser amounts of corticosteroid receptors, GCs had no effect on the adriamycin dose-response. Surprisingly, when tested with dichlorofluorescein for levels of reactive oxygen species (ROS), GCs increased ROS by approximately 10% basally and at all adriamycin doses in both hippocampal and cortical cultures. Thus, greater generation of ROS does not account for the increased susceptibility of the hippocampus to oxidative damage. PMID:8812153

McIntosh, L J; Sapolsky, R M

1996-10-01

341

Reactive oxygen species in spermatozoa: methods for monitoring and significance for the origins of genetic disease and infertility  

PubMed Central

Human spermatozoa generate low levels of reactive oxygen species in order to stimulate key events, such as tyrosine phosphorylation, associated with sperm capacitation. However, if the generation of these potentially pernicious oxygen metabolites becomes elevated for any reason, spermatozoa possess a limited capacity to protect themselves from oxidative stress. As a consequence, exposure of human spermatozoa to intrinsically- or extrinsically- generated reactive oxygen intermediates can result in a state of oxidative stress characterized by peroxidative damage to the sperm plasma membrane and DNA damage to the mitochondrial and nuclear genomes. Oxidative stress in the male germ line is associated with poor fertilization rates, impaired embryonic development, high levels of abortion and increased morbidity in the offspring, including childhood cancer. In this review, we consider the possible origins of oxidative damage to human spermatozoa and reflect on the important contribution such stress might make to the origins of genetic disease in our species.

Baker, Mark A; Aitken, R John

2005-01-01

342

Nitric Oxide and Reactive Oxygen Species Production Causes Progressive Damage in Rats after Cessation of Silica Inhalation  

Microsoft Academic Search

Our laboratory has previously reported results from a rat silica inhalation study which determined that, even after silica exposure ended, pulmonary inflammation and damage progressed with subsequent fibrosis development. In the present study, the re- lationship between silica exposure, nitric oxide (NO) and reactive oxygen species (ROS) production, and the resultant pulmonary damage is investigated in this model. Rats were

D. W. Porter; L. L. Millecchia; P. Willard; V. A. Robinson; D. Ramsey; J. McLaurin; A. Khan; K. Brumbaugh; C. M. Beighley; A. Teass; V. Castranova

2005-01-01

343

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

Microsoft Academic Search

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

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

2006-01-01

344

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

345

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

Microsoft Academic Search

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

Peter Kovacic; Ratnasamy Somanathan

346

Hepatocyte Growth Factor Suppresses Production of Reactive Oxygen Species and Release of Eosinophil-Derived Neurotoxin from Human Eosinophils  

Microsoft Academic Search

Background:Reactive oxygen species (ROS) and eosinophilic granule proteins such as eosinophil-derived neurotoxin (EDN) are known to damage bronchial tissue and cause airway hyperresponsiveness (AHR) in asthma. Hepatocyte growth factor (HGF) regulates various biological activities and is known to be a multifunctional factor. In our previous study, we found that HGF suppressed allergic airway inflammation and AHR in a murine model

Wataru Ito; Masahide Takeda; Miyoshi Fujita; Yumiko Kamada; Hikari Kato; Takahito Chiba; Kazutoshi Yamaguchi; Shigeharu Ueki; Hiroyuki Kayaba; Arihiko Kanehiro; Junichi Chihara

2008-01-01

347

Simultaneous analysis of reactive oxygen species and reduced glutathione content in living cells by polychromatic flow cytometry  

Microsoft Academic Search

Reactive oxygen species (ROS) are continuously produced in the cell as a consequence of aerobic metabolism, and are controlled by several antioxidant mechanisms. An accurate measurement of ROS is essential to evaluate the redox status of the cell, or the effects of molecules with the pro-oxidant or antioxidant activity. Here we report a cytofluorimetric technique for measuring simultaneously, at the

Roberta Ferraresi; Leonarda Troiano; Erika Roat; Lara Gibellini; Linda Bertoncelli; Milena Nasi; Marcello Pinti; Andrea Cossarizza

2009-01-01

348

Reactive Oxygen Species Facilitate Translocation of Hormone Sensitive Lipase to the Lipid Droplet During Lipolysis in Human Differentiated Adipocytes  

Microsoft Academic Search

In obesity, there is an increase in reactive oxygen species (ROS) within adipose tissue caused by increases in inflammation and overnutrition. Hormone sensitive lipase (HSL) is part of the canonical lipolytic pathway and critical for complete lipolysis. This study hypothesizes that ROS is a signal that integrates regulation of lipolysis by targeting HSL. Experiments were performed with human differentiated adipocytes

Sarah A. Krawczyk; Jorge F. Haller; Tom Ferrante; Raphael A. Zoeller; Barbara E. Corkey

2012-01-01

349

Curcumin potentiates doxorubicin-induced apoptosis in H9c2 cardiac muscle cells through generation of reactive oxygen species  

Microsoft Academic Search

Doxorubicin (DOX) is a widely used chemotherapy agent. The major adverse effect of DOX treatment in cancer patients is the onset of cardiomyopathy and heart failure. Reactive oxygen species (ROS) are proposed to be responsible for DOX cardiotoxicity. Curcumin, a natural compound extracted from Curcuma Longa L., is known for its anti-oxidant properties. It has been identified as increased apoptosis

Leila Hosseinzadeh; Javad Behravan; Fatemeh Mosaffa; Gholamreza Bahrami; Ahmadreza Bahrami; Gholamreza Karimi

2011-01-01

350

Mutagenicity and cytotoxicity of reactive oxygen and nitrogen species in the MN11 murine tumor cell line  

Microsoft Academic Search

There is increasing evidence that endogenously generated reactive oxygen (ROS) and reactive nitrogen (RNS) species at sites of inflammation and in tumors may be genotoxic. We have developed a murine tumor model (MN-11) in which mutations at the hypoxanthine phosphoribosyltransferase (HPRT) locus, arising both in vitro and in vivo, can be detected. In the present report, we describe an in

Jagdeep K Sandhu; H. Chaim Birnboim

1997-01-01

351

Coordinated Behavior of Mitochondria in Both Space and Time: A Reactive Oxygen Species-Activated Wave of Mitochondrial Depolarization  

Microsoft Academic Search

Reactive oxygen species (ROS) can trigger a transient burst of mitochondrial ROS production via ROS activation of the mitochondrial permeability transition pore (MPTP), a phenomenon termed ROS-induced ROS release (RIRR). The goal of this study was to investigate if the generation of ROS in a discrete region of a cardiomyocyte could serve to propagate RIRR-mediated mitochondrial depolarizations throughout a cell.

Nathan R. Brady; Steven P. Elmore; Johannes J. H. G. M. van Beek; Klaas Krab; Pierre J. Courtoy; Louis Hue; Hans V. Westerhoff

2004-01-01

352

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

Microsoft Academic Search

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

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

2000-01-01

353

Effects of dietary carbohydrate on delayed onset muscle soreness and reactive oxygen species after contraction induced muscle damage  

Microsoft Academic Search

Background: Delayed onset muscle soreness (DOMS) occurs after unaccustomed exercise and has been suggested to be attributable to reactive oxygen species (ROS). Previous studies have shown increased ROS after lengthening contractions, attributable to invading phagocytes. Plasma glucose is a vital fuel for phagocytes, therefore carbohydrate (CHO) status before exercise may influence ROS production and DOMSObjective: To examine the effect of

G L Close; T Ashton; T Cable; D Doran; C Noyes; F McArdle; D P M MacLaren

2005-01-01

354

Characterization of surface and bulk oxygen species of three way catalysts by O 2 TPD and H 2 TPR  

Microsoft Academic Search

The deactivation of three way catalysts (TWC) can be studied by the determination of the change of some of their properties such as: specific surface area, catalytic activity or precious metal dispersion. Two qualitative and quantitative methods have been investigated in order to characterize TWC oxygen species: Temperature Programmed Desorption (O2 TPD) and Temperature Programmed Reduction in hydrogen (H2 TPR).TPD

C. Bouly; K. Chandes; D. Maret; D. Bianchi

1995-01-01

355

Mitochondrial Reactive Oxygen Species Trigger Hypoxia-Inducible Factor-Dependent Extension of the Replicative Life Span during Hypoxia  

Microsoft Academic Search

Physiological hypoxia extends the replicative life span of human cells in culture. Here, we report that hypoxic extension of replicative life span is associated with an increase in mitochondrial reactive oxygen species (ROS) in primary human lung fibroblasts. The generation of mitochondrial ROS is necessary for hypoxic activation of the transcription factor hypoxia-inducible factor (HIF). The hypoxic extension of replicative

Eric L. Bell; Tatyana A. Klimova; James Eisenbart; Paul T. Schumacker; Navdeep S. Chandel

2007-01-01

356

Role of mitochondrial reactive oxygen species in hypoxia-dependent increase in intracellular calcium in pulmonary artery myocytes  

Microsoft Academic Search

Previous studies examining the role of mitochondria-derived reactive oxygen species (ROS) in hypoxic responses have been mainly conducted in isolated lungs and cultured pulmonary artery smooth muscle cells (PASMCs) using mitochondrial inhibitors, and yielded largely conflicting results. Here we report that in freshly isolated mouse PASMCs, which are devoid of the mixed responses from multi-types of cells in lungs and

Qing-Song Wang; Yun-Min Zheng; Ling Dong; Ye-Shih Ho; Zhongmao Guo; Yong-Xiao Wang

2007-01-01

357

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

Microsoft Academic Search

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

Antonio Valencia; Irene E Kochevar

2008-01-01

358

Phagocyte-Derived Reactive Oxygen Species Do Not Influence the Progression of Murine Blood-Stage Malaria Infections  

Microsoft Academic Search

functional NADPH oxidase and thus the ability to produce phagocyte-derived reactive oxygen species. We found that the absence of functional NADPH oxidase in the gene knockout mice had no effect on the parasitemia or total parasite burden in mice infected with either resolving (Plasmodium yoelii and Plasmodium chabaudi K562) or fatal (Plasmodium berghei ANKA, Plasmodium berghei K173 and Plasmodium vinckei

S. M. Potter; A. J. Mitchell; W. B. Cowden; L. A. Sanni; M. Dinauer; J. B. de Haan; N. H. Hunt

2005-01-01

359

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

EPA Science Inventory

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

360

Reactive oxygen and nitrogen species induce protein and DNA modifications driving arthrofibrosis following total knee arthroplasty  

PubMed Central

Background Arthrofibrosis, occurring in 3%-4% of patients following total knee arthroplasty (TKA), is a challenging condition for which there is no defined cause. The hypothesis for this study was that disregulated production of reactive oxygen species (ROS) and nitrogen species (RNS) mediates matrix protein and DNA modifications, which result in excessive fibroblastic proliferation. Results We found increased numbers of macrophages and lymphocytes, along with elevated amounts of myeloperoxidase (MPO) in arthrofibrotic tissues when compared to control tissues. MPO expression, an enzyme that generates ROS/RNS, is usually limited to neutrophils and some macrophages, but was found by immunohistochemistry to be expressed in both macrophages and fibroblasts in arthrofibrotic tissue. As direct measurement of ROS/RNS is not feasible, products including DNA hydroxylation (8-OHdG), and protein nitrosylation (nitrotyrosine) were measured by immunohistochemistry. Quantification of the staining showed that 8-OHdg was significantly increased in arthrofibrotic tissue. There was also a direct correlation between the intensity of inflammation and ROS/RNS to the amount of heterotopic ossification (HO). In order to investigate the aberrant expression of MPO, a real-time oxidative stress polymerase chain reaction array was performed on fibroblasts isolated from arthrofibrotic and control tissues. The results of this array confirmed the upregulation of MPO expression in arthrofibrotic fibroblasts and highlighted the downregulated expression of the antioxidants, superoxide dismutase1 and microsomal glutathione S-transferase 3, as well as the significant increase in thioredoxin reductase, a known promoter of cell proliferation, and polynucleotide kinase 3'-phosphatase, a key enzyme in the base excision repair pathway for oxidative DNA damage. Conclusion Based on our current findings, we suggest that ROS/RNS initiate and sustain the arthrofibrotic response driving aggressive fibroblast proliferation and subsequent HO.

2009-01-01

361

Surface functionalization of titanium dioxide nanoparticles: Photo-stability and reactive oxygen species (ROS) generation  

NASA Astrophysics Data System (ADS)

Metal oxide nanoparticles are becoming increasingly prevalent in society for applications of sunscreens, cosmetics, paints, biomedical imaging, and photovoltaics. Due to the increased surface area to volume ratio of nanoparticles compared to bulk materials, it is important to know the health and safety impacts of these materials. One mechanism of toxicity of nominally "safe" materials such as TiO 2 is through the photocatalytic generation of reactive oxygen species (ROS). ROS production and ligand degradation can affect the bioavailability of these particles in aqueous organisms. We have investigated ROS generation by functionalized TiO2 nanoparticles and its influence on aggregation and bioavailability and toxicity to zebrafish embryos/larvae. For these studies we investigated anatase TiO2 nanoparticles. For application purposes and solution stability, the TiO2 nanoparticles were functionalized with a variety of ligands such as citrate, 3,4-dihydroxybenzaldehyde, and ascorbate. We quantitatively examined the amount of ROS produced in aqueous solution using fluorescent probes and see that more ROS is produced under UV light than in the dark control. Our measurements show that TiO2 toxicity reaches a maximum for nanoparticles with smaller diameters, and is correlated with surface area dependent changes in ROS generation. In an effort to reduce toxicity through control of the surface and surface ligands, we synthesized anatase nanoparticles of different sizes, functionalized them with different ligands, and examined the resulting ROS generation and ligand stability. Using a modular ligand containing a hydrophobic inner region and a hydrophilic outer region, we synthesized water-stable nanoparticles, via two different chemical reactions, having much-reduced ROS generation and thus reduced toxicity. These results suggest new strategies for making safer nanoparticles while still retaining their desired properties. We also examine the degradation of the different ligands on the surface of the particles using XPS and FTIR. The combination of ROS production and ligand degradation can affect the bioavailability of these particles in aqueous species.

Louis, Kacie M.

362

Toxic effects of MPP + and MPTP in PC12 cells independent of reactive oxygen species formation  

Microsoft Academic Search

MPTP is a toxin presumed to damage dopamine-secreting neurons by an oxygen free radical-mediated mechanism. Two steps in MPTP metabolism are the primary candidates for oxygen free radical generation: (a) MPTP oxidation to MPP+ by a monoamine oxidase and (b) NADH dehydrogenase inhibition by MPP+. In order to test the idea that MPTP toxicity is mediated by oxygen free radicals,

Carlos Fonck; Michel Baudry

2001-01-01

363

Paclitaxel induces vascular endothelial growth factor expression through reactive oxygen species production.  

PubMed

The antineoplastic drug paclitaxel is known to block cells in the G2/M phase of the cell cycle through stabilization of microtubules. The development of paclitaxel resistance in tumors is one of the most significant obstacles to successful therapy. Vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) are important regulators of neovascularization. HIF-1 regulates VEGF expression at the transcriptional level. Here, we investigated whether paclitaxel treatment affects VEGF expression for the development of paclitaxel resistance. Paclitaxel treatment induced dose-dependent cell death and increased VEGF expression. Paclitaxel also induced nuclear factor-kappaB activation and stabilized HIF-1alpha, which stimulated luciferase activity of HIF-1alpha response element on VEGF gene. As paclitaxel treatment produced reactive oxygen species (ROS), VEGF expression was increased by H2O2 treatment and reduced by various ROS scavengers such as N-acetyl-L-cysteine, pyrrolidine dithiocarbamate and diphenylene iodonium. Paclitaxel-induced cell death was aggravated by incubation with those ROS scavengers. Collectively, this suggests that paclitaxel-induced VEGF expression could be mediated by paclitaxel-induced ROS production through nuclear factor-kappaB activation and HIF-1alpha stabilization, which could affect resistance induction to antitumor therapeutics during cancer treatment. PMID:18322419

Kim, Hyun Sun; Oh, Jin Mi; Jin, Dong Hoon; Yang, Kyu-Hwan; Moon, Eun-Yi

2008-01-01

364

Wogonin potentiates cisplatin-induced cancer cell apoptosis through accumulation of intracellular reactive oxygen species.  

PubMed

Chemoresistance to cisplatin is a major limitation of cisplatin-based chemotherapy in the clinic. The combination of cisplatin with other agents has been recognized as a promising strategy to overcome cisplatin resistance. Previous studies have shown that wogonin (5,7-dihydroxy-8-methoxyflavone), a flavonoid isolated from the root of the medicinal herb Scutellaria baicalensis Georgi, sensitizes cancer cells to chemotheraputics such as etoposide, adriamycin, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TNF. However, the effect of wogonin on cisplatin-induced cytotoxicity has not been previously reported. In this study, the non-small cell lung cancer cell line A549 and the cervical cancer cell line HeLa were treated with wogonin or cisplatin individually or in combination. It was found for the first time that wogonin is able to sensitize cisplatin-induced apoptosis in both A549 cells and HeLa cells as indicated by the potentiation of activation of caspase-3, and cleavage of the caspase-3 substrate PARP in wogonin and cisplatin co-treated cells. Importantly, wogonin robustly induced H2O2 accumulation in these cells, which substantially contributes to the sensitization of cisplatin cytotoxicity by wogonin, as two reactive oxygen species scavengers, butylated hydroxyanisole (BHA) and N-acetyl-L-cysteine (NAC), significantly suppressed the potentiated cytotoxicity caused by wogonin and cisplatin co-treatment. The results from this study provide important new evidence supporting the potential use of wogonin as a cisplatin sensitizer for cancer therapy. PMID:22665077

He, Fan; Wang, Qiong; Zheng, Xue-Lian; Yan, Jia-Qi; Yang, Lan; Sun, Hong; Hu, Li-Na; Lin, Yong; Wang, Xia

2012-08-01

365

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.

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

2008-01-01

366

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

PubMed

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

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

2013-12-01

367

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

PubMed Central

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

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

2013-01-01

368

TNF dually mediates resistance and susceptibility to mycobacteria via mitochondrial reactive oxygen species.  

PubMed

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

Roca, Francisco J; Ramakrishnan, Lalita

2013-04-25

369

Induction of apoptosis by cordycepin via reactive oxygen species generation in human leukemia cells.  

PubMed

Cordycepin (3'-deoxyadenosin), a specific polyadenylation inhibitor, is the main functional component in Cordyceps militaris, one of the top three renowned traditional Chinese medicines. Cordycepin has been shown to possess many pharmacological activities including immunological stimulation, and anti-bacterial, anti-viral, and anti-tumor effects. However, the mechanisms underlying its anti-cancer mechanisms are not yet understood. In this study, the apoptotic effects of cordycepin were investigated in human leukemia cells. Treatment with cordycepin significantly inhibited cell growth in a concentration-dependent manner by inducing apoptosis but not necrosis. This induction was associated with generation of reactive oxygen species (ROS), mitochondrial dysfunction, activation of caspases, and cleavage of poly(ADP-ribose) polymerase protein. However, apoptosis induced by cordycepin was attenuated by caspase inhibitors, indicating an important role for caspases in cordycepin responses. Administration of N-acetyl-l-cysteine, a scavenger of ROS, also significantly inhibited cordycepin-induced apoptosis and activation of caspases. These results support a mechanism whereby cordycepin induces apoptosis of human leukemia cells through a signaling cascade involving a ROS-mediated caspase pathway. PMID:21310227

Jeong, Jin-Woo; Jin, Cheng-Yun; Park, Cheol; Hong, Su Hyun; Kim, Gi-Young; Jeong, Yong Kee; Lee, Jae-Dong; Yoo, Young Hyun; Choi, Yung Hyun

2011-06-01

370

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

PubMed

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

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

2013-11-01

371

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

372

Mouse Melanoma Cell Migration is Dependent on Production of Reactive Oxygen Species under Normoxia Condition  

PubMed Central

Cell migration plays a role in many physiological and pathological processes. Reactive oxygen species (ROS) produced in mammalian cells influence intracellular signaling processes which in turn regulate various biological activities. Here, we investigated whether melanoma cell migration could be controlled by ROS production under normoxia condition. Cell migration was measured by wound healing assay after scratching confluent monolayer of B16F10 mouse melanoma cells. Cell migration was enhanced over 12 h after scratching cells. In addition, we found that ROS production was increased by scratching cells. ERK phosphorylation was also increased by scratching cells but it was decreased by the treatment with ROS scavengers, N-acetylcysteine (NAC). Tumor cell migration was inhibited by the treatment with PD98059, ERK inhibitor, NAC or DPI, well-known ROS scavengers. Tumor cell growth as judged by succinate dehydrogenase activity was inhibited by NAC treatment. When mice were intraperitoneally administered with NAC, the intracellular ROS production was reduced in peripheral blood mononuclear cells. In addition, B16F10 tumor growth was significantly inhibited by in vivo treatment with NAC. Collectively, these findings suggest that tumor cell migration and growth could be controlled by ROS production and its downstream signaling pathways, in vitro and in vivo.

Im, Yun-Sun; Ryu, Yun-Kyoung; Moon, Eun-Yi

2012-01-01

373

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.

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

2012-01-01

374

Bid-induced mitochondrial membrane permeabilization waves propagated by local reactive oxygen species (ROS) signaling  

PubMed Central

Bid-induced mitochondrial membrane permeabilization and cytochrome c release are central to apoptosis. It remains a mystery how tiny amounts of Bid synchronize the function of a large number of discrete organelles, particularly in mitochondria-rich cells. Looking at cell populations, the rate and lag time of the Bid-induced permeabilization are dose-dependent, but even very low doses lead eventually to complete cytochrome c release. By contrast, individual mitochondria display relatively rapid and uniform kinetics, indicating that the dose dependence seen in populations is due to a spreading of individual events in time. We report that Bid-induced permeabilization and cytochrome c release regularly demonstrate a wave-like pattern, propagating through a cell at a constant velocity without dissipation. Such waves do not depend on caspase activation or permeability transition pore opening. However, reactive oxygen species (ROS) scavengers suppressed the coordination of cytochrome c release and also inhibited Bid-induced cell death, whereas both superoxide and hydrogen peroxide sensitized mitochondria to Bid-induced permeabilization. Thus, Bid engages a ROS-dependent, local intermitochondrial potentiation mechanism that amplifies the apoptotic signal as a wave.

Garcia-Perez, Cecilia; Roy, Soumya Sinha; Naghdi, Shamim; Lin, Xuena; Davies, Erika; Hajnoczky, Gyorgy

2012-01-01

375

Respiratory long-term facilitation following intermittent hypoxia requires reactive oxygen species formation.  

PubMed

Acute intermittent hypoxia (AIH) elicits a form of respiratory plasticity known as long-term facilitation (LTF). LTF is a progressive and sustained increase in respiratory motor output as expressed in phrenic and hypoglossal (XII) nerve activity. Since reactive oxygen species (ROS) play important roles in several forms of neuroplasticity, and ROS production is increased by intermittent hypoxia, we tested the hypothesis that ROS are necessary for phrenic and XII LTF following AIH. Urethane-anesthetized, paralyzed, vagotomized and pump-ventilated Sprague-Dawley rats were exposed to AIH (11% O2, 3, 5 min episodes, 5 min intervals), and both phrenic and XII nerve activity were monitored for 60 min post-AIH. Although phrenic and XII LTF were observed in control rats, i.v. manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP), a superoxide anion scavenger, attenuated both phrenic and XII LTF in a dose dependent manner. Localized application of MnTMPyP (5.5 mM; 10 microl) to the intrathecal space of the cervical spinal cord (C4) abolished phrenic, but not XII LTF. Thus, ROS are necessary for AIH-induced respiratory LTF, and the relevant ROS appear to be localized near respiratory motor nuclei since cervical MnTMPyP injections impaired phrenic (and not XII) LTF. Phrenic LTF is a novel form of ROS-dependent neuroplasticity since its ROS-dependence resides in the spinal cord. PMID:18207649

MacFarlane, P M; Mitchell, G S

2008-03-01

376

Synergistic Triggering of Superoxide Flashes by Mitochondrial Ca2+ Uniport and Basal Reactive Oxygen Species Elevation*  

PubMed Central

Mitochondrial superoxide flashes reflect a quantal, bursting mode of reactive oxygen species (ROS) production that arises from stochastic, transient opening of the mitochondrial permeability transition pore (mPTP) in many types of cells and in living animals. However, the regulatory mechanisms and the exact nature of the flash-coupled mPTP remain poorly understood. Here we demonstrate a profound synergistic effect between mitochondrial Ca2+ uniport and elevated basal ROS production in triggering superoxide flashes in intact cells. Hyperosmotic stress potently augmented the flash activity while simultaneously elevating mitochondrial Ca2+ and ROS. Blocking mitochondrial Ca2+ transport by knockdown of MICU1 or MCU, newly identified components of the mitochondrial Ca2+ uniporter, or scavenging mitochondrial basal ROS markedly diminished the flash response. More importantly, whereas elevating Ca2+ or ROS production alone was inefficacious in triggering the flashes, concurrent physiological Ca2+ and ROS elevation served as the most powerful flash activator, increasing the flash incidence by an order of magnitude. Functionally, superoxide flashes in response to hyperosmotic stress participated in the activation of JNK and p38. Thus, physiological levels of mitochondrial Ca2+ and ROS synergistically regulate stochastic mPTP opening and quantal ROS production in intact cells, marking the flash as a coincidence detector of mitochondrial Ca2+ and ROS signals.

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

2013-01-01

377

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

PubMed

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

2014-03-01

378

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.

2013-01-01

379

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.

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

2014-01-01

380

Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling.  

PubMed

Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism as well as in cellular response to xenobiotics, cytokines, and bacterial invasion. Oxidative stress refers to the imbalance due to excess ROS or oxidants over the capability of the cell to mount an effective antioxidant response. Oxidative stress results in macromolecular damage and is implicated in various disease states such as atherosclerosis, diabetes, cancer, neurodegeneration, and aging. Paradoxically, accumulating evidence indicates that ROS also serve as critical signaling molecules in cell proliferation and survival. While there is a large body of research demonstrating the general effect of oxidative stress on signaling pathways, less is known about the initial and direct regulation of signaling molecules by ROS, or what we term the "oxidative interface." Cellular ROS sensing and metabolism are tightly regulated by a variety of proteins involved in the redox (reduction/oxidation) mechanism. This review focuses on the molecular mechanisms through which ROS directly interact with critical signaling molecules to initiate signaling in a broad variety of cellular processes, such as proliferation and survival (MAP kinases, PI3 kinase, PTEN, and protein tyrosine phosphatases), ROS homeostasis and antioxidant gene regulation (thioredoxin, peroxiredoxin, Ref-1, and Nrf-2), mitochondrial oxidative stress, apoptosis, and aging (p66Shc), iron homeostasis through iron-sulfur cluster proteins (IRE-IRP), and ATM-regulated DNA damage response. PMID:22286106

Ray, Paul D; Huang, Bo-Wen; Tsuji, Yoshiaki

2012-05-01

381

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

PubMed

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

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

2014-07-01

382

Electrical stimulation of human embryonic stem cells: cardiac differentiation and the generation of reactive oxygen species.  

PubMed

Exogenous electric fields have been implied in cardiac differentiation of mouse embryonic stem cells and the generation of reactive oxygen species (ROS). In this work, we explored the effects of electrical field stimulation on ROS generation and cardiogenesis in embryoid bodies (EBs) derived from human embryonic stem cells (hESC, line H13), using a custom-built electrical stimulation bioreactor. Electrical properties of the bioreactor system were characterized by electrochemical impedance spectroscopy (EIS) and analysis of electrical currents. The effects of the electrode material (stainless steel, titanium-nitride-coated titanium, titanium), length of stimulus (1 and 90 s) and age of EBs at the onset of electrical stimulation (4 and 8 days) were investigated with respect to ROS generation. The amplitude of the applied electrical field was 1 V/mm. The highest rate of ROS generation was observed for stainless steel electrodes, for signal duration of 90 s and for 4-day-old EBs. Notably, comparable ROS generation was achieved by incubation of EBs with 1 nM H(2)O(2). Cardiac differentiation in these EBs was evidenced by spontaneous contractions, expression of troponin T and its sarcomeric organization. These results imply that electrical stimulation plays a role in cardiac differentiation of hESCs, through mechanisms associated with the intracellular generation of ROS. PMID:19720058

Serena, Elena; Figallo, Elisa; Tandon, Nina; Cannizzaro, Christopher; Gerecht, Sharon; Elvassore, Nicola; Vunjak-Novakovic, Gordana

2009-12-10

383

Insulin Regulates Glucose Consumption and Lactate Production through Reactive Oxygen Species and Pyruvate Kinase M2  

PubMed Central

Although insulin is known to regulate glucose metabolism and closely associate with liver cancer, the molecular mechanisms still remain to be elucidated. In this study, we attempt to understand the mechanism of insulin in promotion of liver cancer metabolism. We found that insulin increased pyruvate kinase M2 (PKM2) expression through reactive oxygen species (ROS) for regulating glucose consumption and lactate production, key process of glycolysis in hepatocellular carcinoma HepG2 and Bel7402 cells. Interestingly, insulin-induced ROS was found responsible for the suppression of miR-145 and miR-128, and forced expression of either miR-145 or miR-128 was sufficient to abolish insulin-induced PKM2 expression. Furthermore, the knockdown of PKM2 expression also inhibited cancer cell growth and insulin-induced glucose consumption and lactate production, suggesting that PKM2 is a functional downstream effecter of insulin. Taken together, this study would provide a new insight into the mechanism of insulin-induced glycolysis.

Li, Qi; Liu, Xue; Yin, Yu; Zheng, Ji-Tai; Jiang, Cheng-Fei; Wang, Jing; Shen, Hua; Li, Chong-Yong; Wang, Min; Liu, Ling-Zhi; Jiang, Bing-Hua

2014-01-01

384

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.

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

385

The Impact of Various Reactive Oxygen Species on the Formation of Neutrophil Extracellular Traps  

PubMed Central

The formation of neutrophil extracellular traps (NETs) depends on the generation of reactive oxygen species (ROS). Previous studies revealed that both NADPH oxidase and myeloperoxidase (MPO) are required for NET release. However, the contribution of various ROS as well as the role of mitochondria-derived ROS has not been addressed so far. In the present study we aimed to investigate in a systematic and comprehensive manner the contribution of various ROS and ROS-generating pathways to the PMA-induced NET release. By using specific inhibitors, the role of both NADPH oxidase- and mitochondria-derived ROS as well as the contribution of superoxide dismutase (SOD) and MPO on the NET release was assessed. We could demonstrate that NADPH oxidase function is crucial for the formation of NETs. In addition, we could clearly show the involvement of MPO-derived ROS in NET release. Our results, however, did not provide evidence for the role of SOD- or mitochondria-derived ROS in NET formation.

Kirchner, Tina; Moller, Sonja; Klinger, Matthias; Solbach, Werner; Laskay, Tamas; Behnen, Martina

2012-01-01

386

Effective generation of reactive oxygen species in the mycobacterial phagosome requires K+ efflux from the bacterium.  

PubMed

Efficient killing of mycobacteria by host macrophages depends on a number of mechanisms including production of reactive oxygen species (ROS) by the phagosomal NADPH oxidase, NOX2. Survival of pathogenic mycobacteria in the phagosome relies on the ability to control maturation of the phagosome such that it is biologically and chemically altered in comparison to phagosomes containing non-pathogenic bacteria. In this study we show that the action of NOX2 to produce ROS in the mycobacterial phagosome is paradoxically dependent on a bacterial potassium transporter. We show that a Mycobacterium bovis BCG mutant (BCGDeltakef), deficient in a Kef-type K+ transporter, exhibits an increased intracellular survival phenotype in resting and activated macrophages, yet retains the ability to inhibit phagosome acidification, and does not show increased resistance to acidic conditions or ROS. Addition of a ROS scavenger replicates this phenotype in macrophages infected with wild-type BCG, and the production of ROS by macrophages infected with BCGDeltakef is substantially decreased compared with those infected with wild-type BCG. Our results suggest that increased intracellular survival of BCGDeltakef is mediated by inducing a decreased macrophage oxidative burst, and are consistent with Kef acting to alter the ionic contents of the phagosome and promoting NOX2 production of ROS. PMID:20331644

Butler, Rachel E; Cihlarova, Vera; Stewart, Graham R

2010-08-01

387

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.

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

388

Bioconvertible vitamin antioxidants improve sunscreen photoprotection against UV-induced reactive oxygen species.  

PubMed

The ability of sunscreens and antioxidants to deactivate highly destructive reactive oxygen species in human skin has remained inconclusive. Two-photon fluorescence imaging microscopy was used to determine the effect of sunscreen/antioxidant combinations upon UV-induced ROS generation in ex vivo human skin. A sunscreen combination containing octylmethoxycinnamate (Parsol MCX) and avobenzone (Parsol 1789) at SPF 8 and SPF 15 was tested for its ability to prevent UV radiation from generating ROS in the viable epidermal strata of ex vivo human skin. A UV dose equivalent to two hours of North American solar UV was used to irradiate the skin. Each sunscreen reduced the amount of ROS induced in the viable strata by a value consistent with the SPF level. UV photons that were not absorbed/scattered by the sunscreen formulations generated ROS within the viable epidermal layers. The addition of the bioconvertible antioxidants vitamin E acetate and sodium ascorbyl phosphate (STAY-C 50) improves photoprotection by converting to vitamins E and C, respectively, within the skin. The bioconversion forms an antioxidant reservoir that deactivates the ROS generated (within the strata granulosum, spinosum, and basale) by the UV photons that the sunscreens do not block in the stratum corneum. PMID:14730375

Hanson, Kerry M; Clegg, Robert M

2003-01-01

389

Extracellular ultrathin fibers sensitive to intracellular reactive oxygen species: Formation of intercellular membrane bridges  

SciTech Connect

Membrane bridges are key cellular structures involved in intercellular communication; however, dynamics for their formation are not well understood. We demonstrated the formation and regulation of novel extracellular ultrathin fibers in NIH3T3 cells using confocal and atomic force microscopy. At adjacent regions of neighboring cells, phorbol 12-myristate 13-acetate (PMA) and glucose oxidase induced ultrathin fiber formation, which was prevented by Trolox, a reactive oxygen species (ROS) scavenger. The height of ROS-sensitive ultrathin fibers ranged from 2 to 4 nm. PMA-induced formation of ultrathin fibers was inhibited by cytochalasin D, but not by Taxol or colchicine, indicating that ultrathin fibers mainly comprise microfilaments. PMA-induced ultrathin fibers underwent dynamic structural changes, resulting in formation of intercellular membrane bridges. Thus, these fibers are formed by a mechanism(s) involving ROS and involved in formation of intercellular membrane bridges. Furthermore, ultrastructural imaging of ultrathin fibers may contribute to understanding the diverse mechanisms of cell-to-cell communication and the intercellular transfer of biomolecules, including proteins and cell organelles.

Jung, Se-Hui; Park, Jin-Young; Joo, Jung-Hoon; Kim, Young-Myeong; Ha, Kwon-Soo, E-mail: ksha@kangwon.ac.kr

2011-07-15

390

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

PubMed

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. PMID:24813286

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

2014-09-15

391

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

PubMed Central

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

Miliauskas, Skaidrius; Sakalauskas, Raimundas

2013-01-01

392

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

PubMed Central

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

Cap, Michal; Vachova, Libuse; Palkova, Zdena

2012-01-01

393

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

PubMed

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

2014-06-01

394

Notch1 increases Snail expression under high reactive oxygen species conditions in hepatocellular carcinoma cells.  

PubMed

Abstract Notch1 and reactive oxygen species (ROS) modulate important pathways associated with tumor development and progression. Notably, Notch1 expression is upregulated in 41.8% of hepatocellular carcinoma (HCC) patients and ROS levels increases as HCC progresses from Grade I to Grade III. It has been established that Notch1 and ROS modulate Snail expression in malignant tumors; however, the mechanism regulating Snail protein expression is not yet known. In this study, we observed that Notch1 and ROS cooperatively increase the levels of Snail protein in Huh7 (hepatoma) cells. On its own, signaling through Notch1 increases transcription of Snail without changing protein levels. In contrast, the combined activation of the Notch1 and ROS-induced phosphoinositide 3-kinase/Akt (PI3K/Akt) signaling pathways resulted in the high expression of Snail protein. This increase in Snail expression was associated with increased Huh7 cells invasiveness. Furthermore, we observed that correlation between Snail and Notch1 expression was the strongest in advanced grade HCC tissue. In conclusion, Notch1 and ROS-induced PI3K/Akt signals cooperatively increase Snail expression and may induce malignancy in HCC. PMID:24684482

Kim, H S; Jung, G

2014-07-01

395

The impact of reactive oxygen species and genetic mitochondrial mutations in Parkinson's disease.  

PubMed

The exact pathogenesis of Parkinson's disease (PD) is still unknown and proper mechanisms that correspond to the disease remain unidentified. It is understood that PD is age-related; as age increases, the chance of onset responds accordingly. Although there are no current means of curing PD, the understanding of reactive oxygen species (ROS) provides significant insight to possible treatments. Complex I deficiencies of the respiratory chain account for the majority of unfavorable neural apoptosis generation in PD. Dopaminergic neurons are severely damaged as a result of the deficiency. Symptoms such as inhibited cognitive ability and loss of smooth motor function are the results of such impairment. The genetic mutations of Parkinson's related proteins such as PINK1 and LRRK2 contribute to mitochondrial dysfunction which precedes ROS formation. Various pathways are inhibited by these mutations, and inevitably causing neural cell damage. Antioxidants are known to negate the damaging effects of free radical overexpression. This paper expands on the specific impact of mitochondrial genetic change and production of free radicals as well as its correlation to the neurodegeneration in Parkinson's disease. PMID:23954870

Zuo, Li; Motherwell, Michael S

2013-12-10

396

?,?-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.

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

397

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

PubMed

Increasing evidence indicates that reactive oxygen species (ROS), consisting of superoxide, hydrogen peroxide, and multiple others, do not only cause oxidative stress, but rather may function as signaling molecules that promote health by preventing or delaying a number of chronic diseases, and ultimately extend lifespan. While high levels of ROS are generally accepted to cause cellular damage and to promote aging, low levels of these may rather improve systemic defense mechanisms by inducing an adaptive response. This concept has been named mitochondrial hormesis or mitohormesis. We here evaluate and summarize more than 500 publications from current literature regarding such ROS-mediated low-dose signaling events, including calorie restriction, hypoxia, temperature stress, and physical activity, as well as signaling events downstream of insulin/IGF-1 receptors, AMP-dependent kinase (AMPK), target-of-rapamycin (TOR), and lastly sirtuins to culminate in control of proteostasis, unfolded protein response (UPR), stem cell maintenance and stress resistance. Additionally, consequences of interfering with such ROS signals by pharmacological or natural compounds are being discussed, concluding that particularly antioxidants are useless or even harmful. PMID:24910588

Ristow, Michael; Schmeisser, Kathrin

2014-05-01

398

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

399

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.

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

2011-01-01

400

Candida albicans Induces Arginine Biosynthetic Genes in Response to Host-Derived Reactive Oxygen Species  

PubMed Central

The interaction of Candida albicans with phagocytes of the host's innate immune system is highly dynamic, and its outcome directly impacts the progression of infection. While the switch to hyphal growth within the macrophage is the most obvious physiological response, much of the genetic response reflects nutrient starvation: translational repression and induction of alternative carbon metabolism. Changes in amino acid metabolism are not seen, with the striking exception of arginine biosynthesis, which is upregulated in its entirety during coculture with macrophages. Using single-cell reporters, we showed here that arginine biosynthetic genes are induced specifically in phagocytosed cells. This induction is lower in magnitude than during arginine starvation in vitro and is driven not by an arginine deficiency within the phagocyte but instead by exposure to reactive oxygen species (ROS). Curiously, these genes are induced in a narrow window of sublethal ROS concentrations. C. albicans cells phagocytosed by primary macrophages deficient in the gp91phox subunit of the phagocyte oxidase do not express the ARG pathway, indicating that the induction is dependent on the phagocyte oxidative burst. C. albicans arg pathway mutants are retarded in germ tube and hypha formation within macrophages but are not notably more sensitive to ROS. We also find that the ARG pathway is regulated not by the general amino acid control response but by transcriptional regulators similar to the Saccharomyces cerevisiae ArgR complex. In summary, phagocytosis induces this single amino acid biosynthetic pathway in an ROS-dependent manner.

Jimenez-Lopez, Claudia; Collette, John R.; Brothers, Kimberly M.; Shepardson, Kelly M.; Cramer, Robert A.; Wheeler, Robert T.

2013-01-01

401

Inactive ERBB receptors cooperate with reactive oxygen species to suppress cancer progression.  

PubMed

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

2013-11-01

402

In vitro reactive oxygen species production by histatins and copper(I,II).  

PubMed

The ability of the histidine-rich peptides, histatin-5 (Hst-5) and histatin-8 (Hst-8), to support the generation of reactive oxygen species during the Cu-catalyzed oxidation of ascorbate and cysteine has been evaluated. High levels of hydrogen peroxide (70-580 mol/mol Cu/h) are produced by aqueous solutions containing Cu(II), Hst-8 or Hst-5, and a reductant, either ascorbate or cysteine, as determined by the postreaction Amplex Red assay. When the reactions are conducted in the presence of superoxide dismutase, the total hydrogen peroxide produced is decreased, more so in the presence of the peptides (up to 50%), suggesting the intermediacy of superoxide in these reactions. On the other hand, the presence of sodium azide or sodium formate, traps for hydroxyl radicals, has no appreciable effect on the total hydrogen peroxide production for the Cu-Hst systems. EPR spin-trapping studies using 5-(2,2-dimethyl-1,3-propoxy cyclophosphoryl)-5-methyl-1-pyrroline N-oxide (CYPMPO) in the cysteine-Cu(II) reactions reveal the formation of the CYPMPO-hydroperoxyl and CYPMPO-hydroxyl radical adducts in the presence of Hst-8, whereas only the latter was observed with Cu alone. PMID:18975018

Houghton, Eric A; Nicholas, Kenneth M

2009-02-01

403

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.

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

2014-01-01

404

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.

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

2014-01-01