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Sample records for accumulate reactive oxygen

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-01

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

  2. Reactive oxygen species accumulation and homeostasis are involved in plant immunity to an opportunistic fungal pathogen.

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    Taheri, Parissa; Kakooee, Tahereh

    2017-09-01

    Alternaria blight is a major and destructive disease of potato worldwide. In recent years, A. tenuissima is recognized as the most prevalent species of this phytopathogenic fungus in potato fields of Asian countries, which causes high yield losses every year. Any potato cultivar with complete resistance to this disease is not recognized, so far. Therefore, screening resistance levels of potatoes and identification of plant defense mechanisms against this fungus might be important for designing novel and effective disease management strategies for controlling the disease. In this research, the role of reactive oxygen species, antioxidants, lignin and phenolics in potato basal resistance to A. tenuissima was compared in the partially resistant Ramus and susceptible Bamba cultivars. Priming O 2 - and H 2 O 2 production and enhanced activity of peroxidase (POX) and catalase (CAT) during interaction with A. tenuissima were observed in Ramus cultivar. Application of ROS generating systems and scavengers revealed critical role of O 2 - and H 2 O 2 in potato defense, which was associated with lignification and phenolics production. More OH - and lipid peroxidation in the susceptible Bamba compared to Ramus cultivar showed their negative effects on resistance. Priming the POX and CAT activity, in correlation with upregulation of the corresponding genes was observed in Ramus. The POX and CAT inhibitors increased disease progress, which was related with decreased lignification. This assay demonstrated not only POX-dependency of lignification, but also its dependence on CAT. However, POX had more importance than CAT in potato defense and in lignification. These findings highlight the function of ROS accumulation and homeostasis in potato resistance against A. tenuissima. Copyright © 2017 Elsevier GmbH. All rights reserved.

  3. Furfural induces reactive oxygen species accumulation and cellular damage in Saccharomyces cerevisiae

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    Slininger Patricia J

    2010-01-01

    Full Text Available Abstract Background Biofuels offer a viable alternative to petroleum-based fuel. However, current methods are not sufficient and the technology required in order to use lignocellulosic biomass as a fermentation substrate faces several challenges. One challenge is the need for a robust fermentative microorganism that can tolerate the inhibitors present during lignocellulosic fermentation. These inhibitors include the furan aldehyde, furfural, which is released as a byproduct of pentose dehydration during the weak acid pretreatment of lignocellulose. In order to survive in the presence of furfural, yeast cells need not only to reduce furfural to the less toxic furan methanol, but also to protect themselves and repair any damage caused by the furfural. Since furfural tolerance in yeast requires a functional pentose phosphate pathway (PPP, and the PPP is associated with reactive oxygen species (ROS tolerance, we decided to investigate whether or not furfural induces ROS and its related cellular damage in yeast. Results We demonstrated that furfural induces the accumulation of ROS in Saccharomyces cerevisiae. In addition, furfural was shown to cause cellular damage that is consistent with ROS accumulation in cells which includes damage to mitochondria and vacuole membranes, the actin cytoskeleton and nuclear chromatin. The furfural-induced damage is less severe when yeast are grown in a furfural concentration (25 mM that allows for eventual growth after an extended lag compared to a concentration of furfural (50 mM that prevents growth. Conclusion These data suggest that when yeast cells encounter the inhibitor furfural, they not only need to reduce furfural into furan methanol but also to protect themselves from the cellular effects of furfural and repair any damage caused. The reduced cellular damage seen at 25 mM furfural compared to 50 mM furfural may be linked to the observation that at 25 mM furfural yeast were able to exit the furfural

  4. Cardiomyocyte hypertrophy induced by Endonuclease G deficiency requires reactive oxygen radicals accumulation and is inhibitable by the micropeptide humanin.

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    Blasco, Natividad; Cámara, Yolanda; Núñez, Estefanía; Beà, Aida; Barés, Gisel; Forné, Carles; Ruíz-Meana, Marisol; Girón, Cristina; Barba, Ignasi; García-Arumí, Elena; García-Dorado, David; Vázquez, Jesús; Martí, Ramon; Llovera, Marta; Sanchis, Daniel

    2018-06-01

    The endonuclease G gene (Endog), which codes for a mitochondrial nuclease, was identified as a determinant of cardiac hypertrophy. How ENDOG controls cardiomyocyte growth is still unknown. Thus, we aimed at finding the link between ENDOG activity and cardiomyocyte growth. Endog deficiency induced reactive oxygen species (ROS) accumulation and abnormal growth in neonatal rodent cardiomyocytes, altering the AKT-GSK3β and Class-II histone deacethylases (HDAC) signal transduction pathways. These effects were blocked by ROS scavengers. Lack of ENDOG reduced mitochondrial DNA (mtDNA) replication independently of ROS accumulation. Because mtDNA encodes several subunits of the mitochondrial electron transport chain, whose activity is an important source of cellular ROS, we investigated whether Endog deficiency compromised the expression and activity of the respiratory chain complexes but found no changes in these parameters nor in ATP content. MtDNA also codes for humanin, a micropeptide with possible metabolic functions. Nanomolar concentrations of synthetic humanin restored normal ROS levels and cell size in Endog-deficient cardiomyocytes. These results support the involvement of redox signaling in the control of cardiomyocyte growth by ENDOG and suggest a pathway relating mtDNA content to the regulation of cell growth probably involving humanin, which prevents reactive oxygen radicals accumulation and hypertrophy induced by Endog deficiency. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Cross talk between increased intracellular zinc (Zn2+) and accumulation of reactive oxygen species in chemical ischemia.

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    Slepchenko, Kira G; Lu, Qiping; Li, Yang V

    2017-10-01

    Both zinc (Zn 2+ ) and reactive oxygen species (ROS) have been shown to accumulate during hypoxic-ischemic stress and play important roles in pathological processes. To understand the cross talk between the two of them, here we studied Zn 2+ and ROS accumulation by employing fluorescent probes in HeLa cells to further the understanding of the cause and effect relationship of these two important cellular signaling systems during chemical-ischemia, stimulated by oxygen and glucose deprivation (OGD). We observed two Zn 2+ rises that were divided into four phases in the course of 30 min of OGD. The first Zn 2+ rise was a transient, which was followed by a latent phase during which Zn 2+ levels recovered; however, levels remained above a basal level in most cells. The final phase was the second Zn 2+ rise, which reached a sustained plateau called Zn 2+ overload. Zn 2+ rises were not observed when Zn 2+ was removed by TPEN (a Zn 2+ chelator) or thapsigargin (depleting Zn 2+ from intracellular stores) treatment, indicating that Zn 2+ was from intracellular storage. Damaging mitochondria with FCCP significantly reduced the second Zn 2+ rise, indicating that the mitochondrial Zn 2+ accumulation contributes to Zn 2+ overload. We also detected two OGD-induced ROS rises. Two Zn 2+ rises preceded two ROS rises. Removal of Zn 2+ reduced or delayed OGD- and FCCP-induced ROS generation, indicating that Zn 2+ contributes to mitochondrial ROS generation. There was a Zn 2+ -induced increase in the functional component of NADPH oxidase, p47 phox , thus suggesting that NADPH oxidase may mediate Zn 2+ -induced ROS accumulation. We suggest a new mechanism of cross talk between Zn 2+ and mitochondrial ROS through positive feedback processes that eventually causes excessive free Zn 2+ and ROS accumulations during the course of ischemic stress. Copyright © 2017 the American Physiological Society.

  6. Cadmium toxicity in Maize (Zea mays L.): consequences on antioxidative systems, reactive oxygen species and cadmium accumulation.

    Science.gov (United States)

    Anjum, Shakeel Ahmad; Tanveer, Mohsin; Hussain, Saddam; Bao, Mingchen; Wang, Longchang; Khan, Imran; Ullah, Ehsan; Tung, Shahbaz Atta; Samad, Rana Abdul; Shahzad, Babar

    2015-11-01

    Increased cadmium (Cd) accumulation in soils has led to tremendous environmental problems, with pronounced effects on agricultural productivity. Present study investigated the effects of Cd stress imposed at various concentrations (0, 75, 150, 225, 300, 375 μM) on antioxidant activities, reactive oxygen species (ROS), Cd accumulation, and productivity of two maize (Zea mays L.) cultivars viz., Run Nong 35 and Wan Dan 13. Considerable variations in Cd accumulation and in behavior of antioxidants and ROS were observed under Cd stress in both maize cultivars, and such variations governed by Cd were concentration dependent. Exposure of plant to Cd stress considerably increased Cd concentration in all plant parts particularly in roots. Wan Dan 13 accumulated relatively higher Cd in root, stem, and leaves than Run Nong 35; however, in seeds, Run Nong 35 recorded higher Cd accumulation. All the Cd toxicity levels starting from 75 μM enhanced H2O2 and MDA concentrations and triggered electrolyte leakage in leaves of both cultivars, and such an increment was more in Run Nong 35. The ROS were scavenged by the enhanced activities of superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, and glutathione peroxidase in response to Cd stress, and these antioxidant activities were higher in Wan Dan 13 compared with Run Nong 35 at all Cd toxicity levels. The grain yield of maize was considerably reduced particularly for Run Nong 35 under different Cd toxicity levels as compared with control. The Wan Dan 13 was better able to alleviate Cd-induced oxidative damage which was attributed to more Cd accumulation in roots and higher antioxidant activities in this cultivar, suggesting that manipulation of these antioxidants and enhancing Cd accumulation in roots may lead to improvement in Cd stress tolerance.

  7. Reactive oxygen species and hormone signaling cascades in endophytic bacterium induced essential oil accumulation in Atractylodes lancea.

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    Zhou, Jia-Yu; Li, Xia; Zhao, Dan; Deng-Wang, Meng-Yao; Dai, Chuan-Chao

    2016-09-01

    Pseudomonas fluorescens induces gibberellin and ethylene signaling via hydrogen peroxide in planta . Ethylene activates abscisic acid signaling. Hormones increase sesquiterpenoid biosynthesis gene expression and enzyme activity, inducing essential oil accumulation. Atractylodes lancea is a famous Chinese medicinal plant, whose main active components are essential oils. Wild A. lancea has become endangered due to habitat destruction and over-exploitation. Although cultivation can ensure production of the medicinal material, the essential oil content in cultivated A. lancea is significantly lower than that in the wild herb. The application of microbes as elicitors has become an effective strategy to increase essential oil accumulation in cultivated A. lancea. Our previous study identified an endophytic bacterium, Pseudomonas fluorescens ALEB7B, which can increase essential oil accumulation in A. lancea more efficiently than other endophytes; however, the underlying mechanisms remain unknown (Physiol Plantarum 153:30-42, 2015; Appl Environ Microb 82:1577-1585, 2016). This study demonstrates that P. fluorescens ALEB7B firstly induces hydrogen peroxide (H2O2) signaling in A. lancea, which then simultaneously activates gibberellin (GA) and ethylene (ET) signaling. Subsequently, ET activates abscisic acid (ABA) signaling. GA and ABA signaling increase expression of HMGR and DXR, which encode key enzymes involved in sesquiterpenoid biosynthesis, leading to increased levels of the corresponding enzymes and then an accumulation of essential oils. Specific reactive oxygen species and hormone signaling cascades induced by P. fluorescens ALEB7B may contribute to high-efficiency essential oil accumulation in A. lancea. Illustrating the regulation mechanisms underlying P. fluorescens ALEB7B-induced essential oil accumulation not only provides the theoretical basis for the inducible synthesis of terpenoids in many medicinal plants, but also further reveals the complex and diverse

  8. Decitabine induces delayed reactive oxygen species (ROS) accumulation in leukemia cells and induces the expression of ROS generating enzymes.

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    Fandy, Tamer E; Jiemjit, Anchalee; Thakar, Manjusha; Rhoden, Paulette; Suarez, Lauren; Gore, Steven D

    2014-03-01

    Azanucleoside DNA methyltransferase (DNMT) inhibitors are currently approved by the U.S. Food and Drug Administration for treatment of myelodysplastic syndrome. The relative contributions of DNMT inhibition and other off-target effects to their clinical efficacy remain unclear. Data correlating DNA methylation reversal and clinical response have been conflicting. Consequently, it is necessary to investigate so-called off-target effects and their impact on cell survival and differentiation. Flow cytometry was used for cell cycle, apoptosis, and reactive oxygen species (ROS) accumulation analysis. Gene expression analysis was performed using real-time PCR. DNA methylation was detected by methylation-specific PCR. Mitochondrial membrane potential was analyzed using JC-1 dye staining. Western blotting was used for quantitative protein expression analysis. 5-Aza-2'-deoxycytidine (DAC) induced cell-cycle arrest and apoptosis in leukemia cells. p53 expression was dispensable for DAC-induced apoptosis. DAC induced delayed ROS accumulation in leukemia cells but not in solid tumor cells and p53 expression was dispensable for ROS increase. ROS increase was deoxycytidine kinase dependent, indicating that incorporation of DAC into nuclear DNA is required for ROS generation. ROS accumulation by DAC was caspase-independent and mediated the dissipation of the mitochondrial membrane potential. Concordantly, ROS scavengers diminished DAC-induced apoptosis. DAC induced the expression of different NADPH oxidase isoforms and upregulated Nox4 protein expression in an ATM-dependent manner, indicating the involvement of DNA damage signaling in Nox4 upregulation. These data highlight the importance of mechanisms other than DNA cytosine demethylation in modulating gene expression and suggest investigating the relevance of ROS accumulation to the clinical activity of DAC. ©2014 AACR

  9. Blue-light induced accumulation of reactive oxygen species is a consequence of the Drosophila cryptochrome photocycle.

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    Louis-David Arthaut

    Full Text Available Cryptochromes are evolutionarily conserved blue-light absorbing flavoproteins which participate in many important cellular processes including in entrainment of the circadian clock in plants, Drosophila and humans. Drosophila melanogaster cryptochrome (DmCry absorbs light through a flavin (FAD cofactor that undergoes photoreduction to the anionic radical (FAD•- redox state both in vitro and in vivo. However, recent efforts to link this photoconversion to the initiation of a biological response have remained controversial. Here, we show by kinetic modeling of the DmCry photocycle that the fluence dependence, quantum yield, and half-life of flavin redox state interconversion are consistent with the anionic radical (FAD•- as the signaling state in vivo. We show by fluorescence detection techniques that illumination of purified DmCry results in enzymatic conversion of molecular oxygen (O2 to reactive oxygen species (ROS. We extend these observations in living cells to demonstrate transient formation of superoxide (O2•-, and accumulation of hydrogen peroxide (H2O2 in the nucleus of insect cell cultures upon DmCry illumination. These results define the kinetic parameters of the Drosophila cryptochrome photocycle and support light-driven electron transfer to the flavin in DmCry signaling. They furthermore raise the intriguing possibility that light-dependent formation of ROS as a byproduct of the cryptochrome photocycle may contribute to its signaling role.

  10. An atmospheric-pressure cold plasma leads to apoptosis in Saccharomyces cerevisiae by accumulating intracellular reactive oxygen species and calcium

    International Nuclear Information System (INIS)

    Ma, R N; Zhang, Q; Tian, Y; Su, B; Zhang, J; Fang, J; Feng, H Q; Liang, Y D

    2013-01-01

    A non-thermal plasma is known to induce apoptosis of various cells but the mechanism is not yet clear. A eukaryotic model organism Saccharomyces cerevisiaewas used to investigate the cellular and biochemical regulations of cell apoptosis and cell cycle after an atmospheric-pressure cold plasma treatment. More importantly, intracellular calcium (Ca 2+ ) was first involved in monitoring the process of plasma-induced apoptosis in this study. We analysed the cell apoptosis and cell cycle by flow cytometry and observed the changes in intracellular reactive oxygen species (ROS) and Ca 2+ concentration, cell mitochondrial membrane potential (Δψ m ) as well as nuclear DNA morphology via fluorescence staining assay. All experimental results indicated that plasma-generated ROS leads to the accumulation of intracellular ROS and Ca 2+ that ultimately contribute to apoptosis associated with cell cycle arrest at G1 phase through depolarization of Δψ m and fragmenting nuclear DNA. This work provides a novel insight into the physical and biological mechanism of apoptosis induced by a plasma which could benefit for promoting the development of plasmas applied to cancer therapy. (paper)

  11. Reactive Oxygen Species-Induced TXNIP Drives Fructose-Mediated Hepatic Inflammation and Lipid Accumulation Through NLRP3 Inflammasome Activation

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    Zhang, Xian; Zhang, Jian-Hua; Chen, Xu-Yang; Hu, Qing-Hua; Wang, Ming-Xing; Jin, Rui; Zhang, Qing-Yu; Wang, Wei; Wang, Rong; Kang, Lin-Lin; Li, Jin-Sheng; Li, Meng

    2015-01-01

    Abstract Aims: Increased fructose consumption predisposes the liver to nonalcoholic fatty liver disease (NAFLD), but the mechanisms are elusive. Thioredoxin-interacting protein (TXNIP) links oxidative stress to NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and this signaling axis may be involved in fructose-induced NAFLD. Here, we explore the role of reactive oxygen species (ROS)-induced TXNIP overexpression in fructose-mediated hepatic NLRP3 inflammasome activation, inflammation, and lipid accumulation. Results: Rats were fed a 10% fructose diet for 8 weeks and treated with allopurinol and quercetin during the last 4 weeks. Five millimolars of fructose-exposed hepatocytes (primary rat hepatocytes, rat hepatic parenchymal cells [RHPCs], HLO2, HepG2) were co-incubated with antioxidants or caspase-1 inhibitor or subjected to TXNIP or NLRP3 siRNA interference. Fructose induced NLRP3 inflammasome activation and pro-inflammatory cytokine secretion, janus-activated kinase 2/signal transducers and activators of transcription 3-mediated inflammatory signaling, and expression alteration of lipid metabolism-related genes in cultured hepatocytes and rat livers. NLRP3 silencing and caspase-1 suppression blocked these effects in primary rat hepatocytes and RHPCs, confirming that inflammasome activation alters hepatocyte lipid metabolism. Hepatocellular ROS and TXNIP were increased in animal and cell models. TXNIP silencing blocked NLRP3 inflammasome activation, inflammation, and lipid metabolism perturbations but not ROS induction in fructose-exposed hepatocytes, whereas antioxidants addition abrogated TXNIP induction and diminished the detrimental effects in fructose-exposed hepatocytes and rat livers. Innovation and Conclusions: This study provides a novel mechanism for fructose-induced NAFLD pathogenesis by which the ROS-TXNIP pathway mediates hepatocellular NLRP3 inflammasome activation, inflammation and lipid accumulation. Antioxidant

  12. ETV6/RUNX1 Induces Reactive Oxygen Species and Drives the Accumulation of DNA Damage in B Cells

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    Hans-Peter Kantner

    2013-11-01

    Full Text Available The t(12;21(p13;q22 chromosomal translocation is the most frequent translocation in childhood B cell precursor-acute lymphoblastic leukemia and results in the expression of an ETV6/RUNX1 fusion protein. The frequency of ETV6/RUNX1 fusions in newborns clearly exceeds the leukemia rate revealing that additional events occur in ETV6/RUNX1-positive cells for leukemic transformation. Hitherto, the mechanisms triggering these second hits remain largely elusive. Thus, we generated a novel ETV6/RUNX1 transgenic mouse model where the expression of the fusion protein is restricted to CD19+ B cells. These animals harbor regular B cell development and lack gross abnormalities. We established stable pro-B cell lines carrying the ETV6/RUNX1 transgene that allowed us to investigate whether ETV6/RUNX1 itself favors the acquisition of second hits. Remarkably, these pro-B cell lines as well as primary bone marrow cells derived from ETV6/RUNX1 transgenic animals display elevated levels of reactive oxygen species (ROS as tested with ETV6/RUNX1 transgenic dihydroethidium staining. In line, intracellular phospho-histone H2AX flow cytometry and comet assay revealed increased DNA damage indicating that ETV6/RUNX1 expression enhances ROS. On the basis of our data, we propose the following model: the expression of ETV6/RUNX1 creates a preleukemic clone and leads to increased ROS levels. These elevated ROS favor the accumulation of secondary hits by increasing genetic instability and doublestrand breaks, thus allowing preleukemic clones to develop into fully transformed leukemic cells.

  13. BMI-1 Mediates Estrogen-Deficiency-Induced Bone Loss by Inhibiting Reactive Oxygen Species Accumulation and T Cell Activation.

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    Li, Jinbo; Wang, Qian; Yang, Renlei; Zhang, Jiaqi; Li, Xing; Zhou, Xichao; Miao, Dengshun

    2017-05-01

    Previous studies have shown that estrogen regulates bone homeostasis through regulatory effects on oxidative stress. However, it is unclear how estrogen deficiency triggers reactive oxygen species (ROS) accumulation. Recent studies provide evidence that the B lymphoma Mo-MLV insertion region 1 (BMI-1) plays a critical role in protection against oxidative stress and that this gene is directly regulated by estrogen via estrogen receptor (ER) at the transcriptional level. In this study, ovariectomized mice were given drinking water with/without antioxidant N-acetyl-cysteine (NAC, 1 mg/mL) supplementation, and compared with each other and with sham mice. Results showed that ovariectomy resulted in bone loss with increased osteoclast surface, increased ROS levels, T cell activation, and increased TNF and RANKL levels in serum and in CD4 T cells; NAC supplementation largely prevented these alterations. BMI-1 expression levels were dramatically downregulated in CD4 T cells from ovariectomized mice. We supplemented drinking water to BMI-1-deficient mice with/without NAC and compared them with each other and with wild-type (WT) mice. We found that BMI-1 deficiency mimicked alterations observed in ovariectomy whereas NAC supplementation reversed all alterations induced by BMI-1 deficiency. Because T cells are critical in mediating ovariectomy-induced bone loss, we further assessed whether BMI-1 overexpression in lymphocytes can protect against estrogen deficiency-induced osteoclastogenesis and bone loss by inhibiting oxidative stress, T cell activation, and RANKL production. When WT and Eμ-BMI-1 transgenic mice with BMI-1 specifically overexpressed in lymphocytes were ovariectomized and compared with each other and with WT sham mice, we found that BMI-1 overexpression in lymphocytes clearly reversed all alterations induced by ovariectomy. Results from this study indicate that estrogen deficiency downregulates BMI-1 and subsequently increases ROS, T cell activation, and

  14. Alleviation of reactive oxygen species enhances PUFA accumulation in Schizochytrium sp. through regulating genes involved in lipid metabolism

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    Sai Zhang

    2018-06-01

    Full Text Available The unicellular heterotrophic thraustochytrids are attractive candidates for commercial polyunsaturated fatty acids (PUFA production. However, the reactive oxygen species (ROS generated in their aerobic fermentation process often limits their PUFA titer. Yet, the specific mechanisms of ROS involvement in the crosstalk between oxidative stress and intracellular lipid synthesis remain poorly described. Metabolic engineering to improve the PUFA yield in thraustochytrids without compromising growth is an important aspect of economic feasibility. To fill this gap, we overexpressed the antioxidative gene superoxide dismutase (SOD1 by integrating it into the genome of thraustochytrid Schizochytrium sp. PKU#Mn4 using a novel genetic transformation system. This study reports the ROS alleviation, enhanced PUFA production and transcriptome changes resulting from the SOD1 overexpression. SOD1 activity in the recombinant improved by 5.2–71.6% along with 7.8–38.5% decline in ROS during the fermentation process. Interestingly, the total antioxidant capacity in the recombinant remained higher than wild-type and above zero in the entire process. Although lipid profile was similar to that of wild-type, the concentrations of major fatty acids in the recombinant were significantly (p ≤ 0.05 higher. The PUFA titer increased up to 1232 ± 41 mg/L, which was 32.9% higher (p ≤ 0.001 than the wild type. Transcriptome analysis revealed strong downregulation of genes potentially involved in β-oxidation of fatty acids in peroxisome and upregulation of genes catalyzing lipid biosynthesis. Our results enrich the knowledge on stress-induced PUFA biosynthesis and the putative role of ROS in the regulation of lipid metabolism in oleaginous thraustochytrids. This study provides a new and alternate strategy for cost-effective industrial fermentation of PUFA. Keywords: Polyunsaturated fatty acids, Schizochytrium sp., Superoxide dismutase, Transgene

  15. Reactive Oxygen Species

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    Franchina, Davide G.; Dostert, Catherine; Brenner, Dirk

    2018-01-01

    T cells are a central component of defenses against pathogens and tumors. Their effector functions are sustained by specific metabolic changes that occur upon activation, and these have been the focus of renewed interest. Energy production inevitably generates unwanted products, namely reactive...... and transcription factors, influencing the outcome of the T cell response. We discuss here how ROS can directly fine-tune metabolism and effector functions of T cells....... oxygen species (ROS), which have long been known to trigger cell death. However, there is now evidence that ROS also act as intracellular signaling molecules both in steady-state and upon antigen recognition. The levels and localization of ROS contribute to the redox modeling of effector proteins...

  16. Gelidium elegans, an edible red seaweed, and hesperidin inhibit lipid accumulation and production of reactive oxygen species and reactive nitrogen species in 3T3-L1 and RAW264.7 cells.

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    Jeon, Hui-Jeon; Seo, Min-Jung; Choi, Hyeon-Son; Lee, Ok-Hwan; Lee, Boo-Yong

    2014-11-01

    Gelidium elegans is an edible red alga native to the intertidal area of northeastern Asia. We investigated the effect of G. elegans extract and its main flavonoids, rutin and hesperidin, on lipid accumulation and the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in 3T3-L1 and RAW264.7 cells. Our data show that G. elegans extract decreased lipid accumulation and ROS/RNS production in a dose-dependent manner. The extract also inhibited the mRNA expression of adipogenic transcription factors, such as peroxisome proliferator-activated receptor gamma and CCAAT/enhancer-binding protein alpha, while enhancing the protein expression of the antioxidant enzymes superoxide dismutases 1 and 2, glutathione peroxidase, and glutathione reductase compared with controls. In addition, lipopolysaccharide-induced nitric oxide production was significantly reduced in G. elegans extract-treated RAW264.7 cells. In analysis of the effects of G. elegans flavonoids on lipid accumulation and ROS/RNS production, only hesperidin showed an inhibitory effect on lipid accumulation and ROS production; rutin did not affect adipogenesis and ROS status. The antiadipogenic effect of hesperidin was evidenced by the downregulation of peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, and fatty acid binding protein 4 gene expression. Collectively, our data suggest that G. elegans is a potential food source containing antiobesity and antioxidant constituents. Copyright © 2014 John Wiley & Sons, Ltd.

  17. Stress Sensitivity Is Associated with Differential Accumulation of Reactive Oxygen and Nitrogen Species in Maize Genotypes with Contrasting Levels of Drought Tolerance

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    Yang, Liming; Fountain, Jake C.; Wang, Hui; Ni, Xinzhi; Ji, Pingsheng; Lee, Robert D.; Kemerait, Robert C.; Scully, Brian T.; Guo, Baozhu

    2015-01-01

    Drought stress decreases crop growth, yield, and can further exacerbate pre-harvest aflatoxin contamination. Tolerance and adaptation to drought stress is an important trait of agricultural crops like maize. However, maize genotypes with contrasting drought tolerances have been shown to possess both common and genotype-specific adaptations to cope with drought stress. In this research, the physiological and metabolic response patterns in the leaves of maize seedlings subjected to drought stress were investigated using six maize genotypes including: A638, B73, Grace-E5, Lo964, Lo1016, and Va35. During drought treatments, drought-sensitive maize seedlings displayed more severe symptoms such as chlorosis and wilting, exhibited significant decreases in photosynthetic parameters, and accumulated significantly more reactive oxygen species (ROS) and reactive nitrogen species (RNS) than tolerant genotypes. Sensitive genotypes also showed rapid increases in enzyme activities involved in ROS and RNS metabolism. However, the measured antioxidant enzyme activities were higher in the tolerant genotypes than in the sensitive genotypes in which increased rapidly following drought stress. The results suggest that drought stress causes differential responses to oxidative and nitrosative stress in maize genotypes with tolerant genotypes with slower reaction and less ROS and RNS production than sensitive ones. These differential patterns may be utilized as potential biological markers for use in marker assisted breeding. PMID:26492235

  18. Stress Sensitivity Is Associated with Differential Accumulation of Reactive Oxygen and Nitrogen Species in Maize Genotypes with Contrasting Levels of Drought Tolerance

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    Liming Yang

    2015-10-01

    Full Text Available Drought stress decreases crop growth, yield, and can further exacerbate pre-harvest aflatoxin contamination. Tolerance and adaptation to drought stress is an important trait of agricultural crops like maize. However, maize genotypes with contrasting drought tolerances have been shown to possess both common and genotype-specific adaptations to cope with drought stress. In this research, the physiological and metabolic response patterns in the leaves of maize seedlings subjected to drought stress were investigated using six maize genotypes including: A638, B73, Grace-E5, Lo964, Lo1016, and Va35. During drought treatments, drought-sensitive maize seedlings displayed more severe symptoms such as chlorosis and wilting, exhibited significant decreases in photosynthetic parameters, and accumulated significantly more reactive oxygen species (ROS and reactive nitrogen species (RNS than tolerant genotypes. Sensitive genotypes also showed rapid increases in enzyme activities involved in ROS and RNS metabolism. However, the measured antioxidant enzyme activities were higher in the tolerant genotypes than in the sensitive genotypes in which increased rapidly following drought stress. The results suggest that drought stress causes differential responses to oxidative and nitrosative stress in maize genotypes with tolerant genotypes with slower reaction and less ROS and RNS production than sensitive ones. These differential patterns may be utilized as potential biological markers for use in marker assisted breeding.

  19. Iron-dependent formation of reactive oxygen species and glutathione depletion after accumulation of magnetic iron oxide nanoparticles by oligodendroglial cells

    International Nuclear Information System (INIS)

    Hohnholt, Michaela C.; Dringen, Ralf

    2011-01-01

    Magnetic iron oxide nanoparticles (IONP) are currently used for various neurobiological applications. To investigate the consequences of a treatment of brain cells with such particles, we have applied dimercaptosuccinate (DMSA)-coated IONP that had an average hydrodynamic diameter of 60 nm to oligodendroglial OLN-93 cells. After exposure to 4 mM iron applied as DMSA–IONP, these cells increased their total specific iron content within 8 h 600-fold from 7 to 4,200 nmol/mg cellular protein. The strong iron accumulation was accompanied by a change in cell morphology, although the cell viability was not compromized. DMSA–IONP treatment caused a concentration-dependent increase in the iron-dependent formation of reactive oxygen species and a decrease in the specific content of the cellular antioxidative tripeptide glutathione. During a 16 h recovery phase in IONP-free culture medium following exposure to DMSA–IONP, OLN-93 cells maintained their high iron content and replenished their cellular glutathione content. These data demonstrate that viable OLN-93 cells have a remarkable potential to deal successfully with the consequences of an accumulation of large amounts of iron after exposure to DMSA–IONP.

  20. Morus alba Accumulates Reactive Oxygen Species to Initiate Apoptosis via FOXO-Caspase 3-Dependent Pathway in Neuroblastoma Cells.

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    Kwon, Young Hwi; Bishayee, Kausik; Rahman, Ataur; Hong, Jae Seung; Lim, Soon-Sung; Huh, Sung-Oh

    2015-07-01

    Morus alba root extract (MARE) has been used to treat hyperglycaemic conditions in oriental medicine. Here, we studied whether MARE possesses a cytotoxic effect on neuroblastoma. To check the cytotoxicity generated by MARE was whether relatively higher against the cancer cells rather than normal cells, we chose a neuroblastoma cell line (B103) and a normal cell line (Rat-2). A CCK assay revealed that MARE (10 μg/ml) reduced cell viability to approximately 60% compared to an untreated control in B103 cells. But in Rat-2 cells, MARE induced relatively lower cytotoxicity. To investigate the mechanisms underlying the cytotoxic effect of MARE, we used flow cytometry combined with immunoblot analyses. We found that MARE-treatment could accumulate ROS and depolarize mitochondria membrane potential of B103 cells. Further treatment with MARE in B103 cells also could damage DNA and induce apoptosis. An expression study of p-Akt also suggested that there was a reduction in cellular proliferation and transcription along with the process of apoptosis, which was further evidenced by an increase in Bax and cleaved-caspase 3 activity. Together, our findings suggest that MARE produces more cytotoxicity in cancer cells while having a relatively attenuated effect on normal cells. As such, MARE may be a safer option in cancer therapeutics, and it also shows potential for the patients with symptoms of hyperglycemia and cancer.

  1. A bHLH gene from Tamarix hispida improves abiotic stress tolerance by enhancing osmotic potential and decreasing reactive oxygen species accumulation.

    Science.gov (United States)

    Ji, Xiaoyu; Nie, Xianguang; Liu, Yujia; Zheng, Lei; Zhao, Huimin; Zhang, Bing; Huo, Lin; Wang, Yucheng

    2016-02-01

    Basic helix-loop-helix (bHLH) leucine-zipper transcription factors play important roles in abiotic stress responses. However, their specific roles in abiotic stress tolerance are not fully known. Here, we functionally characterized a bHLH gene, ThbHLH1, from Tamarix hispida in abiotic stress tolerance. ThbHLH1 specifically binds to G-box motif with the sequence of 'CACGTG'. Transiently transfected T. hispida plantlets with transiently overexpressed ThbHLH1 and RNAi-silenced ThbHLH1 were generated for gain- and loss-of-function analysis. Transgenic Arabidopsis thaliana lines overexpressing ThbHLH1 were generated to confirm the gain- and loss-of-function analysis. Overexpression of ThbHLH1 significantly elevates glycine betaine and proline levels, increases Ca(2+) concentration and enhances peroxidase (POD) and superoxide dismutase (SOD) activities to decrease reactive oxygen species (ROS) accumulation. Additionally, ThbHLH1 regulates the expression of the genes including P5CS, BADH, CaM, POD and SOD, to activate the above physiological changes, and also induces the expression of stress tolerance-related genes LEAs and HSPs. These data suggest that ThbHLH1 induces the expression of stress tolerance-related genes to improve abiotic stress tolerance by increasing osmotic potential, improving ROS scavenging capability and enhancing second messenger in stress signaling cascades. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Meclofenamic Acid Reduces Reactive Oxygen Species Accumulation and Apoptosis, Inhibits Excessive Autophagy, and Protects Hair Cell-Like HEI-OC1 Cells From Cisplatin-Induced Damage

    Directory of Open Access Journals (Sweden)

    He Li

    2018-05-01

    Full Text Available Hearing loss is the most common sensory disorder in humans, and a significant number of cases is due to the ototoxicity of drugs such as cisplatin that cause hair cell (HC damage. Thus, there is great interest in finding agents and mechanisms that protect HCs from ototoxic drug damage. It has been proposed that epigenetic modifications are related to inner ear development and play a significant role in HC protection and HC regeneration; however, whether the m6A modification and the ethyl ester form of meclofenamic acid (MA2, which is a highly selective inhibitor of FTO (fatmass and obesity-associated enzyme, one of the primary human demethylases, can affect the process of HC apoptosis induced by ototoxic drugs remains largely unexplored. In this study, we took advantage of the HEI-OC1 cell line, which is a cochlear HC-like cell line, to investigate the role of epigenetic modifications in cisplatin-induced cell death. We found that cisplatin injury caused reactive oxygen species accumulation and increased apoptosis in HEI-OC1 cells, and the cisplatin injury was reduced by co-treatment with MA2 compared to the cisplatin-only group. Further investigation showed that MA2 attenuated cisplatin-induced oxidative stress and apoptosis in HEI-OC1 cells. We next found that the cisplatin-induced upregulation of autophagy was significantly inhibited after MA2 treatment, indicating that MA2 inhibited the cisplatin-induced excessive autophagy. Our findings show that MA2 has a protective effect and improves the viability of HEI-OC1 cells after cisplatin treatment, and they provide new insights into potential therapeutic targets for the amelioration of cisplatin-induced ototoxicity.

  3. Reactivity of Trapped and Accumulated Electrons in Titanium Dioxide Photocatalysis

    Directory of Open Access Journals (Sweden)

    Shigeru Kohtani

    2017-10-01

    Full Text Available Electrons, photogenerated in conduction bands (CB and trapped in electron trap defects (Tids in titanium dioxide (TiO2, play crucial roles in characteristic reductive reactions. This review summarizes the recent progress in the research on electron transfer in photo-excited TiO2. Particularly, the reactivity of electrons accumulated in CB and trapped at Tids on TiO2 is highlighted in the reduction of molecular oxygen and molecular nitrogen, and the hydrogenation and dehalogenation of organic substrates. Finally, the prospects for developing highly active TiO2 photocatalysts are discussed.

  4. Reactive oxygen species, health and longevity

    OpenAIRE

    Vittorio Emanuele Bianchi; Giancarlo Falcioni

    2016-01-01

    Reactive oxygen species (ROS) are considered responsible of ageing in animal and humans. Mitochondria are both source and target of ROS. Various strategies to reduce ROS production have been considered to extend lifespan. Caloric restriction, exercise, and antioxidants are thought to be able to protect cells from structural and functional damage. However, there is evidence that ROS production has a detrimental effect on health, but at physiological levels are necessary to stimulate longevity....

  5. Imaging Reactive Oxygen Species in Arthritis

    Directory of Open Access Journals (Sweden)

    Wei-Tsung Chen

    2004-07-01

    Full Text Available Reactive oxygen species (ROS have been shown to play a role in the pathogenesis of arthritides. Luminol was used as the primary reporter of ROS and photons resulting from the chemiluminescence reaction were detected using a super-cooled CCD photon counting system. Luminol was injected intravenously into groups of animals with different models of arthritis. Imaging signal correlated well with the severity of arthritis in focal and pan-arthritis as determined by histological measurement of ROS by formazan. Measurements were highly reproducible, sensitive, and repeatable. In vivo chemiluminescence imaging is expected to become a useful modality to elucidate the role of ROS in the pathogenesis of arthritides and in determining therapeutic efficacy of protective therapies.

  6. Reactive oxygen species, health and longevity

    Directory of Open Access Journals (Sweden)

    Vittorio Emanuele Bianchi

    2016-09-01

    Full Text Available Reactive oxygen species (ROS are considered responsible of ageing in animal and humans. Mitochondria are both source and target of ROS. Various strategies to reduce ROS production have been considered to extend lifespan. Caloric restriction, exercise, and antioxidants are thought to be able to protect cells from structural and functional damage. However, there is evidence that ROS production has a detrimental effect on health, but at physiological levels are necessary to stimulate longevity. They play an important effect on secondary signal transduction stimulating innate immunology and mitochondriogenesis. During exercise at moderate intensity, skeletal muscles generate ROS that are necessary for the remodelling of the muscular cells. Physical inactivity determines excessive ROS production and muscle atrophy. Caloric restriction (CR can reduce ROS generation and improve longevity while antioxidant supplementation has shown a negative effect on longevity reducing the muscle adaptation to exercise and increasing mortality risk in patients with chronic diseases. The role of ROS in chronic diseases in also influenced by sex steroids that decrease in aging. The physiology of longevity is the result of integrated biological mechanisms that influence mitochondrial function and activity. The main objective of this review is to evaluate the effects of ROS on mitochondriogenesis and lifespan extension.

  7. Dietary isothiocyanate sulforaphene induces reactive oxygen ...

    African Journals Online (AJOL)

    intracellular oxygen species (ROS) measurement, mitochondrial membrane depolarization and western blot analysis were performed in four time-intervals to explore sulforaphene activity. ..... proteins were transferred to PVDF membranes.

  8. Oxygen negative glow: reactive species and emissivity

    International Nuclear Information System (INIS)

    Sahli, Khaled

    1991-01-01

    This research thesis addresses the study of a specific type of oxygen plasma created by electron beams (1 keV, 20 mA/cm"2), negative glow of a luminescent discharge in abnormal regime. The objective is to test the qualities of this plasma as source of two 'active' species of oxygen (singlet molecular oxygen and atomic oxygen) which are useful in applications. The experiment mainly bears on the use of VUV (120 to 150 nm) absorption spectroscopy measurements of concentrations of these both species, and on the recording of plasma emissivity space profiles in the visible region (450 to 850 nm). It appears that low concentrations of singlet oxygen definitely exclude this type of discharge for iodine laser applications. On the contrary, concentrations measured for atomic oxygen show it is a good candidate for the oxidation of large surfaces by sheets of beams. The satisfying comparison of emissivity results with a published model confirm the prevailing role of fast electrons, and gives evidence of an important effect of temperature: temperature can reach 1000 K, and this is in agreement with the presented measurement [fr

  9. Reactive oxygen species, essential molecules, during plant-pathogen interactions.

    Science.gov (United States)

    Camejo, Daymi; Guzmán-Cedeño, Ángel; Moreno, Alexander

    2016-06-01

    Reactive oxygen species (ROS) are continually generated as a consequence of the normal metabolism in aerobic organisms. Accumulation and release of ROS into cell take place in response to a wide variety of adverse environmental conditions including salt, temperature, cold stresses and pathogen attack, among others. In plants, peroxidases class III, NADPH oxidase (NOX) locates in cell wall and plasma membrane, respectively, may be mainly enzymatic systems involving ROS generation. It is well documented that ROS play a dual role into cells, acting as important signal transduction molecules and as toxic molecules with strong oxidant power, however some aspects related to its function during plant-pathogen interactions remain unclear. This review focuses on the principal enzymatic systems involving ROS generation addressing the role of ROS as signal molecules during plant-pathogen interactions. We described how the chloroplasts, mitochondria and peroxisomes perceive the external stimuli as pathogen invasion, and trigger resistance response using ROS as signal molecule. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. REACTIVE OXYGEN SPECIES AT THE CROSSROADS OF INFLAMMASOME AND INFLAMMATION

    Directory of Open Access Journals (Sweden)

    Anantha eHarijith

    2014-09-01

    Full Text Available Inflammasomes form a crucial part of the innate immune system. These are multi-protein oligomer platforms that are composed of intracellular sensors which are coupled with caspase and interleukin activating systems. Nod-like receptor protein (NLRP 3, and 6 and NLRC4 and AIM2 are the prominent members of the inflammasome family. Inflammasome activation leads to pyroptosis, a process of programmed cell death distinct from apoptosis through activation of Caspase and further downstream targets such as IL-1β and IL-18 leading to activation of inflammatory cascade. Reactive oxygen species (ROS serve as important inflammasome activating signals. ROS activate inflammasome through mitogen-activated protein kinases (MAPK and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2. Dysregulation of inflammasome is plays a significant role in various pathological process. Viral infections such as Dengue and Respiratory syncytial virus activate inflammasomes. Crystal compounds in silicosis and gout also activate ROS. In diabetes, inhibition of autophagy with resultant accumulation of dysfunctional mitochondria leads to enhanced ROS production activating inflammasomes. Activation of inflammasomes can be dampened by antioxidants such as SIRT-1. Inflammasome and related cascade could serve as future therapeutic targets for various pathological conditions.

  11. Reactive oxygen species (ROS) and cancer: Role of antioxidative nutraceuticals.

    Science.gov (United States)

    Prasad, Sahdeo; Gupta, Subash C; Tyagi, Amit K

    2017-02-28

    Extensive research over the past half a century indicates that reactive oxygen species (ROS) play an important role in cancer. Although low levels of ROS can be beneficial, excessive accumulation can promote cancer. One characteristic of cancer cells that distinguishes them from normal cells is their ability to produce increased numbers of ROS and their increased dependence on an antioxidant defense system. ROS are produced as a byproduct intracellularly by mitochondria and other cellular elements and exogenously by pollutants, tobacco, smoke, drugs, xenobiotics, and radiation. ROS modulate various cell signaling pathways, which are primarily mediated through the transcription factors NF-κB and STAT3, hypoxia-inducible factor-1α, kinases, growth factors, cytokines and other proteins, and enzymes; these pathways have been linked to cellular transformation, inflammation, tumor survival, proliferation, invasion, angiogenesis, and metastasis of cancer. ROS are also associated with epigenetic changes in genes, which is helpful in diagnosing diseases. This review considers the role of ROS in the various stages of cancer development. Finally, we provide evidence that nutraceuticals derived from Mother Nature are highly effective in eliminating cancer cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2012-07-03

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

  13. Reactive oxygen species-driven HIF1α triggers accelerated glycolysis in endothelial cells exposed to low oxygen tension

    International Nuclear Information System (INIS)

    Paik, Jin-Young; Jung, Kyung-Ho; Lee, Jin-Hee; Park, Jin-Won; Lee, Kyung-Han

    2017-01-01

    Endothelial cells and their metabolic state regulate glucose transport into underlying tissues. Here, we show that low oxygen tension stimulates human umbilical vein endothelial cell 18 F–fluorodeoxyglucose ( 18 F–FDG) uptake and lactate production. This was accompanied by augmented hexokinase activity and membrane Glut-1, and increased accumulation of hypoxia-inducible factor-1α (HIF1α). Restoration of oxygen reversed the metabolic effect, but this was blocked by HIF1α stabilization. Hypoxia-stimulated 18 F–FDG uptake was completely abrogated by silencing of HIF1α expression or by a specific inhibitor. There was a rapid and marked increase of reactive oxygen species (ROS) by hypoxia, and ROS scavenging or NADPH oxidase inhibition completely abolished hypoxia-stimulated HIF1α and 18 F–FDG accumulation, placing ROS production upstream of HIF1α signaling. Hypoxia-stimulated HIF1α and 18 F–FDG accumulation was blocked by the protein kinase C (PKC) inhibitor, staurosporine. The phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin, blocked hypoxia-stimulated 18 F–FDG uptake and attenuated hypoxia-responsive element binding of HIF1α without influencing its accumulation. Thus, ROS-driven HIF1α accumulation, along with PKC and PI3K signaling, play a key role in triggering accelerated glycolysis in endothelial cells under hypoxia, thereby contributing to 18 F–FDG transport.

  14. Effects of proline on photosynthesis, root reactive oxygen species ...

    African Journals Online (AJOL)

    Effects of 0.2 mM proline applied to saline nutrient solution on biomass, chlorophyll content, photosynthetic parameters, reactive oxygen species and antioxidant enzymes activities of two melon cultivars (cv. Yuhuang and cv. Xuemei) were examined. Results indicate that exogenous proline increased the fresh and dry ...

  15. Formation of reactive oxygen species in rat epithelial cells upon ...

    Indian Academy of Sciences (India)

    In our study, we investigated the influence of fly ash on the promotion of early inflammatory reactions like the formation of reactive oxygen species (ROS) in rat lung epithelial cells (RLE-6TN). Furthermore, we determined the formation of nitric oxide (NO). The cells show a clear dose-response relationship concerning the ...

  16. Luminometric determination of antioxidant capacity towards individual reactive oxygen species

    Czech Academy of Sciences Publication Activity Database

    Komrsková, D.; Lojek, Antonín; Hrbáč, J.; Číž, Milan

    2005-01-01

    Roč. 3, č. 1 (2005), S25 [Cells VI - Biological Days /18./. 24.10.2005-26.10.2005, České Budějovice] R&D Projects: GA ČR(CZ) GA524/01/1219 Institutional research plan: CEZ:AV0Z50040507 Keywords : chemiluminescence * reactive oxygen species * scavenger Subject RIV: BO - Biophysics

  17. Are mitochondrial reactive oxygen species required for autophagy?

    Energy Technology Data Exchange (ETDEWEB)

    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); Maeda, Akihiro; Ji, Jing [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); Greenberger, Joel S. [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

    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.

  18. Are mitochondrial reactive oxygen species required for autophagy?

    International Nuclear Information System (INIS)

    Jiang, Jianfei; Maeda, Akihiro; Ji, Jing; Baty, Catherine J.; Watkins, Simon C.; Greenberger, Joel S.; Kagan, Valerian E.

    2011-01-01

    Highlights: → Autophageal and apoptotic pathways were dissected in cytochrome c deficient cells. → Staurosporine (STS)-induced autophagy was not accompanied by ROS generation. → Autophagy was detectable in mitochondrial DNA deficient ρ 0 cells. → 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 2 O 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 ρ 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.

  19. Mitochondria and Reactive Oxygen Species: Physiology and Pathophysiology

    Directory of Open Access Journals (Sweden)

    Subhashini Bolisetty

    2013-03-01

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

  20. Reactive oxygen species and nitric oxide signaling in bystander cells.

    Science.gov (United States)

    Jella, Kishore Kumar; Moriarty, Roisin; McClean, Brendan; Byrne, Hugh J; Lyng, Fiona M

    2018-01-01

    It is now well accepted that radiation induced bystander effects can occur in cells exposed to media from irradiated cells. The aim of this study was to follow the bystander cells in real time following addition of media from irradiated cells and to determine the effect of inhibiting these signals. A human keratinocyte cell line, HaCaT cells, was irradiated (0.005, 0.05 and 0.5 Gy) with γ irradiation, conditioned medium was harvested after one hour and added to recipient bystander cells. Reactive oxygen species, nitric oxide, Glutathione levels, caspase activation, cytotoxicity and cell viability was measured after the addition of irradiated cell conditioned media to bystander cells. Reactive oxygen species and nitric oxide levels in bystander cells treated with 0.5Gy ICCM were analysed in real time using time lapse fluorescence microscopy. The levels of reactive oxygen species were also measured in real time after the addition of extracellular signal-regulated kinase and c-Jun amino-terminal kinase pathway inhibitors. ROS and glutathione levels were observed to increase after the addition of irradiated cell conditioned media (0.005, 0.05 and 0.5 Gy ICCM). Caspase activation was found to increase 4 hours after irradiated cell conditioned media treatment (0.005, 0.05 and 0.5 Gy ICCM) and this increase was observed up to 8 hours and there after a reduction in caspase activation was observed. A decrease in cell viability was observed but no major change in cytotoxicity was found in HaCaT cells after treatment with irradiated cell conditioned media (0.005, 0.05 and 0.5 Gy ICCM). This study involved the identification of key signaling molecules such as reactive oxygen species, nitric oxide, glutathione and caspases generated in bystander cells. These results suggest a clear connection between reactive oxygen species and cell survival pathways with persistent production of reactive oxygen species and nitric oxide in bystander cells following exposure to irradiated cell

  1. First kinetic discrimination between carbon and oxygen reactivity of enols.

    Science.gov (United States)

    García-Río, Luis; Mejuto, Juan C; Parajó, Mercedes; Pérez-Lorenzo, Moisés

    2008-11-07

    Nitrosation of enols shows a well-differentiated behavior depending on whether the reaction proceeds through the carbon (nucleophilic catalysis is observed) or the oxygen atom (general acid-base catalysis is observed). This is due to the different operating mechanisms for C- and O-nitrosation. Nitrosation of acetylacetone (AcAc) shows a simultaneous nucleophilic and acid-base catalysis. This simultaneous catalysis constitutes the first kinetic evidence of two independent reactions on the carbon and oxygen atom of an enol. The following kinetic study allows us to determine the rate constants for both reaction pathways. A similar reactivity of the nucleophilic centers with the nitrosonium ion is observed.

  2. Reactive oxygen species production and discontinuous gas exchange in insects

    OpenAIRE

    Boardman, Leigh; Terblanche, John S.; Hetz, Stefan K.; Marais, Elrike; Chown, Steven L.

    2011-01-01

    While biochemical mechanisms are typically used by animals to reduce oxidative damage, insects are suspected to employ a higher organizational level, discontinuous gas exchange mechanism to do so. Using a combination of real-time, flow-through respirometry and live-cell fluorescence microscopy, we show that spiracular control associated with the discontinuous gas exchange cycle (DGC) in Samia cynthia pupae is related to reactive oxygen species (ROS). Hyperoxia fails to increase mean ROS produ...

  3. HIF and reactive oxygen species regulate oxidative phosphorylation in cancer

    Czech Academy of Sciences Publication Activity Database

    Hervouet, E.; Čížková, Alena; Demont, J.; Vojtíšková, Alena; Pecina, Petr; Franssen-van Hal, N.; Keijer, J.; Simonnet, H.; Ivánek, Robert; Kmoch, S.; Godinot, C.; Houštěk, Josef

    2008-01-01

    Roč. 29, č. 8 (2008), s. 1528-1537 ISSN 0143-3334 R&D Projects: GA MŠk(CZ) 1M0520; GA ČR GA303/07/0781 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z50520514 Keywords : carcinoma * mitochondrial biogenesis * reactive oxygen species Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.930, year: 2008

  4. Targeted modulation of reactive oxygen species in the vascular endothelium

    OpenAIRE

    Shuvaev, Vladimir V.; Muzykantov, Vladimir R.

    2011-01-01

    Endothelial cells lining vascular luminal surface represent an important site of signaling and injurious effects of reactive oxygen species (ROS) produced by other cells and endothelium itself in ischemia, inflammation and other pathological conditions. Targeted delivery of ROS modulating enzymes conjugated with antibodies to endothelial surface molecules (vascular immunotargeting) provides site-specific interventions in the endothelial ROS, unattainable by other formulations including PEG-mo...

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

    Science.gov (United States)

    Yen, A. S.

    2002-01-01

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

  6. Toxicological and pathophysiological roles of reactive oxygen and nitrogen species

    International Nuclear Information System (INIS)

    Roberts, Ruth A.; Smith, Robert A.; Safe, Stephen; Szabo, Csaba; Tjalkens, Ronald B.; Robertson, Fredika M.

    2010-01-01

    'Oxidative and Nitrative Stress in Toxicology and Disease' was the subject of a symposium held at the EUROTOX meeting in Dresden 15th September 2009. Reactive oxygen (ROS) and reactive nitrogen species (RNS) produced during tissue pathogenesis and in response to viral or chemical toxicants, induce a complex series of downstream adaptive and reparative events driven by the associated oxidative and nitrative stress. As highlighted by all the speakers, ROS and RNS can promote diverse biological responses associated with a spectrum of disorders including neurodegenerative/neuropsychiatric and cardiovascular diseases. Similar pathways are implicated during the process of liver and skin carcinogenesis. Mechanistically, reactive oxygen and nitrogen species drive sustained cell proliferation, cell death including both apoptosis and necrosis, formation of nuclear and mitochondrial DNA mutations, and in some cases stimulation of a pro-angiogenic environment. Here we illustrate the pivotal role played by oxidative and nitrative stress in cell death, inflammation and pain and its consequences for toxicology and disease pathogenesis. Examples are presented from five different perspectives ranging from in vitro model systems through to in vivo animal model systems and clinical outcomes.

  7. Mechanisms of group A Streptococcus resistance to reactive oxygen species.

    Science.gov (United States)

    Henningham, Anna; Döhrmann, Simon; Nizet, Victor; Cole, Jason N

    2015-07-01

    Streptococcus pyogenes, also known as group A Streptococcus (GAS), is an exclusively human Gram-positive bacterial pathogen ranked among the 'top 10' causes of infection-related deaths worldwide. GAS commonly causes benign and self-limiting epithelial infections (pharyngitis and impetigo), and less frequent severe invasive diseases (bacteremia, toxic shock syndrome and necrotizing fasciitis). Annually, GAS causes 700 million infections, including 1.8 million invasive infections with a mortality rate of 25%. In order to establish an infection, GAS must counteract the oxidative stress conditions generated by the release of reactive oxygen species (ROS) at the infection site by host immune cells such as neutrophils and monocytes. ROS are the highly reactive and toxic byproducts of oxygen metabolism, including hydrogen peroxide (H2O2), superoxide anion (O2•(-)), hydroxyl radicals (OH•) and singlet oxygen (O2*), which can damage bacterial nucleic acids, proteins and cell membranes. This review summarizes the enzymatic and regulatory mechanisms utilized by GAS to thwart ROS and survive under conditions of oxidative stress. © FEMS 2015.

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

    Science.gov (United States)

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

    2012-02-01

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

  9. Magnetic nanoparticles: reactive oxygen species generation and potential therapeutic applications

    Science.gov (United States)

    Mai, Trang; Hilt, J. Zach

    2017-07-01

    Magnetic nanoparticles have been demonstrated to produce reactive oxygen species (ROS), which play a major role in various cellular pathways, via Fenton and Haber-Weiss reaction. ROS act as a double-edged sword inside the body. At normal conditions, the generation of ROS is in balance with their elimination by scavenger systems, and they can promote cell proliferation as well as differentiation. However, at an increased level, they can cause damages to protein, lead to cellular apoptosis, and contribute to many diseases including cancer. Many recent studies proposed a variety of strategies to either suppress toxicity of ROS generation or exploit the elevated ROS levels for cancer therapy.

  10. Reactive oxygen species inhibit catalytic activity of peptidylarginine deiminase

    DEFF Research Database (Denmark)

    Damgaard, Dres; Bjørn, Mads Emil; Jensen, Peter Østrup

    2017-01-01

    on calcium and reducing conditions. However, reactive oxygen species (ROS) have been shown to induce citrullination of histones in granulocytes. Here we examine the ability of H2O2 and leukocyte-derived ROS to regulate PAD activity using citrullination of fibrinogen as read-out. H2O2 at concentrations above...... from stimulated leukocytes was unaffected by exogenously added H2O2 at concentrations up to 1000 µM. The role of ROS in regulating PAD activity may play an important part in preventing hypercitrullination of proteins....

  11. Pre-Transplantation Blockade of TNF-α-Mediated Oxygen Species Accumulation Protects Hematopoietic Stem Cells.

    Science.gov (United States)

    Ishida, Takashi; Suzuki, Sachie; Lai, Chen-Yi; Yamazaki, Satoshi; Kakuta, Shigeru; Iwakura, Yoichiro; Nojima, Masanori; Takeuchi, Yasuo; Higashihara, Masaaki; Nakauchi, Hiromitsu; Otsu, Makoto

    2017-04-01

    Hematopoietic stem cell (HSC) transplantation (HSCT) for malignancy requires toxic pre-conditioning to maximize anti-tumor effects and donor-HSC engraftment. While this induces bone marrow (BM)-localized inflammation, how this BM environmental change affects transplanted HSCs in vivo remains largely unknown. We here report that, depending on interval between irradiation and HSCT, residence within lethally irradiated recipient BM compromises donor-HSC reconstitution ability. Both in vivo and in vitro we demonstrate that, among inflammatory cytokines, TNF-α plays a role in HSC damage: TNF-α stimulation leads to accumulation of reactive oxygen species (ROS) in highly purified hematopoietic stem/progenitor cells (HSCs/HSPCs). Transplantation of flow-cytometry-sorted murine HSCs reveals damaging effects of accumulated ROS on HSCs. Short-term incubation either with an specific inhibitor of tumor necrosis factor receptor 1 signaling or an antioxidant N-acetyl-L-cysteine (NAC) prevents TNF-α-mediated ROS accumulation in HSCs. Importantly, pre-transplantation exposure to NAC successfully demonstrats protective effects in inflammatory BM on graft-HSCs, exhibiting better reconstitution capability than that of nonprotected control grafts. We thus suggest that in vivo protection of graft-HSCs from BM inflammation is a feasible and attractive approach, which may lead to improved hematopoietic reconstitution kinetics in transplantation with myeloablative conditioning that inevitably causes inflammation in recipient BM. Stem Cells 2017;35:989-1002. © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  12. Calcific Uremic Arteriolopathy: Pathophysiology, Reactive Oxygen Species and Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Kurt M. Sowers

    2010-01-01

    Full Text Available Calcific uremic arteriolopathy (CUA/calciphylaxis is an important cause of morbidity and mortality in patients with chronic kidney disease requiring renal replacement. Once thought to be rare, it is being increasingly recognized and reported on a global scale. The uremic milieu predisposes to multiple metabolic toxicities including increased levels of reactive oxygen species and inflammation. Increased oxidative stress and inflammation promote this arteriolopathy by adversely affecting endothelial function resulting in a prothrombotic milieu and significant remodeling effects on vascular smooth muscle cells. These arteriolar pathological effects include intimal hyperplasia, inflammation, endovascular fibrosis and vascular smooth muscle cell apoptosis and differentiation into bone forming osteoblast-like cells resulting in medial calcification. Systemic factors promoting this vascular condition include elevated calcium, parathyroid hormone and hyperphosphatemia with consequent increases in the calcium × phosphate product. The uremic milieu contributes to a marked increased in upstream reactive oxygen species—oxidative stress and subsequent downstream increased inflammation, in part, via activation of the nuclear transcription factor NFκB and associated downstream cytokine pathways. Consitutive anti-calcification proteins such as Fetuin-A and matrix GLA proteins and their signaling pathways may be decreased, which further contributes to medial vascular calcification. The resulting clinical entity is painful, debilitating and contributes to the excess morbidity and mortality associated with chronic kidney disease and end stage renal disease. These same histopathologic conditions also occur in patients without uremia and therefore, the term calcific obliterative arteriolopathy could be utilized in these conditions.

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

    Science.gov (United States)

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

    2014-09-01

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

  14. Reactive oxygen species in health and disease : Finding the right balance

    NARCIS (Netherlands)

    van der Wijst, Monique

    2016-01-01

    When oxygen takes up an electron, reactive oxygen species are formed. These free radicals can react with important molecules in our body (DNA, proteins), just like iron rusts (oxidation). Too many reactive oxygen species, called oxidative stress, result in cellular damage causing either cell death

  15. Photoluminescent Gold Nanoclusters in Cancer Cells: Cellular Uptake, Toxicity, and Generation of Reactive Oxygen Species.

    Science.gov (United States)

    Matulionyte, Marija; Dapkute, Dominyka; Budenaite, Laima; Jarockyte, Greta; Rotomskis, Ricardas

    2017-02-10

    In recent years, photoluminescent gold nanoclusters have attracted considerable interest in both fundamental biomedical research and practical applications. Due to their ultrasmall size, unique molecule-like optical properties, and facile synthesis gold nanoclusters have been considered very promising photoluminescent agents for biosensing, bioimaging, and targeted therapy. Yet, interaction of such ultra-small nanoclusters with cells and other biological objects remains poorly understood. Therefore, the assessment of the biocompatibility and potential toxicity of gold nanoclusters is of major importance before their clinical application. In this study, the cellular uptake, cytotoxicity, and intracellular generation of reactive oxygen species (ROS) of bovine serum albumin-encapsulated (BSA-Au NCs) and 2-(N-morpholino) ethanesulfonic acid (MES)capped photoluminescent gold nanoclusters (Au-MES NCs) were investigated. The results showed that BSA-Au NCs accumulate in cells in a similar manner as BSA alone, indicating an endocytotic uptake mechanism while ultrasmall Au-MES NCs were distributed homogeneously throughout the whole cell volume including cell nucleus. The cytotoxicity of BSA-Au NCs was negligible, demonstrating good biocompatibility of such BSA-protected Au NCs. In contrast, possibly due to ultrasmall size and thin coating layer, Au-MES NCs exhibited exposure time-dependent high cytotoxicity and higher reactivity which led to highly increased generation of reactive oxygen species. The results demonstrate the importance of the coating layer to biocompatibility and toxicity of ultrasmall photoluminescent gold nanoclusters.

  16. Photoluminescent Gold Nanoclusters in Cancer Cells: Cellular Uptake, Toxicity, and Generation of Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Marija Matulionyte

    2017-02-01

    Full Text Available In recent years, photoluminescent gold nanoclusters have attracted considerable interest in both fundamental biomedical research and practical applications. Due to their ultrasmall size, unique molecule-like optical properties, and facile synthesis gold nanoclusters have been considered very promising photoluminescent agents for biosensing, bioimaging, and targeted therapy. Yet, interaction of such ultra-small nanoclusters with cells and other biological objects remains poorly understood. Therefore, the assessment of the biocompatibility and potential toxicity of gold nanoclusters is of major importance before their clinical application. In this study, the cellular uptake, cytotoxicity, and intracellular generation of reactive oxygen species (ROS of bovine serum albumin-encapsulated (BSA-Au NCs and 2-(N-morpholino ethanesulfonic acid (MEScapped photoluminescent gold nanoclusters (Au-MES NCs were investigated. The results showed that BSA-Au NCs accumulate in cells in a similar manner as BSA alone, indicating an endocytotic uptake mechanism while ultrasmall Au-MES NCs were distributed homogeneously throughout the whole cell volume including cell nucleus. The cytotoxicity of BSA-Au NCs was negligible, demonstrating good biocompatibility of such BSA-protected Au NCs. In contrast, possibly due to ultrasmall size and thin coating layer, Au-MES NCs exhibited exposure time-dependent high cytotoxicity and higher reactivity which led to highly increased generation of reactive oxygen species. The results demonstrate the importance of the coating layer to biocompatibility and toxicity of ultrasmall photoluminescent gold nanoclusters.

  17. Chaetocin reactivates the lytic replication of Epstein-Barr virus from latency via reactive oxygen species.

    Science.gov (United States)

    Zhang, Shilun; Yin, Juan; Zhong, Jiang

    2017-01-01

    Oxidative stress, regarded as a negative effect of free radicals in vivo, takes place when organisms suffer from harmful stimuli. Some viruses can induce the release of reactive oxygen species (ROS) in infected cells, which may be closely related with their pathogenicity. In this report, chaetocin, a fungal metabolite reported to have antimicrobial and cytostatic activity, was studied for its effect on the activation of latent Epstein-Barr virus (EBV) in B95-8 cells. We found that chaetocin remarkably up-regulated EBV lytic transcription and DNA replication at a low concentration (50 nmol L -1 ). The activation of latent EBV was accompanied by an increased cellular ROS level. N-acetyl-L-cysteine (NAC), an ROS inhibitor, suppressed chaetocin-induced EBV activation. Chaetocin had little effect on histone H3K9 methylation, while NAC also significantly reduced H3K9 methylation. These results suggested that chaetocin reactivates latent EBV primarily via ROS pathways.

  18. The bystander effect: is reactive oxygen species the driver?

    International Nuclear Information System (INIS)

    Szumiel, I.

    2003-01-01

    The paper reviews selected examples of the bystander effect, such as clonogenic survival decrease, chromosomal aberrations and mutations. The similarities and differences between the biological effects in directly targeted and bystander cells are briefly discussed. Also reviewed are the experimental data which support the role of reactive oxygen species (ROS), especially *O 2 - , as mediators of the bystander effect. Endogenously generated ROS, due to activation of NAD(P)H oxidases, play a kay role in the introduction of DNA damage in bystander cells. All the observed effects in bystander cells, such as alteration in gene expression patterns, chromosomal aberrations, sister chromatid exchanges, mutations, genome instability and neoplastic transformation are the consequence of DNA damage. (author)

  19. Mechanisms of nanotoxicity: Generation of reactive oxygen species

    Directory of Open Access Journals (Sweden)

    Peter P. Fu

    2014-03-01

    Full Text Available Nanotechnology is a rapidly developing field in the 21st 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.

  20. Redox mechanism of reactive oxygen species in exercise

    Directory of Open Access Journals (Sweden)

    Feng He

    2016-11-01

    Full Text Available It is well known that regular exercise benefits health. However, unaccustomed and/or exhaustive exercise can generate excessive reactive oxygen species (ROS, leading to oxidative stress-related tissue damage and impaired muscle contractility. ROS are produced in both aerobic and anaerobic exercise. Although mitochondria, NADPH oxidases and xanthine oxidase have all been identified as contributors to ROS production, the exact redox mechanisms underlying exercise-induced oxidative stress remain elusive. Interestingly, moderate exposure to ROS is necessary to induce the body’s adaptive responses such as the activation of antioxidant defense mechanisms. Dietary antioxidant manipulation can also reduce ROS levels and muscle fatigue, as well as enhance exercise recovery. To elucidate the complex role of ROS in exercise, this article updates on new findings of ROS origins within skeletal muscles associated with various types of exercises such as endurance, sprint and mountain climbing, corresponding antioxidant defense systems as well as dietary manipulation against damage caused by ROS.

  1. Serum Reactive Oxygen Metabolite Levels Predict Severe Exacerbations of Asthma

    Science.gov (United States)

    Nakamoto, Keitaro; Watanabe, Masato; Sada, Mitsuru; Inui, Toshiya; Nakamura, Masuo; Honda, Kojiro; Wada, Hiroo; Mikami, Yu; Matsuzaki, Hirotaka; Horie, Masafumi; Noguchi, Satoshi; Yamauchi, Yasuhiro; Koyama, Hikari; Kogane, Toshiyuki; Kohyama, Tadashi; Takizawa, Hajime

    2016-01-01

    Background and Purpose Bronchial asthma (BA) is a chronic airway disease characterized by airway hyperresponsiveness and remodeling, which are intimately linked to chronic airway inflammation. Reactive oxygen species (ROS) such as hydrogen peroxide are generated by inflammatory cells that are involved in the pathogenesis of BA. However, the role of ROS in the management of BA patients is not yet clear. We attempted to determine the role of ROS as a biomarker in the clinical setting of BA. Subjects and Methods We enrolled patients with BA from 2013 through 2015 and studied the degrees of asthma control, anti-asthma treatment, pulmonary function test results, fractional exhaled nitric oxide (FeNO), serum reactive oxygen metabolite (ROM) levels, and serum levels of interleukin (IL)-6 and IL-8. Results We recruited 110 patients with BA. Serum ROM levels correlated with white blood cell (WBC) count (rs = 0.273, p = 0.004), neutrophil count (rs = 0.235, p = 0.014), CRP (rs = 0.403, p < 0.001), and IL-6 (rs = 0.339, p < 0.001). Serum ROM levels and IL-8 and CRP levels negatively correlated with %FEV1 (rs = -0.240, p = 0.012, rs = -0.362, p < 0.001, rs = -0.197, p = 0.039, respectively). Serum ROM levels were significantly higher in patients who experienced severe exacerbation within 3 months than in patients who did not (339 [302–381] vs. 376 [352–414] CARR U, p < 0.025). Receiver-operating characteristics analysis showed that ROM levels correlated significantly with the occurrence of severe exacerbation (area under the curve: 0.699, 95% CI: 0.597–0.801, p = 0.025). Conclusions Serum levels of ROM were significantly associated with the degrees of airway obstruction, WBC counts, neutrophil counts, IL-6, and severe exacerbations. This biomarker may be useful in predicting severe exacerbations of BA. PMID:27776186

  2. Reactive oxygen species in disease: Rebuttal of a conventional concept

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    Luis Vitetta

    2015-09-01

    Full Text Available The production of intracellular reactive oxygen species and reactive nitrogen species has long been proposed as leading to the random deleterious modification of macromolecules (i.e., nucleic acids, proteins with an associated progressive development of the age associated systemic diseases (e.g., diabetes, Parkinson’s disease as well as contributing to the ageing process.   Superoxide anion (hydrogen peroxide and nitric oxide (peroxynitrite comprise regulated intracellular second messenger pro-oxidant systems, with specific sub-cellular locales of production and are essential for the normal function of the metabolome and cellular electro-physiology.  We have posited that the formation of superoxide anion and its metabolic product hydrogen peroxide, and nitric oxide, do not conditionally lead to random damage of macromolecular species such as nucleic acids or proteins.  Under normal physiological conditions their production is intrinsically regulated that is very much consistent with their second messenger purpose of function.   We further propose that the concept of an orally administered small molecule antioxidant as a therapy to abrogate free radical activity (to control oxidative stress is a chimera.  As such we consider that free radicals are not a major overwhelming player in the development of the chronic diseases or the ageing process.

  3. Endogenous mechanisms of reactive oxygen species (ROS generation

    Directory of Open Access Journals (Sweden)

    Agata Sarniak

    2016-11-01

    Full Text Available The main cellular source of reactive oxygen species (ROS is mitochondrial respiratory chain and active NADPH responsible for “respiratory burst” of phagocytes. Whatsmore ROS are produced in endoplasmic reticulum, peroxisomes, with the participation of xanthine and endothelial oxidase and during autoxidation process of small molecules. Mitochondrial respiratory chain is the main cellular source of ROS. It is considered that in aerobic organisms ROS are mainly formed during normal oxygen metabolism, as byproducts of oxidative phosphorylation, during the synthesis of ATP. The intermembranous phagocyte enzyme – activated NADPH oxidase, responsible for the “respiratory burst” of phagocytes, which is another source of ROS, plays an important role in defense of organism against infections.The aim of this article is to resume actuall knowledge about structure and function of the mitochondrial electron transport chain in which ROS are the byproducts and about NADPH oxidase as well as the function of each of its components in the “respiratory burst” of phagocytes.

  4. Photosensitizing Nanoparticles and The Modulation of Reactive Oxygen Species generation

    Directory of Open Access Journals (Sweden)

    Dayane Batista Tada

    2015-05-01

    Full Text Available The association of PhotoSensitizer (PS molecules with nanoparticles (NPs forming photosensitizing NPs, has emerged as a therapeutic strategy to improve PS tumor targeting, to protect PS from deactivation reactions and to enhance both PS solubility and circulation time. Since association with NPs usually alters PS photophysical and photochemical properties, photosensitizing NPs are an important tool to modulate reactive oxygen species (ROS generation. Depending on the design of the photosensitizing NP, i.e., type of PS, the NP material and the method applied for the construction of the photosensitizing NP, the deactivation routes of the excited state can be controlled, allowing the generation of either singlet oxygen or other ROS. Controlling the type of generated ROS is desirable not only in biomedical applications, as in Photodynamic Therapy where the type of ROS affects therapeutic efficiency, but also in other technological relevant fields like energy conversion, where the electron and energy transfer processes are necessary to increase the efficiency of photoconversion cells. The current review highlights some of the recent developments in the design of Photosensitizing NPs aimed at modulating the primary photochemical events after light absorption.

  5. Mitochondrial Signaling in Plants Under Hypoxia: Use of Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS)

    DEFF Research Database (Denmark)

    Hebelstrup, Kim; Møller, Ian Max

    2015-01-01

    Hypoxia commonly occurs in roots in water-saturated soil and in maturing and germinating seeds. We here review the role of the mitochondria in the cellular response to hypoxia with an emphasis on the turnover of Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) and their potential...

  6. Friend or foe? Reactive oxygen species production, scavenging and signaling in plant response to environmental stresses.

    Science.gov (United States)

    Czarnocka, Weronika; Karpiński, Stanisław

    2018-01-10

    In the natural environment, plants are exposed to a variety of biotic and abiotic stress conditions that trigger rapid changes in the production and scavenging of reactive oxygen species (ROS). The production and scavenging of ROS is compartmentalized, which means that, depending on stimuli type, they can be generated and eliminated in different cellular compartments such as the apoplast, plasma membrane, chloroplasts, mitochondria, peroxisomes, and endoplasmic reticulum. Although the accumulation of ROS is generally harmful to cells, ROS play an important role in signaling pathways that regulate acclimatory and defense responses in plants, such as systemic acquired acclimation (SAA) and systemic acquired resistance (SAR). However, high accumulations of ROS can also trigger redox homeostasis disturbance which can lead to cell death, and in consequence, to a limitation in biomass and yield production. Different ROS have various half-lifetimes and degrees of reactivity toward molecular components such as lipids, proteins, and nucleic acids. Thus, they play different roles in intra- and extra-cellular signaling. Despite their possible damaging effect, ROS should mainly be considered as signaling molecules that regulate local and systemic acclimatory and defense responses. Over the past two decades it has been proven that ROS together with non-photochemical quenching (NPQ), hormones, Ca 2+ waves, and electrical signals are the main players in SAA and SAR, two physiological processes essential for plant survival and productivity in unfavorable conditions. Copyright © 2018. Published by Elsevier Inc.

  7. Use the Protonmotive Force: Mitochondrial Uncoupling and Reactive Oxygen Species.

    Science.gov (United States)

    Berry, Brandon J; Trewin, Adam J; Amitrano, Andrea M; Kim, Minsoo; Wojtovich, Andrew P

    2018-04-04

    Mitochondrial respiration results in an electrochemical proton gradient, or protonmotive force (pmf), across the mitochondrial inner membrane. The pmf is a form of potential energy consisting of charge (∆ψ m ) and chemical (∆pH) components, that together drive ATP production. In a process called uncoupling, proton leak into the mitochondrial matrix independent of ATP production dissipates the pmf and energy is lost as heat. Other events can directly dissipate the pmf independent of ATP production as well, such as chemical exposure or mechanisms involving regulated mitochondrial membrane electrolyte transport. Uncoupling has defined roles in metabolic plasticity and can be linked through signal transduction to physiologic events. In the latter case, the pmf impacts mitochondrial reactive oxygen species (ROS) production. Although capable of molecular damage, ROS also have signaling properties that depend on the timing, location, and quantity of their production. In this review, we provide a general overview of mitochondrial ROS production, mechanisms of uncoupling, and how these work in tandem to affect physiology and pathologies, including obesity, cardiovascular disease, and immunity. Overall, we highlight that isolated bioenergetic models-mitochondria and cells-only partially recapitulate the complex link between the pmf and ROS signaling that occurs in vivo. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Targeted modulation of reactive oxygen species in the vascular endothelium.

    Science.gov (United States)

    Shuvaev, Vladimir V; Muzykantov, Vladimir R

    2011-07-15

    'Endothelial cells lining vascular luminal surface represent an important site of signaling and injurious effects of reactive oxygen species (ROS) produced by other cells and endothelium itself in ischemia, inflammation and other pathological conditions. Targeted delivery of ROS modulating enzymes conjugated with antibodies to endothelial surface molecules (vascular immunotargeting) provides site-specific interventions in the endothelial ROS, unattainable by other formulations including PEG-modified enzymes. Targeting of ROS generating enzymes (e.g., glucose oxidase) provides ROS- and site-specific models of endothelial oxidative stress, whereas targeting of antioxidant enzymes SOD and catalase offers site-specific quenching of superoxide anion and H(2)O(2). These targeted antioxidant interventions help to clarify specific role of endothelial ROS in vascular and pulmonary pathologies and provide basis for design of targeted therapeutics for treatment of these pathologies. In particular, antibody/catalase conjugates alleviate acute lung ischemia/reperfusion injury, whereas antibody/SOD conjugates inhibit ROS-mediated vasoconstriction and inflammatory endothelial signaling. Encapsulation in protease-resistant, ROS-permeable carriers targeted to endothelium prolongs protective effects of antioxidant enzymes, further diversifying the means for targeted modulation of endothelial ROS. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Mechanisms of nanotoxicity: generation of reactive oxygen species.

    Science.gov (United States)

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

    2014-03-01

    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. Copyright © 2014. Published by Elsevier B.V.

  10. Salicylic acid signaling inhibits apoplastic reactive oxygen species signaling.

    Science.gov (United States)

    Xu, Enjun; Brosché, Mikael

    2014-06-04

    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. 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. 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.

  11. Light irradiation helps magnetotactic bacteria eliminate intracellular reactive oxygen species.

    Science.gov (United States)

    Li, Kefeng; Wang, Pingping; Chen, Chuanfang; Chen, Changyou; Li, Lulu; Song, Tao

    2017-09-01

    Magnetotactic bacteria (MTB) demonstrate photoresponse. However, little is known about the biological significance of this behaviour. Magnetosomes exhibit peroxidase-like activity and can scavenge reactive oxygen species (ROS). Magnetosomes extracted from the Magnetospirillum magneticum strain AMB-1 show enhanced peroxidase-like activity under illumination. The present study investigated the effects of light irradiation on nonmagnetic (without magnetosomes) and magnetic (with magnetosomes) AMB-1 cells. Results showed that light irradiation did not affect the growth of nonmagnetic and magnetic cells but significantly increased magnetosome synthesis and reduced intracellular ROS level in magnetic cells. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to analyse the expression level of magnetosome formation-associated genes (mamA, mms6, mms13 and mmsF) and stress-related genes (recA, oxyR, SOD, amb0664 and amb2684). Results showed that light irradiation upregulated the expression of mms6, mms13 and mmsF. Furthermore, light irradiation upregulated the expression of stress-related genes in nonmagnetic cells but downregulated them in magnetic cells. Additionally, magnetic cells exhibited stronger phototactic behaviour than nonmagnetic ones. These results suggested that light irradiation could heighten the ability of MTB to eliminate intracellular ROS and help them adapt to lighted environments. This phenomenon may be related to the enhanced peroxidase-like activity of magnetosomes under light irradiation. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  12. Generation of Reactive Oxygen Species from Silicon Nanowires

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    Stephen S. Leonard

    2014-01-01

    Full Text Available Processing and synthesis of purified nanomaterials of diverse composition, size, and properties is an evolving process. Studies have demonstrated that some nanomaterials have potential toxic effects and have led to toxicity research focusing on nanotoxicology. About two million workers will be employed in the field of nanotechnology over the next 10 years. The unknown effects of nanomaterials create a need for research and development of techniques to identify possible toxicity. Through a cooperative effort between National Institute for Occupational Safety and Health and IBM to address possible occupational exposures, silicon-based nanowires (SiNWs were obtained for our study. These SiNWs are anisotropic filamentary crystals of silicon, synthesized by the vapor-liquid-solid method and used in bio-sensors, gas sensors, and field effect transistors. Reactive oxygen species (ROS can be generated when organisms are exposed to a material causing cellular responses, such as lipid peroxidation, H 2 O 2 production, and DNA damage. SiNWs were assessed using three different in vitro environments (H 2 O 2 , RAW 264.7 cells, and rat alveolar macrophages for ROS generation and possible toxicity identification. We used electron spin resonance, analysis of lipid peroxidation, measurement of H 2 O 2 production, and the comet assay to assess generation of ROS from SiNW and define possible mechanisms. Our results demonstrate that SiNWs do not appear to be significant generators of free radicals.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-04-27

    Highlights: Black-Right-Pointing-Pointer Matairesinol suppresses mitochondrial ROS generation during hypoxia. Black-Right-Pointing-Pointer Matairesinol exhibits potent anti-angiogenic activity both in vitro and in vivo. Black-Right-Pointing-Pointer Matairesinol could be a basis for the development of novel anti-angiogenic agents. -- Abstract: Mitochondrial reactive oxygen species (mROS) are involved in cancer initiation and progression and function as signaling molecules in many aspects of hypoxia and growth factor-mediated signaling. Here we report that matairesinol, a natural small molecule identified from the cell-based screening of 200 natural plants, suppresses mROS generation resulting in anti-angiogenic activity. A non-toxic concentration of matairesinol inhibited the proliferation of human umbilical vein endothelial cells. The compound also suppressed in vitro angiogenesis of tube formation and chemoinvasion, as well as in vivo angiogenesis of the chorioallantoic membrane at non-toxic doses. Furthermore, matairesinol decreased hypoxia-inducible factor-1{alpha} in hypoxic HeLa cells. These results demonstrate that matairesinol could function as a novel angiogenesis inhibitor by suppressing mROS signaling.

  14. Pleiotropic Effects of Biguanides on Mitochondrial Reactive Oxygen Species Production

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    Alena Pecinova

    2017-01-01

    Full Text Available Metformin is widely prescribed as a first-choice antihyperglycemic drug for treatment of type 2 diabetes mellitus, and recent epidemiological studies showed its utility also in cancer therapy. Although it is in use since the 1970s, its molecular target, either for antihyperglycemic or antineoplastic action, remains elusive. However, the body of the research on metformin effect oscillates around mitochondrial metabolism, including the function of oxidative phosphorylation (OXPHOS apparatus. In this study, we focused on direct inhibitory mechanism of biguanides (metformin and phenformin on OXPHOS complexes and its functional impact, using the model of isolated brown adipose tissue mitochondria. We demonstrate that biguanides nonspecifically target the activities of all respiratory chain dehydrogenases (mitochondrial NADH, succinate, and glycerophosphate dehydrogenases, but only at very high concentrations (10−2–10−1 M that highly exceed cellular concentrations observed during the treatment. In addition, these concentrations of biguanides also trigger burst of reactive oxygen species production which, in combination with pleiotropic OXPHOS inhibition, can be toxic for the organism. We conclude that the beneficial effect of biguanides should probably be associated with subtler mechanism, different from the generalized inhibition of the respiratory chain.

  15. Role of Melanin in Melanocyte Dysregulation of Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Noah C. Jenkins

    2013-01-01

    Full Text Available We have recently reported a potential alternative tumor suppressor function for p16 relating to its capacity to regulate oxidative stress and observed that oxidative dysregulation in p16-depleted cells was most profound in melanocytes, compared to keratinocytes or fibroblasts. Moreover, in the absence of p16 depletion or exogenous oxidative insult, melanocytes exhibited significantly higher basal levels of reactive oxygen species (ROS than these other epidermal cell types. Given the role of oxidative stress in melanoma development, we speculated that this increased susceptibility of melanocytes to oxidative stress (and greater reliance on p16 for suppression of ROS may explain why genetic compromise of p16 is more commonly associated with predisposition to melanoma rather than other cancers. Here we show that the presence of melanin accounts for this differential oxidative stress in normal and p16-depleted melanocytes. Thus the presence of melanin in the skin appears to be a double-edged sword: it protects melanocytes as well as neighboring keratinocytes in the skin through its capacity to absorb UV radiation, but its synthesis in melanocytes results in higher levels of intracellular ROS that may increase melanoma susceptibility.

  16. Correlation between Mitochondrial Reactive Oxygen and Severity of Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Gabriel G. Dorighello

    2016-01-01

    Full Text Available Atherosclerosis has been associated with mitochondria dysfunction and damage. Our group demonstrated previously that hypercholesterolemic mice present increased mitochondrial reactive oxygen (mtROS generation in several tissues and low NADPH/NADP+ ratio. Here, we investigated whether spontaneous atherosclerosis in these mice could be modulated by treatments that replenish or spare mitochondrial NADPH, named citrate supplementation, cholesterol synthesis inhibition, or both treatments simultaneously. Robust statistical analyses in pooled group data were performed in order to explain the variation of atherosclerosis lesion areas as related to the classic atherosclerosis risk factors such as plasma lipids, obesity, and oxidative stress, including liver mtROS. Using three distinct statistical tools (univariate correlation, adjusted correlation, and multiple regression with increasing levels of stringency, we identified a novel significant association and a model that reliably predicts the extent of atherosclerosis due to variations in mtROS. Thus, results show that atherosclerosis lesion area is positively and independently correlated with liver mtROS production rates. Based on these findings, we propose that modulation of mitochondrial redox state influences the atherosclerosis extent.

  17. Mitochondrial Reactive Oxygen Species Trigger Hypoxia-Induced Transcription

    Science.gov (United States)

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

    1998-09-01

    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 (ρ 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) ρ 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 ρ 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.

  18. Real-Time In Vivo Monitoring of Reactive Oxygen Species in Guard Cells.

    Science.gov (United States)

    Park, Ky Young; Roubelakis-Angelakis, Kalliopi A

    2018-01-01

    The intra-/intercellular homeostasis of reactive oxygen species (ROS), and especially of superoxides (O 2 .- ) and hydrogen peroxide (O 2 .- ) participate in signalling cascades which dictate developmental processes and reactions to biotic/abiotic stresses. Polyamine oxidases terminally oxidize/back convert polyamines generating H 2 O 2 . Recently, an NADPH-oxidase/Polyamine oxidase feedback loop was identified to control oxidative burst under salinity. Thus, the real-time localization/monitoring of ROS in specific cells, such as the guard cells, can be of great interest. Here we present a detailed description of the real-time in vivo monitoring of ROS in the guard cells using H 2 O 2 - and O 2 .- specific fluorescing probes, which can be used for studying ROS accumulation generated from any source, including the amine oxidases-dependent pathway, during development and stress.

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

    Science.gov (United States)

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

    2014-04-01

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

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

    Science.gov (United States)

    Schillinger, Kurt J.; Patel, Vickas V.

    2012-01-01

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

  1. ent-Jungermannenone C Triggers Reactive Oxygen Species-Dependent Cell Differentiation in Leukemia Cells.

    Science.gov (United States)

    Yue, Zongwei; Xiao, Xinhua; Wu, Jinbao; Zhou, Xiaozhou; Liu, Weilong; Liu, Yaxi; Li, Houhua; Chen, Guoqiang; Wu, Yingli; Lei, Xiaoguang

    2018-02-23

    Acute myeloid leukemia (AML) is a hematologic malignancy that is characterized by clonal proliferation of myeloid blasts. Despite the progress that has been made in the treatment of various malignant hematopoietic diseases, the effective treatment of AML remains very challenging. Differentiation therapy has emerged as a promising approach for leukemia treatment, and new and effective chemical agents to trigger the differentiation of AML cells, especially drug-resistant cells, are urgently required. Herein, the natural product jungermannenone C, a tetracyclic diterpenoid isolated from liverworts, is reported to induce cell differentiation in AML cells. Interestingly, the unnatural enantiomer of jungermannenone C (1) was found to be more potent than jungermannenone C in inducing cell differentiation. Furthermore, compound 1 targets peroxiredoxins I and II by selectively binding to the conserved cysteine residues and leads to cellular reactive oxygen species accumulation. Accordingly, ent-jungermannenone C (1) shows potential for further investigation as an effective differentiation therapy against AML.

  2. [Relationship among the Oxygen Concentration, Reactive Oxygen Species and the Biological Characteristics of Mouse Bone Marrow Hematopoietic Stem Cells].

    Science.gov (United States)

    Ren, Si-Hua; He, Yu-Xin; Ma, Yi-Ran; Jin, Jing-Chun; Kang, Dan

    2016-02-01

    To investigate the effects of oxygen concentration and reactive oxygen species (ROS) on the biological characteristics of hematopoietic stem cells (HSC) and to analyzed the relationship among the oxygen concentration, ROS and the biological characteristics of mouse HSC through simulation of oxygen environment experienced by PB HSC during transplantation. The detection of reactive oxygen species (ROS), in vitro amplification, directional differentiation (BFU-E, CFU-GM, CFU-Mix), homing of adhesion molecules (CXCR4, CD44, VLA4, VLA5, P-selectin), migration rate, CFU-S of NOD/SCID mice irradiated with sublethal dose were performed to study the effect of oxgen concentration and reactive oxygen species on the biological characteristics of mouse BM-HSC and the relationship among them. The oxygen concentrations lower than normal oxygen concentration (especially hypoxic oxygen environment) could reduce ROS level and amplify more Lin(-) c-kit(+) Sca-1(+) BM HSC, which was more helpful to the growth of various colonies (BFU-E, CFU-GM, CFU-Mix) and to maintain the migratory ability of HSC, thus promoting CFU-S growth significantly after the transplantation of HSC in NOD/SCID mice irradiated by a sublethal dose. BM HSC exposed to oxygen environments of normal, inconstant oxygen level and strenuously thanging of oxygen concentration could result in higher level of ROS, at the same time, the above-mentioned features and functional indicators were relatively lower. The ROS levels of BM HSC in PB HSCT are closely related to the concentrations and stability of oxygen surrounding the cells. High oxygen concentration results in an high level of ROS, which is not helpful to maintain the biological characteristics of BM HSC. Before transplantation and in vitro amplification, the application of antioxidancs and constant oxygen level environments may be beneficial for transplantation of BMMSC.

  3. Molecular and biochemical mechanisms in teratogenesis involving reactive oxygen species

    International Nuclear Information System (INIS)

    Wells, Peter G.; Bhuller, Yadvinder; Chen, Connie S.; Jeng, Winnie; Kasapinovic, Sonja; Kennedy, Julia C.; Kim, Perry M.; Laposa, Rebecca R.; McCallum, Gordon P.; Nicol, Christopher J.; Parman, Toufan; Wiley, Michael J.; Wong, Andrea W.

    2005-01-01

    Developmental pathologies may result from endogenous or xenobiotic-enhanced formation of reactive oxygen species (ROS), which oxidatively damage cellular macromolecules and/or alter signal transduction. This minireview focuses upon several model drugs (phenytoin, thalidomide, methamphetamine), environmental chemicals (benzo[a]pyrene) and gamma irradiation to examine this hypothesis in vivo and in embryo culture using mouse, rat and rabbit models. Embryonic prostaglandin H synthases (PHSs) and lipoxygenases bioactivate xenobiotics to free radical intermediates that initiate ROS formation, resulting in oxidation of proteins, lipids and DNA. Oxidative DNA damage and embryopathies are reduced in PHS knockout mice, and in mice treated with PHS inhibitors, antioxidative enzymes, antioxidants and free radical trapping agents. Thalidomide causes embryonic DNA oxidation in susceptible (rabbit) but not resistant (mouse) species. Embryopathies are increased in mutant mice deficient in the antioxidative enzyme glucose-6-phosphate dehydrogenase (G6PD), or by glutathione (GSH) depletion, or inhibition of GSH peroxidase or GSH reductase. Inducible nitric oxide synthase knockout mice are partially protected. Inhibition of Ras or NF-kB pathways reduces embryopathies, implicating ROS-mediated signal transduction. Atm and p53 knockout mice deficient in DNA damage response/repair are more susceptible to xenobiotic or radiation embryopathies, suggesting a teratological role for DNA damage, consistent with enhanced susceptibility to methamphetamine in ogg1 knockout mice with deficient repair of oxidative DNA damage. Even endogenous embryonic oxidative stress carries a risk, since untreated G6PD- or ATM-deficient mice have increased embryopathies. Thus, embryonic processes regulating the balance of ROS formation, oxidative DNA damage and repair, and ROS-mediated signal transduction may be important determinants of teratological risk

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

    Science.gov (United States)

    Lushchak, Volodymyr I

    2014-12-05

    Reactive oxygen species (ROS) initially considered as only damaging agents in living organisms further were found to play positive roles also. This paper describes ROS homeostasis, principles of their investigation and technical approaches to investigate ROS-related processes. Especial attention is paid to complications related to experimental documentation of these processes, their diversity, spatiotemporal distribution, relationships with physiological state of the organisms. Imbalance between ROS generation and elimination in favor of the first with certain consequences for cell physiology has been called "oxidative stress". Although almost 30years passed since the first definition of oxidative stress was introduced by Helmut Sies, to date we have no accepted classification of oxidative stress. In order to fill up this gape here classification of oxidative stress based on its intensity is proposed. Due to that oxidative stress may be classified as basal oxidative stress (BOS), low intensity oxidative stress (LOS), intermediate intensity oxidative stress (IOS), and high intensity oxidative stress (HOS). Another classification of potential interest may differentiate three categories such as mild oxidative stress (MOS), temperate oxidative stress (TOS), and finally severe (strong) oxidative stress (SOS). Perspective directions of investigations in the field include development of sophisticated classification of oxidative stresses, accurate identification of cellular ROS targets and their arranged responses to ROS influence, real in situ functions and operation of so-called "antioxidants", intracellular spatiotemporal distribution and effects of ROS, deciphering of molecular mechanisms responsible for cellular response to ROS attacks, and ROS involvement in realization of normal cellular functions in cellular homeostasis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. The influence of endogenously generated reactive oxygen species on the inotropic and chronotropic effects of adrenoceptor and ET-receptor stimulation

    NARCIS (Netherlands)

    Sand, Carsten; Peters, Stephan L. M.; Pfaffendorf, Martin; van Zwieten, Pieter A.

    2003-01-01

    Reactive oxygen species (ROS) play a role in cardiovascular diseases such as heart failure and hypertension. Furthermore, increasing evidence has accumulated suggesting that ROS can also be formed subsequent to the stimulation of various receptors, thus functioning as second messengers. The

  6. Involvement of oxygen reactive species in the cellular response of carcinoma cells to irradiation

    International Nuclear Information System (INIS)

    Tulard, A.

    2004-06-01

    After a presentation of oxygen reactive species and their sources, the author describes the enzymatic and non-enzymatic anti-oxidative defenses, the physiological roles of oxygen reactive species, the oxidative stress, the water radiolysis, the anti-oxidative enzymes and the effects of ionizing radiations. The author then reports an investigation on the contribution of oxygen reactive species in the cellular response to irradiation, and an investigation on the influence of the breathing chain on the persistence of a radio-induced oxidative stress. He also reports a research on molecular mechanisms involved in the cellular radio-sensitivity

  7. DMPD: NF-kappaB activation by reactive oxygen species: fifteen years later. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16723122 NF-kappaB activation by reactive oxygen species: fifteen years later. Gloi...svg) (.html) (.csml) Show NF-kappaB activation by reactive oxygen species: fifteen years later. PubmedID 167...23122 Title NF-kappaB activation by reactive oxygen species: fifteen years later.

  8. Reactive oxygen species as a signal in glucose-stimulated insulin secretion.

    Science.gov (United States)

    Pi, Jingbo; Bai, Yushi; Zhang, Qiang; Wong, Victoria; Floering, Lisa M; Daniel, Kiefer; Reece, Jeffrey M; Deeney, Jude T; Andersen, Melvin E; Corkey, Barbara E; Collins, Sheila

    2007-07-01

    One of the unique features of beta-cells is their relatively low expression of many antioxidant enzymes. This could render beta-cells susceptible to oxidative damage but may also provide a system that is sensitive to reactive oxygen species as signals. In isolated mouse islets and INS-1(832/13) cells, glucose increases intracellular accumulation of H2O2. In both models, insulin secretion could be stimulated by provision of either exogenous H2O2 or diethyl maleate, which raises intracellular H2O2 levels. Provision of exogenous H2O2 scavengers, including cell permeable catalase and N-acetyl-L-cysteine, inhibited glucose-stimulated H2O2 accumulation and insulin secretion (GSIS). In contrast, cell permeable superoxide dismutase, which metabolizes superoxide into H2O2, had no effect on GSIS. Because oxidative stress is an important risk factor for beta-cell dysfunction in diabetes, the relationship between glucose-induced H2O2 generation and GSIS was investigated under various oxidative stress conditions. Acute exposure of isolated mouse islets or INS-1(832/13) cells to oxidative stressors, including arsenite, 4-hydroxynonenal, and methylglyoxal, led to decreased GSIS. This impaired GSIS was associated with increases in a battery of endogenous antioxidant enzymes. Taken together, these findings suggest that H2O2 derived from glucose metabolism is one of the metabolic signals for insulin secretion, whereas oxidative stress may disturb its signaling function.

  9. Nitric Oxide and Reactive Oxygen Species in the Pathogenesis of Preeclampsia

    Directory of Open Access Journals (Sweden)

    Keiichi Matsubara

    2015-03-01

    Full Text Available Preeclampsia (PE is characterized by disturbed extravillous trophoblast migration toward uterine spiral arteries leading to increased uteroplacental vascular resistance and by vascular dysfunction resulting in reduced systemic vasodilatory properties. Its pathogenesis is mediated by an altered bioavailability of nitric oxide (NO and tissue damage caused by increased levels of reactive oxygen species (ROS. Furthermore, superoxide (O2− rapidly inactivates NO and forms peroxynitrite (ONOO−. It is known that ONOO− accumulates in the placental tissues and injures the placental function in PE. In addition, ROS could stimulate platelet adhesion and aggregation leading to intravascular coagulopathy. ROS-induced coagulopathy causes placental infarction and impairs the uteroplacental blood flow in PE. The disorders could lead to the reduction of oxygen and nutrients required for normal fetal development resulting in fetal growth restriction. On the other hand, several antioxidants scavenge ROS and protect tissues against oxidative damage. Placental antioxidants including catalase, superoxide dismutase (SOD, and glutathione peroxidase (GPx protect the vasculature from ROS and maintain the vascular function. However, placental ischemia in PE decreases the antioxidant activity resulting in further elevated oxidative stress, which leads to the appearance of the pathological conditions of PE including hypertension and proteinuria. Oxidative stress is defined as an imbalance between ROS and antioxidant activity. This review provides new insights about roles of oxidative stress in the pathophysiology of PE.

  10. Prodrugs activated by reactive oxygen species for use in the treatment of inflammatory diseases and cancer

    DEFF Research Database (Denmark)

    2018-01-01

    Prodrugs activated predominantly or exclusively in inflammatory tissue, more particularly prodrugs of methotrexate and derivatives thereof, which are selectively activated by Reactive Oxygen Species (ROS) in inflammatory tissues associated with cancer and inflammatory diseases, as well as method...

  11. Mitochondrion-derived reactive oxygen species lead to enhanced amyloid beta formation

    NARCIS (Netherlands)

    Leuner, K.; Schutt, T.; Kurz, C.; Eckert, S.H.; Schiller, C.; Occhipinti, A.; Mai, S.; Jendrach, M.; Eckert, G.P.; Kruse, S.E.; Palmiter, R.D.; Brandt, U.; Drose, S.; Wittig, I.; Willem, M.; Haass, C.; Reichert, A.S.; Muller, W.E.

    2012-01-01

    AIMS: Intracellular amyloid beta (Abeta) oligomers and extracellular Abeta plaques are key players in the progression of sporadic Alzheimer's disease (AD). Still, the molecular signals triggering Abeta production are largely unclear. We asked whether mitochondrion-derived reactive oxygen species

  12. Solar light-induced production of reactive oxygen species by single walled carbon nanotubes in water

    Science.gov (United States)

    Photosensitizing processes of engineered nanomaterials (ENMs) which include photo-induced production of reactive oxygen species (ROS) convert light energy into oxidizing chemical energy that mediates transformations of nanomaterials. The oxidative stress associated with ROS may p...

  13. Oxygen pathway modeling estimates high reactive oxygen species production above the highest permanent human habitation.

    Directory of Open Access Journals (Sweden)

    Isaac Cano

    Full Text Available The production of reactive oxygen species (ROS from the inner mitochondrial membrane is one of many fundamental processes governing the balance between health and disease. It is well known that ROS are necessary signaling molecules in gene expression, yet when expressed at high levels, ROS may cause oxidative stress and cell damage. Both hypoxia and hyperoxia may alter ROS production by changing mitochondrial Po2 (PmO2. Because PmO2 depends on the balance between O2 transport and utilization, we formulated an integrative mathematical model of O2 transport and utilization in skeletal muscle to predict conditions to cause abnormally high ROS generation. Simulations using data from healthy subjects during maximal exercise at sea level reveal little mitochondrial ROS production. However, altitude triggers high mitochondrial ROS production in muscle regions with high metabolic capacity but limited O2 delivery. This altitude roughly coincides with the highest location of permanent human habitation. Above 25,000 ft., more than 90% of exercising muscle is predicted to produce abnormally high levels of ROS, corresponding to the "death zone" in mountaineering.

  14. Norvaline is accumulated after a down-shift of oxygen in Escherichia coli W3110

    Directory of Open Access Journals (Sweden)

    Bernhardt Jörg

    2008-10-01

    Full Text Available Abstract Background Norvaline is an unusual non-proteinogenic branched-chain amino acid which has been of interest especially during the early enzymological studies on regulatory mutants of the branched-chain amino acid pathway in Serratia marcescens. Only recently norvaline and other modified amino acids of the branched-chain amino acid synthesis pathway got attention again when they were found to be incorporated in minor amounts in heterologous proteins with a high leucine or methionine content. Earlier experiments have convincingly shown that norvaline and norleucine are formed from pyruvate being an alternative substrate of α-isopropylmalate synthase, however so far norvaline accumulation was not shown to occur in non-recombinant strains of E. coli. Results Here we show that oxygen limitation causes norvaline accumulation in E. coli K-12 W3110 during grow in glucose-based mineral salt medium. Norvaline accumulates immediately after a shift to oxygen limitation at high glucose concentration. On the contrary free norvaline is not accumulated in E. coli W3110 in aerobic cultures. The analysis of medium components, supported by transcriptomic studies proposes a purely metabolic overflow mechanism from pyruvate into the branched chain amino acid synthesis pathway, which is further supported by the significant accumulation of pyruvate after the oxygen downshift. The results indicate overflow metabolism from pyruvate as necessary and sufficient, but deregulation of the branched chain amino acid pathway may be an additional modulating parameter. Conclusion Norvaline synthesis has been so far mainly related to an imbalance of the synthesis of the branched chain amino acids under conditions were pyruvate level is high. Here we show that simply a downshift of oxygen is sufficient to cause norvaline accumulation at a high glucose concentration as a consequence of the accumulation of pyruvate and its direct chain elongation over α-ketobutyrate and

  15. Reactivity of amino acid anions with nitrogen and oxygen atoms.

    Science.gov (United States)

    Wang, Zhe-Chen; Li, Ya-Ke; He, Sheng-Gui; Bierbaum, Veronica M

    2018-02-14

    For many decades, astronomers have searched for biological molecules, including amino acids, in the interstellar medium; this endeavor is important for investigating the hypothesis of the origin of life from space. The space environment is complex and atomic species, such as nitrogen and oxygen atoms, are widely distributed. In this work, the reactions of eight typical deprotonated amino acids (glycine, alanine, cysteine, proline, aspartic acid, histidine, tyrosine, and tryptophan) with ground state nitrogen and oxygen atoms are studied by experiment and theory. These amino acid anions do not react with nitrogen atoms. However, the reactions of these ions with oxygen atoms show an intriguing variety of ionic products and the reaction rate constants are of the order of 10 -10 cm 3 s -1 . Density functional calculations provide detailed mechanisms of the reactions, and demonstrate that spin conversion is essential for some processes. Our study provides important data and insights for understanding the kinetic and dynamic behavior of amino acids in space environments.

  16. Production of reactive oxygen species from abraded silicates. Implications for the reactivity of the Martian soil

    Science.gov (United States)

    Bak, Ebbe N.; Zafirov, Kaloyan; Merrison, Jonathan P.; Jensen, Svend J. Knak; Nørnberg, Per; Gunnlaugsson, Haraldur P.; Finster, Kai

    2017-09-01

    The results of the Labeled Release and the Gas Exchange experiments conducted on Mars by the Viking Landers show that compounds in the Martian soil can cause oxidation of organics and a release of oxygen in the presence of water. Several sources have been proposed for the oxidizing compounds, but none has been validated in situ and the cause of the observed oxidation has not been resolved. In this study, laboratory simulations of saltation were conducted to examine if and under which conditions wind abrasion of silicates, a process that is common on the Martian surface, can give rise to oxidants in the form of hydrogen peroxide (H2O2) and hydroxyl radicals (ṡOH). We found that silicate samples abraded in simulated Martian atmospheres gave rise to a significant production of H2O2 and ṡOH upon contact with water. Our experiments demonstrated that abraded silicates could lead to a production of H2O2 facilitated by atmospheric O2 and inhibited by carbon dioxide. Furthermore, during simulated saltation the silicate particles became triboelectrically charged and at pressures similar to the Martian surface pressure we observed glow discharges. Electrical discharges can cause dissociation of CO2 and through subsequent reactions lead to a production of H2O2. These results indicate that the reactions linked to electrical discharges are the dominant source of H2O2 during saltation of silicates in a simulated Martian atmosphere, given the low pressure and the relatively high concentration of CO2. Our experiments provide evidence that wind driven abrasion could enhance the reactivity of the Martian soil and thereby could have contributed to the oxidation of organic compounds and the O2 release observed in the Labeled Release and the Gas Exchange experiments. Furthermore, the release of H2O2 and ṡOH from abraded silicates could have a negative effect on the persistence of organic compounds in the Martian soil and the habitability of the Martian surface.

  17. Reactive oxygen species produced by irradiation of some phthalocyanine derivatives

    Czech Academy of Sciences Publication Activity Database

    Černý, J.; Karásková, M.; Rakušan, J.; Nešpůrek, Stanislav

    2010-01-01

    Roč. 210, č. 1 (2010), s. 82-88 ISSN 1010-6030 R&D Projects: GA AV ČR KAN400720701 Institutional research plan: CEZ:AV0Z40500505 Keywords : singlet oxygen * photosensitizer * phthalocyanine Subject RIV: CG - Electrochemistry Impact factor: 2.243, year: 2010

  18. Effects of the Oxygenation level on Formation of Different Reactive Oxygen Species During Photodynamic Therapy

    OpenAIRE

    Price, Michael; Heilbrun, Lance; Kessel, David

    2013-01-01

    We examined the effect of the oxygenation level on efficacy of two photosensitizing agents, both of which target lysosomes for photodamage but via different photochemical pathways. Upon irradiation, the chlorin termed NPe6 forms singlet oxygen in high yield while the bacteriopheophorbide WST11 forms only oxygen radicals (in an aqueous environment). Photokilling efficacy by WST11 in cell culture was impaired when the atmospheric oxygen concentration was reduced from 20% to 1%, while photokilli...

  19. Organic carbon accumulation and reactivity in central Swedish lakes during the Holocene

    Science.gov (United States)

    Chmiel, H.; Kokic, J.; Niggemann, J.; Dittmar, T.; Sobek, S.

    2012-04-01

    Sedimentation and burial of particulate organic carbon (POC), received from terrestrial sources and from lake internal primary production, are responsible for the progressive accumulation and long-term storage of organic matter in lake basins. For lakes in the boreal zone of central Sweden it can be presumed, that the onset of POC accumulation occurred during the early Holocene (˜8000 BP.) after the retreat of the Scandinavian ice sheet. In this study we investigated carbon mass accumulation rates (CMARs), as well as sources and reactivity of deposited organic material, for seven lakes in central Sweden (60°N, 15°E), in order to obtain a detailed temporal resolution of carbon burial and preservation in boreal lakes. Sediment long-cores were sampled in March 2011 from the ice, and CMARs were calculated from water contents, dry bulk densities, carbon contents and radiocarbon (14C) ages of the depth profiles. To indicate the sources of the organic material and characterize its diagenetic state, we determined carbon-nitrogen ratios (C/N) as well as amounts and compositions of lignin phenols. The transitions from organic rich sediment layers to glacial till deposits were found to be in sediment depths of ˜3 m in each lake. POC contents were on average highest (25-34 wt. % C), in small lakes (≤ 0.07 km2) and lowest (10-18 wt. % C) in the larger lakes (≥ 165 km2). The CMARs over the Holocene showed significant variations and were on average lower in the early Holocene, compared to recent accumulation rates. C/N values and the composition of lignin phenols further provided indications of important changes in organic matter source and reactivity over the Holocene. In summary, our data suggest that boreal lake sediments were a significantly stronger sink for organic carbon during the last ~150 years than during earlier periods of the Holocene.

  20. Antifungal Effect of Arabidopsis SGT1 Proteins via Mitochondrial Reactive Oxygen Species.

    Science.gov (United States)

    Park, Seong-Cheol; Cheong, Mi Sun; Kim, Eun-Ji; Kim, Jin Hyo; Chi, Yong Hun; Jang, Mi-Kyeong

    2017-09-27

    The highly conserved SGT1 (suppressor of the G2 alleles of skp1) proteins from Arabidopsis are known to contribute to plant resistance to pathogens. While SGT1 proteins respond to fungal pathogens, their antifungal activity is not reported and the mechanism for this inhibition is not well understood. Therefore, recombinant Arabidopsis SGT1 proteins were cloned, expressed, and purified to evaluate their antifungal activity, resulting in their potent inhibition of pathogen growth. Dye-labeled proteins are localized to the cytosol of Candida albicans cells without the disruption of the cell membrane. Moreover, we showed that entry of the proteins into C. albicans cells resulted in the accumulation of reactive oxygen species (ROS) and cell death via altered mitochondrial potential. Morphological changes of C. albicans cells in the presence of proteins were visualized by scanning electron microscopy. Our data suggest that AtSGT1 proteins play a critical role in plant resistance to pathogenic fungal infection and they can be classified to a new plant antifungal protein.

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

    Science.gov (United States)

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

    2013-11-01

    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 β-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), γ-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.

  2. Interaction between Mitochondrial Reactive Oxygen Species, Heme Oxygenase, and Nitric Oxide Synthase Stimulates Phagocytosis in Macrophages

    Directory of Open Access Journals (Sweden)

    Andrea Müllebner

    2018-01-01

    Full Text Available BackgroundMacrophages are cells of the innate immune system that populate every organ. They are required not only for defense against invading pathogens and tissue repair but also for maintenance of tissue homeostasis and iron homeostasis.AimThe aim of this study is to understand whether heme oxygenase (HO and nitric oxide synthase (NOS contribute to the regulation of nicotinamide adenine dinucleotide phosphate oxidase (NOX activity and phagocytosis, two key components of macrophage function.MethodsThis study was carried out using resting J774A.1 macrophages treated with hemin or vehicle. Activity of NOS, HO, or NOX was inhibited using specific inhibitors. Reactive oxygen species (ROS formation was determined by Amplex® red assay, and phagocytosis was measured using fluorescein isothiocyanate-labeled bacteria. In addition, we analyzed the fate of the intracellular heme by using electron spin resonance.ResultsWe show that both enzymes NOS and HO are essential for phagocytic activity of macrophages. NOS does not directly affect phagocytosis, but stimulates NOX activity via nitric oxide-triggered ROS production of mitochondria. Treatment of macrophages with hemin results in intracellular accumulation of ferrous heme and an inhibition of phagocytosis. In contrast to NOS, HO products, including carbon monoxide, neither clearly affect NOX activity nor clearly affect phagocytosis, but phagocytosis is accelerated by HO-mediated degradation of heme.ConclusionBoth enzymes contribute to the bactericidal activity of macrophages independently, by controlling different pathways.

  3. Reactive oxygen species signaling and stomatal movement: Current updates and future perspectives

    Directory of Open Access Journals (Sweden)

    Rachana Singh

    2017-04-01

    Full Text Available Reactive oxygen species (ROS, a by-product of aerobic metabolism were initially studied in context to their damaging effect but recent decades witnessed significant advancements in understanding the role of ROS as signaling molecules. Contrary to earlier views, it is becoming evident that ROS production is not necessarily a symptom of cellular dysfunction but it might represent a necessary signal in adjusting the cellular machinery according to the altered conditions. Stomatal movement is controlled by multifaceted signaling network in response to endogenous and environmental signals. Furthermore, the stomatal aperture is regulated by a coordinated action of signaling proteins, ROS-generating enzymes, and downstream executors like transporters, ion pumps, plasma membrane channels, which control the turgor pressure of the guard cell. The earliest hallmarks of stomatal closure are ROS accumulation in the apoplast and chloroplasts and thereafter, there is a successive increase in cytoplasmic Ca2+ level which rules the multiple kinases activity that in turn regulates the activity of ROS-generating enzymes and various ion channels. In addition, ROS also regulate the action of multiple proteins directly by oxidative post translational modifications to adjust guard cell signaling. Notwithstanding, an active progress has been made with ROS signaling mechanism but the regulatory action for ROS signaling processes in stomatal movement is still fragmentary. Therefore, keeping in view the above facts, in this mini review the basic concepts and role of ROS signaling in the stomatal movement have been presented comprehensively along with recent highlights.

  4. α-Syntrophin stabilizes catalase to reduce endogenous reactive oxygen species levels during myoblast differentiation.

    Science.gov (United States)

    Moon, Jae Yun; Choi, Su Jin; Heo, Cheol Ho; Kim, Hwan Myung; Kim, Hye Sun

    2017-07-01

    α-Syntrophin is a component of the dystrophin-glycoprotein complex that interacts with various intracellular signaling proteins in muscle cells. The α-syntrophin knock-down C2 cell line (SNKD), established by infecting lentivirus particles with α-syntrophin shRNA, is characterized by a defect in terminal differentiation and increase in cell death. Since myoblast differentiation is accompanied by intensive mitochondrial biogenesis, the generation of intracellular reactive oxygen species (ROS) is also increased during myogenesis. Two-photon microscopy imaging showed that excessive intracellular ROS accumulated during the differentiation of SNKD cells as compared with control cells. The formation of 4-hydroxynonenal adduct, a byproduct of lipid peroxidation during oxidative stress, significantly increased in differentiated SNKD myotubes and was dramatically reduced by epigallocatechin-3-gallate, a well-known ROS scavenger. Among antioxidant enzymes, catalase was significantly decreased during differentiation of SNKD cells without changes at the mRNA level. Of interest was the finding that the degradation of catalase was rescued by MG132, a proteasome inhibitor, in the SNKD cells. This study demonstrates a novel function of α-syntrophin. This protein plays an important role in the regulation of oxidative stress from endogenously generated ROS during myoblast differentiation by modulating the protein stability of catalase. © 2017 Federation of European Biochemical Societies.

  5. Reactive oxygen species dynamics in roots of salt sensitive and salt tolerant cultivars of rice.

    Science.gov (United States)

    Saini, Shivani; Kaur, Navdeep; Pati, Pratap Kumar

    2018-06-01

    Salinity stress is one of the major constraints for growth and survival of plants that affects rice productivity worldwide. Hence, in the present study, roots of two contrasting salinity sensitive cultivars, IR64 (IR64, salt sensitive) and Luna Suvarna (LS, salt tolerant) were compared with regard to the levels of reactive oxygen species (ROS) to derive clues for their differential salt stress adaptation mechanisms. In our investigation, the tolerant cultivar exhibited longer primary roots, more lateral roots, higher root number leading to increased root biomass, with respect to IR64. It was observed that LS roots maintained higher level of H 2 O 2 in comparison to IR64. The activities of various enzymes involved in enzymatic antioxidant defense mechanism (SOD, CAT, GPX, DHAR and MDHAR) were found to be greater in LS roots. Further, the higher transcript level accumulation of genes encoding ROS generating (RbohA, RbohD and RbohE) and scavenging enzymes (Fe-SOD, Chloroplastic Cu/Zn-SOD, CAT and DHAR) were noticed in the roots of tolerant cultivar, LS. Moreover, the content of other stress markers such as total protein and proline were also elevated in LS roots. While, the expression of proline biosynthesis gene (P5CS) and proline catabolism gene (PDH) was observed to be lower in LS. Copyright © 2018. Published by Elsevier Inc.

  6. Effects of the oxygenation level on formation of different reactive oxygen species during photodynamic therapy.

    Science.gov (United States)

    Price, Michael; Heilbrun, Lance; Kessel, David

    2013-01-01

    We examined the effect of the oxygenation level on efficacy of two photosensitizing agents, both of which target lysosomes for photodamage, but via different photochemical pathways. Upon irradiation, the chlorin termed NPe6 forms singlet oxygen in high yield while the bacteriopheophorbide WST11 forms only oxygen radicals (in an aqueous environment). Photokilling efficacy by WST11 in cell culture was impaired when the atmospheric oxygen concentration was reduced from 20% to 1%, while photokilling by NPe6 was unaffected. Studies in a cell-free system revealed that the rates of photobleaching of these agents, as a function of the oxygenation level, were correlated with results described above. Moreover, the rate of formation of oxygen radicals by either agent was more sensitive to the level of oxygenation than was singlet oxygen formation by NPe6. These data indicate that the photochemical process that leads to oxygen radical formation is more dependent on the oxygenation level than is the pathway leading to formation of singlet oxygen. © 2013 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2013 The American Society of Photobiology.

  7. Fanconi anemia links reactive oxygen species to insulin resistance and obesity.

    Science.gov (United States)

    Li, Jie; Sipple, Jared; Maynard, Suzette; Mehta, Parinda A; Rose, Susan R; Davies, Stella M; Pang, Qishen

    2012-10-15

    Insulin resistance is a hallmark of obesity and type 2 diabetes. Reactive oxygen species (ROS) have been proposed to play a causal role in insulin resistance. However, evidence linking ROS to insulin resistance in disease settings has been scant. Since both oxidative stress and diabetes have been observed in patients with the Fanconi anemia (FA), we sought to investigate the link between ROS and insulin resistance in this unique disease model. Mice deficient for the Fanconi anemia complementation group A (Fanca) or Fanconi anemia complementation group C (Fancc) gene seem to be diabetes-prone, as manifested by significant hyperglycemia and hyperinsulinemia, and rapid weight gain when fed with a high-fat diet. These phenotypic features of insulin resistance are characterized by two critical events in insulin signaling: a reduction in tyrosine phosphorylation of the insulin receptor (IR) and an increase in inhibitory serine phosphorylation of the IR substrate-1 in the liver, muscle, and fat tissues from the insulin-challenged FA mice. High levels of ROS, spontaneously accumulated or generated by tumor necrosis factor alpha in these insulin-sensitive tissues of FA mice, were shown to underlie the FA insulin resistance. Treatment of FA mice with the natural anti-oxidant Quercetin restores IR signaling and ameliorates the diabetes- and obesity-prone phenotypes. Finally, pairwise screen identifies protein-tyrosine phosphatase (PTP)-α and stress kinase double-stranded RNA-dependent protein kinase (PKR) that mediate the ROS effect on FA insulin resistance. These findings establish a pathogenic and mechanistic link between ROS and insulin resistance in a unique human disease setting. ROS accumulation contributes to the insulin resistance in FA deficiency by targeting both PTP-α and PKR.

  8. Reactive species formed on proteins exposed to singlet oxygen

    DEFF Research Database (Denmark)

    Davies, Michael Jonathan

    2004-01-01

    Singlet oxygen ((1)O(2)) is believed to be generated in biological systems by a range of endogenous processes (e.g. enzymatic and chemical reactions) and exogenous stimuli (e.g. UV or visible light in the presence of a sensitiser). Kinetic data is consistent with proteins being a major target...... hydroperoxides, which can be reduced to the corresponding alcohols; other products arising from radical intermediates can also be generated, particularly in the presence of UV light and metal ions. With His side-chains, poorly characterised peroxides are also formed. Reaction with Met and Cys has been proposed...

  9. Ratiometric reactive oxygen species nanoprobe for noninvasive in vivo imaging of subcutaneous inflammation/infection

    OpenAIRE

    Zhou, Jun; Weng, Hong; Huang, Yihui; Gu, Yueqing; Tang, Liping; Hu, Wenjing

    2016-01-01

    Release of reactive oxygen species (ROS) accompanied with acute inflammation and infection often results in cell death and tissue injury. Several ROS-reactive bioluminescent probes have been investigated in recent years to detect ROS activity in vivo. Unfortunately, these probes cannot be used to quantify the degree of ROS activity and inflammatory responses due to the fact that the extent of the bioluminescent signals is also probe-concentration dependent. To address this challenge, we fabri...

  10. Effects of drying methods on the low temperature reactivity of Victorian brown coal to oxygen

    Energy Technology Data Exchange (ETDEWEB)

    Unal, S.; Wood, D.G.; Harris, I.J. (University of Marmara, Istanbul (Turkey). Ataturk Faculty of Education, Division of Science Education)

    1992-02-01

    The effects of air drying and thermal dewatering on the low temperature oxygen reactivity of Victorian brown coal have been investigated in the temperature range 35-55{degree}C and at 100 kPa oxygen pressure using coal samples ground to {lt} 100 mesh. An attempt has also been made to relate the low temperature oxygen reactivity of the coal to its free radical concentration as measured prior to oxidation. Two rate models, the Schmidt and Winmill models, have been adapted to include the initial free radical concentration of the coal samples as the drying method sensitivity parameter in lieu of the concentration of oxygen-reactive sites in the coal material. The experimental results show that air drying, which reduces the free radical concentration of the coal, causes a decline in its oxygen reactivity whereas thermal dewatering, which causes an increase in the free radical concentration of the coal, enhances its oxygen reactivity. Air drying does not affect the distribution of the consumed oxygen in the oxidation products. A difference is observed in the case of the thermally dewatered coal samples. The correlation of the two rate models adopted is considered equally satisfactory. However, only the values obtained for the two activation energies in the Winmill model reflect the changes caused by thermal dewatering in the oxidation pattern of the coal. The activation energy values obtained from the two models are within the range of those quoted in the literature for the abstraction of hydrogen from various arene structures by free radicals. 35 refs., 10 figs., 8 tabs.

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

    Science.gov (United States)

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

    2013-01-01

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

  12. Are mitochondria a permanent source of reactive oxygen species?

    Science.gov (United States)

    Staniek, K; Nohl, H

    2000-11-20

    The observation that in isolated mitochondria electrons may leak out of the respiratory chain to form superoxide radicals (O(2)(radical-)) has prompted the assumption that O(2)(radical-) formation is a compulsory by-product of respiration. Since mitochondrial O(2)(radical-) formation under homeostatic conditions could not be demonstrated in situ so far, conclusions drawn from isolated mitochondria must be considered with precaution. The present study reveals a link between electron deviation from the respiratory chain to oxygen and the coupling state in the presence of antimycin A. Another important factor is the analytical system applied for the detection of activated oxygen species. Due to the presence of superoxide dismutase in mitochondria, O(2)(radical-) release cannot be realistically determined in intact mitochondria. We therefore followed the release of the stable dismutation product H(2)O(2) by comparing most frequently used H(2)O(2) detection methods. The possible interaction of the detection systems with the respiratory chain was avoided by a recently developed method, which was compared with conventional methods. Irrespective of the methods applied, the substrates used for respiration and the state of respiration established, intact mitochondria could not be made to release H(2)O(2) from dismutating O(2)(radical-). Although regular mitochondrial respiration is unlikely to supply single electrons for O(2)(radical-) formation our study does not exclude the possibility of the respiratory chain becoming a radical source under certain conditions.

  13. Interaction of plant growth regulators and reactive oxygen species to regulate petal senescence in wallflowers (Erysimum linifolium).

    Science.gov (United States)

    Salleh, Faezah Mohd; Mariotti, Lorenzo; Spadafora, Natasha D; Price, Anna M; Picciarelli, Piero; Wagstaff, Carol; Lombardi, Lara; Rogers, Hilary

    2016-04-02

    In many species floral senescence is coordinated by ethylene. Endogenous levels rise, and exogenous application accelerates senescence. Furthermore, floral senescence is often associated with increased reactive oxygen species, and is delayed by exogenously applied cytokinin. However, how these processes are linked remains largely unresolved. Erysimum linifolium (wallflower) provides an excellent model for understanding these interactions due to its easily staged flowers and close taxonomic relationship to Arabidopsis. This has facilitated microarray analysis of gene expression during petal senescence and provided gene markers for following the effects of treatments on different regulatory pathways. In detached Erysimum linifolium (wallflower) flowers ethylene production peaks in open flowers. Furthermore senescence is delayed by treatments with the ethylene signalling inhibitor silver thiosulphate, and accelerated with ethylene released by 2-chloroethylphosphonic acid. Both treatments with exogenous cytokinin, or 6-methyl purine (which is an inhibitor of cytokinin oxidase), delay petal senescence. However, treatment with cytokinin also increases ethylene biosynthesis. Despite the similar effects on senescence, transcript abundance of gene markers is affected differentially by the treatments. A significant rise in transcript abundance of WLS73 (a putative aminocyclopropanecarboxylate oxidase) was abolished by cytokinin or 6-methyl purine treatments. In contrast, WFSAG12 transcript (a senescence marker) continued to accumulate significantly, albeit at a reduced rate. Silver thiosulphate suppressed the increase in transcript abundance both of WFSAG12 and WLS73. Activity of reactive oxygen species scavenging enzymes changed during senescence. Treatments that increased cytokinin levels, or inhibited ethylene action, reduced accumulation of hydrogen peroxide. Furthermore, although auxin levels rose with senescence, treatments that delayed early senescence did not affect

  14. Singlet oxygen reactivity in water-rich solvent mixtures

    Directory of Open Access Journals (Sweden)

    Cristina Sousa

    2008-01-01

    Full Text Available The 3-methylindole (3MI oxygenation sensitized by psoralen (PSO has been investigated in 100%, 20% and 5% O2-saturated water/dioxane (H2O/Dx mixtures. The lowering of the ¹O2* chemical rate when water (k chem∆3MI = 1.4 × 109 M-1 s-1 is replaced by deuterated water (k chem∆3MI = 1.9 × 108 M-1 s-1 suggests that hydrogen abstraction is involved in the rate determining step. A high dependence of the chemical rate constant on water concentration in H2O/Dx mixtures was found showing that water molecules are absolutely essential for the success of the 3MI substrate oxidation by ¹O2* in water-rich solvent mixtures.

  15. Super-oxidation of silicon nanoclusters: magnetism and reactive oxygen species at the surface

    Energy Technology Data Exchange (ETDEWEB)

    Lepeshkin, Sergey; Baturin, Vladimir; Tikhonov, Evgeny; Matsko, Nikita; Uspenskii, Yurii; Naumova, Anastasia; Feya, Oleg; Schoonen, Martin A.; Oganov, Artem R.

    2016-01-01

    Oxidation of silicon nanoclusters depending on the temperature and oxygen pressure is explored from first principles using the evolutionary algorithm, and structural and thermodynamic analysis. From our calculations of 90 SinOm clusters we found that under normal conditions oxidation does not stop at the stoichiometric SiO2 composition, as it does in bulk silicon, but goes further placing extra oxygen atoms on the cluster surface. These extra atoms are responsible for light emission, relevant to reactive oxygen species and many of them are magnetic. We argue that the super-oxidation effect is size-independent and discuss its relevance to nanotechnology and miscellaneous applications, including biomedical ones.

  16. Multiple antioxidant proteins protect Chlorobaculum tepidum against oxygen and reactive oxygen species

    DEFF Research Database (Denmark)

    Li, Hui; Jubelirer, Sara; Garcia Costas, Amaya M

    2009-01-01

    include cytochrome bd quinol oxidase, NADH oxidase, rubredoxin oxygen oxidoreductase, several thiol peroxidases, alkyl hydroperoxide reductase, superoxide dismutase, methionine sulfoxide reductase, and rubrerythrin. To test the physiological functions of some of these proteins, ten genes were...

  17. Regulation of reactive oxygen and nitrogen species by salicylic acid in rice plants under salinity stress conditions

    Science.gov (United States)

    Mun, Bong-Gyu; Khan, Abdul Latif; Waqas, Muhammad; Kim, Hyun-Ho; Shahzad, Raheem; Imran, Muhammad

    2018-01-01

    This study investigated the regulatory role of exogenous salicylic acid (SA) in rice and its effects on toxic reactive oxygen and nitrogen species during short-term salinity stress. SA application (0.5 and 1.0 mM) during salinity-induced stress (100 mM NaCl) resulted in significantly longer shoot length and higher chlorophyll and biomass accumulation than with salinity stress alone. NaCl-induced reactive oxygen species production led to increased levels of lipid peroxidation in rice plants, which were significantly reduced following SA application. A similar finding was observed for superoxide dismutase; however, catalase (CAT) and ascorbate peroxidase (APX) were significantly reduced in rice plants treated with SA and NaCl alone and in combination. The relative mRNA expression of OsCATA and OsAPX1 was lower in rice plants during SA stress. Regarding nitrogenous species, S-nitrosothiol (SNO) was significantly reduced initially (one day after treatment [DAT]) but then increased in plants subjected to single or combined stress conditions. Genes related to SNO biosynthesis, S-nitrosoglutathione reductase (GSNOR1), NO synthase-like activity (NOA), and nitrite reductase (NIR) were also assessed. The mRNA expression of GSNOR1 was increased relative to that of the control, whereas OsNOA was expressed at higher levels in plants treated with SA and NaCl alone relative to the control. The mRNA expression of OsNR was decreased in plants subjected to single or combination treatment, except at 2 DAT, compared to the control. In conclusion, the current findings suggest that SA can regulate the generation of NaCl-induced oxygen and nitrogen reactive species in rice plants. PMID:29558477

  18. Involvement of reactive oxygen species in the electrochemical inhibition of barnacle (Amphibalanus amphitrite) settlement

    Science.gov (United States)

    Rodolfo E. Perez-Roa; Marc A. Anderson; Dan Rittschof; Christopher G. Hunt; Daniel R. Noguera

    2009-01-01

    The role of reactive oxygen species (ROS) in electrochemical biofouling inhibition was investigated using a series of abiotic tests and settlement experiments with larvae of the barnacle Amphibalanus amphitrite, a cosmopolitan fouler. Larval settlement, a measure of biofouling potential, was reduced from 43% ± 14% to 5% ± 6% upon the application of...

  19. Lysosome-Targeting Amplifiers of Reactive Oxygen Species as Anticancer Prodrugs

    Czech Academy of Sciences Publication Activity Database

    Daum, S.; Reshetnikov, M.S.V.; Šíša, Miroslav; Dumych, T.; Lootsik, M. D.; Bilyy, R.; Bila, E.; Janko, C.; Alexiou, C.; Herrmann, M.; Sellner, L.; Mokhir, A.

    2017-01-01

    Roč. 56, č. 49 (2017), s. 15545-15549 ISSN 1433-7851 Institutional support: RVO:61389030 Keywords : aminoferrocene * cancer * lysosomes * prodrugs * reactive oxygen species Subject RIV: ED - Physiology OBOR OECD: Organic chemistry Impact factor: 11.994, year: 2016

  20. Silkworm (Bombyx mori) hemocytes do not produce reactive oxygen metabolites as a part of defense mechanisms

    Czech Academy of Sciences Publication Activity Database

    Hyršl, P.; Číž, Milan; Kubala, Lukáš; Lojek, Antonín

    2004-01-01

    Roč. 49, č. 3 (2004), s. 315-319 ISSN 0015-5632 R&D Projects: GA AV ČR IBS5004009 Institutional research plan: CEZ:AV0Z5004920 Keywords : hemocytes * Bombyx mori * reactive oxygen species Subject RIV: BO - Biophysics Impact factor: 1.034, year: 2004

  1. Herbivore derived fatty acid-amides elicit reactive oxygen species burst in plants

    Science.gov (United States)

    The formation of a reactive oxygen species (ROS) burst is a central response of plants to many forms of stress including pathogen attack, several abiotic stresses, damage and insect infestation. These ROS act as a direct defense as well as signaling and regulatory molecules. Perception of microbe or...

  2. Radiation induces aerobic glycolysis through reactive oxygen species

    International Nuclear Information System (INIS)

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

    2013-01-01

    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

  3. Reactive Oxygen Species on the Early Earth and Survival of Bacteria

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  5. Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release

    Science.gov (United States)

    Zorov, Dmitry B.; Juhaszova, Magdalena; Sollott, Steven J.

    2014-01-01

    Byproducts of normal mitochondrial metabolism and homeostasis include the buildup of potentially damaging levels of reactive oxygen species (ROS), Ca2+, etc., which must be normalized. Evidence suggests that brief mitochondrial permeability transition pore (mPTP) openings play an important physiological role maintaining healthy mitochondria homeostasis. Adaptive and maladaptive responses to redox stress may involve mitochondrial channels such as mPTP and inner membrane anion channel (IMAC). Their activation causes intra- and intermitochondrial redox-environment changes leading to ROS release. This regenerative cycle of mitochondrial ROS formation and release was named ROS-induced ROS release (RIRR). Brief, reversible mPTP opening-associated ROS release apparently constitutes an adaptive housekeeping function by the timely release from mitochondria of accumulated potentially toxic levels of ROS (and Ca2+). At higher ROS levels, longer mPTP openings may release a ROS burst leading to destruction of mitochondria, and if propagated from mitochondrion to mitochondrion, of the cell itself. The destructive function of RIRR may serve a physiological role by removal of unwanted cells or damaged mitochondria, or cause the pathological elimination of vital and essential mitochondria and cells. The adaptive release of sufficient ROS into the vicinity of mitochondria may also activate local pools of redox-sensitive enzymes involved in protective signaling pathways that limit ischemic damage to mitochondria and cells in that area. Maladaptive mPTP- or IMAC-related RIRR may also be playing a role in aging. Because the mechanism of mitochondrial RIRR highlights the central role of mitochondria-formed ROS, we discuss all of the known ROS-producing sites (shown in vitro) and their relevance to the mitochondrial ROS production in vivo. PMID:24987008

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    Hepatitis B virus (HBV) infection induces reactive oxygen species (ROS) production and has been associated with the development of hepatocellular carcinoma (HCC). ROS are also an important factor in HCC because the accumulated ROS leads to abnormal cell proliferation and chromosome mutation. In oxidative stress, heat shock protein 90 (Hsp90) and glutathione (GSH) function as part of the defense mechanism. Hsp90 prevents cellular component from oxidative stress, and GSH acts as antioxidants scavenging ROS in the cell. However, it is not known whether molecules regulated by oxidative stress are involved in HBV capsid assembly. Based on the previous study that Hsp90 facilitates HBV capsid assembly, which is an important step for the packing of viral particles, here, we show that ROS enrich Hsp90-driven HBV capsid formation. In cell-free system, HBV capsid assembly was facilitated by ROS with Hsp90, whereas it was decreased without Hsp90. In addition, GSH inhibited the function of Hsp90 to decrease HBV capsid assembly. Consistent with the result of cell-free system, ROS and buthionine sulfoximine (BS), an inhibitor of GSH synthesis, increased HBV capsid formation in HepG2.2.15 cells. Thus, our study uncovers the interplay between ROS and Hsp90 during HBV capsid assembly. - Highlights: • We examined H 2 O 2 and GSH modulate HBV capsid assembly. • H 2 O 2 facilitates HBV capsid assembly in the presence of Hsp90. • GSH inhibits function of Hsp90 in facilitating HBV capsid assembly. • H 2 O 2 and GSH induce conformation change of Hsp90

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoon Sik, E-mail: yumshak@naver.com; Seo, Hyun Wook, E-mail: suruk@naver.com; Jung, Guhung, E-mail: drjung@snu.ac.kr

    2015-02-13

    Hepatitis B virus (HBV) infection induces reactive oxygen species (ROS) production and has been associated with the development of hepatocellular carcinoma (HCC). ROS are also an important factor in HCC because the accumulated ROS leads to abnormal cell proliferation and chromosome mutation. In oxidative stress, heat shock protein 90 (Hsp90) and glutathione (GSH) function as part of the defense mechanism. Hsp90 prevents cellular component from oxidative stress, and GSH acts as antioxidants scavenging ROS in the cell. However, it is not known whether molecules regulated by oxidative stress are involved in HBV capsid assembly. Based on the previous study that Hsp90 facilitates HBV capsid assembly, which is an important step for the packing of viral particles, here, we show that ROS enrich Hsp90-driven HBV capsid formation. In cell-free system, HBV capsid assembly was facilitated by ROS with Hsp90, whereas it was decreased without Hsp90. In addition, GSH inhibited the function of Hsp90 to decrease HBV capsid assembly. Consistent with the result of cell-free system, ROS and buthionine sulfoximine (BS), an inhibitor of GSH synthesis, increased HBV capsid formation in HepG2.2.15 cells. Thus, our study uncovers the interplay between ROS and Hsp90 during HBV capsid assembly. - Highlights: • We examined H{sub 2}O{sub 2} and GSH modulate HBV capsid assembly. • H{sub 2}O{sub 2} facilitates HBV capsid assembly in the presence of Hsp90. • GSH inhibits function of Hsp90 in facilitating HBV capsid assembly. • H{sub 2}O{sub 2} and GSH induce conformation change of Hsp90.

  8. Role of reactive oxygen species in the radiation response of human hematopoietic stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Masaru Yamaguchi

    Full Text Available Hematopoietic stem/progenitor cells (HSPCs, which are present in small numbers in hematopoietic tissues, can differentiate into all hematopoietic lineages and self-renew to maintain their undifferentiated phenotype. HSPCs are extremely sensitive to oxidative stressors such as anti-cancer agents, radiation, and the extensive accumulation of reactive oxygen species (ROS. The quiescence and stemness of HSPCs are maintained by the regulation of mitochondrial biogenesis, ROS, and energy homeostasis in a special microenvironment called the stem cell niche. The present study evaluated the relationship between the production of intracellular ROS and mitochondrial function during the proliferation and differentiation of X-irradiated CD34(+ cells prepared from human placental/umbilical cord blood HSPCs. Highly purified CD34(+ HSPCs exposed to X-rays were cultured in liquid and semi-solid medium supplemented with hematopoietic cytokines. X-irradiated CD34(+ HSPCs treated with hematopoietic cytokines, which promote their proliferation and differentiation, exhibited dramatically suppressed cell growth and clonogenic potential. The amount of intracellular ROS in X-irradiated CD34(+ HSPCs was significantly higher than that in non-irradiated cells during the culture period. However, neither the intracellular mitochondrial content nor the mitochondrial superoxide production was elevated in X-irradiated CD34(+ HSPCs compared with non-irradiated cells. Radiation-induced gamma-H2AX expression was observed immediately following exposure to 4 Gy of X-rays and gradually decreased during the culture period. This study reveals that X-irradiation can increase persistent intracellular ROS in human CD34(+ HSPCs, which may not result from mitochondrial ROS due to mitochondrial dysfunction, and indicates that substantial DNA double-strand breakage can critically reduce the stem cell function.

  9. Combined effect of protein and oxygen on reactive oxygen and nitrogen species in the plasma treatment of tissue

    Science.gov (United States)

    Gaur, Nishtha; Szili, Endre J.; Oh, Jun-Seok; Hong, Sung-Ha; Michelmore, Andrew; Graves, David B.; Hatta, Akimitsu; Short, Robert D.

    2015-09-01

    The influence of protein and molecular, ground state oxygen (O2) on the plasma generation, and transport of reactive oxygen and nitrogen species (RONS) in tissue are investigated. A tissue target, comprising a 1 mm thick gelatin film (a surrogate for real tissue), is placed on top of a 96-well plate; each well is filled with phosphate buffered saline (PBS, pH 7.4) containing one fluorescent or colorimetric reporter that is specific for one of three RONS (i.e., H2O2, NO2-, or OH•) or a broad spectrum reactive oxygen species reporter (2,7-dichlorodihydrofluorescein). A helium cold atmospheric plasma (CAP) jet contacts the top of the gelatin surface, and the concentrations of RONS generated in PBS are measured on a microplate reader. The data show that H2O2, NO2-, or OH• are generated in PBS underneath the target. Independently, measurements are made of the O2 concentration in the PBS with and without the gelatin target. Adding bovine serum albumin protein to the PBS or gelatin shows that protein either raises or inhibits RONS depending upon the O2 concentration. Our results are discussed in the context of plasma-soft tissue interactions that are important in the development of CAP technology for medicine, biology, and food manufacturing.

  10. Modulation of cisplatin-induced reactive oxygen species production by fullerene C(60 in normal and transformed lymphoid cells

    Directory of Open Access Journals (Sweden)

    D. V. Franskevych

    2016-02-01

    Full Text Available The early response of normal (Wistar rat thymocytes and transformed (mice lymphoid leukemia L1210 cells to treatment with anticancer drug cisplatin or to combined treatment with cisplatin and carbon nanostructure fullerene C60 was studied. We demonstrated with fluorescent probes DCFH-DA and TMRE that cisplatin at concentration 1 μg/ml induced reactive oxygen species (ROS production and decreased the value of mitochondrial membrane potential in both cell types. The combined treatment with cisplatin (1 μg/ml and fullerene C60 (7.2 μg/ml was shown to be followed by oppositely directed modulation of ROS production in thymocytes and L1210 cells. Cisplatin-induced ROS production was intensified in L1210 cells, while in thymocytes it was decreased. It is supposed that the different effects of combined treatment are associated with peculiarities of fullerene C60 accumulation and localization in normal and cancer cells.

  11. Tributyltin chloride disrupts aortic vascular reactivity and increases reactive oxygen species production in female rats.

    Science.gov (United States)

    Ximenes, Carolina Falcão; Rodrigues, Samya Mere Lima; Podratz, Priscila Lang; Merlo, Eduardo; de Araújo, Julia Fernandez Puñal; Rodrigues, Lívia Carla Melo; Coitinho, Juliana Barbosa; Vassallo, Dalton Valentim; Graceli, Jones Bernardes; Stefanon, Ivanita

    2017-11-01

    Organotin compounds, such as tributyltin (TBT), are environment contaminants that induce bioaccumulation and have potential toxic effects on marine species and mammals. TBT have been banned by the International Maritime Organization in 2003. However, the assessment of butyltin and metal contents in marine sediments has demonstrated high residual levels of TBT in some cases exceeding 7000 ng Sn g -1 . The acceptable daily intake (ADI) level for TBT established by the World Health Organization is 0.5 μg/kg bw/day is based on genotoxicity, reproduction, teratogenicity, immunotoxicity, and mainly neurotoxicity. However, their effect on the cardiovascular system is not well understood. In this study, female rats were exposed to 0.5 μg/kg/day of TBT for 15 days with the goal of understanding the effect of TBT on vascular function. Female Wistar rats were treated daily by gavage and divided into control (n = 10) and TBT (n = 10) groups. The aortic rings were incubated with phenylephrine in both the presence and absence of endothelium. The phenylephrine concentration-response curves were generated by exposing endothelium-intact samples to N G -nitro-L-arginine methyl ester (L-NAME), apocynin, superoxide dismutase (SOD), catalase, tiron, and allopurinol. Acetylcholine (ACh) and sodium nitroprusside (SNP) were used to evaluate the relaxation response. Exposure to TBT reduced serum 17β-estradiol E 2 levels and increased vascular reactivity. After incubation with L-NAME, the vascular reactivity to phenylephrine was significantly higher. Apocynin, SOD, catalase, and tiron decreased the vascular reactivity to phenylephrine to a significantly greater extent in TBT-treated rats than in the control rat. The relaxation induced by ACh and SNP was significantly reduced in TBT rats. Exposure to TBT induced aortic wall atrophy and increased superoxide anion production and collagen deposition. These results provide evidence that exposing rats to the current ADI for TBT (0.5

  12. Photofunctional Co-Cr Alloy Generating Reactive Oxygen Species for Photodynamic Applications

    Directory of Open Access Journals (Sweden)

    Kang-Kyun Wang

    2013-01-01

    Full Text Available We report the fabrication of photofunctional Co-Cr alloy plate that is prepared by a simple modification process for photodynamic application. Photoinduced functionality is provided by the photosensitizer of hematoporphyrin (Hp that initially generates reactive oxygen species (ROS such as superoxide anion radical and singlet oxygen. The photosensitizer with carboxyl group was chemically bonded to the surface of the Co-Cr alloy plate by esterification reaction. Microstructure and elemental composition of the Co-Cr alloy plate were checked with scanning electron microscopy (SEM and energy dispersive X-ray spectrometer (EDS. Fabrication of the photofunctionality of the Co-Cr alloy plate was confirmed with X-ray photoelectron spectroscopy (XPS, reflectance UV-Vis absorption, and emission spectroscopy. Reactive oxygen generation from the photofunctional Co-Cr alloy plate was confirmed by using the decomposition reaction of 1,3-diphenylisobenzofuran (DPBF. The results suggest that the immobilized photosensitizer molecules on the surface of Co-Cr alloy plate still possess their optical and functional properties including reactive oxygen generation. To open the possibility for its application as a photodynamic material to biological system, the fabricated photofunctional Co-Cr alloy is applied to the decomposition of smooth muscle cells.

  13. Characterization and re-activation of oxygen sensors for use in liquid lead-bismuth

    International Nuclear Information System (INIS)

    Kurata, Yuji; Abe, Yuji; Futakawa, Masatoshi; Oigawa, Hiroyuki

    2010-01-01

    Control of oxygen concentration in liquid lead-bismuth is one of the most important tasks to develop accelerator driven systems. In order to improve the reliability of oxygen sensors, re-activation treatments were investigated as well as characterization of oxygen sensors for use in liquid lead-bismuth. The oxygen sensor with a solid electrolyte of yttria-stabilized zirconia and a Pt/gas reference electrode showed almost the same electromotive force values in gas and liquid lead-bismuth, respectively, as the theoretical ones at temperatures above 400 deg. C or 450 deg. C. After long-term use of 6500 h, the outputs of the sensor became incorrect in liquid lead-bismuth. The state of the sensor that indicated incorrect outputs could not be recovered by cleaning with a nitric acid. However, it was found that the oxygen sensor became a correct sensor indicating theoretical values in liquid lead-bismuth after re-activation by the Pt-treatment of the outer surface of the sensor.

  14. Retinal hemodynamic oxygen reactivity assessed by perfusion velocity, blood oximetry and vessel diameter measurements

    DEFF Research Database (Denmark)

    Klefter, Oliver Niels; Lauritsen, Anne Øberg; Larsen, Michael

    2015-01-01

    PURPOSE: To test the oxygen reactivity of a fundus photographic method of measuring macular perfusion velocity and to integrate macular perfusion velocities with measurements of retinal vessel diameters and blood oxygen saturation. METHODS: Sixteen eyes in 16 healthy volunteers were studied at two...... is a valid method for assessing macular perfusion. Results were consistent with previous observations of hyperoxic blood flow reduction using blue field entoptic and laser Doppler velocimetry. Retinal perfusion seemed to be regulated around individual set points according to blood glucose levels. Multimodal...

  15. Reactive oxygen species and associated reactivity of peroxymonosulfate activated by soluble iron species.

    Science.gov (United States)

    Watts, Richard J; Yu, Miao; Teel, Amy L

    2017-10-01

    The activation of peroxymonosulfate by iron (II), iron (III), and iron (III)-EDTA for in situ chemical oxidation (ISCO) was compared using nitrobenzene as a hydroxyl radical probe, anisole as a hydroxyl radical+sulfate radical probe, and hexachloroethane as a reductant+nucleophile probe. In addition, activated peroxymonosulfate was investigated for the treatment of the model groundwater contaminants perchloroethylene (PCE) and trichloroethylene (TCE). The relative activities of hydroxyl radical and sulfate radical in the degradation of the probe compounds and PCE and TCE were isolated using the radical scavengers tert-butanol and isopropanol. Iron (II), iron (III), and iron (III)-EDTA effectively activated peroxymonosulfate to generate hydroxyl radical and sulfate radical, but only a minimal flux of reductants or nucleophiles. Iron (III)-EDTA was a more effective activator than iron (II) and iron (III), and also provided a non-hydroxyl radical, non-sulfate radical degradation pathway. The contribution of sulfate radical relative to hydroxyl radical followed the order of anisole>TCE>PCE >nitrobenzene; i.e., sulfate radical was less dominant in the oxidation of more oxidized target compounds. Sulfate radical is often assumed to be the primary oxidant in activated peroxymonosulfate and persulfate systems, but the results of this research demonstrate that the reactivity of sulfate radical with the target compound must be considered before drawing such a conclusion. Published by Elsevier B.V.

  16. Reactive oxygen species and associated reactivity of peroxymonosulfate activated by soluble iron species

    Science.gov (United States)

    Watts, Richard J.; Yu, Miao; Teel, Amy L.

    2017-10-01

    The activation of peroxymonosulfate by iron (II), iron (III), and iron (III)-EDTA for in situ chemical oxidation (ISCO) was compared using nitrobenzene as a hydroxyl radical probe, anisole as a hydroxyl radical + sulfate radical probe, and hexachloroethane as a reductant + nucleophile probe. In addition, activated peroxymonosulfate was investigated for the treatment of the model groundwater contaminants perchloroethylene (PCE) and trichloroethylene (TCE). The relative activities of hydroxyl radical and sulfate radical in the degradation of the probe compounds and PCE and TCE were isolated using the radical scavengers tert-butanol and isopropanol. Iron (II), iron (III), and iron (III)-EDTA effectively activated peroxymonosulfate to generate hydroxyl radical and sulfate radical, but only a minimal flux of reductants or nucleophiles. Iron (III)-EDTA was a more effective activator than iron (II) and iron (III), and also provided a non-hydroxyl radical, non-sulfate radical degradation pathway. The contribution of sulfate radical relative to hydroxyl radical followed the order of anisole > > TCE > PCE > > nitrobenzene; i.e., sulfate radical was less dominant in the oxidation of more oxidized target compounds. Sulfate radical is often assumed to be the primary oxidant in activated peroxymonosulfate and persulfate systems, but the results of this research demonstrate that the reactivity of sulfate radical with the target compound must be considered before drawing such a conclusion.

  17. Release of intracellular Calcium increase production of mitochondrial reactive oxygen species in renal distal epithelial cells

    DEFF Research Database (Denmark)

    Bjerregaard, Henning F.

    peroxide (H2O2) has traditionally been regarded as toxic by-products of aerobic metabolism. However, recent findings indicate that H2O2 act as a signalling molecule. The aim of the present study was to monitor, in real time, the rates of ROS generation in order to directly determine their production......Release of intracellular Calcium increase production of mitochondrial reactive oxygen species in renal distal epithelial cells. Henning F. Bjerregaard, Roskilde University, Department of Science, Systems and Models , 4000 Roskilde, Denmark. HFB@ RUC.DK Reactive oxygen species (ROS) like, hydrogen...... to G-protein stimulation of phospholipase C and release of inositol -3 phosphate. Cd (0.4 mM) treatment of A6 cells enhanced the ROS production after one minutes incubation. The production rate was constant for at least 10 to 20 min. Experiments showed that the Cd induced increase in ROS production...

  18. Staphyloxanthin photobleaching sensitizes methicillin-resistant Staphylococcus aureus to reactive oxygen species attack

    Science.gov (United States)

    Dong, Pu-Ting; Mohammad, Haroon; Hui, Jie; Wang, Xiaoyu; Li, Junjie; Liang, Lijia; Seleem, Mohamed N.; Cheng, Ji-Xin

    2018-02-01

    Given that the dearth of new antibiotic development loads an existential burden on successful infectious disease therapy, health organizations are calling for alternative approaches to combat methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we report a drug-free photonic approach to eliminate MRSA through photobleaching of staphyloxanthin, an indispensable membrane-bound antioxidant of S. aureus. The photobleaching process, uncovered through a transient absorption imaging study and quantitated by absorption spectroscopy and mass spectrometry, decomposes staphyloxanthin, and sensitizes MRSA to reactive oxygen species attack. Consequently, staphyloxanthin bleaching by low-level blue light eradicates MRSA synergistically with external or internal reactive oxygen species. The effectiveness of this synergistic therapy is validated in MRSA culture, MRSAinfected macrophage cells. Collectively, these findings highlight broad applications of staphyloxanthin photobleaching for treatment of MRSA infections.

  19. Celastrol targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent cytotoxicity in tumor cells

    Directory of Open Access Journals (Sweden)

    Xu Yuanji

    2011-05-01

    Full Text Available Abstract Background Celastrol is an active ingredient of the traditional Chinese medicinal plant Tripterygium Wilfordii, which exhibits significant antitumor activity in different cancer models in vitro and in vivo; however, the lack of information on the target and mechanism of action of this compound have impeded its clinical application. In this study, we sought to determine the mode of action of celastrol by focusing on the processes that mediate its anticancer activity. Methods The downregulation of heat shock protein 90 (HSP90 client proteins, phosphorylation of c-Jun NH2-terminal kinase (JNK, and cleavage of PARP, caspase 9 and caspase 3 were detected by western blotting. The accumulation of reactive oxygen species (ROS was analyzed by flow cytometry and fluorescence microscopy. Cell cycle progression, mitochondrial membrane potential (MMP and apoptosis were determined by flow cytometry. Absorption spectroscopy was used to determine the activity of mitochondrial respiratory chain (MRC complexes. Results Celastrol induced ROS accumulation, G2-M phase blockage, apoptosis and necrosis in H1299 and HepG2 cells in a dose-dependent manner. N-acetylcysteine (NAC, an antioxidative agent, inhibited celastrol-induced ROS accumulation and cytotoxicity. JNK phosphorylation induced by celastrol was suppressed by NAC and JNK inhibitor SP600125 (SP. Moreover, SP significantly inhibited celastrol-induced loss of MMP, cleavage of PARP, caspase 9 and caspase 3, mitochondrial translocation of Bad, cytoplasmic release of cytochrome c, and cell death. However, SP did not inhibit celastrol-induced ROS accumulation. Celastrol downregulated HSP90 client proteins but did not disrupt the interaction between HSP90 and cdc37. NAC completely inhibited celastrol-induced decrease of HSP90 client proteins, catalase and thioredoxin. The activity of MRC complex I was completely inhibited in H1299 cells treated with 6 μM celastrol in the absence and presence of NAC

  20. Real-time in vivo detection of biomaterial-induced reactive oxygen species

    OpenAIRE

    Liu, Wendy F.; Ma, Minglin; Bratlie, Kaitlin M.; Dang, Tram T.; Langer, Robert; Anderson, Daniel G.

    2010-01-01

    The non-specific host response to implanted biomaterials is often a key challenge of medical device design. To evaluate biocompatibility, measuring the release of reactive oxygen species (ROS) produced by inflammatory cells in response to biomaterial surfaces is a well-established method. However, the detection of ROS in response to materials implanted in vivo has not yet been demonstrated. Here, we develop a bioluminescence whole animal imaging approach to observe ROS released in response to...

  1. Reactive oxygen species formation during tetanic contractions in single isolated Xenopus myofibers

    OpenAIRE

    Zuo, Li; Nogueira, Leonardo; Hogan, Michael C.

    2011-01-01

    Contracting skeletal muscle produces reactive oxygen species (ROS) that have been shown to affect muscle function and adaptation. However, real-time measurement of ROS in contracting myofibers has proven to be difficult. We used amphibian (Xenopus laevis) muscle to test the hypothesis that ROS are formed during contractile activity in isolated single skeletal muscle fibers and that this contraction-induced ROS formation affects fatigue development. Single myofibers were loaded with 5 μM dihyd...

  2. Low Po2 conditions induce reactive oxygen species formation during contractions in single skeletal muscle fibers

    OpenAIRE

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

    2013-01-01

    Contractions in whole skeletal muscle during hypoxia are known to generate reactive oxygen species (ROS); however, identification of real-time ROS formation within isolated single skeletal muscle fibers has been challenging. Consequently, there is no convincing evidence showing increased ROS production in intact contracting fibers under low Po2 conditions. Therefore, we hypothesized that intracellular ROS generation in single contracting skeletal myofibers increases during low Po2 compared wi...

  3. Surface-Selective Preferential Production of Reactive Oxygen Species on Piezoelectric Ceramics for Bacterial Killing

    OpenAIRE

    Tan, Guoxin; Wang, Shuangying; Zhu, Ye; Zhou, Lei; Yu, Peng; Wang, Xiaolan; He, Tianrui; Chen, Junqi; Mao, Chuanbin; Ning, Chengyun

    2016-01-01

    Reactive oxygen species (ROS) can be used to kill bacterial cells, and thus the selective generation of ROS from material surfaces is an emerging direction in antibacterial material discovery. We found the polarization of piezoelectric ceramic causes the two sides of the disk to become positively and negatively charged, which translate into cathode and anode surfaces in an aqueous solution. Because of the microelectrolysis of water, ROS are preferentially formed on the cathode surface. Conseq...

  4. (3) Melatonin Protects Oocytes and Granulosa Cells from Reactive Oxygen Species during the Ovulatory Process

    OpenAIRE

    田村, 博史; Hiroshi, TAMURA; 山口大学大学院医学系研究科産科婦人科学; Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine

    2009-01-01

    Reactive oxygen species (ROS) are produced within the follicle especially during the ovulatory process. ROS play a physiological role in the process of ovulation, e.g. follicle rapture. However, excessive amount of ROS causes oxidative stress and damages oocytes and luteinized granulosa cells. On the other hand, antioxidant defense systems including superoxide dismutase (SOD) or glutathione (GSH) are present in follicles. The balance between ROS and antioxidants within the follicle seems to b...

  5. Global Inhibition of Reactive Oxygen Species (ROS) Inhibits Paclitaxel-Induced Painful Peripheral Neuropathy

    OpenAIRE

    Fidanboylu, Mehmet; Griffiths, Lisa A.; Flatters, Sarah J. L.

    2011-01-01

    Paclitaxel (Taxol (R)) is a widely used chemotherapeutic agent that has a major dose limiting side-effect of painful peripheral neuropathy. Currently there is no effective therapy for the prevention or treatment of chemotherapy-induced painful peripheral neuropathies. Evidence for mitochondrial dysfunction during paclitaxel-induced pain was previously indicated with the presence of swollen and vacuolated neuronal mitochondria. As mitochondria are a major source of reactive oxygen species (ROS...

  6. Contribution of reactive oxygen species to the pathogenesis of pulmonary arterial hypertension

    Science.gov (United States)

    Naik, Jay S.; Weise-Cross, Laura; Detweiler, Neil D.; Herbert, Lindsay M.; Yellowhair, Tracylyn R.; Resta, Thomas C.

    2017-01-01

    Pulmonary arterial hypertension is associated with a decreased antioxidant capacity. However, neither the contribution of reactive oxygen species to pulmonary vasoconstrictor sensitivity, nor the therapeutic efficacy of antioxidant strategies in this setting are known. We hypothesized that reactive oxygen species play a central role in mediating both vasoconstrictor and arterial remodeling components of severe pulmonary arterial hypertension. We examined the effect of the chemical antioxidant, TEMPOL, on right ventricular systolic pressure, vascular remodeling, and enhanced vasoconstrictor reactivity in both chronic hypoxia and hypoxia/SU5416 rat models of pulmonary hypertension. SU5416 is a vascular endothelial growth factor receptor antagonist and the combination of chronic hypoxia/SU5416 produces a model of severe pulmonary arterial hypertension with vascular plexiform lesions/fibrosis that is not present with chronic hypoxia alone. The major findings from this study are: 1) compared to hypoxia alone, hypoxia/SU5416 exposure caused more severe pulmonary hypertension, right ventricular hypertrophy, adventitial lesion formation, and greater vasoconstrictor sensitivity through a superoxide and Rho kinase-dependent Ca2+ sensitization mechanism. 2) Chronic hypoxia increased medial muscularization and superoxide levels, however there was no effect of SU5416 to augment these responses. 3) Treatment with TEMPOL decreased right ventricular systolic pressure in both hypoxia and hypoxia/SU5416 groups. 4) This effect of TEMPOL was associated with normalization of vasoconstrictor responses, but not arterial remodeling. Rather, medial hypertrophy and adventitial fibrotic lesion formation were more pronounced following chronic TEMPOL treatment in hypoxia/SU5416 rats. Our findings support a major role for reactive oxygen species in mediating enhanced vasoconstrictor reactivity and pulmonary hypertension in both chronic hypoxia and hypoxia/SU5416 rat models, despite a

  7. Neuroprotection of taurine against reactive oxygen species is associated with inhibiting NADPH oxidases.

    Science.gov (United States)

    Han, Zhou; Gao, Li-Yan; Lin, Yu-Hui; Chang, Lei; Wu, Hai-Yin; Luo, Chun-Xia; Zhu, Dong-Ya

    2016-04-15

    It is well established that taurine shows potent protection against glutamate-induced injury to neurons in stroke. The neuroprotection may result from multiple mechanisms. Increasing evidences suggest that NADPH oxidases (Nox), the primary source of superoxide induced by N-methyl-d-aspartate (NMDA) receptor activation, are involved in the process of oxidative stress. We found that 100μM NMDA induced oxidative stress by increasing the reactive oxygen species level, which contributed to the cell death, in vitro. Neuron cultures pretreated with 25mM taurine showed lower percentage of death cells and declined reactive oxygen species level. Moreover, taurine attenuated Nox2/Nox4 protein expression and enzyme activity and declined intracellular calcium intensity during NMDA-induced neuron injury. Additionally, taurine also showed neuroprotection against H2O2-induced injury, accompanying with Nox inhibition. So, we suppose that protection of taurine against reactive oxygen species during NMDA-induced neuron injury is associated with Nox inhibition, probably in a calcium-dependent manner. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Matthias Totzeck

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

  9. Manipulation of environmental oxygen modifies reactive oxygen and nitrogen species generation during myogenesis

    Directory of Open Access Journals (Sweden)

    Rachel McCormick

    2016-08-01

    Data demonstrate that satellite cell proliferation increased when cells were grown in 6% O2 compared with 20% O2. Myoblasts grown in 20% O2 showed an increase in DCF fluorescence and DHE oxidation compared with myoblasts grown at 6% O2. Myotubes grown in 20% O2 also showed an increase in DCF and DAF-FM fluorescence and DHE oxidation compared with myotubes grown in 6% O2. The catalase and MnSOD contents were also increased in myoblasts and myotubes that were maintained in 20% O2 compared with myoblasts and myotubes grown in 6% O2. These data indicate that intracellular RONS activities in myoblasts and myotubes at rest are influenced by changes in environmental oxygen concentration and that the increased ROS may influence myogenesis in a negative manner.

  10. CO2 reactivity and brain oxygen pressure monitoring in severe head injury.

    Science.gov (United States)

    Carmona Suazo, J A; Maas, A I; van den Brink, W A; van Santbrink, H; Steyerberg, E W; Avezaat, C J

    2000-09-01

    To investigate the effect of hyperventilation on cerebral oxygenation after severe head injury. A prospective, observational study. Neurointensive care unit at a university hospital. A total of 90 patients with severe head injury (Glasgow Coma Scale score brain tissue oxygen pressure (PbrO2) was performed as a measure of cerebral oxygenation. Arterial PCO2 was decreased each day over a 5-day period for 15 mins by increasing minute volume on the ventilator setting to 20% above baseline. Arterial blood gas analysis was performed before and after changing ventilator settings. Multimodality monitoring, including PbrO2, was performed in all patients. Absolute and relative PbrO2/PaCO2 reactivity was calculated. Outcome at 6 months was evaluated according to the Glasgow Outcome Scale. Effective hyperventilation, defined by a decrease of PaCO2 > or =2 torr (0.27 kPa), was obtained in 218 (84%) of 272 tests performed. Baseline PaCO2 averaged 32.3 +/- 4.5 torr (4.31 +/- 0.60 kPa). Average reduction in PaCO2 was 3.8 +/- 1.7 torr (0.51 +/- 0.23 kPa). PbrO2 decreased by 2.8 +/- 3.7 torr (0.37 +/- 0.49 kPa; p < .001) from a baseline value of 26.5 +/- 11.6 torr (3.53 +/- 1.55 kPa). PbrO2/PaCO2 reactivity was low on day 1 (0.8 +/- 2.3 torr [0.11 +/- 0.31 kPa]), increasing on subsequent days to 6.1 +/- 4.4 torr (0.81 +/- 0.59 kPa) on day 5. PbrO2/PaCO2 reactivity on days 1 and 2 was not related to outcome. In later phases in patients with unfavorable outcome, relative reactivity was increased more markedly, reaching statistical significance on day 5. Increased hyperventilation causes a significant reduction in PbrO2, providing further evidence for possible increased risk of secondary ischemic damage during hyperventilation. The low PbrO2/PaCO2 reactivity on day 1 indicates the decreased responsiveness of cerebral microvascular vessels to PaCO2 changes, caused by generalized vascular narrowing. The increasing PbrO2/PaCO2 reactivity from days 2 to 5 suggests that the risk of

  11. The surface reactivity of acrylonitrile with oxygen atoms on an analogue of interstellar dust grains

    Science.gov (United States)

    Kimber, Helen J.; Toscano, Jutta; Price, Stephen D.

    2018-06-01

    Experiments designed to reveal the low-temperature reactivity on the surfaces of interstellar dust grains are used to probe the heterogeneous reaction between oxygen atoms and acrylonitrile (C2H3CN, H2C=CH-CN). The reaction is studied at a series of fixed surface temperatures between 14 and 100 K. After dosing the reactants on to the surface, temperature-programmed desorption, coupled with time-of-flight mass spectrometry, reveals the formation of a product with the molecular formula C3H3NO. This product results from the addition of a single oxygen atom to the acrylonitrile reactant. The oxygen atom attack appears to occur exclusively at the C=C double bond, rather than involving the cyano(-CN) group. The absence of reactivity at the cyano site hints that full saturation of organic molecules on dust grains may not always occur in the interstellar medium. Modelling the experimental data provides a reaction probability of 0.007 ± 0.003 for a Langmuir-Hinshelwood style (diffusive) reaction mechanism. Desorption energies for acrylonitrile, oxygen atoms, and molecular oxygen, from the multilayer mixed ice their deposition forms, are also extracted from the kinetic model and are 22.7 ± 1.0 kJ mol-1 (2730 ± 120 K), 14.2 ± 1.0 kJ mol-1 (1710 ± 120 K), and 8.5 ± 0.8 kJ mol-1 (1020 ± 100 K), respectively. The kinetic parameters we extract from our experiments indicate that the reaction between atomic oxygen and acrylonitrile could occur on interstellar dust grains on an astrophysical time-scale.

  12. Photochemical Cycling of Reactive Oxygen Species in Hydrothermal Springs: Impacts on Biosignature Preservation

    Science.gov (United States)

    Mave, M. A.; Hinman, N. W.; Stevens, L.

    2017-12-01

    Biosignatures can be preserved via rapid entombment by aqueous minerals in a system. Wilson et al. (2000) found that high UV flux leads to increased production of reactive oxygen species (ROS), which promote iron (Fe) oxidation, and possible accumulation on microbial surfaces, leading to detectable microfossils. Hydrogen peroxide (H2O2) is a measurable ROS that serves as proxy for less stable ROS. Overall diel cycling of H2O2 is likely controlled by changes in photoreactive speciation of Fe (McKnight et al., 1988) in Fe-rich systems. To test this hypothesis, we conducted a 48-hour photochemical field study of Elk Pool in the Norris Geyser Basin at Yellowstone National Park in July, 2017 in which we measured UVA and UVB, along with H2O2 via the scopoletin fluorescence quenching method (Holm et al., 1987). Measurements were taken every few hours, and we found that maximum ROS production occurred during maximum UV irradiation. We also ran several experiments on-site in which we collected and altered spring water to either inactivate or catalyze naturally occurring reactions as well as to isolate primary mechanisms responsible for production of H2O2. Experiments were run in UV permeable Whirlpak bags and Fisherbrand tubes. Elk Pool showed only trace Fe content (pH 4) at the time of our study, so Fe-silica coated petrographic slides were added to the tube experiments (Fe-added experiments). Both sets of experiments included filtered and unfiltered spring water to differentiate biotic from abiotic mechanisms, and both UV-exposed and dark controls to separate UV-induced mechanisms for ROS formation. UV-exposed water always had greater ROS than dark experiments. Filtered spring water had higher ROS concentrations than unfiltered water, except when Fe was added. In the Fe-added experiments, unfiltered spring water had slightly greater ROS production relative to filtered water and had the lowest pH and highest aqueous Fe content after 7 hours. All Fe-added experiments showed

  13. Comparative Study of Different Methods to Determine the Role of Reactive Oxygen Species Induced by Zinc Oxide Nanoparticles

    Directory of Open Access Journals (Sweden)

    Nigar A. Najim

    2016-08-01

    Full Text Available Accumulation of reactive oxygen species (ROS followed by an increase in oxidative stress is associated with cellular responses to nanoparticle induced cell damages. Finding the best method for assessing intracellular ROS production is the key step in the detection of oxidative stress induced injury. This study evaluates and compares four different methods for the measurement of intracellular ROS generation using fluorogenic probe, 2´,7´-dichlorofluorescein diacetate (DCFH-DA. Hydrogen peroxide (H2O2 was utilised as a positive control to assess the reactivity of the probe. Spherically shaped zinc oxide (ZnO nanoparticles with an average particle size of 85.7 nm were used to determine the diverse roles of ROS in nanotoxicity in Hs888Lu and U937 cell lines. The results showed that different methods exhibit different patterns of ROS measurement. In conclusion this study found that the time point at which the DCFH-DA is added to the reaction, the incubation time and the oxidative species that is responsible for the oxidation of DCFH, have impact on the intracellular ROS measurement.

  14. The mystery of gold's chemical activity: local bonding, morphology and reactivity of atomic oxygen.

    Science.gov (United States)

    Baker, Thomas A; Liu, Xiaoying; Friend, Cynthia M

    2011-01-07

    Recently, gold has been intensely studied as a catalyst for key synthetic reactions. Gold is an attractive catalyst because, surprisingly, it is highly active and very selective for partial oxidation processes suggesting promise for energy-efficient "green" chemistry. The underlying origin of the high activity of Au is a controversial subject since metallic gold is commonly thought to be inert. Herein, we establish that one origin of the high activity for gold catalysis is the extremely reactive nature of atomic oxygen bound in 3-fold coordination sites on metallic gold. This is the predominant form of O at low concentrations on the surface, which is a strong indication that it is most relevant to catalytic conditions. Atomic oxygen bound to metallic Au in 3-fold sites has high activity for CO oxidation, oxidation of olefins, and oxidative transformations of alcohols and amines. Among the factors identified as important in Au-O interaction are the morphology of the surface, the local binding site of oxygen, and the degree of order of the oxygen overlayer. In this Perspective, we present an overview of both theory and experiments that identify the reactive forms of O and their associated charge density distributions and bond strengths. We also analyze and model the release of Au atoms induced by O binding to the surface. This rough surface also has the potential for O(2) dissociation, which is a critical step if Au is to be activated catalytically. We further show the strong parallels between product distributions and reactivity for O-covered Au at low pressure (ultrahigh vacuum) and for nanoporous Au catalysts operating at atmospheric pressure as evidence that atomic O is the active species under working catalytic conditions when metallic Au is present. We briefly discuss the possible contributions of oxidants that may contain intact O-O bonds and of the Au-metal oxide support interface in Au catalysis. Finally, the challenges and future directions for fully

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

    Science.gov (United States)

    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...

  16. Thiazolidinone prodrugs activated by reactive oxygen species for use in the treatment of inflammatory diseases and cancer

    DEFF Research Database (Denmark)

    2018-01-01

    Prodrugs activated predominantly or exclusively in inflammatory tissue, more particularly prodrugs of methotrexate and derivatives thereof, which are selectively activated by Reactive Oxygen Species (ROS) in inflammatory tissues associated with cancer and inflammatory diseases, as well as method...

  17. Oxoferryl-Porphyrin Radical Catalytic Intermediate in Cytochrome bd Oxidases Protects Cells from Formation of Reactive Oxygen Species*

    Science.gov (United States)

    Paulus, Angela; Rossius, Sebastiaan Gijsbertus Hendrik; Dijk, Madelon; de Vries, Simon

    2012-01-01

    The quinol-linked cytochrome bd oxidases are terminal oxidases in respiration. These oxidases harbor a low spin heme b558 that donates electrons to a binuclear heme b595/heme d center. The reaction with O2 and subsequent catalytic steps of the Escherichia coli cytochrome bd-I oxidase were investigated by means of ultra-fast freeze-quench trapping followed by EPR and UV-visible spectroscopy. After the initial binding of O2, the O–O bond is heterolytically cleaved to yield a kinetically competent heme d oxoferryl porphyrin π-cation radical intermediate (compound I) magnetically interacting with heme b595. Compound I accumulates to 0.75–0.85 per enzyme in agreement with its much higher rate of formation (∼20,000 s−1) compared with its rate of decay (∼1,900 s−1). Compound I is next converted to a short lived heme d oxoferryl intermediate (compound II) in a phase kinetically matched to the oxidation of heme b558 before completion of the reaction. The results indicate that cytochrome bd oxidases like the heme-copper oxidases break the O–O bond in a single four-electron transfer without a peroxide intermediate. However, in cytochrome bd oxidases, the fourth electron is donated by the porphyrin moiety rather than by a nearby amino acid. The production of reactive oxygen species by the cytochrome bd oxidase was below the detection level of 1 per 1000 turnovers. We propose that the two classes of terminal oxidases have mechanistically converged to enzymes in which the O–O bond is broken in a single four-electron transfer reaction to safeguard the cell from the formation of reactive oxygen species. PMID:22287551

  18. Reactive oxygen species modulator 1, a novel protein, combined with carcinoembryonic antigen in differentiating malignant from benign pleural effusion.

    Science.gov (United States)

    Chen, Xianmeng; Zhang, Na; Dong, Jiahui; Sun, Gengyun

    2017-05-01

    The differential diagnosis of malignant pleural effusion and benign pleural effusion remains a clinical problem. Reactive oxygen species modulator 1 is a novel protein overexpressed in various human tumors. The objective of this study was to evaluate the diagnostic value of joint detection of reactive oxygen species modulator 1 and carcinoembryonic antigen in the differential diagnosis of malignant pleural effusion and benign pleural effusion. One hundred two consecutive patients with pleural effusion (including 52 malignant pleural effusion and 50 benign pleural effusion) were registered in this study. Levels of reactive oxygen species modulator 1 and carcinoembryonic antigen were measured by enzyme-linked immunosorbent assay and radioimmunoassay, respectively. Results showed that the concentrations of reactive oxygen species modulator 1 both in pleural fluid and serum of patients with malignant pleural effusion were significantly higher than those of benign pleural effusion (both p pleural fluid reactive oxygen species modulator 1 were 61.54% and 82.00%, respectively, with the optimized cutoff value of 589.70 pg/mL. However, the diagnostic sensitivity and specificity of serum reactive oxygen species modulator 1 were only 41.38% and 86.21%, respectively, with the cutoff value of 27.22 ng/mL, indicating that serum reactive oxygen species modulator 1 may not be a good option in the differential diagnosis of malignant pleural effusion and benign pleural effusion. The sensitivity and specificity of pleural fluid carcinoembryonic antigen were 69.23% and 88.00%, respectively, at the cutoff value of 3.05 ng/mL, while serum carcinoembryonic antigen were 80.77% and 72.00% at the cutoff value of 2.60 ng/mL. The sensitivity could be raised to 88.17% in parallel detection of plural fluid reactive oxygen species modulator 1 and carcinoembryonic antigen concentration, and the specificity could be improved to 97.84% in serial detection.

  19. The Escherichia coli BtuE protein functions as a resistance determinant against reactive oxygen species.

    Directory of Open Access Journals (Sweden)

    Felipe A Arenas

    2011-01-01

    Full Text Available This work shows that the recently described Escherichia coli BtuE peroxidase protects the bacterium against oxidative stress that is generated by tellurite and by other reactive oxygen species elicitors (ROS. Cells lacking btuE (ΔbtuE displayed higher sensitivity to K(2TeO(3 and other oxidative stress-generating agents than did the isogenic, parental, wild-type strain. They also exhibited increased levels of cytoplasmic reactive oxygen species, oxidized proteins, thiobarbituric acid reactive substances, and lipoperoxides. E. coli ΔbtuE that was exposed to tellurite or H(2O(2 did not show growth changes relative to wild type cells either in aerobic or anaerobic conditions. Nevertheless, the elimination of btuE from cells deficient in catalases/peroxidases (Hpx(- resulted in impaired growth and resistance to these toxicants only in aerobic conditions, suggesting that BtuE is involved in the defense against oxidative damage. Genetic complementation of E. coli ΔbtuE restored toxicant resistance to levels exhibited by the wild type strain. As expected, btuE overexpression resulted in decreased amounts of oxidative damage products as well as in lower transcriptional levels of the oxidative stress-induced genes ibpA, soxS and katG.

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

    Science.gov (United States)

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

    2011-06-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    A.J. Gomes

    2001-11-01

    Full Text Available 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 10(9 M-1 s-1 for KA and 1.0 x 10(9 M-1 s-1 for PL, similar to that of ethanol (1.4 x 10(9 M-1 s-1. With superoxide anions generated by the xanthine/hypoxanthine system, KA and PL (0.2-1.0 mg/ml inhibited ·O2-dependent reduction of nitroblue tetrazolium by up to 30 and 31%, respectively. In the detection of ¹O2 by rose bengal irradiation, PL at 1.0 mg/ml quenched singlet oxygen by 43% relative to azide and KA by 36%. The present study demonstrates that PL showed an antioxidant effect, scavenging three of four reactive oxygen species tested here. Unlike KA, PL did not significantly scavenge hydrogen peroxide.

  3. Reactive oxygen species explicit dosimetry (ROSED) of a type 1 photosensitizer

    Science.gov (United States)

    Ong, Yi Hong; Kim, Michele M.; Huang, Zheng; Zhu, Timothy C.

    2018-02-01

    Type I photodynamic therapy (PDT) is based on the use of photochemical reactions mediated through an interaction between a tumor-selective photosensitizer, photoexcitation with a specific wavelength of light, and production of reactive oxygen species (ROS). The goal of this study is to develop a model to calculate reactive oxygen species concentration ([ROS]rx) after Tookad®-mediated vascular PDT. Mice with radiation-induced fibrosarcoma (RIF) tumors were treated with different light fluence and fluence rate conditions. Explicit measurements of photosensitizer drug concentration were made via diffuse reflective absorption spectrum using a contact probe before and after PDT. Blood flow and tissue oxygen concentration over time were measured during PDT as a mean to validate the photochemical parameters for the ROSED calculation. Cure index was computed from the rate of tumor regrowth after treatment and was compared against three calculated dose metrics: total light fluence, PDT dose, reacted [ROS]rx. The tumor growth study demonstrates that [ROS]rx serves as a better dosimetric quantity for predicting treatment outcome, as a clinically relevant tumor growth endpoint.

  4. Real-Time Discrimination and Versatile Profiling of Spontaneous Reactive Oxygen Species in Living Organisms with a Single Fluorescent Probe.

    Science.gov (United States)

    Zhang, Ruilong; Zhao, Jun; Han, Guangmei; Liu, Zhengjie; Liu, Cui; Zhang, Cheng; Liu, Bianhua; Jiang, Changlong; Liu, Renyong; Zhao, Tingting; Han, Ming-Yong; Zhang, Zhongping

    2016-03-23

    Fluorescent probes are powerful tools for the investigations of reactive oxygen species (ROS) in living organisms by visualization and imaging. However, the multiparallel assays of several ROS with multiple probes are often limited by the available number of spectrally nonoverlapping chromophores together with large invasive effects and discrepant biological locations. Meanwhile, the spontaneous ROS profilings in various living organs/tissues are also limited by the penetration capability of probes across different biological barriers and the stability in reactive in vivo environments. Here, we report a single fluorescent probe to achieve the effective discrimination and profiling of hydroxyl radicals (•OH) and hypochlorous acid (HClO) in living organisms. The probe is constructed by chemically grafting an additional five-membered heterocyclic ring and a lateral triethylene glycol chain to a fluorescein mother, which does not only turn off the fluorescence of fluorescein, but also create the dual reactive sites to ROS and the penetration capability in passing through various biological barriers. The reactions of probe with •OH and HClO simultaneously result in cyan and green emissions, respectively, providing the real-time discrimination and quantitative analysis of the two ROS in cellular mitochondria. Surprisingly, the accumulation of probes in the intestine and liver of a normal-state zebrafish and the transfer pathway from intestine-to-blood-to-organ/tissue-to-kidney-to-excretion clearly present the profiling of spontaneous •OH and HClO in these metabolic organs. In particular, the stress generation of •OH at the fresh wound of zebrafish is successfully visualized for the first time, in spite of its extremely short lifetime.

  5. Effect of polyunsaturated fatty acids on the reactive oxygen and nitrogen species production by raw 264.7 macrophages

    Czech Academy of Sciences Publication Activity Database

    Ambrožová, Gabriela; Pekarová, Michaela; Lojek, Antonín

    2010-01-01

    Roč. 49, č. 3 (2010), s. 133-139 ISSN 1436-6207 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : polyunsaturated fatty acids * reactive oxygen species * reactive nitrogen species Subject RIV: BO - Biophysics Impact factor: 3.343, year: 2010

  6. Further Controversies About Brain Tissue Oxygenation Pressure-Reactivity After Traumatic Brain Injury

    DEFF Research Database (Denmark)

    Andresen, Morten; Donnelly, Joseph; Aries, Marcel

    2018-01-01

    arterial pressure and intracranial pressure. A new ORx index based on brain tissue oxygenation and cerebral perfusion pressure (CPP) has been proposed that similarly allows for evaluation of cerebrovascular reactivity. Conflicting results exist concerning its clinical utility. METHODS: Retrospective......BACKGROUND: Continuous monitoring of cerebral autoregulation is considered clinically useful due to its ability to warn against brain ischemic insults, which may translate to a relationship with adverse outcome. It is typically performed using the pressure reactivity index (PRx) based on mean...... analysis was performed in 85 patients with traumatic brain injury (TBI). ORx was calculated using three time windows of 5, 20, and 60 min. Correlation coefficients and individual "optimal CPP" (CPPopt) were calculated using both PRx and ORx, and relation to patient outcome investigated. RESULTS...

  7. Changes in Cerebral Partial Oxygen Pressure and Cerebrovascular Reactivity During Intracranial Pressure Plateau Waves.

    Science.gov (United States)

    Lang, Erhard W; Kasprowicz, Magdalena; Smielewski, Peter; Pickard, John; Czosnyka, Marek

    2015-08-01

    Plateau waves in intracranial pressure (ICP) are frequently recorded in neuro intensive care and are not yet fully understood. To further investigate this phenomenon, we analyzed partial pressure of cerebral oxygen (pbtO2) and a moving correlation coefficient between ICP and mean arterial blood pressure (ABP), called PRx, along with the cerebral oxygen reactivity index (ORx), which is a moving correlation coefficient between cerebral perfusion pressure (CPP) and pbtO2 in an observational study. We analyzed 55 plateau waves in 20 patients after severe traumatic brain injury. We calculated ABP, ABP pulse amplitude (ampABP), ICP, CPP, pbtO2, heart rate (HR), ICP pulse amplitude (ampICP), PRx, and ORx, before, during, and after each plateau wave. The analysis of variance with Bonferroni post hoc test was used to compare the differences in the variables before, during, and after the plateau wave. We considered all plateau waves, even in the same patient, independent because they are separated by long intervals. We found increases for ICP and ampICP according to our operational definitions for plateau waves. PRx increased significantly (p = 0.00026), CPP (p pressure remains stable in ICP plateau waves, while cerebral autoregulatory indices show distinct changes, which indicate cerebrovascular reactivity impairment at the top of the wave. PbtO2 decreases during the waves and may show a slight overshoot after normalization. We assume that this might be due to different latencies of the cerebral blood flow and oxygen level control mechanisms. Other factors may include baseline conditions, such as pre-plateau wave cerebrovascular reactivity or pbtO2 levels, which differ between studies.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    International Nuclear Information System (INIS)

    Hartwig, J.F.

    1990-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Hartwig, J.F.

    1990-12-01

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

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

    DEFF Research Database (Denmark)

    Quinlan, Casey L; Perevoschikova, Irina V; Goncalves, Renata L S

    2013-01-01

    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...

  12. Redox state, reactive oxygen species and adaptive growth in colonial hydroids.

    Science.gov (United States)

    Blackstone, N W

    2001-06-01

    Colonial metazoans often encrust surfaces over which the food supply varies in time or space. In such an environment, adaptive colony development entails adjusting the timing and spacing of feeding structures and gastrovascular connections to correspond to this variable food supply. To investigate the possibility of such adaptive growth, within-colony differential feeding experiments were carried out using the hydroid Podocoryna carnea. Indeed, such colonies strongly exhibited adaptive growth, developing dense arrays of polyps (feeding structures) and gastrovascular connections in areas that were fed relative to areas that were starved, and this effect became more consistent over time. To investigate mechanisms of signaling between the food supply and colony development, measurements were taken of metabolic parameters that have been implicated in signal transduction in other systems, particularly redox state and levels of reactive oxygen species. Utilizing fluorescence microscopy of P. carnea cells in vivo, simultaneous measurements of redox state [using NAD(P)H] and hydrogen peroxide (using 2',7'-dichlorofluorescin diacetate) were taken. Both measures focused on polyp epitheliomuscular cells, since these exhibit the greatest metabolic activity. Colonies 3-5h after feeding were relatively oxidized, with low levels of peroxide, while colonies 24h after feeding were relatively reduced, with high levels of peroxide. The functional role of polyps in feeding and generating gastrovascular flow probably produced this dichotomy. Polyps 3-5h after feeding contract maximally, and this metabolic demand probably shifts the redox state in the direction of oxidation and diminishes levels of reactive oxygen species. In contrast, 24h after feeding, polyps are quiescent, and this lack of metabolic demand probably shifts the redox state in the direction of reduction and increases levels of reactive oxygen species. Within-colony differential feeding experiments were carried out on

  13. Surface-Selective Preferential Production of Reactive Oxygen Species on Piezoelectric Ceramics for Bacterial Killing.

    Science.gov (United States)

    Tan, Guoxin; Wang, Shuangying; Zhu, Ye; Zhou, Lei; Yu, Peng; Wang, Xiaolan; He, Tianrui; Chen, Junqi; Mao, Chuanbin; Ning, Chengyun

    2016-09-21

    Reactive oxygen species (ROS) can be used to kill bacterial cells, and thus the selective generation of ROS from material surfaces is an emerging direction in antibacterial material discovery. We found the polarization of piezoelectric ceramic causes the two sides of the disk to become positively and negatively charged, which translate into cathode and anode surfaces in an aqueous solution. Because of the microelectrolysis of water, ROS are preferentially formed on the cathode surface. Consequently, the bacteria are selectively killed on the cathode surface. However, the cell experiment suggested that the level of ROS is safe for normal mammalian cells.

  14. A reactive empirical bond order (REBO) potential for hydrocarbon-oxygen interactions

    International Nuclear Information System (INIS)

    Ni, Boris; Lee, Ki-Ho; Sinnott, Susan B

    2004-01-01

    The expansion of the second-generation reactive empirical bond order (REBO) potential for hydrocarbons, as parametrized by Brenner and co-workers, to include oxygen is presented. This involves the explicit inclusion of C-O, H-O, and O-O interactions to the existing C-C, C-H, and H-H interactions in the REBO potential. The details of the expansion, including all parameters, are given. The new, expanded potential is then applied to the study of the structure and chemical stability of several molecules and polymer chains, and to modelling chemical reactions among a series of molecules, within classical molecular dynamics simulations

  15. Impact of reactive oxygen species on antioxidant capacity of male reproductive system.

    Science.gov (United States)

    Riaz, Muhammad; Mahmood, Zahed; Shahid, Muhammad; Saeed, M Usman Qamar; Tahir, Imtiaz Mahmood; Shah, Sm Ali; Munir, Naveed; El-Ghorab, Ahmed

    2016-09-01

    The present research work was aimed to study the mutual interaction of reactive oxygen species (ROS) and basal cells antioxidant capacity in the male reproductive system and to further establish the association between selected heavy metals and stress markers. Total oxidant status (TOS) and total antioxidant status (TAS) of serum and seminal plasma were determined by automated photometric methods. The concentrations of Selenium (Se), Lead (Pb), and Cadmium (Cd) were determined by using atomic absorption spectrophotometer. The TOS was increased significantly (P male infertility. © The Author(s) 2015.

  16. Arterial Spin Labeling and Blood Oxygen Level-Dependent MRI Cerebrovascular Reactivity in Cerebrovascular Disease

    DEFF Research Database (Denmark)

    Smeeing, Diederik P J; Hendrikse, Jeroen; Petersen, Esben T

    2016-01-01

    BACKGROUND: The cerebrovascular reactivity (CVR) results of blood oxygen level-dependent (BOLD) and arterial spin labeling (ASL) MRI studies performed in patients with cerebrovascular disease (steno-occlusive vascular disease or stroke) were systematically reviewed. SUMMARY: Thirty-one articles...... found a significant lower ASL CVR in the ipsilateral hemispheres of patients compared to controls. KEY MESSAGES: This review brings support for a reduced BOLD and ASL CVR in the ipsilateral hemisphere of patients with cerebrovascular disease. We suggest that future studies will be performed in a uniform...... way so reference values can be established and could be used to guide treatment decisions in patients with cerebrovascular disease....

  17. Physical properties and band structure of reactive molecular beam epitaxy grown oxygen engineered HfO{sub 2{+-}x}

    Energy Technology Data Exchange (ETDEWEB)

    Hildebrandt, Erwin; Kurian, Jose; Alff, Lambert [Institute of Materials Science, Technische Universitaet Darmstadt, 64287 Darmstadt (Germany)

    2012-12-01

    We have conducted a detailed thin film growth structure of oxygen engineered monoclinic HfO{sub 2{+-}x} grown by reactive molecular beam epitaxy. The oxidation conditions induce a switching between (111) and (002) texture of hafnium oxide. The band gap of oxygen deficient hafnia decreases with increasing amount of oxygen vacancies by more than 1 eV. For high oxygen vacancy concentrations, defect bands form inside the band gap that induce optical transitions and p-type conductivity. The resistivity changes by several orders of magnitude as a function of oxidation conditions. Oxygen vacancies do not give rise to ferromagnetic behavior.

  18. Electrical and optical properties of reactive DC magnetron sputtered silver oxide thin films: role of oxygen

    Energy Technology Data Exchange (ETDEWEB)

    Kumar Barik, Ullash; Srinivasan, S; Nagendra, C L; Subrahmanyam, A

    2003-04-01

    Silver oxide thin films have been prepared on soda lime glass substrates at room temperature (300 K) by reactive DC Magnetron sputtering technique using pure silver metal target; the oxygen flow rates have been varied in the range 0.00-2.01 sccm. The X-ray diffraction data on these films show a systematic change from metallic silver to silver (sub) oxides. The electrical resistivity increases with increasing oxygen flow. The films show a p-type behavior (by both Hall and Seebeck measurements) for the oxygen flow rates of 0.54, 1.09 and 1.43 sccm. The refractive index of the films (at 632.8 nm) decreases with increasing oxygen content and is in the range 1.167-1.145, whereas the p-type films show a higher refractive index (1.186-1.204). The work function of these silver oxide films has been measured by Kelvin Probe technique. The results, in specific, the p-type conductivity in the silver oxide films, have been explained on the basis of the theory of partial ionic charge proposed by Sanderson.

  19. Electrical and optical properties of reactive DC magnetron sputtered silver oxide thin films: role of oxygen

    International Nuclear Information System (INIS)

    Kumar Barik, Ullash; Srinivasan, S.; Nagendra, C.L.; Subrahmanyam, A.

    2003-01-01

    Silver oxide thin films have been prepared on soda lime glass substrates at room temperature (300 K) by reactive DC Magnetron sputtering technique using pure silver metal target; the oxygen flow rates have been varied in the range 0.00-2.01 sccm. The X-ray diffraction data on these films show a systematic change from metallic silver to silver (sub) oxides. The electrical resistivity increases with increasing oxygen flow. The films show a p-type behavior (by both Hall and Seebeck measurements) for the oxygen flow rates of 0.54, 1.09 and 1.43 sccm. The refractive index of the films (at 632.8 nm) decreases with increasing oxygen content and is in the range 1.167-1.145, whereas the p-type films show a higher refractive index (1.186-1.204). The work function of these silver oxide films has been measured by Kelvin Probe technique. The results, in specific, the p-type conductivity in the silver oxide films, have been explained on the basis of the theory of partial ionic charge proposed by Sanderson

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

    Science.gov (United States)

    Criado, Susana; García, Norman A

    2010-01-01

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

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

    Science.gov (United States)

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

    2013-09-01

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

  2. Luteolin as reactive oxygen generator by X-ray and UV irradiation

    Science.gov (United States)

    Toyama, Michiru; Mori, Takashi; Takahashi, Junko; Iwahashi, Hitoshi

    2018-05-01

    Non-toxic X-ray-responsive substances can be used in the radiosensitization of cancer, like porphyrin mediated radiotherapy. However, most X-ray-responsive substances are toxic. To find novel non-toxic X-ray-responsive substances, we studied the X-ray and UV reactivity of 40 non-toxic compounds extracted from plants. Dihydroethidium was used as an indicator to detect reactive oxygen species (ROS) generated by the compounds under X-ray or UV irradiation. We found that 13 of the investigated compounds generated ROS under X-ray irradiation and 17 generated ROS under UV irradiation. Only 4 substances generated ROS under both X-ray and UV. In particular, luteolin exhibited the highest activity among the investigated compounds; therefore, the ROS generated by luteolin were thoroughly characterized. To identify the ROS, we employed a combination of ROS detection reagents and their quenchers. O2·- generation by luteolin was monitored using dihydroethidium and superoxide dismutase (as an O2·- quencher). OH· and 1O2 generation was determined using aminophenyl fluorescein with ethanol (OH· quencher) and Singlet Oxygen Sensor Green® with NaN3 (1O2 quencher), respectively. Generation of O2·- under X-ray and UV irradiation was observed; however, no OH· or 1O2 was detected. The production of ROS from luteolin is surprising, because luteolin is a well-known antioxidant.

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

    Science.gov (United States)

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

    2009-08-01

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

  4. Effects of Reactive Oxygen Species on Tubular Transport along the Nephron.

    Science.gov (United States)

    Gonzalez-Vicente, Agustin; Garvin, Jeffrey L

    2017-03-23

    Reactive oxygen species (ROS) are oxygen-containing molecules naturally occurring in both inorganic and biological chemical systems. Due to their high reactivity and potentially damaging effects to biomolecules, cells express a battery of enzymes to rapidly metabolize them to innocuous intermediaries. Initially, ROS were considered by biologists as dangerous byproducts of respiration capable of causing oxidative stress, a condition in which overproduction of ROS leads to a reduction in protective molecules and enzymes and consequent damage to lipids, proteins, and DNA. In fact, ROS are used by immune systems to kill virus and bacteria, causing inflammation and local tissue damage. Today, we know that the functions of ROS are not so limited, and that they also act as signaling molecules mediating processes as diverse as gene expression, mechanosensation, and epithelial transport. In the kidney, ROS such as nitric oxide (NO), superoxide (O₂ - ), and their derivative molecules hydrogen peroxide (H₂O₂) and peroxynitrite (ONO₂ - ) regulate solute and water reabsorption, which is vital to maintain electrolyte homeostasis and extracellular fluid volume. This article reviews the effects of NO, O₂ - , ONO₂ - , and H₂O₂ on water and electrolyte reabsorption in proximal tubules, thick ascending limbs, and collecting ducts, and the effects of NO and O₂ - in the macula densa on tubuloglomerular feedback.

  5. Reactive oxygen species in the paraventricular nucleus of the hypothalamus alter sympathetic activity during metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    JOSIANE CAMPOS CRUZ

    2015-12-01

    Full Text Available The paraventricular nucleus of the hypothalamus (PVN contains heterogeneous populations of neurons involved in autonomic and neuroendocrine regulation. The PVN plays an important role in the sympathoexcitatory response to increasing circulating levels of angiotensin II (Ang-II, which activates AT1 receptors in the circumventricular organs (OCVs, mainly in the subfornical organ (SFO. Circulating Ang-II induces a de novo synthesis of Ang-II in SFO neurons projecting to pre-autonomic PVN neurons. Activation of AT1 receptors induces intracellular increases in reactive oxygen species (ROS, leading to increases in sympathetic nerve activity (SNA. Chronic sympathetic nerve activation promotes a series of metabolic disorders that characterizes the metabolic syndrome (MetS: dyslipidemia, hyperinsulinemia, glucose intolerance, hyperleptinemia and elevated plasma hormone levels, such as noradrenaline, glucocorticoids, leptin, insulin and Ang-II. This review will discuss the contribution of our laboratory and others regarding the sympathoexcitation caused by peripheral Ang-II-induced reactive oxygen species along the subfornical organ and paraventricular nucleus of the hypothalamus. We hypothesize that this mechanism could be involved in metabolic disorders underlying MetS.

  6. Candida albicans Biofilms Do Not Trigger Reactive Oxygen Species and Evade Neutrophil Killing

    Science.gov (United States)

    Xie, Zhihong; Thompson, Angela; Sobue, Takanori; Kashleva, Helena; Xu, Hongbin; Vasilakos, John; Dongari-Bagtzoglou, Anna

    2012-01-01

    Neutrophils are found within Candida albicans biofilms in vivo and could play a crucial role in clearing the pathogen from biofilms forming on catheters and mucosal surfaces. Our goal was to compare the antimicrobial activity of neutrophils against developing and mature C. albicans biofilms and identify biofilm-specific properties mediating resistance to immune cells. Antibiofilm activity was measured with the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)2H-tetrazolium-5-carboxanilide assay and a molecular Candida viability assay. Reactive oxygen species generation was assessed by measuring fluorescence of 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate, acetyl ester in preloaded neutrophils. We found that mature biofilms were resistant to leukocytic killing and did not trigger reactive oxygen species, even though neutrophils retained their viability and functional activation potential. Beta-glucans found in the extracellular matrix negatively affected antibiofilm activities. We conclude that these polymers act as a decoy mechanism to prevent neutrophil activation and that this represents an important innate immune evasion mechanism of C. albicans biofilms. PMID:23033146

  7. Reactive oxygen species and lipid peroxidation product-scavenging ability of yogurt organisms.

    Science.gov (United States)

    Lin, M Y; Yen, C L

    1999-08-01

    The antioxidative activity of the intracellular extracts of yogurt organisms was investigated. All 11 strains tested, including five strains of Streptococcus thermophilus and six strains of Lactobacillus delbrueckii ssp. bulgaricus, demonstrated an antioxidative effect on the inhibition of linoleic acid peroxidation. The antioxidative effect of intracellular extracts of 10(8) cells of yogurt organisms was equivalent to 25 to 96 ppm butylated hydroxytoluene, which indicated that all strains demonstrated excellent antioxidative activity. The scavenging of reactive oxygen species, hydroxyl radical, and hydrogen peroxide was studied for intracellular extracts of yogurt organisms. All strains showed reactive oxygen species-scavenging ability. Lactobacillus delbrueckii ssp. bulgaricus Lb demonstrated the highest hydroxyl radical-scavenging ability at 234 microM. Streptococcus thermophilus MC and 821 and L. delbrueckii ssp. bulgaricus 448 and 449 scavenged the most hydrogen peroxide at approximately 50 microM. The scavenging ability of lipid peroxidation products, t-butylhydroperoxide and malondialdehyde, was also evaluated. Results showed that the extracts were not able to scavenge the t-butylhydroperoxide. Nevertheless, malondialdehyde was scavenged well by most strains.

  8. Hydrous Ferric Oxides in Sediment Catalyze Formation of Reactive Oxygen Species during Sulfide Oxidation

    Directory of Open Access Journals (Sweden)

    Sarah A. Murphy

    2016-11-01

    Full Text Available Abstract: This article describes the formation of reactive oxygen species as a result of the oxidation of dissolved sulfide by Fe(III-containing sediments suspended in oxygenated seawater over the pH range 7.00 and 8.25. Sediment samples were obtained from across the coastal littoral zone in South Carolina, US, at locations from the beach edge to the forested edge of a Spartina dominated estuarine salt marsh and suspended in aerated seawater. Reactive oxygen species (superoxide and hydrogen peroxide production was initiated in sediment suspensions by the addition of sodium bisulfide. The subsequent loss of HS-, formation of Fe(II (as indicated by Ferrozine, and superoxide and hydrogen peroxide were monitored over time. The concentration of superoxide rose from the baseline and then persisted at an apparent steady state concentration of approximately 500 nanomolar at pH 8.25 and 200 nanomolar at pH 7.00 respectively until >97% hydrogen sulfide was consumed. Measured superoxide was used to predict hydrogen peroxide yield based on superoxide dismutation. Dismutation alone quantitatively predicted hydrogen peroxide formation at pH 8.25 but over predicted hydrogen peroxide formation at pH 7 by a factor of approximately 102. Experiments conducted with episodic spikes of added hydrogen peroxide indicated rapid hydrogen peroxide consumption could account for its apparent low instantaneous yield, presumably the result of its reaction with Fe(II species, polysulfides or bisulfite. All sediment samples were characterized for total Fe, Cu, Mn, Ni, Co and hydrous ferric oxide by acid extraction followed by mass spectrometric or spectroscopic characterization. Sediments with the highest loadings of hydrous ferric oxide were the only sediments that produced significant dissolved Fe(II species or ROS as a result of sulfide exposure.

  9. Furfural Induces Reactive Oxygen Species Accumulation and Cellular Damage in Saccharomyces Cerevisiae

    Science.gov (United States)

    Background: Biofuels offer a viable alternative to petroleum-based fuel. However, current methods are not sufficient and technology to use lignocellulosic biomass as a fermentation substrate faces several challenges. One challenge is the need of a robust fermentative microorganism that can tolera...

  10. Reactive oxygen species production, induced by atmospheric modification, alter conidial quality of Beauveria bassiana.

    Science.gov (United States)

    Pérez-Guzmán, D; Montesinos-Matías, R; Arce-Cervantes, O; Gómez-Quiroz, L E; Loera, O; Garza-López, P M

    2016-08-01

    The aim of this study was to determine the relationship between reactive oxygen species (ROS) production and conidial infectivity in Beauveria bassiana. Beauveria bassiana Bb 882.5 was cultured in solid-state culture (SSC) using rice under three oxygen conditions (21%, or pulses at 16 and 26%). Hydrophobicity was determined using exclusion phase assay. Bioassays with larvae or adults of Tenebrio molitor allowed the measurements of infectivity parameters. A fluorometric method was used for ROS quantification (superoxide and total peroxides). NADPH oxidase (NOX) activity was determined by specific inhibition. Conidial hydrophobicity decreased by O2 pulses. Mortality of larvae was only achieved with conidia harvested from cultures under 21% O2 ; whereas for adult insects, the infectivity parameters deteriorated in conidia obtained after pulses at 16 and 26% O2 . At day 7, ROS production increased after 16 and 26% O2 treatments. NOX activity induced ROS production at early stages of the culture. Modification of atmospheric oxygen increases ROS production, reducing conidial quality and infectivity. This is the first study in which conidial infectivity and ROS production in B. bassiana has been related, enhancing the knowledge of the effect of O2 pulses in B. bassiana. © 2016 The Society for Applied Microbiology.

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

    Directory of Open Access Journals (Sweden)

    Waris Gulam

    2006-05-01

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

  12. The role of reactive oxygen species in the degradation of lignin derived dissolved organic matter

    Science.gov (United States)

    Waggoner, Derek C.; Wozniak, Andrew S.; Cory, Rose M.; Hatcher, Patrick G.

    2017-07-01

    Evidence suggests that reactive oxygen species (ROS) are important in transforming the chemical composition of the large pool of terrestrially-derived dissolved organic matter (DOM) exported from land to water annually. However, due to the challenges inherent in isolating the effects of individual ROS on DOM composition, the role of ROS in the photochemical alteration of DOM remains poorly characterized. In this work, terrestrial DOM was independently exposed to singlet oxygen (1O2), and superoxide (O2-rad under controlled laboratory conditions). Using ultra-high resolution mass spectrometry to track molecular level alterations of DOM by ROS, these findings suggest exposure to 1O2 (generated using Rose Bengal and visible light) removed formulas with an O/C > 0.3, and primarily resulted in DOM comprised of formulas with higher oxygen content, while O2-rad exposure (from KO2 in DMSO) removed formulas with O/C 1.5). Comparison of DOM altered by ROS in this study to riverine and coastal DOM showed that (20-80%) overlap in formulas, providing evidence for the role of ROS in shaping the composition of DOM exported from rivers to oceans.

  13. Developing the next generation of graphene-based platforms for cancer therapeutics: The potential role of reactive oxygen species.

    Science.gov (United States)

    Tabish, Tanveer A; Zhang, Shaowei; Winyard, Paul G

    2018-05-01

    Graphene has a promising future in applications such as disease diagnosis, cancer therapy, drug/gene delivery, bio-imaging and antibacterial approaches owing to graphene's unique physical, chemical and mechanical properties alongside minimal toxicity to normal cells, and photo-stability. However, these unique features and bioavailability of graphene are fraught with uncertainties and concerns for environmental and occupational exposure. Changes in the physicochemical properties of graphene affect biological responses including reactive oxygen species (ROS) production. Lower production of ROS by currently available theranostic agents, e.g. magnetic nanoparticles, carbon nanotubes, gold nanostructures or polymeric nanoparticles, restricts their clinical application in cancer therapy. Oxidative stress induced by graphene accumulated in living organs is due to acellular factors which may affect physiological interactions between graphene and target tissues and cells. Acellular factors include particle size, shape, surface charge, surface containing functional groups, and light activation. Cellular responses such as mitochondrial respiration, graphene-cell interactions and pH of the medium are also determinants of ROS production. The mechanisms of ROS production by graphene and the role of ROS for cancer treatment, are poorly understood. The aim of this review is to set the theoretical basis for further research in developing graphene-based theranostic platforms. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Developing the next generation of graphene-based platforms for cancer therapeutics: The potential role of reactive oxygen species

    Directory of Open Access Journals (Sweden)

    Tanveer A. Tabish

    2018-05-01

    Full Text Available Graphene has a promising future in applications such as disease diagnosis, cancer therapy, drug/gene delivery, bio-imaging and antibacterial approaches owing to graphene's unique physical, chemical and mechanical properties alongside minimal toxicity to normal cells, and photo-stability. However, these unique features and bioavailability of graphene are fraught with uncertainties and concerns for environmental and occupational exposure. Changes in the physicochemical properties of graphene affect biological responses including reactive oxygen species (ROS production. Lower production of ROS by currently available theranostic agents, e.g. magnetic nanoparticles, carbon nanotubes, gold nanostructures or polymeric nanoparticles, restricts their clinical application in cancer therapy. Oxidative stress induced by graphene accumulated in living organs is due to acellular factors which may affect physiological interactions between graphene and target tissues and cells. Acellular factors include particle size, shape, surface charge, surface containing functional groups, and light activation. Cellular responses such as mitochondrial respiration, graphene-cell interactions and pH of the medium are also determinants of ROS production. The mechanisms of ROS production by graphene and the role of ROS for cancer treatment, are poorly understood. The aim of this review is to set the theoretical basis for further research in developing graphene-based theranostic platforms.

  15. Effects of ambient ozone on reactive oxygen species and antioxidant metabolites in leaves of pea (pisum sativum l.) plants

    International Nuclear Information System (INIS)

    Hassan, I.A.; Almeelbi, T.; Basahi, J.M.

    2017-01-01

    The differential response of two pea plants (Pisum sativum L. cultivars Little Marvel and Victory) to ambient O3 grown under open top chambers (OTCs) was analyzed and compared. Reactive oxygen species (ROS) generation, antioxidant metabolites such as ascorbate/glutathione as well as a series of enzymes for scavenging ROS were analyzed, all aiming to reveal the differential behavior of two closely related plants when exposed to ambient O3.Antioxidant levels and activities of related enzymes in response to ambient were noticeably different among Little Marvel and Victory plants. However, the response was cultivar-specific. There was higher accumulation of ROS and relatively lower induction of antioxidants and more inhibition in photosynthetic rates in Victory than Little Marvel. There was a good correlation between tolerance to O3 and high endogenous levels of antioxidant metabolites such as ascorbate (As), glutathione reductase (GR), superoxide dismutase (SOD), reduced (GSH) and oxidized glutathione (GSSG) in pea plants. These portrays a higher sensitivity of Victory to ambient O3.To the best of our knowledge, this is one of the very few studies attempted to describe the changes in contents of antioxidants and activities of related enzymes in leaves of two closely related cultivars to further ourunderstanding on the defense mechanism and strategies under ambient O3. The results highlighted the possible roles of antioxidants in O3 detoxification through activation an adaptive survival mechanism allowing the plant to complete its life cycle even under oxidative stressful conditions. (author)

  16. Achillolide A Protects Astrocytes against Oxidative Stress by Reducing Intracellular Reactive Oxygen Species and Interfering with Cell Signaling

    Directory of Open Access Journals (Sweden)

    Anat Elmann

    2016-03-01

    Full Text Available Achillolide A is a natural sesquiterpene lactone that we have previously shown can inhibit microglial activation. In this study we present evidence for its beneficial effects on astrocytes under oxidative stress, a situation relevant to neurodegenerative diseases and brain injuries. Viability of brain astrocytes (primary cultures was determined by lactate dehydrogenase (LDH activity, intracellular ROS levels were detected using 2′,7′-dichlorofluorescein diacetate, in vitro antioxidant activity was measured by differential pulse voltammetry, and protein phosphorylation was determined using specific ELISA kits. We have found that achillolide A prevented the H2O2-induced death of astrocytes, and attenuated the induced intracellular accumulation of reactive oxygen species (ROS. These activities could be attributed to the inhibition of the H2O2-induced phosphorylation of MAP/ERK kinase 1 (MEK1 and p44/42 mitogen-activated protein kinases (MAPK, and to the antioxidant activity of achillolide A, but not to H2O2 scavenging. This is the first study that demonstrates its protective effects on brain astrocytes, and its ability to interfere with MAPK activation. We propose that achillolide A deserves further evaluation for its potential to be developed as a drug for the prevention/treatment of neurodegenerative diseases and brain injuries where oxidative stress is part of the pathophysiology.

  17. ACCERBATIN, a small molecule at the intersection of auxin and reactive oxygen species homeostasis with herbicidal properties.

    Science.gov (United States)

    Hu, Yuming; Depaepe, Thomas; Smet, Dajo; Hoyerova, Klara; Klíma, Petr; Cuypers, Ann; Cutler, Sean; Buyst, Dieter; Morreel, Kris; Boerjan, Wout; Martins, José; Petrášek, Jan; Vandenbussche, Filip; Van Der Straeten, Dominique

    2017-07-10

    The volatile two-carbon hormone ethylene acts in concert with an array of signals to affect etiolated seedling development. From a chemical screen, we isolated a quinoline carboxamide designated ACCERBATIN (AEX) that exacerbates the 1-aminocyclopropane-1-carboxylic acid-induced triple response, typical for ethylene-treated seedlings in darkness. Phenotypic analyses revealed distinct AEX effects including inhibition of root hair development and shortening of the root meristem. Mutant analysis and reporter studies further suggested that AEX most probably acts in parallel to ethylene signaling. We demonstrated that AEX functions at the intersection of auxin metabolism and reactive oxygen species (ROS) homeostasis. AEX inhibited auxin efflux in BY-2 cells and promoted indole-3-acetic acid (IAA) oxidation in the shoot apical meristem and cotyledons of etiolated seedlings. Gene expression studies and superoxide/hydrogen peroxide staining further revealed that the disrupted auxin homeostasis was accompanied by oxidative stress. Interestingly, in light conditions, AEX exhibited properties reminiscent of the quinoline carboxylate-type auxin-like herbicides. We propose that AEX interferes with auxin transport from its major biosynthesis sites, either as a direct consequence of poor basipetal transport from the shoot meristematic region, or indirectly, through excessive IAA oxidation and ROS accumulation. Further investigation of AEX can provide new insights into the mechanisms connecting auxin and ROS homeostasis in plant development and provide useful tools to study auxin-type herbicides. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  18. Protective effects of kaempferol against reactive oxygen species-induced hemolysis and its antiproliferative activity on human cancer cells.

    Science.gov (United States)

    Liao, Wenzhen; Chen, Luying; Ma, Xiang; Jiao, Rui; Li, Xiaofeng; Wang, Yong

    2016-05-23

    The protective effects of kaempferol against reactive oxygen species (ROS)-induced hemolysis and its antiproliferative activity on human cancer cells were evaluated in this study. Kaempferol exhibited strong cellular antioxidant ability (CAA) with a CAA value of 59.80 ± 0.379 μM of quercetin (QE)/100 μM (EC50 = 7.74 ± 0.049 μM). Pretreatment with kaempferol significantly attenuated the ROS-induced hemolysis of human erythrocyte (87.4% hemolysis suppressed at 100 μg/mL) and reduced the accumulation of toxic lipid peroxidation product malondialdehyde (MDA). The anti-hemolytic activity of kaempferol was mainly through scavenging excessive ROS and preserving the intrinsic antioxidant enzymes (superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx) activities in normal levels. Additionally, kaempferol showed significant antiproliferative activity on a panel of human cancer cell lines including human breast carcinoma (MCF-7) cells, human stomach carcinoma (SGC-7901) cells, human cervical carcinoma (Hela) cells and human lung carcinoma (A549) cells. Kaemperol induced apoptosis of MCF-7 cells accompanied with nuclear condensation and mitochondria dysfunction. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Effect of stationary magnetic field strengths of 150 and 200 mT on reactive oxygen species production in soybean.

    Science.gov (United States)

    Shine, M B; Guruprasad, K N; Anand, Anjali

    2012-07-01

    Our previous investigation reported the beneficial effect of pre-sowing magnetic treatment for improving germination parameters and biomass accumulation in soybean. In this study, soybean seeds treated with static magnetic fields of 150 and 200 mT for 1 h were evaluated for reactive oxygen species (ROS) and activity of antioxidant enzymes. Superoxide and hydroxyl radicals were measured in embryos and hypocotyls of germinating seeds by electron paramagnetic resonance spectroscopy and kinetics of superoxide production; hydrogen peroxide and antioxidant activities were estimated spectrophotometrically. Magnetic field treatment resulted in enhanced production of ROS mediated by cell wall peroxidase while ascorbic acid content, superoxide dismutase and ascorbate peroxidase activity decreased in the hypocotyl of germinating seeds. An increase in the cytosolic peroxidase activity indicated that this antioxidant enzyme had a vital role in scavenging the increased H(2)O(2) produced in seedlings from the magnetically treated seeds. Hence, these studies contribute to our first report on the biochemical basis of enhanced germination and seedling growth in magnetically treated seeds of soybean in relation to increased production of ROS. Copyright © 2012 Wiley Periodicals, Inc.

  20. A role for nuclear translocation of tripeptidyl-peptidase II in reactive oxygen species-dependent DNA damage responses

    Energy Technology Data Exchange (ETDEWEB)

    Preta, Giulio; Klark, Rainier de [Center for Molecular Medicine (CMM), Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm (Sweden); Glas, Rickard, E-mail: rickard.glas@ki.se [Center for Molecular Medicine (CMM), Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm (Sweden)

    2009-11-27

    Responses to DNA damage are influenced by cellular metabolism through the continuous production of reactive oxygen species (ROS), of which most are by-products of mitochondrial respiration. ROS have a strong influence on signaling pathways during responses to DNA damage, by relatively unclear mechanisms. Previous reports have shown conflicting data on a possible role for tripeptidyl-peptidase II (TPPII), a large cytosolic peptidase, within the DNA damage response. Here we show that TPPII translocated into the nucleus in a p160-ROCK-dependent fashion in response to {gamma}-irradiation, and that nuclear expression of TPPII was present in most {gamma}-irradiated transformed cell lines. We used a panel of nine cell lines of diverse tissue origin, including four lymphoma cell lines (T, B and Hodgkins lymphoma), a melanoma, a sarcoma, a colon and two breast carcinomas, where seven out of nine cell lines showed nuclear TPPII expression after {gamma}-irradiation. Further, this required cellular production of ROS; treatment with either N-acetyl-Cysteine (anti-oxidant) or Rotenone (inhibitor of mitochondrial respiration) inhibited nuclear accumulation of TPPII. The local density of cells was important for nuclear accumulation of TPPII at early time-points following {gamma}-irradiation (at 1-4 h), indicating a bystander effect. Further, we showed that the peptide-based inhibitor Z-Gly-Leu-Ala-OH, but not its analogue Z-Gly-(D)-Leu-Ala-OH, excluded TPPII from the nucleus. This correlated with reduced nuclear expression of p53 as well as caspase-3 and -9 activation in {gamma}-irradiated lymphoma cells. Our data suggest a role for TPPII in ROS-dependent DNA damage responses, through alteration of its localization from the cytosol into the nucleus.

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

    Science.gov (United States)

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

    2013-03-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Floriane L'Haridon

    2011-07-01

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

  3. Reactive Oxygen Species Generated by NADPH Oxidases Promote Radicle Protrusion and Root Elongation during Rice Seed Germination

    Directory of Open Access Journals (Sweden)

    Wen-Yan Li

    2017-01-01

    Full Text Available Seed germination is a complicated biological process that requires regulation through various enzymatic and non-enzymatic mechanisms. Although it has been recognized that reactive oxygen species (ROS regulate radicle emergence and root elongation in a non-enzymatic manner during dicot seed germination, the role of ROS in monocot seed germination remains unknown. NADPH oxidases (NOXs are the major ROS producers in plants; however, whether and how NOXs regulate rice seed germination through ROS generation remains unclear. Here, we report that diphenyleneiodinium (DPI, a specific NOX inhibitor, potently inhibited embryo and seedling growth—especially that of the radicle and of root elongation—in a dose-dependent manner. Notably, the DPI-mediated inhibition of radicle and root growth could be eliminated by transferring seedlings from DPI to water. Furthermore, ROS production/accumulation during rice seed germination was quantified via histochemistry. Superoxide radicals (O2−, hydrogen peroxide (H2O2 and hydroxyl radicals (•OH accumulated steadily in the coleorhiza, radicle and seedling root of germinating rice seeds. Expression profiles of the nine typical NOX genes were also investigated. According to quantitative PCR, OsNOX5, 7 and 9 were expressed relatively higher. When seeds were incubated in water, OsNOX5 expression progressively increased in the embryo from 12 to 48 h, whereas OsNOX7 and 9 expressions increased from 12 to 24 h and decreased thereafter. As expected, DPI inhibits the expression at predetermined time points for each of these genes. Taken together, these results suggest that ROS produced by NOXs are involved in radicle and root elongation during rice seed germination, and OsNOX5, 7 and 9 could play crucial roles in rice seed germination. These findings will facilitate further studies of the roles of ROS generated by NOXs during seed germination and seedling establishment and also provide valuable information for the

  4. Lysosomal membrane permeabilization: Carbon nanohorn-induced reactive oxygen species generation and toxicity by this neglected mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Mei, E-mail: happy_deercn@163.com [Nanotube Research Center, National Institute of Advanced Industrial Science and Technology 5-2, 1-1-1 Higashi, Tsukuba 305-8565 (Japan); Zhang, Minfang; Tahara, Yoshio; Chechetka, Svetlana; Miyako, Eijiro [Nanotube Research Center, National Institute of Advanced Industrial Science and Technology 5-2, 1-1-1 Higashi, Tsukuba 305-8565 (Japan); Iijima, Sumio [Nanotube Research Center, National Institute of Advanced Industrial Science and Technology 5-2, 1-1-1 Higashi, Tsukuba 305-8565 (Japan); Faculty of Science and Technology, Meijo University, 1-501 Shiogamaguchi, Tenpaku, Nagoya 468-8502 (Japan); Yudasaka, Masako, E-mail: m-yudasaka@aist.go.jp [Nanotube Research Center, National Institute of Advanced Industrial Science and Technology 5-2, 1-1-1 Higashi, Tsukuba 305-8565 (Japan)

    2014-10-01

    Understanding the molecular mechanisms responsible for the cytotoxic effects of carbon nanomaterials is important for their future biomedical applications. Carbon nanotubular materials induce the generation of reactive oxygen species (ROS), which causes cell death; however, the exact details of this process are still unclear. Here, we identify a mechanism of ROS generation that is involved in the apoptosis of RAW264.7 macrophages caused by excess uptake of carbon nanohorns (CNHs), a typical type of carbon nanotubule. CNH accumulated in the lysosomes, where they induced lysosomal membrane permeabilization (LMP) and the subsequent release of lysosomal proteases, such as cathepsins, which in turn caused mitochondrial dysfunction and triggered the generation of ROS in the mitochondria. The nicotinamide adenine dinucleotide phosphate oxidase was not directly involved in CNH-related ROS production, and the ROS generation cannot be regulated by mitochondrial electron transport chain. ROS fed back to amplify the mitochondrial dysfunction, leading to the subsequent activation of caspases and cell apoptosis. Carbon nanotubules commonly accumulate in the lysosomes after internalization in cells; however, lysosomal dysfunction has not attracted much attention in toxicity studies of these materials. These results suggest that LMP, a neglected mechanism, may be the primary reason for carbon nanotubule toxicity. - Highlights: • We clarify an apoptotic mechanism of RAW264.7 cells caused by carbon nanohorns. • In the meantime, the mechanism of CNH-induced ROS generation is identified. • LMP is the initial factor of CNH-induced ROS generation and cell death. • Cathepsins work as mediators that connect LMP and mitochondrial dysfunction.

  5. Reactive oxygen species and nitric oxide in plant mitochondria: origin and redundant regulatory systems.

    Science.gov (United States)

    Blokhina, Olga; Fagerstedt, Kurt V

    2010-04-01

    Plant mitochondria differ from their mammalian counterparts in many respects, which are due to the unique and variable surroundings of plant mitochondria. In green leaves, plant mitochondria are surrounded by ample respiratory substrates and abundant molecular oxygen, both resulting from active photosynthesis, while in roots and bulky rhizomes and fruit carbohydrates may be plenty, whereas oxygen levels are falling. Several enzymatic complexes in mitochondrial electron transport chain (ETC) are capable of reactive oxygen species (ROS) formation under physiological and pathological conditions. Inherently connected parameters such as the redox state of electron carriers in the ETC, ATP synthase activity and inner mitochondrial membrane potential, when affected by external stimuli, can give rise to ROS formation via complexes I and III, and by reverse electron transport (RET) from complex II. Superoxide radicals produced are quickly scavenged by superoxide dismutase (MnSOD), and the resulting H(2)O(2) is detoxified by peroxiredoxin-thioredoxin system or by the enzymes of ascorbate-glutathione cycle, found in the mitochondrial matrix. Arginine-dependent nitric oxide (NO)-releasing activity of enzymatic origin has been detected in plant mitochondria. The molecular identity of the enzyme is not clear but the involvement of mitochondria-localized enzymes responsible for arginine catabolism, arginase and ornithine aminotransferase has been shown in the regulation of NO efflux. Besides direct control by antioxidants, mitochondrial ROS production is tightly controlled by multiple redundant systems affecting inner membrane potential: NAD(P)H-dependent dehydrogenases, alternative oxidase (AOX), uncoupling proteins, ATP-sensitive K(+) channel and a number of matrix and intermembrane enzymes capable of direct electron donation to ETC. NO removal, on the other hand, takes place either by reactions with molecular oxygen or superoxide resulting in peroxynitrite, nitrite or nitrate

  6. Inverse correlation between reactive oxygen species in unwashed semen and sperm motion parameters as measured by a computer-assisted semen analyzer.

    Science.gov (United States)

    Takeshima, Teppei; Yumura, Yasushi; Yasuda, Kengo; Sanjo, Hiroyuki; Kuroda, Shinnosuke; Yamanaka, Hiroyuki; Iwasaki, Akira

    2017-01-01

    This study investigated the correlation between sperm motion parameters obtained by a computer-assisted semen analyzer and levels of reactive oxygen species in unwashed semen. In total, 847 patients, except for azoospermic patients were investigated. At the time of each patient's first consultation, semen parameters were measured using SMAS™ or CellSoft 3000™, and production of reactive oxygen species was measured using a computer-driven LKB Wallac Luminometer 1251 Analyzer. The patients were divided into two groups: reactive oxygen species - positive and negative. The semen parameters within each group were measured using one of the two computer-assisted semen analyzer systems and then compared. Correlations between reactive oxygen species levels and sperm motion parameters in semen from the reactive oxygen species - positive group were also investigated. Reactive oxygen species were detected in semen samples of 282 cases (33.3%). Sperm concentration (P semen damage sperm concentration, motility, and other sperm motion parameters.

  7. Accumulation of Fe oxyhydroxides in the Peruvian oxygen deficient zone implies non-oxygen dependent Fe oxidation

    Science.gov (United States)

    Heller, Maija I.; Lam, Phoebe J.; Moffett, James W.; Till, Claire P.; Lee, Jong-Mi; Toner, Brandy M.; Marcus, Matthew A.

    2017-08-01

    Oxygen minimum zones (OMZs) have been proposed to be an important source of dissolved iron (Fe) into the interior ocean. However, previous studies in OMZs have shown a sharp decrease in total dissolved Fe (dFe) and/or dissolved Fe(II) (dFe(II)) concentrations at the shelf-break, despite constant temperature, salinity and continued lack of oxygen across the shelf-break. The loss of both total dFe and dFe(II) suggests a conversion of the dFe to particulate form, but studies that have coupled the reduction-oxidation (redox) speciation of both dissolved and particulate phases have not previously been done. Here we have measured the redox speciation and concentrations of both dissolved and particulate forms of Fe in samples collected during the U.S. GEOTRACES Eastern tropical Pacific Zonal Transect (EPZT) cruise in 2013 (GP16). This complete data set allows us to assess possible mechanisms for loss of dFe. We observed an offshore loss of dFe(II) within the oxygen deficient zone (ODZ), where dissolved oxygen is undetectable, accompanied by an increase in total particulate Fe (pFe). Total pFe concentrations were highest in the upper ODZ. X-ray absorption spectroscopy revealed that the pFe maximum was primarily in the Fe(III) form as Fe(III) oxyhydroxides. The remarkable similarity in the distributions of total particulate iron and nitrite suggests a role for nitrite in the oxidation of dFe(II) to pFe(III). We present a conceptual model for the rapid redox cycling of Fe that occurs in ODZs, despite the absence of oxygen.

  8. Mechanism of artemisinin phytotoxicity action: induction of reactive oxygen species and cell death in lettuce seedlings.

    Science.gov (United States)

    Yan, Zhi-Qiang; Wang, Dan-Dan; Ding, Lan; Cui, Hai-Yan; Jin, Hui; Yang, Xiao-Yan; Yang, Jian-She; Qin, Bo

    2015-03-01

    Artemisinin has been recognized as an allelochemical that inhibits growth of several plant species. However, its mode of action is not well clarified. In this study, the mechanism of artemisinin phytotoxicity on lettuce seedlings was investigated. Root and shoot elongation of lettuce seedlings were inhibited by artemisinin in a concentration-dependent manner. The compound effectively arrested cell division and caused loss of cell viability in root tips of lettuce. Overproduction of reactive oxygen species (ROS) was induced by artemisinin. Lipid peroxidation, proline overproduction and reduction of chlorophyll content in lettuce seedlings were found after treatments. These results suggested that artemisinin could induce ROS overproduction, which caused membrane lipids peroxidation and cell death, and impacted mitosis and physiological processes, resulting in growth inhibition of receptor plants. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Okada Futoshi

    2005-09-01

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

  10. Research on killing Escherichia Coli by reactive oxygen species based on strong ionization discharging plasma

    International Nuclear Information System (INIS)

    Li, Y J; Tian, Y P; Zhang, Z T; Li, R H; Cai, L J; Gao, J Y

    2013-01-01

    Reactive oxygen species solution produced by strong ionization discharging plasma was used to kill Escherichia coli by spraying. Several effect factors such as pH value, solution temperature, spraying time and exposure time were observed in this study, and their effects on killing rate of Escherichia coli were discussed and analysed. Results show that the treating efficiency of ROS solution for Escherichia coli is higher in alkaline solution than that in acid solution. The killing rate of Escherichia coli increases while the spraying time and exposure time are longer and the temperature is lower. The effects of different factors on killing rate of Escherichia coli are as follows: spraying time > pH value > exposure time > solution temperature.

  11. Enhanced reactive oxygen species through direct copper sulfide nanoparticle-doxorubicin complexation

    Science.gov (United States)

    Li, Yajuan; Cupo, Michela; Guo, Liangran; Scott, Julie; Chen, Yi-Tzai; Yan, Bingfang; Lu, Wei

    2017-12-01

    CuS-based nanostructures loading the chemotherapeutic agent doxorubicin (DOX) exerted excellent cancer photothermal chemotherapy under multi-external stimuli. The DOX loading was generally designed through electrostatic interaction or chemical linkers. However, the interaction between DOX molecules and CuS nanoparticles has not been investigated. In this work, we use PEGylated hollow copper sulfide nanoparticles (HCuSNPs) to directly load DOX through the DOX/Cu2+ chelation process. Distinctively, the synthesized PEG-HCuSNPs-DOX release the DOX/Cu2+ complexes into surrounding environment, which generate significant reactive oxygen species (ROS) in a controlled manner by near-infrared laser. The CuS nanoparticle-mediated photothermal ablation facilitates the ROS-induced cancer cell killing effect. Our current work reveals a DOX/Cu2+-mediated ROS-enhanced cell-killing effect in addition to conventional photothermal chemotherapy through the direct CuS nanoparticle-DOX complexation.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    This study was designed to enhance our understanding of how reactive oxygen species (ROS), generated ex situ by ionized gas (plasma), can affect the regulation of signalling processes within cells. A model system, comprising of a suspension of phospholipid vesicles (cell mimics) encapsulating a ROS reporter, was developed to study the plasma delivery of ROS into cells. For the first time it was shown that plasma unequivocally delivers ROS into cells over a sustained period and without compromising cell membrane integrity. An important consideration in cell and biological assays is the presence of serum, which significantly reduced the transfer efficiency of ROS into the vesicles. These results are key to understanding how plasma treatments can be tailored for specific medical or biotechnology applications. Further, the phospholipid vesicle ROS reporter system may find use in other studies involving the application of free radicals in biology and medicine. (fast track communication)

  13. Temperature controls oxidative phosphorylation and reactive oxygen species production through uncoupling in rat skeletal muscle mitochondria.

    Science.gov (United States)

    Jarmuszkiewicz, Wieslawa; Woyda-Ploszczyca, Andrzej; Koziel, Agnieszka; Majerczak, Joanna; Zoladz, Jerzy A

    2015-06-01

    Mitochondrial respiratory and phosphorylation activities, mitochondrial uncoupling, and hydrogen peroxide formation were studied in isolated rat skeletal muscle mitochondria during experimentally induced hypothermia (25 °C) and hyperthermia (42 °C) compared to the physiological temperature of resting muscle (35 °C). For nonphosphorylating mitochondria, increasing the temperature from 25 to 42 °C led to a decrease in membrane potential, hydrogen peroxide production, and quinone reduction levels. For phosphorylating mitochondria, no temperature-dependent changes in these mitochondrial functions were observed. However, the efficiency of oxidative phosphorylation decreased, whereas the oxidation and phosphorylation rates and oxidative capacities of the mitochondria increased, with increasing assay temperature. An increase in proton leak, including uncoupling protein-mediated proton leak, was observed with increasing assay temperature, which could explain the reduced oxidative phosphorylation efficiency and reactive oxygen species production. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Reactive Oxygen Species-Mediated Mechanisms of Action of Targeted Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Hanna-Riikka Teppo

    2017-01-01

    Full Text Available Targeted cancer therapies, involving tyrosine kinase inhibitors and monoclonal antibodies, for example, have recently led to substantial prolongation of survival in many metastatic cancers. Compared with traditional chemotherapy and radiotherapy, where reactive oxygen species (ROS have been directly linked to the mediation of cytotoxic effects and adverse events, the field of oxidative stress regulation is still emerging in targeted cancer therapies. Here, we provide a comprehensive review regarding the current evidence of ROS-mediated effects of antibodies and tyrosine kinase inhibitors, use of which has been indicated in the treatment of solid malignancies and lymphomas. It can be concluded that there is rapidly emerging evidence of ROS-mediated effects of some of these compounds, which is also relevant in the context of drug resistance and how to overcome it.

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

    Science.gov (United States)

    Mcgee, H. A., Jr.

    1973-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Marcia Cristina Paes

    2011-01-01

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

  17. Restraining reactive oxygen species in Listeria monocytogenes promotes the apoptosis of glial cells.

    Science.gov (United States)

    Li, Sen; Li, Yixuan; Chen, Guowei; Zhang, Jingchen; Xu, Fei; Wu, Man

    2017-07-01

    Listeria monocytogenes is a facultative anaerobic foodborne pathogen that can traverse the blood-brain barrier and cause brain infection. L. monocytogenes infection induces host cell apoptosis in several cell types. In this study, we investigated the apoptosis of human glioma cell line U251 invaded by L. monocytogenes and evaluated the function of bacterial reactive oxygen species (ROS) during infection. Bacterial ROS level was reduced by carrying out treatment with N-acetyl cysteine (NAC) and diphenyleneiodonium chloride (DPI). After infection, the apoptosis of U251 cells was examined by flow cytometry assay and propidium iodide staining. DPI and NAC efficiently decreased ROS level in L. monocytogenes without affecting bacterial growth. Moreover, the apoptosis of glial cells was enhanced upon invasion of DPI- and NAC-pretreated L. monocytogenes. Results indicate that the apoptosis of glial cells can be induced by L. monocytogenes, and that the inhibition of bacterial ROS increases the apoptosis of host cells.

  18. Inactivation of pyruvate dehydrogenase kinase 2 by mitochondrial reactive oxygen species.

    Science.gov (United States)

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

    2012-10-12

    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 (H(2)O(2)) 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. H(2)O(2) derives from superoxide (O(2)(.)), and we show that conditions that inhibit PDHK2 also inactivate the TCA cycle enzyme, aconitase. These findings suggest that under conditions of high mitochondrial O(2)(.) production, such as may occur under nutrient excess and low ATP demand, the increase in O(2)() and H(2)O(2) may provide feedback signals to modulate mitochondrial metabolism.

  19. The Injury and Therapy of Reactive Oxygen Species in Intracerebral Hemorrhage Looking at Mitochondria

    Directory of Open Access Journals (Sweden)

    Jie Qu

    2016-01-01

    Full Text Available Intracerebral hemorrhage is an emerging major health problem often resulting in death or disability. Reactive oxygen species (ROS have been identified as one of the major damaging factors in ischemic stroke. However, there is less discussion about ROS in hemorrhage stroke. Metabolic products of hemoglobin, excitatory amino acids, and inflammatory cells are all sources of ROS, and ROS harm the central nervous system through cell death and structural damage, especially disruption of the blood-brain barrier. We have considered the antioxidant system of the CNS itself and the drugs aiming to decrease ROS after ICH, and we find that mitochondria are key players in all of these aspects. Moreover, when the mitochondrial permeability transition pore opens, ROS-induced ROS release, which leads to extensive liberation of ROS and mitochondrial failure, occurs. Therefore, the mitochondrion may be a significant target for elucidating the problem of ROS in ICH; however, additional experimental support is required.

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

    Science.gov (United States)

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

    2014-09-01

    This study was designed to enhance our understanding of how reactive oxygen species (ROS), generated ex situ by ionized gas (plasma), can affect the regulation of signalling processes within cells. A model system, comprising of a suspension of phospholipid vesicles (cell mimics) encapsulating a ROS reporter, was developed to study the plasma delivery of ROS into cells. For the first time it was shown that plasma unequivocally delivers ROS into cells over a sustained period and without compromising cell membrane integrity. An important consideration in cell and biological assays is the presence of serum, which significantly reduced the transfer efficiency of ROS into the vesicles. These results are key to understanding how plasma treatments can be tailored for specific medical or biotechnology applications. Further, the phospholipid vesicle ROS reporter system may find use in other studies involving the application of free radicals in biology and medicine.

  1. Horseradish peroxidase embedded in polyacrylamide nanoparticles enables optical detection of reactive oxygen species

    DEFF Research Database (Denmark)

    Poulsen, A.K.; Scharff-Poulsen, Anne Marie; Olsen, L.F.

    2007-01-01

    We have synthesized and characterized new nanometer-sized polyacrylamide particles containing horseradish peroxidase and fluorescent dyes. Proteins and dyes are encapsulated by radical polymerization in inverse microemulsion. The activity of the encapsulated enzyme has been examined and it mainta......We have synthesized and characterized new nanometer-sized polyacrylamide particles containing horseradish peroxidase and fluorescent dyes. Proteins and dyes are encapsulated by radical polymerization in inverse microemulsion. The activity of the encapsulated enzyme has been examined...... for quantification of hydrogen peroxide and other reactive oxygen species in microenvironments, and we propose that the particles may find use as nanosensors for use in, e.g., living cells. (C) 2007 Elsevier Inc. All rights reserved....

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

    Science.gov (United States)

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

    2014-03-01

    Nano-iron metal and nano-iron oxides are among the most widely used engineered and naturally occurring nanostructures, and the increasing incidence of biological exposure to these nanostructures has raised concerns about their biotoxicity. Reactive oxygen species (ROS)-induced oxidative stress is one of the most accepted toxic mechanisms and, in the past decades, considerable efforts have been made to investigate the ROS-related activities of iron nanostructures. In this review, we summarize activities of nano-iron metal and nano-iron oxides in ROS-related redox processes, addressing in detail the known homogeneous and heterogeneous redox mechanisms involved in these processes, intrinsic ROS-related properties of iron nanostructures (chemical composition, particle size, and crystalline phase), and ROS-related bio-microenvironmental factors, including physiological pH and buffers, biogenic reducing agents, and other organic substances. Copyright © 2014. Published by Elsevier B.V.

  3. Using consensus bayesian network to model the reactive oxygen species regulatory pathway.

    Directory of Open Access Journals (Sweden)

    Liangdong Hu

    Full Text Available Bayesian network is one of the most successful graph models for representing the reactive oxygen species regulatory pathway. With the increasing number of microarray measurements, it is possible to construct the bayesian network from microarray data directly. Although large numbers of bayesian network learning algorithms have been developed, when applying them to learn bayesian networks from microarray data, the accuracies are low due to that the databases they used to learn bayesian networks contain too few microarray data. In this paper, we propose a consensus bayesian network which is constructed by combining bayesian networks from relevant literatures and bayesian networks learned from microarray data. It would have a higher accuracy than the bayesian networks learned from one database. In the experiment, we validated the bayesian network combination algorithm on several classic machine learning databases and used the consensus bayesian network to model the Escherichia coli's ROS pathway.

  4. Reactive Oxygen and Nitrogen Species in the Development of Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    David J.R. Fulton

    2017-07-01

    Full Text Available Pulmonary arterial hypertension (PAH is a progressive disease of the lung vasculature that involves the loss of endothelial function together with inappropriate smooth muscle cell growth, inflammation, and fibrosis. These changes underlie a progressive remodeling of blood vessels that alters flow and increases pulmonary blood pressure. Elevated pressures in the pulmonary artery imparts a chronic stress on the right ventricle which undergoes compensatory hypertrophy but eventually fails. How PAH develops remains incompletely understood and evidence for the altered production of reactive oxygen and nitrogen species (ROS, RNS respectively in the pulmonary circulation has been well documented. There are many different types of ROS and RNS, multiple sources, and collective actions and interactions. This review summarizes past and current knowledge of the sources of ROS and RNS and how they may contribute to the loss of endothelial function and changes in smooth muscle proliferation in the pulmonary circulation.

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

    Science.gov (United States)

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

    2014-01-01

    Neuronal communication imposes a heavy metabolic burden in maintaining ionic gradients essential for action potential firing and synaptic signalling. Although cellular metabolism is known to regulate excitatory neurotransmission, it is still unclear whether the brain’s energy supply affects inhibitory signalling. Here we show that mitochondrial-derived reactive oxygen species (mROS) regulate the strength of postsynaptic GABAA receptors at inhibitory synapses of cerebellar stellate cells. Inhibition is strengthened through a mechanism that selectively recruits α3-containing GABAA receptors into synapses with no discernible effect on resident α1-containing receptors. Since mROS promotes the emergence of postsynaptic events with unique kinetic properties, we conclude that newly recruited α3-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.

  6. Nitric Oxide is Required for Homeostasis of Oxygen and Reactive Oxygen Species in Barley Roots under Aerobic Conditions

    DEFF Research Database (Denmark)

    Gupta, Kapuganti J; Hebelstrup, Kim; Kruger, Nicholas J

    2014-01-01

    Oxygen, the terminal electron acceptor for mitochondrial electron transport, is vital for plants because of its role in the production of ATP by oxidative phosphorylation. While photosynthetic oxygen production contributes to the oxygen supply in leaves, reducing the risk of oxygen limitation of ...... electron transport chain (Gupta et al., 2011). Thus, NO could influence oxygen consumption under normal aerobic conditions in roots, and it is this specific function that is assessed here.......Oxygen, the terminal electron acceptor for mitochondrial electron transport, is vital for plants because of its role in the production of ATP by oxidative phosphorylation. While photosynthetic oxygen production contributes to the oxygen supply in leaves, reducing the risk of oxygen limitation...

  7. Reactive oxygen species and transcript analysis upon excess light treatment in wild-type Arabidopsis thaliana vs a photosensitive mutant lacking zeaxanthin and lutein

    Directory of Open Access Journals (Sweden)

    Roncaglia Enrica

    2011-04-01

    Full Text Available Abstract Background Reactive oxygen species (ROS are unavoidable by-products of oxygenic photosynthesis, causing progressive oxidative damage and ultimately cell death. Despite their destructive activity they are also signalling molecules, priming the acclimatory response to stress stimuli. Results To investigate this role further, we exposed wild type Arabidopsis thaliana plants and the double mutant npq1lut2 to excess light. The mutant does not produce the xanthophylls lutein and zeaxanthin, whose key roles include ROS scavenging and prevention of ROS synthesis. Biochemical analysis revealed that singlet oxygen (1O2 accumulated to higher levels in the mutant while other ROS were unaffected, allowing to define the transcriptomic signature of the acclimatory response mediated by 1O2 which is enhanced by the lack of these xanthophylls species. The group of genes differentially regulated in npq1lut2 is enriched in sequences encoding chloroplast proteins involved in cell protection against the damaging effect of ROS. Among the early fine-tuned components, are proteins involved in tetrapyrrole biosynthesis, chlorophyll catabolism, protein import, folding and turnover, synthesis and membrane insertion of photosynthetic subunits. Up to now, the flu mutant was the only biological system adopted to define the regulation of gene expression by 1O2. In this work, we propose the use of mutants accumulating 1O2 by mechanisms different from those activated in flu to better identify ROS signalling. Conclusions We propose that the lack of zeaxanthin and lutein leads to 1O2 accumulation and this represents a signalling pathway in the early stages of stress acclimation, beside the response to ADP/ATP ratio and to the redox state of both plastoquinone pool. Chloroplasts respond to 1O2 accumulation by undergoing a significant change in composition and function towards a fast acclimatory response. The physiological implications of this signalling specificity are

  8. Reactive oxygen species and transcript analysis upon excess light treatment in wild-type Arabidopsis thaliana vs a photosensitive mutant lacking zeaxanthin and lutein

    Science.gov (United States)

    2011-01-01

    Background Reactive oxygen species (ROS) are unavoidable by-products of oxygenic photosynthesis, causing progressive oxidative damage and ultimately cell death. Despite their destructive activity they are also signalling molecules, priming the acclimatory response to stress stimuli. Results To investigate this role further, we exposed wild type Arabidopsis thaliana plants and the double mutant npq1lut2 to excess light. The mutant does not produce the xanthophylls lutein and zeaxanthin, whose key roles include ROS scavenging and prevention of ROS synthesis. Biochemical analysis revealed that singlet oxygen (1O2) accumulated to higher levels in the mutant while other ROS were unaffected, allowing to define the transcriptomic signature of the acclimatory response mediated by 1O2 which is enhanced by the lack of these xanthophylls species. The group of genes differentially regulated in npq1lut2 is enriched in sequences encoding chloroplast proteins involved in cell protection against the damaging effect of ROS. Among the early fine-tuned components, are proteins involved in tetrapyrrole biosynthesis, chlorophyll catabolism, protein import, folding and turnover, synthesis and membrane insertion of photosynthetic subunits. Up to now, the flu mutant was the only biological system adopted to define the regulation of gene expression by 1O2. In this work, we propose the use of mutants accumulating 1O2 by mechanisms different from those activated in flu to better identify ROS signalling. Conclusions We propose that the lack of zeaxanthin and lutein leads to 1O2 accumulation and this represents a signalling pathway in the early stages of stress acclimation, beside the response to ADP/ATP ratio and to the redox state of both plastoquinone pool. Chloroplasts respond to 1O2 accumulation by undergoing a significant change in composition and function towards a fast acclimatory response. The physiological implications of this signalling specificity are discussed. PMID:21481232

  9. Protective effects of myricitrin against osteoporosis via reducing reactive oxygen species and bone-resorbing cytokines

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Qiang; Gao, Bo; Wang, Long; Hu, Ya-Qian; Lu, Wei-Guang; Yang, Liu; Luo, Zhuo-Jing; Liu, Jian, E-mail: liujianhq@sina.com

    2014-11-01

    Oxidative stress is a crucial pathogenic factor in the development of osteoporosis. Myricitrin, isolated from Myrica cerifera, is a potent antioxidant. We hypothesized that myricitrin possessed protective effects against osteoporosis by partially reducing reactive oxygen species (ROS) and bone-resorbing cytokines in osteoblastic MC3T3-E1 cells and human bone marrow stromal cells (hBMSCs). We investigated myricitrin on osteogenic differentiation under oxidative stress. Hydrogen peroxide (H{sub 2}O{sub 2}) was used to establish an oxidative cell injury model. Our results revealed that myricitrin significantly improved some osteogenic markers in these cells. Myricitrin decreased lipid production and reduced peroxisome proliferator-activated receptor gamma-2 (PPARγ2) expression in hBMSCs. Moreover, myricitrin reduced the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and IL-6 and partially suppressed ROS production. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Our results demonstrated that myricitrin supplementation reduced serum malondialdehyde (MDA) activity and increased reduced glutathione (GSH) activity. Importantly, it ameliorated the micro-architecture of trabecular bones in the 4th lumbar vertebrae (L4) and distal femur. Taken together, these results indicated that the protective effects of myricitrin against osteoporosis are linked to a reduction in ROS and bone-resorbing cytokines, suggesting that myricitrin may be useful in bone metabolism diseases, particularly osteoporosis. - Highlights: • Myricitrin protects MC3T3-E1 cells and hBMSCs from oxidative stress. • It is accompanied by a decrease in oxidative stress and bone-resorbing cytokines. • Myricitrin decreases serum reactive oxygen species to some degree. • Myricitrin partly reverses ovariectomy effects in vivo. • Myricitrin may represent a beneficial anti-osteoporosis treatment method.

  10. Blood oxygen-level dependent functional assessment of cerebrovascular reactivity: Feasibility for intraoperative 3 Tesla MRI.

    Science.gov (United States)

    Fierstra, Jorn; Burkhardt, Jan-Karl; van Niftrik, Christiaan Hendrik Bas; Piccirelli, Marco; Pangalu, Athina; Kocian, Roman; Neidert, Marian Christoph; Valavanis, Antonios; Regli, Luca; Bozinov, Oliver

    2017-02-01

    To assess the feasibility of functional blood oxygen-level dependent (BOLD) MRI to evaluate intraoperative cerebrovascular reactivity (CVR) at 3 Tesla field strength. Ten consecutive neurosurgical subjects scheduled for a clinical intraoperative MRI examination were enrolled in this study. In addition to the clinical protocol a BOLD sequence was implemented with three cycles of 44 s apnea to calculate CVR values on a voxel-by-voxel basis throughout the brain. The CVR range was then color-coded and superimposed on an anatomical volume to create high spatial resolution CVR maps. Ten subjects (mean age 34.8 ± 13.4; 2 females) uneventfully underwent the intraoperative BOLD protocol, with no complications occurring. Whole-brain CVR for all subjects was (mean ± SD) 0.69 ± 0.42, whereas CVR was markedly higher for tumor subjects as compared to vascular subjects, 0.81 ± 0.44 versus 0.33 ± 0.10, respectively. Furthermore, color-coded functional maps could be robustly interpreted for a whole-brain assessment of CVR. We demonstrate that intraoperative BOLD MRI is feasible in creating functional maps to assess cerebrovascular reactivity throughout the brain in subjects undergoing a neurosurgical procedure. Magn Reson Med 77:806-813, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  11. Reactive oxygen metabolites (ROMs) are associated with cardiovascular disease in chronic hemodialysis patients.

    Science.gov (United States)

    Bossola, Maurizio; Vulpio, Carlo; Colacicco, Luigi; Scribano, Donata; Zuppi, Cecilia; Tazza, Luigi

    2012-02-11

    The aim of our study was to measure reactive oxygen metabolites (ROMs) in chronic hemodialysis (HD) patients and evaluate the possible association with cardiovascular disease (CVD) and mortality. We measured ROMs in 76 HD patients and correlated with CVD, cardiovascular (CV) events in the follow-up and all-cause and CVD-related mortality. The levels of ROMs presented a median value of 270 (238.2-303.2) CARR U (interquartile range). We created a ROC curve (ROMs levels vs. CVD) and we identified a cut-off point of 273 CARR U. Patients with ROMs levels ≥273 CARR U were significantly older, had higher C-reactive protein levels and lower creatinine concentrations. The prevalence of CVD was higher in patients with ROMs levels ≥273 (87.1%) than in those with ROMs levels <273 CARR U (17.7%; p<0.0001). ROMs levels were significantly higher in patients with CVD (317±63.8) than in those without (242.7±49.1; p<0.0001). At multiple regression analysis, age, creatinine and C-reactive protein were independent factors associated with ROMs. At multiple logistic regression analysis the association between ROMs and CVD was independent (OR: 1.02, 95% CI: 1.00-1.05; p=0.03). Twenty six patients developed cardiovascular (CV) events during the follow-up. Of these, seven were in the group with ROMs levels <273 CARR U and 19 in the group with ROMs levels ≥273 CARR U. The logistic regression analysis showed that both age (OR: 1.06, 95% CI: 1.01-1.12; p=0.013) and ROMs levels (OR: 1.10, 95% CI: 1.00-1.02; p=0.045) were independently associated with CV events in the follow-up. ROMs are independently associated with CVD and predict CV events in chronic HD patients.

  12. Influence of Vitamins on Secondary Reactive Oxygen Species Production in Sera of Patients with Resectable NSCLC

    Directory of Open Access Journals (Sweden)

    Thierry Patrice

    2016-07-01

    Full Text Available Background: Singlet oxygen (1O2 oxidizes targets through the production of secondary reactive oxygen species (SOS. Cancers induce oxidative stress changing with progression, the resulting antioxidant status differing from one patient to the other. The aim of this study was to determine the oxidative status of patients with resectable Non-Small cell lung cancers (NSCLC and the potential influence of antioxidants, compared to sera from healthy donors. Materials and Methods: Serum samples from 10 women and 28 men, 19 adenocarcinomas (ADK, 15 patients N1 or M1 were submitted to a photoreaction producing 1O2. Then, samples were supplemented with vitamins (Vit C, Vit E, or glutathione (GSH. Results: Squamous cell carcinomas (SCC and metastatic SCCs induced a lower SOS rate. While Vit C increased SOS in controls as in patients with metastases, Vit E or the combination of Vit E and C strongly reduced SOS. GSH alone lightly decreased SOS in controls but had no effect in patients either alone or combined with Vit C. Conclusion: In “early” lung cancers, SOS are comparable or lower than for healthy persons. The role of Vitamins varies with gender, cancer type, and metastases. This suggests that an eventual supplementation should be performed on a per-patient basis to evidence any effect.

  13. Involvement of reactive oxygen species (ROS) in the induction of genetic instability by radiation

    International Nuclear Information System (INIS)

    Tominaga, Hideyuki; Kodama, Seiji; Suzuki, Keiji; Watanabe, Masami; Matsuda, Naoki

    2004-01-01

    Radiation generates reactive oxygen species (ROS) that interact with cellular molecules, including DNA, lipids, and proteins. To know how ROS contribute to the induction of genetic instability, we examined the effect of the anti-ROS condition, using both ascorbic acid phosphate (APM) treatment or a low oxygen condition, on the induction of delayed reproductive cell death and delayed chromosome aberrations. The primary surviving colonies of mouse m5S-derived cl. 2011-14 cells irradiated with 6 Gy of X-rays were replated and allowed to form secondary colonies. The anti-ROS treatments were applied to either preirradiation culture or postirradiation cultures for primary or secondary colony formation. Both anti-ROS conditions relieved X-ray-induced acute cell killing to a similar extent. These anti-ROS conditions also relieved genetic instability when those conditions were applied during primary colony formation. However, no effect was observed when the conditions were applied during preirradiation culture and secondary colony formation. We also demonstrated that the amounts of ROS in X-ray-irradiated cells rapidly increase and then decrease at 6 hr postirradiation, and the levels of ROS then gradually decrease to a baseline within 2 weeks. The APM treatment kept the ROS production at a lower level than an untreated control. These results suggest that the cause of genetic instability might be fixed by ROS during a 2-week postirradiation period. (author)

  14. Induction of radiation resistance and radio-protective mechanism. On the reactive oxygen and free radical

    International Nuclear Information System (INIS)

    Yukawa, Osami

    2003-01-01

    Radical scavenging system for reactive oxygen species (ROS) leading to radio-protection is reviewed on findings in animals, tissues and cells. Protection against oxygen toxicity in evolution can be seen in anaerobes' superoxide dismutase (SOD) over 3500 million years ago. ROS is generated endogenously and also by radiation. However, the intracellular sites of the generated ROS are different depending on its cause. The protection is done through enzymes like SOD, peroxidase, catalase, glutathione-related enzymes and through substances like GSH, α-tocopherol, ascorbic acid etc. Induction of ROS scavenging substances related with radio-resistance includes the responses to the low dose radiation (5-50 cGy) in those enzymes described above; to middle to high dose radiation (1-30 Gy) in a similar and in other unknown mechanisms; to exposure of ROS like H 2 O 2 at low concentration; and to antioxidant treatment. The cross-resistance between radiation and drugs suggests necessity of this induction. (N.I.)

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

    Science.gov (United States)

    Pospíšil, Pavel

    2014-07-01

    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. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  16. Excess post-hypoxic oxygen consumption is independent from lactate accumulation in two cyprinid fishes

    DEFF Research Database (Denmark)

    Genz, J.; Jyde, M.B.; Svendsen, Jon Christian

    2013-01-01

    the increase in oxygen consumption in fish required following strenuous exercise or low environmental oxygen availability has been frequently considered, the primary contributing mechanism remains unknown. This study utilized the close relationship but strongly divergent physiology between C. carpio and C...

  17. Toxicity of nano-TiO2 on algae and the site of reactive oxygen species production

    International Nuclear Information System (INIS)

    Li, Fengmin; Liang, Zhi; Zheng, Xiang; Zhao, Wei; Wu, Miao; Wang, Zhenyu

    2015-01-01

    Highlights: • The growth of two species of algae was inhibited under nano-TiO 2 exposure. • Oxidative stress was one of the mechanisms of toxicity of nano-TiO 2 on algae. • The site of ROS production was the electron transfer chain of chloroplast. - Abstract: Given the extensive use of nanomaterials, they may enter aquatic environments and harm the growth of algae, which are primary producers in an aquatic ecosystem. Thus, the balance of an aquatic ecosystem may be destroyed. In this study, Karenia brevis and Skeletonema costatum were exposed to nano-TiO 2 (anatase, average particle size of 5–10 nm, specific surface area of 210 ± 10 m 2 g −1 ) to assess the effects of nano-TiO 2 on algae. The findings of transmission electron microscopy-energy dispersive X-ray spectroscopy (TEM-EDX) and scanning electron microscopy (SEM) demonstrate aggregation of nano-TiO 2 in the algal suspension. Nano-TiO 2 was also found to be inside algal cells. The growth of the two species of algae was inhibited under nano-TiO 2 exposure. The 72 h EC 50 values of nano-TiO 2 to K. brevis and S. costatum were 10.69 and 7.37 mg L −1 , respectively. TEM showed that the cell membrane of K. brevis was destroyed and its organelles were almost undistinguished under nano-TiO 2 exposure. The malondialdehyde (MDA) contents of K. brevis and S. costatum significantly increased compared with those of the control (p < 0.05). Meanwhile, superoxide dismutase (SOD) and catalase activities (CAT) of K. brevis and S. costatum changed in different ways. The reactive oxygen species (ROS) levels in both species were significantly higher than those of the control (p < 0.05). The site of ROS production and accumulation in K. brevis and S. costatum under nano-TiO 2 exposure was explored with the addition of inhibitors of different electron transfer chains. This study indicated that nano-TiO 2 in algal suspensions inhibited the growth of K. brevis and S. costatum. This effect was attributed to oxidative

  18. Toxicity of nano-TiO{sub 2} on algae and the site of reactive oxygen species production

    Energy Technology Data Exchange (ETDEWEB)

    Li, Fengmin, E-mail: lifengmin@ouc.edu.cn [Key Laboratory of Marine Environmental Science and Ecology, Ministry of Education, College of Environmental Science and Technology, Ocean University of China, Qingdao 266100 (China); Liang, Zhi [Key Laboratory of Marine Environmental Science and Ecology, Ministry of Education, College of Environmental Science and Technology, Ocean University of China, Qingdao 266100 (China); Zheng, Xiang, E-mail: zhengxiang7825@sina.com [School of Environment and Natural Resources, Renmin University of China, Beijing 100872 (China); Zhao, Wei; Wu, Miao; Wang, Zhenyu [Key Laboratory of Marine Environmental Science and Ecology, Ministry of Education, College of Environmental Science and Technology, Ocean University of China, Qingdao 266100 (China)

    2015-01-15

    Highlights: • The growth of two species of algae was inhibited under nano-TiO{sub 2} exposure. • Oxidative stress was one of the mechanisms of toxicity of nano-TiO{sub 2} on algae. • The site of ROS production was the electron transfer chain of chloroplast. - Abstract: Given the extensive use of nanomaterials, they may enter aquatic environments and harm the growth of algae, which are primary producers in an aquatic ecosystem. Thus, the balance of an aquatic ecosystem may be destroyed. In this study, Karenia brevis and Skeletonema costatum were exposed to nano-TiO{sub 2} (anatase, average particle size of 5–10 nm, specific surface area of 210 ± 10 m{sup 2} g{sup −1}) to assess the effects of nano-TiO{sub 2} on algae. The findings of transmission electron microscopy-energy dispersive X-ray spectroscopy (TEM-EDX) and scanning electron microscopy (SEM) demonstrate aggregation of nano-TiO{sub 2} in the algal suspension. Nano-TiO{sub 2} was also found to be inside algal cells. The growth of the two species of algae was inhibited under nano-TiO{sub 2} exposure. The 72 h EC{sub 50} values of nano-TiO{sub 2} to K. brevis and S. costatum were 10.69 and 7.37 mg L{sup −1}, respectively. TEM showed that the cell membrane of K. brevis was destroyed and its organelles were almost undistinguished under nano-TiO{sub 2} exposure. The malondialdehyde (MDA) contents of K. brevis and S. costatum significantly increased compared with those of the control (p < 0.05). Meanwhile, superoxide dismutase (SOD) and catalase activities (CAT) of K. brevis and S. costatum changed in different ways. The reactive oxygen species (ROS) levels in both species were significantly higher than those of the control (p < 0.05). The site of ROS production and accumulation in K. brevis and S. costatum under nano-TiO{sub 2} exposure was explored with the addition of inhibitors of different electron transfer chains. This study indicated that nano-TiO{sub 2} in algal suspensions inhibited the growth

  19. The Synergistic Effect of Proteins and Reactive Oxygen Species on Electrochemical Behaviour of 316L Stainless Steel for Biomedical Applications

    Science.gov (United States)

    Simionescu, N.; Benea, L.; Dumitrascu, V. M.

    2018-06-01

    The stainless steels, especially 316L type is the most used metallic biomaterials for biomedical applications due to their good biocompatibility, low price, excellent corrosion resistance, availability, easy processing and high strength. Due to these favorable properties 316L stainless steel has become the most attractive biomaterial for dental implants, stents and orthopedic implants. However an implant material in the human body is exposed to an action effect of other molecules, including proteins (such as albumin) and reactive oxygen species (such as hydrogen peroxide - H2O2 ) produced by bacteria and immune cells. In the literature there are few studies to follow the effect of proteins and reactive oxygen species on 316L stainless steel used as implant material and are still unclear. The degree of corrosion resistance is the first criterion in the use of a metallic biomaterial in the oral or body environment. The aim of this research work is to investigate the influence of proteins (albumin) and reactive oxygen species (H2O2 ) in combination, taking into account the synergistic effect of these two factors on 316L stainless steel. Albumin is present in the body near implants and reactive oxygen species could appear in inflammatory processes as well. The study shows that the presence of albumin and reactive species influences the corrosion resistance of 316L stainless steel in biological solutions. In this research work the corrosion behavior of 316L stainless steel is analyzed by electrochemical methods such as: open circuit potential (OCP), Electrochemical Impedance Spectroscopy (EIS). It was found that, the electrochemical results are in a good agreement with micro photographs taken before and after corrosion assays. The albumin and reactive oxygen species have influence on 316L stainless steel behavior.

  20. Singlet oxygen treatment of tumor cells triggers extracellular singlet oxygen generation, catalase inactivation and reactivation of intercellular apoptosis-inducing signaling☆

    Science.gov (United States)

    Riethmüller, Michaela; Burger, Nils; Bauer, Georg

    2015-01-01

    Intracellular singlet oxygen generation in photofrin-loaded cells caused cell death without discrimination between nonmalignant and malignant cells. In contrast, extracellular singlet oxygen generation caused apoptosis induction selectively in tumor cells through singlet oxygen-mediated inactivation of tumor cell protective catalase and subsequent reactivation of intercellular ROS-mediated apoptosis signaling through the HOCl and the NO/peroxynitrite signaling pathway. Singlet oxygen generation by extracellular photofrin alone was, however, not sufficient for optimal direct inactivation of catalase, but needed to trigger the generation of cell-derived extracellular singlet oxygen through the interaction between H2O2 and peroxynitrite. Thereby, formation of peroxynitrous acid, generation of hydroxyl radicals and formation of perhydroxyl radicals (HO2.) through hydroxyl radical/H2O2 interaction seemed to be required as intermediate steps. This amplificatory mechanism led to the formation of singlet oxygen at a sufficiently high concentration for optimal inactivation of membrane-associated catalase. At low initial concentrations of singlet oxygen, an additional amplification step needed to be activated. It depended on singlet oxygen-dependent activation of the FAS receptor and caspase-8, followed by caspase-8-mediated enhancement of NOX activity. The biochemical mechanisms described here might be considered as promising principle for the development of novel approaches in tumor therapy that specifically direct membrane-associated catalase of tumor cells and thus utilize tumor cell-specific apoptosis-inducing ROS signaling. PMID:26225731

  1. Singlet oxygen treatment of tumor cells triggers extracellular singlet oxygen generation, catalase inactivation and reactivation of intercellular apoptosis-inducing signaling.

    Science.gov (United States)

    Riethmüller, Michaela; Burger, Nils; Bauer, Georg

    2015-12-01

    Intracellular singlet oxygen generation in photofrin-loaded cells caused cell death without discrimination between nonmalignant and malignant cells. In contrast, extracellular singlet oxygen generation caused apoptosis induction selectively in tumor cells through singlet oxygen-mediated inactivation of tumor cell protective catalase and subsequent reactivation of intercellular ROS-mediated apoptosis signaling through the HOCl and the NO/peroxynitrite signaling pathway. Singlet oxygen generation by extracellular photofrin alone was, however, not sufficient for optimal direct inactivation of catalase, but needed to trigger the generation of cell-derived extracellular singlet oxygen through the interaction between H2O2 and peroxynitrite. Thereby, formation of peroxynitrous acid, generation of hydroxyl radicals and formation of perhydroxyl radicals (HO2(.)) through hydroxyl radical/H2O2 interaction seemed to be required as intermediate steps. This amplificatory mechanism led to the formation of singlet oxygen at a sufficiently high concentration for optimal inactivation of membrane-associated catalase. At low initial concentrations of singlet oxygen, an additional amplification step needed to be activated. It depended on singlet oxygen-dependent activation of the FAS receptor and caspase-8, followed by caspase-8-mediated enhancement of NOX activity. The biochemical mechanisms described here might be considered as promising principle for the development of novel approaches in tumor therapy that specifically direct membrane-associated catalase of tumor cells and thus utilize tumor cell-specific apoptosis-inducing ROS signaling. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Determination of reactive oxygen species from ZnO micro-nano structures with shape-dependent photocatalytic activity

    Energy Technology Data Exchange (ETDEWEB)

    He, Weiwei; Zhao, Hongxiao; Jia, Huimin [Key Laboratory of Micro-Nano Materials for Energy Storage and Conversion of Henan Province, Institute of Surface Micro and Nano Materials, Xuchang University, Henan 461000 (China); Yin, Jun-Jie [Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, College Park, MD 20740 (United States); Zheng, Zhi, E-mail: zhengzhi99999@gmail.com [Key Laboratory of Micro-Nano Materials for Energy Storage and Conversion of Henan Province, Institute of Surface Micro and Nano Materials, Xuchang University, Henan 461000 (China)

    2014-05-01

    Graphical abstract: ZnO micro/nano structures with shape dependent photocatalytic activity were prepared by hydrothermal reaction. The generations of hydroxyl radical, superoxide and singlet oxygen from irradiated ZnO were identified precisely by electron spin resonance spectroscopy. The type of reactive oxygen species was determined by band gap structure of ZnO. - Highlights: • ZnO micro/nano structures with different morphologies were prepared by solvothermal reaction. • Multi-pod like ZnO structures exhibited superior photocatalytic activity. • The generations of hydroxyl radical, superoxide and singlet oxygen from irradiated ZnO were characterized precisely by electron spin resonance spectroscopy. • The type of reactive oxygen species was determined by band gap structure of ZnO. - Abstract: ZnO micro/nano structures with different morphologies have been prepared by the changing solvents used during their synthesis by solvothermal reaction. Three typical shapes of ZnO structures including hexagonal, bell bottom like and multi-pod formed and were characterized by scanning electron microscopy and X-ray diffraction. Multi pod like ZnO structures exhibited the highest photocatalytic activity toward degradation of methyl orange. Using electron spin resonance spectroscopy coupled with spin trapping techniques, we demonstrate an effective way to identify precisely the generation of hydroxyl radicals, superoxide and singlet oxygen from the irradiated ZnO multi pod structures. The type of reactive oxygen species formed was predictable from the band gap structure of ZnO. These results indicate that the shape of micro-nano structures significantly affects the photocatalytic activity of ZnO, and demonstrate the value of electron spin resonance spectroscopy for characterizing the type of reactive oxygen species formed during photoexcitation of semiconductors.

  3. Determination of reactive oxygen species from ZnO micro-nano structures with shape-dependent photocatalytic activity

    International Nuclear Information System (INIS)

    He, Weiwei; Zhao, Hongxiao; Jia, Huimin; Yin, Jun-Jie; Zheng, Zhi

    2014-01-01

    Graphical abstract: ZnO micro/nano structures with shape dependent photocatalytic activity were prepared by hydrothermal reaction. The generations of hydroxyl radical, superoxide and singlet oxygen from irradiated ZnO were identified precisely by electron spin resonance spectroscopy. The type of reactive oxygen species was determined by band gap structure of ZnO. - Highlights: • ZnO micro/nano structures with different morphologies were prepared by solvothermal reaction. • Multi-pod like ZnO structures exhibited superior photocatalytic activity. • The generations of hydroxyl radical, superoxide and singlet oxygen from irradiated ZnO were characterized precisely by electron spin resonance spectroscopy. • The type of reactive oxygen species was determined by band gap structure of ZnO. - Abstract: ZnO micro/nano structures with different morphologies have been prepared by the changing solvents used during their synthesis by solvothermal reaction. Three typical shapes of ZnO structures including hexagonal, bell bottom like and multi-pod formed and were characterized by scanning electron microscopy and X-ray diffraction. Multi pod like ZnO structures exhibited the highest photocatalytic activity toward degradation of methyl orange. Using electron spin resonance spectroscopy coupled with spin trapping techniques, we demonstrate an effective way to identify precisely the generation of hydroxyl radicals, superoxide and singlet oxygen from the irradiated ZnO multi pod structures. The type of reactive oxygen species formed was predictable from the band gap structure of ZnO. These results indicate that the shape of micro-nano structures significantly affects the photocatalytic activity of ZnO, and demonstrate the value of electron spin resonance spectroscopy for characterizing the type of reactive oxygen species formed during photoexcitation of semiconductors

  4. The role of UCP 1 in production of reactive oxygen species by mitochondria isolated from brown adipose tissue

    Czech Academy of Sciences Publication Activity Database

    Dlasková, Andrea; Clarke, K.J.; Porter, R. K.

    2010-01-01

    Roč. 1797, č. 8 (2010), s. 1470-1476 ISSN 0005-2728 Institutional research plan: CEZ:AV0Z50110509 Keywords : Mitochondria * Reactive oxygen species * Uncoupling protein 1 Subject RIV: ED - Physiology Impact factor: 5.132, year: 2010

  5. Intracellular expression of reactive oxygen species-generating NADPH oxidase NOX4 in normal and cancer thyroid tissues

    NARCIS (Netherlands)

    Weyemi, Urbain; Caillou, Bernard; Talbot, Monique; Ameziane-El-Hassani, Rabii; Lacroix, Ludovic; Lagent-Chevallier, Odile; Al Ghuzlan, Abir; Roos, Dirk; Bidart, Jean-Michel; Virion, Alain; Schlumberger, Martin; Dupuy, Corinne

    2010-01-01

    NADPH oxidase 4 (NOX4) belongs to the NOX family that generates reactive oxygen species (ROS). Function and tissue distribution of NOX4 have not yet been entirely clarified. To date, in the thyroid gland, only DUOX1/2 NOX systems have been described. NOX4 mRNA expression, as shown by real-time PCR,

  6. Induction of molecular endpoints by reactive oxygen species in human lung cells predicted by physical chemical properties of engineered nanoparticles

    Science.gov (United States)

    A series of six titanium dioxide and two cerium oxide engineered nanomaterials were assessed for their ability to induce cytotoxicity, reactive oxygen species (ROS), and various types of DNA and protein damage in human respiratory BEAS-2B cells exposed in vitro for 72 hours at se...

  7. Surgery-induced reactive oxygen species enhance colon carcinoma cell binding by disrupting the liver endothelial cell lining

    NARCIS (Netherlands)

    Gül, Nuray; Bögels, Marijn; Grewal, Simran; van der Meer, Anne Jan; Rojas, Lucy Baldeon; Fluitsma, Donna M.; van den Tol, M. Petrousjka; Hoeben, Kees A.; van Marle, Jan; de Vries, Helga E.; Beelen, Robert H. J.; van Egmond, Marjolein

    2011-01-01

    Resection of primary colorectal cancer is associated with enhanced risk of development of liver metastases. It was previously demonstrated that surgery initiated an early inflammatory response resulting in elevated tumour cell adhesion in the liver. Because reactive oxygen species (ROS) are shown to

  8. Surgery-induced reactive oxygen species enhance colon carcinoma cell binding by disrupting the liver endothelial cell lining

    NARCIS (Netherlands)

    Gül, N.; Bögels, M.; Grewal, S.; van der Meer, A.J.; Rojas, L.B.; Fluitsma, D.M.; van den Tol, M.P.; Hoeben, K.A.; van Marle, J.; de Vries, H.E.; Beelen, R.H.J.; van Egmond, M.

    2011-01-01

    Objective: Resection of primary colorectal cancer is associated with enhanced risk of development of liver metastases. It was previously demonstrated that surgery initiated an early inflammatory response resulting in elevated tumour cell adhesion in the liver. Because reactive oxygen species (ROS)

  9. Surgery-induced reactive oxygen species enhance colon carcinoma cell binding by disrupting the liver endothelial cell lining

    NARCIS (Netherlands)

    Gul, N.; Bogels, M.; Grewal, S.; van der Meer, A.J.; Rojas, L.B.; Fluitsma, D.M.; van den Tol, M.P.; Hoeben, K.A.; van Marle, J.; de Vries, H.E.; Beelen, R.H.J.; van Egmond, M.

    2011-01-01

    Objective Resection of primary colorectal cancer is associated with enhanced risk of development of liver metastases. It was previously demonstrated that surgery initiated an early inflammatory response resulting in elevated tumour cell adhesion in the liver. Because reactive oxygen species (ROS)

  10. Role of histamine receptors in the effects of histamine on the production of reactive oxygen species by whole blood phagocytes

    Czech Academy of Sciences Publication Activity Database

    Vašíček, Ondřej; Lojek, Antonín; Jančinová, V.; Nosál, R.; Číž, Milan

    2014-01-01

    Roč. 100, č. 1 (2014), s. 67-72 ISSN 0024-3205 R&D Projects: GA MŠk(CZ) LD11010 Institutional support: RVO:68081707 Keywords : Histamine * Histamine receptors * Reactive oxygen species Subject RIV: BO - Biophysics Impact factor: 2.702, year: 2014

  11. Effects of oxygen addition in reactive cluster beam deposition of tungsten by magnetron sputtering with gas aggregation

    International Nuclear Information System (INIS)

    Polášek, J.; Mašek, K.; Marek, A.; Vyskočil, J.

    2015-01-01

    In this work, we investigated the possibilities of tungsten and tungsten oxide nanoclusters generation by means of non-reactive and reactive magnetron sputtering with gas aggregation. It was found that in pure argon atmosphere, cluster aggregation proceeded in two regimes depending on argon pressure in the aggregation chamber. At the lower pressure, cluster generation was dominated by two-body collisions yielding larger clusters (about 5.5 nm in diameter) at lower rate. At higher pressures, cluster generation was dominated by three-body collisions yielding smaller clusters (3–4 nm in diameter) at higher rate. The small amount of oxygen admixture in the aggregation chamber had considerable influence on cluster aggregation process. At certain critical pressure, the presence of oxygen led to the raise of deposition rate and cluster size. Resulting clusters were composed mostly of tungsten trioxide. The oxygen pressure higher than critical led to the target poisoning and the decrease in the sputtering rate. Critical oxygen pressure decreased with increasing argon pressure, suggesting that cluster aggregation process was influenced by atomic oxygen species (namely, O"− ion) generated by oxygen–argon collisions in the magnetron plasma. - Highlights: • Formation of tungsten and tungsten oxide clusters was observed. • Two modes of cluster aggregation in pure argon atmosphere were found. • Dependence of cluster deposition speed and size on oxygen admixture was observed. • Changes of dependence on oxygen with changing argon pressure were described.

  12. Effects of oxygen addition in reactive cluster beam deposition of tungsten by magnetron sputtering with gas aggregation

    Energy Technology Data Exchange (ETDEWEB)

    Polášek, J., E-mail: xpolasekj@seznam.cz [Department of Surface and Plasma Science, Faculty of Mathematics and Physic, Charles University, V Holešovičkách 2, Prague 8, CZ-18000 (Czech Republic); Mašek, K. [Department of Surface and Plasma Science, Faculty of Mathematics and Physic, Charles University, V Holešovičkách 2, Prague 8, CZ-18000 (Czech Republic); Marek, A.; Vyskočil, J. [HVM Plasma Ltd., Na Hutmance 2, Prague 5, CZ-158 00 (Czech Republic)

    2015-09-30

    In this work, we investigated the possibilities of tungsten and tungsten oxide nanoclusters generation by means of non-reactive and reactive magnetron sputtering with gas aggregation. It was found that in pure argon atmosphere, cluster aggregation proceeded in two regimes depending on argon pressure in the aggregation chamber. At the lower pressure, cluster generation was dominated by two-body collisions yielding larger clusters (about 5.5 nm in diameter) at lower rate. At higher pressures, cluster generation was dominated by three-body collisions yielding smaller clusters (3–4 nm in diameter) at higher rate. The small amount of oxygen admixture in the aggregation chamber had considerable influence on cluster aggregation process. At certain critical pressure, the presence of oxygen led to the raise of deposition rate and cluster size. Resulting clusters were composed mostly of tungsten trioxide. The oxygen pressure higher than critical led to the target poisoning and the decrease in the sputtering rate. Critical oxygen pressure decreased with increasing argon pressure, suggesting that cluster aggregation process was influenced by atomic oxygen species (namely, O{sup −} ion) generated by oxygen–argon collisions in the magnetron plasma. - Highlights: • Formation of tungsten and tungsten oxide clusters was observed. • Two modes of cluster aggregation in pure argon atmosphere were found. • Dependence of cluster deposition speed and size on oxygen admixture was observed. • Changes of dependence on oxygen with changing argon pressure were described.

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

    Directory of Open Access Journals (Sweden)

    Schudt Christian

    2005-07-01

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

  14. Reactive-ion etching of nylon fabric meshes using oxygen plasma for creating surface nanostructures

    International Nuclear Information System (INIS)

    Salapare, Hernando S.; Darmanin, Thierry; Guittard, Frédéric

    2015-01-01

    Graphical abstract: - Highlights: • Reactive-ion etching (RIE) is employed to nylon 6,6 fabrics to achieve surface texturing and improved wettability. • FTIR spectra of the treated samples exhibited decreased transmittance of amide and carboxylic acid groups due to etching. • Etching is enhanced for higher power plasma treatments and for samples with larger mesh sizes. • Decreased crystallinity was achieved after plasma treatment. • Higher power induced higher negative DC self-bias voltage on the samples that favored anisotropic and aggressive etching. - Abstract: A facile one-step oxygen plasma irradiation in reactive ion etching (RIE) configuration is employed to nylon 6,6 fabrics with different mesh sizes to achieve surface nanostructures and improved wettability for textile and filtration applications. To observe the effects of power and irradiation time on the samples, the experiments were performed using constant irradiation time in varying power and using constant power in varying irradiation times. Results showed improved wettability after the plasma treatment. The FTIR spectra of all the treated samples exhibited decreased transmittance of the amide and carboxylic acid groups due to surface etching. The changes in the surface chemistry are supported by the SEM data wherein etching and surface nanostructures were observed for the plasma-treated samples. The etching of the surfaces is enhanced for higher power plasma treatments. The thermal analysis showed that the plasma treatment resulted in decreased crystallinity. Surface chemistry showed that the effects of the plasma treatment on the samples have no significant difference for all the mesh sizes. However, surface morphology showed that the sizes of the surface cracks are the same for all the mesh sizes but samples with larger mesh sizes exhibited enhanced etching as compared to the samples with smaller mesh sizes. Higher power induced higher negative DC self-bias voltage on the samples that

  15. Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production

    DEFF Research Database (Denmark)

    Jing, Enxuan; Emanuelli, Brice; Hirschey, Matthew D

    2011-01-01

    Sirt3 is a member of the sirtuin family of protein deacetylases that is localized in mitochondria and regulates mitochondrial function. Sirt3 expression in skeletal muscle is decreased in models of type 1 and type 2 diabetes and regulated by feeding, fasting, and caloric restriction. Sirt3 knockout...... mice exhibit decreased oxygen consumption and develop oxidative stress in skeletal muscle, leading to JNK activation and impaired insulin signaling. This effect is mimicked by knockdown of Sirt3 in cultured myoblasts, which exhibit reduced mitochondrial oxidation, increased reactive oxygen species......, activation of JNK, increased serine and decreased tyrosine phosphorylation of IRS-1, and decreased insulin signaling. Thus, Sirt3 plays an important role in diabetes through regulation of mitochondrial oxidation, reactive oxygen species production, and insulin resistance in skeletal muscle....

  16. Exposure to ultrafine particles, intracellular production of reactive oxygen species in leukocytes and altered levels of endothelial progenitor cells

    International Nuclear Information System (INIS)

    Jantzen, Kim; Møller, Peter; Karottki, Dorina Gabriela; Olsen, Yulia; Bekö, Gabriel; Clausen, Geo; Hersoug, Lars-Georg; Loft, Steffen

    2016-01-01

    Exposure to particles in the fine and ultrafine size range has been linked to induction of low-grade systemic inflammation, oxidative stress and development of cardiovascular diseases. Declining levels of endothelial progenitor cells within systemic circulation have likewise been linked to progression of cardiovascular diseases. The objective was to determine if exposure to fine and ultrafine particles from indoor and outdoor sources, assessed by personal and residential indoor monitoring, is associated with altered levels of endothelial progenitor cells, and whether such effects are related to leukocyte-mediated oxidative stress. The study utilized a cross sectional design performed in 58 study participants from a larger cohort. Levels of circulating endothelial progenitor cells, defined as either late (CD34 + KDR + cells) or early (CD34 + CD133 + KDR + cells) subsets were measured using polychromatic flow cytometry. We additionally measured production of reactive oxygen species in leukocyte subsets (lymphocytes, monocytes and granulocytes) by flow cytometry using intracellular 2′,7′-dichlorofluoroscein. The measurements encompassed both basal levels of reactive oxygen species production and capacity for reactive oxygen species production for each leukocyte subset. We found that the late endothelial progenitor subset was negatively associated with levels of ultrafine particles measured within the participant residences and with reactive oxygen species production capacity in lymphocytes. Additionally, the early endothelial progenitor cell levels were positively associated with a personalised measure of ultrafine particle exposure and negatively associated with both basal and capacity for reactive oxygen species production in lymphocytes and granulocytes, respectively. Our results indicate that exposure to fine and ultrafine particles derived from indoor sources may have adverse effects on human vascular health.

  17. Mobile phone radiation induces reactive oxygen species production and DNA damage in human spermatozoa in vitro.

    Directory of Open Access Journals (Sweden)

    Geoffry N De Iuliis

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

  18. A reactive oxygen species activation mechanism contributes to JS-K-induced apoptosis in human bladder cancer cells.

    Science.gov (United States)

    Qiu, Mingning; Chen, Lieqian; Tan, Guobin; Ke, Longzhi; Zhang, Sai; Chen, Hege; Liu, Jianjun

    2015-10-13

    Reactive oxygen species (ROS) and cellular oxidant stress are regulators of cancer cells. The alteration of redox status, which is induced by increased generation of ROS, results in increased vulnerability to oxidative stress. The aim of this study is to investigate the influence of O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, C13H16N6O8) on proliferation and apoptosis in bladder cancer cells and explored possible ROS-related mechanisms. Our results indicated that JS-K could suppress bladder cancer cell proliferation in a concentration- and time-dependent manner and induce apoptosis and ROS accumulation in a concentration-dependent manner. With increasing concentrations of JS-K, expression of proteins that are involved in cell apoptosis increased in a concentration-dependent manner. Additionally, the antioxidant N-acetylcysteine (NAC) reversed JS-K-induced cell apoptosis; conversely, the prooxidant oxidized glutathione (GSSG) exacerbated JS-K-induced cell apoptosis. Furthermore, we found that nitrites, which were generated from the oxidation of JS-K-released NO, induced apoptosis in bladder cancer cells to a lower extent through the ROS-related pathway. In addition, JS-K was shown to enhance the chemo-sensitivity of doxorubicin in bladder cancer cells. Taken together, the data suggest that JS-K-released NO induces bladder cancer cell apoptosis by increasing ROS levels, and nitrites resulting from oxidation of NO have a continuous apoptosis-inducing effect.

  19. Different Reactive Oxygen Species Lead to Distinct Changes of Cellular Metal Ions in the Eukaryotic Model Organism Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Peter J. Rogers

    2011-11-01

    Full Text Available Elemental uptake and export of the cell are tightly regulated thereby maintaining the ionomic homeostasis. This equilibrium can be disrupted upon exposure to exogenous reactive oxygen species (ROS, leading to reduction or elevation of the intracellular metal ions. In this study, the ionomic composition in the eukaryotic model organism Saccharomyces cerevisiae was profiled using the inductively-coupled plasma optical emission spectrometer (ICP-OES following the treatment with individual ROS, including hydrogen peroxide, cumen hydroperoxide, linoleic acid hydroperoxide (LAH, the superoxide-generating agent menadione, the thiol-oxidising agent diamide [diazine-dicarboxylic acid-bis(dimethylamide], dimedone and peroxynitrite. The findings demonstrated that different ROS resulted in distinct changes in cellular metal ions. Aluminium (Al3+ level rose up to 50-fold after the diamide treatment. Cellular potassium (K+ in LAH-treated cells was 26-fold less compared to the non-treated controls. The diamide-induced Al3+ accumulation was further validated by the enhanced Al3+ uptake along the time course and diamide doses. Pre-incubation of yeast with individual elements including iron, copper, manganese and magnesium failed to block diamide-induced Al3+ uptake, suggesting Al3+-specific transporters could be involved in Al3+ uptake. Furthermore, LAH-induced potassium depletion was validated by a rescue experiment in which addition of potassium increased yeast growth in LAH-containing media by 26% compared to LAH alone. Taken together, the data, for the first time, demonstrated the linkage between ionomic profiles and individual oxidative conditions.

  20. Extracellular Redox Regulation of Intracellular Reactive Oxygen Generation, Mitochondrial Function and Lipid Turnover in Cultured Human Adipocytes.

    Directory of Open Access Journals (Sweden)

    Albert R Jones

    Full Text Available Many tissues play an important role in metabolic homeostasis and the development of diabetes and obesity. We hypothesized that the circulating redox metabolome is a master metabolic regulatory system that impacts all organs and modulates reactive oxygen species (ROS production, lipid peroxidation, energy production and changes in lipid turnover in many cells including adipocytes.Differentiated human preadipocytes were exposed to the redox couples, lactate (L and pyruvate (P, β-hydroxybutyrate (βOHB and acetoacetate (Acoc, and the thiol-disulfides cysteine/ cystine (Cys/CySS and GSH/GSSG for 1.5-4 hours. ROS measurements were done with CM-H2DCFDA. Lipid peroxidation (LPO was assessed by a modification of the thiobarbituric acid method. Lipolysis was measured as glycerol release. Lipid synthesis was measured as 14C-glucose incorporated into lipid. Respiration was assessed using the SeaHorse XF24 analyzer and the proton leak was determined from the difference in respiration with oligomycin and antimycin A.Metabolites with increasing oxidation potentials (GSSG, CySS, Acoc increased adipocyte ROS. In contrast, P caused a decrease in ROS compared with L. Acoc also induced a significant increase in both LPO and lipid synthesis. L and Acoc increased lipolysis. βOHB increased respiration, mainly due to an increased proton leak. GSSG, when present throughout 14 days of differentiation significantly increased fat accumulation, but not when added later.We demonstrated that in human adipocytes changes in the external redox state impacted ROS production, LPO, energy efficiency, lipid handling, and differentiation. A more oxidized state generally led to increased ROS, LPO and lipid turnover and more reduction led to increased respiration and a proton leak. However, not all of the redox couples were the same suggesting compartmentalization. These data are consistent with the concept of the circulating redox metabolome as a master metabolic regulatory system.

  1. Phototoxicity Evaluation of Pharmaceutical Substances with a Reactive Oxygen Species Assay Using Ultraviolet A

    Science.gov (United States)

    Lee, Yong Sun; Yi, Jung-Sun; Lim, Hye Rim; Kim, Tae Sung; Ahn, Il Young; Ko, Kyungyuk; Kim, JooHwan; Park, Hye-Kyung; Sohn, Soo Jung; Lee, Jong Kwon

    2017-01-01

    With ultraviolet and visible light exposure, some pharmaceutical substances applied systemically or topically may cause phototoxic skin irritation. The major factor in phototoxicity is the generation of reactive oxygen species (ROS) such as singlet oxygen and superoxide anion that cause oxidative damage to DNA, lipids and proteins. Thus, measuring the generation of ROS can predict the phototoxic potential of a given substance indirectly. For this reason, a standard ROS assay (ROS assay) was developed and validated and provides an alternative method for phototoxicity evaluation. However, negative substances are over-predicted by the assay. Except for ultraviolet A (UVA), other UV ranges are not a major factor in causing phototoxicity and may lead to incorrect labeling of some non-phototoxic substances as being phototoxic in the ROS assay when using a solar simulator. A UVA stimulator is also widely used to evaluate phototoxicity in various test substances. Consequently, we identified the applicability of a UVA simulator to the ROS assay for photoreactivity. In this study, we tested 60 pharmaceutical substances including 50 phototoxins and 10 non-phototoxins to predict their phototoxic potential via the ROS assay with a UVA simulator. Following the ROS protocol, all test substances were dissolved in dimethyl sulfoxide or sodium phosphate buffer. The final concentration of the test solutions in the reaction mixture was 20 to 200 μM. The exposure was with 2.0~2.2 mW/cm2 irradiance and optimization for a relevant dose of UVA was performed. The generation of ROS was compared before and after UVA exposure and was measured by a microplate spectrophotometer. Sensitivity and specificity values were 85.7% and 100.0% respectively, and the accuracy was 88.1%. From this analysis, the ROS assay with a UVA simulator is suitable for testing the photoreactivity and estimating the phototoxic potential of various test pharmaceutical substances. PMID:28133512

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-02-21

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

  3. Release of proteins from intact chloroplasts induced by reactive oxygen species during biotic and abiotic stress.

    Science.gov (United States)

    Kwon, Kwang-Chul; Verma, Dheeraj; Jin, Shuangxia; Singh, Nameirakpam D; Daniell, Henry

    2013-01-01

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

  4. Release of proteins from intact chloroplasts induced by reactive oxygen species during biotic and abiotic stress.

    Directory of Open Access Journals (Sweden)

    Kwang-Chul Kwon

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

  5. Involvement of Reactive Oxygen Species in Sonodynamically Induced Apoptosis Using a Novel Porphyrin Derivative

    Directory of Open Access Journals (Sweden)

    Nagahiko Yumita, Yumiko Iwase, Koji Nishi, Hajime Komatsu, Kazuyoshi Takeda, Kenji Onodera, Toshio Fukai, Toshihiko Ikeda, Shin-ichiro Umemura, Kazuho Okudaira, Yasunori Momose

    2012-01-01

    Full Text Available In this study, we investigated the induction of apoptosis by ultrasound in the presence of the novel porphyrin derivative DCPH-P-Na(I. HL-60 cells were exposed to ultrasound for up to 3 min in the presence and absence of DCPH-P-Na(I, and the induction of apoptosis was examined by analyzing cell morphology, DNA fragmentation, and caspase-3 activity. Reactive oxygen species were measured by means of ESR and spin trapping technique. Cells treated with 8 μM DCPH-P-Na(I and ultrasound clearly showed membrane blebbing and cell shrinkage, whereas significant morphologic changes were not observed in cells exposed to either ultrasound or DCPH-P-Na(I alone. Also, DNA ladder formation and caspase-3 activation were observed in cells treated with both ultrasound and DCPH-P-Na(I but not in cells treated with ultrasound or DCPH-P-Na(I alone. In addition, the combination of DCPH-P-Na(I and the same acoustical arrangement of ultrasound substantially enhanced nitroxide generation by the cells. Sonodynamically induced apoptosis, caspase-3 activation, and nitroxide generation were significantly suppressed by histidine. These results indicate that the combination of ultrasound and DCPH-P-Na(I induced apoptosis in HL-60 cells. The significant reduction in sonodynamically induced apoptosis, nitroxide generation, and caspase-3 activation by histidine suggests active species such as singlet oxygen are important in the sonodynamic induction of apoptosis. These experimental results support the possibility of sonodynamic treatment for cancer using the induction of apoptosis.

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

    Science.gov (United States)

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

    2011-01-01

    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. PMID:21483483

  7. Biocompatible ZnS:Mn quantum dots for reactive oxygen generation and detection in aqueous media

    Science.gov (United States)

    Diaz-Diestra, Daysi; Beltran-Huarac, Juan; Bracho-Rincon, Dina P.; González-Feliciano, José A.; González, Carlos I.; Weiner, Brad R.; Morell, Gerardo

    2015-12-01

    We report here the versatility of Mn-doped ZnS quantum dots (ZnS:Mn QDs) synthesized in aqueous medium for generating reactive oxygen species and for detecting cells. Our experiments provide evidence leading to the elimination of Cd-based cores in CdSe/ZnS systems by substitution of Mn-doped ZnS. Advanced electron microscopy, X-ray diffraction, and optical spectroscopy were applied to elucidate the formation, morphology, and dispersion of the products. We study for the first time the ability of ZnS:Mn QDs to act as immobilizing agents for Tyrosinase (Tyr) enzyme. It was found that ZnS:Mn QDs show no deactivation of Tyr enzyme, which efficiently catalyzed the hydrogen peroxide (H2O2) oxidation and its eventual reduction (-0.063 V vs. Ag/AgCl) on the biosensor surface. The biosensor showed a linear response in the range of 12 μmol/L-0.1 mmol/L at low operation potential. Our observations are explained in terms of a catalase-cycled kinetic mechanism based on the binding of H2O2 to the axial position of one of the active copper sites of the oxy-Tyr during the catalase cycle to produce deoxy-Tyr. A singlet oxygen quantum yield of 0.62 in buffer and 0.54 in water was found when ZnS:Mn QDs were employed as a photosensitizer in the presence of a chemical scavenger and a standard dye. These results are consistent with a chemical trapping energy transfer mechanism. Our results also indicate that ZnS:Mn QDs are well tolerated by HeLa Cells reaching cell viabilities as high as 88 % at 300 µg/mL of QDs for 24 h of incubation. The ability of ZnS:Mn QDs as luminescent nanoprobes for bioimaging is also discussed.

  8. Met-myoglobin formation, accumulation, degradation, and myoglobin oxygenation monitoring based on multiwavelength attenuance measurement in porcine meat

    Science.gov (United States)

    Nguyen, Thien; Phan, Kien Nguyen; Lee, Jee-Bum; Kim, Jae Gwan

    2016-05-01

    We propose a simple, rapid, and nondestructive method to investigate formation, accumulation, and degradation of met-myoglobin (met-Mb) and myoglobin oxygenation from the interior of porcine meat. For the experiment, color photos and attenuance spectra of porcine meat (well-bled muscle, fat, and mixed) were collected daily to perform colorimetric analysis and to obtain the differences of attenuance between 578 and 567 nm (A578-A567) and between 615 and 630 nm (A630-A615), respectively. Oxy-, deoxy-, and met-myoglobin concentration changes over storage time were also calculated using Beer-Lamberts' law with reflectance intensities at 557, 582, and 630 nm. The change of A578-A567 was well matched with the change of myoglobin oxygenation, and the change of A630-A615 corresponded well with the formation and degradation of met-Mb. In addition, attenuation differences, A578-A567 and A630-A615, were able to show the formation of met-Mb earlier than colorimetric analysis. Therefore, the attenuance differences between wavelengths can be indicators for estimating myoglobin oxygenation and met-Mb formation, accumulation, and degradation, which enable us to design a simple device to monitor myoglobin activities in porcine meat.

  9. Mitochondrial Reactive Oxygen Species and Kidney Hypoxia in the Development of Diabetic Nephropathy.

    Science.gov (United States)

    Schiffer, Tomas A; Friederich-Persson, Malou

    2017-01-01

    The underlying mechanisms in the development of diabetic nephropathy are currently unclear and likely consist of a series of dynamic events from the early to late stages of the disease. Diabetic nephropathy is currently without curative treatments and it is acknowledged that even the earliest clinical manifestation of nephropathy is preceded by an established morphological renal injury that is in turn preceded by functional and metabolic alterations. An early manifestation of the diabetic kidney is the development of kidney hypoxia that has been acknowledged as a common pathway to nephropathy. There have been reports of altered mitochondrial function in the diabetic kidney such as altered mitophagy, mitochondrial dynamics, uncoupling, and cellular signaling through hypoxia inducible factors and AMP-kinase. These factors are also likely to be intertwined in a complex manner. In this review, we discuss how these pathways are connected to mitochondrial production of reactive oxygen species (ROS) and how they may relate to the development of kidney hypoxia in diabetic nephropathy. From available literature, it is evident that early correction and/or prevention of mitochondrial dysfunction may be pivotal in the prevention and treatment of diabetic nephropathy.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  11. Reactive oxygen species acts as executor in radiation enhancement and autophagy inducing by AgNPs.

    Science.gov (United States)

    Wu, Hao; Lin, Jun; Liu, Peidang; Huang, Zhihai; Zhao, Peng; Jin, Haizhen; Ma, Jun; Wen, Longping; Gu, Ning

    2016-09-01

    Malignant glioma is one of the most common intracranial tumor with a dismal prognosis. The radiosensitizing effect of silver nanoparticles (AgNPs) on glioma both in vitro and in vivo were demonstrated in the previous studies of our group. However, the underlying mechanism is still unclear. In this present study, the use of antioxidants is employed for the regulating of reactive oxygen species (ROS) in U251 cells treated with various agents, and the results shows that ROS played an essential role in the autophagy inducing and radiosensitization effect of AgNPs. Moreover, the inhibition of protective autophagy with 3-MA is another way to increase ROS, resulting in the increasing of cell death and apoptosis. Taken together, understanding the relationship between the elevated ROS and autophagy and the effect of ROS should be useful to the clinical applications of AgNPs. These findings could potentially be exploited for new therapeutic strategies in glioma radiotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-15

    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.

  13. Controllable generation of reactive oxygen species by femtosecond-laser irradiation

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-02-24

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

  14. Development of nitroxide radicals–containing polymer for scavenging reactive oxygen species from cigarette smoke

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  15. [Comparison of reactive oxygen species production in neat semen and washed spermatozoa].

    Science.gov (United States)

    Svobodová, M; Oborná, I; Fingerová, H; Novotný, J; Brezinová, J; Radová, L; Vyslouzilová, J; Horáková, J; Grohmannová, J

    2009-12-01

    To determine Reactive Oxygen Species (ROS) production in neat semen and spermatozoa suspension using chemiluminescence and to examine correlation between both methods. Prospective laboratory study. Department of Obstetric and Gynecology, University Hospital, Olomouc. The study included fertile volunteers (FV, n = 17), men from infertile couples (NM, n = 19) and men with idiopathic infertility (NMI, n = 15). ROS levels were determined by the same method in neat and washed semen samples. The ROS production in neat semen was lower than that in spermatozoa suspension. There was no significant diference in ROS production between volunteers and males from infertile couples. There was a significant correlation between log ROS in neat semen and in spermatozoa suspension in studied groups (FV r = 0.85, p = 1.5 x 10(-5); NM r = 0.76, p neat semen is simpler, faster and better reflecting the actual level of oxidative stress than the same measurement in spermatozoa suspension. The implementation of this method can complement the algorithm of diagnostics and treatment of male infertility and be helpful in selection of patients for antioxidant or antibiotic treatment.

  16. Real-time in vivo detection of biomaterial-induced reactive oxygen species.

    Science.gov (United States)

    Liu, Wendy F; Ma, Minglin; Bratlie, Kaitlin M; Dang, Tram T; Langer, Robert; Anderson, Daniel G

    2011-03-01

    The non-specific host response to implanted biomaterials is often a key challenge of medical device design. To evaluate biocompatibility, measuring the release of reactive oxygen species (ROS) produced by inflammatory cells in response to biomaterial surfaces is a well-established method. However, the detection of ROS in response to materials implanted in vivo has not yet been demonstrated. Here, we develop a bioluminescence whole animal imaging approach to observe ROS released in response to subcutaneously-implanted materials in live animals. We compared the real-time generation of ROS in response to two representative materials, polystyrene and alginate, over the course of 28 days. High levels of ROS were observed near polystyrene, but not alginate implants, and persisted throughout the course of 28 days. Histological analysis revealed that high levels of ROS correlated not only with the presence of phagocytic cells at early timepoints, but also fibrosis at later timepoints, suggesting that ROS may be involved in both the acute and chronic phase of the foreign body response. These data are the first in vivo demonstration of ROS generation in response to implanted materials, and describe a novel technique to evaluate the host response. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Challenging the dogma of mitochondrial reactive oxygen species overproduction in diabetic kidney disease.

    Science.gov (United States)

    Coughlan, Melinda T; Sharma, Kumar

    2016-08-01

    The paradigm that high glucose drives overproduction of superoxide from mitochondria as a unifying theory to explain end organ damage in diabetes complications has been tightly held for more than a decade. With the recent development of techniques and probes to measure the production of distinct reactive oxygen species (ROS) in vivo, this widely held dogma is now being challenged with the emerging view that specific ROS moieties are essential for the function of specific intracellular signaling pathways and represent normal mitochondrial function. This review will provide a balanced overview of the dual nature of ROS, detailing current evidence for ROS overproduction in diabetic kidney disease, with a focus on cell types and sources of ROS. The technical aspects of measurement of mitochondrial ROS, both in isolated mitochondria and emerging in vivo methods will be discussed. The counterargument, that mitochondrial ROS production is reduced in diabetic complications, is consistent with a growing recognition that stimulation of mitochondrial biogenesis and oxidative phosphorylation activity reduces inflammation and fibrosis. It is clear that there is an urgent need to fully characterize ROS production paying particular attention to spatiotemporal aspects and to factor in the relevance of ROS in the regulation of cellular signaling in the pathogenesis of diabetic kidney disease. With improved tools and real-time imaging capacity, a greater understanding of the complex role of ROS will be able to guide novel therapeutic regimens. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  18. Reactive Oxygen Species Regulate the Inflammatory Function of NKT Cells through Promyelocytic Leukemia Zinc Finger.

    Science.gov (United States)

    Kim, Yeung-Hyen; Kumar, Ajay; Chang, Cheong-Hee; Pyaram, Kalyani

    2017-11-15

    Reactive oxygen species (ROS) are byproducts of aerobic metabolism and contribute to both physiological and pathological conditions as second messengers. ROS are essential for activation of T cells, but how ROS influence NKT cells is unknown. In the present study, we investigated the role of ROS in NKT cell function. We found that NKT cells, but not CD4 or CD8 T cells, have dramatically high ROS in the spleen and liver of mice but not in the thymus or adipose tissues. Accordingly, ROS-high NKT cells exhibited increased susceptibility and apoptotic cell death with oxidative stress. High ROS in the peripheral NKT cells were primarily produced by NADPH oxidases and not mitochondria. We observed that sorted ROS-high NKT cells were enriched in NKT1 and NKT17 cells, whereas NKT2 cells were dominant in ROS-low cells. Furthermore, treatment of NKT cells with antioxidants led to reduced frequencies of IFN-γ- and IL-17-expressing cells, indicating that ROS play a role in regulating the inflammatory function of NKT cells. The transcription factor promyelocytic leukemia zinc finger (PLZF) seemed to control the ROS levels. NKT cells from adipose tissues that do not express PLZF and those from PLZF haplodeficient mice have low ROS. Conversely, ROS were highly elevated in CD4 T cells from mice ectopically expressing PLZF. Thus, our findings demonstrate that PLZF controls ROS levels, which in turn governs the inflammatory function of NKT cells. Copyright © 2017 by The American Association of Immunologists, Inc.

  19. Small molecule CP-31398 induces reactive oxygen species-dependent apoptosis in human multiple myeloma.

    Science.gov (United States)

    Arihara, Yohei; Takada, Kohichi; Kamihara, Yusuke; Hayasaka, Naotaka; Nakamura, Hajime; Murase, Kazuyuki; Ikeda, Hiroshi; Iyama, Satoshi; Sato, Tsutomu; Miyanishi, Koji; Kobune, Masayoshi; Kato, Junji

    2017-09-12

    Reactive oxygen species (ROS) are normal byproducts of a wide variety of cellular processes. ROS have dual functional roles in cancer cell pathophysiology. At low to moderate levels, ROS act as signaling transducers to activate cell proliferation, migration, invasion, and angiogenesis. In contrast, high levels of ROS induce cell death. In multiple myeloma (MM), ROS overproduction is the trigger for apoptosis induced by several anticancer compounds, including proteasome inhibitors. However, no drugs for which oxidative stress is the main mechanism of action are currently used for treatment of MM in clinical situations. In this study, we demonstrate that the p53-activating small molecule CP-31398 (CP) effectively inhibits the growth of MM cell lines and primary MM isolates from patients. CP also suppresses the growth of MM xenografts in mice. Mechanistically, CP was found to induce intrinsic apoptosis in MM cells via increasing ROS production. Interestingly, CP-induced apoptosis occurs regardless of the p53 status, suggesting that CP has additional mechanisms of action. Our findings thus indicate that CP could be an attractive candidate for treatment of MM patients harboring p53 abnormalities; this satisfies an unmet clinical need, as such individuals currently have a poor prognosis.

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

    Science.gov (United States)

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

    2011-01-28

    Although it is thought that the major factor responsible for cell damage is reactive oxygen species (ROS), our recent studies have shown that acrolein is more toxic than ROS. Thus, the relative importance of acrolein and ROS in cell damage during brain infarction was compared using photochemically induced thrombosis model mice. The levels of acrolein-conjugated albumin, and of 4-hydroxynonenal (HNE)-conjugated albumin and 8-OHdG were evaluated as indicators of damage produced by acrolein and ROS, respectively. The increase in acrolein-conjugated albumin was much greater than the increase in HNE-conjugated albumin or 8-OHdG, suggesting that acrolein is more strongly involved in cell damage than ROS during brain infarction. It was also shown that infarction led more readily to RNA damage than to DNA or phospholipid damage. As a consequence, polyamines were released from RNA, and acrolein was produced from polyamines, especially from spermine by spermine oxidase. Production of acrolein from spermine by spermine oxidase was clarified using spermine synthase-deficient Gy mice and transglutaminase 2-knockout mice, in which spermine content is negligible or spermidine/spermine N(1)-acetyltransferase activity is elevated. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Acrolein activates matrix metalloproteinases by increasing reactive oxygen species in macrophages.

    Science.gov (United States)

    O'Toole, Timothy E; Zheng, Yu-Ting; Hellmann, Jason; Conklin, Daniel J; Barski, Oleg; Bhatnagar, Aruni

    2009-04-15

    Acrolein is a ubiquitous component of environmental pollutants such as automobile exhaust, cigarette, wood, and coal smoke. It is also a natural constituent of several foods and is generated endogenously during inflammation or oxidation of unsaturated lipids. Because increased inflammation and episodic exposure to acrolein-rich pollutants such as traffic emissions or cigarette smoke have been linked to acute myocardial infarction, we examined the effects of acrolein on matrix metalloproteinases (MMPs), which destabilize atherosclerotic plaques. Our studies show that exposure to acrolein resulted in the secretion of MMP-9 from differentiated THP-1 macrophages. Acrolein-treatment of macrophages also led to an increase in reactive oxygen species (ROS), free intracellular calcium ([Ca2+](i)), and xanthine oxidase (XO) activity. ROS production was prevented by allopurinol, but not by rotenone or apocynin and by buffering changes in [Ca2+](I) with BAPTA-AM. The increase in MMP production was abolished by pre-treatment with the antioxidants Tiron and N-acetyl cysteine (NAC) or with the xanthine oxidase inhibitors allopurinol or oxypurinol. Finally, MMP activity was significantly stimulated in aortic sections from apoE-null mice containing advanced atherosclerotic lesions after exposure to acrolein ex vivo. These observations suggest that acrolein exposure results in MMP secretion from macrophages via a mechanism that involves an increase in [Ca2+](I), leading to xanthine oxidase activation and an increase in ROS production. ROS-dependent activation of MMPs by acrolein could destabilize atherosclerotic lesions during brief episodes of inflammation or pollutant exposure.

  2. Acrolein activates matrix metalloproteinases by increasing reactive oxygen species in macrophages

    International Nuclear Information System (INIS)

    O'Toole, Timothy E.; Zheng Yuting; Hellmann, Jason; Conklin, Daniel J.; Barski, Oleg; Bhatnagar, Aruni

    2009-01-01

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

  3. Plasmonic photocatalyst-like fluorescent proteins for generating reactive oxygen species

    Science.gov (United States)

    Leem, Jung Woo; Kim, Seong-Ryul; Choi, Kwang-Ho; Kim, Young L.

    2018-03-01

    The recent advances in photocatalysis have opened a variety of new possibilities for energy and biomedical applications. In particular, plasmonic photocatalysis using hybridization of semiconductor materials and metal nanoparticles has recently facilitated the rapid progress in enhancing photocatalytic efficiency under visible or solar light. One critical underlying aspect of photocatalysis is that it generates and releases reactive oxygen species (ROS) as intermediate or final products upon light excitation or activation. Although plasmonic photocatalysis overcomes the limitation of UV irradiation, synthesized metal/semiconductor nanomaterial photocatalysts often bring up biohazardous and environmental issues. In this respect, this review article is centered in identifying natural photosensitizing organic materials that can generate similar types of ROS as those of plasmonic photocatalysis. In particular, we propose the idea of plasmonic photocatalyst-like fluorescent proteins for ROS generation under visible light irradiation. We recapitulate fluorescent proteins that have Type I and Type II photosensitization properties in a comparable manner to plasmonic photocatalysis. Plasmonic photocatalysis and protein photosensitization have not yet been compared systemically in terms of ROS photogeneration under visible light, although the phototoxicity and cytotoxicity of some fluorescent proteins are well recognized. A comprehensive understanding of plasmonic photocatalyst-like fluorescent proteins and their potential advantages will lead us to explore new environmental, biomedical, and defense applications.

  4. Reactive oxygen species production and Brugia pahangi survivorship in Aedes polynesiensis with artificial Wolbachia infection types.

    Directory of Open Access Journals (Sweden)

    Elizabeth S Andrews

    Full Text Available Heterologous transinfection with the endosymbiotic bacterium Wolbachia has been shown previously to induce pathogen interference phenotypes in mosquito hosts. Here we examine an artificially infected strain of Aedes polynesiensis, the primary vector of Wuchereria bancrofti, which is the causative agent of Lymphatic filariasis (LF throughout much of the South Pacific. Embryonic microinjection was used to transfer the wAlbB infection from Aedes albopictus into an aposymbiotic strain of Ae. polynesiensis. The resulting strain (designated "MTB" experiences a stable artificial infection with high maternal inheritance. Reciprocal crosses of MTB with naturally infected wild-type Ae. polynesiensis demonstrate strong bidirectional incompatibility. Levels of reactive oxygen species (ROS in the MTB strain differ significantly relative to that of the wild-type, indicating an impaired ability to regulate oxidative stress. Following a challenge with Brugia pahangi, the number of filarial worms achieving the infective stage is significantly reduced in MTB as compared to the naturally infected and aposymbiotic strains. Survivorship of MTB differed significantly from that of the wild-type, with an interactive effect between survivorship and blood feeding. The results demonstrate a direct correlation between decreased ROS levels and decreased survival of adult female Aedes polynesiensis. The results are discussed in relation to the interaction of Wolbachia with ROS production and antioxidant expression, iron homeostasis and the insect immune system. We discuss the potential applied use of the MTB strain for impacting Ae. polynesiensis populations and strategies for reducing LF incidence in the South Pacific.

  5. Reactive oxygen species inactivation improves pancreatic capillary blood flow in caerulein-induced pancreatitis in rats

    Directory of Open Access Journals (Sweden)

    Meirelles Jr. Roberto Ferreira

    2003-01-01

    Full Text Available PURPOSE: Reactive oxygen species (ROS inactivation was studied to determine alterations in the pancreatic capillary blood flow (PCBF during caerulein-induced pancreatitis in rats. METHODS: A laser-Doppler flowmeter to measure PCBF and N-t-Butyl-Phenylnitrone (PBN compound to inactivate ROS were used. Forty rats were divided in groups: 1 control; 2 caerulein; 3 PBN; 4 caerulein+PBN. Serum biochemistry and histopathological analyses were performed. RESULTS: PCBF measured a mean of 109.08 ± 14.54%, 68.24 ± 10.47%, 102.18 ± 10.23% and 87.73 ± 18.72% in groups 1, 2, 3 and 4, respectively. PCBF in groups 2 and 4 decreased 31.75 ± 16.79% and 12.26 ± 15.24%, respectively. Serum amylase was 1323.70 ± 239.10 U/l, 2184.60 ± 700.46 U/l, 1379.80 ± 265.72 U/l and 1622.10 ± 314.60 U/l in groups 1, 2, 3 and 4, respectively. There was a significant difference in the PCBF and serum amylase when compared groups 2 and 4. Cytoplasmatic vacuolation was present in groups 2 and 4. Otherwise, no qualitative changes were seen. CONCLUSION: ROS inactivation improves PCBF and minimizes the serum amylase increase during caerulein-induced pancreatitis. ROS effect may be one of the leading causative events in this model of acute pancreatitis.

  6. Controllable generation of reactive oxygen species by femtosecond-laser irradiation

    Science.gov (United States)

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

    2014-02-01

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

  7. Detection of the Level of Reactive Oxygen Species Induced by Ionizing Radiation in Cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Kyu; Chung, Dong Min; Kim, Jin-Hong [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-05-15

    By definition, the direct effect is referred to interaction between photon and DNA molecule, whereas the indirect effect is mediated by the reactive oxygen species (ROS) generated by radiolysis and subsequent reaction. It has been reported that ROS produced after exposure to IR can react with cellular materials such as DNA, proteins, carbohydrates and lipids. ROS is free radicals such as the superoxide anion, hydroxyl radicals and the non-radical hydrogen peroxide. Cells generate ROS during aerobic metabolism. Excessive production of ROS can lead to oxidative stress, genetic alteration and even cell death. It has been reported that ROS plays a critical role in radiation-induced cell injury. Thus, it is of great interest to determine the radiation-induced ROS level. Many kinds of methods to detect the level of ROS have been developed so far. There were random changes of fluorescence intensity in the treatment after irradiation. This result meant that this protocol was not appropriate for determination of radiation-induced ROS. On the other hand, the fluorescence intensity was increased in a dose-dependent manner when the cells were treated with the DCFH-DA solution before irradiation. Conclusions can be drawn from the experimental results of this study. In order to properly measure the ROS level in the cells exposed to ionizing radiation, the cells should be treated with the DCFH-DA solution before irradiation.

  8. Effects of menadione, a reactive oxygen generator, on leukotriene secretion from RBL-2H3 cells.

    Science.gov (United States)

    Kawamura, Fumio; Nakanishi, Mamoru; Hirashima, Naohide

    2010-01-01

    Reactive oxygen species (ROS) are produced in various cells and affect many biological processes. We previously reported that 2-methyl-1,4-naphtoquinone (menadione) inhibited Ca(2+) influx from the extracellular medium and exocytosis evoked by antigen stimulation in the mast cell line, RBL-2H3. Mast cells release various inflammatory mediators such as leukotrienes (LTs) and cytokines in addition to the exocytotic secretion of histamine. In this study, we investigated the effects of menadione on LT release in RBL-2H3. Treatment of RBL cells with menadione inhibited LTC(4) secretion induced by antigen stimulation. To elucidate the mechanism of this inhibition, we examined the effects of menadione on the activation process of 5-lipoxygenase that is responsible for the synthesis of LTs from arachidonic acid. Menadione did not affect the phosophorylation of mitogen activated protein (MAP) kinases, extracellular signal-regulated kinase (ERK) and p38, which regulates phosphorylation of 5-lipoxygenase. However, menadione inhibited the translocation of 5-lipoxygenase from the cytoplasm to the nuclear membrane. Together with the result that LT secretion was severely impaired in the absence of extracellular Ca2(2+), it is suggested that ROS produced by menadione inhibited LT secretion through impaired Ca2(2+) influx and 5-lipoxygenase translocation to the nuclear membrane.

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

    International Nuclear Information System (INIS)

    Kang, Kyoung Ah; Lee, Hyung Chul; Lee, Je-Jung

    2014-01-01

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

  10. Tuning of redox regulatory mechanisms, reactive oxygen species and redox homeostasis under salinity stress

    Directory of Open Access Journals (Sweden)

    Hossain eSazzad

    2016-05-01

    Full Text Available Soil salinity is a crucial environmental constraint which limits biomass production at many sites on a global scale. Saline growth conditions cause osmotic and ionic imbalances, oxidative stress and perturb metabolism, e.g. the photosynthetic electron flow. The plant ability to tolerate salinity is determined by multiple biochemical and physiological mechanisms protecting cell functions, in particular by regulating proper water relations and maintaining ion homeostasis. Redox homeostasis is a fundamental cell property. Its regulation includes control of reactive oxygen species (ROS generation, sensing deviation from and readjustment of the cellular redox state. All these redox related functions have been recognized as decisive factors in salinity acclimation and adaptation. This review focuses on the core response of plants to overcome the challenges of salinity stress through regulation of ROS generation and detoxification systems and to maintain redox homeostasis. Emphasis is given to the role of NADH oxidase (RBOH, alternative oxidase (AOX, the plastid terminal oxidase (PTOX and the malate valve with the malate dehydrogenase isoforms under salt stress. Overwhelming evidence assigns an essential auxiliary function of ROS and redox homeostasis to salinity acclimation of plants.

  11. The Role of Reactive Oxygen Species and Autophagy in Periodontitis and Their Potential Linkage

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    Chengcheng Liu

    2017-06-01

    Full Text Available Periodontitis is a chronic inflammatory disease that causes damage to periodontal tissues, which include the gingiva, periodontal ligament, and alveolar bone. The major cause of periodontal tissue destruction is an inappropriate host response to microorganisms and their products. Specifically, a homeostatic imbalance between reactive oxygen species (ROS and antioxidant defense systems has been implicated in the pathogenesis of periodontitis. Elevated levels of ROS acting as intracellular signal transducers result in autophagy, which plays a dual role in periodontitis by promoting cell death or blocking apoptosis in infected cells. Autophagy can also regulate ROS generation and scavenging. Investigations are ongoing to elucidate the crosstalk mechanisms between ROS and autophagy. Here, we review the physiological and pathological roles of ROS and autophagy in periodontal tissues. The redox-sensitive pathways related to autophagy, such as mTORC1, Beclin 1, and the Atg12-Atg5 complex, are explored in depth to provide a comprehensive overview of the crosstalk between ROS and autophagy. Based on the current evidence, we suggest that a potential linkage between ROS and autophagy is involved in the pathogenesis of periodontitis.

  12. Reactive oxygen species induced by Streptococcus pyogenes invasion trigger apoptotic cell death in infected epithelial cells.

    Science.gov (United States)

    Aikawa, Chihiro; Nozawa, Takashi; Maruyama, Fumito; Tsumoto, Kohei; Hamada, Shigeyuki; Nakagawa, Ichiro

    2010-06-01

    Streptococcus pyogenes (group A streptococcus, GAS), one of the most common pathogens of humans, attaches and invades into human pharyngeal or skin epithelial cells. We have previously reported that induction of apoptosis is associated with GAS invasion, which induces mitochondrial dysfunction and apoptotic cell death. We demonstrate here that GAS-induced apoptosis is mediated by reactive oxygen species (ROS) production. Both the induction of apoptosis and ROS production markedly increased upon invasion of wild-type GAS strain JRS4 into HeLa cells; however, the apoptotic response was not observed in fibronectin-binding protein F1-disrupted mutant SAM1-infected cells. In Bcl-2-overexpressing HeLa cells (HBD98-2-4), the induction of apoptosis, ROS production and mitochondrial dysfunction were significantly suppressed, whereas the numbers of invaded GAS was not different between HeLa (mock cells) and the HeLa HBD98-2-4 cells. Whereas Rac1 activation occurred during GAS invasion, ROS production in GAS-infected cells was clearly inhibited by transfection with the Rac1 mutants (L37 or V12L37), but not by the dominant active mutant (V12L61) or by the dominant negative mutant (N17). These observations indicate that GAS invasion triggers ROS production through Rac1 activation and generated ROS induced mitochondrial dysfunction leading to cellular apoptosis.

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

    International Nuclear Information System (INIS)

    Perez-de-Arce, Karen; Foncea, Rocio; Leighton, Federico

    2005-01-01

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

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

    Science.gov (United States)

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

    2015-03-01

    Iron (Fe) homeostasis is integrated with the production of reactive oxygen species (ROS), and distribution at the root tip participates in the control of root growth. Excess Fe increases ferritin abundance, enabling the storage of Fe, which contributes to protection of plants against Fe-induced oxidative stress. AtFer1 and AtFer3 are the two ferritin genes expressed in the meristematic zone, pericycle and endodermis of the Arabidopsis thaliana root, and it is in these regions that we observe Fe stained dots. This staining disappears in the triple fer1-3-4 ferritin mutant. Fe excess decreases primary root length in the same way in wild-type and in fer1-3-4 mutant. In contrast, the Fe-mediated decrease of lateral root (LR) length and density is enhanced in fer1-3-4 plants due to a defect in LR emergence. We observe that this interaction between excess Fe, ferritin, and root system architecture (RSA) is in part mediated by the H2O2/O2·- balance between the root cell proliferation and differentiation zones regulated by the UPB1 transcription factor. Meristem size is also decreased in response to Fe excess in ferritin mutant plants, implicating cell cycle arrest mediated by the ROS-activated SMR5/SMR7 cyclin-dependent kinase inhibitors pathway in the interaction between Fe and RSA. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  15. The Emerging Role of Reactive Oxygen Species Signaling during Lateral Root Development.

    Science.gov (United States)

    Manzano, Concepción; Pallero-Baena, Mercedes; Casimiro, Ilda; De Rybel, Bert; Orman-Ligeza, Beata; Van Isterdael, Gert; Beeckman, Tom; Draye, Xavier; Casero, Pedro; Del Pozo, Juan C

    2014-07-01

    Overall root architecture is the combined result of primary and lateral root growth and is influenced by both intrinsic genetic programs and external signals. One of the main questions for root biologists is how plants control the number of lateral root primordia and their emergence through the main root. We recently identified S-phase kinase-associated protein2 (SKP2B) as a new early marker for lateral root development. Here, we took advantage of its specific expression pattern in Arabidopsis (Arabidopsis thaliana) in a cell-sorting and transcriptomic approach to generate a lateral root-specific cell sorting SKP2B data set that represents the endogenous genetic developmental program. We first validated this data set by showing that many of the identified genes have a function during root growth or lateral root development. Importantly, genes encoding peroxidases were highly represented in our data set. Thus, we next focused on this class of enzymes and showed, using genetic and chemical inhibitor studies, that peroxidase activity and reactive oxygen species signaling are specifically required during lateral root emergence but, intriguingly, not for primordium specification itself. © 2014 American Society of Plant Biologists. All Rights Reserved.

  16. Dim artificial light at night affects mating, reproductive output, and reactive oxygen species in Drosophila melanogaster.

    Science.gov (United States)

    McLay, Lucy Katherine; Nagarajan-Radha, Venkatesh; Green, Mark Philip; Jones, Therésa Melanie

    2018-05-07

    Humans are lighting the night-time environment with ever increasing extent and intensity, resulting in a variety of negative ecological effects in individuals and populations. Effects of light at night on reproductive fitness traits are demonstrated across taxa however, the mechanisms underlying these effects are largely untested. One possible mechanism is that light at night may result in perturbed reactive oxygen species (ROS) and oxidative stress levels. Here, we reared Drosophila melanogaster under either dim (10 lx) light or no light (0 lx) at night for three generations and then compared mating and lifetime oviposition patterns. In a second experiment, we explored whether exposure to light at night treatments resulted in variation in ROS levels in the heads and ovaries of six, 23- and 36-day-old females. We demonstrate that dim light at night affects mating and reproductive output: 10 lx flies courted for longer prior to mating, and female oviposition patterns differed to 0 lx females. ROS levels were lower in the ovaries but not heads, of 10 lx compared with 0 lx females. We suggest that reduced ROS levels may reflect changes in ovarian physiology and cell signaling, which may be related to the differences observed in oviposition patterns. Taken together, our results indicate negative consequences for invertebrates under more stressful, urban, lit conditions and further investigation into the mechanisms driving these changes is warranted to manage invertebrate communities in a brighter future. © 2018 Wiley Periodicals, Inc.

  17. Photoreactivity of Metal-Organic Frameworks in Aqueous Solutions: Metal Dependence of Reactive Oxygen Species Production.

    Science.gov (United States)

    Liu, Kai; Gao, Yanxin; Liu, Jing; Wen, Yifan; Zhao, Yingcan; Zhang, Kunyang; Yu, Gang

    2016-04-05

    Promising applications of metal-organic frameworks (MOFs) in various fields have raised concern over their environmental fate and safety upon inevitable discharge into aqueous environments. Currently, no information regarding the transformation processes of MOFs is available. Due to the presence of repetitive π-bond structure and semiconductive property, photochemical transformations are an important fate process that affects the performance of MOFs in practical applications. In the current study, the generation of reactive oxygen species (ROS) in isoreticular MIL-53s was studied. Scavengers were employed to probe the production of (1)O2, O2(•-), and •OH, respectively. In general, MIL-53(Cr) and MIL-53(Fe) are dominated by type I and II photosensitization reactions, respectively, and MIL-53(Al) appears to be less photoreactive. The generation of ROS in MIL-53(Fe) may be underestimated due to dismutation. Further investigation of MIL-53(Fe) encapsulated diclofenac transformation revealed that diclofenac can be easily transformed by MIL-53(Fe) generated ROS. However, the cytotoxicity results implied that the ROS generated from MIL-53s have little effect on the viability of the human hepatocyte (HepG2) cell line. These results suggest that the photogeneration of ROS by MOFs may be metal-node dependent, and the application of MIL-53s as drug carriers needs to be carefully considered due to their high photoreactivity.

  18. Global Plant Stress Signaling: Reactive Oxygen Species at the Cross-Road

    Directory of Open Access Journals (Sweden)

    Nasser eSewelam

    2016-02-01

    Full Text Available Current technologies have changed biology into a data-intensive field and significantly increased our understanding of signal transduction pathways in plants. However, global defense signaling networks in plants have not been established yet. Considering the apparent intricate nature of signaling mechanisms in plants (due to their sessile nature, studying the points at which different signaling pathways converge, rather than the branches, represents a good start to unravel global plant signaling networks. In this regard, growing evidence shows that the generation of reactive oxygen species (ROS is one of the most common plant responses to different stresses, representing a point at which various signaling pathways come together. In this review, the complex nature of plant stress signaling networks will be discussed. An emphasis on different signaling players with a specific attention to ROS as the primary source of the signaling battery in plants will be presented. The interactions between ROS and other signaling components, e.g. calcium, redox homeostasis, membranes, G-proteins, MAPKs, plant hormones and transcription factors will be assessed. A better understanding of the vital roles ROS are playing in plant signaling would help innovate new strategies to improve plant productivity under the circumstances of the increasing severity of environmental conditions and the high demand of food and energy worldwide

  19. Cold stress increases reactive oxygen species formation via TRPA1 activation in A549 cells.

    Science.gov (United States)

    Sun, Wenwu; Wang, Zhonghua; Cao, Jianping; Cui, Haiyang; Ma, Zhuang

    2016-03-01

    Reactive oxygen species (ROS) are responsible for lung damage during inhalation of cold air. However, the mechanism of the ROS production induced by cold stress in the lung is still unclear. In this work, we measured the changes of ROS and the cytosolic Ca(2+) concentration ([Ca(2+)]c) in A549 cell. We observed that cold stress (from 20 to 5 °C) exposure of A549 cell resulted in an increase of ROS and [Ca(2+)]c, which was completely attenuated by removing Ca(2+) from medium. Further experiments showed that cold-sensing transient receptor potential subfamily member 1 (TRPA1) agonist (allyl isothiocyanate, AITC) increased the production of ROS and the level of [Ca(2+)]c in A549 cell. Moreover, HC-030031, a TRPA1 selective antagonist, significantly inhibited the enhanced ROS and [Ca(2+)]c induced by AITC or cold stimulation, respectively. Taken together, these data demonstrated that TRPA1 activation played an important role in the enhanced production of ROS induced by cold stress in A549 cell.

  20. Controlled intracellular generation of reactive oxygen species in human mesenchymal stem cells using porphyrin conjugated nanoparticles.

    Science.gov (United States)

    Lavado, Andrea S; Chauhan, Veeren M; Zen, Amer Alhaj; Giuntini, Francesca; Jones, D Rhodri E; Boyle, Ross W; Beeby, Andrew; Chan, Weng C; Aylott, Jonathan W

    2015-09-14

    Nanoparticles capable of generating controlled amounts of intracellular reactive oxygen species (ROS), that advance the study of oxidative stress and cellular communication, were synthesized by functionalizing polyacrylamide nanoparticles with zinc(II) porphyrin photosensitisers. Controlled ROS production was demonstrated in human mesenchymal stem cells (hMSCs) through (1) production of nanoparticles functionalized with varying percentages of Zn(II) porphyrin and (2) modulating the number of doses of excitation light to internalized nanoparticles. hMSCs challenged with nanoparticles functionalized with increasing percentages of Zn(II) porphyrin and high numbers of irradiations of excitation light were found to generate greater amounts of ROS. A novel dye, which is transformed into fluorescent 7-hydroxy-4-trifluoromethyl-coumarin in the presence of hydrogen peroxide, provided an indirect indicator for cumulative ROS production. The mitochondrial membrane potential was monitored to investigate the destructive effect of increased intracellular ROS production. Flow cytometric analysis of nanoparticle treated hMSCs suggested irradiation with excitation light signalled controlled apoptotic cell death, rather than uncontrolled necrotic cell death. Increased intracellular ROS production did not induce phenotypic changes in hMSC subcultures.

  1. Reactive oxygen radicals and gaseous transmitters in carotid body activation by intermittent hypoxia.

    Science.gov (United States)

    Prabhakar, Nanduri R; Peng, Ying-Jie; Yuan, Guoxiang; Nanduri, Jayasri

    2018-05-01

    Sleep apnea is a prevalent respiratory disease characterized by periodic cessation of breathing during sleep causing intermittent hypoxia (IH). Sleep apnea patients and rodents exposed to IH exhibit elevated sympathetic nerve activity and hypertension. A heightened carotid body (CB) chemoreflex has been implicated in causing autonomic abnormalities in IH-treated rodents and in sleep apnea patients. The purpose of this article is to review the emerging evidence showing that interactions between reactive oxygen species (ROS) and gaseous transmitters as a mechanism cause hyperactive CB by IH. Rodents treated with IH exhibit markedly elevated ROS in the CB, which is due to transcriptional upregulation of pro-oxidant enzymes by hypoxia-inducible factor (HIF)-1 and insufficient transcriptional regulation of anti-oxidant enzymes by HIF-2. ROS, in turn, increases cystathionine γ-lyase (CSE)-dependent H 2 S production in the CB. Blockade of H 2 S synthesis prevents IH-evoked CB activation. However, the effects of ROS on H 2 S production are not due to direct effects on CSE enzyme activity but rather due to inactivation of heme oxygenase-2 (HO-2), a carbon monoxide (CO) producing enzyme. CO inhibits H 2 S production through inactivation of CSE by PKG-dependent phosphorylation. During IH, reduced CO production resulting from inactivation of HO-2 by ROS releases the inhibition of CO on CSE thereby increasing H 2 S. Inhibiting H 2 S synthesis prevented IH-evoked sympathetic activation and hypertension.

  2. Screening reactive oxygen species scavenging properties of platinum nanoparticles on a microfluidic chip.

    Science.gov (United States)

    Zheng, Wenfu; Jiang, Bo; Hao, Yi; Zhao, Yuyun; Zhang, Wei; Jiang, Xingyu

    2014-09-12

    Hyperglycemia, hyperlipidemia and inflammation are key risk factors for atherosclerosis and can lead to overproduction of reactive oxygen species (ROS), which plays a critical role in vascular endothelial dysfunction and subsequent progress of atherosclerosis. However, there is currently a lack of effective drugs that deal with ROS. Platinum nanoparticles (Pt-NPs) have proven to be promising antioxidant drugs in vitro and in vivo. To optimize the efficacy of Pt-NP based drugs, we synthesized and characterized the ROS scavenging properties of three kinds of small molecules that capped Pt-NPs (Pt-AMP-NPs, Pt-ATT-NPs, Pt-MI-NPs) on a blood vessel-mimicking microfluidic chip. The Pt-NPs showed superior superoxide dismutase (SOD)-like functions and can scavenge ROS and recover compromised cell-cell junctions under hyperglycemic, hyperlipidemic and proinflammatory conditions. Amongst these NPs, Pt-AMP-NPs showed the most superior antioxidant properties, suggesting its potency to serve as a novel drug to treat vascular diseases such as atherosclerosis. Our microfluidic chip, providing physiological hemodynamic conditions for the experiments, is potentially a promising tool for a wide range of biological research on the vascular system.

  3. The Role of Reactive Oxygen Species (ROS in the Biological Activities of Metallic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Ahmed Abdal Dayem

    2017-01-01

    Full Text Available Nanoparticles (NPs possess unique physical and chemical properties that make them appropriate for various applications. The structural alteration of metallic NPs leads to different biological functions, specifically resulting in different potentials for the generation of reactive oxygen species (ROS. The amount of ROS produced by metallic NPs correlates with particle size, shape, surface area, and chemistry. ROS possess multiple functions in cellular biology, with ROS generation a key factor in metallic NP-induced toxicity, as well as modulation of cellular signaling involved in cell death, proliferation, and differentiation. In this review, we briefly explained NP classes and their biomedical applications and describe the sources and roles of ROS in NP-related biological functions in vitro and in vivo. Furthermore, we also described the roles of metal NP-induced ROS generation in stem cell biology. Although the roles of ROS in metallic NP-related biological functions requires further investigation, modulation and characterization of metallic NP-induced ROS production are promising in the application of metallic NPs in the areas of regenerative medicine and medical devices.

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

    Science.gov (United States)

    Sakuma, Satoru; Miyoshi, Emi; Sadatoku, Namiko; Fujita, Junko; Negoro, Miki; Arakawa, Yukio; Fujimoto, Yohko

    2009-09-15

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

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

    International Nuclear Information System (INIS)

    Radogna, Flavia; Paternoster, Laura; De Nicola, Milena; Cerella, Claudia; Ammendola, Sergio; Bedini, Annalida; Tarzia, Giorgio; Aquilano, Katia; Ciriolo, Maria; Ghibelli, Lina

    2009-01-01

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

  6. Regulation of radiation protective agents on cell damage induced by reactive oxygen species

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Hee; Lee, Si Eun; Ju, Eun Mi; Gao, Eu Feng [Kyung Hee University, Seoul (Korea)

    2002-04-01

    In this study, we developed candidates of new radio-protective agents and elucidated the regulation mechanism of these candidates on cell damage induced by reactive oxygen species. The methanol extracts and ethylacetate fractions of NP-1, NP-5, NP-7, NP-11, NP-12 and NP-14 showed higher radical scavenging activity. The extracts of NP-7, NP-12 and NP-14 showed strong protective effect against oxidative damage induced by UV and H{sub 2}O{sub 2}. The most of samples enhanced SOD, CAT and GPX activity in V79-4 cells. The protective effect of samples on H{sub 2}O{sub 2}-induced apoptosis was observed with microscope and flow cytometer. Cells exposed to H{sub 2}O{sub 2} exhibit distinct morphological features of programmed cell death, such as nuclear fragmentation and increase in the percentage of cells with a sub-G1 DNA content. However, cells which was pretreated with samples significantly reduced the characteristics of apoptotic cells. Their morphological observation and DNA profiles were similar to those of the control cells. NP-14 which had excellent antioxidant activity restored G2/M arrest induced by oxidative stress. These data suggested that natural medicinal plants protected H{sub 2}O{sub 2}-induced apoptosis. 42 refs., 29 figs., 11 tabs. (Author)

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

    International Nuclear Information System (INIS)

    Haase, Hajo; Engelhardt, Gabriela; Hebel, Silke; Rink, Lothar

    2011-01-01

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

  8. N-acetyltransferase Mpr1 confers ethanol tolerance on Saccharomyces cerevisiae by reducing reactive oxygen species

    Energy Technology Data Exchange (ETDEWEB)

    Du, Xiaoyi [Fukui Prefectural Univ., Fukui (Japan). Dept. of Bioscience; Takagi, Hiroshi [Nara Inst. of Science and Technology, Ikoma, Nara (Japan). Graduate School of Biological Sciences

    2007-07-15

    N-Acetyltransferase Mpr1 of Saccharomyces cerevisiae can reduce intracellular oxidation levels and protect yeast cells under oxidative stress, including H{sub 2}O{sub 2}, heat-shock, or freeze-thaw treatment. Unlike many antioxidant enzyme genes induced in response to oxidative stress, the MPR1 gene seems to be constitutively expressed in yeast cells. Based on a recent report that ethanol toxicity is correlated with the production of reactive oxygen species (ROS), we examined here the role of Mpr1 under ethanol stress conditions. The null mutant of the MPR1 and MPR2 genes showed hypersensitivity to ethanol stress, and the expression of the MPR1 gene conferred stress tolerance. We also found that yeast cells exhibited increased ROS levels during exposure to ethanol stress, and that Mpr1 protects yeast cells from ethanol stress by reducing intracellular ROS levels. When the MPR1 gene was overexpressed in antioxidant enzyme-deficient mutants, increased resistance to H{sub 2}O{sub 2} or heat shock was observed in cells lacking the CTA1, CTT1, or GPX1 gene encoding catalase A, catalase T, or glutathione peroxidase, respectively. These results suggest that Mpr1 might compensate the function of enzymes that detoxify H{sub 2}O{sub 2}. Hence, Mpr1 has promising potential for the breeding of novel ethanol-tolerant yeast strains. (orig.)

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

    Science.gov (United States)

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

    2008-07-15

    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 in the presence of superoxide anion (O2(-)), hydrogen peroxide (H2O2) or hydroxyl radical (OH) and their scavengers. The presence of OH accelerated significantly disassembly of cellular wall polysaccharides in terms of the increase in contents of total sugars released and uronic acid, and the decrease in molecular mass of soluble polysaccharides, using gel permeation chromatography. However, the treatment with H2O2 or O2(-) showed no significant effect on the disassembly of cellular wall polysaccharides. Furthermore, the degradation of the de-esterified AEIR was more susceptible to OH attack than the esterified AEIR. In addition, the effect of OH could be inhibited in the presence of OH scavenger. This study suggests that disassembly of cellular wall polysaccharides could be initiated by OH as the solublisation of the polysaccharides increased, which, in turn, accelerated fruit softening. Copyright © 2008 Elsevier Ltd. All rights reserved.

  10. Horseradish Peroxidase-Encapsulated Hollow Silica Nanospheres for Intracellular Sensing of Reactive Oxygen Species

    Science.gov (United States)

    Chen, Hsin-Yi; Wu, Si-Han; Chen, Chien-Tsu; Chen, Yi-Ping; Chang, Feng-Peng; Chien, Fan-Ching; Mou, Chung-Yuan

    2018-04-01

    Reactive oxygen species (ROS) have crucial roles in cell signaling and homeostasis. Overproduction of ROS can induce oxidative damage to various biomolecules and cellular structures. Therefore, developing an approach capable of monitoring and quantifying ROS in living cells is significant for physiology and clinical diagnoses. Some cell-permeable fluorogenic probes developed are useful for the detection of ROS while in conjunction with horseradish peroxidase (HRP). Their intracellular scenario is however hindered by the membrane-impermeable property of enzymes. Herein, a new approach for intracellular sensing of ROS by using horseradish peroxidase-encapsulated hollow silica nanospheres (designated HRP@HSNs), with satisfactory catalytic activity, cell membrane permeability, and biocompatibility, was prepared via a microemulsion method. These HRP@HSNs, combined with selective probes or targeting ligands, could be foreseen as ROS-detecting tools in specific organelles or cell types. As such, dihydrorhodamine 123-coupled HRP@HSNs were used for the qualitative and semi-quantitative analysis of physiological H2O2 levels in activated RAW 264.7 macrophages. We envision that this HSNs encapsulating active enzymes can be conjugated with selective probes and targeting ligands to detect ROS in specific organelles or cell types of interest.

  11. Salinomycin induces autophagy in colon and breast cancer cells with concomitant generation of reactive oxygen species.

    Directory of Open Access Journals (Sweden)

    Berlinda Verdoodt

    Full Text Available BACKGROUND: Salinomycin is a polyether ionophore antibiotic that has recently been shown to induce cell death in human cancer cells displaying multiple mechanisms of drug resistance. The underlying mechanisms leading to cell death after salinomycin treatment have not been well characterized. We therefore investigated the role of salinomycin in caspase dependent and independent cell death in colon cancer (SW480, SW620, RKO and breast cancer cell lines (MCF-7, T47D, MDA-MB-453. METHODOLOGY/PRINCIPAL FINDINGS: We detected features of apoptosis in all cell lines tested, but the executor caspases 3 and 7 were only strongly activated in RKO and MDA-MB-453 cells. MCF-7 and SW620 cells instead presented features of autophagy such as cytoplasmic vacuolization and LC3 processing. Caspase proficient cell lines activated autophagy at lower salinomycin concentrations and before the onset of caspase activation. Salinomycin also led to the formation of reactive oxygen species (ROS eliciting JNK activation and induction of the transcription factor JUN. Salinomycin mediated cell death could be partially inhibited by the free radical scavenger N-acetyl-cysteine, implicating ROS formation in the mechanism of salinomycin toxicity. CONCLUSIONS: Our data indicate that, in addition to its previously reported induction of caspase dependent apoptosis, the initiation of autophagy is an important and early effect of salinomycin in tumor cells.

  12. Reactive Oxygen Species and Antioxidant in Seminal Plasma and Their Impact on Male Fertility

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    Mohammad Eid Hammadeh

    2009-01-01

    Full Text Available Spermatozoa generate reactive oxygen species (ROS in physiological amounts, which play arole in sperm functions during sperm capacitation, acrosome reaction (AR, and oocyte fusion. Inaddition, damaged sperm are likely to be the source of ROS. The most important ROS producedby human sperm are hydrogen peroxide, superoxide anion and hydroxyl radicals. Besides, humanseminal plasma and sperm possess an antioxidant system to scavenge ROS and prevent ROS relatedcellular damage. Under normal circumstances, there is an appropriate balance between oxidants andantioxidants. A shift in the levels of ROS towards pro-oxidants in semen can induce oxidative stress(OS on spermatozoa.Male infertility is associated with increased ROS and decreased total antioxidant activity in theseminal plasma. ROS induce nuclear DNA strand breaks. Besides, due to a high polyunsaturatedfatty acid content human sperm plasma membranes are highly sensitive to ROS induced lipidperoxidation thus decreasing membrane fluidity. This will result in increased lipid peroxidation(LPO, decreased sperm motility, viability, function and ultimately lead to infertility. The protectiveaction of antioxidants against the deleterious effect of ROS on cellular lipids, proteins and DNA hasbeen supported by several scientific studies.The purpose of the present review is to address the possible relationship between ROS andantioxidants production in seminal plasma, and the role they may play in influencing the outcomeof assisted reproductive technology (ART.

  13. Quorum sensing circuit and reactive oxygen species resistance in Deinococcus sp.

    Science.gov (United States)

    Fernandez-Bunster, G; Gonzalez, C; Barros, J; Martinez, M

    2012-12-01

    Genus Deinococcus is characterized by an increased resistance toward reactive oxygen species (ROS). The chromosome of five strains belonging to this genus has been sequenced and the presence of a luxS-like gene was deduced from their genome sequences. The aim of this study was to assess if a complete QS circuit is present in Deinococcus sp. and if this QS is associated with ROS. Primers for searching luxS-like gene and the putative receptor gene, namely ai2R, were designed. AI-2 signal production was evaluated by luminescence analysis using Vibrio harveyi BB170 as reporter strain. AI-2 signal was also evaluated by competitive assays using cinnamaldehyde, ascorbic acid, and 3-mercaptopropionic acid as interfering molecules. Potassium tellurite and metronidazole were used as oxidative stressors. A luxS-like gene as well as an ai2R gene was detected in strain UDEC-P1 by PCR. Cell-free supernatant of strain UDEC-P1 culture induced luminescence in V. harveyi BB170, and this property was inhibited with the three interfering molecules. The oxidative stressors metronidazole and potassium tellurite decreased Deinococcus sp. viability, but increased luminescence of the reporter strain. The results demonstrate that both a functional luxS-like gene and a putative receptor for AI-2 signal are present in Deinococcus sp. strain UDEC-P1. This finding also suggests that a complete QS circuit is present in this genus, which could be related to oxidative stress.

  14. Alpha-synuclein induces lysosomal rupture and cathepsin dependent reactive oxygen species following endocytosis.

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    David Freeman

    Full Text Available α-synuclein dysregulation is a critical aspect of Parkinson's disease pathology. Recent studies have observed that α-synuclein aggregates are cytotoxic to cells in culture and that this toxicity can be spread between cells. However, the molecular mechanisms governing this cytotoxicity and spread are poorly characterized. Recent studies of viruses and bacteria, which achieve their cytoplasmic entry by rupturing intracellular vesicles, have utilized the redistribution of galectin proteins as a tool to measure vesicle rupture by these organisms. Using this approach, we demonstrate that α-synuclein aggregates can induce the rupture of lysosomes following their endocytosis in neuronal cell lines. This rupture can be induced by the addition of α-synuclein aggregates directly into cells as well as by cell-to-cell transfer of α-synuclein. We also observe that lysosomal rupture by α-synuclein induces a cathepsin B dependent increase in reactive oxygen species (ROS in target cells. Finally, we observe that α-synuclein aggregates can induce inflammasome activation in THP-1 cells. Lysosomal rupture is known to induce mitochondrial dysfunction and inflammation, both of which are well established aspects of Parkinson's disease, thus connecting these aspects of Parkinson's disease to the propagation of α-synuclein pathology in cells.

  15. Sibutramine provokes apoptosis of aortic endothelial cells through altered production of reactive oxygen and nitrogen species.

    Science.gov (United States)

    Morikawa, Yoshifumi; Shibata, Akinobu; Okumura, Naoko; Ikari, Akira; Sasajima, Yasuhide; Suenami, Koichi; Sato, Kiyohito; Takekoshi, Yuji; El-Kabbani, Ossama; Matsunaga, Toshiyuki

    2017-01-01

    Overdose administration of sibutramine, a serotonin-noradrenalin reuptake inhibitor, is considered to elicit severe side effects including hypertension, whose pathogenic mechanism remains unclear. Here, we found that 48-h incubation with >10μM sibutramine provokes apoptosis of human aortic endothelial (HAE) cells. Treatment with the lethal concentration of sibutramine facilitated production of reactive oxygen species (ROS), altered expression of endoplasmic reticulum stress response genes (heat shock protein 70 and C/EBP homologous protein), and inactivated 26S proteasome-based proteolysis. The treatment also decreased cellular level of nitric oxide (NO) through lowering of expression and activity of endothelial NO synthase. These results suggest that ROS production and depletion of NO are crucial events in the apoptotic mechanism and may be linked to the pathogenesis of vasoconstriction elicited by the drug. Compared to sibutramine, its metabolites (N-desmethylsibutramine and N-didesmethylsibutramine) were much less cytotoxic to HAE cells, which hardly metabolized sibutramine. In contrast, both the drug and metabolites showed low cytotoxicity to hepatic HepG2 cells with high metabolic potency and expression of cytochrome P450 (CYP) 3A4. The cytotoxicity of sibutramine to HepG2 and Chang Liver cells was remarkably augmented by inhibition and knockdown of CYP3A4. This study also suggests an inverse relationship between sibutramine cytotoxicity and CYP3A4-mediated metabolism into the N-desmethyl metabolites. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Levels of semenogelin in human spermatozoa decrease during capacitation: involvement of reactive oxygen species and zinc.

    Science.gov (United States)

    de Lamirande, E; Lamothe, G

    2010-07-01

    Semenogelin (Sg), the main protein of human semen coagulum, prevents sperm capacitation. The objective of this study was to examine the role of Sg and its mechanism of action. Sg blocked sperm capacitation triggered by various stimuli, via inhibition of superoxide anion (O(2)*-; luminescence assay) and nitric oxide (NO*; tested using diaminofluorescein) generation. Triton-soluble and -insoluble sperm fractions contained Sg and Sg peptides (immunoblotting), the level of which decreased with initiation of capacitation. This drop was prevented by superoxide dismutase and NO* synthase inhibitor and was reproduced by addition of O(2)*- and NO*. Zinc (Zn(2+)) blocked and a zinc chelator (TPEN) promoted the decline in Sg levels. There was a decreased labelling of Sg on the head in capacitating spermatozoa with the two fixation techniques tested (immunocytochemistry). Reactive oxygen species (ROS) (O(2)*- and NO*) caused, these changes, and zinc prevented them. Spermatozoa quickly internalized Sg upon incubation and Sg was then rapidly degraded in a zinc-inhibitable manner. Sg blocked capacitation mainly via inhibition of ROS generation. Spermatozoa appeared permeable to Sg and processed Sg in a zinc-inhibitable fashion. ROS themselves could promote sperm disposal of Sg which maybe one of the mechanisms that allows initiation of capacitation.

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

    Science.gov (United States)

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

    2007-03-01

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

  18. Roles of Reactive Oxygen Species in Anticancer Therapy with Salvia miltiorrhiza Bunge

    Directory of Open Access Journals (Sweden)

    Yu-Chiang Hung

    2016-01-01

    Full Text Available Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS in anticancer therapy with Salvia miltiorrhiza Bunge (Danshen. Danshen, including its lipophilic and hydrophilic constituents, is potentially beneficial for treating various cancers. The mechanisms of ROS-related anticancer effects of Danshen vary depending on the specific type of cancer cells involved. Danshen may enhance TNF-α-induced apoptosis, upregulate caspase-3, caspase-8, caspase-9, endoplasmic reticulum stress, P21, P53, Bax/Bcl-2, DR5, and AMP-activated protein kinase, or activate the p38/JNK, mitogen-activated protein kinase, and FasL signaling pathways. Conversely, Danshen may downregulate human telomerase reverse transcriptase mRNA, telomerase, survivin, vascular endothelial growth factor/vascular endothelial growth factor receptor 2, CD31, NF-κB, Erk1/2, matrix metalloproteinases, microtubule assembly, and receptor tyrosine kinases including epidermal growth factor receptors, HER2, and P-glycoprotein and inhibit the PI3K/Akt/mTOR or estrogen receptor signaling pathways. Therefore, Danshen may inhibit cancer cells proliferation through antioxidation on tumor initiation and induce apoptosis or autophagy through ROS generation on tumor progression, tumor promotion, and tumor metastasis. Based on the available evidence regarding its anticancer properties, this review provides new insights for further anticancer research or clinical trials with Danshen.

  19. Anxiety-induced plasma norepinephrine augmentation increases reactive oxygen species formation by monocytes in essential hypertension.

    Science.gov (United States)

    Yasunari, Kenichi; Matsui, Tokuzo; Maeda, Kensaku; Nakamura, Munehiro; Watanabe, Takanori; Kiriike, Nobuo

    2006-06-01

    An association between anxiety and depression and increased blood pressure (BP) and cardiovascular disease risk has not been firmly established. We examined the hypothesis that anxiety and depression lead to increased plasma catecholamines and to production of reactive oxygen species (ROS) by mononuclear cells (MNC) in hypertensive individuals. We also studied the role of BP in this effect. In Protocol 1, a cross-sectional study was performed in 146 hypertensive patients to evaluate whether anxiety and depression affect BP and ROS formation by MNC through increasing plasma catecholamines. In Protocol 2, a 6-month randomized controlled trial using a subtherapeutic dose of the alpha(1)-adrenergic receptor antagonist doxazosin (1 mg/day) versus placebo in 86 patients with essential hypertension was performed to determine whether the increase in ROS formation by MNC was independent of BP. In Protocol 1, a significant relationship was observed between the following: trait anxiety and plasma norepinephrine (r = 0.32, P anxiety may increase plasma norepinephrine and increase ROS formation by MNC independent of BP in hypertensive patients.

  20. Nicorandil prevents sirolimus-induced production of reactive oxygen species, endothelial dysfunction, and thrombus formation

    Directory of Open Access Journals (Sweden)

    Ken Aizawa

    2015-03-01

    Full Text Available Sirolimus (SRL is widely used to prevent restenosis after percutaneous coronary intervention. However, its beneficial effect is hampered by complications of thrombosis. Several studies imply that reactive oxygen species (ROS play a critical role in endothelial dysfunction and thrombus formation. The present study investigated the protective effect of nicorandil (NIC, an anti-angina agent, on SRL-associated thrombosis. In human coronary artery endothelial cells (HCAECs, SRL stimulated ROS production, which was prevented by co-treatment with NIC. The preventive effect of NIC on ROS was abolished by 5-hydroxydecanoate but not by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. NIC also inhibited SRL-induced up-regulation of NADPH oxidase subunit p22phox mRNA. Co-treatment with NIC and SRL significantly up-regulated superoxide dismutase 2. NIC treatment significantly improved SRL-induced decrease in viability of HCAECs. The functional relevance of the preventive effects of NIC on SRL-induced ROS production and impairment of endothelial viability was investigated in a mouse model of thrombosis. Pretreatment with NIC inhibited the SRL-induced acceleration of FeCl3-initiated thrombus formation and ROS production in the testicular arteries of mice. In conclusion, NIC prevented SRL-induced thrombus formation, presumably due to the reduction of ROS and to endothelial protection. The therapeutic efficacy of NIC could represent an additional option in the prevention of SRL-related thrombosis.

  1. The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system.

    Science.gov (United States)

    Kietzmann, Thomas; Petry, Andreas; Shvetsova, Antonina; Gerhold, Joachim M; Görlach, Agnes

    2017-06-01

    Cardiovascular diseases are among the leading causes of death worldwide. Reactive oxygen species (ROS) can act as damaging molecules but also represent central hubs in cellular signalling networks. Increasing evidence indicates that ROS play an important role in the pathogenesis of cardiovascular diseases, although the underlying mechanisms and consequences of pathophysiologically elevated ROS in the cardiovascular system are still not completely resolved. More recently, alterations of the epigenetic landscape, which can affect DNA methylation, post-translational histone modifications, ATP-dependent alterations to chromatin and non-coding RNA transcripts, have been considered to be of increasing importance in the pathogenesis of cardiovascular diseases. While it has long been accepted that epigenetic changes are imprinted during development or even inherited and are not changed after reaching the lineage-specific expression profile, it becomes more and more clear that epigenetic modifications are highly dynamic. Thus, they might provide an important link between the actions of ROS and cardiovascular diseases. This review will provide an overview of the role of ROS in modulating the epigenetic landscape in the context of the cardiovascular system. This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc. © 2017 The British Pharmacological Society.

  2. Generation of Reactive Oxygen Species via NOXa Is Important for Development and Pathogenicity of Mycosphaerella graminicola.

    Science.gov (United States)

    Choi, Yoon-E; Lee, Changsu; Goodwin, Stephen B

    2016-03-01

    The ascomycete fungus Mycosphaerella graminicola (synonym Zymoseptoria tritici) is an important pathogen of wheat causing economically significant losses. The primary nutritional mode of this fungus is thought to be hemibiotrophic. This pathogenic lifestyle is associated with an early biotrophic stage of nutrient uptake followed by a necrotrophic stage aided possibly by production of a toxin or reactive oxygen species (ROS). In many other fungi, the genes CREA and AREA are important during the biotrophic stage of infection, while the NOXa gene product is important during necrotrophic growth. To test the hypothesis that these genes are important for pathogenicity of M. graminicola, we employed an over-expression strategy for the selected target genes CREA, AREA, and NOXa, which might function as regulators of nutrient acquisition or ROS generation. Increased expressions of CREA, AREA, and NOXa in M. graminicola were confirmed via quantitative real-time PCR and strains were subsequently assayed for pathogenicity. Among them, the NOXa over-expression strain, NO2, resulted in significantly increased virulence. Moreover, instead of the usual filamentous growth, we observed a predominance of yeast-like growth of NO2 which was correlated with ROS production. Our data indicate that ROS generation via NOXa is important to pathogenicity as well as development in M. graminicola.

  3. Controllable generation of reactive oxygen species by femtosecond-laser irradiation

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

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    Akkarawut Kowitdamrong

    2013-01-01

    Full Text Available 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.

  5. (±)-2-Chloropropionic acid elevates reactive oxygen species formation in human neutrophil granulocytes

    International Nuclear Information System (INIS)

    Aam, B.B.; Fonnum, F.

    2006-01-01

    (±)-2-Chloropropionic acid (2-CPA) is a neurotoxic compound which kills cerebellar granule cells in vivo, and makes cerebellar granule cells in vitro produce reactive oxygen species (ROS). We have studied the effect of 2-CPA on ROS formation in human neutrophil granulocytes in vitro. We found an increased formation of ROS after 2-CPA exposure using three different methods; the fluorescent probe DCFH-DA and the chemiluminescent probes lucigenin and luminol. Four different inhibitors of ROS formation were tested on the cells in combination with 2-CPA to characterize the signalling pathways. The spin-trap s-PBN, the ERK1/2 inhibitor U0126 and the antioxidant Vitamin E inhibited the 2-CPA-induced ROS formation completely, while the mitochondrial transition permeability pore blocker cyclosporine A inhibited the ROS formation partly. We also found that 2-CPA induced an increased nitric oxide production in the cells by using the Griess reagent. The level of reduced glutathione, measured with the DTNB assay, was decreased after exposure to high concentrations of 2-CPA. Western blotting analysis showed that 2-CPA exposure led to an elevated phosphorylation of ERK MAP kinase. This phosphorylation was inhibited by U0126. Based on these experiments it seems like the mechanisms for 2-CPA induced toxicity involves ROS formation and is similar in neutrophil granulocytes as earlier shown in cerebellar granule cells. This also implies that 2-CPA may be immunotoxic

  6. The Effect of Reactive Oxygen Species on Embryo Quality in IVF.

    Science.gov (United States)

    Siristatidis, Charalampos; Vogiatzi, Paraskevi; Varounis, Christos; Askoxylaki, Marily; Chrelias, Charalampos; Papantoniou, Nikolaos

    2016-01-01

    BACKROUND/AIM: Reactive oxygen species (ROS) are involved in critical biological processes in human reproduction. The aim of this study was to evaluate the association of embryo quality following in vitro fertilization (IVF), with ROS levels in the serum and follicular fluid (FF). Eighty-five participants underwent ovarian stimulation and IVF; ROS levels were measured in blood samples on the day of oocyte retrieval and in the FF from follicular aspirates using enzyme-linked immunosorbent assay. These values were associated with the quality of embryos generated. Univariable zero-inflated Poisson model revealed that ROS levels at both oocyte retrieval and in FF were not associated with the number of grade I, II, III and IV embryos (p>0.05). Age, body mass index, stimulation protocol and smoking status were not associated with the number of embryos of any grade (p>0.05). Neither ROS levels in serum nor in FF are associated with the quality of embryos produced following IVF. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. Generation of reactive oxygen species from porous silicon microparticles in cell culture medium.

    Science.gov (United States)

    Low, Suet Peng; Williams, Keryn A; Canham, Leigh T; Voelcker, Nicolas H

    2010-06-01

    Nanostructured (porous) silicon is a promising biodegradable biomaterial, which is being intensively researched as a tissue engineering scaffold and drug-delivery vehicle. Here, we tested the biocompatibility of non-treated and thermally-oxidized porous silicon particles using an indirect cell viability assay. Initial direct cell culture on porous silicon determined that human lens epithelial cells only poorly adhered to non-treated porous silicon. Using an indirect cell culture assay, we found that non-treated microparticles caused complete cell death, indicating that these particles generated a toxic product in cell culture medium. In contrast, thermally-oxidized microparticles did not reduce cell viability significantly. We found evidence for the generation of reactive oxygen species (ROS) by means of the fluorescent probe 2',7'-dichlorofluorescin. Our results suggest that non-treated porous silicon microparticles produced ROS, which interacted with the components of the cell culture medium, leading to the formation of cytotoxic species. Oxidation of porous silicon microparticles not only mitigated, but also abolished the toxic effects.

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

    Science.gov (United States)

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

    2012-07-01

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

  9. Pseudomonas syringae enhances herbivory by suppressing the reactive oxygen burst in Arabidopsis.

    Science.gov (United States)

    Groen, Simon C; Humphrey, Parris T; Chevasco, Daniela; Ausubel, Frederick M; Pierce, Naomi E; Whiteman, Noah K

    2016-01-01

    Plant-herbivore interactions have evolved in the presence of plant-colonizing microbes. These microbes can have important third-party effects on herbivore ecology, as exemplified by drosophilid flies that evolved from ancestors feeding on plant-associated microbes. Leaf-mining flies in the genus Scaptomyza, which is nested within the paraphyletic genus Drosophila, show strong associations with bacteria in the genus Pseudomonas, including Pseudomonas syringae. Adult females are capable of vectoring these bacteria between plants and larvae show a preference for feeding on P. syringae-infected leaves. Here we show that Scaptomyza flava larvae can also vector P. syringae to and from feeding sites, and that they not only feed more, but also develop faster on plants previously infected with P. syringae. Our genetic and physiological data show that P. syringae enhances S. flava feeding on infected plants at least in part by suppressing anti-herbivore defenses mediated by reactive oxygen species. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Alpha-particles microbeam irradiation: impact of reactive oxygen species in bystander effect

    International Nuclear Information System (INIS)

    Hanot, M.

    2008-11-01

    Ionizing radiation-induced bystander effects arise in bystander cells that receive signals from directly irradiated cells. To date, free radicals are believed to play an active role in the bystander response, but this is incompletely characterized. To mark temporal and spatial impacts of bystander effect, we employed a precise α-particle microbeam to target a small fraction of sub-confluent osteoblastic cell cultures (MC3T3-E1). We identified the cellular membrane and mitochondria like two distinct places generating reactive oxygen species. The global oxidative stress observed after irradiation was significantly attenuated after filipin treatment, evidencing the pivotal role of membrane in MC3T3-E1 cells bystander response. To determine impact of bystander effect at a cell level, cellular consequences of this membrane-dependant bystander effect were then investigated. A variable fraction of the cell population (10 to 100%) was individually targeted. In this case, mitotic death and micronuclei yield both increased in bystander cells as well as in targeted cells demonstrating a role of bystander signals between irradiated cells in an autocrine or paracrine manner. Our results indicate a complex interaction of direct irradiation and bystander signals that lead to a membrane-dependant amplification of cell responses. (author)

  11. High salt-induced excess reactive oxygen species production resulted in heart tube malformation during gastrulation.

    Science.gov (United States)

    Gao, Lin-Rui; Wang, Guang; Zhang, Jing; Li, Shuai; Chuai, Manli; Bao, Yongping; Hocher, Berthold; Yang, Xuesong

    2018-09-01

    An association has been proved between high salt consumption and cardiovascular mortality. In vertebrates, the heart is the first functional organ to be formed. However, it is not clear whether high-salt exposure has an adverse impact on cardiogenesis. Here we report high-salt exposure inhibited basement membrane breakdown by affecting RhoA, thus disturbing the expression of Slug/E-cadherin/N-cadherin/Laminin and interfering with mesoderm formation during the epithelial-mesenchymal transition(EMT). Furthermore, the DiI + cell migration trajectory in vivo and scratch wound assays in vitro indicated that high-salt exposure restricted cell migration of cardiac progenitors, which was caused by the weaker cytoskeleton structure and unaltered corresponding adhesion junctions at HH7. Besides, down-regulation of GATA4/5/6, Nkx2.5, TBX5, and Mef2c and up-regulation of Wnt3a/β-catenin caused aberrant cardiomyocyte differentiation at HH7 and HH10. High-salt exposure also inhibited cell proliferation and promoted apoptosis. Most importantly, our study revealed that excessive reactive oxygen species(ROS)generated by high salt disturbed the expression of cardiac-related genes, detrimentally affecting the above process including EMT, cell migration, differentiation, cell proliferation and apoptosis, which is the major cause of malformation of heart tubes. © 2018 Wiley Periodicals, Inc.

  12. Phenolic extract of Dialium guineense pulp enhances reactive oxygen species detoxification in aflatoxin B₁ hepatocarcinogenesis.

    Science.gov (United States)

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

    2014-08-01

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

  13. The Role of Mitochondrial Reactive Oxygen Species in Cardiovascular Injury and Protective Strategies

    Directory of Open Access Journals (Sweden)

    Danina M. Muntean

    2016-01-01

    Full Text Available Ischaemia/reperfusion (I/R injury of the heart represents a major health burden mainly associated with acute coronary syndromes. While timely coronary reperfusion has become the established routine therapy in patients with ST-elevation myocardial infarction, the restoration of blood flow into the previously ischaemic area is always accompanied by myocardial injury. The central mechanism involved in this phenomenon is represented by the excessive generation of reactive oxygen species (ROS. Besides their harmful role when highly generated during early reperfusion, minimal ROS formation during ischaemia and/or at reperfusion is critical for the redox signaling of cardioprotection. In the past decades, mitochondria have emerged as the major source of ROS as well as a critical target for cardioprotective strategies at reperfusion. Mitochondria dysfunction associated with I/R myocardial injury is further described and ultimately analyzed with respect to its role as source of both deleterious and beneficial ROS. Furthermore, the contribution of ROS in the highly investigated field of conditioning strategies is analyzed. In the end, the vascular sources of mitochondria-derived ROS are briefly reviewed.

  14. Osimertinib induces autophagy and apoptosis via reactive oxygen species generation in non-small cell lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Zheng-Hai; Cao, Wen-Xiang; Su, Min-Xia; Chen, Xiuping; Lu, Jin-Jian, E-mail: jinjianlu@umac.mo

    2017-04-15

    Osimertinib (OSI), also known as AZD9291, is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has been approved for the treatment of non-small cell lung cancer (NSCLC) patients harboring EGFR T790M mutation. Herein, we indicated for the first time that OSI increased the accumulations of cytoplasmic vacuoles, the expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II), and the formation of GFP-LC3 puncta in various cancer cells. The OSI-induced expression of LC3-II was further increased when combined treatment with chloroquine (CQ), an autophagy inhibitor, and the mRFP-EGFP-LC3 plasmid-transfected cells exposed to OSI led to the production of more red-fluorescent puncta than green-fluorescent puncta, indicating OSI induced autophagic flux in the NSCLC cells. Knockdown of EGFR showed no effect on the OSI-induced expression of LC3-II in NCI-H1975 cells. In addition, OSI increased reactive oxygen species (ROS) generation and scavenge of ROS via pretreatment with N-acetyl-L-cysteine (NAC), catalase (CAT), or vitamin E (Vita E) significantly inhibited OSI-induced the accumulations of cytoplasmic vacuoles, the expression of LC3-II, as well as the formation of GFP-LC3 puncta. Combinative treatment with CQ could not remarkably change the OSI-induced cell viability decrease, whereas the OSI-induced cell viability decrease and apoptosis could be reversed through pretreatment with NAC, CAT, and Vita E, respectively. Taken together, this is the first report that OSI induces an accompanied autophagy and the generation of ROS is critical for the OSI-induced autophagy, cell viability decrease, and apoptosis in NSCLC cells. - Highlights: • Osimertinib induced the expressions of cytoplasmic vacuoles and autophagic markers in different cancer cells. • Osimertinib induced autophagic flux in NSCLC NCI-H1975 and HCC827 cell lines. • ROS generation contributed to osimertinib-induced cytoplasmic

  15. Osimertinib induces autophagy and apoptosis via reactive oxygen species generation in non-small cell lung cancer cells

    International Nuclear Information System (INIS)

    Tang, Zheng-Hai; Cao, Wen-Xiang; Su, Min-Xia; Chen, Xiuping; Lu, Jin-Jian

    2017-01-01

    Osimertinib (OSI), also known as AZD9291, is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has been approved for the treatment of non-small cell lung cancer (NSCLC) patients harboring EGFR T790M mutation. Herein, we indicated for the first time that OSI increased the accumulations of cytoplasmic vacuoles, the expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II), and the formation of GFP-LC3 puncta in various cancer cells. The OSI-induced expression of LC3-II was further increased when combined treatment with chloroquine (CQ), an autophagy inhibitor, and the mRFP-EGFP-LC3 plasmid-transfected cells exposed to OSI led to the production of more red-fluorescent puncta than green-fluorescent puncta, indicating OSI induced autophagic flux in the NSCLC cells. Knockdown of EGFR showed no effect on the OSI-induced expression of LC3-II in NCI-H1975 cells. In addition, OSI increased reactive oxygen species (ROS) generation and scavenge of ROS via pretreatment with N-acetyl-L-cysteine (NAC), catalase (CAT), or vitamin E (Vita E) significantly inhibited OSI-induced the accumulations of cytoplasmic vacuoles, the expression of LC3-II, as well as the formation of GFP-LC3 puncta. Combinative treatment with CQ could not remarkably change the OSI-induced cell viability decrease, whereas the OSI-induced cell viability decrease and apoptosis could be reversed through pretreatment with NAC, CAT, and Vita E, respectively. Taken together, this is the first report that OSI induces an accompanied autophagy and the generation of ROS is critical for the OSI-induced autophagy, cell viability decrease, and apoptosis in NSCLC cells. - Highlights: • Osimertinib induced the expressions of cytoplasmic vacuoles and autophagic markers in different cancer cells. • Osimertinib induced autophagic flux in NSCLC NCI-H1975 and HCC827 cell lines. • ROS generation contributed to osimertinib-induced cytoplasmic

  16. TrxR2 deficiencies promote chondrogenic differentiation and induce apoptosis of chondrocytes through mitochondrial reactive oxygen species

    International Nuclear Information System (INIS)

    Yan, Jidong; Xu, Jing; Fei, Yao; Jiang, Congshan; Zhu, Wenhua; Han, Yan; Lu, Shemin

    2016-01-01

    Thioredoxin reductase 2 (TrxR2) is a selenium (Se) containing protein. Se deficiency is associated with an endemic osteoarthropathy characterized by impaired cartilage formation. It is unclear whether TrxR2 have roles in cartilage function. We examined the effects of TrxR2 on chondrogenic ATDC5 cells through shRNA-mediated gene silencing of TrxR2. We demonstrated TrxR2 deficiencies could enhance chondrogenic differentiation and apoptosis of ATDC5 cells. TrxR2 deficiencies increased accumulation of cartilage glycosaminoglycans (GAGs) and mineralization. TrxR2 deficiencies also stimulated expression of extracellular (ECM) gene including Collagen II and Aggrecan. The enhanced chondrogenic properties were further confirmed by activation of Akt signaling which are required for chondrogenesis. In addition, TrxR2 deficiencies promoted chondrocyte proliferation through acceleration of cell cycle progression by increase in both S and G2/M phase cell distribution accompanied with induction of parathyroid hormone-related protein (PTHrP). Moreover, TrxR2 deficiencies induced chondrocyte death via apoptosis and increased cell sensitivity to exogenous oxidative stress. Furthermore, TrxR2 deficiencies induced emission of mitochondrial reactive oxygen species (ROS) without alteration of mitochondrial membrane potential and intracellular ATP content. Finally, treatment of TrxR2 deficiency cells with N-acetylcysteine (NAC) inhibited mitochondrial ROS production and chondrocyte apoptosis. NAC also prevented chondrogenic differentiation of TrxR2 deficiency cells by suppression of ECM gene expression, GAGs accumulation and mineralization, as well as attenuation of Akt signaling. Thus, TrxR2-mediated mitochondrial integrity is indispensable for chondrogenic differentiation of ATDC5 cells. TrxR2 deficiency-induced impaired proliferation and death of chondrocytes may be the pathological mechanism of the osteoarthropathy due to Se deficiency. Notably, this study also uncover the roles of

  17. TrxR2 deficiencies promote chondrogenic differentiation and induce apoptosis of chondrocytes through mitochondrial reactive oxygen species

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Jidong [Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061 (China); Xu, Jing [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061 (China); Fei, Yao [College of Life Sciences, Northwest University, Xi’an, Shaanxi Province 710069 (China); Jiang, Congshan; Zhu, Wenhua; Han, Yan [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061 (China); Lu, Shemin, E-mail: lushemin@xjtu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061 (China); Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education of China (China)

    2016-05-15

    Thioredoxin reductase 2 (TrxR2) is a selenium (Se) containing protein. Se deficiency is associated with an endemic osteoarthropathy characterized by impaired cartilage formation. It is unclear whether TrxR2 have roles in cartilage function. We examined the effects of TrxR2 on chondrogenic ATDC5 cells through shRNA-mediated gene silencing of TrxR2. We demonstrated TrxR2 deficiencies could enhance chondrogenic differentiation and apoptosis of ATDC5 cells. TrxR2 deficiencies increased accumulation of cartilage glycosaminoglycans (GAGs) and mineralization. TrxR2 deficiencies also stimulated expression of extracellular (ECM) gene including Collagen II and Aggrecan. The enhanced chondrogenic properties were further confirmed by activation of Akt signaling which are required for chondrogenesis. In addition, TrxR2 deficiencies promoted chondrocyte proliferation through acceleration of cell cycle progression by increase in both S and G2/M phase cell distribution accompanied with induction of parathyroid hormone-related protein (PTHrP). Moreover, TrxR2 deficiencies induced chondrocyte death via apoptosis and increased cell sensitivity to exogenous oxidative stress. Furthermore, TrxR2 deficiencies induced emission of mitochondrial reactive oxygen species (ROS) without alteration of mitochondrial membrane potential and intracellular ATP content. Finally, treatment of TrxR2 deficiency cells with N-acetylcysteine (NAC) inhibited mitochondrial ROS production and chondrocyte apoptosis. NAC also prevented chondrogenic differentiation of TrxR2 deficiency cells by suppression of ECM gene expression, GAGs accumulation and mineralization, as well as attenuation of Akt signaling. Thus, TrxR2-mediated mitochondrial integrity is indispensable for chondrogenic differentiation of ATDC5 cells. TrxR2 deficiency-induced impaired proliferation and death of chondrocytes may be the pathological mechanism of the osteoarthropathy due to Se deficiency. Notably, this study also uncover the roles of

  18. The effect of carbon and boron on the accumulation of vacancy-oxygen complexes in silicon

    International Nuclear Information System (INIS)

    Akhmetov, V.D.; Bolotov, V.V.

    1980-01-01

    By means of IR-absorption measurements the dose dependencies of the concentrations of vacancy-oxygen complexes (VO), interstitial oxygen atoms (Osub(I)), substitutional carbon atoms (Csub(S)) and interstitial carbon-oxygen complexes (Csub(I)Osub(I)) in n- and p-type silicon irradiated with 1.1 MeV electrons have been investigated. The observed increase of the production rate of VO-complexes with the rise of carbon and boron atoms concentrations (these impurities act as sinks for silicon interstitial atoms) has been explained in terms of annihilation of the vacancies and interstitials on the oxygen atoms. The results obtained show that boron atoms are more effective sinks than carbon atoms for the interstitial silicon atoms. That seems to be connected not only with the higher probability of boron injection into interstitial position but also with the further capture of interstitial silicon atoms on the interstitial boron, i.e. with the interstitial cluster formation. (author)

  19. Impact of plasma jet vacuum ultraviolet radiation on reactive oxygen species generation in bio-relevant liquids

    Energy Technology Data Exchange (ETDEWEB)

    Jablonowski, H.; Hammer, M. U.; Reuter, S. [Center for Innovation Competence plasmatis, Felix-Hausdorff-Str. 2, 17489 Greifswald (Germany); Leibniz Institute for Plasma Science and Technology, INP Greifswald e.V. Felix-Hausdorff-Str. 2, 17489 Greifswald (Germany); Bussiahn, R.; Weltmann, K.-D.; Woedtke, Th. von [Leibniz Institute for Plasma Science and Technology, INP Greifswald e.V. Felix-Hausdorff-Str. 2, 17489 Greifswald (Germany)

    2015-12-15

    Plasma medicine utilizes the combined interaction of plasma produced reactive components. These are reactive atoms, molecules, ions, metastable species, and radiation. Here, ultraviolet (UV, 100–400 nm) and, in particular, vacuum ultraviolet (VUV, 10–200 nm) radiation generated by an atmospheric pressure argon plasma jet were investigated regarding plasma emission, absorption in a humidified atmosphere and in solutions relevant for plasma medicine. The energy absorption was obtained for simple solutions like distilled water (dH{sub 2}O) or ultrapure water and sodium chloride (NaCl) solution as well as for more complex ones, for example, Rosewell Park Memorial Institute (RPMI 1640) cell culture media. As moderate stable reactive oxygen species, hydrogen peroxide (H{sub 2}O{sub 2}) was studied. Highly reactive oxygen radicals, namely, superoxide anion (O{sub 2}{sup •−}) and hydroxyl radicals ({sup •}OH), were investigated by the use of electron paramagnetic resonance spectroscopy. All species amounts were detected for three different treatment cases: Plasma jet generated VUV and UV radiation, plasma jet generated UV radiation without VUV part, and complete plasma jet including all reactive components additionally to VUV and UV radiation. It was found that a considerable amount of radicals are generated by the plasma generated photoemission. From the experiments, estimation on the low hazard potential of plasma generated VUV radiation is discussed.

  20. [Changes of vascular reactivity and reactive oxygen species in conditions of varying duration of permanent stay in the alienation zone in mice].

    Science.gov (United States)

    Tkachenko, M M; Kotsiuruba, A V; Baziliuk, O V; Horot', I V; Sahach, V F

    2010-01-01

    Peculiarities of changes in the vascular reactivity and in the content of reactive forms of oxygen and stable metabolites of nitric oxide (NO) were studied in the aorta preparations of C57BL/6 and BALB/c mice of the two age groups (6 and 18 mo.), which were born and permanently kept in the Chernobyl alienation zone. The results obtained showed a disturbance of acetylcholine-induced endothelium-dependent reactions of relaxation of smooth muscles of the thoracic aorta. A lower level of NO synthesis and lower level of oxidative arginase metabolism of arginine corresponded to a higher degree of damage of endothelium-dependent reactions of relaxation of the thoracic aorta smooth muscles. A decrease of NO synthesis in conditions of permanent effects of low doses of radiation was conditioned by an increase of generation of reactive forms of oxygen, namely, superoxide and hydroxyl radicals, which might be formed in mitochondria. In conditions of permanent effects of low doses of radiation a lesser level of protein nitrosothilation, same as lesser one of generation of OH-radical, corresponded to a higher level of damage of endothelium-dependent reactions.

  1. Comparative study of activities in reactive oxygen species production/defense system in mitochondria of rat brain and liver, and their susceptibility to methylmercury toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Mori, N.; Hirayama, K. [Kumamoto University, School of Health Science, Kumamoto (Japan); Yasutake, A. [National Institute for Minamata Disease, Minamata (Japan)

    2007-11-15

    The involvement of oxidative stress has been suggested as a mechanism for neurotoxicity caused by methylmercury (MeHg), but the mechanism for MeHg selective toxicity in the central nervous system is still unclear. In this research, to clarify the mechanism of selective neurotoxicity caused by MeHg, the oxygen consumption levels, the reactive oxygen species (ROS) production rates and several antioxidant levels in mitochondria were compared among the cerebrum, cerebellum and liver of male Wistar rats. In addition, the alterations of these indexes were examined in MeHg-intoxicated rats (oral administration of 10 mg/kg day, for 5 days). Although the cerebrum and cerebellum in intact rats showed higher mitochondrial oxygen consumption levels and ROS production rates than the liver, glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities were much lower in the cerebrum and cerebellum than in the liver. Especially, the cerebellum showed the highest oxygen consumption and ROS production rate and the lowest mitochondrial glutathione (GSH) levels among the tissues examined. In the MeHg-treated rats, decrease in the oxygen consumption and increase in the ROS generation were found only in the cerebellum mitochondria, despite a lower Hg accumulation in the mitochondrial fraction compared to the liver. Since MeHg treatment produced an enhancement of ROS generation in cerebellum mitochondria supplemented with succinate substrates, MeHg-induced oxidative stress might affect the complex II-III mediated pathway in the electron transfer chain in the cerebellum mitochondria. Our study suggested that inborn factors, high production system activity and low defense system activity of ROS in the brain, would relate to the high susceptibility of the central nervous system to MeHg toxicity. (orig.)

  2. Radiation-Driven Formation of Reactive Oxygen Species in Oxychlorine-Containing Mars Surface Analogues

    Science.gov (United States)

    Georgiou, Christos D.; Zisimopoulos, Dimitrios; Kalaitzopoulou, Electra; Quinn, Richard C.

    2017-04-01

    The present study demonstrates that γ-radiolyzed perchlorate-containing Mars soil salt analogues (in a CO2 atmosphere) generate upon H2O wetting the reactive oxygen species (ROS) superoxide radical (O2•-), hydrogen peroxide (H2O2), and hydroxyl radicals (•OH). This study also validates that analogue radiolysis forms oxychlorine species that, in turn, can UV-photolyze to •OH upon UV photolysis. This investigation was made possible by the development of a new assay for inorganic-origin O2•- and H2O2 determination and by the modification of a previous assay for soil •OH. Results show that radiolyzed Mg(ClO4)2 generates H2O2 and •OH; and when included as part of a mixture analogous to the salt composition of samples analyzed at the Mars Phoenix site, the analogue generated O2•-, H2O2, and •OH, with •OH levels 150-fold higher than in the radiolyzed Mg(ClO4)2 samples. Radiolyzed Mars Phoenix site salt analogue that did not contain Mg(ClO4)2 generated only •OH also at 150-fold higher concentration than Mg(ClO4)2 alone. Additionally, UV photolysis of the perchlorate γ radiolysis product chlorite (ClO2-) generated the oxychlorine products trihalide (Cl3-), chlorine dioxide (ClO2•), and hypochlorite (ClO-), with the formation of •OH by UV photolysis of ClO-. While the generation of ROS may have contributed in part to 14CO2 production in the Viking Labeled Release (LR) experiment and O2 (g) release in the Viking Gas Exchange (GEx) experiment, our results indicate that they are not likely to be the major contributor to the LR and GEx results. However, due to their highly reactive nature, they are expected to play a significant role in the alteration of organics on Mars. Additionally, experiments with hypochlorite show that the thermal stability of NaClO is in the range of the thermal stability observed for thermally liable oxidant responsible for the Viking LR results.

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

    Directory of Open Access Journals (Sweden)

    Frazer David

    2010-11-01

    Full Text Available Abstract Background Welding fumes consist of a wide range of complex metal oxide particles which can be deposited in all regions of the respiratory tract. The welding aerosol is not homogeneous and is generated mostly from the electrode/wire. Over 390,000 welders were reported in the U.S. in 2008 while over 1 million full-time welders were working worldwide. Many health effects are presently under investigation from exposure to welding fumes. Welding fume pulmonary effects have been associated with bronchitis, metal fume fever, cancer and functional changes in the lung. Our investigation focused on the generation of free radicals and reactive oxygen species from stainless and mild steel welding fumes generated by a gas metal arc robotic welder. An inhalation exposure chamber located at NIOSH was used to collect the welding fume particles. Results Our results show that hydroxyl radicals (.OH were generated from reactions with H2O2 and after exposure to cells. Catalase reduced the generation of .OH from exposed cells indicating the involvement of H2O2. The welding fume suspension also showed the ability to cause lipid peroxidation, effect O2 consumption, induce H2O2 generation in cells, and cause DNA damage. Conclusion Increase in oxidative damage observed in the cellular exposures correlated well with .OH generation in size and type of welding fumes, indicating the influence of metal type and transition state on radical production as well as associated damage. Our results demonstrate that both types of welding fumes are able to generate ROS and ROS-related damage over a range of particle sizes; however, the stainless steel fumes consistently showed a significantly higher reactivity and radical generation capacity. The chemical composition of the steel had a significant impact on the ROS generation capacity with the stainless steel containing Cr and Ni causing more damage than the mild steel. Our results suggest that welding fumes may cause acute

  4. Biocompatible ZnS:Mn quantum dots for reactive oxygen generation and detection in aqueous media

    International Nuclear Information System (INIS)

    Diaz-Diestra, Daysi; Beltran-Huarac, Juan; Bracho-Rincon, Dina P.; González-Feliciano, José A.; González, Carlos I.; Weiner, Brad R.; Morell, Gerardo

    2015-01-01

    We report here the versatility of Mn-doped ZnS quantum dots (ZnS:Mn QDs) synthesized in aqueous medium for generating reactive oxygen species and for detecting cells. Our experiments provide evidence leading to the elimination of Cd-based cores in CdSe/ZnS systems by substitution of Mn-doped ZnS. Advanced electron microscopy, X-ray diffraction, and optical spectroscopy were applied to elucidate the formation, morphology, and dispersion of the products. We study for the first time the ability of ZnS:Mn QDs to act as immobilizing agents for Tyrosinase (Tyr) enzyme. It was found that ZnS:Mn QDs show no deactivation of Tyr enzyme, which efficiently catalyzed the hydrogen peroxide (H 2 O 2 ) oxidation and its eventual reduction (−0.063 V vs. Ag/AgCl) on the biosensor surface. The biosensor showed a linear response in the range of 12 μmol/L–0.1 mmol/L at low operation potential. Our observations are explained in terms of a catalase-cycled kinetic mechanism based on the binding of H 2 O 2 to the axial position of one of the active copper sites of the oxy-Tyr during the catalase cycle to produce deoxy-Tyr. A singlet oxygen quantum yield of 0.62 in buffer and 0.54 in water was found when ZnS:Mn QDs were employed as a photosensitizer in the presence of a chemical scavenger and a standard dye. These results are consistent with a chemical trapping energy transfer mechanism. Our results also indicate that ZnS:Mn QDs are well tolerated by HeLa Cells reaching cell viabilities as high as 88 % at 300 µg/mL of QDs for 24 h of incubation. The ability of ZnS:Mn QDs as luminescent nanoprobes for bioimaging is also discussed.Graphical Abstract

  5. Interconnection of reactive oxygen species chemistry across the interfaces of atmospheric, environmental, and biological processes.

    Science.gov (United States)

    Anglada, Josep M; Martins-Costa, Marilia; Francisco, Joseph S; Ruiz-López, Manuel F

    2015-03-17

    Oxidation reactions are ubiquitous and play key roles in the chemistry of the atmosphere, in water treatment processes, and in aerobic organisms. Ozone (O3), hydrogen peroxide (H2O2), hydrogen polyoxides (H2Ox, x > 2), associated hydroxyl and hydroperoxyl radicals (HOx = OH and HO2), and superoxide and ozonide anions (O2(-) and O3(-), respectively) are the primary oxidants in these systems. They are commonly classified as reactive oxygen species (ROS). Atmospheric chemistry is driven by a complex system of chain reactions of species, including nitrogen oxides, hydroxyl and hydroperoxide radicals, alkoxy and peroxy radicals, and ozone. HOx radicals contribute to keeping air clean, but in polluted areas, the ozone concentration increases and creates a negative impact on plants and animals. Indeed, ozone concentration is used to assess air quality worldwide. Clouds have a direct effect on the chemical composition of the atmosphere. On one hand, cloud droplets absorb many trace atmospheric gases, which can be scavenged by rain and fog. On the other hand, ionic species can form in this medium, which makes the chemistry of the atmosphere richer and more complex. Furthermore, recent studies have suggested that air-cloud interfaces might have a significant impact on the overall chemistry of the troposphere. Despite the large differences in molecular composition, concentration, and thermodynamic conditions among atmospheric, environmental, and biological systems, the underlying chemistry involving ROS has many similarities. In this Account, we examine ROS and discuss the chemical characteristics common to all of these systems. In water treatment, ROS are key components of an important subset of advanced oxidation processes. Ozonation, peroxone chemistry, and Fenton reactions play important roles in generating sufficient amounts of hydroxyl radicals to purify wastewater. Biochemical processes within living organisms also involve ROS. These species can come from pollutants in

  6. Biocompatible ZnS:Mn quantum dots for reactive oxygen generation and detection in aqueous media

    Energy Technology Data Exchange (ETDEWEB)

    Diaz-Diestra, Daysi; Beltran-Huarac, Juan, E-mail: juan.beltran1@upr.edu; Bracho-Rincon, Dina P.; González-Feliciano, José A.; González, Carlos I.; Weiner, Brad R.; Morell, Gerardo [University of Puerto Rico, Molecular Sciences Research Center (United States)

    2015-12-15

    We report here the versatility of Mn-doped ZnS quantum dots (ZnS:Mn QDs) synthesized in aqueous medium for generating reactive oxygen species and for detecting cells. Our experiments provide evidence leading to the elimination of Cd-based cores in CdSe/ZnS systems by substitution of Mn-doped ZnS. Advanced electron microscopy, X-ray diffraction, and optical spectroscopy were applied to elucidate the formation, morphology, and dispersion of the products. We study for the first time the ability of ZnS:Mn QDs to act as immobilizing agents for Tyrosinase (Tyr) enzyme. It was found that ZnS:Mn QDs show no deactivation of Tyr enzyme, which efficiently catalyzed the hydrogen peroxide (H{sub 2}O{sub 2}) oxidation and its eventual reduction (−0.063 V vs. Ag/AgCl) on the biosensor surface. The biosensor showed a linear response in the range of 12 μmol/L–0.1 mmol/L at low operation potential. Our observations are explained in terms of a catalase-cycled kinetic mechanism based on the binding of H{sub 2}O{sub 2} to the axial position of one of the active copper sites of the oxy-Tyr during the catalase cycle to produce deoxy-Tyr. A singlet oxygen quantum yield of 0.62 in buffer and 0.54 in water was found when ZnS:Mn QDs were employed as a photosensitizer in the presence of a chemical scavenger and a standard dye. These results are consistent with a chemical trapping energy transfer mechanism. Our results also indicate that ZnS:Mn QDs are well tolerated by HeLa Cells reaching cell viabilities as high as 88 % at 300 µg/mL of QDs for 24 h of incubation. The ability of ZnS:Mn QDs as luminescent nanoprobes for bioimaging is also discussed.Graphical Abstract.

  7. Oxygen engineering of HfO{sub 2-x} thin films grown by reactive molecular beam epitaxy

    Energy Technology Data Exchange (ETDEWEB)

    Hildebrandt, Erwin; Kurian, Jose; Alff, Lambert [Institut fuer Materialwissenschaft, TU-Darmstadt (Germany); Zaumseil, Peter; Schroeder, Thomas [IHP, Frankfurt, Oder (Germany)

    2010-07-01

    Reactive molecular beam epitaxy (R-MBE) is an ideal tool for tailoring physical properties of thin films to specific needs. For the development of cutting-edge oxides for thin film applications a precise control of oxygen defects is crucial. R-MBE in combination with rf-activated oxygen allows reproducibly growing oxide thin films with precise oxidation conditions enabling oxygen engineering. R-MBE was used to grow Hf and HfO{sub 2{+-}}{sub x} thin films with different oxidation conditions on sapphire single crystal substrates. Structural characterization was carried out using rotating anode x-ray diffraction revealing highly textured to epitaxial thin films on c-cut sapphire. Furthermore, switching of film orientation by varying the oxidation conditions was observed demonstrating the role of oxygen in the growth procedure. The investigation of electrical properties using a four probe measurement setup showed conductivities in the range of 1000 {mu}{omega}cm for oxygen deficient HfO{sub 2-x} thin films. Optical properties were investigated using a photospectrometer and additionally x-ray photoelectron spectroscopy was carried out to study the band gap and valence states. Both techniques were used to monitor the oxygen content in deficient HfO{sub 2-x} thin films. Our results demonstrate the importance of oxygen engineering even in the case of 'simple' oxides.

  8. Effects of oxygen contents on the electrochromic properties of tungsten oxide films prepared by reactive magnetron sputtering

    International Nuclear Information System (INIS)

    Lu, H.-H.

    2008-01-01

    The electrochromism have been extensively investigated due to their potential applications such as smart window of architecture and automobile glazing to save energy and modulate the transmittance of light and solar radiation. The objective of this study is to investigate the effects of sputtering conditions on the microstructure and electrochromic properties of tungsten oxide films prepared by dc reactive magnetron sputtering. Experimental results showed that the deposition rate of WO 3-y films decreased with increasing oxygen flow rate. XRD and Raman spectra analysis suggests that the WO 3-y films deposited at various oxygen flow rates are poor crystallinity or amorphous. The transmission change between colored and bleached states at a wavelength of 550 nm was 61.4% as the oxygen content was 60%. The coloration efficiency slightly increases with increasing oxygen flow rate in the low oxygen content region and reaching a maximum value of 38.94 cm 2 /C at 60% oxygen content. In addition, the films deposited at 60% oxygen content showed a good reversibility. The effects of lithium ions intercalated on the transmission of WO 3-y films were also discussed

  9. Antioxidant enzyme expression and reactive oxygen species damage in prostatic intraepithelial neoplasia and cancer.

    Science.gov (United States)

    Bostwick, D G; Alexander, E E; Singh, R; Shan, A; Qian, J; Santella, R M; Oberley, L W; Yan, T; Zhong, W; Jiang, X; Oberley, T D

    2000-07-01

    Oxidative stress results in damage to cellular structures and has been linked to many diseases, including cancer. The authors sought to determine whether the expression of three major antioxidant enzymes, copper-zinc superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), and catalase, was altered in human prostate carcinoma and its likely precursor, high grade prostatic intraepithelial neoplasia (PIN). The level of reactive oxygen species damage was evaluated by measuring the expression of the DNA adduct 8-hydroxydeoxyguanosine. The authors evaluated the tissue expression of the antioxidant enzymes in prostate carcinoma by immunohistochemistry, immunogold electron microscopy, and enzymatic assay. The polymerase chain reaction was used to amplify and screen tissue specimens for the genes of SOD1, SOD2, and extracellular SOD (SOD3). Matched paraffin embedded tissue sections were evaluated by RNA in situ hybridization for expression of SOD1 and immunohistochemically for the DNA adduct 8-hydroxydeoxyguanosine. All prostatic tissues, including cancer, displayed immunoreactivity for the three antioxidant enzymes in epithelial cells, with no staining of the stroma, inflammatory cells, or endothelial cells. The number of immunoreactive cells was greater in benign epithelium than in PIN and cancer for each enzyme. The mean percentage and intensity of immunoreactive cells was greatest for SOD2, intermediate for SOD1, and lower for catalase. Staining in cancer was heterogeneous. Immunogold ultrasound studies revealed strong mitochondrial labeling for SOD2, which was greater in benign epithelium than in cancer; SOD1 labeling was invariably weaker, with nuclear labeling in benign epithelium and cytoplasmic labeling in cancer cells. There was no difference in enzyme activity for the three antioxidant enzymes between benign epithelium and cancer. No mutations were found in the 5 exons of SOD1, 5 exons of SOD2, and 3 exons of SOD3, except for 3 of 20 cases with

  10. AKTIVITAS REACTIVE OXYGEN SPECIES MAKROFAG AKIBAT STIMULASI GEL LIDAH BUAYA PADA INFEKSI Salmonella typhimurium

    Directory of Open Access Journals (Sweden)

    R. Susanti

    2012-09-01

    Full Text Available Reactive Oxygen Species (ROS merupakan salah satu lethal chemical yang dapatmembunuh dan mengeliminasi bakteri pada sel fagosit. Lidah Buaya (Aloevera banyak dipakai sebagai pengobatan tradisional, tetapi belum ada buktiilmiah sampai tingkat seluler apalagi subseluler dalam hal efek imunostimulanpada penyakit infeksi. Tujuan penelitian ini adalah untuk mengetahui aktivitasimunostimulan dari gel lidah buaya yang ditunjukkan oleh aktivitas ROS makrofagsecara in vivo terhadap infeksi bakteri patogen Salmonella typhimurium. Sebanyak24 ekor mencit BABL/c betina umur 8-10 minggu berat 20-30 gram dikelompokkansecara acak menjadi empat kelompok, masing-masing kelompok enam ekor.Kelompok kontrol tidak diberi gel Aloe vera, sementara kelompok P1, P2, dan P3berturut-turut diberi gel Aloe vera 0,5 ml/ekor/hari; 1,0 ml/ekor/hari, dan 1,5ml/ekor/hari. Pemberian gel Aloe vera dilakukan selama sembilan hari. Pada harike-6, mencit diinfeksi bakteri patogen Salmonella typhimurium intraperitoneal105 CFU. Selanjutnya pada hari ke-10 mencit didislokasi dan dibedah, diambilmakrofag dari peritoneum untuk dianalisis produksi ROS-nya. Hasil penelitianmenunjukkan bahwa pemberian gel Aloe vera berpengaruh signi..ikan terhadappeningkatan produksi ROS makrofag mencit BALB/c yang diinfeksi Salmonellatyphimurium. Terdapat perbedaan secara signi..ikan antara kelompok kontroldengan kelompok P1, P2, dan P3, tetapi tidak terdapat perbedaan signi..ikan antarkelompok P1, P2, dan P3. Pemberian gel Aloe vera dosis 0,5 ml/ekor/hari sudahmampu meningkatkan produksi ROS makrofag. Reactive Oxygen Species (ROS is one of lethal chemicals that can kill and eliminatebacteria in phagocytic cells. Aloe vera is widely used as traditional medicine, but thereis no scienti..ic evidence to prove the effect of immunostimulatory of the Aloe vera gel oninfectious disease in the cellular or subcellular level. This research aims to determinethe immunostimulatory activity of Aloe vera gel showed by

  11. Controlled intracellular generation of reactive oxygen species in human mesenchymal stem cells using porphyrin conjugated nanoparticles

    Science.gov (United States)

    Lavado, Andrea S.; Chauhan, Veeren M.; Alhaj Zen, Amer; Giuntini, Francesca; Jones, D. Rhodri E.; Boyle, Ross W.; Beeby, Andrew; Chan, Weng C.; Aylott, Jonathan W.

    2015-08-01

    Nanoparticles capable of generating controlled amounts of intracellular reactive oxygen species (ROS), that advance the study of oxidative stress and cellular communication, were synthesized by functionalizing polyacrylamide nanoparticles with zinc(ii) porphyrin photosensitisers. Controlled ROS production was demonstrated in human mesenchymal stem cells (hMSCs) through (1) production of nanoparticles functionalized with varying percentages of Zn(ii) porphyrin and (2) modulating the number of doses of excitation light to internalized nanoparticles. hMSCs challenged with nanoparticles functionalized with increasing percentages of Zn(ii) porphyrin and high numbers of irradiations of excitation light were found to generate greater amounts of ROS. A novel dye, which is transformed into fluorescent 7-hydroxy-4-trifluoromethyl-coumarin in the presence of hydrogen peroxide, provided an indirect indicator for cumulative ROS production. The mitochondrial membrane potential was monitored to investigate the destructive effect of increased intracellular ROS production. Flow cytometric analysis of nanoparticle treated hMSCs suggested irradiation with excitation light signalled controlled apoptotic cell death, rather than uncontrolled necrotic cell death. Increased intracellular ROS production did not induce phenotypic changes in hMSC subcultures.Nanoparticles capable of generating controlled amounts of intracellular reactive oxygen species (ROS), that advance the study of oxidative stress and cellular communication, were synthesized by functionalizing polyacrylamide nanoparticles with zinc(ii) porphyrin photosensitisers. Controlled ROS production was demonstrated in human mesenchymal stem cells (hMSCs) through (1) production of nanoparticles functionalized with varying percentages of Zn(ii) porphyrin and (2) modulating the number of doses of excitation light to internalized nanoparticles. hMSCs challenged with nanoparticles functionalized with increasing percentages of Zn

  12. Induction of Tca8113 tumor cell apoptosis by icotinib is associated with reactive oxygen species mediated p38-MAPK activation.

    Science.gov (United States)

    Yang, Cailing; Yan, Jianguo; Yuan, Guoyan; Zhang, Yinghua; Lu, Derong; Ren, Mingxin; Cui, Weigang

    2014-08-01

    Icotinib, a selective EGFR tyrosine kinase inhibitor (EGFR-TKI), has been shown to exhibit anti-tumor activity against several tumor cell lines. However, the exact molecular mechanism of icotinib's anti-tumor effect remains unknown. This study aims to examine the zytotoxic effect of icotinib on Tca8113 cells and its potential molecular mechanism. Icotinib significantly resulted in dose-dependent cell death as determined by MTT assay, accompanied by increased levels of Bax and DNA fragmentation. Icotinib could also induce Reactive Oxygen Species (ROS) generation. Further studies confirmed that scavenging of reactive oxygen species by N-acetyl-L-cysteine (NAC), and pharmacological inhibition of MAPK reversed icotinib-induced apoptosis in Tca8113 cells. Our data provide evidence that icotinib induces apoptosis, possibly via ROS-mediated MAPK pathway in Tca8113 cells.

  13. Role of xanthine oxidase and reactive oxygen intermediates in LPS- and TNF-induced pulmonary edema.

    Science.gov (United States)

    Faggioni, R; Gatti, S; Demitri, M T; Delgado, R; Echtenacher, B; Gnocchi, P; Heremans, H; Ghezzi, P

    1994-03-01

    We studied the role of reactive oxygen intermediates (ROI) in lipopolysaccharide (LPS)-induced pulmonary edema. LPS treatment (600 micrograms/mouse, IP) was associated with a marked induction of the superoxide-generating enzyme xanthine oxidase (XO) in serum and lung. Pretreatment with the antioxidant N-acetylcysteine (NAC)--1 gm/kg orally, 45 minutes before LPS--or with the XO inhibitor allopurinol (AP)--50 mg/kg orally at -1 hour and +3 hours--was protective. On the other hand nonsteroidal antiinflammatory drugs (ibuprofen, indomethacin, and nordihydroguaiaretic acid) were ineffective. These data suggested that XO might be involved in the induction of pulmonary damage by LPS. However, treatment with the interferon inducer polyriboinosylic-polyribocytidylic acid, although inducing XO to the same extent as LPS, did not cause any pulmonary edema, indicating that XO is not sufficient for this toxicity of LPS. To define the possible role of cytokines, we studied the effect of direct administration of LPS (600 micrograms/mouse, IP), tumor necrosis factor (TNF, 2.5 or 50 micrograms/mouse, IV), interleukin-1 (IL-1 beta, 2.5 micrograms/mouse, IV), interferon-gamma (IFN-gamma, 2.5 micrograms/mouse, IV), or their combination at 2.5 micrograms each. In addition to LPS, only TNF at the highest dose induced pulmonary edema 24 hours later. LPS-induced pulmonary edema was partially inhibited by anti-IFN-gamma antibodies but not by anti-TNF antibodies, anti-IL-1 beta antibodies, or IL-1 receptor antagonist (IL-1Ra).

  14. Modulation of adipocyte lipogenesis by octanoate: involvement of reactive oxygen species

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    Han Jianrong

    2006-07-01

    Full Text Available Abstract Background Octanoate is a medium-chain fatty acid (MCFA that is rich in milk and tropical dietary lipids. It also accounts for 70% of the fatty acids in commercial medium chain triglycerides (MCT. Use of MCT for weight control tracks back to early 1950s and is highlighted by recent clinical trials. The molecular mechanisms of the weight reduction effect remain not completely understood. The findings of significant amounts of MCFA in adipose tissue in MCT-fed animals and humans suggest a direct influence of MCFA on fat cell functions. Methods 3T3-L1 adipocytes were treated with octanoate in a high glucose culture medium supplemented with 10% fetal bovine serum and 170 nM insulin. The effects on lipogenesis, fatty acid oxidation, cellular concentration of reactive oxygen species (ROS, and the expression and activity of peroxisome proliferator receptor gamma (PPARγ and its associated lipogenic genes were assessed. In selected experiments, long-chain fatty acid oleate, PPARγ agonist troglitazone, and antioxidant N-acetylcysteine were used in parallel. Effects of insulin, L-carnitine, and etomoxir on β-oxidation were also measured. Results β-oxidation of octanoate was primarily independent of CPT-I. Treatment with octanoate was linked to an increase in ROS in adipocytes, a decrease in triglyceride synthesis, and reduction of lipogenic gene expression. Co-treatment with troglitazone, N-acetylcysteine, or over-expression of glutathione peroxidase largely reversed the effects of octanoate. Conclusion These findings suggest that octanoate-mediated inactivation of PPARγ might contribute to the down regulation of lipogenic genes in adipocytes, and ROS appears to be involved as a mediator in this process.

  15. Impact of hypothalamic reactive oxygen species in the control of energy metabolism and food intake

    Directory of Open Access Journals (Sweden)

    Anne eDrougard

    2015-02-01

    Full Text Available Hypothalamus is a key area involved in the control of metabolism and food intake via the integrations of numerous signals (hormones, neurotransmitters, metabolites from various origins. These factors modify hypothalamic neurons activity and generate adequate molecular and behavioral responses to control energy balance. In this complex integrative system, a new concept has been developed in recent years, that includes reactive oxygen species (ROS as a critical player in energy balance. ROS are known to act in many signaling pathways in different peripheral organs, but also in hypothalamus where they regulate food intake and metabolism by acting on different types of neurons, including proopiomelanocortin (POMC and agouti-related protein (AgRP/neuropeptide Y (NPY neurons. Hypothalamic ROS release is under the influence of different factors such as pancreatic and gut hormones, adipokines (leptin, apelin,..., neurotransmitters and nutrients (glucose, lipids,.... The sources of ROS production are multiple including NADPH oxidase, but also the mitochondria which is considered as the main ROS producer in the brain. ROS are considered as signaling molecules, but conversely impairment of this neuronal signaling ROS pathway contributes to alterations of autonomic nervous system and neuroendocrine function, leading to metabolic diseases such as obesity and type 2 diabetes.In this review we focus our attention on factors that are able to modulate hypothalamic ROS release in order to control food intake and energy metabolism, and whose deregulations could participate to the development of pathological conditions. This novel insight reveals an original mechanism in the hypothalamus that controls energy balance and identify hypothalamic ROS signaling as a potential therapeutic strategy to treat metabolic disorders.

  16. Integration of intracellular telomerase monitoring by electrochemiluminescence technology and targeted cancer therapy by reactive oxygen species.

    Science.gov (United States)

    Zhang, Huairong; Li, Binxiao; Sun, Zhaomei; Zhou, Hong; Zhang, Shusheng

    2017-12-01

    Cancer therapies based on reactive oxygen species (ROS) have emerged as promising clinical treatments. Electrochemiluminescence (ECL) technology has also attracted considerable attention in the field of clinical diagnosis. However, studies about the integration of ECL diagnosis and ROS cancer therapy are very rare. Here we introduce a novel strategy that employs ECL technology and ROS to fill the above vacancy. Briefly, an ITO electrode was electrodeposited with polyluminol-Pt NPs composite films and modified with aptamer DNA to capture HL-60 cancer cells with high specificity. After that, mesoporous silica nanoparticles (MSNs) filled with phorbol 12-myristate 13-acetate (PMA) were closed by the telomerase primer DNA (T-primer DNA) and aptamer. After aptamer on MSN@PMA recognized and combined with the HL-60 cancer cells with high specificity, T-primer DNA on MSN@PMA could be moved away from the MSN@PMA surface after extension by telomerase in the HL-60 cancer cells and PMA was released to induce the production of ROS by the HL-60 cancer cells. After that, the polyluminol-Pt NPs composite films could react with hydrogen peroxide (a major ROS) and generate an ECL signal. Thus the intracellular telomerase activity of the HL-60 cancer cells could be detected in situ . Besides, ROS could induce apoptosis in the HL-60 cancer cells with high efficacy by causing oxidative damage to the lipids, protein, and DNA. Above all, the designed platform could not only detect intracellular telomerase activity instead of that of extracted telomerase, but could also kill targeted tumors by ECL technology and ROS.

  17. Pivotal Roles of Ginsenoside Rg3 in Tumor Apoptosis Through Regulation of Reactive Oxygen Species.

    Science.gov (United States)

    Sun, Hwa Yeon; Lee, Jun Hee; Han, Yong-Seok; Yoon, Yeo Min; Yun, Chul Won; Kim, Jae Heon; Song, Yun Seob; Lee, Sang Hun

    2016-09-01

    Elevated production of reactive oxygen species (ROS) is observed in various cancer types and pathophysiological conditions. In cancer cells, ROS induce cell proliferation, genetic instability, and a malignant phenotype. Ginsenoside Rg3 is the main pharmacologically active component in ginseng and has been reported to have an antioxidant effect. To overcome lung cancer by regulating the ROS level, we investigated the antitumor effect and mechanism of Rg3 and its antioxidative property on Lewis lung carcinoma (LLC) cells. Inhibition of ROS was suppressed in LLC cells by Rg3 treatment, and these cells were used to investigate the antioxidant, antiproliferative, and antitumor effects in LLC cells. ROS production was increased in cells grown in serum-containing media (conditioned media) compared to those grown in serum-free media. The high level of ROS induced LLC cell proliferation, but treatment with Rg3 (200 ng/ml) resulted in reduction of ROS, leading to inhibition of cell proliferation. Treatment with Rg3 significantly reduced cyclin and cyclin-dependent kinase expression in LLC cells. Additionally, Rg3 treatment significantly suppressed activation of mitogen-activated protein kinases and induced LLC cell apoptosis through activation of pro-apoptotic proteins and suppression of anti-apoptotic proteins. Taken together, these findings demonstrate the role of Rg3 in reduction of the intracellular ROS level, attenuation of proliferation via augmentation of cell cycle- and cell proliferation-associated proteins, and activation of apoptosis through regulation of apoptosis-associated proteins in LLC. These findings suggest that Rg3 could be used as a therapeutic agent in lung cancer. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance

    International Nuclear Information System (INIS)

    Watanabe, Tomoyuki; Saotome, Masao; Nobuhara, Mamoru; Sakamoto, Atsushi; Urushida, Tsuyoshi; Katoh, Hideki; Satoh, Hiroshi; Funaki, Makoto; Hayashi, Hideharu

    2014-01-01

    Purpose: Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance. Methods and Results: DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨ m ) depolarization, exhibited attenuated insulin signaling and 2-deoxy-D-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H 2 O 2 ), they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨ m depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H 2 O 2 -induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨ m depolarization and impaired 2-DG uptake, however they improved insulin signaling. Conclusions: A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. - Highlights: • DRP1 promotes mitochondrial fragmentation and insulin-resistance. • A mutual enhancement between DRP1 and ROS ipromotes insulin-resistance. • Palmitate increases DRP1 expression and induces insulin-resistance. • Inhibition of DRP or ROS

  19. Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Tomoyuki [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Saotome, Masao, E-mail: msaotome@hama-med.ac.jp [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Nobuhara, Mamoru; Sakamoto, Atsushi; Urushida, Tsuyoshi; Katoh, Hideki; Satoh, Hiroshi [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Funaki, Makoto [Clinical Research Center for Diabetes, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima 770-8503 (Japan); Hayashi, Hideharu [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan)

    2014-05-01

    Purpose: Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance. Methods and Results: DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨ{sub m}) depolarization, exhibited attenuated insulin signaling and 2-deoxy-D-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H{sub 2}O{sub 2}), they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨ{sub m} depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H{sub 2}O{sub 2}-induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨ{sub m} depolarization and impaired 2-DG uptake, however they improved insulin signaling. Conclusions: A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. - Highlights: • DRP1 promotes mitochondrial fragmentation and insulin-resistance. • A mutual enhancement between DRP1 and ROS ipromotes insulin-resistance. • Palmitate increases DRP1 expression and induces insulin

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-08-24

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

  1. A high precision method for quantitative measurements of reactive oxygen species in frozen biopsies.

    Directory of Open Access Journals (Sweden)

    Kirsti Berg

    Full Text Available OBJECTIVE: An electron paramagnetic resonance (EPR technique using the spin probe cyclic hydroxylamine 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH was introduced as a versatile method for high precision quantification of reactive oxygen species, including the superoxide radical in frozen biological samples such as cell suspensions, blood or biopsies. MATERIALS AND METHODS: Loss of measurement precision and accuracy due to variations in sample size and shape were minimized by assembling the sample in a well-defined volume. Measurement was carried out at low temperature (150 K using a nitrogen flow Dewar. The signal intensity was measured from the EPR 1st derivative amplitude, and related to a sample, 3-carboxy-proxyl (CP• with known spin concentration. RESULTS: The absolute spin concentration could be quantified with a precision and accuracy better than ±10 µM (k = 1. The spin concentration of samples stored at -80°C could be reproduced after 6 months of storage well within the same error estimate. CONCLUSION: The absolute spin concentration in wet biological samples such as biopsies, water solutions and cell cultures could be quantified with higher precision and accuracy than normally achievable using common techniques such as flat cells, tissue cells and various capillary tubes. In addition; biological samples could be collected and stored for future incubation with spin probe, and also further stored up to at least six months before EPR analysis, without loss of signal intensity. This opens for the possibility to store and transport incubated biological samples with known accuracy of the spin concentration over time.

  2. PKCα promotes generation of reactive oxygen species via DUOX2 in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Wang, Jiajun; Shao, Miaomiao; Liu, Min; Peng, Peike; Li, Lili; Wu, Weicheng; Wang, Lan; Duan, Fangfang; Zhang, Mingming; Song, Shushu; Jia, Dongwei; Ruan, Yuanyuan; Gu, Jianxin

    2015-01-01

    Hepatocellular carcinoma (HCC) remains the second leading cause of cancer-related death worldwide, and elevated rates of reactive oxygen species (ROS) have long been considered as a hallmark of almost all types of cancer including HCC. Protein kinase C alpha (PKCα), a serine/threonine kinase among conventional PKC family, is recognized as a major player in signal transduction and tumor progression. Overexpression of PKCα is commonly observed in human HCC and associated with its poor prognosis. However, how PKCα is involved in hepatocellular carcinogenesis remains not fully understood. In this study, we found that among the members of conventional PKC family, PKCα, but not PKCβI or βII, promoted ROS production in HCC cells. PKCα stimulated generation of ROS by up-regulating DUOX2 at post-transcriptional level. Depletion of DUOX2 abrogated PKCα-induced activation of AKT/MAPK pathways as well as cell proliferation, migration and invasion in HCC cells. Moreover, the expression of DUOX2 and PKCα was well positively correlated in both HCC cell lines and patient samples. Collectively, our findings demonstrate that PKCα plays a critical role in HCC development by inducing DUOX2 expression and ROS generation, and propose a strategy to target PKCα/DUOX2 as a potential adjuvant therapy for HCC treatment. - Highlights: • PKCα promotes the generation of ROS in hepatocellular carcinoma. • PKCα induces ROS production by up-regulating DUOX2 at post-transcriptional level. • DUOX2 is required for PKCα-induced AKT/MAPK activation and tumor progression in HCC. • The expression of PKCα is positively correlated with DUOX2 in HCC

  3. Convergent Evolution of Pathogen Effectors toward Reactive Oxygen Species Signaling Networks in Plants.

    Science.gov (United States)

    Jwa, Nam-Soo; Hwang, Byung Kook

    2017-01-01

    Microbial pathogens have evolved protein effectors to promote virulence and cause disease in host plants. Pathogen effectors delivered into plant cells suppress plant immune responses and modulate host metabolism to support the infection processes of pathogens. Reactive oxygen species (ROS) act as cellular signaling molecules to trigger plant immune responses, such as pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity. In this review, we discuss recent insights into the molecular functions of pathogen effectors that target multiple steps in the ROS signaling pathway in plants. The perception of PAMPs by pattern recognition receptors leads to the rapid and strong production of ROS through activation of NADPH oxidase Respiratory Burst Oxidase Homologs (RBOHs) as well as peroxidases. Specific pathogen effectors directly or indirectly interact with plant nucleotide-binding leucine-rich repeat receptors to induce ROS production and the hypersensitive response in plant cells. By contrast, virulent pathogens possess effectors capable of suppressing plant ROS bursts in different ways during infection. PAMP-triggered ROS bursts are suppressed by pathogen effectors that target mitogen-activated protein kinase cascades. Moreover, pathogen effectors target vesicle trafficking or metabolic priming, leading to the suppression of ROS production. Secreted pathogen effectors block the metabolic coenzyme NADP-malic enzyme, inhibiting the transfer of electrons to the NADPH oxidases (RBOHs) responsible for ROS generation. Collectively, pathogen effectors may have evolved to converge on a common host protein network to suppress the common plant immune system, including the ROS burst and cell death response in plants.

  4. Convergent Evolution of Pathogen Effectors toward Reactive Oxygen Species Signaling Networks in Plants

    Directory of Open Access Journals (Sweden)

    Nam-Soo Jwa

    2017-09-01

    Full Text Available Microbial pathogens have evolved protein effectors to promote virulence and cause disease in host plants. Pathogen effectors delivered into plant cells suppress plant immune responses and modulate host metabolism to support the infection processes of pathogens. Reactive oxygen species (ROS act as cellular signaling molecules to trigger plant immune responses, such as pathogen-associated molecular pattern (PAMP-triggered immunity (PTI and effector-triggered immunity. In this review, we discuss recent insights into the molecular functions of pathogen effectors that target multiple steps in the ROS signaling pathway in plants. The perception of PAMPs by pattern recognition receptors leads to the rapid and strong production of ROS through activation of NADPH oxidase Respiratory Burst Oxidase Homologs (RBOHs as well as peroxidases. Specific pathogen effectors directly or indirectly interact with plant nucleotide-binding leucine-rich repeat receptors to induce ROS production and the hypersensitive response in plant cells. By contrast, virulent pathogens possess effectors capable of suppressing plant ROS bursts in different ways during infection. PAMP-triggered ROS bursts are suppressed by pathogen effectors that target mitogen-activated protein kinase cascades. Moreover, pathogen effectors target vesicle trafficking or metabolic priming, leading to the suppression of ROS production. Secreted pathogen effectors block the metabolic coenzyme NADP-malic enzyme, inhibiting the transfer of electrons to the NADPH oxidases (RBOHs responsible for ROS generation. Collectively, pathogen effectors may have evolved to converge on a common host protein network to suppress the common plant immune system, including the ROS burst and cell death response in plants.

  5. Reactive oxygen species in unstimulated hemocytes of the pacific oyster Crassostrea gigas: a mitochondrial involvement.

    Directory of Open Access Journals (Sweden)

    Ludovic Donaghy

    Full Text Available 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 (Δψ(m of hemocytes. First, this work confirmed the specificity of JC-10 probe to measure Δψ(m in oyster hemocytes, without being affected by ΔpH, 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 Δψ(m and ΔpH. 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.

  6. Electron Paramagnetic Resonance Measurements of Reactive Oxygen Species by Cyclic Hydroxylamine Spin Probes.

    Science.gov (United States)

    Dikalov, Sergey I; Polienko, Yuliya F; Kirilyuk, Igor

    2018-05-20

    Oxidative stress contributes to numerous pathophysiological conditions such as development of cancer, neurodegenerative, and cardiovascular diseases. A variety of measurements of oxidative stress markers in biological systems have been developed; however, many of these methods are not specific, can produce artifacts, and do not directly detect the free radicals and reactive oxygen species (ROS) that cause oxidative stress. Electron paramagnetic resonance (EPR) is a unique tool that allows direct measurements of free radical species. Cyclic hydroxylamines are useful and convenient molecular probes that readily react with ROS to produce stable nitroxide radicals, which can be quantitatively measured by EPR. In this work, we critically review recent applications of various cyclic hydroxylamine spin probes in biology to study oxidative stress, their advantages, and the shortcomings. Recent Advances: In the past decade, a number of new cyclic hydroxylamine spin probes have been developed and their successful application for ROS measurement using EPR has been published. These new state-of-the-art methods provide improved selectivity and sensitivity for in vitro and in vivo studies. Although cyclic hydroxylamine spin probes EPR application has been previously described, there has been lack of translation of these new methods into biomedical research, limiting their widespread use. This work summarizes "best practice" in applications of cyclic hydroxylamine spin probes to assist with EPR studies of oxidative stress. Additional studies to advance hydroxylamine spin probes from the "basic science" to biomedical applications are needed and could lead to better understanding of pathological conditions associated with oxidative stress. Antioxid. Redox Signal. 28, 1433-1443.

  7. Impact of hypothalamic reactive oxygen species in the regulation of energy metabolism and food intake.

    Science.gov (United States)

    Drougard, Anne; Fournel, Audren; Valet, Philippe; Knauf, Claude

    2015-01-01

    Hypothalamus is a key area involved in the control of metabolism and food intake via the integrations of numerous signals (hormones, neurotransmitters, metabolites) from various origins. These factors modify hypothalamic neurons activity and generate adequate molecular and behavioral responses to control energy balance. In this complex integrative system, a new concept has been developed in recent years, that includes reactive oxygen species (ROS) as a critical player in energy balance. ROS are known to act in many signaling pathways in different peripheral organs, but also in hypothalamus where they regulate food intake and metabolism by acting on different types of neurons, including proopiomelanocortin (POMC) and agouti-related protein (AgRP)/neuropeptide Y (NPY) neurons. Hypothalamic ROS release is under the influence of different factors such as pancreatic and gut hormones, adipokines (leptin, apelin,…), neurotransmitters and nutrients (glucose, lipids,…). The sources of ROS production are multiple including NADPH oxidase, but also the mitochondria which is considered as the main ROS producer in the brain. ROS are considered as signaling molecules, but conversely impairment of this neuronal signaling ROS pathway contributes to alterations of autonomic nervous system and neuroendocrine function, leading to metabolic diseases such as obesity and type 2 diabetes. In this review we focus our attention on factors that are able to modulate hypothalamic ROS release in order to control food intake and energy metabolism, and whose deregulations could participate to the development of pathological conditions. This novel insight reveals an original mechanism in the hypothalamus that controls energy balance and identify hypothalamic ROS signaling as a potential therapeutic strategy to treat metabolic disorders.

  8. Iron and Reactive Oxygen Species: Friends or Foes of Cancer Cells?

    Science.gov (United States)

    Bystrom, Laura M.

    2014-01-01

    Abstract Significance: In this review, the dual nature of both iron and reactive oxygen species (ROS) will be explored in normal and cancer cell metabolism. Although iron and ROS play important roles in cellular homeostasis, they may also contribute to carcinogenesis. On the other hand, many studies have indicated that abrogation of iron metabolism, elevation of ROS, or modification of redox regulatory mechanisms in cancer cells, should be considered as therapeutic approaches for cancer. Recent Advances: Drugs that target different aspects of iron metabolism may be promising therapeutics for cancer. The ability of iron chelators to cause iron depletion and/or elevate ROS levels indicates that these types of compounds have more potential as antitumor medicines than originally expected. Other natural and synthetic compounds that target pathways involved in ROS homeostasis also have potential value alone or in combination with current chemotherapeutics. Critical Issues: Although ROS induction and iron depletion may be targets for cancer therapies, the optimal therapeutic strategies have yet to be identified. This review highlights some of the research that strives to identify such therapeutics. Future Directions: More studies are needed to better understand the role of iron and ROS in carcinogenesis not only as cancer promoters, but also as cytotoxic agents to cancer cells and cancer stem cells (CSCs). Moreover, the structure–activity effects of iron chelators and other compounds that increase ROS and/or disrupt iron metabolism need to be further evaluated to assess the effectiveness and selectivity of these compounds against both cancer and CSCs. Antioxid. Redox Signal. 20, 1917–1924. PMID:23198911

  9. Live Candida albicans Suppresses Production of Reactive Oxygen Species in Phagocytes▿ †

    Science.gov (United States)

    Wellington, Melanie; Dolan, Kristy; Krysan, Damian J.

    2009-01-01

    Production of reactive oxygen species (ROS) is an important aspect of phagocyte-mediated host responses. Since phagocytes play a crucial role in the host response to Candida albicans, we examined the ability of Candida to modulate phagocyte ROS production. ROS production was measured in the murine macrophage cell line J774 and in primary phagocytes using luminol-enhanced chemiluminescence. J774 cells, murine polymorphonuclear leukocytes (PMN), human monocytes, and human PMN treated with live C. albicans produced significantly less ROS than phagocytes treated with heat-killed C. albicans. Live C. albicans also suppressed ROS production in murine bone marrow-derived macrophages from C57BL/6 mice, but not from BALB/c mice. Live C. albicans also suppressed ROS in response to external stimuli. C. albicans and Candida glabrata suppressed ROS production by phagocytes, whereas Saccharomyces cerevisiae stimulated ROS production. The cell wall is the initial point of contact between Candida and phagocytes, but isolated cell walls from both heat-killed and live C. albicans stimulated ROS production. Heat-killed C. albicans has increased surface exposure of 1,3-β-glucan, a cell wall component that can stimulate phagocytes. To determine whether surface 1,3-β-glucan exposure accounted for the difference in ROS production, live C. albicans cells were treated with a sublethal dose of caspofungin to increase surface 1,3-β-glucan exposure. Caspofungin-treated C. albicans was fully able to suppress ROS production, indicating that suppression of ROS overrides stimulatory signals from 1,3-β-glucan. These studies indicate that live C. albicans actively suppresses ROS production in phagocytes in vitro, which may represent an important immune evasion mechanism. PMID:18981256

  10. Induction of apoptosis by plumbagin through reactive oxygen species-mediated inhibition of topoisomerase II

    International Nuclear Information System (INIS)

    Kawiak, Anna; Piosik, Jacek; Stasilojc, Grzegorz; Gwizdek-Wisniewska, Anna; Marczak, Lukasz; Stobiecki, Maciej; Bigda, Jacek; Lojkowska, Ewa

    2007-01-01

    Reactive oxygen species (ROS) have been recognized as key molecules, which can selectively modify proteins and therefore regulate cellular signalling including apoptosis. Plumbagin, a naphthoquinone exhibiting antitumor activity, is known to generate ROS and has been found to inhibit the activity of topoisomerase II (Topo II) through the stabilization of the Topo II-DNA cleavable complex. The objective of this research was to clarify the role of ROS and Topo II inhibition in the induction of apoptosis mediated by plumbagin. As determined by the comet assay, plumbagin induced DNA cleavage in HL-60 cells, whereas in a cell line with reduced Topo II activity-HL-60/MX2, the level of DNA damage was significantly decreased. The onset of DNA strand break formation in HL-60 cells was delayed in comparison with the generation of intracellular ROS. In HL-60/MX2 cells, ROS were generated at a similar rate, whereas a significant reduction in the level of DNA damage was detected. The pretreatment of cells with N-acetylcysteine (NAC) attenuated plumbagin-induced DNA damage, pointing out to the involvement of ROS generation in cleavable complex formation. These results suggest that plumbagin-induced ROS does not directly damage DNA but requires the involvement of Topo II. Furthermore, experiments carried out using light spectroscopy indicated no direct interactions between plumbagin and DNA. The induction of apoptosis was significantly delayed in HL-60/MX2 cells indicating the involvement of Topo II inhibition in plumbagin-mediated apoptosis. Thus, these findings strongly suggest ROS-mediated inhibition of Topo II as an important mechanism contributing to the apoptosis-inducing properties of plumbagin

  11. Low Po2 conditions induce reactive oxygen species formation during contractions in single skeletal muscle fibers

    Science.gov (United States)

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

    2013-01-01

    Contractions in whole skeletal muscle during hypoxia are known to generate reactive oxygen species (ROS); however, identification of real-time ROS formation within isolated single skeletal muscle fibers has been challenging. Consequently, there is no convincing evidence showing increased ROS production in intact contracting fibers under low Po2 conditions. Therefore, we hypothesized that intracellular ROS generation in single contracting skeletal myofibers increases during low Po2 compared with a value approximating normal resting Po2. Dihydrofluorescein was loaded into single frog (Xenopus) fibers, and fluorescence was used to monitor ROS using confocal microscopy. Myofibers were exposed to two maximal tetanic contractile periods (1 contraction/3 s for 2 min, separated by a 60-min rest period), each consisting of one of the following treatments: high Po2 (30 Torr), low Po2 (3–5 Torr), high Po2 with ebselen (antioxidant), or low Po2 with ebselen. Ebselen (10 μM) was administered before the designated contractile period. ROS formation during low Po2 treatment was greater than during high Po2 treatment, and ebselen decreased ROS generation in both low- and high-Po2 conditions (P Po2. Force was reduced >30% for each condition except low Po2 with ebselen, which only decreased ∼15%. We concluded that single myofibers under low Po2 conditions develop accelerated and more oxidative stress than at Po2 = 30 Torr (normal human resting Po2). Ebselen decreases ROS formation in both low and high Po2, but only mitigates skeletal muscle fatigue during reduced Po2 conditions. PMID:23576612

  12. Effect of magnesium on reactive oxygen species production in the thigh muscles of broiler chickens.

    Science.gov (United States)

    Liu, Y X; Guo, Y M; Wang, Z

    2007-02-01

    1. The objective of the present study was to investigate the effect of magnesium (Mg) on reactive oxygen species (ROS) production in the thigh muscles of broiler chickens. A total of 96 1-d-old male Arbor Acre broiler chickens were randomly allocated into two groups, fed either on low-Mg or control diets containing about 1.2 g/kg or 2.4 g Mg/kg dry matter. 2. The low-Mg diet significantly increased malondialdehyde (MDA) concentration and decreased glutathione (GSH) in the thigh muscles of broiler chickens. ROS production in the thigh muscle homogenate was significantly higher in the low-Mg group than in the control group. Compared with the control, muscle Mg concentration of broiler chickens from the low-Mg group decreased by 9.5%. 3. Complex II and III activities of the mitochondrial electron transport chain in broilers on low-Mg diet increased by 23 and 35%, respectively. Significant negative correlations between ROS production and the activities of mitochondrial electron transport chain (ETC) complexes were observed. 4. The low-Mg diet did not influence contents of iron (Fe) or calcium (Ca) in the thigh muscles of broiler chickens and did not influence unsaturated fatty acid composition (except C18:2) in the thigh muscles. 5. A low-Mg diet decreased Mg concentration in the thigh muscles of broiler chickens and then induced higher activities of mitochondrial ETC, consequently increasing ROS production. These results suggest that Mg modulates the oxidation-anti-oxidation system of the thigh muscles at least partly through affecting ROS production.

  13. Modulation of Neutrophil Extracellular Trap and Reactive Oxygen Species Release by Periodontal Bacteria.

    Science.gov (United States)

    Hirschfeld, Josefine; White, Phillipa C; Milward, Michael R; Cooper, Paul R; Chapple, Iain L C

    2017-12-01

    Oral bacteria are the main trigger for the development of periodontitis, and some species are known to modulate neutrophil function. This study aimed to explore the release of neutrophil extracellular traps (NETs), associated antimicrobial proteins, and reactive oxygen species (ROS) in response to periodontal bacteria, as well as the underlying pathways. Isolated peripheral blood neutrophils were stimulated with 19 periodontal bacteria. NET and ROS release, as well as the expression of NET-bound antimicrobial proteins, elastase, myeloperoxidase, and cathepsin G, in response to these species was measured using fluorescence-based assays. NET and ROS release was monitored after the addition of NADP (NADPH) oxidase pathway modulators and inhibitors of Toll-like receptors (TLRs). Moreover, bacterial entrapment by NETs was visualized microscopically, and bacterial killing was assessed by bacterial culture. Certain microorganisms, e.g., Veillonella parvula and Streptococcus gordonii , stimulated higher levels of ROS and NET release than others. NETs were found to entrap, but not kill, all periodontal bacteria tested. NADPH oxidase pathway modulators decreased ROS production but not NET production in response to the bacteria. Interestingly, TLR inhibitors did not impact ROS and NET release. These data suggest that the variability in the neutrophil response toward different bacteria may contribute to the pathogenesis of periodontal diseases by mechanisms such as bacterial avoidance of host responses and activation of neutrophils. Moreover, our results indicate that bacterium-stimulated NET release may arise in part via NADPH oxidase-independent mechanisms. The role of TLR signaling in bacterium-induced ROS and NET release needs to be further elucidated. Copyright © 2017 American Society for Microbiology.

  14. Green synthesized silver nanoparticles destroy multidrug resistant bacteria via reactive oxygen species mediated membrane damage

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    Balaram Das

    2017-09-01

    Full Text Available The growing need of antimicrobial agent for novel therapies against multi-drug resistant bacteria has drawn researchers to green nanotechnology. Especially, eco-friendly biosynthesis of silver nanoparticles (Ag NPs has shown its interesting impact against bacterial infection in laboratory research. In this study, a simple method was developed to form Ag NPs at room temperature, bio-reduction of silver ions from silver nitrate salt by leaf extract from Ocimum gratissimum. The Ag NPs appear to be capped with plant proteins, but are otherwise highly crystalline and pure. The Ag NPs have a zeta potential of −15 mV, a hydrodynamic diameter of 31 nm with polydispersity index of 0.65, and dry sizes of 18 ± 3 nm and 16 ± 2 nm, based on scanning and transmission electron microscopy respectively. The minimum inhibitory concentration (MIC of the Ag NPs against a multi-drug resistant Escherichia coli was 4 μg/mL and the minimum bactericidal concentration (MBC was 8 μg/mL, while the MIC and MBC against a resistant strain of Staphylococcus aureus were slightly higher at 8 μg/mL and 16 μg/mL respectively. Further, the Ag NPs inhibited biofilm formation by both Escherichia coli and S. aureus at concentrations similar to the MIC for each strain. Treatment of E. coli and S. aureus with Ag NPs resulted in damage to the surface of the cells and the production of reactive oxygen species. Both mechanisms likely contribute to bacterial cell death. In summary, this new method appears promising for green biosynthesis of pure Ag NPs with potent antimicrobial activity.

  15. Reactive oxygen species mediate TNFR1 increase after TRPV1 activation in mouse DRG neurons

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    Westlund Karin N

    2009-06-01

    Full Text Available Abstract Background Transient receptor potential vanilloid subtype 1 (TRPV1 is activated by low pH/protons and is well known to be involved in hyperalgesia during inflammation. Tumor necrosis factor α (TNF-α, a proinflammatory cytokine, is involved in nociceptive responses causing hyperalgesia through TNF receptor type 1 (TNFR1 activation. Reactive oxygen species (ROS production is also prominently increased in inflamed tissue. The present study investigated TNFR1 receptors in primary cultured mouse dorsal root ganglion (DRG neurons after TRPV1 activation and the involvement of ROS. C57BL/6 mice, both TRPV1 knockout and wild type, were used for immunofluorescent and live cell imaging. The L4 and L5 DRGs were dissected bilaterally and cultured overnight. TRPV1 was stimulated with capsaicin or its potent analog, resiniferatoxin. ROS production was measured with live cell imaging and TNFR1 was detected with immunofluorescence in DRG primary cultures. The TRPV1 knockout mice, TRPV1 antagonist, capsazepine, and ROS scavenger, N-tert-Butyl-α-phenylnitrone (PBN, were employed to explore the functional relationship among TRPV1, ROS and TNFR1 in these studies. Results The results demonstrate that TRPV1 activation increases TNFR1 receptors and ROS generation in primary cultures of mouse DRG neurons. Activated increases in TNFR1 receptors and ROS production are absent in TRPV1 deficient mice. The PBN blocks increases in TNFR1 and ROS production induced by capsaicin/resiniferatoxin. Conclusion TRPV1 activation increases TNFR1 in cultured mouse DRG neurons through a ROS signaling pathway, a novel sensitization mechanism in DRG neurons.

  16. Longevity of animals under reactive oxygen species stress and disease susceptibility due to global warming

    Science.gov (United States)

    Paital, Biswaranjan; Panda, Sumana Kumari; Hati, Akshaya Kumar; Mohanty, Bobllina; Mohapatra, Manoj Kumar; Kanungo, Shyama; Chainy, Gagan Bihari Nityananda

    2016-01-01

    The world is projected to experience an approximate doubling of atmospheric CO2 concentration in the next decades. Rise in atmospheric CO2 level as one of the most important reasons is expected to contribute to raise the mean global temperature 1.4 °C-5.8 °C by that time. A survey from 128 countries speculates that global warming is primarily due to increase in atmospheric CO2 level that is produced mainly by anthropogenic activities. Exposure of animals to high environmental temperatures is mostly accompanied by unwanted acceleration of certain biochemical pathways in their cells. One of such examples is augmentation in generation of reactive oxygen species (ROS) and subsequent increase in oxidation of lipids, proteins and nucleic acids by ROS. Increase in oxidation of biomolecules leads to a state called as oxidative stress (OS). Finally, the increase in OS condition induces abnormality in physiology of animals under elevated temperature. Exposure of animals to rise in habitat temperature is found to boost the metabolism of animals and a very strong and positive correlation exists between metabolism and levels of ROS and OS. Continuous induction of OS is negatively correlated with survivability and longevity and positively correlated with ageing in animals. Thus, it can be predicted that continuous exposure of animals to acute or gradual rise in habitat temperature due to global warming may induce OS, reduced survivability and longevity in animals in general and poikilotherms in particular. A positive correlation between metabolism and temperature in general and altered O2 consumption at elevated temperature in particular could also increase the risk of experiencing OS in homeotherms. Effects of global warming on longevity of animals through increased risk of protein misfolding and disease susceptibility due to OS as the cause or effects or both also cannot be ignored. Therefore, understanding the physiological impacts of global warming in relation to

  17. Pentose Phosphate Shunt Modulates Reactive Oxygen Species and Nitric Oxide Production Controlling Trypanosoma cruzi in Macrophages

    Directory of Open Access Journals (Sweden)

    Sue-jie Koo

    2018-02-01

    Full Text Available Metabolism provides substrates for reactive oxygen species (ROS and nitric oxide (NO generation, which are a part of the macrophage (Mφ anti-microbial response. Mφs infected with Trypanosoma cruzi (Tc produce insufficient levels of oxidative species and lower levels of glycolysis compared to classical Mφs. How Mφs fail to elicit a potent ROS/NO response during infection and its link to glycolysis is unknown. Herein, we evaluated for ROS, NO, and cytokine production in the presence of metabolic modulators of glycolysis and the Krebs cycle. Metabolic status was analyzed by Seahorse Flux Analyzer and mass spectrometry and validated by RNAi. Tc infection of RAW264.7 or bone marrow-derived Mφs elicited a substantial increase in peroxisome proliferator-activated receptor (PPAR-α expression and pro-inflammatory cytokine release, and moderate levels of ROS/NO by 18 h. Interferon (IFN-γ addition enhanced the Tc-induced ROS/NO release and shut down mitochondrial respiration to the levels noted in classical Mφs. Inhibition of PPAR-α attenuated the ROS/NO response and was insufficient for complete metabolic shift. Deprivation of glucose and inhibition of pyruvate transport showed that Krebs cycle and glycolysis support ROS/NO generation in Tc + IFN-γ stimulated Mφs. Metabolic profiling and RNAi studies showed that glycolysis-pentose phosphate pathway (PPP at 6-phosphogluconate dehydrogenase was essential for ROS/NO response and control of parasite replication in Mφ. We conclude that IFN-γ, but not inhibition of PPAR-α, supports metabolic upregulation of glycolytic-PPP for eliciting potent ROS/NO response in Tc-infected Mφs. Chemical analogs enhancing the glucose-PPP will be beneficial in controlling Tc replication and dissemination by Mφs.

  18. Curcumin-induced inhibition of cellular reactive oxygen species generation: novel therapeutic implications.

    Science.gov (United States)

    Balasubramanyam, M; Koteswari, A Adaikala; Kumar, R Sampath; Monickaraj, S Finny; Maheswari, J Uma; Mohan, V

    2003-12-01

    There is evidence for increased levels of circulating reactive oxygen species (ROS) in diabetics, as indirectly inferred by the findings of increased lipid peroxidation and decreased antioxidant status. Direct measurements of intracellular generation of ROS using fluorescent dyes also demonstrate an association of oxidative stress with diabetes. Although phenolic compounds attenuate oxidative stress-related tissue damage, there are concerns over toxicity of synthetic phenolic antioxidants and this has considerably stimulated interest in investigating the role of natural phenolics in medicinal applications. Curcumin (the primary active principle in turmeric, Curcuma longa Linn.) has been claimed to represent a potential antioxidant and antiinflammatory agent with phytonutrient and bioprotective properties. However there are lack of molecular studies to demonstrate its cellular action and potential molecular targets. In this study the antioxidant effect of curcumin as a function of changes in cellular ROS generation was tested. Our results clearly demonstrate that curcumin abolished both phorbol-12 myristate-13 acetate (PMA) and thapsigargin-induced ROS generation in cells from control and diabetic subjects. The pattern of these ROS inhibitory effects as a function of dose-dependency suggests that curcumin mechanistically interferes with protein kinase C (PKC) and calcium regulation. Simultaneous measurements of ROS and Ca2+ influx suggest that a rise in cytosolic Ca2+ may be a trigger for increased ROS generation. We suggest that the antioxidant and antiangeogenic actions of curcumin, as a mechanism of inhibition of Ca2+ entry and PKC activity, should be further exploited to develop suitable and novel drugs for the treatment of diabetic retinopathy and other diabetic complications.

  19. PKCα promotes generation of reactive oxygen species via DUOX2 in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiajun; Shao, Miaomiao; Liu, Min; Peng, Peike; Li, Lili; Wu, Weicheng; Wang, Lan [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Duan, Fangfang [Institute of Biomedical Science, Fudan University, Shanghai (China); Zhang, Mingming; Song, Shushu [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Jia, Dongwei, E-mail: jiadongwei@fudan.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Ruan, Yuanyuan, E-mail: yuanyuanruan@fudan.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Institute of Biomedical Science, Fudan University, Shanghai (China)

    2015-08-07

    Hepatocellular carcinoma (HCC) remains the second leading cause of cancer-related death worldwide, and elevated rates of reactive oxygen species (ROS) have long been considered as a hallmark of almost all types of cancer including HCC. Protein kinase C alpha (PKCα), a serine/threonine kinase among conventional PKC family, is recognized as a major player in signal transduction and tumor progression. Overexpression of PKCα is commonly observed in human HCC and associated with its poor prognosis. However, how PKCα is involved in hepatocellular carcinogenesis remains not fully understood. In this study, we found that among the members of conventional PKC family, PKCα, but not PKCβI or βII, promoted ROS production in HCC cells. PKCα stimulated generation of ROS by up-regulating DUOX2 at post-transcriptional level. Depletion of DUOX2 abrogated PKCα-induced activation of AKT/MAPK pathways as well as cell proliferation, migration and invasion in HCC cells. Moreover, the expression of DUOX2 and PKCα was well positively correlated in both HCC cell lines and patient samples. Collectively, our findings demonstrate that PKCα plays a critical role in HCC development by inducing DUOX2 expression and ROS generation, and propose a strategy to target PKCα/DUOX2 as a potential adjuvant therapy for HCC treatment. - Highlights: • PKCα promotes the generation of ROS in hepatocellular carcinoma. • PKCα induces ROS production by up-regulating DUOX2 at post-transcriptional level. • DUOX2 is required for PKCα-induced AKT/MAPK activation and tumor progression in HCC. • The expression of PKCα is positively correlated with DUOX2 in HCC.

  20. Sites of reactive oxygen species generation by mitochondria oxidizing different substrates

    Directory of Open Access Journals (Sweden)

    Casey L. Quinlan

    2013-01-01

    Full Text Available Mitochondrial radical production is important in redox signaling, aging and disease, but the relative contributions of different production sites are poorly understood. We analyzed the rates of superoxide/H2O2 production from different defined sites in rat skeletal muscle mitochondria oxidizing a variety of conventional substrates in the absence of added inhibitors: succinate; glycerol 3-phosphate; palmitoylcarnitine plus carnitine; or glutamate plus malate. In all cases, the sum of the estimated rates accounted fully for the measured overall rates. There were two striking results. First, the overall rates differed by an order of magnitude between substrates. Second, the relative contribution of each site was very different with different substrates. During succinate oxidation, most of the superoxide production was from the site of quinone reduction in complex I (site IQ, with small contributions from the flavin site in complex I (site IF and the quinol oxidation site in complex III (site IIIQo. However, with glutamate plus malate as substrate, site IQ made little or no contribution, and production was shared between site IF, site IIIQo and 2-oxoglutarate dehydrogenase. With palmitoylcarnitine as substrate, the flavin site in complex II (site IIF was a major contributor (together with sites IF and IIIQo, and with glycerol 3-phosphate as substrate, five different sites all contributed, including glycerol 3-phosphate dehydrogenase. Thus, the relative and absolute contributions of specific sites to the production of reactive oxygen species in isolated mitochondria depend very strongly on the substrates being oxidized, and the same is likely true in cells and in vivo.

  1. Salicylic Acid Alleviates Aluminum Toxicity in Soybean Roots through Modulation of Reactive Oxygen Species Metabolism

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    Ning Liu

    2017-11-01

    Full Text Available As an important signal molecule, salicylic acid (SA improves plant tolerance to aluminum (Al stress. The objective of this study was to investigate the effects of exogenous SA application on the dynamics of endogenous SA and reactive oxygen species in soybean (Glycine max L. exposed to Al stress. The roots of soybean seedlings were exposed to a combination of AlCl3 (30 μM and SA (10 μM/PAC (100 μM, paclobutrazol, SA biosynthesis inhibitor for 3, 6, 9, and 12 h. Al stress induced an increase in endogenous SA concentration in a time-dependent manner, also verified by the up-regulated expression of GmNPR1, an SA-responsive gene. Al stress increased the activities of phenylalanine ammonia-lyase (PAL and benzoic acid 2-hydroxylase (BA2H, and the contents of SA, O2- and malondialdehyde (MDA in the root apex. The application of exogenous SA increased PAL and BA2H, and reduced O2- and MDA contents in soybean roots under Al stress. PAC inhibited the SA induced increase in BA2H activity. In addition, the SA application resulted in a rapid increase in hydrogen peroxide (H2O2 concentration under Al stress, followed by a sharp decrease. Compared with the plants exposed to Al alone, Al+SA plants possessed higher activities of superoxide dismutase, peroxidase, and ascorbate peroxidase, and lower catalase activity, indicating that SA alleviated Al-induced oxidative damage. These results suggested that PAL and BA2H were involved in Al-induced SA production and showed that SA alleviated the adverse effects of Al toxicity by modulating the cellular H2O2 level and the antioxidant enzyme activities in the soybean root apex.

  2. Vascular smooth muscle modulates endothelial control of vasoreactivity via reactive oxygen species production through myoendothelial communications.

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    Marie Billaud

    Full Text Available BACKGROUND: Endothelial 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 SMC to endothelial control of vasomotor tone. METHODOLOGY/PRINCIPAL FINDINGS: In small intrapulmonary arteries, quantitative RT-PCR, Western Blot analyses and immunofluorescent labeling evidenced connexin (Cx 37, 40 and 43 in EC and/or SMC. Functional experiments showed that the Cx-mimetic peptide targeted against Cx 37 and Cx 43 ((37,43Gap27 (1 reduced contractile and calcium responses to serotonin (5-HT simultaneously recorded in pulmonary arteries and (2 abolished the diffusion in SMC of carboxyfluorescein-AM loaded in EC. Similarly, contractile and calcium responses to 5-HT were decreased by superoxide dismutase and catalase which, catabolise superoxide anion and H(2O(2, respectively. Both Cx- and ROS-mediated effects on the responses to 5-HT were reversed by L-NAME, a NO synthase inhibitor or endothelium removal. Electronic paramagnetic resonance directly demonstrated that 5-HT-induced superoxide anion production originated from the SMC. Finally, whereas 5-HT increased NO production, it also decreased cyclic GMP content in isolated intact arteries. CONCLUSIONS/SIGNIFICANCE: These data demonstrate that agonist-induced ROS production in SMC targeting EC via myoendothelial gap junctions reduces endothelial NO-dependent control of pulmonary vasoreactivity. Such SMC modulation of endothelial control may represent a signaling pathway controlling vasoreactivity under not only physiological but also pathological conditions that often implicate excessive ROS production.

  3. Reactive oxygen species are crucial for hydroxychavicol toxicity toward KB epithelial cells.

    Science.gov (United States)

    Jeng, J H; Wang, Y J; Chang, W H; Wu, H L; Li, C H; Uang, B J; Kang, J J; Lee, J J; Hahn, L J; Lin, B R; Chang, M C

    2004-01-01

    Betel quid (BQ) chewing shows a strong correlation to the incidence of oral submucous fibrosis (OSF), leukoplakia and oral cancer. BQ contains mainly areca nut, lime, Piper betle leaf (PBL) and the inflorescence of P. betle (IPB). Hydroxychavicol (4-allyl-catechol, HC), as a major phenolic compound in PBL and IPB, is shown to induce oxidative stress, glutathione (GSH) depletion and cell cycle deregulation. Using bivariate BrdU/PI flow cytometry, KB cells in DNA synthesis (S phase) are shown to be sensitive to the toxic effect of HC and show cell cycle arrest and apoptosis following exposure to 0.1 and 0.3 mM HC. HC-induced apoptosis and cell cycle arrest are associated with mitochondrial membrane potential (delta Psim) depolarization as revealed by a decrease in rhodamine fluorescence. N-acetyl-L-cysteine (1 mM), superoxide dismutase (100 U/ml) and catalase (1000 U/ml) were effective in prevention of HC-induced GSH depletion (as indicated by chloromethylfluorescein fluorescence), reactive oxygen species (ROS) production (by dichlorofluorescein fluorescence), cell cycle arrest and apoptosis. However, dimethylthiourea (2 mM), neocuproine (1 mM), 1,10-phenanthroline (200 microM) and desferrioxamine (0.5 mM) showed little effect on HC-induced cell changes. HC elevated the cellular and mitochondrial GSH levels at moderate concentrations (0.05-0.1 mM), whereas at a concentration of 0.3 mM, inhibitory effects were noted. These results indicate that HC consumption may be associated with BQ-chewing-related oral mucosal diseases via GSH depletion, ROS production, mitochondrial dysfunction, cell cycle disturbance and the induction of apoptosis. These events are related to the production of superoxide radicals and hydrogen peroxide.

  4. Global inhibition of reactive oxygen species (ROS inhibits paclitaxel-induced painful peripheral neuropathy.

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    Mehmet Fidanboylu

    Full Text Available Paclitaxel (Taxol® is a widely used chemotherapeutic agent that has a major dose limiting side-effect of painful peripheral neuropathy. Currently there is no effective therapy for the prevention or treatment of chemotherapy-induced painful peripheral neuropathies. Evidence for mitochondrial dysfunction during paclitaxel-induced pain was previously indicated with the presence of swollen and vacuolated neuronal mitochondria. As mitochondria are a major source of reactive oxygen species (ROS, the aim of this study was to examine whether pharmacological inhibition of ROS could reverse established paclitaxel-induced pain or prevent the development of paclitaxel-induced pain. Using a rat model of paclitaxel-induced pain (intraperitoneal 2 mg/kg paclitaxel on days 0, 2, 4 & 6, the effects of a non-specific ROS scavenger, N-tert-Butyl-α-phenylnitrone (PBN and a superoxide selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL were compared. Systemic 100 mg/kg PBN administration markedly inhibited established paclitaxel-induced mechanical hypersensitivity to von Frey 8 g and 15 g stimulation and cold hypersensitivity to plantar acetone application. Daily systemic administration of 50 mg/kg PBN (days -1 to 13 completely prevented mechanical hypersensitivity to von Frey 4 g and 8 g stimulation and significantly attenuated mechanical hypersensitivity to von Frey 15 g. Systemic 100 mg/kg TEMPOL had no effect on established paclitaxel-induced mechanical or cold hypersensitivity. High dose (250 mg/kg systemic TEMPOL significantly inhibited mechanical hypersensitivity to von Frey 8 g & 15 g, but to a lesser extent than PBN. Daily systemic administration of 100 mg/kg TEMPOL (day -1 to 12 did not affect the development of paclitaxel-induced mechanical hypersensitivity. These data suggest that ROS play a causal role in the development and maintenance of paclitaxel-induced pain, but such effects cannot be attributed to superoxide radicals

  5. Longevity of animals under reactive oxygen species stress and disease susceptibility due to global warming.

    Science.gov (United States)

    Paital, Biswaranjan; Panda, Sumana Kumari; Hati, Akshaya Kumar; Mohanty, Bobllina; Mohapatra, Manoj Kumar; Kanungo, Shyama; Chainy, Gagan Bihari Nityananda

    2016-02-26

    The world is projected to experience an approximate doubling of atmospheric CO2 concentration in the next decades. Rise in atmospheric CO2 level as one of the most important reasons is expected to contribute to raise the mean global temperature 1.4 °C-5.8 °C by that time. A survey from 128 countries speculates that global warming is primarily due to increase in atmospheric CO2 level that is produced mainly by anthropogenic activities. Exposure of animals to high environmental temperatures is mostly accompanied by unwanted acceleration of certain biochemical pathways in their cells. One of such examples is augmentation in generation of reactive oxygen species (ROS) and subsequent increase in oxidation of lipids, proteins and nucleic acids by ROS. Increase in oxidation of biomolecules leads to a state called as oxidative stress (OS). Finally, the increase in OS condition induces abnormality in physiology of animals under elevated temperature. Exposure of animals to rise in habitat temperature is found to boost the metabolism of animals and a very strong and positive correlation exists between metabolism and levels of ROS and OS. Continuous induction of OS is negatively correlated with survivability and longevity and positively correlated with ageing in animals. Thus, it can be predicted that continuous exposure of animals to acute or gradual rise in habitat temperature due to global warming may induce OS, reduced survivability and longevity in animals in general and poikilotherms in particular. A positive correlation between metabolism and temperature in general and altered O2 consumption at elevated temperature in particular could also increase the risk of experiencing OS in homeotherms. Effects of global warming on longevity of animals through increased risk of protein misfolding and disease susceptibility due to OS as the cause or effects or both also cannot be ignored. Therefore, understanding the physiological impacts of global warming in relation to

  6. Testosterone improves erectile function through inhibition of reactive oxygen species generation in castrated rats

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    Rui Li

    2016-05-01

    Full Text Available Testosterone is overwhelmingly important in regulating erectile physiology. However, the associated molecular mechanisms are poorly understood. The purpose of this study was to explore the effects and mechanisms of testosterone in erectile dysfunction (ED in castrated rats. Forty male Sprague-Dawley rats were randomized to four groups (control, sham-operated, castration and castration-with-testosterone-replacement. Reactive oxygen species (ROS production was measured by dihydroethidium (DHE staining. Erectile function was assessed by the recording of intracavernous pressure (ICP and mean arterial blood pressure (MAP. Protein expression levels were examined by western blotting. We found that castration reduced erectile function and that testosterone restored it. Nitric oxide synthase (NOS activity was decrease in the castrated rats, and testosterone administration attenuated this decrease (each p < 0.05. The testosterone, dihydrotestosterone, cyclic guanosine monophosphate (cGMP and cyclic adenosine monophosphate (cAMP concentrations were lower in the castrated rats, and testosterone restored these levels (each p < 0.05. Furthermore, the cyclooxygenase-2 (COX-2 and prostacyclin synthase (PTGIS expression levels and phospho-endothelial nitric oxide synthase (p-eNOS, Ser1177/endothelial nitric oxide synthase (eNOS ratio were reduced in the castrated rats compared with the controls (each p < 0.05. In addition, the p40phox and p67phox expression levels were increased in the castrated rats, and testosterone reversed these changes (each p < 0.05. Overall, our results demonstrate that testosterone ameliorates ED after castration by reducing ROS production and increasing the activity of the eNOS/cGMP and COX-2/PTGIS/cAMP signaling pathways.

  7. Induction of reactive oxygen species in marine phytoplankton under crude oil exposure.

    Science.gov (United States)

    Ozhan, Koray; Zahraeifard, Sara; Smith, Aaron P; Bargu, Sibel

    2015-12-01

    Exposure of phytoplankton to the water-accommodated fraction of crude oil can elicit a number of stress responses, but the mechanisms that drive these responses are unclear. South Louisiana crude oil was selected to investigate its effects on population growth, chlorophyll a (Chl a) content, antioxidative defense, and lipid peroxidation, for the marine diatom, Ditylum brightwellii, and the dinoflagellate, Heterocapsa triquetra, in laboratory-based microcosm experiments. The transcript levels of several possible stress-responsive genes in D. brightwellii were also measured. The microalgae were exposed to crude oil for up to 96 h, and Chl a content, superoxide dismutase (SOD), the glutathione pool (GSH and GSSG), and lipid peroxidation content were analyzed. The cell growth of both phytoplankton species was inhibited with increasing crude oil concentrations. Crude oil exposure did not affect Chl a content significantly in cells. SOD activities showed similar responses in both species, being enhanced at 4- and 8-mg/L crude oil exposure. Only H. triquetra demonstrated enhanced activity in GSSG pool and lipid peroxidation at 8-mg/L crude oil exposure, suggesting that phytoplankton species have distinct physiological responses and tolerance levels to crude oil exposure. This study indicated the activation of reactive oxygen species (ROS) in phytoplankton under crude oil exposure; however, the progressive damage in cells is still unknown. Thus, ROS-related damage in nucleic acid, lipids, proteins, and DNA, due to crude oil exposure could be a worthwhile subject of study to better understand crude oil toxicity at the base of the food web.

  8. Salicylic acid alleviates aluminum toxicity in soybean roots through modulation of reactive oxygen species metabolism

    Science.gov (United States)

    Liu, Ning; Song, Fengbin; Zhu, Xiancan; You, Jiangfeng; Yang, Zhenming; Li, Xiangnan

    2017-11-01

    As an important signal molecule, salicylic acid (SA) improves plant tolerance to aluminum (Al) stress. The objective of this study was to investigate the effects of exogenous SA application on the dynamics of endogenous SA and reactive oxygen species in soybean (Glycine max L.) exposed to Al stress. The roots of soybean seedlings were exposed to a combination of AlCl3 (30 μM) and SA (10 μM)/PAC (100 μM, paclobutrazol, SA biosynthesis inhibitor) for 3, 6, 9 and 12 h. Al stress induced an increase in endogenous SA concentration in a time-dependent manner, also verified by the up-regulated expression of GmNPR1, an SA-responsive gene. Al stress increased the activities of phenylalanine ammonia-lyase (PAL) and benzoic acid 2-hydroxylase (BA2H), and the contents of SA, O2- and malondialdehyde (MDA) in the root apex. The application of exogenous SA increased PAL and BA2H, and reduced O2- and MDA contents in soybean roots under Al stress. PAC inhibited the SA induced increase in BA2H activity. In addition, the SA application resulted in a rapid increase in hydrogen peroxide (H2O2) concentration under Al stress, followed by a sharp decrease. Compared with the plants exposed to Al alone, Al+SA plants possessed higher activities of superoxide dismutase, peroxidase and ascorbate peroxidase, and lower catalase activity, indicating that SA alleviated Al-induced oxidative damage. These results suggested that PAL and BA2H were involved in Al-induced SA production and showed that SA alleviated the adverse effects of Al toxicity by modulating the cellular H2O2 level and the antioxidant enzyme activities in the soybean root apex.

  9. AMPK signaling in skeletal muscle during exercise: Role of reactive oxygen and nitrogen species.

    Science.gov (United States)

    Morales-Alamo, David; Calbet, Jose A L

    2016-09-01

    Reactive oxygen and nitrogen species (RONS) are generated during exercise depending on intensity, duration and training status. A greater amount of RONS is released during repeated high-intensity sprint exercise and when the exercise is performed in hypoxia. By activating adenosine monophosphate-activated kinase (AMPK), RONS play a critical role in the regulation of muscle metabolism but also in the adaptive responses to exercise training. RONS may activate AMPK by direct an indirect mechanisms. Directly, RONS may activate or deactivate AMPK by modifying RONS-sensitive residues of the AMPK-α subunit. Indirectly, RONS may activate AMPK by reducing mitochondrial ATP synthesis, leading to an increased AMP:ATP ratio and subsequent Thr(172)-AMPK phosphorylation by the two main AMPK kinases: LKB1 and CaMKKβ. In presence of RONS the rate of Thr(172)-AMPK dephosphorylation is reduced. RONS may activate LKB1 through Sestrin2 and SIRT1 (NAD(+)/NADH.H(+)-dependent deacetylase). RONS may also activate CaMKKβ by direct modification of RONS sensitive motifs and, indirectly, by activating the ryanodine receptor (Ryr) to release Ca(2+). Both too high (hypoxia) and too low (ingestion of antioxidants) RONS levels may lead to Ser(485)-AMPKα1/Ser(491)-AMPKα2 phosphorylation causing inhibition of Thr(172)-AMPKα phosphorylation. Exercise training increases muscle antioxidant capacity. When the same high-intensity training is applied to arm and leg muscles, arm muscles show signs of increased oxidative stress and reduced mitochondrial biogenesis, which may be explained by differences in RONS-sensing mechanisms and basal antioxidant capacities between arm and leg muscles. Efficient adaptation to exercise training requires optimal exposure to pulses of RONS. Inappropriate training stimulus may lead to excessive RONS formation, oxidative inactivation of AMPK and reduced adaptation or even maladaptation. Theoretically, exercise programs should be designed taking into account the

  10. Fetal programming alters reactive oxygen species production in sheep cardiac mitochondria.

    Science.gov (United States)

    von Bergen, Nicholas H; Koppenhafer, Stacia L; Spitz, Douglas R; Volk, Kenneth A; Patel, Sonali S; Roghair, Robert D; Lamb, Fred S; Segar, Jeffrey L; Scholz, Thomas D

    2009-04-01

    Exposure to an adverse intrauterine environment is recognized as an important risk factor for the development of cardiovascular disease later in life. Although oxidative stress has been proposed as a mechanism for the fetal programming phenotype, the role of mitochondrial O(2)(*-) (superoxide radical) production has not been explored. To determine whether mitochondrial ROS (reactive oxygen species) production is altered by in utero programming, pregnant ewes were given a 48-h dexamethasone (dexamethasone-exposed, 0.28 mg.kg(-1) of body weight.day(-1)) or saline (control) infusion at 27-28 days gestation (term=145 days). Intact left ventricular mitochondria and freeze-thaw mitochondrial membranes were studied from offspring at 4-months of age. AmplexRed was used to measure H(2)O(2) production. Activities of the antioxidant enzymes Mn-SOD (manganese superoxide dismutase), GPx (glutathione peroxidase) and catalase were measured. Compared with controls, a significant increase in Complex I H(2)O(2) production was found in intact mitochondria from dexamethasone-exposed animals. The treatment differences in Complex I-driven H(2)O(2) production were not seen in mitochondrial membranes. Consistent changes in H(2)O(2) production from Complex III in programmed animals were not found. Despite the increase in H(2)O(2) production in intact mitochondria from programmed animals, dexamethasone exposure significantly increased mitochondrial catalase activity, whereas Mn-SOD and GPx activities were unchanged. The results of the present study point to an increase in the rate of release of H(2)O(2) from programmed mitochondria despite an increase in catalase activity. Greater mitochondrial H(2)O(2) release into the cell may play a role in the development of adult disease following exposure to an adverse intrauterine environment.

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

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang-Hyun; Jang, Hae-Dong, E-mail: haedong@hnu.kr

    2015-02-15

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

  12. Mining the enzymes involved in the detoxification of reactive oxygen species (ROS) in sugarcane.

    Science.gov (United States)

    Kurama, Eiko E; Fenille, Roseli C; Rosa, Vicente E; Rosa, Daniel D; Ulian, Eugenio C

    2002-07-01

    Summary Adopting the sequencing of expressed sequence tags (ESTs) of a sugarcane database derived from libraries induced and not induced by pathogens, we identified EST clusters homologous to genes corresponding to enzymes involved in the detoxification of reactive oxygen species. The predicted amino acids of these enzymes are superoxide dismutases (SODs), glutathione-S-transferase (GST), glutathione peroxidase (GPX), and catalases. Three MnSOD mitochondrial precursors and 10 CuZnSOD were identified in sugarcane: the MnSOD mitochondrial precursor is 96% similar to the maize MnSOD mitochondrial precursor and, of the 10 CuZnSOD identified, seven were 98% identical to maize cytosolic CuZnSOD4 and one was 67% identical to putative peroxisomal CuZnSOD from Arabidopsis. Three homologues to class Phi GST were 87-88% identical to GST III from maize. Five GPX homologues were identified: three were homologous to cytosolic GPX from barley, one was 88% identical to phospholipid hydroperoxide glutathione peroxidase (PHGPX) from rice, and the last was 71% identical to GPX from A. thaliana. Three enzymes similar to maize catalase were identified in sugarcane: two were similar to catalase isozyme 3 and catalase chain 3 from maize, which are mitochondrial, and one was similar to catalase isozyme 1 from maize, whose location is peroxisomal subcellular. All enzymes were induced in all sugarcane libraries (flower, seed, root, callus, leaves) and also in the pathogen-induced libraries, except for CuZnSOD whose cDNA was detected in none of the libraries induced by pathogens (Acetobacter diazotroficans and Herbaspirillum rubrisubalbicans). The expression of the enzymes SOD, GST, GPX, and catalases involved in the detoxification was examined using reverse transcriptase-polymerase chain reaction in cDNA from leaves of sugarcane under biotic stress conditions, inoculated with Puccinia melanocephala, the causal agent of sugarcane rust disease.

  13. Reactive Oxygen Species and Their Implications on CD4+ T Cells in Type 1 Diabetes.

    Science.gov (United States)

    Previte, Dana M; Piganelli, Jon D

    2017-11-28

    Previous work has indicated that type 1 diabetes (T1D) pathology is highly driven by reactive oxygen species (ROS). One way in which ROS shape the autoimmune response demonstrated in T1D is by promoting CD4 + T cell activation and differentiation. As CD4 + T cells are a significant contributor to pancreatic β cell destruction in T1D, understanding how ROS impact their development, activation, and differentiation is critical. Recent Advances: CD4 + T cells themselves generate ROS via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression and electron transport chain activity. Moreover, T cells can also be exposed to exogenous ROS generated by other immune cells (e.g., macrophages and dendritic cells) and β cells. Genetically modified animals and ROS inhibitors have demonstrated that ROS blockade during activation results in CD4 + T cell hyporesponsiveness and reduced diabetes incidence. Critical Issues and Future Directions: Although the majority of studies with regard to T1D and CD4 + T cells have been done to examine the influence of redox on CD4 + T cell activation, this is not the only circumstance in which a T cell can be impacted by redox. ROS and redox have also been shown to play roles in CD4 + T cell-related tolerogenic mechanisms, including thymic selection and regulatory T cell-mediated suppression. However, the effect of these mechanisms with respect to T1D pathogenesis remains elusive. Therefore, pursuing these avenues may provide valuable insight into the global role of ROS and redox in autoreactive CD4 + T cell formation and function. Antioxid. Redox Signal. 00, 000-000.

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

    International Nuclear Information System (INIS)

    Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro; Takahashi, Yutaka

    2012-01-01

    Highlights: ► Cellular senescence plays an important role in tumorigenesis and aging process. ► We demonstrated IGF-I enhanced cellular senescence in primary confluent cells. ► IGF-I enhanced cellular senescence in the ROS and p53-dependent manner. ► These results may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. -- Abstract: Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated β-galactosidase (SA-β-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, γH2AX, the increased levels of p53 and p21 proteins, and activated SA-β-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-β-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.

  15. Reactive Oxygen Species and Mitochondrial Homeostasis as Regulators of Stem Cell Fate and Function.

    Science.gov (United States)

    Tan, Darren Q; Suda, Toshio

    2018-07-10

    The precise role and impact of reactive oxygen species (ROS) in stem cells, which are essential for lifelong tissue homeostasis and regeneration, remain of significant interest to the field. The long-term regenerative potential of a stem cell compartment is determined by the delicate balance between quiescence, self-renewal, and differentiation, all of which can be influenced by ROS levels. Recent Advances: The past decade has seen a growing appreciation for the importance of ROS and redox homeostasis in various stem cell compartments, particularly those of hematopoietic, neural, and muscle tissues. In recent years, the importance of proteostasis and mitochondria in relation to stem cell biology and redox homeostasis has garnered considerable interest. Here, we explore the reciprocal relationship between ROS and stem cells, with significant emphasis on mitochondria as a core component of redox homeostasis. We discuss how redox signaling, involving cell-fate determining protein kinases and transcription factors, can control stem cell function and fate. We also address the impact of oxidative stress on stem cells, especially oxidative damage of lipids, proteins, and nucleic acids. We further discuss ROS management in stem cells, and present recent evidence supporting the importance of mitochondrial activity and its modulation (via mitochondrial clearance, biogenesis, dynamics, and distribution [i.e., segregation and transfer]) in stem cell redox homeostasis. Therefore, elucidating the intricate links between mitochondria, cellular metabolism, and redox homeostasis is envisioned to be critical for our understanding of ROS in stem cell biology and its therapeutic relevance in regenerative medicine. Antioxid. Redox Signal. 00, 000-000.

  16. Genomic evidence of reactive oxygen species elevation in papillary thyroid carcinoma with Hashimoto thyroiditis.

    Science.gov (United States)

    Yi, Jin Wook; Park, Ji Yeon; Sung, Ji-Youn; Kwak, Sang Hyuk; Yu, Jihan; Chang, Ji Hyun; Kim, Jo-Heon; Ha, Sang Yun; Paik, Eun Kyung; Lee, Woo Seung; Kim, Su-Jin; Lee, Kyu Eun; Kim, Ju Han

    2015-01-01

    Elevated levels of reactive oxygen species (ROS) have been proposed as a risk factor for the development of papillary thyroid carcinoma (PTC) in patients with Hashimoto thyroiditis (HT). However, it has yet to be proven that the total levels of ROS are sufficiently increased to contribute to carcinogenesis. We hypothesized that if the ROS levels were increased in HT, ROS-related genes would also be differently expressed in PTC with HT. To find differentially expressed genes (DEGs) we analyzed data from the Cancer Genomic Atlas, gene expression data from RNA sequencing: 33 from normal thyroid tissue, 232 from PTC without HT, and 60 from PTC with HT. We prepared 402 ROS-related genes from three gene sets by genomic database searching. We also analyzed a public microarray data to validate our results. Thirty-three ROS related genes were up-regulated in PTC with HT, whereas there were only nine genes in PTC without HT (Chi-square p-value < 0.001). Mean log2 fold changes of up-regulated genes was 0.562 in HT group and 0.252 in PTC without HT group (t-test p-value = 0.001). In microarray data analysis, 12 of 32 ROS-related genes showed the same differential expression pattern with statistical significance. In gene ontology analysis, up-regulated ROS-related genes were related with ROS metabolism and apoptosis. Immune function-related and carcinogenesis-related gene sets were enriched only in HT group in Gene Set Enrichment Analysis. Our results suggested that ROS levels may be increased in PTC with HT. Increased levels of ROS may contribute to PTC development in patients with HT.

  17. Non-thermal dielectric barrier discharge plasma induces angiogenesis through reactive oxygen species.

    Science.gov (United States)

    Arjunan, Krishna Priya; Friedman, Gary; Fridman, Alexander; Clyne, Alisa Morss

    2012-01-07

    Vascularization plays a key role in processes such as wound healing and tissue engineering. Non-thermal plasma, which primarily produces reactive oxygen species (ROS), has recently emerged as an efficient tool in medical applications including blood coagulation, sterilization and malignant cell apoptosis. Liquids and porcine aortic endothelial cells were treated with a non-thermal dielectric barrier discharge plasma in vitro. Plasma treatment of phosphate-buffered saline (PBS) and serum-free medium increased ROS concentration in a dose-dependent manner, with a higher concentration observed in serum-free medium compared with PBS. Species concentration inside cells peaked 1 h after treatment, followed by a decrease 3 h post treatment. Endothelial cells treated with a plasma dose of 4.2 J cm(-2) had 1.7 times more cells than untreated samples 5 days after plasma treatment. The 4.2 J cm(-2) plasma dose increased two-dimensional migration distance by 40 per cent compared with untreated control, while the number of cells that migrated through a three-dimensional collagen gel increased by 15 per cent. Tube formation was also enhanced by plasma treatment, with tube lengths in plasma-treated samples measuring 2.6 times longer than control samples. A fibroblast growth factor-2 (FGF-2) neutralizing antibody and ROS scavengers abrogated these angiogenic effects. These data indicate that plasma enhanced proliferation, migration and tube formation is due to FGF-2 release induced by plasma-produced ROS. Non-thermal plasma may be used as a potential tool for applying ROS in precise doses to enhance vascularization.

  18. Comparison of Mitochondrial Reactive Oxygen Species Production of Ectothermic and Endothermic Fish Muscle

    Directory of Open Access Journals (Sweden)

    Lilian Wiens

    2017-09-01

    Full Text Available Recently we demonstrated that the capacity of isolated muscle mitochondria to produce reactive oxygen species, measured as H2O2 efflux, is temperature-sensitive in isolated muscle mitochondria of ectothermic fish and the rat, a representative endothermic mammal. However, at physiological temperatures (15° and 37°C for the fish and rat, respectively, the fraction of total mitochondrial electron flux that generated H2O2, the fractional electron leak (FEL, was far lower in the rat than in fish. Those results suggested that the elevated body temperatures associated with endothermy may lead to a compensatory decrease in mitochondrial ROS production relative to respiratory capacity. To test this hypothesis we compare slow twitch (red muscle mitochondria from the endothermic Pacific bluefin tuna (Thunnus orientalis with mitochondria from three ectothermic fishes [rainbow trout (Oncorhynchus mykiss, common carp (Cyprinus carpio, and the lake sturgeon (Acipenser fulvescens] and the rat. At a common assay temperature (25°C rates of mitochondrial respiration and H2O2 efflux were similar in tuna and the other fishes. The thermal sensitivity of fish mitochondria was similar irrespective of ectothermy or endothermy. Comparing tuna to the rat at a common temperature, respiration rates were similar, or lower depending on mitochondrial substrates. FEL was not different across fish species at a common assay temperature (25°C but was markedly higher in fishes than in rat. Overall, endothermy and warming of Pacific Bluefin tuna red muscle may increase the potential for ROS production by muscle mitochondria but the evolution of endothermy in this species is not necessarily associated with a compensatory reduction of ROS production relative to the respiratory capacity of mitochondria.

  19. Sibutramine provokes apoptosis of aortic endothelial cells through altered production of reactive oxygen and nitrogen species

    Energy Technology Data Exchange (ETDEWEB)

    Morikawa, Yoshifumi [Forensic Science Laboratory, Gifu Prefectural Police Headquarters, Gifu 500-8501 (Japan); Shibata, Akinobu; Okumura, Naoko; Ikari, Akira [Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu 501-1196 (Japan); Sasajima, Yasuhide; Suenami, Koichi; Sato, Kiyohito; Takekoshi, Yuji [Forensic Science Laboratory, Gifu Prefectural Police Headquarters, Gifu 500-8501 (Japan); El-Kabbani, Ossama [Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Matsunaga, Toshiyuki, E-mail: matsunagat@gifu-pu.ac.jp [Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu 501-1196 (Japan)

    2017-01-01

    Overdose administration of sibutramine, a serotonin-noradrenalin reuptake inhibitor, is considered to elicit severe side effects including hypertension, whose pathogenic mechanism remains unclear. Here, we found that 48-h incubation with > 10 μM sibutramine provokes apoptosis of human aortic endothelial (HAE) cells. Treatment with the lethal concentration of sibutramine facilitated production of reactive oxygen species (ROS), altered expression of endoplasmic reticulum stress response genes (heat shock protein 70 and C/EBP homologous protein), and inactivated 26S proteasome-based proteolysis. The treatment also decreased cellular level of nitric oxide (NO) through lowering of expression and activity of endothelial NO synthase. These results suggest that ROS production and depletion of NO are crucial events in the apoptotic mechanism and may be linked to the pathogenesis of vasoconstriction elicited by the drug. Compared to sibutramine, its metabolites (N-desmethylsibutramine and N-didesmethylsibutramine) were much less cytotoxic to HAE cells, which hardly metabolized sibutramine. In contrast, both the drug and metabolites showed low cytotoxicity to hepatic HepG2 cells with high metabolic potency and expression of cytochrome P450 (CYP) 3A4. The cytotoxicity of sibutramine to HepG2 and Chang Liver cells was remarkably augmented by inhibition and knockdown of CYP3A4. This study also suggests an inverse relationship between sibutramine cytotoxicity and CYP3A4-mediated metabolism into the N-desmethyl metabolites. - Highlights: • Treatment with sibutramine, an anorexiant, induces endothelial cell apoptosis. • The apoptotic mechanism includes induction of ROS and NO depletion. • There is an inverse relationship between sibutramine cytotoxicity and its metabolism.

  20. The oxygen reactivity index and its relation to sensor technology in patients with severe brain lesions.

    Science.gov (United States)

    Dengler, Julius; Frenzel, Christin; Vajkoczy, Peter; Horn, Peter; Wolf, Stefan

    2013-08-01

    The oxygen reactivity index (ORx) has been introduced to assess the status of cerebral autoregulation after traumatic brain injury (TBI) or subarachnoid hemorrhage (SAH). Currently, there is some controversy about whether the ORx depends on the type of PbrO2-sensor technology used for its calculation. To examine if the probe technology does matter, we compared the ORx and the resulting optimal cerebral perfusion pressures (CPPopt) of simultaneously implanted Licox (CC1.SB, Integra Neuroscience, France) and Neurovent-PTO (Raumedic, Germany) probes in patients after aneurysmal SAH or severe TBI. Licox and Raumedic probes were implanted side by side in 11 patients after TBI or SAH. ORx and CPPopt were recorded continuously. The equivalence of both probes was examined using Bland-Altman analyses. The mean difference in ORx was 0.1, with Licox producing higher values. The limits of agreement regarding ORx ranged from -0.6 to +0.7. When both probes' ORx values were compared in each patient, no specific pattern in their relationship was seen. The mean difference in CPPopt was 0 mmHg with limits of agreement between -16.5 and +16.4 mmHg. Owing to the rather limited number of patients, we view the results of this study as preliminary. The main result is that Licox and Raumedic showed consistent differences in ORx and CPPopt. Therefore, ORx values of both probes cannot be interchanged and should not be viewed as equivalent. This should be taken into consideration when discussing ORx data generated by different PbrO2 probe types.

  1. Light-Emitting Photon-Upconversion Nanoparticles in the Generation of Transdermal Reactive-Oxygen Species.

    Science.gov (United States)

    Prieto, Martin; Rwei, Alina Y; Alejo, Teresa; Wei, Tuo; Lopez-Franco, Maria Teresa; Mendoza, Gracia; Sebastian, Victor; Kohane, Daniel S; Arruebo, Manuel

    2017-12-06

    Common photosensitizers used in photodynamic therapy do not penetrate the skin effectively. In addition, the visible blue and red lights used to excite such photosensitizers have shallow penetration depths through tissue. To overcome these limitations, we have synthesized ultraviolet- and visible-light-emitting, energy-transfer-based upconversion nanoparticles and coencapsulated them inside PLGA-PEG (methoxy poly(ethylene glycol)-b-poly(lactic-co-glycolic acid)) nanoparticles with the photosensitizer protoporphyrin IX. Nd 3+ has been introduced as a sensitizer in the upconversion nanostructure to allow its excitation at 808 nm. The subcytotoxic doses of the hybrid nanoparticles have been evaluated on different cell lines (i.e., fibroblasts, HaCaT, THP-1 monocytic cell line, U251MG (glioblastoma cell line), and mMSCs (murine mesenchymal stem cells). Upon NIR (near infrared)-light excitation, the upconversion nanoparticles emitted UV and VIS light, which consequently activated the generation of reactive-oxygen species (ROS). In addition, after irradiating at 808 nm, the resulting hybrid nanoparticles containing both upconversion nanoparticles and protoporphyrin IX generated 3.4 times more ROS than PLGA-PEG nanoparticles containing just the same dose of protoporphyrin IX. Their photodynamic effect was also assayed on different cell cultures, demonstrating their efficacy in selectively killing treated and irradiated cells. Compared to the topical application of the free photosensitizer, enhanced skin permeation and penetration were observed for the nanoparticulate formulation, using an ex vivo human-skin-permeation experiment. Whereas free protoporphyrin IX remained located at the outer layer of the skin, nanoparticle-encapsulated protoporphyrin IX was able to penetrate through the epidermal layer slightly into the dermis.

  2. Reactive oxygen species play no role in the candidacidal activity of the salivary antimicrobial peptide histatin 5

    OpenAIRE

    Veerman, Enno C. I.; Nazmi, Kamran; van '​t HOF, Wim; Bolscher, Jan G. M.; den Hertog, Alice L.; Nieuw Amerongen, Arie V.

    2004-01-01

    The mechanism of action of antimicrobial peptides is still a matter of debate. The formation of ROS (reactive oxygen species) has been suggested to be the crucial step in the fungicidal mechanism of a number of antimicrobial peptides, including histatin 5 and lactoferrin-derived peptides. In the present study we have investigated the effects of histatin 5 and of a more amphipathic synthetic derivative, dhvar4, on the generation of ROS in the yeast Candida albicans, using dihydroethidium as an...

  3. Decorative black TiCxOy film fabricated by DC magnetron sputtering without importing oxygen reactive gas

    Science.gov (United States)

    Ono, Katsushi; Wakabayashi, Masao; Tsukakoshi, Yukio; Abe, Yoshiyuki

    2016-02-01

    Decorative black TiCxOy films were fabricated by dc (direct current) magnetron sputtering without importing the oxygen reactive gas into the sputtering chamber. Using a ceramic target of titanium oxycarbide (TiC1.59O0.31), the oxygen content in the films could be easily controlled by adjustment of total sputtering gas pressure without remarkable change of the carbon content. The films deposited at 2.0 and 4.0 Pa, those are higher pressure when compared with that in conventional magnetron sputtering, showed an attractive black color. In particular, the film at 4.0 Pa had the composition of TiC1.03O1.10, exhibited the L* of 41.5, a* of 0.2 and b* of 0.6 in CIELAB color space. These values were smaller than those in the TiC0.29O1.38 films (L* of 45.8, a* of 1.2 and b* of 1.2) fabricated by conventional reactive sputtering method from the same target under the conditions of gas pressure of 0.3 Pa and optimized oxygen reactive gas concentration of 2.5 vol.% in sputtering gas. Analysis of XRD and XPS revealed that the black film deposited at 4.0 Pa was the amorphous film composed of TiC, TiO and C. The adhesion property and the heat resisting property were enough for decorative uses. This sputtering process has an industrial advantage that the decorative black coating with color uniformity in large area can be easily obtained by plain operation because of unnecessary of the oxygen reactive gas importing which is difficult to be controlled uniformly in the sputtering chamber.

  4. Production of Reactive Oxygen Species by Multipotent Stromal Cells/Mesenchymal Stem Cells Upon Exposure to Fas Ligand

    OpenAIRE

    Rodrigues, Melanie; Turner, Omari; Stolz, Donna; Griffith, Linda G.; Wells, Alan

    2011-01-01

    Multipotent stromal cells (MSCs) can be differentiated into osteoblasts and chondrocytes, making these cells candidates to regenerate cranio-facial injuries and lesions in long bones. A major problem with cell replacement therapy, however, is the loss of transplanted MSCs at the site of graft. Reactive oxygen species (ROS) and nonspecific inflammation generated at the ischemic site have been hypothesized to lead to MSCs loss; studies in vitro show MSCs dying both in the presence of ROS or cyt...

  5. Role of reactive oxygen species and Bcl-2 family proteins in TNF-α-induced apoptosis of lymphocytes.

    Science.gov (United States)

    Ryazanceva, N V; Novickiy, V V; Zhukova, O B; Biktasova, A K; Chechina, O E; Sazonova, E V; Belkina, M V; Chasovskih, N Yu; Khaitova, Z K

    2010-08-01

    We studied the in vitro apoptosis-inducing effect of recombinant TNF-α (rTNF-α) on blood lymphocytes from healthy donors. rTNF-α-induced apoptosis was accompanied by an increase in the number of cells with low mitochondrial transmembrane potential, increased intracellular content of reactive oxygen species, reduced content of Bcl-2, Bcl-xL, and Bax proteins, and elevated Bad content. The molecular mechanisms of these changes are discussed.

  6. The effect of silicon on iron plaque formation and arsenic accumulation in rice genotypes with different radial oxygen loss (ROL).

    Science.gov (United States)

    Wu, Chuan; Zou, Qi; Xue, Sheng-Guo; Pan, Wei-Song; Huang, Liu; Hartley, William; Mo, Jing-Yu; Wong, Ming-Hung

    2016-05-01

    Rice is one of the major pathways of arsenic (As) exposure in human food chain, threatening over half of the global population. Greenhouse pot experiments were conducted to examine the effects of Si application on iron (Fe) plaque formation, As uptake and rice grain As speciation in indica and hybrid rice genotypes with different radial oxygen loss (ROL) ability. The results demonstrated that Si significantly increased root and grain biomass. Indica genotypes with higher ROL induced greater Fe plaque formation, compared to hybrid genotypes and sequestered more As in Fe plaque. Silicon applications significantly increased Fe concentrations in iron plaque of different genotypes, but it decreased As concentrations in the roots, straws and husks by 28-35%, 15-35% and 32-57% respectively. In addition, it significantly reduced DMA accumulation in rice grains but not inorganic As accumulation. Rice of indica genotypes with higher ROL accumulated lower concentrations of inorganic As in grains than hybrid genotypes with lower ROL. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Cell viability, reactive oxygen species, apoptosis, and necrosis in myoblast cultures exposed to low-level infrared laser.

    Science.gov (United States)

    Alexsandra da Silva Neto Trajano, Larissa; da Silva, Camila Luna; de Carvalho, Simone Nunes; Cortez, Erika; Mencalha, André Luiz; de Souza da Fonseca, Adenilson; Stumbo, Ana Carolina

    2016-07-01

    Low-level infrared laser is considered safe and effective for treatment of muscle injuries. However, the mechanism involved on beneficial effects of laser therapy are not understood. The aim was to evaluate cell viability, reactive oxygen species, apoptosis, and necrosis in myoblast cultures exposed to low-level infrared laser at therapeutic fluences. C2C12 myoblast cultures at different (2 and 10 %) fetal bovine serum (FBS) concentrations were exposed to low-level infrared laser (808 nm, 100 mW) at different fluences (10, 35, and 70 J/cm(2)) and evaluated after 24, 48, and 72 h. Cell viability was evaluated by WST-1 assay; reactive oxygen species (ROS), apoptosis, and necrosis were evaluated by flow cytometry. Cell viability was decreased atthe lowest FBS concentration. Laser exposure increased the cell viability in myoblast cultures at 2 % FBS after 48 and 72 h, but no significant increase in ROS was observed. Apoptosis was decreased at the higher fluence and necrosis was increased at lower fluence in myoblast cultures after 24 h of laser exposure at 2 % FBS. No laser-induced alterations were obtained at 10 % FBS. Results show that level of reactive oxygen species is not altered, at least to those evaluated in this study, but low-level infrared laser exposure affects cell viability, apoptosis, and necrosis in myoblast cultures depending on laser fluence and physiologic conditions of cells.

  8. Nitrite accumulation from simultaneous free-ammonia and free-nitrous-acid inhibition and oxygen limitation in a continuous-flow biofilm reactor.

    Science.gov (United States)

    Park, Seongjun; Chung, Jinwook; Rittmann, Bruce E; Bae, Wookeun

    2015-01-01

    To achieve nitrite accumulation for shortcut biological nitrogen removal (SBNR) in a biofilm process, we explored the simultaneous effects of oxygen limitation and free ammonia (FA) and free nitrous acid (FNA) inhibition in the nitrifying biofilm. We used the multi-species nitrifying biofilm model (MSNBM) to identify conditions that should or should not lead to nitrite accumulation, and evaluated the effectiveness of those conditions with experiments in continuous flow biofilm reactors (CFBRs). CFBR experiments were organized into four sets with these expected outcomes based on the MSNBM as follows: (i) Control, giving full nitrification; (ii) oxygen limitation, giving modest long-term nitrite build up; (iii) FA inhibition, giving no long-term nitrite accumulation; and (iv) FA inhibition plus oxygen limitation, giving major long-term nitrite accumulation. Consistent with MSNBM predictions, the experimental results showed that nitrite accumulated in sets 2-4 in the short term, but long-term nitrite accumulation was maintained only in sets 2 and 4, which involved oxygen limitation. Furthermore, nitrite accumulation was substantially greater in set 4, which also included FA inhibition. However, FA inhibition (and accompanying FNA inhibition) alone in set 3 did not maintained long-term nitrite accumulation. Nitrite-oxidizing bacteria (NOB) activity batch tests confirmed that little NOB or only a small fraction of NOB were present in the biofilms for sets 4 and 2, respectively. The experimental data supported the previous modeling results that nitrite accumulation could be achieved with a lower ammonium concentration than had been required for a suspended-growth process. Additional findings were that the biofilm exposed to low dissolved oxygen (DO) limitation and FA inhibition was substantially denser and probably had a lower detachment rate. © 2014 Wiley Periodicals, Inc.

  9. Analyses of associations between reactive oxygen metabolites and antioxidant capacity and related factors among healthy adolescents.

    Science.gov (United States)

    Tamae, Kazuyoshi; Eto, Toshiharu; Aoki, Kazuhiro; Nakamaru, Shingo; Koshikawa, Kazunori; Sakuma, Kazuhiko; Hirano, Takeshi

    2013-12-01

    Evidence based on epidemiologic investigations using biochemical parameter is meaningful for health promotion and administration among adolescents. We conducted Reactive Oxygen Metabolites (ROM) and Biological Antioxidant Potentials (BAP) tests, along with a questionnaire survey, for a sample of 74 high school students (16.51±0.11 years of aged mean±SE), to investigate the associations between ROM, BAP, and related factors, including BMI and blood biochemical data. Venous blood samples (approximately 7cc) were collected. At the same time, each individual's information was obtained from the questionnaire. The mental health status was investigated using the Center for Epidemiologic Study Depression scale (CES-D) included in the same questionnaire. The mean values and standard errors of all variables were calculated. In addition, the relationships between ROM and BAP with these factors were analyzed. The results revealed the preferred levels of ROM (261.95 ± 9.52 U.CARR) and, BAP (2429.89±53.39 µmol/L) and blood biochemical data. Few significant relationships between two markers and related factors were found. So, we detected a cluster with an imbalance between ROM and BAP, which means low antioxidant ability, whereas the other clusters had conditions with moderate balance or good balance between them. Moreover, we determined the Oxidative stress-Antioxidant capacity ratio (OAR), using the ROM and BAP values, in order to clarify the characteristic of the detected clusters.However, comparative analyses across the three clusters did not yield significant differences in all related factors. No correlations between ROM, BAP and related factors were indicated, although significant association between ROM and BAP was observed (R2=0.1156, R=0.340, P=0.013). The reason for these results can be explained by the influences of good health and young age. On the other hand, present study suggests that some latent problems among adolescents may be related to unhealthy

  10. On the Effects of Reactive Oxygen Species and Nitric Oxide on Red Blood Cell Deformability

    Directory of Open Access Journals (Sweden)

    Lukas Diederich

    2018-05-01

    Full Text Available The main function of red blood cells (RBCs is the transport of respiratory gases along the vascular tree. To fulfill their task, RBCs are able to elastically deform in response to mechanical forces and, pass through the narrow vessels of the microcirculation. Decreased RBC deformability was observed in pathological conditions linked to increased oxidative stress or decreased nitric oxide (NO bioavailability, like hypertension. Treatments with oxidants and with NO were shown to affect RBC deformability ex vivo, but the mechanisms underpinning these effects are unknown. In this study we investigate whether changes in intracellular redox status/oxidative stress or nitrosation reactions induced by reactive oxygen species (ROS or NO may affect RBC deformability. In a case-control study comparing RBCs from healthy and hypertensive participants, we found that RBC deformability was decreased, and levels of ROS were increased in RBCs from hypertensive patients as compared to RBCs from aged-matched healthy controls, while NO levels in RBCs were not significantly different. To study the effects of oxidants on RBC redox state and deformability, RBCs from healthy volunteers were treated with increasing concentrations of tert-butylhydroperoxide (t-BuOOH. We found that high concentrations of t-BuOOH (≥ 1 mM significantly decreased the GSH/GSSG ratio in RBCs, decreased RBC deformability and increased blood bulk viscosity. Moreover, RBCs from Nrf2 knockout (KO mice, a strain genetically deficient in a number of antioxidant/reducing enzymes, were more susceptible to t-BuOOH-induced impairment in RBC deformability as compared to wild type (WT mice. To study the role of NO in RBC deformability we treated RBC suspensions from human volunteers with NO donors and nitrosothiols and analyzed deformability of RBCs from mice lacking the endothelial NO synthase (eNOS. We found that NO donors induced S-nitrosation of the cytoskeletal protein spectrin, but did not affect

  11. HIV antiretroviral drug combination induces endothelial mitochondrial dysfunction and reactive oxygen species production, but not apoptosis

    International Nuclear Information System (INIS)

    Jiang Bo; Hebert, Valeria Y.; Li, Yuchi; Mathis, J. Michael; Alexander, J. Steven; Dugas, Tammy R.

    2007-01-01

    Numerous reports now indicate that HIV patients administered long-term antiretroviral therapy (ART) are at a greater risk for developing cardiovascular diseases. Endothelial dysfunction is an initiating event in atherogenesis and may contribute to HIV-associated atherosclerosis. We previously reported that ART induces direct endothelial dysfunction in rodents. In vitro treatment of human umbilical vein endothelial cells (HUVEC) with ART indicated endothelial mitochondrial dysfunction and a significant increase in the production of reactive oxygen species (ROS). In this study, we determined whether ART-induced endothelial dysfunction is mediated via mitochondria-derived ROS and whether this mitochondrial injury culminates in endothelial cell apoptosis. Two major components of ART combination therapy, a nucleoside reverse transcriptase inhibitor and a protease inhibitor, were tested, using AZT and indinavir as representatives for each. Microscopy utilizing fluorescent indicators of ROS and mitochondria demonstrated the mitochondrial localization of ART-induced ROS. MnTBAP, a cell-permeable metalloporphyrin antioxidant, abolished ART-induced ROS production. As a final step in confirming the mitochondrial origin of the ART-induced ROS, HUVEC were transduced with a cytosolic- compared to a mitochondria-targeted catalase. Transduction with the mitochondria-targeted catalase was more effective than cytoplasmic catalase in inhibiting the ROS and 8-isoprostane (8-iso-PGF 2α ) produced after treatment with either AZT or indinavir. However, both mitochondrial and cytoplasmic catalase attenuated ROS and 8-iso-PGF 2α production induced by the combination treatment, suggesting that in this case, the formation of cytoplasmic ROS may also occur, and thus, that the mechanism of toxicity in the combination treatment group may be different compared to treatment with AZT or indinavir alone. Finally, to determine whether ART-induced mitochondrial dysfunction and ROS production

  12. The tripeptide feG regulates the production of intracellular reactive oxygen species by neutrophils

    Directory of Open Access Journals (Sweden)

    Davison Joseph S

    2006-06-01

    Full Text Available Abstract Background The D-isomeric form of the tripeptide FEG (feG is a potent anti-inflammatory agent that suppresses type I hypersensitivity (IgE-mediated allergic reactions in several animal species. One of feG's primary actions is to inhibit leukocyte activation resulting in loss of their adhesive and migratory properties. Since activation of neutrophils is often associated with an increase in respiratory burst with the generation of reactive oxygen species (ROS, we examined the effect of feG on the respiratory burst in neutrophils of antigen-sensitized rats. A role for protein kinase C (PKC in the actions of feG was evaluated by using selective isoform inhibitors for PKC. Results At 18h after antigen (ovalbumin challenge of sensitized Sprague-Dawley rats a pronounced neutrophilia occurred; a response that was reduced in animals treated with feG (100 μg/kg. With antigen-challenged animals the protein kinase C (PKC activator, PMA, significantly increased intracellular ROS of circulating neutrophils, as determined by flow cytometry using the fluorescent probe dihydrorhodamine-123. This increase was prevented by treatment with feG at the time of antigen challenge. The inhibitor of PKCδ, rottlerin, which effectively prevented intracellular ROS production by circulating neutrophils of animals receiving a naïve antigen, failed to inhibit PMA-stimulated ROS production if the animals were challenged with antigen. feG treatment, however, re-established the inhibitory effects of the PKCδ inhibitor on intracellular ROS production. The extracellular release of superoxide anion, evaluated by measuring the oxidative reduction of cytochrome C, was neither modified by antigen challenge nor feG treatment. However, hispidin, an inhibitor of PKCβ, inhibited the release of superoxide anion from circulating leukocytes in all groups of animals. feG prevented the increased expression of the β1-integrin CD49d on the circulating neutrophils elicited by antigen

  13. Adrenaline and reactive oxygen species elicit proteome and energetic metabolism modifications in freshly isolated rat cardiomyocytes

    International Nuclear Information System (INIS)

    Costa, Vera Marisa; Silva, Renata; Tavares, Ludgero Canario; Vitorino, Rui; Amado, Francisco; Carvalho, Felix; Bastos, Maria de Lourdes; Carvalho, Marcia; Carvalho, Rui Albuquerque; Remiao, Fernando

    2009-01-01

    The sustained elevation of plasma and interstitial catecholamine levels, namely adrenaline (ADR), and the generation of reactive oxygen species (ROS) are well recognized hallmarks of several cardiopathologic conditions, like cardiac ischemia/reperfusion (I/R) and heart failure (HF). The present work aimed to investigate the proteomics and energetic metabolism of cardiomyocytes incubated with ADR and/or ROS. To mimic pathologic conditions, freshly isolated calcium-tolerant cardiomyocytes from adult rat were incubated with ADR alone or in the presence of a system capable of generating ROS [(xanthine with xanthine oxidase) (XXO)]. Two-dimensional electrophoresis with matrix-assisted laser desorption/ionization and time-of-flight mass spectrometer analysis were used to define protein spot alterations in the cardiomyocytes incubated with ADR and/or ROS. Moreover, the energetic metabolism and the activity of mitochondrial complexes were evaluated by nuclear magnetic resonance and spectrophotometric determinations, respectively. The protein extract was mainly constituted by cardiac mitochondrial proteins and the alterations found were included in five functional classes: (i) structural proteins, notably myosin light chain-2; (ii) redox regulation proteins, in particular superoxide dismutase (SOD); (iii) energetic metabolism proteins, encompassing ATP synthase alpha chain and dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex; (iv) stress response proteins, like the heat shock proteins; and (v) regulatory proteins, like cytochrome c and voltage-dependent anion channel 1. The XXO system elicited alterations in cardiac contractile proteins, as they showed high levels of cleavage, and also altered energetic metabolism, through increased lactate and alanine levels. The cardiomyocytes incubation with ADR resulted in an accentuated increase in mitochondrial complexes activity and the decrease in alanine/lactate ratio, thus reflecting a high

  14. Production of reactive oxygen species during the aerobic and anaerobic exercise

    Directory of Open Access Journals (Sweden)

    Edilson Serpeloni Cyrino

    2006-06-01

    Full Text Available The protective effect of physical exercise against diseases is well established in literature, although it is known that exercising generates free radicals. Despite the mitochondria being the main source of free radicals, the processes of ischemia, inflammation, and reperfusion can also form free radicals. The purpose of this literature review was to investigate the impact of both aerobic and anaerobic physical exercise on the generation of reactive oxygen species (ROS. We verified that cellular and tissue damage by free radicals, caused by lipid peroxidation and inflammation, occurs in both types of physical exercises, especially in high intensity efforts. There are indications that ROS generation during physical exercise cannot be modulated by regular training, however, the cellular environment can increase antioxidant endogenous concentration to compensate for that stress. Moreover, ROS regulation can differently occur in aerobic and anaerobic exercises. Therefore, the control of oxidative stress may be very important, particularly, in anaerobic exercises. RESUMOO efeito protetor do exercício físico contra doenças está bem estabelecido na literatura, embora haja conhecimento de que sua prática gera radicais livres. Apesar de a mitocôndria ser a principal fonte de radicais livres, os processos de isquemia, inflamação e reperfusão também podem causar formação de radicais livres. Apartir de uma ampla revisão da literatura, o objetivo deste estudo foi investigar o impacto do exercício físico sob condições de aerobiose e anaerobiose sobre a geração de espécies reativas de oxigênio (ERO. Verificou-se que o dano celular e tecidual por radicais livres, causado por peroxidação lipídica e inflamação, ocorre em ambos os tipos de exercícios físicos, sobretudo em esforços de alta intensidade. Existem indicações de que a geração de ERO durante o exercício físico não pode ser modulada pelo treinamento regular, contudo, o

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

    Directory of Open Access Journals (Sweden)

    Lambeth J David

    2007-07-01

    Full Text Available Abstract Background NADPH-oxidases (Nox and the related Dual oxidases (Duox play varied biological and pathological roles via regulated generation of reactive oxygen species (ROS. Members of the Nox/Duox family have been identified in a wide variety of organisms, including mammals, nematodes, fruit fly, green plants, fungi, and slime molds; however, little is known about the molecular evolutionary history of these enzymes. Results We assembled and analyzed the deduced amino acid sequences of 101 Nox/Duox orthologs from 25 species, including vertebrates, urochordates, echinoderms, insects, nematodes, fungi, slime mold amoeba, alga and plants. In contrast to ROS defense enzymes, such as superoxide dismutase and catalase that are present in prokaryotes, ROS-generating Nox/Duox orthologs only appeared later in evolution. Molecular taxonomy revealed seven distinct subfamilies of Noxes and Duoxes. The calcium-regulated orthologs representing 4 subfamilies diverged early and are the most widely distributed in biology. Subunit-regulated Noxes represent a second major subdivision, and appeared first in fungi and amoeba. Nox5 was lost in rodents, and Nox3, which functions in the inner ear in gravity perception, emerged the most recently, corresponding to full-time adaptation of vertebrates to land. The sea urchin Strongylocentrotus purpuratus possesses the earliest Nox2 co-ortholog of vertebrate Nox1, 2, and 3, while Nox4 first appeared somewhat later in urochordates. Comparison of evolutionary substitution rates demonstrates that Nox2, the regulatory subunits p47phox and p67phox, and Duox are more stringently conserved in vertebrates than other Noxes and Nox regulatory subunits. Amino acid sequence comparisons identified key catalytic or regulatory regions, as 68 residues were highly conserved among all Nox/Duox orthologs, and 14 of these were identical with those mutated in Nox2 in variants of X-linked chronic granulomatous disease. In addition to

  16. Generation of reactive oxygen species and charge carriers in plasmonic photocatalytic Au@TiO2 nanostructures with enhanced activity.

    Science.gov (United States)

    He, Weiwei; Cai, Junhui; Jiang, Xiumei; Yin, Jun-Jie; Meng, Qingbo

    2018-06-13

    The combination of semiconductor and plasmonic nanostructures, endowed with high efficiency light harvesting and surface plasmon confinement, has been a promising way for efficient utilization of solar energy. Although the surface plasmon resonance (SPR) assisted photocatalysis has been extensively studied, the photochemical mechanism, e.g. the effect of SPR on the generation of reactive oxygen species and charge carriers, is not well understood. In this study, we take Au@TiO2 nanostructures as a plasmonic photocatalyst to address this critical issue. The Au@TiO2 core/shell nanostructures with tunable SPR property were synthesized by the templating method with post annealing thermal treatment. It was found that Au@TiO2 nanostructures exhibit enhanced photocatalytic activity in either sunlight or visible light (λ > 420 nm). Electron spin resonance spectroscopy with spin trapping and spin labeling was used to investigate the enhancing effect of Au@TiO2 on the photo-induced reactive oxygen species and charge carriers. The formation of Au@TiO2 core/shell nanostructures resulted in a dramatic increase in light-induced generation of hydroxyl radicals, singlet oxygen, holes and electrons, as compared with TiO2 alone. This enhancement under visible light (λ > 420 nm) irradiation may be dominated by SPR induced local electrical field enhancement, while the enhancement under sunlight irradiation is dominated by the higher electron transfer from TiO2 to Au. These results unveiled that the superior photocatalytic activity of Au@TiO2 nanostructures correlates with enhanced generation of reactive oxygen species and charge carriers.

  17. Myricetin-induced apoptosis of triple-negative breast cancer cells is mediated by the iron-dependent generation of reactive oxygen species from hydrogen peroxide.

    Science.gov (United States)

    Knickle, Allison; Fernando, Wasundara; Greenshields, Anna L; Rupasinghe, H P Vasantha; Hoskin, David W

    2018-05-06

    Myricetin is a dietary phytochemical with anticancer activity; however, the effect of myricetin on breast cancer cells remains unclear. Here, we show that myricetin inhibited the growth of triple-negative breast cancer (TNBC) cells but was less inhibitory for normal cells. The effect of myricetin was comparable to epigallocatechin gallate and doxorubicin, and greater than resveratrol and cisplatin. Myricetin-treated TNBC cells showed evidence of early and late apoptosis/necrosis, which was associated with intracellular reactive oxygen species (ROS) accumulation, extracellular regulated kinase 1/2 and p38 mitogen-activated protein kinase activation, mitochondrial membrane destabilization and cytochrome c release, and double-strand DNA breaks. The antioxidant N-acetyl-cysteine protected myricetin-treated TNBC cells from cytotoxicity due to DNA damage. Myricetin also induced hydrogen peroxide (H 2 O 2 ) production in cell-free culture medium, as well as in the presence of TNBC cells and normal cells. In addition, deferriprone-mediated inhibition of intracellular ROS generation via the iron-dependent Fenton reaction and inhibition of extracellular ROS accumulation with superoxide dismutase plus catalase prevented myricetin-induced cytotoxicity in TNBC cell cultures. We conclude that the cytotoxic effect of myricetin on TNBC cells was due to oxidative stress initiated by extracellular H 2 O 2 formed by autoxidation of myricetin, leading to intracellular ROS production via the Fenton reaction. Copyright © 2018. Published by Elsevier Ltd.

  18. Natriuretic peptide receptor A inhibition suppresses gastric cancer development through reactive oxygen species-mediated G2/M cell cycle arrest and cell death.

    Science.gov (United States)

    Li, Zheng; Wang, Ji-Wei; Wang, Wei-Zhi; Zhi, Xiao-Fei; Zhang, Qun; Li, Bo-Wen; Wang, Lin-Jun; Xie, Kun-Ling; Tao, Jin-Qiu; Tang, Jie; Wei, Song; Zhu, Yi; Xu, Hao; Zhang, Dian-Cai; Yang, Li; Xu, Ze-Kuan

    2016-10-01

    Natriuretic peptide receptor A (NPRA), the major receptor for atrial natriuretic peptide (ANP), has been implicated in tumorigenesis; however, the role of ANP-NPRA signaling in the development of gastric cancer remains unclear. Immunohistochemical analyses indicated that NPRA expression was positively associated with gastric tumor size and cancer stage. NPRA inhibition by shRNA induced G2/M cell cycle arrest, cell death, and autophagy in gastric cancer cells, due to accumulation of reactive oxygen species (ROS). Either genetic or pharmacologic inhibition of autophagy led to caspase-dependent cell death. Therefore, autophagy induced by NPRA silencing may represent a cytoprotective mechanism. ROS accumulation activated c-Jun N-terminal kinase (JNK) and AMP-activated protein kinase (AMPK). ROS-mediated activation of JNK inhibited cell proliferation by disturbing cell cycle and decreased cell viability. In addition, AMPK activation promoted autophagy in NPRA-downregulated cancer cells. Overall, our results indicate that the inhibition of NPRA suppresses gastric cancer development and targeting NPRA may represent a promising strategy for the treatment of gastric cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Rap1 signaling is required for suppression of Ras-generated reactive oxygen species and protection against oxidative stress in T lymphocytes

    NARCIS (Netherlands)

    Remans, Philip H. J.; Gringhuis, Sonja I.; van Laar, Jacob M.; Sanders, Marjolein E.; Papendrecht-van der Voort, Ellen A. M.; Zwartkruis, Fried J. T.; Levarht, E. W. Nivine; Rosas, Marcela; Coffer, Paul J.; Breedveld, Ferdinand C.; Bos, Johannes L.; Tak, Paul P.; Verweij, Cornelis L.; Reedquist, Kris A.

    2004-01-01

    Transient production of reactive oxygen species (ROS) plays an important role in optimizing transcriptional and proliferative responses to TCR signaling in T lymphocytes. Conversely, chronic oxidative stress leads to decreased proliferative responses and enhanced transcription of inflammatory gene

  20. Relationships between human vitality and mitochondrial respiratory parameters, reactive oxygen species production and dNTP levels in peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Maynard, Scott; Keijzers, Guido; Gram, Martin

    2013-01-01

    . Therefore, we measured a number of cellular parameters related to mitochondrial activity in peripheral blood mononuclear cells (PBMCs) isolated from middle-aged men, and tested for association with vitality. These parameters estimate mitochondrial respiration, reactive oxygen species (ROS) production...

  1. Lanthanide ions (III) as sensitizers of melatonin oxidation in reaction mixtures providing reactive species of oxygen and nitrogen

    Energy Technology Data Exchange (ETDEWEB)

    Kaczmarek, Małgorzata, E-mail: mkaczmar@amu.edu.pl

    2015-06-15

    Chemiluminescence (CL) of the reactive systems providing strong oxidants (reactive species of oxygen and nitrogen) containing lanthanide ions (III) and melatonin, was studied. Kinetic curves of emission decay and spectral distributions of chemiluminescence were obtained. Analysis of differences in the intensity of chemiluminescence and CL spectra proved that excitation of Tb(III) and Dy(III) ions takes place with the energy transfer from the products of melatonin oxidation: N{sup 1}-acetyl-N{sup 2}-formyl-5-methoxykynuramine (AFMK) and N{sup 1}-acetyl-5-methoxykynuramine (AMK) to the lanthanide ions. In the system Fe(II)/Fe(III)–H{sub 2}O{sub 2}–Mel–Tb(III) a linear correlation was established between the integrated CL intensity and melatonin concent. - Highlights: • Chemiluminescence (CL) of melatonin (Mel) oxidation by reactive species of oxygen and nitrogen. • Tb(III) and Dy(III) ions as sensitizers of a melatonin oxidation process. • New CL method for determination of melatonin in pharmaceutical preparations based on CL of Fe(II)/Fe(III)–H{sub 2}O{sub 2}–Mel–Tb(III) system.

  2. The relationship between lipid accumulation product, visceral adiposity index and high-sensitivity C-reactive protein in healthy adults

    Directory of Open Access Journals (Sweden)

    Yan ZHANG

    2013-03-01

    Full Text Available Objective  To investigate the correlation between lipid accumulation product (LAP, visceral adiposity index (VAI and high-sensitivity C-reactive protein (hs-CRP in adults, and explore whether to use such correlation as indications is superior to the traditional body fat index based on body mass index (BMI, waist circumference (WC, waist-hip ratio (WHR and waist-height ratio (WHtR. Methods  The present work was a cross-sectional study involving 501 healthy adults (321 males and 180 females from the community of Chongqing Municipality. Anthropometric indexes [height, weight, WC, hip circumference (HC], blood pressure (BP, fasting lipid profile and levels of fasting and post-load glucose, insulin and hs-CRP were measured, and BMI, WHR, WHtR, fasting insulin resistant homeostasis model assessment (HOMA-IR, LAP and VAI were calculated. The correlations between hs-CRP and other variables were analyzed. Results  Following the elevation of titer of the hs-CRP, LAP, VAI, BMI, WC, WHR, WHtR, BP, glucose level, HOMA-IR, insulin, triglyceride (TG, low-density lipoprotein cholesterol (LDL-C and apolipoprotein B (ApoB increased (P<0.05, while high-density lipoprotein cholesterol (HDL-C and apolipoprotein A1 (ApoA1 levels declined (P<0.0001. Pearson's correlation analysis demonstrated that hs-CRP was correlated with all variances (P<0.01 except for total cholesterol (TC (P=0.181 and LDL -C (P=0.325. According to forward stepwise multiple regression analysis with hs-CRP as the dependent variance, WC was the only variance entering the regression model. Conclusion  LAP, VAI levels are correlated with hs-CRP level but not the major determinant factors of hs-CRP. WC is stronger than other variances in the association with hs-CRP in adults, and is still an independent predictor of inflammation.

  3. Heavy-metal-induced reactive oxygen species: phytotoxicity and physicochemical changes in plants.

    Science.gov (United States)

    Shahid, Muhammad; Pourrut, Bertrand; Dumat, Camille; Nadeem, Muhammad; Aslam, Muhammad; Pinelli, Eric

    2014-01-01

    As a result of the industrial revolution, anthropogenic activities have enhanced there distribution of many toxic heavy metals from the earth's crust to different environmental compartments. Environmental pollution by toxic heavy metals is increasing worldwide, and poses a rising threat to both the environment and to human health.Plants are exposed to heavy metals from various sources: mining and refining of ores, fertilizer and pesticide applications, battery chemicals, disposal of solid wastes(including sewage sludge), irrigation with wastewater, vehicular exhaust emissions and adjacent industrial activity.Heavy metals induce various morphological, physiological, and biochemical dysfunctions in plants, either directly or indirectly, and cause various damaging effects. The most frequently documented and earliest consequence of heavy metal toxicity in plants cells is the overproduction of ROS. Unlike redox-active metals such as iron and copper, heavy metals (e.g, Pb, Cd, Ni, AI, Mn and Zn) cannot generate ROS directly by participating in biological redox reactions such as Haber Weiss/Fenton reactions. However, these metals induce ROS generation via different indirect mechanisms, such as stimulating the activity of NADPH oxidases, displacing essential cations from specific binding sites of enzymes and inhibiting enzymatic activities from their affinity for -SH groups on the enzyme.Under normal conditions, ROS play several essential roles in regulating the expression of different genes. Reactive oxygen species control numerous processes like the cell cycle, plant growth, abiotic stress responses, systemic signalling, programmed cell death, pathogen defence and development. Enhanced generation of these species from heavy metal toxicity deteriorates the intrinsic antioxidant defense system of cells, and causes oxidative stress. Cells with oxidative stress display various chemical,biological and physiological toxic symptoms as a result of the interaction between ROS and

  4. Reactive oxygen species' role in endothelial dysfunction by electron paramagnetic resonance

    Science.gov (United States)

    Wassall, Cynthia D.

    The endothelium is a single layer of cells lining the arteries and is involved in many physiological reactions which are responsible for vascular tone. Free radicals are important participants in these chemical reactions in the endothelium. Here we quantify free radicals, ex vivo, in biological tissue with continuous wave electron paramagnetic resonance (EPR). In all of the experiments in this thesis, we use a novel EPR spin trapping technique that has been developed for tissue segments. EPR spin trapping is often considered the 'gold standard' in reactive oxygen species (ROS) detection because of its sensitivity and non-invasive nature. In all experiments, tissue was placed in physiological saline solution with 190-mM PBN (N-tert -butyl-α-phenylnitrone), 10% by volume dimethyl-sulphoxide (DMSO) for cryopreservation, and incubated in the dark for between 30 minutes up to 2 hours at 37°C while gently being stirred. Tissue and supernatant were then loaded into a syringe and frozen at -80°C until EPR analysis. In our experiments, the EPR spectra were normalized with respect to tissue volume. Conducting experiments at liquid nitrogen temperature leads to some experimental advantages. The freezing of the spin adducts renders them stable over a longer period, which allows ample time to analyze tissue samples for ROS. The dielectric constant of ice is greatly reduced over its liquid counterpart; this property of water enables larger sample volumes to be inserted into the EPR cavity without overloading it and leads to enhanced signal detection. Due to Maxwell-Boltzmann statistics, the population difference goes up as the temperature goes down, so this phenomenon enhances the signal intensity as well. With the 'gold standard' assertion in mind, we investigated whether slicing tissue to assay ROS that is commonly used in fluorescence experiments will show more free radical generation than tissue of a similar volume that remains unsliced. Sliced tissue exhibited a 76

  5. E-Cigarette Aerosol Exposure Induces Reactive Oxygen Species, DNA Damage, and Cell Death in Vascular Endothelial Cells.

    Science.gov (United States)

    Anderson, Chastain; Majeste, Andrew; Hanus, Jakub; Wang, Shusheng

    2016-12-01

    Cigarette smoking remains one of the leading causes of preventable death worldwide. Vascular cell death and dysfunction is a central or exacerbating component in the majority of cigarette smoking related pathologies. The recent development of the electronic nicotine delivery systems known as e-cigarettes provides an alternative to conventional cigarette smoking; however, the potential vascular health risks of e-cigarette use remain unclear. This study evaluates the effects of e-cigarette aerosol extract (EAE) and conventional cigarette smoke extract (CSE) on human umbilical vein endothelial cells (HUVECs). A laboratory apparatus was designed to produce extracts from e-cigarettes and conventional cigarettes according to established protocols for cigarette smoking. EAE or conventional CSE was applied to human vascular endothelial cells for 4-72 h, dependent on the assay. Treated cells were assayed for reactive oxygen species, DNA damage, cell viability, and markers of programmed cell death pathways. Additionally, the anti-oxidants α-tocopherol and n-acetyl-l-cysteine were used to attempt to rescue e-cigarette induced cell death. Our results indicate that e-cigarette aerosol is capable of inducing reactive oxygen species, causing DNA damage, and significantly reducing cell viability in a concentration dependent fashion. Immunofluorescent and flow cytometry analysis indicate that both the apoptosis and programmed necrosis pathways are triggered by e-cigarette aerosol treatment. Additionally, anti-oxidant treatment provides a partial rescue of the induced cell death, indicating that reactive oxygen species play a causal role in e-cigarette induced cytotoxicity. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Multiphase composition changes and reactive oxygen species formation during limonene oxidation in the new Cambridge Atmospheric Simulation Chamber (CASC)

    Science.gov (United States)

    Gallimore, Peter J.; Mahon, Brendan M.; Wragg, Francis P. H.; Fuller, Stephen J.; Giorio, Chiara; Kourtchev, Ivan; Kalberer, Markus

    2017-08-01

    The chemical composition of organic aerosols influences their impacts on human health and the climate system. Aerosol formation from gas-to-particle conversion and in-particle reaction was studied for the oxidation of limonene in a new facility, the Cambridge Atmospheric Simulation Chamber (CASC). Health-relevant oxidising organic species produced during secondary organic aerosol (SOA) formation were quantified in real time using an Online Particle-bound Reactive Oxygen Species Instrument (OPROSI). Two categories of reactive oxygen species (ROS) were identified based on time series analysis: a short-lived component produced during precursor ozonolysis with a lifetime of the order of minutes, and a stable component that was long-lived on the experiment timescale (˜ 4 h). Individual organic species were monitored continuously over this time using Extractive Electrospray Ionisation (EESI) Mass Spectrometry (MS) for the particle phase and Proton Transfer Reaction (PTR) MS for the gas phase. Many first-generation oxidation products are unsaturated, and we observed multiphase aging via further ozonolysis reactions. Volatile products such as C9H14O (limonaketone) and C10H16O2 (limonaldehyde) were observed in the gas phase early in the experiment, before reacting again with ozone. Loss of C10H16O4 (7-hydroxy limononic acid) from the particle phase was surprisingly slow. A combination of reduced C = C reactivity and viscous particle formation (relative to other SOA systems) may explain this, and both scenarios were tested in the Pretty Good Aerosol Model (PG-AM). A range of characterisation measurements were also carried out to benchmark the chamber against existing facilities. This work demonstrates the utility of CASC, particularly for understanding the reactivity and health-relevant properties of organic aerosols using novel, highly time-resolved techniques.

  7. Regulation of Cys-based protein tyrosine phosphatases via reactive oxygen and nitrogen species in mast cells and basophils

    Czech Academy of Sciences Publication Activity Database

    Heneberg, Petr; Dráber, Petr

    2005-01-01

    Roč. 12, č. 16 (2005), s. 1859-1871 ISSN 0929-8673 R&D Projects: GA ČR(CZ) GA204/03/0594; GA ČR(CZ) GA301/03/0596; GA AV ČR(CZ) IAA5052310; GA MZd(CZ) NR8079; GA MŠk(CZ) 1M0506; GA MŠk(CZ) 1P04OE158 Institutional research plan: CEZ:AV0Z50520514 Keywords : mast cell * tyrosine phosphatase * reactive oxygen species Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.904, year: 2005

  8. Titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation

    Directory of Open Access Journals (Sweden)

    Yoon TH

    2012-03-01

    Full Text Available Ki-Chun Yoo1, Chang-Hwan Yoon1, Dongwook Kwon2, Kyung-Hwan Hyun1, Soo Jung Woo1, Rae-Kwon Kim1, Eun-Jung Lim1, Yongjoon Suh1, Min-Jung Kim1, Tae Hyun Yoon2, Su-Jae Lee11Laboratory of Molecular Biochemistry, 2Laboratory of Nanoscale Characterization and Environmental Chemistry, Department of Chemistry, Hanyang University, Seoul, Republic of KoreaBackground: Titanium dioxide (TiO2 has been widely used in many areas, including biomedicine, cosmetics, and environmental engineering. Recently, it has become evident that some TiO2 particles have a considerable cytotoxic effect in normal human cells. However, the molecular basis for the cytotoxicity of TiO2 has yet to be defined.Methods and results: In this study, we demonstrated that combined treatment with TiO2 nanoparticles sized less than 100 nm and ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-dependent upregulation of Fas and conformational activation of Bax in normal human cells. Treatment with P25 TiO2 nanoparticles with a hydrodynamic size distribution centered around 70 nm (TiO2P25–70 together with ultraviolet A irradiation-induced caspase-dependent apoptotic cell death, accompanied by transcriptional upregulation of the death receptor, Fas, and conformational activation of Bax. In line with these results, knockdown of either Fas or Bax with specific siRNA significantly inhibited TiO2-induced apoptotic cell death. Moreover, inhibition of reactive oxygen species with an antioxidant, N-acetyl-L-cysteine, clearly suppressed upregulation of Fas, conformational activation of Bax, and subsequent apoptotic cell death in response to combination treatment using TiO2P25–70 and ultraviolet A irradiation.Conclusion: These results indicate that sub-100 nm sized TiO2 treatment under ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-mediated upregulation of the death receptor, Fas, and activation of the preapoptotic protein

  9. Fluorescent boronate-based polymer nanoparticles with reactive oxygen species (ROS)-triggered cargo release for drug-delivery applications

    Czech Academy of Sciences Publication Activity Database

    Jäger, Eliezer; Höcherl, Anita; Janoušková, Olga; Jäger, Alessandro; Hrubý, Martin; Konefal, Rafal; Netopilík, Miloš; Pánek, Jiří; Šlouf, Miroslav; Ulbrich, Karel; Štěpánek, Petr

    2016-01-01

    Roč. 8, č. 13 (2016), s. 6958-6963 ISSN 2040-3364 R&D Projects: GA MŠk(CZ) 7F14009; GA MPO(CZ) FR-TI4/625; GA MŠk(CZ) LH14292; GA MŠk(CZ) LO1507; GA TA ČR(CZ) TE01020118 Institutional support: RVO:61389013 Keywords : reactive oxygen species (ROS) * responsive nanoparticles * fluorescence life -time imaging (FLIM) Subject RIV: CC - Organic Chemistry Impact factor: 7.367, year: 2016

  10. ACCERBATIN, a small molecule at the intersection of auxin and reactive oxygen species homeostasis with herbicidal properties

    Czech Academy of Sciences Publication Activity Database

    Hu, Y.; Depaepe, T.; Smet, D.; Hoyerová, Klára; Klíma, Petr; Cuypers, J.; Cutler, S.; Buyst, D.; Morreel, K.; Boerjan, W.; Martins, J.; Petrášek, Jan; Vandenbussche, F.; Van Der Straeten, D.

    2017-01-01

    Roč. 68, č. 15 (2017), s. 4185-4203 ISSN 0022-0957 R&D Projects: GA MŠk LD15137 Institutional support: RVO:61389030 Keywords : apical hook development * root hair development * arabidopsis-thaliana seedlings * ethylene biosynthesis * shoot gravitropism * cell elongation * abiotic stress * abscisic-acid * plant-growth * gene family * Arabidopsis * auxin homeostasis * chemical genetics * ethylene signaling * herbicide * quinoline carboxamide * reactive oxygen species * triple response Subject RIV: EA - Cell Biology OBOR OECD: Plant sciences, botany Impact factor: 5.830, year: 2016

  11. Amplifying the manganese scavenging potential of Streptococcus zooepidemicus to reactive oxygen species during production of hyaluronic acid.

    Science.gov (United States)

    Mashitah, M D; Masitah, H; Ramachandran, K B

    2004-05-01

    Streptococcus zooepidemicus (SZ) is an aerotolerant bacteria and its ability to survive under reactive oxidant challenge raises the question of the existence of a defense system. Thus growth, hyaluronic acid (HA) and hydrogen peroxide (H2O2) production by SZ in the presence of increasing concentration of Mn2+ were studied. The results suggested that the tested strain supported growth and HA production in cultures treated with 1 and 10 mM of Mn2+ regardless of H2O2 presence in the medium. This showed that SZ have acquired elaborate defense mechanisms to scavenge oxygen toxicity and thus protect cells from direct and indirect effect of this radical. In contrast, cells treated with 25 mM Mn2+ were sensitive, in which, the HA production was reduced considerably. Thus showing that the oxygen scavenger systems of the cells may be fully saturated at this concentration.

  12. Role of reactive oxygen species in rheumatoid arthritis synovial T lymphocytes

    NARCIS (Netherlands)

    Remans, Philip Herman Jozef

    2006-01-01

    In rheumatoid arthritis, an inflammatory infiltrate accumulates and persists in the synovial membrane. Synovial T cells display a number of particular characteristics. While displaying markers of recent activation, synovial T lymphocytes respond poorly to mitogenic stimuli and their cytokine

  13. Emerging roles of hypoxia-inducible factors and reactive oxygen species in cancer and pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Shigeo Saito

    2015-06-01

    Full Text Available Eukaryotic organisms require oxygen homeostasis to maintain proper cellular function for survival. During conditions of low oxygen tension (hypoxia, cells activate the transcription of genes that induce an adaptive response, which supplies oxygen to tissues. Hypoxia and hypoxia-inducible factors (HIFs may contribute to the maintenance of putative cancer stem cells, which can continue self-renewal indefinitely and express stemness genes in hypoxic stress environments (stem cell niches. Reactive oxygen species (ROS have long been recognized as toxic by-products of aerobic metabolism that are harmful to living cells, leading to DNA damage, senescence, or cell death. HIFs may promote a cancer stem cell state, whereas the loss of HIFs induces the production of cellular ROS and activation of proteins p53 and p16Ink4a, which lead to tumor cell death and senescence. ROS seem to inhibit HIF regulation in cancer cells. By contrast, controversial data have suggested that hypoxia increases the generation of ROS, which prevents hydroxylation of HIF proteins by inducing their transcription as negative feedback. Moreover, hypoxic conditions enhance the generation of induced pluripotent stem cells (iPSCs. During reprogramming of somatic cells into a PSC state, cells attain a metabolic state typically observed in embryonic stem cells (ESCs. ESCs and iPSCs share similar bioenergetic metabolisms, including decreased mitochondrial number and activity, and induced anaerobic glycolysis. This review discusses the current knowledge regarding the emerging roles of ROS homeostasis in cellular reprogramming and the implications of hypoxic regulation in cancer development.

  14. Role of dissolved oxygen on the degradation mechanism of Reactive Green 19 and electricity generation in photocatalytic fuel cell.

    Science.gov (United States)

    Lee, Sin-Li; Ho, Li-Ngee; Ong, Soon-An; Wong, Yee-Shian; Voon, Chun-Hong; Khalik, Wan Fadhilah; Yusoff, Nik Athirah; Nordin, Noradiba

    2018-03-01

    In this study, a membraneless photocatalytic fuel cell with zinc oxide loaded carbon photoanode and platinum loaded carbon cathode was constructed to investigate the impact of dissolved oxygen on the mechanism of dye degradation and electricity generation of photocatalytic fuel cell. The photocatalytic fuel cell with high and low aeration rate, no aeration and nitrogen purged were investigated, respectively. The degradation rate of diazo dye Reactive Green 19 and the electricity generation was enhanced in photocatalytic fuel cell with higher dissolved oxygen concentration. However, the photocatalytic fuel cell was still able to perform 37% of decolorization in a slow rate (k = 0.033 h -1 ) under extremely low dissolved oxygen concentration (approximately 0.2 mg L -1 ) when nitrogen gas was introduced into the fuel cell throughout the 8 h. However, the change of the UV-Vis spectrum indicates that the intermediates of the dye could not be mineralized under insufficient dissolved oxygen level. In the aspect of electricity generation, the maximum short circuit current (0.0041 mA cm -2 ) and power density (0.00028 mW cm -2 ) of the air purged photocatalytic fuel cell was obviously higher than that with nitrogen purging (0.0015 mA cm -2 and 0.00008 mW cm -2 ). Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Sustained Na+/H+ exchanger activation promotes gliotransmitter release from reactive hippocampal astrocytes following oxygen-glucose deprivation.

    Directory of Open Access Journals (Sweden)

    Pelin Cengiz

    Full Text Available Hypoxia ischemia (HI-related brain injury is the major cause of long-term morbidity in neonates. One characteristic hallmark of neonatal HI is the development of reactive astrogliosis in the hippocampus. However, the impact of reactive astrogliosis in hippocampal damage after neonatal HI is not fully understood. In the current study, we investigated the role of Na(+/H(+ exchanger isoform 1 (NHE1 protein in mouse reactive hippocampal astrocyte function in an in vitro ischemia model (oxygen/glucose deprivation and reoxygenation, OGD/REOX. 2 h OGD significantly increased NHE1 protein expression and NHE1-mediated H(+ efflux in hippocampal astrocytes. NHE1 activity remained stimulated during 1-5 h REOX and returned to the basal level at 24 h REOX. NHE1 activation in hippocampal astrocytes resulted in intracellular Na(+ and Ca(2+ overload. The latter was mediated by reversal of Na(+/Ca(2+ exchange. Hippocampal astrocytes also exhibited a robust release of gliotransmitters (glutamate and pro-inflammatory cytokines IL-6 and TNFα during 1-24 h REOX. Interestingly, inhibition of NHE1 activity with its potent inhibitor HOE 642 not only reduced Na(+ overload but also gliotransmitter release from hippocampal astrocytes. The noncompetitive excitatory amino acid transporter inhibitor TBOA showed a similar effect on blocking the glutamate release. Taken together, we concluded that NHE1 plays an essential role in maintaining H(+ homeostasis in hippocampal astrocytes. Over-stimulation of NHE1 activity following in vitro ischemia disrupts Na(+ and Ca(2+ homeostasis, which reduces Na(+-dependent glutamate uptake and promotes release of glutamate and cytokines from reactive astrocytes. Therefore, blocking sustained NHE1 activation in reactive astrocytes may provide neuroprotection following HI.

  16. Site-Specific Reactivity of Copper Chabazite Zeolites with Nitric Oxide, Ammonia, and Oxygen

    DEFF Research Database (Denmark)

    Godiksen, Anita; Isaksen, Oliver L.; Rasmussen, Søren B.

    2018-01-01

    In-situ electron paramagnetic resonance (EPR) spectroscopy was applied to dilute copper chabazite (CHA) zeolites under gas flows relevant for the selective catalytic reduction of NO with ammonia (NH3-SCR). Under both reducing and oxidizing conditions, we observed differences in reactivity between...

  17. Interfacial microstructure and shear strength of reactive air brazed oxygen transport membrane ceramic-metal alloy joints

    Science.gov (United States)

    FR, Wahid Muhamad; Yoon, Dang-Hyok; Raju, Kati; Kim, Seyoung; Song, Kwang-sup; Yu, Ji Haeng

    2018-01-01

    To fabricate a multi-layered structure for maximizing oxygen production, oxygen transport membrane (OTM) ceramics need to be joined or sealed hermetically metal supports for interfacing with the peripheral components of the system. Therefore, in this study, Ag-10 wt% CuO was evaluated as an effective filler material for the reactive air brazing of dense Ce0.9Gd0.1O2-δ-La0.7Sr0.3MnO3±δ (GDC-LSM) OTM ceramics. Thermal decomposition in air and wetting behavior of the braze filler was performed. Reactive air brazing was performed at 1050 °C for 30 min in air to join GDC-LSM with four different commercially available high temperature-resistant metal alloys, such as Crofer 22 APU, Inconel 600, Fecralloy, and AISI 310S. The microstructure and elemental distribution of the ceramic-ceramic and ceramic-metal interfaces were examined from polished cross-sections. The mechanical shear strength at room temperature for the as-brazed and isothermally aged (800 °C for 24 h) joints of all the samples was compared. The results showed that the strength of the ceramic-ceramic joints was decreased marginally by aging; however, in the case of metal-ceramic joints, different decreases in strengths were observed according to the metal alloy used, which was explained based on the formation of different oxide layers at the interfaces.

  18. The association of elevated reactive oxygen species levels from neutrophils with low-grade inflammation in the elderly

    Directory of Open Access Journals (Sweden)

    Suzuki Katsuhiko

    2008-10-01

    Full Text Available Abstract Background Reactive oxygen species (ROS, including free radicals, oxygen ions, and peroxides, are implicated in cell damage. The objective of this study was to investigate whether the spontaneous production of ROS from neutrophils changes with age and is associated with the conventional inflammatory markers. Results Thirty-seven elderly subjects (median age, 87, range 70–95 years and 22 young subjects (median age, 26, range 21–37 years participated in this study. Circulating levels of C-reactive protein, serum amyloid A, tumor necrosis factor-α, interleukin (IL-1, IL-6, IL-8, monocyte chemotactic protein-1, and heat shock protein (HSP70 were measured with enzyme-linked immunosorbent assays. The N-formyl-methionyl-leucyl-phenylalanine and lipopolysaccharide-stimulated ROS of neutrophils were quantified by flow cytometry. Both spontaneous ROS production and circulating levels of inflammatory markers were higher in the elderly group than in the younger group. In addition, spontaneous ROS production by neutrophils was negatively associated with HSP70 in plasma. We could not find the association between spontaneous ROS production by neutrophils and the other inflammatory markers including cytokines. Conclusion The results suggest that spontaneous ROS production from neutrophils may increase with age and represent the different aspect of age-associated immune dysregulation.

  19. Reactive oxygen species scavengers ameliorate mechanical allodynia in a rat model of cancer-induced bone pain

    Directory of Open Access Journals (Sweden)

    Ya-Qun Zhou

    2018-04-01

    Full Text Available Cancer-induced bone pain (CIBP is a frequent complication in patients suffering from bone metastases. Previous studies have demonstrated a pivotal role of reactive oxygen species (ROS in inflammatory and neuropathic pain, and ROS scavengers exhibited potent antinociceptive effect. However, the role of spinal ROS remains unclear. In this study, we investigated the analgesic effect of two ROS scavengers in a well-established CIBP model. Our results found that intraperitoneal injection of N-tert-Butyl-α-phenylnitrone (PBN, 50 and 100 mg/kg and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol, 100 and 200 mg/kg significantly suppressed the established mechanical allodynia in CIBP rats. Moreover, repeated injection of PBN and Tempol showed cumulative analgesic effect without tolerance. However, early treatment with PBN and Tempol failed to prevent the development of CIBP. Naive rats received repetitive injection of PBN and Tempol showed no significant change regarding the nociceptive responses. Finally, PBN and Tempol treatment notably suppressed the activation of spinal microglia in CIBP rats. In conclusion, ROS scavengers attenuated established CIBP by suppressing the activation of microglia in the spinal cord. Keywords: Cancer-induced bone pain, Reactive oxygen species, PBN, Tempol

  20. The role of reactive oxygen species in near-ultraviolet (320-400 nm) light inactivation of Escherichia coli

    International Nuclear Information System (INIS)

    Sammartano, L.J.

    1988-01-01

    The purpose of the present study was to further elucidate the mechanism of near-UV inactivation in Escherichia coli. Several genetic and biochemical techniques were employed to examine the role of oxygen reactive species in near-UV mediated damage to DNA and membrane components, and to identify endogenous photosensitizers. The results demonstrate that the near-UV inactivation process is initiated when the radiant energy is absorbed by components of the respiratory chain, including cytochromes. The absorption of energy causes the chromophore to be electronically excited into the triplet state which leads to subsequent generation of oxygen reactive species within the membrane. The first line of cellular defense against this oxidative stress is a complex network of antioxidants and scavengers, including catalase, superoxide dismutase and glutathione reductase. E. coli cells also have a second line of defense that incorporates repair systems. In this study evidence is provided for an excision repair pathway that is unique to near-UV mediated damage. Results suggest that a unique, but as yet unidentified, DNA lesion occurs in near-UV irradiated cells. Evidence is also presented that shows near-UV mediated damage also occurs in the membrane

  1. Exposure of Bacterial Biofilms to Electrical Current Leads to Cell Death Mediated in Part by Reactive Oxygen Species.

    Science.gov (United States)

    Brinkman, Cassandra L; Schmidt-Malan, Suzannah M; Karau, Melissa J; Greenwood-Quaintance, Kerryl; Hassett, Daniel J; Mandrekar, Jayawant N; Patel, Robin

    2016-01-01

    Bacterial biofilms may form on indwelling medical devices such as prosthetic joints, heart valves and catheters, causing challenging-to-treat infections. We have previously described the 'electricidal effect', in which bacterial biofilms are decreased following exposure to direct electrical current. Herein, we sought to determine if the decreased bacterial quantities are due to detachment of biofilms or cell death and to investigate the role that reactive oxygen species (ROS) play in the observed effect. Using confocal and electron microscopy and flow cytometry, we found that direct current (DC) leads to cell death and changes in the architecture of biofilms formed by Gram-positive and Gram-negative bacteria. Reactive oxygen species (ROS) appear to play a role in DC-associated cell death, as there was an increase in ROS-production by Staphylococcus aureus and Staphylococcus epidermidis biofilms following exposure to DC. An increase in the production of ROS response enzymes catalase and superoxide dismutase (SOD) was observed for S. aureus, S. epidermidis and Pseudomonas aeruginosa biofilms following exposure to DC. Additionally, biofilms were protected from cell death when supplemented with antioxidants and oxidant scavengers, including catalase, mannitol and Tempol. Knocking out SOD (sodAB) in P. aeruginosa led to an enhanced DC effect. Microarray analysis of P. aeruginosa PAO1 showed transcriptional changes in genes related to the stress response and cell death. In conclusion, the electricidal effect results in death of bacteria in biofilms, mediated, at least in part, by production of ROS.

  2. Efficacy of the Reactive Oxygen Species Generated by Immobilized TiO2 in the Photocatalytic Degradation of Diclofenac

    Directory of Open Access Journals (Sweden)

    B. Di Credico

    2015-01-01

    Full Text Available We report on the photodegradation of diclofenac (DCF by hydrothermal anatase nanocrystals either free or immobilized in porous silica matrix (TS in connection to the type and amount of reactive oxygen species (ROS, in order to have deeper insight into their role in the photocatalysis and to provide an effective tool to implement the DCF mineralization. TiO2 and TS exhibit a remarkable efficiency in the DCF abatement, supporting that the utilization of anatase nanoparticles with the highly reactive {001}, {010}, and {101} exposed surfaces can be an effective way for enhancing the photooxidation even of the persistent pollutants. Furthermore, the hydrothermal TiO2, when immobilized in silica matrix, preserves its functional properties, combining high photoactivity with an easy technical use and recovery of the catalyst. The catalysts performances have been related to the presence of OH•, O21, and O2-• species by electron paramagnetic resonance spin-trap technique. The results demonstrated that the ROS concentration increases with the increase of photoactivity and indicated a significant involvement of O21 in the DCF degradation. The efficacy of TiO2 when immobilized on a silica matrix was associated with the high ROS life time and with the presence of singlet oxygen, which contributes to the complete photomineralization of DCF.

  3. Inorganic Polyphosphates Regulate Hexokinase Activity and Reactive Oxygen Species Generation in Mitochondria of Rhipicephalus (Boophilus) microplus Embryo

    Science.gov (United States)

    Fraga, Amanda; Moraes, Jorge; da Silva, José Roberto; Costa, Evenilton P.; Menezes, Jackson; da Silva Vaz Jr, Itabajara; Logullo, Carlos; da Fonseca, Rodrigo Nunes; Campos, Eldo

    2013-01-01

    The physiological roles of polyphosphates (poly P) recently found in arthropod mitochondria remain obscure. Here, the possible involvement of poly P with reactive oxygen species generation in mitochondria of Rhipicephalus microplus embryos was investigated. Mitochondrial hexokinase and scavenger antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione reductase were assayed during embryogenesis of R. microplus. The influence of poly P3 and poly P15 were analyzed during the period of higher enzymatic activity during embryogenesis. Both poly Ps inhibited hexokinase activity by up to 90% and, interestingly, the mitochondrial membrane exopolyphosphatase activity was stimulated by the hexokinase reaction product, glucose-6-phosphate. Poly P increased hydrogen peroxide generation in mitochondria in a situation where mitochondrial hexokinase is also active. The superoxide dismutase, catalase and glutathione reductase activities were higher during embryo cellularization, at the end of embryogenesis and during embryo segmentation, respectively. All of the enzymes were stimulated by poly P3. However, superoxide dismutase was not affected by poly P15, catalase activity was stimulated only at high concentrations and glutathione reductase was the only enzyme that was stimulated in the same way by both poly Ps. Altogether, our results indicate that inorganic polyphosphate and mitochondrial membrane exopolyphosphatase regulation can be correlated with the generation of reactive oxygen species in the mitochondria of R. microplus embryos. PMID:23983617

  4. Reactive oxygen species modulator 1 (Romo1) as a novel diagnostic marker for lung cancer-related malignant effusion

    Science.gov (United States)

    Lee, Seung Hyeun; Park, Myung Jae; Choi, Sue In; Lee, Eun Joo; Lee, Sang Yeub; In, Kwang Ho

    2017-01-01

    Abstract Reactive oxygen species modulator 1 (Romo1) is a novel protein that plays an important role in intracellular reactive oxygen species generation. Recently, Romo1 has been suggested to have diagnostic and prognostic potential in lung cancer. However, there is no data on the diagnostic value of Romo1 level in malignant pleural effusion. We evaluated the clinical usefulness of Romo1 in pleural fluid for the diagnosis of malignant effusion in lung cancer patients. Pleural fluid Romo1 level was measured using enzyme-linked immunosorbent assay and compared between lung cancer-associated malignant effusion (n = 53; 29 adenocarcinomas and 24 squamous cell carcinomas) and benign pleural effusions (n = 91; 31 tuberculous pleurisy, 30 parapneumonic effusion, and 30 transudate). The discriminative power of Romo1 for lung cancer-associated malignant effusion was determined using receiver operating characteristic (ROC) curve analysis and compared with those of other tumor markers. Median Romo1 level in lung cancer-associated malignant effusion was 99.3 ng/mL, which was significantly higher than that in benign pleural effusions (P effusion from benign effusions was 67.0 ng/mL with a sensitivity of 73.8% and a specificity of 84.1%. The area under the curve was 0.837 (95% confidence interval [CI]: 0.750–0.886), which was significantly better than that of cytokeratin 19 fragments (P effusion. PMID:28121949

  5. Oxygen accumulation in photobioreactors

    NARCIS (Netherlands)

    Fonseca e Sousa, da C.A.

    2013-01-01

    Phototropic microalgae are regarded as a promising feedstock for sustainable biodiesel production, as microalgae can use natural sunlight as light source and are able to utilize CO2from flue gases and nutrients (P, N) from waste streams. To make large-scale outdoor microalgae

  6. Cadmium accumulation in and tolerance of rice (Oryza sativa L.) varieties with different rates of radial oxygen loss

    International Nuclear Information System (INIS)

    Wang, M.Y.; Chen, A.K.; Wong, M.H.; Qiu, R.L.; Cheng, H.; Ye, Z.H.

    2011-01-01

    Cadmium (Cd) uptake and tolerance were investigated among 20 rice cultivars based on a field experiment (1.2 mg Cd kg -1 in soil) and a soil pot trial (control, 100 mg Cd kg -1 ), and rates of radial oxygen loss (ROL) were measured under a deoxygenated solution. Significant differences were found among the cultivars in: (1) brown rice Cd concentrations (0.11-0.29 mg kg -1 ) in a field soil, (2) grain Cd tolerance (34-113%) and concentrations (2.1-6.5 mg kg -1 ) in a pot trial, and (3) rates of ROL (15-31 mmol O 2 kg -1 root d.w. h -1 ). Target hazard quotients were calculated for the field experiment to assess potential Cd risk. Significant negative relationships were found between rates of ROL and concentrations of Cd in brown rice or straw under field and greenhouse conditions, indicating that rice cultivars with higher rates of ROL had higher capacities for limiting the transfer of Cd to rice and straw. - Highlights: → There are significant differences in brown rice Cd concentrations and rates of ROL among the rice cultivars. → The rates of ROL are significantly correlated with concentrations of Cd in brown rice. → Rice cultivars with higher rates of ROL have higher capacities for limiting the transfer of Cd to rice and straw. - Rice cultivars with high rates of ROL tended to accumulate low Cd in grains.

  7. Generation and Role of Reactive Oxygen and Nitrogen Species Induced by Plasma, Lasers, Chemical Agents, and Other Systems in Dentistry

    Science.gov (United States)

    Jha, Nayansi; Ryu, Jae Jun

    2017-01-01

    The generation of reactive oxygen and nitrogen species (RONS) has been found to occur during inflammatory procedures, during cell ischemia, and in various crucial developmental processes such as cell differentiation and along cell signaling pathways. The most common sources of intracellular RONS are the mitochondrial electron transport system, NADH oxidase, and cytochrome P450. In this review, we analyzed the extracellular and intracellular sources of reactive species, their cell signaling pathways, the mechanisms of action, and their positive and negative effects in the dental field. In dentistry, ROS can be found—in lasers, photosensitizers, bleaching agents, cold plasma, and even resin cements, all of which contribute to the generation and prevalence of ROS. Nonthermal plasma has been used as a source of ROS for biomedical applications and has the potential for use with dental stem cells as well. There are different types of dental stem cells, but their therapeutic use remains largely untapped, with the focus currently on only periodontal ligament stem cells. More research is necessary in this area, including studies about ROS mechanisms with dental cells, along with the utilization of reactive species in redox medicine. Such studies will help to provide successful treatment modalities for various diseases. PMID:29204250

  8. Dependence of size and size distribution on reactivity of aluminum nanoparticles in reactions with oxygen and MoO3

    International Nuclear Information System (INIS)

    Sun, Juan; Pantoya, Michelle L.; Simon, Sindee L.

    2006-01-01

    The oxidation reaction of aluminum nanoparticles with oxygen gas and the thermal behavior of a metastable intermolecular composite (MIC) composed of the aluminum nanoparticles and molybdenum trioxide are studied with differential scanning calorimetry (DSC) as a function of the size and size distribution of the aluminum particles. Both broad and narrow size distributions have been investigated with aluminum particle sizes ranging from 30 to 160 nm; comparisons are also made to the behavior of micrometer-size particles. Several parameters have been used to characterize the reactivity of aluminum nanoparticles, including the fraction of aluminum that reacts prior to aluminum melting, heat of reaction, onset and peak temperatures, and maximum reaction rates. The results indicate that the reactivity of aluminum nanoparticles is significantly higher than that of the micrometer-size samples, but depending on the measure of reactivity, it may also depend strongly on the size distribution. The isoconversional method was used to calculate the apparent activation energy, and the values obtained for both the Al/O 2 and Al/MoO 3 reaction are in the range of 200-300 kJ/mol

  9. Repetitive Hyperbaric Oxygenation Attenuates Reactive Astrogliosis and Suppresses Expression of Inflammatory Mediators in the Rat Model of Brain Injury

    Directory of Open Access Journals (Sweden)

    Irena Lavrnja

    2015-01-01

    Full Text Available The exact mechanisms by which treatment with hyperbaric oxygen (HBOT exerts its beneficial effects on recovery after brain injury are still unrevealed. Therefore, in this study we investigated the influence of repetitive HBOT on the reactive astrogliosis and expression of mediators of inflammation after cortical stab injury (CSI. CSI was performed on male Wistar rats, divided into control, sham, and lesioned groups with appropriate HBO. The HBOT protocol was as follows: 10 minutes of slow compression, 2.5 atmospheres absolute (ATA for 60 minutes, and 10 minutes of slow decompression, once a day for 10 consecutive days. Data obtained using real-time polymerase chain reaction, Western blot, and immunohistochemical and immunofluorescence analyses revealed that repetitive HBOT applied after the CSI attenuates reactive astrogliosis and glial scarring, and reduces expression of GFAP (glial fibrillary acidic protein, vimentin, and ICAM-1 (intercellular adhesion molecule-1 both at gene and tissue levels. In addition, HBOT prevents expression of CD40 and its ligand CD40L on microglia, neutrophils, cortical neurons, and reactive astrocytes. Accordingly, repetitive HBOT, by prevention of glial scarring and limiting of expression of inflammatory mediators, supports formation of more permissive environment for repair and regeneration.

  10. Pathophysiology and prevention of photoaging : the role of melanin, reactive oxygen species and infiltrating neutrophils

    NARCIS (Netherlands)

    Rijken, F.

    2011-01-01

    Photoaging of human skin involves epidermal and dermal changes. The hallmark of photoaged skin is an accumulation of elastotic material in the mid and upper dermis, so-called solar elastosis. This elastotic material is mostly derived from degraded elastic fibers and consists mainly of insoluble

  11. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system and proinflammatory cytokines in hypertension

    International Nuclear Information System (INIS)

    Su, Qing; Qin, Da-Nian; Wang, Fu-Xin; Ren, Jun; Li, Hong-Bao; Zhang, Meng; Yang, Qing; Miao, Yu-Wang; Yu, Xiao-Jing; Qi, Jie; Zhu, Zhiming; Zhu, Guo-Qing; Kang, Yu-Ming

    2014-01-01

    Aims: To explore whether reactive oxygen species (ROS) scavenger (tempol) in the hypothalamic paraventricular nucleus (PVN) attenuates renin–angiotensin system (RAS) and proinflammatory cytokines (PICs), and decreases the blood pressure and sympathetic activity in angiotensin II (ANG II)-induced hypertension. Methods and results: Male Sprague–Dawley rats were infused intravenously with ANG II (10 ng/kg per min) or normal saline (NS) for 4 weeks. These rats were treated with bilateral PVN infusion of oxygen free radical scavenger tempol (TEMP, 20 μg/h) or vehicle (artificial cerebrospinal fluid, aCSF) for 4 weeks. ANG II infusion resulted in increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). These ANG II-infused rats also had higher levels of gp91 phox (a subunit of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), and interleukin-1beta (IL-1β) in the PVN than the control animals. Treatment with PVN infusion of TEMP attenuated the overexpression of gp91 phox , ACE and IL-1β within the PVN, and decreased sympathetic activity and MAP in ANG II-infused rats. Conclusion: These findings suggest that ANG II infusion induces elevated PICs and oxidative stress in the PVN, which contribute to the sympathoexcitation in hypertension. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system, proinflammatory cytokines and oxidative stress in ANG II-induced hypertension. - Highlights: • The effect of chronic inhibiting PVN superoxide on hypertension was investigated. • ANG II infusion induced increased proinflammatory cytokines and superoxide in PVN. • ANG II infusion resulted in oxidative stress, sympathoexcitation and hypertension. • Chronic inhibiting PVN superoxide attenuates RAS and cytokines in hypertension

  12. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system and proinflammatory cytokines in hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Su, Qing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China); Wang, Fu-Xin [Department of Neurology, The First Affiliated Hospital of Jiamusi University, Jiamusi 154002 (China); Ren, Jun [Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY 82071 (United States); Li, Hong-Bao; Zhang, Meng; Yang, Qing; Miao, Yu-Wang; Yu, Xiao-Jing; Qi, Jie [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhu, Zhiming [Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, The Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China)

    2014-04-15

    Aims: To explore whether reactive oxygen species (ROS) scavenger (tempol) in the hypothalamic paraventricular nucleus (PVN) attenuates renin–angiotensin system (RAS) and proinflammatory cytokines (PICs), and decreases the blood pressure and sympathetic activity in angiotensin II (ANG II)-induced hypertension. Methods and results: Male Sprague–Dawley rats were infused intravenously with ANG II (10 ng/kg per min) or normal saline (NS) for 4 weeks. These rats were treated with bilateral PVN infusion of oxygen free radical scavenger tempol (TEMP, 20 μg/h) or vehicle (artificial cerebrospinal fluid, aCSF) for 4 weeks. ANG II infusion resulted in increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). These ANG II-infused rats also had higher levels of gp91{sup phox} (a subunit of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), and interleukin-1beta (IL-1β) in the PVN than the control animals. Treatment with PVN infusion of TEMP attenuated the overexpression of gp91{sup phox}, ACE and IL-1β within the PVN, and decreased sympathetic activity and MAP in ANG II-infused rats. Conclusion: These findings suggest that ANG II infusion induces elevated PICs and oxidative stress in the PVN, which contribute to the sympathoexcitation in hypertension. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system, proinflammatory cytokines and oxidative stress in ANG II-induced hypertension. - Highlights: • The effect of chronic inhibiting PVN superoxide on hypertension was investigated. • ANG II infusion induced increased proinflammatory cytokines and superoxide in PVN. • ANG II infusion resulted in oxidative stress, sympathoexcitation and hypertension. • Chronic inhibiting PVN superoxide attenuates RAS and cytokines in hypertension.

  13. Establishment and intra-/inter-laboratory validation of a standard protocol of reactive oxygen species assay for chemical photosafety evaluation.

    Science.gov (United States)

    Onoue, Satomi; Hosoi, Kazuhiro; Wakuri, Shinobu; Iwase, Yumiko; Yamamoto, Toshinobu; Matsuoka, Naoko; Nakamura, Kazuichi; Toda, Tsuguto; Takagi, Hironori; Osaki, Naoto; Matsumoto, Yasuhiro; Kawakami, Satoru; Seto, Yoshiki; Kato, Masashi; Yamada, Shizuo; Ohno, Yasuo; Kojima, Hajime

    2013-11-01

    A reactive oxygen species (ROS) assay was previously developed for photosafety evaluation of pharmaceuticals, and the present multi-center study aimed to establish and validate a standard protocol for ROS assay. In three participating laboratories, two standards and 42 coded chemicals, including 23 phototoxins and 19 nonphototoxic drugs/chemicals, were assessed by the ROS assay according to the standardized protocol. Most phototoxins tended to generate singlet oxygen and/or superoxide under UV-vis exposure, but nonphototoxic chemicals were less photoreactive. In the ROS assay on quinine (200 µm), a typical phototoxic drug, the intra- and inter-day precisions (coefficient of variation; CV) were found to be 1.5-7.4% and 1.7-9.3%, respectively. The inter-laboratory CV for quinine averaged 15.4% for singlet oxygen and 17.0% for superoxide. The ROS assay on 42 coded chemicals (200 µm) provided no false negative predictions upon previously defined criteria as compared with the in vitro/in vivo phototoxicity, although several false positives appeared. Outcomes from the validation study were indicative of satisfactory transferability, intra- and inter-laboratory variability, and predictive capacity of the ROS assay. Copyright © 2012 John Wiley & Sons, Ltd.

  14. Hybrid TiO2 -Ruthenium Nano-photosensitizer Synergistically Produces Reactive Oxygen Species in both Hypoxic and Normoxic Conditions.

    Science.gov (United States)

    Gilson, Rebecca C; Black, Kvar C L; Lane, Daniel D; Achilefu, Samuel

    2017-08-28

    Photodynamic therapy (PDT) is widely used to treat diverse diseases, but its dependence on oxygen to produce cytotoxic reactive oxygen species (ROS) diminishes the therapeutic effect in a hypoxic environment, such as solid tumors. Herein, we developed a ROS-producing hybrid nanoparticle-based photosensitizer capable of maintaining high levels of ROS under both normoxic and hypoxic conditions. Conjugation of a ruthenium complex (N3) to a TiO 2 nanoparticle afforded TiO 2 -N3. Upon exposure of TiO 2 -N3 to light, the N3 injected electrons into TiO 2 to produce three- and four-fold more hydroxyl radicals and hydrogen peroxide, respectively, than TiO 2 at 160 mmHg. TiO 2 -N3 maintained three-fold higher hydroxyl radicals than TiO 2 under hypoxic conditions via N3-facilitated electron-hole reduction of adsorbed water molecules. The incorporation of N3 transformed TiO 2 from a dual type I and II PDT agent to a predominantly type I photosensitizer, irrespective of the oxygen content. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Influence of reactive oxygen species during deposition of iron oxide films by high power impulse magnetron sputtering

    Science.gov (United States)

    Stranak, V.; Hubicka, Z.; Cada, M.; Bogdanowicz, R.; Wulff, H.; Helm, C. A.; Hipp